Polyomavirus Nephropathy Research Articles

Polyomavirus Nephropathy with Crescent Formation

Polyomavirus Nephropathy with Crescent Formation

BK Polyomavirus Nephropathy After Kidney Transplantation from HCV-Infected Donor to HCV-Uninfected Recipient

BK Polyomavirus Nephropathy After Kidney Transplantation from HCV-Infected Donor to HCV-Uninfected Recipient

Clinical Efficacy of Intravenous Immunoglobulin for BK Polyomavirus-Associated Nephropathy After Living Kidney Transplantation.

PurposeBK polyomavirus (BKPyV)-associated nephropathy (BKPyVAN) is one of the most difficult infections to be treated after kidney transplantation. Although patients with BKPyVAN usually received a reduction of immunosuppressive agents, the majority of these patients undergo the loss of the graft kidney without any effective treatment afterward. Therefore, development of more effective therapy for BKPyVAN is eagerly expected.Patients and MethodsAmong patients who underwent a kidney transplantation between January 2016 and April 2019 at our hospital, there were five cases of BKPyVAN. After the initial diagnosis, all patients discontinued administration of mycophenolate mofetil (MMF), which was not enough to diminish decoy cells in urine cytology test. Therefore, all patients received additional intravenous immunoglobulin (IVIG) (100 mg/kg/day) therapy for five days and were evaluated for the therapeutic effect of IVIG with immunohistochemical examination using re-biopsy samples of the graft kidney.ResultsAfter IVIG therapy, 2 cases showed negative decoy cells in urine and 3 cases showed a drastic decrease of plasma BK virus load. Importantly, simian virus (SV) 40 large T antigens diminished after IVIG administration in all cases, which degraded polyomavirus nephropathy classification.ConclusionAlthough it is difficult to treat BKPyVAN after kidney transplant, IVIG therapy was considered to a promising treatment to improve severity of BKPyVAN especially in cases that dose reduction of immunosuppressive agents was ineffective.

A Primer on Machine Learning.

A Primer on Machine Learning.

The 2018 Banff Working Group classification of definitive polyomavirus nephropathy: A multicenter validation study in the modern era.

Polyomavirus nephropathy (PVN) remained inadequately classified until 2018 when the Banff Working Group published a new 3‐tier morphologic classification scheme derived from in‐depth statistical analysis of a large multinational patient cohort. Here we report a multicenter “modern‐era” validation study that included 99 patients with definitive PVN transplanted post January 1, 2009 and followed the original 2018 study design. Results validate the PVN classification, that is, the 3 PVN disease classes predicted clinical presentation, allograft function, and outcome independent of therapeutic intervention. PVN class 1 compared to classes 2 and 3 was diagnosed earlier (16.9 weeks posttransplant [median], P = .004), and showed significantly better function at 24 months postindex biopsy (serum creatinine 1.75 mg/dl, geometric mean, vs class 2: P = .037, vs class 3: P = .013). Class 1 presented during long‐term follow‐up with a low graft failure rate: 5% class 1, vs 30% class 2, vs 50% class 3 (P = .009). Persistent PVN was associated with an increased risk for graft failure (and functional decline in class 2 at 24 months postdiagnosis; serum creatinine with persistence: 2.48 mg/dL vs 1.65 with clearance, geometric means, P = .018). In conclusion, we validate the 2018 Banff Working Group PVN classification that provides significant clinical information and enhances comparative data analysis.

BK Virus Nephropathy: Prevalence, Impact and Management Strategies.

BK virus reactivation as a result of therapeutic immunosuppression following renal transplant can result in BK polyomavirus nephropathy and renal allograft loss. This is a complex and challenging clinical problem with a range of management options and practices reported in literature. The current standard for early diagnosis and treatment is surveillance by measuring viral DNA in blood using qPCR. Immunosuppression reduction is the cornerstone of effective management but is associated with a risk of acute rejection following treatment.

