Relationship of Chronic Inflammatory Markers and Dyslipidaemia to Atherosclerotic vascular disease in different categories of chronic kidney disease patients
Date
2018
Authors
Oguntola, Stephen Olawale
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Abstract
Background: Cardiovascular disease (CVD) is the leading cause of mortality among CKD patients,
responsible for 40-50 % of all-cause mortality in CKD. Chronic kidney disease patients have
been shown to be more likely to succumb to CVD than progress to ESKD. Atherosclerotic
vascular disease (AsVD) has been described as an inflammatory disease because of the central
role of chronic inflammation and lipid disorders in its aetiopathogenesis. The contributions of
these two risk factors have not been well studied in a broad spectrum of CKD patients among
black Africans. This study evaluated the relationship of chronic inflammation, dyslipidaemia
and APOL1 risk variants to AsVD among black South Africans with CKD stage 3, peritoneal
dialysis (PD) and haemodialysis (HD) patients and kidney transplant recipients (KTRs).
Methods
This was a cross-sectional study of 40 adult (18-65 years) non-diabetic CKD patients, kidney
disease outcome quality initiative (KDOQI stage 3), 40 PD patients, 40 HD patients, 41 KTRs
and 41 age- and sex-matched healthy controls. An interviewer-administered questionnaire was
used to obtain information on participants’ sociodemographic and cardiovascular risk factors.
Anthropometric parameters were measured. Blood samples were obtained and serum was
analysed for baseline tests, lipoprotein and inflammatory biomarkers. Genomic DNA was
extracted from whole blood by modified salting out method and APOL1 genotyping was carried
out using restriction fragment length polymorphism. Echocardiography was performed on all
patients and carotid intima media thickness (CIMT) was assessed in both right and left carotid
arteries at 1cm proximal to the carotid bulb. Atherosclerotic vascular disease was defined by
the combination of increased CIMT values (> 0.55 mm) and the presence of carotid plaques.
Results: Prevalence of AsVD was highest among PD patients (70 %), and occurred in 47.5 % of stage
3CKD and HD patients, 46.3 % of KTRs and 17.1 % of controls, (p < 0.01). Comparison of
the kidney disease groups (CKD stage 3, PD and HD) with controls showed significant
difference in waist-hip ratio (WHR), systolic blood pressure (SBP), mean arterial blood
pressure (MABP), serum creatinine (Scr), estimated glomerular filtration rate (eGFR), total
cholesterol (TC), triglyceride (TG), low density lipoprotein (LDL-C), high density lipoprotein
(HDL-C-C), Castelli 1, Castelli 2, atherogenic coefficient (AC), non-HDL-C cholesterol,
calcium, phosphate, calcium-phosphate products (CaXPO4), serum albumin, ejection fraction
(EF), left atrial diameter (LAD) and left ventricular mass index (LVMI). Comparison between
the kidney disease group (CKD stage 3, PD and HD) who had AsVD with those who did not,
showed significantly higher age, WHR, LAD, mitral valve deceleration time, LVMI and serum
creatinine. Among KTRs, positive correlation was seen between CIMT and LAD, LVMI,
Castelli 2 and Lipoprotein combined index (LCI).
Pentraxin-3 levels were significantly higher in all the kidney disease groups (stage 3 CKD, PD,
HD and KTRs) compared to controls. high sensitivity C-reactive protein (hsCRP) and tumour
necrosis factor-alpha (TNF-α) levels were significantly higher in ESKD patients compared to
controls. Pentraxin-3 correlated positively with CIMT among KTRs (r = 0.336, p = 0.032) and
with other inflammatory markers when all kidney disease groups were combined (except for
hsCRP). An inverse correlation was seen between pentraxin-3 and eGFR (r = -0.171, p = 0.030)
and serum albumin (r = -0.168, p = 0.033). The levels of Lp (a) and Lp-PLA2 were increased
while levels of APO A1 were reduced in all kidney disease groups compared to controls.
On multivariate analysis, age (> 40 years), male gender, low HDL-C levels and elevated Lp (a)
levels independently predicted AsVD after adjusting for BMI, WHR, TC, TG, HDL-C, LDL
C, inflammatory markers, Lp-PLA2 and APO A1. Lipoprotein (a) predicted AsVD better than
other lipid markers evidenced by higher area under the curve (AUC). No significant difference
was seen in the utility of the lipid biomarkers in predicting AsVD (except when female kidney
disease patients were analysed separately).
The odds of AsVD was more than 11-fold increased in patients who had hypertension
attributable CKD with high risk APOL1 variants, [OR 11.85, 95 % CI – (1.08 – 129.91), p =
0.043]; this relationship was lost when all kidney disease patients, regardless of aetiology was
used in the analysis, (OR 0.84 (95 % CI – 0.22 – 3.28; p – 0.802).
Conclusion: Atherosclerotic vascular disease is common in kidney disease patients and most prevalent
among PD patients compared to CKD stage 3, HD and KTRs. Dyslipidaemia and inflammation
are common among kidney disease patients. Lipoprotein(a) predicted AsVD better than other
lipid biomarkers (Lp-PLA2, APO A1) and lipid profile parameters (LDL-C, TG, TC). Age (>
40 years), male gender, low HDL-C and elevated Lp (a) independently predicted AsVD when
all kidney disease patients were combined, while APOL1 risk variants independently predicted
AsVD among patients with hypertension attributable kidney disease.
Description
A thesis submitted in fulfilment of the requirements for the degree of Doctor of Philosophy in Internal Medicine Johannesburg, 2018