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R Sabra

Publications and source records attributed to R Sabra.

17 recordsLinked to original sources
PubMed1992

Effect of amphotericin B on intracellular calcium levels in cultured glomerular mesangial cells.

Amphotericin B induces a reduction in the glomerular filtration rate due, in part, to a decrease in the glomerular capillary ultrafiltration coefficient (Kf), possibly resulting from mesangial cell contraction. The present study has examined the effect of amphotericin B on intracellular free calcium concentrations ([Ca2+]i) in cultured glomerular mesangial cells, using the fluorescent probe, fura-2. Under control conditions, amphotericin B caused a concentration-dependent increase in [Ca2+]i with a 231 +/- 52 nM increase at a concentration of 10(-6) M. This increase was almost completely inhibited when Ca2+ ions were omitted from the cell medium (an increase of 34 +/- 7 nM, P less than 0.0001). Replacement of extracellular Na+ ions with N-methylglucamine caused a marked inhibition of the amphotericin B-induced rise in [Ca2+]i (28 +/- 5 nM, P less than 0.0001). Diltiazem (20 microM) also suppressed the rise in [Ca2+]i seen with amphotericin B (36 +/- 6 nM, P less than 0.0001). In contrast, theophylline (20 microM) enhanced the response to amphotericin B (351 +/- 51 nM rise, P less than 0.001). The results suggest that amphotericin B-induced mesangial cell contraction is secondary to Ca2+ entry from the extracellular space through voltage-dependent calcium channels. The dependence of the response on extracellular Na+ suggests that Na+ entry induces depolarization of the membrane and opening of voltage-dependent calcium channels.

Amphotericin B↗
PubMed1992

Acute and chronic effects of flucytosine on amphotericin B nephrotoxicity in rats.

The combination of intravenous flucytosine (FC) in 0.9% saline (NaCl) and amphotericin B (AmB) provides synergistic antifungal activity and is associated with a lower incidence of nephrotoxicity than with AmB treatment alone. This study was conducted to examine whether flucytosine can influence renal function and whether it can modify the acute and chronic renal responses to AmB in the rat. In the in situ perfused rat kidney, FC at a concentration of 10 mg/kg/min for 15 min had a vasodilator effect, increasing renal blood flow by 2.5 +/- 0.7 ml/min, an effect not observed with vehicle. After the infusion of FC was stopped for 15 min, AmB induced a decrease in renal blood flow similar to that with both FC and vehicle. In a second series of studies, AmB (5 mg/kg/day intraperitoneally) was administered to four groups of rats for 7 days. In addition, the following groups received the intravenous daily interventions indicated: group 1, 5% dextrose in water (15 ml/kg/12 h); group 2, FC (150 mg/kg/12 h) in 0.9% saline (15 ml/kg/12 h); group 3, 0.9% saline (15 ml/kg/12 h); and group 4, FC (150 mg/kg/12 h) in 5% dextrose in water. Group 1 sustained a 77% decrease in creatinine clearance over the 7 days and a threefold increase in serum creatinine concentration (P of < 0.05). Groups 2, 3, and 4 sustained significantly less nephrotoxicity, with no change in serum creatinine concentration and only 38, 41, and 53% decreases in creatinine clearance, respectively (P of < 0.05), compared with that for group 1. AmB levels in renal tissue varied inversely to creatinine clearance (r of 0.57, P of < or = 0.005). However, no significant differences were found in levels in tissue between groups (P of 0.06). The results of this study suggest that FC has a small but significant effect in reducing chronic AmB-induced nephrotoxicity. This amelioration of renal injury is independent of saline administration. There was evidence that the extent of renal uptake of AmB related to the efficiency of renal function at the end of the experiment.

Amphotericin B↗
PubMed1992

Influence of the adenosine receptor antagonist, CGS 15943A, on renal function after reconstruction of chronic renal artery stenosis in the dog.

