Calf muscle metabolism of six patients with end-stage chronic renal failure undergoing maintenance hemodialysis and of six control subjects was studied using 31P nuclear magnetic resonance spectroscopy at 4.7 Tesla. Spectra were obtained at rest, during exercise and recovery. At rest, the inorganic phosphate, ATP and phosphocreatine concentrations, and the intracellular pH were similar in both groups of subjects. In the patients, the maximum workload achieved at the end of exercise led to a 84% and 46% depletion of phosphocreatine and ATP, respectively; under this condition, the intracellular pH fell to 6.50 +/- 0.09. In control subjects, a maximum workload caused no change in ATP concentration at the end of exercise, but a phosphocreatine depletion and an intracellular pH fall similar to those observed in the patients. Although the rate of phosphocreatine depletion during exercise was not different in the two groups of subjects, the decrease in intracellular pH was more rapid in the patients than in control subjects. At the end of maximum exercise, the rates of recovery of both phosphocreatine and intracellular pH were significantly reduced in the muscle of hemodialysis patients when compared to normal subjects. These results suggest that, in the calf muscle of hemodialysis patients, energy production via oxidative metabolism is impaired and compensated for by an increase in anaerobic glycolysis.

The accuracy of methods for measurement of creatinine in plasma, urine and dialysate is of great importance in continuous ambulatory peritoneal dialysis (CAPD) patients, to assess the adequacy of CAPD (creatinine clearance) and to monitor the nutritional status (creatinine kinetic lean body mass). The methods most widely employed for creatinine determination are Jaffe's reaction and the enzymatic method, however these techniques may suffer from glucose interference, particularly for dialysate. We compared creatinine values obtained by Jaffe's reaction, the enzymatic method and high pressure liquid chromatography (HPLC) for three creatinine calibration curves prepared in three dialysis solutions with various concentrations of glucose and for plasma, urine and dialysate of 40 CAPD patients. High values of intercept of creatinine calibration curves were observed only with Jaffe's reaction and the enzymatic method in dialysis solutions. In plasma, urine and dialysate, creatinine values obtained by HPLC were always found to be lower than those measured by the other two methods. Concerning creatinine measurement in plasma and urine, Jaffe's reaction and the enzymatic method appeared equivalent. However it must be noted that, in dialysates, the enzymatic method may have glucose interference, and the use of a correcting factor for glucose with Jaffe's reaction is convenient. Nevertheless HPLC remains a method of reference. It is concluded that, for the CAPD patient, follow-up by creatinine kinetic lean body mass or creatinine clearance is possible provided that the same creatinine assay method is used in all biological fluids.

Gamma-L-glutamyl-L-dopa (or gludopa), a dopamine (DA) prodrug, is selectively metabolized in vivo by the kidney through the sequential action of two renal enzymes, gamma-glutamyl transpeptidase (gamma-GT) and aromatic L-amino acid decarboxylase (AADC). This study was designed to analyze, in vitro, the factors regulating gludopa metabolism and its renal vascular effects. Rat kidneys were perfused in closed circuit with a cell-free perfusion buffer containing 6% bovine serum albumin (BSA). Adding gludopa (final concentration 10(-5) M in the perfusate) led to the release of DA both into urine and perfusate (0.53 +/- 0.21 and 1.38 +/- 0.28 nmol/min/g kidney wt, respectively, during the first 5 min after substrate addition, N = 5, mean +/- SEM). Total DA release (urine plus perfusate) was 73.7 +/- 15.8 nmol/g kidney wt within 30 minutes of recirculation. In non-filtering kidneys, total DA release in the recirculating medium was lower (12.5 +/- 1.4 nmol/g kidney wt, P less than 0.01). Glomerular filtration and access to the gamma-GT on the brush border membrane of proximal tubular cells are therefore required for the maximal conversion rate of gludopa. On filtering kidneys, L-dopa was also converted to DA, but at a higher rate than gludopa (total DA formed within 30 min of recirculation = 131.2 +/- 31.9 nmol/g kidney wt) and this rate was not reduced in non-filtering kidneys (224.2 +/- 41.7 nmol/g kidney wt DA formed within 30 min). Metabolic conversion of L-dopa by AADC is thus preserved in the case of an approach via the basolateral side of the proximal tubular cells. The renal vascular effects of gludopa were studied after vascular tone had been restored by continuous perfusion of PGF2 alpha and after the inhibition of alpha- and beta-adrenoceptors. Gludopa (3.10(-6) to 4.10(-5) M) elicited concentration-dependent renal vasodilatation.(ABSTRACT TRUNCATED AT 250 WORDS)

In order to improve knowledge about the mechanisms underlying the alterations of energy metabolism recently observed in the skeletal muscle of patients suffering from chronic renal failure, this study was designed to test (1) whether changes in the activity of key enzymes of energy metabolism occur in the muscle of these patients, and if so (2) whether the different muscle fiber types are equally altered in their metabolic machinery. For this, the maximum activities of 14 enzymes were measured in individual muscle fibers microdissected from biopsies of rectus abdominis muscle obtained from seven normal subjects and seven patients with end-stage renal failure before renal replacement therapy. A large decrease in the activities of beta-hydroxyacyl-coenzyme A dehydrogenase, a key enzyme of the beta-oxidation pathway, of citrate synthase, which initiates the tricarboxylic acid cycle, and of fructose-1,6-bisphosphatase, which contributes to the synthesis of glycogen from lactate, was observed in the three fiber types (slow-twitch oxidative, fast-twitch oxidative-glycolytic, and fast-twitch glycolytic). A smaller reduction of the activities of phosphofructokinase and/or pyruvate kinase, two key enzymes of glycolysis, was also observed in slow-twitch oxidative and/or fast-twitch oxidative-glycolytic fibers. These results demonstrate that the abnormalities of muscle energy metabolism observed in patients with chronic renal failure are due, at least in part, to intrinsic changes in the key enzymes of major energy-providing pathways; they also offer a satisfactory explanation for the defect of oxidative metabolism recently demonstrated in the muscle of these patients.