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Cytomegalovirus (CMV) infection detrimentally influences graft survival in kidney transplant recipients, with the risk primarily determined by recipient and donor serostatus. However, recipient CD8 + T cells play a crucial role in CMV control. The optimal preventive strategy (prophylaxis vs. pre-emptive treatment), particularly for seropositive (intermediate risk) recipients, remains uncertain. We investigated CD8 + T cell subpopulation dynamics and CMV occurrence (DNAemia ≥ 100 IU/mL) in 65 kidney transplant recipients, collecting peripheral blood mononuclear cells before (T1) and 1 year after transplantation (T2). Comparing the two timepoints, we found an increase in granulocyte, monocyte and CD3 + CD8 + T cells numbers, while FoxP3 + CD25 + , LAG-3 + and PD-1 + frequencies were reduced at T2. CMV DNAemia occurred in 33 recipients (55.8%) during the first year. Intermediate risk patients were disproportionally affected by posttransplant CMV ( N = 29/45, 64.4%). Intermediate risk recipients developing CMV after transplantation exhibited lower leukocyte, monocyte, and granulocyte counts and higher FoxP3 + CD25 + frequencies in CD3 + CD8 + T cells pre-transplantation compared to patients staying CMV negative. Pre-transplant FoxP3 + CD25 + in CD3 + CD8 + T cells had the best discriminatory potential for CMV infection prediction within the first year after transplantation (AUC: 0.746). The FoxP3 + CD25 + CD3 + CD8 + T cell subset may aid in selecting intermediate risk kidney transplant recipients for CMV prophylaxis., Competing Interests: Authors VP and BP were employed by CBmed GmbH. KE received congress-support and speaker fees by Chiesi and Astellas. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Mooslechner, Schuller, Pfeifer, Klötzer, Prietl, Kirsch, Stiegler, Sucher, Sourij, Rosenkranz and Eller.)

Background: Whenever the kidney standard allocation (SA) algorithms according to the Eurotransplant (ET) Kidney Allocation System or the Eurotransplant Senior Program fail, rescue allocation (RA) is initiated. There are 2 procedurally different modes of RA: recipient oriented extended allocation (REAL) and competitive rescue allocation (CRA). The objective of this study was to evaluate the association of patient survival and graft failure with RA mode and whether or not it varied across the different ET countries., Methods: The ET database was retrospectively analyzed for donor and recipient clinical and demographic characteristics in association with graft outcomes of deceased donor renal transplantation (DDRT) across all ET countries and centers from 2014 to 2021 using Cox proportional hazards methods., Results: Seventeen thousand six hundred seventy-nine renal transplantations were included (SA 15 658 [89%], REAL 860 [4.9%], and CRA 1161 [6.6%]). In CRA, donors were older, cold ischemia times were longer, and HLA matches were worse in comparison with REAL and especially SA. Multivariable analyses showed comparable graft and recipient survival between SA and REAL; however, CRA was associated with shorter graft survival. Germany performed 76% of all DDRTs after REAL and CRA and the latter mode reduced waiting times by up to 2.9 y., Conclusions: REAL and CRA are used differently in the ET countries according to national donor rates. Both RA schemes optimize graft utilization, lead to acceptable outcomes, and help to stabilize national DDRT programs, especially in Germany., Competing Interests: The authors declare no funding or conflicts of interest., (Copyright © 2023 Wolters Kluwer Health, Inc. All rights reserved.)

