Influence of Mortality on Estimating the Risk of Kidney Failure in People with Stage 4 CKD

Abstract

Background: Most kidney failure risk calculators are based on methods that censor for death. Because mortality is high in people with severe, nondialysis-dependent CKD, censoring for death may overestimate their risk of kidney failure.

Methods: Using 2002-2014 population-based laboratory and administrative data for adults with stage 4 CKD in Alberta, Canada, we analyzed the time to the earliest of kidney failure, death, or censoring, using methods that censor for death and methods that treat death as a competing event factoring in age, sex, diabetes, cardiovascular disease, eGFR, and albuminuria. Stage 4 CKD was defined as a sustained eGFR of 15-30 ml/min per 1.73 m².

Results: Of the 30,801 participants (106,447 patient-years at risk; mean age 77 years), 18% developed kidney failure and 53% died. The observed risk of the combined end point of death or kidney failure was 64% at 5 years and 87% at 10 years. By comparison, standard risk calculators that censored for death estimated these risks to be 76% at 5 years and >100% at 7.5 years. Censoring for death increasingly overestimated the risk of kidney failure over time from 7% at 5 years to 19% at 10 years, especially in people at higher risk of death. For example, the overestimation of 5-year absolute risk ranged from 1% in a woman without diabetes, cardiovascular disease, or albuminuria and with an eGFR of 25 ml/min per 1.73 m² (9% versus 8%), to 27% in a man with diabetes, cardiovascular disease, albuminuria >300 mg/d, and an eGFR of 20 ml/min per 1.73 m² (78% versus 51%).

Conclusions: Kidney failure risk calculators should account for death as a competing risk to increase their accuracy and utility for patients and providers.

Keywords: Competing risks; chronic kidney disease; kidney failure.

Graphical abstract

Figure 1.

Calculated versus observed risks at 5 years. NIF censors for competing events. CKD without kidney failure indicates individuals who are still in the initial state when study ends. Lost indicates observations with incomplete follow-up (separate event category used only in this analysis). The reference line indicates maximum possible risk.

Figure 2.

Crude CIFs and NIFs overall. NIF censors for competing events. The reference line indicates maximum possible risk. In the stacked function plots the blue area represents the risk of death, the red area represents the risk of kidney failure, and the area above the top curve is probability of being alive without kidney failure.

Figure 3.

Overlaid model-based CIFs and NIFs by sex and baseline risk. CIFs (solid lines) and NIFs (dashed lines) estimated from the final cause-specific hazard model of kidney failure or death (Supplemental Table 3). Maroon lines: high-risk person (person with diabetes, cardiovascular disease, albuminuria >300 mg/d, and an eGFR of 20 ml/min per m²); navy lines: low-risk person (person without diabetes or cardiovascular disease, and with an eGFR of 25 ml/min per m² and albuminuria <30 mg/d). In all cases age is 75 years.

Figure 4.

Stacked model-based CIFs and NIFs. CIFs and NIFs estimated from the final cause-specific hazard model of kidney failure or death (Supplemental Table 3). The reference line indicates maximum possible risk. Top panels: female sex, bottom panels: male sex. Left panels: low-risk person (person without diabetes or cardiovascular disease, and with an eGFR of 25 ml/min per m² and albuminuria <30 mg/d); right panels: high-risk person (person with diabetes and cardiovascular disease, an eGFR of 20 ml/min per m², and albuminuria >300 mg/d). In all cases age is 75 years.