IMPORTANCE Kidney failure risk prediction has implications for disease management, including advance care planning in adults with severe (ie, estimated glomerular filtration rate [eGFR] category 4,... Show moreIMPORTANCE Kidney failure risk prediction has implications for disease management, including advance care planning in adults with severe (ie, estimated glomerular filtration rate [eGFR] category 4, [G4]) chronic kidney disease (G4-CKD). Existing prediction tools do not account for the competing risk of death.OBJECTIVE To compare predictions of kidney failure (defined as estimated glomerular filtration rate [eGFR] <10 mL/min/1.73 m(2) or initiation of kidney replacement therapy) from models that do and do not account for the competing risk of death in adults with G4-CKD.DESIGN, SETTING, AND PARTICIPANTS This prognostic study linked population-based laboratory and administrative data (2002-2017) from 2 Canadian provinces (Alberta and Manitoba) to compare 3 kidney risk models: the standard Cox regression, cause-specific Cox regression, and Fine-Gray subdistribution hazard model. Participants were adults with incident G4-CKD (eGFR 15-29 mL/min/1.73 m(2)). Data analysis occurred between July and December 2020.MAIN OUTCOMES AND MEASURES The performance of kidney risk models at prespecified times and across categories of baseline characteristics, using calibration, reclassification, and discrimination (for competing risks). Predictive characteristics were age, sex, albuminuria, eGFR, diabetes, and cardiovascular disease.RESULTS The development and validation cohorts included 14 619 (7070 [48.4%] men; mean [SD] age, 74.1 [12.8] years) and 2295 (1152 [50.2] men; mean [SD] age, 71.9 [14.0] years) adults, respectively. The 3 models had comparable calibration up to 2 years from entry. Beyond 2 years, the standard Cox regression overestimated the risk of kidney failure. At 4 years, for example, risks predicted from standard Cox were 40% for people whose observed risks were less than 30%. At 2 years (risk cutoffs 10%-20%) and 5 years (risk cutoffs 15%-30%), 788 (5.4%) and 2162 (14.8%) people in the development cohort were correctly reclassified into lower- or higher-risk categories by the Fine-Gray model and incorrectly reclassified by standard Cox regression (the opposite was observed in 272 patients [1.9%] and 0 patients, respectively). In the validation cohort, 115 (5.0%) individuals and 389 (16.9%) individuals at 2 and 5 years, respectively, were correctly reclassified into lower- or higher-risk categories by the Fine-Gray model and incorrectly reclassified by the standard Cox regression; the opposite was observed in 98 (4.3%) individuals and 0 individuals, respectively. Differences in discrimination emerged at 4 to 5 years in the development cohort and at 1 to 2 years in the validation cohort (0.85 vs 0.86 and 0.78 vs 0.8, respectively). Performance differences were minimal during the entire follow-up in people at lower risk of death (ie, aged <= 65 years or without cardiovascular disease or diabetes) and greater in those with a higher risk of death. At 5 years, for example, in people aged 65 years or older, predicted risks from standard Cox were 50% where observed risks were less than 30%. Similar miscalibration was observed at 5 years in people with albuminuria greater than 30 mg/mmol, diabetes, or cardiovascular disease.CONCLUSIONS AND RELEVANCE In this study, predictions about the risk of kidney failure were minimally affected by consideration of competing risks during the first 2 years after developing G4-CKD. However, traditional methods increasingly overestimated the risk of kidney failure with longer follow-up time, especially among older patients and those with more comorbidity. Show less
Ravani, P.; Quinn, R.; Fiocco, M.; Liu, P.; Al-Wahsh, H.; Lam, N.; ... ; Tonelli, M. 2020
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... Show moreIMPORTANCE 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 m2) 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/1.73m2). 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 age-related conditions, the expected increase in the burden of kidney failure in the older adults may be less dramatic than expected. Show less
Ravani, P.; Fiocco, M.; Liu, P.; Quinn, R.R.; Hemmelgarn, B.; James, M.; ... ; Tonelli, M. 2019
BACKGROUND AND OBJECTIVES Patients with the hereditary disease Alport syndrome commonly require renal replacement therapy (RRT) in the second or third decade of life. This study compared age at... Show moreBACKGROUND AND OBJECTIVES Patients with the hereditary disease Alport syndrome commonly require renal replacement therapy (RRT) in the second or third decade of life. This study compared age at onset of RRT, renal allograft, and patient survival in men with Alport syndrome receiving various forms of RRT (peritoneal dialysis, hemodialysis, or transplantation) with those of men with other renal diseases. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS Patients with Alport syndrome receiving RRT identified from 14 registries in Europe were matched to patients with other renal diseases. A linear spline model was used to detect changes in the age at start of RRT over time. Kaplan-Meier method and Cox regression analysis were used to examine patient and graft survival. RESULTS Age at start of RRT among patients with Alport syndrome remained stable during the 1990s but increased by 6 years between 2000-2004 and 2005-2009. Survival of patients with Alport syndrome requiring dialysis or transplantation did not change between 1990 and 2009. However, patients with Alport syndrome had better renal graft and patient survival than matched controls. Numbers of living-donor transplantations were lower in patients with Alport syndrome than in matched controls. CONCLUSIONS These data suggest that kidney failure in patients with Alport syndrome is now being delayed compared with previous decades. These patients appear to have superior patient survival while undergoing dialysis and superior patient and graft survival after deceased-donor kidney transplantation compared with patients receiving RRT because of other causes of kidney failure. Show less
Carrero, J.J.; Jager, D.J. de; Verduijn, M.; Ravani, P.; Meester, J. de; Heaf, J.G.; ... ; Jager, K.J. 2011
