title: Metabolic acidosis aggravates experimental acute kidney injury.
abstract: OBJECTIVE
  Ischemia/reperfusion (I/R) injury and metabolic acidosis (MA) are two critical conditions that may simultaneously occur in clinical practice. The result of this combination can be harmful to the kidneys, but this issue has not been thoroughly investigated. The present study evaluated the influence of low systemic pH on various parameters of kidney function in rats that were subjected to an experimental model of renal I/R injury.
  
  
  METHODS
  Metabolic acidosis was induced in male Wistar rats by ingesting ammonium chloride (NH4Cl) in tap water, beginning 2 days before ischemic insult and maintained during the entire study. Ischemia/reperfusion was induced by clamping both renal arteries for 45 min, followed by 48 h of reperfusion. Four groups were studied: control (subjected to sham surgery, n=8), I/R (n=8), metabolic acidosis (MA; 0.28 M NH4Cl solution and sham surgery, n=6), and MA+I/R (0.28 M NH4Cl solution plus I/R, n=9).
  
  
  RESULTS
  Compared with I/R rats, MA+I/R rats exhibited higher mortality (50 vs. 11%, p=0.03), significant reductions of blood pH, plasma bicarbonate (pBic), and standard base excess (SBE), with a severe decline in the glomerular filtration rate and tubular function. Microscopic tubular injury signals were detected. Immunofluorescence revealed that the combination of MA and I/R markedly increased nuclear factor κB (NF-κB) and heme-oxygenase 1 (HO-1), but it did not interfere with the decrease in endothelial nitric oxide synthase (eNOS) expression that was caused by I/R injury.
  
  
  CONCLUSIONS
  Acute ischemic kidney injury is exacerbated by acidic conditions.
authors.affiliation: Graduate Program in Pharmaceutical Sciences, Federal University of Ceará, Fortaleza, CE, Brazil.
authors.forename: Patrícia Andréa da Fonseca
authors.initials: PA
authors.lastname: Magalhães
authors.affiliation: Department of Physiology and Pharmacology, Federal University of Ceará, Fortaleza, CE, Brazil.
authors.forename: Teresinha Silva
authors.initials: TS
authors.lastname: de Brito
authors.affiliation: Analytic Centre, Federal University of Ceará, Fortaleza, CE, Brazil.
authors.forename: Rosemayre Souza
authors.initials: RS
authors.lastname: Freire
authors.affiliation: Department of Physiology and Pharmacology, Federal University of Ceará, Fortaleza, CE, Brazil.
authors.forename: Moisés Tolentino Bento
authors.initials: MT
authors.lastname: da Silva
authors.affiliation: Department of Physiology and Pharmacology, Federal University of Ceará, Fortaleza, CE, Brazil.
authors.forename: Armênio Aguiar
authors.initials: AA
authors.lastname: dos Santos
authors.affiliation: Department of Physiology and Pharmacology, Federal University of Ceará, Fortaleza, CE, Brazil.
authors.forename: Mariana Lima
authors.initials: ML
authors.lastname: Vale
authors.affiliation: Department of Pathology, Federal University of Ceará, Fortaleza, CE, Brazil.
authors.forename: Dalgimar Beserra
authors.initials: DB
authors.lastname: de Menezes
authors.affiliation: Department of Clinical and Toxicological Analysis, Federal University of Ceará, Fortaleza, CE, Brazil.
authors.forename: Alice Maria Costa
authors.initials: AM
authors.lastname: Martins
authors.affiliation: Department of Clinical Medicine, Federal University of Ceará, Fortaleza, CE, Brazil; Universidade de Fortaleza, UNIFOR, Fortaleza, CE, Brazil.
authors.forename: Alexandre Braga
authors.initials: AB
authors.lastname: Libório
mesh_terms: D000138:Acidosis / Q000139:chemically induced / Q000150:complications* / Q000473:pathology; D058186:Acute Kidney Injury / Q000150:complications* / Q000401:mortality / Q000473:pathology; D000643:Ammonium Chloride; D000818:Animals; D001639:Bicarbonates / Q000097:blood; D006419:Heme Oxygenase (Decyclizing) / Q000378:metabolism; D006863:Hydrogen-Ion Concentration; D007677:Kidney Function Tests; D008297:Male; D016328:NF-kappa B / Q000378:metabolism; D052250:Nitric Oxide Synthase Type III / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D012077:Renal Artery / Q000473:pathology; D015427:Reperfusion Injury / Q000401:mortality / Q000473:pathology; D014883:Water-Electrolyte Imbalance
chemical_list: D001639:Bicarbonates; D016328:NF-kappa B; D000643:Ammonium Chloride; D052250:Nitric Oxide Synthase Type III; C496316:Nos3 protein, rat; D006419:Heme Oxygenase (Decyclizing); C491523:Hmox1 protein, rat
keywords: Acute kidney injury; Heme-oxygenase 1; Metabolic acidosis; Nuclear factor κB; Renal injury