Skip to main content
PMC home page
The Journal of Physiology logoLink to The Journal of Physiology
. 1976 Feb;255(2):399–414. doi: 10.1113/jphysiol.1976.sp011286

Lactate metabolism in the isolated perfused rat kidney: relations to renal function and gluconeogenesis.

J J Cohen, J R Little
PMCID: PMC1309254  PMID: 1255526

Abstract

In the intact dog, decreases in both glomerular filtration rate and net renal Na+ reabsorption due to raised ureteral pressure were not associated with a decrease in renal lactate oxidation rate, although total renal CO2 production decreased in proportion to the changes in net renal reabsorption of Na+ and glomerular filtration rate. 2. In order to determine whether, in the absence of other added substrates, the metabolism of lactate supports only the 'basal' renal metabolism or can enhance renal function as well, the rate of lactate utilization and decarboxylation by the isolated perfused rat kidney have been quantified in relation to renal function and one measure of renal basal metabolism, glucose production. 3. The perfusate was Krebs-Ringer bicarbonate (pH 7-35-7-48) with Fraction V bovine serum albumin, 6g/100 ml. L-(+)-lactate was added to raise the lactate concentration from endogenous levels to 2-5, 5-0 or 10 mM. 4. We determined: net lactate utilization rate, lactate decarboxylation rate (14CO2 produced from L-(+)-[U-14C]lactate), net glucose production rate, and net re-absorptive rate of Na+. 5. The apparent Km and Vmax for lactate oxidation were 2-1 mM and 1-29 mumole.g-1.min-1 respectively. There was no apparent maximum for total lactate utilization rate due to continuing increases in glucose production rate as lactate concentration was raised. At ca. 10 mM lactate, glucose production accounted for about half of the total lactate utilized. Therefore the basal energy requirements of the kidney need not be constant since glucose production increases as lactate concentration is raised. 6. Both lactate oxidation rate and lactate utilization rate were significantly correlated with the net reabsorption of Na+ by the renal tubules, with the percentage of filtered Na+ reabsorbed and with the glomerular filtration rate. The major fraction of the net renal reabsorption of Na+ was probably supported by the metabolism of substrates either bound to albumin or derived from renal tissue since the percentage of filtered Na+ reabsorbed increased from ca. 78%, when no lactate was added, to 97% when initial lactate concentration was 10 mM. Therefore, addition of lactate increased both the basal mebabolism and tubular function. However, these observations do not permit us to conclude whether it was the presence of lactate, or its utilization by oxidative or by other pathways which enhanced net renal reabsorption of Na+ and the glomerular filtration rate.

