Acid Load and Phosphorus Homeostasis in CKD

Background The kidneys maintain acid-base homeostasis through excretion of acid as either ammonium or as titratable acids that primarily use phosphate as a buffer. In chronic kidney disease (CKD), ammoniagenesis is impaired, promoting metabolic acidosis. Metabolic acidosis stimulates phosphaturic hormones, parathyroid hormone (PTH) and fibroblast growth factor 23 (FGF-23) in vitro, possibly to increase urine titratable acid buffers, but this has not been confirmed in humans. We hypothesized that higher acid load and acidosis would associate with altered phosphorus homeostasis, including higher urinary phosphorus excretion and serum PTH and FGF-23. Study Design Cross-sectional. Setting & Participants 980 participants with CKD enrolled in the Chronic Renal Insufficiency Cohort (CRIC) Study. Predictors Net acid excretion as measured in 24-hour urine, potential renal acid load (PRAL) estimated from food frequency questionnaire responses, and serum bicarbonate concentration < 22 mEq/L. Outcome & Measurements 24-hour urine phosphorus and calcium excretion and serum phosphorus, FGF-23, and PTH concentrations. Results Using linear and log-linear regression adjusted for demographics, kidney function, comorbid conditions, body mass index, diuretic use, and 24-hour urine creatinine excretion, we found that 24-hour urine phosphorus excretion was higher at higher net acid excretion, higher PRAL, and lower serum bicarbonate concentration (each P < 0.05). Serum phosphorus concentration was also higher with higher net acid excretion and lower serum bicarbonate concentration (each P = 0.001). Only higher net acid excretion associated with higher 24-hour urine calcium excretion ( P < 0.001). Neither net acid excretion nor PRAL was associated with FGF-23 or PTH concentrations. PTH, but not FGF-23, concentration ( P = 0.2) was 26% (95% CI, 13%-40%) higher in participants with a serum bicarbonate concentration