Background:Kidney allograft inflammation spans a heterogeneous spectrum of phenotypes defined by the Banff 2022 classification. We assessed whether urinary C-X-C motif chemokine ligand 9 (uCXCL9) normalized to creatinine (uCXCL9:Cr) captures inflammatory burden across this spectrum and provides incremental diagnostic utility beyond standard variables. Methods:We analyzed 3181 biopsy-urine pairs from a development cohort (1341 biopsies from 921 patients) and an independent external validation cohort (1840 biopsies from 917 patients). Associations with Banff 2022 diagnostic categories were evaluated using multinomial logistic regression with stability-based selection. Incremental performance was assessed using the Hand & Till multiclass area under the curve (AUC) and decision curve analysis. Results:uCXCL9:Cr demonstrated a graded increase across the inflammatory spectrum, with lowest levels in biopsies without specific lesions (median 4.55 ng/mmol), intermediate levels in antibody-mediated phenotypes (15.14), higher levels in acute T cell-mediated rejection (TCMR; 46.11), and the highest levels in mixed inflammatory patterns (53.18-134.05; P < 0.001). Levels increased proportionally with microvascular and tubulointerstitial activity scores (all P < 0.001). In multivariable multinomial analyses, uCXCL9:Cr was independently associated with each inflammatory category across the Banff 2022 spectrum (relative risk ratio [RRR] range: 1.68-3.44; all P ≤ 0.004). Addition of uCXCL9:Cr increased multiclass AUC from 0.797 to 0.831 in the development cohort and from 0.801 to 0.821 in the validation cohort (both P = 0.001). Incorporation of uCXCL9 was associated with a potential reduction in unnecessary biopsies in decision-curve analyses. Conclusion:uCXCL9 reflects active kidney-graft inflammation across modern Banff phenotypes and provides clinically meaningful diagnostic information beyond standard variables, supporting its potential to inform biopsy decisions and monitoring in kidney transplant recipients, pending prospective validation.

BACKGROUND:Among kidney transplant recipients (KTRs) with BK polyomavirus (BKPyV)-associated nephropathy (BKPyVN), the dynamics of BKPyV replication are not well established. We aim to investigate BKPyV genetic diversity and evolution following kidney transplant. METHODS:We retrospectively analyzed 32 KTRs with a biopsy-proven diagnosis of BKPyVN. Stored plasma and kidney biopsies were tested for BKPyV viral load, and BKPyV whole genome sequencing was performed on BKPyV-positive samples. RESULTS:A total of 104 samples positive for BKPyV DNA detection were sequenced, among which 83 were included in the analysis. BKPyV-I was the most frequent genotype detected, followed by BKPyV-IVc2 and BKPyV-II. At BKPyVN diagnosis (median [IQR], 12 [8-17] months posttransplant), whole genome sequencing identified the same BKPyV subtype in the plasma and kidney biopsy for all patients but one. Alignment of BKPyV consensus sequences between the 2 compartments at the time of BKPyVN showed similarity >99% but identified single-nucleotide polymorphisms in 13 of 23 cases, including 25% APOBEC-associated mutations. Among the 16 KTRs with ≥2 consecutive BKPyV-positive samples available for analysis, consensus sequence showed a different BKPyV subtype in pre-BKPyVN kidney biopsies as compared with BKPyVN in 9 patients. Before BKPyVN diagnosis, minority variants on the VP1 sequence were identified in 10 of 11 kidney biopsy samples and 5 of 10 plasma samples. CONCLUSIONS:Among KTRs with BKPyVN, we show that BKPyV viral populations change over time, with the coexistence of several viral populations in early samples as compared with BKPyVN, as a result of APOBEC-mediated editing and replication-driven diversification within the kidney allograft.

