Skip to main content
SpringerLink
Log in

Intra- and extrarenal factors of oedema formation in the nephrotic syndrome

  • Invited Review
  • Published:
Pediatric Nephrology Aims and scope Submit manuscript

Abstract

The role of intra- and extrarenal factors in oedema formation in children with nephrotic syndrome is reviewed. Oedema reflects an abnormal accumulation of fluid within the interstitial tissue. At the capillary level oedema develops when increased lymph flow is no longer effective for the removal of interstitial fluid and the maintenance of intravascular volume. Alterations of intrarenal haemodynamics and tubular sodium reabsorption contribute to sodium retention. Recent studies suggest that during oedema formation reduced effective circulatory volume triggers changes in various hormonal systems, such as renin-angiotensin-aldosterone, noradrenaline, dopamine, vasopressin, prostaglandins and natriuretic factors, which contribute to sodium and water retention. It appears that the release of atrial natriuretic peptide following central volume expansion is responsible for the increased urine flow and natriuresis after intravenous administration of albumin.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Similar content being viewed by others

References

  1. Brenner B, Hostetter TH, Humes HD (1978) Molecular basis of proteinuria of glomerular origin. N Engl J Med 298:826–833

    Google Scholar 

  2. Robson AM, Giangiacomo J, Kienstra RA, Nagvi ST, Ingelfinger JR (1974) Normal glomerular permeability and its modification by minimal change nephrotic syndrome. J Clin Invest 54:1190–1199

    Google Scholar 

  3. Kerjaschki D, Vernillo AT, Fahrquhar MG (1985) Reduced sialylation of podocalyxin — the major sialoprotein of the rat kidney glomerulus — in aminonucleoside nephrosis. Am J Pathol 18: 343–349

    Google Scholar 

  4. Bliss DJ, Brewer DB (1985) Increased albumin and normal dextrose clearances in protein overload proteinuria in the rat. Clin Sci 69: 321–326

    Google Scholar 

  5. Levin M, Smith C, Walters MDS, Gascoine P, Barratt TM (1985) Steroid-responsive nephrotic syndrome: a generalised disorder of membrane negative change. Lancet II: 239–242

    Google Scholar 

  6. Vehaskari VM, Chang CT, Stevens JK, Robson AM (1984) The effects of polycations on vascular permeability in the rat. J Clin Invest 73: 1053–1061

    Google Scholar 

  7. Intaglietta M, Zweifach BW (1974) Microcirculatory basis of fluid exchange. Adv Biol Med Phys 15: 111–115

    Google Scholar 

  8. Seifter JL, Skorecki KL, Stivelmen JG, Haupert G, Brenner BM (1986) Control of extracellular fluid volume and pathophysiology of edema formation. In: Brenner BM, Rector FL (eds) The kidney. Sauders, Philadelphia, pp 343–384

    Google Scholar 

  9. Zweifach BW (1972) Capillary filtration and mechanism of edema formation. Pflügers Arch 336 [Suppl]: S81-S85

    Google Scholar 

  10. Guyton AC (1964) Interstitial fluid pressure. Pressur-volume curves of interstitial space. Circ Res 16:452–460

    Google Scholar 

  11. Koomans HA, Kortlandt W, Geers AB, Dorhout Mees EJ (1985) Lowered protein content of tissue fluid in patients with the nephrotic syndrome: observations during disease and recovery. Nephron 40: 391–395

    Google Scholar 

  12. Skorecki KL, Brenner BM (1981) Body fluid homeostasis in man. A contemporary overview. Am J Med 70: 77–88

    Google Scholar 

  13. Bennhold H, Klaus D, Scheinlen PG (1960) Volume regulation and renal function in analbuminemia. Lancet II: 1169–1170

    Google Scholar 

  14. Kaloyanides GJ (1983) Edema. In: Massry SG, Glassock RJ (eds) Textbook of nephrology. Williams and Wilkins, Baltimore, pp 4.30–4.40

    Google Scholar 

  15. Zilleruelo G, Strauss J (1982) Management of nephrotic edema. In: Strauss J (ed) Hypertension, fluid-electrolytes and tubulopathies in pediatric nephrology. Martinus Nijhoff, The Hague, pp 189–205

    Google Scholar 

  16. Dworkin L, Ichikawa I, Brenner BM (1983) Hormonal modulation of glomerular function. Am J Physiol 244: F95-F104

    Google Scholar 

  17. Ichikawa I, Rennke HG, Hoyer, JR, Badr KF, Schor N, Troy JL, Lechene CP, Brenner BM (1983) Role of intrarenal mechanism in the impaired salt excretion of experimental nephrotic syndrome. J Clin Invest 71: 91–103