Surgical reconstruction of chronic renal artery stenosis may correct the anatomical defect but not result in an initial improvement in function of the revascularized kidney. The functional and hemodynamic changes associated with surgical correction of the one-clip, two-kidney, canine model of renovascular hypertension were studied. In 14 dogs, a surgical clip was placed across the proximal renal artery and tightened to decrease perfusion pressure (RPP) and blood flow (RBF). One month later, measurements were obtained distal to the constriction, before and 30 min after vascular reconstruction. Surgical reconstruction was associated with a rise in RPP (86%, P less than .001), renal vascular resistance (47%, P less than .001) and RBF (22%, P less than .05). Creatinine clearance (CCr) remained unchanged, but a significant negative association existed between initial CCr and change in CCr. The role of adenosine in mediating these changes was examined using the selective receptor antagonist, CGS 15943A (CGS), or its vehicle. After vascular reconstruction, vehicle dogs sustained a marked increase in renal vascular resistance, with a 60 +/- 8 mm Hg rise in RPP, but only an 18% rise in RBF. In contrast, renal vascular resistance was unchanged in the CGS group, with a 56 +/- 7 mm Hg increase in RPP and a 69% increase in RBF (P less than .0001). CCr was not changed by either vascular reconstruction or CGS 15943A. Vascular reconstruction was associated with increases in urinary flow rate and sodium excretion in both groups, but this change was significantly greater in the CGS group.(ABSTRACT TRUNCATED AT 250 WORDS)

Adenosine↗
PubMed1991

Effect of salt supplementation on amphotericin B nephrotoxicity.

It has been suggested that salt loading protects against amphotericin B-induced nephrotoxicity. The influence of saline loading on the nephrotoxic response to amphotericin B (50 mg/dose given i.v. over 4 hr 3 X/week for 10 weeks) was assessed in two groups of ten patients each who were diagnosed with mucocutaneous leishmaniasis. Patients were randomized to receive either 1 liter of 0.9% saline or 1 liter of 5% dextrose in water, administered i.v. over one hour in a double-blinded manner, directly prior to amphotericin B administration. Renal function was monitored on a weekly basis two days after the last dose of amphotericin B. Baseline characteristics were similar in both groups except for a slightly higher serum creatinine concentration (Cr) in the saline group (0.8 +/- 0.05 vs. 0.6 +/- 0.04 mg/dl). Baseline sodium (Na) excretion was relatively high (262 +/- 23 mmol/day in the dextrose group and 224 +/- 17 mmol/day in the saline group). None of the patients sustained an increase in Cr to values greater than 1.7 mg/dl. Although mean Cr remained within normal, there was a significant difference between the two groups over the ten week period, with the dextrose group sustaining a significant increase in Cr and the saline group remaining unchanged. Serum potassium (K) levels fell in both groups necessitating oral K supplementation. The saline group required significantly greater amounts of K supplementation to maintain a normal serum K. Amphotericin B caused a rapid reduction in the acidification ability of the kidney in response to an ammonium chloride load. Under these conditions, the saline group had a poorer ability to acidify the urine.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗
PubMed1991

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

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 and GFR were measured over 15 min before, during, and after the infusion. Control rats were maintained on a normal salt diet; a second group of rats received a salt-depleted diet, and a third group received a high-salt intake. Four other groups were kept on a normal diet and received theophylline (0.5 mumol/kg/min into the renal artery, intra-arterially [i.a.]), dibutyryl cyclic AMP (85 micrograms/min, i.a.), the 5'-nucleotidase inhibitor adenosine alpha,beta-methylene diphosphate (4 mg/kg, intramuscularly), or diltiazem (20 micrograms/kg/min, i.a.). Control rats had a prompt 50% decrease in RBF in response to amphotericin B. This was sustained over the 15-min infusion period and was accompanied by a decrease in creatinine clearance (CLCR) (from 0.83 +/- 0.08 to 0.40 +/- 0.09 ml/min; P less than 0.05). On stopping the infusion, RBF returned quickly to baseline but CLCR continued to decrease further (to 0.35 +/- 0.07 ml/min; P less than 0.05). Salt loading, theophylline, and diltiazem administration prevented the decreases in both RBF and CLCR. Both RBF and CLCR responses in the remaining groups were not significantly different from those in controls. The results of this study reveal a protective effect of salt loading and theophylline against amphotericin B nephrotoxicity in the rat but deny a role for adenosine in mediating these effects. They further suggest that theophylline inhibits the acute responses by a mechanism unrelated to either adenosine receptor blockade or phosphodiesterase inhibition and that calcium influx into the cells is probably responsible for the acute changes in RBF and GFR in response to amphotericin B.

