New Trial Results on Diabetic Kidney Disease
On April 15, 2019, two landmark clinical trials in diabetic kidney disease were published in The Lancet and the New England Journal of Medicine. They were co-authored respectively by Dr. Donald Kohan, professor of medicine in the Division of Nephrology & Hypertension and Dr. Tom Greene, Departments of Population Health Science and Internal Medicine.
The Lancet's recently published Study of Diabetic Nephropathy with Atrasentan (SONAR) randomized 2,648 patients. Researchers found that treatment with an endothelin A receptor antagonist, atrasentan, reduced the risk of adverse kidney outcome (composite of doubling of serum creatinine, end-stage kidney disease or death from kidney failure) by 35% (hazard ratio 0·65 [95% CI 0·49–0·88]) in patients with pre-existing type 2 diabetes and kidney disease. The accompanying editorial in the Lancet noted that “along with newer glucose-lowering drugs (sodium glucose co-transporter-2 inhibitors…), atrasentan is poised to join the selection of drugs for treatment of patients with diabetes and chronic kidney disease”. Dr. Kohan, an expert on endothelin biology, provided crucial background rationale from preclinical data, as well as guidance on study design, safety considerations and biologic interpretation of the data, and was a member of the Steering Committee of this trial.
Published in the New England Journal of Medicine, Evaluation of the Effects of Canagliflozin on Renal and Cardiovascular Outcomes in Participants With Diabetic Nephropathy (CREDENCE), randomized 4,401 patients and showed that treatment with the sodium glucose cotransporter inhibitor, canagliflozin, reduced the risk of adverse kidney or cardiac outcomes (composite of doubling of serum creatinine, end-stage kidney disease or death from kidney or cardiovascular causes) by 30% (hazard ratio 0.70 [95% CI 0.59-0.82]) in patients with pre-existing type 2 diabetes and kidney disease. The accompanying editorial stated that the importance of CREDENCE “cannot be overstated” and that “such data are certain to be welcomed by patients with diabetes and chronic kidney disease and by the clinicians who treat them”. Dr. Greene helped with the study design and analysis plan, and was a member of the Steering Committee for this seminal trial.
Together, these two studies represent the first breakthroughs in more than 20 years in strategies to slow chronic kidney disease progression in diabetic patients.