Potential and Uncertainties of RejectClass in Acute Kidney Graft Dysfunction: An Independent Validation Study.

BACKGROUND: Kidney graft rejections are classified based on the Banff classification. The RejectClass algorithm, initially derived from a cohort comprising mostly protocol biopsies, identifies data-driven phenotypes of acute rejection and chronic pathology using Banff lesion scores. It also provides composite scores for inflammation activity and chronicity. This study independently evaluates the performance of RejectClass in a cohort consisting entirely of indication biopsies. METHODS: We retrospectively applied RejectClass to 441 patients from the German TRABIO (TRAnsplant BIOpsies) cohort who had received indication biopsies. The primary endpoint was death-censored graft failure during 2 y of follow-up. RESULTS: The application of RejectClass to our cohort demonstrated moderately comparable phenotypic features with the derivation cohort, and most clusters indicated an elevated risk of graft loss. However, the reproduction of all phenotypes and the associated risks of graft failure, as depicted in the original studies, was not fully accomplished. In contrast, adjusted Cox proportional hazards analyses substantiated that both the inflammation score and the chronicity score are independently associated with graft loss, exhibiting hazard ratios of 1.7 (95% confidence interval, 1.2-2.3; P = 0.002) and 2.2 (95% confidence interval, 1.8-2.6; P < 0.001), respectively, per 0.25-point increment (scale: 0.0-1.0). CONCLUSIONS: The composite inflammation and chronicity scores may already have direct utility in quantitatively assessing the disease stage. Further refinement and validation of RejectClass clusters are necessary to achieve more reliable and accurate phenotyping of rejection.

Rescue Allocation Modes in Eurotransplant Kidney Transplantation: Recipient Oriented Extended Allocation Versus Competitive Rescue Allocation-A Retrospective Multicenter Outcome Analysis.

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.

Blood group-specific apheresis in combination with daratumumab as a rescue therapy of acute antibody-mediated rejection in a case of ABO- and human leukocyte antigen-incompatible kidney transplantation.

We report a case of antibody-mediated rejection treated with the human CD38 monoclonal antibody daratumumab in a 58-year-old female patient with end-stage kidney disease due to autosomal dominant polycystic kidney disease who received an ABO- and human leukocyte antigen antibody-incompatible living donor kidney transplant. The patient experienced an episode of severe antibody-mediated rejection within the first week of transplantation. Blood-group-antibody selective immunoadsorption in combination with administration of four doses of daratumumab (each 1800 mg s.c.) led to a persistent decrease of ABO- and more interestingly donor-specific human leukocyte antigen antibody reactivity and resulted in clinical and histopathological remission with full recovery of graft function, which has remained stable until post-transplant day 212. This case illustrates the potential of targeting CD38 in antibody-mediated rejection.

Human peritoneal tight junction, transporter and channel expression in health and kidney failure, and associated solute transport.

Next to the skin, the peritoneum is the largest human organ, essentially involved in abdominal health and disease states, but information on peritoneal paracellular tight junctions and transcellular channels and transporters relative to peritoneal transmembrane transport is scant. We studied their peritoneal localization and quantity by immunohistochemistry and confocal microscopy in health, in chronic kidney disease (CKD) and on peritoneal dialysis (PD), with the latter allowing for functional characterizations, in a total of 93 individuals (0-75 years). Claudin-1 to -5, and -15, zonula occludens-1, occludin and tricellulin, SGLT1, PiT1/SLC20A1 and ENaC were consistently detected in mesothelial and arteriolar endothelial cells, with age dependent differences for mesothelial claudin-1 and arteriolar claudin-2/3. In CKD mesothelial claudin-1 and arteriolar claudin-2 and -3 were more abundant. Peritonea from PD patients exhibited increased mesothelial and arteriolar claudin-1 and mesothelial claudin-2 abundance and reduced mesothelial and arteriolar claudin-3 and arteriolar ENaC. Transperitoneal creatinine and glucose transport correlated with pore forming arteriolar claudin-2 and mesothelial claudin-4/-15, and creatinine transport with mesothelial sodium/phosphate cotransporter PiT1/SLC20A1. In multivariable analysis, claudin-2 independently predicted the peritoneal transport rates. In conclusion, tight junction, transcellular transporter and channel proteins are consistently expressed in peritoneal mesothelial and endothelial cells with minor variations across age groups, specific modifications by CKD and PD and distinct associations with transperitoneal creatinine and glucose transport rates. The latter deserve experimental studies to demonstrate mechanistic links.Clinical Trial registration: The study was performed according to the Declaration of Helsinki and is registered at www.clinicaltrials.gov (NCT01893710).

