Effect of pentoxifylline on inflammatory markers in non-diabetic chronic kidney disease patients: A prospective, interventional, open label.

Abstract

Background: Pentoxifylline (PTX), a methylxanthine derivative, has been shown to exert notable anti-inflammatory and antiproteinuric actions in diabetic kidney disease, contributing to improved sodium handling, attenuation of renal hypertrophy, and reductions in tumour necrosis factor-alpha (TNF-α), interleukin-6 levels, and albuminuria.

Aim: To determine the impact of PTX on inflammatory biomarkers and the progression of chronic kidney disease (CKD) in non-diabetic patients.

Methods: This prospective, interventional, open label, randomized controlled clinical study was conducted on 42 participants aged 18 years or older, of both genders, with CKD stages 3 or 4 and proteinuria < 1 g/24 hours. Participants were placed into two equal groups. Group 1 had standard therapy, including angiotensin-converting enzyme inhibitors (ACEIs; ramipril 1.25 mg), calcium acetate (700 mg), alfacalcidol (0.25 µg), antihypertensives, and diuretics. Group 2 had the same standard therapy plus PTX 400 mg (Trental^®) two times per day for six consecutive months.

Results: There was no significant relationship between TNF-α and high-sensitivity C-reactive protein (hs-CRP) and participants' gender in both groups. An essential direct correlation was observed between TNF-α and creatinine in both groups. A critical direct correlation was observed between hs-CRP and calcium in group B. There was a significant inverse correlation between the change in TNF-α and estimated glomerular filtration rate, as well as between the change in TNF-α and the urinary protein-to-creatinine ratio. The change in protein creatinine ratio noted in group 2 was mainly due to changes in mean arterial pressure, followed by changes in TNF-α.

Conclusion: In non-diabetic CKD patients, adjunctive treatment with PTX was associated with significant decreases in C-reactive protein levels and proteinuria. The reduction in proteinuria was mainly explained by changes in mean arterial pressure, followed by changes in TNF-α, indicating that hemodynamic factors may play a more prominent role than inflammatory modulation in mediating this effect.