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.

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.

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.

What happens after graft loss? A large, long-term, single-center observation.

The number of patients returning to dialysis after graft failure increases. Surprisingly, little is known about the clinical and immunological outcomes of this cohort. We retrospectively analyzed 254 patients after kidney allograft loss between 1997 and 2017 and report clinical outcomes such as mortality, relisting, retransplantations, transplant nephrectomies, and immunization status. Of the 254 patients, 49% had died 5 years after graft loss, while 27% were relisted, 14% were on dialysis and not relisted, and only 11% were retransplanted 5 years after graft loss. In the complete observational period, 111/254 (43.7%) patients were relisted. Of these, 72.1% of patients were under 55 years of age at time of graft loss and only 13.5% of patients were ≥65 years. Age at graft loss was associated with relisting in a logistic regression analysis. In the complete observational period, 42 patients (16.5%) were retransplanted. Only 4 of those (9.5%) were ≥65 years at time of graft loss. Nephrectomy had no impact on survival, relisting, or development of dnDSA. Patients after allograft loss have a high overall mortality. Immunization contributes to long waiting times. Only a very limited number of patients are retransplanted especially when ≥65 years at time of graft loss.

The relationship between proteinuria and allograft survival in patients with transplant glomerulopathy: a retrospective single-center cohort study.

Proteinuria and transplant glomerulopathy (TG) are common in kidney transplantation. To date, there is limited knowledge regarding proteinuria in different types of TG and its relationship to allograft survival. A retrospective cohort analysis of TG patients from indication biopsies was performed to investigate the relationship of proteinuria, histology, and graft survival. One hundred and seven (57.5%) out of 186 TG patients lost their grafts with a median survival of 14 [95% confidence interval (CI) 10-22] months after diagnosis. Proteinuria ≥1 g/24 h at the time of biopsy was detected in 87 patients (46.8%) and the median of proteinuria was 0.89 (range 0.05-6.90) g/24 h. TG patients with proteinuria ≥1 g/24 h had worse 5-year graft survival (29.9% vs. 53.5%, P = 0.001) compared with proteinuria <1 g/24 h. Proteinuria was associated with graft loss in univariable Cox regression [hazard ratio (HR) 1.25, 95% CI, 1.11-1.41, P < 0.001], and in multivariable analysis (adjusted HR 1.26, 95% CI 1.11-1.42, P < 0.001) independent of other risk factors including creatinine at biopsy, positive C4d, history of rejection, and Banff lesion score mesangial matrix expansion. In this cohort of TG patients, proteinuria at indication biopsy is common and associated with a higher proportion of graft loss.

eHealth in transplantation.

eHealth ("electronic" Health) is a new field in medicine that has the potential to change medical care, increase efficiency, and reduce costs. In this review, we analyzed the current status of eHealth in transplantation by performing a PubMed search over the last 5 years with a focus on clinical studies for post-transplant care. We retrieved 463 manuscripts, of which 52 clinical reports and eight randomized controlled trials were identified. Most studies were on kidney (n = 19), followed by liver (n = 10), solid organ (n = 7), bone-marrow (n = 6), and lung transplantation (n = 6). Eleven articles included adolescents/children. Investigated eHealth features covered the whole spectrum with mobile applications for patients (n = 24) and video consultations (n = 18) being most frequent. Prominent topics for patient apps were self-management (n = 16), adherence (n = 14), symptom-reporting (11), remote monitoring of vital signs (n = 8), educational (n = 7), and drug reminder (n = 7). In this review, we discuss opportunities and strengths of such new eHealth solutions, the implications for successful implementation into the healthcare process, the human factor, data protection, and finally, the need for better evidence from prospective clinical trials in order to confirm the claims on better patient care, potential efficiency gains and cost savings.

Microvascular inflammation is a risk factor in kidney transplant recipients with very late conversion from calcineurin inhibitor-based regimens to belatacept.