INTRODUCTION:Somatostatin analogues reduce liver and kidney cyst volume in autosomal dominant polycystic kidney disease (ADPKD), but randomized trials have not demonstrated a consistent benefit on kidney function decline. We tested whether the analogue lanreotide slows glomerular filtration rate (GFR) decline over three years in adults with ADPKD stages 2/3. METHODS:In this randomized, double-blind, placebo-controlled trial, we enrolled adults with ADPKD and measured GFR (mGFR) 30-89 ml/min/1.73 m2. Patients were randomized to receive monthly injections of lanreotide 120 mg or 0.9% sodium chloride placebo for three years. The primary endpoint was mGFR slope (iohexol clearance) assessed at baseline, weeks 72 and 144 and analyzed with a linear mixed-effects model (LMM). Secondary endpoints included annual estimated GFR decline (creatinine-based, assessed at 11 scheduled visits), kidney events, quality of life, and safety. Due to slow enrollment, recruitment stopped after 144 of 180 planned participants. All randomized participants were included in the analysis (intention-to-treat). RESULTS:The primary endpoint was not met: the model-derived annualized between-arm difference in mGFR trajectory was -0.3 ml/min/1.73 m2 per year (95% confidence interval -3.4 to 2.8). The time × lanreotide coefficient from the pre-specified creatinine-eGFR LMM was significant +1.2 ml/min/1.73 m2 per year (0.27 to 2.15); however, this signal was not replicated by cystatin C-eGFR nor urinary creatinine clearance, consistent with a non-GFR effect on creatinine physiology. Rates of kidney events and quality-of-life scores were similar between arms. Gastrointestinal adverse events were more frequent with lanreotide. Hypoglycemia occurred in 11.1% of lanreotide-treated versus 1.4% of placebo-treated participants. CONCLUSIONS:Lanreotide did not slow mGFR decline in adults with stage 2/3 ADPKD. The creatinine-eGFR signal is exploratory, not supported by muscle-mass-independent markers, and should be interpreted in the context of a negative primary endpoint. An unexpected hypoglycemia signal warrants proactive monitoring when considering lanreotide in this population. TRIAL REGISTRATION:Registered at ClinicalTrials.gov with study number NCT02127437.

Kidney transplant recipients are highly susceptible to infections due to chronic immunosuppression. Signal joint T cell receptor excision circles (sjTRECs), markers of thymic output, have emerged as potential indicators of immune competence, but their clinical relevance in transplantation remains unclear. In this single-center retrospective study, sjTREC levels were measured at transplantation in 733 kidney recipients and categorized into 4 strata. Posttransplant infections were assessed using Cox models adjusted for demographic, clinical, and immunologic variables. During follow-up, 508 patients (69.3%) developed an infection after a mean time of 1.17 ± 1.61 years. The 3-year cumulative incidence increased among sjTREC strata, from 52.4% to 86.7% (P < .0001). In multivariable analysis, older recipient age (hazard ratio [HR], 1.01; 95% confidence interval [CI], 1.00-1.02; P = .007), thymoglobulin induction (HR, 1.35; 95% CI, 1.13-1.62; P = .001), and lower sjTREC levels (log-transformed; HR, 0.73; 95% CI, 0.63-0.86; P < .001) were independently associated with infection. Sensitivity analyses confirmed consistent results across pathogen-specific models and after accounting for death as a competing event. A nonsignificant age interaction (P = .084) suggested possible attenuation in young recipients. Lower sjTREC levels at transplantation are independently associated with higher posttransplant infection risk, supporting their use for immune risk stratification in kidney transplantation.

Introduction:Kidney histology preparation requires a multistep process that is usually responsible for delayed results. This study introduces dynamic full-field optical coherence tomography (D-FF-OCT) as a label-free alternative to overcome the limitations of traditional histopathology for on-site kidney pathology assessment. Methods:Two patient cohorts were considered, with a total of 31 patients included in the study; one cohort involved patients requiring biopsy of transplant kidney, and the other involved patients requiring biopsy of native kidney. The clinical and biological data were prospectively collected. Histopathological analysis of kidney biopsies was conducted using both conventional stains and dynamic D-FF-OCT imaging. Results:D-FF-OCT enabled the recognition of most kidney structures. The results showed a significant correlation between this technology and conventional stains for the evaluation of both interstitial fibrosis (IF) (r = 0.61, P < 0.001) and tubular atrophy (TA) (r = 0.60, P < 0.001). Although many lesions could be identified such as interstitial inflammation, acute tubular necrosis, glomerular crescents, and vascular intimal thickening; other recognitions such as glomerular membranous deposits, vascular amyloidosis, and peritubular capillaritis will require confirmation in larger cohorts. Conclusion:This study demonstrates the potential of D-FF-OCT imaging for on-site analysis of kidney biopsies, providing rapid and high-resolution images without extensive sample preparation.

