Expression of renal vitamin D receptors and metabolizing enzymes in IgA nephropathy

Abstract

Aim: One of the main causes of end-stage renal disease (ESRD) in the world is IgA nephropathy (IgAN). Since kidney is a key player in vitamin D metabolism, we investigated the expression of renal vitamin D receptors (VDR) and metabolizing enzymes in IgA nephropathy patients (IgAN-P).

Methods: The sample included twelve IgAN-P who underwent ultrasound-guided renal biopsies and five controls who underwent nephrectomy due to clear renal carcinoma. Immunofluorescent staining was used to determine the expression of VDR, 25-hydroxyvitamin D3 -alpha-hydroxylase (1alpha-OHase) and vitamin D3 24-hydroxylase (CYP24A1).

Results: Significant increase in expression of VDR, which was prominent in distal tubular cells (DTCs) in tissues from IgAN-P, was found in comparison to the controls (p = 0.0368). The expression of 1alpha-OHase, calcitriol synthesizing enzyme, was significantly lower in IgAN-P, in comparison with controls (p < 0.0001). The opposite, expression of CYP24A1 (vitamin D degrading enzyme), was significantly higher in IgAN-P in comparison with controls (p = 0.0003). Additionally, we found significant negative correlation between percentage of CYP24A1 immunoreactive nuclei in proximal tubular cells (PTCs) and estimated glomerular filtration rate (eGFR) in IgAN-P (r = -0.6139; p = 0.0337).

Conclusions: Our research indicates substantially decreased renal calcitriol production and increased vitamin D degradation in kidneys of IgAN-P, but larger studies are needed to confirm our results.

Keywords: 1alpha-OHase; CYP24A1; IgA nephropathy; Kidney biopsy; VDR.