BackgroundKidney transplantation (KT) from elderly donors (aged ≥65 years) with acute kidney injury (AKI) remains controversial and these organs might be underutilized. To date, clear evidence supporting the safety of KT from donors with AKI exists solely for younger donor populations. We hypothesized that, when appropriately selected, graft survival and function in recipients of kidneys from AKI and non-AKI donors aged ≥65 years are comparable.MethodsWe conducted a retrospective cohort study analyzing KT outcomes from donors aged ≥65 years with and without AKI that were performed between 2006 and 2021 at three German transplant centers. AKI was defined according to KDIGO criteria. Death-censored graft survival, overall graft survival, patient survival up to 7 years, eGFR up to 5 years as well as incidence of delayed graft function and biopsy proven acute rejection were compared. Kaplan-Meier analyses and multivariable Cox regression were performed.ResultsOf 685 KT recipients, 183 received kidneys from AKI donors, and 502 from non-AKI donors. Most KTs were from donors with KDIGO stage 1 AKI (n = 151; 81.6%). Delayed graft function occurred similarly often in AKI and non-AKI recipients (32.8% vs. 32.8%, p = 1.0). Death-censored graft survival was comparable between AKI and non-AKI groups (7 years: 59.0% vs. 61.3%; p = 0.87). Median eGFR at 12 months was 33.8 mL/min/1.73 m2 (IQR 27.3, 44.2) in the AKI group and 35.5 mL/min/1.73 m2 (IQR 26.3, 44.8) in the non-AKI group (p = 0.79). These results remained unchanged after adjustment for known risk factors of graft survival in the multivariable Cox regression.ConclusionIn this study, KT from ≥65-year-old donors with mostly mild AKI resulted in similar short and long-term graft survival and function compared to KT from ≥65-year-old donors without AKI. These findings support the utilization of AKI kidneys from elderly donors to expand the donor pool without compromising outcomes.

IgG4-related disease (IgG4-RD) is a rare immune-mediated, fibroinflammatory disease with heterogenous presentations and no standardized treatment recommendations. This study investigates long-term efficacy and safety of current therapeutic strategies with a focus on rituximab. A retrospective analysis was conducted on 24 patients diagnosed with IgG4-RD at a German tertiary center (2010–2020) using the 2020 revised comprehensive diagnostic criteria. Patients were recruited from Rheumatology and Nephrology. Data included organ involvement, laboratory results, histology, treatments, relapses, therapy-related damage, and comorbidities. The cohort included 12 males and 12 females, median age at diagnosis 53 (95

A history of cardiopulmonary resuscitation (CPR) is common in donation after brain death (DBD) donors. While good outcomes have been demonstrated for kidney transplantation (KT) from younger CPR donors (aged typically 18–50 years), it is unclear whether this is true for the growing cohort of ≥65-year-old KT donors. To this end, all KTs from ≥65-year-old DBD donors performed at three German transplant centers from January 2006 to December 2023 (n = 680) were retrospectively analyzed and outcomes of KTs from donors with and without a history of CPR were compared (n = 81 and n = 599, respectively). No significant differences were observed regarding the incidence of delayed graft function (DGF) as well as regarding 1- and 5-year graft function between the CPR and no-CPR groups (DGF: 27.2% vs. 33.1%, p = 0.40; 1-year eGFR (mL/min): 33.3 vs. 35.0, p = 0.75; 5-year eGFR: 35.8 vs. 37.3, p = 0.75, respectively). Death-censored graft survival (73.8% vs. 66.0%, p = 0.24) and patient survival (78.7% vs. 73.5% p = 0.61) were comparable after 5 years between the CPR and no-CPR groups. The results were confirmed by multivariable Cox regression analysis. In conclusion, our results indicate that ≥65-year-old DBD donors with a history of CPR are potentially suitable for KT without impairing allograft outcomes.

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.

