Acute renal injury

Acute renal failure secondary to ischemia-reperfusion or nephro-toxins represents a major cause of morbidity and mortality in hospitalized patients, particularly in the intensive care unit setting. The proximal tubule region of the nephron suffers the most damage in acute renal injury and is therefore the target site of therapeutic interventions. While several experimental therapies have been attempted to prevent or hasten recovery from acute renal injury,... 

Renal Effects. Rabbits, guinea pigs, rats, and mice dermally exposed to uranyl nitrate hexahydrate for 1 day showed proteinuria for up to 10 days, followed by recovery to control values. The degree of proteinuria did not correlate well with the applied dose of uranium. Rabbits had elevated blood NPN at doses over 270 mg U/kg. The animals that died from dermal exposure to uranium had microscopic renal damage typical of uranium poisoning. The kidneys of the animals that did not die were essentially normal, which may reflect repair of acute renal injury (Orcutt 1949). Chemically induced renal failure caused 100% mortality in male Wistar rats after 5 daily exposures to 237 or 1,928 mg U/kg/day as uranyl nitrate hexahydrate or ammonium uranyl tricarbonate, respectively, applied in a water-Vaseline emulsion (De Rey et al. 1983). Deaths from renal failure were also reported in this study for male Wistar rats that received daily apphcations of 1,965 mg U/kg as uranyl acetate dihydrate for 1-11 days. 

Lin F. Stem cells in kidney regeneration following acute renal injury. Pediatric Research 59 74R-78R, 2006. 

Patschan D, Plotkin M, and Goligorsky MS. Therapeutic use of stem and endothelial progenitor cells in acute renal injury ca ira. Current Opinion in Pharmacology 6 176-183,2006. 

Mishra J, Dent C,Tarabishi R, et al. Neutrophil gelatinase-associated lipocalin (NGAL) as a biomarker for acute renal injury after cardiac surgery. Lancet 2005 365 1231-1238. 

Trof RJ, Di Maggio F, Leemreis J, Groeneveld AB. Biomarkers of acute renal injury and renal failure. Shock 206 26 245-253. 

Ischemic, nephrotoxic, and septic rodent models of acute renal injury were developed to study mechanisms of acute kidney injury. Decreasing renal blood flow is critical in the pathophysiology of AKI in humans. Ischemic and other animal models are used to reproduce the morphological features of human disease. 

Mishra J, Dent C, Tarabishi R, Mitsnefes MM, Ma Q, Kelly C, Ruff SM, Zahedi K, Shao M, Bean J, Mori K, Barasch J, Devarajan P Neutrophil gelatinase-associated lipocalin (NGAL) as a biomarker for acute renal injury after cardiac surgery.fsee comment]. Lancet 365 1231-1238,2005... 

Flammerman M. Growth factors and apoptosis in acute renal injury. Curr Opin Nephrol Flypertens7 419-424,1998. 

Verhelst D, Moulin P, Haufroid V, WitteboleX, Jadoul M, Hantson P. Acute renal injury following methanol poisoning analysis of... 

Kuehnel E, Fisher P. 1986. Acute renal injury limited to the upper poles following gasoline ingestion. Kidney Int 29 304. 

The major risk factor for acute renal failure is an elevated lithium concentration, particularly in association with dehydration. Concomitant therapy with neuroleptic agents may contribute. Chronic nephrotoxicity may result from cumulative damage due to repeated episodes of acute renal injury. 

I. Mechanism of toxicity. Arsine is a potent hemolytic agent. Recent investigations suggest that hemolysis occurs en arsine interacts with heme to fomi a reactive intermediate that alters transmembrane ion flux and greatly increases intracellular calcium. Note Arsenite and other oxidized fomis of arsenic do not cause hemolysis. Deposition of massive amounts of hemoglobin in the renal tubule can cause acute renal injury. Massive hemolysis also decreases systemic oxygen delivery and creates hypoxic stress, and arsine and/or its reaction products exert direct cytotoxic effects on multiple organs. 

McDuffie JE, Sablad M, Ma J, and Snook S. Urinary parameters predictive of cisplatin-induced acute renal injury in dogs. Cytokine. 52(3) 156-62, Dec 2010. 

In a randomised study on the safety and tolerability of spironolactone (25 mg per day) in addition to RAS blocker in 115 nondiabetic patients with early CKD (eGFR>30ml/min/1.73 m ), acute renal injury occurred in three patients, with a significant reduction in eGFR (25-29%) [39]. 

A retrospective chart review conducted over 3years revelled an acute kidney injury rate of 11.2% in those receiving treatment with TMP-SMZ for six or more days [140 ]. A comparison of adverse events between standard dose and high dose TMP-SMX (four double strength tablets per day) revealed an increased risk of hyperkalaemia (3.46% vs 0.81%), acute renal injury (3.67% vs 1.63%) and rash (1.83% vs 0.20%) [141 j. 

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