Abstract
Vitamin D reduces albuminuria in patients with chronic kidney disease (CKD) but its effects on glomerular podocytes are not entirely understood. To evaluate if cholecalciferol supplementation reduces the levels of podocyte-associated urine mRNAs in patients with CKD. A total of 27 patients with stages 2 to 4 CKD and suboptimal serum vitamin D [25(OH)D] levels were treated with cholecalciferol for 6 months. Serum 25(OH)D level, estimated glomerular filtration rate (eGFR), proteinuria, and urine mRNA of nephrin, podocin, podocalyxin, transient receptor potential cation channel 6, vascular endothelial growth factor A, and transforming growth factor beta were assessed before and after intervention. eGFR declined at an average rate of -4.71 mL/min/1.73 m2 (p = 0.010 vs. baseline), being 28 ± 16 mL/min/1.73 m2 at six months. No changes in proteinuria or mineral and bone metabolism parameters were observed after cholecalciferol supplementation. Urinary podocyte-associated mRNAs did not change significantly after treatment. However, patients who achieved 25(OH)D level > 20 ng/mL at six months showed a trend of reduction of urinary nephrin and podocin mRNA levels; in patients with 25(OH)D that remained < 20 ng/mL there was a significant increase in urinary podocalyxin, and a trend of higher expression of urinary nephrin and podocin mRNA. Six months of cholecalciferol supplementation had no effect on urine podocyte-associated mRNA profile of patients with advanced CKD. The protective effect of vitamin D or its analogues on the glomerular podocyte should be investigated in early stages of CKD with a longer treatment period.
Highlights
Vitamin D reduces albuminuria in patients with chronic kidney disease (CKD) but its effects on glomerular podocytes are not entirely understood
Experimental studies demonstrated that vitamin D 1-α-hydroxylase and vitamin D receptor (VDR) are expressed on podocyte suggesting that these cells are able to synthesize active vitamin D, 1.25-dihydroxyvitamin D, which can act via paracrine and/or autocrine signaling pathways.14 1.25-dihydroxyvitamin D interacts intracellularly with the VDR, and this complex is translocated to the nucleus and binds to vitamin D response elements stimulating transcription of slit diaphragm-associated proteins such as nephrin and podocin.[9,15]
After six months of oral cholecalciferol supplementation, serum 25(OH)D levels increased by 90.4% in patients with baseline 25(OH) D levels < 20 ng/mL (p < 0.001), and a smaller but significant 66% increase in serum 25(OH)D was noted in patients with baseline 25(OH)D ≥ 20 ng/mL (p = 0.005); those increases reflect the effectiveness of the prescribed treatment
Summary
Vitamin D reduces albuminuria in patients with chronic kidney disease (CKD) but its effects on glomerular podocytes are not entirely understood. Suboptimal serum vitamin D level is a common finding in patients with chronic kidney disease (CKD).[1,2] Several observational studies have demonstrated an association between vitamin D deficiency and increased albuminuria, lower glomerular filtration rate (GFR), and higher mortality risk.[3,4,5] Both experimental and clinical studies have suggested that vitamin D receptor (VDR) activation can reduce albuminuria, glomerular hyperfiltration, podocyte loss, glomerulosclerosis, interstitial fibrosis, and even all-cause and cardiovascular mortality.[6,7,8,9,10,11,12] vitamin D could have antiproteinuric and renoprotective effects possibly through different mechanisms, including anti-fibrotic, antiinflammatory, and anti-apoptotic inflammatory, and anti-apoptotic pathways.[13].
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