The Effect of Pentoxifylline on Proteinuria in Diabetic Kidney Disease: A Meta-analysis

Background: Pentoxifylline is a potential therapeutic agent for diabetic kidney disease because it has anti-inflammatory, antifibrotic, and hemorheological properties. Study Design: Systematic review and meta-analysis of randomized controlled trials. Setting, Population, & Intervention: Adult patients with diabetic kidney disease who received oral pentoxifylline. Selection Criteria for Studies: We searched bibliographic databases for trials involving pentoxifylline that reported proteinuria, glomerular filtration rate, or blood pressure. Outcomes: The primary outcome measure was the effect of pentoxifylline on proteinuria stratified by whether pentoxifylline was compared with renin-angiotensin system blockade. Results: 10 studies including a total of 476 participants with a median duration of 6 months were identified. Pentoxifylline significantly decreased proteinuria (weighted mean difference, -278 mg/d of protein; 95% confidence interval [CI], -398 to -159; P < 0.001) compared with placebo or usual care. Compared with captopril, the decrease in proteinuria with pentoxifylline was similar (weighted mean difference, 0 mg/d of protein; 95% CI, -17 to 18; P = 0.9). Secondary analysis showed that patients with microalbuminuria had a nonsignificant decrease in protein excretion (weighted mean difference, -87 mg/d; 95% CI, -201 to 27; P = 0.1), whereas those with overt proteinuria (protein > 300 mg/d) had a significant decrease (weighted mean difference, -502 mg/d; 95% CI, -805 to -198; P = 0.001). No significant changes in systolic or diastolic blood pressure or glomerular filtration rate were found. Limitations: Quality scores of studies were low, and there was significant heterogeneity. Conclusions: Available evidence suggests that pentoxifylline may decrease proteinuria in patients with diabetic nephropathy. To confirm these findings, large high-quality studies are required.