i 

 

 

 

EVALUATION OF POTENTIAL KIDNEY DONORS 

AND OUTCOMES POST-DONATION AT 

CHARLOTTE MAXEKE JOHANNESBURG ACADEMIC HOSPITAL 

(1983 – 2015) 

 

 

Chandni Dayal 

 

A research report submitted to the Faculty of Health Sciences, University of 

Witwatersrand, Johannesburg, in partial fulfilment of the requirements for the degree of 

Master of Medicine in the branch of Internal Medicine 

 

Johannesburg, 2019 

 

 



ii 

DECLARATION 

 

I, Chandni Dayal, hereby declare that this research report is my own unaided work. It is being 

submitted for the degree of Master of Medicine in the branch of Internal Medicine. This 

research report is submitted in the publishable format as recognised by the Faculty of 

Health Sciences. I further declare that this work has not been submitted before for any 

degree or examination at this or any other University. 

 

 

_____________________________  

3rd day of June, 2019 

  



iii 

 

 

 

 

 

For my parents, 

Prakash and Nirmal Dayal 

  



iv 

PUBLICATIONS AND PRESENTATIONS ARISING FROM THIS RESEARCH 

 

1. Awarded best poster presentation at the South African Renal Society Congress, Cape 

Town, 11 September 2016 

 Published abstract resulting: Dayal C, Diana N, Davies M, Meyers AM, Paget G. 

Failure to launch: Exclusion from living kidney donation at Charlotte Maxeke 

Johannesburg Academic Hospital (1983-2015). African Journal of Nephrology 

2016;19:48. 

2. Oral presentation at the South African Renal Society Congress, Cape Town, 9-11 

September 2016 

 Published abstract resulting: Dayal C, Diana N, Davies M, Meyers AM, Paget G. 

Long-term outcomes in accepted living kidney donors at Charlotte Maxeke 

Johannesburg Academic Hospital (1983-2015). African Journal of Nephrology 

2016;19:35. 

3. Oral presentation to the Wits Donald Gordon Medical Centre Renal unit, Johannesburg, 

13 October 2016 

4. Oral presentation to the Charlotte Maxeke Johannesburg Academic Hospital 

Department of Internal Medicine, Johannesburg, 10 February 2017 

 

 



v 

ETHICAL CONSIDERATIONS 

 

Permission for this retrospective study was obtained from Prof. G. Paget (Head of 

Nephrology, Department of Internal Medicine, Charlotte Maxeke Johannesburg Academic 

Hospital), Ms. G. Bogoshi (Chief Executive Officer, Charlotte Maxeke Johannesburg 

Academic Hospital), and the Human Research Ethics Committee of the University of 

Witwatersrand (Clearance number M150923). 

  



vi 

ABSTRACT 

Background 

Living kidney donation has emerged as a key therapeutic modality for end-stage kidney 

disease due to the global chronic shortage of renal allografts. However, the potential 

benefits to the recipient of a living donor kidney must be balanced against donor safety. In 

demographically diverse populations, there is a paucity of data regarding the living donor 

evaluation process and outcomes following donation. 

 

Objectives 

This study was undertaken to describe donation patterns, characterise reasons for non-

donation and evaluate long-term morbidity and mortality following living kidney donation 

in the South African context. 

 

Methods 

A retrospective analysis of all Potential Living Donors (PLDs) evaluated at a single centre 

over a 32-year period was conducted. Of the total cohort of 1208 PLDs, 298 were Accepted 

Living Donors (ALDs), resulting in 910 Failed Living Donors (FLDs). Data collected included 

donor demographics. In addition, in the ALD group, clinical and laboratory parameters at 

various points in donor follow-up, as well as mortality data was noted. In the FLD group 

reason for donor exclusion was documented. 



vii 

Results 

Of the 1208 PLDs, 697 (58%) were female. The majority (559; 46%) were of Black African 

descent, and related to the intended recipient (991; 82%). 

Outcome of PLD evaluation varied significantly by race (p<0.001), with only a third of Black 

PLDs being accepted for donation. Black vs. Caucasian PLDs were more likely to fail work-

up (52.1% vs. 39.3%; p<0.001) and be excluded for medical reasons (44% vs. 35%; p<0.001). 

Leading medical exclusions included hypertension, HIV and obesity. 

In the ALD cohort, median follow-up time was 44 months (IQR 13.8 – 93.5 months). 

Hypertension was documented in 12.8% of ALDs at most recent follow-up compared to 

4.7% of ALDs pre-donation (p=0.06). There was a significant increase in Albumin Excretion 

Rate (AER) following donation (p<0.001). There was a significant decline in the CKD-EPI 

eGFR between pre-donation (91.7 ± 19.1 ml /min/1.73 m2) and the most recent visit post-

donation (72.5 ± 20 ml/min/1.73 m2; p<0.001). 27% of ALDs had a CKD-EPI eGFR<60 

ml/min/1.73 m2 at most recent visit, however none required renal replacement therapy. 

There were 5 documented deaths, all unrelated to the development of renal dysfunction. 

Black ethnicity was not associated with increased risk of adverse outcome following 

donation. 

 

Conclusions 

There is a high exclusion rate for PLDs. Black PLDs are more likely to be excluded than 

Caucasian counterparts due to significant comorbidity. Although limited by high rates of 



viii 

donors lost to follow-up, it is concerning that a quarter of ALDs developed an eGFR<60 

ml/min/1.73 m2 at last follow-up, with a significant increase in AER. 

  



ix 

ACKNOWLEDGEMENTS 

 

I wish to acknowledge the following people for the roles they have played in the completion 

of this report: 

 Dr. Nina Diana and Dr. Malcolm Davies – for assistance as supervisors of this study, review 

of the prepared manuscript, and constant support. 

 Professor Anthony Meyers and Professor Graham Paget – for encouragement and 

guidance. 

 Dr. Avinash Dayal, Dr. Sunaina Paima, Dr. Nida Siddiqui and Sr. Anne Morolo – for 

invaluable aid with record gathering. 

  

 

  



x 

 TABLE OF CONTENTS  

DECLARATION ................................................................................................................... ii 

PUBLICATIONS AND PRESENTATIONS ARISING FROM THIS RESEARCH ............... iv 

ETHICAL CONSIDERATIONS ............................................................................................ v 

ABSTRACT .......................................................................................................................... vi 

ACKNOWLEDGEMENTS .................................................................................................... ix 

LIST OF TABLES ................................................................................................................ xiii 

ABBREVIATIONS / NOMENCLATURE ........................................................................... xiv 

 

CHAPTER 1: PROTOCOL AND EXTENTED REVIEW OF THE LITERATURE ................. 1 

1. BACKGROUND ................................................................................................... 1 

1.1. Introduction ....................................................................................................... 1 

1.2. Physiology of uninephrectomy ....................................................................... 2 

1.3. Clinical context .................................................................................................. 3 

1.4. An overview of Failed Living Donors ............................................................. 5 

1.4.1. Medical reasons for donor exclusion ................................................................... 5 

1.4.2. Non-medical reasons for donor exclusion .......................................................... 6 

1.4.2.1. Immunological factors ......................................................................................... 6 

1.4.2.2. Psychosocial factors ............................................................................................. 6 

1.4.3. Outcome of donor evaluation by ethnicity ......................................................... 7 

1.5. An overview of Accepted Living Donors ....................................................... 8 

1.5.1. A pre-2014 perspective ........................................................................................ 8 

1.5.1.1. Renal outcomes ................................................................................................... 8 

1.5.1.2. Non-renal outcomes ............................................................................................ 9 

1.5.2. Critical analysis of pre-2014 data ....................................................................... 9 

1.5.3. Current data on living donation ....................................................................... 10 

1.5.3.1. Renal outcomes ................................................................................................. 10 

1.5.3.2. Donor Mortality ................................................................................................. 11 

1.5.4. Medically complex donors ................................................................................. 12 

1.5.5. Effect of race on donor outcome........................................................................ 12 

1.5.6. Donor ESKD risk projection ................................................................................ 13 

1.5.7. Measurement of renal outcomes post donation: eGFR ..................................... 15 



xi 

1.5.8. Donor follow-up ................................................................................................. 15 

1.5.8.1. Barriers to donor follow-up ............................................................................... 16 

1.5.8.2. Improving donor follow-up ............................................................................... 16 

1.6. The South African context ............................................................................. 17 

1.7. Summary ........................................................................................................... 18 

2. OBJECTIVES ...................................................................................................... 20 

2.1. Primary Objective ............................................................................................ 20 

2.2. Secondary Objectives ...................................................................................... 20 

3. METHODOLOGY .............................................................................................. 21 

3.1. Study design ..................................................................................................... 21 

3.2 Data collection ................................................................................................. 21 

3.2.1 Data collection for failed living donors ........................................................... 21 

3.2.2 Data collection for accepted living donors ...................................................... 22 

3.3 Definition of variables.................................................................................... 24 

3.3.1 Classification of donors .................................................................................... 24 

3.3.2 Hypertension ..................................................................................................... 24 

3.3.3 Albuminuria ....................................................................................................... 25 

3.3.4 Glomerular filtration rate .................................................................................. 25 

3.3.5 Chronic kidney disease ..................................................................................... 26 

3.3.6 Body mass index ............................................................................................... 27 

3.3.7 Isolated medical abnormalities ........................................................................ 28 

4. STATISTICAL ANALYSIS ................................................................................. 29 

5. ETHICS ............................................................................................................... 30 

6. TIMING .............................................................................................................. 30 

7. FUNDING .......................................................................................................... 30 

8. POTENTIAL LIMITATIONS .............................................................................. 31 

9. REFERENCES ..................................................................................................... 32 

 

CHAPTER 2: PROPOSED MANUSCRIPT ....................................................................... 44 

ABSTRACT ........................................................................................................................ 44 

INTRODUCTION .............................................................................................................. 45 

RESULTS ............................................................................................................................ 47 

DISCUSSION ..................................................................................................................... 56 



xii 

MATERIALS AND METHODS ......................................................................................... 63 

DISCLOSURE ..................................................................................................................... 65 

ACKNOWLEDGEMENTS .................................................................................................. 65 

REFERENCES ..................................................................................................................... 66 

CHAPTER 3: APPENDICES .............................................................................................. 74 

APPENDIX A: Data collection sheets ............................................................................ 74 

i. Data collection sheet for failed living donors .................................................. 74 

ii. Data collection sheet for accepted living donors ........................................... 76 

APPENDIX B: Ethics clearance certificate .................................................................... 80 

APPENDIX C: Plagiarism report .................................................................................... 81 

        

 

  

  



xiii 

LIST OF TABLES 

 

Chapter Table Title Page 

1 1.1 Revised KDOQI classification for chronic kidney disease 27 

1 1.2 WHO international classification of BMI 28 

2 2.1 Donor demographics 51 

2 2.2 Reasons for non-donation 52 

2 2.3 Donor exclusion stratified by ethnicity 53 

2 2.4 Comparative clinical parameters in accepted living donors 53 

2 2.5 Logistic regression analysis of variables associated with an 

eGFR<60 ml/min/1.73m2 at most recent follow-up 
54 

2 2.6 Accepted donor ethnicity and parameters at most recent 

follow up visit 
55 

2 2.7 Parameters associated with defaulting post-donation 

follow-up 
55 

 

 

 

 

 

