Some Effects of Ammonium Salts on Renal Histology and Function in the Dog

Abstract

NH₄CI was infused into the left renal artery of anesthetized dogs at 50–125 µM/kg/min for up to 110 min. Renal blood flow declined early then increased to supra-control levels during infusion. Kidneys perfused at 125 µM/kg/min for 90 min showed patchy to confluent mixtures of cortical necrosis and tubular necrosis. Experimental kidneys invariably showed lower urine osmolality than contralateral controls 48 h after perfusion. Kidneys with necrosis showed depressed creatinine clearance as well. Renal artery infusion of NH4 acetate or intravenous infusion of NaHCO₃ during arterial infusion of NH₄CI prevented significant acidosis and caused minimal histological changes, but depression of urine osmolality was not prevented. It is concluded that renal ammonium concentrations up to 40 µM/liter for 90 min does not cause tubular necrosis but does impair urine concentration. Severe tissue damage followed renal exposure to high ammonium concentrations in the presence of metabolic or renal acidosis.

Mechanisms of Metabolic Acidosis–Induced Kidney Injury in Chronic Kidney Disease

“…36,37 Sustained acid exposure causes cortical and tubular necrosis, and treating metabolic acidosis with calcium citrate in 5/6 nephrectomized rats ameliorated glomerular and tubule-interstitial damage as measured by reduction of glomerular and tubular proliferating cell nuclear antigen, a sensitive marker of direct cellular damage in the kidney. [164][165][166][167][168] Oral NaHCO 3 treatment in patients who were acidemic reduced tubular protein catabolism and markers of tubular injury. 166 In these studies, kidney tubular catabolism of technetrium-99m-labeled aprotinin, measuring both metabolism and fractional excretion of this tubule-specific protein, was reduced after treatment; additionally, urinary N-acetyl-b-Dglucosaminidase, an index of kidney tubulointerstitial injury and glomerular filtration, was reduced, suggesting that treating acidosis has the potential to protect kidney tubule structure and function.…”

Ammonia toxicity: from head to toe?

“…Furthermore, ammonia administered to rats lead to disturbances in renal sodium handling that was preceded by activation of kidney mitogen activated protein kinases/extracellular signal regulated kinases (MAPK/ERKs) signaling pathways, and consequently renal injury (Bento et al, 2005). It has been shown that kidneys perfused with ammonium salts results in cortical and tubular necrosis, with necrotic kidneys demonstrating depressed creatinine clearance (Orvell and Wesson, 1976). Ammonia exposure also inhibits tubular cell proliferation in primary rabbit proximal tubular epithelial cells, therefore affecting cell replication (Rabkin et al, 1993).…”

Liver Transplant Patients with High Levels of Preoperative Serum Ammonia Are at Increased Risk for Postoperative Acute Kidney Injury: A Retrospective Study

“…Moreover, in acute hepatic failure, the N-methyl D aspartate receptor is activated, which contributes to kidney damage caused by hyperammonemia [ 36 ]. Ammonium salts in the kidneys causes cortical and coronary necrosis, and necrotic kidneys show a decrease in Cr clearance [ 37 , 38 ]. Overall, these findings suggest that hyperammonemia leads to kidney dysfunction and continued kidney damage.…”