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Effect of Calcineurin Inhibitor-Free Everolimus-Based Immunosuppressive Regimen on Albuminuria and Glomerular Filtration Rate after Heart Transplantation

Nelson, Lærke M.; Andreassen, Arne K.; Andersson, Bert; Gude, Einar; Eiskjær, Hans; Rådegran, Göran LU ; Dellgren, Göran; Gullestad, Lars and Gustafsson, F (2017) In Transplantation 101(11). p.2793-2800
Abstract

BACKGROUND: Albuminuria in maintenance heart transplantation (HTx) is associated with poor renal response when switching to a calcineurin inhibitor (CNI)-lowered or free immunosuppressive regimen using everolimus (EVR), but the significance of albuminuria associated with EVR treatment after early CNI withdrawal in de novo HTx is unknown. METHODS: We tested if glomerular filtration rate (mGFR, measured by CrEDTA clearance) was associated with urine albumin/creatinine ratio (UACR) post-HTx in a subgroup of patients included in the SCHEDULE trial, where de novo HTx patients (n=115) were randomized to EVR with complete CNI elimination 7–11 weeks post-HTx or standard CNI immunosuppression. RESULTS: In 66 patients UACR measures were available... (More)

BACKGROUND: Albuminuria in maintenance heart transplantation (HTx) is associated with poor renal response when switching to a calcineurin inhibitor (CNI)-lowered or free immunosuppressive regimen using everolimus (EVR), but the significance of albuminuria associated with EVR treatment after early CNI withdrawal in de novo HTx is unknown. METHODS: We tested if glomerular filtration rate (mGFR, measured by CrEDTA clearance) was associated with urine albumin/creatinine ratio (UACR) post-HTx in a subgroup of patients included in the SCHEDULE trial, where de novo HTx patients (n=115) were randomized to EVR with complete CNI elimination 7–11 weeks post-HTx or standard CNI immunosuppression. RESULTS: In 66 patients UACR measures were available at 1 year. In 7 patients in the EVR group a CNI was reintroduced within 12 months. Median mGFR was significantly higher in the EVR group both 1 and 3 years post-HTx (p=0.0004, p=0.03). Median UACR at 1 year was significantly higher in the EVR group (p=0.002). There was no correlation between log(UACR) at 1 year and mGFR at 1 or 3 years (r=−0.01, p=0.9; r=0.15, p=0.26), and in the EVR group nor between log(UACR) at 1 year and change in mGFR (Δ1-3 years) (r=0.27, p=0.14). Excluding patients in the EVR group in whom a CNI was reintroduced did not significantly change the results. CONCLUSIONS: The effects of EVR with early CNI withdrawal after HTx on albuminuria and renal function appear dissociated; hence the clinical significance of albuminuria in this setting is uncertain and should not necessarily rule out EVR-based immunosuppression.

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author
organization
publishing date
type
Contribution to journal
publication status
published
subject
in
Transplantation
volume
101
issue
11
pages
2793 - 2800
publisher
Lippincott Williams & Wilkins
external identifiers
  • scopus:85013656532
  • wos:000417235900034
ISSN
0041-1337
DOI
10.1097/TP.0000000000001706
language
English
LU publication?
yes
id
de5c6761-e706-4cf2-adb4-0c41d7ffbe5b
date added to LUP
2017-03-13 11:22:00
date last changed
2018-01-16 13:24:45
@article{de5c6761-e706-4cf2-adb4-0c41d7ffbe5b,
  abstract     = {<p>BACKGROUND: Albuminuria in maintenance heart transplantation (HTx) is associated with poor renal response when switching to a calcineurin inhibitor (CNI)-lowered or free immunosuppressive regimen using everolimus (EVR), but the significance of albuminuria associated with EVR treatment after early CNI withdrawal in de novo HTx is unknown. METHODS: We tested if glomerular filtration rate (mGFR, measured by CrEDTA clearance) was associated with urine albumin/creatinine ratio (UACR) post-HTx in a subgroup of patients included in the SCHEDULE trial, where de novo HTx patients (n=115) were randomized to EVR with complete CNI elimination 7–11 weeks post-HTx or standard CNI immunosuppression. RESULTS: In 66 patients UACR measures were available at 1 year. In 7 patients in the EVR group a CNI was reintroduced within 12 months. Median mGFR was significantly higher in the EVR group both 1 and 3 years post-HTx (p=0.0004, p=0.03). Median UACR at 1 year was significantly higher in the EVR group (p=0.002). There was no correlation between log(UACR) at 1 year and mGFR at 1 or 3 years (r=−0.01, p=0.9; r=0.15, p=0.26), and in the EVR group nor between log(UACR) at 1 year and change in mGFR (Δ1-3 years) (r=0.27, p=0.14). Excluding patients in the EVR group in whom a CNI was reintroduced did not significantly change the results. CONCLUSIONS: The effects of EVR with early CNI withdrawal after HTx on albuminuria and renal function appear dissociated; hence the clinical significance of albuminuria in this setting is uncertain and should not necessarily rule out EVR-based immunosuppression.</p>},
  author       = {Nelson, Lærke M. and Andreassen, Arne K. and Andersson, Bert and Gude, Einar and Eiskjær, Hans and Rådegran, Göran and Dellgren, Göran and Gullestad, Lars and Gustafsson, F},
  issn         = {0041-1337},
  language     = {eng},
  month        = {02},
  number       = {11},
  pages        = {2793--2800},
  publisher    = {Lippincott Williams & Wilkins},
  series       = {Transplantation},
  title        = {Effect of Calcineurin Inhibitor-Free Everolimus-Based Immunosuppressive Regimen on Albuminuria and Glomerular Filtration Rate after Heart Transplantation},
  url          = {http://dx.doi.org/10.1097/TP.0000000000001706},
  volume       = {101},
  year         = {2017},
}