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

Ravani, Pietro; Fiocco, Marta; Liu, Ping; Quinn, Robert R.; Hemmelgarn, Brenda R.; James, Matthew T.; Lam, Ngan N.; Manns, Braden; Oliver, Matthew J.; Strippoli, Giovanni F.M.

doi:10.1681/asn.2019060640

Cited by 45 publications

(60 citation statements)

References 28 publications

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“…We assessed the relationship between age and the hazard ratio (HR) of kidney failure and death (ie, the change in magnitude of the hazard as age increases) considering categories of age in crude analyses (<65, 65-74, 75-84, and ≥85 years) 7 and age as a continuous variable in model-based analyses.…”

Section: Methodsmentioning

confidence: 99%

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Investigating the Relationship Between Age and Kidney Failure in Adults With Category 4 Chronic Kidney Disease

Al-Wahsh

Lam

Liu

et al. 2020

Can J Kidney Health Dis

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Background: In people with severe chronic kidney disease (CKD), there is an inverse relationship between age and kidney failure. If this relationship is the same at any age (linear), one effect (hazard ratio) will be sufficient for accurate risk prediction; if it is nonlinear, the effect will vary with age. Objective: To investigate the relationship between age and kidney failure in adults with category G4 chronic kidney disease (G4 CKD). Methods: We performed a population-based study using linked administrative databases in Alberta, Canada, to study adults with G4 CKD (estimated glomerular filtration rate [eGFR] = 15-30 mL/min/1.73 m2) and without previously documented eGFR <15 mL/min/1.73 m2 or renal replacement. We used cause-specific Cox regression to model the relationship between age and the hazard of kidney failure (the earlier of eGFR <10 mL/min/1.73 m2 or receipt of renal replacement) and death, incorporating spline terms to capture any nonlinear effect of age. We included sex, diabetes mellitus, cardiovascular disease, albuminuria, and eGFR in all models. Results: Of the 27 823 participants (97 731 patient-years at risk; mean age = 76 years, ±13), 19% developed kidney failure and 51% died. The decline in the hazard of kidney failure associated with a given increase in age was not constant but became progressively larger as people aged; that is, the hazard ratio became progressively smaller (closer to 0). Assuming an eGFR of 25 mL/min/1.73 m2, for every 10-year increase in age, the hazard ratio declined from 0.76 (95% confidence interval = 0.73-0.79) at age 50 years to 0.43 (95% confidence interval = 34-56) at age 80 years in people without cardiovascular disease, and from 0.75 (95% confidence interval = 0.70-0.79) at age 50 years to 0.36 (95% confidence interval = 0.29-0.45) at age 80 years in people with cardiovascular disease. Conclusions: The relationship between kidney failure and age varies with age. An age-dependent effect, rather than a constant effect, needs to be specified to accurately predict risk. These findings have implications for risk prediction and advanced care planning.

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Section: Methodsmentioning

confidence: 99%

“… 6 In a population-based study, 75% of people newly diagnosed with G4 CKD are 70 years of age or older. 7 Although the risk of kidney failure is much smaller than the risk of death in this elderly population, 7 existing guidelines place considerable emphasis on preparing all people with G4 CKD for renal replacement. 1 , 2 …”

Section: Introductionmentioning

confidence: 99%

Investigating the Relationship Between Age and Kidney Failure in Adults With Category 4 Chronic Kidney Disease

Al-Wahsh

Lam

Liu

et al. 2020

Can J Kidney Health Dis

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Section: Introductionmentioning

confidence: 99%

“… 9 For example, the global number of people living with dementia more than doubled from 1990 to 2016, 10 and approximately 60% of people aged 80 years or older have at least 3 chronic disorders. 11 However, death is a competing risk for developing kidney failure, 12 and some but not all older people with advanced CKD will live long enough to develop kidney failure. Studies that assessed the association between age and kidney failure in people with CKD reported rates or relative hazards 13 , 14 , 15 from which absolute risks cannot be obtained directly in the presence of competing events.…”

Section: Introductionmentioning

confidence: 99%

Association of Age With Risk of Kidney Failure in Adults With Stage IV Chronic Kidney Disease in Canada

