Office or home versus 24-hour blood pressure measurement in stable kidney transplant recipients.

BACKGROUND AND HYPOTHESIS: The aim of this study was to quantify hypertension control and evaluate concordance between all commonly available blood pressure modalities in kidney transplant recipients (KTR). METHODS: For this prospective cross-sectional study 89 stable KTR were recruited at the Charité Transplant Outpatient Clinic. For each study participant office (manual office blood pressure 'MOBP' and automated office blood pressure 'AOBP'), 7-day home (HBPM) and 24-hour ambulatory blood pressure measurement (24h-ABPM) were performed. RESULTS: 80 of the 89 patients recruited had sufficient blood pressure recordings. Mean blood pressure for MOBP, AOBP, HBPM and 24h-ABPM was 129/73, 126/71, 131/85 and 130/81 mmHg, respectively. Uncontrolled hypertension, as defined by 24h-ABPM (mean ≥ 130/80 mmHg), was present in 53 (66%) patients. MOBP, AOBP and HBPM classified 19 (24%), 22 (28%) and 41 (51%) patients respectively as 'uncontrolled hypertensive'. The Bland-Altman plot showed good agreement between systolic MOBP, AOBP, HBPM and Daytime-ABPM (mean bias ± SD: -1 ± 13 mmHg, -4 ± 13 mmHg, 1 ± 10 mmHg, respectively). Uncontrolled nighttime hypertension was present in 74 (93%) KTR, with 71 (89%) patients showing a non-physiological dipping pattern. Moderate positive correlation between Daytime-ABPM/HBPM and Nighttime-ABPM (Pearson Correlation Coefficients: 0.62-0.73), followed by MOBP/AOBP (Pearson Correlation Coefficients: 0.49-0.59) was noted. eGFR and proteinuria displayed weak correlation with 24h-, Daytime- and Nighttime-ABPM (absolute values of Pearson Correlation Coefficients: 0.04-0.41). No robust association with either 24h-, Daytime- or Nighttime-ABPM was observed for volume status exams. CONCLUSIONS: Masked hypertension is highly prevalent in KTR, especially due to high rates of uncontrolled nighttime hypertension. HBPM shows the narrowest limits of agreement with Daytime-ABPM. Daytime-ABPM and HBPM show the highest, albeit clinically insufficient, correlation with Nighttime-ABPM. Systematic integration of 24h-ABPM into clinical practice, as proposed by the '2023 ESH Guidelines for the Management of arterial hypertension', should not be withheld for the KTR population. Clinical trials evaluating treatment of hypertension in KTR are urgently needed.

Plasma NGAL levels in stable kidney transplant recipients and the risk of allograft loss.

BACKGROUND: The objective of this study was to investigate the utility of neutrophil gelatinase-associated lipocalin (NGAL) and calprotectin (CPT) to predict long-term graft survival in stable kidney transplant recipients (KTR). METHODS: A total of 709 stable outpatient KTR were enrolled >2 months post-transplant. The utility of plasma and urinary NGAL (pNGAL, uNGAL) and plasma and urinary CPT at enrollment to predict death-censored graft loss was evaluated during a 58-month follow-up. RESULTS: Among biomarkers, pNGAL showed the best predictive ability for graft loss and was the only biomarker with an area under the curve (AUC) > 0.7 for graft loss within 5 years. Patients with graft loss within 5 years (n = 49) had a median pNGAL of 304 [interquartile range (IQR) 235-358] versus 182 (IQR 128-246) ng/mL with surviving grafts (P < .001). Time-dependent receiver operating characteristic analyses at 58 months indicated an AUC for pNGAL of 0.795, serum creatinine-based Chronic Kidney Disease Epidemiology Collaboration estimated glomerular filtration rate (eGFR) had an AUC of 0.866. pNGAL added to a model based on conventional risk factors for graft loss with death as competing risk (age, transplant age, presence of donor-specific antibodies, presence of proteinuria, history of delayed graft function) had a strong independent association with graft loss {subdistribution hazard ratio (sHR) for binary log-transformed pNGAL [log2(pNGAL)] 3.4, 95% confidence interval (CI) 2.24-5.15, P < .0001}. This association was substantially attenuated when eGFR was added to the model [sHR for log2(pNGAL) 1.63, 95% CI 0.92-2.88, P = .095]. Category-free net reclassification improvement of a risk model including log2(pNGAL) in addition to conventional risk factors and eGFR was 54.3% (95% CI 9.2%-99.3%) but C-statistic did not improve significantly. CONCLUSIONS: pNGAL was an independent predictor of renal allograft loss in stable KTR from one transplant center but did not show consistent added value when compared with baseline predictors including the conventional marker eGFR. Future studies in larger cohorts are warranted.

