BK Virus Nephropathy Research Articles

APOBEC3B Signature Mutations Benefit BK Polyomavirus

BK polyomavirus (BKV) causes nephropathy in kidney transplant recipients (KTRs). The virus has also been implicated as a possible cause of bladder and kidney cancers. Two KTRs who developed BKV nephropathy followed by renal carcinoma both showed a swarm of BKV sequence variants encoding non-silent mutations in surface loops of the viral major coat protein. The appearance and disappearance of these mutations over time suggests intra-patient evolution of the virus. Some of the observed mutations conferred resistance to antibody-mediated neutralization. The mutations also modified the spectrum of receptor glycans the virus engages during the infectious entry process. Nearly all observed mutations are consistent with DNA damage caused by APOBEC3B, an antiviral cytosine deaminase. This is intriguing in light of a recent report showing that BKV induces APOBEC3B expression. The results indicate that polyomaviruses can employ APOBEC3B to acquire beneficial site-specific mutations, conceivably with carcinogenic consequences for the host.

Identification of potential key protein interaction networks of BK virus nephropathy in patients receiving kidney transplantation

We aim to identify the key protein interaction networks and implicated pathways of BK virus nephropathy (BKVN) via bioinformatic methods. The microarray data GSE75693 of 30 patients with stable kidney transplantation and 15 with BKVN were downloaded and analyzed by using the limma package to identify differentially expressed genes (DEGs). Then the gene ontology (GO) functional enrichment analysis and the Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis were done to investigate the molecular function (MF), biological process (BP), cellular components (CC) and pathways of DEGs. Finally, protein-protein interactions (PPIs) were constructed, and the hub proteins were identified. As a result, 249 up-regulated genes and 253 down-regulated genes of BKVN patients were selected based on criteria of P > 0.01 and fold change >2.0. GO and KEGG showed that DEGs were mainly located in nucleus and cytosol, and were implicated in the immune responses. In the PPI analysis, 26 up-regulated and 8 down-regulated proteins composed the pivotal interaction network. CXCL10, EGF and STAT1 were identified as hub proteins in BKVN. In conclusion, CXCL10, EGF and STAT1 may induce kidney injuries by promoting inflammation and prohibiting reparation of tissue damage in BKVN.

249 BK Virus Nephropathy in Native Kidney

249 BK Virus Nephropathy in Native Kidney

Abnormalities in Protocol Graft Kidney Biopsy 6 Months Posttransplantation in a Tertiary Care Center Hospital of Nepal

BackgroundIncreasing graft survival is the prime focus of every transplantation program. Detection of subclinical abnormalities with the help of protocol renal graft biopsies performed at predetermined intervals after transplantation has been one of the approaches.The objective was to study the abnormalities in protocol renal graft biopsy specimens at 6 months posttransplantation. MethodsThis was a hospital-based observational descriptive study. It included the recipients who underwent kidney transplantation between October 2014 and September 2015. The recipients were followed up postoperatively on an outpatient basis, as per the institution protocol. At 6 months posttransplantation, protocol graft biopsy was performed in all patients with normal functioning allograft without proteinuria after obtaining informed written consent. ResultsA total of 57 patients with chronic kidney disease underwent renal transplantation during the study period. Protocol biopsy was performed in 47 recipients.Subclinical rejection was found in 4 (8.5%) recipients. Two recipients had significant tubulitis and interstitial inflammation. One of them showed features of Banff Type IA cellular rejection (t2, i2) and another showed Banff Type IB cellular rejection (t3, i2). Biopsy specimen of 1 recipient showed significant glomerulitis and peritubular capillaritis (g3, ptc1). Another recipient showed significant peritubular capillaritis (ptc2) with C4d positivity. IgA nephropathy was present in 6 (12.8%) recipients. BK virus nephropathy was found in 2 (4.3%) recipients. ConclusionThis study demonstrates that abnormal histologic findings occur in protocol graft biopsy specimens at 6 months post renal transplantation in patients without any clinical or laboratory abnormalities.

