Development of proteinuria and focal segmental glomerulosclerosis during direct‐acting antiviral therapy for hepatitis C virus infection

Hogan, Jonathan J.; Lim, Mary Ann; Palmer, Matthew; Bloom, Roy D.; Chung, Raymond T.; Sise, Meghan E.

doi:10.1002/hep.29125

Cited by 21 publications

(11 citation statements)

References 4 publications

(7 reference statements)

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“…Importantly, during this time no patients were noted to develop significant proteinuria or AKI, and none developed HCV‐related kidney disease. This reassuring finding is in accordance with larger series in KT recipients, and in contrast to previously published case reports of proteinuria and focal segmental glomerulosclerosis developing in KT recipients . Finally, it is important to note that no patients developed fibrosing cholestatic hepatitis or other forms of aggressive HCV despite the use of standard induction therapy, including thymoglobulin or basiliximab.…”

Section: Discussionsupporting

confidence: 90%

Liver, simultaneous liver‐kidney, and kidney transplantation from hepatitis C‐positive donors in hepatitis C‐negative recipients: A single‐center study

Crismale

Khalid

Bhansali

et al. 2019

Clinical Transplantation

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Transplantation of organs from hepatitis C virus (HCV)-antibody (Ab) and -nucleic acid test (NAT) positive donors into HCV-negative recipients has been proposed to expand the donor pool and shorten waiting times. Data on early single-center outcomes are lacking. Nineteen liver (LT, including seven simultaneous liver-kidney [SLKT]) and 17 kidney transplant (KT) recipients received organs from HCV (+) donors; of these, 13 were HCV NAT (+) in each group. All patients who received organs from HCV NAT (+) donors developed HCV viremia post-transplant except for 2 KT recipients. Patients were treated with a variety of direct-acting antiviral regimens, with high rates of sustained virologic response among those with at least 12 weeks of follow-up past the end of treatment: 12/13 (92%) and 8/8 (100%) among LT/SLKT, and KT recipients. Median time to treatment start was 42 days (interquartile range[IQR] 35-118 days) and 40 days (IQR 26-73) post-LT/SLKT and KT, respectively. One death occurred in a SLKT recipient unrelated to HCV or its treatment. There was no significant increase in rejection, proteinuria, or changes in immunosuppression in any group. Organs from HCV-viremic donors can be utilized for HCV-uninfected recipients with good short-term outcomes. K E Y W O R D Shepatitis C virus, hepatitis C-positive donors, kidney transplantation, liver transplantation 2 of 11 | CRISMALE Et AL. unacceptable due to the low efficacy and high risks associated with IFN-based therapy post-transplantation. Such organs were therefore reserved for transplantation into those already with HCV infection. Even among these patients, the persistence of HCV infection post-transplantation was associated with poor outcomes and led to worse post-transplant survival. 4,5 However, the advent of highly effective direct-acting antiviral therapy (DAAs) has led to post-transplantation HCV cure rates exceeding 95%, and with it, a negation of the ill effects of HCV previously seen in both LT and KT recipients. 6,7 A number of clinical trials, along with data from the HCV-TARGET cohort, have demonstrated the efficacy and safety of the use of these agents in the post-transplant setting. 8,9 In the HCV-TARGET cohort, adverse events leading to treatment discontinuation were uncommon, affecting only 1.6%. 8 Newer agents, including glecaprevir/ pibrentasvir (GLE/PIB), have similarly been shown to be safe and efficacious. 10 Indeed, recently published data derived from the Scientific Registry of Transplant Recipients (SRTR) suggest equivalent 1-and3-year survival among HCV-infected patients undergoing LT. 6 In the United States, the potential pool of HCV-positive organs is growing, largely due to a rising incidence of HCV in persons who inject drugs. There is significant geographic and demographic overlap between the opioid epidemic and incident HCV infection. 11 Data suggest that up to 52% of HCV-infected individuals are concentrated in 9 US states, the majority of which have a significant burden of patients suffering with opioid addiction. 12 Drug overdose...

