Search

Background Salt and water disturbances often occur during acute kidney allograft dysfunction that contribute to graft failure, but this condition has been poorly investigated in the alloreactivity setting. We evaluated the tissue expression of aquaporins (AQP1 and AQP2) and the epithelial sodium channel (ENAC) in kidney biopsy specimens from sensitized kidney transplant recipients. Methods Eighty-six biopsy specimens from 33 sensitized patients were divided into 3 groups according to clinical context: time-zero (n = 9), protocol (n = 9), and indication (n = 68). The indication biopsy specimens were further divided into 3 subgroups according to the presence of acute tubular necrosis or rejection. Normal kidney tissue samples (n = 6) served as the control specimens. Immmunohistochemical expression of AQP1, AQP2, and ENAC was determined by using image analyzing software. Results Significantly lower AQP1 expression was observed in the time-zero and indication biopsy specimens with rejection compared with control specimens ( P = .03 and P = .04, respectively). AQP2 expression was significantly lower in patients with an indication biopsy specimen compared with control and protocol biopsy specimens ( P = .05 and P = .005). For ENAC, a lower expression was noted in the indication biopsy specimens compared with the control specimens ( P = .04). Both AQP1 and AQP2 tissue expressions were significantly correlated to urine output ( r = 0.45 and r = 0.32; P = .001 and P = .02), and AQP2 was correlated with the glomerular filtration rate estimated by using the Modification of Diet in Renal Disease Study equation at biopsy ( r = 0.23; P = .05). Conclusions These findings partially confirm previous experimental data showing downregulation of AQP1 expression after ischemia/reperfusion injury and during rejection. AQP2 downregulation seems to be rejection-independent, occurring during deteriorating or poor kidney graft function. [ABSTRACT FROM AUTHOR]

In the face of growing transplant waitlists and aging donors, sound pre-transplant evaluation of organ offers is paramount. However, many transplant centres lack clear criteria on organ acceptance. Often, previous scores for donor characterisation have not been validated for the Eurotransplant population and are not established to support graft acceptance decisions. Here, we investigated 1353 kidney transplantations at three different German centres to develop and validate novel statistical models for the prediction of early adverse graft outcome (EAO), defined as graft loss or CKD ≥4 within three months. The predictive models use generalised estimating equations (GEE) accounting for potential correlations between paired grafts from the same donor. Discriminative accuracy and calibration were determined via internal and external validation in the development (935 recipients, 309 events) and validation cohort (418 recipients, 162 events) respectively. The expert model is based on predictor ratings by senior transplant nephrologists, while for the data-driven model variables were selected via high-dimensional lasso generalised estimating equations (LassoGee). Both models show moderate discrimination for EAO (C-statistic expert model: 0,699, data-driven model 0,698) with good calibration. In summary, we developed novel statistical models that represent current clinical consensus and are tailored to the older deceased donor population. Compared to KDRI, our described models are sparse with only four and three predictors respectively and account for paired grafts from the same donor, while maintaining a discriminative accuracy equal or better than the established KDRI-score., 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. The author(s) declared that they were an editorial board member of Frontiers, at the time of submission. This had no impact on the peer review process and the final decision., (Copyright © 2025 Mahler, Friedl, Nusshag, Speer, Benning, Göth, Schaier, Sommerer, Mieth, Mehrabi, Michalski, Renders, Bachmann, Heemann, Krautter, Schwenger, Echterdiek, Zeier, Morath and Kälble.)

Introduction: The impact of deceased donor characteristics on kidney transplant outcomes is controversial. Correspondingly, the predictive performance of deceased donor scores remains moderate, and many transplant centers lack validated criteria for graft acceptance decisions. To better dissect donor-related risk from recipient and periprocedural variables, we analyzed outcomes of kidney donor pairs transplanted in different individuals., Methods: This study explored (a)symmetry of early outcomes of 328 cadaveric kidney transplant recipients from 164 donor pairs transplanted at three Eurotransplant centers. The primary discriminatory factor was (a)symmetry of partner graft function, defined as early graft loss or impaired graft function [estimated glomerular filtration rate (eGFR) <30 mL/min] 3 months after transplantation. We reasoned that a relevant impact of donor factors would result in a high concordance rate of limited graft function or failure., Results: The observed number of symmetric graft failure after transplantation was less than statistically expected (3 months: 1 versus 2, p = 0.89; and 12 months: 3 versus 5, p = 0.26). However, we found a trend toward an impaired 5-year graft survival of grafts with good function 3 months after transplantation but a failed or impaired partner graft compared to symmetrically well-functioning grafts (p = 0.09). Subsequently, we explored the impact of individual donor and recipient variables on early transplant outcomes. Generalized estimating equations after feature selection with LassoGEE bootstrap selected donor age, donor body mass index, and donor eGFR as the relevant risk factors., Discussion: Our findings indicate that donor factors impact early outcomes in kidney transplantation but may have a limited role in long-term graft survival, once a graft has been accepted for transplantation. Utilizing donor-based clinical scores has the potential to aid clinicians in acceptance decisions, giving them an estimate of individual posttransplant outcomes. However, the ultimate decision for acceptance should rest with clinicians, who must consider the complex interplay of donor factors, as well as recipient and periprocedural characteristics., 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 © 2024 Mahler, Friedl, Nusshag, Speer, Benning, Göth, Schaier, Sommerer, Mieth, Mehrabi, Renders, Heemann, Krautter, Schwenger, Echterdiek, Zeier, Morath and Kälble.)

