Despite a well-established risk of chronic kidney disease (CKD) after allogeneic hematopoietic cell transplant (AlloHCT), the benefits of using nephrotoxic anti-infective agents to treat serious peri-transplant infections often outweigh this risk. While there is no consensus on the optimal management of post-AlloHCT Human Herpes Virus 6 (HHV6) reactivation, the nephrotoxic drug foscarnet is often used, though its long-term impact on renal function has not been established. We retrospectively reviewed 987 adult patients transplanted between 2002 and 2016, of which 45.3% (n=447) were exposed to foscarnet. The most frequent indications for foscarnet treatment were CMV (n=257, 57.5%) and HHV6 (n=139, 31.1%). In the first 3 months post-transplant, patients exposed vs. unexposed had similar rates of acute kidney injury and acute kidney failure (defined as 3x baseline Creatinine (Cr) or <75% baseline estimated glomerular filtration rate (eGFR), 61.6% vs. 58.7%; p=0.42 and 28.1% vs. 26.6%; p=0.64, respectively. There was no difference in the eGFR at 3 months (p=0.36), but patients treated with foscarnet had significantly lower median eGFRs (mL/min/1.73m) at 6 months (69.3, Interquartile Range [IQR] 51.4 - 92.8 vs. 77.4, IQR 57.3 - 99.3; p=0.009), and 12 months (67.8, IQR 52.7 - 85.0 vs. 80.7, IQR 63.1 - 102.0; p<0.001), respectively. There was also a significant difference in the decline in eGFR from baseline to 12 months (median 32.8, IQR 14.6 - 53.2 vs. 21.9 IQR 6.4 - 37.4; p<0.001), irrespective of the duration of foscarnet treatment. Multivariate analysis revealed that patients treated with foscarnet were more likely to experience a >30% decrease in eGFR from baseline to 12 months compared to those who were not (Odds Ratio 2.30, 95% CI 1.40 – 3.78; p=0.001). We conclude that foscarnet use following AlloHCT had a profound impact on long term renal function independent of other transplant related factors.Copyright © 2020 Elsevier Ltd. All rights reserved.
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Gena G Foster
Michael J Grant
Samantha M Thomas
Blake Cameron
Doug Raiff
Kelly Corbet
Gavin Loitsch
Christopher Ferreri
Mitchell Horwitz
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