Graft Survival In Transplant Recipients Research Articles

Impact of Mannose-Binding Lectin (MBL) on Graft Survival in Transplant Recipients with IgAN

Impact of Mannose-Binding Lectin (MBL) on Graft Survival in Transplant Recipients with IgAN

Memories of rejection

Transplantation Long-term graft survival after organ transplantation can be hindered by immune-mediated allograft rejection; therefore, understanding these immune responses is crucial to developing new transplant-supporting therapies. Tissue-resident memory T cells (TRMs), a subset of memory T cells that reside in barrier tissues and do not recirculate, are detectable in transplanted organs, but it is unclear whether they contribute to allograft rejection. Abou-Daya et al. created a mouse model of T cell–mediated kidney transplant rejection, showing that adoptively transferred, kidney antigen–specific effector T cells differentiated into functional, nonrecirculating antigen-specific TRMs in the transplanted kidneys. These kidney antigen–specific TRMs induced allograft rejection. Targeting alloreactive TRMs might improve long-term graft survival in transplant recipients. Sci. Immunol. 6 , eabc8122 (2021).

DelCFHR3-1 influences graft survival in transplant patients with IgA nephropathy via complement-mediated cellular senescence.

IgA nephropathy (IgAN) is a frequent cause of chronic kidney disease (CKD) and progressive renal impairment. A native renal biopsy diagnosis of IgAN is a predictor of graft loss, with a relative risk of 47% but it is difficult to predict graft survival and progressive allograft dysfunction in these patients. Deletion of complement factor H-related genes 1 and 3 (delCFHR3-1) has been associated with a decreased risk of developing IgAN on native kidneys, but the impact on the graft in IgAN-transplanted patients is unknown. We hypothesized that delCFHR3-1 is also associated with the processes that influence graft survival in transplant recipients with IgAN and tested whether cellular senescence is involved in mediating graft damage. We found that patients carrying two copies of CFHR1-3 had a worse outcome (P=.000321) and presented increased FHR1 deposits at glomerular and tubulointerstitial level associated with higher expression of the senescence marker p16INK4a (P=.001) and tubulointerstitial fibrosis (P=.005). Interestingly, FHR1 deposits were associated with increased complement activation as demonstrated by C5b-9 deposits. These data support both the role of FHR1 in mediating complement activation and tubular senescence, and suggest the possibility of genotyping delCFHR3-1 to predict graft survival in IgAN-transplanted patients.

The Effect of Different Glycaemic States on Renal Transplant Outcomes.

Background. Optimal glycaemic targets following transplantation are unknown. Understanding the impact of DM and posttransplant diabetes mellitus (PTDM) may improve patient and graft survival in transplant recipients. Aim. To determine the perioperative and one-year outcomes after renal transplantation and whether these outcomes are affected by preexisting DM, PTDM, or glycaemia during transplant admission. Method. Adult recipients of renal transplants from a single centre over 5.5 years were retrospectively reviewed. Measured outcomes during transplant admission included glycaemia and complications (infective complications, acute rejection, and return to dialysis) and, at 12 months, glycaemic control and complications (cardiovascular complication, graft failure). Results. Of 148 patients analysed, 29 (19.6%) had DM and 27 (18.2%) developed PTDM. Following transplantation, glucose levels were higher in patients with DM and PTDM. DM patients had a longer hospital stay, had more infections, and were more likely return to dialysis. PTDM patients had increased rates of acute rejection and return to dialysis. At 1 year after transplant, there were more cardiovascular complications in DM patients compared to those without DM. Conclusions. Compared to patients without DM, patients with DM or PTDM are more likely to suffer from complications perioperatively and at 12 months. Perioperative glycaemia is associated with graft function and may be a modifiable risk.

Genotypic variation and outcomes in kidney transplantation: donor and recipient effects

The genetic composition of a donor impacts long term allograft survival after kidney transplantation. Effects of the recipient’s genetic make-up, particularly variation in immune response pathway genes are less certain. A report in this issue of Kidney International reveals improved graft survival in transplant recipients with lower copy numbers of the complement 4 gene (C4) after receipt of deceased donor kidneys. Genomics breakthroughs in nephrology and immunology will likely revolutionize the field of transplant medicine.