Here, we retrospectively evaluated the informational yield of 338 post-reperfusion kidney transplant biopsies (including 95 living donations) assessed according to BANFF for the histological characteristics interstitial fibrosis and tubular atrophy (IF/TA), glomerulosclerosis, arteriosclerosis, and acute tubular injury (ATI). Associations with delayed graft function (DGF) and death-censored graft survival were explored through Cox-regression analyses. The maximum follow-up time was 11.4 years, with DGF observed in 108 (32%) cases. After deceased donation there was no association between DGF and histologic parameters. Univariable Cox-regression unveiled an association of IF/TA and glomerulosclerosis with long-term death-censored graft survival (HR per 10% increase: IF/TA 1.63; 95% CI 1.17-2.28; p = 0.003; glomerulosclerosis 1.19; 95% CI 1.01-1.39; p = 0.031). In multivariable Cox regression analyses, adjusted for recognized clinical risk variables like expanded criteria donor-status, donor age, history of diabetes, and HLA-mismatches, only IF/TA maintained association over the total observation period in deceased donations and in the total cohort. Arteriosclerosis and ATI were not associated with clinical outcome after deceased donation. Especially ATI did not affect delayed graft function if only deceased donations were considered. Our data underlines the role of organ quality for transplant outcome prior to acute lesions such as ATI during the transplantation process.

Background: Coagulation disorders, including both bleeding and thrombotic complications, are common in patients undergoing hemodialysis (HD). Here, we aimed to characterize platelet function in patients undergoing hemodialysis three times per week, compared to healthy controls. Methods: Platelet function was assessed using the Multiplate analyzer (Roche), which is based on multiple electrode impedance aggregometry. Platelet aggregation was induced using adenosine diphosphate (ADP), and the area under the curve (AUC) served as the primary endpoint. In addition, platelet counts and C-reactive protein (CRP) levels were measured. To further evaluate nitric oxide (NO)-mediated inhibition of platelet aggregation, blood samples were incubated with the NO donor, sodium nitroprusside (SNP), and the phosphodiesterase 5A (PDE5A) inhibitor, sildenafil. Results: A total of 60 patients undergoing HD and 67 healthy controls were included in the analysis. Patients receiving HD treatment had significantly lower platelet counts compared to healthy controls (226.9 ± 53.47 vs. 246.7 ± 47.21 G/L, p = 0.029). Platelet aggregation was markedly reduced in patients undergoing HD compared to controls (462.0 ± 266.54 vs. 644.5 ± 254.44 AU × min, p < 0.001) with a significant correlation for platelet count (r = 0.42, p = 0.001) and systemic inflammation as indicated by CRP levels (r = 0.28, p = 0.035). Following SNP and sildenafil administration, inhibition of platelet aggregation remained more pronounced in patients undergoing HD. However, the change in platelet aggregation after SNP/sildenafil treatment did not differ significantly between the groups. Conclusions: Patients undergoing HD exhibit altered platelet function, indicated by reduced aggregation and platelet counts, as well as an association with systemic inflammation. Multiple electrode impedance aggregometry appears to be a feasible method for detecting platelet function alterations in patients receiving HD treatment. Responsiveness to NO donors was preserved in patients undergoing HD. Further studies are needed to identify the underlying mechanisms, particularly the role of NO signaling in platelet dysfunction in patients undergoing HD.

ObjectivesIL26 levels are elevated in the blood and synovial fluid of patients with inflammatory arthritis. IL26 can be produced by Th17 cells and locally within joints by tissue-resident cells. IL26 induces osteoblast mineralization in vitro. As osteoproliferation and Th17 cells are important factors in the pathogenesis of axial spondyloarthritis (axSpA), we aimed to clarify the cellular sources of IL26 in spondyloarthritis.MethodsSerum, peripheral blood mononuclear cells (n = 15–35) and synovial tissue (n = 3–9) of adult patients with axSpA, psoriatic arthritis (PsA) and rheumatoid arthritis (RA) and healthy controls (HCs, n = 5) were evaluated by ELISA, flow cytometry including PrimeFlow assay, immunohistochemistry and immunofluorescence and quantitative PCR.ResultsSynovial tissue of axSpA patients shows significantly more IL26-positive cells than that of HCs (p < 0.01), but numbers are also elevated in PsA and RA patients. Immunofluorescence shows co-localization of IL26 with CD68, but not with CD3, SMA, CD163, cadherin-11, or CD90. IL26 is elevated in the serum of RA and PsA (but not axSpA) patients compared with HCs (p < 0.001 and p < 0.01). However, peripheral blood CD4+ T cells from axSpA and PsA patients show higher positivity for IL26 in the PrimeFlow assay compared with HCs. CD4+ memory T cells from axSpA patients produce more IL26 under Th17-favoring conditions (IL-1β and IL-23) than cells from PsA and RA patients or HCs.ConclusionIL26 production is increased in the synovial tissue of SpA and can be localized to CD68+ macrophage-like synoviocytes, whereas circulating IL26+ Th17 cells are only modestly enriched. Considering the osteoproliferative properties of IL26, this offers new therapeutic options independent of Th17 pathways.

