BK Virus Nephropathy Research Articles

Outcomes of kidney retransplantation after graft loss as a result of BK virus nephropathy in the era of newer immunosuppressant agents.

We conducted this study using the updated 2005-2016 Organ Procurement and Transplantation Network database to assess clinical outcomes of retransplant after allograft loss as a result of BK virus-associated nephropathy (BKVAN). Three hundred forty-one patients had first graft failure as a result of BKVAN, whereas 13260 had first graft failure as a result of other causes. At median follow-up time of 4.70years after the second kidney transplant, death-censored graft survival at 5years for the second renal allograft was 90.6% for the BK group and 83.9% for the non-BK group. In adjusted analysis, there was no difference in death-censored graft survival (P=.11), acute rejection (P=.49), and patient survival (P=.13) between the 2 groups. When we further compared death-censored graft survival among the specific causes for first graft failure, the BK group had better graft survival than patients who had prior allograft failure as a result of acute rejection (P<.001) or disease recurrence (P=.003), but survival was similar to those with chronic allograft nephropathy (P=.06) and other causes (P=.05). The better allograft survival in the BK group over acute rejection and disease recurrence remained after adjusting for potential confounders. History of allograft loss as a result of BKVAN should not be a contraindication to retransplant among candidates who are otherwise acceptable.

Effect of simultaneous presence of anti-blood group A/B and -HLA antibodies on clinical outcomes in kidney transplantation across positive crossmatch: a nationwide cohort study

ABO-incompatible (ABOi) and positive crossmatch (XM) kidney transplantation (KT) have been considered immunologically challenging. The present study analyzed the clinical outcomes in XM positive KT based on ABO incompatibility. We used data from the Korea Organ Transplantation Registry, a nationwide database, and a single-center registry. A total of 263 patients with positive XM were divided into an ABO compatible (ABOc) & XM positive (ABOc/XM+, n = 176) group and an ABOi & XM positive (ABOi/XM+, n = 87) group. The overall rejection rate one year after KT was significantly higher in the ABOi/XM+ group than in the ABOc/XM+ group (P < 0.01). A total of four mortalities occurred, all in the ABOi/XM+ patients (P < 0.01). There were no differences in surgical complications or the occurrence of infection-related complications, including BK virus nephropathy. Multivariate analysis indicated that female vs. male (odds ratio (OR), 2.27; P = 0.03), DSA class I (MFI/1000) (OR, 1.10; P = 0.03), DSA class II (MFI/1000) (OR, 1.10; P < 0.01), and ABOi & XM+ status (OR, 2.38; P < 0.01) were significant risk factors for acute rejection during the year after transplantation. Overall graft survival was inferior in ABOi/XM+ patients than in ABOc/XM+ patients (P = 0.02). ABO incompatibility in XM-positive KT patients was found to be a significant risk factor for the development of rejection within one year after transplantation as well as for long-term graft survival. The anti-blood group A, B and anti-HLA antibodies may show synergistic activity.

Histopathology of Chronic Kidney Disease after Allogeneic Hematopoietic Cell Transplantation: A Multi-Center Observational Study of Kidney Biopsies