Five-year follow-up of a phase I trial of donor-derived modified immune cell infusion in kidney transplantation.

Background: The administration of modified immune cells (MIC) before kidney transplantation led to specific immunosuppression against the allogeneic donor and a significant increase in regulatory B lymphocytes. We wondered how this approach affected the continued clinical course of these patients. Methods: Ten patients from a phase I clinical trial who had received MIC infusions prior to kidney transplantation were retrospectively compared to 15 matched standard-risk recipients. Follow-up was until year five after surgery. Results: The 10 MIC patients had an excellent clinical course with stable kidney graft function, no donor-specific human leukocyte antigen antibodies (DSA) or acute rejections, and no opportunistic infections. In comparison, a retrospectively matched control group receiving standard immunosuppressive therapy had a higher frequency of DSA (log rank P = 0.046) and more opportunistic infections (log rank P = 0.033). Importantly, MIC patients, and in particular the four patients who had received the highest cell number 7 days before surgery and received low immunosuppression during follow-up, continued to show a lack of anti-donor T lymphocyte reactivity in vitro and high CD19+CD24hiCD38hi transitional and CD19+CD24hiCD27+ memory B lymphocytes until year five after surgery. Conclusions: MIC infusions together with reduced conventional immunosuppression were associated with good graft function during five years of follow-up, no de novo DSA development and no opportunistic infections. In the future, MIC infusions might contribute to graft protection while reducing the side effects of immunosuppressive therapy. However, this approach needs further validation in direct comparison with prospective controls. Trial registration: https://clinicaltrials.gov/, identifier NCT02560220 (for the TOL-1 Study). EudraCT Number: 2014-002086-30.

Individualised immunosuppression with intravenously administered donor-derived modified immune cells compared with standard of care in living donor kidney transplantation (TOL-2 Study): protocol for a multicentre, open-label, phase II, randomised controlled trial.

INTRODUCTION: Donor-derived modified immune cells (MIC) induced long-term specific immunosuppression against the allogeneic donor in preclinical models of transplantation. In a phase I clinical trial (TOL-1 Study), MIC treatment resulted in a cellular phenotype that was directly and indirectly suppressive to the recipient's immune system allowing for reduction of conventional immunosuppressive therapy. Here, we describe a protocol for a randomised controlled, multicentre phase-IIb clinical trial of individualised immunosuppression with intravenously administered donor MIC compared with standard-of-care (SoC) in living donor kidney transplantation (TOL-2 Study). METHODS AND ANALYSIS: Sixty-three living donor kidney transplant recipients from six German transplant centres are randomised 2:1 to treatment with MIC (MIC group, N=42) or no treatment with MIC (control arm, N=21). MIC are manufactured from donor peripheral blood mononuclear cells under Good Manufacturing Practice conditions. The primary objective of this trial is to determine the efficacy of MIC treatment together with reduced conventional immunosuppressive therapy in terms of achieving an operational tolerance-like phenotype compared with SoC 12 months after MIC administration. Key secondary endpoints are the number of patient-relevant infections as well as a composite of biopsy-proven acute rejection, graft loss, graft dysfunction or death. Immunosuppressive therapy of MIC-treated patients is reduced during follow-up under an extended immunological monitoring including human leucocyte antigen-antibody testing, and determination of lymphocyte subsets, for example, regulatory B lymphocytes (Breg) and antidonor T cell response. A Data Safety Monitoring Board has been established to allow an independent assessment of safety and efficacy. ETHICS AND DISSEMINATION: Ethical approval has been provided by the Ethics Committee of the Medical Faculty of the University of Heidelberg, Heidelberg, Germany (AFmu-580/2021, 17 March 2022) and from the Federal Institute for Vaccines and Biomedicines, Paul-Ehrlich-Institute, Langen, Germany (Vorlage-Nr. 4586/02, 21 March 2022). Written informed consent will be obtained from all patients and respective donors prior to enrolment in the study. The results from the TOL-2 Study will be published in peer-reviewed medical journals and will be presented at symposia and scientific meetings. TRIAL REGISTRATION NUMBER: NCT05365672.