BACKGROUND: In de novo kidney transplant recipients (KTR) treatment with belatacept has been established as a comparable option as maintenance immunosuppression, preferably as a strategy to convert from calcineurin inhibitor (CNI)- to belatacept-based immunosuppression. Switch to belatacept demonstrated improved renal function in patients with CNI-induced nephrotoxicity, but risk of transplant rejection and the development of donor-specific antibodies (DSA) are still a matter of debate. Only few data are available in patients at increased immunological risk and late after transplantation. METHODS: We analyzed 30 long-term KTR (including 2 combined pancreas-KTR) converted from CNI to belatacept > 60 months after transplantation with moderate to severe graft dysfunction (GFR ≤ 45 mL/min). Biopsies were classified according to the Banff 2015 criteria. Group differences were assessed in a univariate analysis using Mann Whitney U or Chi square test, respectively. Multivariate analysis of risk factors for treatment failure was performed using a binary logistic regression model including significant predictors from univariate analysis. Fifty-six KTR matched for donor and recipient characteristics were used as a control cohort remaining under CNI-treatment. RESULTS: Patient survival in belatacept cohort at 12/24 months was 96.7%/90%, overall graft survival was 76.7 and 60.0%, while graft survival censored for death was 79.3%/66.7%. In patients with functioning grafts, median GFR improved from 22.5 mL/min to 24.5 mL/min at 24 months. Positivity for DSA at conversion was 46.7%. From univariate analysis of risk factors for graft loss, GFR < 25 mL/min (p = 0.042) and Banff microvascular inflammation (MVI) sum score ≥ 2 (p = 0.023) at conversion were significant at 24 months. In the analysis of risk factors for treatment failure, a MVI sum score ≥ 2 was significant univariately (p = 0.023) and in a bivariate (p = 0.037) logistic regression at 12 months. DSA-positivity was neither associated with graft loss nor treatment failure. The control cohort had comparable graft survival outcomes at 24 months, albeit without increase of mean GFR in patients with functioning grafts (ΔGFR of - 3.6 ± 8.5 mL/min). CONCLUSION: Rescue therapy with conversion to belatacept is feasible in patients with worsening renal function, even many years after transplantation. The benefit in patients with MVI and severe GFR impairment remains to be investigated.

Immunologic outcome in elderly kidney transplant recipients: is it time for HLA-DR matching?

BACKGROUND: The Eurotransplant Senior Program (ESP) neglects HLA matching for elderly (≥65 years) kidney transplant recipients (KTR). Few data regarding the influence of DR matching on clinical and immunologic outcome in elderly KTR exist. METHODS: This retrospective long-term observational study included 244 elderly out of n = 972 adult KTR between 2004 and 2014. Data analysis included patient and graft survival, biopsy-proven rejections [T-cell-mediated rejections (TCMR) and antibody-mediated rejections] and development of de novo donor-specific HLA antibodies (DSA). Outcome data were assessed over a maximum period of 10 years. RESULTS: Due to the nature of the ESP, elderly KTR showed significantly more HLA mismatches, shorter time on dialysis and shorter cold ischaemia time. Elderly KTR had significantly worse graft and patient survival, and after 7 years, the rate of de novo DSA (33 versus 25%, P = 0.034) and TCMR (39 versus 27%, P < 0.001) was significantly higher compared with younger KTR. Multivariate analysis identified donor age, delayed graft function and HLA-DR mismatches as independent risk factors for TCMR. Within the group of elderly KTR, HLA-DR mismatches were associated with a significantly higher incidence of TCMR and development of de novo DSA. Occurrence of TCMR and de novo DSA in elderly KTR resulted in significantly worse graft survival. CONCLUSIONS: In elderly KTR, HLA-DR mismatches are independent risk factors for TCMR and the development of all classes of de novo DSA, both of which significantly impair graft survival. Introduction of HLA-DR matching in elderly KTR might significantly improve immunologic and overall outcome.

Clinical outcome of norovirus infection in renal transplant patients.

Transplant patients are at increased risk for developing severe norovirus (NoV) infections with secondary complications such as rejection episodes and acute transplant failure. This single-center retrospective study included all kidney transplant patients tested positive for NoV RNA between January 2007 and December 2011. Data were compared to a control group of 528 kidney transplant patients without NoV infection. Sixty-five kidney transplant patients were recorded NoV RNA positive. Of these, 26 patients (40%) presented with acute transplant failure (AKI). In 43 patients (66.2%), dose reduction in immunosuppression was performed, and of 22 patients receiving tacrolimus, four patients (18.2%) showed toxic trough levels above 15 ng/mL at time of diagnosis. In three patients (4.6%), indicated therapeutic procedures had to be postponed due to prolonged severe diarrhea. Ten patients (15.4%) developed chronic NoV infection. One-year patient and graft survival in NoV patients and controls was 92.3% and 96.4%, respectively (n.s.). Compared to controls, eGFR was already significantly lower before NoV infection and loss of eGFR relative to baseline over 12 and 36 months was significantly higher in NoV-infected patients. In particular, patients initially presenting with AKI experienced a long-term loss of transplant function. Risk factors for NoV infection were immunosuppression containing steroids and antirejection therapy.

