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  1. Article ; Online: Diagnosing Polyomavirus Nephropathy without a Biopsy: Validation of the Urinary PyV-Haufen-Test in a Proof-of-Concept Study including Uromodulin Knock-out-Mice.

    Nickeleit, Volker / Butcher, Dalton / Thompson, Bawana D / Rivier, Lauraine H / Singh, Harsharan K

    The Journal of infectious diseases

    2024  

    Abstract: Background: Polyomavirus nephropathy (PyVN) leads to kidney transplant dysfunction and loss. Since a definitive diagnosis requires an invasive kidney biopsy, a timely diagnosis is often hampered. In this clinical dilemma the PyV-haufen-test, centering ... ...

    Abstract Background: Polyomavirus nephropathy (PyVN) leads to kidney transplant dysfunction and loss. Since a definitive diagnosis requires an invasive kidney biopsy, a timely diagnosis is often hampered. In this clinical dilemma the PyV-haufen-test, centering around the detection of three-dimensional PyV aggregates in the urine, might provide crucial diagnostic information.
    Methods: A multistep experimental design. Hypothesis: PyV-haufen form within the kidneys under high concentrations of uromodulin, a kidney specific protein; PyV-haufen are kidney-specific-disease-markers.
    Results: Investigative step A showed colocalization of uromodulin with aggregated PyV (i) in ten kidneys with PyVN by immunohistochemistry, (ii) in urine samples containing PyV-haufen by electron microscopy/immunogold labeling (n = 3), and (iii) in urine samples containing PyV-haufen by immunoprecipitation assays (n = 4). Investigative step B: In in-vitro experiments only high uromodulin concentrations of ≥ 1.25 mg/mL aggregated PyV, as is expected to occur within injured nephrons. In contrast, in voided urine samples (n = 59) uromodulin concentrations were below aggregation concentrations (1.2 -19.6 µg/mL). Investigative step C: 0/11 (0%) uromodulin KO-/- mice with histologic signs of PyVN showed urinary PyV-haufen shedding compared to 10/14 (71%) WT+/+ mice.
    Conclusion: PyV-haufen form within kidneys under high uromodulin concentrations. Thus, PyV-haufen detected in the urine are specific biomarkers for intra-renal disease, i.e. definitive PyVN.
    Language English
    Publishing date 2024-03-01
    Publishing country United States
    Document type Journal Article
    ZDB-ID 3019-3
    ISSN 1537-6613 ; 0022-1899
    ISSN (online) 1537-6613
    ISSN 0022-1899
    DOI 10.1093/infdis/jiae107
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  2. Article: Renal allograft biopsies: a guide of ins and outs for best results.

    Nickeleit, Volker

    Ceskoslovenska patologie

    2015  Volume 51, Issue 4, Page(s) 181–186

    Abstract: Renal allograft biopsies remain the best diagnostic tool to investigate the type and degree of graft injury, provide therapeutic and prognostic information and to assess the extent of irreversible chronic organ damage - if done right. This review ... ...

    Abstract Renal allograft biopsies remain the best diagnostic tool to investigate the type and degree of graft injury, provide therapeutic and prognostic information and to assess the extent of irreversible chronic organ damage - if done right. This review highlights pertinent aspects relevant not only for collecting optimal tissue samples but also for rendering diagnoses. Pathologists and clinicians are provided with "take home messages" and practical tips what to do, what to avoid and what to keep in mind.
    MeSH term(s) Allografts ; Biopsy, Needle/methods ; Graft Rejection/diagnosis ; Humans ; Kidney/pathology ; Kidney Transplantation ; Prognosis
    Language English
    Publishing date 2015
    Publishing country Czech Republic
    Document type Journal Article ; Review
    ZDB-ID 138273-1
    ISSN 1210-7875 ; 0009-0611 ; 0371-1854
    ISSN 1210-7875 ; 0009-0611 ; 0371-1854
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  3. Article ; Online: Classifying Polyomavirus Nephropathy: The "Banff" Initiative.

