Chronic Kidney Disease Gets 2 Proven Breakthrough Treatments in Back to Back Trials
Chronic kidney disease has long been one of the most challenging conditions in medicine, with very few therapeutic options capable of meaningfully slowing disease progression. That changed dramatically with the publication of two landmark clinical trials, CREDENCE and SONAR, which together demonstrated that two different drug classes can significantly reduce the risk of kidney failure and cardiovascular death in patients with chronic kidney disease and diabetes.
For the estimated 850 million people worldwide living with kidney disease, and the 280 million whose condition is caused by diabetes, these findings represent the most significant advance in diabetic nephropathy treatment in years.
Why Chronic Kidney Disease Has Been So Difficult to Treat
Chronic kidney disease is a progressive condition in which the kidneys gradually lose their ability to filter waste, regulate fluid balance, and maintain overall metabolic health. As the disease advances, patients face increasing risks of end stage renal disease requiring dialysis or transplantation, as well as serious cardiovascular complications that significantly raise mortality.
Until recently, RAAS blockade using ACE inhibitors or angiotensin receptor blockers was the only therapeutic intervention shown to meaningfully slow chronic kidney disease progression. While effective, RAAS blockade does not stop disease progression entirely, and many patients continue to deteriorate despite treatment. This left a critical gap in the management of diabetic nephropathy, the form of chronic kidney disease caused by diabetes.
“850 million people worldwide are affected by kidney disease, a worrying figure, and one that continues to rise,” said Professor Carmine Zoccali, President of the ERA-EDTA. “In about one third of these patients, around 280 million people, diabetes is the cause of kidney failure.”
The CREDENCE Trial: SGLT2 Inhibitors Cut Kidney Failure Risk by 34%
The CREDENCE trial was a double blind randomized controlled study evaluating canagliflozin, an oral SGLT2 inhibitor, in patients with type 2 diabetes and chronic kidney disease with albuminuria who were already receiving standard RAAS therapy. Patients had an estimated glomerular filtration rate (GFR) between 30 and 90 ml per minute per 1.73 m2 and significant albuminuria.
The primary outcome was a composite endpoint including end stage kidney disease (dialysis, transplantation, or sustained GFR below 15), doubling of serum creatinine levels, or death from renal or cardiovascular causes.
The results were so compelling that the trial was stopped early. At the time of stopping, 4,401 patients had been randomized, with a median follow up of 2.62 years. The relative risk of the renal specific composite endpoint was reduced by 34 percent in the canagliflozin group compared to placebo. The risk of end stage kidney disease alone was reduced by 32 percent. The treatment group also showed a lower risk of cardiovascular death.
“We are glad that we now have evidence that we can help our patients with this medication,” said Professor Zoccali. “SGLT2 inhibitors add to the armamentarium for the treatment of diabetic nephropathy.”
The CREDENCE results established SGLT2 inhibitors as a major new pillar in the management of chronic kidney disease, particularly for patients with diabetic nephropathy.
The SONAR Trial: Atrasentan Reduces Renal Events by 35%
Published just one day before CREDENCE, the SONAR trial evaluated atrasentan, an endothelin receptor antagonist, in a selected population of patients with diabetes and chronic kidney disease who had demonstrated a favorable response to the medication during a pre-enrollment run in period.
This innovative enrichment strategy, enrolling only patients who responded to treatment before randomization, was designed to maximize the signal in a population where treatment response is heterogeneous.
The results were equally impressive. Atrasentan reduced the composite renal outcome of end stage kidney disease and doubling of serum creatinine by 35 percent compared to placebo, with a hazard ratio of 0.65 (95% CI 0.49 to 0.88; p=0.0047).
The SONAR findings are particularly notable because they point toward a future in which chronic kidney disease treatment may be personalized based on individual drug response, a concept with significant implications for clinical trial design and patient selection.
Two New Treatments, Two Different Targets: What This Means for Patients
The near simultaneous publication of CREDENCE and SONAR was a watershed moment for the nephrology community. For the first time, clinicians treating patients with chronic kidney disease and diabetic nephropathy have two new evidence based options with distinct mechanisms of action that could potentially be combined.
“For years no new treatment option had proved to be safe and effective and thus no new drug could be introduced into clinical practice,” said Professor Zoccali. “Now we have two new treatments with different therapeutic targets, which we might even combine.”
Patients with chronic kidney disease are also at elevated cardiovascular risk, making the cardiovascular benefits seen in the CREDENCE trial especially important. Reducing both kidney disease progression and cardiovascular mortality simultaneously with a single therapy represents a meaningful improvement in overall patient outcomes.
Supporting Nephrology Trials at FOMAT
Both the CREDENCE and SONAR trials represent the kind of large scale, rigorous Phase III research that advances treatment standards for chronic kidney disease globally. Behind every landmark result is a network of experienced research sites, skilled investigators, and well managed patient populations.
FOMAT Medical Research supports clinical trials in nephrology and metabolic conditions through our national network of community based investigators. We have experience enrolling patients with chronic kidney disease, diabetic nephropathy, and related comorbidities across Phase I through Phase IV studies. Contact our team to learn how FOMAT can support your next nephrology or endocrinology trial.
Source: R&D Magazine