Nephrotoxic effects of amphotericin B, including renal tubular acidosis

Douglas, J. B.; Healy, J. K.

doi:10.1016/0002-9343(69)90067-9

Cited by 125 publications

(36 citation statements)

References 29 publications

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“…These patients still have an inability to acidify the urine (pH.5.5) without a significant drop in plasma bicarbonate. Some forms of dRTA are due to a back-leak of protons resulting from the exposure of the patient to pharmacologic agents that damage the tubular plasma membrane, such as amphotericin (138). However, these patients will often display signs and symptoms associated with principal as well as intercalated cell dysfunction.…”

Section: Intercalated Cell Dysfunction and The Pathogenesis Of Distalmentioning

confidence: 99%

“…Amphotericin can cause a generalized dysfunction of the kidney tubule, including intercalated cells, because it damages the plasma membrane and causes an H 1 back-leak of protons due to the exposure (138,153). On the other hand, some conditions, such as Sjögren syndrome and some cases of systemic lupus erythematosus, that can present with dRTA due to more predominant intercalated cell dysfunction.…”

Section: Acquired Intercalated Cell Dysfunctionmentioning

confidence: 99%

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Collecting Duct Intercalated Cell Function and Regulation

Roy¹,

Al‐bataineh²,

Pastor-Soler

2015

Clinical Journal of the American Society of Nephrology

202

213

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Intercalated cells are kidney tubule epithelial cells with important roles in the regulation of acid-base homeostasis. However, in recent years the understanding of the function of the intercalated cell has become greatly enhanced and has shaped a new model for how the distal segments of the kidney tubule integrate salt and water reabsorption, potassium homeostasis, and acid-base status. These cells appear in the late distal convoluted tubule or in the connecting segment, depending on the species. They are most abundant in the collecting duct, where they can be detected all the way from the cortex to the initial part of the inner medulla. Intercalated cells are interspersed among the more numerous segment-specific principal cells. There are three types of intercalated cells, each having distinct structures and expressing different ensembles of transport proteins that translate into very different functions in the processing of the urine. This review includes recent findings on how intercalated cells regulate their intracellular milieu and contribute to acid-base regulation and sodium, chloride, and potassium homeostasis, thus highlighting their potential role as targets for the treatment of hypertension. Their novel regulation by paracrine signals in the collecting duct is also discussed. Finally, this article addresses their role as part of the innate immune system of the kidney tubule.

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Section: Intercalated Cell Dysfunction and The Pathogenesis Of Distalmentioning

confidence: 99%

Section: Acquired Intercalated Cell Dysfunctionmentioning

confidence: 99%

Collecting Duct Intercalated Cell Function and Regulation

Roy¹,

Al‐bataineh²,

Pastor-Soler

2015

Clinical Journal of the American Society of Nephrology

202

213

View full text Add to dashboard Cite

show abstract

“…Amphotericin B induces RTA type 1 by increasing membrane permeability in the collecting duct. This results in backdiffusion of secreted H + ions and K + wasting, which leads to hypokalemia [92,93]. Patients with significant proteinuria (>3 g/l) seem to have a reduced risk of renal tubular toxic effects caused by amphotericin B [94], which might be related to a reduced concentration of free amphotericin B in tubular fluid.…”

Section: Amphotericin Bmentioning

confidence: 99%

Drug-induced acid-base disorders

et al. 2014

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The incidence of acid-base disorders (ABDs) is high, especially in hospitalized patients. ABDs are often indicators for severe systemic disorders. In everyday clinical practice, analysis of ABDs must be performed in a standardized manner. Highly sensitive diagnostic tools to distinguish the various ABDs include the anion gap and the serum osmolar gap. Drug-induced ABDs can be classified into five different categories in terms of their pathophysiology: (1) metabolic acidosis caused by acid overload, which may occur through accumulation of acids by endogenous (e.g., lactic acidosis by biguanides, propofol-related syndrome) or exogenous (e.g., glycol-dependant drugs, such as diazepam or salicylates) mechanisms or by decreased renal acid excretion (e.g., distal renal tubular acidosis by amphotericin B, nonsteroidal antiinflammatory drugs, vitamin D); (2) base loss: proximal renal tubular acidosis by drugs (e.g., ifosfamide, aminoglycosides, carbonic anhydrase inhibitors, antiretrovirals, oxaliplatin or cisplatin) in the context of Fanconi syndrome; (3) alkalosis resulting from acid and/or chloride loss by renal (e.g., diuretics, penicillins, aminoglycosides) or extrarenal (e.g., laxative drugs) mechanisms; (4) exogenous bicarbonate loads: milk-alkali syndrome, overshoot alkalosis after bicarbonate therapy or citrate administration; and (5) respiratory acidosis or alkalosis resulting from drug-induced depression of the respiratory center or neuromuscular impairment (e.g