Cardio-renal interaction - Clinical trials update 2022.

AIMS: Chronic kidney disease is a common cardiovascular risk indicator and strongly associated with increased morbidity and mortality. The heart and kidneys are pathophysiologically closely connected, which becomes particularly obvious in patients with cardiorenal syndrome. This review summarizes clinically relevant studies on the cardio-renal interaction published in 2021 and 2022. DATA SYNTHESIS: Selected trials published in high-impact journals were chosen from the database Pubmed and included in this review. New evidence about the selective mineralocorticoid receptor antagonist finerenone and the renoprotective sodium-glucose co-transporter-2-inhibitors (SGLT2-Inhibitors) are discussed and we update on novel insights about the treatment of arterial hypertension in patients with severe chronic kidney disease with the thiazide-like diuretic chlorthalidone. Finally, data on infective endocarditis in patients on chronic hemodialysis and the treatment of secondary hyperparathyroidism with the calcimimetic drug etelcalcetide in patients with end stage kidney disease are critically reviewed. CONCLUSION: Several important studies investigating cardio-renal interactions were recently published may affect clinical practice. The graphical abstract (Fig. 1) depicts the most relevant clinical studies investigating cardio-renal interactions.

Kidney disease and thyroid dysfunction: the chicken or egg problem.

Patients with non-dialysis-dependant chronic kidney disease (NDD-CKD) and dialysis-dependant chronic kidney disease (DD-CKD) frequently also suffer from thyroid disorders, especially hypothyroidism which is found two to five times more often among them compared to the general population. Emerging research has illustrated the potential prognostic implications of this association as NDD-CKD and DD-CKD patients with hypothyroidism have been shown to have higher mortality rates, and treatment of subclinical hypothyroidism in NDD-CKD patients has been reported to attenuate the decline of glomerular filtration rate over time. This review illustrates the bidirectional, multi-layered interplay between the kidneys and the thyroid gland explaining how pathologies in one organ will affect the other and vice versa. Additionally, it outlines the impact of thyroid disorders on routine parameters of kidney function (especially serum creatinine and serum cystatin C) that nephrologists should be aware of in their clinical practice. Lastly, it summarizes the emerging evidence from clinical studies on how treatment of subclinical hypothyroidism in NDD-CKD and DD-CKD patients may potentially have beneficial effects on kidney function as well as mortality. While most of the research in this area has been performed on adult patients, we specifically discuss what is currently known about thyroid dysfunctions in paediatric CKD patients as well and provide management suggestions. The evidence accumulated so far clearly indicates that further, prospective studies with meticulous methodology are warranted to refine our understanding of thyroid disorders in paediatric and adult CKD patients and establish optimal treatment pathways.

Study protocol: the TRAnsplant BIOpsies (TRABIO) study - a prospective, observational, multicentre cohort study to assess the treatment of kidney graft rejections.