Health-related quality of life (HRQOL) improves after kidney transplantation (KT) but declines over time. Studies on the effect of early postoperative basal insulin therapy on HRQOL after KT, especially KTRs at high risk of developing post-transplant diabetes mellitus (PTDM) are missing. Data from a randomized controlled trial on 148 non-diabetic KTRs were analyzed. HRQOL using the KDQOL-SF™ was compared in KTRs who either received early postoperative basal insulin therapy or standard-of-care and in KTRs at risk of developing PTDM. Determinants of HRQOL outcomes were investigated using multivariable linear regression analysis. In total, 148 patients completed the KDQOL-SF at baseline. Standard-of-care or early basal insulin therapy after KT did not influence HRQOL. Overall, KT improved the mental (MCS) and physical component summary (PCS) scores at 6-month after KT, which remained stable during further follow-up visits. However, patients at high-risk for PTDM had significantly greater impairment in the PCS score (baseline, 24 months) without differences in MCS scores. In the multivariable regression analysis, allograft function and hemoglobin levels were associated with decreased MCS and PCS scores, respectively. A limitation of the study is the fact that only around 50% of the ITP-NODAT study patients participated in the HRQOL evaluation. Still, our data clearly show that early basal insulin therapy does not affect HRQOL after KT but is negatively influenced by classical clinical factors and PTDM-risk at 24 months after KT. The latter might be influenced by older age., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Odler, Huemer, Schwaiger, Borenich, Kurnikowski, Krall, Hafner-Giessauf, Eleftheriadis, Bachmann, Faura, José Pérez-Sáez, Pascual, Budde, Rosenkranz, Hecking and Eller.)

Immunosuppression is an essential prerequisite for successful transplantation. In order to reduce the sometimes-considerable side effects, combination therapies with different agents are used. This article aims to provide an up-to-date overview of immunosuppression after liver and kidney transplantation., Competing Interests: Erklärung zu finanziellen InteressenForschungsförderung erhalten: nein; Honorar/geldwerten Vorteil für Referententätigkeit: nein; Bezahlter Berater/interner Schulungsreferent/Gehaltsempfänger: nein; Patent/Geschäftsanteile/Aktien (Autor/Partner, Ehepartner, Kinder) an Firma (Sponsor der Veranstaltung): nein; Patent/Geschäftsanteile/Aktien (Autor/Partner, Ehepartner, Kinder) an Firma (Nicht-Sponsor der Veranstaltung): nein.Erklärung zu nichtfinanziellen InteressenDie Autorinnen/Autoren geben an, dass kein Interessenkonflikt besteht., (Thieme. All rights reserved.)

Background: At Eurotransplant (ET), kidneys are transferred to "rescue allocation" (RA), whenever the standard allocation (SA) algorithms Eurotransplant Kidney Allocation System (ETKAS) and Eurotransplant Senior Program (ESP) fail. We analyzed the outcome of RA., Methods: Retrospective patient clinical and demographic characteristics association analyses were performed with graft outcomes for 2422 recipients of a deceased donor renal transplantation (DDRT) after RA versus 25 481 after SA from 71 centers across all ET countries from 2006 to 2018., Results: Numbers of DDRTs after RA increased over the time, especially in Germany. RA played a minor role in ESP versus ETKAS (2.7% versus 10.4%). RA recipients and donors were older compared with SA recipients and donors, cold ischemia times were longer, waiting times were shorter, and the incidence of primary nonfunction was comparable. Among ETKAS recipients, HLA matching was more favorable in SA (mean 3.7 versus 2.5). In multivariate modeling, the incidence of graft loss in ETKAS recipients was reduced in RA compared with SA (subdistribution hazard ratio, 0.80; 95% confidence interval [0.70-0.91], P < 0.001), whereas other outcomes (mortality, death with functioning graft (DwFG)) were not significantly different. None of the 3 outcomes were significantly different when comparing RA with SA within the ESP program., Conclusions: Facing increased waiting times and mortality on dialysis due to donor shortage, this study reveals encouragingly positive DDRT outcomes following RA. This supports the extension of RA to more patients and as an alternative tool to enable transplantation in patients in countries with prohibitively long waiting times or at risk of deterioration., Competing Interests: The authors declare no funding or conflicts of interest., (Copyright © 2022 Wolters Kluwer Health, Inc. All rights reserved.)

