Higher Renal Net Acid, but Not Higher Phosphate Excretion During Growth Associates With Lower Adult Circulating Uromodulin

Abstract

Objectives

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 (PO₄)-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 on the associations of P-In and endogenous acid loads of 3-17-year-old healthy participants (n = 358) of the Dortmund Nutritional and Anthropometric Longitudinally Designed study (Dortmund, Germany), with their circulating uromodulin levels later in adulthood. Urinary (PO₄)excretion, 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. Multilinear regression models adjusted for anthropometric, renal, and blood parameters were conducted to examine the prospective relationships of preadulthood urinary biomarkers with adult circulating uromodulin.

Results

Uromodulin associated inversely with NAE (P_for-trend < .03) and positively with urinary pH (P_for-trend = .05; lowest pH-quintile vs. highest quintile: P = .03), but not significantly with uPRAL and (PO₄) excretion during growth.

Conclusions

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.