INTRODUCTION: Despite continued efforts, long-term outcomes of kidney transplantation remain unsatisfactory. Kidney graft rejections are independent risk factors for graft failure. At the participating centres of the TRAnsplant BIOpsies study group, a common therapeutic standard has previously been defined for the treatment of graft rejections. The outcomes of this strategy will be assessed in a prospective, observational cohort study. METHODS AND ANALYSIS: A total of 800 kidney transplantation patients will be enrolled who undergo a graft biopsy because of deteriorating kidney function. Patients will be stratified according to the Banff classification, and the influence of the treatment strategy on end points will be assessed using regression analysis. Primary end points will be all-cause mortality and graft survival. Secondary end points will be worsening of kidney function (≥30% decline of estimated Glomerular Filtration Rate [eGFR] or new-onset large proteinuria), recurrence of graft rejection and treatment response. Baseline data and detailed histopathology data will be entered into an electronic database on enrolment. During a first follow-up period (within 14 days) and subsequent yearly follow-ups (for 5 years), treatment strategies and clinical course will be recorded. Recruitment at the four participating centres started in September 2016. As of August 2020, 495 patients have been included. ETHICS AND DISSEMINATION: Ethical approval for the study has been obtained from the ethics committee of Kiel (AZ B 278/16) and was confirmed by the committees of Munich, Mainz and Stuttgart. The results will be reported in a peer-reviewed journal, according to the Strengthening the Reporting of Observational Studies in Epidemiology criteria. TRIAL REGISTRATION NUMBER: ISRCTN78772632; Pre-results.

Outcome of kidney transplantations from ≥65-year-old deceased donors with acute kidney injury.

Kidney transplantation (KT) from donors with acute kidney injury (AKI) has been associated with delayed graft function (DGF) but similar graft survival compared with KT from donors without AKI. Kidneys from ≥65-year-old donors with comorbidities are more susceptible to cold ischemia time (CIT) and DGF and it is unknown whether such elderly kidneys with AKI can also be transplanted with satisfactory outcomes. All KTs from ≥65-year-old donors performed at our center from 1999 to 2019 (n = 233) were retrospectively analyzed and short- as well as long-term outcomes were compared for KTs from donors with (n = 64) and without AKI (n = 169). There were no significant differences regarding the frequency of DGF as well as the estimated glomerular filtration rate (eGFR) 1 and 3 years post-transplant between the no-AKI and the AKI group (DGF: no-AKI 30.2% vs. AKI 40.6%, P = .17; eGFR at 1-year: 31.9 ml/min/1.73 m2 vs. 35.5 ml/min/1.73 m2 , P = .32; at 3-years: 33.8 ml/min/1.73 m2 vs. 40.9 ml/min/1.73 m2 , P = .18; respectively). Death-censored graft survival and patient survival were also not significantly different. Multivariable Cox regression analysis did not identify AKI as a significant risk factor for graft loss or death. Following careful donor and recipient selection, kidneys from ≥65-year-old AKI donors may potentially be transplanted with satisfactory outcomes.

Influence of Calcineurin Inhibitor Choice on Outcomes in Kidney Transplant Recipients Aged ≥60 Y: A Collaborative Transplant Study Report.

BACKGROUND: Patients aged ≥60 y represent the fastest growing population among kidney transplant recipients and waitlist patients. They show an elevated infection risk and are frequently transplanted with multiple human leukocyte antigen mismatches. Whether the choice of calcineurin inhibitor influences graft survival, mortality, or key secondary outcomes such as infections in this vulnerable recipient population is unknown. METHODS: A total of 31 177 kidney transplants from deceased donors performed between 2000 and 2019 at European centers and reported to the Collaborative Transplant Study were analyzed using multivariable Cox and logistic regression analyses. All recipients were ≥60 y old and received tacrolimus (Tac) or cyclosporine A on an intention-to-treat basis, combined with mycophenolic acid or azathioprine plus/minus steroids. RESULTS: The risk of 3-y death-censored graft loss and patient mortality did not differ significantly between Tac- and cyclosporine A-treated patients (hazard ratio 0.98 and 0.95, P = 0.74 and 0.20, respectively). No difference was found in the overall risk of hospitalization for infection (hazard ratio = 0.95, P = 0.19); however, a lower incidence of rejection treatment (hazard ratio = 0.81, P < 0.001) was observed in Tac-treated patients. Assessment of pathogen-specific hospitalizations revealed no difference in the risk of hospitalization due to bacterial infection (odds ratio = 1.00, P = 0.96), but a significantly higher risk of hospitalization due to human polyomavirus infection was found among Tac-treated patients (odds ratio = 2.45, P = 0.002). The incidence of de novo diabetes was higher for Tac-based immunosuppression (odds ratio = 1.79, P < 0.001). CONCLUSIONS: Calcineurin inhibitor selection has no significant influence on death-censored graft survival, mortality, and overall infection risk in ≥60-y-old kidney transplant recipients.

