Background Glomerular filtration rate (GFR) estimation is crucial in renal transplantation. While creatinine-based estimating equations (eGFRcrea) are widely used, their performance is suboptimal due to non-GFR determinants. Recent KDIGO guidelines recommend greater use of cystatin C-based equations, either alone (eGFR(cys)) or combined with creatinine (eGFRcrea+cys). This study compared the performance of Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) (2009/2021) and European Kidney Function Consortium (EKFC) equations in a large cohort of kidney transplant recipients, also analyzing discordance between eGFRcrea and eGFRcys. Methods This multicenter retrospective study included 1348 stable kidney transplant recipients from France and the Netherlands. Measured GFR (mGFR) served as the reference. Creatinine and cystatin C were measured using standardized assays. Performance was assessed using bias, P20, P30 and imprecision. Discordance was defined as >20% difference between eGFRcrea and eGFR(cys). Results EKFC equations outperformed CKD-EPI counterparts for all biomarkers. EKFCcrea+cys had the highest P30 (87.6%) and was the only unbiased combined equation. Discordant eGFR results were common between eGFRcrea and eGFR(cys) (42% with EKFC, >50% with CKD-EPI). Combined equations showed better performance in discordant groups, particularly with EKFC. CKD-EPI equations performed poorly in patients with eGFRcrea lower than eGFR(cys). Conclusion EKFC equations-especially EKFCcrea+cys-provide superior accuracy in KTR. Discordance between eGFRcrea and eGFR(cys) is frequent, reinforcing the value of combined equations. Future studies should validate these findings across diverse populations and assess the prognostic impact of discordant GFR estimates.

Nephrogenetics provides an innovative etiological approach to chronic kidney disease (CKD). However, genetic testing remains complex, costly, and generates a large number of data, requiring targeted use. In 2023, Doreille A. et coll. proposed the Allogenomics Score (SAG) predictive for a positive molecular diagnosis, based on age, CKD stage, family history, and nosological category. A SAG below -2.230916 was associated with a negative predictive value (NPV) of 94 %. We test the SAG in a monocentric study (2023-2025), including 185 patients who underwent exome sequencing filtered on a 304-gene panel. Variants were ACMG-classified, and the individual SAG was calculated. Concordance between the a priori clinical hypothesis and the a posteriori molecular diagnosis was assessed using κ Cohen's coefficient. The median SAG was -1.32 (-2.14; -0.35), corresponding to a predicted probability of positive test of 21 %, with an observed diagnostic yield of 28 %. Clinico-molecular concordance was excellent (92.3 %, κ = 0.86). The probability of a positive genetic diagnosis was significantly associated with SAG (p = 0.042), but no significant association was observed with the -2.230916 threshold (which showed NPV of 84 % in our cohort). These findings indicate excellent clinico-molecular concordance but suboptimal performance of the proposed SAG threshold in clinical routine.

BACKGROUND:Subclinical kidney allograft acute rejection (SCR) corresponds to "the unexpected histological evidence of acute rejection in a stable patient". The diagnosis of SCR relies on surveillance biopsy. Positron emission tomography (PET/CT) after injection of F18-fluorodeoxyglucose ([18F]FDG) has been proposed as a non-invasive screening approach. In the present multicenter prospective study, we assess the diagnostic yield [18F]FDGPET/CT to rule out SCR in stable KTR at 3 months post KTx. METHODS:From 01/2021-03/2025, we prospectively combined surveillance biopsy and [18F]FDGPET/CT at ~3 months post transplantation in adult kidney transplant recipients from 4 independent imaging centers. The mean standardized uptake value (mSUV) was measured in kidney cortex and referenced as a ratio to psoas muscle mSUV (mSUVR). RESULTS:Our multicenter cohort of 185 patients was categorized according to the Banff-2022 classification as: normal (n = 158); borderline (n = 18); SCR (n = 9, including 6 T-cell-mediated rejection and 3 microvascular inflammation). No significant correlation was observed between the mSUVR and ti score (R = 0.032, p-value = 0.67). The mSUVR reached 2.33 [1.97-2.93], 2.71 [2.50-3.33] and 2.42 [2.27-3.14] in normal, borderline and SCR groups, respectively. In multivariate models stratified by center, the risk of non-normal histology (n = 27, including borderline and SCR) increased with donor age (OR=1.05 [1.01-1.1], p = 0.02) but not with the mSUVR (OR=4.11 [0.91-18.48], p = 0.07). The Z-score of mSUVR was significantly associated with the risk of non-normal histology (OR=1.542 [1.02-2.33, p = 0.04). The risk of biopsy-proven SCR (n = 9) was not significantly associated with mSUVR. CONCLUSIONS:The mSUVR of [18F]FDG PET/CT does not reliably rule out SCR on surveillance biopsy.

