SP050KIDNEY Involvement in Hematological Neoplasms. Clinico-Pathological Study of 11 Cases

Abstracts SP048 EXPANDING THE UTILIZATION OF FORMALIN-FIXED, PARAFFIN-EMBEDDED ARCHIVES: FEASIBILITY OF MIRNASEQUENCING FOR DISEASE EXPLORATION AND BIOMARKER DEVELOPMENT FROM BIOPSIES WITH CLEAR CELL RENAL CELL CARCINOMA Ph Strauss7, E Koch7, HP Marti7,1, C Beisland7,3, A Scherer8,5, S Leh2,7, A Flatberg4, V Beisvag4, L Landolt7, T Skogstrand1,6, O Eikrem7,1 1 Department of Medicine, Haukeland University Hospital, Bergen, Norway, 2Department of Pathology, Haukeland University Hospital, Bergen, Norway, 3Department of Urology, Haukeland University Hospital, Bergen, Norway, 4Department of Clinical and Molecular Medicine, Norwegian University of Science and Technology, Trondheim, Norway, 5 Spheromics, Spheromics, Kontiolahti, Finland, 6Department of Biomedicine, University of Bergen, Bergen, Norway, 7Department of Clinical Medicine, University of Bergen, Bergen, Norway and 8Institute for Molecular Medicine Finland, University of Helsinki, Helsinki, Finland INTRODUCTION AND AIMS: Novel predictive tools for clear cell renal cell carcinoma (ccRCC) are urgently needed. microRNAs (miRNAs) have been increasingly investigated for their predictive value, and formalin-fixed paraffin-embedded biopsy archives may potentially be a valuable source of miRNA sequencing material, as they remain an underused resource. METHODS: Core biopsies of both cancerous and adjacent normal tissues were obtained from patients (n¼12) undergoing nephrectomy. After miRNA sequencing, several analyses were performed, including classifier evaluation, obesity-related inquiries, survival analysis using publicly available datasets, comparisons to the current literature and ingenuity pathway analyses. RESULTS: In a comparison of tumour vs normal, 182 miRNAs were found with significant differential expression. miR-155 was of particular interest as it predicted poor survival (hazard ratios of 2.58 and 1.81), classified all ccRCC samples correctly, and correlated well with tumour size (R2¼0.83). CONCLUSIONS: In conclusion formalin-fixed paraffin-embedded biopsy tissues are a viable source of miRNA sequencing material. miRNA-155-5p represents a promising cancer classifier, prognostic marker and therapeutic target in ccRCC that merits further investigation. RESULTS: UUO mice exhibited marked interstitial fibrosis in renal tissue stained with HE and Masson’s trichrome. Treatment with SKLB023 significantly reduced interstitial fibrosis score. What more, expression of pro-fibrogenic marker a-SMA was significantly increased compared with control and UUO group, SKLB023 could significant decrease it by usingimmunofluorescence. The modulation of the gut microbiota was observed after treatment with SKLB023, with increasing similarity between the composition of gut microbiota in the UUO group and that of the control group. This fact was correlated with the change of serum levels of TNF-a, IL-1b and IL-6 between the three groups. CONCLUSIONS: In general, our data showed the antifibrotic benefits of SKLB023 and the association between the gut microbiota with renal interstitial fibrosis, which would provide new insights into the roles of the SKLB023 for renal interstitial fibrosis treatment via microbiota modulation. SP050 KIDNEY INVOLVEMENT IN HEMATOLOGICAL NEOPLASMS. CLINICO-PATHOLOGICAL STUDY OF 11 CASES mezAngel Panizo2, Loreto Fernandez-Lorente1, Joaquin Manrique1, Marisa Go ~ o1 Dorronsoro2, Itziar Castan 1 Nephrology, Complejo Hospitalario de Navarra, Pamplona, Spain and 2Pathology, Complejo Hospitalario de Navarra, Pamplona, Spain INTRODUCTION AND AIMS: Kidney injury can be a complication of hematopoietic neoplasia by both direct and indirect mechanisms. Depending on the type and stage of the malignancy, the spectrum of kidney pathology can be particularly wide. Usually, the kidney infiltration by lymphoma/leukemia is bilateral, asymptomatic, and is diagnosed or suspected in late stages. On the other hand, kidney infiltration can present as acute kidney failure or moderate chronic kidney disease. Very few cases of lymphoma/ leukemia diagnosed by percutaneous kidney biopsy have been reported. METHODS: We reviewed the cases of percutaneous renal biopsies or nephrectomy with leukemia or lymphoma diagnosis between 1990 and 2017. Clinical, radiological and follow-up data were obtained from the clinical history. The biopsies as well as the IHC and molecular results of each case were reviewed. RESULTS: We identified 11 patients (6 male and 5 female). Age: 25-81 years (median 70 years). Radical nephrectomy (3 cases) or needle biopsy (8 cases) showed 8 diffuse large B cell lymphomas (6 DLBCL NOS, 1 DLBCL T-cell rich and 1 intravascular DLBCL), 1 extranodal marginal lymphoma, 1 T cell lymphoblastic lymphoma and 1 myeloid sarcoma. In 2 cases, lymphoma coexisted with renal carcinoma. The hematopoietic neoplasia represented 11/655 (1.68%) renal neoplasms diagnosed during 26 years. Radiologically, 5 patients (45.5%) presented multiple intraparenchymal nodules, 4 single renal mass and 2 diffuse infiltration with an overall increase in renal size. Four patients presented bilateral lesions. Of the 11 cases, 5 had a presumptive clinical diagnosis of renal carcinoma. Two patients had only nodal disease in addition