Prognostic models for chronic kidney disease: a systematic review and external validation

van Rijn MHC, van de Luijtgaarden M, van Zuilen AD, Blankestijn PJ, Wetzels JFM, Debray TPA, van den Brand JAJG

Background: Accurate risk prediction is needed in order to provide personalized healthcare for chronic kidney disease (CKD) patients. An overload of prognosis studies is being published, ranging from individual biomarker studies to full prediction studies. We aim to systematically appraise published prognosis studies investigating multiple biomarkers and their role in risk predictions. Our primary objective was to investigate if the prognostic models that are reported in the literature were of sufficient quality and to externally validate them.

Methods: We undertook a systematic review and appraised the quality of studies reporting multivariable prognosis models for end-stage renal disease (ESRD), cardiovascular (CV) events and mortality in CKD patients. We subsequently externally validated these models in a randomized trial that included patients from a broad CKD population.

Results: We identified 91 papers describing 36 multivariable models for prognosis of ESRD, 50 for CV events, 46 for mortality and 17 for a composite outcome. Most studies were deemed of moderate quality. Moreover, they often adopted different definitions for the primary outcome and rarely reported full model equations (21% of the included studies). External validation was performed in the Multifactorial Approach and Superior Treatment Efficacy in Renal Patients with the Aid of Nurse Practitioners trial (n = 788, with 160 events for ESRD, 79 for CV and 102 for mortality). The 24 models that reported full model equations showed a great variability in their performance, although calibration remained fairly adequate for most models, except when predicting mortality (calibration slope >1.5).

Conclusions: This review shows that there is an abundance of multivariable prognosis models for the CKD population. Most studies were considered of moderate quality, and they were reported and analysed in such a manner that their results cannot directly be used in follow-up research or in clinical practice.