A Triple-Blind Randomized Controlled Trial on Impacts of Pioglitazone on Oxidative Stress Markers in Diabetic Kidney Transplant Recipients

Abstract

Background: Oxidative stress as a major mediator of adverse outcomes in kidney transplant recipients who are prone to oxidative stress-mediated injury by pre-transplant and post-transplant conditions. Objectives: The purpose of this study was to assess the effects of Pioglitazone on oxidative stress biomarkers and blood glucose control in diabetic patients receiving insulin after kidney transplantation. Methods: In a triple-blind randomized placebo-controlled trial, sixty-two kidney transplanted diabetic patients (40 men and 24 women) were followed for 4 months after randomly assigned to the placebo group and Pioglitazone group (30 mg/d). All of the patients continued their insulin therapy irrespective of the group that they were assigned to evaluate the effects of the addition of pioglitazone on blood glucose and oxidative stress biomarkers, Malondialdehyde (MDA) and total protein carbonyls (TPC) serum levels. Results: At baseline, there were no statistically significant differences in glycemic control levels and oxidative markers between the two groups. After 4 months of intervention, a significant improvement occurred in HBA1c in the Pioglitazone group. The changes of Hemoglobin A1c (HBA1c) during 4 months of follow up in the Pioglitazone group show improvement in glucose control were as HBA1c in the placebo group increased by 0.3% (P = 0.0001). Moreover, at the end of the study, the MDA level was significantly lower in the Pioglitazone group (P < 0.0001, 1.22 - 3.90). Regarding the serum level of TPC, the changes were not statistically different at baseline and also at the end of the study between two groups. Conclusions: Administration of Pioglitazone in addition to insulin in diabetic kidney transplant patients not only improved glycemic control (evidenced by HBA1c) but also significantly decreased oxidative stress markers such as MDA.

Post-Transplant Diabetes: Prevalence, Risk, and Management Challenges

“…A similar study compared pioglitazone and insulin in PTDM; the authors concluded that both agents reduce HbA1c, result in a better lipid profile, and have similar weight gain. None of the two agents showed any interactions with immunosuppressive medications [92]. Many other studies concurred with these findings; Luther and Baldwin [90] found similar findings in a single-arm study using pioglitazone in PTDM.…”

Protective Effects of Pioglitazone on Cognitive Impairment and the Underlying Mechanisms: A Review of Literature

“… 102 , 103 Pioglitazone has also been found to reduce oxidative stress through a reduction in the levels of MDA and inhibition of ROS production and inflammatory pathways; this further verifies its potent antioxidant activity. 104 All these findings indicate the role of pioglitazone against stress in the brain via regulation of TRX1, p47phox, and gp91phox activity, and the levels of MDA and ROS.…”

Diabetic Kidney Disease in Post-Kidney Transplant Patients

“…Most studies are small case series with similar results (Table 2). The largest study-a double-blind randomized controlled trial by Kharazmkia et al comparing pioglitazone plus insulin versus placebo plus insulin-found a decrease in blood in HgbA1C among those kidney transplant recipients on pioglitazone and no effect on cyclosporin levels [66].…”