Metabolic acidosis aggravates experimental acute kidney injury.

Abstract

AIMS:

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.

MAIN 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).

KEY FINDINGS:

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.

SIGNIFICANCE:

Acute ischemic kidney injury is exacerbated by acidic conditions.

• Authors: Patrícia Andréa da Fonseca Magalhães, Teresinha Silva de Brito, Rosemayre Souza Freire, Moisés Tolentino Bento da Silva, Armênio Aguiar dos Santos, Mariana Lima Vale, Dalgimar Beserra de Menezes, Alice Maria Costa Martins, Alexandre Braga Libório
• Journal: Life sciences (Life Sci) Vol. 146 Pg. 58-65 (Feb 01 2016) ISSN: 1879-0631 [Electronic] Netherlands
• PMID: 26773857 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2016 Elsevier Inc. All rights reserved.

Chemical References

• Bicarbonates
• NF-kappa B
• Ammonium Chloride
• Nitric Oxide Synthase Type III
• Nos3 protein, rat
• Heme Oxygenase (Decyclizing)
• Hmox1 protein, rat

Topics

• Acidosis (chemically induced, complications, pathology)
• Acute Kidney Injury (complications, mortality, pathology)
• Ammonium Chloride
• Animals
• Bicarbonates (blood)
• Heme Oxygenase (Decyclizing) (metabolism)
• Hydrogen-Ion Concentration
• Kidney Function Tests
• Male
• NF-kappa B (metabolism)
• Nitric Oxide Synthase Type III (metabolism)
• Rats
• Rats, Wistar
• Renal Artery (pathology)
• Reperfusion Injury (mortality, pathology)
• Water-Electrolyte Imbalance