Abstract: Immune thrombotic thrombocytopenic purpura (iTTP) is a rare, life-threatening autoimmune disorder caused by a disintegrin and metalloproteinase with thrombospondin type 1 motif, member 13 (ADAMTS13) deficiency. Caplacizumab, an anti-von Willebrand factor nanobody, is approved for iTTP treatment, reducing the need for therapeutic plasma exchange (TPE) and improving platelet count recovery and survival. We conducted a retrospective study on 42 acute iTTP cases in Austria and Germany, treated with a modified regimen aimed at avoiding TPE if platelet count increased after the first caplacizumab dose. Baseline characteristics and patient outcomes were compared with a control group of 59 patients with iTTP receiving frontline treatment with TPE, caplacizumab, and immunosuppression. The main outcome was the time to platelet count normalization. Secondary outcomes included clinical response, exacerbation, refractory iTTP, iTTP-related deaths, and the time to platelet count doubling. The median time to platelet count normalization was similar between the 2 cohorts (3 and 4 days; P = .31). There were no significant differences in clinical response, exacerbations, refractoriness, iTTP-related deaths, or time to platelet count doubling, reflecting the short-term treatment response. Four patients did not respond to the first caplacizumab dose, and TPE was subsequently initiated. Cytomegalovirus infection, HIV/hepatitis B virus coinfection, an ovarian teratoma with associated antiplatelet antibodies, and multiple platelet transfusions before the correct diagnosis may have impeded the immediate treatment response in these patients. In conclusion, caplacizumab and immunosuppression alone, without TPE, rapidly controlled thrombotic microangiopathy and achieved a sustained clinical response in iTTP. Our study provides a basis for TPE-free iTTP management in experienced centers via shared decision-making between patients and treating physicians., (© 2024 American Society of Hematology. Published by Elsevier Inc. All rights are reserved, including those for text and data mining, AI training, and similar technologies.)

Background: Preformed donor-specific HLA antibodies (DSA) are a well-known risk factor in kidney transplantation. There is still considerable debate, however, about the optimal risk stratification among patients with preformed DSA. Additionally, data on the prognostic value of different crossmatch assays in DSA-positive patients are scarce., Methods: DSA-positive living kidney transplant recipients were selected from a multicenter study examining 4233 consecutive renal transplants. An additional 7 patients from 2 further centers were included. Flow cytometric crossmatches (FXM), Luminex-based crossmatches, and virtual crossmatches based on C1q- and C3d-binding antibodies (C1qXM and C3dXM) were performed retrospectively using pretransplant sera and lymphocytes isolated from fresh samples. These samples were obtained from 44 donor and recipient pairs from 12 centers. Clinical outcome data and the control group without DSA were compiled from the previous study and were supplemented by data on 10-y death-censored graft survival (10yGS)., Results: Between 19% (C3dXM) and 46% (FXM) of crossmatches were positive. Crossmatch-positive patients showed high incidences of antibody-mediated rejection (AMR) within 6 mo (up to 60% in B-cell FXM+ patients). The incidence of AMR in crossmatch-negative patients ranged between 5% (FXM-) and 13% (C1qXM-). 10yGS was significantly impaired in patients with positive T-cell FXM and total FXM compared with both patients without DSA and those with DSA with negative FXM., Conclusions: Especially FXM are useful for risk stratification, as the outcome of DSA-positive, FXM-negative patients is similar to that of DSA-negative patients, whereas FXM-positive patients have both more AMR and decreased 10yGS. Because of their lower sensitivity, the significance of Luminex-based crossmatches, C1qXM, and C3dXM would have to be examined in patients with stronger DSA., (Copyright © 2024 The Author(s). Transplantation Direct. Published by Wolters Kluwer Health, Inc.)

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.)

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., Competing Interests: F.A.v.S.-H. and B.K. are supported by the Medical Faculty of the Christian-Albrechts-University Kiel. J.H.B. and J.S. were supported by the Federal Ministry of Education and Research 
(Bundesministerium für Bildung und Forschung [BMBF], KMU-innovativ: grant 13GW0399B). H.U.Z. was supported by the BMBF within the framework of the e:Med research and funding concept (grant 01ZX1912A). The other authors declare no conflicts of interest., (Copyright © 2024 The Author(s). Published by Wolters Kluwer Health, Inc.)

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., Competing Interests: The authors declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article., (© The Author(s) 2023.)

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)., (© 2023. Springer Nature Limited.)

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 + CD24 hi CD38 hi transitional and CD19 + CD24 hi CD27 + 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., Competing Interests: MSa, CMo, CK, GO, MZ, MSm, PT, and ASm together with the University of Heidelberg, are co-founders of TolerogenixX GmbH, Heidelberg, Germany, a biotechnology company that holds licenses for MIC treatment. CK, GO, and PT hold a patent for MIC treatment. MSa, CMo, CK, GO, CSü, MZ, MSm, PT, AS, and VD together with the University of Heidelberg and TolerogenixX GmbH filed a patent application for MIC treatment. 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 © 2023 Schaier, Morath, Wang, Kleist, Opelz, Tran, Scherer, Pham, Ekpoom, Süsal, Ponath, Kälble, Speer, Benning, Nusshag, Mahler, Pego da Silva, Sommerer, Hückelhoven-Krauss, Czock, Mehrabi, Schwab, Waldherr, Schnitzler, Merle, Schwenger, Krautter, Kemmner, Fischereder, Stangl, Hauser, Kälsch, Krämer, Böhmig, Müller-Tidow, Reiser, Zeier, Schmitt, Terness, Schmitt and Daniel.)

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., (© 2022. The Author(s), under exclusive licence to International Pediatric Nephrology Association.)