Background. Kidney transplant recipients with preformed donor-specific antibodies (DSAs) are at higher risk for antibody-mediated rejection (AMR) and graft failure. This study assesses outcomes during a 15-y period, comparing patients with high levels of preformed DSAs to a matched cohort of recipients without DSA. Methods. This retrospective study includes 95 patients with high levels of preformed DSAs, defined by DSA levels (mean fluorescence intensity > 3000). Using propensity score matching, 88 of these patients were matched to 154 recipients without DSA based on age, sex, transplant year, cold ischemia time, and other clinical factors. Outcomes included occurrence of AMR, T cell–mediated rejection, and long-term allograft and patient survival. Results. The mean follow-up after transplantation was 11.9 ± 5.6 y. Among the matched patients, kidney allograft survival rates after transplantation at 5, 10, and 15 y were 90.5%, 79.5%, and 72.8% for the patients without preformed DSA and 86.7%, 60.2%, and 47.6% for the patients with high levels of preformed DSAs (P = 0.002). The patient survival rates after transplantation at 5, 10, and 15 y were 91.3%, 72.3%, and 57.9% for the patients without preformed DSA and 86.4%, 71.2%, and 49.0% for the patients with high levels of preformed DSAs (P = 0.206). More AMR occurred in the patients with high levels of preformed DSAs (P < 0.001) without significant difference in T cell–mediated rejection (P = 0.203). Conclusions. Although patients with high levels of preformed DSAs have a higher risk of graft loss, their long-term survival did not differ significantly from recipients without DSA, supporting the use of intensive immunosuppression in this population.

Introduction Post-kidney transplant (KT) hyperparathyroidism (PT-HPT) is common and linked to adverse outcomes, yet the contributions of calcium bioavailability and parathyroid responsiveness remain poorly defined. Here, we studied the trajectory of oral calcium-mediated PTH suppression (CMPS) in PT-HPT and its association with PTH control in the first year post-KT. Methods This single-center prospective cohort study evaluated 657 KT recipients at 3 (M3) and 12 (M12) months post-KT with an oral calcium loading test, and assessed measured glomerular filtration rate (mGFR), bone turnover markers, and dual X-ray absorptiometry. Results At M3, hyperparathyroidism was evident in 71% patients, with a median CMPS of 31%. Impaired PTH suppression was associated with blunted increases in ionized calcium in 30% of patients, suggesting impaired intestinal calcium absorption. Despite a decline in mGFR over time, calcium-PTH dynamics improved by M12, with a leftward shift in the curve across all groups. Patients with higher baseline CMPS had significantly lower PTH at M12 (87 vs. 99 pg/ml), despite higher initial PTH and less frequent calcimimetic use (5.5% vs. 12%). Bone mineral density increased across all groups, with greater gain at the hip than the lumbar spine in patients with higher baseline PTH suppression. Higher baseline CMPS was independently associated with lower M12 PTH levels, after adjusting for potential confounders. The association remained significant in a sensitivity analysis excluding patients with blunted increases in serum ionized or urinary calcium suggestive of calcium absorption. Conclusions Oral calcium-mediated PTH suppression at M3 post-KT was linked to lower PTH levels at one year, suggesting that both parathyroid gland responsiveness and calcium bioavailability are associated with favorable outcomes in PT-HPT. This test may also help stratifying PT-HPT subtypes for tailored management.

BK polyomavirus (BKPyV) infection remains a major concern after kidney transplantation, increasing the risk of graft loss in the absence of specific antiviral agent now available. Here, we investigated the impact of HLA diversity on the control of posttransplant BKPyV replication. High HLA evolutionary divergence (HED) at the DQ locus in the donor was an independent predictor of BKPyV-free outcome. More generally, we highlighted the protective effect of highly divergent pairs of HLA-DQ heterodimers corresponding to heterozygous HLA-DQα01/non-DQα01 combinations. We then defined a functional divergence metrics assessed by the similarity of peptide-binding motifs between pairs of HLA-DQ molecules. Greater functional divergence correlated with the size of the BKPyV-derived DQ-bound immunopeptidome and a lower risk of BKPyV reactivation, thus providing a molecular basis for the observed genetic differences. Together, these data provide evidence for a direct link between donor HLA-DQ genetic and functional divergence, diversity of the DQ-bound immunopeptidome, and control of viral infection, likely reflecting stronger antiviral T cell responses.

