Search

Rationale & Objective: Higher urine net acid excretion (NAE) is associated with slower chronic kidney disease progression, particularly in patients with diabetes mellitus. To better understand potential mechanisms and assess modifiable components, we explored independent predictors of NAE in the CRIC (Chronic Renal Insufficiency Cohort) Study., Study Design: Cross-sectional., Setting & Participants: A randomly selected subcohort of adults with chronic kidney disease enrolled in the CRIC Study with NAE measurements., Predictors: A comprehensive set of variables across prespecified domains including demographics, comorbid conditions, medications, laboratory values, diet, physical activity, and body composition., Outcome: 24-hour urine NAE., Analytical Approach: NAE was defined as the sum of urine ammonium and calculated titratable acidity in a subset of CRIC participants. 22 individuals were excluded for urine pH < 4 (n = 1) or ≥7.4 (n = 19) or extreme outliers of NAE values (n = 2). From an analytic sample of 978, we identified the association of individual variables with NAE in the selected domains using linear regression. We estimated the percent variance explained by each domain using the adjusted R 2 from a domain-specific model., Results: Mean NAE was 33.2 ± 17.4 (SD) mEq/d. Multiple variables were associated with NAE in models adjusted for age, sex, estimated glomerular filtration rate (eGFR), race/ethnicity, and body surface area, including insulin resistance, dietary potential renal acid load, and a variety of metabolically active medications (eg, metformin, allopurinol, and nonstatin lipid agents). Body size, as indicated by body surface area, body mass index, or fat-free mass; race/ethnicity; and eGFR also were independently associated with NAE. By domains, more variance was explained by demographics, body composition, and laboratory values, which included eGFR and serum bicarbonate level., Limitations: Cross-sectional; use of stored biological samples., Conclusions: NAE relates to several clinical domains including body composition, kidney function, and diet, but also to metabolic factors such as insulin resistance and the use of metabolically active medications., (Published by Elsevier Inc.)

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 <22 versus ≥22 mEq/L (P<0.001). Primary results were similar if stratified by estimated glomerular filtration rate categories or adjusted for iothalamate glomerular filtration rate (n=359), total energy intake, dietary phosphorus, or urine urea nitrogen excretion, when available., Limitations: Possible residual confounding by kidney function or nutrition; urine phosphorus excretion was included in calculation of the titratable acid component of net acid excretion., Conclusions: In CKD, higher acid load and acidosis associate independently with increased circulating phosphorus concentration and augmented phosphaturia, but not consistently with FGF-23 or PTH concentrations. This may be an adaptation that increases titratable acid excretion and thus helps maintain acid-base homeostasis in CKD. Understanding whether administration of base can lower phosphorus concentrations requires testing in interventional trials., (Copyright © 2017 National Kidney Foundation, Inc. Published by Elsevier Inc. All rights reserved.)

Uric acid is the end product of purine degradation in humans. It is a weak acid with a pK of 5.35 in urine. In acidic urine the undissociated form of uric acid predominates and is poorly soluble, leading to crystalluria and stone formation. Uric acid stones account for 5% to 10% of all stones in the United States. Acidic urine, hyperuricosuria, and low urine volume are the risk factors for uric acid stone formation. Uric acid stones may be idiopathic or secondary to a systemic disease such as gout. Treatment includes alkalinization of the urine, high fluid intake, and reduction of uric acid excretion if it is abnormal.