Renal handling of albumin in normal rat

Abstract

To the Editor: The study by Eppel et al presents surprising new data on the glomerular filtration of albumin and subsequent tubular reabsorption of intact albumin back to the circulation in rat kidney[1Eppel G.A. Osicka T.M. Pratt L.M. Jablonski P. Howden B.O. Glasgow E.F. Comper W.D. The return of glomerular-filtered albumin to the rat renal vein.Kidney Int. 1999; 55: 1861-1870Abstract Full Text Full Text PDF PubMed Scopus (68) Google Scholar]. From their Table 4, the concentration of albumin in the glomerular ultrafiltrate can be calculated to be 2.3 mg/mL. Previous reported values in rat and dog have varied between <0.001 and 0.05 mg/mL (reviewed in[2Maack T. Renal handling of proteins and polypeptides.Handbook of Physiology. Renal Physiology, Washington DC, American Physiological Society. edited by Windhager EE. Oxford University Press, New York1992: 2039Google Scholar]). The value presented by Eppel et al is thus a factor 45 higher than the highest concentrations reported. Based on their experiments the authors suggest a high capacity cellular reabsorption mechanism in the very early part of the proximal tubule, providing an explanation why previous micropuncture studies did not find the high concentration of albumin suggested by this study. The authors furthermore suggest that the reabsorption is transcellular. However, immunohistochemistry for endogenous albumin in the initial part of rat proximal tubule (Fig. 1A), reveals no difference in the intracellular concentration of albumin as compared to later parts of segment 1 of the proximal tubule. Furthermore, there is no evidence to suggest a transtubular transport of intact albumin, neither at the light microscope level nor at the electron microscope level (Fig. 1B). Albumin is always localized either in apical endosomes or in lysosomes as shown by double labeling for albumin and cathepsin B. A possible explanation for the results presented by Eppel et al is that the injected, probably in part denatured albumin, binds to the basolateral membrane of the tubules followed by a subsequent slow release simulating a transtubular transport of intact albumin. This mode of action was demonstrated by Ottosen et al in a series of elegant papers[3Ottosen P.D. Bode F. Madsen K.M. Maunsbach A.B. Renal handling of lysozyme in the rat.Kidney Int. 1979; 15: 246-254Abstract Full Text PDF PubMed Scopus (21) Google Scholar], also reviewed by Christensen and Nielsen[4Christensen E.I. Nielsen S. Structural and functional features of protein handling in the kidney proximal tubule.Semin Nephrol. 1991; 11: 414-439PubMed Google Scholar], to explain the unexpected findings of Mack et al of a similar apparent transtubular transport of protein[5Maack T. Mackensie D.D.S. Kinter W.B. Intracellular pathways of renal reabsorption of lysozyme.Am J Physiol. 1971; 221: 1609-1616PubMed Google Scholar].