Background. Efficacy and safety of belatacept have not been specifically reported for kidney transplantations from donors after circulatory death. Methods. In this retrospective multicenter paired kidney study, we compared the outcome of kidney transplantations with a belatacept-based to a calcineurin inhibitor (CNI)-based immunosuppression. We included all kidney transplant recipients from donors after uncontrolled or controlled circulatory death performed in our center between February 2015 and October 2020 and treated with belatacept (n = 31). The control group included the recipients of the contralateral kidney that were treated with CNI in 8 other centers (tacrolimus n = 29, cyclosporine n = 2). Results. There was no difference in the rate of delayed graft function. A higher incidence of biopsy-proven rejections was noted in the belatacept group (24 versus 6 episodes). Estimated glomerular filtration rate (eGFR) was significantly higher in the belatacept group at 3-, 12-, and 36-mo posttransplant, but the slope of eGFR was similar in the 2 groups. During a mean follow-up of 4.1 y, 12 patients discontinued belatacept and 2 patients were switched from CNI to belatacept. For patients who remained on belatacept, eGFR mean value and slope were significantly higher during the whole follow-up. At 5 y, eGFR was 80.7 ± 18.5 with belatacept versus 56.3 ± 22.0 mL/min/1.73 m2 with CNI (P = 0.003). No significant difference in graft and patient survival was observed. Conclusions. The use of belatacept for kidney transplants from either uncontrolled or controlled donors after circulatory death resulted in a better medium-term renal function for patients remaining on belatacept despite similar rates of delayed graft function and higher rates of cellular rejection.

