ECP 2022 Abstract Book

Virchows Archiv (2022) 481 (Suppl 1):S1–S364 13 PS-04-003 Chief renal medullary osmolytes NaCl and urea differen- tially modulate tubular cellcytokine expression and monocyte recruitment J. Schmitz*, N. Brauns, A.M. Hüsing, M. Flechsig, T. Lepletier Glomb, H. Haller, J.H. Bräsen, S. von Vietinghoff *Nephropathology Unit, Institute of Pathology, Hannover Medical School, Germany Background & objectives: Extreme electrolyte concentrations characterize the renal medulla. Renal immune cells are sentinels against ascending bacteria but also promote detrimental inflam- mation. Here, we investigated how the renal main osmolytes, NaCl and urea, regulate tubular cell cytokine expression and monocyte chemotaxis. Methods: Normal kidneys, transplant surveillance and minimal change biopsies were stained for macrophages, monocytes and cytokines using immunofluorescence and RNA in situ hybridiza- tion. Tissue cytokine concentrations were measured with ELISA. Clinical data, immunosuppressant and diuretic medication were extracted from the records. Human renal tubular cells (HK2) were exposed to NaCl, urea or mannitol. Gene expression was assessed by gene array analysis. Results: In the healthy human kidney, more monocytes were detected in medulla than cortex. The monocyte gradient was attenu- ated in patients with medullary NaCl depletion by loop diuretic therapy and in nephrotic syndrome. Renal tubular epithelial cell gene expression responded similarly to NaCl and tonicity control mannitol, but not urea. NaCl significantly upregulated chemotactic cytokines, e.g., CCL2 and CSF1. This induction was inhibited by ROS scavenger n-acetylcysteine. In contrast urea, the main medul- lary osmolyte in catabolism, dampened tubular epithelial cytokine expression. NaCl-, but not urea stimulated tubular epithelium or cytokine combinations promoted human classical monocyte migration. Consistently, gene array data revealed renal medullary chemokine and monocyte marker decrease in catabolic mice. Conclusion: Our results depict two different renal medullary scenarios depending on whether NaCl or urea is the main osmolyte: The energy intense state with tubular cell cytokine production and recruited myeloid cells in the presence of elevated NaCl may aid antibacterial host response. Less cytokine production and stable myeloid cell populations in presence of elevated urea concentrations may benefit organisms with limited energy supply which may also limit detrimental inflammation. This could be a basis for additional management strategies of patients. Funding: NB was supported by a Hannover Biomedical Research School stipend, JS and JHB by Jackstädt Stiftung and German Ministry for Education and Research (BMBF 13GW0399B), and SvV by grants from MHH HilF2019 and MHH Transplant Centre and Deutsche Forschungsgemeinschaft (450775971 and EXC2151 – 390873048). PS-04-004 Adverse renal effects of immune checkpoint inhibitors: presen- tation of 12 patients undergoing renal biopsy K. Palamaris, A. Stofas*, D. Alexandris, I. Giatras, A. Patereli, H. Theodoropoulou, A. Koutsovasili, C. Kaitatzoglou, E. Psimenou, K. Stylianou, A. Gerakis, N. Alevizopoulos, S. Theocharis, E. Kas- tritis, H. Gakiopoulou *1st Department of Pathology, School of Medicine, National and Kapodistrian University of Athens, Greece Background & objectives: The immunomodulatory activity of immune checkpoint inhibitors (ICIs) often elicits a broad spectrum of immune-related adverse effects (IRAEs), in multiple tissues, including kidney. We present a case series of renal IRAEs with various clinical and histological manifestations. Methods: Twelve patients, bearing a wide range of solid malig- nancies, received either PDL-1, or a combination of PDL-1 and CTLA-4 inhibitors. Following ICIs administration, clinical signs indicative of renal toxicity included acute kidney injury (AKI), proteinuria, nephrotic syndrome and/or haematuria. All patients underwent renal biopsy, which was processed for light micros- copy, immunofluorescence, and when tissue sufficed, electron microscopy. Results: The most frequent clinical presentation was AKI and the most frequent pathologic alteration was tubulointerstitial nephritis (TIN) encountered in six cases. In one of these cases, TIN was accompanied by IgA glomerulonephritis. Two patients, present- ing with nephrotic syndrome, exhibited a secondary “lupus-like” membranous glomerulopathy. In one of the latter patients, there was TIN as well. Among the remaining three patients with AKI, two displayed acute tubular injury as the most prominent finding, while in the third, a combination of membranoproliferative glomer- ulonephritis and thrombotic microangiopathy was identified. The last patient developed nephrotic syndrome and a secondary renal amyloidosis was detected, on a rheumatoid arthritis background presenting after the initiation of ICIs. Conclusion: Our findings harmonize with bibliographical data that identify TIN as the most frequent histological lesion related to ICIs administration. The preferential involvement of tubulointerstitial tissue could be associated with the higher expression levels of PD-1 on tubular epithelial cells, compared to glomeruli. On the other hand, both secondary “lupus-like” membranous glomerulopathy and secondary amyloidosis upon rheumatoid arthritis, are postu- lated to emerge as a consequence of a systemic immune system reconstruction, induced by immune-checkpoints inhibition. PS-04-005 Compensatory and regenerative potential in kidneys of newborns from mothers with complicated pregnancy by preeclampsia and iron deficiency anaemia M. Myroshnychenko*, N. Kapustnyk, A. Shapkin, T. Moiseienko, I. Torianyk, V. Ivannik, T. Chastii, I. Mozhaiev *Kharkiv National Medical University, Ukraine Background & objectives: Preeclampsia (PE) and iron deficiency anaemia (IDA) are pregnancy complications that have a negative effect on women health, their offspring. The objective was to reveal the compensatory and regenerative potential in newborns kidneys that developed under maternal PE, IDA conditions. Methods: The study material was the tissue of kidneys of new- borns from mothers with physiological pregnancy (n=28) (group (G) 1); complicated pregnancy by PE of varying degrees of severity (n=78) (G 2), IDA of varying degrees of severity (n=85) (G 3). Histological, immunohistochemical, morphometrical, statistical methods were used. Results: In newborns kidneys of G 2-3 it was revealed a deficiency of nephrons with the presence of alterative changes in them, hypertrophy of glomeruli with hyperplasia of capillary loops mainly in G 3. Proliferative activity of nephrons structural elements increased in G 2 (Ki-67 proliferative index (PI) – (21.3±2.1)%), G 3 (Ki-67 PI – (38.9±2.7)%) compared with G 1 (Ki-67 PI – (12.5±1.9)%), however, was more pronounced in G 3. In G 2 and especially G 3, there was compensatory angiogenesis activation, as evidenced by an increase in the number of vessels in stroma in these groups (G 2 – 8.3±1.2, G 3 – 11.4±2.1) compared to G 1 (5.6±0.9). Conclusion: In kidneys of newborns from mothers whose preg- nancy was complicated by PE and IDA, compensatory and S85