TY - JOUR T1 - Impaired Vitamin D Signaling Is Associated With Frequent Development of Renal Cell Tumor in End-stage Kidney Disease JF - Anticancer Research JO - Anticancer Res SP - 6525 LP - 6530 DO - 10.21873/anticanres.14676 VL - 40 IS - 11 AU - JANOS DOCS AU - DANIEL BANYAI AU - TIBOR FLASKO AU - ARPAD SZANTO AU - GYULA KOVACS Y1 - 2020/11/01 UR - http://ar.iiarjournals.org/content/40/11/6525.abstract N2 - Background/Aim: End-stage kidney disease is characterized by chronic inflammation and frequent development of cancer. The level of circulating vitamin D is generally low in patients with end-stage renal disease (ESRD). Experimental studies have implicated the role of dysfunctional vitamin D metabolism in tumorigenesis. Patients and Methods: We analyzed the expression of vitamin D receptor (VDR), cytochrome P450 family 27 subfamily B member 1 (CYP27B1) and cytochrome P450 family 24 subfamily A member 1 (CYP24A1), the key genes involved in vitamin D signaling, in kidneys from patients with ESRD, tissue microarrays containing ESRD-associated renal cell tumors, as well as in their precursor lesions by immunohistochemistry. Results: Kidneys from patients with ESRD showed strong structural rearrangement with only few tubules and epithelial cell groups embedded in fibrotic-inflammatory stroma. Only an estimated 1-3% of the epithelial cells showed positive staining with antibodies to VDR, CYP27B1 and CYP24A1, which contrasted with the 100%, 40-50% and 40-50% of positively stained cells, respectively, found in normal kidneys. Down-regulation of the vitamin D signaling proteins was found in patients with renal cancer, with the exception of tumors and their precursors occurring exclusively in ESRD. Conclusion: The significantly reduced activity of CYP27B1 in kidney from patients with ESRD explains the low level of circulating vitamin D. We suggest that the lack of anti-tumorigenic effect of vitamin D is a crucial factor in the frequent development of unique types of renal cell cancer in in patients with ESRD. ER -