Normothermic Regional Perfusion in Controlled Donation After Circulatory Determination of Death Simultaneous Pancreas - Kidney Transplantation.

BACKGROUND: Simultaneous pancreas-kidney transplantation is the optimal treatment for patients with type 1 diabetes and renal failure. The use of pancreas grafts from donation after circulatory death (DCD), using normothermic regional perfusion (NRP), is still marginal worldwide, mainly due to possible additional risks of graft dysfunction and complications compared with grafts from donors after brain death. METHODS: Case series of patients who underwent simultaneous pancreas-kidney transplantation after DCD-NRP between January 2018 and September 2022. This study evaluated early postoperative grafts and survival outcomes. RESULTS: Four patients were included. One patient lost the pancreatic graft due to arterial thrombosis requiring transplantectomy. Another patient required a laparotomy due to hemoperitoneum. Overall, 1-year pancreas and kidney graft survival was 75% and 100%, respectively. One patient developed a lymphoma during the follow-up. CONCLUSION: The use of pancreas grafts from DCD after NRP preservation is safe and feasible. Comparative studies with donors after brain death grafts and larger series are required to confirm the feasibility of DCD-NRP pancreas transplantation.

Changes over time in the causes of death with a functioning graft in kidney transplantation recipients.

INTRODUCTION: Death with a functioning graft (DWFG) is the most frequent cause of loss of kidney transplantation (KT). OBJECTIVE: To analyze the evolution of the causes of DWFG and the frequency of the types of cancer causing DWFG. METHODS: Retrospective study of KT in Andalusia from 1984 to 2018. We analyzed the evolution according to eras (1984-1995; 1996-2007; 2008-2018) and according to post-transplant period (early death: first year post-KT; late death: after first year post-KT). RESULTS: A total of 9905 KT were performed, registering 1861 DWFG. The most frequent causes were cardiovascular disease (25.1%), infections (21.5%) and cancer (19.9%). In early death we did not observe changes, and infections were always the main cause. In late death, cardiovascular death decreased (1984-1995: 35.2%, 1996-2007: 22.6%, 2008-2018: 23.9%), but infections (1984-1995: 12.5%, 1996-2007: 18.3%, 2008-2018: 19.9%) and, above all, cancer-related deaths increased (1984-1995: 21.8%, 1996-2007: 29%, 2008-2018: 26.8%) (P < .001). In the multivariable analysis for late death due to cardiovascular disease, recipient age, retransplantation, diabetes, and the first period were risk factors, while the risk of late death due to cancer and infections was associated with recent eras. In the first year after transplantation, the most frequent neoplasia causing DWFG was post-transplant lymphoproliferative disease, and after the first year, it was lung cancer, without differences when it was analyzed by eras. CONCLUSIONS: Despite the greater comorbidity of the recipients, cardiovascular deaths have decreased. Cancer has been the main cause of late death in recent years. Lung cancer is the most frequent malignancy that causes DWFG in our transplant patients.

Short- and Long-Term Intestinal Complications After Combined Pancreas-Kidney Transplantation.

BACKGROUND: Simultaneous pancreas-kidney (SPK) transplantation is the treatment of choice in patients with type 1 diabetes and end-stage renal disease, because it improves survival and quality of life. Currently, enteric exocrine drainage is the most commonly used method. Intestinal complications continue to be a major cause of posttransplant morbidity despite improvements in surgical technique. This study analyzed early and late intestinal complications related to SPK transplantation. MATERIALS AND METHODS: We performed a retrospective analysis of 100 adult patients undergoing SPK transplantation between January 2009 and December 2019. We performed systemic venous drainage and exocrine enteric drainage with duodenojejunostomy. Statistical analysis was performed using SPSS v2. This study was performed in accordance with the Declaration of Istanbul and the 1964 Declaration of Helsinki. Informed consent was obtained from all participants involved in the study. RESULTS: Intestinal complications were reported in 18 patients. Ten patients (10%) had the following early intestinal complications including: ileus (n = 4), intestinal obstruction (n = 2), graft volvulus (n = 1), duodenal graft fistula (n = 1), and jejunal fistula after pancreas transplantation (n = 1). Two cases required relaparotomy: graft repositioning with Roux-en-Y conversion (n = 1) and Y-roux conversion (n = 1). Eight patients had repeated episodes of intestinal obstruction (8%), of whom 2 required surgery for resolution with 100% postoperative mortality. CONCLUSIONS: SPK transplantation with enteric drainage via duodenojejunostomy has a low rate of short- and long-term postoperative intestinal complications. Surgery in patients with recurrent intestinal obstruction has a high mortality risk and should be performed in reference transplant centers.

