Reduced Nephrotoxicity of Conventional Amphotericin B Therapy after Minimal Nephroprotective Measures: Animal Experiments and Clinical Study

Mayer, Jiřı́; Doubek, Michael; Doubek, Jaroslav; Horký, Drahomír; Scheer, P.; Štěpánek, M.

doi:10.1086/341662

Cited by 77 publications

(60 citation statements)

References 42 publications

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“…Volume expansion might also mitigate the nephrotoxicities of filtered urate [22][23][24] and hemoglobin 25 and of Shiga toxin's effects on renal tubular epithelial cells 26 and monocytes 27 that are independent of thrombotic changes. Indeed, salt loading protects against presumably nonthrombotic nephrotoxicity, such as that caused by amphotericin, 28 and isotonic saline prevents nephropathy caused by radiocontrast media better than does hypotonic saline. 29 It is interesting that unlike a Minnesota study that suggested that antibiotic administration was related to a milder course of HUS, 30 we detected no statistically significant association between antibiotic administration and development of either oligoanuria or nonoligoanuria.…”

Section: Discussionmentioning

confidence: 99%

Relative Nephroprotection DuringEscherichia coliO157:H7 Infections: Association With Intravenous Volume Expansion

et al. 2005

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ABSTRACT. Objective. The hemolytic uremic syndrome (HUS) consists of hemolytic anemia, thrombocytopenia, and renal failure. HUS is often precipitated by gastrointestinal infection with Shiga toxin-producing Escherichia coli and is characterized by a variety of prothrombotic host abnormalities. In much of the world, E coli O157:H7 is the major cause of HUS. HUS can be categorized as either oligoanuric (which probably signifies acute tubular necrosis) or nonoligoanuric. Children with oligoanuric renal failure during HUS generally require dialysis, have more complicated courses, and are probably at increased risk for chronic sequelae than are children who experience nonoligoanuric HUS. Oligoanuric HUS should be avoided, if possible. The presentation to medical care of a child with definite or possible E coli O157:H7 infections but before HUS ensues affords a potential opportunity to ameliorate the course of the subsequent renal failure. However, it is not known whether events that occur early in E coli O157:H7 infections, particularly measures to expand circulating volume, affect the likelihood of experiencing oligoanuric HUS if renal failure develops. We attempted to assess whether pre-HUS interventions and events, especially the volume and sodium content of intravenous fluids administered early in illness, affect the risk for developing oligoanuric HUS after E coli O157:H7 infections.Methods. We performed a prospective cohort study of 29 children with HUS that was confirmed microbiologically to be caused by E coli O157:H7. Infected children were enrolled when they presented with acute bloody diarrhea or as contacts of patients who were known to be infected with E coli O157:H7, or if they had cultureconfirmed infection, or if they presented with HUS. HUS was defined as hemolytic anemia (hematocrit <30%, with fragmented erythrocytes on peripheral-blood smear), thrombocytopenia (platelet count of <150 000/mm 3 ), and renal insufficiency (serum creatinine concentration that exceeded the upper limit of normal for age). A wide range of pre-HUS variables, including demographic factors, clinical history, medications given, initial laboratory values, and volume and content of parenteral fluid administered, were recorded and entered into analysis. Estimates of odds ratios were adjusted for possible confounding effects using logistic regression analysis. Twenty-nine children who were <10 years old, had HUS confirmed to be caused by E coli O157:H7, and were hospitalized at the Children's Hospital and Regional Medical Center, Seattle, were studied. The main outcome measured was development of oligoanuric renal failure. Oligoanuria was defined as a urine output <0.5 mL/kg per hour for at least 24 consecutive hours.Results. As a group, the children with oligoanuric renal failure presented to medical attention and were evaluated with laboratory testing later than the children with nonoligoanuric renal failure. On initial assessments, the children with oligoanuric outcomes had higher white blood cell counts, lower platelet counts...