Background Renal dysfunction is a common complication of allogeneic hematopoietic cell transplantation (Allo-HCT) with proven negative impact on early and long-term mortality. The cumulative incidence of chronic kidney disease(CKD) after Allo- HCT varies from 13~60% in adult studies to as high as 62% in children. So far, most knowledge on chronic renal impairment in the context of Allo-HCT is based on clinical and laboratory findings. Causes of CKD are diverse, usually overlapping, and poorly understood. Kidney biopsies are performed in less than 5% patients with CKD, the pathophysiology of idiopathic CKD remains obscure. We conducted a multi-center clinicopathologic study of Allo-HCT patients with CKD to described the histopathologic spectrum of renal manifestations. Methods and Results Between 2005 and 2018, 24 recipients(17 males and 7 females) of Allo-HCT underwent kidney biopsy for either proteinuria or deterioration of kidney function at four centers. The median age was 43.8 (7.2~54.3) years, and the median time from Allo-HCT to kidney biopsy was 17.2(2.0~74.6)months. Evidence for GVHD was found in 20 (83.3%) patients. Among the 24 patients, 10 patients had a large amount of proteinuria (24-hour urine protein &gt; 3.5 g/L), and 12 patients had elevated serum creatinine (Scr &gt;110μmol/l). The most common pathological findings of kidney biopsy were GVHD (n=8), membranous nephropathy (MN, n=5), thrombotic microangiopathy (TMA, n=4), BK virus nephropathy (n=2), and we also found ischemic nephropathy, chronic interstitial nephritis, minimal change disease (MCD), GVHD with TMA, MN with focal segmental glomerular sclerosis (FSGS), MCD with acute tubular injury, BK virus nephropathy combined with calcineurin inhibitor nephrotoxicity in one case. The follow-up data showed 3 died of recurrent malignancy, 6 loss to follow-up , the median follow-up time was 18.3(12.3~120.2)months. Of the 18 patients, 8 (44.4%) had an estimated glomerular filtration rate (eGFR) of less than 60 ml/(min1.73m2), 5 (27.8%) still had moderate proteinuria. Conclusions A wide spectrum of renal pathologic findings can be observed in Allo-HCT patients. Either severe proteinuria or elevated serum creatinine were common presentations in this unique setting, which can be due to GVHD , MN, TMA, BK virus nephropathy , MCD, FSGS, and overlapping lesions. Kidney biopsies are necessary to establish the underlying cause of CKD in Allo-HCT patients. Disclosures No relevant conflicts of interest to declare.

HLA-G 3′ untranslated region gene variants are promising prognostic factors for BK polyomavirus replication and acute rejection after living-donor kidney transplant

The immunosuppressive non-classical human leukocyte antigen-G (HLA-G) promotes transplant tolerance as well as viral immune escape. HLA-G expression is associated with regulatory elements targeting certain single nucleotide polymorphisms (SNPs) in the HLA-G 3′ untranslated region (UTR). Thus, we evaluated the impact of HLA-G 3′UTR polymorphisms as surrogate markers for BK polyomavirus (BKPyV) replication or nephropathy (PyVAN) and acute cellular and antibody mediated rejection (ACR/AMR) in 251 living-donor kidney-transplant recipient pairs. After sequencing of the HLA-G 3′UTR, fourteen SNPs between +2960 and +3227 and the 14 bp insertion/deletion polymorphism, which arrange as UTR haplotypes, were identified. The UTR-4 haplotype in donors and recipients was associated with occurrence of BKPyV/PyVAN compared to the other UTR haplotypes. While the UTR-4 recipient haplotype provided protection against AMR, the UTR-2 donor haplotype was deleteriously associated with ACR/AMR. Deduction of the UTR-2/4 haplotypes to specific SNPs revealed that the +3003C variant (unique for UTR-4) in donors as well as in recipients is responsible for BKPyV/PyVAN and also provides protection against AMR; whereas the +3196G variant (unique for UTR-2) promotes allograft rejection. Thus, HLA-G 3′UTR variants are promising genetic predisposition markers both in donors and recipients that may help to predict susceptibility to either viral infectious complication of BKPyV or allograft rejection.

Identification of BK Virus Genotypes in Recipients of Renal Transplant in Vietnam