Patients with hematologic malignancies still face a significant risk of severe coronavirus disease 2019 (COVID-19). The severe acute respiratory syndrome coronavirus type 2 (SARS-CoV-2)-neutralizing monoclonal antibody combination tixagevimab/cilgavimab (TIX/CGB) could be administered to immunocompromised patients for pre-exposure prophylaxis (PrEP) before the emergence of TIX/CGB-resistant COVID-19 Omicron variants. TIX/CGB application could be carried out regardless of the host’s immune response to previous active SARS-CoV-2 vaccinations or infections. Because the efficacy of COVID-19 PrEP remains unclear, especially in SARS-CoV-2-seropositive patients, German national guidelines recommended TIX/CGB PrEP only for SARS-CoV-2-seronegative patients in addition to an intensified active vaccination schedule. Having followed these guidelines, we now report the characteristics and outcomes of 54 recipients of TIX/CGB PrEP in SARS-CoV-2-seronegative patients with hematological disease from a German tertiary medical center and compare them to 125 seropositive patients who did not receive any PrEP. While the number of patients with B-cell lymphomas was significantly higher in the seronegative cohort (33 (61%) vs. 18 (14%) cases, p < 0.01), patients with myeloid diseases were significantly more frequent in the seropositive cohort (51 (41%) vs. 5 (9%) cases, p < 0.01). Strikingly, patients who had undergone allogeneic hematopoietic stem cell transplantation were significantly more likely (forty-nine (39%) vs. six (11%) cases, p < 0.01) to be SARS-CoV-2 seropositive. We observed that prophylactic application of TIX/CGB PrEP to a highly vulnerable group of SARS-CoV-2-seronegative patients resulted in a similar number of COVID-19 breakthrough infections compared to the untreated seropositive control group (16 (32%) vs. 39 (36%), p = 0.62) and comparable COVID-19-related outcomes like hospitalization and oxygen requirement throughout an extended follow-up period of 12 months. In conclusion, our results support the tailored approach of administering TIX/CGB PrEP only to SARS-CoV-2-seronegative patients during the COVID-19 pandemic and might provide a rationale for similar strategies during future outbreaks/diseases, especially in times of initial limited availability and/or financial constraints.

Aims/Purpose: Patients with rheumatoid arthritis (RA) have a high risk of developing cardiovascular diseases due to endothelial dysfunction, which is a risk factor for cardiovascular events. The retinal Vessel Analyzer (RVA, IMEDOS Systems) can capture retinal vessels non‐invasively in real‐time and analyse their dynamic responses to stimuli. Methods: In order to assess the structural and functional changes in the retinal microvasculature, a non‐invasive Retinal Vessels Analyzer (RVA) was used to study 44 patients with RA (mean age 57.4 ± 13.2 years) and compare them to a control group of 44 age‐matched healthy individuals. The RVA was used to measure various parameters, including the Central Retinal Artery Equivalent (CRAE), Central Retinal Vein Equivalent (CRVE), and Arterio‐Venous Ratio (AVR), as well as the response of the retinal vessels to flickering light. After a 50 s baseline, rectangular shape, monochromatic flickering light (530–600 nm) of 12.5 Hz for 20 s was applied three times. The dilation of retinal vessels after flicker light stimulation was analysed. Results: The results of the study showed that patients with RA had significantly higher CRVE and lower AVR compared to the control group ( p = 0.04 and p = 0.01, respectively), indicating structural changes in the retinal microvasculature. The patients with RA also had a significantly stronger arterial dilation response to flickering light compared to the control group ( n = 43), indicating functional changes in the retinal microvasculature. In patients with moderate to high disease activity according to the Disease Activity Score (DAS‐28 > 3.2) ( n = 9), there was a negative significant correlation between the maximum arterial diameter (aMAX) and interleukin‐6 (IL‐6). Conclusions: These findings suggest that RVA can be a useful tool for detecting structural and functional changes in the retinal microvasculature of patients with RA and that the disease activity and inflammation in RA may be related to these changes. However, the study notes that a larger cohort with a wider range of disease activity is needed to fully understand the effect of chronic inflammatory diseases on endothelial function.