The Detection of BK Virus by Quantitative PCR of Plasma as Screening Test to Identify Renal Transplant Recipients at Risk of BK Virus Nephropathy

Background: BK virus infection and nephritis are increasing problems in renal transplant recipients (RTRs). Increasing prevalence of this infection and nephritis have been correlated with newer immunosuppressive agent in recent years. Routine post-transplant screening for BK viremia prior to the occurrence of nephritis and the reduction in immunosuppressive therapy for subjects with BKV infection appear to be attractive objectives. Objectives: This study performed to screening for BK virus in blood to identify RTRs at risk of development BKV associated nephritis (BKVN) .

BK virus-associated collecting duct carcinoma of the renal allograft in a kidney-pancreas allograft recipient.

BK polyomavirus (BKV) nephropathy is a major concern in renal transplantation. Its main consequence is graft loss, which occurs in more than 50% of the cases. De novo renal cell carcinoma in renal allograft is a very rare event. Most of these tumors are papillary or clear cell carcinomas. We report herein the first case of collecting duct carcinoma of the renal allograft in a kidney-pancreas allograft adult recipient. Collecting duct carcinoma occurs long after the cure of a BKV nephropathy. At this time, BKV viremia and viruria were negative as well as the immunostaining for SV40 in the non-tumor kidney. The viral oncoprotein Tag persists only in the tumor cells. To preserve pancreas graft function, we maintained immunosuppression levels. After a 9-months follow-up, the evolution was free from clinical and radiological progression. The oncogenic role of BKV remains controversial in human cancers. However, strong experimental data have shown an association between BKV infection and urologic neoplasms. Further works might precise the exact role of polyomaviruses in renal carcinogenesis. In the meantime, clinical vigilance for early diagnostic of these tumors is mandatory after BKV nephropathy.

282 - Kidney Dysfunction Post-Allogeneic Transplant: High Incidence of TMA and Kidney GvHD

Abstract Introduction: Kidney dysfunction is an important problem in adult recipients of allogeneic stem cell transplantation (HSCT) and independently predicts overall survival and non-relapse mortality. Kidney dysfunction occurs in ~50% of transplant recipients. More than 20% of all survivors of HSCT in long-term follow up develop chronic kidney disease. However, there is currently limited data on the cause and consequences of kidney dysfunction in adult recipients after allogeneic HSCT. Common causes of kidney dysfunction after HSCT include chemotherapy or radiation toxicity, infections, sepsis, hepatic sinusoidal obstruction, drug toxicities due to immunosuppressive medications, thrombotic microangiopathy, as well as acute or graft versus host disease (GvHD). Kidney biopsies are seldom obtained and hence the tissue diagnosis in these patients often remains speculative. Early identification of the causes of kidney dysfunction may help define preventive and therapeutic strategies and improve outcome. Hence, in August 2016, we designed a prospective study at our center to systematically evaluate kidney dysfunction in adult recipients of allogeneic HSCT. Herein we present our initial report of 8 kidney biopsies. Methods: All adult HSCT recipients with kidney dysfunction were evaluated by Nephrologists to determine the need for kidney biopsy. Kidney dysfunction was defined as either (i) acute kidney failure or (ii) proteinuria. Acute kidney failure was defined by the ‘ Kidney Disease: Improving Global Outcomes (KDIGO)‘ criteria. Proteinuria was defined as (i) spot urine albumin to creatinine ratio of ≥1 (equivalent to ≥1 g in 24 hours). Kidney biopsies were done under ultrasound guidance and the tissue specimens were interrogated by light, immunofluorescence and electron microscopy. Results: A total of 8 HSCT recipients (including one patient who had a biopsy prior to Aug 2016) underwent kidney biopsies. The patient and transplant characteristics are summarized in Table 1. Seven of the 8 pts had AML. One patient had NHL in CR2. Four patients received a MUD transplant. Two received MRD transplants. Two received combined haploidentical and single unit cord blood transplant (haplo-cord). Six of the 8 patients received conditioning with fludarabine and melphalan. One patient received additional 400 Gy TBI. One patient received additional azacytidine. Median time to neutrophil engraftment was 13.5 days (range 9-20). Median time to platelet engraftment was 19 days (range 14-76). There were no cases of graft failure. All patients also demonstrated either acute or chronic GvHD of other organs - most commonly skin. All kidney biopsies were performed without complications. Kidney biopsies were done at median 254 days after transplantation (range 126-680). Baseline serum creatinine (mg/dL) prior to transplant was 0.95 (median, range 0.65-1.1, reference range: 0.64-1.27 mg/dL). Creatinine at time of biopsy: 3.0 (median, range 1.53-5.07). Urine albumin/creatinine ratio: 832 (median, range 55-2864, reference range: The kidney biopsy findings are summarized in Table 2. All patients had evidence of endothelial cell injury, either acute or chronic. Three patients had features suggestive of GvHD of the kidney while one patient had BK virus nephropathy. Four of the 8 recipients died; 80 days (median, range 39-124) from the biopsy, 346 days (median, range 178-804) from transplantation. The clinical outcome is summarized in Table 3. Conclusions: Kidney biopsies post-transplant are an important diagnostic tool that should be considered for prolonged kidney dysfunction or proteinuria, particularly in the setting of other post-transplant complications. Our single-center biopsy results highlight the under-recognition of kidney dysfunction complications and complexities observed post-transplant. All kidney biopsies performed were instrumental in treatment planning. Further investigation is needed to define criteria for diagnosis and to understand the pathophysiology. This requires multi-disciplinary engagement as well as a proactive approach for obtaining kidney biopsies. With appropriate transfusion support, percutaneous kidney biopsies were performed safely without complication. Download : Download high-res image (217KB) Download : Download full-size image Disclosures No relevant conflicts of interest to declare.