ObjectivesThis study aims to investigate the prevalence and distribution of BK polyomavirus (BKV) genotypes in recipients of renal transplant in Vietnam. MethodsOne hundred six patients who underwent renal transplantation were included in this study. These patients were from the Department of Nephrology, Military Hospital 103, Vietnam Military Medical University. Quantification and genotyping of the BK virus was performed using in-house molecular methods from urine and plasma samples. ResultsBKV infection was detected in 82 patients (77.4%), including 58 patients who had the presence of both BK viremia and BK viruria, and 24 patients (22.60%) with BKV positive findings in the urine alone. Particularly, 16 patients (15.09%) had high BK viremia >104 copies/mL and 20 patients (18.9%) had BK viruria >107 copies/mL. BK virus nephropathy (BKVN) was confirmed in 6 patients (5.66%) by immunohistochemistry examination. Genotyping of BKV was performed successfully in 50 out of the 82 patients, with 36 out of 50 (72%) belonging to the BKV-I subtype and 14 out of 50 (28%) belonging to the BKV-IV subtype; no cases of genotypes II or III were observed. Using phylogenetic analysis of the subgroups, the BKV-I/b-1 subtype was found the predominant subgroup (100%), whereas BKV-IV included 21.43% of IV/a-1, 6.67% of IV/a-2, and 50% of IV/c-1, respectively. There remain 3 cases of BKV-IV (21.43%) that could not be categorized into any subgroups. In the 6 patients diagnosed BKVN, 5 of them were infected with subgroup I/b-1 (83.3%) and 1 patient was infected with subgroup IV/c-1 (16.7%). No significant difference between BKV genotypes was observed in relation to age, sex, HLA mismatch, viral load, BKVN, and immunosuppressive therapy. ConclusionsThis research indicated a high prevalence of BKV infection and BKV-I was predominant, followed by BKV-IV among recipients of renal transplant in Vietnam.

Cellular and viral miRNA expression in polyomavirus BK infection.

Polyomavirus BK (BKV) is an important pathogen in kidney transplant patients. Regulation of BKV encoded microRNAs (miRNAs) is not well understood. Therefore, tubular epithelial cells infected with BKV were examined for changes in small RNA expression. The observed changes were further evaluated by real-time PCR and RNA-seq analysis of renal allograft biopsies. BKV-miR-B1-5p and BKV-miR-B1-3p showed a 1000-fold increase over 12days but did not prevent cell lysis. Downregulation of host miR-10b and miR-30a could be confirmed on all three platforms evaluated. Whereas, the BKV genome expressed more 3p than 5p miRNA species, the reverse was true for the human genome. Decreased expression of TP53INP2, and increased expression of BCL2A1, IL-6, IL8 and other proinflammatory cytokines were shown in biopsies with BKV nephropathy. No change in expression was seen in miR-10a dependent expression of NKG2D ligands ULBP3, MICA, or MICB. In conclusion, BKV infection results in regulation of cellular genes regulated by and possibly amenable to therapies targeting miR-10 and miR-30.

Clinical Prognosis of Renal Retransplant Patients: A Single-Center Experience

BackgroundRetransplantation is a treatment option in patients with end-stage renal failure due to graft loss. Outcomes of these patients due to high immunologic risk remain unclear. The aim of this study was to evaluate outcomes of renal retransplantation patients retrospectively. MethodsRenal retransplant patients in our unit were evaluated retrospectively between 2010 and 2018. Patients’ demographic characteristics, primary diseases, the causes of prior graft loss, immunologic status, desensitization protocols, the induction and maintenance treatments, the complications during the follow-up period, numbers of acute rejections, and the clinical prognosis were all detected from the patients’ files. ResultsWe retrospectively evaluated 17 patients who underwent a second or third renal allograft. Of these, 16 received a second and the remaining 1 patient received a third renal allograft. Immunologically, all of the 17 patients had negative flow cytometry crossmatch, 1 patient had a positive complement-dependent cytotoxicity crossmatch (Auto 12%), 16 patients had positive panel reactive antibody, the median HLA-mismatch was 3.5, and the score of donor-specific antibody relative intensity score (RIS) was 6.4 ± 6.3. Ten pretransplant patients had desensitization treatment. While scores for HLA-MM and HLA-RIS in the patients who had a desensitization therapy were determined higher, no statistical difference was observed (respectively, P = .28 and .55). No acute rejection episode developed. BK virus DNA viremia was detected in 4 patients during the posttransplant 6th month. We observed no patient death or no graft loss during the follow-up period. ConclusionAlthough the retransplant patients who had a graft loss previously have high immunologic risks, retransplantation is reliable in these patients, but they should be followed up carefully in terms of BKV nephropathy.

Urinary levels of CCL2 and CXCL10 chemokines as potential biomarkers of ongoing pathological processes in kidney allograft: an association with BK virus nephropathy.

