Michel Pellet

Lactate and pyruvate metabolism in isolated human kidney tubules

To our knowledge, uptake of lactate and pyruvate by the human kidney in vivo in normal subjects has not as yet been studied. These substrates are not taken up from the blood by the kidneys of patients afflicted with diabetes mellitus [I]. However, they are removed by the human kidney in vivo in certain other pathological states. This was first demonstrated in patients with various renal diseases [2] and, later observed [3] in obese patients following prolonged starvation. Since most of our knowledge concerning the metabolism of lactate and pyruvate has been derived from arterio-venous measurements, the metabolic fate of these substrates in the human kidney remains uncertain. Complete oxidation of lactate was calculated [2] to account for 35% of renal oxygen consumption. However, it was concluded [3] that all the lactate and pyruvate carbon skeletons removed by the kidney were converted to glucose. In an attempt to clarify this subject, we studied the metabolism of lactate and pyruvate in isolated human kidney tubules. The data indicate that lactate and pyruvate may serve as the carbon sources of glucose and alanine in human kidneys, and that, at physiological concentration (1 mM), complete oxidation of lactate is very limited.

Lactate and pyruvate metabolism in dog renal outer medulla. Effects of oleate and ketone bodies

Abstract 1. 1. The removal of l -lactate and pyruvate (1 or 5 mM) by tubular fragments isolated from the dog renal outer medulla and incubated in Krebs-Henseleit medium with 95% O 2 –5% CO 2 , is concentration-dependent and linear over a 60 min period. 2. 2. The release of 14 CO 2 from [l- 14 C]lactate or [1- 14 C]pyruvate showed that the major fraction of the lactate and pyruvate removed was metabolized via pyruvate dehydrogenase. 3. 3. Oleate inhibited lactate utilization and lactate conversion into pyruvate, as well as the release of 14 CO 2 from [1- 14 C]lactate. 4. 4. Oleate and ketone bodies (which were removed by the tubular fragments) decreased pyruvate utilization and the release of 14 CO 2 from [1- 14 C]pyruvate, but increased the conversion of pyruvate into lactate.

Effect of Acidosis, Alkalosis and Monofluoroacetate Administration on Citrate and ATP Content of Rat Renal Medulla and Papilla

1. --Renal distribution of citrate showed that there is an increase in citrate content from cortex to medulla and a decrease from medulla to papilla. Alkalosis produced an increase in citrate content and acidosis a decrease in renal citrate content, in each of the studied renal area. Monofluoroacetate produced no significant change in citrate content of medulla or papilla; it did not interfere with the acido-basic related changes in cortex citrate content, but its effect was additive. 2. --Renal distribution of ATP significantly decreased from cortex to medulla and from medulla to papilla. Acid or basic diet had no influence on intratissular ATP content. Fluoroacetate decreased renal ATP content.

Intrarenal distribution of citrate in the dog during antidiuresis and diuresis

SummaryThe intrarenal distribution of citrate was evaluated in the dog during antidiuresis and osmotic diuresis, by using the specific citrate assay method of Moellering and Gruber. The measurements were made on tissue samples taken from four different regions throughout the kidney: cortex, outer and inner medulla, and papilla. During antidiuresis, a characteristic distribution of citrate was observed with highest levels in the papilla and lowest ones in the outer medulla. A medullary concentration gradient for citrate was found. Mannitol greatly decreased papillary citrate and sodium, but no changes in outer and inner medullary citrate occured. The results could not be explained by the citrate contained either in the trapped urine or blood in the tissue. It is suggested that citrate accumulation in the inner regions of renal medulla may be accounted for by countercurrent mechanisms or regional differences in renal citrate metabolism.

L'Excrétion rénale du citrate chez le chien

SummaryClearance measurements were made in 15 dogs in order to study the urinary citrate excretion. The citrate determination is performed in blood plasma and urine, with an enzymatic specific method. The authors find that more than 99% of the citrate filtered through the glomerulus is reabsorbed. The greater sensitivity, specificity and accuracy of the enzymatic method, which has been compared with the usual chemical methods, may explain the discrepancy between these data and the results published by other authors. These results are consistent with the hypothesis that citrate is filtered, reabsorbed and not secreted by the tubule in the dog.