Abstract | BACKGROUND: Renin-angiotensin-aldosterone system (RAAS) blockade provides renoprotective effects in chronic kidney disease (CKD); yet progressive renal function loss remains common. Dietary sodium restriction potentiates the renoprotective effects of RAAS blockade. Vitamin D receptor activator (VDRA) treatment reduces proteinuria, inflammation and fibrosis, but whether these effects depend on sodium intake has not been studied. We hypothesized that the renoprotective effects of VDRA treatment, with or without RAAS blockade, are modulated by sodium intake. METHODS: Six weeks after the induction of adriamycin nephrosis in Wistar rats, i.e. with established proteinuria, animals were treated with the VDRA paricalcitol, lisinopril, the combination, or vehicle; each treatment was given during either a high- (2% NaCl) or a low- sodium (0.05% NaCl) diet for 6 weeks. We assessed proteinuria, blood pressure, renal macrophage accumulation and renal expression of the pre-fibrotic marker alpha-smooth muscle actin (α-SMA) at the end of the treatment. RESULTS: CONCLUSION: The renoprotective effects of the VDRA paricalcitol are blood pressure independent but do depend on dietary sodium status. The combination of RAAS blockade, dietary sodium restriction and VDRA may be a promising intervention to further retard renal function loss in CKD.
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Authors | Katarina Mirkovic, Anne-Roos S Frenay, Jacob van den Born, Harry van Goor, Gerjan Navis, Martin H de Borst, NIGRAM consortium |
Journal | Nephrology, dialysis, transplantation : official publication of the European Dialysis and Transplant Association - European Renal Association
(Nephrol Dial Transplant)
Vol. 32
Issue 8
Pg. 1293-1301
(Aug 01 2017)
ISSN: 1460-2385 [Electronic] England |
PMID | 26311058
(Publication Type: Journal Article)
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Copyright | © The Author 2015. Published by Oxford University Press on behalf of ERA-EDTA. All rights reserved. |
Chemical References |
- Angiotensin-Converting Enzyme Inhibitors
- Bone Density Conservation Agents
- Ergocalciferols
- Receptors, Calcitriol
- Sodium Chloride, Dietary
- Sodium, Dietary
- paricalcitol
- Lisinopril
- Peptidyl-Dipeptidase A
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Topics |
- Angiotensin-Converting Enzyme Inhibitors
(therapeutic use)
- Animals
- Blood Pressure
(drug effects)
- Bone Density Conservation Agents
(pharmacology)
- Diet, Sodium-Restricted
- Ergocalciferols
(pharmacology)
- Glomerulonephritis, Membranous
(etiology, metabolism, prevention & control)
- Glomerulosclerosis, Focal Segmental
(etiology, metabolism, prevention & control)
- Kidney
(drug effects, metabolism, pathology)
- Lisinopril
(pharmacology)
- Male
- Peptidyl-Dipeptidase A
(chemistry)
- Proteinuria
(complications)
- Rats
- Rats, Wistar
- Receptors, Calcitriol
(metabolism)
- Renin-Angiotensin System
(drug effects)
- Sodium Chloride, Dietary
(administration & dosage)
- Sodium, Dietary
(pharmacology)
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