Early prognostic markers that identify high‑risk kidney transplant recipients may lead to optimization of immunosuppressive therapy and improved long‑term outcomes. The aim of this study was to assess whether the measurement of urinary concentrations of CCL2 and CXCL10 chemokines can be a valuable noninvasive tool for identifying ongoing pathological processes in a kidney allograft. The study included 40 patients who underwent a protocol biopsy within 1‑year post kidney transplant. The urinary concentrations of CCL2 and CXCL10 with reference to creatinine in urine were assayed in all patients. On the basis of biopsy results, a study group was selected (n = 25), including patients with a diagnosis of interstitial fibrosis and tubular atrophy grades II to III (n = 16), BK virus (BKV) nephropathy (n = 4), or mild inflammatory lesions fulfilling the criteria for mild rejection processes or borderline lesions (n = 11). Patients with normal biopsy results were included in a control group (n = 15). The ratio of CCL2 to creatinine (CCL2:Cr) was a significant independent predictor of BKV ephropathy (odds ratio, 1.1; 95% CI, 1.0-1.2; P = 0.04). The CXCL10:Cr ratio was not found to be an independent predictor of BKV nephropathy (odds ratio, 1.3; 95% CI, 0.99-1.71; P = 0.06). The CCL2:Cr and CXCL10:Cr ratios may predict BKV nephropathy. The diagnostic value of CCL2 and CXCL10 in BKV infection should be further evaluated.

A urinary Common Rejection Module (uCRM) score for non-invasive kidney transplant monitoring.

A Common Rejection Module (CRM) consisting of 11 genes expressed in allograft biopsies was previously reported to serve as a biomarker for acute rejection (AR), correlate with the extent of graft injury, and predict future allograft damage. We investigated the use of this gene panel on the urine cell pellet of kidney transplant patients. Urinary cell sediments collected from patients with biopsy-confirmed acute rejection, borderline AR (bAR), BK virus nephropathy (BKVN), and stable kidney grafts with normal protocol biopsies (STA) were analyzed for expression of these 11 genes using quantitative polymerase chain reaction (qPCR). We assessed these 11 CRM genes for their abundance, autocorrelation, and individual expression levels. Expression of 10/11 genes were elevated in AR when compared to STA. Psmb9 and Cxcl10could classify AR versus STA as accurately as the 11-gene model (sensitivity = 93.6%, specificity = 97.6%). A uCRM score, based on the geometric mean of the expression levels, could distinguish AR from STA with high accuracy (AUC = 0.9886) and correlated specifically with histologic measures of tubulitis and interstitial inflammation rather than tubular atrophy, glomerulosclerosis, intimal proliferation, tubular vacuolization or acute glomerulitis. This urine gene expression-based score may enable the non-invasive and quantitative monitoring of AR.

Infectious Complications of Induction Therapies in Kidney Transplantation.

BackgroundCytomegalovirus (CMV) and BK virus (BKV) are post-transplant opportunistic viral infections that affect patient and graft survival. This study was designed to evaluate the risk of BKV nephropathy and CMV disease in kidney transplant recipients who received induction therapy with ATG or basiliximab.Material/MethodsWe retrospectively analyzed information on 257 adult patients who underwent kidney transplantation between January 2007 and 2017. Patients were categorized into 3 groups according to the induction therapies. The primary endpoint was the onset of CMV disease or biopsy-confirmed BKV nephropathy. The secondary endpoints were biopsy-proven rejection episodes, graft loss, loss to follow-up, and death.ResultsWe followed 257 patients for a median of 55.5 months. The incidence of CMV disease was significantly higher in the only ATG group compared to the group without induction treatment (p<0.001). There was no significant difference in the incidence of BKV nephropathy among groups (p>0.05). The dosage of ATG (OR, 10.685; 95% CI, 1.343 5 to 85.009; P=0.025) was independent risk factor for death.ConclusionsThis study demonstrated that a higher dosage of ATG in high-risk patients is associated with an increased risk of CMV disease and patient death, also, reducing the dosage may be a rational strategy for increasing graft and patient’s survival.

Cytomegalovirus prevention strategies and the risk of BK polyomavirus viremia and nephropathy.

