Pentoxifylline may reduce proteinuria in patients with diabetic kidney disease, according to a meta-analysis of 10 randomized controlled trials. The analysis found that pentoxifylline led to a statistically significant decline in proteinuria compared to standard renin-angiotensin system blockade alone, with an effect size similar to full-dose ACE inhibitors. However, the included studies had small sample sizes and short durations. Pentoxifylline did not significantly affect glomerular filtration rate, blood pressure, or adverse effects. Larger and longer term studies are still needed to determine if pentoxifylline can delay kidney function decline in diabetic kidney disease.

1. Focus on P entoxifylline Journal Club May 20 th 2008 Christos Argyropoulos

11. PTX in Renal Transplantation Evaluable patients: 69 patients randomized in the PTX group and 68 in the placebo group (out of the 140).

12. PTX in Renal Transplantation Early (3 months) events

13. PTX in Renal Transplantation Outcome of renal function during the first month after transplantation, in all patients, treated or not with PTX and CsA during the same period No difference in the rapidity of recovery of renal function

14. PTX in Renal Transplantation Cumulative incidence of adverse effects in the first 6 months No difference in the incidence of DGF There was no difference in the overall survival rates at 1 year between the treated and placebo group (patient survival: 94.3% vs. 94%; graft survival: 80% vs. 78%) Immunosuppressive treatments and CsA trough levels at 6 months and 1 year. There was no difference in the incidence of hypertension at 1 year between the groups

16. PTX in Renal Transplantation 67% 93.5% 97% 59% 89.3% 72%

17. PTX in Renal Transplantation near – ITT analysis (137 patients) Actual 95% (CI) (from the Table stats) : 1.01-3.48

19. PTX in Renal Transplantation What did the study demonstrate? Does it contradict/confirm previous studies? How substantial is the treatment effect? How safe is the proposed treatment ? Is the proposed mechanism of action/interpretation of the results a plausible one? Did the investigators studied signal or noise w.r.t. a key variable/predictor of allograft loss (are the data robust) ? Are the results applicable to our patient population/local practice patterns? Is the dosing regimen convenient ? Are further studies truly needed in this case? How would one study pentoxifylline in the 21 st century?

34. Small studies (median number of participants 45 ) Total # of participants 476 Median duration of tx: 6 months (range 2-12) 9/10: parallel group design 4: standard of care comparisons 2: head to head comparisons 4: drug vs placebo

36. PTX in Diabetic Kidney Disease Proteinuria

37. PTX in Diabetic Kidney Disease Overt Proteinuria (> 300mg/d)

38. PTX in Diabetic Kidney Disease Microalbuminuria