Objectives: Living kidney donors provide a unique setting to study functional and metabolic consequences after organ donation. Since the lack of data of the homoeostasis of numerous vitamin D metabolites in these healthy subjects, the aim of this study was to assess the vitamin D metabolism before and after kidney donation., Methods: We investigated the 25-dihydroxyvitamin D 2 (25[OH]D 2 ), 25-dihydroxyvitamin D 3 (25[OH]D 3 ), 1,25-dihydroxyvitamin D 3 (1,25[OH] 2 D 3 ), 24,25-dihydroxyvitamin D 3 (24,25[OH] 2 D 3 ), 25,26-dihydroxyvitamin D 3 (25,26[OH] 2 D 3 ), and the native vitamin D2 (ergocalciferol) and vitamin D3 (cholecalciferol) in a well characterized study cohort of 32 healthy living kidney donors before and after organ donation., Results: Thirty-two healthy subjects after kidney donation had significantly lower median (interquartile range) 1,25(OH) 2 D 3 serum concentrations (88.6 [62.6-118.8] vs. 138.0 [102.6-152.4] pmol/L, p<0.001) and significantly higher median 25(OH)D 2 serum levels (1.80 [1.19-2.19] vs. 1.11 [0.74-1.59] nmol/L, p=0.019) than before donation. Similar serum concentrations of 25(OH)D 3 and 25,26(OH) 2 D 3 were observed before and after donation. The 24,25(OH) 2 D 3 blood levels distinctly decreased after organ donation (4.1 [2.3-5.3] vs. 5.3 [2.2-6.9] nmol/L, p=0.153). Native vitamin D2 (0.10 [0.08-0.14] vs. 0.08 [0.06-0.12] nmol/L, p=0.275) was slightly increased and vitamin D3 (1.6 [0.6-7.2] vs. 2.5 [0.9-8.6] nmol/L, p=0.957) decreased after kidney donation., Conclusions: Living kidney donors were found with decreased 1,25(OH) 2 D 3 and 24,25(OH) 2 D 3 , increased 25(OH)D 2 and consistent 25(OH)D 3 and 25,26(OH) 2 D 3 serum concentrations after organ donation. The current study advances the understanding on vitamin D metabolism suggesting that altered hydroxylase-activities after donation is accompanied by compensatory elevated dietary-related 25(OH)D 2 blood concentrations., (© 2022 Walter de Gruyter GmbH, Berlin/Boston.)

Background: Post-transplantation diabetes mellitus (PTDM) might be preventable., Methods: This open-label, multicenter randomized trial compared 133 kidney transplant recipients given intermediate-acting insulin isophane for postoperative afternoon glucose ≥140 mg/dl with 130 patients given short-acting insulin for fasting glucose ≥200 mg/dl (control). The primary end point was PTDM (antidiabetic treatment or oral glucose tolerance test-derived 2 hour glucose ≥200 mg/dl) at month 12 post-transplant., Results: In the intention-to-treat population, PTDM rates at 12 months were 12.2% and 14.7% in treatment versus control groups, respectively (odds ratio [OR], 0.82; 95% confidence interval [95% CI], 0.39 to 1.76) and 13.4% versus 17.4%, respectively, at 24 months (OR, 0.71; 95% CI, 0.34 to 1.49). In the per-protocol population, treatment resulted in reduced odds for PTDM at 12 months (OR, 0.40; 95% CI, 0.16 to 1.01) and 24 months (OR, 0.54; 95% CI, 0.24 to 1.20). After adjustment for polycystic kidney disease, per-protocol ORs for PTDM (treatment versus controls) were 0.21 (95% CI, 0.07 to 0.62) at 12 months and 0.35 (95% CI, 0.14 to 0.87) at 24 months. Significantly more hypoglycemic events (mostly asymptomatic or mildly symptomatic) occurred in the treatment group versus the control group. Within the treatment group, nonadherence to the insulin initiation protocol was associated with significantly higher odds for PTDM at months 12 and 24., Conclusions: At low overt PTDM incidence, the primary end point in the intention-to-treat population did not differ significantly between treatment and control groups. In the per-protocol analysis, early basal insulin therapy resulted in significantly higher hypoglycemia rates but reduced odds for overt PTDM-a significant reduction after adjustment for baseline differences-suggesting the intervention merits further study. Clinical Trial registration number: NCT03507829., (Copyright © 2021 by the American Society of Nephrology.)