Polyomavirus BK (BKV) is the cause of polyomavirus-associated nephropathy resulting in premature graft loss. There are limited data regarding the role of cytomegalovirus (CMV) infection and its prevention in developing BKV viremia and PVAN. In a prospective study, we analyzed 207 consecutive renal transplant recipients previously enrolled in 2 randomized trials evaluating different CMV prevention regimens with routine screening for BKV and CMV. Of these, 59 received valganciclovir and 100 valacyclovir prophylaxis; 48 patients were managed by preemptive therapy. At 3years, the incidence of BKV viremia and PVAN was 28% and 5%, respectively. CMV DNAemia developed in 55% and CMV disease in 6%. Both BKV viremia (42% vs 23% vs 21%, P=.006) and PVAN (12% vs 2% vs 2%, P=.011) were increased in patients treated with valganciclovir prophylaxis compared to valacyclovir and preemptive therapy. Using multivariate Cox proportional hazard regression, valganciclovir prophylaxis was independent predictor of BKV viremia (hazard ratio [HR]=2.38, P=.002) and PVAN (HR=4.73, P=.026). In contrast, the risk of subsequent BKV viremia was lower in patients with antecedent CMV DNAemia (HR=0.50, P=.018). These data suggest valganciclovir prophylaxis may be associated with increased risk of BKV viremia and PVAN. CMV DNAemia did not represent a risk for BKV.

BK polyoma virus nephropathy in hematopoietic cell transplant recipients

Background: The epidemiology of BK polyoma virus nephropathy in hematopoietic cell transplant recipients is poorly characterized. Kidney dysfunction after hematopoietic cell transplant is often attributed to treatment toxicities and kidney biopsies are rarely performed. Methods: We reviewed pathology-confirmed BK polyoma virus nephropathy cases in adult and pediatric patients who had undergone a hematopoietic cell transplant between 1 January 2015 and 31 December 2017 at our institution. Plasma and urine BK polyoma virus was assessed by a quantitative polymerase chain reaction assay and were obtained at the clinician discretion. Glomerular filtration rate was estimated by the Chronic Kidney Disease Epidemiology Collaboration equation. BK polyoma virus nephropathy was scored by the Banff Working Group Proposal. Results: Eight (7 adult and 1 pediatric) cases of BK polyoma virus nephropathy were identified among 685 hematopoietic cell transplant recipients, 14 of whom had undergone a kidney biopsy. Five patients (62.5%) had received a CD34+-selected peripheral blood hematopoietic cell transplant; two had received a cord blood allograft and one an unmodified peripheral blood hematopoietic cell transplant. Two patients developed acute graft-versus-host disease grade II. Early post–hematopoietic cell transplant BK polyoma viruria was documented with onset at a median of 54 days (range, 6–91) post–hematopoietic cell transplant and median urine BK polyoma viral load was 9.6 log10 copies/mL (range, 8.6–10.0). BK polyoma virus nephropathy was diagnosed at a median of 267 days after hematopoietic cell transplant (range, 133–637). At BK polyoma virus nephropathy diagnosis, all patients had decreased renal function with glomerular filtration rate (median 29 mL/min/1.73 m2; range, 9–98 ) and creatinine (median 2.4 mg/dL; range, 0.8–7.5) ; median plasma BK polyoma viral load was 6.3 log10 copies/mL (range, 5.5–7.1) and median CD4+ lymphocyte count was 82 cell/mcL (range, 21–172). Conclusions: We report eight biopsy-proven BK polyoma virus nephropathies in hematopoietic cell transplant recipients from a single center. BK polyoma virus nephropathy should be considered in hematopoietic cell transplant recipients with worsening kidney function and high BK polyoma viremia.

Epidemiology of and Risk Factors for BK Polyomavirus Replication and Nephropathy in Pediatric Renal Transplant Recipients: An International CERTAIN Registry Study.

