Minesh Khatri1, Joshua Zitovsky2, Dale Lee3, Kamal Nayyar4, Melissa Fazzari5, Candace Grant4. 1. Division of Nephrology, Department of Medicine, NYU Winthrop Hospital, 200 Old Country Rd, Ste 135, Mineola, NY, 11501, USA. minesh.khatri@gmail.com. 2. Department of Biostatistics, University of North Carolina, Chapel Hill, NC, USA. 3. Department of Medicine, NYU Winthrop Hospital, Mineola, NY, USA. 4. Division of Nephrology, Department of Medicine, NYU Winthrop Hospital, 200 Old Country Rd, Ste 135, Mineola, NY, 11501, USA. 5. Department of Epidemiology and Population Health, Albert Einstein College of Medicine, Bronx, NY, USA.
Abstract
BACKGROUND: Limited data suggest serum chloride levels associate with mortality in heart failure, chronic kidney disease (CKD), and pulmonary arterial hypertension. Randomized trials have also shown that administration of crystalloid intravenous fluids with lower chloride concentration may have better renal outcomes. However, chloride has not been studied longitudinally for CKD progression. METHODS: We used a prospective cohort of subjects with stage 3 and 4 CKD recruited from a nephrology clinic at a single medical center. Linear regression, linear regression with generalized estimating equations, and Cox proportional hazards models were created for outcomes of overall change in estimated glomerular filtration rate (eGFR), longitudinal changes in eGFR, and time to > 30% decline in eGFR, respectively. Baseline chloride was modeled continuously and categorically, and models were adjusted for potential confounders. RESULTS: Median follow-up was 1.7 years. Baseline median age was 72 years and median eGFR was 35.7 mL/min/1.73m2. In multivariable analysis, higher serum chloride associated with worsened eGFR decline. Every 1 mEq/L increase in chloride associated with an overall eGFR decline of 0.32 mL/min/1.73m2 (p = 0.003), while the difference in eGFR decline in the highest quartile of chloride was 3.4 mL/min/1.73m2 compared to the lowest quartile (p = 0.004). No association between serum chloride and time to 30% decline in eGFR was observed in multivariable analysis (hazard ratio 1.05 per 1 mEq/L increase in serum chloride, p = 0.103). CONCLUSIONS: In CKD patients, higher serum chloride associated with a modestly steeper rate of eGFR decline, and may be a useful biomarker to predict CKD progression. Further studies are needed to determine causality.
BACKGROUND: Limited data suggest serum chloride levels associate with mortality in heart failure, chronic kidney disease (CKD), and pulmonary arterial hypertension. Randomized trials have also shown that administration of crystalloid intravenous fluids with lower chloride concentration may have better renal outcomes. However, chloride has not been studied longitudinally for CKD progression. METHODS: We used a prospective cohort of subjects with stage 3 and 4 CKD recruited from a nephrology clinic at a single medical center. Linear regression, linear regression with generalized estimating equations, and Cox proportional hazards models were created for outcomes of overall change in estimated glomerular filtration rate (eGFR), longitudinal changes in eGFR, and time to > 30% decline in eGFR, respectively. Baseline chloride was modeled continuously and categorically, and models were adjusted for potential confounders. RESULTS: Median follow-up was 1.7 years. Baseline median age was 72 years and median eGFR was 35.7 mL/min/1.73m2. In multivariable analysis, higher serum chloride associated with worsened eGFR decline. Every 1 mEq/L increase in chloride associated with an overall eGFR decline of 0.32 mL/min/1.73m2 (p = 0.003), while the difference in eGFR decline in the highest quartile of chloride was 3.4 mL/min/1.73m2 compared to the lowest quartile (p = 0.004). No association between serum chloride and time to 30% decline in eGFR was observed in multivariable analysis (hazard ratio 1.05 per 1 mEq/L increase in serum chloride, p = 0.103). CONCLUSIONS: In CKD patients, higher serum chloride associated with a modestly steeper rate of eGFR decline, and may be a useful biomarker to predict CKD progression. Further studies are needed to determine causality.
Authors: Joana Krämer; Rui Kang; Laura M Grimm; Luisa De Cola; Pierre Picchetti; Frank Biedermann Journal: Chem Rev Date: 2022-01-07 Impact factor: 60.622