Building a Better Predictive Model for Progression to Kidney Failure

By Megan Brooks

July 21, 2021

NEW YORK (Reuters Health) - A new risk equation can accurately estimate the risk of chronic kidney disease (CKD) progressing to end-stage kidney disease (ESKD), the development team from France and Germany reports.

The "Z6" risk equation is based on six routine laboratory tests: serum creatinine, albumin, cystatin C, urea, hemoglobin and urine albumin-to-creatinine ratio.

The Z6 risk score was developed using a cohort of 4,915 CKD patients and validated in three independent cohorts with a total of 3,063 CKD patients. Patients were followed-up for roughly five years for progression to ESKD requiring kidney replacement therapy (KRT).

In the development cohort, Z6 achieved a median C value of 0.909 at two years after the baseline visit, whereas the four-variable Tangri (T4) risk equation achieved a median C value of 0.855, the researchers report in the American Journal of Kidney Diseases.

In the three independent validation cohorts, the Z6 risk score achieved median C values of 0.894, 0.921 and 0.891, compared to 0.882, 0.913 and 0.862 with the T4 equation.

Identifying CKD patients who are at risk of progressing to ESRD requiring KRT is important for clinical decision-making and trial enrollment, say Dr. Peter Oefner, of the Institute of Functional Genomics, in Regensberg, Germany, and colleagues.

A Z6 risk equation showed "good discrimination of CKD patients at risk of progressing to kidney replacement therapy both in the development cohort and in three independent validation cohorts," they report.

The researchers caution that the Z6 risk equation was derived and validated only in white European cohorts and the tool's accuracy should be examined in more diverse patient populations.

They acknowledge that there is still room for improvement by considering additional variables, such as emerging biomarkers related to tubular damage, inflammation and fibrosis. Separate consideration of kidney diseases of different etiology may also improve the performance of the risk model.

Dr. Ankur Shah of the Division of Kidney Diseases and Hypertension at Warren Alpert Medical School of Brown University, in Providence, Rhode Island, said this study is "very interesting and would be immediately useful to nephrologist in counseling their patients regarding risk of progression to kidney failure."

"In clinical practice this study can be used to identify patients in whom resources should be targeted or whom closer follow-up may be indicated. Patients at higher risk of progression to kidney failure could also be educated earlier on dialysis therapies," Dr. Shah, who was not involved in the study, told Reuters Health by email.

"The primary limitation of this study is the lack of diversity of the population in which it was developed and tested. Applicability to a diverse population will need to be shown in further confirmation studies prior to widespread use," Dr. Shah said.

"In the studied population, this equation would be a useful adjunct the commonly used kidney failure risk equation developed by Tangri et al. The equation is also limited by the need for serum cystatin-c measurement, a biomarker of kidney disease that is widely available but used infrequently in routine clinical practice," Dr. Shah noted.

The research did not have commercial funding, and the authors have no conflicts of interest.

SOURCE: American Journal of Kidney Diseases, online July 20, 2021.