Corporate restart Renalguard Solutions Inc. has raised a $14.5 million series A round to get its device through an ongoing U.S. pivotal trial to protect against contrast-induced acute kidney injury and onto the market. Renalguard is designed to measure patient urine output in real-time and then to match that amount to hydration introduced during catheterization procedures.

The Milford, Mass.-based company aims to have pivotal data in early 2018, which could be followed later next year by a PMA approval from the FDA. The financing will also go to support development of the device in additional indications as well as to back marketing in Europe, where it has had a broad CE mark since 2008 for balancing patient fluids for up to 14 days.

CLEARING OUT CONTRAST

The technology behind Renalguard comes out of medical device industry incubator Coridea, run by industry gurus Mark Gelfand and Howard Levin, who have been behind a number of industry success stories including Ardian Inc. and Respicardia Inc.

An estimated 10 percent to 20 percent of patients who undergo cardiovascular diagnostic and interventional procedures are at-risk of developing contrast-induced nephropathy (CIN). This is an acute form of kidney injury resulting from damage caused by the exposure of kidneys to the dye itself.

Renalguard works by synchronizing the measurements of a urine collection set with the operation of a hydration fusion set. The idea is to match patient output to the milliliter in real-time. This is expected to produce higher urine rates than standard diuretics alone, thereby helping to protect the kidneys.

"Contrast is very good at what it does, which is stopping x-ray. If you can get patients urinating, you can flush those toxins out and let the kidney rest," observed Renalguard President Andrew Halpert in an interview with Medical Device Daily. But he cautioned that simply increasing hydration, as well as under-hydration, during catheterization procedures both lead to less urine output and can result in increased acute kidney injury.

Either under- or over-hydration via standard infusion can lower urine rates, increasing kidney exposure to the toxic contrast agent. With an increase in the rate at which contrast is expelled, this is expected to reduce the oxidative stress on nephrons within the kidney, making them less susceptible to damage.

Post-procedure kidney damage is a key predictor of patient outcomes, as well, so preventing that may actually help to improve success rates of cardiac catheterization procedures.

PUT TO THE TEST

Renalguard has been in a series of European trials comparing it to various standard-of-care approaches as well as examining outcomes. One found results with the system to be superior to overnight hydration, while another found it was better than sodium bicarbonate hydration.

In terms of patient outcomes, a trial resulted in a significant reduction in post-procedural acute kidney injury following transcatheter aortic valve replacement (TAVR). Finally, another found significant improvement in long-term outcomes for patients versus standard therapy.

The CIN-RG adaptive-design pivotal trial is underway in the U.S. It will enroll at least 326 patients and up to 652 patients, depending upon a sample size re-estimation after the study hits a threshold of 163 patients. It is being randomized 1:1 to standard-of-care or Renalguard treatment, with a primary outcome measure of incidence of contrast induced nephropathy within 72 hours.

There are a number of standard-of-care approaches physicians can use to try to moderate the detrimental effects of contrast on the kidneys. They can hydrate the patient, use diuretics to induce urination and try to limit the volume of contrast used.

Halpert noted that Renalguard already has about 1,500 patients worth of data out of Europe, so on the U.S. pivotal trial front he's "very optimistic about what our results will look like."

FROM RESTRUCTURING TO COMMERCIAL STRATEGY

The company that became Renalguard has a decades-long history that stretches back to a founding in the 1980s and winds through a couple of medical device technologies and a time as a public company.

It was refocused specifically on kidney protection in 2004 and then taken private in 2014. Lien holder Genesis Capital, which had helped fund the public iteration, continued to support it in this series A round.

The new financing was led by Exigent Capital with participation by Genesis and other private equity investors. Alan Adler, former CEO and chairman of Oridion Medical, has joined the Renalguard board to represent Exigent.

"Acute kidney injury (AKI) caused by cardiac interventional procedures is a serious and costly health care problem that is not currently remedied by any viable solution," said Adler.

He continued, "After spending much time extensively reviewing the published clinical data related to Renalguard therapy and speaking with leading clinical practitioners who have become dedicated users of this technology, I am convinced that Renalguard has the potential to become the standard-of-care for significantly reducing the incidence of AKI in the huge number of patients undergoing these procedures."

Renalguard already is commercializing on its own in Europe, where it is getting particularly strong uptake in Germany and Italy, Halpert said. The company could do so in the U.S. as well, assuming an FDA approval, but a partnership would bring more value to the table.

"I want to see this used in every catheterization patient around the world that's at-risk; the value proposition is obvious," he said. He sees the ideal potential strategic partner as one that already has catheterization lab products, particularly those who could benefit broadly with a systematic means to improve outcomes in procedures such as TAVR.

"This is not a me-too device, it takes a sales force that can speak to physiology. But there could also be a massive economic benefit as we move to value-based payments," said Halpert. "Cath labs are becoming much more concerned with 'what's our rate of complications and how is that going to impact our payments?'"

He concluded, "Renalguard is the only thing that's been shown to reduce the incidence of acute kidney injury, and it can improve patient outcomes."