Proteinuria, the pathogenesis of nephrotic edema and the progression of renal diseases

Research output: Contribution to journalArticle

Abstract

In children and adolescents, proteinuria exceeding 300 mg/day is abnormal. The glomerular capillary wall carries negative charges. This inhibits filtration of proteins because they are also negatively charged. Proteinuria may be due to 'overflow' when plasma protein level is higher than normal, or to tubular disease, but pathological proteinuria is most often of glomerular origin. Depending on its etiology, it is associated with a decrease in glomerular basement membrane negative charges, or with structural changes due to immunological mechanisms, or to hemodynamic changes. Nephrotic edema is due to salt and water retention. This is most commonly due to intrarenal factors. However, in the childhood nephrotic syndrome salt and water retention is largely secondary to hypovolemia. The pathogenesis of glomerular sclerosis is multifactorial and incompletely understood. Experimental studies have demonstrated progressive renal injury to initially normal remnant nephrons following reduction in nephron number. Clinical studies suggest that remnant nephrons in diseased human kidneys are also subject to progressive injury. Morphological studies in patients with a variety of renal diseases either have demonstrated hypertrophy (presumably reflecting hyperperfusion and hyperfiltration) or glomerulosclerosis. One can assume that in certain cases sclerosis is a consequence of the increased filtered load reaching the glomerular tuft (hyperfiltration). Pathological glomerular proteinuria is one of the risk factors leading to the progression of glomerular diseases resulting in glomerulosclerosis. In immune-mediated renal injury progressive renal failure is characterized by the development of proteinuria and glomerular sclerosis. The mechanisms responsible for the failure of remnant nephrons in patients with kidneys damaged by disease are the same as those responsible for sclerosis or remnant glomeruli in animals subjected to renal ablation. Proteinuria affects glomerular function and morphology by four different pathways. (1) It alters the regulation of fluid volumes and sodium homeostasis with activation of vasoactive hormone systems. Altered balance between vasoconstrictive and vasodilating results in an increased intraglomerular pressure. (2) Hyperlipidemia due to proteinuria represents a higher risk for systemic and intrarenal atherogenesis and thus atherosclerosis. (3) Transcapillary 'albumin space' which may induce subendothelial hyalinosis occurs also within the systemic vasculature. (4) Protein deposits within the glomerular mesangium stimulate mesangial matrix proliferation and fibrin production. All those sequences of events may be present simultaneously and their effects are additive in the progression of glomerular sclerosis.

Original languageEnglish
Pages (from-to)3-13
Number of pages11
JournalChildren's Hospital Quarterly
Volume5
Issue number1
Publication statusPublished - 1993

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Proteinuria
Disease Progression
Edema
Sclerosis
Kidney
Nephrons
Kidney Diseases
Atherosclerosis
Wounds and Injuries
Glomerular Mesangium
Salts
Glomerular Basement Membrane
Hypovolemia
Water
Nephrotic Syndrome
Hyperlipidemias
Fibrin
Hypertrophy
Renal Insufficiency
Blood Proteins

ASJC Scopus subject areas

  • Pediatrics, Perinatology, and Child Health

Cite this

Proteinuria, the pathogenesis of nephrotic edema and the progression of renal diseases. / Tulassay, T.

In: Children's Hospital Quarterly, Vol. 5, No. 1, 1993, p. 3-13.

Research output: Contribution to journalArticle

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