Development and Validation of a Multivariable Prediction Model for Kidney Failure in Early Autosomal Dominant Polycystic Kidney Disease

Key Points – Data were collected from a cohort of 759 patients with autosomal dominant polycystic kidney disease that were followed for a median of 10.2 years. Prognostic models were developed to predict kidney failure using routinely obtained clinical information and externally validated. Risk predictions had good discrimination and calibration over a time horizon of 15 years. Background – Autosomal dominant polycystic kidney disease (ADPKD) is a common cause of kidney failure. Progression is highly variable, and accurate prognostic information is needed to guide early treatment decisions. The objective of this study was to develop a multivariable predictive model for progression to kidney failure.Methods – We developed prognostic models using Cox regression for the outcome of kidney failure, defined as eGFR <15 ml/min per 1.73 m2, dialysis, or kidney transplantation. The development dataset consisted of participants in the Consortium for Radiologic Imaging Studies of Polycystic Kidney Disease (CRISP) and Halt Progression of Polycystic Kidney Disease study A (HALT-A) studies. The validation dataset consisted of patients with ADPKD in the Mayo clinical registry aged 15–49 years, with eGFR ≥60 ml/min per 1.73 m2. Predictor variables in the base model were age, sex, creatinine or eGFR, ADPKD genotype, and Mayo Imaging Class. Clinical and laboratory data were evaluated in the full model.Results – The development cohort included 759 patients with baseline eGFR of 91±29 ml/min per 1.73 m2 (mean±SD), of whom 16% reached end point after median (interquartile range) follow-up of 10.2 (5.5–16.7) years. The validation cohort included 535 patients with baseline eGFR of 90±31 ml/min per 1.73 m2 (mean±SD), of whom 11% reached end point after median (interquartile range) follow-up of 5.5 (1.5–13.7) years. The full model, including age, sex, serum creatinine, Mayo Imaging Class, total carbon dioxide, hemoglobin, diastolic BP, and body mass index, had a C-index of 0.81 (95% confidence interval, 0.72 to 0.90) in the validation cohort and 0.75 (95% confidence interval, 0.62 to 0.88) when ADPKD genotype was also included. Risk predictions from base and full models were well-calibrated out to 15 years.Conclusions – In persons with early ADPKD and preserved eGFR, a model using routinely obtained clinical information quantified risk of kidney failure over 15 years.