Amphotericin B↗
PubMed1991

Sodium retention and hepatic function after two-thirds hepatectomy in the rat.

Recently it was suggested that the onset of sodium retention in experimental cirrhosis in rats is related to a critical threshold of hepatic function, as assessed by the aminopyrine breath test. The aim of this study was to evaluate whether sodium retention occurred after two-thirds hepatectomy in rats and to investigate the relationship between sodium retention and changes in hepatic function associated with liver regeneration in this model. Sodium balance, creatinine clearance, serum sodium and the aminopyrine rate constant of elimination were evaluated daily for 4 days after surgery in partially hepatectomized (n = 6) and sham-operated rats (n = 6). All rats in the partial hepatectomy group exhibited sodium retention (sodium balance greater than 0.7 mmol/day) 24 hr after surgery. This was associated with a 62% reduction of the aminopyrine rate constant of elimination. Spontaneous natriuresis which occurred between 2 and 4 days after surgery, was associated with an increase in the aminopyrine rate constant of elimination (from 0.73 +/- 0.02 x 10(-2) min-1 on the last day of sodium retention to 0.95 +/- 0.04 x 10(-2) min-1 on the first day of natriuresis [p less than 0.05]). In contrast, no change in creatinine clearance occurred over the same period. A negative curvilinear association was found between sodium balance and the aminopyrine rate constant of elimination in all animals (r = -0.72, p less than 0.001). These observations indicate that natriuresis is related to the recovery of liver function, not to changes in creatinine clearance. In conclusion, the concept of a critical threshold of liver function below which sodium retention occurs has been substantiated in this model of hepatic dysfunction.

Analysis of Variance↗
PubMed1990

The onset of sodium retention in experimental cirrhosis in rats is related to a critical threshold of liver function.

Although sodium retention is a common complication in advanced liver disease, the relationship between liver and kidney function in cirrhosis has not been well established. The objective of this study was to investigate this relationship in an experimental model of cirrhosis induced in phenobarbital-treated rats by weekly intragastric administration of carbon tetrachloride. Liver function, measured by the aminopyrine breath test, and urinary sodium excretion on a constant salt diet, were measured weekly. Administration of carbon tetrachloride led to cirrhosis, sodium retention, ascites and a reduction in liver function as measured by the amino pyrine breath test in all 15 rats surviving the first 8 wk. The time to develop sodium retention (defined as a decrease in urinary sodium excretion rate to less than 0.3 mmol/24 hr) varied from 9 to 19 wk. The aminopyrine breath test rate constant of elimination was reduced from 24 x 10(-3) min-1 +/- 2 x 10(-3) min-1 at the start of carbon tetrachloride administration by 61% +/- 10% at the time sodium retention occurred. A linear decrease was seen in aminopyrine breath test rate constant of elimination in the weeks preceding the onset of sodium retention. Sodium retention occurred when aminopyrine breath test rate contant of elimination was reduced to a critical threshold of 10 x 10(-3) +/- 1 x 10(-3) min-1, and then permitted to recover above this level by withdrawal of carbon tetrachloride. Sodium retention occurred when the aminopyrine breath test rate constant of elimination fell below the threshold; this was followed by spontaneous diuresis when aminopyrine breath test rate constant of elimination improved above 10 x 10(-3) +/- 1 x 10(-3) min-1.(ABSTRACT TRUNCATED AT 250 WORDS)

Aminopyrine↗
PubMed1990

Renal and systemic hemodynamics in experimental cirrhosis in rats: relation to hepatic function.

The onset of sodium retention in the phenobarbital and carbon tetrachloride model of cirrhosis in the rat is preceded by a linear decrease in hepatic function as measured by the aminopyrine breath test. Sodium retention occurs when liver function decreases below a critical threshold. Changes in systemic hemodynamics may be responsible for initiating the development of renal sodium retention. The objective of this study was to investigate the relationship between hepatic function and systemic and renal hemodynamics of experimental cirrhosis in rats maintained on a constant salt diet. Cirrhosis was induced in phenobarbital-treated rats by weekly administration of carbon tetrachloride. The aminopyrine breath test served as a measure of hepatic function. Three groups of animals were studied to evaluate the contribution of changes in systemic and renal hemodynamics to the onset of sodium retention: a group with sodium retention and aminopyrine breath test results just below the critical threshold, a group without sodium retention and aminopyrine breath test results just above the critical threshold and a phenobarbital-treated control group. In each group, urinary sodium excretion, renal plasma flow, glomerular filtration rate, mean arterial pressure and arterial and renal venous plasma renin activities were determined. A progressive, significant reduction in mean arterial pressure was seen, comparing controls with the other two groups. No differences in renal plasma flow were observed between the three groups, but glomerular filtration rate and filtration fraction were slightly reduced in the sodium-retaining group compared with the non-retaining group and controls.(ABSTRACT TRUNCATED AT 250 WORDS)