NephroCAGE-German-Canadian Consortium on AI for Improved Kidney Transplantation Outcome: Protocol for an Algorithm Development and Validation Study.

BACKGROUND: Recent advances in hardware and software enabled the use of artificial intelligence (AI) algorithms for analysis of complex data in a wide range of daily-life use cases. We aim to explore the benefits of applying AI to a specific use case in transplant nephrology: risk prediction for severe posttransplant events. For the first time, we combine multinational real-world transplant data, which require specific legal and technical protection measures. OBJECTIVE: The German-Canadian NephroCAGE consortium aims to develop and evaluate specific processes, software tools, and methods to (1) combine transplant data of more than 8000 cases over the past decades from leading transplant centers in Germany and Canada, (2) implement specific measures to protect sensitive transplant data, and (3) use multinational data as a foundation for developing high-quality prognostic AI models. METHODS: To protect sensitive transplant data addressing the first and second objectives, we aim to implement a decentralized NephroCAGE federated learning infrastructure upon a private blockchain. Our NephroCAGE federated learning infrastructure enables a switch of paradigms: instead of pooling sensitive data into a central database for analysis, it enables the transfer of clinical prediction models (CPMs) to clinical sites for local data analyses. Thus, sensitive transplant data reside protected in their original sites while the comparable small algorithms are exchanged instead. For our third objective, we will compare the performance of selected AI algorithms, for example, random forest and extreme gradient boosting, as foundation for CPMs to predict severe short- and long-term posttransplant risks, for example, graft failure or mortality. The CPMs will be trained on donor and recipient data from retrospective cohorts of kidney transplant patients. RESULTS: We have received initial funding for NephroCAGE in February 2021. All clinical partners have applied for and received ethics approval as of 2022. The process of exploration of clinical transplant database for variable extraction has started at all the centers in 2022. In total, 8120 patient records have been retrieved as of August 2023. The development and validation of CPMs is ongoing as of 2023. CONCLUSIONS: For the first time, we will (1) combine kidney transplant data from nephrology centers in Germany and Canada, (2) implement federated learning as a foundation to use such real-world transplant data as a basis for the training of CPMs in a privacy-preserving way, and (3) develop a learning software system to investigate population specifics, for example, to understand population heterogeneity, treatment specificities, and individual impact on selected posttransplant outcomes. INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): DERR1-10.2196/48892.

COVID-19 Outcomes in Kidney Transplant Recipients in a German Transplant Center.

Kidney transplant recipients (KTRs) show higher morbidity and mortality from COVID-19 than the general population and have an impaired response to vaccination. We analyzed COVID-19 incidence and clinical outcomes in a single-center cohort of approximately 2500 KTRs. Between 1 February 2020 and 1 July 2022, 578 KTRs were infected with SARS-CoV-2, with 25 (4%) recurrent infections. In total, 208 KTRs (36%) were hospitalized, and 39 (7%) died. Among vaccinated patients, infection with the Omicron variant had a mortality of 2%. Unvaccinated patients infected with the Omicron variant showed mortality (9% vs. 11%) and morbidity (hospitalization 52% vs. 54%, ICU admission 12% vs. 18%) comparable to the pre-Omicron era. Multivariable analysis revealed that being unvaccinated (OR = 2.15, 95% CI [1.38, 3.35]), infection in the pre-Omicron era (OR = 3.06, 95% CI [1.92, 4.87]), and higher patient age (OR = 1.04, 95% CI [1.03, 1.06]) are independent risk factors for COVID-19 hospitalization, whereas a steroid-free immunosuppressive regimen was found to reduce the risk of COVID-19 hospitalization (OR = 0.51, 95% CI [0.33, 0.79]). This suggests that both virological changes in the Omicron variant and vaccination reduce the risk for morbidity and mortality from COVID-19 in KTRs. Our data extend the knowledge from the general population to KTRs and provide important insights into outcomes during the Omicron era.

Predictors of graft failure after first detection of de novo donor-specific HLA antibodies in kidney transplant recipients.