Severe Diarrhea in Renal Transplant Patients: Results of the DIDACT Study

Diarrhea is common in transplant recipients. While the majority of cases are mild and transient, some are severe and prolonged, which can threaten graft survival through dehydration. While it is known that some immunosuppressive agents can elicit diarrhea, there does not appear to be any consensus on the role that other nonimmunosuppressive causes can play in transplant patients. The aim of the present open, nonrandomized, multicenter study was to identify nonimmunosuppressive factors involved in severe diarrhea in renal transplant patients. Patients (n = 108) with severe diarrhea (>/=3 stools/day for >/=7 days) were enrolled from 16 Belgian transplant centers. Patients were diagnosed according to an agreed flowchart that consisted of identification of possible infections, followed by changes in empirical and immunosuppressive treatment. Approximately 50% of patients experienced resolution of severe diarrhea following treatment for infections, dietary problems or diarrhea-causing concomitant medications. In conclusion, a large proportion of the severe diarrhea observed in renal transplant recipients is not associated with immunosuppressive therapy and can be treated through anti-infectives, changes to concomitant medication and other empirical treatments. Correct diagnosis of the cause of severe diarrhea in such patients should help to protect graft survival in transplant recipients.

Managing Breast Cancer in the Renal Transplant Patient: A Unique Dilemma

Improvements in immunosuppression have increased patient and graft survival in transplant recipients. As a result, there is greater risk of neoplastic processes such as breast cancer. Treatment in this population is complicated by the necessary immunosuppression, vascular accesses, and transplant grafts. General surgeons may expect to encounter more of these complex patients in the community setting. We sought to evaluate the surgical treatment of breast cancer in patients with renal transplants. Hospital and private physician records were queried to identify patients who developed breast cancer after a renal or pancreatic/renal transplantation. These charts were reviewed for demographics, type of breast cancer and treatment, location of dialysis access, and complications. From June 1, 1994, to May 31, 2004, 14 patients were identified. Eight patients had functioning transplants. All patients underwent operative interventions. Ten patients underwent adjuvant treatment. Three had functioning transplants and chose not to risk the graft with cessation of immunotherapy. However, no patient with functioning transplants who underwent chemotherapy developed organ failure. Breast cancer after transplantation poses a unique dilemma. The threat of transplanted organ failure is a major concern to these patients and often supersedes adjuvant therapies.

Sirolimus therapy in orthotopic liver transplant recipients with calcineurin inhibitor related chronic renal insufficiency

Calcineurin inhibitor-related renal toxicity affects patient and graft survival in transplant recipients. Our clinical experience has revealed sirolimus to be an effective agent in treating renal insufficiency related to calcineurin inhibitor toxicity. Methods We performed a retrospective review of the medical records of OLT recipients suffering from chronic renal insufficiency and treated with sirolimus at the University of Miami. Results Fourteen patients (nine men and five women) of mean age 57 years who had been treated with tacrolimus for at least 30 days were converted to sirolimus after developing nephrotoxicity. Mean creatinine clearances collected on day 0, 30, 60, and 90 after conversion were 40.1 mL/min, 49.6 mL/min, 53.9 mL/min, and 51.4 mL/min, respectively. Episodes of acute cellular rejection were not increased during the sirolimus conversion. Conclusion This retrospective review suggests that OLT patients suffering from tacrolimus-related renal insufficiency successfully converted to sirolimus may benefit from this therapy.

Selective T cell receptor Vbeta gene usage by alloreactive T cells responding to defined HLA-DR alleles.

