Metabolic acidosis aggravates experimental acute kidney injury

详细信息    查看全文

• 作者：Patrí ; cia André ; a da Fonseca Magalhã ; es^a ; Teresinha Silva de Brito^b ; Rosemayre Souza Freire^c ; Moisé ; s Tolentino Bento da Silva^b ; Arm&ecirc ; nio Aguiar dos Santos^b ; Mariana Lima Vale^b ; Dalgimar Beserra de Menezes^d ; Alice Maria Costa Martins^e ; Alexandre Braga Libó ; rio^f ; ^g
• 关键词：Metabolic acidosis ; Renal injury ; Heme-oxygenase 1 ; Nuclear factor κB ; Acute kidney injury
• 刊名：Life Sciences
• 出版年：2016
• 出版时间：1 February 2016
• 年：2016
• 卷：146
• 期：Complete
• 页码：58-65
• 全文大小：1443 K

文摘

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.