Acute kidney injury induce

In 1982, we classified exercise-related acute renal failure into two types myoglobinuric acute renal failure, as had previously been reported, and non-myoglobin-related acute renal failure (exercise-induced acute renal failure). In 2002, the latter was named ALPE (Acute renal failure with severe Loin pain and Patchy renal ischemia after anaerobic Exercise) [4]. The term acute kidney injury (AKI) has recently been proposed as a patho-physiologically more correct alternative to the term acute renal failure. Therefore, exercise-induced acute renal failure in this book may be replaced by exercise-induced acute kidney injury. 

Mechanisms of drug induced acute kidney injury... 

Traditionally, when searching for the etiology of AKI, the clinician s will subdivides the potential causes of a sudden decline of GFR into one of three general pathophysiologic processes pre renal failure, intrarenal failure or post renal failure [1]. Recently, Miet et al [ 52] in discussing drug-induce acute kidney injury detailed two additional mechanisms that need to be considered in addition to those outlined in Table 2. 

Schetz M, Dasta J, Goidstein S, and GoiperT. 2005. Drug-induced acute kidney injury. CurrOpin Crit Care 11 555-565. 

The mechanisms of the changes in cell viability during renal injury are incompletely understood. Most of the experimental data have been derived from the ischemia-reperfusion model of acute kidney injury and have focused on necrotic cell death. Because as many as 50% of patients have ischemia-induced acute kidney injury, the observations should be relevant to a large portion of the patients at risk. Also, different stresses initiate common biochemical events, so that understanding the relevant pathways of one stress will most likely be apphcable to others. What follows is a detailed analysis of some of the pathways currently thought to execute cell death in a variety of nephrotoxic insults. 

Renal ischemia/reperfusion injury in vivo activates caspase-1 and caspase-3 [62, 70]. In a murine model of ischemia/ reperfusion injury, ZVAD-fmk, a pancaspase inhibitor, was shown to attenuate reperfusion-induced DNA damage (as determined by TUNEL assay) and inflammation [65]. Down-regulation of caspase-3 and caspase-8 by siRNA provided protection from acute kidney injury in a mice model of ischemia-reperfusion injury (71). Recent studies by Edelstein et al. [66, 72] help estabhsh a hnk between the inflammatory aspects of the ischemic/reperfusion injury and caspase activation. In these studies it was observed that caspase 1 deficient mice were protected from ischemia-reperfusion... 

In the early 1940s, the effect of induced ischemic myopafhy on renal perfusion in the rabbit was studied. It was conclusively demonstrated in this model that there was extreme renal cortical vasoconstriction with preservation of the medullary circulation [17]. This early first demonstration of posttrauma tic vasomotor nephropathy was independently confirmed 20 years later in the USA when preferential renal cortical ischemia was demonstrated in acute kidney injury in man. Since then, many animals have been used to study pathogenesis of AKL Rats and mice are the most popular experimental animals now. Dogs and rabbits are now less often used. Rats and mice are becoming more and more acceptable animals because they are easy to breed. Pigs are also being used [18,19]. 

Yasuda H, Yuen PS, Hu X, Zhou H, Star RA Simvastatin improves sepsis-induced mortality and acute kidney injury via renal vascular effects. Kidney International 69 1535-1542, 2006... 

Rosenberger C, Goldfarb M, Shina A, Bachmann S, Frei L), Eckardt K-U, SchraderT, Rosen S, and Heyman SN. Evidence for Sustained Renal Hypoxia and Transient Hypoxia Adaptation in Experimental Rhabdomyolysis-induced Acute Kidney Injury. Nephrol Dial Transplant doi 10.1093/ndt/gfm808,2007. 

