Abstract
BackgroundMetabolic 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.MethodsThe 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.ResultsComposite 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.ConclusionsOur investigation suggests that Na–Cl is an independent predictor of CKD progression, especially among patients with CKD stage G4 and those with anemia.
Highlights
Metabolic acidosis is a well-known complication of chronic kidney disease (CKD), in stages 4 and 5, and reduces the serum level of sodium bicarbonate, which is important for attenuating the rate of kidney disease progression [1,2,3,4,5,6,7]
The exclusion criteria were patients with polycystic kidney disease, human immunodeficiency virus infection, cirrhosis, active cancer, or cancer treatment in the past 2 years; transplant recipients; patients with a history of previous or current dialysis; pregnant patients; and patients who did not provide informed consent. In addition to these previously published exclusion criteria [10], four additional exclusion criteria were used in our ad hoc analysis: (1) an estimated glomerular filtration rate (eGFR) < 15 mL/min/1.73 m2 at baseline, as this has been reported to reflect anion accumulation [11], (2) missing sodium or chloride concentration at baseline, (3) malignancy, and (4) a serum albumin level < 3.0 g/dL, as low Na–Cl levels may be mistakenly observed in patients with hypoalbuminemia [12, 13]
Group differences were observed in the serum albumin level, urine albumin-to-creatinine ratio (UACR), Hb level, eGFR, use of ACEIs/ ARBs, use of loop diuretics, a history of Cardiovascular disease (CVD), and diabetes mellitus (DM)
Summary
Metabolic acidosis is a well-known complication of chronic kidney disease (CKD), in stages 4 and 5, and reduces the serum level of sodium bicarbonate, which is important for attenuating the rate of kidney disease progression [1,2,3,4,5,6,7]. 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. 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
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