Pentoxifylline and cardiorenal outcomes in advanced CKD with untreated dyslipidemia: a longitudinal cohort study

BACKGROUND: Patients with advanced chronic kidney disease (CKD) and dyslipidemia are at high risk of kidney failure and cardiovascular events, yet many do not receive lipid-lowering therapy. Pentoxifylline (PTX) has anti-inflammatory and antifibrotic properties, but its association with hard cardiorenal outcomes remains uncertain. METHODS: We conducted a retrospective cohort study of adults with stage 3b-5 CKD and dyslipidemia enrolled in a pre-end-stage renal disease program from 2007 to 2018. Patients receiving lipid-lowering therapy were excluded. PTX initiators were matched 1:1 to nonusers using propensity score matching. The primary outcome was progression to end-stage kidney disease (ESKD). Secondary outcomes included major adverse cardiovascular events (MACE), 50% estimated glomerular filtration rate decline within 2 years, and doubling of serum creatinine. Sensitivity analyses included time-varying exposure, lag, and landmark analyses. RESULTS: Among 3,542 eligible patients, 2,776 were included in the matched cohort. PTX use was associated with lower risks of ESKD (hazard ratio [HR], 0.85; 95% confidence interval [CI], 0.75-0.96) and MACE (HR, 0.80; 95% CI, 0.65-0.98). No significant associations were observed for short-term kidney function decline or creatinine doubling. Time-related sensitivity analyses attenuated estimates toward the null but did not suggest harm. CONCLUSION: In patients with advanced CKD and untreated dyslipidemia, PTX use was associated with lower risks of kidney failure in propensity score-matched analyses, whereas the association with cardiovascular events was less robust after sensitivity analyses. These findings require cautious interpretation and further validation.