Acute kidney injury can be severe with foscarnet. Some degree of kidney injury has been reported to occur in as many as two-thirds of patients treated with foscarnet and has been a dose-limiting toxicity in 10-20% of cases [51-56]. Despite dose reduction or discontinuation of foscarnet, azotemia typically progresses for at least a few days before resolving. It may be possible to continue foscarnet at reduced doses in some patients with mild azotemia. Foscarnet-induced AKI is usually reversible, although temporary dialysis may be required [57]. Recovery may be slow, particularly in patients with preexisting kidney insufficiency. Elevated serum creatinine concentrations may persist for several months after discontinuation of foscarnet. Foscarnet nephrotoxicity may be also associated with mild proteinuria. Volume expansion with isotonic saline was effective in reducing the incidence of foscarnet nephrotoxicity to 13%, compared to 66% in non-hydrated historical controls, and allowed patients with prior kidney insufficiency to receive foscarnet without further reduction of kidney function [54, 58]. Intermittent, rather than continuous, infusion of foscarnet may also reduce the incidence of nephrotoxicity [52]. 

Acute tubular necrosis, tubulointerstitial nephritis, and glomerulonephritis have been described in patients with foscarnet-induced acute kidney injury [54, 59-62]. Kidney biopsy specimens from patients who had received foscarnet have, in several reports, shown the presence of crystals within glomerular capillaries... 

Patients with chronic renal impairment because of diminished renal prostaglandin production may also be at increased risk of NSAID-induced renal failure. NSAID-induced acute kidney injury has been documented in patients with asymptomatic, but mild chronic renal failure, defined as a recruitment serum creatinine between 133 pmol/L and 265 pmol/L (1.5 and 3.0 mg/dl) [45]. Baseline excretion of urinary prostaglandin and 6-keto-prostaglandin F was quantitatively lower in the individuals who developed NSAID-induced renal decompensation than in those who did not. Upon initiation of ibuprofen, urinary prostaglandin excretion fell in all patients, but trough concentrations were quantitatively lower in the subset of patients who experienced acute kidney injury. 

Diuretics are among the most frequently prescribed drugs for the treatment of both edematous and non-edematous states. With respect to the latter category, they are most often utilized in the therapy of hypertension. They may injure the kidney either reversibly or irremediably, a distinction which often depends upon whether they have induced functional or anatomic damage. Ordinarily, the former type of disorder reverses more rapidly than the latter. However, anatomical lesions, for example those that may be associated with acute kidney injury, may also respond to the removal of the offending agent. 

In 2003, Desmeules et al. described a new pattern of renal failure resulting from the use of OSPS [29]. A 71-year-old female with a baseline creatinine of 1.0 mg/ dl presented with acute kidney injury and a creatinine of 4.5 mg/ dl two weeks following the use of OSPS. Renal biopsy revealed numerous tubular calcium phosphate deposits. Scanning electron microscopy and energy-dispersive x-ray microanalysis revealed that the calcium phosphate deposits formed crystals of hydroxyapatite. The patient s creatinine declined to 1.7 mg/dl at one year of follow-up. The authors described the process as "phosphosoda-induced nephrocalcinosis" and proposed the term "acute phosphate nephropathy". 

Heroin nephropathy/clinical course Amyloidosis associated with intravenous drug abuse HIV nephropathy and its relationship to heroin nephropathy Acute kidney injury due to drug-induced rhabdomyolysis Cocaine-induced renal disease 598 599 601 603 605... 

Acute kidney injury due to drug-induced rhabdomyolysis... 

Almost half of the reported patients with acute kidney injury due to rhabdomyolysis have required dialy tic support. Nevertheless, the majority of patients regain significant renal function. The mortality from drug-induced rhabdomyolysis and ATN has been low despite the common occurrence of intercurrent infection. This may be related to the patients being young and without prior multisystem disease. 

Initial treatment of the acute kidney injury consists of intravascular volume repletion and restoration of the blood pressure. Treatment with mannitol, alkaliniza-tion of the urine and diuretics have all been tried with variable success [110, 111, 122,127]. Clearly, supportive care and dialytic intervention when necessary are crucial to allow for adequate recovery. Hemodialysis may be more effective than peritoneal dialysis in highly catabolic patients with rhabdomyolysis-induced renal failure. 

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