BACKGROUND:Although all-cause and cause-specific mortality trends are well studied in the general population, these trends were less explored in kidney transplant recipients with and without diabetes. Our aim was to examine time trends in (cause-specific) mortality in adult first kidney transplant recipients with and without diabetes as the cause of kidney failure in European countries. METHODS:We included adult patients who received a first kidney transplant between 2005 and 2022 from twelve European countries contributing data to the European Renal Association (ERA) Registry. We followed patients for a maximum of 5 years. We calculated age- and sex-standardised mortality rates, and the absolute and relative mortality differences between those with and without diabetes. Time trends were analyzed using Joinpoint regression. RESULTS:In total, 134,231 adults received a kidney transplant between 2005 and 2022, and 20,753 (15.5%) of them had diabetes as the cause of kidney failure. Mortality rates for kidney transplant recipients with diabetes were almost twice as high as for recipients without diabetes (45.5 deaths per 1000 person-years (py) and 24.9 per 1000 py, respectively). The higher mortality of recipients with diabetes was mainly due to excess cardiovascular mortality and infection-related mortality. Trends in all-cause and cause-specific mortality remained stable over time up to the COVID-19 pandemic for recipients with and without diabetes. During the COVID-19 pandemic, both groups experienced an increase in mortality rates, mainly driven by an increase in infection-related mortality. CONCLUSIONS:Contrary to trends observed in the general population, age- and sex-standardised all-cause and cardiovascular mortality rates among kidney transplant recipients, irrespective of diabetes status, did not improve over time. In addition, in contrast to the general population, the cardiovascular mortality gap in kidney transplant recipients with and without diabetes did not narrow over time.

Rationale: This study evaluates TBS for estimating bone microarchitecture in ESRD patients using HR-pQCT as the reference technique. Main results: TBS correlates significantly with vBMD and bone microarchitecture, unlike aBMD. Significance: TBS may complement bone health assessment in ESRD patients by offering additional information alongside aBMD. Given the high fracture risk, non-invasive techniques for assessing bone fragility in chronic kidney disease (CKD) remain important. Trabecular bone score (TBS) may provide additional information that could help guide treatment and follow-up decisions. The aim of this study is to investigate whether TBS reflects bone microarchitecture in end-stage renal disease (ESRD) patients, using high-resolution peripheral quantitative computed tomography (HR-pQCT) as the reference technique. Additionally, we aim to identify parameters associated with a low TBS. Seventy-five ESRD patients were included at the time of kidney transplantation (KTx). Areal bone mineral density (aBMD) was analyzed using dual-energy X-ray absorptiometry (DXA). TBS was assessed from the L1-L4 area during DXA. Volumetric BMD (vBMD) and bone microarchitecture at tibia and radius sites were analyzed using HR-pQCT. In ESRD patients, those with TBS < 1.370 were older and had a higher body mass index (BMI). In contrast to T-score-based classification (≤ -2.5 or > -2.5), low TBS was linked to significantly lower trabecular and cortical vBMD, reduced trabecular bone volume fraction (BV/TV) and trabecular number (Tb.N), and increased trabecular separation (Tb.Sp). In multivariate analysis, older age, higher BMI, and lower Tb.N remained independently associated with low TBS, while no HR-pQCT parameters were linked to low aBMD (T-score ≤ -2.5). TBS correlates with both trabecular and cortical parameters measured by HR-pQCT, potentially offering a complementary perspective on bone microstructure compared to aBMD. At the time of KTx, a low TBS appears to better discriminate patients with significantly lower vBMD than aBMD alone.

