Concurrent cytomegalovirus glomerulitis and BK polyomavirus-associated nephropathy in a kidney allograft biopsy

The presence of B-cell clusters in allogenic T cell-mediated rejection (TCMR) of kidney allografts is linked to more severe disease entities. In this study we characterized B-cell infiltrates in patients with TCMR and examined the role of serum CXCL-13 in these patients and experimentally. CXCL-13 serum levels were analyzed in 73 kidney allograft recipients at the time of allograft biopsy. In addition, four patients were evaluated for CXCL13 levels during the first week after transplantation. ELISA was done to measure CXCL-13 serum levels. For further mechanistic understanding, a translational allogenic kidney transplant (ktx) mouse model for TCMR was studied in BalbC recipients of fully mismatched transplants with C57BL/6 donor kidneys. CXCL-13 serum levels were measured longitudinally, CD20 and CD3 composition and CXCL13 mRNA in tissue were examined by flow cytometry and kidneys were examined by histology and immunohistochemistry. We found significantly higher serum levels of the B-cell chemoattractant CXCL13 in patients with TCMR compared to controls and patients with borderline TCMR. Moreover, in patients with acute rejection within the first week after ktx, a >5-fold CXCL13 increase was measured and correlated with B-cell infiltrates in the biopsies. In line with the clinical findings, TCMR in mice correlated with increased systemic serum-CXCL13 levels. Moreover, renal allografts had significantly higher CXCL13 mRNA expression than isogenic controls and showed interstitial CD20+ B-cell clusters and CD3+ cell infiltrates accumulating in the vicinity of renal vessels. CXCL13 blood levels correlate with B-cell involvement in TCMR and might help to identify patients at risk of a more severe clinical course of rejection.

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ADVERSE IMPACT OF MILD HYPERTENSION POST TRANSPLANT ON 1 YEAR CHRONIC INTERSTIAL FIBROSIS AND TUBULAR ATROPY SCORES IN KIDNEY ALLOGRAFT BIOPSY AMONG A COHORT ON RAPID STEROID WITHDRAWL PROTOCOL.

Transplantation Journal ◽

10.1097/00007890-201007272-00715 ◽

2010 ◽

Vol 90 ◽

pp. 387

Author(s):

H. Chakkera ◽

Y. Devarapalli ◽

D. Mulligan ◽

M. Mazur ◽

K. Hamawi ◽

...

Keyword(s):

Mild Hypertension ◽

Adverse Impact ◽

Kidney Allograft ◽

Post Transplant ◽

Allograft Biopsy

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Kidney allograft biopsy: timing to complications

Clinical Nephrology ◽

10.5414/cnp74039 ◽

2010 ◽

Vol 74 (07) ◽

pp. 39-45 ◽

Cited By ~ 15

Author(s):

Z. Yablon ◽

P. Recupero ◽

J. McKenna ◽

J. Vella ◽

M.G. Parker

Keyword(s):

Kidney Allograft ◽

Allograft Biopsy

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Unusual Case of Lipoprotein Glomerulopathy First Diagnosed in a Protocol Kidney Allograft Biopsy

Kidney International Reports ◽

10.1016/j.ekir.2018.09.020 ◽

2019 ◽

Vol 4 (2) ◽

pp. 350-354 ◽

Cited By ~ 2

Author(s):

Ibrahim Batal ◽

Gaia Fakhoury ◽

Emily Groopman ◽

Vivette D. D’Agati ◽

Heather Morris

Keyword(s):

Unusual Case ◽

Lipoprotein Glomerulopathy ◽

Kidney Allograft ◽

Allograft Biopsy

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The Urinary Polyomavirus-Haufen Test: A Highly Predictive Non-Invasive Biomarker to Distinguish “Presumptive” from “Definitive” Polyomavirus Nephropathy: How to Use It—When to Use It—How Does It Compare to PCR Based Assays?

Viruses ◽

10.3390/v13010135 ◽

2021 ◽

Vol 13 (1) ◽

pp. 135

Author(s):

Volker Nickeleit ◽

Vicki G. Davis ◽

Bawana Thompson ◽

Harsharan K. Singh

Keyword(s):

Transplant Recipients ◽

Kidney Transplant Recipients ◽

Non Invasive ◽

Allograft Biopsy ◽

Bk Polyomavirus ◽

Invasive Method ◽

Report Data ◽

Tight Association ◽

Decoy Cell ◽

Cell Shedding

“Definitive” biopsy proven polyomavirus nephropathy (PyVN), usually caused by BK polyomavirus (BKPyV), remains a significant infection of kidney transplants. Diagnosis depends upon an allograft biopsy and outcome depends upon early intervention. Here, we report data on a non-invasive biomarker for PyVN, the urinary PyV-Haufen test. Test results were compared to those of conventional laboratory assays targeting PyV replication, i.e., BKPy-viremia, -viruria and urinary decoy cell shedding. Of 809 kidney transplant recipients, 228 (28%) showed PyV replication with decoy cell shedding and/or BKPy-viremia by quantitative PCR; only a subset of 81/228 (36%) showed “definitive” PyVN. Sensitivity and specificity for identifying patients with PyVN was: 100% and 98%, respectively, urinary PyV-Haufen test; 50% and 54%, respectively, urinary decoy cell shedding; 97% and 32%, respectively, BKPy-viremia with cut-off of ≥250 viral copies/mL; 66% and 80%, respectively, for BKPy-viremia ≥104 viral copies/mL. The PyV-Haufen test showed a very strong correlation with the severity of PyVN (Spearman’s ρ = 0.84) and the Banff PyVN disease classes (p < 0.001). In comparison, BKPy-viremia and -viruria levels by PCR displayed modest correlations with PyVN severity (Spearman’s ρ = 0.35 and 0.36, respectively) and were not significantly associated with disease classes. No association was found between decoy cell shedding and PyVN severity or disease classes. Pilot data demonstrated that PyVN resolution with decreasing Banff pvl-scores was reflected by a gradual decrease in PyV-Haufen shedding; such a tight association was not noted for BKPy-viremia. In conclusion, urinary PyV-Haufen testing is a highly specific, non-invasive method to accurately diagnose patients with “definitive” PyVN and to optimize patient management. Assay specifics are discussed.