Significance of revised criteria for chronic active T cell-mediated rejection in the 2017 Banff classification: Surveillance by 1-year protocol biopsies for kidney transplantation.

Diagnostic criteria for chronic active T cell-mediated rejection (CA-TCMR) were revised in the Banff 2017 consensus, but it is unknown whether the new criteria predict graft prognosis of kidney transplantation. We enrolled 406 kidney allograft recipients who underwent a 1-year protocol biopsy (PB) and investigated the diagnostic significance of Banff 2017. Interobserver reproducibility of the 3 diagnosticians showed a substantial agreement rate of 0.68 in Fleiss's kappa coefficient. Thirty-three patients (8%) were classified as CA-TCMR according to Banff 2017, and 6 were previously diagnosed as normal, 12 as acute TCMR, 10 with borderline changes, and 5 as CA-TCMR according to Banff 2015 criteria. Determinant factors of CA-TCMR were cyclosporine use (vs tacrolimus), previous acute rejection, and BK polyomavirus-associated nephropathy. In survival analysis, the new diagnosis of CA-TCMR predicted a composite graft endpoint defined as doubling serum creatinine or death-censored graft loss (log-rank test, P<.001). In multivariate analysis, CA-TCMR was associated with the second highest risk of the composite endpoint (hazard ratio: 5.42; 95% confidence interval, 2.02-14.61; P<.001 vs normal) behind antibody-mediated rejection. In conclusion, diagnosis of CA-TCMR in Banff 2017 may facilitate detecting an unfavorable prognosis of kidney allograft recipients who undergo a 1-year PB.

Prevalence of BK Virus in Renal Transplant at a Single Center: Experience With Our Ureteral Reimplantation Surgical Technique.

BK polyomavirus is one of the main causes of chronic renal failure and ureteral stenosis in kidney transplant recipients, affecting approximately 15% of kidney transplant patients during the first year after transplant. The immunosuppressive treatment used in these recipients allows a reactivation of the virus by allowing infection, which can manifest from viruria, viremia, or nephropathy. The use of ureteral stents in renal transplant to prevent postoperative complications has been associated with an increase in BK polyomavirus nephropathy. Our objective was to describe associations between viruria and viremia and our reimplantation surgical technique and ureteral stenting. We conducted a retrospective review of 184 transplant recipients who were seen at our center between January 2013 and December 2016. To define possible risk factors from analysis of different variables, we categorized patients into 3 groups: patients who did not present with either viremia or viruria caused by BK virus, patients who presented with viremia, and patients who presented with viruria. We found that 127 transplant recipients (69%) presented with neither BK viruria nor BK viremia, 11 recipients (6%) presented with BK viremia, and 46 recipients (25%) presented with BK viruria. No patient in the study had BK polyomavirus nephropathy. Our type of ureteral stenting has a low rate of BK viruria and BK viremia compared with other studies. In addition, with our technique, the ureteral stent removal procedure does not require an invasive endoscopic procedure, thereby avoiding the consequent economic and assistance inconvenience typically associated with an endoscopic procedure.