 



xiv 

ABBREVIATIONS / NOMENCLATURE 

51Cr-EDTA Chromium-51-ethylene-diamine-tetra-acetic-acid 

ACS Acute coronary syndrome 

AER Albumin excretion rate 

ALD Accepted living donor 

APOL1 Apolipoprotein L1 

BMI Body mass index 

CI Confidence interval 

CKD Chronic kidney disease 

CKD-EPI Chronic Kidney Disease Epidemiology Collaboration 

CMJAH Charlotte Maxeke Johannesburg Academic Hospital 

CMV Cytomegalovirus  

COPD Chronic obstructive pulmonary disease 

CrCl Creatinine clearance 

CTA Computed tomography angiogram 

EBV Epstein-Barr virus 

eGFR Estimated glomerular filtration rate 

ESKD End-stage kidney disease 

FLD Failed living donor 

GFR Glomerular filtration rate 

HepBsAg Hepatitis B surface antigen 

HepCAb Hepatitis C antibody 

HIV Human immunodeficiency virus 



xv 

HLA Human Leukocyte Antigen 

HR Hazard ratio 

IHD Ischemic heart disease 

IMA Isolated medical abnormality 

KDIGO Kidney Disease Improving Global Outcomes 

KDOQI Kidney Disease Outcomes Quality Initiative 

NSAIDs Non-steroidal anti-inflammatory drugs 

PLD Potential living donor 

PSA Prostate-specific antigen 

RLD Related living donor 

RRT Renal replacement therapy 

SA South Africa 

sCr Serum creatinine 

TB Tuberculosis 

UTIs Urinary tract infections 



  1 

CHAPTER 1: PROTOCOL AND EXTENTED REVIEW OF THE LITERATURE 

 

1. BACKGROUND 

1.1. Introduction 

As the burden of end-stage kidney disease (ESKD) escalates globally, the growing demand 

for renal allografts cannot be met by deceased donors alone. [1, 2] This escalation is of 

particular concern in developing countries, as it is estimated that by the year 2030 in excess 

of 70% of patients with ESKD will reside in middle- and low-income countries, such as those 

in sub-Saharan Africa. [3, 4] Transplantation is the preferred modality of renal replacement 

therapy (RRT), having significantly better morbidity and mortality rates compared to long 

term dialysis. [5] Living donor transplants are known to offer improved allograft survival 

rates over deceased donor grafts. [5] In addition, living kidney donation offers the potential 

to significantly expand the kidney donor pool. [2] Rates of living kidney donation are 

increasing globally, with a twofold rise in the number of living donor transplants reported 

over the last decade in countries where registry data is available. [6]  

 

Living donation necessitates healthy individuals to undergo major surgery without any 

direct self-benefit. [7] The advantages of living donor transplantation for the recipient must 

therefore be balanced against ensuring donor safety, both in the selection process of 

potential living donors (PLDs) and the post-donation care of accepted living donors (ALDs). 

[8-11] 

 



2 

To date, the outcome of living donation for donors has largely been assessed in the 

developed world. [6] Emerging studies now suggest that the risk of adverse outcomes 

amongst ALDs may have been underestimated. [12-14] There is a paucity of data amongst 

demographically diverse populations in the developing world. [15] 

 

 

1.2. Physiology of uninephrectomy 

Micro-puncture animal studies have informed much of what is understood about the 

pathophysiological sequelae of nephron mass reduction resulting from donor harvesting. 

[16, 17] 

 

Uninephrectomy induces a series of both structural and functional adaptations at a 

glomerular level. [16] An increase in renal plasma flow in the remaining kidney results in 

sustained single nephron hyperfiltration, which is accompanied by a rise in intraglomerular 

pressure. [17] The release of various growth factors and cytokines mediates glomerular 

hypertrophy which is reflected by an increase in the renal volume. [16, 17] 

 

These compensatory mechanisms facilitate the maintenance of a post-donation estimated 

filtration rate (eGFR) that is comparable to normal renal function, despite a loss of half the 

renal mass. [16] Delanaye et al. reported that the average post-donation eGFR reaches 65-

70% of the pre-donation value (in donors ≤ 60 years of age) and that the progressive decline 

in eGFR following donation mirrors that which occurs with normal senescence. [18] 

 



3 

However, long-term sustained hyperfiltration may cause maladaptive alterations to remnant 

glomeruli which in turn lead to progressive renal injury. [16, 17] In animal models, 

hyperfiltrating glomeruli undergo morphological changes ultimately resulting in focal and 

segmental glomerulosclerosis. [17] This is postulated to be the pathophysiological 

mechanism accounting for the long-term complications arising post uninephrectomy, 

including the development of proteinuria, hypertension and progression to ESKD. [16]  

 

A key consideration with regard to the animal model is that a 5/6 reduction in nephron 

mass of the experimental rat is not physiologically equivalent to a loss of half the nephron 

mass in an otherwise healthy individual. [19] A recent study by Lenihan et al. analysed 

glomerular dynamics following donation and suggested that single nephron hyperfiltration 

occurs largely independent of maladaptive glomerular hypertension. [20] This is thought to 

account for the observation that adverse renal outcomes occur relatively infrequently 

amongst living kidney donors. [21] 

 

An additional concern is the adverse impact of nephron mass reduction on cardiovascular 

health. Numerous human studies have demonstrated an elevation in biomarkers associated 

with endothelial dysfunction and atherosclerosis following uninephrectomy. [22 – 25] 

 

 

1.3. Clinical context 

The practice of living kidney donation has evolved considerably since the first successful 

live donor transplant over sixty years ago. [26] Advances in therapy have led to renal 



4 

transplantation emerging as the preferred treatment modality for ESKD, with live donor 

pools accounting for a significant number of kidney transplants worldwide. [2, 6]  

 

Living donation encompasses both related and unrelated donors. Unrelated donors may 

either be directed or purely altruistic. [11] Living donor paired exchanges and donor chains 

offer the potential to increase the utilisation of living donors in otherwise incompatible 

donor-recipient pairs. [27, 28] 

 

As guided by the Kidney Disease Improving Global Outcomes (KDIGO) organization which 

developed an international standard of care for the live kidney donor, PLDs undergo an 

extensive multidisciplinary assessment prior to being accepted for living donation. [29] It is 

not uncommon for this rigorous work-up to detect occult disease in the prospective donor. 

[29] PLDs who are not accepted for donation are called failed living donors (FLDs). Multiple 

studies report similarly high rates of FLDs, ranging between 47-62%, with prospective Black 

donors most likely to be excluded. [30-34] 

 

Regarding outcomes in ALDs, older data appeared to show no difference in the long-term 

medical outcomes in living kidney donors as compared to the general population with some 

studies even suggesting that kidney donors ‘live longer’. [35, 36]. More recent studies, which 

have compared outcomes in ALDs to appropriately matched controls, have been less 

reassuring. [12-14] African-American donors were consistently under-represented in these 

studies, although the estimated risk of adverse outcome is believed to be highest in this 

population group. [15, 37, 38] 



5 

1.4. An overview of Failed Living Donors 

Characterising the reasons for donor exclusion may identify modifiable factors that can be 

addressed in order to safely expand living donor pools. [33, 39]  

1.4.1. Medical reasons for donor exclusion 

Medical contraindications prevail universally as the most common reason for donor 

exclusion. [30-34] 

 

Enhanced pre-donation screening highlights the declining health of the aging general 

population, as well as the growing burden of non-communicable disease globally. [4, 39, 

40] It is estimated that roughly 10% of the world’s population has chronic kidney disease 

(CKD), most of which is asymptomatic. [4, 41] Given this estimation, it can be extrapolated 

that roughly five million South Africans have underlying CKD. [42] Hypertension and 

diabetes constitute the main causes, mirroring global trends. [40, 42-44] Underlying both 

these disorders is the worldwide epidemic of obesity. The South African population’s obesity 

rate is 49%, double the global rate. [44, 45] Numerous studies have found obesity, 

hypertension and diabetes to be the most prevalent medical reasons for potential donors 

failing to ultimately donate a kidney. [30-34] 

 

In addition, sub-Saharan Africa has a high prevalence of human immunodeficiency virus 

(HIV). [4] The potential for donor exclusion due to communicable disease is therefore 

greater in this region. [4, 39, 42] 

 



6 

1.4.2. Non-medical reasons for donor exclusion 

 

1.4.2.1. Immunological factors 

ABO and cross-match incompatibility amongst donor-recipient pairs have historically been 

major limiting factors in living kidney donation. [30-32, 34]  

 

Previously, immunological factors resulted in the exclusion of at least one-third of otherwise 

suitable donors. [46] In recent years, however, novel approaches have emerged to 

circumvent these immunological barriers. [47, 48] These include the use of immune 

modulatory therapy to allow HLA-desensitisation and ABO incompatible transplantation. 

[46-48] In addition, kidney exchange and domino-paired anonymous donation programs 

offer a cost effective alternative, without the added risk of complications arising from the 

use of additional intense immunosuppression needed to overcome immunological factors. 

[27, 48] 

 

The outcomes of these strategies have thus far been reassuring, with similar graft survival 

rates being demonstrated as compared to standard living donor transplants. [27, 28, 46, 47] 

This further highlights their importance in sustaining an expansion in living donor pools. 

[48] 

 

1.4.2.2. Psychosocial factors 

All PLDs undergo mandatory evaluation to determine psychosocial suitability for donation. 

[39] During this process, motive for donation, socioeconomic support structures, and 



7 

general psychosocial wellbeing are assessed. [39] Aside from cultural factors, an increasingly 

common phenomenon is non-donation among medically suitable candidates who 

voluntarily withdraw from donation due to concerns regarding their prognosis following 

donation as well as fear of the potential complications of the surgical procedure itself. [30, 

31, 33] Targeted donor education programs which can address such concerns early on in 

the evaluation process could potentially enhance living donor transplant rates by at least 

10%. [33] 

 

1.4.3. Outcome of donor evaluation by ethnicity 

Weng et al. highlighted that Black (vs. non-Black) potential donors were more likely to be 

excluded for medical reasons, most notably hypertension and obesity. [34] Furthermore, a 

prospective cohort study determined the overall odds of donation to be 52% lower in 

African Americans as compared to Caucasians (OR 0.48; p<0.001), with similarly high rates 

of exclusion for diseases of lifestyle. [50] 

 

African American donors are more likely to decide against donation. [33, 34, 50, 51] Reasons 

for this disparity in willingness to donate among African Americans were outlined in a study 

by Purnell et al. [52] Key issues highlighted include medical mistrust and cultural beliefs 

pertaining to bodily integrity. Gill et al. found socioeconomic inequality to be a significant 

barrier. [53] The incidence of living donation was lower amongst African American 

populations in the lowest income quintile (incidence rate ratio 0.84; 95% CI [0.78-0.90]). 

 



8 

In view of the above, various strategies have been proposed to enhance living donation 

rates in the African American population. [51, 54, 55] These include improved preventative 

medical care and educational programs to address unique concerns related to living 

donation in this subgroup. [51, 55] 

 

 

1.5. An overview of Accepted Living Donors 

 

1.5.1. A pre-2014 perspective 

Older reports of long-term donor follow-up suggested that the risks of uninephrectomy 

were of limited clinical significance, with outcomes amongst living donors being 

comparable (if not superior) to that of the general population. [18, 35, 36, 58, 59, 64-66] 

1.5.1.1. Renal outcomes 

In a large longitudinal study by Ibrahim et al. 85% of a predominantly Caucasian cohort of 

donors were found to have a preserved GFR of greater than 60 ml/min/1.73 m2 at a mean 

of 12 years following donation. [35] When compared to the general population, no 

additional risk of accelerated decline in GFR, hypertension or albuminuria was demonstrated 

post-donation. The incidence of ESKD was found to be significantly lower than that of the 

general American population, at a rate of 180 cases per million per year, as compared to 

268 cases per million per year respectively (p<0.001). [35] These findings were consistent 

with numerous other studies that reported relatively benign renal outcomes following 

donation. [56-64] 



9 

1.5.1.2. Non-renal outcomes 

A number of reports have compared long-term donor survival to population-based 

estimates. One such study by Fehrman-Ekholm et al. conducted over a 30-year follow up 

period found that donor longevity exceeded that of the general Swedish population, as 

survival rates were found to be superior in the donor group by 29% (p<0.001). [36] In 

addition, a Norwegian study reported that cardiovascular and overall mortality amongst 

donors were similar to demographically matched controls. [65] Major cardiovascular event 

rates were also found to be lower in donors compared to non-donors (2.8 vs. 4.1 events per 

1000 person years, HR 0.66, 95% CI [0.48-0.90]). [66] 

 

1.5.2. Critical analysis of pre-2014 data 

Numerous concerns have been raised regarding study methodologies used in the reports 

prior to 2014, which favoured the interpretation of better outcomes amongst donors. [64, 

