Acid excretion is impaired in calcium oxalate stone formers

Silva, P. H. I.; Dhayat, N. A.; Fuster, D. G.; Seeger, H.; Ritter, A.; Ernandez, T.; Buchkremer, F.; Roth, B.; Bonny, O.; Rubio-Aliaga, I.; Wagner, C. A.

doi:10.1101/2024.09.30.615797

bioRxiv · 10.1101/2024.09.30.615797

Acid excretion is impaired in calcium oxalate stone formers

Silva, P. H. I.·Dhayat, N. A.·Fuster, D. G.·Seeger, H.·Ritter, A.·Ernandez, T.·Buchkremer, F.·Roth, B.·Bonny, O.·Rubio-Aliaga, I.·Wagner, C. A.

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Abstract

BackgroundUrine pH is a key factor in kidney stone formation. We aimed to identify whether acid excretion capacity is disturbed in calcium oxalate (CaOx) or calcium phosphate (CaP) stone formers. MethodUrinary, serum, clinical, and anthropomorphic baseline data were obtained from the Swiss Kidney Stone Cohort, a prospective, longitudinal, and multi-centric observational study. We included in this study 193 non-stone formers (NSF, confirmed by negative CT scan), and 309 CaOx and 28 CaP stone formers. Titratable acids, net acid excretion (NAE), NAE capacity (NAEC) and acid-base (AB) score were calculated. Logistic regression analyses were used to estimate the potential associations of various acid-base variables with the occurrence of CaOx kidney stones. ResultsCaOx stone formers showed a disturbed capacity to excrete acids in comparison to NSF (NAEC NSF = 3.49{+/-}12.6 mmol/24h; CaOx = -1.06{+/-}13.10; CaP = 0.97{+/-}14.70 and AB score NSF = 20.5{+/-}6.36 mmol/24h; CaOx = 17.9{+/-} 6.53; CaP = 18.8{+/-}6.10). The correlation between urine calcium and urine pH was altered in CaOx stone formers and between urine calcium and NAE was stronger in CaP stone formers. Logistic models showed that urinary ammonium was negatively associated with CaOx stone formation (unadjusted model, odds ratio 0.43[0.32-0.58], p< 0.001 for CaOx). Urine calcium was positively associated with CaOx kidney stones (2.85 [2.11-3.92], p<0.001). Similar results were obtained after adjusting for age, sex, and BMI. Replacing urine ammonium, pH, and phosphate with NAEC or ammonium and pH with AB score in our logistic regression models showed that NAEC and AB score are strongly associated with CaOx kidney stone formation. ConclusionAmmonium excretion, NAEC and AB score are associated with the occurrence of CaOx kidney stones suggesting a potential role of proximal tubule dysfunction in their formation. CaP stone formers exhibit a disproportionately higher calcium excretion when acid excretion increases. Key learning pointsO_ST_ABSWhat was knownC_ST_ABSUrine pH is a strong determinant in the formation of various urologically relevant crystals. Impaired urine acidification capacity has been observed in individuals who form calcium phosphate and uric acid stones. This study addsWhen compared to non-stone formers, calcium oxalate stone formers are marked by a reduced capacity of excreting acids when urine pH becomes more acidic. Potential impactThe calculation of net acid excretion capacity and acid-base score are novel tools to identify those under potential higher risk of developing calcium oxalate stones.

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Silva, P. H. I., Dhayat, N. A., Fuster, D. G., Seeger, H., Ritter, A., Ernandez, T., Buchkremer, F., Roth, B., Bonny, O., Rubio-Aliaga, I., Wagner, C. A.. 2024-10-01. Acid excretion is impaired in calcium oxalate stone formers. https://doi.org/10.1101/2024.09.30.615797

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