Background:Isolated microhematuria (IMH) can signal hidden glomerular disease, necessitating detailed evaluations for potential kidney donors, including kidney biopsies. The optimal strategy for deciding on kidney biopsies remains unclear. While the British Transplant Society supports dipstick analysis, KDIGO focuses solely on urine microscopy. This study explored the correlation between kidney biopsy outcomes and results from dipstick urinalysis and urine microscopy in potential kidney donors. Methods:This retrospective study encompassed all potential kidney donors who received kidney biopsies following a positive urine dipstick result for IMH, irrespective of whether red blood cells (RBCs) were found on urine microscopy. We performed sensitivity and specificity analyses to assess the effectiveness of microscopy and dipstick urinalysis in identifying histological abnormalities in the kidney biopsies. Results:Approximately 49% of potential donors-133 out of 271-who had kidney biopsies due to positive dipstick tests showed negative results in urine microscopy for RBCs. In total, 168 donor candidates, or 62%, had abnormal findings in their biopsies, with nearly half of those diagnosed with immunoglobulin A nephropathy having negative urine microscopy results. Furthermore, 58% of potential donors with negative urine microscopy results-77 out of 133-also exhibited abnormal biopsy findings. The urine microscopy test displayed a sensitivity of 54.2% (95% confidence interval 46.6-61.5) and a specificity of 54.4% (95% confidence interval 44.8-63.7) for detecting abnormal biopsy results. Conclusion:This study highlighted a significant presence of donors with IMH with underlying glomerular lesions. Using urine microscopy showed limited sensitivity and specificity in identifying abnormal histopathological results. Relying solely on urine microscopy may miss critical pathologies like IgAN in prospective kidney donors. The persistence of IMH during dipstick urinalysis calls for kidney biopsy in potential donors. These findings suggest that our results be incorporated into future global guideline formulations.

Introduction: PAK is criticized compared to continued insulin therapy for increasing risks of renal graft loss and higher mortality early after transplantation Methods: The pancreas transplant program at KFSH&RC, Saudi Arabia was restarted in December 2014. All recipients of either SPK or PAK, including retransplants received exocrine drainage into the third part of the recipient duodenum.Prospective data collection approved by the Research Advisory Committee (“Organ Transplant Registry”, RAC 2121012). This study being a retrospective analysis of an approved standard operative procedure did not require additional ethical review. Results: 23 pancreas after kidney transplants have been perfomed in 20 recipients from 12/2014 until 04/2023. All recipients underwent living donor KTX 3.9 years (median; range 0.5-23) prior PAK. Median time of insulin dependency prior pancreas transplantation was 22.6 years (range,13.5–40.5 years). PAK recipient average age at time of transplant was 35.4 years, sex distribution was 17 male: 5 female. The average pancreas donor risk index amounted to 1.78. Patient survival at a median follow-up of 6.7 years post PAK was 100%.Complete insulin independence at 1,3 and 5 years post PAK was 70, 60 and 55%, respectively. 11 pancreas grafts in 9 recipients were lost due to rejection episodes. One pancreas graft was lost due to early thrombosis at POD 2. In same patient the only renal allograft loss was observed 2.5 years post PAK resulting in an overall kidney allograft survival of 95 percent at follow-up. Three recipients underwent pancreas retransplantaiton with a permanent success rate of 33%. All recipients (n=2) of LD-ABOi kidney transplantation lost their pancreas allograft for immunological reasons at 90 and 1080 days post PAK, respectively. Mean creatinine at time of PAK was 92 µmol/l (range 60-121). There was no statistical difference for creatinine in recipients with fuctioning versus a failed pancreatic allografts at 0.5,1, 3 and 5 years post months PAK or PAK loss, respectively.PAK pancreas allograft outcome is clearly inferior when compared to simultaneous pancreas and kidney transplantation at the same center (SPK pancreas allograft survival 95% @1 and 3 years and 92% @ 5 years). Given the limited resources of first dialysis and secondly deceased donor organs in a middle eastern country (about 3 deceased organ donors per million population per year) living donor kidney transplantation followed by PAK is a valuable option for patients suffering of end stage renal diesease secondary to diabetic nephropathy. Favourable recipient and renal allograft outcomes are linked to a center based intense follow-up Conclusion: Despite a very limited organ donor pool providing high risk donor allografts PAK are comparable ti international standars. Mid term renal allograft survial of 97% and a recipient survival of 100% at 6.7 year of follow-up are encouraging.