Prediction of Early BK Virus Infection in Kidney Transplant Recipients by the Number of Cells With Intranuclear Inclusion Bodies (Decoy Cells).

BackgroundBK virus (BKV) is the cause of nephropathy. Because BKV nephropathy can progress to graft loss, early diagnosis of BKV infection is very important. In this study, we aimed to investigate the utility of quantifying cells with intranuclear inclusion bodies (decoy cells) in urinary sediment for the screening and monitoring of BKV infection in renal transplant recipients at our hospital.MethodsThis was a retrospective single-center study. Urine sediment examination was performed at each outpatient visit, and the number of decoy cells was measured in the whole microscopic field. Patients (n = 41) were divided into the BK viremia group (blood positive for BKV DNA by polymerase chain reaction [PCR]) and non-BK viremia group (blood negative for BKV DNA by PCR), and the decoy cell count in urinary sediments was examined.ResultsThe maximum decoy cell count was significantly higher (P = 0.04) in the BK viremia group than in the non-BK viremia group. In the receiver operating characteristic curve for the maximum decoy cells, the cutoff value was 507 cells. The area under the receiver operating characteristic curve was 0.8774 (95% confidence interval, 0.7739-0.9810). The number of decoy cells at the time of appearance in the BK viremia group was not significantly different from that in the non-BK viremia group. However, the BK viremia group showed an increasing trend, whereas the non-BK viremia group showed a decreasing trend, in the number of decoy cells. There was a positive correlation between the number of decoy cells and the data from the urine BKV-DNA PCR quantification (correlation coefficient [r] = 0.74).ConclusionsMeasurement of decoy cells in urinary sediments may predict early BKV infection, and if performed quickly, it may be useful for screening and continuous monitoring of BKV infection in renal transplant recipients.

Polyomavirus BK Nephropathy-Associated Transcriptomic Signatures: A Critical Reevaluation.

BackgroundRecent work using DNA microarrays has suggested that genes related to DNA replication, RNA polymerase assembly, and pathogen recognition receptors can serve as surrogate tissue biomarkers for polyomavirus BK nephropathy (BKPyVN).MethodsWe have examined this premise by looking for differential regulation of these genes using a different technology platform (RNA-seq) and an independent set 25 biopsies covering a wide spectrum of diagnoses.ResultsRNA-seq could discriminate T cell–mediated rejection from other common lesions seen in formalin fixed biopsy material. However, overlapping RNA-seq signatures were found among all disease processes investigated. Specifically, genes previously reported as being specific for the diagnosis of BKPyVN were found to be significantly upregulated in T cell–mediated rejection, inflamed areas of fibrosis/tubular atrophy, as well as acute tubular injury.ConclusionsIn conclusion, the search for virus specific molecular signatures is confounded by substantial overlap in pathogenetic mechanisms between BKPyVN and nonviral forms of allograft injury. Clinical heterogeneity, overlapping exposures, and different morphologic patterns and stage of disease are a source of substantial variability in “Omics” experiments. These variables should be better controlled in future biomarker studies on BKPyVN, T cell–mediated rejection, and other forms of allograft injury, before widespread implementation of these tests in the transplant clinic.

