Abstract

Abstract Background and Aims Symptomatic kidney stone formers experience excess rates of cardiovascular events and are at increased risk of chronic kidney disease and its progression. Little is known about the cardiovascular outcomes of persons with kidney failure in whom nephrolithiasis or urolithiasis was listed as their presumed cause of kidney failure. Method We used the United States Renal Data Service (USRDS), a national kidney failure registry, to identify all persons initiating dialysis between 1/1/1996 and 9/30/2015. Patients were required to have Medicare fee-for-service coverage on day 90 of dialysis, which served as index date. The presumed cause of kidney failure was abstracted from information reported on the Medical Evidence Report (form CMS-2728) and categorized as: nephro-/urolithiasis, diabetes, hypertension, glomerulonephritis, cystic kidney disease, other urologic cause, and other cause. Eligible patients were then followed for the occurrence of a major adverse cardiovascular event (MACE; nonfatal myocardial infarction, nonfatal stroke, or cardiovascular mortality) using claims-based algorithms and causes of death reported in the Death Notification (form CMS-2746). Multivariable Cox regression models were fit while controlling for incident year, sociodemographic characteristics, initial dialysis modality, reported comorbidities and disabilities, biometric data (body mass index [BMI], eGFR, serum albumin, hemoglobin). Multiple imputation was used for missing data. Both cause-specific and Fine-Gray sub-distribution hazard ratios (HR) with corresponding 95% confidence intervals (CI) were estimated. Results Of 2,000,072 persons with incident kidney failure, 1,048,006 (52.4%) were alive and satisfied all inclusion criteria on day 90 (71.9% of the excluded due had no Medicare coverage). Among those, 2207 (0.2%) had nephro-/urolithiasis as cause of kidney failure, while 47% had diabetes, 30.4% had hypertension, 8.1% had GN, and 1.6% had cystic kidney disease listed. Persons with nephro-/urolithiasis tended to be older, more likely to be female and non-Hispanic white, had lower rates of most comorbidities, higher serum albumin and hemoglobin concentrations and lower BMI and eGFR at dialysis initiation. The composite cardiovascular event rate (MI, stroke, cardiovascular death; 721 events) was 74.4/1000 person years for nephro-/urolithiasis. Compared with those whose cause was nephro-/urolithiasis, persons whose cause of kidney failure was listed as diabetes had fully adjusted 57% (95% CI, 46%-69%) higher hazards of MACE and those in whom it was attributed to hypertension the hazards were 33% (95% CI, 24%-44%) higher. While no difference in the hazards of MACE was observed compared with persons with glomerulonephritis (HR 0.97; 95% CI, 0.90-1.05), those with cystic kidney disease had a 14% (95% CI, 7%-20%) lower hazards of MACE than those with nephro-/urolithiasis. Qualitatively similar results were obtained when examining the individual components of MACE as well as when considering kidney transplant and non-cardiovascular death as competing risks. However, competing risk analysis substantially attenuated the magnitude of the associations with diabetes and hypertension as reported cause of kidney failure. Limitations include heterogeneity of the underlying pathology among patients with nephro-/urolithiasis as well as the possibility that some patients with nephro-/urolithiasis were not captured if a different cause of kidney disease was listed. Conclusion Patients with kidney failure presumably from nephro- or urolithiasis have distinct cardiovascular risk profiles, with lower major cardiovascular event rates compared with patients whose kidney failure was due to diabetes or hypertension, but slightly higher rates compared with those with cystic kidney disease.

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