Sarat Kuppachi

BK Virus in the Kidney Transplant Patient

Abstract:BK virus, a member of the polyomavirus family, is a well-recognized cause of irreversible graft failure after kidney transplantation. Awareness of the relationship between BK infection and immunosuppression along with better understanding of its pathogenesis has contributed to increasing rates of its diagnosis. Current therapies are aimed at early diagnosis, limiting inflammation caused by the virus and elimination of the virus through different strategies. The epidemiology, pathogenesis and the different modalities of therapy available are discussed in this review along with the approach to retransplantation in the setting of graft failure from BK infection.

BK polyoma virus infection and renal disease in non-renal solid organ transplantation

BK virus (BKV) is a non-enveloped DNA virus of the polyomaviridae family that causes an interstitial nephritis in immunosuppressed patients. BKV nephropathy is now a leading cause of chronic kidney disease and early allograft failure following kidney transplantation. It is also known to cause renal disease with a progressive decline in kidney function in non-renal solid organ transplant (NRSOT) recipients, although the disease may not be recognized nor its impact appreciated in this patient population. In this report, we review the existing literature to highlight our current understanding of its incidence in NRSOT populations, the approaches to diagnosis and the potential treatment options.

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 55 697 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.

An unexpected surge in plasma BKPyV viral load heralds the development of BKPyV associated metastatic bladder cancer in a lung transplant recipient with BKPyV nephropathy

We report a lung transplant recipient who developed BK polyoma virus (BKPyV) DNAemia and BKPyV nephropathy. With careful management of his immunosuppression he achieved significant reduction in BKPyV DNAemia and stabilization of his kidney function. He later developed a high‐grade bladder cancer and shortly thereafter he experienced a major upsurge in the level of BKPyV DNAemia that coincided with the discovery of hepatic metastasis. Retrospectively, the bladder cancer and the hepatic secondary tumor stained uniformly for SV40 large T antigen, and the BKPyV DNA sequences identified in plasma corresponded to BKPyV DNA within hepatic tissue, indicating that the spike in BKPyV load was likely derived from the circulating tumor cells or cell‐free tumor DNA following metastases of a BKV‐associated cancer. To the best of our knowledge, this is the first description of a surge in BKPyV load in a patient with controlled BKPyVN that heralded the appearance of a metastatic urothelial malignancy. This report discusses the literature on BKPyV‐associated malignancies and the possibility that unexplained increases in BKPyV DNAemia may be a biomarker for metastatic BKPyV‐related urothelial cancer.

Bilateral basal ganglia lesions in end-stage kidney disease presenting as acute chorea

Acute movement disorder associated with bilateral basal ganglia (AMDBBG) lesions is a syndrome that affects patients with diabetic uremia and, for reasons yet unclear, has been reported mostly in patients from Asia [1–3]. We report the case of a diabetic female with end-stage kidney disease (ESKD) who developed chorea with bilateral basal ganglia lesions. The unique radiological findings associated with this condition are described.

The challenge in diagnosing de novo minimal change disease after transplantation.

A man with end-stage kidney disease (ESKD) secondary to renal coloboma syndrome received an en bloc kidney transplant from a 5-month-old donor. He was induced with thymoglobulin and discharged on tacrolimus, mycophenolate mofetil, and prednisone. Three months later, he was without complaint, had a creatinine of 1.4 mg/dL, and urine protein creatinine ratio (UPCR) of 5.7. He tested negative for hepatitis B, hepatitis C, and human immunodeficiency viruses. A kidney biopsy revealed immature-appearing glomeruli with moderate mesangial matrix expansion and focal mesangial hypercellularity. There was no interstitial inflammation and minimal interstitial fibrosis or tubular atrophy. Immunofluorescence examination was negative for immunoglobulins or complement deposits. Ultrastructural evaluation showed diffuse epithelial foot process effacement and podocyte injury. There were no electron dense deposits. Tubuloreticular inclusions were noted (Figure 1), because of which he underwent polymerase chain reaction testing for cytomegalovirus, BK virus and Epstein-Barr virus, all of which were negative. He was diagnosed to have de novo minimal change disease (MCD) and treated with prednisone 1 mg/kg daily and lisinopril 5 mg daily. Eight weeks later, his UPCR was 0.5, and prednisone was tapered over the next 2 months. His UPCR further decreased to 0.1. Twenty months after the diagnosis his UPCR is 0.1 and creatinine 0.9 mg/dL. Minimal change disease is characterized by the clinical picture of nephrotic syndrome without a reduction in glomerular filtration rate where a kidney biopsy shows normal glomeruli on light microscopy (or only minimal mesangial prominence), negative or low-level staining for C3, immunoglobulin M staining on immunofluorescence microscopy, and diffuse foot process effacement on electron microscopy. It was hypothesized to be caused by a secreted factor resulting from systemic T-cell dysfunction that damages the glomerular basement membrane. Some recent studies have suggested that podocyte expression of B7-1(CD-80)

Acute antibody-mediated renal allograft rejection associated with HLA-Cw17 antibody

Detection of donor-specific human leukocyte antigen (HLA) antibodies is an important part of diagnosis of antibody-mediated rejection (AMR) in the renal transplant population. Donor-specific antibodies (DSA) against HLA-C, a Class 1 major histocompatibility gene product, are not considered to be of major importance in renal transplant rejection. Typing for HLA-C is not a routine part of pre- and post-transplant evaluation. In roughly 10% of biopsy-proven C4d-positive rejections, DSA are not detected by standard testing protocols. In some of these cases, minor HLA and non-HLA antibodies have been implicated. The role of HLA-C antibodies in this patient group is not clear. We present a patient with acute renal graft dysfunction 21 months post-transplant. The allograft biopsy showed features of AMR with diffuse margination of inflammatory cells and diffuse C4d staining in peritubular capillaries. HLA-Cw17 antibody was detected by single-bead antigen Luminex assay, which was further confirmed by a mock flow crossmatch. This case highlights the importance of checking anti-HLA-Cw antibodies in patients with AMR and no detectable DSA using standard methods.