    Google Scholar 

  18. Yamauichi H, Hopper J (1964) Hypovolemic shock and hypotension as a complication in the nephrotic syndrome. Ann Intern Med 60: 242–254

    Google Scholar 

  19. Chamerlein MJ, Pringle A, Wrong DM (1966) Oliguric renal failure in the nephrotic syndrome. Q J Med 35: 215–235

    Google Scholar 

  20. Dorhout Mees EJ, Roos JC, Boer P, Yoe OH, Simatupang TA (1979) Observations on edema formation in the nephrotic syndrome in adults with minimal lesions. Am J Med 67: 378–384

    Google Scholar 

  21. Berg U, Bohlin AB (1982) Renal hemodynamics in minimal change nephrotic syndrome in childhood. Int J Pediatr Nephrol 3: 187–192

    Google Scholar 

  22. Löwenstein J, Schacht RG, Baldwin DS (1981) Renal failure in minimal change nephrotic syndrome. Am J Med 70: 227–233

    Google Scholar 

  23. Gur A, Adefuin PY, Siegel NJ, Hayslett JP (1976) A study of renal handling of water in lipoid nephrosis. Pediatr Res 10: 197–201

    Google Scholar 

  24. Kuroda S, Aynedjian HS, Bank N (1979) A micropuncture study of renal sodium retention in nephrotic syndrome in rats: evidence for increased resistance to tubular fluid flow. Kidney Int 16: 561–571

    Google Scholar 

  25. Berlyne GM, Sutton J, Brown C, Feinroth MU, Feinroth M, Adler AJ, Friedman EA (1981) Renal salt and water handling in water immersion in the nephrotic syndrome. Clin Sci 61: 605–610

    Google Scholar 

  26. Krishna GG, Danovitch GM (1982) Effects of water immersion on renal function in the nephrotic syndrome. Kidney Int 21: 395–401

    Google Scholar 

  27. Grausz H, Lieberman R, Earley LE (1972) Effect of plasma albumin on sodium reabsorption in pateints with nephrotic syndrome. Kidney Int 1: 47–54

    Google Scholar 

  28. Bernard DB, Alexander EA, Couser WG Levinski NG (1978) Renal sodium retention during volume expansion in experimental nephrotic syndrome. Kidney Int 14: 478–485

    Google Scholar 

  29. Bohlin AB, Berg U (1984) Renal water handling in minimal change nephrotic syndrome. Int J Pediatr Nephrol 5: 93–98

    Google Scholar 

  30. Baeyer H, Liew JB van, Klassen J, Boylan JW, Manz N, Muir P (1976) Filtration of protein in the anti-glomerular basement nephrotic rat: a micropuncture study. Kidney Int 10: 425–437

    Google Scholar 

  31. Bohlin AB, Berg U (1984) Renal sodium handling in minimal change nephrotic syndrome. Arch Dis Child 59: 825–830

    Google Scholar 

  32. Hollenberg NK Schuhman G (1985) Renal perfusion in sodium-retaining state. In: Seldin DW, Giebisch G (eds) The kidney: physiology and pathophysiology. Raven Press, New York, pp 1119–1136

    Google Scholar 

  33. Metcoff J, Janeway CA (1961) Studies on the pathogenesis of nephrotic edema. J Pediatr 58: 640–685

    Google Scholar 

  34. Garrett ES, Weber CE (1967) Changes in blood volume produced by treatment in the nephrotic syndrome. Lancet II: 798–799

    Google Scholar 

  35. Jensen H, Rossing N, Anderson SN, Jarnum S (1967) Albumin metabolism in the nephrotic syndrome in adults. Clin Sci 33: 445–457

    Google Scholar 

  36. Usberti M, Federico S, Meccariello S, Cianciaruso B, Balletta M, Pecoraro C, Sacca L, Ungaro B, Psanti N, Andreucci VE (1984) Role of plasma vasopressin in the impairment of water excretion in the nephrotic syndrome. Kidney Int 25: 422–429

    Google Scholar 

  37. Eisenberg S (1968) Blood volume in persons with edema and the nephrotic syndrome. Am J Med Sci 255: 320–326

    Google Scholar 

  38. Meltzer JI, Keim HJ, Laragh JH, Sealey JE, Jan KM, Chien S (1979) Nephrotic syndrome: vasoconstriction of hypovolemic types indicated by renin-sodium profiling. Ann Intern Med 91: 688–696

    Google Scholar 

  39. Epstein FH (1982) Underfilling versus overflow in hepatic ascites. N Engl J Med 307: 1577–1578

    Google Scholar 

  40. Eisenberg S (1963) Postural changes in plasma volume in hypalbuminemia. Arch Intern Med 112 544–549

    Google Scholar 

  41. Geers AB, Koomans HA, Boer P, Dorhout Mees EJ (1984) Plasma and blood volumes in patients with the nephrotic syndrome. Nephron 38: 170–173

