Association between urinary chloride excretion and progression of coronary artery calcification in patients with nondialysis chronic kidney disease: results from the KNOW-CKD study

Abstract

Background: Urine chloride has recently been suggested as a biomarker of renal tubule function in patients with nondialysis chronic kidney disease (CKD), as low urinary chloride concentration is associated with an increased risk of CKD progression. We investigate the association between urinary chloride excretion and the progression of coronary artery calcification (CAC).

Methods: A total of 1,065 patients with nondialysis CKD were divided into tertiles by spot urine chloride-to-creatinine ratios. The 1st, 2nd, and 3rd tertiles were defined as low, moderate, and high urinary chloride excretion, respectively. The study outcome was CAC progression, which was defined as an increase in coronary artery calcium score of more than 200 Agatston units during the 4-year follow-up period.

Results: Compared to moderate urinary chloride excretion, high urinary chloride excretion was associated with decreased risk of CAC progression (adjusted odds ratio, 0.379; 95% confidence interval, 0.190-0.757), whereas low urinary chloride excretion was not associated with risk of CAC progression. Restricted cubic spine depicted an inverted J-shaped curve, with a significant reduction in the risk of CAC progression in subjects with high spot urine chloride-to-creatinine ratios.

Conclusion: High urinary chloride excretion is associated with decreased risk of CAC progression in patients with nondialysis CKD.

Keywords: Biomarkers; Chronic renal insufficiency; Coronary artery disease; Urine chloride.

Figure 1.. Flow diagram of the study participants.

CACS, coronary artery calcium score; Cl^–/Cr, chloride-to-creatinine ratio; Cr, creatinine; SD, standard deviation; T1, 1st tertile; T2, 2nd tertile; T3, 3rd tertile.

Figure 2.. Restricted cubic spline of spot urine Cl–/Cr on the risk of CAC progression.

Adjusted OR of spot urine Cl^–/Cr as a continuous variable for the progression of CAC is depicted. The model was adjusted for age, sex, Charlson comorbidity index, primary renal disease, current smoking status, medication (ACEi/ARBs, diuretics, number of anti-HTN drugs, statins), BMI, SBP, hemoglobin, albumin, fasting glucose, HDL-C, TG, 25(OH) vitamin D, hsCRP, eGFR, spot urine ACR, and CACS at the baseline. ACEi, angiotensin-converting enzyme inhibitor; ACR, albumin-to-creatinine ratio; ARB, angiotensin receptor blocker; BMI, body mass index; CACS, coronary artery calcium score; Cl^–/Cr, chloride-to-creatinine ratio; eGFR, estimated glomerular filtration rate; HDL-C, high-density lipoprotein cholesterol; hsCRP, high-sensitivity C-reactive protein; HTN, hypertension; OR, odds ratio; SBP, systolic blood pressure; T1, 1st tertile; T2, 2nd tertile; T3, 3rd tertile; TG, triglyceride.