BK polyomavirus-associated nephropathy (BKPyVAN) constitutes a serious cause of kidney allograft failure, but large-scale data in pediatric renal transplant recipients and a comprehensive analysis of specific risk factors are lacking. We analyzed the data of 313 patients in the Cooperative European Pediatric Renal Transplant Initiative Registry, with an observation period of 3.3 years (range, 1-5). The net state of immunosuppressive therapy was assessed by the modified Vasudev score. Presumptive BKPyVAN (defined as sustained [>3 wk] high-level BK viremia >10 copies/mL) within 5 years posttransplant occurred in 49 (15.8%) of 311 patients, and biopsy-proven BKPyVAN in 14 (4.5%) of 313. BKPyV viremia was observed in 115 (36.7%) of 311 patients, of whom 11 (9.6%) of 115 developed viremia late, that is, after the second year posttransplant. In 6 (12.5%) of 48 patients with high-level viremia and in 3 (21.4%) of 14 with BKPyVAN, this respective event occurred late. According to multivariable analysis, BKPyV viremia and/or BKPyVAN were associated not only with a higher net state of immunosuppression (odds ratio [OR], 1.3; P < 0.01) and with tacrolimus-based versus ciclosporin-based immunosuppression (OR, 3.6; P < 0.01) but also with younger recipient age (OR, 1.1 per y younger; P < 0.001) and obstructive uropathy (OR, 12.4; P < 0.01) as primary renal disease. Uncontrolled BKPyV replication affects a significant proportion of pediatric renal transplant recipients and is associated with unique features of epidemiology and risk factors, such as young recipient age, obstructive uropathy, and overall intensity of immunosuppressive therapy. BKPyV surveillance should be considered beyond 2 years posttransplant in pediatric patients at higher risk.

FP767No association between BK viremia and graft failure, In the absence of BKV nephropathy

FP767No association between BK viremia and graft failure, In the absence of BKV nephropathy

Successful Treatment for BK Virus Nephropathy by Leflunomide in a Kidney Transplant Patient: A Case Report

IntroductionThe immunosuppressant agents in kidney transplantation (KT) may lead to various complications such as opportunistic infections and malignancies. BK virus associated nephropathy is a significant complication following KT, and it can result in graft failure. BK virus causes tubulointerstitial nephritis, ureter stenosis, and even graft failure in KT recipients with impaired immune system. We described a 63-year-old woman, who was a hepatitis C carrier and on dialysis for 22 years before KT, who received cadaveric-donor KT 2 years previously. She reported decreasing urine output and general weakness. The serum creatinine level was slightly increased from 2.94 to 4.38 mg/dL. MethodsImmunosuppressant medications including prednisolone, everolimus, cyclosporin, and mycophenolate sodium were continued as maintenance therapy post KT. Kidney biopsy was performed due to deterioration of graft function. ResultsThe kidney biopsy showed consistent results with early-stage polyomavirus nephropathy, characterized by focal viral cytopathic changes with positive immunohistochemical signals and mesangial proliferative glomerulonephritis, immune-complex-mediated (Fig 1 and Fig 2). Negative C4d staining at peritubular capillary was reported. The dosage of mycophenolate sodium was tapered from 720 to 360 mg daily and that of everolimus increased from 0.5 to 1.0 mg daily due to BK viral infection with BK nephropathy. The serum creatinine level was 2.75 mg/dL after treatment. ConclusionEarly detection of BK nephropathy and decreasing immunosuppressant agents are the mainstay of treatment. Substituting leflunomide for mycophenolate sodium and increasing dosage of everolimus has been proposed to solve BK nephropathy. We presented that the use of leflunomide in such situation is in a timely manner.

Clinical Significance of Renal Allograft Protocol Biopsies: A Single Tertiary Center Experience in Malaysia.

