Predictors and the Subsequent Risk of End-Stage Renal Disease – Usefulness of 30% Decline in Estimated GFR over 2 Years

Abstract

BackgroundA goal of searching risk factors for chronic kidney disease (CKD) is to halt progressing to end-stage renal disease (ESRD) by potential intervention. To predict the future ESRD, 30% decline in estimated GFR over 2 years was examined in comparison with other time-dependent predictors.MethodsCKD patients who had measurement of serum creatinine at baseline and 2 years were enrolled (n = 701) and followed up to 6 years. Time-dependent parameters were calculated as time-averaged values over 2 years by a trapezoidal rule. Risk factors affecting the incidence of ESRD were investigated by the extended Cox proportional hazard model with baseline dataset and 2-year time-averaged dataset. Predictive significance of 30% decline in estimated GFR over 2 years for ESRD was analyzed.ResultsFor predicting ESRD, baseline estimated GFR and proteinuria were the most influential risk factors either with the baseline dataset or the 2-year time-averaged dataset. Using the 2-year time-averaged dataset, 30% decline in estimated GFR over 2 years by itself showed the highest HR of 31.6 for ESRD whereas addition of baseline estimated GFR, proteinuria, serum albumin and hemoglobin yielded a better model by a multivariate Cox regression model. This novel surrogate was mostly associated with time-averaged proteinuria over 2 years with the cut-off of ~1 g/g creatinine.ConclusionThese results suggest that decline in estimated GFR and proteinuria are the risk factors while serum albumin and hemoglobin are the protective factors by the time-to-event analysis. Future incidence of ESRD is best predicted by 30% decline in eGFR over 2 years that can be modified by intervention to proteinuria, hemoglobin, uric acid, phosphorus, blood pressure and use of renin-angiotensin system inhibitors in the follow-up of 2 years.

Guidelines for clinical evaluation of chronic kidney disease

“…To date, epidemiological cohort studies on CKD patients in Japan have reported the correlation between percentage changes in eGFR and risk of ESRD [18,20]. According to the study on CKD patients by Chang et al, decrease in percentage changes in eGFR of more than 30% over 2 years correlated with ESRD strongly [18].…”

“…To date, epidemiological cohort studies on CKD patients in Japan have reported the correlation between percentage changes in eGFR and risk of ESRD [18,20]. According to the study on CKD patients by Chang et al, decrease in percentage changes in eGFR of more than 30% over 2 years correlated with ESRD strongly [18]. On the other hand, in a CKD Japan Cohort (Chronic Kidney Disease Japan Cohort, CKD-JAC) study, the relationship between patient distribution and risk of ESRD based on percentage changes in eGFR over 1-2 years indicated 30 or 40% to be the surrogate endpoints [18].…”

“…[17], the results from the NKF-FDA Working Group may not be simply extrapolated to Japanese. For Japanese CKD patients, a small study with 701 subjects demonstrated that a 30% decrease in eGFR over 2 years was strongly related to ESRD risk [18], but large-scale studies are needed for definite conclusions. As clinical trial endpoints, the decrease in albuminuria/proteinuria is frequently used, but the validity of surrogate endpoints replacing suppression of progress to ESRD has yet to be reviewed adequately.…”

Hematuria is a risk factor towards end-stage renal disease - A propensity score analysis

“…The retrospective CKD cohort already reported (n = 803) was used [9][10][11][12], and in the current study the propensity score analysis was used in such a way as used in the previously published articles [9,12]. Inclusion criteria consisted of CKD stage 3 to 4, age 20 to 84 years and follow-up period ≥ 1 year.…”

“…Death was treated as censoring because the present study focused on the effect of hematuria on the subsequent ESRD rather than the risk of mortality [11]. Competing risk method was not employed due to a small portion of death censoring (n = 10).…”