Solid-organ transplant patients, including kidney transplant recipients (KTRs) are at high risk of severe forms of coronavirus disease 2019 (COVID-19) infection1 and fail to mount a robust and sustained humoral response to COVID-19 vaccines,2 despite reinforced schemes (Reference S1, SDC, https://links.lww.com/TP/C770).3 In this context, the use of anti-severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) monoclonal antibodies, because preexposure prophylactic strategy has been dramatically helpful to provide passive protection against COVID-19. However, currently available monoclonal antibodies are no longer effective at neutralizing the most recent Omicron variants of SARS-CoV-2.4,5 Hence, vaccination is the unique remaining prophylactic tool against COVID-19 in vulnerable individuals. Unlike KTRs, patients with chronic kidney disease, including those undergoing long-term dialysis, have shown potent vaccine responses against SARS-Cov-2, reaching antibody levels close to those observed in the general population (Reference S3, SDC, https://links.lww.com/TP/C770). Whether a pretransplant vaccination improves the response to subsequent doses after transplantation has yet to be established. To address this important question, we aimed to investigate the trajectory of the SARS-CoV-2-specific humoral immune response following a booster dose in KTRs who had received at least 2 vaccine shots before the transplantation. This retrospective single-center study (Necker Hospital, Paris, France) enrolled all consecutive patients, transplanted between June and December 2021, following a minimum of 2 vaccine doses before the kidney transplantation (KT), in the absence of concurrent immunosuppressive therapy. Forty-nine patients (25 men [51.0%], median age of 57.2 y, interquartile range 42.9–68.1) were enrolled (Table S1 and Material S1, SDC, https://links.lww.com/TP/C770). At time of KT, most patients (93.6%) displayed a positive SARS-CoV-2 serology and 66% showed an anti-Spike IgG titer >264 binding antibody unit (BAU)/mL (median titer of 809 [128.5–3210.0]). In the 26 KTRs who did not receive an additional vaccine shot after transplantation, antibody titers decreased to 131 BAU/mL at M3 and to 136 BAU/mL (24.5–662.5) at the last follow-up, after a median posttransplant time of 5.0 (3.0–6.9) mo (Table S1, SDC, https://links.lww.com/TP/C770). Twenty-three KTRs (46.9%) received a booster dose of messenger RNA COVID-19 vaccine after KT. The median time between KT and first dose was 13.4 wk (11.1–22.1). Nineteen (82.6%) received only 1 posttransplant dose, while 4 patients (17.4%) received an additional one. Most patients exhibited a strong postvaccinal humoral response after one injection: 20 patients (90.9%) showed a postvaccinal anti-Spike titer > 264 BAU/mL (versus 10 before vaccine) and anti-Spike IgG titers increased significantly from 172.0 (48.0–698.5) to 1220.0 (583.8–3299.5), P = 0.0004 (Figure 1). Compared to responders, the nonresponders (to one posttransplant dose) were significantly older, were given more frequently rituximab at induction, and had received a greater number of vaccine doses before KT (Table S2, SDC, https://links.lww.com/TP/C770). One of the nonresponders after the first dose developed an effective response after the second. Interestingly, a strong recall humoral response also occurred in KTRs treated with belatacept after one vaccine dose (anti-Spike IgG titers increased from 590.5 [118.3–987] to 3641.5 BAU/mL [2898.5–3819]), whereas belatacept was found to dramatically hamper the antibody response to COVID-19 vaccine in patients who were vaccine-naive at the time of transplantation (Reference S1, SDC, https://links.lww.com/TP/C770).2Figure 1.: Evolution of anti-SARS-CoV-2 spike IgG at day 0 postkidney transplantation, before and after 1 injection of anti-SARS-CoV-2 mRNA vaccination in 23 KTRs who received anti-SARS-CoV-2 vaccination before transplantation. BAU, binding antibody unit; KT, kidney transplantation; KTR, kidney transplant recipient; mRNA, messenger RNA; SARS-CoV-2, severe acute respiratory syndrome coronavirus 2.Eleven patients (22.4%) experienced COVID-19 after KT, including 2 breakthrough infections following posttransplant dose. All but one cases were infected with the Omicron variants (Delta variant in one case). Three patients were admitted to hospital, two of whom experienced a severe infection requiring intensive care unit and eventually died. These latter were infected with the Omicron variants, displayed a weak anti-spike response and were not administered preventive mAbs before COVID-19. Our study is limited by its retrospective nature, by the relatively small number of patients and the lack of data about neutralizing antibodies (which are a better measure of protection than the commercially available anti-spike antibody assay) and vaccine-specific cellular response. However, it clearly demonstrates that a pretransplant vaccination against COVID-19 before KT significantly improves the response to vaccine after KT. Anti-SARS-CoV-2 vaccination is recommended in dialysis patients, who are exposed to severe forms of COVID-19 (Reference S6, SDC, https://links.lww.com/TP/C770). Our data further stress the importance of vaccination in patients on the waiting list for solid-organ transplantation. Pretransplant priming of vaccine-specific responses can dramatically improve the posttransplant vaccine response through the recall stimulation of a preexisting memory response.

