Chronic Interstitial Damage in Proteinuria

Tubulointerstitial injury is seen in some patients with glomerular proteinuria and when present is a poor prognostic indicator. However, the mechanism by which proteinuria results in tubular and interstitial damage is unknown. Activation of the complement system has been implicated in many forms of tissue injury, including immune–mediated renal disease. Immunohistochemical studies suggest that complement is deposited on the tubular epithelium in proteinuric states raising the possibility that complement activation may contribute to tubular injury. In this review, we discuss how complement proteins reach the tubular epithelium and why the complement system is activated at this site. We also discuss the effects this may have on tubular cells and how this could result in progressive interstitial disease. The possibility that complement inhibition may reduce progression of tubulointerstitial injury is also considered.

[1]  G. Remuzzi,et al.  Urinary protein excretion rate is the best independent predictor of ESRF in non-diabetic proteinuric chronic nephropathies. "Gruppo Italiano di Studi Epidemiologici in Nefrologia" (GISEN). , 1998, Kidney international.

[2]  R. Vaughan,et al.  Contribution of renal secreted complement C3 to the circulating pool in humans. , 1998, Journal of immunology.

[3]  G. Cerullo,et al.  Sub-lytic terminal complement complex (TCC) stimulates renal proximal tubular epithelial cells (PTEC) to express adhesion molecules and to secrete proinflammatory and fibrogenic mediators , 1998 .

[4]  S. Sacks,et al.  Compartmental Localization of Complement Component Transcripts in the Normal Human Kidney , 1997, Nephron.

[5]  L. Gesualdo,et al.  Progression of renal damage in human glomerulonephritides: is there sleight of hand in winning the game? , 1997, Kidney International.

[6]  T. Koji,et al.  Intraglomerular C3 synthesis in rats with passive Heymann nephritis. , 1997, The American journal of pathology.

[7]  N. Hotta,et al.  The role of complement in the pathogenesis of tubulointerstitial lesions in rat mesangial proliferative glomerulonephritis. , 1997, Journal of the American Society of Nephrology : JASN.

[8]  N. Hotta,et al.  Role of complement in acute tubulointerstitial injury of rats with aminonucleoside nephrosis. , 1997, The American journal of pathology.

[9]  P. Verroust,et al.  Evidence for increased synthesis of complement C4 in the renal epithelium of rats with passive Heymann nephritis. , 1997, Journal of the American Society of Nephrology : JASN.

[10]  S. Sacks,et al.  Effects of complement inhibition with soluble complement receptor-1 on vascular injury and inflammation during renal allograft rejection in the rat. , 1996, The American journal of pathology.

[11]  S. Sacks,et al.  Complement synthesis in the injured kidney: does it have a role in immune complex glomerulonephritis? , 1996, Journal of the American Society of Nephrology : JASN.

[12]  C. Combe,et al.  Fibronectin production by human tubular cells: the effect of apical protein. , 1996, Kidney international.

[13]  K. Harris,et al.  The role of proteinuria in the progression of chronic renal failure. , 1996, American journal of kidney diseases : the official journal of the National Kidney Foundation.

[14]  M. Raftery,et al.  Urinary C5b-9 excretion and clinical course in idiopathic human membranous nephropathy. , 1995, Kidney international.

[15]  G. Remuzzi,et al.  The renal toxicity of sustained glomerular protein traffic. , 1995, Laboratory investigation; a journal of technical methods and pathology.

[16]  E. Alexopoulos,et al.  The pathogenetic significance of C5b-9 in IgA nephropathy. , 1995, Nephrology, dialysis, transplantation : official publication of the European Dialysis and Transplant Association - European Renal Association.

[17]  P. Mathieson,et al.  Expression and tissue localization of donor‐specific complement C3 synthesized in human renal allografts , 1995, European journal of immunology.

[18]  J. S. Owen,et al.  Human high density lipoproteins stimulate endothelin-1 release by cultured human renal proximal tubular cells. , 1994, Kidney international.

[19]  A. Pani,et al.  Local transcription of complement C3 in human allograft rejection. Evidence for a pathogenic role and correlation to histology and outcome. , 1994, Transplantation.

[20]  Y. Yuzawa,et al.  Localization of the complement regulatory proteins in the normal human kidney. , 1994, Kidney international.

[21]  V. Della Pietra,et al.  Alternative pathway activation of complement by cultured human proximal tubular epithelial cells. , 1994, Kidney international.

[22]  G. Coles,et al.  Proteinuria--a direct cause of renal morbidity? , 1994, Kidney international.

[23]  S. Sacks,et al.  Endogenous complement C3 synthesis in immune complex nephritis , 1993, The Lancet.

[24]  D. Witte,et al.  Differential expression of complement C3 and C4 in the human kidney. , 1993, The Journal of clinical investigation.

[25]  M. Daha,et al.  IFN-γ mediates stimulation of complement C4 biosynthesis in human proximal tubular epithelial cells , 1993 .

[26]  L. Ruilope,et al.  Long-term beneficial effects of angiotensin-converting enzyme inhibition in patients with nephrotic proteinuria. , 1992, American journal of kidney diseases : the official journal of the National Kidney Foundation.