67] 

 

A primary concern has been that of selection bias generated by the use of the general 

population as a control group, as it represents a high risk comparator to live donors who 

are thoroughly screened and thus intrinsically healthier at baseline. [67] Additional concerns 

include the reliability of the data due to restrictive sample sizes, short follow-up durations 

and limited ethnic diversity amongst donor cohorts. [64, 67] 

 



10 

These shortcomings underscore the need to undertake studies that determine attributable 

risk by comparing donors to appropriate controls, namely matched, healthy non-donor 

population groups with large cohort numbers and long duration of follow-up. [68] 

 

1.5.3. Current data on living donation 

Few studies have compared long-term outcomes between donors and healthy matched 

non-donors. These studies highlight evolving concerns pertaining to morbidity and 

mortality following kidney donation. [68] Moreover, emerging prospective data on long-

term donor follow-up has provided valuable new insight into donor nephrectomy 

outcomes. [69] 

1.5.3.1. Renal outcomes 

In the first prospective study conducted on living donors to date, Janki et al. assessed 100 

donors over a median follow-up time of 10 years at two Dutch transplant centres. [70] There 

was a significant decline in the eGFR of 12.9 ml/min/1.73 m2 (p<0.001) at follow-up. One-

fifth of the cohort had an eGFR between 30-60 ml/min/1.73 m2 at the study end-point. [70] 

In a report subsequently published by the same primary investigator, variables associated 

with an accelerated decline in renal function following donation were evaluated in a 

prospective cohort of 190 donors. [71] Over a 5-year follow-up period, a 33.6% decline in 

mean eGFR was noted following donor nephrectomy, with longitudinal analysis revealing a 

lower eGFR among male donors and older age (p<0.001). In this cohort, renal function had 

stabilized after an expected initial decrement immediately following nephrectomy and no 

donor required the institution of RRT.  



11 

Conversely, two reports suggest that living donors are at increased risk of developing ESKD 

as compared to matched controls. Mjøen et al. studied a large cohort of Caucasian living 

donors in Norway and found an eleven-fold increase in the relative risk of ESKD after donor 

nephrectomy. [12] The second, a US-based study by Muzalle et al. included 96214 donors 

with a median follow-up of 8 years. [14] Here, the estimated risk of ESKD was found to be 

7.9-fold higher in living donors. Importantly however, the absolute 15-year incidence of 

ESKD in both these studies remained low at less than 1%. [68] 

 

Although an uncommon occurrence, prior living donors who require RRT have favourable 

post-transplant outcomes, particularly in the US where waiting times for kidney transplant 

are brief as national policy allocates priority to these patients. [72] Event rates for acute 

dialysis following donation are also low. [60, 73] 

1.5.3.2. Donor Mortality 

In a retrospective cohort, Mjøen et al. showed that all-cause mortality in the first decade 

following donation remained comparable to healthy matched non-donor groups. [12] 

However, at 25 years, survival curves diverged, with the cumulative all-cause mortality 

increasing by 5% amongst donors. Over a median follow-up of fifteen years, the same study 

also found an increased risk of cardiovascular mortality amongst donors (HR 1.4; p<0.001). 

In contrast, prospective studies by Janki et al. report reassuring donor survival over mean 

follow-up periods of between 5 and 10 years, with mortality being due to causes unrelated 

to donation. [70, 71] 

 

 



12 

1.5.4. Medically complex donors 

Critical organ shortages have led to the emergence of expanded criteria for donor eligibility, 

in order to augment living donor pools. [74] 

 

Previously published data reported uncertainty in the long-term outcomes of donors with 

preceding isolated medical abnormalities (IMAs), including those who were older (≥ 65 

years of age) or had pre-existing risk factors for CKD such as obesity (BMI 30-35 kg/m2) and 

pre-existing hypertension (stage 1 controlled on a single agent with no end-organ damage). 

[75] However, recent literature in this regard has largely been reassuring. A 2014 systematic 

review including studies using appropriately matched cohorts reported favourable 

outcomes with the use of older donors (up to the age of 70), as well as obese donors 

(irrespective of body mass index). [74] Despite concerns around a greater degree of pre-

existing glomerulopaenia in hypertensive donors, outcomes in this subgroup have been 

comparable to that of normotensive donors. [71, 76-79] 

 

These findings are supported physiologically by the demonstration of similar compensatory 

changes in the remaining kidney of medically complex donors as compared to standard 

donors. [80] 

 

1.5.5. Effect of race on donor outcome 

Comparative studies are limited but have highlighted that Black donors have an increased 

risk of adverse post-donation outcomes as compared to Caucasian donors. [15, 37, 38, 59] 



13 

Over a median follow-up of 6.3 years, the risk of peri-operative mortality was reported to 

be threefold greater amongst Black donors. [64] Following donation, the all cause risk of re-

hospitalisation also greater amongst this subgroup (HR 2.6, 95% CI [1.54-3.03]). [81] There 

was however no statistically significant cause to account for these findings among black 

donors. [64, 81] 

 

At 7 year follow-up, the incidence of renal disease, including proteinuria and nephrotic 

syndrome, was higher amongst black donors as compared to Caucasian counterparts. [38] 

Lentine et al. showed that Black donors have a greater post-nephrectomy risk of developing 

hypertension (HR 1.52; 95% CI [1.23-1.88]) and diabetes (HR 2.31; 95% CI [1.33-3.62]). [15] 

In addition, Black donors were twice as likely to develop CKD. [15] The absolute risk of ESKD 

has consistently been shown to be greater in Black donors. [14, 59] 

 

A study of donation patterns revealed that Black donors are more likely to be related to the 

recipient than Caucasian donors (88% vs. 74%; p=0.007). [82] Genetic factors, including the 

identification of coding variants in the Apolipoprotein L1 (APOL1) gene, are thought to 

underlie the elevated risk for adverse renal outcomes amongst Black patients, although this 

association is yet to be proven amongst Black living kidney donors. [83-87] 

 

1.5.6. Donor ESKD risk projection 

In order to inform donor counselling and selection, various models have been developed 

to estimate the projected long-term risk of ESKD following uninephrectomy. [13, 88-91] 

 



14 

The first extrapolated data is from the Mjøen et al. cohort of 1901 Caucasian donors. [12] In 

this model, with the assumption that all donors live to 80 years of age and that the incidence 

of ESKD remains constant with time, the estimated risk of a 60-year old PLD developing 

ESKD is predicted to be 1 in 150. With a younger age at donation, the estimated risk of 

ESKD incrementally increases, being 1 in 75 for a 40-year old PLD, and 1 in 50 in a 20-year 

old PLD. [13] Furthermore, a risk calculator developed by Ibrahim et al. to assess renal 

outcomes that portend ESKD in Caucasian donors found that the development of post-

donation diabetes and hypertension was associated with a two-fold higher risk of ESKD. 

[88] 

 

The only model that included risk projection amongst racially diverse donors was generated 

using US population based data. [89] In this report, the projected risk of ESKD amongst 

PLDs over a 15-year time period was found to be 3.5 - 5.3 times greater than the projected 

risk in the absence of donation. Furthermore, the risk of ESKD was identified as being 

highest amongst young Black PLDs – an average 40 year old Black donor had a 3.9 times 

higher 15-year risk of developing ESKD as compared to a Caucasian donor of the same age 

and baseline characteristics. [89]  

 

Recent studies highlight a strong genetic component to the ESKD risk profile in living kidney 

donors; donors who are first-degree relatives to the recipient have consistently been shown 

to have a significantly greater predicted risk for ESKD following donation. [90, 91] 

  

 



15 

1.5.7. Measurement of renal outcomes post donation: eGFR 

Post uninephrectomy, the assessment of renal function in donors requires a reliable method 

for the determination of GFR. This allows for the timeous identification of a possible decline 

in renal function following donation. [92, 93]  

 

Ideally, GFR should be accurately measured in donors as concerns have been expressed 

regarding the use of creatinine-based equations to estimate renal function in individuals 

with a single kidney. [93] In practise however, calculated estimates of GFR are cost effective, 

and are therefore of particular relevance in resource limited settings. [92] Although many 

studies have applied the Cockroft-Gault or Modification of Diet in Renal Diseases formulas, 

the estimate now recommended for use in the assessment of renal function in living donors 

following uninephrectomy is the Chronic Kidney Disease Epidemiological Collaboration 

(CKD-EPI) equation. [92,93] This formula has been shown to closely approximate measured 

GFRs in living donors and has superior precision and accuracy as compared to other 

creatinine-based equations. [94]   

 

1.5.8. Donor follow-up 

The need for structured donor follow-up is critical – particularly in an era where medically 

complex donors are frequently utilised and longitudinal data reveal a risk of comorbidity 

following donation. [74, 95] Monitoring of donors facilitates the early diagnosis and timeous 

institution of therapy where indicated, thus minimising the risk of potential complications. 

[96] Nevertheless, donor follow-up rates remain universally low. [97-99] In a 2015 report, 

Keshvani et al. noted that, by two years following donation, 40% of all transplant centres 



16 

lose contact with more than two-thirds of their donors. [100] This underscores the likelihood 

that potential adverse donor outcomes are substantially underreported. [67]  

 

1.5.8.1. Barriers to donor follow-up 

Incomplete donor follow-up can be attributed to both donor and transplant centre factors. 

[100, 101] Schold et al. highlighted that younger age at donation, Black race, poor health 

literacy and distance of domicile in relation to follow-up centre were all independent risk 

factors for low follow-up rates. [101] This is consistent with Weng et al.’s report which 

identified similar risk factors. [102] Weng et al. also noted that amongst donors who had 

pursued follow-up, only 8% had been assessed by a nephrologist following donation. [102] 

In addition, higher rates of donor defaulting are reported amongst transplant centres with 

a higher volume of living donor transplants per year, as well as those with limited resources 

to trace patients following donation. [101] 

 

1.5.8.2. Improving donor follow-up 

The institution of targeted strategies to augment donor follow-up has led to improved 

donor compliance at many transplant centres. [100-103] In the Keshvani et al. cohort, 

increased efforts to telephonically contact donors for follow-up, patient education classes 

conducted by a dedicated transplant nurse as well as reimbursement of donors for transport 

costs incurred by follow-up visits were all shown to significantly improve donor follow-up 

at 2 years (p<0.001). [100] Dedicated initiatives to improve follow-up in particular at-risk 



17 

subgroups such as younger donors and those with lower educational attainment have also 

been of benefit. [101] 

 

 

1.6. The South African context 

The lack of access to RRT in developing countries has been well documented. [4] In South 

Africa (SA), the burgeoning HIV/AIDS epidemic has demanded a disproportionate quantum 

of healthcare resources, further limiting the provision of RRT. [44,104,105] As a result, a 

significant number of South Africans are at risk of premature death due to ESKD. [3]  

 

Living kidney donation thus offers a cost-effective measurement to facilitate definitive RRT 

in the South African setting. [104] Living donor transplant rates are however low across 

many centres in SA, with only 93 performed in the year 2014 despite the rapidly growing 

demand for donor organs. [104,105] Of further concern is that the risks associated with 

living donation have historically been poorly defined in demographically diverse 

populations. [15] 

 

To date, only four studies relating to living kidney donation in South Africa have been 

undertaken. The first, conducted in Johannesburg in 1986 by O’ Donnell et al. studied 33 

living related donors over a mean follow-up period of 5.8 years. [106] Donors were found 

to have substantial rise in diastolic blood pressure (p<0.001), as well as inclination towards 

a significant decline in creatinine clearance following donation (p 0.0558). In a series by 

Naicker et al. 135 related living donors were reviewed over a ten year period. [107] The 



18 

majority of donors in this cohort were female (63%) and of Indian origin (58%), with a mean 

age of 34 years. Here, blood pressure post nephrectomy remained essentially unchanged, 

although three donors demonstrated clinically significant proteinuria following donation. 

