The clinical investigator

, Volume 70, Issue 9, pp 843–856 | Cite as

The glomerular mesangium: capillary support function and its failure under experimental conditions

  • K. V. Lemley
  • M. Elger
  • I. Koeppen-Hagemann
  • M. Kretzler
  • M. Nagata
  • T. Sakai
  • S. Uiker
  • W. Kriz
Guest Lecture, “Gesellschaft für Nephrologie”, 23rd Congress


We present a structural analysis of the ability of the biomechanical unit consisting of mesangium and glomerular basement membrane to maintain normal capillary architecture in the face of mechanical challenges due to high intraglomerular pressures. Capillary support function may be considered in terms of the stabilization of local form (development of wall tension against capillary dilation) and global form (centripetal fixation of capillary loops to maintain higher order form). The pathologic consequences of the loss of this support are illustrated by way of experimental models of mechanical mesangial failure. Such failure may express itself as mesangial widening, increased transmesangial macromolecule “traffic,” ballooning of capillary segments, and unfolding of capillary loops. Mechanisms are described by which these structural changes may lead to segmental glomerular sclerosis.

Key words

Kidney Glomerulus Mesangium Mesangial failure Electron microscopy Animal models 


Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.


  1. 1.
    Bagchus WM, Hoedemaeker PJ, Rozing J, Bakker WW (1986) Glomerulonephritis induced by monoclonal anti-Thy 1.1 antibodies. A sequential histological and ultrastructural study in the rat. Lab Invest 55:680–687.PubMedPubMedCentralGoogle Scholar
  2. 2.
    Blantz RC, Konnen KS, Tucker BJ (1976) Angiotensin II effects upon the glomerular microcirculation and ultrafiltration coefficient of the rat. J Clin Invest 57:419–434.CrossRefGoogle Scholar
  3. 3.
    Drenckhahn D, Schnittler H, Nobiling R, Kriz W (1990) Ultrastructural organization of contractile proteins in rat glomerular mesangial cells. Am J Pathol 137:1343–1351.PubMedPubMedCentralGoogle Scholar
  4. 4.
    Dworkin LD, Brenner BM (1992) Biophysical basis of glomerular filtration. In: Seldin DW, Giebisch G (eds) The kidney: physiology and pathophysiology, 2nd edn. Raven, New York, p 979.Google Scholar
  5. 5.
    Dworkin LD, Ichikawa I, Brenner BM (1983) Hormonal modulation of glomerular function. Am J Physiol 244:F95-F104.PubMedGoogle Scholar
  6. 6.
    Dworkin LD, Hostetter TH, Rennke HG, Brenner BM (1984) Hemodynamic basis for glomerular injury in rats with desoxycorticosterone-salt hypertension. J Clin Invest 73:1448–1461.CrossRefGoogle Scholar
  7. 7.
    Elger M, Sakai T, Kriz W (1990) Role of mesangial cell contraction in adaptation of the glomerular tuft to changes in extracellular volume. Pflugers Arch 415:598–605.CrossRefGoogle Scholar
  8. 8.
    Grond J, Koudstaal J, Elema JD (1985) Mesangial function and glomerular sclerosis in rats with aminonucleoside nephrosis. Kidney Int 27:405–410.CrossRefGoogle Scholar
  9. 9.
    Keane WF, Raij L (1985) Relationship among altered glomerular barrier permselectivity, angiotensin II, and mesangial uptake of macromolecules. Lab Invest 52:599–604.PubMedGoogle Scholar
  10. 10.
    Kondo Y, Akikusa B (1982) Chronic Masugi nephritis in the rat. An electron microscopic study on evolution and consequences of glomerular capsular adhesions. Acta Path Jpn 32:231–242.Google Scholar
  11. 11.
    Kriz W, Elger M, Lemley KV, Sakai T (1990) Mesangial cell-glomerular basement membrane connections counteract glomerular capillary and mesangium expansion. Am J Nephrol 10:4–13.CrossRefGoogle Scholar
  12. 12.
    Kriz W, Elger M, Lemley KV, Sakai T (1990) Structure of the glomerular mesangium: a biomechanical interpretation. Kidney Int 38 [Suppl 30]:S2-S9.Google Scholar
  13. 13.
    Kriz W, Hackenthal E, Münter K, Nagata M, Nobiling R, Sakai T (1991) The isolated perfused rat kidney: a model to study glomerular mesangial failure. Contr Nephrol (in press).Google Scholar
  14. 14.
