Mycophenolate mofetil-related leukopenia in children and young adults following kidney transplantation: Influence of genes and drugs

Charles D. Varnell; Tsuyoshi Fukuda; Cassie L. Kirby; Lisa J. Martin; Barry L. Warshaw; Hiren P. Patel; Deepa H. Chand; Gina Marie Barletta; Scott K. Van Why; Rene G. VanDeVoorde; Donald J. Weaver; Amy Wilson; Priya S. Verghese; Alexander A. Vinks; Larry A. Greenbaum; Jens Goebel; David K. Hooper

doi:10.1111/petr.13033

Mycophenolate mofetil-related leukopenia in children and young adults following kidney transplantation: Influence of genes and drugs

Charles D. Varnell, Tsuyoshi Fukuda, Cassie L. Kirby, Lisa J. Martin, Barry L. Warshaw, Hiren P. Patel, Deepa H. Chand, Gina Marie Barletta, Scott K. Van Why, Rene G. VanDeVoorde, Donald J. Weaver, Amy Wilson, Priya S. Verghese, Alexander A. Vinks, Larry A. Greenbaum, Jens Goebel, David K. Hooper

Division of Nephrology, Hypertension & Apheresis

Research output: Contribution to journal › Article › peer-review

20 Scopus citations

Abstract

MMF is commonly prescribed following kidney transplantation, yet its use is complicated by leukopenia. Understanding the genetics mediating this risk will help clinicians administer MMF safely. We evaluated 284 patients under 21 years of age for incidence and time course of MMF-related leukopenia and performed a candidate gene association study comparing the frequency of 26 SNPs between cases with MMF-related leukopenia and controls. We matched cases by induction, steroid duration, race, center, and age. We also evaluated the impact of induction and SNPs on time to leukopenia in all cases. Sixty-eight (24%) patients had MMF-related leukopenia, of which 59 consented for genotyping and 38 were matched with controls. Among matched pairs, no SNPs were associated with leukopenia. With non-depleting induction, UGT2B7-900A>G (rs7438135) was associated with increased risk of MMF-related leukopenia (P =.038). Time to leukopenia did not differ between patients by induction agent, but 2 SNPs (rs2228075, rs2278294) in IMPDH1 were associated with increased time to leukopenia. MMF-related leukopenia is common after transplantation. UGT2B7 may influence leukopenia risk especially in patients without lymphocyte-depleting induction. IMPDH1 may influence time course of leukopenia after transplant.

Original language	English
Article number	e13033
Journal	Pediatric transplantation
Volume	21
Issue number	7
DOIs	https://doi.org/10.1111/petr.13033
State	Published - Nov 2017

Keywords

adverse effects
kidney transplantation
leukopenia

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10.1111/petr.13033

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Varnell, C. D., Fukuda, T., Kirby, C. L., Martin, L. J., Warshaw, B. L., Patel, H. P., Chand, D. H., Barletta, G. M., Van Why, S. K., VanDeVoorde, R. G., Weaver, D. J., Wilson, A., Verghese, P. S., Vinks, A. A., Greenbaum, L. A., Goebel, J., & Hooper, D. K. (2017). Mycophenolate mofetil-related leukopenia in children and young adults following kidney transplantation: Influence of genes and drugs. Pediatric transplantation, 21(7), Article e13033. https://doi.org/10.1111/petr.13033

@article{40236f0968ea448e9e9c6f1a2b3be2a7,

title = "Mycophenolate mofetil-related leukopenia in children and young adults following kidney transplantation: Influence of genes and drugs",

abstract = "MMF is commonly prescribed following kidney transplantation, yet its use is complicated by leukopenia. Understanding the genetics mediating this risk will help clinicians administer MMF safely. We evaluated 284 patients under 21 years of age for incidence and time course of MMF-related leukopenia and performed a candidate gene association study comparing the frequency of 26 SNPs between cases with MMF-related leukopenia and controls. We matched cases by induction, steroid duration, race, center, and age. We also evaluated the impact of induction and SNPs on time to leukopenia in all cases. Sixty-eight (24%) patients had MMF-related leukopenia, of which 59 consented for genotyping and 38 were matched with controls. Among matched pairs, no SNPs were associated with leukopenia. With non-depleting induction, UGT2B7-900A>G (rs7438135) was associated with increased risk of MMF-related leukopenia (P =.038). Time to leukopenia did not differ between patients by induction agent, but 2 SNPs (rs2228075, rs2278294) in IMPDH1 were associated with increased time to leukopenia. MMF-related leukopenia is common after transplantation. UGT2B7 may influence leukopenia risk especially in patients without lymphocyte-depleting induction. IMPDH1 may influence time course of leukopenia after transplant.",