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“…It is characterized by an increase in the tubular permeability, leading to the inability of the kidneys to concentrate the urine (5, 13, 16, 38); to distal tubular acidosis (11,16,20,38); and to potassium, sodium, and magnesium wasting (4,11,16,37,38). This effect is probably due to the direct interaction of AmB with the cell membrane (12, 15) and could be related to the ability of the antibiotic to alter the membrane permeability (1).…”

mentioning

confidence: 99%

“…This effect is probably due to the direct interaction of AmB with the cell membrane (12, 15) and could be related to the ability of the antibiotic to alter the membrane permeability (1). AmB also induces a decrease in the glomerular filtration rate and in the renal blood flow (11,13,14,16,39 lytic acitivity of AmB by decreasing its affinity for the cellular membranes (29a). However, we previously showed that cholesterol is not necessary in the structure of the surfactant to diminish or even suppress the hemolytic activity of AmB.…”

mentioning

confidence: 99%

Comparison of nephrotoxicities of different polyoxyethyleneglycol formulations of amphotericin B in rats

Tasset

Préat

Bernard

et al. 1992

Antimicrob Agents Chemother

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The aim of the present study was to assess whether amphotericin B (AmB)-Myrj 59, AmB-polyoxyethyleneglycol 24 cholesterol (PC), and AmB-Synperonic A50 (SA50) were less nephrotoxic than AmB-deoxycholate (DC). Rats were treated with the different AmB formulations (10 mg/kg of body weight) intraperitoneally or with the surfactants alone. A group of control rats receiving the vehicle was also examined. After 6 days of daily intraperitoneal inijections of AmB-DC, decreased body weight and glomerular filtration rate as well as increased degree of diuresis, uremia, microalbuminuria, and N-acetyl-O-D-glucosaminidase excretion in urine were noted. Urinary excretion of potassium and sodium was also decreased in AmB-DC-treated rats. Most of these effects were more pronounced with AmB-PC and AmB-SA50. In contrast, AmB-Myrj 59 was less nephrotoxic than AmB-DC. Indeed, after 6 days of treatment with AmB-Myrj 59, the natriuria, kaliuria, albuminuria, and glomerular filtration rates were unchanged compared with those of controls. Moreover, the body weight loss and uremia increase of the rats treated by AmB-Myrj 59 were less than those of the rats treated with the commercial preparation. Among the surfactants, only PC was toxic for the rats. The intrinsic toxicity of PC and the higher systemic exposure to AmB could contribute to increased toxicities ofAmB-PC and AmB-SA50, respectively. AmB-Myrj 59 was less nephrotoxic than AmB-DC at equivalent areas under the plasma concentration-time curves. These preliminary results suggest that this formulation could be a good alternative to the commercial product.Amphotericin B (AmB) is a polyene antibiotic which is widely used in the treatment of systemic mycoses despite two major disadvantages. First, AmB is poorly water soluble, and the commercial preparation (Fungizone) consists of a colloidal solubilization of the drug in a micellar solution of deoxycholate (AmB-DC). Second, toxicity of the polyene limits its clinical use. Particularly, the chronic nephrotoxicity which affects up to 80% of the patients treated with AmB-DC (13) can sometimes lead the clinician to lower the dose or to prematurely discontinue therapy (8,46). Usually, renal function returns to normal upon withdrawal of therapy (5), although sometimes permanent damage is sustained (49).The mechanism of this nephrotoxicity is not yet well understood. It is characterized by an increase in the tubular permeability, leading to the inability of the kidneys to concentrate the urine (5, 13, 16, 38); to distal tubular acidosis (11,16,20,38); and to potassium, sodium, and magnesium wasting (4,11,16,37,38). This effect is probably due to the direct interaction of AmB with the cell membrane (12, 15) and could be related to the ability of the antibiotic to alter the membrane permeability (1). AmB also induces a decrease in the glomerular filtration rate and in the renal blood flow (11,13,14,16,39 lytic acitivity of AmB by decreasing its affinity for the cellular membranes (29a). However, we previously showed that cholesterol is not nece...

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Nephrotoxic effects of amphotericin B, including renal tubular acidosis

Cited by 125 publications

References 29 publications

Collecting Duct Intercalated Cell Function and Regulation

Collecting Duct Intercalated Cell Function and Regulation

Drug-induced acid-base disorders

Comparison of nephrotoxicities of different polyoxyethyleneglycol formulations of amphotericin B in rats

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