"Higher renal net acid, but not higher phosphate excretion during growth associates with lower adult circulating uromodulin"

Objective: Uromodulin is the most abundant urinary protein in healthy subjects which under physiological conditions protects against kidney stone formation. Acid-base imbalances, especially states with acidic urine, increase the risk for uric acid and oxalate stones, but lower it for phosphate-containing stones. Whether habitual high acid loads and high dietary phosphorus intake (P-In) themselves may influence plasma uromodulin concentrations in the long-term is not known.

Methods: we prospectively examined biomarker-based the associations of P-In and endogenous acid loads of 3-17 years old healthy participants (n=358) of the DONALD study (Dortmund, Germany) with their circulating uromodulin levels later in adulthood. Urinary phosphate excretion (PO₄-Ex), net acid excretion (NAE), potential renal acid load (uPRAL), and pH were analyzed in 24-hour urine samples repeatedly collected during growth. Circulating uromodulin was analyzed in adult fasting blood samples. Individual means of age- and sex-stratified standard-deviation-scores of growth- and nutritional biomarker-related parameters were calculated. Multi-linear regression models adjusted for anthropometric, renal, and blood parameters were conducted to examine the prospective relationships of pre-adulthood urinary biomarkers with adult circulating uromodulin.

Results: Uromodulin associated inversely with NAE (P_for-trend<0.03) and positively with urinary pH (P_for-trend=0.05; lowest pH-quintile vs. highest quintile: P=0.03), but not significantly with uPRAL and PO₄-Ex during growth.

Conclusion: the known increased urolithiasis risk associated with high endogenous acid production may be further augmented by a high NAE-related reduction of the stone-formation inhibitor uromodulin. Despite not observing a significant association with uPRAL, the potential of habitual low-PRAL diets to raise uromodulin needs to be further studied.