    Nickeleit, Volker / Singh, H K / Davis, Vicki G / Seshan, Surya V

    Transplant international : official journal of the European Society for Organ Transplantation

    2022  Volume 35, Page(s) 10299

    MeSH term(s) Humans ; Kidney Diseases/virology ; Polyomavirus ; Polyomavirus Infections/virology
    Language English
    Publishing date 2022-03-17
    Publishing country Switzerland
    Document type Letter ; Comment
    ZDB-ID 639435-8
    ISSN 1432-2277 ; 0934-0874
    ISSN (online) 1432-2277
    ISSN 0934-0874
    DOI 10.3389/ti.2022.10299
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  4. Article ; Online: Renal comorbidities in collapsing variant focal segmental glomerulosclerosis: more than a coincidence?

    Gougeon, Francois / Singh, Harsharan K / Nickeleit, Volker

    Nephrology, dialysis, transplantation : official publication of the European Dialysis and Transplant Association - European Renal Association

    2021  Volume 37, Issue 2, Page(s) 311–317

    Abstract: Background: Collapsing focal segmental glomerulosclerosis (FSGS) has various underlying etiologies and often leads to renal failure. The impact of biopsy-proven renal comorbidities in promoting collapsing glomerulopathy (CG) has not been systematically ... ...

    Abstract Background: Collapsing focal segmental glomerulosclerosis (FSGS) has various underlying etiologies and often leads to renal failure. The impact of biopsy-proven renal comorbidities in promoting collapsing glomerulopathy (CG) has not been systematically evaluated in large comparative studies. Those data are reported here.
    Methods: Biopsies with the initial diagnosis of CG in native (n = 321) or transplant kidneys (n = 30) were identified in the University of North Carolina nephropathology database (1 January 2011 to 1 January 2016). Two cohorts were defined: 'sole' CG without and 'accompanied' CG with significant morphologic renal comorbidities. Tip-variant FSGS (T-FSGS) and time-matched biopsies served as control cohorts for comparative analyses.
    Results: CG was significantly more common in native (4.4%) and transplant biopsies (4.1%) compared with T-FSGS (0.7 and <0.1%, respectively, difference versus CG P < 0.01). 'Associated' disease was significantly more common in CG (native: 151/321; 47.0%, transplant: 21/30; 70%, P < 0.05) versus T-FSGS (native: 14/51; 27.5%, transplant: exceptional; all differences versus CG P < 0.05). In native biopsies with 'accompanied' CG but not in control groups, stenosing vasculopathies including thrombotic microangiopathies were significantly more prevalent (P < 0.01). In transplants, the high incidence of 'accompanied' CG was linked to de novo diseases, mainly rejection and vascular injury. In native kidneys, membranous glomerulopathies were prevalent in 'accompanied' T-FSGS (36%) and CG (14%) (difference versus time-matched controls P < 0.01 and P < 0.05, respectively); they were uncommon in transplants.
    Conclusions: CG but not T-FSGS shows a high rate of comorbidities, with prominent vasculopathies presumably driving 'ischemic' CG-specific glomerular injury and also the disease course. These findings facilitate future studies into therapy, prognosis and reversibility of 'accompanied' CG.
    MeSH term(s) Glomerulonephritis, Membranous/pathology ; Glomerulosclerosis, Focal Segmental/diagnosis ; Glomerulosclerosis, Focal Segmental/epidemiology ; Glomerulosclerosis, Focal Segmental/etiology ; Humans ; Kidney/pathology ; Kidney Failure, Chronic/complications ; Kidney Glomerulus/pathology
    Language English
    Publishing date 2021-01-05
    Publishing country England
    Document type Journal Article
    ZDB-ID 90594-x
    ISSN 1460-2385 ; 0931-0509
    ISSN (online) 1460-2385
    ISSN 0931-0509
    DOI 10.1093/ndt/gfaa327
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  5. Article ; Online: Foretelling the future: predicting graft outcome by evaluating kidney baseline transplant biopsies.

