SUN-120 ASSOCIATION BETWEEN SERUM MIDKINE AND RENAL OUTCOMES IN ELDERLY WOMEN

Abstract

Midkine (MK) is heparin-binding cytokine which has been shown to mediate kidney injury and dysfunction via its immunomodulatory functions such as neutrophil and macrophage trafficking, lymphocyte activation, and induction of chemokines. While this has been demonstrated in a number of experimental studies, the extent of the association between Midkine and kidney disease at the population level remains largely unknown. The aims of this study were to determine the association between serum MK and longitudinal changes in kidney function and chronic kidney disease (CKD)-related clinical events in a large cohort of elderly women with long-term clinical follow-up. This was a prospective study of ageing women. Serum MK was measured in 1998 (baseline). Associations between baseline serum MK with change in estimated glomerular filtration rate (eGFR) at 5 and 10 years were analysed using linear regression analyses, adjusting for age, body mass index (BMI), diabetes, use of blood pressure lowering medications, use of statins and prevalent atherosclerotic vascular disease (ASVD). Associations between baseline serum MK and rapid renal decline at 5 years, defined as an annual eGFR decline of greater than 3 mL/min/1.73m2, and CKD-related hospitalisations and deaths at 14.5 years as a composite outcome were examined using logistic and Cox regression analyses respectively, adjusting for similar risk factors. The baseline cohort consisted of women aged over 70 years, with a median age of 75. Throughout the follow-up period of 15 years, there were a total of 206 deaths, and 46 CKD-related hospitalisations and deaths. Baseline serum MK was not associated with 5 and 10 year eGFR change (standardised β coefficient = -0.070, 95% CI = -3.548-0.843, p = 0.226; standardised β coefficient = -0.116, 95% CI = -6.470-0.514, p = 0.094, respectively), or the risk of rapid renal decline at 5 years (odds ratio = 1.85, 95% CI = 0.76-4.49, p = 0.175) in multivariable-adjusted models. Compared to below-median, above-median baseline serum MK was associated with a two-fold increased risk of CKD-related hospitalisations and deaths at 14.5 years (hazard ratio = 1.96, 95% CI = 1.07-3.62, p = 0.030) after adjusting for known risk factors. In older women with mild to moderate renal dysfunction, elevated serum MK is associated with CKD-related hospitalisation and death events. Further prospective studies are needed to determine the prognostic importance of increased MK activity with CKD.