Standard biomarker tests miss many patients who develop kidney failure. Also, many patients who are not at high risk end up in clinical trials, adding expense when they will not help researchers prove anything.
Chronic kidney disease (CKD) and end-stage renal disease (ESRD) are among the most debilitating and expensive complications of having diabetes. Now, researchers at the Joslin Diabetes Center have developed a new test to identify which patients are most likely to develop these conditions.
Findings about the new test were published by the journal Kidney International.
Standard biomarker tests, which looked at urinary albumin to creatinine ratio (ACR) and an estimated glomerular filtration rate, missed a large portion of patients at risk of ESRD. These tests were also used to find candidates for clinical trials.
But if they found the wrong patients, said Joslin’s Andrzej S. Krolewski, MD, PhD, the trials would not be adequately powered, and, as he put it, “you don’t prove anything.”
In 2012, Krolewski, who is head of the section on Genetics and Epidemiology at Joslin, and his research team discovered another possible way to test for ESRD risk: they found a link between tumor necrosis factor receptor 1 (TNFR1) and declining renal function. The link was found in patients with type 1 and type 2 disease. With this finding, they set out to develop a real-world test that could use this marker instead.
Using data for patients with diabetes and later stages of CKD, the researchers enrolled patients who had been followed for between 4 and 15 years. Krolewski and his colleagues found that a combination of an old biomarker (ACR) with this new one (TNFR1) could more accurately predict who was at high risk of ESRD. They found that this test had a sensitivity value of 72% for predicting those at risk, and an 81% positive prognostic value, meaning it identified patients who developed ESRD within 3 years.
“Remarkably, when we use the TNF receptor to analyze risk of ESRD, the risk was almost identical for both type 1 and type 2 diabetes,” Krolewski said in a statement. “This implies that the etiologies are similar. This is a very important observation because in the medical community, the impression is that the progression of ESRD in type 1 is somehow different from type 2. As a result, many clinical trials do not include patients with type 1.”
Also, he said, it could mean that the TNF receptor is a therapeutic target.
Finding better ways to identify and treat those at risk of ESRD would save millions if more patients could avoid dialysis. The cost of ESRD is so high—dialysis centers bill commercial insurers up to $200,000 a year per patient—that these patients occupy a special category of Medicaid, since so few could pay for care on their own.
Because the test more accurately pinpoints who is at risk of ESRD, Krolewski said it could be used to dramatically reduce the number of patients needed for clinical trials. “If our criterion is used in the recruitment of patients, you will not need 2000 to 3000 patients for a clinical trial; you will only need 400 patients.”
Yamanouchi M, Skupien J, Monika A, et al. Improved clinical trial enrollment criterion to identify patients with diabetes at risk of end-stage renal disease [published online April 7, 2017]. Kidney Intl. 2017: doi: 10.1016/j.kint.2017.02.010.