Aminopyrine↗
PubMed1990

Role of sodium in protection by extended-spectrum penicillins against tobramycin-induced nephrotoxicity.

Salt depletion is known to potentiate aminoglycoside nephrotoxicity, while salt replacement attenuates it. Recent studies have shown that ticarcillin protects against tobramycin and gentamicin nephrotoxicity. It has been suggested that this protection is due to an interaction between ticarcillin and the aminoglycoside. However, it can also be explained by the salt load associated with ticarcillin administration. This study was conducted to examine this question. Tobramycin was administered to eight groups of rats at 100 mg/kg per day intraperitoneally for 10 days. Group 1 rats were salt depleted, while group 2 rats were on a normal salt diet. Rats in groups 3 through 8 were also salt depleted but received, in addition, the following interventions intraperitoneally: group 3, ticarcillin, 300 mg/kg per day (0.37 to 0.39 meq of Na supplement per day); group 4, ticarcillin, 300 mg per day (1.56 meq of Na supplement per day); group 5, ticarcillin, 300 mg/kg per day, and NaCl supplement (1.17 to 1.19 meq/day), resulting in a total load of 1.56 meq/day; group 6, piperacillin, 400 mg/day (0.76 meq of Na supplement per day and equimolar to the ticarcillin dose [300 mg/day] in group 4 rats); group 7, piperacillin, 400 mg/day, and NaCl supplement (0.8 meq/day) for a total Na load of 1.56 meq/day; and group 8, 1.56 meq of Na per day as NaCl. Rats in groups 2, 4, 5, 7, and 8, which received a normal salt diet or its equivalent Na supplement, had no significant change in creatinine clearance (CLCR) over the 10-day period. The remaining groups sustained significant reductions in CLCR, as follows: group 1, -53.0% (P < 0.05); group 3, -66.2% (P < 0.05); group 6, -79.8% (P < 0.05). A positive correlation was found between the concentration of tobramycin in the kidneys and the percent change in CLCR at the end of the study. Concentrations of drugs in plasma were highest in group 1 rats, lowest in the rats in groups in which protection was observed, and moderately elevated in the remaining groups of rats. The results of this study suggest the following: (i) that the protective effect of ticarcillin against tobramycin nephrotoxicity is secondary to the obligatory sodium load associated with it, (ii) pharmacokinetic and pharmacodynamic interactions between salt and tobramycin are proposed to explain this effect, (iii) the nephrotoxicity of tobramycin is probably related to the degree of accumulation of the drug in the kidney, and (iv) an in vivo interaction between tobramycin and ticarcillin does not contribute to the protective effect of the penicillin but may influence concentrations in plasma, especially under conditions of severe renal impairment.

Animals↗
PubMed1990

[Reflux nephropathy].

A corticopapillary scar is a frequent finding on urography in patients with vesicoureteral reflux. It is considered a typical sign of so-called reflux nepropathy. It develops most frequently in children aged 5-7 years and has a negative impact on the growth of the kidney. In its development three factors participate: ureterovesical reflux, intrarenal reflux associated with so-called refluxing papillas and urinary infection. The inflammatory cicatrical process may affect the whole kidney--small shrivelled kidney--or only a portion of the kidney. The development of scars is explained by the so-called bing-bang theory according to which all refluxing papillae are affected at the same time by the first urinary infection. This position develops in particular in case of inadequate treatment of acute pyelonephritis, Deformity of normal papillae caused by various factors explains, however, the development of renal scars in children aged 8-12 years or even in adults. The growing kidney tolerates poorly not only urinary infections and scar formation but also hydrodynamic disorders associated with vesicoureteral reflux. Therefore it is important to diagnose and treat vesicoureteral reflux already at an early age. For the time being it is important o consider asymptomatic bacteriuria and any urinary infection in children a clinical marker calling for examination for the possible presence of vesicoureteral reflux.