Introduction Due to chronic inflammation, maintenance hemodialysis (MHD) patients continue to show excess mortality. Acetate-free citrate-buffered A concentrates could be a way to improve the biocompatibility of the procedure, reduce chronic inflammation, and thus in the long term improve the prognosis of patients. Methods Using a pre-post design (3 months of acetate followed by 3 months of citrate-acidified A concentrates in standard bicarbonate-based dialysate hemodialysis, CiaHD) and linear mixed model analysis in 61 stable HD patients, we assessed the impact of CiaHD on counts and phenotypes of peripheral T cells and monocytes by flow cytometry. Results Switching to CiaHD left C-reactive protein (CRP) levels and leucocyte counts unaffected. However, CiaHD increased lymphocyte counts ex vivo. Furthermore, we found a decrease in total CD3+CD4+CD69+ ((109/L), mean ± SD: acetate, 0.04 ± 1.0 versus citrate, 0.02 ± 0.01; P = 0.02) activated cells, while the number of CD28+ T cells remained stable. No differences were noted regarding T-cell exhaustion marker expression, CD14+CD16+ monocyte counts, and PMN-MDSCs. Conclusion Compared with acetate, CiaHD has a minor impact on lymphocyte counts and CD4+T-cell activation, which was independent of systemic CRP and ionized magnesium, calcium levels, and other dialysis prescription modalities.

Renal ischemia-reperfusion injury (IRI) is associated with reduced allograft survival, and each additional hour of cold ischemia time increases the risk of graft failure and mortality following renal transplantation. Receptor-interacting protein kinase 3 (RIPK3) is a key effector of necroptosis, a regulated form of cell death. Here, we evaluate the first-in-human RIPK3 expression dataset following IRI in kidney transplantation. The primary analysis included 374 baseline biopsy samples obtained from renal allografts 10 minutes after onset of reperfusion. RIPK3 was primarily detected in proximal tubular cells and distal tubular cells, both of which are affected by IRI. Time-to-event analysis revealed that high RIPK3 expression is associated with a significantly higher risk of one-year transplant failure and prognostic for one-year (death-censored) transplant failure independent of donor and recipient associated risk factors in multivariable analyses. The RIPK3 score also correlated with deceased donation, cold ischemia time and the extent of tubular injury.

Dear Editor, Adult-onset Still’s disease (AOSD) is an autoinflammatory disease with to-date unexplained aetiology. Secondary hemophagocytic lymphohistiocytosis (HLH), here referred to as macrophage activation syndrome HLH (MAS-HLH) is the most devastating complication of AOSD [1]. Signs of evolution include antibiotic-resistant fever, hepatosplenomegaly, hyperferritinaemia, hypertriglyceridaemia, fibrinogen consumption, bi- or trilinear cytopenia, as well as hemophagocytosis in bone marrow [2]. Yet, low sensitivity and diagnostic delay of bone marrow histopathology, baseline hyperferritinaemia and organomegaly make prompt recognition of MAS-HLH particularly challenging in the context of AOSD. However, rigorous and instant immunosuppressive therapy upon recognition is lifesaving [1]. Herein, we report a 23-year-old Caucasian woman who had been diagnosed with AOSD 2 years ago based on recurrent febrile episodes including pharyngitis, cervical lymphadenopathy, salmon-coloured rash (Fig. 1A), arthritis, lymphadenopathy and hepatosplenomegaly (informed consent has been obtained from relatives). Treatment with MTX (15 mg/week s.c.), anakinra (100 mg/day s.c.) and tocilizumab (162 mg/week s.c.) was not effective, and she was dependent on low- to medium-dose glucocorticoids (up to 20 mg prednisolone per day). Ten, 6 and 2 weeks before the events reported here, the patient experienced disease flares after discontinuation (initially) or tapering (more recently) of prednisolone, respectively, and had to be treated with high-dose prednisolone (60 mg/day) to blunt fevers. Canakinumab (300 mg/4 weeks) was initiated as an approved steroid-sparing agent. Lymph node histology and bone marrow puncture were obtained to exclude lymphoma or multicentric Castleman’s disease. At this stage (2 weeks prior to her final admission), suspected MAS-HLH was not confirmed by histological bone marrow examination. However, F-fluorodeoxyglucose (FDG)-PET-CT scan had revealed focal hepatic tracer enhancement of uncertain significance (Fig. 1B). Aside from mild anaemia, cytopenia was absent, and elevated serum ferritin levels (up to 4500 pg/ml) decreased upon prednisolone therapy (Fig. 1C).