BACKGROUND: De novo donor-specific antibodies (dnDSAs) may cause antibody-mediated rejection and graft dysfunction. Little is known about the clinical course after first detection of dnDSAs during screening in asymptomatic patients. We aimed to assess the value of estimated glomerular filtration rate (eGFR) and proteinuria to predict graft failure in patients with dnDSAs and their potential utility as surrogate endpoints. METHODS: All 400 kidney transplant recipients with dnDSAs at our centre (1 March 2000-31 May 2021) were included in this retrospective study. The dates of graft loss, rejection, doubling of creatinine, ≥30% eGFR decline, proteinuria ≥500 mg/g and ≥1000 mg/g were registered from the first dnDSA appearance. RESULTS: During 8.3 years of follow-up, graft failure occurred in 33.3% of patients. Baseline eGFR and proteinuria correlated with 5-year graft loss (area under the receiver operating characteristics curve 0.75 and 0.80, P < .001). Creatinine doubled after a median of 2.8 years [interquartile range (IQR) 1.5-5.0] from dnDSA and the time from doubling creatinine to graft failure was 1.0 year (IQR 0.4-2.9). Analysing eGFR reduction ≥30% as a surrogate endpoint (148/400), the time from dnDSA to this event was 2.0 years (IQR 0.6-4.2), with a positive predictive value (PPV) of 45.9% to predict graft loss, which occurred after 2.0 years (IQR 0.8-3.2). The median time from proteinuria ≥500 mg/g and ≥1000 mg/g to graft failure was identical, 1.8 years, with a PPV of 43.8% and 49.0%, respectively. Composite endpoints did not improve PPV. Multivariable analysis showed that rejection was the most important independent risk factor for all renal endpoints and graft loss. CONCLUSIONS: Renal function, proteinuria and rejection are strongly associated with graft failure in patients with dnDSA and may serve as surrogate endpoints.

A single centre in-depth analysis of death with a functioning kidney graft and reasons for overall graft failure.

BACKGROUND: High numbers of unknown classifications and inconsistent methodologies in previous studies make the interpretation of causes leading to graft loss difficult. In addition, data on a holistic view looking at both death with a functioning graft (DWFG) and death-censored graft failure (DCGF) are sparse. METHODS: In this single-centre study we included 1477 adult kidney transplants performed between 1997 and 2017, of which all 286 DWFGs until the end of observation were analysed and causes for death assigned. Additionally, the results were compared with the causes of 303 DCGFs of the same cohort to evaluate the impact of causes for overall graft loss. RESULTS: The most frequent causes for DWFG were cardiovascular disease (CVD) in 30.8%, malignancy in 28.3% and infections in 21%. Only 9.4% of reasons for DWFG were unknown. Sudden death occurred in 40% (35/88) of patients classified as DWFG due to CVD. Overall graft loss was related to the effect of immunosuppression in 36.2% [infection 20.9% (123/589), malignancy 15.3% (90/589)] and CVD in 22.4% (132/589). In 27.4% (161/589), graft failure was associated with underimmunosuppression (rejection). For infections (60 DWFG, 63 DCGF) and CVD (88 DWFG, 44 DCGF), a considerable overlap was observed between DWFG and DCGF. For patients >70 years of age at transplantation, medical events accounted for 78% of overall graft losses and only 6.5% were associated with rejection. CONCLUSIONS: DWFG and DCGF share more causes for graft loss than previously reported and sudden death plays an underestimated role in death with a functioning graft.

Letermovir Rescue Therapy in Kidney Transplant Recipients with Refractory/Resistant CMV Disease.

(1) Background: CMV infections remain a problem after kidney transplantation, particularly if patients are refractory or resistant (r/r) to treatment with valganciclovir (VGCV) or ganciclovir (GCV). (2) Methods: In a single-center retrospective study, kidney transplant recipients (KTR) receiving letermovir (LTV) as rescue therapy for VGCV-/GCV-r/r CMV disease were analyzed regarding CMV history, immunosuppression, and outcomes. (3) Results: Of 201 KTR treated for CMV between 2017 and 2022, 8 patients received LTV following treatment failure with VGCV/GCV. All patients received CMV prophylaxis with VGCV according to the center's protocol, and 7/8 patients had a high-risk (D+/R-) CMV constellation. In seven of eight cases, rising CMV levels occurred during prophylaxis. In seven of eight patients, a mutation in UL97 associated with a decreased response to VGCV/GCV was detected. In four of eight patients, LTV resulted in CMV clearance after 24 ± 10 weeks (16-39 weeks), two of eight patients stabilized at viral loads <2000 cop/mL (6-20 weeks), and two of eight patients developed LTV resistance (range 8-10 weeks). (4) Conclusion: LTV, which is currently evaluated for CMV prophylaxis in kidney transplantation, also shows promising results for the treatment of patients with VGCV/GCV resistance despite the risk of developing LTV resistance. Additional studies are needed to further define its role in the treatment of patients with CMV resistance.

