A Predictive Model for Progression of CKD to Kidney Failure Based on Routine Laboratory Tests

Rationale & Objective Stratification of chronic kidney disease (CKD) patients at risk for progressing to end-stage kidney disease (ESKD) requiring kidney replacement therapy (KRT) is important for clinical decisionmaking and trial enrollment. Study Design Four independent prospective observational cohort studies. Setting & Participants The development cohort was comprised of 4,915 CKD patients and three independent validation cohorts were comprised of a total of 3,063. Patients were followed-up for approximately five years. New Predictors & Established Predictors 22 demographic, anthropometric and laboratory variables commonly assessed in CKD patients. Outcomes Progression to ESKD requiring KRT. Analytical Approach A Least Absolute Shrinkage and Selection Operator (LASSO) Cox proportional hazards model was fit to select laboratory variables that best identified patients at high risk for ESKD. Model discrimination and calibration were assessed and compared against the 4-variable Tangri (T4) risk equation. Both used a resampling approach within the development cohort and in the validation cohorts using cause-specific concordance (C) statistics, net reclassification improvement, and calibration graphs. Results The newly derived 6-variable (Z6) risk score included serum creatinine, albumin, cystatin C and urea, as well as hemoglobin and the urine albumin-to-creatinine ratio. Based on the resampling approach, Z6 achieved a median C value of 0.909 (95% CI, 0.868-0.937) at two years after the baseline visit, whereas the T4 achieved a median C value of 0.855 (95% CI, 0.799-0.915). In the three independent validation cohorts, Z6 C values were 0.894, 0.921, and 0.891, whereas the T4 C values were 0.882, 0.913, and 0.862. Limitations The Z6 was both derived and tested only in White European cohorts. Conclusions A new risk equation, based on six routinely available laboratory tests facilitates identification of patients with CKD who are at high risk of progressing to ESK