The post-donation serum creatinine was found to be within normal limits, despite a mean 

rise of 33.4% over the follow-up period. The findings of the third study by Abdu et al. 

highlighted the need to encourage living donation and facilitate donor follow-up, which 

was noted to be poor in roughly 40% of the cohort. [108] The final report described reasons 

for donor exclusion in 117 prospective donors at a Cape Town centre. [109] In this study, 

only 17% of donors ultimately donated, with the remainder excluded for predominantly 

immunological and medical reasons such as obesity, hypertension and CKD.  

 

 

1.7. Summary 

Living kidney donation has emerged as the preferred strategy to ameliorate the growing 

demand for renal allografts worldwide. [6] It is thus essential that the transplant community 

investigates methods to sustain living donor pools without compromising donor safety. [29, 

39] This is particularly relevant as recent data highlights a substantial risk for adverse 

outcomes amongst prior living donors, although outcomes in racially diverse populations 

have been poorly characterised. [15, 35, 36] In order to tailor the informed consent process, 

attention to long-term outcomes amongst diverse living kidney donors is needed. [37, 67] 

  

The present study was undertaken in an effort to evaluate living kidney donation in the 

South African context with a view to identifying reasons for donor exclusion which may in 



19 

future facilitate the assessment of potentially modifiable barriers to donation, and in an 

attempt to characterise long-term morbidity and mortality following donation which may 

better inform the consent process for prospective donors in this setting. 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 



20 

2. OBJECTIVES 

2.1. Primary Objective 

 To determine donor morbidity and mortality after donation. 

 Analysis of morbidity will focus on the development of 

a. New onset hypertension following donation (BP ≥140/90) 

b. Chronic kidney disease following donation, defined as the development of either 

of the following 

i. New onset proteinuria (AER >300mg/day)  

ii. An eGFR <60 ml/min/1.73 m² (using the CKD-EPI formula) 

 

2.2. Secondary Objectives 

 To determine the reasons for exclusion of potential donors from living kidney donation 

 To determine the prevalence of ESKD following donation (eGFR <15 ml/min/1.73 m² 

using the CKD-EPI formula) 

 To determine potential risk factors associated with proteinuria and/or a reduced eGFR 

post kidney donation, by evaluating – 

a. donor demographics 

b. the presence of isolated medical abnormalities prior to donation, defined by: 

- a borderline pre-donation 51Cr-EDTA GFR (<80 ml/min/1.73 m²) 

- pre-existing hypertension (well controlled on a single agent with no end-

organ damage) 

- class I obesity (BMI 30-35 kg/m²) 

 To determine the proportion of patients lost to follow-up post donation 



21 

3. METHODOLOGY 

 

3.1. Study design 

A single centre retrospective observational study will be conducted of all patients attending 

the Living Donor Clinic in the Renal Unit at CMJAH over a 32-year period between 01 

January 1983 and 31 July 2015. The closing date for sampling reflects the period of protocol 

submission for this study. 

 

The cohort will be comprised of 1208 potential living donors, of which: 

 910 are failed living donors, assessed between 01 January 1990 and 31 July 2015 

 298 are accepted living donors, assessed between 01 January 1983 and 31      

     July 2015 

 

3.2 Data collection 

3.2.1 Data collection for failed living donors  

Data collection for failed living donors will comprise the following parameters: 

 

 Demographic data – age at assessment, gender and ethnicity 

 Family history of the donor 

 Relation to the intended recipient – whether related, unrelated or altruistic 

 The outcome of eligibility evaluation 



22 

 If excluded from living donation, reasons for non-donation will be documented, which 

will be categorised as:  

- donor-recipient related, 

- donor-related, 

- recipient-related, or 

- miscellaneous. 

 The indications and findings of any renal biopsy undertaken on a donor will be recorded 

 

3.2.2 Data collection for accepted living donors 

Data collection for accepted living donors will comprise the following parameters:  

 

 Demographic information – gender, ethnicity, age at donation (as well as age at each 

follow-up point) 

 Family history of the accepted donor 

 Details pertaining to the donation, specifically: 

- relation to the recipient, as well as cause of renal failure in the recipient 

- the date of donation 

- the graft outcome (if known) 

 The last follow-up date at the Living Donor Clinic and the approximate number of post-

donation follow-up visits 

 Domicile in relation to the Living Donor Clinic (in kilometres from transplant centre)  

 The reason for lost to follow-up (if known) 

 Baseline characteristics at donation, including: 



23 

- Body mass index 

- Urine albumin : creatinine ratio 

- Systolic blood pressure 

- Diastolic blood pressure 

- Baseline serum creatinine 

- eGFR as defined by an isotope study, the chromium-51-ethylene-diamine-tetra-

aceticacid scan (51Cr EDTA scan) as well as the CKD-EPI formula 

- Habits, including smoking status and history of alcohol consumption 

- History of pre-existing medical condition(s) 

 Characteristics at follow-up (correlated with time after donation), including: 

- Body mass index 

- Urine albumin : creatinine ratio 

- Systolic blood pressure 

- Diastolic blood pressure 

- Serum creatinine 

- eGFR as defined by the CKD-EPI formula 

- Habits, including smoking status and alcohol consumption 

- Development of co-morbid disease  

- History of nephrotoxic drug intake 

The above variables will be retrospectively collected from data recorded at the patients’ first 

follow-up visit post-donation, one-year post-donation visit, and at the most recent follow-

up visit. 



24 

 Mortality data will be collected in accepted living donors that demised during the study 

period, and will include: 

- age at death 

- the time from donation to mortality 

- cause of death, whether related to renal disease, a cardiovascular event or other 

cause 

 

 

3.3 Definition of variables 

 

3.3.1 Classification of donors 

 Potential living donors (PLDs) – refer to all donors assessed at the CMJAH Living 

Donor Clinic 

 Failed living donors (FLDs) – refer to the sub-group of PLDs excluded from living 

kidney donation 

 Accepted living donors (ALDs) – refer to the subgroup of PLDs that ultimately 

donated a kidney 

 

 

3.3.2 Hypertension 

Defined as per the Eighth Joint National Committee (JNC8) guidelines for blood  

pressure targets: 



25 

 For donors with a current age of more than sixty years: 

- a systolic blood pressure of more than 150mmHg, with 

- a diastolic blood pressure of more than 90mmHg 

 For donors with a current age of less than sixty years: 

- a systolic blood pressure of more than 140mmHg, with 

- a diastolic blood pressure of more than 90mmHg 

 

3.3.3 Albuminuria 

Quantified as per the revised Kidney Disease Improving Global Outcomes (KDIGO) chronic 

kidney disease classification into three stages of albuminuria based on the albumin 

excretion rate (AER) in milligrams per day (mg/day): 

 A1: Normal or mildly increased (AER <30 mg/day) 

 A2: Moderately increased (AER between 30 - 300 mg/day) 

 A3: Severely increased (AER >300 mg/day, with nephrotic range proteinuria 

defined as >3500 mg/day) 

 

3.3.4 Glomerular filtration rate 

 

 Pre-donation GFR will be defined: 

- as per isotope study: 51Cr EDTA scan 

- as calculated by the Chronic Kidney Disease Epidemiology Collaboration 

(CKD-EPI) formula, expressed as: 

 



26 

GFR =  141 × min (Scr /κ, 1) α × max (Scr /κ, 1)-1.209 × 0.993Age × 1.018 [if 

female] × 1.159 [if black] 

 

where: GFR  = glomerular filtration rate in ml/min/1,73m2 

Scr  = serum creatinine in mg/dL 

κ  = 0.7 for females and 0.9 for males 

α  = -0.329 for females and -0.411 for males 

min  indicates the minimum of Scr /κ or 1, and 

max  indicates the maximum of Scr /κ or 1. 

 

   Post-donation GFR will be calculated by the CKD-EPI formula, as expressed above. 

 

3.3.5 Chronic kidney disease 

Defined as per the revised Kidney Disease Outcomes Quality Initiative (KDOQI) as either 

kidney damage or GFR<60 ml/min/1.73 m² for ≥ 3 months. Kidney damage encompasses 

pathological abnormalities or markers of damage, including biochemical or radiological 

abnormalities. GFR is further classified into stages (table 1.1). 

 

 

 

 

 

 



27 

Table 1.1 | Revised KDOQI classification for chronic kidney disease 

GFR Stages GFR (ml/min/1,73 m2)  Classification 

1 >90 Normal 

2 60 – 89 Mildly decreased 

3a 45 – 59 Mildly to moderately decreased 

3b 30 – 44 Moderately to severely decreased 

4 15 – 29 Severely decreased 

5 <15 ESKD  

 

 

3.3.6 Body mass index  

 

 BMI will be calculated as weight (in kilograms) divided by height (in meters) 

squared. 

 It will then be sub-classified as per the World Health Organisation (WHO) 

international BMI classification (table 1.2). 

 

 

 

 

 

 

 



28 

Table 1.2 | WHO international classification of BMI 

Classification BMI (kg/m2) 

Underweight < 18.5 

Normal Range 18.5 to 24.99 

Overweight 

Pre-obese 

Obese 

- Obese Class I 

- Obese Class II 

- Obese Class III 

≥ 25 

25 to 29.99 

≥ 30 

30 to 34.99 

35 to 39.99 

≥ 40 

 

 

3.3.7 Isolated medical abnormalities  

Refers to donors with any of the following characteristics prior to donation: 

 A borderline 51Cr-EDTA GFR <80 ml/min/1.73 m2 

 Pre-existing hypertension well-controlled on a single agent with no end-     

     organ damage 

 Class I obesity (BMI 30 - 35 kg/m2 ) 

 

 



29 

4. STATISTICAL ANALYSIS 

 Data analysis will be conducted using STATISTICA 12, a software package developed by 

StatSoft 

 All data will be tabulated in a Microsoft Excel spreadsheet 

 The distribution of continuous variables will be analysed using the Shapiro Wilk W test 

and by visual inspection of the histogram plot. The central measurement will be 

indicated by the mean for normally distributed variables and by the median for non-

parametric data; dispersion will be presented as standard deviation and interquartile 

range, respectively.  

 The categorical variables will be presented as percentages 

 Statistical comparisons will be performed with the Student’s t-test for continuous 

normally distributed variables and the chi-squared test for categorical variables. Where 

appropriate, the one-way ANOVA and Wilcoxon matched pairs testing will be applied.  

 For the accepted donor cohort, a multiple linear regression analysis will be performed 

to identify independent factors associated with a reduced eGFR of <60 ml/min/1.73 m2 

at last follow-up.  

 The Cox proportional hazard model will be applied to assess variables which impact on 

donor follow-up. If last follow-up is more than six months before the study end-point, 

donor defaulting will be assumed.  

 A p-value of less than 0.05 will be considered to indicate statistical significance. 

 



30 

5. ETHICS 

 Permission for this study was obtained from the Human Research Ethics Committee 

(Medical) – Clearance Certificate Number: M150923 (Chapter 3 – Appendix B). Permission 

to access patient records was obtained from the Head of Nephrology at CMJAH, as well 

as the Clinical Director and CEO of the institution.  

 Patient confidentiality will be maintained by randomly allocating each patient record to 

a study number, allowing patient data to be kept strictly anonymous. All collected data 

and inferences thereof will then be analysed collectively. 

 

 

6. TIMING 

Gantt chart showing the timeline of the study:  

 

 

7. FUNDING 

All funding for this study will be borne by the author. 



31 

8. POTENTIAL LIMITATIONS 

 Information bias may occur as a result of poor record keeping or incomplete data in the 

records 

 Patients lost to follow-up may underpower the capacity of the study to assess certain 

outcomes 

 

 

 

 

 

 

 

 

 

 

 



32 

9. REFERENCES 

1. Wetmore JB, Collins AJ. Global challenges posed by the growth of end-stage renal   

disease. Ren Replace Ther 2016;2:15.  

2. White S, Chadban SJ, Jan S, Chapman JR, Cass A. How can we achieve global equity 

in provision of renal replacement therapy? Bull World Health Organ 2008;86:229-237 

3. Moosa MR, Kidd M. The dangers of rationing dialysis treatment: the dilemma facing 

a developing country. Kidney Int 2006;70:1107-1114. 