Evaluation of a clinical decision support system for detection of patients at risk after kidney transplantation.

Patient care after kidney transplantation requires integration of complex information to make informed decisions on risk constellations. Many machine learning models have been developed for detecting patient outcomes in the past years. However, performance metrics alone do not determine practical utility. We present a newly developed clinical decision support system (CDSS) for detection of patients at risk for rejection and death-censored graft failure. The CDSS is based on clinical routine data including 1,516 kidney transplant recipients and more than 100,000 data points. In a reader study we compare the performance of physicians at a nephrology department with and without the CDSS. Internal validation shows AUC-ROC scores of 0.83 for rejection, and 0.95 for graft failure. The reader study shows that predictions by physicians converge toward the CDSS. However, performance does not improve (AUC-ROC; 0.6413 vs. 0.6314 for rejection; 0.8072 vs. 0.7778 for graft failure). Finally, the study shows that the CDSS detects partially different patients at risk compared to physicians. This indicates that the combination of both, medical professionals and a CDSS might help detect more patients at risk for graft failure. However, the question of how to integrate such a system efficiently into clinical practice remains open.

The natural history of de novo donor-specific HLA antibodies after kidney transplantation.

Background: De novo donor-specific HLA antibodies (dnDSA) are key factors in the diagnosis of antibody-mediated rejection (ABMR) and related to graft loss. Methods: This retrospective study was designed to evaluate the natural course of dnDSA in graft function and kidney allograft survival and to assess the impact of mean fluorescence intensity (MFI) evolution as detected by annual Luminex® screening. All 400 kidney transplant recipients with 731 dnDSA against the last graft (01/03/2000-31/05/2021) were included. Results: During 8.3 years of follow-up, ABMR occurred in 24.8% and graft loss in 33.3% of the cases, especially in patients with class I and II dnDSA, and those with multiple dnDSA. We observed frequent changes in MFI with 5-year allograft survivals post-dnDSA of 74.0% in patients with MFI reduction ≥ 50%, 62.4% with fluctuating MFI (MFI reduction ≥ 50% and doubling), and 52.7% with doubling MFI (log-rank p < 0.001). Interestingly, dnDSA in 168 (24.3%) cases became negative at some point during follow-up, and 38/400 (9.5%) patients became stable negative, which was associated with better graft survival. Multivariable analysis revealed the importance of MFI evolution and rejection, while class and number of dnDSA were not contributors in this model. Conclusion: In summary, we provide an in-depth analysis of the natural course of dnDSA after kidney transplantation, first evidence for the impact of MFI evolution on graft outcomes, and describe a relevant number of patients with a stable disappearance of dnDSA, related to better allograft survival.

Remote Patient Management May Reduce All-Cause Mortality in Patients With Heart-Failure and Renal Impairment.

