Vitamin D: a new hope for chronic kidney disease?

Li, Min; Batuman, Vecihi

doi:10.1038/ki.2009.390

Cited by 14 publications

(15 citation statements)

References 15 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…In support of this, the VDR agonists decrease oxidative stress and proinflammatory cytokines and prevent RAS activation (including the AT 1 R) (42). Furthermore, paricalcitol inhibited renin transcription, countering the compensatory ACEI-induced rise in renin, thus achieving a more complete blockade of the RAS (22). Vitamin D analogs may enhance the renoprotective effects of RAS inhibitors.…”

Section: Discussionmentioning

confidence: 95%

“…Of particular interest are the pleiotropic actions of vitamin D and its analogs, which are mediated by the vitamin D receptor (VDR), a ligand-dependent transcription factor that belongs to the steroid nuclear receptor gene family (8,34). Furthermore, VDR activators have not only suppressant effects on the renin-angiotensin system (RAS), but also anti-inflammatory and antifibrotic ones (16,17,22). Thus paricalcitol (19-nor-1,25-dihydroxyvitamin D 2 ) is able to ameliorate renal interstitial fibrosis in obstructive nephropathy (40).…”

mentioning

confidence: 99%

See 1 more Smart Citation

Role of mitochondria in paricalcitol-mediated cytoprotection during obstructive nephropathy

García

Altamirano

Mazzei

et al. 2012

American Journal of Physiology-Renal Physiology

View full text Add to dashboard Cite

Vitamin D slows the progression of chronic kidney disease. Furthermore, activators of vitamin D receptors (VDR) have suppressant effects on the renin-angiotensin system, as well as anti-inflammatory and antifibrotic actions. This study aimed to evaluate the cytoprotective effects of paricalcitol, a VDR activator, at the mitochondrial level using an obstructive nephropathy model [unilateral ureteral obstruction (UUO)]. Rats subjected to UUO and controls were treated daily with vehicle or paricalcitol. The control group underwent a sham surgery. The treatment was done for 15 days (30 ng/kg). The following were determined: biochemical parameters; fibrosis; apoptosis; mitochondrial morphology; VDR, AT(1) receptor, and NADPH oxidase 4 expression; and NADPH oxidase activity (in total and in mitochondrial fractions from the renal cortex). VDR activation prevented fibrosis (20 ± 5 vs. 60 ± 10%) and the number of TUNEL-positive apoptotic cells (10 ± 3 vs. 25 ± 4) in UUO. Biochemical, histological, and molecular studies suggest mitochondrial injury. Electron microscopy revealed in UUO electronically luminous material in the nucleus. Some mitochondria were increased in size and contained dilated crests and larger than normal spaces in their interiors. These changes were not present with paricalcitol treatment. Additionally, high AT(1)-receptor mRNA and NADPH activity was reverted in mitochondrial fractions from obstructed paricalcitol-treated animals (0.58 ± 0.06 vs. 0.95 ± 0.05 relative densitometry units and 9,000 ± 800 vs. 15,000 ± 1,000 relative fluorescence units·μg protein(-1)·min(-1), respectively). These changes were consistent with an improvement in VDR expression (0.75 ± 0.05 vs. 0.35 ± 0.04 relative densitometry units). These results suggest that paricalcitol confers a protective effect and reveal, as well, a possible AT(1) receptor-dependent protective effect that occurs at the mitochondrial level.

show abstract

Section: Discussionmentioning

confidence: 95%

mentioning

confidence: 99%

Role of mitochondria in paricalcitol-mediated cytoprotection during obstructive nephropathy

García

Altamirano

Mazzei

et al. 2012

American Journal of Physiology-Renal Physiology

View full text Add to dashboard Cite

show abstract

“…Furthermore, VDR activators have not only suppressant effects on the renin-angiotensin system (RAS) but also antiinflammatory and anti-fibrotic ones (Husain et al 2009;Husain et al 2010;Li and Batuman 2009). Thus, calcitriol protects renovascular function in hypertension by downregulating AT 1 receptors and reducing oxidative stress (Dong et al 2012).…”

