Effect of Nephrectomy After Allograft Failure on Inflammation, Erythropoiesis, Donor-Specific Antibodies, and Outcome of Re-Transplantation.

BACKGROUND Morbidity and mortality rates are high for patients returning to dialysis after renal graft failure. Keeping failed kidney transplants in situ with concomitant minimization or withdrawal of immunosuppression is standard of care in many transplant centers. It is unclear, however, whether the resulting allospecific immune response can cause a microinflammatory milieu. The present work investigated the impact of allograft nephrectomy on systemic inflammation, erythropoiesis, and donor-specific antibodies (DSA). MATERIAL AND METHODS We performed a retrospective analysis evaluating C-reactive protein (CRP), hemoglobin concentration (Hb), ferritin, iron substitution dosages, erythropoietin dosages, and DSA in 92 transplant recipients with allograft failure, of whom 49 did not (Group A) and 43 did undergo transplant nephrectomy (Group B). Blood samples and clinical data were obtained 3-6 months after returning to dialysis. We additionally assessed outcome of kidney re-transplantation in a 10-year follow-up. RESULTS There was no significant difference in Hb concentrations, ferritin concentrations, CRP concentrations, iron, and EPO substitution dosages between the 2 groups. Patients undergoing nephrectomy had a significantly higher prevalence of DSA (65.1% vs 38.8%, P<0.0001). In the 10-year follow-up, 3 patients (12%) of Group B and none in Group A had allograft failure after primary successful re-transplantation. CONCLUSIONS Keeping a kidney graft in situ after returning to dialysis did not lead to an increase in microinflammation. Although DSA develops in more than 50% of patients after an allograft nephrectomy, the outcome of a renal re-transplantation seems to be unaffected. Thus, both strategies are feasible options in kidney transplant recipients after return to dialysis.

[Pancreas transplantation-clinic, technique, and histological assessment]. / Pankreastransplantation ­ Klinik, Technik und histologische Beurteilung.

BACKGROUND: In Germany pancreas transplants are performed in only a few selected and specialized centres, usually combined with a kidney transplant. Knowlegde of the indications for and techniques of transplantation as well as of the histopathological assessment for rejection in pancreas and duodenal biopsies is not very widespread. AIM: To give an overview of the development and status quo in pancreas-kidney-transplantation in Germany summarizing the experience of the largest German pancreas transplant centre and to give a résumé of the results of histological diagnoses of biopsy specimens submitted between 06/2017 and 12/2020. Moreover, a detailed description and illustration of histological findings is included. MATERIAL AND METHODS: A thorough literature search for aspects of the history, technique and indication for pancreas transplantation was performed and discussed in the context of the local experience and technical particularities specific for the transplant centre in Bochum. The occurrence of complications was compared with international reports. Results of pancreas and duodenal biopsies submitted to Erlangen between 06/2017 and 12/2020 for histological evaluation, which were evaluated according to the Banff classification, were summarized. For a better understanding key histological findings of pancreas rejection and differential diagnoses were illustrated and discussed. RESULTS: A total of 93 pancreas transplant specimens and 3 duodenal biopsies were included. 34.4% of pancreas specimens did not contain representative material for a diagnosis. In the remaining 61 biopsies 24.6% showed no rejection, 62.3% were diagnosed with acute T-cell mediated rejection (TCMR) and 8.2% with signs suspicious of antibody-mediated rejection (ABMR). Acute acinary epithelial injury was seen in 59%, pancreatitis in 8.2% and allograft fibrosis was reported in as many as 54.1%. Calcineurin-inhibitor toxicity was discussed in only 4.9%. CONCLUSION: Pancreas-kidney-transplantation and standardized histological assessment of the transplanted pancreas or rarely duodenum with reporting according to the updated Banff classification of pancreas transplants or previous reports of duodenal rejection are important mainstays in the management of patients with diabetes.

Challenges Associated with Pancreas and Kidney Retransplantation-A Retrospective Analysis.

