Renal Net Acid Excretion During Growth and eGFR, Creatinine Clearance, and Albuminuria in Young Adulthood

Rationale & Objective: Metabolic acidosis and reduced serum bicarbonate levels are known to contribute to kidney disease progression. Whether habitual high net endogenous acid production early in life may have consequences for long-term kidney function is not known. To date, no longitudinal study has examined the relationships between regular net acid excretion (NAE) during childhood and adolescence and later adult albumin excretion, estimated glomerular filtration rate (eGFR), and creatinine clearance (CLCr). Study Design: Open cohort study examining healthy children from infancy to adulthood. Setting & Participants: Study participants with multiple 24-hour urine collections between ages 3 and 17 years who provided a blood sample between ages 18 and 35 years. Exposure: Pre-adulthood NAE and its components ammonium excretion, titratable acidity, and pH. Outcomes: Adults’ eGFR, CLCr, and albumin-creatinine ratio (ACR). Analytical Approach: Sex- and age-stratified standard deviation scores calculated for anthropometric and urinary biomarkers were averaged for each individual, and the relationships between urinary exposures and adulthood eGFR, CLCr, and ACR were examined using multiple linear regression analysis. Regression models were adjusted for pre-adulthood nutrition-related renal biomarker standard deviation scores and various adult parameters. Results: In fully adjusted models, children’s and adolescents’ repeatedly measured renal NAE and titratable acidity had a strong inverse association and their 24-hour urinary pH had a highly significant positive association with eGFR in adulthood. Similar findings were seen for CLCr. Pre-adulthood ammonium excretion had a significant positive relationship only with ACR in adulthood. Limitations: Outcomes determined only once. Conclusions: These exclusively biomarker-based findings strongly suggest that habitually increased NAE and corresponding low urinary pH values in the normal range in childhood and adolescence are already related to incipient signs of kidney function decline in adulthood. Hence, as an important kidney health prevention measure, habitual consumption of alkalizing fruit- and vegetable-rich diets with clear ammoniagenic and NAE-lowering efficiency should start early in childhood. Plain-Language Summary: Metabolic acidosis negatively affects kidney function. Whether habitually high renal net acid excretion early in life may already negatively affect kidney function in the long run is not known. By examining healthy children’s and adolescents’ acid excretion and urinary pH values in 24-hour urine samples, repeatedly collected during ages 3-17 years, we demonstrated that higher acid excretion and lower urinary pH are adversely related to glomerular filtration rate, creatinine clearance, and partially to albuminuria later in adulthood. These findings strongly suggest that regularly increased acid loads to the body during childhood and adolescence are already involved in adversely influencing kidney function, indicating the importance of early alkalizing fruit- and vegetable-rich nutrition for long-term kidney health.