Introduction: Magnesium (Mg 2+ ) deficiency is a common finding in the early phase after kidney transplantation (KT) and has been linked to immune dysfunction and infections. Data on the association of hypomagnesemia and the rate of infections in kidney transplant recipients (KTRs) are sparse., Methods: We conducted a single-center retrospective cohort study of KTRs transplanted between 2005 and 2015. Laboratory data, including serum Mg 2+ (median time of the Mg 2+ measurement from KT: 29 days), rate of infections including mainly urinary tract infections (UTI), and common transplant-related viral infections (CMV, polyoma, EBV) in the early phase after KT were recorded. The primary outcome was the incidence of infections within one year after KT, while secondary outcomes were hospitalization due to infection, incidence rates of long-term (up to two years) infections, and all-cause mortality., Results: We enrolled 376 KTRs of whom 229 patients (60.9%) suffered from Mg 2+ deficiency defined as a serum Mg 2+ < 0.7 mmol/L. A significantly higher incidence rate of UTIs and viral infections was observed in patients with versus without Mg 2+ deficiency during the first year after KT (58.5% vs. 47.6%, p = 0.039 and 69.9% vs. 51.7%, p < 0.001). After adjustment for potential confounders, serum Mg 2+ deficiency remained an independent predictor of both UTIs and viral infections (odds ratio (OR): 1.73, 95% CI: 1.04-2.86, p = 0.035 and OR: 2.05, 95% CI: 1.23-3.41, p = 0.006). No group differences according to Mg 2+ status in hospitalizations due to infections and infection incidence rates in the 12-24 months post-transplant were observed. In the Cox regression analysis, Mg 2+ deficiency was not significantly associated with all-cause mortality (HR: 1.15, 95% CI: 0.70-1.89, p = 0.577)., Conclusions: KTRs suffering from Mg 2+ deficiency are at increased risk of UTIs and viral infections in the first year after KT. Interventional studies investigating the effect of Mg 2+ supplementation on Mg 2+ deficiency and viral infections in KTRs are needed.

Objectives: The mucoprotein uromodulin is considered to correlate with glomerular filtration rates (GFR) in patients with chronic kidney disease (CKD). Here we investigated how serum uromodulin is associated with measured GFR using inulin-clearance and GFR estimated by CKD-EPI (Chronic Kidney Disease Epidemiology Collaboration) equation in healthy subjects., Methods: We assessed possible correlations between uromodulin serum concentrations, inulin-GFR and CKD-EPI-GFR in a well characterized study cohort of 112 healthy living kidney donors with two kidneys before and 64 with one kidney after kidney donation. A subgroup of 32 individuals, which presented data before and after nephrectomy, was assessed separately., Results: All 112 healthy living kidney donors with two kidneys revealed individual serum uromodulin concentrations between 60.1 and 450.5 µg/L. Sixty-four healthy kidney donors after nephrectomy had significantly lower median (interquartile range) serum uromodulin concentrations (124 [101-166] vs. 185 [152-238] µg/L), inulin-GFR (67.3 [60.6-74.6] vs. 93.5 [82.1-104.4] mL/min/1.73 m 2 ), and CKD-EPI-GFR (61.2 [53.1-69.7] vs. 88.6 [80.0-97.1] mL/min/1.73 m 2 ) as compared to the 112 donors before donation (p<0.001). The subgroup of 32 subjects, which presented data before and after nephrectomy, showed almost the same pattern of kidney function. No statistically relevant associations were found between serum uromodulin and inulin-GFR or CKD-EPI-GFR regarding this healthy population., Conclusions: These novel findings indicate that - in contrast to patients with CKD - serum uromodulin concentrations are not correlated with measured and estimated GFR in healthy individuals., (© 2020 Walter de Gruyter GmbH, Berlin/Boston.)

