Fluid Overload and Cardiorenal Care: What Happens When Diuretics Stop Working?

Nuwellis CEO Mike McCormick discusses the heart-kidney cycle in fluid overload, how diuretic resistance is recognized and why researchers are looking at breathing, hospital discharge and other outcomes alongside fluid removal.

After a heart procedure, Mike McCormick’s grandfather developed fluid overload and acute kidney injury. Within the same hospital stay, he was placed on dialysis and remained on it for three years.

Witnessing his grandfather’s decline firsthand reshaped how Mike, the President and CEO of Nuwellis, a medical technology company focused on fluid management, understood the delicate relationship between the heart and kidneys.

“I knew as a device side person, there’s got to be better ways to manage fluid overload so that a surgical trip doesn’t end up in such a bad complication,” he said.

In this Xtalks Clinical Edge interview, Mike discusses how fluid overload affects patients, why the heart-kidney relationship can complicate treatment, what clinicians look for when diuretics stop working and how treatment timing and patient selection can tell us about the results.

Symptoms and Clinical Burden of Fluid Overload

Fluid overload occurs when the body retains more water and sodium than it can effectively manage. Excess fluid can collect in the legs and abdomen, while congestion in the lungs can make breathing difficult.

Patients may also experience fatigue, reduced appetite and difficulty lying flat because of shortness of breath. When congestion becomes significant, hospitalization may be required.

“It’s not simply a cosmetic swelling,” Mike said.

Fluid overload is often associated with heart failure, but Mike also sees it in critical care, cardiac surgery and pediatric care. Clinicians across these settings face a similar challenge: removing enough fluid to relieve congestion while keeping blood pressure and kidney function stable.

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Cardiorenal Syndrome: The Heart-Kidney Connection

Cardiorenal syndrome is when problems in the heart and kidneys begin to reinforce each other.

The two organs work together to regulate blood flow and fluid balance, so when heart function declines, blood flow to the kidneys can drop too. As Mike explained, “If the heart is not working well, then the perfusion to the kidney slows down and the kidney can slow down. The kidney can respond by actually preserving water and sodium, which further increases the workload on the heart.”

Relieving congestion requires careful monitoring. Clinicians need to remove enough fluid to help the patient while watching blood pressure and kidney function throughout treatment.

Identifying Diuretic Resistance and the Role of Ultrafiltration

Diuretics are generally the first-line treatment for removing excess fluid. Clinicians then monitor urine output, body weight, symptoms and kidney function to determine whether the patient is responding as expected.

Clinicians may increase the dose or switch to a different diuretic. “If they still have that persistent swelling in that patient, that shows that that patient is most likely diuretic resistant,” Mike said.

If the patient becomes resistant, mechanical ultrafiltration may then provide another option for fluid removal. Mike called it “another tool in the toolbox” for patients who are not responding adequately to diuretics.

“You know exactly how much fluid should come off in ultrafiltration, and you’re constantly evaluating the patient’s blood pressure to make sure it’s the right therapy,” he said.

Evaluating Clinical Trial Endpoints and Patient-Centered Outcomes

Patient selection, treatment timing and study protocols can all influence how fluid management trials are interpreted.

Studies do not always ask the same questions in the same groups of patients. When and how a therapy is introduced can shape the results researchers see.

“To me, the takeaway isn’t whether ultrafiltration works or doesn’t work,” Mike said. “The takeaway is always that you have to use the right therapy at the right time for the patients and monitor the results.”

Aside from weight loss, fluid volume removed and creatinine levels, Mike suggested that other patient-centered endpoints should also be considered when evaluating treatment.

“We always like the numbers,” he said. “But I think the other thing that’s really, really important is how did the patient do? Did their breathing get better? Are they feeling better? Did they go home? Did they leave the hospital?”

Fluid Management Challenges in Pediatric Intensive Care

Recognizing poor treatment response early is an important research question. Mike highlighted the need to better identify when patients are developing diuretic resistance and which therapies may be appropriate as their response changes.

This is also something to consider in children, where fluid management brings its own clinical considerations.

“Pediatric patients are not just small adults,” Mike emphasized. “They have their own complications, particularly in the cardiorenal syndrome.”

Among critically ill children treated in pediatric and neonatal intensive care settings, Mike identified early signs of decline and treatment response as areas clinicians should watch closely.

Having better indicators of how patients respond to different therapies could help care teams recognize changes quickly and refine treatment for each patient, Mike concluded.