Expanding targets of vitamin D receptor activation: Downregulation of several RAS components in the kidney

Medical School, University of Tampere, Department of Internal Medicine, Tampere University Hospital, Tampere, Finland.
Kidney International (Impact Factor: 8.56). 01/2009; 74(11):1371-3. DOI: 10.1038/ki.2008.424
Source: PubMed


Vitamin D receptor (VDR) activation has a beneficial influence on the progression of experimental renal insufficiency, and reduced renal tissue renin expression may play a role in this process. Freundlich and co-workers now report that VDR activation also suppresses the expression of angiotensinogen, angiotensin II type 1 receptor, and renin receptor in the kidneys of 5/6 nephrectomized rats, effects associated with reduced blood pressure and urinary protein excretion and with alleviated renal tissue damage.

Download full-text


Available from: Ilkka Pörsti, Nov 10, 2014
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Chronic kidney disease (CKD) is a common and costly medical condition, and currently available therapeutic options remain unsatisfactory. Vitamin D analogues are widely used for the bone and mineral disorder associated with CKD. However, accumulating evidence suggests that vitamin D analogues may have actions other than their effects on bone and mineral metabolism. In this article, we review the following aspects on the use of vitamin D analogues for the treatment of CKD: (1) epidemiological studies showing that patients with late-stage CKD have better survival than untreated patients; (2) animal studies showing that vitamin D analogues may retard the progression of CKD; (3) human studies on the anti-proteinuric and possibly renal protecting effects of vitamin D analogues in CKD and (4) the potential mechanisms of its therapeutic benefit. Nonetheless, definitive proof of the clinical benefits by randomized control trial would be necessary before one could advocate the routine use of vitamin D analogues for the treatment of CKD patients.
    Full-text · Article · May 2009 · CKJ: Clinical Kidney Journal
  • [Show abstract] [Hide abstract]
    ABSTRACT: A 73-year-old man was admitted with complaints of a 2-month history of generalized weakness and numbness. Laboratory examination revealed hypercalcemia, metabolic alkalosis, and kidney injury, similar to the traditional milk-alkali syndrome. The clinical history and the response to therapy indicated that alphacalcidol and thiazide taken daily were the cause. Recently, it has been recommended the term "milk-alkali syndrome" be replaced by "calcium-alkali syndrome", which broadens the definition of the condition. This case suggests that the calcium-alkali syndrome can occur without calcium and alkali, but rather with alphacalcidol and a thiazide diuretic.
    No preview · Article · Apr 2010 · Internal Medicine
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: During kidney allograft rejection, CXC chemokine ligand 10 (CXCL10)-CXC chemokine receptor 3 (CXCR3) trafficking between peripheral blood and tissues initiates alloresponse and perpetuates a self-inflammatory loop; thus, CXCL10-CXCR3 axis could represent a pharmacologic target. In this perspective, immunosuppressors targeting graft-resident cells, beside immune cells, could be very advantageous. Vitamin D receptor (VDR) agonists exhibit considerable immunomodulatory properties. This study aimed to investigate whether elocalcitol and BXL-01-0029 could decrease the expression of CXCL10 in activated renal tubular cells in vitro and thus be useful in kidney allograft rejection treatment. Experiments were performed in human tubular renal cells stimulated with interferon-gamma + tumor necrosis factor-alpha with and without VDR agonists, tacrolimus, sirolimus, hydrocortisone, methylprednisolone, cyclosporin A and mycophenolate mofetil. CXCL10 protein secretion and gene expression were measured by ELISA and by quantitative PCR. Specific inhibitors were used to investigate intracellular pathways involved in tubular cells activation. For IC(50) determination and comparison, dose-response curves with VDR agonists, tacrolimus and mycophenolic acid were performed. Elocalcitol and BXL-01-0029 inhibited CXCL10 secretion by renal cells, without affecting cell viability, while almost all the immunosuppressors were found to be ineffective, except for tacrolimus and mycophenolate mofetil. BXL-01-0029 was the most potent drug and, notably, it was found to be capable of allowing reduction in tacrolimus-inhibitory doses. Our data suggest that BXL-01-0029 could potentially be a dose-reducing agent for conventional immunosuppressors in kidney rejection management.
    Full-text · Article · Mar 2010 · Transplant International
Show more