Efficacy and safety of combining pentoxifylline with angiotensin-converting enzyme inhibitor or angiotensin II receptor blocker in diabetic nephropathy: a meta-analysis

Pentoxifylline (PTF) has anti-inflammatory properties, which may be beneficial for diabetic nephropathy (DN). A meta-analysis was conducted to assess the additive effect of pentoxifylline and its safety among patients with type 2 DN under blockade of angiotensin system. Relevant studies were searched from PubMed, CBM, EMBASE, CENTRAL and Cochrane renal group specialized register. All RCTs that compared the benefits and harms of pentoxifylline and ACEI/ARB with ACEI/ARB alone for DN were included. Pertinent data were extracted independently by two authors. Meta-analyses were performed when more than one study provided data on a comparable outcome. Standard mean differences (SMDs) for proteinuria and albuminuria, mean differences (MDs) for systolic blood pressure (SBP), diastolic blood pressure (DBP), HbA1c, serum creatinine (Scr), creatinine clearance (CrCl) and urine tumor necrosis factor-alpha (UTNF-alpha), 95 % confidence intervals (CIs) were calculated, and heterogeneity was assessed with the I (2) test. Adverse effects were assessed using descriptive techniques. Eight studies including 587 patients with a median duration of 5 months were identified. Compared with ACEI/ARB alone, the combination of PTF and ACEI/ARB significantly reduced proteinuria (SMD 0.76, 95 % CI 0.52-0.99), albuminuria (SMD 0.36, 95 % CI 0.12-0.59) and UTNF-alpha (MD 1.56 ng/g, 95 % CI 0.09-3.03). However, no statistically significant changes were observed for SBP, DBP, HbA1c, Scr and CrCl. The most frequent adverse effects in patients treated with PTF were gastrointestinal symptoms (28/298) and dizziness (7/298), but in most cases, these symptoms were mild, only six participants withdrew due to intractable nausea and vomiting. Pentoxifylline can significantly provide additive antiproteinuric effect independent from the decrease in BP or improvement in glycemic control in DN patients under blockade of angiotensin system. Further large, multicenter, high-quality studies with long duration are necessary to prove whether it really has renoprotective effects in this patient population.