BACKGROUND:Kidney transplant recipients (KTRs) who have a highly impaired immune response are in need of intensified and safe vaccination strategies to achieve seroconversion and prevent severe disease.METHODS:We searched the Web of Science Core Collection, the Cochrane COVID-19 Study Register and the WHO COVID-19 global literature on coronavirus disease from January 2020 to 22 July 2022 for prospective studies that assessed immunogenicity and efficacy after three or more SARS-CoV-2 vaccine doses.RESULTS:In 37 studies on 3429 patients, de novo seroconversion after three and four vaccine doses ranged from 32 to 60% and 25 to 37%. Variant-specific neutralization was 59 to 70% for Delta and 12 to 52% for Omicron. Severe disease after infection was rarely reported but all concerned KTRs lacked immune responses after vaccination. Studies investigating the clinical course of COVID-19 found remarkably higher rates of severe disease than in the general population. Serious adverse events and acute graft rejections were very rare. Substantial heterogeneity between the studies limited their comparability and summary.CONCLUSION:Additional SARS-CoV-2 vaccine doses are potent and safe in general terms as well as regarding transplant-specific outcomes whilst the Omicron wave remains a significant threat to KTRs without adequate immune responses.

BackgroundThe increasing organ shortage in kidney transplantation leads to the necessity to use kidneys previously considered unsuitable for transplantation. Numerous studies illustrate the need for a better decision guidance rather than only the classification into kidneys from standard or expanded criteria donors referred to as SCD/ECD-classification. The kidney donor profile index (KDPI) exhibits a score utilizing a much higher number of donor characteristics. Moreover, graft biopsies provide an opportunity to assess organ quality.MethodsIn a single center analysis 383 kidney transplantations (277 after deceased and 106 after living donation) performed between January 1st, 2006, and December 31st, 2016, retrospectively underwent SCD/ECD and KDPI scoring. Thereby, the quality of deceased donor kidneys was assessed by using the KDPI and the living donor kidneys by using the living KDPI, in the further analysis merged as (L)KDPI. Baseline biopsies taken 10 min after the onset of reperfusion were reviewed for chronic and acute lesions. Survival analyses were performed using Kaplan-Meier analysis and Cox proportional hazards analysis within a 5-year follow-up.ResultsThe (L)KDPI correlated with glomerulosclerosis (r = 0.30, p < 0.001), arteriosclerosis (r = 0.33, p < 0.001), interstitial fibrosis, and tubular atrophy (r = 0.28, p < 0.001) as well as the extent of acute tubular injury (r = 0.20, p < 0.001). The C-statistic of the (L)KDPI concerning 5-year death censored graft survival was 0.692. Around 48% of ECD-kidneys were classified as (L)KDPI<85%. In a multivariate Cox proportional hazard analysis including (preformed) panel reactive antibodies, cold ischemia time, (L)KDPI, and SCD/ECD-classification, the (L)KDPI was significantly associated with risk of graft loss (hazard ratio per 10% increase in (L)KDPI: 1.185, 95% confidence interval: 1.033–1.360, p = 0.025). Survival analysis revealed decreased death censored (p < 0.001) and non-death censored (p < 0.001) graft survival in kidneys with an increasing (L)KDPI divided into groups of <35, 35–85, and >85%, respectively.ConclusionWith a higher granularity compared to the SCD/ECD-classification the (L)KDPI is a promising tool to judge graft quality. The correlation with chronic and acute histological lesions in post-reperfusion kidney biopsies underlines the descriptive value of the (L)KDPI. However, its prognostic value is limited and underlines the urgent need for a more precise prognostic tool adopted to European kidney transplant conditions.