265 BK-Virus Positive Invasive High-Grade Urothelial Carcinoma in an 8-Year-Old Renal Transplant Recipient With BK Virus Nephropathy

Urothelial carcinoma is extremely rare in children and may be fundamentally different than in adults. Fewer than 30 cases have been reported in patients under 10 years old. BK polyomavirus infection is a major problem in transplantation, especially in renal transplant recipients. According to literature, 1%-10% of renal transplant recipients develop polyomavirus-associated nephropathy. The possibility that BK polyomavirus may be carcinogenic in humans is controversial, but SV40 large T antigen is known to inhibit tumor suppressors pRB and p53, and to transform some cell lines in culture. Adult renal transplant recipients have a 3-5x increased risk of urothelial carcinoma. The cystoprostatectomy specimen from an 8-year-old boy with a history of renal transplantation was processed according to standard procedure, and evaluated using H&E and immunohistochemical stains (IHC). Additional ancillary testing included molecular studies for BK virus using PCR for VP1 and identity testing using HLA typing. The patient was an 8-year-old ex 32-week gestation twin boy with a history of chronic kidney disease and developmental delay. He had end-stage renal disease of unclear etiology and underwent kidney transplantation five years earlier from a living non-related donor who was a smoker. He had been immunosuppressed since transplantation, and his course was complicated by uncontrolled BK viremia and BK nephropathy despite prolonged treatment. Five years after his renal transplant, he was noted to have gross painless hematuria. Biopsy of a bladder lesion showed high-grade urothelial carcinoma, and ureteroscopy of native and transplant ureters showed no gross malignancy. He underwent cystoprostatectomy and bilateral native nephroureterectomies with cutaneous ureterostomy from the transplant kidney. Histological examination of the bladder revealed invasive high-grade urothelial carcinoma with micropapillary features with invasion into muscularis propria. Lymphovascular invasion was also noted. The bilateral native kidneys were atrophic with simple cysts and chronic inflammation. The prostate, bilateral seminal vesicles, vas deferens, and distal transplant ureter cuff were negative for tumor. Immunohistochemical staining of the tumor for SV40 antigen showed strong and diffuse staining. In contrast, immunohistochemistry for viral protein VP1 was negative. Molecular testing for BK virus by PCR for VP1 was positive. Immunohistochemistry for mismatch repair proteins showed normal, preserved expression. Identity testing confirmed that the tumor cells belonged to the patient and not to the donor. BK virus positivity has been reported in rare cases of urothelial carcinomas, mainly in adult transplant patients. To our knowledge, this is the first reported incidence of BK virus-associated urothelial carcinoma in a pediatric patient. Absence of late VP1 expression by IHC in conjunction with positive SV40 staining and positive BK virus PCR is consistent with a non-productive BK virus infection. Pathologists should be aware that identity testing should be considered in transplant patients with urothelial carcinoma to confirm the genetic origin of the tumor. Micropapillary differentiation may be a feature of BK virus-associated carcinoma.

BK Virus nephropathy in living donor renal allograft recipients: An observational study from a large transplant center in India.

BK virus is a polyoma virus which remains in latent phase in the urinary tract, particularly in the renal tubular epithelial cells. In immunosuppressed patients, it is activated and manifests as tubule-interstitial nephritis causing renal allograft dysfunction. A total of 402 patients who underwent renal allograft biopsy from 2013 to 2016 were included in this study; six patients were diagnosed to have BK virus nephropathy. Histopathology showed ground glass intra-nuclear inclusions accompanied by acute tubular injury, interstitial inflammation, and varying degree of interstitial fibrosis and tubular atrophy. Patients were managed with reduction in the overall immunosuppression. Only one patient progressed to graft failure on follow-up. The overall prevalence of polyoma virus at our center is 1.49%.

Fluoroquinolones and BK Virus Nephropathy: A Myth or a Reality.