Background: Remote patient management (RPM) in heart failure (HF) patients has been investigated in several prospective randomized trials. The Telemedical Interventional Management in Heart Failure II (TIM-HF2)-trial showed reduced all-cause mortality and hospitalizations in heart failure (HF) patients using remote patient management (RPM) vs. usual care (UC). We report the trial's results for prespecified eGFR-subgroups. Methods: TIM-HF2 was a prospective, randomized, controlled, parallel-group, unmasked (with randomization concealment), multicenter trial. A total of 1,538 patients with stable HF were enrolled in Germany from 2013 to 2017 and randomized to RPM (+UC) or UC. Using CKD-EPI-formula at baseline, prespecified subgroups were defined. In RPM, patients transmitted their vital parameters daily. The telemedical center reviewed and co-operated with the patient's General Practitioner (GP) and cardiologist. In UC, patients were treated by their GPs or cardiologist applying the current guidelines for HF management and treatment. The primary endpoint was the percentage of days lost due to unplanned cardiovascular hospitalizations or death, secondary outcomes included hospitalizations, all-cause, and cardiovascular mortality. Results: Our sub analysis showed no difference between RPM and UC in both eGFR-subgroups for the primary endpoint (<60 ml/min/1.73 m2: 40.9% vs. 43.6%, p = 0.1, ≥60 ml/min/1.73 m2 26.5 vs. 29.3%, p = 0.36). In patients with eGFR < 60 ml/min/1.73 m2, 1-year-survival was higher in RPM than UC (89.4 vs. 84.6%, p = 0.02) with an incident rate ratio (IRR) 0.67 (p = 0.03). In the recurrent event analysis, HF hospitalizations and all-cause death were lower in RPM than UC in both eGFR-subgroups (<60 ml/min/1.73 m2: IRR 0.70, p = 0.02; ≥60 ml/min/1.73 m2: IRR 0.64, p = 0.04). In a cox regression analysis, age, NT-pro BNP, eGFR, and BMI were associated with all-cause mortality. Conclusion: RPM may reduce all-cause mortality and HF hospitalizations in patients with HF and eGFR < 60 ml/min/1.73 m2. HF hospitalizations and all-cause death were lower in RPM in both eGFR-subgroups in the recurrent event analysis. Further studies are needed to investigate and confirm this finding.

Poor Outcomes in Patients With Transplant Glomerulopathy Independent of Banff Categorization or Therapeutic Interventions.

Background: Transplant glomerulopathy (TG) may indicate different disease entities including chronic AMR (antibody-mediated rejection). However, AMR criteria have been frequently changed, and long-term outcomes of allografts with AMR and TG according to Banff 2017 have rarely been investigated. Methods: 282 kidney allograft recipients with biopsy-proven TG were retrospectively investigated and diagnosed according to Banff'17 criteria: chronic AMR (cAMR, n = 72), chronic active AMR (cAAMR, n = 76) and isolated TG (iTG, n = 134). Of which 25/72 (34.7%) patients of cAMR group and 46/76 (60.5%) of cAAMR group were treated with antihumoral therapy (AHT). Results: Up to 5 years after indication biopsy, no statistically significant differences were detected among iTG, cAMR and cAAMR groups in annual eGFR decline (-3.0 vs. -2.0 vs. -2.8 ml/min/1.73 m2 per year), 5-year median eGFR (21.5 vs. 16.0 vs. 20.0 ml/min/1.73 m2), 5-year graft survival rates (34.1 vs. 40.6 vs. 31.8%) as well as urinary protein excretion during follow-up. In addition, cAMR and cAAMR patients treated with AHT had similar graft and patient survival rates in comparison with those free of AHT, and similar comparing with iTG group. The TG scores were not associated with 5-year postbiopsy graft failure; whereas the patients with higher scores of chronic allograft scarring (by mm-, ci- and ct-lesions) had significantly lower graft survival rates than those with mild scores. The logistic-regression analysis demonstrated that Banff mm-, ah-, t-, ci-, ct-lesions and the eGFR level at biopsy were associated with 5-year graft failure. Conclusions: The occurrence of TG is closely associated with graft failure independent of disease categories and TG score, and the long-term clinical outcomes were not influenced by AHT. The Banff lesions indicating progressive scarring might be better suited to predict an unfavorable outcome.

Initial Experience With SARS-CoV-2-Neutralizing Monoclonal Antibodies in Kidney or Combined Kidney-Pancreas Transplant Recipients.

Background: Antiviral drugs have shown little impact in patient infected with acute respiratory coronavirus 2 (SARS-CoV-2). Especially for immunocompromised persons positive for SARS-CoV-2, novel treatments are warranted. Recently, the U.S. FDA has granted an emergency use authorization (EUA) to two monoclonal antibodies (mAb) targeting the viral spike protein: bamlanivimab and casivirimab and imdevimab. As per the EUA, all SARS-CoV-2 positive organ transplant recipients can receive mAb treatment. Patients and methods: We queried our center's transplant registry to identify SARS-CoV-2 infected recipients treated with single doses of either Bamlanivimab or casivirimab/imdevimab up to May 31, 2021. We analyzed clinical outcomes, renal function and virus-specific antibodies. The co-primary endpoints were hospitalization due to COVID-19 and SARS-CoV-2 RT-PCR negativity. Results: Thirteen patients at a median interval of 55 (IQR, 26-110) months from transplant were treated: 8 with bamlanivimab and 5 with casivirimab/imdevimab. In all, 4/13 (31%) patients were hospitalized at some time, while 11/13 (85%) achieved PCR negativity. 2/4 hospitalized patients received mAb as rescue treatment. Overall mortality was 23%, with one death attributable to transplant-associated lymphoma. All six patients infected with the B 1.1.7 variant were alive at last contact. Conclusion: mAb treatment appears effective when administered early to SARS-CoV-2-infected transplant recipients.

