BK virus-induced tubulo-interstitial nephritis in a renal transplant recipient

We present a case of renal BK virus infection with renal allograft dysfunction. Renal allograft biopsy showed mononuclear infiltrates in the interstitium and viral inclusions in the tubular epithelial cells. Infected cells were stained with an anti-polyomavirus antibody. The polymerase chain reaction (PCR) performed on blood, urine, and on the DNA extracted from renal tissue showed the presence of the BK virus DNA sequence. The immunosuppressive therapy including tacrolimus, prednisone, and mycophenolate mofetil was reduced leading to an improvement of the renal function. BK virus infection is now recognized as a cause of renal allograft dysfunction, and has been observed with increasing frequency in recent years. Reactivation of the latent virus occurs in immunocompromised hosts such as organ recipients with immunosuppressive treatment. Histologically, renal BK virus infection is characterized by a lymphocytic interstitial infiltrate, and could mimic acute rejection. The pathologist should diagnose the viral infection and may be helped by urine cytology and immunohistochemistry. An accurate diagnosis is important because antirejection therapy favors the decline of the renal function. Enhanced new immunotherapy protocols seem to be the main risk factor for this infection. The response to reduced immunosuppression is variable with reports of an end stage renal failure in 70% of the patients after 18 months.     

Association of JC virus with tubulointerstitial nephritis in a renal allograft recipient

A renal allograft transplant patient with tubulointerstitial nephritis was examined for possible involvement of human polyomaviruses. Biopsy of the allograft kidney revealed inflammatory interstitial infiltration with tubulitis and typical inclusion bodies in the nucleus of the tubulo-epithelium. Glomeruli showed duplication and lamination of Bowman's capsule with enlargement of the parietal and visceral epithelia. Immunohistochemical analysis on the graft section using a JC virus (JCV) VP1 peptide-specific antibody showed positive staining. Paracrystalline arrays of naked viral particles with diameters of 40 nm were visualized in the nuclear inclusions under an electron microscope. Molecular examination using the polymerase chain reaction (PCR) and DNA sequencing revealed that the JCV was involved in the nephritis. The results indicated that JCV may be associated with tubulointerstitial nephritis.     

Human polyomavirus (BK) infection and ureteric stenosis in renal allograft recipients.

Human polyomavirus (BK) was detected in two renal allograft recipients as a result of routine examination of Papanicolaou-stained smears of urinary sediment in the light microscope. Infection with this recently identified virus was confirmed by virus isolation and electron microscopy. The cytological, histological, and ultrastructural changes due to the virus are described, and virus excretion is correlated with the clinical progress of the patients and the pathological findings. The transplant ureters in both patients were found to be ulcerated and stenosed, and virus-infected cells were observed in the ureteric epithelium. We suggest that the administration of high-dose steroids in transplantation may permit active infection with human polyomavirus to occur in ureteric epithelium which has been damaged by ischaemia or inflammation.     

Distribution of BK polyomavirus genotypes in Tunisian renal transplant recipients

BK polyomavirus (BKV) is a ubiquitous virus in humans that remains latent in the urogenital tract after a primary infection during childhood. The virus, which is reactivated frequently and excreted in urine, can cause nephropathy in renal transplant recipients. BKV sequences are classified into four subtypes (I-IV). Subtype I and IV are divided further into four and six subgroups, respectively. To characterize the subtypes of BKV prevalent in Tunisia, the presence of the virus was investigated by real-time PCR in urine samples from 77 renal transplant recipients. For subtype identification, a DNA fragment in the VP1 coding region, amplified by nested PCR from positive samples, was sequenced and a phylogenetic analysis was performed. In the studied population, subtype I (75.5%), II (14.5%), and IV (2.5%) were identified with a clear predominance of subtype Ib-2 (73%) as observed in European population. This study suggests that in North Africa, the BKV genotype distribution is similar to that of Europe and different from that of sub-Saharan Africa.     

