Effect of pentoxifylline in addition to losartan on proteinuria and GFR in CKD: A 12-month randomized trial

Background: Pentoxifylline potently inhibits cell proliferation, inflammation, and extracellular matrix accumulation. Human studies have proved its antiproteinuric effect in patients with glomerular diseases. Its benefit in addition to angiotensin receptor blockade in patients with chronic kidney disease is not clear. Study Design: Randomized controlled study. Setting & Participants: 85 patients with estimated glomerular filtration rate (eGFR) of 10 to 60 mL/min/1.73 m(2) and proteinuria with protein greater than 500 mg/g of creatinine on treatment with losartan, 100 mg/d, for longer than 6 months were screened in National Taiwan University Hospital. Intervention: In the first stage (12 months), group 1 served as control and group 2 was administered pentoxifylline. In the second stage (6 months), both groups were administered pentoxifylline. The pentoxifylline dose was 400 mg twice daily for patients with eGFR of 30 to 60 mL/min/1.73 m(2) or once daily for patients with eGFR of 10 to 29 mL/min/1.73 m(2). Outcomes: Proteinuria and eGFR. Measurements: Proteinuria was assessed as total protein-creatinine ratio, eGFR was computed by using the Modification of Diet in Renal Disease Study equation. Results: 27 and 29 patients were randomly assigned to groups 1 and 2, respectively. In the first stage, pentoxifylline decreased median proteinuria from 1,140 to 800 mg/g (median change, -23.9%) compared with 1,410 to 1,810 mg/g (median change, 13.8%) in the control group. The difference between groups was 38.7% (95% confidence interval, 25.7 to 51.6; P < 0.001). The change in proteinuria was related to the change in urinary tumor necrosis factor a and monocyte chemoattractant protein 1 excretion (R = 0.64 and R 0.55, respectively; P < 0.001 for both). In the second stage, pentoxifylline reproduced the change in proteinuria in group 1. Limitations: Small sample size, disease of late stages, open-labeled study. Conclusions: Pentoxifylline added to losartan therapy for 1 year decreased proteinuria in patients with CKD stages 3 to 5. A large-scale clinical trial is necessary to confirm this result.