New Test Identifies Patients With Diabetes Who Are at High Risk of Kidney Failure
BOSTON -- April 19, 2017 -- Researchers have developed a prognostic tool that accurately predicts the risk of end stage renal disease (ESRD) in patients with both type 1 and type 2 diabetes.
The new test could help doctors assess disease risk in their patients and guide researchers to develop more effective therapies to prevent or treat kidney failure.
The findings are published early online ahead of the print issue of the journal Kidney International.
In the past, doctors have relied mostly on 2 biomarkers -- urinary albumin to creatinine ratio (ACR) and estimated glomerular filtration rate (eGFR) -- to identify those at higher risk of kidney failure and also to select patients for clinical trials. However, researchers say that those criteria miss a large proportion of patients who are at high risk of the disease and fail to predict accurately time of onset of ESRD.
“Overall efficiency and cost effectiveness of clinical trials depends on the diagnostic tools used to enrol study patients,” said senior author Andrzej S. Krolewski, MD, Joslin Diabetes Center, Boston, Massachusetts. “If you recruit people who are not at risk of progressing to ESRD during the clinical trial period, statistical power declines and you can’t prove anything.”
In 2012, Dr. Krolewski and his team made a very important discovery when they found a link between tumour necrosis factor receptor 1 (TNFR1) and declining renal function in patients with type 1 and type 2 diabetes. Building on this breakthrough research, the researchers sought to translate that discovery into a practical prognostic test that doctors could use to assess care and enrol patients in clinical trials.
For the current study, the researchers used data from a population of patients with both diabetes and chronic kidney disease (stage 3 and 4) enrolled in follow-up studies conducted by Dr. Krolewski and his team at the Joslin Diabetes Center and followed for 4 to 15 years.
Using an analytic tool called the classification and regression trees (CARTs), the researchers found that specific values of 2 biomarkers -- circulating level of TNFR1 and ACR combined -- indicated high risk of ESRD. The team then validated these findings in a cohort of patients with type 2 diabetes. They found that the prognostic test for type 2 diabetes was similar to type 1.
Overall the composite prognostic criterion had a sensitivity value of 72% and positive prognostic value (detecting those who developed ESRD in 3 years) of 81%.
“Remarkably, when we used the TNF receptor to analyse risk of ESRD, the risk was almost identical for both type 1 and type 2 diabetes,” said Dr. Krolewski. “This implies that the etiologies are similar. This is a very important observation because in the medical community, the impression is that the progression to ESRD in type 1 is somehow different from type 2. As a result, many clinical trials do not include patients with type 1.”
In addition, the team applied this simple enrolment criterion to a hypothetical 3-year clinical trial to evaluate the impact on reducing the sample size while increasing the statistical power.
“Currently, about 80% of patients in these clinical trials provide no useful information,” said Dr. Krolewski. “If our criterion is used in the recruitment of patients, you will not need 2,000 or 3,000 patients for a clinical trial, you will only need 400 patients.”
This discovery also opens the door to using the TNF receptor as a therapeutic target.
SOURCE: Joslin Diabetes Center
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