The inferior impact of antibody-mediated rejection on the clinical outcome of kidney allografts that develop de novo thrombotic microangiopathy.

BACKGROUND: Antibody-mediated rejection (AMR) can induce and develop thrombotic microangiopathy (TMA) in renal allografts. A definitive AMR (dAMR) co-presents three diagnostic features. A suspicious AMR (sAMR) is designated when one of the three features is missing. METHODS: Thirty-two TMA cases overlapping with AMR (AMR+ TMA) were studied, which involved 14 cases of sAMR+ TMA and 18 cases of dAMR+ TMA. Thirty TMA cases free of AMR features (AMR- TMA) were enrolled as control group. RESULTS: The ratio of complete response to treatment was similar between AMR- TMA and AMR+ TMA group (23.3% vs. 12.5%, p = 0.33), or between sAMR+ TMA and dAMR+ TMA group (14.3% vs. 11.1%, p = 0.79). At eight yr post-transplantation, the death-censored graft survival (DCGS) rate of AMR- TMA group was 62.8%, which was significantly higher than 28.0% of AMR+ TMA group (p = 0.01), but similar between sAMR+ TMA and dAMR+ TMA group (30.0% vs. 26.7%, p = 0.92). Overall, the intimal arteritis and the broad HLA (Human leukocyte antigens) mismatches were closely associated with over time renal allograft failure. CONCLUSION: The AMR+ TMA has inferior long-term graft survival, but grafts with sAMR+ TMA or dAMR+ TMA have similar characteristics and clinical courses.

Experience with belatacept rescue therapy in kidney transplant recipients.

In kidney transplant recipients with chronic graft dysfunction, long-term immunosuppression with calcineurin inhibitors (CNIs) or mTOR inhibitors (mTORi) can be challenging due to adverse effects, such as nephrotoxicity and proteinuria. Seventy-nine kidney transplant recipients treated with CNI-based or mTORi-based maintenance immunosuppression who had CNI-induced nephrotoxicity or severe adverse events were switched to belatacept. Mean time from transplantation to belatacept conversion was 69.0 months. Mean estimated glomerular filtration rate (eGFR) ± standard deviation at baseline was 26.1 ± 15.0 ml/min/1.73 m2 , increasing to 34.0 ± 15.2 ml/min/1.73 m2 at 12 months postconversion (P < 0.0005). Renal function improvements were also seen in patients with low eGFR (<25 ml/min/1.73 m2 ) or high proteinuria (>500 mg/l) at conversion. The Kaplan-Meier estimates for patient and graft survival at 12 months were 95.0% and 85.6%, respectively. The discontinuation rate due to adverse events was 7.9%. One case of post-transplant lymphoproliferative disorder occurred at 17 months postconversion. For comparison, a historical control group of 41 patients converted to mTORi-based immunosuppression because of biopsy-confirmed CNI-induced toxicity was examined; eGFR increased from 27.6 ± 7.2 ml/min/1.73 m2 at baseline to 31.1 ± 11.9 ml/min/1.73 m2 at 12 months (P = 0.018). Belatacept-based immunosuppression may be an alternative regimen for kidney transplant recipients with CNI- or mTORi-induced toxicity.

Pretransplant virtual PRA and long-term outcomes of kidney transplant recipients.

Virtual panel-reactive antibodies (vPRA) have been implemented to gauge sensitization worldwide. It is unclear how it associates with long-term outcomes, and its correlation with peak (pPRA) or actual (aPRA) has not been studied. We retrospectively reviewed data from 18- to 65-year-old kidney-only transplant patients during 1.1.1996-31.7.2011 in our center. PRAs were calculated based on solid-phase techniques. Of the 726 qualified cases, regardless of the PRA type, sensitized patients (PRA > 5%) had more females and previous transplant. Highly sensitized (HS, PRA > 50%) had longer waiting time, lower transplant rate, less living donor, more delayed graft function, and acute rejection. The conformity between vPRA and pPRA in HS was 75%, 57% between pPRA and aPRA. Forty-three percent (61/142) patients whose pPRA was >5% had no detectable aPRA and maintained similar outcomes as sensitized patients. Multivariate analysis showed consistently lower death-censored graft survival in HS defined by vPRA [HR 2.086 (95% CI 1.078-4.037), P < 0.05] and pPRA [HR 2.139 (95% CI 1.024-4.487), P < 0.05]. Both vPRA and pPRA provided reliable way estimating sensitization and predicting long-term graft survival, while aPRA might underestimate true sensitization. vPRA might be the most objective parameter to gauge sensitization.