keywords = "adverse effects, kidney transplantation, leukopenia",

author = "Varnell, {Charles D.} and Tsuyoshi Fukuda and Kirby, {Cassie L.} and Martin, {Lisa J.} and Warshaw, {Barry L.} and Patel, {Hiren P.} and Chand, {Deepa H.} and Barletta, {Gina Marie} and {Van Why}, {Scott K.} and VanDeVoorde, {Rene G.} and Weaver, {Donald J.} and Amy Wilson and Verghese, {Priya S.} and Vinks, {Alexander A.} and Greenbaum, {Larry A.} and Jens Goebel and Hooper, {David K.}",

note = "Publisher Copyright: {\textcopyright} 2017 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd",

year = "2017",

month = nov,

doi = "10.1111/petr.13033",

language = "English",

volume = "21",

journal = "Pediatric transplantation",

issn = "1397-3142",

number = "7",

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Varnell, CD, Fukuda, T, Kirby, CL, Martin, LJ, Warshaw, BL, Patel, HP, Chand, DH, Barletta, GM, Van Why, SK, VanDeVoorde, RG, Weaver, DJ, Wilson, A, Verghese, PS, Vinks, AA, Greenbaum, LA, Goebel, J & Hooper, DK 2017, 'Mycophenolate mofetil-related leukopenia in children and young adults following kidney transplantation: Influence of genes and drugs', Pediatric transplantation, vol. 21, no. 7, e13033. https://doi.org/10.1111/petr.13033

TY - JOUR

T1 - Mycophenolate mofetil-related leukopenia in children and young adults following kidney transplantation

T2 - Influence of genes and drugs

AU - Varnell, Charles D.

AU - Fukuda, Tsuyoshi

AU - Kirby, Cassie L.

AU - Martin, Lisa J.

AU - Warshaw, Barry L.

AU - Patel, Hiren P.

AU - Chand, Deepa H.

AU - Barletta, Gina Marie

AU - Van Why, Scott K.

AU - VanDeVoorde, Rene G.

AU - Weaver, Donald J.

AU - Wilson, Amy

AU - Verghese, Priya S.

AU - Vinks, Alexander A.

AU - Greenbaum, Larry A.

AU - Goebel, Jens

AU - Hooper, David K.

PY - 2017/11

Y1 - 2017/11

N2 - MMF is commonly prescribed following kidney transplantation, yet its use is complicated by leukopenia. Understanding the genetics mediating this risk will help clinicians administer MMF safely. We evaluated 284 patients under 21 years of age for incidence and time course of MMF-related leukopenia and performed a candidate gene association study comparing the frequency of 26 SNPs between cases with MMF-related leukopenia and controls. We matched cases by induction, steroid duration, race, center, and age. We also evaluated the impact of induction and SNPs on time to leukopenia in all cases. Sixty-eight (24%) patients had MMF-related leukopenia, of which 59 consented for genotyping and 38 were matched with controls. Among matched pairs, no SNPs were associated with leukopenia. With non-depleting induction, UGT2B7-900A>G (rs7438135) was associated with increased risk of MMF-related leukopenia (P =.038). Time to leukopenia did not differ between patients by induction agent, but 2 SNPs (rs2228075, rs2278294) in IMPDH1 were associated with increased time to leukopenia. MMF-related leukopenia is common after transplantation. UGT2B7 may influence leukopenia risk especially in patients without lymphocyte-depleting induction. IMPDH1 may influence time course of leukopenia after transplant.

AB - MMF is commonly prescribed following kidney transplantation, yet its use is complicated by leukopenia. Understanding the genetics mediating this risk will help clinicians administer MMF safely. We evaluated 284 patients under 21 years of age for incidence and time course of MMF-related leukopenia and performed a candidate gene association study comparing the frequency of 26 SNPs between cases with MMF-related leukopenia and controls. We matched cases by induction, steroid duration, race, center, and age. We also evaluated the impact of induction and SNPs on time to leukopenia in all cases. Sixty-eight (24%) patients had MMF-related leukopenia, of which 59 consented for genotyping and 38 were matched with controls. Among matched pairs, no SNPs were associated with leukopenia. With non-depleting induction, UGT2B7-900A>G (rs7438135) was associated with increased risk of MMF-related leukopenia (P =.038). Time to leukopenia did not differ between patients by induction agent, but 2 SNPs (rs2228075, rs2278294) in IMPDH1 were associated with increased time to leukopenia. MMF-related leukopenia is common after transplantation. UGT2B7 may influence leukopenia risk especially in patients without lymphocyte-depleting induction. IMPDH1 may influence time course of leukopenia after transplant.

KW - adverse effects

KW - kidney transplantation

KW - leukopenia

UR - http://www.scopus.com/inward/record.url?scp=85028729570&partnerID=8YFLogxK

U2 - 10.1111/petr.13033

DO - 10.1111/petr.13033

M3 - Article

C2 - 28869324

AN - SCOPUS:85028729570

SN - 1397-3142

VL - 21

JO - Pediatric transplantation

JF - Pediatric transplantation

IS - 7

M1 - e13033

ER -

Mycophenolate mofetil-related leukopenia in children and young adults following kidney transplantation: Influence of genes and drugs

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