Association between serum Na–Cl level and renal function decline in chronic kidney disease: results from the chronic kidney disease Japan cohort (CKD-JAC) study

BACKGROUND: Metabolic acidosis, which reduces serum bicarbonate levels, contributes to the progression of chronic kidney disease (CKD). The difference between sodium and chloride (Na–Cl) may theoretically predict serum bicarbonate levels. This study aimed to evaluate serum Na–Cl level as a risk factor for renal function decline among patients who participated in the chronic kidney disease Japan cohort (CKD-JAC) study. METHODS: The association between low Na–Cl concentration (< 34 mmol/L) and composite renal function decline events (any initiation of renal replacement therapy or 50% decline in estimated glomerular filtration rate) was evaluated among 2143 patients with CKD stage G3a-4. Using Cox regression analysis, hazard ratios (HRs) were estimated after adjusting for the following covariates: age, sex, diabetes mellitus, diabetic nephropathy, cardiovascular disease, anemia, angiotensin-converting enzyme inhibitors and angiotensin II receptor antagonists, loop diuretics, cigarette smoking, body mass index, serum albumin, systolic blood pressure, urine albumin-to-creatinine ratio, and CKD stage. RESULTS: Composite renal function decline events were observed in 405 patients (18.9%) over the 4-year follow-up period. Low serum Na–Cl level (< 34 mmol/L) was independently associated with a greater risk for composite renal function decline events (HR 1.384; 95% confidence interval [CI], 1.116–1.717). Subgroup analyses identified that the association between low Na–Cl level and composite renal function decline events was stronger among patients with CKD stage G4 and those with anemia. CONCLUSIONS: Our investigation suggests that Na–Cl is an independent predictor of CKD progression, especially among patients with CKD stage G4 and those with anemia. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1007/s10157-018-1631-x) contains supplementary material, which is available to authorized users.