P1626LIQUID BIOPSY IN RENAL TRANSPLANT: THE ROLE OF DONOR-DERIVED CELL-FREE DNA TO DETECT REJECTION

Abstract Background and Aims Circulating donor-derived cell-free DNA (dd-cfDNA) has recently been proposed as an early non-invasive marker for renal allograft rejection (Bloom et al, J. Am. Soc. Nephrol. 2017;28, 2221–2232). Recent studies demonstrated its potential role in the detection of any kind of rejection with better performance in detecting antibody-mediated rejection (ABMR) (Huang et al, Am J Transplant. 2019;19:1663–1670). However, at the current cutoff value for a positive test, the test seems to be affected by low sensitivity for T-cell mediated rejection (TCMR) and false positive results in the setting of non-rejection related damage. In the present study, the performance of dd-cfDNA is assessed on a retrospective series of transplant renal biopsies. Method Sixty-three renal biopsies from 52 allograft recipients with available dd-cfDNA results, evaluated between November 2017 and December 2019 at Vanderbilt University Medical Center, Nashville, Tennessee, were reviewed. Clinical and histological features along with the final diagnosis were recorded. Renal allograft rejection was classified following Banff 2013 criteria. Pearson’s chi-squared test was used to compare cases positive and negative for dd-cfDNA. Receiving operator curve (ROC) analysis was used to assess the performance of the test in detecting any rejection and ABMR. A p-value of &amp;lt;0.05 was considered statistically significant. Results The patients were 53±12.5 years old, 43% were men, 51% and 49% were Caucasian and African-American, respectively. The median value of dd-cfDNA was 2.6% for ABMR and 2.4% for any kind of rejection, statistically different from the group without rejection (0.56%, p = 0.002 and 0.0003, respectively). TCMR failed to demonstrate a statistically significant difference in dd-cfDNA levels vs controls (1.8% vs 0.56%, p = 0.627). The comparison of groups with positive and negative dd-cfDNA test is reported in Figure (panel A). Positive patients demonstrated a higher rate of findings associated with ABMR such as DSA positivity, moderate microcirculation inflammation, and transplant glomerulopathy, in addition to diagnostic ABMR and chronic/active ABMR. Moreover, a significant difference was found between the two groups in the rate of any kind of rejection. ROC analysis for any ABMR (Figure, panel B) demonstrated an AUC of 0.76 (95% CI 0.61-0.91) with a sensitivity (Sn) of 92.3%, a specificity (Sp) of 60%, a positive predictive value (PPV) of 37.5% and a negative predictive value (NPP) of 96.8%. ROC analysis for any kind of rejection (Figure, panel C) demonstrated an AUC of 0.84 (95% CI 0.74-0.94) with a Sn of 94.1%, a Sp of 65.2%, a PPV of 50% and a NPP of 96.8%. Among the patients with positive dd-cfDNA and without rejection (n=16, 51%), allograft biopsy demonstrated borderline TCMR in 4, acute tubular injury in 8, chronic pyelonephritis in 1, mild interstitial fibrosis in 1, and 2 with minimal histological abnormalities. Notably, none of the cases with a positive test were diagnosed with polyomavirus nephropathy. Conclusion Similar to previous studies, dd-cfDNA represents a sensitive test for detection of ABMR, with high performance in any rejection setting with the Banff 2013 criteria. However, the high rate of false positive results and the presence of undetected T-cell mediated events (e.g. borderline cases) at the current recommended cut-off value for positivity limits its employment as a surrogate for the renal biopsy.

