#1430 Acid excretion is disturbed in calcium oxalate and calcium phosphate stone formers in the Swiss kidney stone cohort
Authors: Silva Pedro Henrique Imenez , Aliaga Isabel Rubio , Fuster Daniel , Seeger Harald , Ernandez Thomas , Buchkremer Florian , Dhayat Nasser , Ritter Alexander , Segerer Stephan , Roth Beat , Bonny Olivier , Wagner Carsten 
Published: May 2024

Abstract

Background and Aims
Kidney stone is a highly prevalent disease worldwide that causes high morbidity and may increase the risk for chronic kidney disease. Urine pH influences the crystallization of some types of kidney stones, such as calcium phosphate and uric acid. This study aimed to identify whether other acid-base parameters are associated with stone formation in the Swiss kidney stone cohort.

Method
Urinary, serum, clinical, and anthropomorphic baseline data were obtained from the Swiss Kidney Stone Cohort, a prospective, longitudinal, and multi-centric observational study. We included 200 non-stone formers (NSF, determined by CT scan), and 265 calcium oxalate (CaOx) and 113 calcium phosphate (CaP) stone formers with complete data for urine pH (collected under oil). Titratable acids were calculated based on urine phosphate and creatinine levels and urine bicarbonate based on urine pH. Net acid excretion (NAE) was calculated and NAE capacity (NAEC), the NAE for a given urine pH, which reveals the ability of kidneys to excrete acids, was calculated from the residuals of the relation between urine pH and NAE. Logistic regression analyses were used to estimate the potential contributions of various acid-base variables to the occurrence of CaOx or CaP kidney stones. Odds ratio (OR) are reported as “OR [95% confidence interval]”

Results
CaOx stone formers were slightly older than NSF individuals and CaP stone formers (NSF = 42.9 ± 13.6 y.o., CaOx = 47.3 ± 14.3 y.o., CaP = 43.3 ± 12.9 y.o.), slightly more overweight (NSF = 25.0 ± 4.15, CaOx = 27.1 ± 4.72, CaP = 25.9 ± 4.55), and had a higher prevalence of males (NSF = 56.0%, CaOx= 72.1%, CaP = 59.3%), but had similar baseline estimated glomerular filtration rate (NSF = 97.1 ± 16.5, CaOx = 96.3 ± 18.3, CaP = 99.5 ± 18.0 ml/min/1.73 m2). Hypertension, type 2 diabetes, pyelonephritis, and nephrocalcinosis were more prevalent among people with either type of kidney stones in comparison with NSFs, while inflammatory bowel disease was more common among CaOx stone formers in comparison with NSF individuals. CaOx and CaP stone formers showed disturbed capacity of excreting acids in relation to NSF (NAEC NSF = 1.81 ± 8.21 µmol/min; CaOx = −1.35 ± 8.45, P &lt; .001; CaP = −0.89 ± 7.66, P = .016) and lower 24 h urine excretion of ammonium (NSF = 19.8 ± 8.70 µmol/min; CaOx = 17.4 ± 8.54, P = .012; CaP = 16.5 ± 8.23, P = .005), but also of citrate, oxalate, and potassium (Table 1). In addition, CaOx exhibited a lower urine volume. In contrast, both CaOx and CaP excreted more calcium (NSF = 3.12 ± 1.85 µmol/min; CaOx = 3.82 ± 1.91 p &lt;0.001; CaP = 4.63 ± 2.27, p &lt;0.001). Urine pH was more acidic in CaOx (p &lt; 0.001) in comparison with NSFs and CaP (P = .004), NSF = 6.05 ± 0.51; CaOx = 5.86 ± 0.53; CaP = 6.16 ± 0.62. The correlations between urine pH and both urine calcium and ammonium were disturbed in CaOx stone formers and shifted in CaP stone formers (Fig. 1). Logistic models including urine ammonium, pH, citrate, phosphate, potassium, calcium, magnesium, oxalate, protein, and volume showed that ammonium is negatively associated with both CaOx and CaP stone formation (unadjusted model OR 0.41[0.26-0.57], p&lt; 0.001 for CaOx and OR 0.42[0.26–0.67], P &lt; .001 for CaP) and urine calcium is positively associated with kidney stones (OR 2.37 [1.72-3.43], P &lt; .001 for CaOx and OR 5.82 [3.6–10.1], P &lt; .001 for CaP). Similar results were obtained after adjustment for age, sex, and BMI. Removing urine ammonium, pH, and phosphate from our logistic model and adding NAEC rendered comparable goodness of fit and model complexity. Holding all other independent variables constant, the odds of CaOx associated with NAEC were 0.45 [0.33–0.61], P &lt; .001 and with calcium of 2.6 [1.91–3.64], P &lt; .001. For CaP, NAEC was still associated with it, but urine magnesium showed a lower odds ratio value (0.44 [0.27–0.72], P = .001 vs 0.54 [0.36–0.80], P = .003). Urine citrate was only associated with CaOx stones.

Conclusion
Baseline urine ammonium and net acid excretion capacity are strongly associated with the occurrence of CaOx and CaP kidney stones. Reduced NAEC indicates that poor control of ammonium excretion is a hallmark of both types of kidney stones, although more strongly apparent in CaOx.