Incidence of Lymphoproliferative Disorders After Renal Transplantation is Down, but the Poor Prognosis Remains. Multicenter 32-Year Cohort Study.

BACKGROUND: Post-transplant lymphoproliferative disorders represent rare but serious complications of kidney transplantation. METHODS: We assessed incidence, risk factors, and outcomes in 21,546 patients receiving grafts between 1990 and 2009. Data were compared by decade of transplant (1990-1999 vs 2000-2009). Patients were followed for at least 12 years over a 32-year study period. RESULTS: In total, 331 patients (1.5%) developed PTLD: 189 of 9740 transplanted in the first decade, and 142 of 11,806 in the second. Incidence decreased significantly (19.40 vs12.02 cases/1000 patients; P < .001). Mean age at diagnosis was 50.2 years (standard deviation 14.7), and the median time from transplant to PTLD diagnosis was 48 months (interquartile range, 14.7-77.5), with no difference between cohorts. The origin of PTLD was mostly (86%) B-cell proliferation. No classical risk factors were reported in 31.7% of affected patients. Compared with 2000 to 2009, in 1990 to 1999 there was a higher frequency of induction therapy (P = .023) and detection of the Epstein-Barr virus in lymphoproliferative tissue (71.3% vs 52.7% P = .019). After diagnosis, 1- and 5-year patient survival was 51% and 38%. Graft survival was 48% and 33%. Survival was stable throughout the study period. CONCLUSION: Post-transplant lymphoproliferative disorders have a low and decreasing incidence, but the poor prognosis has not changed.

First Report in the Literature of Biopsy-Proven Noncollapsing Focal Segmental Glomerulosclerosis Relapse in a Second Renal Transplant Presenting With Thrombotic Microangiopathy: A Case Report.

Primary focal segmental glomerulosclerosis (FSGS) is a podocytopathy with an irregular response to immunosuppressive therapies. FSGS relapse occurs in 30% to 80% of kidney grafts, and poor survival outcomes include large proteinuria and the nephrotic syndrome's cardinal clinical features. Thrombotic microangiopathy (TMA) is caused by endothelial injury due to complement dysregulation including acute kidney injury, proteinuria, and severe hypertension common renal presentations. Both pathologies have well-described genetic forms, but their relationship remains uncertain. FSGS lesions can be found in kidney biopsy specimens in patients with TMA, and TMA has been reported in patients with collapsing glomerulopathy. However, this combination has not been clearly described in renal transplant recipients. We present the case of a 22-year-old man who received his second kidney allograft and developed an early graft disfunction with nephrotic syndrome and clinical TMA. His background was remarkable for primary, biopsy-confirmed FSGS in childhood, and he started hemodialysis in 2006 and received a living donor kidney graft the same year. He presented with a FSGS relapse with malignant hypertension and seizures in the first posttransplant month and had an irregular response to plasma exchange and rituximab, and dialysis was reinitiated 10 years later. A total of 3 biopsies were performed after his second kidney transplant showing the evolution of a FSGS relapse with histologic and clinical TMA in the absence of identified genetic mutations. Partial responses to treatments with plasma exchange, eculizumab, and rituximab were obtained, but the allograft was lost after 26 months. This case is the first report of concomitant FSGS and TMA in a renal transplant recipient.

A Single-Center Experience With Third and Fourth Kidney Transplants and Second Kidney Transplant After Pancreas-Kidney Transplant: Surgical Aspects and Outcomes.