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., Competing Interests: Competing interests: CM, ASchmitt, MS, CK, GO, PT, MZ and MSchaier together with the University of Heidelberg, are cofounders of TolerogenixX GmbH, Heidelberg, Germany, a biotechnology company that holds licenses for MIC treatment. CK, GO, and PT hold a patent for MIC treatment. CM, ASchmitt, MSchmitt, CK, GO, CSüsal, PT, MZ, VD and MSchaier together with the University of Heidelberg and TolerogenixX GmbH filed a patent application for MIC treatment. JR is cofounder and shareholder of Trisaq, a biopharmaceutical company that develops novel therapy for kidney diseases., (© Author(s) (or their employer(s)) 2022. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

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., Competing Interests: Declaration of competing interest FM is supported by Deutsche Gesellschaft für Kardiologie (DGK), Deutsche Forschungsgemeinschaft (SFB TRR219), and Deutsche Herzstiftung and has received scientific support and/or speaker honoraria from Astra-Zeneca, Bayer, Boehringer Ingelheim, Medtronic, Merck, and ReCor Medical. IE has received speaker honoraria from Pharmacosmos and Astellas. VS has received speaker honoraria from Astra Zeneca and Novartis. MB is supported by the Deutsche Forschungsgemeinschaft (German Research Foundation; TTR 219, project number 322900939) and reports personal fees from Abbott, Amgen, Astra Zeneca, Bayer, Boehringer-Ingelheim, Cytokinetic, Edwards, Medtronic, Novartis, Recor, Servier and Vifor. FG and MK do not have conflicts of interest., (Copyright © 2022 The Italian Diabetes Society, the Italian Society for the Study of Atherosclerosis, the Italian Society of Human Nutrition and the Department of Clinical Medicine and Surgery, Federico II University. Published by Elsevier B.V. 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.)

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 m 2 vs. 35.5 ml/min/1.73 m 2 , P = .32; at 3-years: 33.8 ml/min/1.73 m 2 vs. 40.9 ml/min/1.73 m 2 , 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., (© 2022 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

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., Competing Interests: Competing interests: JW-M has received research support from GSK, DIAMED, Miltenyi Biotech as well as personal fees from Novartis, GSK, Boehringer-Ingelheim, Miltenyi, Vifor and Chiesi (all unrelated to the submitted work)., (© Author(s) (or their employer(s)) 2022. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

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., (© 2021. The Author(s).)

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., Competing Interests: The authors declare no funding or conflicts of interest., (Copyright © 2022 Wolters Kluwer Health, Inc. All rights reserved.)

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., (© 2021. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

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., Competing Interests: The authors declare no funding or conflicts of interest., (Copyright © 2021 Wolters Kluwer Health, Inc. All rights reserved.)

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., (© 2021 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

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., (© 2021. Springer Medizin Verlag GmbH, ein Teil von Springer Nature.)

Due to a widespread organ shortage, the use of expanded criteria donors (ECDs) in kidney transplantation has increased persistently, reaching approximately 40% in recent years. Whether human leucocyte antigen (HLA) matching between donor and recipient should be part of allocation algorithms in transplantation of ECD kidneys, and especially of ECD kidneys from ≥70-year-old donors, is still in question. To this end, 135,529 kidney transplantations performed between 2000 and 2017 and reported to the Collaborative Transplant Study were analysed and the impact of HLA-A+B+DR mismatches on death-censored graft and patient survival as well as on rejection episodes was investigated. Results were stratified according to donor status (standard criteria donor (SCD) versus ECD) and age of ECD. HLA incompatibility increased the five-year death-censored graft failure risk similarly strong in recipients of ECD and SCD transplants (hazard ratio (HR) per HLA mismatch 1.078 and 1.075, respectively; p < .001 for both). Its impact on rejection treatments during the first post-transplant year was also significant but slightly weaker for recipients of ECD transplants (risk ratio (RR) per HLA mismatch 1.10 for ECD transplants and 1.13 for SCD transplants; p < .001 for both). Mortality increased gradually from zero to six HLA mismatches in recipients of SCD transplants, whereas for ECD transplants a significant increase was notable only from zero to more than zero mismatches. A significant but slightly less pronounced impact of HLA incompatibility on graft failure was observed in transplants from ≥70- compared with <70-year-old ECDs (HR per mismatch 1.047 and 1.093; p = .009 and < 0.001, respectively). The influence of HLA mismatches on rejection treatments was the same for both ECD age groups (RR = 1.10, p < .001 and p = .004, respectively). Our data indicate that HLA matching should be part of allocation algorithms not only in transplantation of kidneys from SCDs but also from ECDs., (© 2020 John Wiley & Sons Ltd.)

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.

This consensus paper summarizes the expert consensus and recommendations of the working group "Heart and Kidney" of the German Cardiac Society (DGK) and the German Society of Nephrology (DGfN) on contrast medium-induced acute kidney injury. Potentially nephrotoxic contrast agents containing iodine are frequently used in interventional medicine and for computer tomography diagnostics. Acute kidney injury occurs in approximately 8-17% of patients exposed to contrast media. The risk factors and underlying pathophysiology are discussed and recommendations for the prophylaxis and treatment of contrast medium-induced acute nephropathy are presented.