4. Stanifer JW, Jing B, Tolan S, Helmke N, Mukerjee R, Naicker S, et al. The 

epidemiology of chronic kidney disease in sub-Saharan Africa: a systematic review 

and meta-analysis. Lancet Glob Health 2014;2:e174-181. 

5.  United States Renal Data System. Epidemiology of Kidney Disease in the United 

States. USRDS Annual Data Report, 2017. http://www.usrds.org/adr.aspx (accessed 

July 2018) 

6. Horvat LD, Shariff SZ, Garg AX. Global trends in the rates of living kidney donation. 

Kidney Int 2009;75:1088-1098. 

7. Kanellis J. Justification for living donor kidney transplantation. Nephrology 2010;15(1 

Suppl):S72-S79. 

8. Nemati E, Einollahi B, Lesan Pezeshki M, Porfarziani V, Fattahi MR. Does kidney 

transplantation with deceased or living donor affect graft survival? Nephro Urol Mon 

2014;6:e12182. 

9. Lodhi SA, Meier-Kriesche HU. Kidney allograft survival: the long and short of it. 

Nephrol Dial Transplant 2011;26:15-17. 

10. Davis CL. Preemptive transplantation and the transplant first initiative. Curr Opin 

Nephrol Hypertens 2010;19:592-597. 



33 

11. Davis CL, Delmonico FL. Living-donor kidney transplantation: a review of the current 

practices for the live donor. J Am Soc Nephrol 2005;16:2098-2110. 

12. Mjøen G, Hallan S, Hartmann A, Foss A, Midtvedt K, Oyen O, et al. Long-term risks 

for kidney donors. Kidney Int 2014;86:162-167. 

13. Boudville N, Garg AX. End-stage renal disease in living kidney donors. Kidney Int 

2014;86:20-22. 

14. Muzaale AD, Massie AB, Wang MC, Montgomery RA, McBride MA, Wainright JL, et 

al. Risk of end-stage renal disease following live kidney donation. JAMA 

2014;311:579-586. 

15. Lentine KL, Schnitzler MA, Xiao H, Saab G, Salvalaggio PR, et al. Racial variation in 

medical outcomes among living kidney donors. N Engl J Med 2010;363:724-732. 

16. Hostetter TH, Olson JL, Rennke HG, Venkatachalam MA, Brenner BM. Hyperfiltration 

in remnant nephrons: a potentially adverse response to renal ablation. Am J Physiol 

1981;241:F18-F93. 

17. Shimamura T, Morrison AB. A progressive glomeruloschlerosis occuring in partial 

five-sixths nephrectomised rats. Am J Pathol 1975;79:95-102. 

18. Delanaye P, Weekers L, Dubois BE, Cavalier E, Detry O, Squifflet JP, et al. Outcome of 

the living kidney donor. Nephrol Dial Transplant 2012;27:41-50. 

19. Lenihan CR, Myers BD, Tan JC. Glomerular function and structure in living donors: 

lessons from single nephron studies. Curr Transpl Rep 2016;3:24-32. 

20. Lenihan CR, Busque S, Derby G, Blouch K, Myers BD, Tan JC. Longitudinal study of 

living kidney donor glomerular dynamics after nephrectomy. J Clin Invest 

2015;125:1311-1318. 

21. Blantz RC, Steiner RW. Benign hyperfiltration after living kidney donation. J Clin 

Invest 2015;125:972-974. 

 



34 

22. Yilmaz BA, Caliskan Y, Yilmaz A, Ozkok A, Bilge AK, Deniz G, et al. Cardiovascular-

renal changes after kidney donation: one-year follow-up study. Transplantation 

2015;99:760-764. 

23. Moody WE, Ferro CJ, Edwards NC, Chue CD, Lin EL, Taylor RJ, et al. Cardiovascular 

effects of unilateral nephrectomy in living kidney donors. Hypertension 2016;67:368-

377. 

24. Huan Y, Kapoor S, Deloach S, Ommen E, Meyers K, Townsend RR. Changes in 

biomarkers associated with living kidney donation. Am J Nephrol 2013;38:212-217. 

25. Bellavia D, Cataliotti A, Clemenza F, Baravoglia CH, Luca A, Traina M, et al. Long-term 

structural and functional myocardial adaptations in healthy living kidney donors: A 

Pilot Study. PLoS One 2015;10:e0142103. 

26. Merrill JP, Murray JE, Harrison JH, Guild WR. Successful homotransplantation of the 

human kidney between identical twins. JAMA 1956;160:277-282. 

27. Kute VB, Shah PS, Vanikar AV, Gumber MR, Patel HV, Engineer DP, et al. Increasing 

access to renal transplantation in India through our single-center kidney paired 

donation program: a model for the developing world to prevent commercial 

transplantation. Transpl Int 2014;27:1015-1021. 

28. Kute VB, Gumber MR, Vanikar AV, Shah PR, Patel HV, Engineer DP, et al. Comparison 

of kidney paired donation transplantations with living related donor kidney 

transplantation: implications for national kidney paired donation program. Ren Fail 

2013;35:504-508. 

29. Lentine KL, Kasiske BL, Levey AS, Adams PL, Alberu J, Bakr MA, et al. KDIGO clinical 

practice guideline on the evaluation and care of living kidney donors. 

Transplantation 2017;101(Suppl 8S):S1-S109. 

30. Lapasia JB, Kong SY, Busque S, Scandling JD, Chertow GM, Tan JC. Living donor 

evaluation and exclusion: the Stanford experience. Clin Transplant 2011;25:697-704. 



35 

31. Gozdowska J, Jankowski K, Bieniasz M, Wszola M, Domagala P, Kieszek R, et al. 

Characteristics of potential living kidney donors and recipients: donor 

disqualification reasons-experience of a Polish center. Transplant Proc 2013;45:1347-

1350. 

32. Magden K, Ucar FB, Velioglu A, Arikan H, Yegen SC, Tuglular S, et al. Donor 

contraindications to living kidney donation: A single-center experience. Transplant 

Proc 2015;47:1299-1301. 

33. Moore DR, Feurer ID, Zaydfudim V, Hoy H, Zavala EY, Shaffer D, et al. Evaluation of 

living kidney donors: variables that affect donation. Prog Transplant 2012;22:385-

392. 

34. Weng FL, Dhillon N, Lin Y, Mulgaonkar S, Patel AM. Racial differences in outcomes of 

the evaluation of potential live kidney donors: A retrospective cohort study. Am J 

Nephrol 2012;35:409-415. 

35. Ibrahim HN, Foley R, Tan L, Rogers T, Bailey RF, Guo H, et al. Long term 

consequences of kidney donation.N Engl J Med 2009;360:459-469. 

36. Fehrman-Ekholm I, Elinder CG, Stenbeck M, Tyden G, Groth CG. Kidney donors live 

longer. Transplantation 1997;64:976-978. 

37. Lentine KL, Schnitzler MA, Xiao H, Axelrod D, Garg AX, Tuttle-Newhall JE, et al. 

Consistency of racial variation in medical outcomes among publicly and privately 

insured living kidney donors. Transplantation 2014;97:316-324. 

38. Lentine KL, Schnitzler MA, Garg AX, Xiao H, Axelrod D, Tuttle-Newhall JE, et al. Race, 

relationship and renal diagnoses after living kidney donation. Transplantation 

2015;99:1723-1729. 

39. Delmonico FL, Dew MA. Living donor kidney transplantation in a global 

environment. Kidney Int 2007;71:608-614. 



36 

40. Couser WG, Remuzzi G, Mendis S, Tonelli M. The contribution of chronic kidney 

disease to the global burden of major noncommunicable diseases. Kidney Int 

2011;80:1258-1270. 

41. Hill NR, Fatoba ST, Oke JL, Hirst JA, O'Callaghan CA, Lasserson DS, et al. Global 

prevalence of chronic kidney disease - a systematic review and meta-analysis. PLoS 

One 2016;11:e0158765. 

42. Meyers AM. Chronic kidney disease. S Afr Med J 2015;105:232 

43. Moosa MR, Van der Walt I, Naicker S, Meyers AM. Important causes of chronic 

kidney disease in South Africa. S Afr Med J 2015;105:320-328. 

44. Mayosi BM, Benatar SR. Heath and health care in South Africa-20 years after 

Mandela. N Engl J Med 2014;371:1344-1353. 

45. Ng M, Fleming T, Robinson M, Thomson B, Graetz N, Margono C, et al. Global, 

regional, and national prevalence of overweight and obesity in children and adults 

during 1980–2013: a systematic analysis for the Global Burden of Disease Study 

2013. Lancet 2014;384:766-781. 

46. Koo TY, Yang J. Current progress in ABO-incompatible kidney transplantation. 

Kidney Res Clin Pract 2015;34:170-179. 

47. Wongsaroj P, Kahwaji J, Vo A, Jordan SC. Modern approaches to incompatible 

kidney transplantation. World J Nephrol 2015;4:354-362. 

48. Roodnat JI, Kal-van Gestel JA, Zuidema W, van Noord MA, van de Wetering J, 

Ijzermans JN, et al. Successful expansion of the living donor pool by alternative 

living donation programs. Am J Transplant 2009;9:2150-2156. 

49. Norman SP, Song PX, Hu Y, Ojo AO. Transition from donor candidates to live kidney 

donors: the impact of race and undiagnosed medical disease states. Clin Transplant 

2011;25:136-145. 



37 

50. Morgan SE. Many facets of reluctance: African Americans and the decision (not) to 

donate organs. J Natl Med Assoc 2006;98:695-703. 

51. Sieverdes JC, Nemeth LS, Magwood GS, Baliga PK, Chavin KD, Ruggiero KJ, et al. 

African American kidney transplant patients' perspectives on challenges in the living 

donation process. Prog Transplant 2015;25:164-175. 

52. Purnell TS, Powe NR, Troll MU, Wang NY, Haywood C, LaVeist TA, et al. Measuring 

and explaining racial and ethnic differences in willingness to donate live kidneys in 

the United States. Clin Transplant 2013;27:673-683. 

53. Gill J, Dong J, Rose C, Johnston O, Landsberg D, Gill J. The effect of race and income 

on living kidney donation in the United States. J Am Soc Nephrol 2013;24:1872-

1879. 

54. Lunsford SL, Simpson KS, Chavin KD, Menching KJ, Miles LG, Shilling LM, et al. Racial 

disparities in living kidney donation: is there a lack of willing donors or an excess of 

medically unsuitable candidates? Transplantation 2006;82:876-881. 

55. Lunsford SL, Shilling LM, Chavin KD, Martin MS, Miles LG, Norman ML, et al. Racial 

differences in the living kidney donation experience and implications for education. 

Prog Transplant 2007;17:234-240. 

56. Garg AX, Muirhead N, Knoll G, Yang RC, Prasad GV, Thiessen-Philbrook H, et al. 

Proteinuria and reduced kidney function in living kidney donors: A systematic 

review, meta-analysis, and meta-regression. Kidney Int 2006;70:1801-1810. 

57. Boudville N, Prasad R, Knoll G, Muirhead N, Thiessen-Philbrook H, Yang CW, et al. 

Meta-analysis: Risk for hypertension in living kidney donors. Ann Intern Med 

2006;145:185-196. 

58. Ramcharan T, Matas AJ. Long-term (20-37 years) follow-up of living kidney donors. 

Am J Transplant 2002;2:959-964. 



38 

59. Cherikh WS, Young CJ, Kramer BF, Taranto SE, Randall HB, Fan PY. Ethnic and gender 

related differences in the risk of end-stage renal disease after living kidney donation. 

Am J Transplant 2011;11:1650-1655. 

60. Fehrman-Ekholm I, Duner F, Brink B, Tyden G, Elinder CG. No evidence of 

accelerated loss of kidney function in living kidney donors: Results from a cross-

sectional follow-up. Transplantation 2001;72:444-449. 

61. Fournier C, Pallet N, Cherqaoui Z, Pucheu S, Kreis H, Mejean A, et al. Very long-term 

follow-up of living kidney donors. Transpl Int 2012;25:385-390. 

