For many years, the only specific pharmacologic intervention to decrease end-stage kidney disease in diabetic kidney disease was renin-angiotensin-aldosterone system blockade. Despite the addition of new interventions recently, there remains a need for new therapies. A recent Mini Review published in AJKD by Leehey and Agarwal takes a look at nonspecific phosphodiesterase inhibitor pentoxifylline, which has been shown to have antiproteinuric and anti-inflammatory effects, and small randomized clinical trials and meta-analyses indicate that PTX may have therapeutic benefits in diabetic kidney disease.
Mechanism proposed to explain the anti-inflammatory effects of pentoxifylline. Inhibition of PDE by pentoxifylline increases cAMP levels, thus activating PKA. Active PKA inhibits ubiquitination that drives IκB to proteasome degradation thus preventing p50/p65 translocation and the expression of inflammatory cytokines and other genes. Solid lines denote stimulation, and dashed lines denote inhibition. Abbreviations: 3,5-AMP, 3,5-adenosine monophosphate; ATP, adenosine triphosphate; cAMP, cyclic adenosine-3,5-monophosphate; CRP, C-reactive protein; ICAM1, intercellular adhesion molecule 1; IFNγ, interferon gamma; IκB, inhibitor of κB; IL, interleukin; NF-κB, nuclear factor κB; PDE, phosphodiesterase; PTF, pentoxifylline; TNFα, tumor necrosis factor α; TNFR 1, tumor necrosis factor receptor 1; Ub, ubiquitin; VCAM1, vascular cell adhesion molecule 1. Figure 1 from Leehey et al, Reproduced from Donate-Correa et al (Ref: 19). Released under a CC BY-NC 4.0 license. .
AJKDBlog’s Interviews Editor Timothy Yau chatted with author David Leehey about pentoxifylline’s possible therapeutic benefits in diabetic kidney disease and what to look for from future clinical trials.
If the embedded player above doesn’t work, please click here to watch the video interview. Special thanks to Dr. Leehey for his time and insight!
To view this Mini Review by Leeheyet al [Open Access], please visit AJKD.org:
Title: Is There a Role for Pentoxifylline in Diabetic Kidney Disease? A Mini Review
Authors: David J. Leehey and Rajiv Agarwal
DOI: 10.1053/j.ajkd.2025.09.030