The peritoneal lining of the abdominal cavity consists of a parietal and visceral sheet. The serosa is an interesting organ, which in medical practice is particularly important in the context of chronic peritoneal dialysis (PD). This method of renal replacement therapy utilizes the semipermeability of the peritoneal surface by applying PD solutions of differing osmolarity to eliminate toxic substances and regulate fluid and electrolyte equilibrium. This method is an ideal approach especially for younger patients and is very effective at least for some time. Pre-existing injury to the peritoneum, for example as a consequence of chronic renal insufficiency or associated comorbidities and inflammatory changes that develop during PD, results in a structural remodelling of the serosa. As a consequence, the filtering function of the serosa is lost and PD has to be replaced by another renal replacement therapy. Thorough knowledge of the morphology of peritoneal changes as well as of the risk factors is of paramount importance for therapeutic management and prognosis of PD patients. In order to take this into account, the German Registry In Peritoneal Dialysis (Deutsches Peritonealbiopsieregister, GRIP) was founded a few years ago, which now includes roughly 1700 biopsies, of which detailed clinical and histomorphological information was systematically acquired and collected.

Background: Donor-derived cell-free DNA (dd-cfDNA) is reportedly a valuable tool for graft surveillance following kidney transplantation (KTx). Possible changes in dd-cfDNA(%) reference values over time have not been evaluated. For long-term monitoring after KTx, changes in host cfDNA might represent a biasing factor in dd-cfDNA(%) determinations., Methods: Plasma samples were obtained (n = 929) 12-60 months after engraftment in a cross-sectional cohort of 303 clinically stable KTx recipients. Total cfDNA(copies/mL), dd-cfDNA(%), and dd-cfDNA(copies/mL) were determined using droplet-digital PCR. Stability of threshold values in these stable KTx recipients over time was assessed by 80th, 85th, and 90th quantile regression., Results: Upper percentiles of total cfDNA showed a significant decline of -1902, -3589, and -4753 cp/mL/log(month) (P = 0.014, <0.001, and 0.017, respectively), resulting in increasing dd-cfDNA(%) percentiles by 0.25, 0.46, and 0.72%/log(month) (P = 0.04, 0.001, and 0.002, respectively), with doubling of the 85th percentile value by 5 years. In contrast, dd-cfDNA(cp/mL) was stable during the observation period (P = 0.52, 0.29, and 0.39). In parallel increasing white blood cell counts and decreasing tacrolimus concentrations over time were observed. After 5 years, the median total cfDNA was still 1.6-fold (P < 0.001) higher in KTx recipients than in healthy controls (n = 135) and 1.4-fold (P < 0.001) higher than patients with other medical conditions (n = 364)., Conclusions: The time-dependent decrease of host cfDNA resulted in an apparent increase of dd-cfDNA fraction in stable KTx patients. For long-term surveillance, measurement of absolute dd-cfDNA concentrations appears to be superior to percentages to minimize false positive results., (© American Association for Clinical Chemistry 2020.)

Background: Patients on peritoneal dialysis (PD) may suffer from sodium (Na) and fluid overload, hypertension and increased cardiovascular risk. Low-Na dialysis solution, by increasing the diffusive removal of Na, might improve blood pressure (BP) management., Methods: A glucose-compensated, low-Na PD solution (112 mmol/L Na and 2% glucose) was compared to a standard-Na solution (133 mmol/L Na and 1.5% glucose) in a prospective, randomised, single-blind study in hypertensive patients on PD. One daily exchange of the standard dialysis regimen was substituted by either of the study solutions for 6 months. The primary outcome (response) was defined as either a decrease of 24-h systolic BP (SBP) by ≥6 mmHg or a fall in BP requiring a medical intervention (e.g. a reduction of antihypertensive medication) at 8 weeks., Results: One hundred twenty-three patients were assessed for efficacy. Response criteria were achieved in 34.5% and 29.1% of patients using low- and standard-Na solutions, respectively ( p = 0.51). Small reductions in 24 h, office, and self-measured BP were observed, more marked with low-Na than with standard-Na solution, but only the between-group difference for self-measured SBP and diastolic BP was significant ( p = 0.002 and p = 0.003). Total body water decreased in the low-Na group and increased in the control group, but between-group differences were not significant. Hypotension and dizziness occurred in 27.0% and in 11.1% of patients in the low-Na group and in 16.9% and 4.6% in the control group, respectively., Conclusions: Superiority of low-Na PD solution over standard-Na solution for control of BP could not be shown. The once daily use of a low-Na PD solution was associated with more hypotensive episodes, suggesting the need to reassess the overall concept of how Na-reduced solutions might be incorporated within the treatment schedule.

Delayed graft function (DGF) occurs in a significant proportion of deceased donor kidney transplant recipients and was associated with graft injury and inferior clinical outcome. The aim of the present multi-center study was to identify the immunological and non-immunological predictors of DGF and to determine its influence on outcome in the presence and absence of human leukocyte antigen (HLA) antibodies. 1,724 patients who received a deceased donor kidney transplant during 2008-2017 and on whom a pre-transplant serum sample was available were studied. Graft survival during the first 3 post-transplant years was analyzed by multivariable Cox regression. Pre-transplant predictors of DGF and influence of DGF and pre-transplant HLA antibodies on biopsy-proven rejections in the first 3 post-transplant months were determined by multivariable logistic regression. Donor age ≥50 years, simultaneous pre-transplant presence of HLA class I and II antibodies, diabetes mellitus as cause of end-stage renal disease, cold ischemia time ≥18 h, and time on dialysis >5 years were associated with increased risk of DGF, while the risk was reduced if gender of donor or recipient was female or the reason for death of donor was trauma. DGF alone doubled the risk for graft loss, more due to impaired death-censored graft than patient survival. In DGF patients, the risk of death-censored graft loss increased further if HLA antibodies (hazard ratio HR=4.75, P < 0.001) or donor-specific HLA antibodies (DSA, HR=7.39, P < 0.001) were present pre-transplant. In the presence of HLA antibodies or DSA, the incidence of biopsy-proven rejections, including antibody-mediated rejections, increased significantly in patients with as well as without DGF. Recipients without DGF and without biopsy-proven rejections during the first 3 months had the highest fraction of patients with good kidney function at year 1, whereas patients with both DGF and rejection showed the lowest rate of good kidney function, especially when organs from ≥65-year-old donors were used. In this new era of transplantation, besides non-immunological factors, also the pre-transplant presence of HLA class I and II antibodies increase the risk of DGF. Measures to prevent the strong negative impact of DGF on outcome are necessary, especially during organ allocation for presensitized patients., (Copyright © 2020 Morath, Döhler, Kälble, Pego da Silva, Echterdiek, Schwenger, Živčić-Ćosić, Katalinić, Kuypers, Benöhr, Haubitz, Ziemann, Nitschke, Emmerich, Pisarski, Karakizlis, Weimer, Ruhenstroth, Scherer, Tran, Mehrabi, Zeier and Süsal.)

