ECP 2023 Abstracts

S75 Virchows Archiv (2023) 483 (Suppl 1):S1–S391 13 Conclusion: The findings of this study suggest that PTC is a frequently observed pathological feature in patients with LN. In addition, the severity of PTC appears to be positively associated with high serum creatinine levels, while higher PTC scores are detected in cases with a high activity index. PS-06-002 Investigating viruses as potential causative agents for tubuloint- erstitial nephritis M. Nackenhorst*, L. Leiendecker, A. Kousanadis, T. Wiesner, K. Smith, P. Lyons, W. Weninger, R. Kain *Medical University of Vienna, Austria Background & objectives: Tubulointerstitial diseases pose a particular challenge within the spectrum of renal diseases, as often no specific causative agents can be identified. There is a significant number of cases where morphological characteristics suspicious for a viral aetiology are seen. Methods: 19 FFPE samples were selected for analysis based on histo- morphological signs of viral infection from the tissue archive of the Department of Pathology at the Medical University of Vienna. DNA and RNA were isolated. We custom build a metagenomic pipeline to adapt to the specific challenge of identifying viral sequences which are small in an abundance of host contamination. Results: The quantity and quality of the resulting DNA and RNA was low, presumably because formalin fixation and par- affin embedding cause fracturing of nucleic acids and protein crosslinking. Library generation was possible for DNA samples exclusively. BK-Polyomavirus was identified in 19/19 cases with our custom pipeline. Two other established pipelines showed comparable results. While all metagenomic pipeline results indicated Polyomavirus as a potential candidate, qPCR did not confirm these results. Potential errors such as multiplexing errors and uneven distribution of reads over the genome were investigated in great detail with no indica- tion of having taken place. Conclusion: Finding the underlying cause for tubulointerstitial nephri- tis (TIN) without proven aetiology could pave the path for implement- ing future targeted treatments and can be considered an important goal - not least from a health economical point of view. Viral agents are, however, most likely not a causative agent in TIN. Viruses remain elusive and difficult to identify in metagenomic approaches and there are several caveats to consider when virus hunting. PS-06-003 Direct infiltration of the kidney by clonal lymphocytic or plasma- cytic populations in the context of haematologic abnormalities: a probably underestimated condition K. Palamaris*, P. Korkolopoulou, P. Foukas, E. Lakiotaki, A. Stofas, M. Kaniadaki, A. Chalkia, A. Gerakis, E. Dermitzaki, E. Theodoro- poulou, M. Papasotiriou, K. Stylianou, E. Papachristou, E. Kastritis, H. Gakiopoulou *First Department of Pathology, National and Kapodistrian University of Athens School of Medicine, Greece Background & objectives: Direct infiltration of the renal parenchyma represents a less frequently reported but probably underestimated mode of renal involvement in the context of lymphoproliferative disorders or plasma cell dyscrasias. We present 20 patients with kidney infiltration by a hematologic neoplastic population. Methods: Light microscopy with histochemical and immunohisto- chemical stains (B-cell/T-cell/plasma-cell markers), immunofluores- cence, and electron-microscopy. IgG-subclasses and DNAJB9 inves- tigations. Clonality-testing was used to confirm the clonal nature of the lesions. Main indications of renal biopsies included acute kidney injury and/or proteinuria/nephrotic syndrome. Of note that in 25% of patients there was not known hematologic abnormality before biopsy, while only one patient had multiple-myeloma(MM). Results: Most biopsies showed infiltration by clonal B-cell or plasma- cell populations compatible with chronic-lymphocytic-leukaemia, mar- ginal-zone-lymphoma, Waldenström-macroglobulinemia, diffuse-large- B-cell lymphoma, mantle-cell-lymphoma or MM. In four cases, defined as either B-cell or plasma-cell malignancy, further typing was unattain- able and additional investigations including control for ΜYD88L265P- mutation, were suggested. In 2 biopsies, renal infiltration by chronic- myelomonocytic-leukaemia (CMML) and a T-cell lymphoproliferative disorder was diagnosed, respectively. Clonality-testing confirmed the clonal nature of the populations observed. Besides direct infiltration, in ~40% of patients, additional patterns of monoclonal kidney injury were observed, including monoclonal-immunoglobulin-deposition-disease, proliferative-glomerulonephritis-with-monoclonal-immunoglobulin- deposits, immunotactoid, fibrillary, cryoglobulinemic glomerulone- phritis, and two membranous cases, one with IgG1-restriction and one in the context of CMML, reported for the first time. Conclusion: Direct renal invasion by neoplastic lympho- or plasma- cytic populations in the context of hematologic abnormalities is prob- ably underestimated. Sometimes, the infiltrates are mild and focal and can be easily overlooked and mistaken for inflammation. In cases with- out coexistent glomerular/tubular involvement missing of these infil- trates may lead to erroneous therapeutic decisions. On the other hand, despite the presence of glomerular/tubular monoclonal involvement, infiltrates also deserve further investigation to reveal their neoplastic nature leading to a more appropriate disease staging and therapy. PS-06-004 Macrophage densities in native kidney biopsies correlate with renal dysfunction and predict end-stage renal disease J. Schmitz*, M.B. Pfenning, I. Scheffner, K. Schulte, A. Khalifa, H. Tezval, A. Weidemann, A. Kulschewski, U. Kunzendorf, S. Dietrich, H. Haller, J.T. Kielstein, W. Gwinner, J.H. Bräsen *Hannover Medical School, Institute of Pathology, Nephropathology, Germany Background & objectives: Renal macrophages and monocytes are main players in inflammation. Their relevance on clinical outcomes remains to be determined in native kidney diseases. Precise quantification of innate immune cell infiltration can support morphological diagnostics. Methods: In our cross-sectional study 324 renal biopsies compris- ing 17 disease entities and normal renal tissues for comparison were included. Samples were stained for CD68+ macrophages, CD14+ monocytes and CD163+ alternatively activated macrophages. Cell densities in cortex, medulla and whole renal tissue were precisely quantified by a pixel-based approach (QuPath). Clinical data at time of biopsy and follow-up data were accessible. Results: Biopsies with native kidney diseases presented higher CD68+- and CD163+-macrophage densities than controls (whole renal tissue, cortex, medulla, P<0.001). CD68+-macrophage densi- ties correlated with eGFR and risk of ESRD (defined as requirement of permanent dialysis) in whole cohort and separate diseases (Spear- man’s/Chi Square test, P<0.05): a high cortical CD68+-macrophage density (>median 0.875%) predicted a higher risk of ESRD at follow- up. Multivariable Cox regression revealed a 4-fold higher risk of ESRD when macrophage density was >median (hazard ratio=3.911, P<0.05), whereas % interstitial atrophy/fibrosis had minimal effect (hazard ratio = 1.032, P<0.001). Patient age, global glomerulosclerosis, presenta- tion (acute kidney injury (AKI), AKI on chronic kidney injury (CKD), CKD) and sex had no effect. Conclusion: Innovative predictive data can be generated by increasing pre- cision and objectivity using digitally-based morphologic analyses. Patients