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Section: Discussionsupporting

confidence: 90%

Liver, simultaneous liver‐kidney, and kidney transplantation from hepatitis C‐positive donors in hepatitis C‐negative recipients: A single‐center study

Crismale

Khalid

Bhansali

et al. 2019

Clinical Transplantation

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“…In addition, Hogan et al reported three cases of new‐onset nephrotic range proteinuria in the context of DAA treatment post‐kidney transplant. In these cases, the allograft biopsy at 2‐3 months after initiation of DAA revealed focal segmental glomerulosclerosis (FSGS) . Furthermore, the Transplanting Hepatitis C Kidneys into Negative Kidney Recipients [THINKER] trial group reported one case of FSGS after elbasvir/grazoprevir treatment in a patient with a history of IgA nephropathy before transplantation (Table ).…”

Section: Discussionmentioning

confidence: 99%

Recurrent membranous nephropathy and acute cellular rejection in a patient treated with direct anti‐HCV therapy (ledipasvir/sofosbuvir)

Murakami

Ding

Cohen

et al. 2018

Transplant Infectious Dis

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Direct-acting antiviral agents (DAAs) are very effective therapy for chronic hepatitis C infection, and have revolutionized the treatment of hepatitis C in kidney allograft recipients. Although well tolerated in general, rare renal complications have been reported. We describe a case of recurrent membranous nephropathy and acute cellular rejection in a kidney allograft recipient after DAA (ledipasvir/sofosbuvir) therapy, whose allograft function had been stable for more than 30 years. The patient was presented with nephrotic range proteinuria with stable creatinine. The kidney allograft biopsy revealed recurrent membranous nephropathy with fine granular deposits of IgG1/IgG4 codominance and positive phospholipase A2 receptor (PLA2R) staining. The patient was treated with pulse steroid and rituximab, leading to a decrease in proteinuria. As DAAs are more frequently used, physicians should be aware of immune-related renal complications.

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“…One patient developed focal segmental glomerulosclerosis (FSGS) in the transplanted kidney that was possibly related to DAA therapy. It should be noted that FSGS has been noted in patients with chronic HCV undergoing DAA therapy in 2 other series . There is limited data on how patients with FSGS induced by DAAs should be managed, or if discontinuing DAA therapy improves outcomes.…”

Section: Strategies To Increase Utilization Of Hcv‐infected Kidneysmentioning

confidence: 96%

“…It should be noted that FSGS has been noted in patients with chronic HCV undergoing DAA therapy in 2 other series. 32,42 There is limited data on how patients with FSGS induced by DAAs should be managed, or if discontinuing DAA therapy improves outcomes. Once sufficient clinical trial data is available to determine the safety of strategies to transplant HCV infected kidneys into HCV uninfected kidneys the potential expanded use of these organs is listed in this column.…”

Section: Strategies To Increase Utilization Of Hcv-infected Kidneys Tmentioning

confidence: 99%

Transplantation of hepatitis C virus infected kidneys into hepatitis C virus uninfected recipients

Sise

Chute

Gustafson

et al. 2018

Hemodialysis International

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Long wait times for kidney transplant and the high risk of mortality on dialysis have prompted investigation into strategies to increase organ allocation and decrease discard rates of potentially viable kidneys. Organs from hepatitis C virus (HCV) antibody positive donors are often rejected; nearly 500 HCV-infected kidneys are discarded annually in the United States. Due the opioid epidemic, the number of HCV-infected donors has increased because of a rise in both new HCV infections and drug-related deaths. In the past 5 years, HCV has been transformed into a curable illness with direct-acting antiviral therapies (DAAs) that are effective in >95% of patients treated and are extremely well tolerated. Recent data has shown several direct-acting antiviral combinations are safe and effective after kidney transplant, and can achieve the same high cure rate seen in the general population and without increasing the rate of acute rejection. Because of this, strategies to decrease discard of HCV-infected organs have been devised. Two recent studies have transplanted HCV-uninfected dialysis patients with kidneys from donors actively infected with HCV; recipients were treated with DAA in the peri-transplant period. More research is needed to determine the safety and efficacy of this approach, but it has the potential to dramatically increase the donor pool of available kidneys, shorten waitlist times and ultimately decreases mortality in patients waiting for kidney transplant.

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Development of proteinuria and focal segmental glomerulosclerosis during direct‐acting antiviral therapy for hepatitis C virus infection

Cited by 21 publications

References 4 publications

Liver, simultaneous liver‐kidney, and kidney transplantation from hepatitis C‐positive donors in hepatitis C‐negative recipients: A single‐center study

Liver, simultaneous liver‐kidney, and kidney transplantation from hepatitis C‐positive donors in hepatitis C‐negative recipients: A single‐center study

Recurrent membranous nephropathy and acute cellular rejection in a patient treated with direct anti‐HCV therapy (ledipasvir/sofosbuvir)

Transplantation of hepatitis C virus infected kidneys into hepatitis C virus uninfected recipients

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