Thiazolidinediones and Risk of Long-Term Dialysis in Diabetic Patients with Advanced Chronic Kidney Disease: A Nationwide Cohort Study

Abstract

Thiazolidinediones (TZDs) reduce urinary albumin excretion and proteinuria in diabetic nephropathy. The effect of TZDs on hard renal outcome in diabetic patients with chronic kidney disease (CKD) is unknown. We investigate the association of TZDs and risk of long-term dialysis or death in diabetic patients with advanced CKD. The nationwide population-based cohort study was conducted using Taiwan's National Health Insurance Research Database. From January 2000 to June 2009, 12350 diabetic patients with advanced CKD (serum creatinine levels greater than 6 mg/dL but not yet receiving renal replacement therapy) were selected for the study. We used multivariable Cox regression models and a propensity score-based matching technique to estimate hazard ratios (HRs) for development of long-term dialysis and the composite outcome of long-term dialysis or death for TZD users (n=1224) as compared to nonusers (n=11126). During a median follow-up of 6 months, 8270 (67.0%) patients required long-term dialysis and 2593 (21.0%) patients died before starting long-term dialysis. Using propensity score matched analysis, we found TZD users were associated with a lower risk for long-term dialysis (HR, 0.80; 95% confidence interval [CI], 0.74-0.86) and the composite outcome of long-term dialysis or death (HR, 0.85; 95% CI, 0.80-0.91). The results were consistent across most patient subgroups. Use of TZDs among diabetic patients with advanced CKD was associated with lower risk for progression to end-stage renal disease necessitating long-term dialysis or death. Further randomized controlled studies are required to validate this association.

Fig 1. Flowchart of patient selection.

CKD, chronic kidney disease; ESA, erythropoiesis-stimulating agent; TZD, thiazolidinedione.

Fig 2. Kaplan-Meier curves of study outcomes.

Cumulative incidences for long-term dialysis (a) and long-term dialysis or death (b) among diabetic patients with advanced chronic kidney disease comparing TZD users vs. nonusers. TZD, thiazolidinedione.

Fig 3. Propensity score matched hazard ratios of study outcomes among diabetic patients with advanced chronic kidney disease.

Proper oral antidiabetic drugs excluded the patients using alpha-glucosidase inhibitor and/or metformin. ACEIs, angiotensin converting enzyme inhibitors; ARBs, angiotensin II receptor blockers; CAD, coronary artery disease; CCBs, calcium channel blockers; CI, confidence interval; HR, hazard ratio; NSAIDs, non-steroid anti-inflammatory drugs; OADs, oral antidiabetic drugs; TZD, thiazolidinedione.