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Immunosuppressive Agents and Infectious Risk in Transplantation: Managing the "Net State of Immunosuppression".

ABSTRACT: Successful solid organ transplantation reflects meticulous attention to the details of immunosuppression, balancing risks for graft rejection against risks for infection. The "net state of immune suppression" is a conceptual framework of all factors contributing to infectious risk. Assays that measure immune function in the immunosuppressed transplant recipient relative to infectious risk and allograft function are lacking. The best measures of integrated immune function may be quantitative viral loads to assess the individual's ability to control latent viral infections. Few studies address adjustment of immunosuppression during active infections; thus, confronted with infection in solid organ recipients, the management of immunosuppression is based largely on clinical experience. This review examines known measures of immune function and the immunologic effects of common immunosuppressive drugs and available studies reporting modification of drug regimens for specific infections. These data provide a conceptual framework for the management of immunosuppression during infection in organ recipients.

SUBMITTER: Roberts MB

PROVIDER: S-EPMC8561260 | biostudies-literature | 2021 Oct

REPOSITORIES: biostudies-literature

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Immunosuppressive Agents and Infectious Risk in Transplantation: Managing the "Net State of Immunosuppression".

Roberts Matthew B MB Fishman Jay A JA

Clinical infectious diseases : an official publication of the Infectious Diseases Society of America 20211001 7

Successful solid organ transplantation reflects meticulous attention to the details of immunosuppression, balancing risks for graft rejection against risks for infection. The "net state of immune suppression" is a conceptual framework of all factors contributing to infectious risk. Assays that measure immune function in the immunosuppressed transplant recipient relative to infectious risk and allograft function are lacking. The best measures of integrated immune function may be quantitative vira ...[more]

PMID: 32803228

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Project description:Rationale & objectiveDisorders of bone and mineral metabolism frequently develop with advanced kidney disease, may be exacerbated by immunosuppression after kidney transplantation, and increase the risk of fractures.Study designRetrospective database study.Setting & participantsKidney-only transplant recipients aged ≥18 years from 2005 to 2016 in the United States captured in US Renal Data System records, which integrate Organ Procurement and Transplantation Network/United Network for Organ Sharing records with Medicare billing claims.ExposuresVarious immunosuppression regimens in the first 3 months after kidney transplantation.OutcomesThe development of fractures, as ascertained using diagnostic codes on Medicare billing claims.Analytical approachWe used multivariable Cox regression with inverse propensity weighting to compare the incidence of fractures >3 months-to-3 years after kidney transplantation associated with various immunosuppression regimens compared to a reference regimen of antithymocyte globulin (TMG) or alemtuzumab (ALEM) with tacrolimus + mycophenolic acid + prednisone using inverse probability treatment weighting.ResultsOverall, fractures were identified in 7.5% of kidney transplant recipients (women, 8.8%; men, 6.7%; age < 55 years, 5.9%; age ≥ 55 years, 9.3%). In time-varying regression, experiencing a fracture was associated with a substantially increased risk of subsequent death within 3 months (adjusted hazard ratio [aHR], 3.06; 95% confidence interval [CI], 2.45-3.81). Fractures were also associated with increased Medicare spending (first year: $5,122; second year: $10,890; third year: $11,083; [P < 0.001]). Induction with TMG or ALEM and the avoidance or early withdrawal of steroids significantly reduced the risk of fractures in younger (aHR, 0.63; 95% CI, 0.54-0.73) and older (aHR, 0.83; 95% CI, 0.74-0.94) patients. The avoidance or early withdrawal of steroids with any induction was associated with a reduced risk of fractures in women.LimitationsThis was a retrospective study which lacked data on immunosuppression levels.ConclusionsFractures after kidney transplantation are associated with significantly increased mortality risk and costs. The early avoidance or early withdrawal of steroids after induction with TMG or ALEM reduces the risk of fractures after kidney transplantation and should be considered for patients at high-risk of this complication, including older adults and women.

Project description:BackgroundTorque teno virus load (TTVL) is gaining importance as a surrogate parameter to assess immunocompetence in kidney transplant recipients. Although the dynamics of TTVL have been investigated before, the impact of different induction agents and variations in immunosuppressive maintenance therapies on TTVL remain unknown.MethodsIn this retrospective study, TTVL was quantified in 537 plasma or serum samples from 134 patients transplanted between 2018 and 2021. TTVL was examined pre-transplantation and 30-, 90-, 180-, and 360-days post-transplant. To assess the influence of induction therapy on TTVL, 67 patients receiving anti-thymocyte globulin (ATG) induction were matched with 67 patients receiving an interleukin-2 receptor antagonist (IL2-RA) induction in terms of age, sex, and donor modality.ResultsFollowing transplantation, there was a steep increase in TTVL post-transplant for all patients with peak viral loads at 90 days post-transplant (median TTVL [IQR] 7.97×106, [4.50×105-1.12×108]) followed by subsequently declining viral loads. Compared to patients receiving IL2-RA as induction therapy, patients receiving ATG had significantly higher peak viral loads 3 months post-transplant (median TTVL [IQR] 2.82×107 [3.93×106-1.30×108] vs. median TTVL [IQR] 2.40×106 [5.73×104-2.60×107]; P<0.001). Throughout all post-transplant time points, patients receiving additional rituximab for induction along with higher tacrolimus target levels exhibited the highest TTVL.Patients whose TTVL 3-months post-transplant exceeded the currently proposed cutoff to predict infections within the first year post-transplant [6.2 log10] showed a trend towards a higher risk of being hospitalized with an infection in the following 9 months, albeit without being statistically significant (HR=1.642, P=0.07).ConclusionsHigher TTVL reflects the greater immunosuppressive burden in immunological high-risk patients receiving intensive immunosuppression. The choice of induction agent and intensified immunosuppressive maintenance therapy notably affects TTVL at 3 months post-transplant and beyond, necessitating careful consideration when interpreting and applying TTVL cutoffs to monitor immunocompetence post-transplant.

Dataset Information

Immunosuppressive Agents and Infectious Risk in Transplantation: Managing the "Net State of Immunosuppression".

Publications

Immunosuppressive Agents and Infectious Risk in Transplantation: Managing the "Net State of Immunosuppression".

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