Association between GFR estimated by multiple methods at dialysis commencement and patient survival

Abstract

Background and objectives: The Initiating Dialysis Early and Late study showed that planned early or late initiation of dialysis, based on the Cockcroft and Gault estimation of GFR, was associated with identical clinical outcomes. This study examined the association of all-cause mortality with estimated GFR at dialysis commencement, which was determined using multiple formulas.

Design, setting, participants, & measurements: Initiating Dialysis Early and Late trial participants were stratified into tertiles according to the estimated GFR measured by Cockcroft and Gault, Modification of Diet in Renal Disease, or Chronic Kidney Disease-Epidemiology Collaboration formula at dialysis commencement. Patient survival was determined using multivariable Cox proportional hazards model regression.

Results: Only Initiating Dialysis Early and Late trial participants who commenced on dialysis were included in this study (n=768). A total of 275 patients died during the study. After adjustment for age, sex, racial origin, body mass index, diabetes, and cardiovascular disease, no significant differences in survival were observed between estimated GFR tertiles determined by Cockcroft and Gault (lowest tertile adjusted hazard ratio, 1.11; 95% confidence interval, 0.82 to 1.49; middle tertile hazard ratio, 1.29; 95% confidence interval, 0.96 to 1.74; highest tertile reference), Modification of Diet in Renal Disease (lowest tertile hazard ratio, 0.88; 95% confidence interval, 0.63 to 1.24; middle tertile hazard ratio, 1.20; 95% confidence interval, 0.90 to 1.61; highest tertile reference), and Chronic Kidney Disease-Epidemiology Collaboration equations (lowest tertile hazard ratio, 0.93; 95% confidence interval, 0.67 to 1.27; middle tertile hazard ratio, 1.15; 95% confidence interval, 0.86 to 1.54; highest tertile reference).

Conclusion: Estimated GFR at dialysis commencement was not significantly associated with patient survival, regardless of the formula used. However, a clinically important association cannot be excluded, because observed confidence intervals were wide.

Figure 1.

Bland and Altman plot comparing two different estimated GFR (eGFR) formulas in Initiating Dialysis Early and Late participants at dialysis commencement. (A) Comparison between Cockcroft and Gault (CG) and Modification of Diet in Renal Disease (MDRD) formulas. (B) Comparison between CG and Chronic Kidney Disease-Epidemiology Collaboration (CKD-EPI) formulas. (C) Comparison between MDRD and CKD-EPI formulas. The continuous lines represent the mean difference between the two formulas; the dotted lines represent the upper and lower limits of agreement between the two formulas.

Figure 2.

Kaplan–Meier plots of patient survival based on estimated GFR (eGFR) tertile groups by three different formulas or measured mean urinary urea and creatinine clearance at dialysis commencement in Initiating Dialysis Early and Late trial participants. (A) Cockcroft and Gault (CG) eGFR: the differences between the groups were not statistically significant (log-rank test: P=0.38). (B) Modification of Diet in Renal Disease (MDRD) eGFR: the differences between the groups were highly statistically significant (log-rank test: P<0.001). (C) Chronic Kidney Disease-Epidemiology Collaboration (CKD-EPI) eGFR: the differences between the groups were highly statistically significant (log-rank test: P<0.001). (D) Mean urinary urea and creatinine clearance: the differences between the groups were not statistically significant (log-rank test: P=0.86).

Figure 3.

Forest plot of the association between estimated GFR (eGFR) tertiles at dialysis commencement and patient survival in Initiating Dialysis Early and Late trial participants. In multivariable Cox proportional hazards model analyses, patient survival was not significantly associated with eGFR at dialysis commencement, regardless of the formula used. Older age, women, diabetes mellitus, and cardiovascular disease at dialysis commencement were associated with a significantly increased hazard of death. Cardiovascular disease was defined as the presence of ischemic heart disease, congestive cardiac failure, peripheral vascular disease, or stroke. BMI, body mass index; C+G, Cockcroft and Gault; CI, confidence interval; CKDEPI, Chronic Kidney Disease-Epidemiology Collaboration; MDRD, Modification of Diet in Renal Disease.