Renoprotection with vitamin D: Specific for diabetic nephropathy?

Klaus, Guenter

doi:10.1038/sj.ki.5002693

Cited by 22 publications

(18 citation statements)

References 13 publications

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“…6 -9 Inhibition of the renin-angiotensin system by the vitamin D metabolite has been demonstrated in vitro; animal studies suggest that receptor-mediated vitamin D actions have a renoprotective role in diabetic nephropathy. 6,7 These findings are supported by rat studies that show 1,25(OH)2D3 administration attenuates the development of glomerulosclerosis and the progression of proteinuria through parathyroid hormone-independent antiproliferative actions and decreases in podocyte loss and podocyte hypertrophy. 8,9 These findings may be especially pertinent in individuals with diabetic nephropathy because, in addition to the direct impact on renal function, adequate levels of vitamin D are also associated with decreased insulin resistance and reduced blood pressure, the 2 main, potentially modifiable risk factors for diabetic nephropathy initiation and progression.…”

Section: Introductionsupporting

confidence: 68%

The Association of Vitamin D Deficiency and Insufficiency with Diabetic Nephropathy: Implications for Health Disparities

Díaz¹,

Mainous²,

Carek³

et al. 2009

The Journal of the American Board of Family Medicine

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Section: Introductionsupporting

confidence: 68%

The Association of Vitamin D Deficiency and Insufficiency with Diabetic Nephropathy: Implications for Health Disparities

Díaz¹,

Mainous²,

Carek³

et al. 2009

The Journal of the American Board of Family Medicine

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“…Together these actions of the combination therapy lead to an effective prevention of the development of diabetic nephropathy. Given the multiple functionalities of vitamin D, however, the renoprotective effect of paricalcitol may not be limited to the regulation of the RAS (53). This is the first demonstration that vitamin D analogs can be used to block the compensatory renin increase in a combination therapy with RAS inhibitors.…”

Section: Discussionmentioning

confidence: 88%

Combination therapy with AT1 blocker and vitamin D analog markedly ameliorates diabetic nephropathy: Blockade of compensatory renin increase

Zhang

Ning

et al. 2008

Proc. Natl. Acad. Sci. U.S.A.

260

225

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The renin-angiotensin system (RAS) plays a critical role in the development of diabetic nephropathy, and blockade of the RAS is currently used for treatment of diabetic nephropathy. One major problem for the current RAS inhibitors is the compensatory renin increase, which reduces the efficacy of RAS inhibition. We albuminuria ͉ glomerulosclerosis ͉ renin-angiotensin system D iabetic nephropathy is the most common renal complication that often leads to end-stage kidney disease and high mortality (1). Previous studies have suggested the renin-angiotensin system (RAS) as a major mediator of progressive renal injury in diabetic nephropathy. Drugs targeting the RAS including angiotensin (Ang)-converting enzyme inhibitors (ACEIs) and Ang II type 1 receptor blockers (ARBs) have been shown to reduce the progression of glomerulosclerosis, tubulointerstitial fibrosis, and proteinuria (2-6). The systemic components of the RAS are actually down-regulated in diabetic mellitus (7), whereas renal interstitial Ang II levels are estimated to be 1,000-fold higher than in the plasma (8); therefore, intrarenal RAS is thought to play the major damaging role. In fact, all components of the RAS are present within the kidney (9). Cells in the kidney are able to synthesize renin, prorenin/renin receptor (10), angiotensinogen, and Ang II receptors independent of the systemic RAS (11), making the kidney capable of maintaining a high level of intrarenal Ang II. Intrarenal renin and angiotensinogen levels are induced in diabetic animals (12, 13), and high glucose has been shown to stimulate renin and Ang II synthesis in mesangial cells and podocytes (14-16). Intrarenal Ang II exerts multiple effects on the kidney that promote the progression of renal injury; these include an increase in glomerular capillary pressure, induction of profibrotic and proinflammatory cytokine production, promotion of immune cell infiltration, stimulation of cell proliferation and hypertrophy, up-regulation of extracellular matrix (ECM) synthesis, and damaging of podocytes (17)(18)(19) (21), and null mutant mice lacking the vitamin D receptor (VDR) gene develop hyperreninemia, high blood pressure, and cardiac hypertrophy (22)(23)(24). Our recent studies showed that in diabetic state VDR-null mice developed more severe nephropathy than wild-type mice (25), suggesting that vitamin D plays a protective role against hyperglycemia-induced renal injury by regulation of the RAS. However, whether vitamin D or vitamin D analogs have therapeutic effects in intervention or prevention of diabetic nephropathy remains to be tested.Although RAS inhibitors, including ACEIs and ARBs, are widely used in the therapy of renal and cardiovascular diseases, the major problem of these drugs is the compensatory renin rise due to the disruption of the feedback inhibition of renin production (26). The increase in renin activity stimulates the conversion of Ang I and ultimately Ang II, which largely limits the efficacy of RAS inhibition (27,28). The increased renin can also act through the...

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“…The non-classical effects include actions on the heart and vasculature, regulation of the innate and adaptive immune systems, role in inflammatory and auto-immune diseases, release of insulin by pancreatic β cells, prevention of solid organ tumors and also a possible renoprotective effect [20,21].…”

Section: The Biological Actions Of Vitamin D Metabolitesmentioning

confidence: 99%

The virtues of vitamin D—but how much is too much?

2010

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Vitamin D deficiency is common in healthy adults and children as well as in the chronic kidney disease (CKD) population. What was once a disease of malnourished children in the developing world has re-emerged and reached pandemic proportions. In parallel with this development, there is a growing awareness that vitamin D is not simply a 'calcaemic hormone' but plays an important role in the prevention of cardiovascular disease, infectious and auto-immune conditions, renoprotection, glycaemic control and prevention of some common cancers. Most tissues in the body have a vitamin D receptor and the enzymatic machinery to convert 'nutritional' 25-hydroxyvitamin D to the active form 1,25-dihydroxyvitamin D; it is estimated that 3% of the human genome is regulated by the vitamin D endocrine system. Although there are few well-conducted studies on the benefits of vitamin D therapy, an exuberant use of vitamin D is now seen in the general population and at all stages of CKD. There is emerging evidence that vitamin D may in fact have a therapeutic window, and at least from the effects on the cardiovascular system, more is not necessarily better. In this review, we discuss the role of nutritional vitamin D (ergocalciferol or cholecalciferol) supplementation in CKD patients, interpreting the clinical studies in the light of the vitamin D metabolic pathway and its pluripotent effects. While nutritional vitamin D compounds clearly have numerous beneficial effects, randomised controlled studies are required to determine the effectiveness and optimal dose at different stages of CKD, its concurrent use with activated vitamin D compounds and its safety profile.

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Renoprotection with vitamin D: Specific for diabetic nephropathy?

Cited by 22 publications

References 13 publications

The Association of Vitamin D Deficiency and Insufficiency with Diabetic Nephropathy: Implications for Health Disparities

The Association of Vitamin D Deficiency and Insufficiency with Diabetic Nephropathy: Implications for Health Disparities

Combination therapy with AT1 blocker and vitamin D analog markedly ameliorates diabetic nephropathy: Blockade of compensatory renin increase

The virtues of vitamin D—but how much is too much?

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