Immunosenescence as a reason of individualizing immunosuppressive therapy in kidney transplantation

Transplantation in elderly patients is obviously more challenging due to existing underlying diseases, changes in pharmacokinetics of immunosuppressive drugs, polypragmasy, and transformation of immunoreactivity (immunosenescence). Our review presents data on modification of adaptive and innate immunity during aging. It also considers the possibility of both reduced and adapted immunosuppressive therapy in elderly renal transplant recipients in achieving an optimal balance between efficacy and complications.

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Higher CD19+CD25+ Bregs are independently associated with better graft function in renal transplant recipients

BMC Nephrology ◽

10.1186/s12882-021-02374-2 ◽

2021 ◽

Vol 22 (1) ◽

Author(s):

Eman H. Ibrahim ◽

Mostafa G. Aly ◽

Gerhard Opelz ◽

Christian Morath ◽

Martin Zeier ◽

...

Keyword(s):

Renal Transplant ◽

B Cell ◽

Graft Function ◽

Cell Subset ◽

Immunosuppressive Drugs ◽

Renal Transplant Recipients ◽

Healthy Controls ◽

Transplant Recipients ◽

Significant Positive Association ◽

Ifn Γ

Abstract Background The Identification of B cell subsets with regulatory functions might open the way to new therapeutic strategies in the field of transplantation, which aim to reduce the dose of immunosuppressive drugs and prolong the graft survival. CD25 was proposed as a marker of a B-cell subset with an immunosuppressive action termed Bregs. The effect of CD19 + CD25 + Bregs on graft function in renal transplant recipients has not yet been elucidated. We investigated a potential impact of CD19 + CD25 + Bregs on renal graft function as well as a possible interaction of CD19 + CD25 + Bregs with peripheral Tregs in healthy controls, end-stage kidney disease patients (ESKD), and renal transplant recipients. Moreover, we aimed to investigate the association of CD19 + CD25 + Bregs with serum IL-10, TGF-ß1, and IFN-γ in the same study groups. Method Thirty-one healthy controls, ninety renal transplant recipients, and eighteen ESKD patients were enrolled. We evaluated the CD19 + CD25 + Bregs and Treg absolute counts. Next, we investigated CD19 + CD25 + Bregs as predictors of good graft function in multiple regression and ROC analyses. Finally, we evaluated the association between CD19 + CD25+ Bregs and serum IL-10, TGF-ß, and IFN-γ. Results ESKD patients and renal transplant recipients showed lower counts of CD19 + CD25+ Bregs compared to healthy controls (p < 0.001). Higher CD19 + CD25+ Breg counts were independently associated with a better GFR in renal transplant recipients (unstandardized B coefficient = 9, p = 0.02). In these patients, higher CD19 + CD25+ Bregs were independently associated with higher Treg counts (unstandardized B = 2.8, p = 0.004). In ROC analysis, cut-offs for CD19 + CD25 + Breg counts and serum TGF-ß1 of 0.12 cell/μl and 19,635.4 pg/ml, respectively, were shown to provide a good sensitivity and specificity in identifying GFR ≥ 30 ml/min (AUC = 0.67, sensitivity 77%, specificity 43%; AUC = 0.65, sensitivity 81%, specificity 50%, respectively). Finally, a significant positive association between CD19 + CD25+ Bregs and TGF-ß1 was shown in renal transplant recipients (r = 0.255, p = 0.015). Conclusions Our findings indicate that higher counts of CD19 + CD25+ Bregs are independently associated with better renal function and higher absolute Treg counts in renal transplant recipients.

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Tacrolimus-Based Immunosuppressive Therapy Influences Sex Hormone Profile in Renal-Transplant Recipients—A Research Study

Biology ◽

10.3390/biology10080709 ◽

2021 ◽

Vol 10 (8) ◽

pp. 709

Author(s):

Dagmara Szypulska-Koziarska ◽

Aleksandra Wilk ◽

Małgorzata Marchelek-Myśliwiec ◽

Daria Śleboda-Taront ◽

Barbara Wiszniewska

Keyword(s):