SO030HISTOLOGICAL CHARACTERIZATION OF RENAL BIOPSIES FROM HCV-INFECTED DONORS: A VALUABLE SOURCE OF KIDNEY ALLOGRAFTS

Abstract Background and Aims The introduction of effective direct-acting antiviral agents (DAAs) has allowed safe transplantation of kidneys from HCV positive (HCV+) donors into HCV negative (HCV-) recipients. Some studies demonstrated an increased risk for rejection as well as polyomavirus infection in these situations (Molnar et al, Am J Transplant. 2019 Nov;19(11):3046-3057), possibly due to the development of an inflammatory milieu in the setting of HCV seroconversion and persistent viremia (Durand et al, Am J Transplant. 2019 Nov;19(11):2969-2970). With this concern for HCV-associated renal injury and increased risk for rejection, this retrospective study explores the histologic findings of allograft biopsies from HCV+ donors. Method Fifty renal allograft biopsies from 28 recipients of HCV+ donors evaluated at Vanderbilt University Medical Center between September 2018 and December 2019 were retrospectively reviewed with recording of clinical and histological features, and final diagnoses. All recipients were transplanted under a clinical protocol and were treated with DAA therapy. In the same period of time, 30 renal allograft biopsies from 24 recipients of HCV- donors were selected having the same post-transplant interval as the study cohort. Categorical variables are expressed in percentage and compared using Pearson’s chi-squared test. Continuous variables are expressed as mean±SD and compared used Student t-test. A p-value of &amp;lt;0.05 was considered as statistically significant. Results The complete results of the comparison between the two groups (HCV+ and HCV- donors) are demonstrated in Figure. The differences reaching statistical significance include higher frequency of males and tubulointerstitial fibrosis (IFTA) in the HCV+ group (p = 0.038 and 0.044, respectively) and the higher incidence of DSA positivity and acute tubular injury in the control group (p = 0.001 and 0.029). Notably, no significant differences were noted in terms of antibody-mediated events (microcirculation inflammation, transplant glomerulopathy, C4d positivity, or diagnostic ABMR), or T-cell mediated events including borderline or diagnostic T-cell mediated rejection (Banff 2013). The two groups also demonstrated the same incidence of polyomavirus nephropathy and de novo/recurrent glomerulonephritis. Interestingly, two of the HCV+ cases showed mesangial IgA deposits on immunofluorescence and electron microscopy on the first biopsy, of which one showed persistence of deposits, 18 and 44 days after transplant respectively. Once case demonstrated a de novo focal proliferative IgM-dominant glomerulonephritis on the 7th biopsy, 266 days after transplantation. Conclusion Kidneys from HCV+ donors represent a valuable resource in the era of DAA therapy. This reported experience demonstrates similar frequency of rejection and viral infection affecting allografts from HCV positive and negative donors. The presence of immune complex deposits and glomerulonephritis in some of these cases could represent either a donor-derived injury or an acquired post-seroconversion feature. In conclusion, HCV+ donors appear to be a safe resource for transplantation. Further studies with post-transplant intervals will provide additional characterization of their impact.

Discrepancy analysis comparing molecular and histology diagnoses in kidney transplant biopsies.

Discrepancy analysis comparing two diagnostic platforms offers potential insights into both without assuming either is always correct. Having optimized the Molecular Microscope Diagnostic System (MMDx) in renal transplant biopsies, we studied discrepancies within MMDx (reports and sign-out comments) and between MMDx and histology. Interpathologist discrepancies have been documented previously and were not assessed. Discrepancy cases were classified as "clear" (eg, antibody-mediated rejection [ABMR] vs T cell-mediated rejection [TCMR]), "boundary" (eg, ABMR vs possible ABMR), or "mixed" (eg, Mixed vs ABMR). MMDx report scores showed 99% correlations; sign-out interpretations showed 7% variation between observers, all located around boundaries. Histology disagreed with MMDx in 37% of biopsies, including 315 clear discrepancies, all with implications for therapy. Discrepancies were distributed widely in all histology diagnoses but increased in some scenarios; for example, histology TCMR contained 14% MMDx ABMR and 20% MMDx no rejection. MMDx usually gave unambiguous diagnoses in cases with ambiguous histology, for example, borderline and transplant glomerulopathy. Histology lesions or features associated with more frequent discrepancies (eg, tubulitis, arteritis, and polyomavirus nephropathy) were not associated with increased MMDx uncertainty, indicating that MMDx can clarify biopsies with histologic ambiguity. The patterns of histology-MMDx discrepancies highlight specific histology diagnoses in which MMDx assessment should be considered for guiding therapy.

Combined detection of urine specific gravity and BK viruria on prediction of BK polyomavirus nephropathy in kidney transplant recipients.

