THE METABOLIC SYNDROME IS ASSOCIATED WITH IMPAIRMENT OF LONG-TERM RENAL GRAFT FUNCTION: NOT ALL COMPONENT CRITERIA CONTRIBUTE EQUALLY.

Abstract

O151 Aims: Chronic renal transplant dysfunction (CRTD) remains a leading cause of renal graft loss. Both immunological and non-immunological factors are involved in its development. Several cardiovascular risk factors such as obesity, dyslipidemia, hypertension, and diabetes mellitus have been identified as important non-immunological risk factors for CRTD. These risk factors constitute the metabolic syndrome (MS). As allograft function is a predictor of graft loss, we investigated the association of MS with long-term impairment of renal graft function. Methods: Presence of MS was assessed between Aug 2001 and July 2003 (index date) using NCEP-ATPIII criteria in 606 out of all 847 (72% consent) renal transplant outpatients who were transplanted >1 year before. Patients had MS if 3 or more of the following criteria applied to them: 1) waist circumference >102 cm in men; >88 cm in women 2) serum triglycerides ≥1.70 mmol/L 3) serum HDLc <1.03 mmol/L in men, <1.29 mmol/L in women, 4) blood pressure ≥130/85 mmHg or use of antihypertensives, 5) fasting plasma glucose ≥6.1 mmol/L or use of antidiabetics. Blood was drawn after an overnight fast to determine serum triglycerides, HDL-cholesterol, and plasma glucose levels. Waist circumference, blood pressure, and current medication were determined as well. Renal graft function was assessed as 24h urinary creatinine clearance. Graft function at 1 year posttransplant was considered baseline. Impairment of graft function was defined as the decline in function between baseline and index date. Demographic and transplant characteristics were extracted from our Transplant Center’s Database. Results: A total of 383 out of 606 patients (63%) suffered from MS at a median time of 6 years [2.6-11.4] posttransplant. Patients with MS were significantly older, more often female, more often users of cyclosporine, and had larger posttransplant weight gain. Renal graft function at baseline as well as time elapsed between baseline and index date, were comparable for patients with and without MS. In spite of this, patients with MS had a significantly lower graft function at index date (figure 1). The association of MS with impairment of renal graft function at index date became stronger after adjustment for baseline graft function and time elapsed since baseline in linear regression analysis (-4.1 mL/min, 95%CI [-7.1, -1.1]). The impact of MS did not change appreciably after adjustment for important immunological and non-immunological risk factors for CRTD (-3.1 mL/min, 95%CI [-6.0, -0.2]). However, not all component criteria of MS contributed equally. Only systolic blood pressure and hypertriglyceridemia were strongly associated with impairment of long-term renal graft function. Conclusions: MS as defined by ATPIII criteria is independently associated with impairment of long-term renal graft function, but not all component criteria of MS contribute equally. As the study was cross-sectional in nature, causality can not be inferred. The merit of understanding that a clustering of already established risk factors for CRTD constitutes the metabolic syndrome is not just a semantic one. MS is considered to be more than the sum of its current component criteria, as it is associated with an array of other cardiovascular risk factors such as chronic inflammation, increased oxidative stress, endothelial dysfunction, and insulin resistance. Consequently, identification of MS as a putative risk factor for CRTD might not only imply more rigorous intervention on current component criteria of MS and life-style, but also on other risk factors associated with MS.Figure