Influence of Belatacept- vs. CNI-Based Immunosuppression on Vascular Stiffness and Body Composition.

BACKGROUND: Arterial stiffness and phase angle (PhA) have gained importance as a diagnostic and prognostic parameter in the management of cardiovascular disease. There are few studies regarding the differences in arterial stiffness and body composition between renal transplant recipients (RTRs) receiving belatacept (BELA) vs. calcineurin inhibitors (CNI). Therefore, we investigated the differences in arterial stiffness and body composition between RTRs treated with different immunosuppressants, including BELA. METHODS: In total, 325 RTRs were enrolled in the study (mean age 52.2 years, M -62.7%). Arterial stiffness was determined with an automated oscillometric device. All body composition parameters were assessed, based on bioelectrical impedance analysis (BIA), and laboratory parameters were obtained from the medical files of the patients. RESULTS: We did not detect any significant difference in terms of arterial stiffness and PhA in RTRs undergoing different immunosuppressive regimens, based on CsA, Tac, or BELA. Age was an essential risk factor for greater arterial stiffness. The PhA was associated with age, BMI, time of dialysis before transplantation, and kidney graft function. CONCLUSION: No significant differences in arterial stiffness and PhA were observed in RTRs under different immunosuppressive regimens. While our data provide additional evidence for arterial stiffness and PhA in RTRs, more research is needed to fully explore these cardiovascular risk factors and the impact of different immunosuppressive regimens.

Waiting Time for Second Kidney Transplantation and Mortality.

BACKGROUND AND OBJECTIVES: The median kidney transplant half-life is 10-15 years. Because of the scarcity of donor organs and immunologic sensitization of candidates for retransplantation, there is a need for quantitative information on if and when a second transplantation is no longer associated with a lower risk of mortality compared with waitlisted patients treated by dialysis. Therefore, we investigated the association of time on waiting list with patient survival in patients who received a second transplantation versus remaining on the waiting list. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: In this retrospective study using target trial emulation, we analyzed data of 2346 patients from the Austrian Dialysis and Transplant Registry and Eurotransplant with a failed first graft, aged over 18 years, and waitlisted for a second kidney transplantation in Austria during the years 1980-2019. The differences in restricted mean survival time and hazard ratios for all-cause mortality comparing the treatment strategies "retransplant" versus "remain waitlisted with maintenance dialysis" are reported for different waiting times after first graft loss. RESULTS: Second kidney transplantation showed a longer restricted mean survival time at 10 years of follow-up compared with remaining on the waiting list (5.8 life months gained; 95% confidence interval, 0.9 to 11.1). This survival difference was diminished in patients with longer waiting time after loss of the first allograft; restricted mean survival time differences at 10 years were 8.0 (95% confidence interval, 1.9 to 14.0) and 0.1 life months gained (95% confidence interval, -14.3 to 15.2) for patients with waiting time for retransplantation of <1 and 8 years, respectively. CONCLUSIONS: Second kidney transplant is associated with patient survival compared with remaining waitlisted and treatment by dialysis, but the survival difference diminishes with longer waiting time.

Sirolimus in renal transplant recipients with malignancies in Germany.

BACKGROUND: Renal transplant recipients have an increased cancer risk. The mammalian target of rapamycin inhibitor sirolimus (SRL) has immunosuppressive and antitumour activities but knowledge about its use in recipients with cancer is limited. METHODS: We retrospectively analysed 726 renal allograft recipients converted to SRL from 10 German transplant centres. Patient and graft survival were analysed depending on malignancy status prior to conversion and tumour entity. RESULTS: Malignancy before conversion to SRL was reported in 230 patients, with 137 patients having skin cancers and 101 having solid cancers. Cancer occurred 4.6 ± 9.4 (median 3.0) years after transplantation. Basal cell carcinoma, squamous cell carcinoma and Bowen's disease were the most prevalent skin cancers, while carcinomas of the kidney, colon and breast were the most prevalent solid cancers before conversion. Patients with prior malignancy were older and had better renal function at conversion compared with patients without a history of cancer. After conversion to SRL, cancer incidence rates (IRs) of all tumours were lower compared with rates before conversion. Cancer IRs after conversion were higher in patients with malignancy before conversion compared with those without. Patient survival was worse in patients with solid cancers compared with patients with skin cancers or without malignancies. Biopsy-proven acute rejections in the first year after conversion were less frequent in patients with malignancy compared with those without. Graft survival and renal function in all cancer types were better than in patients converted to SRL without cancers. CONCLUSIONS: Conversion to SRL in patients with a history of cancer is safe regarding renal function and graft survival, while patient survival is largely dependent on tumour entity.

