Association of metabolic acidosis with fractures, falls, protein-calorie malnutrition and failure to thrive in patients with chronic kidney disease

Abstract

Background: The risk of adverse geriatric outcomes such as falls and fractures is high among patients with chronic kidney disease (CKD). Metabolic acidosis is associated with protein catabolism and bone loss in experimental animal and human studies. We sought to quantify the independent association of metabolic acidosis with adverse muscle, bone and functional outcomes in a large US community-based cohort. Methods: The Optum's de-identified Integrated Claims-Clinical dataset of US patients (2007-2017) was used to generate a cohort of patients with nondialysis-dependent CKD who had estimated glomerular filtration rate >10 to <60 mL/min/1.73 m2 and two serum bicarbonate values 12 to <22 mmol/L or 22-29 mmol/L. The primary outcomes were failure to thrive, protein-calorie malnutrition, and fall or fracture. Cox proportional hazards models were used for the primary outcomes for up to 10 years, while logistic regression models were used at 2 years. Results: A total of 51 558 patients qualified for the study, with a median [Interquartile Range (IQR)] follow-up time of 4.2 (2.5-5.8) years. Over a ≤10-year period, for each 1 mmol/L increase in serum bicarbonate, the hazard ratios (adjusted for age, sex, race, estimated glomerular filtration rate, serum albumin, hemoglobin, diabetes and cardiovascular comorbidities) for failure to thrive, protein-calorie malnutrition and fall or fracture were 0.91 [95% confidence interval (CI): 0.90-0.92], 0.91 (95% CI: 0.90-0.92) and 0.95 (95% CI: 0.95-0.96), all P < 0.001, respectively. Conclusions: The presence and severity of metabolic acidosis was a significant, independent risk factor for failure to thrive, protein-calorie malnutrition and fall or fracture in this large community cohort of patients with stage 3-5 CKD.