Background IgG4-related kidney disease is a major manifestation of IgG4-related disease, a systemic fibroinflammatory disorder. However, the clinical and prognostic kidney-related factors in patients with IgG4-related kidney disease are insufficiently defined. Methods We conducted an observational cohort study using data from 35 sites in two European countries. Clinical, biologic, imaging, and histopathologic data; treatment modalities; and outcomes were collected from medical records. Logistic regression was performed to identify the possible factors related to an eGFR <= 30 ml/ min per 1.73 m(2) at the last follow-up. Cox proportional hazards model was performed to assess the factors associated with the risk of relapse. Results We studied 101 adult patients with IgG4-related disease with a median follow-up of 24 (11-58) months. Of these, 87 (86%) patients were male, and the median age was 68 (57-76) years. Eighty-three (82%) patients had IgG4-related kidney disease confirmed by kidney biopsy, with all biopsies showing tubulointerstitial involvement and 16 showing glomerular lesions. Ninety (89%) patients were treated with corticosteroids, and 18 (18%) patients received rituximab as first-line therapy. At the last follow-up, the eGFR was below 30 ml/min per 1.73 m(2) in 32% of patients; 34 (34%) patients experienced a relapse, while 12 (13%) patients had died. By Cox survival analysis, the number of organs involved (hazard ratio [HR], 1.26; 95% confidence interval [CI], 1.01 to 1.55) and low C3 and C4 concentrations (HR, 2.31; 95% CI, 1.10 to 4.85) were independently associated with a higher risk of relapse, whereas first-line therapy with rituximab was protective (HR, 0.22; 95% CI, 0.06 to 0.78). At their last follow-up, 19 (19%) patients had an eGFR <= 30 ml/min per 1.73 m(2). Age (odd ratio [OR], 1.11; 95% CI, 1.03 to 1.20), peak serum creatinine (OR, 2.74; 95% CI, 1.71 to 5.47), and serum IgG4 level >= 5 g/L (OR, 4.46; 95% CI, 1.23 to 19.40) were independently predictive for severe CKD. Conclusions IgG4-related kidney disease predominantly affected middle-aged men and manifested as tubulointerstitial nephritis with potential glomerular involvement. Complement consumption and the number of organs involved were associated with a higher relapse rate, whereas first-line therapy with rituximab was associated with lower relapse rate. Patients with high serum IgG4 concentrations (>= 5 g/L) had more severe kidney disease.

ABSTRACT Background Inter-individual variations of non-glomerular filtration rate (GFR) determinants of serum creatinine, such as muscle mass, account for the imperfect performance of estimated GFR (eGFR) equations. We aimed to develop an equation based on creatinine and total lumbar muscle cross-sectional area measured by unenhanced computed tomography scan at the third lumbar vertebra. Methods The muscle mass–based eGFR (MMB-eGFR) equation was developed in 118 kidney donor candidates (iohexol clearance) using linear regression. Validation cohorts included 114 healthy subjects from another center (51Cr-EDTA clearance, validation population 1), 55 patients with chronic diseases (iohexol, validation population 2), and 60 patients with highly discordant creatinine and cystatin C–based eGFR, thus presumed to have atypical non-GFR determinants of creatinine (51Cr-EDTA, validation population 3). Mean bias was the mean difference between eGFR and measured GFR, precision the standard deviation (SD) of the bias, and accuracy the percentage of eGFR values falling within 20% and 30% of measured GFR. Results In validation population 1, performance of MMB-eGFR was not different from those of CKD-EPICr2009 and CKD-EPICr2021. In validation population 2, MMB-eGFR was unbiased and displayed better precision than CKD-EPICr2009, CKD-EPICr2021 and EKFC (SD of the biases: 13.1 vs 16.5, 16.8 and 15.9 mL/min/1.73 m2). In validation population 3, MMB-eGFR had better precision and accuracy {accuracy within 30%: 75.0% [95% confidence interval (CI) 64.0–86.0] vs 51.5% (95% CI 39.0–64.3) for CKD-EPICr2009, 43.3% (95% CI 31.0–55.9) for CKD-EPICr2021, and 53.3% (95% CI 40.7–66.0) for EKFC}. Difference in bias between Black and white subjects was −2.1 mL/min/1.73 m2 (95% CI −7.2 to 3.0), vs −8.4 mL/min/1.73 m2 (95% CI −13.2 to −3.6) for CKD-EPICr2021. Conclusion MMB-eGFR displayed better performances than equations based on demographics, and could be applied to subjects of various ethnic backgrounds.