Background The role of protocol renal allograft biopsy in kidney transplantation is controversial due to the concern with procedural-related complications; however, its role is slowly evolving. Recent evidence suggests that protocol biopsy is useful in detecting subclinical renal pathology. Early recognition and treatment of renal pathologies can improve long-term outcomes of renal allografts. Methodology A total of 362 renal allograft protocol biopsies were performed in adult recipients of kidney transplantation between 2012 and 2017. After excluding those with poor quality or those performed with a baseline serum creatinine level >200 umol/L, we analyzed 334 (92.3%) biopsies. Histology reports were reviewed and categorized into histoimmunological and nonimmunological changes. The immunological changes were subcategorized into the following: (1) no acute rejection (NR), (2) borderline changes (BC), and (3) subclinical rejection (SCR). Nonimmunological changes were subcategorized into the following: (1) chronicity including interstitial fibrosis/tubular atrophy (IFTA), chronic T-cell-mediated rejection (TCMR), unspecified chronic lesions, and arterionephrosclerosis, (2) de novo glomerulopathy/recurrence of primary disease (RP), and (3) other clinically unsuspected lesions (acute pyelonephritis, calcineurin inhibitors toxicity, postinfective glomerulonephritis, and BK virus nephropathy). Risk factors associated with SCR were assessed. Results For the histoimmunological changes, 161 (48.2%) showed NR, 145 (43.4%) were BC, and 28 (8.4%) were SCR. These clinical events were more pronounced for the first 5 years; our data showed BC accounted for 59 (36.4%), 64 (54.2%), and 22 (40.7%) biopsies within <1 year, 1-5 years, and > 5 years, respectively (p = 0.011). Meanwhile, the incidence for SCR was 6 (3.7%) biopsies in <1 year, 18 (15.3%) in 1-5 years, and 4 (7.4%) in >5 years after transplantation (p=0.003). For the nonimmunological changes, chronicity, de novo glomerulopathy/RP, and other clinically unsuspected lesions were seen in 40 (12%), 10 (3%), and 12 (3.6%) biopsies, respectively. Living-related donor recipients were associated with decreased SCR (p=0.007). Conclusions Despite having a stable renal function, our transplant recipients had a significant number of subclinical rejection on renal allograft biopsies.

Prevalence and Risk Factors of BK Viremia and Clinical Impact of BK Virus Surveillance on Outcomes in Kidney Transplant Recipients: A Single-Center Cross-Sectional Study.

BK virus is a polyomavirus that can cause nephropathy and graft loss after kidney transplant. The aim of our study was to screen the BK viremia prevalence, to understand the value of the inter-vention for BK virus nephropathy, and to determine the risk factors associated with BK viremia after kidney transplant in our center. Our retrospective cross-sectional study included 91 adult kidney transplant recipients who were seen between 2015 and 2017 and who had follow-up from 1 month to over 2 years. BK viremia was evaluated by use of plasma quantitative polymerase chain reaction. The prevalence of BK viremia and the clinical treatments and outcomes of BK virus nephropathy were assessed. The prevalence of BK viremia was 5.5% (5/91 patients). BK virus nephropathy was confirmed by allograft biopsy in 4.4% (4/91 patients) of all patients. Delayed graft function was found to be an independent risk factor for BK viremia (P < .001). Patients with BK viremia had significantly higher serum creatinine levels (P = .04). Patients who were diagnosed with BK viremia at 1 to 5 years after kidney transplant had higher serum creatinine (P = .02) and uric acid levels (P = .02). After reduction or discontinuation of calcineurin inhibitor, BK virus was cleared in all patients with BK virus nephropathy, with higher level of serum creatinine but no graft loss. Delayed graft function was considered as a risk factor for viremia. Early detection of BK viremia replication is important. The strategy of reduction of immunosuppression was effective for BK virus nephropathy and graft function improvement.

Higher Incidence of BK Virus Nephropathy in Pediatric Kidney Allograft Recipients with Alport Syndrome.

A retrospective review was performed to assess the risk factors and outcomes of BK virus infection and nephropathy (BKVN), an early complication in pediatric kidney allograft recipients. The study investigated the incidence, risk factors, and clinical outcomes of BK viremia and BKVN in a Korean population of pediatric patients who received renal transplantation from 2001–2015 at the Seoul National University Hospital. BKVN was defined as biopsy-proven BKVN or plasma BK viral loads >10,000 copies/mL for >3 weeks. BK viremia was defined as a BK viral load >100 copies/mL in blood. Among 168 patients assessed for BK virus status, 30 patients (17.9%) tested positive for BK viremia at a median of 12.6 months after transplantation. BKVN was diagnosed in six patients (3.6%) at a median of 13.4 months after transplantation. Three of the six BKVN patients had Alport syndrome (p = 0.003), despite this disease comprising only 6% of the study population. Every patient with BK viremia and Alport syndrome developed BKVN, while only 11.1% of patients with BK viremia progressed to BKVN in the absence of Alport syndrome. Multivariate analysis revealed that Alport syndrome was associated with BKVN development (hazard ratio 13.2, p = 0.002). BKVN treatment included the reduction of immunosuppression, leflunomide, and intravenous immunoglobulin. No allografts were lost in the two years following the diagnosis of BKVN. In summary, the incidence of BKVN in pediatric kidney allograft recipients was similar to findings in previous reports, but was higher in patients with underlying Alport syndrome.