In several deceased donor kidney allocation systems, organs from elderly donors are allocated primarily to elderly recipients. The Eurotransplant Senior Program (ESP) was implemented in 1999, and since then, especially in Europe, the use of organs from elderly donors has steadily increased. The proportion of ≥60-year-old donors reported to the Collaborative Transplant Study (CTS) by European centers has doubled, from 21% in 2000-2001 to 42% in 2016-2017. Therefore, in the era of organ shortage it is a matter of debate whether kidney organs from elderly donors should only be allocated to elderly recipients or whether <65-year-old recipients can also benefit from these generally as "marginal" categorized organs. To discuss this issue, a European Consensus Meeting was organized by the CTS on April 12, 2018, in Heidelberg, in which 36 experts participated. Based on available evidence, it was unanimously concluded that kidney organs from 65- to 74-year-old donors can also be allocated to 55- to 64-year-old recipients, especially if these organs are from donors with no history of hypertension, no increased creatinine, no cerebrovascular death, and no other reasons for defining a marginal donor, such as diabetes or cancer., (© 2020 Steunstichting ESOT. Published by John Wiley & Sons Ltd.)

Introduction of the nanobody caplacizumab was shown to be effective in the treatment of acquired thrombotic thrombocytopenic purpura (aTTP) in the acute setting. The official recommendations include plasma exchange (PEX), immunosuppression, and the use of caplacizumab for a minimum of 30 days after stopping daily PEX. This study was a retrospective, observational analysis of the use of caplacizumab in 60 patients from 29 medical centers in Germany. Immunosuppressive treatment led to a rapid normalization of ADAMTS13 activities (calculated median, 21 days). In 35 of 60 patients, ADAMTS13 activities started to normalize before day 30 after PEX; in 11 of 60 patients, the treatment was extended beyond day 30; and in 5 patients, it was extended even beyond day 58 due to persistent autoimmune activity. In 34 of 60 instances, caplacizumab was stopped before day 30 with a favorable outcome whenever ADAMTS13 activities were >10%. In contrast, 11 of 34 patients with ADAMTS13 activities <10% at the time of stopping caplacizumab treatment developed a nonfavorable outcome (disease exacerbation or relapse). In some cases, prolongation of the treatment interval to every other day was feasible and resulted in a sustained reduction of von Willebrand factor activity. ADAMTS13 activity measurements are central for a rapid diagnosis in the acute setting but also to tailor disease management. An ADAMTS13 activity-guided approach seems safe for identifying the individual time point when to stop caplacizumab to prevent overtreatment and undertreatment; this approach will result in significant cost savings without jeopardizing the well-being of patients. In addition, von Willebrand factor activity may serve as a biomarker for drug monitoring., (© 2020 by The American Society of Hematology.)

Acquired thrombotic thrombocytopenic purpura (aTTP) is a rare but life-threatening condition. In 2018, the nanobody caplacizumab was approved for the treatment of adults experiencing an acute episode of aTTP, in conjunction with plasma exchange (PEX) and immunosuppression for a minimum of 30 days after stopping daily PEX. We performed a retrospective, observational analysis on the use of caplacizumab in 60 patients from 29 medical centers in Germany during acute disease management. Caplacizumab led to a rapid normalization of the platelet count (median, 3 days; mean 3.78 days). One patient died after late treatment initiation due to aTTP-associated complications. In 2 patients with initial disease presentation and in 4 additional patients with laboratory signs of an exacerbation or relapse after the initial therapy, PEX-free treatment regimens could be established with overall favorable outcome. Caplacizumab is efficacious in the treatment of aTTP independent of timing and ancillary treatment modalities. Based on this real-world experience and published literature, we propose to administer caplacizumab immediately to all patients with an acute episode of aTTP. Treatment decisions regarding the use of PEX should be based on the severity of the clinical presentation and known risk factors. PEX might be dispensable in some patients., (© 2020 by The American Society of Hematology.)

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.)