In September 2022, Belgium implemented a nationally reimbursed HMP service for all ECD and DCD kidneys procured and transplanted within the country. We retrospectively analyzed data from 242 kidney transplantations preserved with continuous HMP between October 2022 and September 2023. Active oxygenation (HMPO2) was applied in DCD donors aged >50 years. One-year outcomes for all HMP kidneys included delayed graft function (DGF) in 14.4%, estimated glomerular filtration rate of 50 mL/min/1.73 m2, 10.1% acute rejection, 96.3% death-censored graft survival, and 98.3% patient survival. DGF rates were lower in ECD kidneys (9.1%) and in DCD ≤50 years (9.5%), while higher in DCD >50 years (19.6%). National transplantation rates of DCD kidneys significantly increased from 90 to 175 per year (p < 0.0001), but not for ECD kidneys (from 45 to 54 per year (p = 0.2965) post-HMP implementation without affecting kidney export. The annual cost savings from reduced dialysis requirements were estimated at €3.59 million. The national implementation of a centralized HMP service in Belgium led to excellent one-year transplant outcomes, increased utilization of ECD and DCD kidneys, and substantial healthcare cost savings. These findings support HMP, and where appropriate HMPO2, as the new standard of care for kidney preservation in Belgium, with potential implications for broader international collaboration.

We report on a 46-year-old female patient with a recent history of kidney transplantation who presented with acute sinusitis. Further investigation revealed rhino-sinusal mucormycosis. Surgical debridement and a five-month antifungal treatment along with the cessation of the immunosuppressive therapy were needed. This approach led to clinical improvement but unfortunately resulted in the loss of the allograft. More than two years after this infection, the clinical and endoscopic outcomes remain favourable. Mucormycosis is a rare opportunistic infection caused by fungi of the Mucorales order, characterized by angio-invasive properties that lead to thrombosis, necrosis and infarction of the affected tissues. Diagnosis primarily relies on imaging, microbiological studies and histopathological examination. Early detection and prompt management are crucial given the poor prognosis of mucormycosis. Treatment involves a combination of surgical debridement, antifungal therapy and management of risk factors such as immunosuppression. Despite an appropriate treatment, mucormycosis remains a serious and potentially life-threatening condition.

Atypical hemolytic uremic syndrome (aHUS) usually results from an overactivation of the alternative complement pathway. As large clinical trials are scarce, patient registries can partially fill the knowledge gap on patient characteristics, management, and outcomes. We here describe the baseline clinical and genetic characteristics as well as the management of all Belgian patients enrolled in the Global aHUS Registry at data cut-off. This observational study prospectively and retrospectively collected data (data cut-off: December 26, 2022) from patients of all ages with a clinical diagnosis of aHUS, irrespective of treatment. A total of 121 Belgian patients were registered in the Global aHUS Registry, resulting in a prevalence of 10.4 aHUS patients per million inhabitants, with a higher proportion of females affected (57.9

Bone abnormalities are common after kidney transplantation (KTx) and are associated with an increased risk of fractures. The pathophysiology of post-KTx bone disorders is multifactorial, with corticosteroid (CS) therapy being a contributor to the loss of bone mineral density (BMD). This study aimed to evaluate the impact of CS withdrawal versus continued CS therapy on BMD evolution in a kidney transplant recipients (KTRs) cohort. We retrospectively analyzed BMD data from 132 patients who underwent KTx between 2005 and 2021. BMD was assessed using dual-energy X-ray absorptiometry at the time of KTx (T0) and two-years post-KTx (2yT). Patients were categorized into two groups: those who discontinued CS (CS−) within the first-year post KTx and those who continued CS therapy (CS+). The mean age at KTx was 52.2 (± 12.6) years, and 62.1

Highly sensitized (HS) kidney transplant (KTx) candidates, that is, typically considered internationally as those with panel-reactive antibody levels of >85%, remain a substantial subpopulation of patients with low chance of receiving a compatible organ. Among its many objectives, Eurotransplant-an international transplant organ allocation network serving 8 European countries-aims to improve the management of HS KTx candidates through its prioritized "acceptable mismatch" (AM) program. However, despite this program, some HS patients within the Eurotransplant network who have panel-reactive antibodies >85% still cannot access donor kidneys. For patients who remain in the AM program for ≥3 y without undergoing transplantation, an additional prioritization strategy has been implemented. This involves defining further AMs to allow for desensitization with imlifidase within the AM program. While the AM desensitization program was being developed, the Belgian Imlifidase Scientific Expert Group within the Eurotransplant network independently recognized the need for guidelines on imlifidase desensitization for real-world use in HS KTx candidates (including both AM and Eurotransplant Kidney Allocation System patients). This article describes the consensus guidelines they subsequently developed, which represent a model that any center within the Eurotransplant region could adapt or apply in clinical practice when treating HS KTx candidates who require imlifidase desensitization. The consensus guidelines include patient eligibility criteria for imlifidase treatment that align with Eurotransplant allocation rules and incorporate posttransplant management strategies for HS patients. These guidelines are dynamic and will be reviewed and updated regularly as Eurotransplant rules change and imlifidase experience grows.