OBJECTIVES: Overall, 25% to 33% of patients on kidney transplant wait lists present with prior graft loss. In addition, the number of patients who require a retransplant seems to be increasing. Here, we describe our experience with patients who had a second kidney transplant after a previous pancreas-kidney transplant or a third or fourth kidney transplant. We focused specifically on the technical aspects and outcomes related to this patient group. MATERIALS AND METHODS: A single-center retrospective study was performed. The cohortincluded 15 patients > 18 years old who had received a second kidney graft after pancreas-kidney transplant or a second or greater kidney graft between 2013 and 2019. RESULTS: Median age of recipients was 45 years (range, 20-58 y). In 10 patients, the transperitoneal approach was selected. In 5 patients, the retroperitoneal heterotopic kidney retransplant technique was used. Early surgical complications (≤ 30 days posttransplant) were reported in 4 patients. Three patients had late ureteral stenosis (> 90 days posttransplant). All grafts were functioning at time of patient discharge. Mean creatinine level was 2.69 mg/dL (range, 1.23-6.26 mg/dL). The 1-year and 2-year graft survivalrates were 85% and 75%, respectively. No grafts were lost because of surgical complications. CONCLUSIONS: Retransplant of a second graft after pancreas-kidney transplant or retransplant of a third or fourth renal graft is challenging but feasible, with evidence of reasonably positive outcomes after retransplant.

HIV infection and renal transplantation.

BACKGROUND: Some aspects of kidney transplant outcome in human immunodeficiency virus (HIV)-infected patients are still controversial. Besides, published experience is scarce in Europe. METHODS: A multicentre case-control study was designed to analyse the outcome of renal transplant in HIV + patients in Spain. Twenty HIV + patients were compared with a matched cohort of 40 HIV - recipients. RESULTS: Post-transplant follow-up period was 39.98 ± 36.51 months. Pre-transplant dialysis duration and the incidence of pre-transplant opportunistic infections were significantly higher for HIV + patients. Following transplantation, HIV + recipients presented lower incidence of immediate renal function and more acute rejection. Graft survival was lower although the difference was not significant (1 year: 85 vs 97.5%; 5 years: 74.4 vs 91%; log-rank P = 0.058). There was no difference in patient survival rates. Eight patients in each group presented hepatitis C (HCV) infection. Coinfected patients were compared with HIV +/HCV - and HIV -/HCV + recipients. Coinfected patients presented more time on dialysis, greater duration of delayed graft function and lower graft survival (HIV +/HCV + vs HIV +/HCV -: log-rank P = 0.009; HIV +/HCV + vs HIV -/HCV +: log-rank P = 0.02). Conversely, when excluding HCV + patients in both groups, graft survival in HIV + and HIV - patients was similar. CONCLUSIONS: The outcome was good, particularly in non-coinfected patients. Coinfected patients constitute an especially high-risk group for kidney transplantation.

Significance of preimplantation analysis of kidney biopsies from expanded criteria donors in long-term outcome.

BACKGROUND: The shortage of organs has led to expanding the criteria for donors. Histologic evaluations before transplantation may enable the identification of organs unsuitable for single implantation. The aim of this study was to evaluate the histologic findings as prognostic factors of allograft survival from expanded criteria donors (ECDs). METHODS: We included a cohort of 136 single transplantations with kidneys from ECD and correlated the preimplantation pathologic findings with graft failure. Renal structures from ECD older (n=104) or younger (n=32) than 60 years were evaluated histologically for renal senescence and rated with a total histologic score. A multivariate Cox analysis was performed to identify predictors of graft failure. RESULTS: Glomerulosclerosis was the most prevalent lesion in biopsies from donors older and younger than 60 years (P=0.002); interstitial fibrosis was more severe in biopsies from older donors (P=0.001); older donors showed a higher prevalence of tubular atrophy (P=0.022), and vascular compartment showed no significant differences. Kidney biopsy-based scoring system ranged from 0 to 15 points, indicating the presence of changes in the renal parenchyma. Biopsies with total histologic scores less than or equal to 5 showed significantly better 5-year graft survival than those with scores more than 5 (P<0.001). A preimplantation score more than 5 points remained an independent predictor of graft failure (hazard ratio 6.95; 95% confidence interval 1.57-30). CONCLUSIONS: Histologic analysis of kidney biopsies before transplantation is a valuable tool for facilitating the selection of viable grafts from ECD donors. When the total score is more than 5, single kidney transplantation from ECD should not be recommended for patients similar to this study population.

