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Combination of Leflunomide and Everolimus for treatment of BK virus nephropathy.

Abstract BK nephropathy (BKN) is a common cause of graft dysfunction following kidney transplantation. Minimization of immunosuppressive therapy remains the first line of therapy, but this may lead to rejection and graft loss. In some cases, despite lowering immunosuppression, BK infection can persist, leading to chronic damage and kidney failure. Currently, there is no specific anti-BK viral therapy. Recent in vitro experiments have demonstrated a reduction in BK viral replication when infected cells are treated with the combination of Leflunomide and Everolimus. This study aims to explore the effect of this drugs combination on viral clearance and graft function in patients with persistent disease despite reduction in immunosuppression. We treated three patients with combination Leflunomide and Everolimus. Data on medical history, biochemical parameters and viral loads were collected. Significant improvement in viral loads was observed in two cases with resolution of viremia in another (Table 1). Two recipients had preserved allograft function. The remaining graft was lost because of combination of obstruction and BKN. No adverse reactions such as bone marrow toxicity were observed. Combination of Leflunomide and Everolimus is safe and should be considered as a rescue therapy in treatment of BKN, especially in those who fail to clear this infection despite reduction of immunosuppressive therapy.
PMID
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Authors

Mayor MeshTerms
Keywords

BK nephropathy

Everolimus

Leflunomide

polyomavirus

Journal Title nephrology (carlton, vic.)
Publication Year Start




PMID- 28247521
OWN - NLM
STAT- MEDLINE
DA  - 20170301
DCOM- 20170313
LR  - 20170313
IS  - 1440-1797 (Electronic)
IS  - 1320-5358 (Linking)
VI  - 22
IP  - 4
DP  - 2017 Apr
TI  - Combination of Leflunomide and Everolimus for treatment of BK virus nephropathy.
PG  - 326-329
LID - 10.1111/nep.12948 [doi]
AB  - BK nephropathy (BKN) is a common cause of graft dysfunction following kidney
      transplantation. Minimization of immunosuppressive therapy remains the first line
      of therapy, but this may lead to rejection and graft loss. In some cases, despite
      lowering immunosuppression, BK infection can persist, leading to chronic damage
      and kidney failure. Currently, there is no specific anti-BK viral therapy. Recent
      in vitro experiments have demonstrated a reduction in BK viral replication when
      infected cells are treated with the combination of Leflunomide and Everolimus.
      This study aims to explore the effect of this drugs combination on viral
      clearance and graft function in patients with persistent disease despite
      reduction in immunosuppression. We treated three patients with combination
      Leflunomide and Everolimus. Data on medical history, biochemical parameters and
      viral loads were collected. Significant improvement in viral loads was observed
      in two cases with resolution of viremia in another (Table 1). Two recipients had 
      preserved allograft function. The remaining graft was lost because of combination
      of obstruction and BKN. No adverse reactions such as bone marrow toxicity were
      observed. Combination of Leflunomide and Everolimus is safe and should be
      considered as a rescue therapy in treatment of BKN, especially in those who fail 
      to clear this infection despite reduction of immunosuppressive therapy.
CI  - (c) 2017 Asian Pacific Society of Nephrology.
FAU - Jaw, Juli
AU  - Jaw J
AD  - Department of Nephrology, St Vincent's Hospital Melbourne, Melbourne, Victoria,
      Australia.
FAU - Hill, Prue
AU  - Hill P
AD  - Department of Anatomical Pathology, St Vincent's Hospital Melbourne, Melbourne,
      Victoria, Australia.
FAU - Goodman, David
AU  - Goodman D
AD  - Department of Nephrology, St Vincent's Hospital Melbourne, Melbourne, Victoria,
      Australia.
LA  - eng
PT  - Case Reports
PT  - Journal Article
PL  - Australia
TA  - Nephrology (Carlton)
JT  - Nephrology (Carlton, Vic.)
JID - 9615568
RN  - 0 (Immunosuppressive Agents)
RN  - 0 (Isoxazoles)
RN  - 9HW64Q8G6G (Everolimus)
RN  - G162GK9U4W (leflunomide)
SB  - IM
MH  - Aged
MH  - BK Virus/*drug effects/immunology
MH  - Drug Substitution
MH  - Drug Therapy, Combination
MH  - Everolimus/*therapeutic use
MH  - Female
MH  - Graft Rejection/immunology/prevention & control/virology
MH  - Graft Survival/drug effects
MH  - Humans
MH  - Immunocompromised Host
MH  - Immunosuppressive Agents/adverse effects/*therapeutic use
MH  - Isoxazoles/*therapeutic use
MH  - Kidney Transplantation/*adverse effects
MH  - Male
MH  - Middle Aged
MH  - Opportunistic Infections/diagnosis/*drug therapy/immunology/virology
MH  - Polyomavirus Infections/diagnosis/*drug therapy/immunology/virology
MH  - Time Factors
MH  - Treatment Outcome
MH  - Tumor Virus Infections/diagnosis/*drug therapy/immunology/virology
MH  - Viral Load
OTO - NOTNLM
OT  - *BK nephropathy
OT  - *Everolimus
OT  - *Leflunomide
OT  - *polyomavirus
EDAT- 2017/03/02 06:00
MHDA- 2017/03/14 06:00
CRDT- 2017/03/02 06:00
PHST- 2016/07/20 [received]
PHST- 2016/10/09 [revised]
PHST- 2016/10/11 [accepted]
AID - 10.1111/nep.12948 [doi]
PST - ppublish
SO  - Nephrology (Carlton). 2017 Apr;22(4):326-329. doi: 10.1111/nep.12948.

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