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Section: Discussionmentioning

confidence: 99%

Relative Nephroprotection DuringEscherichia coliO157:H7 Infections: Association With Intravenous Volume Expansion

et al. 2005

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“…Clinical and experimental data from the last decade point to an important effect of saline loading on the prevention of the loss of renal function in individuals treated with AmphoB. In two trials, there was no significant loss of renal function in sodium chloride-loaded patients [8,10].…”

Section: Discussionmentioning

confidence: 99%

“…Several studies published during the last two decades have shown that nephrotoxicity can be prevented by the use of sodium loading [4,[7][8][9][10][11], slowing drug infusion [12] and through the use of liposomal or lipid-complex amphotericins [13][14][15][16][17].…”

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confidence: 99%

Amphotericin B-related nephrotoxicity in low-risk patients

Berdichevski¹,

Luis²,

Crestana³

et al. 2006

Braz J Infect Dis

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Introduction. Amphotericin B (AmphoB) is the drug of choice for treatment of severe fungal illnesses; however, it is very nephrotoxic. Modified (less toxic) amphotericins are very expensive. In low-risk patients, saline loading would be enough to prevent significant loss of renal function. Material and Methods. Patients with normal renal function and within the first 24 hours of treatment with AmphoB were prospectively enrolled in the study. Patients in intensive care units or who were using vasoactive drugs were excluded. Saline loads were infused before and after the AmphoB treatment. Blood and urine analyses were made at the beginning and at the end of the treatment. Serum creatinine was repeated 30 days after the end of the AmphoB treatment. Results. The mean increase in serum creatinine in the 48 patients was 0.3 (0.18-0.41) mg/dL, due to a mean decrease of 25 (12.8-36.9) mL/min of creatinine clearance (CrCl). Acute renal failure, defined as an increase of more than 50% of the baseline creatinine, occurred in 15 patients (31%). Patients that were on antibiotics, in post-chemotherapy status or those submitted to bone marrow transplantation had the highest risk. Mean serum creatinine and the CrCl levels were no different from baseline values after 30 days. Conclusion. In low-risk patients, the use of AmphoB with prophylactic sodium chloride loading was associated with a small and reversible decrease in renal function. Due to its high cost the use of more expensive therapies for this type of patient does not seem to be justified.

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“…The mechanism that generates toxicity is associated with dysfunction in the renal blood flow resulting in the direct structural lesion in tubule cells, reduction in glomerular filtration rate and, consequently, electrolyte disturbances and acid-base imbalance (Mayer et al, 2002). Thus, the main manifestations of nephrotoxicity are a reduction of glomerular filtration and hypokalemia and hypomagnesemia caused by direct tubular lesion; nephrocalcinosis and renal tubular acidosis might also occur (Klepser, 2011;Longuet et al, 1991).…”

Section: Chronic Side Effects Nephrotoxicitymentioning

confidence: 99%

Difficulties in antifungal therapy with amphotericin B and the continuous search for new formulations: A literature review

Voncik¹,

Fermino²,

Cardoso³

et al. 2016

Afr. J. Pharm. Pharmacol.

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Despite advances in the research on new antifungal agents, Amphotericin B (AmB) is still considered as the antifungal of choice for treating most systemic mycoses due to its potency and broad-spectrum action. However, this drug has limited use because of its toxic effects on kidneys, liver and blood. The search for new and safe formulations of AmB is essential because of the emergence of antifungal resistance to other drugs and the increased number of immunosuppressed patients. Nanoparticles are a promising alternative towards achieving lower toxicity and improved pharmacokinetic properties. This study is a literature review of the use of AmB and the toxicity of formulations. Some of the current new formulations show some advantageous characteristics as compared to AmB. However, there is still need for a continued search for an effectively improved formulation.

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Reduced Nephrotoxicity of Conventional Amphotericin B Therapy after Minimal Nephroprotective Measures: Animal Experiments and Clinical Study

Cited by 77 publications

References 42 publications

Relative Nephroprotection DuringEscherichia coliO157:H7 Infections: Association With Intravenous Volume Expansion

Relative Nephroprotection DuringEscherichia coliO157:H7 Infections: Association With Intravenous Volume Expansion

Amphotericin B-related nephrotoxicity in low-risk patients

Difficulties in antifungal therapy with amphotericin B and the continuous search for new formulations: A literature review

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