Background: Graft-versus-host disease following liver transplantation is a serious and usually fatal complication. Data identifying the risk factors and specifying the diagnosis and treatment options of the disease are scarce and contentious. Moreover, recommendations for therapeutic approaches are similarly sparse. Methods: A systematic review of the literature from 1988 to 2020 on graft-versus-host disease following liver transplantation was performed using the PubMed and MEDLINE databases. Medical subject headings, such as graft-versus-host disease and GvHD were used in combination with solid organ transplant, transplantation, or liver transplant. Following duplicate removal, 9298 articles were screened for suitability. A total of 238 full-text articles were analyzed for eligibility, resulting in 130 eligible articles for meta-analysis. Two hundred twenty-five patients developing graft-versus-host disease following liver transplantation reported herein were mainly published in case reports and case series. Results: Graft-versus-host disease occurred with an incidence of 1.2%. 85% developed following deceased donor liver transplant and 15% following living-related donor liver transplantation. The median follow-up period following liver transplantation was 84 days (interquartile range, 45–180). The median time from liver transplantation to graft-versus-host disease onset was 30 days (interquartile range, 21–42). The main clinical features included skin rash (59%), fever (43%), diarrhea (36%), and pancytopenia (30%). The overall mortality rate was 71%. Neither univariate (HR = 0.999; 95% CI, 0.493–2.023; p = 1.0) nor multivariate Cox regression analysis revealed a significant correlation between adaptation of immunosuppression and survival probability (HR = 1.475; 95% CI, 0.659–3.303; p = 0.3). Conclusions: This systematic review suggests that an increase in immunosuppressive regimen does not yield any survival benefit in patients suffering from graft-versus-host disease following liver transplantation.

BACKGROUND Access to kidney transplantation is limited for elderly patients with end-stage renal disease (ESRD), who often die while on the waiting list or receive kidneys from marginal deceased donors. In our transplantation center, most donated kidneys were from younger living relatives, in whom donations to elderly outcomes were not previously studied. In this study, we aimed to determine the short- and long-term outcomes of patients aged ³65 years to justify the use of kidneys from younger donors in older recipients. We also compared the outcomes between those who received kidneys from living donors (LDs) and deceased donors (DDs). MATERIAL AND METHODS We analyzed the patients' demographic data and the 1-, 5-, and 10-year patient and graft survival rates of patients aged ≥65 years who received kidney transplants between January 2005 and December 2020. RESULTS Among 158 patients, 136 received kidneys from LD and 22 from DD. The mean age was 69 years old. In this cohort, the most common cause of ESRD was diabetes. The graft survival rates were 99%, 96%, and 94% after 1, 5, and 10 years, respectively. Patient survival was 94%, 83%, and 61% after 1, 5, and 10 years, respectively. Delayed graft function rates, 1-year patient survival, and 5- and 10-year graft survival rates were lower in the DD group. Ischemic heart disease and transplantation from DD were independent risk factors for mortality. CONCLUSIONS Our study demonstrated reasonably good patient and graft survival rates in older patients. Outcomes were better in patients who received kidneys from LD.

Abstract Background Calcific aortic valve stenosis (CAVD) is the most prevalent heart valve disease worldwide and, in advanced stages, leads to clinical deterioration and poor prognosis. Until now, no medical treatment is available. Thought to be a merely degenerative disease, we now know that disease initiation and progression are actively regulated by immune cell infiltration, chronic inflammation, osteogenic differentiation of valvular interstitial cells (VIC) and endothelial-to-mesenchymal transition (EndMT) of valvular endothelial cells (VEC). Suppressor of Cytokine Signaling 3 (SOCS3) is known to be a key regulator of inflammation. It promotes the polarisation of macrophages to an inflammatory phenotype and thus, contributes to disease progression in atherosclerosis. In CAVD, not only inflammation but also heterotopic bone formation leads to the thickening and obstruction of the aortic valve cusps and as SOCS3 is one of the main regulators of physiological bone formation, it could play a critical role in the progression of CAVD. Purpose We hypothesize that SOCS3 plays a crucial role during calcification of the aortic valve through regulation of EndMT, calcification of valvular interstitial cells and macrophage polarization. Methods and results In initial screening experiments, we investigated SOCS3-protein expression in explanted human aortic valves from patients undergoing surgical aortic valve replacement. SOCS3 is expressed in both stenotic and non-stenotic valve tissues. Immunofluorescence-staining of human aortic valves shows the co-localisation of SOCS3 with the interstitial cell-marker Vimentin and SOCS1, which is known to regulate macrophage-polarisation together with SOCS3 (Fig. 1). Staining of the macrophage-marker CD68 revealed its co-localisation with calcified areas of the aortic valve cusp. We validated our findings in our in vitro model of VIC calcification using two different calcifying conditions. Upregulation of RUNX2 and BMP2 verified successful osteogenic differentiation of VICs. During osteogenic differentiation for 7 days, SOCS3 and SOCS1 are significantly upregulated (Fig. 2A). We were able to induce EndMT by stimulating VEC with either TNFα or TGFβ/IL1β in vitro. We show that EndMT leads to the loss of endothelial cell markers like eNOS and VWF and to an upregulation of interstitial cell markers (such as Vimentin and α-SMA) and markers of EndMT (SNAI2). During EndMT, we were also able to observe a significant upregulation of SOCS1 and SOCS3 after 7 days (Fig. 2B). Ongoing knockdown experiments will help to elucidate the role of SOCS1 and SOCS3 during initiation and progression of CAVD. Conclusion We aim towards a better understanding of SOCS3 and its role in inflammation and calcification as hallmarks of the pathogenesis of CAVD. Since Zoledronic acid has been shown to induce a decreased expression of SOCS3 in macrophages, this might present as a possible treatment strategy to target SOCS3 therapeutically. Funding Acknowledgement Type of funding sources: Foundation. Main funding source(s): Deutsche Forschungsgemeinschaft