Background: Kidney transplant recipients exhibit a dramatically increased cardiovascular (CV) risk. In 2007, Austrian centres implemented a consensus of comprehensive CV screening programme prior to kidney transplantation (KT). The consensus placed a particular emphasis on screening for coronary artery disease (CAD) with cardiac computed tomography (CT) or coronary angiography (CAG) in patients with diabetes mellitus, known CAD or those having multiple conventional CV risk factors. Here, we investigate if this affected risk stratification and post-transplant CV outcomes., Methods: In a retrospective chart review, we evaluated 551 KTs performed from 2003 to 2015 in our centre. Patients were categorized into three groups: KT before (2003-07), directly after (2008-11) and 5 years after (2012-15) implementation of the consensus. We analysed clinical characteristics, the rate of cardiac CTs and CAGs prior to KT as well as major adverse cardiac events (MACEs) during a 2-year follow-up after KT., Results: The three study groups showed a homogeneous distribution of comorbidities and age. Significantly more cardiac CTs (13.6% versus 10.2% versus 44.8%; P = 0.002) and CAGs (39.6% versus 43.9% versus 56.2%; P = 0.003) were performed after the consensus. Coronary interventions were performed during 42 out of 260 CAGs (16.2%), the cumulative 2-year MACE incidence was 8.7%. Regarding MACE occurrence, no significant difference between the three groups was found., Conclusion: CV risk stratification has become more rigorous and invasive after the implementation of the consensus; however, this was not associated with an improvement in CV outcome., (© The Author(s) 2020. Published by Oxford University Press on behalf of ERA-EDTA.)

In Eurotransplant kidney allocation system (ETKAS), candidates can be considered unlimitedly for repeated re-transplantation. Data on outcome and benefit are indeterminate. We performed a retrospective 15-year patient and graft outcome data analysis from 1464 recipients of a third or fourth or higher sequential deceased donor renal transplantation (DDRT) from 42 transplant centers. Repeated re-DDRT recipients were younger (mean 43.0 vs. 50.2 years) compared to first DDRT recipients. They received grafts with more favorable HLA matches (89.0% vs. 84.5%) but thereby no statistically significant improvement of patient and graft outcome was found as comparatively demonstrated in 1st DDRT. In the multivariate modeling accounting for confounding factors, mortality and graft loss after 3rd and ≥4th DDRT (P < 0.001 each) and death with functioning graft (DwFG) after 3rd DDRT (P = 0.001) were higher as compared to 1st DDRT. The incidence of primary nonfunction (PNF) was also significantly higher in re-DDRT (12.7%) than in 1st DDRT (7.1%; P < 0.001). Facing organ shortage, increasing waiting time, and considerable mortality on dialysis, we question the current policy of repeated re-DDRT. The data from this survey propose better HLA matching in first DDRT and second DDRT and careful selection of candidates, especially for ≥4th DDRT., (© 2020 The Authors. Transplant International published by John Wiley & Sons Ltd on behalf of Steunstichting ESOT.)

Kidney transplantation (KTx) in end-stage renal disease is associated with a significant increase in quality of life (QoL) and self-perceived health, optimally leading to the maintenance of employment or return to work (RTW) in working-age patients. The aim of this study was to assess individual factors including the QoL and mental health of kidney transplant recipients (KTRs) associated with employment after transplantation. A cross-sectional study including working-age patients with a history of KTx after 2012 was conducted at two Austrian study centers (Vienna and Graz). Brief Symptom Inventory (BSI-18), World Health Organization Quality of Life (WHOQOL-Bref) and Workability Index (WAI) were assessed along with detailed questionnaires on employment status. Out of n = 139 KTRs (43.2 ± 9.07 years; 57.6% male), 72 (51.8%) were employed. Employed patients were more frequently in a partnership ( p = 0.018) and had higher education levels ( p = 0.01) and QoL scores (<0.001). Unemployed KTRs reported fatigue and mental health issues more often ( p < 0.001), and had significantly higher anxiety, depression and somatization scores (BSI-18). In unadjusted logistical regression, workability score (WAS; odds ratio (OR) = 3.39; 95% confidence interval (CI) = 1.97-5.82; p < 0.001), partnership (OR = 5.47; 95% CI 1.43-20.91; p = 0.013) and no psychological counseling after KTx (OR = 0.06; 95% CI = 0.003-0.969; p = 0.048) were independently associated with employment. Self-assessed mental health, workability and QoL were significantly associated with employment status after KTx. Thus, in order to facilitate RTW after KTx in Austria, vocational rehabilitation and RTW programs addressing KTRs should focus on increasing social support and care for their mental health.