Background: Peritoneal ultrafiltration (pUF) in refractory heart failure (HF) reduces the incidence of decompensation episodes, which is of particular significance as each episode incrementally adds to mortality. Nevertheless, there are insufficient data about which patient cohort benefits the most. The objective of this study was to compare pUF in HFrEF and HFpEF, focusing on functional status, hospitalizations, surrogate endpoints and mortality., Methods: This study involves 143 patients, who could be classified as either HFpEF (n = 37, 25.9%) or HFrEF (n = 106, 74.1%) and who received pUF due to refractory HF., Results: Baseline eGFR was similar in HFrEF (23.1 ± 10.6 mg/dl) and HFpEF (27.8 ± 13.2 mg/dl). Significant improvements in NYHA class were found in HFpEF (3.19 ± 0.61 to 2.72 ± 0.58, P <  0.001) and HFrEF (3.45 ± 0.52 to 2.71 ± 0.72, P <  0.001). CRP decreased in HFrEF (19.4 ± 17.6 mg/l to 13.7 ± 21.4 mg/l, P = 0.018) and HFpEF (33.7 ± 52.6 mg/l to 17.1 ± 26.3 mg/l, P = 0.004). Body weight was significantly reduced in HFrEF (81.1 ± 14.6 kg to 77.2 ± 15.6 kg, P = 0.003) and HFpEF (86.9 ± 15.8 kg to 83.1 ± 15.9 kg, P = 0.005). LVEF improved only in HFrEF (25.9 ± 6.82% to 30.4 ± 12.2%, P = 0.046). BCR decreased significantly in HFrEF and HFpEF (55.7 ± 21.9 to 34.3 ± 17.9 P > 0.001 and 50.5 ± 68.9 to 37.6 ± 21.9, P = 0.006). Number of hospitalization episodes as well as number of hospitalization days decreased significantly only in HFpEF (total number 2.88 ± 1.62 to 1.25 ± 1.45, P <  0.001, days 40.4 ± 31.7 to 18.3 ± 22.5 days, P = 0.005)., Conclusions: pUF offers various benefits in HFpEF and HFrEF, but there are also substantial differences. In particular, hospitalization rates were found to be significantly reduced in HFpEF patients, indicating a greater medical and economical advantage. However, LVEF was only found to be improved in HFrEF patients. While pUF can now be regarded as an option to supplement classical HF therapy, further studies are desirable to obtain specifications about pUF in HFpEF, HFmEF and HFrEF patients.

Purpose of Review: Due to a substantial lack of kidney donor organs and an increasing number of sensitized recipients, a growing number of kidney transplantations has to be performed across human leukocyte antigen (HLA) and ABO barriers. These transplantations carry an inherent risk of antibody-mediated rejection (AMR) with subsequently impaired graft and patient survival. This review focuses on new developments in desensitization strategies and dedicated programs for sensitized allograft recipients., Recent Findings: Whereas ABO-incompatible kidney transplantation using rituximab-based desensitization achieves long-term survival rates comparable with ABO-compatible kidney transplantation, HLA-incompatible living kidney transplantation shows no definite survival advantage as compared with staying on the waiting list for an HLA-compatible organ. To overcome HLA-incompatibilities dedicated programs for highly sensitized recipients (such as the Eurotransplant Acceptable Mismatch program) have been established. For optimal graft outcome, these programs should be based on proven acceptable mismatches and not just on avoiding unacceptable antigens. Novel desensitizing agents (e.g. complement inhibitors) that specifically inhibit the molecular pathways of AMR have shown promising results in HLA-incompatible kidney transplantation in smaller studies., Summary: Despite ever more challenging conditions, kidney transplantation in highly sensitized patients can be achieved with the use of dedicated programs, well established desensitizing agents and new drugs that specifically inhibit the molecular processes of AMR.

There is a growing shortage of kidney donors leading to extended transplant waiting times associated with increased mortality. To expand the donor pool, clinicians nowadays regularly accept organs from elderly donors, including those aged ≥70 years. There is only limited and conflicting data whether kidneys from these elderly donors allow for satisfactory allograft outcome rates. To asses this question, the 5-year death censored graft survival of 116,870 adult first deceased donor kidney allograft recipients that were transplanted at European centers between 1997 and 2016 and reported to the "Collaborative Transplant Study" were analyzed using Kaplan-Meier analysis and country stratified Cox regression. The combinations of the two transplant periods 1997-2006 and 2007-2016 with the donor age categories 18-49, 50-59, 60-69, and ≥70 years were considered. From 1997-2006 to 2007-2016, the median donor age increased from 50 to 55 years and the proportion of kidneys from ≥60-year-old donors rose from 24.1 to 38.8%. At the same time, the proportion of kidneys from ≥70-year-old donors more than doubled (6.7 vs. 15.4%). Between 1997-2006 and 2007-2016, the 5-year graft survival improved in all donor age categories. During 2007-2016, the 5-year death censored graft survival of kidneys from ≥70-year-old donors was comparable to that of kidneys from 60 to 69-year-old donors during 1997-2006. This was true both for younger recipients (18-64 years) and older recipients (≥65 years). Among the younger recipients, 45-64-year-old recipients showed the best death censored graft survival rates for kidneys from old donors. In the country-stratified Cox regression analysis, compared to the reference of grafts from 18 to 49-year-old donors, the hazard ratio for grafts from ≥70-year-old donors during 2007-2016 was 1.92, exactly the same as the hazard ratio for grafts from 60 to 69-year-old donors during 1997-2006. Our analysis indicates that within only one further decade (1997-2006 vs. 2007-2016) the 5-year death censored graft survival of kidneys from ≥70-year old donors improved to the level of kidneys from 60 to 69-year-old donors in the previous decade., (Copyright © 2019 Echterdiek, Schwenger, Döhler, Latus, Kitterer, Heemann and Süsal.)