    Google Scholar 

  42. Geers AB, Koomans HA, Roos JC, Boer P, Dorhout Mees EJ (1984) Functional relationships in the nephrotic syndrome. Kidney Int 26: 324–330

    Google Scholar 

  43. Geers AB, Koomans HA, Roos JC, Dorhout Mees EJ (1985) Preservation of blood volume during edema removal in nephrotic patients. Kidney Int 28: 652–657

    Google Scholar 

  44. Masuda H, Ito H, Hayashi S, Honda M, Hasegawa O, Koga M (1987) Blood volumes in children with nephrotic syndrome. Pediatr Nephrol 1: C41

    Google Scholar 

  45. Rascher W, Tulassay T (1987) Hormonal regulation of water metabolism in children with nephrotic syndrome. Kidney Int 32 [Suppl 21]: S83-S89

    Google Scholar 

  46. Luetscher JA, Johnson, BB (1954) Observations on the sodium retaining corticoid (aldosterone) in the urine of children and adults in relation to sodium balance and edema. J Clin Invest 33: 1441–1446

    Google Scholar 

  47. Oliver W, Owings CL (1967) Sodium excretion in the nephrotic syndrome. Am J Dis Child 113: 352–362

    Google Scholar 

  48. Medina A, Davies DL, Brown JJ, Fraser R, Lever AF, Mallick NP, Morton JJ, Robertson JIS, Tree M, (1974) A study of the renin-angiotensin system in the nephrotic syndrome. Nephron 12: 233–240

    Google Scholar 

  49. Chonko AM, Bay W, Stein JH, Ferris TF (1977) The role of renin and aldosterone in the salt retention of edema. Am J Med 63: 881–889

    Google Scholar 

  50. Ammenti A, Müller-Wiefel DE, Schärer K, Vecsei P (1980) Mineralocorticoids in the nephrotic syndrome of children. Clin Nephrol 14: 238–245

    Google Scholar 

  51. Boer P, Roos JC, Geyskes GG, Dorhout Mees EJ (1980) Observations on plasma renin substrate in the nephrotic syndrome. Nephron 26: 121–125

    Google Scholar 

  52. Kumagai H, Onoyama K, Iseki K, Omae T (1985) Role of renin angiotensin aldosterone in minimal change nephrotic syndrome. Clin Nephrol 23: 229–235

    Google Scholar 

  53. Rascher W, Tulassay T, Seyberth HW, Himbert U, Lang U, Schärer K (1986) Diuretic and hormonal response to head-out water immersion in nephrotic syndrome. J Pediatr 109: 609–614

    Google Scholar 

  54. Tulassay T, Rascher W, Lang RE, Seyberth HW, Schärer K (1987) Atrial natriuretic peptide and other vasoactive hormones in nephrotic syndrome. Kidney Int 31: 1391–1395

    Google Scholar 

  55. Tobian L, Perry S, Mook J (1962) The relationship of the juxtaglomerular apparatus to sodium retention in experimental nephrosis. Ann Intern Med 57: 382–386

    Google Scholar 

  56. Brown EA, Markandu ND, Sagnella GA, Squires M, Jones BE, MacGregor GA (1982) Evidence that some mechanism other than the renin system causes sodium retention in nephrotic syndrome. Lancet II: 1237–1239

    Google Scholar 

  57. Brown EA, Markandu ND, Roulston JE, Jones BE, Squires M, MacGregor GA (1982) Is the renin-angiotensin-aldosterone system involved in the sodium retention in the nephrotic syndrome? Nephron 32: 102–107

    Google Scholar 

  58. Brown EA, Markandu ND, Sagnella GA, Jones BE, MacGregor GA (1985) Sodium retention in nephrotic syndrome is due to an intrarenal defect: evidence from steroid-induced remission. Nephron 39: 290–295

    Google Scholar 

  59. Dusing R, Vetter H, Kramer HJ (1980) The renin-angiotensin-aldosterone system in patients with nephrotic syndrome. Nephron 25: 187–191

    Google Scholar 

  60. Shapiro M, Hasbargen J, Cosby R, Yee B, Schrier R (1986) Role of aldosterone in the Na retention of patients with nephrotic syndrome. Kidney Int 29: 203

    Google Scholar 

  61. Kelsch RC, Light GS, Oliver WJ (1972) The effect of albumin infusion upon plasma norepinephrine concentration in nephrotic children. J Lab Clin Med 79: 516–525

    Google Scholar 

  62. Bello-Reuss E (1980) Effect of catecholamines on fluid reabsorption by the isolated proximal convoluted tubule. Am J Physiol 238: F347-F352