Full text

PDF
399

Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. Anderson R. E., Synder F. Quantitative collection of 14CO2 in the presence of labeled short-chain acids. Anal Biochem. 1969 Feb;27(2):311–314. doi: 10.1016/0003-2697(69)90038-4. [DOI] [PubMed] [Google Scholar]
  2. Andreucci V. E., Herrera-Acosta J., Rector F. C., Jr, Seldin D. W. Effective glomerular filtration pressure and single nephron filtration rate during hydropenia, elevated ureteral pressure, and acute volume expansion with isotonic saline. J Clin Invest. 1971 Oct;50(10):2230–2234. doi: 10.1172/JCI106719. [DOI] [PMC free article] [PubMed] [Google Scholar]
  3. Bahlmann J., Giebisch G., Ochwadt B., Schoeppe W. Micropuncture study of isolated perfused rat kidney. Am J Physiol. 1967 Jan;212(1):77–82. doi: 10.1152/ajplegacy.1967.212.1.77. [DOI] [PubMed] [Google Scholar]
  4. Bowman R. H., Dolgin J., Coulson R. Furosemide, ethacrynic acid, and iodoacetate on function and metabolism in perfused rat kidney. Am J Physiol. 1973 Feb;224(2):416–424. doi: 10.1152/ajplegacy.1973.224.2.416. [DOI] [PubMed] [Google Scholar]
  5. Bowman R. H. Gluconeogenesis in the isolated perfused rat kidney. J Biol Chem. 1970 Apr 10;245(7):1604–1612. [PubMed] [Google Scholar]
  6. Bowman R. H., Maack T. Effect of albumin concentration and ADH on H2O and electrolyte transport in perfused rat kidney. Am J Physiol. 1974 Feb;226(2):426–430. doi: 10.1152/ajplegacy.1974.226.2.426. [DOI] [PubMed] [Google Scholar]
  7. Brand P. H., Cohen J. J., Bignall M. C. Independence of lactate oxidation from net Na+ reabsorption in dog kidney in vivo. Am J Physiol. 1974 Dec;227(6):1255–1262. doi: 10.1152/ajplegacy.1974.227.6.1255. [DOI] [PubMed] [Google Scholar]
  8. Brenner B. M., Bennett C. M., Berliner R. W. The relationship between glomerular filtration rate and sodium reabsorption by the proximal tubule of the rat nephron. J Clin Invest. 1968 Jun;47(6):1358–1374. doi: 10.1172/JCI105828. [DOI] [PMC free article] [PubMed] [Google Scholar]
  9. Brenner B. M., Troy J. L., Daugharty T. M., MacInnes R. M. Quantitative importance of changes in postglomerular colloid osmotic pressure in mediating glomerulotubular balance in the rat. J Clin Invest. 1973 Jan;52(1):190–197. doi: 10.1172/JCI107164. [DOI] [PMC free article] [PubMed] [Google Scholar]
  10. Brenner B. M., Troy J. L., Daugharty T. M. The dynamics of glomerular ultrafiltration in the rat. J Clin Invest. 1971 Aug;50(8):1776–1780. doi: 10.1172/JCI106667. [DOI] [PMC free article] [PubMed] [Google Scholar]
  11. Brenner B. M., Troy J. L. Postglomerular vascular protein concentration: evidence for a causal role in governing fluid reabsorption and glomerulotublar balance by the renal proximal tubule. J Clin Invest. 1971 Feb;50(2):336–349. doi: 10.1172/JCI106501. [DOI] [PMC free article] [PubMed] [Google Scholar]
  12. Buentig W. E., Earley L. E. Demonstration of independent roles of proximal tubular reabsorption and intratubular load in the phenomenon of glomerulotubular balance during aortic constriction in the rat. J Clin Invest. 1971 Jan;50(1):77–89. doi: 10.1172/JCI106486. [DOI] [PMC free article] [PubMed] [Google Scholar]
  13. Dies F., Ramos G., Avelar E., Matos M. Relationship between renal substrate uptake and tubular sodium reabsorption in the dog. Am J Physiol. 1970 Feb;218(2):411–416. doi: 10.1152/ajplegacy.1970.218.2.411. [DOI] [PubMed] [Google Scholar]
  14. Franke H., Huland H., Weiss C., Unsicker K. Improved net sodium transport of the isolated rat kidney. Z Gesamte Exp Med. 1971;156(4):268–282. doi: 10.1007/BF02045828. [DOI] [PubMed] [Google Scholar]
  15. Gertz K. H., Mangos J. A., Braun G., Pagel H. D. Pressure in the glomerular capillaries of the rat kidney and its relation to arterial blood pressure. Pflugers Arch Gesamte Physiol Menschen Tiere. 1966;288(4):369–374. doi: 10.1007/BF00362581. [DOI] [PubMed] [Google Scholar]
  16. Hanson R. W., Ballard F. J. Citrate, pyruvate, and lactate contaminants of commercial serum albumin. J Lipid Res. 1968 Sep;9(5):667–668. [PubMed] [Google Scholar]
  17. KOLOBOW T., BOWMAN R. L. Construction and evaluation of an alveolar membrane artificial heart-lung. Trans Am Soc Artif Intern Organs. 1963;9:238–243. [PubMed] [Google Scholar]
