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.