BK polyomavirus (BKV) is a challenging problem for the transplant nephrologist. Various strategies have been used to prevent or treat BK virus nephropathy (BKVN). These include reduction in immunosuppression, intravenous immune globulin, cidofovir, leflunomide, and the fluoroquinolone antibiotics. All these agents have their own toxicities. Great interest was shown to use fluoroquinolones to prevent BKVN after its useful experience was reported in bone marrow transplant. Fluoroquinolones being cheap and easily available, attracted nephrologists to use it, for prevention of BKVN. These agents have been shown in vitro studies to be effective. However, there are mixed results about their effectiveness in prevention of BKVN in clinical setting. This review will focus the evidence available for using fluoroquinolones in prevention of BKVN and its usefulness. Furthermore, a way forward to use these agents or not for prevention of BKVN will also be discussed.

Role of urinary viral haufen in diagnosis of polyomavirus nephropathy: A systematic review

Renal biopsy is a gold standard method for diagnosis of BK polyomavirus nephropathy (PVN); however, it is an invasive procedure, and it can be false negative due to sampling error. Many noninvasive screening strategies such as decoy cell in urine and viral load assessments using polymerase chain reaction in urine and in plasma have a limited role in diagnose of PVN. Recently, urinary viral Haufen (UVH) is found to be very useful for diagnosis of PVN. The aim of this study was to evaluate the efficacy of UVH in the diagnosis of PVN in all transplant patients. In this systematic review, we included studies where UVH was used for diagnosis of PVN. We searched PubMed, EMBASE, Google Scholar, and Cochrane database of systematic reviews. Two authors independently selected studies and extracted data for review. Five studies were included in this study. One study reported sensitivity, specificity, positive predictive value, and negative predictive values of UVH against kidney biopsy as 100%, 99%, 97%, and 100%, respectively, for diagnosis of PVN in all type of transplant patients. Second study described technique of UVH estimation. Two studies correlated UVH with severity of PVN. Fifth study demonstrated that UVH formation occurs in the setting of high concentration of Tamm–Horsfall protein in urine and also reported UVH as a marker of PVN in mice. Data were not appropriate for meta-analysis. A limited number of studies showed that UVH may be a novel noninvasive biomarker to diagnosis and to predict the severity of PVN in transplant patients.

Urinary exosomal viral microRNA as a marker of BK virus nephropathy in kidney transplant recipients.

ObjectiveBkv-miR-B1-5p, one of the microRNAs encoded by BK virus, was recently reported to be elevated in the blood among the patients with BK virus nephropathy (BKVN). Urinary exosome was suggested to be a possible source of biomarker for kidney diseases, but it was unknown whether it could contain viral microRNA as well as human microRNAs. The aim of this study was to evaluate whether urinary exosomal BK viral microRNA were expressed during replication and could be used to diagnose BKVN in kidney transplant recipients.Materials and methodsIn a cross-sectional multicenter study, we collected and analyzed 458 graft biopsies from 385 kidney transplant recipients. Urine samples were collected at the time of graft biopsy, and microRNAs in urinary exosome were measured once. For 13 patients with BKVN and 67 age, sex-matched kidney transplant recipients, we measured BK viral microRNA B1-5p, 3p and human microRNA-16 in urinary exosomal fraction and compared the diagnostic value with BK viral load in plasma and urine.ResultsPathology proven BKVN was diagnosed in 13 patients (2.8%). High levels of bkv-miR-B1-5p and bkv-miR-B1-3p were shown in all patients with BKVN. Meanwhile, plasma BK viral load assay (cut-off value of ≥ 4.0 log10 copies/mL) showed false negative in 3 cases and urinary BK viral load assay (cut-off value of ≥ 7.0 log10 copies/mL) showed false negative in 1 case among these 13 patients. The receiver operator characteristics curve analysis for bkv-miR-B1-5p and bkv-miR-B1-5p/miR-16 showed excellent discriminative power for the diagnosis of BKVN, with area under the curve values of 0.989 and 0.985, respectively.ConclusionsThis study suggests that urinary exosomal bkv-miR-B1-5p and bkv-miR-B1-5p/miR-16 could be surrogate markers for the diagnosis of BKVN.

The utility of surveillance biopsies in pediatric kidney transplantation.

