Insulin resistance in chronic kidney disease: its clinical characteristics and prognostic significance

Introduction: Insulin resistance (IR) increases significantly the risk for cardiovascular disease (CV) in the general population. IR is a common metabolic disorder in patients with chronic kidney disease (CKD). However, the influence of IR on the evolution of CKD patients has scarcely been studied. Objective: This study aims to determine whether IR is associated with the progression of CKD, the development of new CV events, or all-cause mortality of non-diabetic patients with CKD stage 4 or 5 not yet on dialysis. Material and methods: The study group consisted of 365 non-diabetic patients (63 16 year, 169 females) with GFR <30 ml/min. The degree of IR was estimated by the Homeostasis Model Assessment parameter (HOMA). The outcome measures were: progression of CKD (composite of initiation of dialysis or doubling of baseline serum creatinine level), new cardiovascular events, and all-cause mortality. Unadjusted and multivariable-adjusted relative risks were calculated for HOMA either as a continuous or qualitative variable (tertiles), using Cox proportional hazards models. Results: Mean HOMA value (+/- SD) was 4.28 +/- 2.07. HOMA values correlated significantly with body mass index (beta = 0.37; p <0.0001), plasma triglycerides (beta = 0.22; p <0.0001), plasma albumin (beta = 0.19; p = 0.007), and serum phosphate (beta = 0.17; p = 0.031). Progression of CKD was observed in 234 patients (64%) with a median follow-up of 542 days. Patients with HOMA values in the lower tertile (<3.13) showed a slower progression of CKD than that of the rest of study patients (log rank 4.16, p <0.05). In adjusted models for age, sex, baseline GFR, body mass index, and proteinuria, HOMA values in the lower tertile entered as an independent variable in the best predictive equation for progression of CKD (HR 0.72, p <0.03). Fifty-one patients developed a new CV event and 103 patients died during the study period (median follow-up of 1,103 days). HOMA did not relate to the development of new CV events or all-cause mortality in unadjusted or adjusted models for age, sex, comorbid index, plasma albumin, and C-reactive protein. Conclusions: In conclusion, progression of renal disease was slower in those non-diabetic CKD patients with low HOMA values; however, HOMA values did not relate to the development of new CV events or all-cause mortality.