Kidney Transplantation After Rescue Allocation-the Eurotransplant Experience: A Retrospective Multicenter Outcome Analysis.

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.

[Current aspects of heart-kidney interactions : Summary of important clinical studies from 2020]. / Aktuelles zur Herz-Nieren-Interaktion : Zusammenfassung wichtiger klinischer Studien aus 2020.

Patients with chronic kidney diseases show an increased cardiovascular morbidity and mortality. Last year a number of important studies on heart-kidney interaction were published, which are summarized and discussed in this article. In the DAPA-CKD study and the SCORED study two different sodium-glucose linked transporter 2 (SGLT2) inhibitors (dapagliflozin and sotagliflozin) were found to improve the prognosis of patients with chronic kidney diseases with and without diabetes. The results of the randomized study on the new mineralocorticoid receptor antagonist finerenon (FIDELIO-DKD) also provided a very promising novel treatment approach for patients with diabetic nephropathy. The published data of the ISCHEMIA-CKD study in patients with coronary heart disease and investigations on the influence of transcatheter aortic valve implantation (TAVI) on renal function as well as another study on acute kidney failure after MitraClip® (Abbott, Chicago, IL, USA) implantation provide important indications for future treatment recommendations. The optimal timing of the initiation of kidney replacement therapy in patients with acute kidney damage in intensive care medicine was investigated in two randomized studies, which are correspondingly discussed.

Impact of the explanting surgeon's impression of donor arteriosclerosis on outcome of kidney transplantations from donors aged ≥65 years.

PURPOSE: Careful donor selection is important for kidney transplantations (KT) from suboptimal donors aged ≥65 years. Several tools such as histopathological assessment of preimplant biopsies have been shown to predict allograft survival and can be applied for selection. Whether the explanting surgeon's appraisal is associated with outcomes of KTs from suboptimal donors is unknown. METHODS: We compared outcomes of KTs from ≥65-year-old deceased donors performed at our centre between 1999 and 2018 for which grading of macroscopic 'donor arteriosclerosis' (n=104) and 'organ quality' (n=208) as judged by the explanting surgeon and documented on the Eurotransplant kidney organ report was available. RESULTS: No association was observed between degree of macroscopic donor arteriosclerosis and death-censored graft survival in univariable or multivariable regression analyses. Compared to KTs from donors with no/mild arteriosclerosis, KTs from donors with moderate/severe arteriosclerosis were associated with a significantly impaired allograft function 3 months, 1 year and 3 years after transplantation (e.g. at 3 years: 176.8 µmol/l vs 137.0 µmol/l, P=0.003). Following multivariable regression analysis, these differences remained significant at 3 months and 3 years after KT. No association was observed between degree of macroscopic arteriosclerosis and mortality or primary non-function as well as no consistent association with delayed graft function and histological arteriosclerosis. Assessment of 'organ quality' was not associated with outcomes. CONCLUSION: Our data suggest that the explanting surgeon's assessment of donor arteriosclerosis is associated with allograft function. Larger studies and better standardization of kidney inspection after explantation are required to further explore the impact of surgeon's appraisal in KT.

[Renal insufficiency in the context of cardio-pulmonary-renal pathophysiology]. / Niereninsuffizienz im Kontext der kardiopulmorenalen Pathophysiologie.

Heart failure and renal insufficiency as well as pulmonary hypertension are pathophysiologically closely associated as a cardio-renal or cardio-pulmonary-renal syndrome. Due to the frequent hospitalization of patients affected by this syndrome, it is of high medical and also health economic relevance. Besides the inhibition of the renin-angiotensin-aldosterone system (RAAS), multimodal treatment options are available with mineralocorticoid receptor antagonists, angiotensin receptor-neprilysin inhibitors and sodium-glucose transporter 2 (SGLT-2) inhibitors. Profound knowledge of the pathophysiology and the therapeutic options is as necessary for an optimized medical care as patient-oriented, transdisciplinary and cross-sectoral care.