Ischemia reperfusion injury (IRI) is a form of sterile inflammation whose severity determines short- and long-term graft fates in kidney transplantation. Neutrophils are now recognized as a key cell type mediating early graft injury, which activates further innate immune responses and intensifies acquired immunity and alloimmunity. Since the macrolide Bryostatin-1 has been shown to block neutrophil transmigration, we aimed to determine whether these findings could be translated to the field of kidney transplantation. To study the effects of Bryostatin-1 on ischemia-elicited neutrophil transmigration, an in vitro model of hypoxia and normoxia was equipped with human endothelial cells and neutrophils. To translate these findings, a porcine renal autotransplantation model with eight hours of reperfusion was used to study neutrophil infiltration in vivo. Graft-specific treatment using Bryostatin-1 (100 nM) was applied during static cold storage. Bryostatin-1 dose-dependently blocked neutrophil activation and transmigration over ischemically challenged endothelial cell monolayers. When applied to porcine renal autografts, Bryostatin-1 reduced neutrophil graft infiltration, attenuated histological and ultrastructural damage, and improved renal function. Our novel findings demonstrate that Bryostatin-1 is a promising pharmacological candidate for graft-specific treatment in kidney transplantation, as it provides protection by blocking neutrophil infiltration and attenuating functional graft injury.

Purpose Atypical variants of the hepatic artery are common and pose a technical challenge for normothermic machine perfusion (NMP). The transplant surgeon has three options when confronted with hepatic arterial variation in a liver graft to be subjected to NMP: to perform arterial reconstruction (i) prior, (ii) during, or (iii) following NMP. Methods Herein, we report our experience and technical considerations with pre-NMP reconstruction. Out of 52 livers, 9 had an atypical hepatic artery (HA): 3 replaced right HA, 3 replaced left HA, 1 accessory left HA, 1 accessory left and right HA, and 1 replaced left and right HA. Results Reconstruction was conducted during back-table preparation. A single vascular conduit was created in all grafts to allow single arterial cannulation for NMP, necessitating only one arterial anastomosis within the recipient. All grafts were subjected to NMP and subsequently successfully transplanted. Conclusion Our approach is being advocated for as it preserves the ability to alter the reconstruction in case of problems resulting from the reconstruction itself, thereby allowing functional evaluation of the reconstruction prior transplantation, permitting simultaneous reperfusion in the recipient, and providing the shortest possible duration for vascular reconstruction once the graft is rewarming non-perfused within the recipient. In addition, in light of the frequency of technically demanding reconstructions with very small vessels, we consider our technique beneficial as the procedure can be performed under ideal conditions at the back-table.

In liver transplantation, older donor age is a well-known risk factor for dismal outcomes, especially due to the high susceptibility of older grafts to ischemia-reperfusion injury. However, whether the factors correlating with impaired graft and patient survival following the transplantation of older grafts follow a linear trend among elderly donors remains elusive. In this study, liver transplantations between January 2006 and May 2018 were analyzed retrospectively. Ninety-two recipients of grafts from donors ≥65 years were identified and divided into two groups: (1) ≥65–69 and (2) ≥ 70 years. One-year patient survival was comparable between recipients of grafts from donors ≥65–69 and ≥70 years (78.9% and 70.0%). One-year graft survival was 73.1% (donor ≥65–69) and 62.5% (donor ≥ 70), while multivariate analysis revealed superior one-year graft survival to be associated with a donor age of ≥65–69. No statistically significant differences were found for rates of primary non-function. The influence of donor age on graft and patient survival appears not to have a distinct impact on dismal outcomes in the range of 65–70 years. The impact of old donor age needs to be balanced with other risk factors, as these donors provide grafts that offer a lifesaving graft function.

