Explanation Found for Diuretic Resistance in Heart Failure

In heart failure patients, the kidneys can be overwhelmed with fluid volume overload. If these patients do not respond to diuretics, treatment is a major challenge.

In heart failure patients, the kidneys can be overwhelmed with fluid volume overload. If these patients do not respond to diuretics, treatment is a major challenge.

Aquaporin2-containing renal tubular cells are the organisms most important in clearing water from the system.

In an effort to determine the pathophysicologic mechanism of diuretic resistance, Parta Hatamizadeh, MD, a nephrologist at the University of Michigan Health System in Ann Arbor MI, reasoned that injury to these kidney cells during acute decompensated heart failure (ADHF) could explain resistance to diuretics.

Hatamizadeh and colleagues looked at urine pellet aquaporin2 mRNA in 39 patients with ADHF. Urine aquaporin to creatine ratio (UAqCr) was used as a marker of the severity of damage to the renal tubular cells that detach from the tubules and later appear in patients’ urine.

He found that ADHF patients with diabetes or hypertension has six times higher UAqCr than patients who did not have those conditions. Post-discharge (UAqCr) was not significantly different from ADHF phase within 1 month of leaving the hospital.

But it was 17-fold lower when measured 3 months after hospital discharge.

The findings suggest that there is persistence renal tubular cell injury several weeks following the clinical stabilization of ADHF. “Impairment of aquaporin2-containing renal tubular cells may contribute to diuretic resistance associated with ADHF,” he wrote. “Higher levels of (UAqCr) in diabetic and hypertensive patients may explain the prior observations of association of diuretic resistance with comorbidities,” he wrote. That could be a useful finding showing UAqCr levels “can be a potential future diagnostic marker and therapeutic target for diuretic resistance in heart failure.”

The study is due to be presented Saturday March 14, in a poster session at the American College of Cardiology meeting in San Diego, CA.