Renal Transplant ◽

Immunosuppressive Therapy ◽

Follicle Stimulating Hormone ◽

Plasma Concentrations ◽

Graft Function ◽

Hormonal Status ◽

Renal Transplant Recipients ◽

Transplant Recipients ◽

Study Results ◽

Stimulating Hormone

It is estimated that approximately 20% of couples suffer from infertility worldwide and within renal-transplant recipients, this problem is 10 times more common. An intake of immunosuppressants may lead to hormonal imbalance. The aim of the study was to investigate the influence of tacrolimus-based therapy on the hormonal status of grafted patients. Blood samples were obtained from patients from the Department of Nephrology, Transplantology, and Internal Medicine of Independent Public Clinical Hospital No. 2, Pomeranian Medical University. All 121 patients had stable graft function for over 6 months. The blood plasma concentrations of luteinizing hormone, follicle-stimulating hormone, prolactin, testosterone, estradiol, cortisol were assessed by the electrochemiluminescence method. We observed decreased levels of prolactin (11.9 ng/mL) and cortisol (87.4 μg/mL) in patients under tacrolimus-based therapy. Tacrolimus-based therapy was also associated with increased testosterone and follicle-stimulating hormone in males, 4.04 ng/mL and 6.9 mLU/mL, respectively, and decreased testosterone levels in females, 0.121 ng/mL. We also assessed that immunosuppressive therapy based on tacrolimus is less nephrotoxic in comparison to other regimens. Concluding, tacrolimus-based therapy may influence the hormonal status of transplant recipients in the current study. Results presented here are believed to be helpful for clinicians and patients, especially within the aspect of willingness for biological offspring.

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Side Effects of Transplant Immunosuppressive Therapy in Post Renal Transplant Recipients, Mazandaran, Northern Iran

Zahedan Journal of Research in Medical Sciences ◽

10.5812/zjrms.6560 ◽

2017 ◽

Vol 19 (4) ◽

Author(s):

Abazar Akbarzadeh Pasha ◽

Shayan Alijanpour ◽

Soraya Khafri ◽

Hoshmand Basim ◽

Mehran Afshang

Keyword(s):

Side Effects ◽

Renal Transplant ◽

Immunosuppressive Therapy ◽

Renal Transplant Recipients ◽

Transplant Recipients ◽

Northern Iran

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CD4+CD25+CD127-Foxp3+ and CD8+CD28- Tregs in Renal Transplant Recipients: Phenotypic Patterns, Association With Immunosuppressive Drugs, and Interaction With Effector CD8+ T Cells and CD19+IL-10+ Bregs

Frontiers in Immunology ◽

10.3389/fimmu.2021.716559 ◽

2021 ◽

Vol 12 ◽

Author(s):

Mostafa G. Aly ◽

Eman H. Ibrahim ◽

Hristos Karakizlis ◽

Rolf Weimer ◽

Gerhard Opelz ◽

...

Keyword(s):

Renal Transplant ◽

Negative Impact ◽

Immunosuppressive Drugs ◽

Acute Cellular Rejection ◽

Renal Transplant Recipients ◽

Transplant Recipients ◽

Regulatory Cells ◽

Transplant Patients ◽

Antibody Induction ◽

Cellular Rejection

IntroductionGaps still exist regarding knowledge on regulatory cells in transplant recipients. We studied the phenotypic patterns of CD4+, CD8+CD28- Tregs, and CD19+IL-10+ Bregs in the blood of healthy controls (HC), end-stage kidney disease patients (ESKD), early and late stable renal transplant recipients (Tx), and transplant recipients with steroid-treated acute cellular rejection 1 week–3 months after successful treatment. We also investigated the relationship between immunosuppressive drugs and the aforementioned regulatory cells in transplant recipients.MethodsWe recruited 32 HC, 83 ESKD, 51 early Tx, 95 late Tx, and 9 transplant patients with a recent steroid-treated acute cellular rejection. Besides CD19+IL-10+ Bregs, we analyzed absolute and relative frequencies of CD4+CD25+CD127-Foxp3+ Tregs and CD8+CD28- Tregs and their expression of IL-10, TGF-ß, IFN-g, and Helios.ResultsWe found a negative correlation between absolute CD4+CD25+CD127-Foxp3+ Treg and relative CD19+IL-10+ Breg frequencies in early Tx recipients (r=-0.433, p=0.015, n=31). In that group, absolute CD4+CD25+CD127-Foxp3+ Tregs were negatively associated with steroid dose and tacrolimus trough levels (r=-0.377, p = 0.021, n=37; r=-0.43, p=0.033, n=25, respectively), opposite to IL-10+ Bregs, whose frequency apparently was not negatively affected by potent immunosuppression early posttransplant. We found also lower CD4+CD25+CD127-Foxp3+ Tregs in patients treated with basiliximab or rATG as compared with ESKD patients (p=0.001 and p <0.001, respectively). No difference in absolute IL-10+ Bregs could be detected among these 3 patient groups. Early Tx recipients showed lower CD4+CD25+CD127-Foxp3+ Tregs within 3 months of antibody induction than after 3 months (p = 0.034), whereas IL-10+ Bregs showed higher relative counts during the first 3 months post antibody induction than after 3 months (p = 0.022). Our findings suggest that IL-10+ Bregs decrease with time posttransplantation independent of the effect of antibody induction and dose of other immunosuppressive drugs.ConclusionThese findings suggest that CD19+IL-10+ Bregs and CD4+CD25+CD127-Foxp3+ Tregs behave in opposite ways during the early posttransplant period, possibly due to a predominant negative impact of high doses of immunosuppressants on Tregs. CD19+IL-10+Bregs do not seem to be suppressed by antibody induction and early potent immunosuppression with chemical drugs.

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