Background:BK polyomavirus (BKPyV)-associated nephropathy (BKPyVAN) is an important cause of dysfunction and failure of renal transplants. This study aimed to assess the diagnostic performance of morning urine specific gravity (MUSG) in diagnosing BKPyVAN in kidney transplant recipients.Methods:A total of 87 patients, including 27 with BKPyVAN, 22 with isolated BKPyV viruria, 18 with T cell-mediated rejection (TCMR), and 20 with stable graft function, were enrolled in the First Affiliated Hospital of Sun Yat-Sen University from March 2015 to February 2017. MUSG at biopsy and during a follow-up period of 24 months after biopsy was collected and analyzed. Receiver operating characteristic (ROC) curve analysis was used to determine the ability of MUSG to discriminate BKPyVAN.Results:At biopsy, the MUSG of BKPyVAN group (1.008 ± 0.003) was significantly lower than that of isolated BK viruria group (1.013 ± 0.004, P < 0.001), TCMR group (1.011 ± 0.003, P = 0.027), and control group (1.014 ± 0.006, P < 0.001). There was no significant difference in MUSG among the isolated BK viruria group, TCMR group, and control group (P = 0.253). In BKPyVAN group, the timing and trend of MUSG elevate were consistent with the timing and trend of the decline of viral load in urine and plasma, reaching a statistical difference at 3 months after treatment (1.012 ± 0.003, P < 0.001) compared with values at diagnosis. ROC analysis indicated that the optimal cut-off value of MUSG for diagnosis of BKPyVAN was 1.009, with an area under the ROC curve (AUC) of 0.803 (95% confidence interval [CI]: 0.721–0.937). For differentiating BKPyVAN and TCMR, the optimal MUSG cut-off value was 1.010, with an AUC of 0.811 (95% CI: 0.687–0.934).Conclusion:Combined detection of MUSG and BKPyV viruria is valuable for predicting BKPyVAN and distinguishing BKPyVAN from TCMR in renal transplant recipients.

Renal transplant patients with preformed anti-HLA antibodies: early biopsy findings and clinical outcomes.

Introduction:Renal fibrosis is the end point of a process that begins at transplant, with ischemia reperfusion and early inflammation, and progresses over time with immunological and non-immunological phenomena. Early identification of morphological markers and intervention could improve graft function and survival.Objective:to evaluate the correlation between intensity and specificity of pre-transplant anti-HLA antibodies and kidney allograft pathology in order to identify early risk factors or markers of allograft dysfunction.Methods:A retrospective cohort of kidney transplant recipients with pre-transplant anti-HLA antibodies who underwent graft biopsy within the first two years post-transplant was divided into two groups according to the specificity of anti-HLA antibodies: nonspecific (non-DSA, n = 29) and specific (DSA+, n = 16). Kidney graft pathology, renal function, and proteinuria were analyzed.Results:general characteristics were similar in both groups, except for the higher dose of thymoglobulin in DSA+ group (p < 0.05). The non-DSA group had higher scores for glomerulosclerosis, interstitial inflammation (i) and interstitial fibrosis (ci) (p < 0.05) and higher incidence of cell-mediated acute rejection. No statistical difference in incidence of antibody-mediated rejection, renal function, and proteinuria was observed during follow up.Discussion and conclusions:the difference in inflammation scores and interstitial fibrosis may be associated to the higher incidence of acute cell-mediated rejection and polyomavirus nephropathy in the Non-DSA group. We also should take into account the protective effect of higher doses of thymoglobulin, reducing ischemia reperfusion injury in the DSA+ group. The short follow-up might have been insufficient to detect long-term changes in allograft tissue, renal function, and proteinuria.

BK polyomavirus-pathogen, paradigm and puzzle.

BK virus is a polyomavirus with seroprevalence rates of 80% in adults. Infection is usually acquired during childhood, and the virus is benign or pathologic depending on immune status. The virus reactivates in immunodeficiency states, mostly among transplant (either kidney or bone marrow) recipients. There are approximately 15 000 renal transplants every year in the USA, of which 5-10% develop BK polyomavirus nephropathy; 50-80% of patients who develop nephropathy go on to develop graft failure. BK virus is associated with BK polyomavirus nephropathy, ureteral stenosis, late-onset hemorrhagic cystitis, bladder cancer and other nonlytic large T-expressing carcinomas. The renal spectrum begins with viruria and can end with graft failure. The clinical spectrum and outcomes vary among transplant patients. New noninvasive diagnostic methods, such as urinary polyomavirus Haufen detected by electron microscopy, are currently under study. Treatment is primarily directed at decreasing immunosuppression but may be associated with graft rejection. Repeat transplantation is encouraged as long as viral clearance in plasma prior to transplant is accomplished. There remain no definitive data regarding the utility of transplant nephrectomy.