Donor-derived cell-free DNA (dd-cfDNA) is a noninvasive biomarker for comprehensive monitoring of allograft injury and rejection in kidney transplantation (KTx). dd-cfDNA quantification of copies/mL plasma (dd-cfDNA[cp/mL]) was compared to dd-cfDNA fraction (dd-cfDNA[%]) at prespecified visits in 189 patients over 1 year post KTx. In patients (N = 15, n = 22 samples) with biopsy-proven rejection (BPR), median dd-cfDNA(cp/mL) was 3.3-fold and median dd-cfDNA(%) 2.0-fold higher (82 cp/mL; 0.57%, respectively) than medians in Stable Phase patients (N = 83, n = 408) without rejection (25 cp/mL; 0.29%). Results for acute tubular necrosis (ATN) were not significantly different from those with biopsy-proven rejection (BPR). dd-cfDNA identified unnecessary biopsies triggered by a rise in plasma creatinine. Receiver operating characteristic (ROC) analysis showed superior performance (P = .02) of measuring dd-cfDNA(cp/mL) (AUC = 0.83) compared to dd-cfDNA(%) (area under the curve [AUC] = 0.73). Diagnostic odds ratios were 7.31 for dd-cfDNA(cp/mL), and 6.02 for dd-cfDNA(%) at thresholds of 52 cp/mL and 0.43%, respectively. Plasma creatinine showed a low correlation (r = 0.37) with dd-cfDNA(cp/mL). In a patient subset (N = 24) there was a significantly higher rate of patients with elevated dd-cfDNA(cp/mL) with lower tacrolimus levels (<8 μg/L) compared to the group with higher tacrolimus concentrations (P = .0036) suggesting that dd-cfDNA may detect inadequate immunosuppression resulting in subclinical graft damage. Absolute dd-cfDNA(cp/mL) allowed for better discrimination than dd-cfDNA(%) of KTx patients with BPR and is useful to avoid unnecessary biopsies., (© 2019 The Authors. American Journal of Transplantation published by Wiley Periodicals, Inc. on behalf of The American Society of Transplantation and the American Society of Transplant Surgeons.)

Background: Residual renal function (RRF) affects sodium and fluid balance. The aim of this analysis was to examine the impact of RRF on the effect of a sodium-reduced peritoneal dialysis fluid (PDF) on blood pressure (BP). Methods: This is a post-hoc analysis of a prospective, randomized, controlled double-blind clinical trial with 82 patients on continuous ambulatory PD (CAPD) treated with a low-sodium (125 mmol/L Na) or a standard-sodium (134 mmol/L Na) PDF. Subgroups according to glomerular filtration rate (GFR) at baseline (≤ / > 6 mL/min/1.73 m 2 ) were analyzed for BP and antihypertensive medication. Results: In the low-GFR group on low-sodium PDF ( N = 26), systolic BP was reduced from 152 ± 24 mmHg at baseline to 137 ± 21 mmHg at week 12, diastolic BP from 90 ± 16 mmHg to 83 ± 11 mmHg. In the low-GFR group on standard-sodium PDF and in the high-GFR group on both PDF types, only minor changes were observed. For the low-GFR subgroup, the confounder-adjusted mean study group difference in systolic BP at week 12 between low-sodium and standard-sodium PDF was -16.9 (95% confidence interval [CI] -27.2 to -6.6) mmHg, for diastolic BP, it was -7.0 (95% CI -12.6 to -1.4) mmHg. In both GFR subgroups, more patients had a reduced daily dose of antihypertensive medication and fewer patients an increased daily dose in the low-sodium compared with the standard-sodium group at week 12. Conclusions: The reduction of BP with a sodium-reduced PDF seems to be more effective in patients with no or low RRF than in patients with residual capacity of renal sodium and fluid control., (Copyright © 2019 International Society for Peritoneal Dialysis.)

Background: Hantavirus infections are endemic worldwide, and its incidence in Europe has been steadily increasing. In Western Europe, hantavirus infections are typically caused by Puumala hantavirus and cause nephropathia epidemica (NE), a mild form of haemorrhagic fever with renal syndrome. Up to now, there is only little data about the course of acute NE in children, but it has been suggested that hantavirus infections take a lighter course in children when compared to adults. We performed a retrospective analysis of adults and children diagnosed with acute NE in two counties in South-Western Germany to investigate if there are differences in the course of the disease., Methods: We reviewed the medical records of 295 adults and 22 children with acute NE regarding clinical presentation, laboratory findings, complications and outcome., Results: Acute kidney injury (AKI) and thrombocytopenia occurred at similar frequencies and severity in both groups. Sudden onset of fever and back/loin pain were two of the three most common symptoms in both adults and children. However, adults presented more frequently with arthralgia and visual disturbances, whereas abdominal pain and nausea/vomiting could be detected more often in children. No significant differences were found in the incidence of complications (haemodialysis, long-term outcome of kidney function, length of hospital stay)., Conclusions: The clinical course of acute NE was similar in adults and children with high frequency of AKI as well as thrombocytopenia, but with full recovery of all patients.

We have previously demonstrated that clementines have in vitro drug interaction potential. To assess the clinical relevance of clementine-drug interaction, two single case experiments with repetitive phenotyping of CYP3A activity were conducted. Although an increment of 43% in the estimated midazolam clearance (eCL met ) was observed during the first experiment in a renal transplant patient on tacrolimus after 4-d consumption of clementines (1 kg/d), and an increment of +89% of eCL met was observed during chronic consumption of clementine juice in a healthy male volunteer, these changes lie within the range of intra-individual variability. Therefore one cannot assure a potential drug interaction due to the clementines, but prescribers should be cautious unless further data emerges. In contrast to the juice used for the in vitro assay comprising several flavonoids, this juice only contained hesperidin and narirutin indicating that the drug interactions potential of clementines might depend on the composition varying from batch to batch., (Copyright © 2019 Elsevier B.V. All rights reserved.)

