Impact of reduced exposure to calcineurin inhibitors on the development of de novo DSA: a cohort of non-immunized first kidney graft recipients between 2007 and 2014
Abstract Background In low-immunological risk kidney transplant recipients (KTRs), reduced exposure to calcineurin inhibitor (CNI) appears particularly attractive for avoiding adverse events, but may increase the risk of developing de novo Donor Specific Antibodies (dnDSA). Methods CNI exposure was...
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| Format: | Article |
| Language: | English |
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BMC
2018-09-01
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| Series: | BMC Nephrology |
| Subjects: | |
| Online Access: | http://link.springer.com/article/10.1186/s12882-018-1014-2 |
| _version_ | 1819017422680621056 |
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| author | S. Girerd J. Schikowski N. Girerd K. Duarte H. Busby N. Gambier M. Ladrière M. Kessler L. Frimat A. Aarnink |
| author_facet | S. Girerd J. Schikowski N. Girerd K. Duarte H. Busby N. Gambier M. Ladrière M. Kessler L. Frimat A. Aarnink |
| author_sort | S. Girerd |
| collection | DOAJ |
| description | Abstract Background In low-immunological risk kidney transplant recipients (KTRs), reduced exposure to calcineurin inhibitor (CNI) appears particularly attractive for avoiding adverse events, but may increase the risk of developing de novo Donor Specific Antibodies (dnDSA). Methods CNI exposure was retrospectively analyzed in 247 non-HLA immunized first KTRs by taking into account trough levels (C0) collected during follow-up. Reduced exposure to CNI was defined as follows: C0 less than the lower limit of the international targets for ≥50% of follow-up. Results During a mean follow-up of 5.0 ± 2.0 years, 39 patients (15.8%) developed dnDSA (MFI ≥1000). Patients with DSA were significantly younger (46.6 ± 13.8 vs. 51.7 ± 14.0 years, p = 0.039), received more frequently poorly-matched grafts (59% with 6–8 A-B-DR-DQ HLA mismatches vs. 34.6%, p = 0.016) and had more frequently a reduced exposure to CNI (92.3% vs. 62.0%, p = 0.0002). Reduced exposure to CNI was associated with an increased risk of dnDSA (multivariable HR = 9.77, p = 0.002). Reduced exposure to CNI had no effect on patient survival, graft loss from any cause including death, or post-transplant cancer. Conclusions Even in a low-immunological risk population, reduced exposure to CNI is associated with increased risk of dnDSA. Benefits and risks of under-immunosuppression must be carefully evaluated before deciding on CNI minimization. |
| first_indexed | 2024-12-21T03:03:17Z |
| format | Article |
| id | doaj.art-a284ade644e9458b8a7a52504285bed0 |
| institution | Directory Open Access Journal |
| issn | 1471-2369 |
| language | English |
| last_indexed | 2024-12-21T03:03:17Z |
| publishDate | 2018-09-01 |
| publisher | BMC |
| record_format | Article |
| series | BMC Nephrology |
| spelling | doaj.art-a284ade644e9458b8a7a52504285bed02022-12-21T19:18:08ZengBMCBMC Nephrology1471-23692018-09-0119111410.1186/s12882-018-1014-2Impact of reduced exposure to calcineurin inhibitors on the development of de novo DSA: a cohort of non-immunized first kidney graft recipients between 2007 and 2014S. Girerd0J. Schikowski1N. Girerd2K. Duarte3H. Busby4N. Gambier5M. Ladrière6M. Kessler7L. Frimat8A. Aarnink9Service de Néphrologie et Transplantation rénale, CHRU Nancy BraboisService de Néphrologie et Transplantation rénale, CHRU Nancy BraboisINSERM, Centre d’Investigations Cliniques Plurithématique 1433, Université de Lorraine, CHRU de Nancy and F-CRIN INI-CRCTINSERM, Centre d’Investigations Cliniques Plurithématique 1433, Université de Lorraine, CHRU de Nancy and F-CRIN INI-CRCTService d’Anatomie pathologique, CHRU Nancy BraboisService de Pharmacologie-Toxicologie, CHRU Nancy BraboisService de Néphrologie et Transplantation rénale, CHRU Nancy BraboisService de Néphrologie et Transplantation rénale, CHRU Nancy BraboisService de Néphrologie et Transplantation rénale, CHRU Nancy BraboisLaboratoire d’Histocompatibilité, CHRU Nancy BraboisAbstract Background In low-immunological risk kidney transplant recipients (KTRs), reduced exposure to calcineurin inhibitor (CNI) appears particularly attractive for avoiding adverse events, but may increase the risk of developing de novo Donor Specific Antibodies (dnDSA). Methods CNI exposure was retrospectively analyzed in 247 non-HLA immunized first KTRs by taking into account trough levels (C0) collected during follow-up. Reduced exposure to CNI was defined as follows: C0 less than the lower limit of the international targets for ≥50% of follow-up. Results During a mean follow-up of 5.0 ± 2.0 years, 39 patients (15.8%) developed dnDSA (MFI ≥1000). Patients with DSA were significantly younger (46.6 ± 13.8 vs. 51.7 ± 14.0 years, p = 0.039), received more frequently poorly-matched grafts (59% with 6–8 A-B-DR-DQ HLA mismatches vs. 34.6%, p = 0.016) and had more frequently a reduced exposure to CNI (92.3% vs. 62.0%, p = 0.0002). Reduced exposure to CNI was associated with an increased risk of dnDSA (multivariable HR = 9.77, p = 0.002). Reduced exposure to CNI had no effect on patient survival, graft loss from any cause including death, or post-transplant cancer. Conclusions Even in a low-immunological risk population, reduced exposure to CNI is associated with increased risk of dnDSA. Benefits and risks of under-immunosuppression must be carefully evaluated before deciding on CNI minimization.http://link.springer.com/article/10.1186/s12882-018-1014-2Kidney transplantationCalcineurin inhibitorsDonor specific antibodiesUnder immunosuppression |
| spellingShingle | S. Girerd J. Schikowski N. Girerd K. Duarte H. Busby N. Gambier M. Ladrière M. Kessler L. Frimat A. Aarnink Impact of reduced exposure to calcineurin inhibitors on the development of de novo DSA: a cohort of non-immunized first kidney graft recipients between 2007 and 2014 BMC Nephrology Kidney transplantation Calcineurin inhibitors Donor specific antibodies Under immunosuppression |
| title | Impact of reduced exposure to calcineurin inhibitors on the development of de novo DSA: a cohort of non-immunized first kidney graft recipients between 2007 and 2014 |
| title_full | Impact of reduced exposure to calcineurin inhibitors on the development of de novo DSA: a cohort of non-immunized first kidney graft recipients between 2007 and 2014 |
| title_fullStr | Impact of reduced exposure to calcineurin inhibitors on the development of de novo DSA: a cohort of non-immunized first kidney graft recipients between 2007 and 2014 |
| title_full_unstemmed | Impact of reduced exposure to calcineurin inhibitors on the development of de novo DSA: a cohort of non-immunized first kidney graft recipients between 2007 and 2014 |
| title_short | Impact of reduced exposure to calcineurin inhibitors on the development of de novo DSA: a cohort of non-immunized first kidney graft recipients between 2007 and 2014 |
| title_sort | impact of reduced exposure to calcineurin inhibitors on the development of de novo dsa a cohort of non immunized first kidney graft recipients between 2007 and 2014 |
| topic | Kidney transplantation Calcineurin inhibitors Donor specific antibodies Under immunosuppression |
| url | http://link.springer.com/article/10.1186/s12882-018-1014-2 |
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