et al. 2020

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IMPORTANCE With population aging, the burden of many age-related chronic conditions, including kidney failure, is increasing globally. OBJECTIVE To investigate the risks of kidney failure and death in adults with incident stage IV chronic kidney disease (CKD). DESIGN, SETTING, AND PARTICIPANTS This population-based cohort study obtained data recorded between July 30, 2002, and March 31, 2014, from the linked laboratory and administrative data set of Alberta Health in Alberta, Canada. All adults of the province of Alberta with stage IV CKD (estimated glomerular filtration rate [eGFR] of 15-30 mL/min/1.73 m 2) were eligible for inclusion. Included individuals were followed up from study entry until the date of kidney failure, death, or censoring, whichever occurred first. Observations were censored at the date of emigration from the province, the study end date (March 31, 2017), or at 10 years after study entry. Data analyses were performed from January 2020 to June 2020. MAIN OUTCOMES AND MEASURES The primary outcome was kidney failure, defined as the earlier of either renal replacement (dialysis or kidney transplant) initiation or severe kidney impairment (eGFR <10 mL/min/1.73 m 2). Incidence of stage IV CKD in Alberta was examined over time, along with the association between age at study entry and the competing risks of kidney failure and death. Cumulative incidence functions (95% CIs) were estimated to summarize absolute risks over time across categories of age, accounting for sex, diabetes, cardiovascular disease, eGFR, and albuminuria. RESULTS The study included 30 801 adults (mean [SD] age, 76.8 [13.3] years; 17 294 women [56.1%]) with stage IV CKD. Of these, 5511 developed kidney failure (17.9%) and 16 285 died (52.9%). The incidence rate of stage IV CKD increased sharply with advancing age; the absolute risk of kidney failure decreased with advancing age, and the risk of death increased, especially in those aged 85 years or older. Compared with the 5-year risk of death, the 5-year risk of kidney failure was higher in people younger than 65 years, similar in people aged 65 to 74 years, and lower for older age groups. For those aged 75 years or older, the risk of death was much higher than the risk of kidney failure: 6-fold higher among those aged 75 to 84 years (0.51 [95% CI, 0.5-0.52] vs 0.09 [95% CI, 0.08-0.09]) and 25-fold higher among those aged 85 years or older (0.75 [95% CI, 0.74-0.76] vs 0.03 [95% CI, 0.02-0.03]). The risk of death was higher than the risk of kidney failure by 24-fold among those aged 85 to 94 years (0.73 [95% CI, 0.72-0.74] vs 0.03 [95% CI, 0.02-0.03]) and by 149-fold among those aged 95 years or older (0.89 [95% CI, 0.87-0.92] vs <0.01 [95% CI, <0.01 to 0.01]). CONCLUSIONS AND RELEVANCE This study found that, although the incidence rate of stage IV CKD increased with advancing age, the absolute risk of kidney failure decreased. Unlike other (continued) Key Points Question Does the risk of kidney failure vary with age in adults with severe chronic kidney disease (CKD)? Findings In...

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“… 26 Although treatment of death as a competing event did not result in significant differences in the initial derivation of the KFRE, 1 we treated death as a competing event in our primary analysis because the cumulative incidence obtained in this manner has been proposed to have a more suitable interpretation for clinical risk prediction. 27 , 28 , 29 , 30 …”

Section: Methodsmentioning

confidence: 99%

The Kidney Failure Risk Equation for Prediction of Allograft Loss in Kidney Transplant Recipients

Chu

Fallahzadeh

et al. 2020

Kidney Medicine

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Rationale & Objective The Kidney Failure Risk Equation (KFRE) is a simple widely validated prediction model using age, sex, estimated glomerular filtration rate, and urinary albumin-creatinine ratio to predict the risk for end-stage kidney disease. Data are limited for its applicability to kidney transplant recipients. Study Design Validation study of the KFRE as a post hoc analysis of the Folic Acid for Vascular Outcomes Reduction in Transplantation (FAVORIT) Trial. Setting & Participants Adult kidney transplant recipients with functioning kidney allografts at least 6 months posttransplantation from 30 centers in the United States, Canada, and Brazil. Participants with estimated glomerular filtration rates < 60 mL/min/1.73 m 2 at study entry were included. Predictor 2- and 5-year kidney failure risk predicted by the KFRE using variables at study entry. Outcome Graft loss, defined by initiation of dialysis. Analytical Approach Discrimination of the KFRE was assessed using C statistics; calibration was assessed by plotting predicted risk against observed cumulative incidence of graft loss. Results 2,889 participants were included. Within 2 years, 98 participants developed graft loss, 107 participants died with a functioning graft, and 129 participants were lost to follow-up, and by 5 years, 252 had developed graft loss, 265 died with a functioning graft, and 1,543 were lost to follow-up. The KFRE demonstrated accurate calibration and discrimination (C statistic, 0.85 [95% CI, 0.81-0.88] at 2 years and 0.81 [95% CI, 0.78-0.84] at 5 years); performance was similar regardless of donor type (living vs deceased) and graft vintage, with the noted exception of poorer calibration for graft vintage less than 2 years. Limitations Unavailable cause of graft loss. Conclusions The KFRE accurately predicted the risk for graft loss among adult kidney transplant recipients with graft vintage longer than 2 years and may be a useful prognostic tool for nephrologists caring for kidney transplant recipients.

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

Cited by 45 publications

References 28 publications

Investigating the Relationship Between Age and Kidney Failure in Adults With Category 4 Chronic Kidney Disease

Investigating the Relationship Between Age and Kidney Failure in Adults With Category 4 Chronic Kidney Disease

Association of Age With Risk of Kidney Failure in Adults With Stage IV Chronic Kidney Disease in Canada

The Kidney Failure Risk Equation for Prediction of Allograft Loss in Kidney Transplant Recipients

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