[27]  F. Cosio,et al.  Measurement of SC5b-9 in urine in patients with the nephrotic syndrome. , 1991, Kidney international.

[28]  T. Welch,et al.  Detection and cellular localization of human C4 gene expression in the renal tubular epithelial cells and other extrahepatic epithelial sources. , 1991, The American journal of pathology.

[29]  M. Daha,et al.  Interleukin 2 mediates stimulation of complement C3 biosynthesis in human proximal tubular epithelial cells. , 1991, The Journal of clinical investigation.

[30]  T. Hostetter,et al.  Role of ammonia in progressive interstitial nephritis. , 1991, American journal of kidney diseases : the official journal of the National Kidney Foundation.

[31]  Jennifer K. Adams,et al.  A relationship between proteinuria and acute tubulointerstitial disease in rats with experimental nephrotic syndrome. , 1991, The American journal of pathology.

[32]  G. Remuzzi,et al.  Is glomerulosclerosis a consequence of altered glomerular permeability to macromolecules? , 1990, Kidney international.

[33]  M. Schönermark,et al.  C5b-8 and C5b-9 modulate the collagen release of human glomerular epithelial cells. , 1990, Kidney international.

[34]  A. Alfrey,et al.  Role of iron in the tubulo-interstitial injury in nephrotoxic serum nephritis. , 1989, Kidney international.

[35]  A. Eddy.  Interstitial nephritis induced by protein-overload proteinuria. , 1989, The American journal of pathology.

[36]  K. Resch,et al.  Activation of glomerular mesangial cells by the terminal membrane attack complex of complement. , 1987, Journal of immunology.

[37]  G. Remuzzi,et al.  Tubulo-interstitial lesions mediate renal damage in adriamycin glomerulopathy. , 1986, Kidney international.

[38]  C. Ponticelli,et al.  Prognostic indicators in idiopathic IgA mesangial nephropathy. , 1986, The Quarterly journal of medicine.

[39]  W. Couser,et al.  Complement membrane attack complex stimulates production of reactive oxygen metabolites by cultured rat mesangial cells. , 1986, The Journal of clinical investigation.

[40]  T. Hostetter,et al.  Pathophysiology of chronic tubulo-interstitial disease in rats. Interactions of dietary acid load, ammonia, and complement component C3. , 1985, The Journal of clinical investigation.

[41]  G. Mazzucco,et al.  The Brush Border of Proximal Tubules of Normal Human Kidney Activates the Alternative Pathway of the Complement System In Vitroa a , 1983, Annals of the New York Academy of Sciences.

[42]  D. Koffler,et al.  Localization of the membrane attack complex (MAC) in experimental immune complex glomerulonephritis , 1983, The Journal of experimental medicine.

[43]  G. Camussi,et al.  In vitro alternative pathway activation of complement by the brush border of proximal tubules of normal rat kidney. , 1982, Journal of immunology.

[44]  D. Koffler,et al.  Renal localization of the membrane attack complex in systemic lupus erythematosus nephritis , 1981, The Journal of experimental medicine.

[45]  P. J. Baker,et al.  Interactions of human, cultured kidney cells with the complement system. , 1981, Kidney international.

[46]  P. Baker,et al.  Activation of human complement by heat-killed, human kidney cells grown in cell culture. , 1980, Journal of immunology.

[47]  C. Chantler,et al.  The long-term prognosis of patients with focal segmental glomerulosclerosis. , 1978, Clinical nephrology.

[48]  Wuding Zhou,et al.  Apical proteins stimulate complement synthesis by cultured human proximal tubular epithelial cells. , 1999, Journal of the American Society of Nephrology : JASN.

[49]  J. Nagy,et al.  Membrane attack complex and membrane cofactor protein are related to tubulointerstitial inflammation in various human glomerulopathies. , 1997, Nephron.

[50]  C. Caserta,et al.  Alternative pathway complement activation induces proinflammatory activity in human proximal tubular epithelial cells. , 1997, Nephrology, dialysis, transplantation : official publication of the European Dialysis and Transplant Association - European Renal Association.

[51]  G. Hänsch,et al.  Induction of matrix protein synthesis in human glomerular mesangial cells by the terminal complement complex. , 1994, Experimental nephrology.

[52]  G. Schreiner,et al.  Contribution of proteinuria to progressive renal injury: consequences of tubular uptake of fatty acid bearing albumin. , 1993, American journal of nephrology.

[53]  M. Daha,et al.  IFN-gamma mediates stimulation of complement C4 biosynthesis in human proximal tubular epithelial cells. , 1993, Kidney international.

[54]  M. Jackson,et al.  Tubular metabolism of aprotinin 99mTc and urinary ammonia: effects of proteinuria. , 1992, Mineral and electrolyte metabolism.

[55]  N. Jones,et al.  Glomerular epithelial cell endocytosis of immune deposits in human lupus nephritis. , 1991, Nephrology, Dialysis and Transplantation.

[56]  M. Schönermark,et al.  Induction of mediator release from human glomerular mesangial cells by the terminal complement components C5b-9. , 1991, International archives of allergy and applied immunology.