Steroid-free immunosuppression after renal transplantation—long-term experience from a single centre

El-Faramawi, Mohamad; Rohr, N; Jespersen, Bente

doi:10.1093/ndt/gfl131

Cited by 16 publications

(12 citation statements)

References 26 publications

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“…PTLD occurred in 1.7% of patients who received kidney transplants between 1996 and 2012 in BC, which is consistent with the range of 1% to 2% that has been reported in the literature. 1 , 7 , 16 - 18 This incidence is not appreciably different from the 6 lymphoma cases Melosky et al reported out of the 478 kidney transplant patients studied between 1986 and 1989. 15 However, Melosky et al followed patients for a mean period of only 26 months, implying a number of late-onset cases were likely not captured, and that the true frequency of PTLD may have been higher than what was reported.…”

Section: Discussionmentioning

confidence: 61%

Posttransplant Lymphoproliferative Disorder in Adults Receiving Kidney Transplantation in British Columbia: A Retrospective Cohort Analysis

Ready

Chernushkin

Partovi

et al. 2018

Can J Kidney Health Dis

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Background:Posttransplant lymphoproliferative disorder (PTLD) is a major complication following kidney transplantation.Objective:We undertook this study to characterize PTLD in kidney transplant patients in British Columbia with regard to incidence, patient and graft survival, histological subtypes, treatment modalities, and management of immunosuppression.Design:Retrospective cohort analysis.Setting:British Columbia.Patients:All adult patients who underwent kidney transplantation in British Columbia between January 1, 1996, and December 31, 2012, were included. Patients less than 18 years of age at the time of first transplant and multiple organ transplant recipients were excluded from analysis.Measurements:Patients with lymphoproliferative disorders that occurred subsequent to kidney transplantation were considered to have developed PTLD.Methods:Cases of PTLD were identified by cross-referencing data abstracted from the provincial transplant agency’s clinical database with the provincial cancer agency’s lymphoma registry. Patients were followed up for the development of PTLD until December 31, 2012, and for outcomes of death and graft failure until December 31, 2014. Data collection was completed via an electronic chart review.Results:Of 2217 kidney transplant recipients, 37 (1.7%) developed PTLD. Nine cases were early-onset PTLD, occurring within 1 year of transplant; of these cases, 6 were known/presumed Epstein-Barr virus mismatch, compared with only 2 of 28 late-onset cases. Patient survival for early-onset PTLD was 100% at 2 years post diagnosis. Late-onset PTLD had survival rates of 71.4% and 67.9% at 1 and 2 years, respectively. PTLD was associated with significantly decreased patient survival (P = .031) and graft survival (uncensored for death, P = .017), with median graft survival of PTLD and non-PTLD patients being 9.5 and 16 years, respectively. Immunosuppressant therapy was reduced in the majority of patients; additional therapies included rituximab monotherapy, CHOP-R, radiation, and surgery.Limitations:Limitations to this study include its retrospective nature and the unknown adherence of patients to prescribed immunosuppressant regimens. In addition, cumulative doses of immunosuppression received and the degree of immunosuppression reduction for PTLD management were not effectively captured.Conclusions:The incidence of PTLD in British Columbia following kidney transplantation was low and consistent with rates reported in the literature. The incidence of late-onset PTLD and its association with reduced patient and graft survival warrant further analysis of patients’ long-term immunosuppression.

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Section: Discussionmentioning

confidence: 61%

Posttransplant Lymphoproliferative Disorder in Adults Receiving Kidney Transplantation in British Columbia: A Retrospective Cohort Analysis

Ready

Chernushkin

Partovi

et al. 2018

Can J Kidney Health Dis

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“…The majority of patients received 100 to 500 mg of intravenous methylprednisolone preoperatively, and treatment with oral prednisolone was started by 20 to 100 mg/d and was tapered to a dose of 7.5 to 10 mg at 3 months and to 5 to 7.5 mg at 9 to 12 months. In the seven patients from Odense University Hospital, no prednisolone treatment was started as part of the routine treatment regimen (20). Rejection episodes, indicated by increased plasma creatinine of 20% or greater for 2 days, or biopsy proven, were treated with intravenous methylprednisolone, 500 mg, for 3 to 5 days.…”