Delayed graft function (DGF) following kidney transplantation is associated with increased risk of graft failure, but biomarkers to predict DGF are scarce. We evaluated serum uromodulin (sUMOD), a potential marker for tubular integrity with immunomodulatory capacities, in kidney transplant recipients and its association with DGF. We included 239 kidney transplant recipients and measured sUMOD pretransplant and on postoperative Day 1 (POD1) as independent variables. The primary outcome was DGF, defined as need for dialysis within one week after transplantation. In total, 64 patients (27%) experienced DGF. In multivariable logistic regression analysis adjusting for recipient, donor and transplant associated risk factors each 10 ng/mL higher pretransplant sUMOD was associated with 47% lower odds for DGF (odds ratio (OR) 0.53, 95% confidence interval (95%-CI) 0.30–0.82). When categorizing pretransplant sUMOD into quartiles, the quartile with the lowest values had 4.4-fold higher odds for DGF compared to the highest quartile (OR 4.41, 95%-CI 1.54–13.93). Adding pretransplant sUMOD to a model containing established risk factors for DGF in multivariable receiver-operating-characteristics (ROC) curve analysis, the area-under-the-curve improved from 0.786 [95%-CI 0.723–0.848] to 0.813 [95%-CI 0.755–0.871, p = 0.05]. SUMOD on POD1 was not associated with DGF. In conclusion, higher pretransplant sUMOD was independently associated with lower odds for DGF, potentially serving as a non-invasive marker to stratify patients according to their risk for developing DGF early in the setting of kidney transplantation.

Background: Atrial fibrillation (AF) is common in hemodialysis patients and contributes to increased mortality. We aimed to examine heart rate variability triangular index (HRVI) in hemodialysis patients with AF as it has recently been reported to predict mortality in AF patients without kidney disease. Methods: A total of 88 patients on hemodialysis with a medical history of AF or newly diagnosed AF underwent 24-h electrocardiography recordings. The primary endpoint of cardiovascular mortality was recorded during a median follow up of 3.0 years. Risk prediction was assessed by Cox regression, both unadjusted and adjusted for the Charlson Comorbidity Index and the Cardiovascular Mortality Risk Score. Results: Median age was 76 years, median dialysis vintage was 27 months. Altogether, 22 and 44 patients died due to cardiovascular and non-cardiovascular causes. In 55% of patients AF was present during the recording. Kaplan-Meier plots of HRVI quartiles suggested a non-linear association between HRVI, cardiovascular, and all-cause mortality which was confirmed in non-linear Cox regression analysis. Adjusted linear Cox regression revealed a hazard ratio of 6.2 (95% CI: 2.1-17.7, p = 0.001) and 2.2 (95% CI: 1.3-3.8, p = 0.002) for the outer quartiles (combined first and fourth quartile) for cardiovascular and all-cause mortality, respectively. Patients in the first quartile were more likely to have sinus rhythm whereas patients in the fourth quartile were more likely to have AF. Conclusions: We found a U-shaped association between HRVI and mortality in hemodialysis AF patients. The results might contribute to risk stratification independent of known risk scores in hemodialysis AF patients.

BACKGROUND:The small number of organ donors forces transplant centres to consider potentially suboptimal kidneys for transplantation. Eurotransplant established an algorithm for rescue allocation (RA) of kidneys repeatedly declined or not allocated within 5 h after procurement. Data on the outcomes and benefits of RA are scarce to date.METHODS:We conducted a retrospective 8-year analysis of transplant outcomes of RA offers based on our in-house criteria catalogue for acceptance and decline of organs and potential recipients.RESULTS:RA donors and recipients were both older compared with standard allocation (SA). RA donors more frequently had a history of hypertension, diabetes or fulfilled expanded criteria donor key parameters. RA recipients had poorer human leucocyte antigen (HLA) matches and longer cold ischaemia times (CITs). However, waiting time was shorter and delayed graft function, primary non-function and biopsy-proven rejections were comparable to SA. Five-year graft and patient survival after RA were similar to SA. In multivariate models accounting for confounding factors, graft survival and mortality after RA and SA were comparable as well.CONCLUSIONS:Facing relevant comorbidities and rapid deterioration with the risk of being removed from the waiting list, kidney transplantation after RA was identified to allow for earlier transplantation with excellent outcome. Data from this survey propose not to reject categorically organs from multimorbid donors with older age and a history of hypertension or diabetes to aim for the best possible HLA matching and to carefully calculate overall expected CIT.