Simultaneous pancreas and kidney transplantation (SPK) is an accepted treatment for diabetic patients with renal failure, and is associated with increased survival and quality of life for recipients. There are only a few publications on the outcomes of simultaneous pancreas-kidney retransplantation (Re-SPK) after previous SPK and the loss of function of both grafts. A total of 55 patients with type 1 diabetes mellitus underwent pancreas retransplantation at our center between January 1994 and March 2021. Twenty-four of these patients underwent Re-SPK after a previous SPK. All 24 operations were technically feasible. Patient survival rate after 3 months, 1 year, and 5 years was 79.2%, 75%, and 66.7%, respectively. The causes of death were septic arterial hemorrhage (n = 3), septic multiorgan failure (n = 2), and was unknown in one patient. Pancreas and kidney graft function after 3 months, 1 year, and 5 years were 70.8% and 66.7%, 66.7% and 62.5%, and 45.8% and 54.2%, respectively. Relaparotomy was performed in 13 out of 24 (54.2%) patients. The results of our study show that Re-SPK, after previously performed SPK, is a technical and immunological challenge, associated with a significantly increased mortality and complication rate; therefore, the indication for Re-SPK should be very strict. Careful preoperative diagnosis is indispensable.

Impact of Histidine-Tryptophan-Ketoglutarate Versus University of Wisconsin Solution on the Outcome of Pancreas Transplant With Cold Ischemic Time ≥12 Hours: A Retrospective Study.

OBJECTIVES: Histidine-tryptophan-ketoglutarate and University of Wisconsin solutions are currently used for pancreas graft preservation. Our hypothesis was whether the use of histidine-tryptophan-ketoglutarate solution is associated with worse pancreas graft survival than University of Wisconsin solution, in general and after prolonged cold ischemic time of ≥12 hours. MATERIALS AND METHODS: This retrospective study investigated the impact of static cold storage in histidine-tryptophan-ketoglutarate (n = 133) versus University of Wisconsin (n = 107) solution on outcomes of 240 pancreas transplant procedures. Patient and graft survival rates were compared after 1, 3, and 5 years in both groups. Serum lipase, amylase, and C-reactive protein levels and incidence of surgical complications were evaluated at postoperative week 1. A subgroup analysis of 96 grafts (52 with histidine-tryptophanketoglutarate/44 with University of Wisconsin) with pancreas graft cold ischemic time ≥12 hours was also performed. RESULTS: At mean follow-up of 75.2 ± 9.9 months, both groups demonstrated comparable short- and long-term patient survival. Overall, pancreas graft survival was slightly better in the histidine-tryptophan-ketoglutarate group (Kaplan-Meier analysis, log-rank P = .013). However, the subgroup analysis of grafts with cold ischemic time ≥12 hours showed slightly better pancreatic graft survival in the University of Wisconsin group, although not significantly (log-rank P = .95). Serum lipase and C-reactive protein levels at postoperative week 1 were higher in the histidinetryptophan-ketoglutarate group. Surgical complications were comparable. Multivariable Cox regression analysis identified neither solution as a risk factor affecting patient and graft survival. CONCLUSIONS: Although a direct comparison between histidine-tryptophan-ketoglutarate and University of Wisconsin showed better pancreas graft survival with histidine-tryptophan-ketoglutarate, the multivariable analysis showed that the perfusion solution does not significantly influence patient and graft survival. However, in the analysis of transplants with cold ischemic time ≥12 hours, pancreas graft survival was slightly better in the University of Wisconsin group, although not significantly.

Impact of donor cardiopulmonary resuscitation on the outcome of simultaneous pancreas-kidney transplantation-a retrospective study.

Previous cardiac arrest in brain-dead donors has been discussed as a potential risk factor in pancreas transplantation (PT), leading to a higher rate of organ refusal. This study aimed to assess the impact of cardiopulmonary resuscitation (CPR) in brain-dead donors on pancreas transplant outcome. A total of 518 type 1 diabetics underwent primary simultaneous pancreas-kidney (SPK) transplantation at our center between 1994 and 2018. Patients were divided into groups, depending on whether their donor had been resuscitated or not. A total of 91 (17.6%) post-CPR donors had been accepted for transplantation (mean duration of cardiac arrest, 19.4 ± 15.6 min). Those donors were younger (P < 0.001), had lower pancreas donor risk index (PDRI, P = 0.003), and had higher serum creatinine levels (P = 0.021). With a median follow-up of 167 months (IQR 82-229), both groups demonstrated comparable short- and long-term patient and graft survival. The resuscitation time (<20 min vs. ≥20 min) also showed no impact, with similar survival rates for both groups. A multivariable Cox regression analysis suggested no statistically significant association between donor CPR and patient or graft survival. Our results indicate that post-CPR brain-dead donors are suitable for PT without increasing the risk of complications.

