The pivotal role of a kidney stone clinic in the management and prevention of recurrent calcium oxalate nephrolithiasis

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