Nonimmunologic mechanisms of glomerular injury.

J. L. Olson, R. H. Heptinstall

Research output: Contribution to journalArticle

Abstract

From the above discussion it is clear that many factors have been invoked in the pathogenesis of progressive glomerular injury. Those which are most important include increased PGC, coagulation, serum lipid abnormalities, and hypertrophy. Although many hemodynamic alterations have been identified, increased PGC was noted most constantly. Furthermore, the loss of autoregulatory capability which was observed in some models with progressive glomerulosclerosis usually resulted in increased PGC. Increased PGC has been associated with augmented dietary protein and is seen in the Munich-Wistar rat made diabetic. Such an increase in PGC could cause direct mechanical injury to endothelial and epithelial cells, as well as be responsible for increased mesangial traffic of macromolecules with the potential for stimulating cellular proliferation and mesangial matrix increase. Additional support for the importance of increased PGC is provided by the protective effect of decreasing PGC with CEI therapy and anemia, and by the enhanced autoregulatory capability in both the Milan and Okamoto hypertensive rats. The significance of coagulation factors is confirmed by the formation of platelet and fibrin thrombi in the development of the glomerular lesions. The sequence of glomerular injury suggests that endothelial damage occurs with subsequent formation of platelet aggregates as a response to this injury. Formation of platelet aggregates may be associated with the production of substances potentially injurious to the endothelial cells. Although blocking the appearance of such thrombi by administration of heparin or thromboxane synthetase inhibitor prevents glomerular injury, the blood pressure lowering effect of these agents complicates the interpretation of the studies. Serum lipid abnormalities are also important factors in the progression of nonimmunologic glomerular injury. Such abnormalities are observed with increased dietary phosphorus or lipid, in the obese Zucker rat, and in rats with diabetes mellitus. Reduction in serum cholesterol by administration of clofibric acid or mevinolin diminishes glomerular injury independent of alterations in glomerular hemodynamics. The possible link between increased serum lipids and augmentation of glomerular injury is at present indirect. The importance of hypertrophy as a contributing factor to the progression of nonimmunologic glomerular injury is suggested by several lines of evidence. Hypertrophy, with increase in glomerular size and caliber of capillary loops, may amplify the effect of increased PGC by further intensifying the tension and mechanical stress on all elements of the capillary wall.(ABSTRACT TRUNCATED AT 400 WORDS)

Original languageEnglish (US)
Pages (from-to)564-578
Number of pages15
JournalLaboratory Investigation
Volume59
Issue number5
StatePublished - Nov 1988

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Wounds and Injuries
Hypertrophy
Lipids
Blood Platelets
Serum
Thrombosis
Endothelial Cells
Clofibric Acid
Dietary Phosphorus
Hemodynamics
Thromboxane-A Synthase
Zucker Rats
Lovastatin
Mechanical Stress
Blood Coagulation Factors
Dietary Proteins
Fibrin
Heparin
Wistar Rats
Anemia

ASJC Scopus subject areas

  • Pathology and Forensic Medicine

Cite this

Olson, J. L., & Heptinstall, R. H. (1988). Nonimmunologic mechanisms of glomerular injury. Laboratory Investigation, 59(5), 564-578.

Nonimmunologic mechanisms of glomerular injury. / Olson, J. L.; Heptinstall, R. H.

In: Laboratory Investigation, Vol. 59, No. 5, 11.1988, p. 564-578.

Research output: Contribution to journalArticle

Olson, JL & Heptinstall, RH 1988, 'Nonimmunologic mechanisms of glomerular injury.', Laboratory Investigation, vol. 59, no. 5, pp. 564-578.
Olson JL, Heptinstall RH. Nonimmunologic mechanisms of glomerular injury. Laboratory Investigation. 1988 Nov;59(5):564-578.
Olson, J. L. ; Heptinstall, R. H. / Nonimmunologic mechanisms of glomerular injury. In: Laboratory Investigation. 1988 ; Vol. 59, No. 5. pp. 564-578.
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