Introduction: Simultaneous pancreas and kidney transplantation (SPK) provides optimal therapy for patients suffering from type I diabetes and associated end-stage renal disease (ESRD). Due to the discrepancy of waiting list candidates and suitable grafts, optimization of donor utilisation is mandatory. Allocating pediatric donor organs has been proposed in order to increase the organ donor pool. We herein report a case series of four SPK recipients receiving infant allografts which were offered by rescue allocation. Method: Mean recipient age was 41.5 years (range 30–66). Three recipients were female. The 66 year old male recipient suffered additionally of chronic cardiac insufficiency and three-vessel disease. Donor age was 3, 7 and twice 24 months. Average donor weight was 10 kg (range 6–15 kg). All surgeries were performed as en-bloc kidney and pancreas “piggy-back“ transplants. Ureteric reconstruction was done by ureterocystostomy or by cystocystostomy using a bladder patch if possible. Exocrine drainage of the donor pancreas was established by side-to-side duodeno-duodenostomy. Results: All patients showed immediate kidney function and were off insulin support at 7–10 days posttransplant despite an average pancreas allograft weight of only 30 grams (range 16–53). Most frequent-complication was post-operative haemorrahge mainly contributing to an average CCI score of 28,8. Median hospital stay was 17 days. Median increase of kidney size was 12 mm (range 5–19 mm) within 6 weeks. At a mean follow-up of 5 months all recipents are off insulin (mean HbA1c 5.2%) and off dialysis (mean creatinine 0,9 mg/dl, GFR 79) without evidence for proteinuria. Conclusion: Infant pancreas and kidney allografts are a feasible source for SPK allografts. Despite the fear of increased surgical complications and impaired function secondary to small islet and nephron mass, this series indicates that infant allografts provide good short-term and promising long-term outcomes for adult recipients.

Background Although most centers perform primary portal vein reperfusion (PV) in orthotopic liver transplantation (OLT) for historical reasons, there is so far no sound evidence as to whether this technique is superior. The present study evaluated the long-term outcome of 3 different reperfusion sequences: PV vs primary arterial (A) vs simultaneous reperfusion (SIM). Material/Methods All patients at our center who underwent OLT (who received a primary, whole-organ liver graft) from 2006 to 2007 were evaluated for analysis. Results A total of 61 patients were found eligible (PV: 25, A: 22, SIM: 14). Twenty-one patients (35%) were still alive after the follow-up period of 12 years. Despite poorer starting conditions such as higher recipient age (59 y (SIM) vs 55 y (A) vs 50 y (PV), P=0.01) and donor age (56 y (SIM) vs 51 y (PV) vs 50 y (A), n.s.), higher MELD scores (22 vs 19 (PV) vs 17 (A), n.s.), as well as a higher number of marginal donor organs (79% (SIM) vs 36% (A/PV), P=0.02), SIM-recipients demonstrated superior outcomes. Overall survival was 8.1 y (SIM), 4.8 y (PV), and 5.9 y (A, n.s.)). None of the SIM-recipients underwent re-transplantation, while the rate was 32% in the PV-group. The 8.1 y graft survival in SIM-recipients was significantly longer than in the other 2 groups, which were 3.3 y (PV) and 5.5 y (A, P=0.013). Conclusions Although SIM-reperfused recipients were the oldest and received grafts of inferior quality, these recipients showed superior results in terms of overall patient and graft survival. Multicentric randomized controlled trials with larger study populations are required to confirm this finding.

The term intestinal failure (IF) is understood as the transient or irreversible loss of the resorptive capacity of the bowels. This includes a multitude of diseases, some of which have anatomical causes and others functional causes. The functional capacity (absorption and motility) of the remaining digestive tract and the bacterial overgrowth and false colonization of the small bowel are of prognostic importance. After exclusion of pathological intestinal findings, such as stenosis and dilatation, initially conservative treatment is employed with the aim of intestinal adaptation. Before failure or complications, initially conservative surgery and then organ replacement by transplantation should be considered. The IF is a temporary or permanent condition. For adults a length of 100cm small bowel without the colon, 60cm still with continuity to the colon and 35cm small bowel with complete preservation of the colon including the ileocecal valve are potentially sufficient for intestinal autonomy.