62. Guvence N, Oskay K, Ayli D. The assessment of long-term clinic and laboratory data 

of living related kidney donors. Transplant Proc 2012;44:1614-1617. 

63. Najarian JS, Chavers BM, McHugh LE, Matas AJ. 20 years or more of follow-up of 

living kidney donors. Lancet 1992;340:807-810. 

64. Segev DL, Muzaale AD, Caffo BS, Mehta SH, Singer AL, Taranto SE, et al. 

Perioperative mortality and long-term survival following live kidney donation. JAMA 

2010;303:959-966. 

65. Mjøen G, Reisaeter A, Hallan S, Line PD, Hartmann A, Midtvedt K, et al. Overall and 

cardiovascular mortality in Norwegian kidney donors compared to the background 

population. Nephrol Dial Transplant 2012;27:443-447. 

66. Garg AX, Meirambayeva A, Huang A, Kim J, Prasad GV, Knoll G, et al. Cardiovascular 

disease in kidney donors: matched cohort study. BMJ 2012;344:e1203. 

67. Ommen ES, Winston JA, Murphy B. Medical risks in living kidney donors: absence of 

proof is not proof of absence. Clin J Am Soc Nephrol 2006;1:885-895. 

68. Lam NN, Lentine KL, Levey AS, Kasiske BL, Garg AX. Long-term medical risks to the 

living kidney donor. Nat Rev Nephrol 2015;11:411-419. 

69. Nazarian SM, Reese PP. Insights from a ten-year, prospective study of live kidney 

donors. Transpl Int 2015;28:1265-1267. 



39 

70. Janki S, Klop KW, Dooper IM, Weimar W, Ijzermans JN, Kok NF. More than a decade 

after live donor nephrectomy: a prospective cohort study. Transpl Int 2015;28:1268-

1275. 

71. Janki S, Dols LF, Timman R, Mulder EEAP, Dooper IMM, van de Wetering J, et al. 

Five-year follow-up after live donor nephrectomy - cross-sectional and longitudinal 

analysis of a prospective cohort within the era of extended donor eligibility criteria. 

Transpl Int 2017;30:266-276. 

72. Potluri V, Harhay MN, Wilson FP, Bloom RD, Reese PP. Kidney transplant outcomes 

for prior living organ donors. J Am Soc Nephrol 2015;26:1188-1194. 

73. Lam N, Huang A, Feldman LS, Gill JS, Karpinski M, Kim J, et al. Acute dialysis risk in 

living kidney donors. Nephrol Dial Transplant 2012;27:3291-3295. 

74. Ahmadi AR, Lafranca JA, Claessens LA, Imamdi RM, Ijzermans JN, Betjes MG, et al. 

Shifting paradigms in eligibility criteria for live kidney donation: a systematic review. 

Kidney Int 2015;87:31-45. 

75. Young A, Storsley L, Garg AX, Treleaven D, Nguan CY, Cuerden MS, et al. Health 

outcomes for living kidney donors with isolated medical abnormalities: a systematic 

review. Am J Transplant 2008;8:1878-1890. 

76. Keller G, Zimmer G, Mall G, Ritz E, Amann K. Nephron number in patients with 

primary hypertension. N Engl J Med 2003;348:101-108. 

77. Lenihan CR, Busque S, Derby G, Blouch K, Myers BD, Tan JC. The association of 

predonation hypertension with glomerular function and number in older living 

kidney donors. J Am Soc Nephrol 2015;26:1261-1267. 

78. Tent H, Sanders JS, Rook M, Hofker HS, Ploeg RJ, Navis G, et al. Effects of preexistent 

hypertension on blood pressure and residual renal function after donor 

nephrectomy. Transplantation 2012;93:412-417. 



40 

79. Sofue T, Inui M, Hara T, Moriwaki K, Kushida Y, Kakehi Y, et al. Short-term prognosis 

of living-donor kidney transplantation from hypertensive donors with high-normal 

albuminuria. Transplantation 2014;97:104-110. 

80. Taner T, Iqbal CW, Textor SC, Stegall MD, Ishitani MB. Compensatory hypertrophy of 

the remaining kidney in medically complex living kidney donors over the long term. 

Transplantation 2015;99:555-559. 

81. Schold JD, Goldfarb DA, Buccini LD, Rodrigue JR, Mandelbrot D, Heaphy EL, et al. 

Hospitalizations following living donor nephrectomy in the United States. Clin J Am 

Soc Nephrol 2014;9:355-365. 

82. Reeves-Daniel A, Bailey A, Assimos D, Westcott C, Adams PL, Hartmann EL, et al. 

Donor-recipient relationships in African American vs. Caucasian live kidney donors. 

Clin Transplant 2011;25:E487-E490. 

83. Satko SG, Freedman BI, Moossavi S. Genetic factors in end-stage renal disease. 

Kidney Int 2005;67(94 Suppl):S46-S49. 

84. Genovese G, Friedman DJ, Ross MD, Lecordier L, Uzureau P, Freedman BI, et al. 

Association of trypanolytic ApoL1 variants with kidney disease in African Americans. 

Science 2010;329:841-845. 

85. Friedman DJ, Kozlitina J, Genovese G, Jog P, Pollak MR. Population-based risk 

assessment of APOL1 on renal disease. J Am Soc Nephrol 2011;22:2098-2105. 

86. Parsa A, Kao WH, Xie D, Astor BC, Li M, Hsu CY, et al. APOL1 risk variants, race, and 

progression of chronic kidney disease. N Engl J Med 2013;369:2183-2196. 

87. Freedman BI, Julian BA. Should kidney donors be genotyped for APOL1 risk alleles? 

Kidney Int 2015;87:671-673. 

88. Ibrahim HN, Foley RN, Reule SA, Spong R, Kukla A, Issa N, et al. Renal function 

profile in White kidney donors: the first 4 decades. J Am Soc Nephrol 2016;27:2885-

2293. 



41 

89. Grams ME, Sang Y, Levey AS, Matsushita K, Ballew S, Chang AR, et al. Kidney-failure 

risk projection for the living kidney-donor candidate. N Engl J Med 2016;374:411-

421. 

90. Massie AB, Muzalle AD, Luo X, Chow EK, Locke JE, Nguyen AQ, et al. Quantifying 

post-donation risk of ESRD in living kidney donors. J Am Soc Nephrol 2017;28:2749-

2755  

91. Wainright JL, Robinson AM, Wilk AR, Klassen DK, Cherikh WS, Stewart DE. Risk of 

ESRD in prior living kidney donors. Am J Transplant 2018;18:1129-1139. 

92. Liborio AB, Barros RM, Esmeraldo RM, Oliveira ML, Silva GB, Daher EF. Creatinine-

based equations predicting chronic kidney disease after kidney donation. Transplant 

Proc 2011;43:2481-2486. 

93. Lujan PR, Chiurchiu C, Douthat W, de Arteaga J, de la Fuente J, Capra RH, et al. CKD-

EPI instead of MDRD for candidates to kidney donation. Transplantation 

2012;94:637-641. 

94. Issa N, Kukla A, Jackson S, Riad SM, Foster MC, Matas AJ, et al. Comparison of 

cystatin C and creatinine-based equations for GFR estimation after living kidney 

donation. Transplantation 2014;98:871-877. 

95. Schold JD, Goldfarb DA, Buccini LD, Rodrigue JR, Mandelbrot DA, Heaphy EL, et al. 

Comorbidity burden and perioperative complications for living kidney donors in the 

United States. Clin J Am Soc Nephrol 2013;8:1773-1782. 

96. Kwapisz M, Kieszek R, Jedrzejko K, Domagala P, Bieniasz M, Gozdowska J, et al. 

Pathologies in living kidney donors diagnosed in the long-term care system. 

Transplant Proc 2016;48:1439-1445. 

97. Kim SH, Hwang HS, Yoon HE, Kim YK, Choi BS, Moon IS, et al. Long-term risk of 

hypertension and chronic kidney disease in living kidney donors. Transplant Proc 

2012;44:632-635. 



42 

98. von Zur-Mühlen B, Berglund D, Yamamoto S, Wadström J. Single-centre long-term 

follow-up of live kidney donors demonstrates preserved kidney function but the 

necessity of a structured lifelong follow-up. Ups J Med Sci 2014;119:236-241. 

99. Khatami MR, Nikravan N, Alimohammadi F. Quality and quantity of health evaluation 

and the follow-up of Iranian living donors. Transplant Proc 2015;47:1092-1095. 

100. Keshvani N, Feurer ID, Rumbaugh E, Dreher A, Zavala E, Stanley M, et al. Evaluating 

the impact of performance improvement initiatives on transplant center reporting 

compliance and patient follow-up after living kidney donation. Am J Transplant 

2015;15:2126-2135. 

101. Schold JD, Buccini LD, Rodrigue JR, Mandelbrot D, Goldfarb DA, Flechner SM, et al. 

Critical factors associated with missing follow-up data for living kidney donors in the 

United States. Am J Transplant 2015;15:2394-2403. 

102. Weng FL, Reese PP, Waterman AD, Soto AG, Demissie K, Mulgaonkar S. Health care 

follow-up by live kidney donors more than three years post-nephrectomy. Clin 

Transplant 2012;26:E300-E306. 

103. Mandelbrot D, Pavlakis M, Karp SJ, Johnson SR, Hanto DW, Rodrigue JR. Practices 

and barriers in long term living kidney donor follow-up: A survey of US transplant 

centres. Transplantation 2009;88:855-860. 

104. Moosa MR, Meyers AM, Gottlich E, Naicker S. An effective approach to chronic 

kidney disease in South Africa. S Afr Med J 2016;106:156-159. 

105. Davids MR, Balbir Singh GK, Marais N, Jacobs JC. South African Renal Registry 

Annual Report 2014. South African Renal Society, Cape Town 2016. 

106. O'Donnell D, Seggie J, Levinson I, Meyers AM, Botha JR, Myburgh JA, et al. Renal 

function after nephrectomy for donor organs. S Afr Med J 1986;69:177-179. 

107. Naicker S, Azor M, Sukool A, Holmes I, Muranda A, Haffejee AA. Follow-up of kidney 

donors at a single center in South Africa. AJN 1998;2:18-20. 



43 

108. Abdu A, Morolo N, Meyers AM, Wadee S, Britz R, Naicker S. Living kidney donor 

transplants over a 16-year period in South Africa: A single center experience. Ann Afr 

Med 2011;10:127-131. 

109. McCurdie FJ, Pascoe MD, Broomberg CJ, Kahn D. Outcome of assessment of 

potential donors for live donor kidney transplants. Transplant Proc 2005;37:605-606. 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 



  44 

CHAPTER 2: PROPOSED MANUSCRIPT 

 

Living kidney donation in a developing country 

Chandni Dayal 1, Malcolm Davies 1, 2, Nina Diana 1, 2 

1 Department of Medicine, Faculty of Health Sciences, University of the Witwatersrand; 2 Division 

of Nephrology, Charlotte Maxeke Johannesburg Academic Hospital, Johannesburg, South Africa 

 

ABSTRACT 

Living kidney donation is increasing in global significance as the preferred therapeutic 

modality to ameliorate the widening demand for renal allografts. There is limited data 

evaluating living donation in developing countries. We assessed reasons for non-donation and 

outcomes following donation amongst a cohort of 1208 ethnically diverse potential living 

donors over a 32-year period at a transplant centre in South Africa. Medical contraindications 

were the commonest reason for donor exclusion. These included hypertension, human 

immunodeficiency virus and obesity. Black donors were more likely to be excluded from 

donation (52.1% vs. 39.3%; p<0.001) particularly for medical reasons (44% vs. 35%; p<0.001). 

