The pivotal role of a kidney stone clinic in the management and prevention of recurrent calcium oxalate nephrolithiasis
Date
2020
Authors
Meyers, Anthony M
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Abstract
Nephrolithiasis occurs in 12 to 15% of males and 5 to 6% of females with frequent
recurrence in about 50% of them. The prevalence of stone disease is unknown in the
South African black population and is of low frequency. The commonest type of
nephrolithiasis in the South African population is calcium oxalate stones. This thesis
involved the study of the epidemiology, causes, pathogenesis and management of
kidney stones in patients with recurrent calcium oxalate stones.
Dedicated stone clinics indicate that there is a 30% lower mortality rate accompanied
by an increase in patient satisfaction, improved recruitment of staff and improved
morale.
Patients and methods
Seven previously published studies, which form the basis for this Doctor of Medicine
degree, were analysed; six in-vivo and one laboratory study. Three of the studies,
analysed the urinary metabolites in a large number of black and white male and female
normal controls. Stone risk factors were studied in a total of five papers, also in a large
number of patients of comparative cohorts with nephrolithiasis. Standard work-up
protocols included dietary, anthropomorphic, serological, 24-hour urinary excretion of
mineral and electrolyte measurements. Special crystallographic techniques were used
in the paper presenting the role of cystine in calcium oxalate stone formation. The
metastable limits of urine were measured using various quantities of cystine in pooled
urine, in spun and filtered as well as ultra-filtered specimens. In addition, particle
numbers, diameter and volume were measured. Promotion of calcium oxalate
formation was measured in the specimens using various concentrations of cystine.
Hypocitraturia was present in ~50% of white stone patients; black controls excreted
much less citrate than whites, 50% of whom fell into the hypocitraturic range.
Therefore, two separate controls for blacks and whites were formulated and validated viii
by statistical evidence and accepted as “good laboratory practice”. Oxalate excretion
in controls and stone formers, whether of black or white ethnicity, male or female, was
similar. Both black normal controls and stone formers excreted less calcium than their
white counterparts. No blacks had calcium phosphate calculi; 20% of the whites did.
The role of calcium phosphate excretion was not assessed in the work-up protocols.
However, in a “post-hoc” exercise, useful data on urinary metabolites, which included
analysis differentiating between the ethnic groups as well as controls versus stone
formers, was extrapolated from the relevant published papers. The presence of
hyperurcosuria with hyperoxaluria or hypercalciuria was present in whites only.
However, due to the invariable presence of hypernatrituria, hypercalciuria cannot be
accepted as truly non-dietary from these and most other reported studies. The in vitro
laboratory experiment demonstrated the ability of cystine to promote calcium oxalate
stones and was an entirely original postulate at the time of publication. The urinary
metastable limit did not change with the varying cystine levels, while particle diameter
and volume increased significantly and proportionately in a dose responsive manner.
The highest dose of cystine increased the calcium oxalate level by 52%. The results
were confirmed in 14C-oxalate experiments as well as scanning electron microscopy,
neither of which revealed any cystine crystals. Thus, adding cystine to undiluted urine
results in marked calcium oxalate precipitation. This study also demonstrated many of
the latest and advanced techniques in the study of crystal formation science known at
the time. Two of the papers dealt with medical management of nephrolithiasis. The
first clearly demonstrated the outstanding efficacy of potassium citrate in the
successful long-term prevention of recurrent stones in these patients. Likewise, the
use of indapamide clearly outperformed hydrochlorothiazide therapy in patients with
hypercalciuria. Significantly superior efficacy and safety parameters were found with
indapamide which is clearly the drug of choice.
Conclusions
Hypocitraturia was present in ~50% of white stone formers and considered to be
pathogenic. The presence of hypocitraturia in the South African black population,
together with their low prevalence of nephrolithiasis warrants further research.
A dedicated renal stone clinic is advocated; such an institution would provide high
quality care of patients, coupled with a high research output; all of which strongly
supports the creation of a dedicated Kidney Stone Institute
Description
A thesis submitted in fulfilment of the requirements for the degree of Doctor of Medicine to the Faculty of Health Sciences, University of the Witwatersrand, Johannesburg, 2020
Keywords
Citation
Meyers, Anthony Molyneux (2020) The pivotal role of a kidney stone clinic in the management and prevention of recurrent calcium oxalate nephrolithiasis, University of the Witwatersrand, Johannesburg, <http://hdl.handle.net/10539/31420>