  18. KRAMER K., DEETJEN P. [Relation of renal oxygen consumption to blood supply and glomerular filtration during variations of the blood pressure]. Pflugers Arch Gesamte Physiol Menschen Tiere. 1960;271:782–796. [PubMed] [Google Scholar]
  19. Khuri R. N., Strieder N., Wiederholt M., Giebisch G. Effects of graded solute diuresis on renal tubular sodium transport in the rat. Am J Physiol. 1975 Apr;228(4):1262–1268. doi: 10.1152/ajplegacy.1975.228.4.1262. [DOI] [PubMed] [Google Scholar]
  20. Knox F. G., Fleming J. S., Rennie D. W. Effects of osmotic diuresis on sodium reabsorption and oxygen consumption of kidney. Am J Physiol. 1966 Apr;210(4):751–759. doi: 10.1152/ajplegacy.1966.210.4.751. [DOI] [PubMed] [Google Scholar]
  21. Krebs H. A., Hems R., Weidemann M. J., Speake R. N. The fate of isotopic carbon in kidney cortex synthesizing glucose from lactate. Biochem J. 1966 Oct;101(1):242–249. doi: 10.1042/bj1010242. [DOI] [PMC free article] [PubMed] [Google Scholar]
  22. LASSEN N. A., MUNCK O., THAYSEN J. H. Oxygen consumption and sodium reabsorption in the kidney. Acta Physiol Scand. 1961 Apr;51:371–384. doi: 10.1111/j.1748-1716.1961.tb02147.x. [DOI] [PubMed] [Google Scholar]
  23. LEE W. H., Jr, KRUMHAAR D., FONKALSRUD E. W., SCHJEIDE O. A., MALONEY J. V., Jr Denaturation of plasma proteins as a cause of morbidity and death after intracardiac operations. Surgery. 1961 Jul;50:29–39. [PubMed] [Google Scholar]
  24. Leal-Pinto E., Park H. C., King F., MacLeod M., Pitts R. F. Metabolism of lactate by the intact functioning kidney of the dog. Am J Physiol. 1973 Jun;224(6):1463–1467. doi: 10.1152/ajplegacy.1973.224.6.1463. [DOI] [PubMed] [Google Scholar]
  25. Little J. R., Cohen J. J. Effect of albumin concentration on function of isolated perfused rat kidney. Am J Physiol. 1974 Mar;226(3):512–517. doi: 10.1152/ajplegacy.1974.226.3.512. [DOI] [PubMed] [Google Scholar]
  26. MILLER L. L., BLY C. G., WATSON M. L., BALE W. F. The dominant role of the liver in plasma protein synthesis; a direct study of the isolated perfused rat liver with the aid of lysine-epsilon-C14. J Exp Med. 1951 Nov;94(5):431–453. doi: 10.1084/jem.94.5.431. [DOI] [PMC free article] [PubMed] [Google Scholar]
  27. Nishiitsutsuji-Uwo J. M., Ross B. D., Krebs H. A. Metabolic activities of the isolated perfused rat kidney. Biochem J. 1967 Jun;103(3):852–862. doi: 10.1042/bj1030852. [DOI] [PMC free article] [PubMed] [Google Scholar]
  28. Owen O. E., Felig P., Morgan A. P., Wahren J., Cahill G. F., Jr Liver and kidney metabolism during prolonged starvation. J Clin Invest. 1969 Mar;48(3):574–583. doi: 10.1172/JCI106016. [DOI] [PMC free article] [PubMed] [Google Scholar]
  29. Pashley D. H., Cohen J. J. Substrate interconversion in dog kidney cortex slices: regulation by ECF-pH. Am J Physiol. 1973 Dec;225(6):1519–1528. doi: 10.1152/ajplegacy.1973.225.6.1519. [DOI] [PubMed] [Google Scholar]
  30. Rector F. C., Jr, Brunner F. P., Seldin D. W. Mechanism of glomerulotubular balance. I. Effect of aortic constriction and elevated ureteropelvic pressure on glomerular filtration rate, fractional reabsorption, transit time, and tubular size in the proximal tubule of the rat. J Clin Invest. 1966 Apr;45(4):590–602. doi: 10.1172/JCI105373. [DOI] [PMC free article] [PubMed] [Google Scholar]
  31. Ross B. D., Epstein F. H., Leaf A. Sodium reabsorption in the perfused rat kidney. Am J Physiol. 1973 Nov;225(5):1165–1171. doi: 10.1152/ajplegacy.1973.225.5.1165. [DOI] [PubMed] [Google Scholar]
  32. Ross B., Leaf A., Silva P., Epstein F. H. Na-K-ATPase in sodium transport by the perfused rat kidney. Am J Physiol. 1974 Mar;226(3):624–629. doi: 10.1152/ajplegacy.1974.226.3.624. [DOI] [PubMed] [Google Scholar]
  33. WEISS C., PASSOW H., ROTHSTEIN A. Autoregulation of flow in isolated rat kidney in the absence of red cells. Am J Physiol. 1959 May;196(5):1115–1118. doi: 10.1152/ajplegacy.1959.196.5.1115. [DOI] [PubMed] [Google Scholar]
  34. Yudkin J., Cohen R. D. The contribution of the kidney to the removal of a lactic acid load under normal and acidotic conditions in the conscious rat. Clin Sci Mol Med. 1975 Feb;48(2):121–131. doi: 10.1042/cs0480121. [DOI] [PubMed] [Google Scholar]

Articles from The Journal of Physiology are provided here courtesy of The Physiological Society

RESOURCES