Here, we report on a patient after kidney transplantation, who developed fever and pneumonitis due to mycophenolic acid (MPA) treatment. Decreasing MPA dosages improved the symptoms, but after rechallenge with higher MPA doses the symptoms recurred. Discontinuation of MPA resulted in a complete resolution of fever within 24 h and a rapid improvement in pneumonitis. In vitro, the patient's polymorphonuclear neutrophils (PMNs) developed increased oxidative burst when incubated with MPA and N-formyl Met-Leu-Phe. We first report on MPA-induced pneumonitis and show that MPA can induce a pro-inflammatory response in kidney-transplanted patients. These pro-inflammatory changes might be due to paradoxical activation of PMNs., (© 2013 The Authors Transplant International © 2013 European Society for Organ Transplantation. Published by Blackwell Publishing Ltd.)

Background: Renal transplantation has been shown to be the best therapeutic option in end-stage renal disease patients. En bloc transplantation of pediatric kidneys into adult recipients (EBKT) is one strategy to increase the donor pool. We here report on 10 to 22 years of follow-up (median of 12.8 years) of patients receiving EBKT in a single-center, retrospective cohort study., Material and Methods: The mean donor age was 14 ± 12 months and mean donor body weight was 8 ± 3 kilograms. Thirteen recipients (6 females, 7 males) were followed for 10 to 22 years. The mean recipient age was 44 ± 13 years at the time of transplantation., Results: Two of 13 patients lost their grafts in the first week because of hemorrhagic infarction of the kidney transplants or sepsis (septic shock). Only 1 patient had an acute cellular rejection, which was successfully treated with steroids and anti-CD3 antibody. Eleven out of 13 patients after EBKT survived and had a functioning graft 10 to 22 years after successful EBKT. The serum creatinine was 1.34 ± 0.6 mg/dl at 5 years (n=11), 1.37 ± 0.7 mg/dl at 10 years (n=11), 1.40 ± 0.6 mg/dl at 15 years (n=4), and 1.08 mg/dl at 20 years after EBKT (n=2). The eGFR, evaluated by using MDRD-2, was 66.5 ± 22 ml/min/m2 at 5 years (n=11), 62 ± 28 ml/min/m2 at 10 years (n=11), 56 ± 23 ml/min/m2 at 15 years (n=4), and 61 ml/min/m2 at 20 years after EBKT (n=2). Proteinuria did not increase significantly within the observation period., Conclusions: In our experience, if the acute post-operative phase is uncomplicated, EBKT has excellent long-term graft and patient survival.

The immunosuppressive agent tacrolimus is now widely used for the prevention of acute and chronic rejection in renal allograft recipients. We here report on three patients, who developed drug-induced fever due to tacrolimus one to five months after renal transplantation. Extensive search for a focus, autoantibodies and virus infection remained inconclusive. Therefore, drug-induced fever was suggested. After discontinuing tacrolimus and switching to cyclosporine A fever completely resolved within 24 h. This report demonstrates that tacrolimus-induced drug fever should be included in the differential diagnosis of fever of unknown origin in renal transplant recipients.

Hemolytic uremic syndrome (HUS) is a rare complication following solid organ transplantation. We report on a patient who underwent renal transplantation using Campath-1H induction and tacrolimus maintenance therapy who developed HUS, which was managed by plasma exchange and switch to Rapamycin. However, graft function could not be restored.

