Foscarnet Nephrotoxicity: Mechanism, Incidence and Prevention

Deray, Gilbert; Martinez, F.; Katlama, Christine; Levaltier, B.; Beaufils, H; Danis, M; Rozenheim, M; Baumelou, A; Dohin, Elisabeth; Gentilini, M

doi:10.1159/000167987

Cited by 210 publications

(83 citation statements)

References 22 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…The relationship of renal insufficiency to foscarnet use was considered possible in 4 of these 5 patients and was judged unevaluatable in the other. The frequency and severity ofrenal toxicity in our study was in the range ofthat in other studies ofallogeneic BMT recipients and AIDS patients [24,25,[28][29][30][31][32].…”

Section: Discussionsupporting

confidence: 62%

“…In that study, only 1 (4%) of27 patients with AIDS and CMV retinitis who received foscarnet with hydration developed acute renal failure. Peak serum creatinine levels in this group of patients were significantly lower than in a historical control group that had received the same foscarnet regimen without hydration [32]. Reduction of renal toxicity would allow a larger proportion of BMT recipients to receive a full course of foscarnet prophylaxis, which may reduce the incidence of CMV infection after transplant.…”

Section: Discussionmentioning

confidence: 80%

“…A recent study suggests that renal toxicity associated with the use offoscarnet can be prevented by hydration with intravenous isotonic saline given daily during treatment [32]. In that study, only 1 (4%) of27 patients with AIDS and CMV retinitis who received foscarnet with hydration developed acute renal failure.…”

Section: Discussionmentioning

confidence: 99%

See 2 more Smart Citations

Phase I-II Trial of Foscarnet for Prevention of Cytomegalovirus Infection in Autologous and Allogeneic Marrow Transplant Recipients

Reusser

Gambertoglio

Lilleby

et al. 1992

Journal of Infectious Diseases

View full text Add to dashboard Cite

The safety and efficacy of foscarnet for prevention of cytomegalovirus (CMV) infection was evaluated in 19 CMV-seropositive bone marrow transplant (BMT) recipients. All patients received intermittent intravenous (iv) foscarnet: 40 mg/kg every 8 h from 7 days before to day 30 after BMT, then 60 mg/kg once a day until day 75. The main toxicity was transient renal dysfunction, with a >50 pmol/L increase in serum creatinine above baseline in 5 of the 7 autograft recipients and in 6 of the 12 allograft recipients. Only 4 allograft recipients developed CMV infection during foscarnet prophylaxis, and no patient showed evidence ofCMV disease. Because 3 allograft recipients receiving concomitant iv amphotericin B showed rapid impairment of renal function, foscarnet prophylaxis should not be given to allograft recipients requiring amphotericin B; otherwise, foscarnet prophylaxis at this dose appears safe after BMT.Infection due to cytomegalovirus (CMV) causes significant morbidity and mortality among bone marrow transplant (BMT) recipients [1]. In two published series, the probability ofCMV infection within the first 100 days after BMT among patients who were CMV-seropositive before transplant was up to 80%and 60%for allograft and autograft recipients, respectively [2,3]. Mortality was primarily related to CMV pneumonia, which developed in 37% of allograft and in 22% of autograft recipients who had evidence of active CMV infection [2,3]. Thus, the prevention of CMV infection and disease after BMT is of foremost importance.Antiviral chemotherapy aimed at preventing reactivation of latent virus may be the most promising approach to CMV prophylaxis both among CMV-seropositive autograft and allograft recipients and among seronegative allograft recipients who have a seropositive marrow donor. CMV drug prophylaxis should cover the early period after BMT in which a deficiency in CMV-specific immunity can contribute to the risk of severe CMV disease [4].The antiviral agent acyclovir given intravenously at high doses was shown to be partially effective in preventing CMV infection and disease among seropositive BMT recipients [5].

show abstract

Section: Discussionsupporting

confidence: 62%

Section: Discussionmentioning

confidence: 80%

See 1 more Smart Citation

Phase I-II Trial of Foscarnet for Prevention of Cytomegalovirus Infection in Autologous and Allogeneic Marrow Transplant Recipients