Mesenchymal stromal cells (MSCs) have immunomodulatory properties and are therefore considered promising tools in kidney transplantation. Although most studies have been conducted with autologous MSCs, using allogeneic MSCs as an off-the-shelf product is more feasible in clinical settings. However, allogeneic MSCs could potentially induce an immune response, which might eventually be directed towards the kidney allograft because of shared human leukocyte antigen (HLA) epitope mismatches between the kidney and MSC donor. In this study, we performed in-depth analyses of two cohorts (n = 20) that received third-party MSC therapy after kidney transplantation. While the Neptune Study from Leiden University Medical Center specifically selected MSC to avoid repeated HLA antigen mismatches between kidney and MSC donors, the study from the University of Liège did not perform specific MSC selection. The comparative analyses of amino acid mismatches between these cohorts showed that MSC selection to avoid repeated HLA mismatches at the split antigen level was not sufficient to prevent repeated mismatches at the amino acid level. However, repeated amino acid mismatches were not associated with the occurrence of donor-specific antibodies (DSAs). Thus, the clinical relevance of repeated amino acid mismatches seems to be limited with regard to the risk of DSA formation. Since DSA formation was limited (3 of 20 patients) in this study, larger studies are required to investigate the relevance of preventing repeated HLA mismatches in allogeneic MSC therapy in kidney transplantation.

Background The impact of immunosuppression on the occurrence of Coronavirus Disease 2019 (COVID-19) remains unclear.Methods We conducted a prospective screening of anti-S1/S2 IgGs against SARS-CoV-2 Spike protein from March, 1 2020 to May, 15 2021 (prior to the vaccination campaign) in a cohort of 713 kidney transplant recipients (KTRs). In a first phase, the factual incidence and seroprevalence of COVID-19 was established in this cohort: cases diagnosed by serology were added to RT-PCR-based diagnoses to obtain the overall incidence of COVID-19 in both symptomatic and asymptomatic KTRs. In the second phase, the kinetics of the post-COVID-19 humoral response were studied, taking into account the severity of the disease defined by the need for oxygen therapy (group S, ”severe”) or not (group nS, ”not severe”).Results The combined diagnostic approaches identified 138 COVID-19 cases (19.2%), with 37 diagnoses by serology (26.8%). The rate of asymptomatic KTRs reached 20.3% (28/138). Thirteen patients (9.4%) died from COVID-19. The seroconversion rate was 91.7% (99/108). The peak anti-S1/S2 IgG level was 85 [30-150] AU/ml and was similar between the S and nS groups (117 [38; 186] AU/ml versus 73 [23; 140] AU/ml). A high probability of persistence of anti-S1/S2 IgG post-COVID-19 was observed, with only 10.1% (7/69) of the patients having negated their serology during the 9-month follow-up.Conclusion Our pragmatic serological screening combined with RT-PCR tests provides a better estimation of the real incidence of COVID-19 in KTRs. A significant proportion of KTRs develop humoral immunity post COVID-19, which most often persists beyond 9 months.

Delayed Graft Function (DGF) is defined as the need for dialysis during the first week after transplantation. DGF is frequent and mostly derived from the ischemia/reperfusion cascade to which the graft is subjected throughout the transplantation process. A graft biopsy is recommended after 7 days of DGF to exclude an episode of acute rejection. Note that DGF per se is associated with an increased risk of acute graft rejection, as well as with a shorter long-term graft survival. Several strategies are being studied to mitigate the ischaemic damage, thereby improving graft quality. Among these, cellular therapy using mesenchymal stromal cells (MSC) is promising, in particular via the administration of MSC in the machine perfusion during the preservation of the graft. We will discuss here the different definitions of DGF and the main predictive factors of DGF, as well as the impact on the graft outcomes. The current strategies to prevent DGF will be briefly reviewed.