Background: Combined kidney pancreas transplantation (PTx) evolved as excellent treatment for diabetic nephropathy. Infections remain common and serious complications., Methods: 217 consecutive enteric drained PTxs performed from 1997 to 2004 were retrospectively analyzed with regard to bloodstream infection. Immunosuppression consisted of antithymocyteglobuline induction, tacrolimus, mycophenolic acid and steroids for the majority of cases. Standard perioperative antimicrobial prophylaxis consisted of pipercillin/tazobactam in combination with ciprofloxacin and fluconazole., Results: One year patient, pancreas and kidney graft survival were 96.4%, 88.5% and 94.8%, surgical complication rate was 35%, rejection rate 30% and rate of infection 59%. In total 46 sepsis episodes were diagnosed in 35 patients (16%) with a median onset on day 12 (range 1-45) post transplant. Sepsis source was intraabdominal infection (IAI) (n = 21), a contaminated central venous line (n = 10), wound infection (n = 5), urinary tract infection (n = 2) and graft transmitted (n = 2). Nine patients (4%) experienced multiple episodes of sepsis. Overall 65 pathogens (IAI sepsis 39, line sepsis 15, others 11) were isolated from blood. Gram positive cocci accounted for 50 isolates (77%): Coagulase negative staphylococci (n = 28, i.e. 43%) (nine multi-resistant), Staphylococcus aureus (n = 11, i.e. 17%) (four multi-resistant), enterococci (n = 9, i.e. 14%) (one E. faecium). Gram negative rods were cultured in twelve cases (18%). Patients with blood borne infection had a two year pancreas graft survival of 76.5% versus 89.4% for those without sepsis (p = 0.036), patient survival was not affected., Conclusion: Sepsis remains a serious complication after PTx with significantly reduced pancreas graft, but not patient survival. The most common source is IAI.

Acute humoral rejection (AHR) is currently perceived as an immunological reaction against donor antigens mediated by complement-binding antibodies. C4d, a split product of complement activation and bound to endothelial cells of the peritubular capillaries, is used as a diagnostic marker for AHR. We report on three patients with biopsy-proven acute humoral rejection who were treated initially with plasmapheresis (PS). As two of the patients did not recover renal function, and biopsy showed persistent C4d staining after PS, immunoadsorption (IAS) was additionally performed on them. In all patients, renal function recovered, and follow-up biopsies in two patients showed complete disappearance of C4d, 29 days and 58 days after transplantation and only minimal residual C4d deposits in one patient 48 days after transplantation. We conclude that successful treatment of AHR is followed by complete resolution of serological and histological markers of AHR, displayed by the disappearance of C4d.

Cytomegalovirus (CMV) infection detrimentally influences graft survival in kidney transplant recipients, with the risk primarily determined by recipient and donor serostatus. However, recipient CD8+ T cells play a crucial role in CMV control. The optimal preventive strategy (prophylaxis vs. pre-emptive treatment), particularly for seropositive (intermediate risk) recipients, remains uncertain. We investigated CD8+ T cell subpopulation dynamics and CMV occurrence (DNAemia ≥ 100 IU/mL) in 65 kidney transplant recipients, collecting peripheral blood mononuclear cells before (T1) and 1 year after transplantation (T2). Comparing the two timepoints, we found an increase in granulocyte, monocyte and CD3+CD8+ T cells numbers, while FoxP3+CD25+, LAG-3+ and PD-1+ frequencies were reduced at T2. CMV DNAemia occurred in 33 recipients (55.8%) during the first year. Intermediate risk patients were disproportionally affected by posttransplant CMV (N = 29/ 45, 64.4%). Intermediate risk recipients developing CMV after transplantation exhibited lower leukocyte, monocyte, and granulocyte counts and higher FoxP3+CD25+ frequencies in CD3+CD8+ T cells pre-transplantation compared to patients staying CMV negative. Pretransplant FoxP3+CD25+ in CD3+CD8+ T cells had the best discriminatory potential for CMV infection prediction within the first year after transplantation (AUC: 0.746). The FoxP3+CD25+ CD3+CD8+ T cell subset may aid in selecting intermediate risk kidney transplant recipients for CMV prophylaxis. [ABSTRACT FROM AUTHOR]