Humans↗
PubMed1990

Interaction between angiotensin II and adenosine in mediating the vasoconstrictor response to intrarenal hypertonic saline infusions in the dog.

Intrarenal artery infusion of hypertonic saline induces a sustained renal vasoconstriction that is most likely mediated by tubuloglomerular feedback. The purpose of this study was to investigate the contribution of angiotensin II and adenosine to this response in normal-salt and salt-deplete states. Intrarenal infusions of hypertonic saline to sodium-deplete dogs caused a renal vaso-constrictor response that was observed between 5 and 10 min into the infusion. This response was attenuated in dogs on a normal-salt diet and in salt-deplete dogs receiving captopril. Intravenous infusion of subpressor doses of angiotensin II to dogs either on a normal-salt intake or on a salt-deplete diet but receiving captopril, restored the vasoconstrictor response to hypertonic saline. The vasoconstrictor response in the presence of an angiotensin II infusion in each of these two groups of dogs was abolished by an intrarenal artery infusion of the adenosine receptor blocker, theophylline. These experiments are consistent with the hypothesis that intrarenal infusion of hypertonic saline enhances the endogenous production of adenosine and that the ability of adenosine to reduce renal blood flow is dependent on the presence of angiotensin II.

Adenosine↗
PubMed1990

Mechanisms of amphotericin B-induced reduction of the glomerular filtration rate: a micropuncture study.

Amphotericin B infusions cause acute reductions in renal plasma flow and glomerular filtration rate. The exact mechanism by which these changes occur has not been identified fully, nor have the effects of the drug on the renal microcirculation been studied adequately. In this study, we examined the effect of intrarenal amphotericin B infusions (0.05 mg/kg/min) on glomerular hemodynamics in the anesthetized rat. Amphotericin B did not affect systemic blood pressure and slightly increased hematocrit (5%), but significantly decreased renal blood flow and glomerular filtration rate by 40 and 35%, respectively. Glomerular micropuncture revealed decreases in single nephron plasma flow and glomerular filtration rate (from 142 +/- 12 to 89 +/- 14 and from 35.3 +/- 2.2 to 22.8 +/- 2.8 nl/min, respectively). These changes were due to significant increases in pre- and postglomerular resistances (from 1.91 +/- 0.17 to 3.95 +/- 0.38 and from 1.30 +/- 0.10 to 2.08 +/- 0.12 10(10) dyn.sec.cm-5, respectively), and to a significant decrease in the glomerular capillary ultrafiltration coefficient which fell from 0.043 +/- 0.008 to 0.032 +/- 0.009 nl/(sec.mm Hg). These results provide further insight into the mechanisms of the acute renal effects of amphotericin B, and suggest possible mediators that may be involved in these effects.

Amphotericin B↗
PubMed1989

Role of sodium in the protective effect of ticarcillin on gentamicin nephrotoxicity in rats.

Coadministration of sodium ticarcillin with an aminoglycoside is known to reduce the nephrotoxicity of the aminoglycoside. However, it is not known whether the penicillin or the obligatory sodium load confers protection. To investigate this, gentamicin has been administered intraperitoneally in doses of 50, 60, or 80 mg/kg per day for 12 days in groups of rats receiving either a normal or a low sodium intake. Alterations in creatinine clearance have been measured. Salt depletion resulted in an enhanced nephrotoxic response with a shift in the dose-response curve to the left. Administration of sodium ticarcillin to rats with a salt-depleted intake at a dose sufficient to replace sodium intake conferred an equal degree of protection to rats with a normal salt intake. We report that the obligatory salt supplement with ticarcillin is sufficient to account for the renal sparing effect of the combination treatment without having to infer a direct chemical interaction of penicillin with the aminoglycoside.

Animals↗
PubMed1989

Sodium status influences chronic amphotericin B nephrotoxicity in rats.