Amongst 298 accepted live donors, estimated glomerular filtration rate dropped below 60 

ml/min/1.73m2 in 27% of patients at median follow-up of 3.7 years, although none required 

the initiation of renal replacement therapy. Following nephrectomy, severely increased 

albuminuria of >300 mg/day was noted in 4% of donors and 12.8% developed new-onset 

hypertension. Five donors demised of causes unrelated to renal outcomes. Black ethnicity was 

not associated with an increased risk of adverse post-donation outcome. This study shows a 



45 

substantial donor exclusion rate with considerable racial variation in the outcome of donor 

evaluation. A proportion of donors demonstrated a significant decline in renal function 

following nephrectomy, highlighting the need for close long-term donor follow-up. 

KEYWORDS: living kidney donation, developing country, potential living donors, donor 

exclusion, donor outcomes 

 

Correspondence: C Dayal, Department of Medicine, Faculty of Health Sciences, University of 

the Witwatersrand; Charlotte Maxeke Johannesburg Academic Hospital Area 551; 7 York Road, 

Parktown, Johannesburg, 2193, South Africa. E-mail: chandnidayal@gmail.com 

 

INTRODUCTION 

The prevalence of end-stage kidney disease (ESKD) continues to rise globally1 and contributes 

significantly to the burden of chronic disease in developing countries.2 It is estimated that by 

the year 2030, in excess of 70% of patients with ESKD will reside in middle and low income 

countries, such as those in sub-Saharan Africa.3 Historically, renal replacement therapy (RRT) 

has been limited in these settings, with access being lowest in Africa, where less than one-fifth 

of individuals needing RRT receive it.4 

 

South Africa faces a unique set of challenges in addressing this RRT gap.5 With the rising 

scourge of communicable diseases including human immunodeficiency virus (HIV) and 

tuberculosis demanding a disproportionate quantum of healthcare resources,6 the provision 

of expensive therapies such as RRT has the potential to exert significant strain on its emerging 



46 

economy.7 Due to pre-existing disparities in the provision of renal care, RRT in South Africa is 

at present largely concentrated in the privately funded sector; 8-10 whilst in the state sector, 

which serves more than 80% of the population, dialysis treatment is rationed with only those 

patients who are eligible for renal transplant being accepted. 7, 9 The present national 

transplant rate of 4.6 per million population in South Africa is on a downward trend,8 well 

below the transplant rates of other middle income countries.2, 8, 11 Without emergent 

intervention to expand the availability of transplantation in the South African population, 

already strained dialysis programs are at risk of collapse.7  The majority of renal transplants in 

the local state sector program are from deceased donors; living donation, whether altruistic or 

donor-directed, offers a mechanism to increase transplantation rates. 

 

Indeed, living kidney donation has been shown to be a cost-effective therapeutic modality to 

ameliorate the growing demand for sustainable RRT in the developing world.1, 2, 9, 12 Living 

donation does, however, require that healthy individuals endure a major surgical procedure 

devoid of any direct self-benefit.12 The numerous advantages of pre-emptive transplantation 

for the recipient must therefore be carefully balanced against maintaining immediate and 

long-term donor safety.13-16   

 

Data suggests that up to two-thirds of potential living donors fail to complete the donation 

process.17-21 Understanding the reasons for non-donation is required to identify possible 

modifiable barriers for intervention in order to augment living donation rates.17,20  Furthermore, 

obtaining informed consent for donation is a challenge as consensus regarding the risks to 

the accepted donor following nephrectomy remain unclear,22 particularly amongst donors of 

black ethnicity who seem to bear the greatest risk of adverse outcomes.23-26 Older reports of 



47 

long-term donor follow-up suggested that the risks of uninephrectomy were of limited clinical 

significance, with donor outcomes largely comparable to that of the general population.27-30 

In contrast, emerging data, with appropriately matched control groups, highlight poorer long 

term survival and an elevated risk of ESKD amongst living donor cohorts. 31-33 

 

There is a paucity of data on the living donor selection process and outcomes at post-donation 

follow-up amongst demographically diverse populations in the developing world. The present 

study was undertaken to evaluate living donation in the South African context. The aim was to 

characterise reasons for non-donation, examine morbidity and mortality following donation, 

and to identify if any differences exist in outcomes among demographic subgroups in this 

setting.  

 

RESULTS 

Between January 1983 and July 2015, 1208 potential living donors were assessed at Charlotte 

Maxeke Johannesburg Academic Hospital (CMJAH), a transplant centre in South Africa. Only a 

quarter (n=298) of assessed patients were accepted for living donation, resulting in 910 failed 

living donors (FLDs).  

 

The demographic characteristics of the potential donor population are presented in Table 2.1. 

The most represented age group was that of 30-39 years (428; 35.4%). The majority of potential 

donors were female (697; 58%), of Black African descent (559; 46%) and biologically related to 

the intended or eventual recipient (991; 82%). 

 



48 

Medical contraindications to donation were the most common cause for donor disqualification 

(363; 39.9%); of which obesity, hypertension and HIV were most prevalent. Immunological 

barriers resulted in the exclusion of a further 19% of potential donors (n=173). A significant 

proportion (222; 25%) of donors were medically suitable but ultimately did not proceed to 

donation. This subgroup encompassed exclusions for recipient-related factors (120; 13.2%) and 

prospective donors who voluntarily withdrew from donation due to lack of further interest 

(102; 11.2%). Eighty-five (9.3%) of referred donors were lost to follow-up during the process of 

evaluation (Table 2.2).  

 

Outcome of donor evaluation varied significantly by race (Table 2.3). Black donors were more 

likely to fail work-up (51.2% vs. 39.3%; p<0.001) and be excluded for medical reasons (44% vs. 

35%; p<0.001). In addition, forty-eight (49.5%) of medically suitable donors who voluntarily 

withdrew were of Black ethnicity. 

 

Median follow-up of the accepted donors was 3.7 years after donation (IQR 1.2-7.8 years). 

Clinical and laboratory parameters for this subgroup at baseline and at three successive post-

donation follow-up points (at first visit, at one-year and at most recent visit) are shown in Table 

2.4. Thirty-eight donors (12.8%) developed hypertension at follow-up, although the frequency 

of new-onset hypertension was not significantly different as compared to baseline (p=0.06). 

Statistically significant increase in both systolic and diastolic blood pressure was detected at 

one-year follow-up (p<0.001). There was a significant increase in albuminuria over time 

between the pre-donation and post-donation (most recent visit) (p<0.001), however the 

albumin excretion rate (AER) remained within normal limits. Thirteen donors (4%) developed 



49 

the primary endpoint of AER>300 mg/day, one of which was a living-unrelated donor that 

developed biopsy-proven membranous glomerulonephritis following donation. 

 

At most recent follow-up, estimated glomerular filtration rate (eGFR), determined using the 

Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) formula, was significantly lower 

compared to baseline measurements (72.5 vs. 91.7 ml/min/1.73 m2 respectively, p<0.001), 

representing a decrease in GFR of 21%. Eighty accepted donors (27%) developed a CKD-EPI-

eGFR of less than 60 ml/min/1.73 m2 at most recent follow-up. Regression analysis identified 

multiple risk factors associated with this outcome (Table 2.5). These included Caucasian 

ethnicity, a lower eGFR at baseline and preceding visits, and an elevated blood pressure at the 

one year visit. However, none of the donors developed ESKD or required the institution of RRT.  

 

Black African ethnicity did not portend an increased risk of adverse outcome at most recent 

follow-up (Table 2.6). Over a longer median follow-up duration post donation, Black donors 

had better serum creatinine levels and calculated eGFR. However, donors of Black African 

origin had higher mean systolic blood pressures at last follow-up, although still within normal 

limits. 

 

Sixty-seven donors (22.5%) had an isolated medical abnormality (IMA) prior to donation. This 

subgroup included donors with a pre-donation body mass index (BMI) of between 30-35 kg/m2 

(n=32); donors with a baseline isotope GFR of less than 80 ml/min/1.73 m2 (n=21) and those 

with pre-existing hypertension, well controlled on a single agent with no end-organ damage 

(n=14). A third of donors with an IMA were of Black African ethnicity. Class I obesity at baseline 

was not associated with an increased risk of developing hypertension (p=0.09) or an eGFR of 



50 

less than 60 ml/min/1.73 m2 (p=0.71) at follow-up. A pre-donation isotope GFR of less than 80 

ml/min/1.73 m2 was associated with an eGFR less than 60 ml/min/1.73 m2 at most recent 

follow-up (p=0.02); the incidence of new onset hypertension was not significantly greater in 

this subgroup (p=0.27). 

 

With respect to non-renal outcomes, in the perioperative period sixteen donors (5.4%) suffered 

from complications including an iatrogenic pneumothorax (n=1); hospital acquired infections 

(n=3); and prolonged pain at the site of the nephrectomy scar (n=11). During the study period 

there were a total of 5 deaths (1.7%), one of which occurred in the immediate post-operative 

period. The remaining four deaths resulted from trauma and were thus unrelated to donation. 

Four donors (1.3%) required psychological support for major depressive disorder (n=2) and 

substance abuse (n=2). 

 

Caucasian donors were more likely to default follow-up (Table 2.7). Donors who resided more 

than 100 kilometres from the transplant centre had significantly shorter durations of post-

donation follow-up. In addition, all donors aged 18-21 years (n=9) at the time of donation 

were lost to follow-up; donors over the age of twenty-one were at significantly lower risk of 

defaulting follow-up. Gender and degree of relationship to the recipient were not associated 

with poorer follow-up. 

 

 

 

 

 



51 

Table 2.1 | Donor demographics 

Characteristic Donors excluded 

n=910 (75.3%) 

Donors accepted 

n=298 (24.7%) 

Total evaluated 

n=1208 

Age (in years) 

18-21 

22-29 

30-39 

40-49 

50-59 

≥60 

 

54 (5.9) ª 

213 (23.4) 

315 (34.6) 

221 (24.2) 

93 (10.2) 

14 (1.53) 

 

9 (3.0) 

71 (23.8) 

113 (37.9) 

85 (28.5) 

19 (6.4) 

1 (0.3) 

 

 

63 (5.2) 

284 (23.5) 

428 (35.4) 

306 (25.3) 

112 (9.3) 

15 (1.2) 

Gender 

Female 

Male 

 

522 (57.4) 

388 (42.6) 

 

175 (58.7) 

123 (41.3) 

 

 

697 (57.7) 

511 (42.3) 

 

Ethnicity 

Black 

Caucasian 

Indian/Asian 

Coloured 

 

474 (52.1) 

358 (39.3) 

38 (4.2) 

40 (4.4) 

 

85 (28.5) 

175 (58.7)  

26 (8.7) 

12 (4.1) 

 

 

559 (46.2) 

533 (44.1) 

64 (5.3) 

52 (4.3) 

Relation to recipient 

Biological 

              First degree relative 

              Other relative 

Non-biological 

              Directed 

              Non-directed 

 

722 (79.0) 

631 (69.0) 

91 (10.0) 

188 (21.0) 

180 (19.7) 

8 (0.9) 

 

269 (90.3) 

256 (85.9) 

13 (4.7) 

29 (9.73) 

29 (9.73) 

0 

 

 

991 (82) 

887 (73.4) 

104 (8.6) 

217 (18.0) 

209 (17.3) 

8 (0.7) 

ª Values are expressed as n (%) 

 

 

 

 

 

 

 

 