Introduction: Although adherence to immunosuppressive medication is the key factor for long-term graft survival today, 20–70% of transplant recipients are nonadherent to their immunosuppressive medication. Objective: A prospective, randomized, controlled single-center feasibility study was designed to evaluate the impact of a step guided multicomponent interprofessional intervention program for patients after kidney or liver transplantation on adherence to their immunosuppressive medication in daily clinical practice. Materials and methods: The intervention consisted of group therapy and daily training as well as individual sessions in a step guided approach. The primary endpoint of the study was adherence to immunosuppression as assessed with the “Basel Assessment of Adherence to Immunosuppressive Medications Scale” (BAASIS). The coefficient of variation (CV%) of Tacrolimus (TAC) through levels and the level of personality functioning was a secondary endpoint. We conducted six monthly follow-up visits. Results: Forty-one age- and sex-matched patients [19 females, 58.5 (SD = 10.56) years old, 22 kidney- and 19 liver transplantation] were randomized to the intervention- (N = 21) or control-group (N = 20). No differences between intervention- and control groups were found in the primary endpoint adherence and CV% of TAC. However, in further exploratory analyses, we observed that individuals with higher impairments in personality functioning showed higher CV% of TAC in the controls. The intervention might compensate personalityrelated susceptibility to poor adherence as evident in CV% of TAC. Discussion: The results of the feasibility study showed that this intervention program was highly accepted in the clinical setting. The Intervention group could compensate higher CV% of TAC after liver or kidney transplantation in individuals with lower levels of personality functioning and non-adherence. [ABSTRACT FROM AUTHOR]

SARS-CoV-2 led to considerable morbidity/mortality worldwide and tremendously impacted on daily life. Strict lockdown measures were implemented early to contain the viral outbreak in Austria. Massive changes in organizational structures of healthcare facilities followed with unclear implications on the care of non-COVID-19-affected patients. We studied the nationwide impact of COVID-19 on kidney transplantation in Austria during the first six months of 2020. Concurrent with general lockdown measures, all kidney transplant activity was suspended from 13 March to 9 April. Nevertheless, between January and June, total transplant (p = 0.48) and procured donor organ numbers (p = 0.6) did not differ significantly from earlier years. Ten (0.18%) of 5512 prevalent Austrian kidney transplant recipients were diagnosed with SARS-CoV-2. The case fatality rate (one death; 10%) in renal transplant patients was less than in other countries but higher than in Austria's general population (2.4%). We conclude that early and strict general lockdown measures imposed by the government allowed an early, however cautious, re-opening of Austrian transplant programs and played a crucial role for the favorable outcomes of SARS-CoV-2 in Austrian kidney transplant patients. Even though it may be uncertain whether similar results may be obtainable in other countries, the findings may support early intervention strategies during similar episodes in the future. [ABSTRACT FROM AUTHOR]

Abstract Background and aims Chronic kidney disease (CKD) is strongly associated with a high burden of cardiovascular morbidity and mortality. Therefore, we aimed to characterize the putative role of microRNAs (miR)s in uremic vascular remodelling and endothelial dysfunction. Methods We investigated the expression pattern of miRs in two independent end-stage renal disease (ESRD) cohorts and in the animal model of uremic DBA/2 mice via quantitative RT-PCR. Moreover, DBA/2 mice were treated with intravenous injections of synthetic miR-142-3p mimic and were analysed for functional and morphological vascular changes by mass spectrometry and wire myography. Results The expression pattern of miRs was regulated in ESRD patients and was reversible after kidney transplantation. Out of tested miRs, only blood miR-142-3p was negatively associated with carotid-femoral pulse-wave velocity in CKD 5D patients. We validated these findings in a murine uremic model and found similar suppression of miR-142-3p as well as decreased acetylcholine-mediated vascular relaxation of the aorta. Therefore, we designed experiments to restore bioavailability of aortic miR-142-3p in vivo via intravenous injection of synthetic miR-142-3p mimic. This intervention restored acetylcholine-mediated vascular relaxation. Conclusions Taken together, we provide compelling evidence, both in humans and in mice, that miR-142-3p constitutes a potential pharmacological agent to prevent endothelial dysfunction and increased arterial stiffness in ESRD. Graphical abstract Image 1 Highlights • Blood miR-142-3p is associated with pulse-wave velocity in uremic patients. • miR-142-3p was associated with decreased vascular relaxation in uremic mice. • Injection of miR-142-3p mimic restored acetylcholine-mediated aortic relaxation. • miR-142-3p might prevent endothelial dysfunction and arterial stiffness in uremia. [ABSTRACT FROM AUTHOR]