Background Calcineurin inhibitors (CNIs) remain the cornerstone of maintenance immunosuppression (IS) after lung transplantation (LTx), although CNI-related life-threatening toxic effects may occur. Belatacept, a novel immunosuppressant that blocks a T-cell co-stimulation pathway, is a non-nephrotoxic drug indicated as an alternative to CNIs in kidney Tx. In LTx, there are only a few reports of belatacept conversion as a CNI-free or CNI-sparing IS treatment. Methods We reviewed a series of 10 LTx recipients with conversion to a CNI-free belatacept IS regimen within the first year post-LTx (n = 7) or a belatacept/low-dose CNI combination after the first year (n = 3). Results Use of belatacept was triggered by severe renal failure in 9 patients and under-IS with previous other IS-related toxicities in 1 patient. Mean estimated glomerular filtration rate after starting belatacept significantly improved at 6 months after initiation and at the last-follow-up (p = 0.006, and p = 0.002 respectively). The incidence of recurrent and/or severe acute cellular rejection (ACR) episodes was high in patients with CNI-free belatacept-based IS (n = 4/7). Chronic graft allograft dysfunction developed in 2 of 9 recipients under belatacept IS. Belatacept was stopped in 6 patients because of recurrent/severe ACR (n = 3), recurrent opportunistic infections (n = 1), center modified policy (n = 1), or other cause (n = 1). Conclusion Early conversion to CNI-free belatacept-based IS improved renal function in this series but was counterbalanced by a high incidence of recurrent ACR, including life-threatening episodes. Other studies are needed to better determine the indications for its use after LTx, possibly with lower immunological risk IS regimens, such as CNI-sparing belatacept.

BackgroundFollowing kidney transplantation, BK virus associated nephropathy (BKVN) occurs in 1 to 10% of kidney transplant recipients (KTR) and represents a major cause of graft loss. We aim at identifying factors associated with biopsy proven BKVN among KTR.MethodsWe conducted a retrospective case-control study including all KTR with a biopsy-proven diagnosis of BKVN between 2005 and 2019. Clinical characteristics and outcome were described. For each case, one control KTR without BKV infection was identified and matched by age, transplant date, and donor status. Factors associated with BKVN diagnosis were identified using exact conditional logistic regression. Comparative survival was described using Kaplan-Meier estimator.ResultsSixty-four cases of BKVN were identified among 1737 new kidney transplantation (3.7% prevalence). Clinical characteristics did not differ between groups, except for a higher c-PRA among cases. BKVN occurred in a median time of 11 (5-14.5) months after KT, and was associated with a significantly impaired graft function at diagnosis. Following BKVN, 61 (95%) of the patients had immunosuppression reduction, which led to BKV DNAemia resolution in 49% of cases. In multivariate analysis, factors associated with BKVN diagnosis were lymphopenia < 500/mm(3) and a prednisone dose > 7.5 mg/day. Median duration of follow-up was 40 months for both groups. BKVN was associated with a significantly increased risk of graft rejection (P = 0.02) and return to dialysis (P = 0.01).ConclusionsBKVN remains a severe complication in KTR and is associated with an increased risk for acute rejection and return to dialysis. Lymphopenia below 500/mm(3) and corticosteroid maintenance therapy are significantly associated with biopsy-proven BKVN diagnosis.

BACKGROUND:Among kidney transplant recipients (KTR) with BK virus associated nephropathy (BKVN), BKV genotypes' evolution and anti-BKV humoral response are not well established. We aim to analyze BKV replication and genetic evolution following transplantation, and characterize concomitant anti-BKV-VP1 humoral response.METHODS:We retrospectively analyzed 32 cases of biopsy-proven BKVN. Stored plasma and kidney biopsies were tested for BKV viral load, and VP1 sequencing performed on positive samples. BKV-VP1 genotype-specific neutralizing antibodies (NAbs) titers were determined at transplantation and BKVN.RESULTS:At the time of BKVN diagnosis, BKV viral load was 8.2 log10 IU/106 cells and 5.4 log10 IU/mL in kidney and plasma, respectively. VP1 sequencing identified the same BKV-subtype in both compartments in 31/32 cases. At the time of transplantation, 8/20 (40%) of biopsies tested positive for BKV detection, whereas concomitant BKV viremia was negative. VP1 sequencing identified a different subtype compared to BKVN in 5/6 of these samples. This was confirmed following transplantation: 8 patients had a BKV+ biopsy before BKV viremia, and VP1 sequencing identified a different subtype compared to BKVN in all of them. After the onset of BKV viremia and prior to BKVN diagnosis, the BKV subtype in BKV+ plasma and kidney biopsy was the same as the one isolated at BKVN. BKV-VP1 NAbs titers were significantly higher at the time of BKVN compared to transplantation (p = .0031), with similar titers across genotypes.CONCLUSION:Altogether, our data suggest that among some KTR with BKVN, the BKV genotype from the donor may not be responsible for BKVN pathogenesis.