Molecular characterization of BK polyomavirus subtypes in renal transplant recipients in Brazil

BK polyomavirus (BKV) is highly prevalent in the world population. Different reports indicate that BKV subtypes and subgroups present an uneven geographical distribution which might be correlated with human migration. However, there is a lack of data on the BKV subtype distribution in the South American population. The occurrence of BKV subtypes and subgroups detected in 51 kidney transplant recipients in Rio de Janeiro, Brazil is described. According to genetic studies, the population in this region descends mainly from European or African immigrants, with a relatively low genetic background from the Amerindians. By sequencing the VP1 region of BKV, subgroups Ib1 and Ia of subtype I were found in 34 (67%) and 15 (29%), respectively, of samples, while subtype II was present in 2 (4%) of the samples. Subtypes III and IV were not detected. Phylogenetic analysis indicated similarities between Brazilian BKV subgroup Ia and East African lineages; and subgroup Ib-1 with Asian and North American lineages, while subtype II samples were similar to sequences from Japan and the UK. This is the first report that describes distribution of BKV subtypes in South America. The high prevalence of BKV subgroup Ia probably reflects the high proportion of African descendants in this population. On the other hand, the predominance of subgroup Ib-1 and the absence of Ib-2 in an area with a high proportion of European ancestry was unexpected. Further studies in South American populations are needed to provide a better understanding of the epidemiology of BKV in this region.     

Cytogenetic findings in acute monocytic leukemia in a renal allograft recipient

Chromosome analysis of bone marrow cells from a patient with acute monocytic leukemia, who had had a renal transplant followed by immunosuppressive treatment 45 months prior to the onset of leukemia, showed an unusual karyotype: 48,XX,+8,+8, t(1q12----pter::11q12----qter), t(4p12----qter::6p11----pter),t(7p22----qter::12q23 ----qter?), t(1q11----qter::17p11----11qter).     

A novel presentation of cryptococcal infection in a renal allograft recipient

The population of immunosuppressed patients is growing rapidly because of the HIV epidemic and the rapid expansion in transplant medicine. These patients may present to a variety of clinical specialties with seemingly innocuous infections. We present here the first Irish case of primary cryptococcal cellulitis. The patient was a 62-year old renal transplant recipient and was immunosuppressed with Cyclosporine, Azathioprine and Prednisolone. He presented with an apparent bacterial cellulitis on the dorsum of the hand that had failed to respond to a 3-week course of oral antibiotics. There was no clinical evidence of systemic infection. There was tissue necrosis present and the area was debrided surgically. Histological examination of debrided tissue revealed necrotic granulomata and budding yeast-like organisms. Cryptococcus neoformans was cultured from this specimen. The patient was treated with oral fluconazole 400 mg daily for 6 weeks with complete healing of the infected area and no evidence of recurrence after 12 months of follow up. This case emphasises the need for a high index of suspicion for atypical infection in the immunocompromised patient.     

Monitoring of polyomavirus BK virus viruria and viremia in renal allograft recipients by use of a quantitative real-time PCR assay: one-year prospective study

We have developed a real-time quantitative PCR (rt-QPCR) assay to detect and kinetically monitor BK virus viruria and viremia in renal transplant recipients (RTRs). A total of 607 urine and 223 plasma samples were collected from 203 individuals including those with BK virus-associated nephropathy (BKVAN) (n = 8), those undergoing routine posttransplant surveillance (SV) (n = 155), those with nontransplant chronic kidney disease (NT-CKD) (n = 20), and healthy living kidney donors (LD) (n = 20). The rt-QPCR assay was found to be highly sensitive and specific, with a wide dynamic range (2.4 to 11 log(10) copies/ml) and very good precision (coefficient of variation, approximately 5.9%). There was a significant difference in the prevalences of viruria and viremia between the BKVAN (100% and 100%) and SV (23% and 3.9%) groups (P < 0.001). No viruria or viremia was detected in LD or in NT-CKD patients. The median (range) peak levels of BK virus viruria and viremia, in log(10) copies/ml, were 10.26 (9.04 to 10.83) and 4.83 (3.65 to 5.86) for the BKVAN group versus 0 (0 to 10.83) and 0 (0 to 5.65) for the SV group, respectively (P < 0.001). When the BK virus load in the urine was <7.0 log(10) copies/ml, no BK virus viremia was detected. When the BK virus load in the urine reached 7.0, 8.0, 9.0, and > or =10.0 log(10) copies/ml, the corresponding detection of BK virus viremia increased to 20, 33, 50, and 100%, respectively. We propose monitoring of BK virus viruria in RTRs, with plasma BK virus load testing reserved for those with viruria levels of > or =7.0 log(10) copies/ml.     

