Prediction of ESRD and death among people with CKD: the Chronic Renal Impairment in Birmingham (CRIB) prospective cohort study

Abstract

Background: Validated prediction scores are required to assess the risks of end-stage renal disease (ESRD) and death in individuals with chronic kidney disease (CKD).

Study design: Prospective cohort study with validation in a separate cohort.

Setting & participants: Cox regression was used to assess the relevance of baseline characteristics to risk of ESRD (mean follow-up, 4.1 years) and death (mean follow-up, 6.0 years) in 382 patients with stages 3-5 CKD not initially on dialysis therapy in the Chronic Renal Impairment in Birmingham (CRIB) Study. Resultant risk prediction equations were tested in a separate cohort of 213 patients with CKD (the East Kent cohort).

Factors: 44 baseline characteristics (including 30 blood and urine assays).

Outcomes: ESRD and all-cause mortality.

Results: In the CRIB cohort, 190 patients reached ESRD (12.1%/y) and 150 died (6.5%/y). Each 30% lower baseline estimated glomerular filtration rate was associated with a 3-fold higher ESRD rate and a 1.3-fold higher death rate. After adjustment for each other, only baseline creatinine level, serum phosphate level, urinary albumin-creatinine ratio, and female sex remained strongly (P < 0.01) predictive of ESRD. For death, age, N-terminal pro-brain natriuretic peptide, troponin T level, and cigarette smoking remained strongly predictive of risk. Using these factors to predict outcomes in the East Kent cohort yielded an area under the receiver operating characteristic curve (ie, C statistic) of 0.91 (95% CI, 0.87-0.96) for ESRD and 0.82 (95% CI, 0.75-0.89) for death.

Limitations: Other important factors may have been missed because of limited study power.

Conclusions: Simple laboratory measures of kidney and cardiac function plus age, sex, and smoking history can be used to help identify patients with CKD at highest risk of ESRD and death. Larger cohort studies are required to further validate these results.

Figure 1

Time to end-stage renal disease (ESRD) and death in the Chronic Renal Impairment in Birmingham (CRIB) Study, by initial chronic kidney disease (CKD) stage. The P value for the log-rank test corresponds to the test of equal survival across all 3 baseline CKD groups. CKD stage was as defined by the National Kidney Foundation's K/DOQI (Kidney Disease Outcomes Quality Initiative) Work Group in 2002: stage 3, estimated glomerular filtration rate (eGFR) of 30-60 mL/min/1.73 m²; stage 4, eGFR of 15-30 mL/min/1.73 m²; and stage 5, eGFR <15 mL/min/1.73 m². eGFR was calculated using the 4-variable Modification of Diet in Renal Disease (MDRD) Study equation. Individuals receiving renal replacement therapy at baseline (either dialysis or a kidney transplant) were excluded from the study.

Figure 2

Age- and sex-adjusted relative risk (RR) of end-stage renal disease (ESRD) and death in the CRIB (Chronic Renal Impairment in Birmingham) Study by baseline estimated glomerular filtration rate (eGFR; calculated using the 4-variable Modification of Diet in Renal Disease [MDRD] Study equation). Both the horizontal and vertical axes are shown on a logarithmic scale. The points in the right hand panel have been adjusted so that the absolute mortality rates they represent are comparable with the absolute ESRD rates represented in the left hand panel (thus, the point at which the 2 lines cross is the level of eGFR above which, in the CRIB cohort, the risk of death started to exceed the risk of ESRD). Abbreviation: CI, confidence interval.

Figure 3

External validation of the CRIB (Chronic Renal Impairment in Birmingham) risk score equations in the East Kent cohort: Kaplan-Meier survival curves by third of the predicted risk distributions (top panels); receiver operating characteristic curves (middle panels); and observed versus predicted annual event rates (bottom panels). The P value for the log-rank test corresponds to the test of equal survival across all 3 predicted risk groups. *Urinary albumin-creatinine ratio was not available in the East Kent cohort; therefore, the measures of discrimination and calibration shown reflect the ability of the other factors (sex, creatinine level, and phosphate level) to predict end-stage renal disease (ESRD) risk. Abbreviations: AUROC, area under the receiver operating characteristic curve (C statistic); CI, confidence interval; NT-pro-BNP, N-terminal pro-brain natriuretic peptide.