Effect of pentoxifylline on renal function and urinary albumin excretion in patients with diabetic kidney disease: the PREDIAN trial

J Am Soc Nephrol. 2015 Jan;26(1):220-9. doi: 10.1681/ASN.2014010012. Epub 2014 Jun 26.

Abstract

Diabetic kidney disease (DKD) is the leading cause of ESRD. We conducted an open-label, prospective, randomized trial to determine whether pentoxifylline (PTF), which reduces albuminuria, in addition to renin-angiotensin system (RAS) blockade, can slow progression of renal disease in patients with type 2 diabetes and stages 3-4 CKD. Participants were assigned to receive PTF (1200 mg/d) (n=82) or to a control group (n=87) for 2 years. All patients received similar doses of RAS inhibitors. At study end, eGFR had decreased by a mean±SEM of 2.1±0.4 ml/min per 1.73 m(2) in the PTF group compared with 6.5±0.4 ml/min per 1.73 m(2) in the control group, with a between-group difference of 4.3 ml/min per 1.73 m(2) (95% confidence interval [95% CI], 3.1 to 5.5 ml/min per 1.73 m(2); P<0.001) in favor of PTF. The proportion of patients with a rate of eGFR decline greater than the median rate of decline (0.16 ml/min per 1.73 m(2) per month) was lower in the PTF group than in the control group (33.3% versus 68.2%; P<0.001). Percentage change in urinary albumin excretion was 5.7% (95% CI, -0.3% to 11.1%) in the control group and -14.9% (95% CI, -20.4% to -9.4%) in the PTF group (P=0.001). Urine TNF-α decreased from a median 16 ng/g (interquartile range, 11-20.1 ng/g) to 14.3 ng/g (interquartile range, 9.2-18.4 ng/g) in the PTF group (P<0.01), with no changes in the control group. In this population, addition of PTF to RAS inhibitors resulted in a smaller decrease in eGFR and a greater reduction of residual albuminuria.

Keywords: albuminuria; chronic kidney disease; diabetic nephropathy; inflammation; progression of chronic renal failure.

Publication types

  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged
  • Albumins / analysis*
  • Diabetes Mellitus, Type 2 / complications
  • Diabetic Nephropathies / drug therapy*
  • Diabetic Nephropathies / urine*
  • Disease Progression
  • Female
  • Glomerular Filtration Rate
  • Humans
  • Inflammation
  • Kidney / drug effects*
  • Male
  • Middle Aged
  • Pentoxifylline / therapeutic use*
  • Prospective Studies
  • Research Design
  • Treatment Outcome

Substances

  • Albumins
  • Pentoxifylline