Age-dependent association between low frequency of CD27/CD28 expression on pp65 CD8+ T cells and cytomegalovirus replication after transplantation.

In this cross-sectional study of 42 solid organ transplant recipients, the association of human cytomegalovirus (HCMV) replication and age with the phenotype of the HCMV-specific CD8(+) T cells was analyzed by using the CMV pp65 HLA-A*0201 pentamer. A correlation between the proportion of CD28(-) HCMV-specific CD8(+) T cells and age was observed in patients without HCMV replication (r = 0.50; P = 0.02) but not in patients with HCMV replication (r = -0.05; P = 0.83), a finding which differs from that observed for total CD8(+) T cells. Within the group of patients younger than 50 years of age, patients with HCVM replication after transplantation had higher percentages of CD28(-) HCMV-specific CD8(+) T cells (85.6 compared with 58.7% for patients without HCMV replication; P = 0.004) and CD27(-) HCMV-specific CD8(+) T cells (90.7 compared with 68.8% for patients without HCMV replication; P = 0.03). However, in patients older than age 50 years, a high frequency of these two subpopulations was observed in patients both with and without previous HCMV replication (for CD28(-) HCMV-specific CD8(+) T cells, 84.4 and 80.9%, respectively [P = 0.39]; for CD27(-) HCMV-specific CD8(+) T cells 86.6 and 81.5%, respectively [P = 0.16]). In conclusion, the present study shows that in the group of recipients younger than age 50 years, HCMV replication after transplantation is associated with a high percentage of CD27(-) and CD28(-) HCMV-specific CD8(+) T cells. These results suggest that the increased percentage of CD27(-) or CD28(-) HCMV-specific subsets can be considered a biomarker of HCMV replication in solid organ transplant recipients younger than age 50 years but not in older patients. Further studies are necessary to define the significance of these changes in HCMV-associated clinical complications posttransplantation.

Cell apoptosis and hemodialysis-induced inflammation.

Hemodialysis patients exhibit a defective immune response leading to an increased susceptibility of infections and neoplasms. Far from being helpful, dialytic therapy per se also may be responsible for this acquired immunodeficiency. Dialysis membranes and bacterial products present in dialysis water may trigger and even perpetuate an abnormal mononuclear cell activation. Upon contact with cellulosic dialysis membranes, monocytes display an increased expression of surface markers of cell activation, such as adhesion molecules CD18, CD49, CD54 and the lipopolysaccharide (LPS) ligand (CD14). Moreover, proinflammatory cytokines as IL-1beta and TNF-alpha are released both in vivo and in vitro when monocytes are exposed to cellulosic membranes. Of special interest is the fact that end-stage renal disease patients undergoing hemodialysis exhibit an increased mononuclear cell apoptosis. This apoptosis is directly related to the degree of biocompatibility of the dialysis membrane. Apoptosis is activated when monocytes enter in contact with the cellulosic dialysis membrane through cell surface receptors linked to G-proteins. In early steps of apoptosis signaling, pertussis toxin-sensitive G proteins are coupled to protein kinase C (PKC)-dependent phosphorylative mechanisms. Furthermore, recent evidence support that the execution phase of apoptosis is mediated by a caspase-3 dependent pathway. Finally, very recent available data support that monocytes subjected to repeated activation suffer a process of accelerated senescence, as demonstrated by the senescent phenotype (CD14 and CD32) expressed and their shortened telomeric length. This senescent profile may generage a defective cellular response in acute stress situations, explaining (at least in part) the altered immune response observed in hemodialysis patients.