Renal tubular damage is associated with poor clinical outcome in patients with peripheral artery disease who underwent endovascular therapy

Abstract

Background: Kidney dysfunction is associated with adverse outcome in patients with peripheral artery disease (PAD). Renal tubulointerstitial damage (RTD) is another type of kidney dysfunction from glomerular damage. RTD is reported to be a risk for future cardiac event in patients with heart disease. However, it remains to be determined whether RTD is predictive of poor clinical outcome in patients with PAD.

Methods and results: RTD markers (urinary N-acetyl-β-D-glucosamidase; NAG and urinary β-2 microglobulin to creatinine ratio) and Glomerular damage markers (cystatin C-based estimated glomerular filtration rate, proteinuria, and microalbuminuria) were measured in 265 consecutive PAD patients who underwent endovascular therapy. Patients were prospectively followed for a median length of 804days, with end points of major adverse cardiovascular and cerebrovascular events (MACCE). Overall, 73% of patients exhibited excess urinary NAG excretion, and values were higher in patients with critical limb ischemia. A multivariate Cox proportional hazard analysis revealed that NAG was an independent predictor of MACCE. When patients were divided according to NAG level, Kaplan-Meier analysis demonstrated that the third tertile was associated with the greatest risk for MACCE. The C index in NAG was the greatest among kidney dysfunction markers. Moreover, the net reclassification index was improved by the addition of NAG to basic predictors including glomerular damage markers.

Conclusion: RTD is common and associated with disease severity and clinical outcome in patients with PAD, indicating that it could be the additional clinical information to glomerular damage in patients with PAD.

Keywords: Clinical outcome; Peripheral artery disease; Renal tubular damage.