BACKGROUND:The power to predict kidney allograft outcomes based on non-invasive assays is limited. Assessment of operational tolerance (OT) patients allows us to identify transcriptomic signatures of true non-responders for construction of predictive models. METHODS:In this observational retrospective study, RNA sequencing of peripheral blood was used in a derivation cohort to identify a protective set of transcripts by comparing 15 OT patients (40% females), from the TOMOGRAM Study (NCT05124444), 14 chronic active antibody-mediated rejection (CABMR) and 23 stable graft function patients ≥15 years (STA). The selected differentially expressed transcripts between OT and CABMR were used in a validation cohort (n = 396) to predict 3-year kidney allograft loss at 3 time-points using RT-qPCR. FINDINGS:Archetypal analysis and classifier performance of RNA sequencing data showed that OT is clearly distinguishable from CABMR, but similar to STA. Based on significant transcripts from the validation cohort in univariable analysis, 2 multivariable Cox models were created. A 3-transcript (ADGRG3, ATG2A, and GNLY) model from POD 7 predicted graft loss with C-statistics (C) 0.727 (95% CI, 0.638-0.820). Another 3-transcript (IGHM, CD5, GNLY) model from M3 predicted graft loss with C 0.786 (95% CI, 0.785-0.865). Combining 3-transcripts models with eGFR at POD 7 and M3 improved C-statistics to 0.860 (95% CI, 0.778-0.944) and 0.868 (95% CI, 0.790-0.944), respectively. INTERPRETATION:Identification of transcripts distinguishing OT from CABMR allowed us to construct models predicting premature graft loss. Identified transcripts reflect mechanisms of injury/repair and alloimmune response when assessed at day 7 or with a loss of protective phenotype when assessed at month 3. FUNDING:Supported by the Ministry of Health of the Czech Republic under grant NV19-06-00031.

Key Points Surgical AVF ligation in KTRs is associated with a significant increase in diastolic BP while systolic BP remains stable.AVF closure in KTRs leads to an improvement of LV and LA morphology and a decrease in serum NT-proBNP levels.There is no significant effect of AVF ligation on kidney allograft function: The eGFR remains stable over time. Background Kidney transplantation is considered as the best kidney replacement therapy, and arteriovenous fistula (AVF) is the preferred vascular access for hemodialysis. The systematic ligation of a functioning AVF in stable kidney transplant recipients (KTRs) remains debatable. Methods In this prospective study, we investigated the hemodynamic effect of the surgical closure of AVF in KTRs. Forty-three KTRs underwent an ambulatory BP monitoring before surgical closure of AVF (T0) and 12 months later (M12), as well as measurement of serum cardiac biomarkers (i.e., soluble suppression of tumorigenicity 2, N-terminal pro b-type natriuretic peptide [NT-proBNP], and galectin-3). Serum tests were also performed 6 months after AVF closure (M6). An echocardiographic examination was performed at each time point. All serum creatinine values were collected to compare the individual eGFR slopes before versus after AVF closure. The latest measure of the AVF flow before kidney transplantation was recorded. Results Diastolic BP significantly rose from T0 to M12: +4.4±7.3 mm Hg (P = 0.0003) for 24h, +3.8±7.4 mm Hg (P = 0.0018) during the day, and +6.3±9.9 mm Hg (P = 0.0002) during the night, leading to an increased proportion of KTRs with European Society of Hypertension (ESH)-defined arterial hypertension after AVF ligation. No change was observed for systolic BP. NT-proBNP significantly dropped between T0 and M6 (345 [190; 553] to 230 [118; 458] pg/ml, P = 0.0001) and then remained stable from M6 to M12 while suppression of tumorigenicity 2 and galectin-3 levels did not change from T0 to M12. We observed a significant decrease in left ventricular (LV) end-diastolic volume, LV end-systolic volume, LV mass, interventricular septum diameter, left atrial volume, and tricuspid annular plane systolic excursion from T0 to M6 and then a stability from M6 to M12. LV ejection fraction and eGFR slope remained stable during the whole study. These observations remained unchanged after adjustment for AVF flow. Conclusion The closure of a patent AVF in KTRs is associated with elevation of diastolic BP, drop in serum NT-proBNP levels, reduction of left ventricular and atrial dimensions, and stability of eGFR slope. Podcast This article contains a podcast at https://dts.podtrac.com/redirect.mp3/www.asn-online.org/media/podcast/K360/2023_12_01_KID0000000000000198.mp3