Surveillance biopsies (SBs) are performed in some pediatric kidney transplant programs, based on data obtained in earlier immunosuppressive eras that the treatment of subclinical acute rejection results in better graft survival. The benefit of SBs for patients on modern immunosuppression regimens is unclear. We have therefore evaluated the clinical utility of SBs in a population of children receiving a kidney transplant. We have performed SBs at 3, 6 and 12months post-transplantation as standard of care at our institution since 2013 in patients on a regimen of rabbit anti-thymocyte globulin, tacrolimus, mycophenolate and rapid steroid taper (RST; steroids maintained in some exceptions). We reviewed pathology reports of 82 SBs from 34 transplants in 34 children for all abnormal findings and adequacy of specimens. Clinical records were reviewed for changes in management resulting from SB findings and for significant procedure complications. Of the 82 biopsies, 41 (50%) had abnormal findings separate from fibrosis, including five Banff Grade I rejections, ten borderline rejections, six calcineurin-inhibitor nephrotoxicity, four BK-virus nephropathy, five recurrent disease and three acute pyelonephritis. Moderate or more fibrosis was present in nine of the 82 (11%) biopsies. Management changes due to SB findings occurred in nine cases (11.0%). The proportion of abnormal findings or management changes did not differ between the RST or steroid-based groups. Patients performing clean intermittent catheterization showed inflammatory changes often read as rejection, but were managed differently. Three biopsies were deemed inadequate. No significant complications occurred. A high percentage of the SBs performed under modern immunosuppression showed abnormal findings even when fibrosis was excluded. However, management changes due to the SB findings were less frequent, although they occurred in a clinically meaningful percentage of cases. Complications or inadequate specimens were rare.

Future directions in the treatment of BK virus nephropathy

Future directions in the treatment of BK virus nephropathy

T cell-mediated rejection is a major determinant of inflammation in scarred areas in kidney allografts.

Inflammation in fibrosis areas (i-IF/TA) of kidney allografts is associated with allograft loss; however, its diagnostic significance remains to be determined. We investigated the clinicohistologic phenotype and determinants of i-IF/TA in a prospective cohort of 1539 kidney recipients undergoing evaluation of i-IF/TA and tubulitis in atrophic tubules (t-IF/TA) on protocol allograft biopsies performed at 1 year posttransplantation. We considered donor, recipient, and transplant characteristics, immunosuppression, and histological diagnoses in 2260 indication biopsies performed within the first year posttransplantation. Nine hundred forty-six (61.5%) patients presented interstitial fibrosis/tubular atrophy (IF/TA Banff grade>0) at 1 year posttransplant, among whom 394 (41.6%) showed i-IF/TA. i-IF/TA correlated with concurrent t-IF/TA (P<.001), interstitial inflammation (P<.001), tubulitis (P<.001), total inflammation (P<.001), peritubular capillaritis (P<.001), interstitial fibrosis (P<.001), and tubular atrophy (P=.02). The independent determinants of i-IF/TA were previous T cell-mediated rejection (TCMR) (P<.001), BK virus nephropathy (P=.007), steroid therapy (P=.039), calcineurin inhibitor therapy (P=.011), inosine-5'-monophosphate dehydrogenase inhibitor therapy (P=.011), HLA-B mismatches (P=.012), and HLA-DR mismatches (P=.044). TCMR patients with i-IF/TA on posttreatment biopsy (N=83/136, 61.0%) exhibited accelerated progression of IF/TA over time (P=.01) and decreased 8-year allograft survival (70.8% vs 83.5%, P=.038) compared to those without posttreatment i-IF/TA. Our results support that i-IF/TA may represent a manifestation of chronic active TCMR.

Treatment for presumed BK polyomavirus nephropathy and risk of urinary tract cancers among kidney transplant recipients in the United States.