BK polyomavirus in solid organ transplantation-Guidelines from the American Society of Transplantation Infectious Diseases Community of Practice.

The present AST-IDCOP guidelines update information on BK polyomavirus (BKPyV) infection, replication, and disease, which impact kidney transplantation (KT), but rarely non-kidney solid organ transplantation (SOT). As pretransplant risk factors in KT donors and recipients presently do not translate into clinically validated measures regarding organ allocation, antiviral prophylaxis, or screening, all KT recipients should be screened for BKPyV-DNAemia monthly until month 9, and then every 3months until 2years posttransplant. Extended screening after 2years may be considered in pediatric KT. Stepwise immunosuppression reduction is recommended for KT patients with plasma BKPyV-DNAemia of >1000copies/mL sustained for 3weeks or increasing to >10000copies/mL reflecting probable and presumptive BKPyV-associated nephropathy, respectively. Reducing immunosuppression is also the primary intervention for biopsy-proven BKPyV-associated nephropathy. Hence, allograft biopsy is not required for treating BKPyV-DNAemic patients with baseline renal function. Despite virological rationales, proper randomized clinical trials are lacking to generally recommend treatment by switching from tacrolimus to cyclosporine-A, from mycophenolate to mTOR inhibitors or leflunomide or by the adjunct use of intravenous immunoglobulins, leflunomide, or cidofovir. Fluoroquinolones are not recommended for prophylaxis or therapy. Retransplantation after allograft loss due to BKPyV nephropathy can be successful if BKPyV-DNAemia is definitively cleared, independent of failed allograft nephrectomy.

Safety of Everolimus With Reduced Calcineurin Inhibitor Exposure in De Novo Kidney Transplants: An Analysis From the Randomized TRANSFORM Study.

The safety profiles of standard therapy versus everolimus with reduced-exposure calcineurin inhibitor (CNI) therapy using contemporary protocols in de novo kidney transplant recipients have not been compared in detail. TRANSFORM was a randomized, international trial in which de novo kidney transplant patients were randomized to everolimus with reduced-exposure CNI (N = 1014) or mycophenolic acid (MPA) with standard-exposure CNI (N = 1012), both with induction and corticosteroids. Within the safety population (everolimus 1014, MPA 1012), adverse events with a suspected relation to study drug occurred in 62.9% versus 59.2% of patients given everolimus or MPA, respectively (P = 0.085). Hyperlipidemia, interstitial lung disease, peripheral edema, proteinuria, stomatitis/mouth ulceration, thrombocytopenia, and wound healing complications were more frequent with everolimus, whereas diarrhea, nausea, vomiting, leukopenia, tremor, and insomnia were more frequent in the MPA group. The incidence of viral infections (17.2% versus 29.2%; P < 0.001), cytomegalovirus (CMV) infections (8.1% versus 20.1%; P < 0.001), CMV syndrome (13.6% versus 23.0%, P = 0.044), and BK virus (BKV) infections (4.3% versus 8.0%, P < 0.001) were less frequent with everolimus. CMV infection was less common with everolimus versus MPA after adjusting for prophylaxis therapy in the D+/R- subgroup (P < 0.001). Study drug was discontinued more frequently due to rejection or impaired healing with everolimus, and more often due to BKV infection or BKV nephropathy with MPA. De novo everolimus with reduced-exposure CNI yielded a comparable incidence, though a distinctly different pattern, of adverse events versus current standard of care. Both regimens are safe and effective, yet their distinct profiles may enable tailoring for individual kidney transplant recipients.