    Google Scholar 

  63. Davies JO, Freeman RH (1976) Mechanism regulating renin release Physiol Rev 56: 1–56

    Google Scholar 

  64. Thames MD (1978) Contribution of cardiopulmonary baroreceptors to the control of the kidney. Fed Proc 37: 1209–1213

    Google Scholar 

  65. Lee MR (1982) Dopamine and the kidney. Clin Sci 62: 439–448

    Google Scholar 

  66. Alexander RW, Gill JR, Yamabe H, Lovenberg W, Keiser HR (1974) Effects of dietary sodium and of acute saline infusion on the interrelationship between dopamine excretion and adrenergic activity in man. J Clin Invest 54: 194–200

    Google Scholar 

  67. Krishna GG, Danovitch GM, Beck FWJ, Sowers JR (1985) Dopaminergic modulation of the natriuretic response to volume expansion. J Lab Clin Med 105: 214–218

    Google Scholar 

  68. Corruzzi P, Biggi A, Musiari L, Ravanetti C, Vescovi PP, Novarini A (1986) Dopamine blockade and natriuresis during water immersion in normal man. Clin Sci 70: 523–526

    Google Scholar 

  69. Rascher W, Lang RE, Unger TH (1985) Vasopressin, cardiovascular regulation and hypertension. In: Ganten D, Pfaff D (eds) Current topics in neuro-endocrinology, vol 4. Springer, Berlin Heidelberg New York, pp 101–136

    Google Scholar 

  70. Schlondorff D, Ardaillou R (1986) Prostaglandins and other arachidonic acid metabolites in the kidney. Kidney Int 29: 108–119

    Google Scholar 

  71. Clive DM, Stoff JS (1984) Renal symptoms associated with nonsteroid antiinflammatory drugs. N Engl J Med 310: 564–572

    Google Scholar 

  72. Donker AJM, Brentjens JRH, Hem GK van der, Arisz L (1978) Treatment of the nephrotic syndrome with indomethacin. Nephron 22: 374–381

    Google Scholar 

  73. Kleinknecht C, Broyer M, Gubler MC, Palcoux JB (1980) Irreversible renal failure after indocin in steroid-resistant nephrosis. N Engl J Med 302: 691

    Google Scholar 

  74. Millet GU, Ruilope LM, Alcasar JM, Prieto C, Tresguerres JF, Garcia Robles R, Radicio JL (1983) Participation of renal prostaglandins in the nephrotic syndrome. Kidney Int 23: 555

    Google Scholar 

  75. Bourgoignie JJ, Hwang KH, Ipacki E, Bricker NS (1974) The presence of a natriuretic factor in urine of patients with chronic uremia. The absence of the factor in nephrotic uremic patients. J Clin Invest 50: 303–311

    Google Scholar 

  76. Favre H, Gourgon M (1982) Absence of production of natriuretic factor following acute saline expansion in nephrotic rats. Clin Sci 63: 317–319

    Google Scholar 

  77. Ballermann BJ, Brenner BM (1985) Biologically active atrial peptides. J Clin Invest 76: 2041–2048

    Google Scholar 

  78. Laragh JH (1985) Atrial natriuretic hormone, the renin-aldosterone axis, and blood pressure — electrolyte homeostasis. N Engl J Med 313: 1330–1340

    Google Scholar 

  79. Needleman P, Greenwald JE (1986) Atriopeptin: a cardiac hormone intimately involved in fluid, electrolyte, and blood pressure homeostasis. N Engl J Med 314: 828–834

    Google Scholar 

Download references

Author information

Author notes

  1. Tivadar Tulassay

    Present address: First Department of Paediatrics, Semmelweis University Medical School, Bokay J. u. 53, H-1083, Budapest, Hungary

  2. Wolfgang Rascher

    Present address: Klinik und Poliklinik für Kinder- und Jugendmedizin, Universitätsklinikum Essen, Hufelandstrasse 55, D-4300, Essen 1, Federal Republic of Germany

Authors and Affiliations

  1. Division of Pediatric Nephrology, Universitäts-Kinderklinik, Im Neuenheimer Field 150, D-6900, Heidelberg, Federal Republic of Germany

    Tivadar Tulassay, Wolfgang Rascher & Karl Schärer

Authors
  1. Tivadar Tulassay
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Wolfgang Rascher
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Karl Schärer
    View author publications

    You can also search for this author in PubMed Google Scholar

Rights and permissions

Reprints and permissions

About this article

Cite this article

Tulassay, T., Rascher, W. & Schärer, K. Intra- and extrarenal factors of oedema formation in the nephrotic syndrome. Pediatr Nephrol 3, 92–100 (1989). https://doi.org/10.1007/BF00859635

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Issue Date:

  • DOI: https://doi.org/10.1007/BF00859635

Key words

Search

Navigation