| Summary: | A Dissertation submitted to the Faculty of Medicine, University of the Witwatersrand, in fulfillment of the requirements for the degree of Master of Medicine, Johannesburg 2017 === Cryptococcal infections, which occur mainly as opportunistic infection in immunosuppressed patients, contributes 20% to HIV-related mortality especially in resource-limited regions like Sub-Saharan Africa with the number of infected people at 6,100,000 in 2012 in South Africa according to UNAIDS.7 Currently, Amphotericin B deoxycholate forms the cornerstone of all treatment protocols for cryptococcal meningitis, especially in these regions. Amphotericin B deoxycholate, the original formulation, is associated with significant risk of nephrotoxicity with up to 80% of those receiving the drug showing an increase in serum creatinine level, a marker of renal function.10 The availability of the safer lipid formulations of amphotericin B are limited by their costs, more so in resource-limited regions.8 However, in South Africa data on Amphotericin B associated nephrotoxicity is sparse.
Aims The aim of this study is, therefore, to describe nephrotoxicity regarding incidence and outcome in patients with cryptococcal meningitis at Klerksdorp/Tshepong Hospital Complex on Amphotericin B administered per local protocol.
Objectives To define the frequency of acute kidney injury (AKI) on amphotericin B in this cohort of patients who had enough data for analysis. To assess whether electrolyte abnormalities predict AKI by multivariable analysis in the cohort in this study To describe overall outcome based on: Mortality. Progression to chronic kidney disease, as evidenced by un-resolving of renal dysfunction for three months or more.3 Need for acute dialysis. Morbidity related to known sequela of cryptococcal meningitis.
Methods
This is a retrospective observational review of amphotericin B nephrotoxicity in patients with cryptococcal meningitis at Klerksdorp/Tshepong Hospital Complex from July 2013 to June 2014 to describe amphotericin B deoxycholate associated nephrotoxicity.
Name and file numbers for patients who tested positive for cryptococcal meningitis, by either cryptococcal latex antigen or India ink on cerebrospinal fluid, were obtained from national health laboratory service (NHLS). 165 names and file number where retrieved but only 53 had sufficient data for the study.
Results
The files reviewed showed that 83% developed acute kidney injury with 5.66% progressing to chronic kidney disease. However, only 28 participants had a record of follow-up attendance. Mortality was 18.87% with no statistically significant association with acute kidney injury. However, mortality was higher in the acute kidney injury group (9:1). None of the study participants received dialysis. There was also a statistically significant association between being on antiretroviral treatment (Tenofovircontaining regimen) and acute kidney injury. The dose of amphotericin B was positively associated with the development of acute kidney injury. 90.56% of the participants received fluid supplementation per protocol recommendations during amphotericin B therapy.
Conclusion
Amphotericin B is a nephrotoxic drug with the risk of AKI significantly increased in patients on Tenofovir, necessitating ART regimen review before initiating therapy. The treatment protocol should be applied more strictly including correct dose, electrolyte and fluid supplementation to minimize nephrotoxic effects. Cryptococcal meningitis in HIVinfected patients on treatment has a mortality of 18.87% in this cohort which was lower
compared to available literature, which estimates mortality at 30 to 40% on amphotericin B based protocols. 12, 16, 21 This cohort did not reveal any other statistically significant occurrence of long-term complications of cryptococcal meningitis. === XL2018
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