Recent case series describe detection of BK polyomavirus (BKV) in urinary tract cancers in kidney transplant recipients, suggesting that BKV could contribute to the development of these cancers. We assessed risk for urinary tract cancers in kidney recipients with or without treatment for presumed BKV nephropathy (tBKVN) using data from the United States Transplant Cancer Match Study (2003-2013). Among 55697 included recipients, 2015 (3.6%) were reported with tBKVN. Relative to the general population, incidence was similarly elevated (approximately 4.5-fold) for kidney cancer in recipients with or without tBKVN, and incidence was not increased in either group for prostate cancer. In contrast, for invasive bladder cancer, incidence was more strongly elevated in recipients with versus without tBKVN (standardized incidence ratios 4.5 vs. 1.7; N=48 cases), corresponding to an incidence rate ratio (IRR) of 2.9 (95% confidence interval [CI] 1.0-8.2), adjusted for sex, age, transplant year, and use of polyclonal antibody induction. As a result, recipients with tBKVN had borderline increased incidence for all urothelial cancers combined (renal pelvis, ureter, and bladder cancers: adjusted IRR 2.2, 95% CI 0.9-5.4; N=89 cases). Together with reports describing BKV detection in tumor tissues, these results support an association between BKV and urothelial carcinogenesis among kidney transplant recipients.

Renal Transplantation in Children with Lower Urinary Tract Dysfunction: A Single-Center Experience

Aim: To evaluate patient and graft survival, as well as the surgical risks of LUTD patients treated at Gazi University Transplantation Center. Renal transplantation in patients with lower urinary tract dysfunction (LUTD) of various origins remains challenging in the field of pediatric transplantation. Patients and Methods: Of 42 pediatric transplantation recipients treated since 2006, LUTD developed in five (12%). Videourodynamic tests were performed on all patients preoperatively, and postoperatively if required. The causes of urological disorders were: Posterior urethral valve (PUV) (n=3), PUV with a neurogenic bladder (n=1), and a meningiomyocele plus a neurogenic bladder (n=1). Continual intermittent catheterization (CIC) was required by three patients for bladder emptying. Three patients received kidneys from deceased donors and two patients received kidneys from living donors. All patients underwent calcineurine-based triple immunosuppressive therapy. No patient underwent pre-transplantation augmentation. Only one patient (with PUV and a neurogenic bladder) underwent an augmentation operation during transplantation surgery. We used the Haberal corner-saving suture technique for ureteral stenting combined with ureteroneocystostomic anastomosis. Results: The mean age at transplantation was 12.2±1.6 years (10-14 years). The median follow-up duration after transplantation was 101 months (68 to 110 months). Two of the five recipients developed BK virus nephropathy (BK). One of the grafts was lost to BK but the other retained normal functioning. No recipient developed urological or surgical complications after transplantation. Three grafts were lost [BK (n=1); chronic allograft nephropathy (n=2)] but the remaining two patients are doing well with median creatinine levels 1.1 mg/dL. The 1-, 3-, and 5-year patient and graft survival rates were: 100%, 100%, 100% and 100%, 100%, 60% respectively. Conclusion: Renal transplantation in children with a LUTD can yield long-term successful outcomes comparable to those in children with non-LUTD. Because of the high complication rates associated with these transplants, careful evaluation, surveillance, and management of pre/post-transplantation periods are essential to optimize these outcomes.

Kidney Disease in Cancer Survivors: Focus on Hematopoietic Stem Cell Transplantation

Kidney disease and hypertension are common among children and adults with cancer, including those undergoing hematopoietic stem cell transplantation (HSCT). While survival has improved over time for patients receiving a HSCT, acute kidney injury (AKI) and chronic kidney disease (CKD) remain associated with significant morbidity and mortality. The mechanisms leading to kidney disease in this population are likely multifactorial and include chemotherapy, other nephrotoxic medications, and infections. Nevertheless, we still do not completely understand why such a large proportion of patients develop kidney disease after HSCT. The growing field of onco-nephrology allows oncologists, transplant providers, and nephrologists to learn about disease processes and treatments relevant to their respective patient populations. Accordingly, we are learning that several mechanisms of injury affecting HSCT recipients also occur in general nephrology and in kidney transplant recipients. For example, complement dysregulation leading to atypical hemolytic uremic syndrome parallels HSCT-associated thrombotic microangiopathy and BK virus nephropathy occurring after kidney transplant can also lead to CKD in HSCT recipients. This review focuses on thrombotic microangiopathy and BK virus infection as potential causes of AKI and CKD after HSCT, which are currently thought to be idiopathic. These diagnoses require a high index of suspicion, emphasizing the importance of close attention to blood pressure, proteinuria, and the measurement and estimation of kidney function in patients undergoing HSCT.