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Abstract: TH-PO072

Evaluation of Nephrotoxicity of Liposomal Amphotericin in Three Administration Regimens for the Treatment of Disseminated Histoplasmosis in AIDS Patients

Session Information

Category: Acute Kidney Injury

  • 102 AKI: Clinical‚ Outcomes‚ and Trials

Authors

  • Rodovalho Guimaraes, Marilia, University of São Paulo School of Medicine, Sao Paulo, Sao Paulo, Brazil
  • Soares, Renata B A, Pontificia Universidade Catolica de Goias, Goiania, GO, Brazil
  • Sanches, Talita R. C., University of São Paulo School of Medicine, Sao Paulo, Sao Paulo, Brazil
  • Godoy, Cássia Silva de Miranda, Pontificia Universidade Catolica de Goias, Goiania, GO, Brazil
  • Falci, Diego R., Pontificia Universidade Catolica do Rio Grande do Sul, Porto Alegre, RS, Brazil
  • Pasqualotto, Alessandro C., Universidade Federal de Ciencias da Saude de Porto Alegre Faculdade de Medicina, Porto Alegre, RS, Brazil
  • Andrade, Lucia, University of São Paulo School of Medicine, Sao Paulo, Sao Paulo, Brazil
Background

HIV infection is now endemic, and disseminated histoplasmosis (DH) is an AIDS-defining disease. One common treatment for DH is liposomal amphotericin B (LAmB), the main side effect of which is nephrotoxicity.

Methods

The main objective of this study was to compare different L-AmB regimens, in terms of their nephrotoxicity, in patients with HIV/AIDS undergoing induction therapy for the treatment of DH. We conducted a prospective exploratory cohort study, nested within a prospective, multicenter, open phase II experimental study, to analyze the nephrotoxicity of induction therapies for DH in HIV/AIDS, followed by oral therapy with itraconazole. Patients were randomized into 3 arms of LAmB administration: 10 mg/kg, single dose (arm 1); 10 mg/kg on day 1, followed by 5 mg/kg on day 3 (arm 2); and 3 mg/kg for 14 days (arm 3). Before and after treatment, we measured levels of cystatin C (cys-C) and fractional excretion of sodium, as well as fractional excretions of potassium and magnesium (FENa, FEK and FEMg, respectively). Means, standard deviations and odds ratios were calculated.

Results

We selected 90 hospitalized patients, each of whom were randomly assigned to one of the three arms (n = 30/arm). There were no statistical differences among the arms regarding patient sex, age, CD4 count or viral load (VL). The mean age was 42 years, and 80% of the patients were men. Of the 90 patients evaluated, 18 (20%) died during hospitalization. The mean VL was 776,243 copies/mm3, and the mean CD4 count was 89±120 cells/mm3. Tubular toxicity was greatest in arm 3, FENa and FEMg being increased in 100% of the patients, whereas FEK was increased in 66%. The values of cys-C were higher than were the creatinine values and correlated more strongly with tubular dysfunction (p<0.001). In arm 1, the increases in FENa and FEMg presented an OR of 12.1 for AKI over a 7-day interval.

Conclusion

The 14-day LAmB infusion regimen proved to be more toxic to the renal tubule than did the two other regimens evaluated. Tubular dysfunction with increased FENa and FEMg appears to correlate well with AKI, and cys-C appears to more sensitive than creatinine for predicting AKI.

Funding

  • Government Support – Non-U.S.