Development and Validation of Residual Kidney Function Estimating Equations in Dialysis Patients

Abstract

Rationale & Objective Measurement of residual kidney function is recommended for the adjustment of the dialysis prescription, but timed urine collections are difficult and prone to errors. Equations to calculate residual kidney function from serum concentrations of endogenous filtration markers and demographic parameters would simplify monitoring of residual kidney function. However, few equations to estimate residual kidney function using serum concentrations of small solutes and low-molecular-weight proteins have been developed and externally validated. Study Design Study of diagnostic test accuracy. Setting & Participants 823 Chinese peritoneal dialysis (PD) patients (development cohort) and 826 PD and hemodialysis patients from the Netherlands NECOSAD study (validation cohort). Tests Compared Equations to estimate residual kidney function (estimated clearance [eCl]) using serum creatinine, urea nitrogen, cystatin C, β 2 -microglobulin (B2M), β-trace protein (BTP), and combinations, as well as demographic variables (age, sex, height, and weight). Equations were developed using multivariable linear regression analysis in the development cohort and then tested in the validation cohort. Equations were compared with published validated equations. Outcomes Residual kidney function measured as urinary clearance (mCl) of urea nitrogen (mCl UN ) and average of creatinine and urea nitrogen clearance (mCl UN-cr ). Results In external validation, bias (difference between mCl and eCl) was within±1.0 unit for all equations. Accuracy (percent of differences within±2.0 units) was significantly better for eCl BTP , eCl B2M , and eCl BTP-B2M than eCl UN-cr for both mCl UN (78%, 80%, and 81% vs 72%; P <0.05 for all) and mCl UN-cr (72%, 78%, and 79% vs 68%; P <0.05 for all). The area under the curve for predicting mCl UN >2.0mL/min was highest for eCl B2M (0.853) and eCl BTP-B2M (0.848). Results were similar for other validated equations. Limitations Development cohort only consisted of PD patients, no gold-standard method for residual kidney function measurement. Conclusions These results confirm the validity and extend the generalizability of residual kidney function estimating equations from serum concentrations of low-molecular-weight proteins without urine collection.