The Measurement of Renal Injury

Abstract

The classical assessment of nephrotoxicity by the measurement of serum urea nitrogen and creatine is insensitive and nonspecific. Selection from a battery of clinical pathology tests allows the sensitive and specific measurement of renal dysfunction and injury. This requires the collection of urine specimens of good technical quality, with appropriate preservation. Interaction of the test article with urinary enzymes should be evaluated prior to their measurement for the assessment of tubular injury. This enables the localization and quantification of the injury within the regions of the nephron. High resolution proton nuclear magnetic resonance spectroscopy, a technique for measurement of low molecular weight metabolites, shows great promise for the evaluation of renal tubular injury in toxicologic studies.

Indices of urine N-acetyl-β-D-glucosaminidase and γ-glutamyl transpeptidase activities in clinically normal adult dogs

“…10 Routine analyses of blood and urine samples that are commonly performed in veterinary medicine detect renal dysfunction in animals only when 66% to 75% of the nephrons become nonfunctional. Values of BUN and sCr concentrations greater than the upper reference limits can be insensitive and nonspecific for detection of acute renal damage 12 and are more likely to indicate a decrease in glomerular filtration rate rather than occurrence of renal tubular injury. Values of BUN and sCr concentrations greater than the upper reference limits can be insensitive and nonspecific for detection of acute renal damage 12 and are more likely to indicate a decrease in glomerular filtration rate rather than occurrence of renal tubular injury.…”

Evaluation of NMR spectral data of urine in conjunction with measured clinical chemistry and histopathology parameters to assess the effects of liver and kidney toxicants

“…Analysis of the clinical chemistry data on days 2 and 3 shows that in general, the renal toxins result in altered levels of CREA and BUN while the hepatotoxins show elevations in the levels of AST and ALT. Increases in BUN are known markers of kidney damage with altered levels of creatinine also found when kidney function is impaired (Loeb, 1998;Emeigh Hart, 2005). Increases in AST and ALT are known markers of liver damage (Jalan and Hayes, 1995;Amacher, 1998).…”

Renal and macrophage aminopeptidase activities in cyclosporin-treated mice

“…These results suggest different sensitivities to Table 2 Lactate dehydrogenase (LDH) activity in soluble (S) and membrane-bound (M) fractions of renal cortex and medulla, and in resident (RE) and thioglycollate-elicited (TGE) macrophages both from control (C) and cyclosporin-treated (CsA) mice CsA between rats and mice. It should also be considered that classical assessment of the glomerular filtration rate, by the measurement of circulating creatinine, is prone to several errors [16]. The development of proteinuria has been preconized as a useful hallmark to distinguish transplant rejection from CsA-induced nephrotoxicity.…”

“…Otherwise, it is well-known that these major APs (APB, APA, CAP, PAP, APN and DPPIV) are highly expressed in the kidney, where they play important roles in the metabolism of different peptides [14]. Increased urinary levels of AP activities have also been associated to renal damage [15,16].…”