Impact of Early Pancreatic Graft Loss on Outcome after Simultaneous Pancreas-Kidney Transplantation (SPKT)-A Landmark Analysis.

(1) Background: Simultaneous pancreas-kidney transplantation (SPKT) is a standard therapeutic option for patients with diabetes mellitus type I and kidney failure. Early pancreas allograft failure is a complication potentially associated with worse outcomes. (2) Methods: We performed a landmark analysis to assess the impact of early pancreas graft loss within 3 months on mortality and kidney graft survival over 10 years. This retrospective single-center study included 114 adult patients who underwent an SPKT between 2005 and 2018. (3) Results: Pancreas graft survival rate was 85.1% at 3 months. The main causes of early pancreas graft loss were thrombosis (6.1%), necrosis (2.6%), and pancreatitis (2.6%). Early pancreas graft loss was not associated with reduced patient survival (p = 0.168) or major adverse cerebral or cardiovascular events over 10 years (p = 0.741) compared to patients with functioning pancreas, after 3 months. Moreover, kidney graft function (p = 0.494) and survival (p = 0.461) were not significantly influenced by early pancreas graft loss. (4) Conclusion: In this study, using the landmark analysis technique, early pancreas graft loss within 3 months did not significantly impact patient or kidney graft survival over 10 years.

Clinicopathologic Features and Risk Factors of Proteinuria in Transplant Glomerulopathy.

Background: Transplant glomerulopathy (TG) is one of the main causes of post-transplant proteinuria (PU). The features and possible risk factors for proteinuria in TG patients are uncertain. Methods: We investigated all patients who had biopsy-proven TG from 2000 to 2018 in our center. The clinical and histological data were compared between two groups with or without PU (cut-off = 0.3 g/day). Spearman correlation analysis was used to evaluate the relationship between PU and pathological changes. The risk factors for PU in TG patients were determined by multivariable logistic regression analysis. Results: One hundred and twenty-five (75.76%) of all enrolled 165 TG patients had proteinuria ≥0.3 g/day at the time of biopsy. TG patients' PU level was significantly correlated with Banff lesion score cg (ρ = 0.247, P = 0.003), and mm (ρ = 0.257, P = 0.012). Systolic blood pressure ≥140 mmHg (OR 2.72, 95% CI 1.04-7.10, P = 0.041), diastolic blood pressure ≥90 mmHg (OR 4.84, 95% CI 1.39-16.82, P = 0.013), peak PRA ≥5% (OR 6.47, 95% CI 1.67-25.01, P = 0.007), positive C4d staining (OR 4.55, 95% CI 1.29-16.11, 0.019), tacrolimus-based regimen (OR 3.5, 95% CI 1.28-9.54, P = 0.014), and calcium channel blocker usage (OR 4.38, 95% CI 1.59-12.09, P = 0.004) were independent risk factors for PU. Conclusions: Proteinuria is common in TG patients. systolic blood pressure ≥140 mmHg, diastolic blood pressure ≥90 mmHg, peak PRA ≥5%, positive C4d staining, tacrolimus-based regimen, and calcium channel blocker usage are associated with proteinuria in TG patients.

Accuracy of a Novel SARS-CoV-2 Antigen-Detecting Rapid Diagnostic Test from Standardized Self-Collected Anterior Nasal Swabs.