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Liver Function Enzymes are Potential Predictive Markers for Kidney Allograft Dysfunction

Advancements in Journal of Urology and Nephrology ◽

10.33140/ajun.02.01.07 ◽

2020 ◽

Vol 2 (1) ◽

Keyword(s):

Liver Function ◽

Estimated Glomerular Filtration Rate ◽

Serum Alkaline Phosphatase ◽

Serum Biomarkers ◽

Kidney Allograft ◽

Individual Level ◽

Allograft Dysfunction ◽

Allograft Biopsy ◽

Allograft Function ◽

Pearson Correlations

Introduction: Biopsy of the allograft is the gold standard for assessing kidney allograft dysfunction. The aim of our pilot study was to identify serum biomarkers that could obviate the need for biopsy. Materials and Methods: We conducted a study to identify the biomarkers in the serum from different groups of chronic kidney disease (CKD) patients and kidney transplanted patients vs. healthy individuals. The four groups (n=25 in each group) were as follows: 1) Patients with unstable kidney allograft transplants requiring biopsy for cause, 2) Patients with stable kidney allograft transplants, 3) Patients with CKD not on immunosuppressive therapy and, 4) healthy subjects. We measured the activity and level of serum alkaline phosphatase (ALP) and other liver enzymes (alanine transaminase (ALT) and aspartate transaminase (AST)) as potential serum biomarkers in acute allograft dysfunction. Results: We found that ALP correlated with allograft biopsy findings, liver function, and clinical outcomes and possibly graft survival. Additionally, AST and ALT were higher in patients with graft rejection compared to non-rejected and stable kidney transplants. Moreover, the low Pearson correlations (r- values) between ALP level with age (r=0.179), gender, body mass index (r=0.236), creatinine (r=0.044) or estimated glomerular filtration rate (r=0.048) suggest that ALP may be an independent biomarker which is relatively unaffected by other individual-level variables. Conclusion: ALP may be a putative biomarker to predict kidney allograft function and rejection. Data also indicated that liver function plays an important role for the overall success of kidney transplantation.

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Conversion from mycophenolate mofetil to mizoribine in the early stages of BK polyomavirus infection could improve kidney allograft prognosis: a single-center study from China

BMC Nephrology ◽

10.1186/s12882-021-02527-3 ◽

2021 ◽

Vol 22 (1) ◽

Author(s):

Ping Li ◽

Dongrui Cheng ◽

Jiqiu Wen ◽

Xuefeng Ni ◽

Kenan Xie ◽

...

Keyword(s):

Mycophenolate Mofetil ◽

Clearance Rate ◽

Preliminary Finding ◽

Common Adverse Effect ◽

Conversion Therapy ◽

Kidney Transplant Recipients ◽

No Donor ◽

Kidney Allograft ◽

Early Stages ◽

Bk Polyomavirus

Abstract Background Some studies have suggested mizoribine (MZR) could inhibit the replication of BK polyomavirus (BKPyV). The purpose of this study was to explore whether conversion from mycophenolate mofetil (MMF) to MZR in the early stages of BKPyV infection can improve kidney allograft prognosis. Methods Twenty-one kidney transplant recipients with BKPyV viruria/viremia and ten with BK polyomavirus-associated allograft nephropathy (BKPyVAN) received MZR conversion therapy were retrospectively identified. The clearance rate of urine and blood BKPyV DNA, change of serum creatinine (SCr), uric acid (UA), hemoglobin (HB), white blood cell (WBC), lymphocyte ratio, platelet (PLT), routine urinalysis, panel reactive antibody (PRA), and gastrointestinal disorders during follow-up of the 2 groups were evaluated and compared. Results After MZR conversion therapy, the clearance rate of urine and blood viral load in BKPyV viruria/viremia group were 85.7 and 100 %, while that in BKPyVAN were 40 and 87.5 %, respectively. Stable SCr were observed in all cases of BKPyV viruria/viremia group, while that of BKPyVAN was only 40 % (P < 0.001) and one even progressed to end-stage renal disease. The results of routine urinalysis in the two groups showed no significant changes before and after MZR conversion therapy. However, in BKPyV viruria/viremia group, four cases developed acute rejection and one had positive PRA-II but no donor specific antibody, requiring conversion back to MMF. Hyperuricemia was the common adverse effect of MZR. Conclusions Conversion from MMF to MZR could help clear BKPyV infection. As compared to BKPyVAN, patients who underwent initiation of MZR conversion therapy in the early stages of BKPyV infection maintained stable allograft function. Prospective studies with larger sample size are needed to ascertain this preliminary finding.

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