L-arginine metabolism in dog kidney and isolated nephron segments.

The renal basic amino acid metabolism often differs in rodents, strict carnivores, and omnivore species. Given the pivotal role of L-arginine and L-ornithine in several metabolic pathways and the fact that the dog is closely related to humans, being also an omnivore, we tested whether L-arginine metabolism and L-ornithine catabolism take place in the dog kidney. We examined the metabolism of L-arginine in dog cortical tubules to integrate local L-arginine metabolism into a general physiological and metabolic framework. To achieve these goals, we first ascertained the protein expression of relevant enzymes by Western blot. L-Arginine catabolism was studied in suspensions of canine cortical proximal tubules, medullary thick ascending limbs, and papillary collecting ducts either incubated without exogenous L-arginine being added (small endogenous quantities) or incubated with L-arginine being added in supraphysiological amounts (2 mmol/L with or without the presence of alternative metabolic substrates, 2 mmol/L L-glutamine, or lactate). The results revealed that dog kidneys consumed L-citrulline and released L-arginine and L-ornithine. Argininosuccinate synthetase and lyase, arginase II, and ornithine aminotransferase were detected in the renal cortex. Arginase II activity was found in a suspension of proximal tubules by measuring the amounts of urea and L-ornithine produced. A fraction of this L-ornithine was further partially metabolized through the intramitochondrial ornithine aminotransferase pathway, leading to changes in L-glutamate, glucose, L-alanine, and ammonia metabolism without L-proline accumulation. Medullary thick ascending limbs expressed a very low arginase activity, whereas papillary collecting ducts did not. In conclusion, the dog kidney produces L-arginine. Part of this L-arginine is further catabolized by arginase II, suggesting that its physiological role was to produce L-ornithine for the body.

Single-slice dynamic computed tomographic determination of glomerular filtration rate by use of Patlak plot analysis in anesthetized pigs.

OBJECTIVE: To compare glomerular filtration rate (GFR) as estimated from Patlak plot analysis by use of single-slice computed tomography (CT) with that obtained from clearance of plasma inulin in pigs. ANIMALS: 8 healthy anesthetized juvenile pigs. PROCEDURES: All pigs underwent precontrast, whole-kidney, helical CT; postcontrast single-slice dynamic CT; and postcontrast, whole-kidney CT for volume determination. On dynamic images, corrected Hounsfield unit values were determined for each kidney and the aorta. A Patlak plot for each kidney was generated, and plasma clearance per unit volume was multiplied by renal volume to obtain whole-animal contrast clearance. Mean GFR determined via inulin clearance (Inu-GFR) was measured from each kidney and correlated to mean GFR determined via CT (CT-GFR) for the left kidney, right kidney, and both kidneys by use of linear regression and Bland-Altman analyses. RESULTS: CT-GFR results from 7 pigs were valid. Total and right kidney Inu-GFR were correlated with total and right kidney CT-GFR (total, R(2) = 0.85; right kidney, R(2) = 0.86). However, left kidney CT-GFR was poorly correlated with left kidney Inu-GFR (R(2) = 0.47). Bland-Altman analysis revealed no significant bias between Inu-GFR and CT-GFR for the left kidney, right kidney, or both kidneys. CONCLUSIONS AND CLINICAL RELEVANCE: CT-GFR as determined by use of a single-slice acquisition technique, low-dose of iohexol, and Patlak plot analysis correlated without bias with Inu-GFR for the right kidney and both kidneys (combined). This technique has promise as an accurate CT-GFR method that can be combined with renal morphologic evaluation.