Fate of finally transplanted deceased donor kidneys initially rejected at other kidney transplantation centers.

OBJECTIVE: We conducted this study to determine whether it is justifiable for transplant centers to reject cadaveric donor organs based on marginal organ quality. There is a growing discrepancy between the demand for renal transplants and the number of transplants conducted. For the many patients on the renal transplant waiting list, this translates into increased dialysis-associated morbidity, mortality and a reduced quality of life. PATIENTS AND METHODS: In our retrospective analysis, we focused on deceased donor kidneys that had been rejected in other transplant centers because of poor organ quality (111 patients) and then accepted for transplantation at our center, compared with a control group consisting of 343 patients. RESULTS: Cold ischemia time was statistically significantly shorter in the control group (11 vs. 12.5 h, p = 0.005). Also, delayed graft function occurred significantly (p = 0.004) more often in the study group (45.9-30.3%). Parameters regarding perioperative data and recipient outcome did not show significant differences and except for 2 time points at 1 week and 3 months, graft function did not differ either. CONCLUSIONS: We propose that acceptance criteria for marginal donor kidneys should be expanded. Centers should reconsider their acceptance criteria in the light of these findings as the results of these transplantations may even be much better if the delay due to reallocation and retransport can be spared.

Pregnancy after Kidney Transplantation-Impact of Functional Renal Reserve, Slope of eGFR before Pregnancy, and Intensity of Immunosuppression on Kidney Function and Maternal Health.

Women of childbearing age show increased fertility after kidney transplantation. Of concern, preeclampsia, preterm delivery, and allograft dysfunction contribute to maternal and perinatal morbidity and mortality. We performed a retrospective single-center study, including 40 women with post-transplant pregnancies after single or combined pancreas-kidney transplantation between 2003 and 2019. Outcomes of kidney function up to 24 months after the end of pregnancy were compared with a matched-pair cohort of 40 transplanted patients without pregnancies. With a maternal survival rate of 100%, 39 out of 46 pregnancies ended up with a live-born baby. The eGFR slopes to the end of 24 months follow-up showed mean eGFR declines in both groups (-5.4 ± 14.3 mL/min in pregnant versus -7.6 ± 14.1 mL/min in controls). We identified 18 women with adverse pregnancy events, defined as preeclampsia with severe end-organ dysfunction. An impaired hyperfiltration during pregnancy was a significant risk contributor for both adverse pregnancy events (p < 0.05) and deterioration of kidney function (p < 0.01). In addition, a declining renal allograft function in the year before pregnancy was a negative predictor of worsening allograft function after 24 months of follow-up. No increased frequency of de novo donor-specific antibodies after delivery could be detected. Overall, pregnancies in women after kidney transplantation showed good allograft and maternal outcomes.

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.

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.

Impact of surgeon experience on complication rates and functional outcomes of 484 deceased donor renal transplants: a single-centre retrospective study.

OBJECTIVE: To determine how postoperative and functional outcomes after deceased donor renal transplantation (DDRT) are related to surgeon experience. PATIENTS AND METHODS: The outcomes of 484 adult DDRT performed by 13 urological surgeons were retrospectively reviewed. After completion of a staged renal transplant training programme under supervision of an attending urological transplant surgeon, the 13 surgeons were either assigned to the inexperienced group (n = 8) or the experienced group (n = 5). Surgeons in the experienced group had performed more than 30 unsupervised DDRT in a standard fashion with routine ureteric stenting. Between 1988 and 2005, inexperienced surgeons performed 152 DDRT, whereas experienced surgeons performed 332 DDRT. RESULTS: Patient and graft survival at 2 hyears were 98% and 94.7%, respectively. Early graft loss in five recipients was unrelated to surgeon experience. Delayed graft function occurred in 29% of cases and median 1-year serum-creatinine was 1.48 mg/dL, with no difference between surgeon groups. Postoperative bleeding and lymphocele formation were the most frequent surgical complications, with an equal distribution between groups. Ureteric complications had a significantly higher incidence among inexperienced surgeons (6.6% versus 2.7%; P = 0.04). CONCLUSION: We conclude that DDRT as performed by inexperienced urological renal transplant surgeons has both acceptable short- and long-term outcomes.

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.