title: Vitamin D deficiency aggravates chronic kidney disease progression after ischemic acute kidney injury.
abstract: BACKGROUND
  Despite a significant improvement in the management of chronic kidney disease (CKD), its incidence and prevalence has been increasing over the years. Progressive renal fibrosis is present in CKD and involves the participation of several cytokines, including Transforming growth factor-β1 (TGF-β1). Besides cardiovascular diseases and infections, several studies show that Vitamin D status has been considered as a non-traditional risk factor for the progression of CKD. Given the importance of vitamin D in the maintenance of essential physiological functions, we studied the events involved in the chronic kidney disease progression in rats submitted to ischemia/reperfusion injury under vitamin D deficiency (VDD).
  
  
  METHODS
  Rats were randomized into four groups: Control; VDD; ischemia/reperfusion injury (IRI); and VDD+IRI. At the 62 day after sham or IRI surgery, we measured inulin clearance, biochemical variables and hemodynamic parameters. In kidney tissue, we performed immunoblotting to quantify expression of Klotho, TGF-β, and vitamin D receptor (VDR); gene expression to evaluate renin, angiotensinogen, and angiotensin-converting enzyme; and immunohistochemical staining for ED1 (macrophages), type IV collagen, fibronectin, vimentin, and α-smooth mucle actin. Histomorphometric studies were performed to evaluate fractional interstitial area.
  
  
  RESULTS
  IRI animals presented renal hypertrophy, increased levels of mean blood pressure and plasma PTH. Furthermore, expansion of the interstitial area, increased infiltration of ED1 cells, increased expression of collagen IV, fibronectin, vimentin and α-actin, and reduced expression of Klotho protein were observed. VDD deficiency contributed to increased levels of plasma PTH as well as for important chronic tubulointerstitial changes (fibrosis, inflammatory infiltration, tubular dilation and atrophy), increased expression of TGF-β1 and decreased expression of VDR and Klotho protein observed in VDD+IRI animals.
  
  
  CONCLUSIONS
  Through inflammatory pathways and involvement of TGF-β1 growth factor, VDD could be considered as an aggravating factor for tubulointerstitial damage and fibrosis progression following acute kidney injury induced by ischemia/reperfusion.
authors.affiliation: Nephrology Department, University of São Paulo School of Medicine, São Paulo, Brazil.
authors.forename: Janaína Garcia
authors.initials: JG
authors.lastname: Gonçalves
authors.affiliation: Nephrology Department, University of São Paulo School of Medicine, São Paulo, Brazil.
authors.forename: Ana Carolina
authors.initials: AC
authors.lastname: de Bragança
authors.affiliation: Nephrology Department, University of São Paulo School of Medicine, São Paulo, Brazil.
authors.forename: Daniele
authors.initials: D
authors.lastname: Canale
authors.affiliation: Nephrology Department, University of São Paulo School of Medicine, São Paulo, Brazil.
authors.forename: Maria Heloisa Massola
authors.initials: MH
authors.lastname: Shimizu
authors.affiliation: Nephrology Department, University of São Paulo School of Medicine, São Paulo, Brazil.
authors.forename: Talita Rojas
authors.initials: TR
authors.lastname: Sanches
authors.affiliation: Nephrology Department, University of São Paulo School of Medicine, São Paulo, Brazil.
authors.forename: Rosa Maria Affonso
authors.initials: RM
authors.lastname: Moysés
authors.affiliation: Nephrology Department, University of São Paulo School of Medicine, São Paulo, Brazil.
authors.forename: Lúcia
authors.initials: L
authors.lastname: Andrade
authors.affiliation: Nephrology Department, University of São Paulo School of Medicine, São Paulo, Brazil.
authors.forename: Antonio Carlos
authors.initials: AC
authors.lastname: Seguro
authors.affiliation: Nephrology Department, University of São Paulo School of Medicine, São Paulo, Brazil.
authors.forename: Rildo Aparecido
authors.initials: RA
authors.lastname: Volpini
mesh_terms: D000199:Actins / Q000378:metabolism; D058186:Acute Kidney Injury; D000808:Angiotensinogen / Q000378:metabolism; D000818:Animals; D018450:Disease Progression; D005353:Fibronectins / Q000378:metabolism; D007668:Kidney; D008297:Male; D051381:Rats; D017208:Rats, Wistar; D018167:Receptors, Calcitriol / Q000378:metabolism; D051436:Renal Insufficiency, Chronic / Q000209:etiology* / Q000378:metabolism* / Q000473:pathology; D012083:Renin / Q000378:metabolism; D015427:Reperfusion Injury / Q000209:etiology* / Q000378:metabolism / Q000473:pathology; D016212:Transforming Growth Factor beta; D053773:Transforming Growth Factor beta1 / Q000378:metabolism; D014808:Vitamin D Deficiency / Q000150:complications* / Q000378:metabolism / Q000503:physiopathology
chemical_list: D000199:Actins; D005353:Fibronectins; D018167:Receptors, Calcitriol; D016212:Transforming Growth Factor beta; D053773:Transforming Growth Factor beta1; D000808:Angiotensinogen; D012083:Renin