Section: Immunosuppressionmentioning

confidence: 99%

New-Onset Diabetes Mellitus after Kidney Transplantation in Denmark

Hornum

Jørgensen²,

Hansen³

et al. 2010

Clinical Journal of the American Society of Nephrology

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Background and objectives: This study aimed to investigate the development of new-onset diabetes mellitus (NODM) in a prospective study of 97 nondiabetic uremic patients.Design, setting, participants, & measurements: Included were 57 kidney recipients (Tx group, age 39 ؎ 13 years) and 40 uremic patients remaining on the waiting list for kidney transplantation (uremic controls, age 47 ؎ 11 years). All were examined at baseline before possible transplantation and after 12 months. The prevalence of diabetes, prediabetes, insulin sensitivity index (ISI), and insulin secretion index (Isecr) were estimated using an oral glucose tolerance test with measurements of plasma glucose and plasma insulin.Results: One year after transplantation NODM was present in 14% (8 of 57) compared with 5% (2 of 40) in the uremic control group (P ‫؍‬ 0.01). ISI in the Tx group deteriorated from 6.8 ؎ 3.9 before transplantation to 4.9 ؎ 2.8 at 12 months after transplantation (P ‫؍‬ 0.005), and a slight increase in Isecr from 37 ؎ 19 to 46 ؎ 22 (P ‫؍‬ 0.02) was seen. No significant changes occurred in the uremic controls (ISI was 7.9 ؎ 5 and 8.5 ؎ 5, and Isecr was 31 ؎ 17 and 28 ؎ 15). Using multivariate ordinal logistic regression, pre-Tx ISI and age predicted NODM (odds ratios: 0.82, P ‫؍‬ 0.01 and 1.06, P ‫؍‬ 0.02, respectively).Conclusions: One year after kidney transplantation, NODM was present in 14% of patients. This was mainly caused by an increase in insulin resistance and was observed despite improvement in insulin secretion.

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“…Interestingly, 10 years later, similar outcomes were found in both groups with 50% of the recipients maintained under CsA monotherapy from the beginning (58). This percentage increased to 70% when induction and MMF were added (59). More recently, the ATLAS study compared two corticosteroid-free TAC-based protocols (TAC/MMF or Bsx/TAC) to a standard TAC/MMF/corticosteroid regimen (60).…”

Section: Corticosteroid Avoidancementioning

confidence: 99%

Immunosuppression minimization in kidney transplantation

Cantarovich

Vistoli²,

Soulillou³

2008

Front Biosci

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Kidney transplantation is considered the best treatment for patients with end-stage renal failure, even in extreme age-groups. Immunosuppression for "life" is, however, mandatory. This chronic, somewhat unselected, inhibition of the host immune system may induce complications, such as cancer and infection, that could counterbalance the benefits achieved by the transplant. In addition, all currently used immunosuppressors have several side-effects, impeding their long-term use. Consequently, drug associations are frequently tested by different centres according to their own practices, resulting in different survival and tolerance profiles. Corticosteroids and calcineurin inhibitors are the cornerstones of current immunosuppressive regimens. However, they are also the main culprits of adverse-events and side-effects encountered after transplantation. Lowering the doses of each drug, or even eliminating them from the immunosuppressive menu, has been evaluated by many groups over the last two decades. This review summarises a huge number of studies dealing with corticosteroid and calcineurin inhibitor minimization, including withdrawal and avoidance trials. It is hard today to propose any practical guidelines on such a controversial topic. Good results are achieved by some groups and bad results by others. The lack of long-term follow-up in randomized studies contributes to this debate. Nevertheless, it seems possible and safe to avoid corticosteroids and/or calcineurin inhibitors in many patients. The application of protocol biopsies as well as new immunological tests to determine the degree of immunosuppression will certainly help transplant physicians to provide more personalized treatment strategies.

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Steroid-free immunosuppression after renal transplantation—long-term experience from a single centre

Cited by 16 publications

References 26 publications

Posttransplant Lymphoproliferative Disorder in Adults Receiving Kidney Transplantation in British Columbia: A Retrospective Cohort Analysis

Posttransplant Lymphoproliferative Disorder in Adults Receiving Kidney Transplantation in British Columbia: A Retrospective Cohort Analysis

New-Onset Diabetes Mellitus after Kidney Transplantation in Denmark

Immunosuppression minimization in kidney transplantation

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