Aims: Each episode of acute decompensated heart failure (HF) incrementally adds to mortality. Peritoneal dialysis (PD) offers an alternative therapeutic option in refractory HF and reduces the incidence of decompensation episodes. The objective of this study was to determine the efficacy of PD, in terms of functional status, surrogate endpoints, rate of hospitalizations, and mortality., Methods and Results: This study is based on the registry of the German Society of Nephrology, involving 159 patients receiving PD treatment due to refractory HF between January 2010 and December 2014. Body weight was reduced by PD (82.2 ± 14.9 to 78.4 ± 14.8 kg, P < 0.001), and significant improvements in New York Heart Association functional class (3.38 ± 0.55 to 2.85 ± 0.49, P < 0.001) were found already after 3 months. Left ventricular ejection fraction did not change (31.5 ± 13.8 to 34.0 ± 15.7%, P = 0.175). C-reactive protein improved with PD treatment (33.7 ± 52.6 to 17.1 ± 26.3 mg/L, P = 0.004). Blood urea nitrogen/creatinine ratio decreased significantly (148.7 ± 68.3 to 106.7 ± 44.8 mg/dL, P < 0.001). Hospitalization rates decreased significantly (total number 2.86 ± 1.88 to 1.90 ± 1.78, P = 0.001, and 39.2 ± 30.7 to 27.1 ± 25.2 days, P = 0.004). One year mortality was 39.6% in end-stage HF patients treated with PD., Conclusions: Peritoneal dialysis offers an additional therapeutic option in end-stage HF and is associated with improved New York Heart Association classification and reduced hospitalization. Although PD treatment was associated with various benefits, further studies are necessary to identify which patients benefit the most from PD., (© 2019 The Authors. ESC Heart Failure published by John Wiley & Sons Ltd on behalf of the European Society of Cardiology.)

Bondage and discipline, dominance and submission, sadism and masochism (BDSM) refers to a variety of primarily erotic practices. Although safety is crucial for most BDSM practitioners, there are violent forms that may cause serious injury. We present the case of 61-year-old man with no history of chronic kidney disease who developed severe acute anuric kidney injury following violent BDSM play. He had been strapped tightly onto a wooden spanking bench and then received approximately 1000 vigorous hits onto his bare buttocks and thighs. Subsequently, he developed haematuria and became anuric. Laboratory testing revealed strongly elevated serum creatinine levels. Kidney biopsy was unremarkable except mild tubulointerstitial damage. Urinary production increased spontaneously again after 4 days, and serum creatinine normalised over the course of 4 weeks. We believe that a combination of intermittent abdominal compartment syndrome and blunt kidney trauma may have been responsible for this severe acute kidney injury., Competing Interests: Competing interests: None declared., (© BMJ Publishing Group Limited 2018. No commercial re-use. See rights and permissions. Published by BMJ.)

Rheumatology and nephrology have some characteristics in common. In some places this leads to the marginalization of the respective other discipline, instead of an interdisciplinary morbidity-oriented approach. In order to cope with the complexity of systemic autoimmune diseases, a care mandate should be defined and interdisciplinary and cross-sectoral structures, such as interdisciplinary boards or special outpatient clinics should be established.

End-stage heart failure (HF) is associated with renal failure (RF). This study aimed to determine the prognostic influence of RF and post-operative hemodialysis on short-term survival following left ventricular assist device (LVAD) implantation. This retrospective study includes 68 patients undergoing LVAD treatment. Kidney function was recorded prior to LVAD implantation, immediately afterwards and after 30 days, noting the need for hemodialysis. Median pre-operative Interagency Registry for Mechanically Assisted Circulatory Support (INTERMACS) classification was 3.47 ± 1.08. 30 days after implantation there was a significant improvement of estimated glomerular filtration rate (eGFR) and reduction of blood urea nitrogen (BUN). Of pre-operative RF parameters, BUN was associated with increased mortality and need for early post-operative hemodialysis. Post-operative hemodialysis was associated with significantly lower short-term survival, while pre-operative hemodialysis did not impact mortality. Post-operative acute kidney injury (AKI) requiring hemodialysis can be regarded as a strong negative prognostic marker for short-term survival. The absence of a clear correlation between most routine RF parameters and survival or the need for early post-operative hemodialysis calls into question the predictive value of pre-operative RF. The negative association of only post-operative hemodialysis on short-term survival emphasises the impact of the occurrence of AKI.

Background: Acute kidney injury (AKI) has both high mortality and morbidity., Objectives: To prevent the occurrence of AKI, current recommendations from the renal section of the DGIIN (Deutschen Gesellschaft für Internistische Intensivmedizin und Notfallmedizin), ÖGIAIN (Österreichischen Gesellschaft für Internistische und Allgemeine Intensivmedizin und Notfallmedizin) and DIVI (Deutschen Interdisziplinären Vereinigung für Intensiv- und Notfallmedizin) are stated., Materials and Methods: The recommendations stated in this paper are based on the current Kidney Disease Improving Global Outcomes (KDIGO) guidelines, the published statements of the "Working Group on Prevention, AKI section of the European Society of Intensive Care Medicine" and the expert knowledge and clinical experience of the authors., Results: Currently there are no approved clinically effective drugs for the prevention of AKI. Therefore the mainstay of prevention is the optimization of renal perfusion by improving the mean arterial pressure (>65 mm Hg, higher target may be considered in hypertensive patients). This can be done by vasopressors, preferably norepinephrine and achieving or maintaining euvolemia. Hyperhydration that can lead to AKI itself should be avoided. In patients with maintained diuresis this can be done by diuretics that are per se no preventive drug for AKI. Radiocontrast enhanced imaging should not be withheld from patients at risk for AKI; if indicated, however, the contrast media should be limited to the smallest possible volume.