Short- and Middle-Term Nephroprotective and Cardioprotective Effects of Pentoxifylline in Patients with Diabetic Nephropathy: A Randomized Controlled Trial

<b>Background/Objectives</b>. Pentoxifylline (PTF) is an effective treatment to delay the progress of Diabetic Nephropathy; it also has beneficial effects on heart failure, two closely related clinical conditions. However, the simultaneous Nephroprotective and Cardioprotective effects of PTF have not been appropriately analyzed. The objective of this study was to analyze if both effects occur together in Diabetic patients. <b>Material and Methods</b>. A Randomized Controlled Trial was performed to compare Placebo (P-G) vs. PTF (400 mg/8 h) (PTF-G) in patients with CKD stages III-IV (KDIGO) due to Diabetic Nephropathy. Creatinine-Cystatin C-based Estimated Glomerular Filtration Rate (eGFRCysCCr) and Microalbuminuria were evaluated at baseline, six, and twelve months. Echocardiographic assessment of heart morphology and function was performed. <b>Results</b>. Ninety-three patients were available for the final analysis, 52 in the PTF group and 41 in the P group. There were no differences in clinical and biochemical parameters between groups at baseline. At 6 months, microalbuminuria changed 27.96 ± 43.06 in P-G and -30.27 ± 41.48 mg/24 h in PTF-G (<i>p</i> < 0.001), eGFRCysCCr changed -1.55 ± 7.10 in P-G and 1.40 ± 7.28 mL/min/1.73 m² in PTF-G (<i>p</i> = 0.083), and left ventricular mass index (LVMI) changed 10.86 ± 16.40 in P-G and -2.71 ± 19.52 g/m² in PTF-G (<i>p</i> = 0.001). At 12 months, microalbuminuria changed 24.10 ± 43.28 in P-G and -43.18 ± 52.13 mg/24 h in PTF-G (<i>p</i> < 0.001), eGFRCysCCr changed -6.55 ± 10.18 in P-G and 0.98 ± 8.17 mL/min/1.73 m² in PTF-G (<i>p</i> = 0.008), and LVMI changed 20.79 ± 20.06 in P-G and -0.82 ± 25.95 g/m² in PTF-G (<i>p</i> = 0.028). No significant adverse events occurred in any group. <b>Conclusions</b>. Pentoxifylline is a safe and effective treatment with combined Nephroprotective and Cardioprotective effects in advanced diabetic nephropathy.