    Nickeleit, Volker

    Journal of the American Society of Nephrology : JASN

    2013  Volume 24, Issue 11, Page(s) 1716–1719

    MeSH term(s) Graft Survival ; Humans ; Kidney/pathology ; Kidney Transplantation
    Language English
    Publishing date 2013-08-29
    Publishing country United States
    Document type Editorial ; Comment
    ZDB-ID 1085942-1
    ISSN 1533-3450 ; 1046-6673
    ISSN (online) 1533-3450
    ISSN 1046-6673
    DOI 10.1681/ASN.2013070761
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  6. Book ; Thesis: Der Einfluß amphiphiler Pharmaka auf die Aktivität der (Na-K)-ATPase des Meerschweinchenherzens

    Nickeleit, Volker

    1988  

    Size 76 S. : Ill., graph. Darst.
    Document type Book ; Thesis
    Thesis / German Habilitation thesis Kiel, Univ., Diss., 1988
    HBZ-ID HT003281526
    Database Catalogue ZB MED Medicine, Health

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  7. Article ; Online: 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?

    Nickeleit, Volker / Davis, Vicki G / Thompson, Bawana / Singh, Harsharan K

    Viruses

    2021  Volume 13, Issue 1

    Abstract: 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 ...

    Abstract "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 ≥10
    MeSH term(s) Biomarkers ; Biopsy ; Disease Management ; Disease Susceptibility ; Humans ; Immunohistochemistry ; Kidney Diseases/diagnosis ; Kidney Diseases/etiology ; Kidney Diseases/therapy ; Kidney Diseases/urine ; Kidney Transplantation ; Polymerase Chain Reaction ; Polyomavirus/physiology ; Polyomavirus/ultrastructure ; Polyomavirus Infections/complications ; Polyomavirus Infections/diagnosis ; Polyomavirus Infections/virology ; Prognosis ; Sensitivity and Specificity ; Treatment Outcome ; Urinalysis/methods ; Urinalysis/standards ; Viral Load
    Chemical Substances Biomarkers
    Language English
    Publishing date 2021-01-19
    Publishing country Switzerland
    Document type Journal Article ; Research Support, Non-U.S. Gov't ; Research Support, N.I.H., Extramural
    ZDB-ID 2516098-9
    ISSN 1999-4915 ; 1999-4915
    ISSN (online) 1999-4915
    ISSN 1999-4915
    DOI 10.3390/v13010135
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  8. Article ; Online: Graft Nephrectomy as Rescue Therapy for Posttransplant Rhizopus Pyelonephritis in a Pediatric Patient.

    Baldwin, Xavier L / Serrano Rodriguez, Pablo / Nickeleit, Volker / Toledo, Alexander

    Experimental and clinical transplantation : official journal of the Middle East Society for Organ Transplantation

    2021  Volume 19, Issue 5, Page(s) 489–492

    Abstract: Rhizopus infection is an often-fatal complication after transplant. We present a 3-year-old pediatric patient with end-stage renal disease due to congenital hypoplastic kidneys who underwent deceased donor renal transplant. Approximately 3 months after ... ...

    Abstract Rhizopus infection is an often-fatal complication after transplant. We present a 3-year-old pediatric patient with end-stage renal disease due to congenital hypoplastic kidneys who underwent deceased donor renal transplant. Approximately 3 months after transplant, the patient underwent renal biopsy for a presentation of fevers, acute kidney injury, and imaging evidence of hydronephrosis. The patient was found to have a Rhizopus infection of the transplanted kidney and underwent transplant nephrectomy. In addition to surgical debridement of the infection, the patient was treated with long-term antifungal therapy for complete eradication. After intervention, the patient has had no clinical or imaging evidence of residual or recurrent disease and has been reactivated on the transplant wait list. The positive outcome in this case highlights the importance of rapid diagnosis and treatment of a lethal complication.
    MeSH term(s) Child, Preschool ; Debridement ; Humans ; Kidney Transplantation/adverse effects ; Mucormycosis/surgery ; Nephrectomy ; Pyelonephritis/drug therapy ; Pyelonephritis/surgery ; Rhizopus
    Language English
    Publishing date 2021-02-19
    Publishing country Turkey
    Document type Case Reports ; Journal Article
    ZDB-ID 2396778-X
    ISSN 2146-8427 ; 1304-0855
    ISSN (online) 2146-8427
    ISSN 1304-0855
    DOI 10.6002/ect.2020.0356
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  9. Article ; Online: Ultrastructural Examination of Glomerular Fibrillary Deposits in Diabetic Nephropathy.