Hallazgos histológicos en biopsia por protocolo asociados con reducción en función renal 12 meses postrasplante, en receptores de trasplante renal con bajo riesgo inmunológico, recibiendo inducción con basiliximab

Introduction: Identifying factors that are associated of allograft function loss might be an important step toward prolonging kidney allograft survival. Purpose: In this study we found to determine the association between histologic changes on 1-year surveillance biopsies and changes in graft function. Methods: Recipients of kidneys from deceased donors (95%) or living donors (5%) trasplanted between 2007 and 2012. The primary end point was reduction in calculated glomerular filtration rate (Cockroft anf Gault) higher 5ml/min 12 months post transplant vs calculated glomerular filtration rate previous surveillance biopsie. Results: This analysis included 114 adults, recipients of kidneys with low immunological risk receiving basiliximab induction from deceased donors (95%) or living donors (5%), transplanted between august 2007 and july 2012. The primary end point was reduction in calculated glomerular filtration rate (Cockroft & Gault) higher 5ml/min 12 months post trasplant . 25 of 114 patientes showing reduction; The histologic changes associated with renal function reduction were glomerulitis (p=0,024), interstitial inflamation (p=0,001), tubulitis (p=0,001), capilaritis (p=0,001), glomerulitis + capilaritis (p=0,001), polyoma virus nephropathy (p=0,04) and subclinical rejection (p=0,015). By regression analyses, interstitial inflamation (OR = 2,11; IC 95%: 1,13-3,95) and capilaritis (0R=7,12; IC 95%:1,57-32,27) were associated with renal function redcution 12 month post-transplant. Conclusion: inflammation and capilaritis in protocol biopsies in first year post-transplant predict loss of graft function and independently of other variables.

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.

P215 Correlation between gene expression and histology in polyomavirus nephropathy

P215 Correlation between gene expression and histology in polyomavirus nephropathy

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.

Prevalence, Risk Factors, Treatment, and Overall Impact of BK Viremia on Kidney Transplantation

BK viremia (BKV) is a recognized and potentially serious problem in renal transplantation. The risk factors and the impact of BKV on renal allograft and patient survival are controversial. This study reports an 8-year, single-center experience on the prevalence, risk factors, and outcomes of BKV in kidney transplant recipients. This is a retrospective analysis of all patients who received a kidney transplant at the University of Kentucky and had BK viral titers available from 2009 to 2017. BKV was defined by a polymerase chain reaction viral load of ≥ 10,000 copies per mL. Demographic, clinical, and laboratory data generated during routine outpatient follow up and inpatients records were collected. Independent risk factors for BKV were determined using uni- and multivariate analysis. Graft and patient survival was compared using Kaplan-Meier analysis, and the severity of polyomavirus nephropathy on biopsy was scored using the Banff 2017 classification. We identified 122 BK positive (19%) and 527 BK negative (81%) patients. BKV developed after a median of 115 days (range, 80–249 days) following kidney transplantation. The 1-, 5-, and 10-year graft survival was 97%, 75%, and 33% in the BKV group and 96%, 85%, and 71% in the BK negative group, respectively. Likewise, the 1-, 5-, and 10-year patient survival was 98%, 84%, and 52% in the BKV group and 98%, 92%, and 84% in the BK negative group. Male sex, age at transplantation, maintenance steroids, and alemtuzumab induction were associated with developing BKV in the multivariate analysis. We concluded that BKV is not uncommon after renal transplantation. The determinants for BKV are male sex, older transplant recipients, and maintenance steroids. BKV adversely affected graft and patient survival. A unified approach for BKV and polyomavirus nephropathy treatment is needed.