BERKELEY, CA (UroToday.com) - Prior work has demonstrated a bidirectional association between chronic kidney disease (CKD) and nephrolithiasis, in which the presence of one predisposes to the presence of the other. In light of this, we have noticed that renal function seems to affect stone composition.
Few studies have examined our observation. Therefore, we used a large clinical database of patients who underwent endourologic intervention to determine if there were any patterns between renal function and stone composition.
Estimated glomerular filtration rate (eGFR) is a better measure of renal function than serum Cr. We noted that differences in eGFR were significantly associated with differences in stone composition, specifically differences in the uric acid content of stones. To formalize our analysis, we felt it most prudent to use an established categorization system, so we used the stages of CKD used in the KDOQI guidelines. Very few of our patients had Stage IV or Stage V disease, so we excluded those patients from our analysis. Some reviewers criticized our usage of the CKD stages, as the diagnosis of CKD relies on evidence of kidney damage (e.g. proteinuria) and not eGFR alone. Another criticism was that eGFR’s strong relationship to age made it a less-than-ideal variable – in other words, there was no way to tell whether differences in stone composition were truly due to eGFR rather than simply to differences in age. While these criticisms are valid, we felt that our classification scheme made clinical sense and was sufficient to test our hypothesis, which was that renal function plays an important role in stone composition.
We were surprised to see such a close linkage between renal function and uric acid content of stones. Patients with a “normal” eGFR (>90 cc/hr) only had a 3% chance of forming a stone that was made primarily of uric acid! In that regard, good renal function seemed to be quite protective against uric stones, while poor renal function would seem to be a significant etiologic factor. The converse was true for calcium phosphate stones, which were not commonly seen in patients with poor renal function; whether or not this is because calcium phosphate stones are more likely to be found in younger patients (for instance, with hyperparathyroidism) is unclear.
The 24-hour urine collections yielded some unexpected results. For example, the prevalence of calcium oxalate stones did not correlate with urinary calcium, urinary oxalate, or calcium oxalate supersaturation index. It is possible that the urinary factors favoring uric acid and/or calcium phosphate stones were stronger that those leading toward calcium oxalate stones, thereby obscuring any trends toward or against the formation of a calcium oxalate stone. An additional possibility is that the risk factors for non-calcium oxalate stones are “weaker” than those for calcium oxalate stones, and therefore only come into play in a minority of stone formers. Another interesting finding was that uric acid excretion did not differ between groups, nor could supersaturation indices explain the high rate of uric acid stones in Group 3 patients. This could be due to precipitation of urates in the 24h-hour urine sample. It may also simply confirm that urine pH, rather than hyperuricosuria, is a stronger factor leading to uric acid stone formation.
The "hidden story" in our study was that calcium oxalate content and the frequency of calcium oxalate stones did not correlate with eGFR. This might be due to the observation that calcium oxalate stone formers have extra-renal etiologic factors such as absorptive hypercalciuria or enteric hyperoxaluria. It might also be the case that the apparent risk of nephrolithiasis conferred by CKD is due to increases in the number of non-calcium oxalate stones, and that our efforts at prevention of calcium oxalate stones need not be directed at the causal agents of CKD, such as diabetes and hypertension. In the same vein, patients who form calcium oxalate stones and who have risk factors for CKD, such as hypertension, diabetes, and obesity, might not need to be counseled on weight loss and diabetic control in order to prevent stones – a longitudinal study on calcium oxalate stone formers with “metabolic” risk factors would be a good way to clarify this issue.
In summary, our study adds to the literature on the etiology of metabolic stone disease and the factors that influence stone composition. Stone disease is a relatively common and oftentimes debilitating condition, and further study on etiology and prevention of certain kinds of stones should continue to be an area of clinical and basic research.
Adam O. Kadlec, MD. as part of Beyond the Abstract on UroToday.com. This initiative offers a method of publishing for the professional urology community. Authors are given an opportunity to expand on the circumstances, limitations etc... of their research by referencing the published abstract.