The nephrotoxic potential of amphotericin B (5 mg/kg per day intraperitoneally for 3 weeks) has been investigated in salt-depleted, normal-salt, and salt-loaded rats. In salt-depleted rats, amphotericin B decreased creatinine clearance linearly with time, with an 85% reduction by week 3. In contrast, in normal-salt rats creatinine clearance was decreased but to a lesser extent at week 2 and 3, and in salt-loaded rats creatinine clearance did not change for 2 weeks and was decreased by 43% at week 3. All rats in the sodium-depleted group had histopathological evidence of patchy tubular cytoplasmic degeneration in tubules that was not observed in any normal-salt or salt-loaded rat. Concentrations of amphotericin B in plasma were not significantly different among the three groups at any time during the study. However, at the end of 3 weeks, amphotericin B levels in the kidneys and liver were significantly higher in salt-depleted and normal-salt rats than those in salt-loaded rats, with plasma/kidney ratios of 21, 14, and 8 in salt-depleted, normal-salt, and salt-loaded rats, respectively. In conclusion, reductions in creatinine clearance and renal amphotericin B accumulation after chronic amphotericin B administration were enhanced by salt depletion and attenuated by sodium loading in rats.

Amphotericin B↗
PubMed1989

Inhibition of renal vasoconstriction induced by intrarenal hypertonic saline by the nonxanthine adenosine antagonist CGS 15943A.

The hypothesis that intrarenal infusions of hypertonic saline induce endogenous release of adenosine to result in renal vasoconstriction has been investigated in salt-deplete dogs using the nonxanthine adenosine receptor antagonist, CGS 15943A. Intrarenal artery infusions of CGS 15943A induced dose-dependent reductions in the renal vasoconstrictor response to bolus doses of adenosine into the renal artery, without altering base-line blood pressure or renal blood flow. Infusion rates of 10 micrograms/min induced an approximate 50% reduction in response, whereas 100 micrograms/min produced a substantially greater response. There was no inhibition of the renal vasoconstrictor response to angiotensin II and norepinephrine by CGS 15943A at a rate of 100 micrograms/min. Changes in RBF after intrarenal infusion of hypertonic saline were compared between further series of salt-deplete dogs receiving intrarenal artery infusions of either vehicle or CGS 15943A (100 micrograms/min). An initial infusion of hypertonic saline to both groups of dogs induced renal vasodilation followed by vasoconstriction. In dogs subsequently infused with CGS 15943A (100 micrograms/min), the initial renal vasodilation response was similar, but there was an abolition of the later vasoconstrictor response. In contrast, the renal blood flow response to hypertonic saline was unchanged in the vehicle-infused dogs. We conclude that CGS 15943A can selectively block the renal blood flow response to exogenous adenosine without altering baseline renal vascular tone and that the ability of CGS 15943A to abolish the renal vasoconstrictor response to intrarenal hypertonic saline is consistent with the hypothesis that endogenous release of adenosine is involved in mediating the reduction in renal blood flow.

Adenosine↗
PubMedDate not supplied

Amphotericin B nephrotoxicity.

The frequency of fungal infections is increasing. Amphotericin B remains the anti-fungal drug of choice for most systemic infections, but a limiting factor for its use is the development of nephrotoxicity. Amphotericin B-induced nephrotoxicity is manifested as azotaemia, renal tubular acidosis, impaired renal concentrating ability and electrolyte abnormalities like hypokalaemia and sodium and magnesium wasting. All these abnormalities occur to varying degrees in almost all patients receiving the drug. Upon withdrawal of therapy renal function gradually returns to baseline, although in some instances permanent damage is sustained, especially when the cumulative dose exceeds 5g. Salt depletion enhances the development of nephrotoxicity. The mechanism of nephrotoxicity involves direct cell membrane actions to increase permeability, as well as indirect effects secondary to activation of intrarenal mechanisms (tubuloglomerular feedback) and/or release of mediators (thromboxane A2). The latter effects are presumably responsible for the observed acute decreases in renal blood flow and filtration rate, responses that are inhibited by several physiological and pharmacological interventions. Changes in intracellular calcium levels may also contribute to the observed effects. In the clinical situation, and in long term models of nephrotoxicity in the rat, salt loading protects against deterioration in renal function; recommendations are made for the optimisation of amphotericin B therapy by salt loading. New preparations of the drug, such as liposomal amphotericin B, may also prove useful in minimising nephrotoxicity while maintaining antifungal activity, but further research is needed with both salt loading and liposomal amphotericin B to confirm or deny their protective effect on kidney function.

Amphotericin B↗