Prerenal factors

Both prerenal factors (dehydration, blood loss, altered vasomotor tone, age-related decreases in renal blood flow in rats) and postrenal factors (obstruction or extravasation of urine to the peritoneal cavity) may cause elevations of the commonly measured analytes that do not reflect primary kidney injury. Plasma analytes also cannot be used to determine the location of renal injury (glomerular versus tubular, or tubular segment affected) (Baum et al. 1975 Corman and Michel 1987 Finco 1997 Newman and Price 1999). 

The precise mechanisms behind the pathogenesis of CIN are as yet unclear. In vitro as well as animal studies suggest a combination of toxic injury to the renal tubules and ischemic injury (prerenal mechanism) partly mediated by reactive oxygen species (19,20). In addition, factors other than osmolality (such as viscosity, hydrophilicity) contribute substantially to the toxic effects of CM (20,21). 

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). 

OKT3, an immunosuppressive monoclonal antibody, can induce systemic vascular changes (leaky syndrome) and prerenal azotemia, presumably by stimulating the release of cytokines (e.g., tumor necrosis factor). These effects are seen more often in poorly hydrated patients. There is also evidence that OKT3 may induce a direct tubular toxicity, since significant numbers of patients developing renal insufficiency also exhibit enzymuria. 

Studies of the pathophysiology of acute renal failure has classically considered both tubular and vascular mechanisms [227,228]. In vitro techniques isolating either the vascular or tubular components have been developed. For example, the use of isolated proximal tubules in suspension or in culture allows the study of tubular mechanisms of injury in the absence of vascular factors [229] [230]. There are both in vitro and in vivo models to study vascular injury in the kidney. In vitro models include the study of vascular smooth muscle cells or endothelial cells in culture. In this section, the in vivo methods to evaluate the renal micro-circulation will be discussed. This is of relevance as many nephrotoxins exert their deleterious effects through pharmacologic actions on the resistance vasculature with parenchymal injury occurring as a consequence of ischemia. In clinical practice nephrotoxins may cause prerenal azotemia as a result of increased renal vascular resistance. Nephrotoxins that cause acute renal failure on a vascular basis include prostaglandin inhibitors e.g. aspirin, non-steroidal anti-... 

---