title: Calcium citrate ameliorates the progression of chronic renal injury.
abstract: BACKGROUND
  Metabolic acidosis is a consequence of chronic renal failure and it may produce bone demineralization, muscle proteolysis, and progression of chronic renal failure. The aim of this study was to evaluate the effects of correction of metabolic acidosis with calcium citrate in an experimental model of renal mass ablation.
  
  
  METHODS
  Wistar rats were subjected to 5/6 nephrectomy and were randomly assigned to one of 4 groups: nontreated (NFX); treated with calcium citrate (1.45 g/100 g feed) (NFX-CIT); treated with captopril (500 mg/L water) (NFX-CAP); or treated with both (NFX-CAP-CIT) during 1, 10, or 20 weeks. Body weight, systolic blood pressure, proteinuria, arterial bicarbonate concentration, urine citrate excretion, plasma calcium, and inulin clearance were measured. Histologic glomerular and tubulointerstitial damage scores were measured at 1, 10, and 20 weeks, and glomerular and tubular proliferating cell nuclear antigen (PCNA)-positive cells, alpha-smooth muscle actin, and desmin staining were studied by immunohistochemistry at 1 and 10 weeks.
  
  
  RESULTS
  The treated groups showed significantly less glomerular and tubulointerstitial cellular proliferation in the first week (P < 0.05), less glomerular cell transdifferentiation and higher plasma bicarbonate at 10 weeks (P < 0.05), as well as diminished histologic glomerular and tubulointerstitial damage scores at 20 weeks (P < 0.05). Inulin clearances were higher (P < 0.05), and urine protein excretion rates were lower (P < 0.05) than in the NFX non-treated group, but arterial blood pressure was not significantly different in the NFX-CIT group.
  
  
  CONCLUSIONS
  Calcium citrate slows the progression of chronic renal injury in the 5/6 NFX model. It improves metabolic acidosis and diminishes cell proliferation and transdifferentiation without changes in systolic blood pressure.
authors.affiliation: Departamento de Fisiopatología, Hospital de Clínicas, Facultad de Medicina, Universidad de la República, Montevideo, Uruguay. palil@chasque.apc.org
authors.forename: Liliana
authors.initials: L
authors.lastname: Gadola
authors.forename: Oscar
authors.initials: O
authors.lastname: Noboa
authors.forename: María Natalia
authors.initials: MN
authors.lastname: Márquez
authors.forename: María José
authors.initials: MJ
authors.lastname: Rodriguez
authors.forename: Nicolás
authors.initials: N
authors.lastname: Nin
authors.forename: José
authors.initials: J
authors.lastname: Boggia
authors.forename: Alejandro
authors.initials: A
authors.lastname: Ferreiro
authors.forename: Silvia
authors.initials: S
authors.lastname: García
authors.forename: Virginia
authors.initials: V
authors.lastname: Ortega
authors.forename: María Luisa
authors.initials: ML
authors.lastname: Musto
authors.forename: Paolo
authors.initials: P
authors.lastname: Ponte
authors.forename: Pablo
authors.initials: P
authors.lastname: Sesser
authors.forename: Carlos
authors.initials: C
authors.lastname: Pizarrosa
authors.forename: Silvana
authors.initials: S
authors.lastname: Ravaglio
authors.forename: Ana
authors.initials: A
authors.lastname: Vallega
mesh_terms: D000468:Alkalies / Q000494:pharmacology*; D000818:Animals; D001639:Bicarbonates / Q000097:blood; D019355:Calcium Citrate / Q000494:pharmacology*; D002216:Captopril / Q000494:pharmacology; D002455:Cell Division; D018450:Disease Progression; D004338:Drug Combinations; D007150:Immunohistochemistry; D007444:Inulin / Q000378:metabolism; D007668:Kidney / Q000378:metabolism / Q000473:pathology; D007676:Kidney Failure, Chronic / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology* / Q000652:urine; D007678:Kidney Glomerulus / Q000473:pathology; D007684:Kidney Tubules / Q000473:pathology; D008297:Male; D009392:Nephrectomy; D011507:Proteinuria / Q000209:etiology / Q000652:urine; D011897:Random Allocation; D051381:Rats; D017208:Rats, Wistar
chemical_list: D000468:Alkalies; D001639:Bicarbonates; D004338:Drug Combinations; D007444:Inulin; D002216:Captopril; D019355:Calcium Citrate