to renal disease and 9 patients had single or multiple extranodal infiltration (6 bone marrow, 1 liver, 1 spleen, 2 skin, 2 CNS, 1 jejunum, and 1 soft tissue) at staging. Follow-up: 7 patients died with disease (1-117 months, median 8 months), 3 were alive disease-free (7-102 months, median 64 months), and1 alive with disease (1 month). CONCLUSIONS: Renal involvement due to hematopoietic neoplasias usually occurs in the context of disseminated disease. Leukemia/lymphoma may show a renal disease with clinical and radiological findings mostly nonspecific. The clinical suspicion of infiltration should arise when patients present with unexplained renal failure or proteinuria and/or bilateral nephromegaly. Percutaneous renal biopsy is essential to establish the correct diagnosis in this situation. Non-Hodgkin B-cell lymphomas predominated, being LDCGB the most common subtype. SP051 ROLE OF NUTRITIONAL STATUS ON THE RISK OF DEVELOPING ACUTE KIDNEY INJURY SP049 GUT MICROBIOTA DRIVES THE ATTENUATION OF RENAL INTERSTITIAL FIBROSIS IN OBSTRUCTIVE NEPHROPATHY BY SKLB023 Yanhuan Feng1, Lingzhi Li1, Fan Guo1, Liang Ma1, Ping Fu1 Kidney Research Institute, Division of Nephrology, West China hospital of Sichuan University, Chengdu, China 1 INTRODUCTION AND AIMS: Renal interstitial fibrosis is the common process underlying the progression of chronic kidney disease to end-stage renal disease and lacking effective treatment therapy. The aim of the study was to investigate the antifibrotic benefits of the novel small-molecule SKLB023 and whether these benefits were affected by modulating the gut-microbiota. METHODS: To discern whether SKLB023 influenced the renal interstitial fibrosis and changed the structure of the gut microbiota during the treatment, unilateral ureteral obstruction (UUO) in mice were obtained. Mice were randomized into three groups (n¼7): (1) sham operated mice (Control group), (2) UUO mice that received daily saline for 7 d by oral gavage (o.g.) after UUO (UUO group), (3) UUO mice treated with SKLB023 50mg/kg/d for 7 d by o.g. after UUO (SKLB023 group). i362 | Abstracts Francisco J Lopez-Hernandez1, Isabel Fuentes-Calvo1, Ana Morales1, Carlos Martinez-Salgado1, Sandra Sancho-Martinez1 1 Physiology & Pharmacology, Biomedical Research Institute of Salamanca, Salamanca, Spain INTRODUCTION AND AIMS: One of the main problems and objectives of public health in developed countries is to prevent and combat the development of the most prevalent chronic diseases (cardiovascular and renal disease, obesity, cancer, etc.), a consequence, in large part, of excessive or unbalanced consumption of specific foods and nutrients. In contrast, in developed countries, hospital malnutrition often goes unnoticed. Different studies have estimated the prevalence of hospital malnutrition in a range between 26.7% and 50%. Malnutrition has a considerable influence on the development of disease and therefore on the evolution of the patient, with significant social and economic consequences. Accordingly, in hospitalized patients, malnutrition may be affecting renal function, due to hemodynamic alterations leading to increased reabsorption of drugs by tubular cells and enhanced nephrotoxicity. If this proves true, preventive action at improving nutritional status will probably reduce both the incidence and the severity of the associated kidney damage, improve patient prognosis and reduce associated costs. Our aim was to study the effect of different degrees of malnutrition on the susceptibility to nephrotoxic drugs in the rat. Downloaded from https://academic.oup.com/ndt/article-abstract/33/suppl_1/i362/4998014 by guest on 03 July 2020 METHODS: Male wistar rats were randomly divided into four groups: control and three hyperoxaluric groups i.e. ethylene glycol alone, ethylene glycol with ammonium chloride and hydroxy-l-proline, respectively. After the induction of hyperoxaluria, 24 hour urine was collected from the rats and THP was isolated from it. To elucidate any changes in the isolated THP conformation its surface hydrophobicity, FTIR spectra were observed and sialic acid content of the protein was estimated. Further, rats were then sacrificed and kidneys were removed and expression of THP and ST-8 in renal tissue was analysed. RESULTS: A concentrated expression of THP near calcium oxalate crystal deposits in the renal tissue of all the hyperoxaluric groups was observed, however no significant altered levels of THP were found at gene level as revealed by the study. Further, hyperoxaluric treatment resulted in the absence of peak at 1462 cm-1 as demonstrated by the FTIR spectrum of THP accompanied by a significant alteration in the extent of hydrophobicity. In addition, sialic acid content of renal tissues and isolated THP was observed to be significantly lowered in the animals exposed to hyperoxaluric insult. CONCLUSIONS: Above mentioned revelations advocate the possibility that hyperoxaluric environment can adversely affect the functional integrity THP by regulating its structural, conformational and functional aspects, thus jeopardising its role in renal stone formation. These findings plausibly could pave a path directed towards the development of novel therapeutic approaches with an aim for remediating urinary glycoproteins. Nephrology Dialysis Transplantation