Reusser

Gambertoglio

Lilleby

et al. 1992

Journal of Infectious Diseases

View full text Add to dashboard Cite

show abstract

“…It is used in immune-compromised patients with life-threatening herpes simplex or cytomegalovirus infections [98,99]. Intensive IV hydration dramatically reduces the incidence of foscarnet-induced acute kidney injury [100]. Foscarnet can lead to acute tubular toxicity; rarely, a direct effect on tubular function can be detected, which may lead to mitochondrial dysfunction, inducing mitochondrial DNA (mtDNA) in renal tubule cells [101].…”

Section: Foscarnetmentioning

confidence: 99%

Drug-induced acid-base disorders

et al. 2014

View full text Add to dashboard Cite

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

show abstract

“…Prehydration with intravenous saline reduces the risk of nephrotoxicity. 24 In a previous study we have shown that foscarnet can prevent CMV infections in patients receiving T celldepleted grafts. 18 We are now reporting a dose-finding study for CMV prophylaxis, designed to test: (a) safety and tolerability of foscarnet; (b) efficacy in preventing CMV Bone Marrow Transplantation disease; and (c) influence of foscarnet prophylaxis on engraftment kinetics.…”

mentioning

confidence: 97%

Foscarnet prophylaxis of cytomegalovirus infections in patients undergoing allogeneic bone marrow transplantation (BMT): a dose-finding study

Bregante

Bertilson

Tedone

et al. 2000

Bone Marrow Transplant

View full text Add to dashboard Cite

Summary:This is a dose-finding study using foscarnet for CMV prophylaxis after allogeneic bone marrow transplantation (BMT) in 20 high risk patients (unrelated donors, or T cell depleted, and/or advanced disease). Foscarnet was started on day ؉1 after BMT and continued until day ؉100. We explored four different dose levels, patients being entered at the lowest dose level until one patient experiences CMV-reactivation, identified as two consecutive positive CMV antigenemias (CMVAgemia). The four dose levels expressed as mg/kg/day between days 1 and 30 (induction) and between days 31 and 100 (maintenance) were respectively: dose level I ‫؍‬ 60/30 (n ‫؍‬ 5); dose level II ‫؍‬ 120/60 (n ‫؍‬ 4); dose level III ‫؍‬ 120/90 (n ‫؍‬ 5) and dose level IV ‫؍‬ 120/120 (n ‫؍‬ 6). All patients showed engraftment: PMN Ն0.5 ؋ 10 9 /l at a median interval of 16, 21, 17, 15 days after BMT, and Plt у30 ؋ 10 9 /l on days 19, 16, 17, 17 respectively. CMVAg-emia was seen in 10 patients at a median interval of 53 days post-BMT (range 33-89) with a median of 10 CMV antigen؉ cells (range 1-16). There was a dose effect of foscarnet on CMVAg-emia: respectively 4/5 patients (80%), 2/4 (50%), 3/5 (60%) and 1/6 (18%) at dose levels I, II, III, IV (P ‫؍‬ 0.1). CMV disease was seen in 3/9 (33%) at dose levels I, II and 0/11 at dose levels III, IV (P ‫؍‬ 0.07). The median number of CMV antigen-positive cells at diagnosis of CMV infection was different: 13 in dose levels I-II and two in dose levels III-IV (P ‫؍‬ 0.01). Increased creatininine was seen in 15 patients with a mean of 1.8 mg% (range 1.5-5.7) and was the cause of discontinuation in nine patients (45%). Renal toxicity was reversible in all nine patients. Overall actuarial TRM at 2 years was 31%: 47% for patients at dose levels I-II and 19% for patients at dose levels III-IV. In conclusion, foscarnet exhibits a dose-dependent prophylactic effect on CMVAg-emia, CMV disease and transplant-related mortality with acceptable and reversible renal toxicity. Bone Marrow Transplantation

show abstract

Foscarnet Nephrotoxicity: Mechanism, Incidence and Prevention

Cited by 210 publications

References 22 publications

Phase I-II Trial of Foscarnet for Prevention of Cytomegalovirus Infection in Autologous and Allogeneic Marrow Transplant Recipients

Phase I-II Trial of Foscarnet for Prevention of Cytomegalovirus Infection in Autologous and Allogeneic Marrow Transplant Recipients

Drug-induced acid-base disorders

Foscarnet prophylaxis of cytomegalovirus infections in patients undergoing allogeneic bone marrow transplantation (BMT): a dose-finding study

Contact Info

Product

Resources

About