Severe COVID-19 associated respiratory failure, poses the one challenge of our days. Assessment and treatment of COVID-19 associated hyperinflammation may be key to improve outcomes. It was speculated that in subgroups of patients secondary hemophagocytic lymphohistiocytosis (sHLH) or cytokine release syndrome (CRS) with features of macrophage activation syndrome might drive severe disease trajectories. If confirmed, profound immunosuppressive therapy would be a rationale treatment approach. Over a median observation period of 11 (IQR: 8; 16) days, 19 consecutive confirmed severe COVID-19-patients admitted to our intensive-care-unit were tested for presence of sHLH by two independent experts. HScores and 2004-HLH diagnostic criteria were assessed. Patients were grouped according to short-term clinical courses: discharge from ICU versus ongoing ARDS or death at time of analysis. The median HScore at admission was 157 (IQR: 98;180), without the key clinical triad of HLH, i.e. progressive cytopenia, persistent fever and organomegaly. Independent expert chart review revealed the absence of sHLH in all cases. No patient reached more than 3/6 of modified HLH 2004 criteria. Nevertheless, patients presented hyperinflammation with peripheral neutrophilic signatures (neutrophil/lymphocyte-ratio > 3.5). The latter best paralleled their short-term clinical courses, with declining relative neutrophil numbers prior to extubation (4.4, [IQR: 2.5;6.3]; n = 8) versus those with unfavourable courses (7.6, [IQR: 5.2;31], n = 9). Our study rules out virus induced sHLH as the leading cause of most severe-COVID-19 trajectories. Instead, an associated innate neutrophilic hyperinflammatory response or virus-associated-CRS appears dominant in patients with an unfavourable clinical course. Therapeutic implications are discussed.

Data on risk factors predicting rapid progression to end-stage renal disease (ESRD) or short-term kidney function decline (i.e., within 1 year) in chronic kidney disease (CKD) are rare but urgently needed to plan treatment. This study describes the association and predictive value of urinary uromodulin (uUMOD) for rapid progression of CKD. We assessed uUMOD, demographic/treatment parameters, estimated glomerular filtration rate (eGFR), and proteinuria in 230 CKD patients stage I-V. ESRD and 25% decline of eGFR was documented at the end of follow-up period and used as a composite endpoint. Association between logarithmic uUMOD and eGFR/proteinuria was calculated using linear regression analysis, adjusting for age, gender, and body mass index. We performed multivariable Cox proportional hazard regression analysis to evaluate the association of uUMOD with the composite endpoint. Therefore, patients were categorized into quartiles. The predictive value of uUMOD for the above outcomes was assessed using receiver-operating characteristic (ROC) curve analysis. Follow-up was 57.3 +/- 18.7 weeks, baseline age was 60 (18;92) years, and eGFR was 38 (6;156) mL/min/1.73m(2). Forty-seven (20.4%) patients reached the composite endpoint. uUMOD concentrations were directly associated with eGFR and inversely associated with proteinuria (beta=0.554 and beta=-0.429, P<.001). In multivariable Cox regression analysis, the first 2 quartiles of uUMOD concentrations had a hazard ratio (HR) of 3.589 [95% confidence interval (95% CI) 1.002-12.992] and 5.409 (95% CI 1.444-20.269), respectively, in comparison to patients of the highest quartile (>= 11.45 mu g/mL) for the composite endpoint. In ROC-analysis, uUMOD predicted the composite endpoint with good sensitivity (74.6%) and specificity (76.6%) at an optimal cut-off at 3.5 mu g/mL and area under the curve of 0.786 (95% CI 0.712-0.860, P<.001). uUMOD was independently associated with ESRD/rapid loss of eGFR. It might serve as a robust predictor of rapid kidney function decline and help to better schedule arrangements for future treatment.