Section: Introductionmentioning

confidence: 99%

Vitamin D receptor-modulated Hsp70/AT1 expression may protect the kidneys of SHRs at the structural and functional levels

García

Altamirano

Mazzei

et al. 2014

Cell Stress and Chaperones

View full text Add to dashboard Cite

Previous hypertension studies have shown that low levels of vitamin D are linked to elevated renin-angiotensin system. The heat shock protein 70 regulates signaling pathways for cellular oxidative stress responses. Hsp70 has been shown to protect against angiotensin II-induced hypertension and exert a cytoprotective effect. Here, we wanted to evaluate whether the vitamin D receptor (VDR) associated with Hsp70/ AT 1 expression may be involved in the mechanism by which paricalcitol provides renal protection in spontaneously hypertensive rats (SHRs). One-month-old female SHRs were treated for 4 months with vehicle, paricalcitol, enalapril, or a combination of both paricalcitol and enalapril. The following were determined: blood pressure; biochemical parameters; fibrosis; apoptosis; mitochondrial morphology; and VDR, AT 1 receptor, and Hsp70 expression in the renal cortex. Blood pressure was markedly reduced by enalapril or the combination but not by paricalcitol alone. However, VDR activation, enalapril or combination, prevented fibrosis, the number of TUNEL-positive apoptotic cells, mitochondrial damage, and NADPH oxidase activity in SHRs. Additionally, high AT 1 receptor expression, like low Hsp70 expression (immunohistochemical/immunofluorescence studies), was reversed in the renal cortices of paricalcitol-and/or enalapriltreated animals (SHRs), and these changes were most marked in the combination therapy group. Finally, all of the recovery parameters were consistent with an improvement in VDR expression. Data suggest that Hsp70/AT 1 modulated by VDR is involved in the mechanism by which paricalcitol provides renal protection in SHRs. We propose that low AT 1 expression through VDR induction could be a consequence of the heat shock response Hsp70-mediated cell protection.

show abstract

“…Our understanding of the molecular mechanisms of kidney injury relies heavily on data from experimental animal models. Thus, there is ample evidence for the beneficial effect of vitamin D receptor activation in experimental kidney injury [16]‐[19]. Based on these experimental data it was hypothesized that paricalcitol inhibition of renin transcription was a key feature of its renoprotective effect [16]‐[19].…”

Section: Discussionmentioning

confidence: 99%

Juxtaglomerular apparatus hyperplasia under dual angiotensin blockade. A footprint of adequate RAS inhibition or a concern for renal fibrosis?

et al. 2012

View full text Add to dashboard Cite

BackgroundDual renin-angiotensin system blockade with angiotensin-converting enzyme inhibitors and angiotensin receptor blockers has been advocated to minimize proteinuria. However, recent trials have questioned the renal safety of this approach. Our understanding on the molecular effects of dual blockade in humans is incomplete.Case presentationWe present a patient with corticoid resistant nephrotic syndrome who developed marked juxtaglomerular apparatus hyperplasia and renin expression in the context of dual angiotensin system blockade.ConclusionsAlthough renin may have profibrotic effects mediated by (pro)renin receptor activation, this report raises questions on the potential consequences of local renin activation on chronic kidney disease in patients with dual angiotensin blockade.

show abstract

Vitamin D: a new hope for chronic kidney disease?

Cited by 14 publications

References 15 publications

Role of mitochondria in paricalcitol-mediated cytoprotection during obstructive nephropathy

Role of mitochondria in paricalcitol-mediated cytoprotection during obstructive nephropathy

Vitamin D receptor-modulated Hsp70/AT1 expression may protect the kidneys of SHRs at the structural and functional levels

Juxtaglomerular apparatus hyperplasia under dual angiotensin blockade. A footprint of adequate RAS inhibition or a concern for renal fibrosis?

Contact Info

Product

Resources

About