BERKELEY, CA (UroToday.com) - Citrate is one of the most important inhibitors in urolithiasis. Hypocitraturia is very common in stone formers.
Dependant on the definition of hypocitraturia and different populations examined, low citrate levels are reported in 15 – 80 % of stone patients. There is a close correlation between urinary pH and citrate levels since systemic and intracellular acidosis are important regulators of the citrate carriers in the renal tubular cells and citrate excretion. In clinical practice, however, we noticed a considerable number of hypocitraturic stone formers with “normal” urine pH levels and an inadequate increase in urinary citrate on oral alkali citrate therapy. In this group of patients, there is obviously no correlation between urine pH and citrate excretion. This may be a sign of defects in the renal tubular citrate carriers NaDC 1 and 3, which is potentially genetically determined. We were interested to search for such patients, to learn their characteristics and the potential relevance for clinical work-up.
In N=350 consecutive stone formers (excluded were patients with urinary tract infection, hypokalemia, and steatorrhea) we found 83 hypocitraturic patients (48 males, 35 females). 14/83 had low urine pH (<6) (hclpH), 69/83 showed normal levels (>6) (hcnpH) as measured in circadian pH-profiles. In the latter group there was a significantly higher recurrence rate (23 vs. 9%). The two groups were not different in serum parameters apart from uric acid (higher in the hclpH group). In urine, only pH (by definition) and calcium (males) were significantly lower in the first group. Citrate did not correlate with urine pH and creatinine in the hcnpH group, only with calcium in both sexes and urea and ammonia in females. In the hclpH patients, there was no significant correlation between citrate and any other parameter tested.
In our series, almost 30% of the stone formers studied revealed hypocitraturia. Amongst these, there was an entity of stone formers with hypocitraturia and “normal” urine pH, which is about 80% of hypocitraturic and about 20% of all stone formers. In these patients, there was no significant correlation between urine pH and citrate excretion, i.e. citrate excretion is not regulated by acid-base balance as usual. In the females, protein consumption could play a role since citrate correlated with the urea excretion. Both in males and females, there was a correlation between citrate and urinary calcium excretion. It is hard to say which parameter is important for the regulation of citrate excretion in this group. Potentially, the hcnpH group are patients in which the citrate carriers of the tubular cells are defect. This defect might be genetically determined.
The hcnpH collective, however, showed a significantly higher recurrence rate than those stone formers with hclpH. The reasons are unclear. One might speculate that the higher urine pH increases supersaturation with respect to calcium phosphate and therefore decreases the upper limit of metastability of calcium phosphate. This decreased metastability of calcium phosphate could promote calcium oxalate stones by permitting Randall’s plaques or calcium phosphate seeds in the thin loops of Henle to form. This theory is consistent with the observation in our series that calcium phosphate stones were only seen in the hcnpH but not in the hclpH group. The increased risk in the hcnpH-group is underlined by the fact that the mean age in the male hcnpH-group was significantly lower than in the hclpH group indicating an earlier onset of stone formation in the hcnpH group.
Summing up, there was a significantly higher recurrence rate in the hcnpH group. Whatever the reasons are, these results demonstrate that the combination of low citrate excretion and “normal” urine pH identifies a high-risk group in stone formers.
Written by:
Walter Ludwig Strohmaier,1 Jürgen Seilnacht,1 and Gernot Schubert2 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.
1Department of Urology and Paediatric Urology, Klinikum Coburg, Germany
2Urinary Stone Laboratory, Labor Berlin Charité Vivantes, Berlin, Germany
Urinary stone formers with hypocitraturia and 'normal' urinary pH are at high risk for recurrence - Abstract
