Effects of Pentoxifylline on Serum Markers of Diabetic Nephropathy in Type 2 Diabetes

OBJECTIVE: To investigate the effects of pentoxifylline (PTX) in combination with losartan compared to the high dose of losartan alone on serum markers of diabetic nephropathy such as HSP70, copeptin, CRP, and TNFα in patients with type 2 diabetes and nephropathy. METHODS: A single-center, randomized, double-blind, open-label clinical trial was conducted. Sixty-two patients were eligible and allocated to “PTX + losartan” and “high-dose losartan” arms of the trial using software for random number generation. The first arm received 400 mg PTX two times a day (BD) plus 50 mg losartan daily, while the second arm received 50 mg losartan two times a day (BD) for 12 weeks. Comparison of the biomarkers’ levels before and after treatment was done using paired sample t test variance. ANCOVA was applied to evaluate the comparative efficacy of the two interventions. The effect size was calculated and reported for each biomarker. RESULTS: Urine albumin excretion (UAE), hs-CRP, and HbA1c significantly decreased in both trial arms compared to the baseline measures. Copeptin and TNFα showed significant differences (after vs before) only in the losartan group (p = 0.017 and p = 0.043, respectively). The losartan arm was more successful in reducing TNFα, copeptin, HSP70, systolic blood pressure (SBP), and diastolic blood pressure (DBP) values (p = 0.045, effect size = 7.3%; p = 0.018, effect size 10.1%; p = 0.046, effect size 4.7%, p = 0.001, effect size 23%; p = 0.012, effect size 10.2%, respectively) and the PTX arm was associated with a superior reduction of UAE and hs-CRP levels (p = 0.018, effect size 9.1%; p = 0.028, effect size 9.2%, respectively). CONCLUSION: Add-on PTX to losartan may have more effective anti-inflammatory and anti-albuminuric roles and therefore may be more applicable in the management of diabetic nephropathy compared with high-dose losartan alone. TRAIL REGISTRATION: Trial number IRCT 20121104011356N10.