    Mené P, Simonson MS, Dunn MJ (1989) Physiology of the mesangial cell. Physiol Rev 69:1347–1424.CrossRefGoogle Scholar
  15. 15.
    Michael AF, Keane WF, Raij L, Vernier RL, Mauer SM (1980) The glomerular mesangium. Kidney Int 17:141–154.CrossRefGoogle Scholar
  16. 16.
    Morita T, Churg J (1983) Mesangiolysis. Kidney Int 24:1–9.CrossRefGoogle Scholar
  17. 17.
    Morita T, Kihara I, Oite T, Yamamoto T, Suzuki Y (1978) Mesangiolysis. Sequential ultrastructural study of Habu venom-induced glomerular lesions. Lab Invest 38:94–102.Google Scholar
  18. 18.
    Mundel P, Gilbert P, Kriz W (1991) Podocytes in glomerulus of rat kidney express a characteristic 44 kD protein. J Histochem Cytochem 39:1047–1056.CrossRefGoogle Scholar
  19. 19.
    Murphy ME, Johnson PC (1975) Possible contribution of basement membrane to the structural rigidity of blood capillaries. Microvasc Res 9:242–245.CrossRefGoogle Scholar
  20. 20.
    Nagata M, Kriz W (1992) Glomerular damage after uninephrectomy in young rats. II. Mechanical stress on podocytes as a pathway to sclerosis. Kidney Int 42.CrossRefGoogle Scholar
  21. 21.
    Nagata M, Schärer K, Kriz W (1992) Glomerular damage after uninephrectomy in young rats. I. Hypertrophy and distortion of capillary architecture. Kidney Int 42.CrossRefGoogle Scholar
  22. 22.
    Olivetti G, Kithier K, Giacomelli F, Wiener J (1981) Glomerular permeability to endogenous proteins in the rat. Effect of acute hypertension. Lab Invest 44:127–137.PubMedGoogle Scholar
  23. 23.
    Olivetti G, Giacomelli F, Wiener J (1985) Morphometry of superficial glomeruli in acute hypertension in the rat. Kidney Int 27:31–38.CrossRefGoogle Scholar
  24. 24.
    Olson JL, Hostetter TH, Rennke HG, Brenner BM, Venkatachalam MA (1982) Altered glomerular permselectivity and progressive sclerosis following extreme ablation of renal mass. Kidney Int 22:112–126.CrossRefGoogle Scholar
  25. 25.
    Remuzzi A, Pata V, Mariano R, Remuzzi G, Brenner BM (1991) Blood flow distribution and local filtration in a geometrically reconstructed glomerular capillary network (abstract). J Am See Nephrol 2:526.Google Scholar
  26. 26.
    Rennke HG, Anderson S, Brenner BM (1989) Structural and functional correlations in the progression of kidney disease. In: Tisher CC, Brenner BM (eds) Renal pathology. Lippincott, Philadelphia, p 43.Google Scholar
  27. 27.
    Saito Y, Kida H, Takeda S, Yoshimura M, Yokoyama H, Koshino Y, Hattori N (1988) Mesangiolysis in diabetic glomeruli: its role in the formation of nodular lesions. Kidney Int 34:389–396.CrossRefGoogle Scholar
  28. 28.
    Sakai T, Kriz W (1987) The structural relationship between mesangial cells and basement membrane of the renal glomerulus. Anat Embryol (Berl) 176:373–386.CrossRefGoogle Scholar
  29. 29.
    Sakai T, Lemley KV, Hackenthal E, Nagata M, Nobiling R, Kriz W (1992) Changes in glomerular structure following acute mesangial failure in the isolated perfused kidney. Kidney Int 41:533–541.CrossRefGoogle Scholar
  30. 30.
    Steinhausen M, Endlich K, Wiegman D (1990) Glomerular blood flow. Kidney Int 38:769–784.CrossRefGoogle Scholar
  31. 31.
    Striker Morel-Maroger L, Killen PD, Chi E, Striker GE (1984) The composition of glomerulosclerosis. I. Studies in focal sclerosis, crescentic glomerulonephritis, and membranoproliferative glomerulonephritis. Lab Invest 51:181–191.Google Scholar
  32. 32.
    Weibel ER (1980) Stereological methods, vol 2. Theoretical foundations. Academic, London, p 92.Google Scholar
  33. 33.
    Yurchenco PD, Tsilibary EC, Charonis AS, Furthmayr H (1986) Models for the self-assembly of basement membrane. J Histochem Cytochem 34:93–102.CrossRefGoogle Scholar

Copyright information

© Springer-Verlag 1992

Authors and Affiliations

  • K. V. Lemley
    • 1
  • M. Elger
    • 1
  • I. Koeppen-Hagemann
    • 1
  • M. Kretzler
    • 1
  • M. Nagata
    • 1
  • T. Sakai
    • 1
  • S. Uiker
    • 1
  • W. Kriz
    • 1
  1. 1.Institut für Anatomic und Zellbiologie IUniversität HeidelbergHeidelbergGermany

Personalised recommendations