Background Antigen-detecting rapid diagnostic tests (Ag-RDT) for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) offer new opportunities for the quick and laboratory-independent identification of infected individuals for control of the SARS-CoV-2 pandemic. Despite the potential benefits, nasopharyngeal sample collection is frequently perceived as uncomfortable by patients and requires trained healthcare personnel with protective equipment. Therefore, anterior nasal self-sampling is increasingly recognized as a valuable alternative. Methods We performed a prospective, single-center, point of care validation of an Ag-RDT using a polypropylene absorbent collector for standardized self-collected anterior nasal swabs. Real-time polymerase chain reaction (RT-PCR) from combined oropharyngeal/nasopharyngeal swabs served as a comparator. Primary endpoint was sensitivity of the standardized Ag-RDT in symptomatic patients with medium or high viral concentration (≥1 million RNA copies on RT-PCR for SARS-CoV-2). Results Between 12 February and 22 March 2021, 388 participants were enrolled. After exclusion of 9 patients for which no PCR result could be obtained, the novel Ag-RDT was evaluated based on 379 participants, of whom 273 were symptomatic and 106 asymptomatic. In 61 samples from symptomatic patients with medium or high viral load (≥1 million RNA copies), the sensitivity of the standardized Ag-RDT was 96.7% (59/61; 95% confidence interval (CI): 88.7-99.6%) for the primary endpoint. In total, 62 positive Ag-RDT results were detected out of 70 RT-PCR positive individuals, yielding an overall sensitivity of 88.6% (95% CI: 78.7-94.9%). Specificity was 99.7% (95% CI: 98.2-100%) in 309 RT-PCR negative individuals. Conclusions Here, we present a validation of a novel Ag-RDT with a standardized sampling process for anterior nasal self-collection, which meets World Health Organisation (WHO) criteria of ≥80% sensitivity and ≥97% specificity. Although less sensitive than RT-PCR, this assay could be beneficial due to its rapid results, ease of use, and suitability for standardized self-testing.

TBase - an Integrated Electronic Health Record and Research Database for Kidney Transplant Recipients.

TBase is an electronic health record (EHR) for kidney transplant recipients (KTR) combining automated data entry of key clinical data (e.g., laboratory values, medical reports, radiology and pathology data) via standardized interfaces with manual data entry during routine treatment (e.g., clinical notes, medication list, and transplantation data). By this means, a comprehensive database for KTR is created with benefits for routine clinical care and research. It enables both easy everyday clinical use and quick access for research questions with highest data quality. This is achieved by the concept of data validation in clinical routine in which clinical users and patients have to rely on correct data for treatment and medication plans and thereby validate and correct the clinical data in their daily practice. This EHR is tailored for the needs of transplant outpatient care and proved its clinical utility for more than 20 years at Charité - Universitätsmedizin Berlin. It facilitates efficient routine work with well-structured, comprehensive long-term data and allows their easy use for clinical research. To this point, its functionality covers automated transmission of routine data via standardized interfaces from different hospital information systems, availability of transplant-specific data, a medication list with an integrated check for drug-drug interactions, and semi-automated generation of medical reports among others. Key elements of the latest reengineering are a robust privacy-by-design concept, modularity, and hence portability into other clinical contexts as well as usability and platform independence enabled by HTML5 (Hypertext Markup Language) based responsive web design. This allows fast and easy scalability into other disease areas and other university hospitals. The comprehensive long-term datasets are the basis for the investigation of Machine Learning algorithms, and the modular structure allows to rapidly implement these into clinical care. Patient reported data and telemedicine services are integrated into TBase in order to meet future needs of the patients. These novel features aim to improve clinical care as well as to create new research options and therapeutic interventions.

Exploring the Complexity of Death-Censored Kidney Allograft Failure.

BACKGROUND: Few studies have thoroughly investigated the causes of kidney graft loss (GL), despite its importance. METHODS: A novel approach assigns each persistent and relevant decline in renal function over the lifetime of a renal allograft to a standardized category, hypothesizing that singular or multiple events finally lead to GL. An adjudication committee of three physicians retrospectively evaluated indication biopsies, laboratory testing, and medical history of all 303 GLs among all 1642 recipients of transplants between January 1, 1997 and December 31, 2017 at a large university hospital to assign primary and/or secondary causes of GL. RESULTS: In 51.2% of the patients, more than one cause contributed to GL. The most frequent primary or secondary causes leading to graft failure were intercurrent medical events in 36.3% of graft failures followed by T cell-mediated rejection (TCMR) in 34% and antibody-mediated rejection (ABMR) in 30.7%. In 77.9%, a primary cause could be attributed to GL, of which ABMR was most frequent (21.5%). Many causes for GL were identified, and predominant causes for GL varied over time. CONCLUSIONS: GL is often multifactorial and more complex than previously thought.