Diuretic Resistance

Abstract

Diuretic resistance is defined as a failure to achieve the therapeutically desired reduction in edema despite a full dose of diuretic. The causes of diuretic resistance include poor adherence to drug therapy or dietary sodium restriction, pharmacokinetic issues, and compensatory increases in sodium reabsorption in nephron sites that are not blocked by the diuretic. To illustrate the pathophysiology and management of diuretic resistance, we describe a patient with nephrotic syndrome. This patient presented with generalized pitting edema and weight gain despite the use of oral loop diuretics. Nephrotic syndrome may cause mucosal edema of the intestine, limiting the absorption of diuretics. In addition, the patient’s kidney function had deteriorated, impairing the tubular secretion of diuretics. He was admitted for intravenous loop diuretic treatment. However, this was ineffective, likely due to compensatory sodium reabsorption by other tubular segments. The combination of loop diuretics with triamterene, a blocker of the epithelial sodium channel, effectively reduced body weight and edema. Recent data suggest that plasmin in nephrotic urine can activate the epithelial sodium channel, potentially contributing to the diuretic resistance in this patient. This case is used to illustrate and review the mechanisms of, and possible interventions for, in diuretic resistance.

Amiloride resolves resistant edema and hypertension in a patient with nephrotic syndrome; a case report

“…Generalized edema is an essential clinical feature of NS independent of various underlying etiologies. Two major hypotheses have been proposed to explain edema formation, the underfill and overfill theory, respectively, which have been recently reviewed (Ellis ; Hoorn and Ellison ; Ray et al. ; Teoh et al.…”

Sodium retention by uPA‐plasmin‐ENaC in nephrotic syndrome—Authors reply

“…The selective uPA‐neutralizing antibody treatment showed a minor and late difference in accumulated Na‐balance, which is likely why weight change was borderline significant. Irrespective of the observed differences and possible explanations, both studies suggest that blocking ENaC function is an appropriate target for the treatment of sodium and fluid retention in NS, which is supported by recent case reports . An ongoing, randomized clinical trial is currently exploring the effect of amiloride in paediatric patients with NS .…”

“…Contrary to the classical view of altered fluid distribution second to a low plasma oncotic pressure, accumulating evidence suggest that oedema formation in NS is because of the aberrant renal sodium retention . It has been shown that pharmacologic blockade of the epithelial sodium channel (ENaC) using amiloride can prevent sodium retention and relieve nephrotic oedema in both rats, mice and humans . As aldosterone is typically in normal range or suppressed in NS, possibly after a variable and short initial increase, the question is what activates ENaC in NS?…”

Can Torsemide and Combination of Loop Diuretics Improve Mortality in Patients with Chronic Heart Failure After Discharge?

“…Second, it is common for clinicians to use multiple diuretics to deal with diuretic resistance. 5,17) Third, since torsemide is more expensive than furosemide in China, combination treatment may reduce the cost for HF patients compared with torsemide and have potential benefits compared with furosemide. It is noteworthy that we assessed the associations between combination treat-LOOP DIURETIC IN CHRONIC HEART FAILURE ment and one-year all-cause and CV mortality compared with furosemide for the first time.…”