Late onset opportunistic infections in a renal allograft recipient: a case report

In renal allograft recipients, infection disease complications remain an important cause of morbidity and mortality during the post-transplant period. This complication occurs more frequently from 1 to 6 months after transplant. The epidemiology of infection during the postoperative period is less well characterized, because recipients routinely reside at home. We describe a case of late onset Candida albicans and HSV-1 esophagitis, and Pneumocystis carinii pneumonia, that occurs 9 years after renal transplantation in a patient with severe CD4+ T-lymphocytopenia and hypogammaglobulinaemia. We underline the importance of monitoring immunosuppressive therapy in these patients and the usefulness of prophylaxis against P. carinii pneumonia     

Reversal of severe lactic acidosis with thiamine in a renal allograft recipient

A 48-year-old female patient with end-stage renal failure developed unexplained severe lactic acidosis (LA) associated with hyperglycemia during robotic-assisted laparoscopic renal transplantation. Initial treatment with sodium bicarbonate and insulin infusion were ineffective in treating acidemia. Postoperatively, intravenous administration of thiamine resulted in rapid improvement of LA and blood sugar levels. Uremia and chronic hemodialysis might be the causes behind the quantitative/qualitative deficiency of thiamine unmasked during the surgical stress. Though a rare entity, acute thiamine deficiency should be considered in the differential diagnosis of unexplained severe LA in patients with chronic kidney disease and hemodialysis who undergo major surgery or admitted to critical illness care units.     

Transplacental transmission of human polyomavirus BK

The presence of BK virus (BKV) and JC virus (JCV) in autopsy materials (placenta, brain, and kidney) of aborted fetuses was investigated by PCR using two sets of primers, specific for the regulatory region (RR) and for the capsid protein VP1, respectively. The RR of BKV was detected in 12 samples of placenta and brain and in nine samples of kidney obtained from 15 fetuses. Out of the 12 positive cases, four placentas, one brain, and three kidney samples also showed the presence of BKV DNA in the VP1 region. Of 12 placentas from a control group with a normal pregnancy outcome, the RR of BKV was detected in six samples, four of which were also positive for the VP1 region. None of the samples from either group was positive for the RR of JCV. In two cases, the nucleotide sequence of the BK RR demonstrated that the viruses isolated from maternal and fetal tissues showed a high homology with one another and had a characteristic deletion of the R₆₃ box compared to the archetype strain. The results indicate that BKV may be transmitted vertically. J. Med. Virol. 56:372–376, 1998 . © 1998 Wiley-Liss, Inc.     

Update on human polyomavirus BK nephropathy

Polyomavirus BK (BKV) has ebeen identified as the main cause of polyomavirus‐associated nephropathy, a major cause of renal allograft failure. Although BKV‐associated nephropathy develops in only 2% to 5% of renal transplant recipients, its prognosis when present is very poor, with irreversible graft failure developing in 45% of affected patients. While the use of urine cytology for the detection of decoy cells has been in use for decades, other diagnostic modalities to detect BKV have emerged, including tissue biopsy, polymerase chain reaction, viral culture, and serology. Currently, there is no consensus regarding the laboratory technique best suited for clinical monitoring. This review article will discuss essential and clinical features of polyomavirus, followed by a discussion pertaining to the various diagnostic modalities that contribute to detecting polyomavirus‐associated nephropathy. Diagn. Cytopathol. 2009. © 2009 Wiley‐Liss, Inc.