Previous studies have provided strong evidence for restricted Vbeta gene usage in response to DR synthetic peptides presented in context by self MHC molecules, i.e., via the indirect pathway of allorecognition. Although numerous studies have suggested a role for the T cell receptor (TCR) beta chain in the direct pathway of allorecognition, it is not clear whether a particular HLA allele elicits a consistent pattern of restricted Vbeta gene usage by resting T cells from different individuals. To address this problem, HLA class II homozygous cell lines that do not express class I antigens were used to study the role of the TCR Vbeta elements in direct recognition of specific DR alleles. Analysis of TCR V gene usage revealed that each DR allele tested elicited the same pattern of preferential Vbeta gene usage in all individuals studied. For example, the DRB1*0101 allele was preferentially recognized by T cells expressing Vbeta2, Vbeta13.1, Vbeta18, and Vbeta20, and the DRB1*1301 caused expansion of Vbeta4-, Vbeta6-, Vbeta8-, and Vbeta18-bearing T cells. Similarly, analysis of TCR V gene usage in response to defined DR alleles expressed on homozygous cell lines that express class I was also made possible by using anti-class I antibodies to block class I recognition and focus the response on the DR molecule. The results showed that the DRB1*1501 allele expressed on two distinct homozygous lines elicited the preferential expansion of Vbeta2, Vbeta8, and Vbeta13.2 T cells. Similarly, the DRB1*0301 allele expressed on normal, Epstein-Barr virus-transformed, or transfected fibroblasts was found to elicit the same pattern of Vbeta expansion and to selectively stimulate T cells bearing Vbeta2, Vbeta16, and Vbeta17 elements. In contrast to this highly reproducible pattern of Vbeta gene usage elicited by specific DR alleles, extensive heterogeneity in the CDR3 region was found and no preferential Jbeta or Valpha gene usage was observed in response to any of the DR alleles tested. The data suggest that, similar to the situation with the indirect pathway, TCR Vbeta elements are involved in the direct pathway of allorecognition. Although some overlap may exist, different sets of Vbeta elements may be preferentially used for each of these pathways. Inasmuch as HLA-identical siblings, but not HLA-identical unrelated individuals, express a very similar TCR repertoire, our data suggest that additional factors are involved in shaping the repertoire. Preferential activation of T-cell subsets by specific DR alleles may play an important role in primary alloresponses, e.g., in mixed lymphocyte reactions, and organ transplantation. Elucidation of the Vbeta specificity of each DR allele may have an impact on therapeutic strategies aimed at blocking specific alloresponse and prolonging graft survival in transplant recipients while avoiding the hazardous sequelae of nonspecific immunosuppression.

Multiple drug combinations with ?low-dose? cyclosporin for renal transplantation

The factors affecting graft survival in transplant recipients receiving cyclosporin (CsA) are still being debated. Our report is based on an analysis of 202 successive transplantations performed in our institution from May 1984 to December 1986, using low-dose CsA as the basic means of immunosuppression. A total of 142 patients received the triple combination CsA, azathioprine (AZA), and corticosteroids. Sixty patients received a prophylactic combination of CsA, corticosteroids, and antilymphocyte globulins (ALG). From January to December 1986, both regimens were compared in a prospective randomized trial. The factors that affect graft survival were analyzed using the Cox multivariate hazard analysis. The relative risks were calculated for pretransplant baseline risk factors and for outcome-dependent post-transplant risk factors for surviving grafts at 1 month. Transplants performed with a prolonged ischemia time and patients whose graft did not function immediately were statistically at higher risk of graft loss. Adding prophylactic ALG to CsA was associated with better graft survival. patients who experienced more than 1 rejection crisis and patients whose 1-month CsA dose was lower than or equal to 5 mg/kg per day were also at significantly higher risk of further graft loss. Neither HLA matching, peak panel reactivity, age of the recipient, occurrence of post-transplant renal dysfunction nor 1-month renal function affected the short-term graft outcome.

Multiple drug combinations with "low-dose" cyclosporin for renal transplantation: Multivariate analysis of risk factors determining short-term graft survival within one renal transplant center

The factors affecting graft survival in transplant recipients receiving cyclosporin (CsA) are still being debated. Our report is based on an analysis of 202 successive transplantations performed in our institution from May 1984 to December 1986, using low-dose CsA as the basic means of immunosuppression. A total of 142 patients received the triple combination CsA, azathioprine (AZA), and corticosteroids. Sixty patients received a prophylactic combination of CsA, corticosteroids, and antilymphocyte globulins (ALG). From January to December 1986, both regimens were compared in a prospective randomized trial. The factors that affect graft survival were analyzed using the Cox multivariate hazard analysis. The relative risks were calculated for pretransplant baseline risk factors and for outcome-dependent post-transplant risk factors for surviving grafts at 1 month. Transplants performed with a prolonged ischemia time and patients whose graft did not function immediately were statistically at higher risk of graft loss. Adding prophylactic ALG to CsA was associated with better graft survival. Patients who experienced more than 1 rejection crisis and patients whose 1-month CsA dose was lower than or equal to 5 mg/kg per day were also at significantly higher risk of further graft loss. Neither HLA matching, peak panel reactivity, age of the recipient, occurrence of post-transplant renal dysfunction nor 1-month renal function affected the short-term graft outcome.