Impact of cardiopulmonary resuscitation on outcome of kidney transplantations from braindead donors aged ≥65 years.

INTRODUCTION: Patients with a history of cardiopulmonary resuscitation (CPR) and subsequent brain death are frequently evaluated for organ donation. Whether kidneys from ≥65-year-old braindead donors with a history of CPR can be transplanted with satisfactory outcomes is unknown. MATERIAL & METHODS: All kidney transplants (KTs) from ≥65-year-old donors performed at our center from 1999 to 2018 (n = 185) were retrospectively analyzed and outcome was compared for KTs from donors with and without a history of CPR (n = 27 and n = 158, respectively). RESULTS: No significant differences in the incidence of delayed graft function (DGF) as well as 1- and 3-year graft function were observed between the CPR and the no-CPR group (DGF: 26.0% vs. 31.0%, p = .76; 1-year serum creatinine: 150.4 µmol/L vs. 177.0 µmol/L, p = .11; 3-year serum creatinine: 150.4 µmol/L vs. 168.2 µmol/L, p = .52, respectively). Death-censored graft survival was comparable after 1 and 5 years (CPR group: 81.5% and 76.7% vs. no-CPR group: 86.6% and 75.7%, p = .70). Likewise, patient survival was not significantly different. Multivariable Cox regression analysis also did not identify CPR as a significant risk factor for graft loss or death. CONCLUSION: Our study suggests that, following stringent donor selection, the outcome of KTs from ≥65-year-old braindead donors with and without a history of CPR is comparable.

Influence of Cold Ischemia Time on the Outcome of Kidney Transplants from Donors Aged 70 Years and Above-A Collaborative Transplant Study Report.

BACKGROUND: The use of kidney allografts from ≥70-y-old donors has increased persistently over the last 20 y. Prolonged cold ischemia time (CIT) is well known to increase graft failure risk. However, despite their growing importance, no data are available on the impact of CIT, specifically on survival of allografts from ≥70-y-old donors. METHODS: In total, 47 585 kidney transplantations from expanded criteria donors (ECDs) performed during 2000-2017 and reported to the Collaborative Transplant Study were analyzed. The impact of CIT on 5-y death-censored graft and patient survival was studied for transplantations from <70-y (n = 33 305) and ≥70-y-old ECDs (n = 14 280). RESULTS: Compared with the reference of ≤12 h CIT, a CIT of 13-18 h did not increase the risk of graft failure significantly, either for recipients of kidneys from <70-y or from ≥70-y-old ECDs. In contrast, graft failure risk increased significantly when CIT exceeded 18 h, both in recipients of kidneys from <70-y and, more pronounced, from ≥70-y-old ECDs (CIT 19-24 h: hazard ratio [HR] = 1.19 and 1.24; P < 0.001; CIT ≥24 h: HR = 1.28 and 1.32, P < 0.001 and P =0.003, respectively). Within the 18-h CIT interval, additional HLA matching further improved survival of ECD transplants significantly, whereas the negative impact of a prolonged CIT >18 h was stronger in ≥65-y-old recipients and for transplants with multiple HLA mismatches. The influence of CIT on patient survival was less pronounced. CONCLUSIONS: CIT, as long it is kept ≤18 h, has no significant impact on survival of kidney transplants, even from ≥70-y-old ECDs.

Kidney injury as post-interventional complication of TAVI.

Transcatheter aortic valve implantation (TAVI) is an accepted treatment approach of aortic stenosis. In the beginning, this technique was executed in high-risk patients only. Today, intermediate-risk patients are also amenable for TAVI, as long as the transfemoral approach is chosen. Numerous predictors have been identified that could lead to periprocedural complications and are defined by patient co-morbidities as well as being inherent to the technical approach. Although vascular complications and postinterventional paravalvular regurgitation have been minimized over the past years by revised technologies and techniques, there is a prevailing individual risk brought about by the specific pathophysiology of the cardiorenal syndrome.