Introduction:
Proteinuria is shown to be associated with increased risk of peripheral artery disease (PAD). However, its association with the risk of lower limb amputation in patients with PAD is unknown.
Hypothesis:
We hypothesized that proteinuria is associated with the risk of amputation in patients with PAD in a graded fashion.
Methods:
We identified 3,388 PAD patients with data on urine dipstick proteinuria within two years prior to PAD diagnosis between 1997 and 2017 in the Geisinger Health System (mean age 69.7 years, 44.8% female, 97.4% non-Hispanic White, 57.8% diabetic). We quantified the association of proteinuria with the risk of amputation using Cox proportional hazards models, adjusting for demographics, calendar year, estimated glomerular filtration rate, HbA1c, comorbidities including diabetic retinopathy/neuropathy, and medication use (antiplatelet drug, statin, and renin-angiotensin system inhibitor).
Results:
There were 55.2% with negative dipstick proteinuria, 11.1% trace, 14.1% with 1+, and 19.5% with ≥2+. A total of 245 patients underwent amputations over a median follow-up of 3.4 years. Incidence rate of amputation was 1.15 per 100 person-years for dipstick negative, 1.47 for trace, 2.11 for 1+, and 3.78 for ≥2+. This dose-response relationship remained similar even after accounting for potential confounders (p-trend=0.015), with particularly evident association for ≥2+ of dipstick (an adjusted hazard ratio of 1.52 [95% confidence interval: 1.08-2.17, p=0.017) (Figure). When we added proteinuria to other covariates, the risk discrimination slightly improved (Δc-statistic 0.007 [0.001-0.014]).
Conclusions:
Higher proteinuria was associated with a greater risk of lower limb amputation among patients with newly diagnosed PAD. Our results suggest the importance of considering proteinuria in risk assessment of limb loss in PAD patients.
Plasma concentrations of lipoproteins and risk of lower-limb peripheral artery disease in people with type 2 diabetes: the SURDIAGENE study
