-
American Journal of Kidney Diseases :... Jan 2017Diuretic 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... (Review)
Review
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, diuretic resistance.
Topics: Drug Resistance; Edema; Humans; Male; Middle Aged; Nephrotic Syndrome; Sodium Potassium Chloride Symporter Inhibitors; Treatment Failure
PubMed: 27814935
DOI: 10.1053/j.ajkd.2016.08.027 -
International Journal of Molecular... Mar 2018Liddle syndrome is an inherited form of low-renin hypertension, transmitted with an autosomal dominant pattern. The molecular basis of Liddle syndrome resides in... (Review)
Review
Liddle syndrome is an inherited form of low-renin hypertension, transmitted with an autosomal dominant pattern. The molecular basis of Liddle syndrome resides in germline mutations of the , and genes, encoding the α, β, and γ-subunits of the epithelial Na⁺ channel (ENaC), respectively. To date, 31 different causative mutations have been reported in 72 families from four continents. The majority of the substitutions cause an increased expression of the channel at the distal nephron apical membrane, with subsequent enhanced renal sodium reabsorption. The most common clinical presentation of the disease is early onset hypertension, hypokalemia, metabolic alkalosis, suppressed plasma renin activity and low plasma aldosterone. Consequently, treatment of Liddle syndrome is based on the administration of ENaC blockers, amiloride and triamterene. Herein, we discuss the genetic basis, clinical presentation, diagnosis and treatment of Liddle syndrome. Finally, we report a new case in an Italian family, caused by a p.Pro618Leu substitution.
Topics: Adolescent; Epithelial Sodium Channels; Humans; Liddle Syndrome; Male; Mutation, Missense; Phenotype
PubMed: 29534496
DOI: 10.3390/ijms19030812 -
Journal of the American Society of... Mar 2015Crystalline nephropathy refers to renal parenchymal deposition of crystals leading to kidney damage. The most common forms of crystalline nephropathy encountered in...
Crystalline nephropathy refers to renal parenchymal deposition of crystals leading to kidney damage. The most common forms of crystalline nephropathy encountered in renal pathology are nephrocalcinosis and oxalate nephropathy. Less frequent types include urate nephropathy, cystinosis, dihydroxyadeninuria, and drug-induced crystalline nephropathy (e.g., caused by indinavir or triamterene). Monoclonal proteins can also deposit in the kidney as crystals and cause tissue damage. This occurs in conditions such as light chain proximal tubulopathy, crystal-storing histiocytosis, and crystalglobulinemia. The latter is a rare complication of multiple myeloma that results from crystallization of monoclonal proteins in the systemic vasculature, leading to vascular injury, thrombosis, and occlusion. In this report, we describe a case of crystalglobulin-induced nephropathy and discuss its pathophysiology and the differential diagnosis of paraprotein-induced crystalline nephropathy.
Topics: Biopsy; Crystallization; Female; Humans; Kidney; Kidney Diseases; Middle Aged; Multiple Myeloma; Serum Globulins
PubMed: 25190731
DOI: 10.1681/ASN.2014050509 -
American Journal of Nephrology 2021Although diuretics are one of the most widely used drugs by nephrologists, their antiproteinuric properties are not generally taken into consideration. (Review)
Review
BACKGROUND
Although diuretics are one of the most widely used drugs by nephrologists, their antiproteinuric properties are not generally taken into consideration.
SUMMARY
Thiazide diuretics have been shown to reduce proteinuria by >35% in several prospective controlled studies, and these values are markedly increased when combined with a low-salt diet. Thiazide-like diuretics (indapamide and chlorthalidone) have shown similar effectiveness. The antiproteinuric effect of mineralocorticoid receptor antagonists (spironolactone, eplerenone, and finerenone) has been clearly established through prospective and controlled studies, and treatment with finerenone reduces the risk of chronic kidney disease progression in type-2 diabetic patients. The efficacy of other diuretics such as amiloride, triamterene, acetazolamide, or loop diuretics has been less explored, but different investigations suggest that they might share the same antiproteinuric properties of other diuretics that should be evaluated through controlled studies. Although the inclusion of sodium-glucose cotransporter-2 inhibitors (SGLT2i) among diuretics is a controversial issue, their renoprotective and cardioprotective properties, confirmed in various landmark trials, constitute a true revolution in the treatment of patients with kidney disease. Recent subanalyses of these trials have shown that the early antiproteinuric effect induced by SGLT2i predicts long-term preservation of kidney function. Key Message: Whether the early reduction in proteinuria induced by diuretics other than finerenone and SGLT2i, as summarized in this review, also translates into long-term renoprotection requires further prospective and observational studies. In any case, it is important for the clinician to be aware of the antiproteinuric properties of drugs so often used in daily clinical practice.
Topics: Angiotensin Receptor Antagonists; Angiotensin-Converting Enzyme Inhibitors; Animals; Chlorthalidone; Combined Modality Therapy; Diet, Sodium-Restricted; Diuresis; Diuretics; Humans; Hypertension; Indapamide; Mineralocorticoid Receptor Antagonists; Natriuresis; Proteinuria; Sodium Chloride Symporters; Sodium Potassium Chloride Symporter Inhibitors; Sodium-Glucose Transporter 2 Inhibitors; Thiazides
PubMed: 34233330
DOI: 10.1159/000517020 -
The American Journal of Medicine Apr 1999Several medications--notably acyclovir, sulfonamides, methotrexate, indinavir, and triamterene--are associated with the production of crystals that are insoluble in... (Review)
Review
Several medications--notably acyclovir, sulfonamides, methotrexate, indinavir, and triamterene--are associated with the production of crystals that are insoluble in human urine. Intratubular precipitation of these crystals can lead to acute renal insufficiency. Many patients who require treatment with these medications have additional risk factors, such as true or effective intravascular volume depletion and underlying renal insufficiency, that increase the likelihood of drug-induced intrarenal crystal deposition. Acute renal failure in this setting may be preventable if it is anticipated by appropriate drug dosing, volume expansion with high urinary flow, and alkalinization of the urine when appropriate. Renal failure may be reversible if the drug is discontinued, and by volume repletion and alkalinization of the urine when appropriate. Management of established renal insufficiency includes volume repletion, dialytic support if necessary, adjustment of drug doses, and avoidance of further exposure to nephrotoxins.
Topics: Acute Kidney Injury; Acyclovir; Humans; Indinavir; Kidney; Methotrexate; Risk; Sulfonamides; Triamterene
PubMed: 10225250
DOI: 10.1016/s0002-9343(99)00041-8