Acute tubular injuries

The inherent limitations of the Jaffe method for determination of creatinine have been discussed in section Assessment of Renal Injury by Serum Chemistry . Factors which result in reduced excretion of creatinine without acute tubular injury (e.g., chronic renal disease in aged animals with pronounced loss of nephron mass, prerenal reduction of GFR) will also result in reduced urine creatinine and falsely elevated enzyme activity when normalized to creatinine (Price 1982, Plummer et al. 1986, Casadevall et al. 1995). 

Two mechanisms responsible for phenylbutazone-induced acute oligo-anuric renal failure include 1) inhibition of uric acid reabsorption, leading to hyperu-ricosuria and, ultimately, bilateral ureteral obstruction due to uric acid stones [112] 2) an idiosyncratic reaction has been reported that results in acute tubular injury without uric acid precipitation [113]. 

Acute tubular necrosis A form of acute renal failure that results from toxic or ischemic (insufficient oxygen) injury to the cells in the proximal tubule of the kidney. 

Renal impairment, including cases of acute renal failure and Fanconi syndrome (renal tubular injury with severe hypophosphatemia), has been reported in association with the use of tenofovir disoproxil fumarate. 

Lieberthal, W. and Nigam, S. K. (1998). Acute renal failure. I. Relative importance of proximal vs. distal tubular injury. Am. J. Physiol. 275 (5 Pt. 2), F623-F631. 

The authors thought that this was the first report of acute transient proximal tubular injury with ecstasy. In contrast to SIADH, there was a high urine output in the presence of hyponatremia and solute diuresis. 

It is worth emphasizing that the same drug is capable of inducing several types of renal injury, e.g. NSAIDs may lead to intrarenal hemodynamic disturbances as well as to acute tubular necrosis, acute interstitial nephritis with or without nephrotic syndrome, and sometimes to various glomerular and arteriolar diseases [50,51]. 

Crystal deposition Particularly important with acyclovir and indinavir, but also noted with sulfonamides, methotrexate and triamterene. This mechanism is becoming more recognized due to the rise in the incidence of tumor-lysis syndrome with AKI. Acute kidney injury caused by tubular obstruction can also occur with a number of drugs (Table 2), due to intratubular precipitation of the... 

Zhang et al [79] recently reported the results of renal biopsies in 104 cases of acute kidney injury complicating CKD. Drug related acute tubulointerstitial neprhritis accounted for 31% of all cases, while an additional 5% had evidence of drug-related acute tubular necrosis by biopsy. NSAIDs were the most common drug responsible for the AKI. 

There is a significant increase in cellular proliferation by surviving proximal tubular cells after renal injury in both animal models [68] and human cases of acute tubular necrosis [43] as measured by PCNA... 

The appearance in the urine of epithelial cells is most likely a result of tubular injury. These cells may be present alone or in casts and be indicative of either acute or chronic tubulointerstitial nephritis. Since casts may dissolve in alkaline urine, an acid urine sample is preferred for analysis. 

ATP depletion, cation shifts and oxygen-derived free radical injury Site of renal ischemia-reperfusion injury A link between proximal and distal tubular injury and recovery Tubuloglomerular feedback and autoregulation Endothelin in ischemia-reperfusion injury Treatment of ischemic acute kidney injury Nephrotoxic injury Cyclosporine... 

Various animal models have been used to study the pathogenesis of acute kidney injury (AKl) and develop therapeutic interventions that prevent or amehorate the severity of tubular injury following an acute ischemic or toxic renal insult. Utilization of animal models has advantages over other in mtro models such as isolated perfused kidneys, isolated proximal tubules, or tubular cell culture. It reproduces the complex interactions of hemodynamics and local tubular factors seen in the whole animal with AKl. 

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... 

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