Outcome of Kidney Transplantation Using Organs From Brain-dead Donors Older Than 75 Years.

PURPOSE: We investigated whether older donor kidneys aged >75 years have acceptable long-term function and if recipients can benefit sufficiently from the transplantation. METHODS: This single-center study retrospectively analyzed patient data from 217 deceased donor kidney transplants performed between 1998 and 2014 as part of the Eurotransplant Senior Program, where the organ donors were ≥65 years old. Depending on donor age, the groups "older donors" (OD; n = 161) and "very old donors" (VOD; n = 56) received transplants from donors aged 65 to 75 years and >75 years, respectively. Donor and recipient clinical characteristics, delayed graft function, estimated glomerular filtration rate, 1-year rejection rate, patient and graft survival, and postoperative complications were investigated. RESULTS: Comparing VOD group vs OD group, the 1-year, 3-year, and 5-year graft survival rates were 80.4% vs 76.4%, 62.5% vs 65.8%, and 42.6% vs 57.3%, respectively. Patient survival rates after 1, 3, and 5 years were 89.3% vs 88.2%, 71.4% vs 78.2%, and 57.5% vs 71.8%, respectively. There were no significant differences between the 2 groups (graft survival P = .107; patient survival P = .126). Kidney graft function after 1, 2, and 3 years was significantly better in the OD group than in the VOD group. No differences were found regarding postoperative complications, rejection rate, and delayed graft function. CONCLUSION: The utilization of selected kidney-grafts from donors >75 years resulted in acceptable outcomes after kidney transplantation and could expand the donor pool. In contrast to the high mortality rate during dialysis, recipients in both groups benefited from transplantation.

Risk factors for acute kidney injury following TA-TAVI or minimally invasive aortic valve replacement: which procedure is less kidney damaging in elderly patients?

BACKGROUND: Acute kidney injury (AKI) represents a major complication following aortic valve replacement in elderly patients. The aim of this study was to determine possible risk factors for AKI and to find the ideal strategy, minimally invasive valve replacement (MIS-AVR) or transapical valve implantation (TA-TAVI), regarding the postoperative renal outcome. METHODS: A total of 133 patients (age ≥ 75 years, 67 male) with severe aortic stenosis were included over 2 years: 42% were treated with MIS-AVR, 58% underwent TA-TAVI procedure. AKI was considered as a postprocedural 1.5× increase in creatinine or an increase of > 0.3 mg/dL/48 hours. Group differences were tested with chi-square or t-test. AKI risk assumption was analyzed in multiple multivariate logistic regression models. RESULTS: EuroSCORE II-related risk assumption was 8.7 ± 6.9 for TA-TAVI and 4.5 ± 5.7 for MIS-AVR (p < 0.001). The overall 30-day survival rate was 93%. Fifty-eight patients developed a risk for AKI and 13 developed a manifest renal injury/failure. Logistic regression analysis revealed a higher AKI risk for TA-TAVI (odds ratio, OR = 2.58; 95% confidence interval, CI = 1.18, 5.63; p = 0.017). EuroSCORE II (OR = 0.98; 95% CI = 0.92, 1.04; p = 0.433); preoperative creatinine (OR = 1.78; 95% CI = 0.67, 4.77; p = 0.249) and estimated glomerular filtration rate (OR = 1.00; 95% CI = 0.97, 1.02; p = 0.655) had no impact on AKI. A regression model adjusting for the variables age, gender, body mass index (BMI), diabetes, and procedure type revealed a higher AKI rate for male gender (OR = 2.41; 95% CI = 1.13, 5.11; p = 0.022). Operation time and radio-contrast media volume had no influence on the AKI-occurrence. There was no correlation between AKI and early mortality. CONCLUSION: A higher risk for AKI after TA-TAVI should be considered in the therapy decision, especially in elderly male patients because MIS-AVR still yields excellent results.