Associations between urinary cysteine-rich protein 61 excretion and kidney function decline in outpatients with chronic kidney disease: a prospective cohort study in Taiwan

Abstract

ObjectivesTo examine whether urinary excretion of cysteine-rich protein 61 (Cyr61), an acknowledged proinflammatory factor in kidney pathologies, increases in chronic kidney disease (CKD) and is associated with subsequent rapid kidney function decline.DesignAn observational cohort study.SettingIn the nephrology outpatient clinics of a tertiary hospital in Taiwan.ParticipantsWe enrolled 138 adult CKD outpatients (n=12, 32, 18, 18, 29 and 29 in stages 1, 2, 3a, 3b, 4 and 5 CKD, respectively) between February and October 2014 and followed them for 1 year. Their mean age was 60.46±13.16 years, and 51 (37%) of them were women.Primary outcome measuresUrinary Cyr61 levels were measured by ELISA. Rapid kidney function decline was defined as an estimated glomerular filtration rate (eGFR) decline rate ≥ 4 mL/min/1.73 m2/year or developing end-stage renal disease during subsequent 3-month or 1-year follow-up period. Models were adjusted for demographic and clinical variables.ResultsThe urine Cyr61-to-creatinine ratio (UCyr61CR) increased significantly in patients with stage 4 or 5 CKD. Multivariable linear regression analysis showed that log(UCyr61CR) was positively correlated with log(urine protein-to-creatinine ratio) (p<0.001) but negatively correlated with baseline eGFR (p<0.001) and hypertension (p=0.007). Complete serum creatinine data during the follow-up were available for 112 patients (81.2%). Among them, multivariable logistic regression identified log(UCyr61CR) was independently associated with rapid kidney function decline (adjusted OR 2.29, 95% CI 1.27 to 4.15) during the subsequent 3 months. UCyr61CR improved the discriminative performance of clinical models to predict 3-month rapid kidney function decline. In contrast, log(UCyr61CR) was not associated with rapid eGFR decline during the entire 1-year follow-up.ConclusionsElevated urinary Cyr61 excretion is associated with rapid short-term kidney function deterioration in patients with CKD. Measuring urinary Cyr61 excretion is clinically valuable for monitoring disease trajectory and may guide treatment planning.