title: New insights into diuretic use in patients with chronic renal disease.
abstract: Patients with chronic renal insufficiency (CRI) or the nephrotic syndrome frequently manifest diuretic resistance. Factors limiting diuretic responsiveness in patients with CRI may include a reduced basal level of fractional Na(+) reabsorption that places an upper limit on diuretic response, and enhanced NaCl reabsorption in downstream segments, combined with a reduced delivery of diuretic to the kidney. Diuretics are secreted by the recently characterized organic anion transporters (OATs), which are expressed in proximal tubule cells. Secretion may be inhibited by retained organic anions, urate, or acidosis. These limitations necessitate an increased diuretic dosage, up to a defined ceiling level, and consideration of the use of a nonrenally metabolized loop diuretic rather than furosemide. Diuretic responsiveness in patients with the nephrotic syndrome is limited by avid Na(+) reabsorption by the terminal nephron. Experimental studies have shown that a reduced serum albumin concentration can increase the volume of distribution of loop diuretics, reduce their tubular secretion, and enhance the inactivation of furosemide within the kidney by glucuronidization. Binding of loop diuretics can curtail their action in the loop of Henle. Recent clinical investigations have challenged the importance of some of these mechanisms that were identified in animal models. Strategies to improve loop diuretic responsiveness include increasing diuretic dosage, concurrent use of a thiazide diuretic to inhibit downstream NaCl reabsorption and attempts to maximally reduce albumin excretion. Strategies to limit albumin excretion include the use of an angiotensin-converting enzyme inhibitor or an angiotensin receptor blocker and appropriate limitation of protein intake. These measures are more logical, effective, and less expensive than infusion of albumin solutions.
authors.affiliation: Division of Nephrology and Hypertension and Center for Hypertension and Renal Disease Research, Georgetown University, Washington DC.
authors.forename: Christopher S
authors.initials: CS
authors.lastname: Wilcox
mesh_terms: D000818:Animals; D002908:Chronic Disease; D004232:Diuretics / Q000493:pharmacokinetics / Q000494:pharmacology / Q000627:therapeutic use*; D004351:Drug Resistance; D006801:Humans; D007674:Kidney Diseases / Q000188:drug therapy*; D007676:Kidney Failure, Chronic / Q000188:drug therapy; D009404:Nephrotic Syndrome / Q000188:drug therapy
chemical_list: D004232:Diuretics