52 

Table 2.2 | Reasons for non-donation 

 n % n % 

DONOR 

RELATED 

FACTORS 

MEDICAL 

Hypertension 90 9.9 

363 39.9 

Human Immunodeficiency Virus 45 4.9 

Obese class I (BMI 30-34) 40 4.4 

Obese class II (BMI 35-39) 40 4.4 

Chronic kidney disease (eGFR <70) 37 4.1 

Hypertension and obesity 29 3.2 

Obese class III (BMI ≥40) 9 1 

Persistent iron deficiency anaemia 8 0.9 

Diabetes 5 0.5 

Persistent microalbuminuria 5 0.5 

Hepatitis B 5 0.5 

Hepatitis C 5 0.5 

Hypertension and chronic kidney disease 4 0.4 

Metabolic syndrome 4 0.4 

Recurrent urinary tract infections 4 0.4 

Tuberculosis 4 0.4 

Familial hypercholesterolemia with atherosclerosis 3 0.3 

Ischaemic heart disease 2 0.2 

Valvular heart disease 2 0.2 

Chronic obstructive pulmonary disease 2 0.2 

Poorly controlled epilepsy 2 0.2 

Von Willebrand Disease 2 0.2 

Primary hyperparathyroidism 2 0.2 

Systemic lupus erythematosus 2 0.2 

Syphilis 2 0.2 

Glomerulonephritis 1 0.1 

Autosomal dominant polycystic kidney disease 1 0.1 

Alport syndrome 1 0.1 

Hashimoto's thyroiditis 1 0.1 

Grave's disease 1 0.1 

Ankylosing spondylitis 1 0.1 

Incidental malignancy 1 0.1 

UROLOGICAL 
Nephrolithiasis 6 0.6 

8 0.9 
Obstructive uropathy 2 0.2 

ANATOMICAL 

Multiple renal arteries bilaterally 14 1.5 

28 3.1 
Congenital renal anomaly 8 0.8 

Fibromuscular dysplasia 5 0.5 

Renal artery stenosis 1 0.1 

PSYCHOSOCIAL 

Withdrew voluntarily 102 11.2 

208 22.9 
Lost to follow-up 85 9.3 

Psychiatric disorder 14 1.5 

Polysubstance abuse 7 0.8 

RECIPIENT RELATED FACTORS 

Transplant candidate demised 47 5.2 

120 13.2 

Alternate donation received (from alternate living 

donor) 
32 3.5 

Transplant candidate became medically ineligible 21 2.3 

Alternate donation received (from deceased donor) 20 2.2 

DONOR-RECIPIENT RELATED 

FACTORS 

ABO incompatibility 96 10.5 
173 19 

Positive cytotoxic antibody cross-match 77 8.5 

MISCELLANEOUS Otherª 10 1.1 10 1.1 

Abbreviations: BMI, Body mass index; eGFR, estimated glomerular filtration rate 

ª Includes donors disqualified for age >70 years, pregnancy and incarceration 



53 

Table 2.3 | Donor exclusion stratified by ethnicity 

 Caucasian Black p-value 

Donor-related factors 

Medical 

Urological 

Anatomical 

Psychosocial 

 

125 (34.9) ª 

6 (1.7) 

23 (6.4) 

77 (21.5) 

 

210 (44.3) 

1 (0.2) 

5 (1.1) 

109 (23.0) 

 

<0.001 

<0.001 

<0.001 

<0.001 

 

Donor-recipient related factors 

Immunological 

 

70 (19.6) 

 

95 (20.0) 

 

<0.001 

 

ª Values are expressed as n (%) 

 

 

Table 2.4 | Comparative clinical parameters in accepted living donors 

 
Pre-

donation 

Post-donation 

p-value First Visit One Year 

Visit 

Most Recent 

Visit 

 

Systolic BP (mmHg) a 

 

Diastolic BP (mmHg) a 

 

Albuminuria (AER in mg/day) b 

 

Serum Creatinine (µmol/L) a 

 

CKD-EPI eGFR (ml/min/1.73m2)a 

 

 

119 (11.8) 

 

73 (9.1) 

 

6 (3-12) 

 

85 (14.6) 

 

91.7 (19.1) 

 

121 (17.3) 

 

75 (11.7) 

 

10 (3-28) 

 

114 (21.0) 

 

70.6 (19.4) 

 

126 (17.1) 

 

78 (12.9) 

 

13 (3-77) 

 

104 (15.7) 

 

86.1 (19.7) 

 

125 (16.0) 

 

79 (10.7) 

 

7 (3-29) 

 

103 (24.3) 

 

72.5 (20.0) 

 

<0.001 c 

 

<0.001 c 

 

<0.001 

 

<0.001 

 

<0.001 

Abbreviations: BP, blood pressure; AER, albumin excretion rate; CKD-EPI eGFR, estimated glomerular filtration 

rate by Chronic Kidney Disease Epidemiology Collaboration equation 

ª Values are mean (± SD) 

b Values are median (± IQR) 

c Applies to analysis commencing at one-year follow-up 

 

 

 

 



54 

Table 2.5 | Logistic regression analysis of variables associated with an eGFR<60 

ml/min/1.73m2 at most recent follow-up 

 Coefficient Wald test p-value 

Age at donation -0.023 0.11 0.73 

Gender 

          Female 

 

0.212 

 

0.15 

 

0.70 

Ethnicity 

Caucasian 

Black 

 

8.165 

0.511 

 

95 (20.0) 

0.58 

 

<0.001 

0.44 

BMI (kg/m2)  

          Pre-donation 

          First visit 

          One-year visit 

 

0.218 

0.025 

0.054 

 

0.40 

0.01 

0.04 

 

0.53 

0.95 

0.80 

CKD-EPI eGFR (ml/min/1.73m2) 

          Pre-donation 

          First visit 

          One-year visit 

 

-0.114 

-0.270 

-0.172 

 

3.96 

6.58 

4.58 

 

0.04 

0.01 

0.03 

AER (mg/day) 

          Pre-donation 

          First visit 

          One-year visit 

 

-0.018 

0.022 

-0.063 

 

0.56 

1.95 

3.54 

 

0.45 

0.16 

0.06 

Systolic BP (mmHg) 

          Pre-donation 

          First visit 

          One-year visit 

 

-0.024 

-0.021 

0.550 

 

0.15 

0.12 

6.94 

 

0.70 

0.73 

0.008 

Diastolic BP (mmHg) 

          Pre-donation 

          First visit 

          One-year visit 

 

0.126 

-0.111 

-0.433 

 

1.33 

2.67 

4.81 

 

0.25 

0.10 

0.03 

Abbreviations: BMI, body mass index; CKD-EPI eGFR, estimated glomerular filtration rate by Chronic Kidney 

Disease Epidemiology Collaboration equation; AER, albumin excretion rate; BP, blood 

pressure; 51 Cr-EDTA GFR, Chromium-51-ethylene-diamine-tetra-acetic-acid glomerular 

filtration rate 

 

 

 

 

 

 

 

 



55 

Table 2.6 | Accepted donor ethnicity and parameters at most recent follow-up visit 

 Caucasian Black p-value 

Follow-up in years ª 

 

2.29 (0.56-6.93) 

 

5.54 (1.75-8.84) 0.0028 

Parameter at most recent follow-up b 

 

Systolic BP (mmHg) 

 

Diastolic BP (mmHg) 

 

Albuminuria (AER in mg/day) 

 

Serum Creatinine (µmol/L) 

 

CKD-EPI eGFR (ml/min/1.73m2) 

 

 

 

115.01 (17.53) 

 

88.75 (13.41) 

 

98.40 (446.22) 

 

104.77 (18.95) 

 

64.44 (15.51) 

 

 

121.21 (18.04) 

 

84.64 (13.07) 

 

47.66 (64.85) 

 

99.07 (21.99) 

 

84.53 (21.33) 

 

 

0.008 

 

0.199 

 

0.298 

 

0.031 

 

<0.0001 

Abbreviations: BP, Blood Pressure; AER, albumin excretion rate; CKD-EPI eGFR, estimated glomerular filtration                                                       

rate by Chronic Kidney Disease Epidemiology Collaboration equation 

a values are median (± IQR) 

b values are mean (± SD) 

 

 

 

Table 2.7 | Parameters associated with defaulting post-donation follow-up 

Parameter Hazard ratio 95% CI p-value 

Age at donation (in years) 

          Age <21 

 

0.2 

 

0.1-0.5 

 

0.001 

Gender 

Female 

Male 

 

0.7 

1.1 

 

0.6-1.0 

0.4-2.9 

 

0.1 

0.6 

Ethnicity 

Black 

Caucasian 

 

0.8 

2.4 

 

0.4-2.0 

1.2-4.7 

 

0.06 

0.008 

Degree of relationship 

          First 

          Second 

          Third 

 

2.0 

5.9 

0.3 

 

0.7-5.9 

1.1-31.5 

0.1-1.5 

 

0.8 

0.1 

0.01 

Domicile from hospital 

          >100 kilometres 

 

1.4 

 

0.8-1.5 

 

0.04 

Abbreviations: CI, confidence interval                                         



56 

DISCUSSION 

Published data on living donation in Africa is limited, relying on small cohort studies.34-37 In 

an analysis of 117 potential donors at a single centre in the Western Cape province of South 

Africa, the donor exclusion rate was 83%. 34 In the first South African study assessing 

outcomes of 33 Caucasian related living donors over thirty years ago, 35 a rise in mean 

diastolic blood pressure with an inclination towards significant decline in creatinine 

clearance was noted at 5-year follow-up. In a later series by Naicker et al.36, 135 donors with 

a similar demographic profile to the present study were assessed over a 10-year period. 

Although limited by 10% of donors being lost to follow-up, no significant difference in 

blood pressure or proteinuria was noted following donation, with a normal mean serum 

creatinine level over the follow-up period. Findings of a subsequent study by Abdu et al. 37 

were similarly reassuring. 

 

This study describes living kidney donation in the context of a developing country. Key 

findings include: 

1. A substantial donor exclusion rate, predominately due to medical contraindications.  

2. A significant decline in eGFR amongst a quarter of donors at most recent follow-up 

(median 3.7 years, IQR 1.2-7.8 years), although none required RRT.  

3. Mortality in this series was low and unrelated to the development of renal dysfunction. 

4. There was variation in outcomes amongst demographic subgroups, both in the donor 

evaluation process and in the decline in renal function following donor nephrectomy. 

Exclusion rates were highest amongst prospective donors of Black African origin. 

However, no greater risk to Black donors was demonstrated following nephrectomy.  



57 

The screening of prospective donors frequently results in the incidental diagnosis of occult 

disorders. Consistent with previous studies, 17-20 medical contraindications were the most 

common reason for non-donation in the present cohort, of which undiagnosed 

hypertension (14%) and obesity (10%) were most prevalent. This reflects the current 

spectrum of non-communicable disease burden in the local population where 

hypertension and obesity rates are amongst the highest in sub-Saharan Africa, 38, 39 at 45% 

and 49% respectively.40 In addition, epidemiological studies attribute the greatest 

proportion of disability adjusted life years lost in South Africa to these conditions.6 The 

high rates of hypertension and obesity in the failed donor group may partly be due to 

genetics; numerous studies support the role of distinct heritable factors that contribute to 

the increased development of these disorders, particularly in populations of black African 

ancestry. 41-43 

 

In contrast to developed settings, 17, 20 the present study shows a significant donor exclusion 

rate due to communicable diseases (6.7%), primarily HIV infection (n=45; 4.9%). The 

prevalence of HIV amongst potential donors in this cohort is however lower than the 

general South African population prevalence of HIV infection. In 2016, the estimated adult 

(aged 15-49 years) seroprevalence rate of HIV in South Africa was 16.6%.8  

 

A reduction in donor disqualification rates for medical reasons can be facilitated by 

improved quality of preventative care provided in primary health care systems.44 This is of 

particular relevance with non-communicable diseases, where enhanced screening at a 



58 

primary healthcare level may aid the timeous institution of therapy, prior to the 

development of complications that limit the use of prospective donors. As in our cohort, 

donors with isolated medical abnormalities including obesity (body mass index 30-35 

kg/m2) and pre-existing hypertension, well controlled on a single agent with no end-organ 

damage, have been accepted in order to expand living donor pools; recent evidence 

supports favourable post donation outcomes amongst these subgroups as compared to 

appropriately matched cohorts. 45, 46 

 

Immunological barriers resulted in the exclusion of 19% of donor candidates. This 

represents an important subgroup where novel modalities including paired donor 

exchanges, potential desensitisation of cross-match positive pairs and ABO-incompatible 

transplantation may be applied to augment living donation rates.47, 48 In developed settings, 

these approaches have increased the utilisation of living donors in otherwise incompatible 

donor-recipient pairs.49-51 

 

Medically suitable donors who voluntarily withdrew accounted for the exclusion of 11.2% 

of failed donors in this study. Similarly high rates have been reported in multiple centres 

across the United States.20, 21 These rep