1,25-Dihydroxyvitamin D₃decreases podocyte loss and podocyte hypertrophy in the subtotally nephrectomized rat

Abstract

1,25(OH)(2)D(3) has antiproliferative effects and promotes cell differentiation. This consideration has provided the rationale for studies in subtotally nephrectomized rats showing that 1,25(OH)(2)D(3) interfered with glomerulosclerosis. The cellular mechanisms involved have remained obscure, however. It was the purpose of the present study to assess glomerular structure and cellular composition in subtotally nephrectomized (SNX) rats treated with nonpharmacological doses of 1,25(OH)(2)D(3). Male Sprague-Dawley rats were sham operated (sham) or underwent SNX under general anesthesia and received either solvent or 1,25(OH)(2)D(3) (3 ng.100 g body wt(-1).day(-1) sc). Blood pressure (BP) and albuminuria were measured. After 16 wk, the remnant renal tissue was perfusion fixed and morphometric and stereological measurements were carried out. The expression of proliferating cellular antigen (PCNA), cyclin-dependent kinase inhibitor p27, Wilms tumor gene (WT1), and desmin, a marker of early podocyte damage, was investigated by immunohistology. BP, serum creatinine, and urinary albumin excretion were significantly higher in SNX than in sham rats. Albuminuria was significantly lower in SNX+1,25(OH)(2)D(3) compared with SNX+solvent rats. Mean glomerular tuft volume was significantly higher in SNX+solvent (2.69 +/- 0.21 gx 10(6) microm(3)) than in sham rats (1.44 +/- 0.17 and 1.28 +/- 0.14 x 10(6) microm(3)); it was significantly (P < 0.05) lower in SNX+1,25(OH)(2)D(3) rats (1.81 +/- 0.16 x 10(6) microm(3)). The main finding was a significantly higher number of podocytes in SNX+1,25(OH)(2)D(3) (88 +/- 9) and sham (98 +/- 17) compared with SNX+solvent rats (81 +/- 8.7). In parallel, the increase in podocyte volume in SNX+solvent rats was abrogated by treatment with 1,25(OH)(2)D(3), and immunohistochemistry revealed less expression of desmin, PCNA, and p27, suggesting less podocyte injury and activation of the cyclin cascade. This study identifies the podocyte as an important target cell for the renoprotective action of 1,25(OH)(2)D(3). This notion is suggested by less evidence of podocyte injury, decreased podocytes loss, and abrogation of podocyte hypertrophy, findings that may also explain less pronounced albuminuria and glomerulosclerosis.

1,25-Dihydroxyvitamin D3 Ameliorates Podocytopenia in Rats with Adriamycin-induced Nephropathy

“…Recent reports indicate that 1,25(OH)2D3 can alleviate podocyte loss and inhibit podocyte hypertrophy in subtotally nephrectomized (SNX) rats (10). These results clearly identify podocyte as a potentially important target for the renoprotective effects of 1,25(OH)2D3.…”

“…Four weeks after injection, when proteinuria was stable, rats were randomly assigned into two groups: nephropathy group (NE, n=12), and nephropathy+1,25(OH)2D3 (ND, n=12), with matched body weight and urinary protein-to-creatinine ratio. Rats in ND group received 1,25(OH)2D3 treatment (3 ng/100 g body weight daily) through a subcutaneous osmotic minipump (10). Normal rats served as control group (NC, n=10).…”

Calcimimetic R-568 or calcitriol: equally beneficial on progression of renal damage in subtotally nephrectomized rats

“…Moreover, beneficial effects of active vitamin D on progression of chronic kidney disease have been documented (13,19).…”

Insuficiência e deficiência de vitamina D em pacientes portadores de doença renal crônica

“…Evidence shows that pleitropic effects of vitamin D go beyond bone and mineral metabolism and the activity of parathyroid glands, thus being possibly related to other potential areas of CKD. It has been demonstrated that vitamin D supplementation has an antiproteinuric effect, 33 to regulate the reninangiotensin-aldosterone, 34 , to reduce histological changes found in glomerulosclerosis, 35 , and, finally, to reduce CKD progression. 4 To sum up even if our population with CKD is in a tropical environment, which leads to more exposure to the sun and, consequently, a higher production and serum levels of 25(OH)D, our study showed that most analyzed patients had serum levels of 25(OH)D below recommended values, especially lower among women and in patients with larger abdominal circumference.…”