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‘On par with the biggest breakthroughs in medicine’: Spokane doctor discovers new kidney disease treatment. An 11,000-person study will start in 2024

Dr. Katherine Tuttle stands April 5 outside Providence Sacred Heart Medical Center.  (Jesse Tinsley/The Spokesman-Review)

A Spokane doctor believes her team of researchers has “broken the code” to fight kidney disease with a new treatment.

Dr. Katherine Tuttle is executive director for research at Providence Inland Northwest Health and one of the leading researchers of kidney disease in the nation.

Tuttle called her team’s  discovery a “breakthrough treatment” that can eventually treat millions of kidney disease patients.

The treatment will be tested next year in an 11,000-person study led by the University of Oxford. The study will be “one of the largest trials ever conducted” on kidney disease, according to Oxford professor Will Herrington.

The drugs researched by Tuttle are “really quite astonishingly effective,” added Harrington, who will conduct the study through the Oxford Nuffield Department of Population Health.

Indiana University School of Medicine Professor Rajiv Agarwal said the research brings “hope and the promise of improvement in kidney care.” Agarwal has written an editorial comment for medical journal The Lancet, which has published Tuttle’s research.

How is kidney disease treated?

Human bodies produce waste and byproduct that must be removed or they build up and cause death. The kidneys siphon off these wastes toxic to the body and filter them out through urine.

But as the kidneys are damaged over time through various processes, they can become less effective.

Without treatment to slow this progression, many patients end up in kidney failure and require a kidney transplant or dialysis for the rest of their life.

Kidney disease is most commonly treated with ACE inhibitors. This class of drugs was created to treat high blood pressure, but was found to reduce damage to organs like the heart and kidney. Since being approved for these conditions in 2001, ACE inhibitors have become the standard of care.

But the impact these drugs have on the kidneys is “really very modest,” according to Tuttle. With an average 16% to 20% improvement to kidney disease, ACE inhibitors “barely make a dent” in the 1 in 5 Americans with kidney disease. They also do not typically halt the progression of kidney disease to kidney failure – when the patient would need to have a kidney transplant or be on dialysis for the rest of their life.

Even with that moderate effect, Tuttle said the drug is not prescribed for most patients with kidney disease because the condition is so underdiagnosed. She pointed to Cure CKD, a Providence-UCLA partnership that maintains a registry of 4 million people with chronic kidney disease or who are at high risk for it.

According to a study of the registry she co-authored, only 25% of those in the registry were getting the treatments they should be.

“We have had such terrible outcomes because the disease is under recognized. It’s markedly undertreated, and the treatments we have are just marginally effective,” she said. “People in our country have kidney disease, but most of them don’t know they have it. Because it’s asymptomatic until the late stages when it has very devastating complications.”

Kidney disease treatment shifted approximately five years ago when a new drug was found to treat it. SGL2 inhibitors were developed as a treatment to prevent diabetes, but studies found they also reduced the risk of kidney and heart failure.

SGL2 inhibitors reduced the risk of kidney failure by 40% if used in conjunction with ACE inhibitors, Tuttle said. Despite these results, the drug combination has not been widely adopted – with only 6% of patients in the registry being prescribed it.

“We have done so little for these patients,” Tuttle said. “We’re now at the point with breakthrough therapies that are really set to change the paradigm. But the key is going to be getting them to the patients, because it doesn’t matter if we have treatments and nobody gets them.”

Tuttle’s discovery

In the new study, Tuttle has combined the two previous drugs with a third called Aldosterone Synthase Inhibitor, which reduces a body hormone that can damage the kidney.

A side effect of both ACE Inhibitors and SGL2 is an increase to aldosterone levels in the long term – reducing the efficacy of both drugs in their treatment of kidney disease. Adding ASI to the treatment plan had a “greatly additive effect” to the other drugs.

The Providence trial enrolled 714 patients in Spokane from February 2022 to July 2023. Approximately half of patients given ASI treatment saw a “clinically meaningful reduction” in damage to the kidney, according to the study. That reduction jumped to 70% of patients when ASI was combined with the other two drugs.

A noted side effect of the ASI treatment was an excess of potassium in the body, which occurred because Aldosterone regulates sodium and potassium.

Should these results be replicated in future studies, the treatment plan discovered in Spokane has the opportunity to be “on par with some of the biggest breakthroughs in medicine,” Tuttle said.

“This is not just a moment in the field of kidney disease, but in that of medicine and the human condition. This is back to the impact of antibiotics for pneumonia in terms of a public health impacts,” she said.

“This is not a rare disease. This is not trivial. And we now have a chance to make huge impact.”

Approximately 1 in 5 people in the United States has some form of kidney disease. While this treatment will not help those who have reached kidney failure and are on dialysis, it has the possibility of preventing millions from reaching that point.

“The way forward is combined treatments to hit multiple disease paths,” Tuttle said.

Herrington said he agrees about the impact these drugs could have on those with kidney disease across the globe.

“We see nearly halving of the rate and risk of kidney disease progression in the trials. They are also well-tolerated drugs,” he said in a statement – noting he is aware of practitioners in the field “moved to tears” when seeing trial results involving SGLT2 inhibitors.

While calling the research “groundbreaking,” Agarwal was more conservative in his predictions for the future.

“If we prove that this thing works, that would be a very large breakthrough. But when you do a small study, and then you replicate it in a large study – we can’t say that’s going to pan out that way or not. That’s why we are doing the research,” Agarwal said.

Next year, Tuttle’s study will be replicated in a global effort led by the University of Oxford in the United Kingdom. Providence Sacred Heart will participate in this study as well.

For those in Spokane with kidney disease, the new trial will begin to enroll patients in the first three months of next year.

“We’re very happy that Providence, and particularly here at Sacred Heart in Spokane, we are a very active clinical trials center, and it is an opportunity for local patients with chronic kidney disease to consider participating in this or another clinical trial,” she said.

Because of the massive size of an 11,000-person trial, the drug regimen is not anticipated to be used in clinical practice for another four years. But should her results be replicated, Tuttle is concerned the treatment will still not be widely adopted.

“I’m confident the research is going to deliver and now the onus is really on the health care systems to deliver, and that means getting these treatments to patients,” she said. “I think what we can say is that our expectation is that if we implement these breakthrough therapies, the number of people on dialysis will dramatically decrease, and many more people will survive and live productive lives.”