    Nagelkerken, Sophie I / Neeskens, Peter H / Rotmans, Joris I / Nickeleit, Volker / Bruijn, Jan A / Bajema, Ingeborg M

    Laboratory investigation; a journal of technical methods and pathology

    2023  Volume 104, Issue 3, Page(s) 100322

    Abstract: Glomerular fibrillary deposits have occasionally been reported in diabetic nephropathy, but no large-scale, ultrastructural evaluation of these deposits has been reported so far. Here, we report our study of glomerular non-Congophilic, DnaJ homolog ... ...

    Abstract Glomerular fibrillary deposits have occasionally been reported in diabetic nephropathy, but no large-scale, ultrastructural evaluation of these deposits has been reported so far. Here, we report our study of glomerular non-Congophilic, DnaJ homolog subfamily B member 9 negative fibrillary deposits in diabetic nephropathy as characterized by transmission electron microscopy. Clinical data from 55 patients with biopsy-confirmed diabetic nephropathy and 18 healthy living donors were reviewed, and their biopsies were evaluated by light microscopy, immunofluorescence, and electron microscopy. Small fibrillary structures with a diameter of 10 ± 1 nm were present in all cases with diabetic nephropathy, regardless of the histologic class. In addition, glomerular fibrillary structures with a diameter of 23 ± 5 nm or 30 ± 7 nm were present in 35 cases. Interestingly, especially the small- and medium-sized fibrils, usually without apparent organization, were comparable with fibrils in fibrillary glomerulopathy. We conclude that glomerular fibrillary deposits occur far more commonly in renal biopsies of patients with diabetic nephropathy than generally considered. This is an important finding because their similarity to fibrils in fibrillary glomerulonephritis may complicate the histologic diagnostic process, especially in cases of overlapping clinical manifestations. Therefore, when encountering fibrillary deposits on electron microscopy, it is important to consider diabetic nephropathy as an alternative diagnosis.
    MeSH term(s) Humans ; Diabetic Nephropathies/pathology ; Kidney Glomerulus/pathology ; Glomerulonephritis ; Microscopy, Electron ; Microscopy, Electron, Transmission ; Diabetes Mellitus
    Language English
    Publishing date 2023-12-30
    Publishing country United States
    Document type Journal Article ; Research Support, Non-U.S. Gov't
    ZDB-ID 80178-1
    ISSN 1530-0307 ; 0023-6837
    ISSN (online) 1530-0307
    ISSN 0023-6837
    DOI 10.1016/j.labinv.2023.100322
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  10. Article ; Online: Pathology: donor biopsy evaluation at time of renal grafting.

    Nickeleit, Volker

    Nature reviews. Nephrology

    2009  Volume 5, Issue 5, Page(s) 249–251

    Abstract: How can we improve the diagnostic value of donor kidney graft biopsies and the management of renal transplant recipients? A recent study developed a morphologic scoring system -- the Maryland Aggregate Pathology Index -- to help predict long-term renal ... ...

    Abstract How can we improve the diagnostic value of donor kidney graft biopsies and the management of renal transplant recipients? A recent study developed a morphologic scoring system -- the Maryland Aggregate Pathology Index -- to help predict long-term renal graft survival from preimplantation donor organ biopsy findings.
    MeSH term(s) Biopsy ; Graft Survival ; Hepatectomy ; Humans ; Kidney/pathology ; Kidney/surgery ; Kidney Transplantation
    Language English
    Publishing date 2009-04-21
    Publishing country England
    Document type Comment ; News
    ZDB-ID 2490366-8
    ISSN 1759-507X ; 1759-5061
    ISSN (online) 1759-507X
    ISSN 1759-5061
    DOI 10.1038/nrneph.2009.50
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