Add-on Pentoxifylline to Losartan Versus Increasing Dose of Losartan on NT-PRO BNP in Type 2 Diabetics With Nephropathy

Addition of pentoxifylline to losartan provides antiproteinuric effects in type 2 diabetes patients with nephropathy that might relate to its effect on N terminal brain natriuretic peptide (NT-pro BNP) and C-reactive protein.

Pentoxifylline is a phosphodiestrase inhibitor with anti-inflammatory effects that was used in type 2 diabetes patients with nephropathy for treatment of diabetes complications.

NT-Pro BNP, which is released from the heart due to wall stress and pressures, is known as a diagnostic and prognostic marker for heart failure and cardiovascular mortality in type 2 diabetes.

• Pentoxifylline (Drug), also known as oxpentifylline: pentoxifylline arm took 400 mg pentoxifylline twice daily plus 50mg losartan daily for 12 weeks.
• Losartan (Drug), also known as Cozaar: losartan arm took 100mg losartan daily for 12 weeks.

Primary outcomes

• N terminal brain natriuretic peptide (NT-pro BNP) [3 months]: N terminal brain natriuretic peptide assessed using ELISA method (zelbio, Germany) with inter- and intra-assay coefficient of variation (CV) <12% and <10%. Measured at baseline, 3rd month

Secondary outcomes

• Highly sensitive C-reactive protein (hsCRP) [3 months]: Highly sensitive C-reactive protein assessed by commercial kits (DRG kit, Germany) using the ELISA (enzyme-linked immunosorbent assay) method with inter- and intra-assay coefficient of variation (CV) of <20%. Measured at baseline, 3rd month
• Urinary albumin excretion [3 months]: Urinary albumin excretion assessed by overnight (12 hour) collection of urine. Measured at baseline, 3rd month
• Blood pressure [3 months]: Systolic and diastolic blood pressure assessed by mercury sphygnomanometry. Patients were placed in a sitting position and after ten minutes rest, two readings from right-side hand with five minutes interval were obtained. Measured at baseline, 3rd month
• estimated glomerular filtration rate [3 months]: estimated glomerular filtration rate calculated using the formula developed by Chronic Kidney Disease Epidemiology Collaboration. Measured at baseline, 3rd month
• serum creatinine concentrations [3 months]: serum creatinine concentrations assessed by Jaffe method. Measured at baseline, 3rd month

Sex: All, ages: 38 Years to 76 Years

Inclusion Criteria:

* age>30 and age<70, urinary albumin excretion (UAE) ≥150 mg/24 h

Exclusion Criteria:

* any infectious or malignant diseases, non-diabetic kidney disease, retinal hemorrhage, acute myocardial infarction, uncontrolled hypertension, pregnancy, unable to follow up, hyperthyroidism, baseline serum potassium concentrations ≥5.5 meq/L, glomerular filtration rate (GFR)<30mL/min/1.73 m and intolerance of pentoxifylline

• Alireza Esteghamati, MD, Study chair, Endocrinology and Metabolism Research Center (EMRC), Vali-Asr Hospital, Tehran University of Medical Sciences, Tehran, Iran