Effect of salt supplementation on amphotericin B nephrotoxicity

Llanos, Alejandro; Cieza, Javier; Bernardo, José F.; Echevarría, Juan; Biaggioni, Italo; Sabra, Ramzi; Branch, Robert A.

doi:10.1038/ki.1991.214

Cited by 121 publications

(69 citation statements)

References 21 publications

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“…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].…”

mentioning

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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mentioning

confidence: 99%

Amphotericin B-related nephrotoxicity in low-risk patients

Berdichevski¹,

Luis²,

Crestana³

et al. 2006

Braz J Infect Dis

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“…This dose has previously been shown to cause a maximnal inhibition of 5'-nucleotidase activity 2 h after intramuscular injection (15); (iii) DB-cAMP (85 ,ug/kg/min i.a., started 30 min prior to amphotericin B and continued throughout the experiment). This dose has previously been shown to induce biological effects in the kidney, without significantly altering the baseline RBF (14); and (iv) diltiazem (20 ,g/kg/min, i.a., started 30 min prior to amphotericin B and continued throughout the experiment). This dose was found, in pilot experiments, to be the highest tolerated dose without changing baseline renal vascular resistance.…”

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confidence: 99%

Mechanisms of amphotericin B-induced decrease in glomerular filtration rate in rats

Sabra

Branch

1991

Antimicrob Agents Chemother

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Mechanisms responsible for the reductions in renal blood flow (RBF) and glomerular filtration rate (GFR) in response to acute infusions of amphotericin B were investigated in vivo in rats. The influence of salt status and the roles of adenosine, cyclic AMP, and calcium influx were examined. Amphotericin B was infused into the renal artery in seven groups of rats at 0.025 mg/kg of body weight per min for 15 min. RBF Amphotericin B infusions induce acute reductions in renal blood flow (RBF) and glomerular filtration rate (GFR) in both rats and dogs (4, 9, 11), due mostly to elevation of renovascular resistance (21). The mechanisms underlying these acute hemodynamic effects have not been completely elucidated. Studies with dogs have suggested that activation of tubuloglomerular feedback (TGF) plays a role in these changes, since both TGF and amphotericin B-induced decreases in GFR are inhibited by the same pharmacologic interventions (salt loading, furosemide, or theophylline administration) (1,7,8,24,31). Unfortunately, these studies were conducted with different species (dogs for amphotericin B and rats for TGF). It is not clear whether both species behave similarly with respect to both TGF and amphotericin B. Therefore, it is important to examine this question since, if true, it would lend greater support to the hypothesis.In chronic models of nephrotoxicity in the rat, salt loading attenuates the decreases in GFR induced by amphotericin B, while salt depletion potentiates them (16, 28). In addition, there are hemodynamic changes similar to those observed after acute infusions of the drug (28). At present, the effect of salt status on the acute renal response of the rat to amphotericin B is unknown, but it is possible that the acute hemodynamic effects of amphotericin B may contribute to the deterioration in renal function observed in chronic models. In order to examine this possibility and to further study the role of TGF, we decided to assess the influence of salt status on the acute responses to amphotericin B in rats.Theophylline inhibits the GFR-lowering effects of both * Corresponding author.TGF activation in rats (17,18) and amphotericin B in dogs (9), but its effect on the amphotericin B response in rats is not known. In the case of TGF, the low concentrations of theophylline used suggested that it was acting through adenosine receptor blockade, but its mechanism of action in the latter case is not clear. Theophylline is known to act by at least two other mechanisms: phosphodiesterase inhibition, which raises intracellular cyclic AMP (cAMP) levels, and induction of changes in intracellular calcium levels (19

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“…26,76,[90][91][92][93][94][95] The risk of amphotericin-induced nephrotoxicity has been shown to double when two or more nephrotoxic agents (e.g. cyclosporin, aminoglycosides or foscarnet) are used concurrently.…”

Section: Hepatotoxicitymentioning

confidence: 99%

“…91 Sodium loading prior to amphotericin use, avoiding hypovolaemia and restricting the concomitant use of other nephrotoxins, can decrease the risk of amphotericin-induced nephrotoxicity. [94][95][96] …”

Section: Hepatotoxicitymentioning

confidence: 99%

Optimizing antifungal drug dosing and monitoring to avoid toxicity and improve outcomes in patients with haematological disorders

Worth

Blyth

Booth

et al. 2008

Internal Medicine Journal

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Antifungal prophylaxis, empirical therapy and treatment of established fungal infections in the haematology population may be associated with significant toxicity or drug interactions leading to sub-therapeutic antifungal drug concentrations and poorer clinical outcomes. These risks may be minimised by clinical assessment, laboratory monitoring of biochemical or haematological indices, avoidance of particular drug combinations and dose modification in certain circumstances. Specific measures, such as the optimal timing of oral drug administration in relation to meals, use of pre-hydration and electrolyte supplementation may also be required. For certain agents, therapeutic drug monitoring (TDM) is warranted where non-compliance, non-linear pharmacokinetics, a narrow therapeutic window, suspected drug interaction or unexpected toxicity are encountered. Pharmacokinetics and pharmacodynamics of clinical relevance to the haematology population are discussed for the azole, polyene and echinocandin classes of antifungal agents. The evidence supporting an association between TDM and enhanced treatment outcomes is presented for individual antifungal drugs, and recommendations for clinical practice are provided. Further randomised study of newer antifungal agents, such as posaconazole, is required to explore the potential for improved clinical outcomes in association with TDM.Understanding a drug's pharmacokinetics and its pharmacodynamic effects affords the clinician the capacity to optimize drug exposure while minimizing or avoiding drug interactions and toxicities. Therapeutic drug monitoring (TDM) may also be employed during the treatment period to ensure that the selected drug dosage falls within the therapeutic window for an individual patient.These clinical caveats are particularly relevant to the haematology population where the frequent requirement for polypharmacy and the complexity of comorbidities can significantly influence the success of antifungal therapy. This section of the guidelines describes the potential drugdrug interactions and toxicities related to antifungal use and how they may be avoided. It also considers the latest

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Effect of salt supplementation on amphotericin B nephrotoxicity

Cited by 121 publications

References 21 publications

Amphotericin B-related nephrotoxicity in low-risk patients

Amphotericin B-related nephrotoxicity in low-risk patients

Mechanisms of amphotericin B-induced decrease in glomerular filtration rate in rats

Optimizing antifungal drug dosing and monitoring to avoid toxicity and improve outcomes in patients with haematological disorders

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