Causes and consequences of proteinuria: the kidney filtration barrier and progressive renal failure

Tryggvason, Karl; Pettersson, E

doi:10.1046/j.1365-2796.2003.01207.x

Cited by 100 publications

(91 citation statements)

References 74 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…Podocytes are polarized epithelial cells, with their interdigitating foot processes forming the outer barrier to urine protein as a high-volume/high-discrimination filter, through which the blood is filtered hydrostatically (30). Podocyte dysfunction leads to proteinuria and progression of renal diseases.…”

Section: Discussionmentioning

confidence: 99%

Overexpression of Cyclooxygenase-2 Predisposes to Podocyte Injury

Cheng¹,

Wang²,

Jo³

et al. 2007

Journal of the American Society of Nephrology

View full text Add to dashboard Cite

Increased podocyte cyclooxygenase-2 (COX-2) expression is seen in rats after renal ablation and Thy-1 nephritis and in cultured murine podocytes in response to mechanical stress. For investigation of whether COX-2 overexpression plays a role in podocyte injury, transgenic B6/D2 mice in which COX-2 expression was driven by a nephrin promoter were established. Selective upregulation of COX-2 expression in podocytes of transgenic mouse kidneys was confirmed by immunoblotting and immunohistochemistry. Whether upregulation of podocyte-specific COX-2 expression enhanced sensitivity to the development of Adriamycin nephropathy was examined. Adriamycin administration induced dramatically more albuminuria and foot process effacement and reduced glomerular nephrin mRNA and immunoreactivity in transgenic mice compared with wild-type littermates. Adriamycin also markedly increased immunoreactive COX-2 expression in podocytes from transgenic mice compared with the wild-type mice. Reverse transcriptase-PCR indicated that this increase represented a stimulation of endogenous COX-2 mRNA expression rather than COX-2 mRNA driven by the nephrin promoter. Balb/C mice, which are susceptible to renal injury by Adriamycin, also increased podocyte COX-2 expression and reduced nephrin expression in response to administration of the drug. Long-term treatment with the COX-2-specific inhibitor SC58236 ameliorated the albuminuria that was induced by Adriamycin in the transgenic mice. SC58236 also reduced Adriamycin-induced foot process effacement in both the COX-2 transgenic mice and Balb/C mice. Therefore, overexpression of COX-2 may predispose podocytes to further injury.

show abstract

Section: Discussionmentioning

confidence: 99%

Overexpression of Cyclooxygenase-2 Predisposes to Podocyte Injury

Cheng¹,

Wang²,

Jo³

et al. 2007

Journal of the American Society of Nephrology

View full text Add to dashboard Cite

show abstract

“…Further study will be necessary to understand the roles of perlecan core protein in the formation of the kidneys. Recent studies have revealed the important roles of slit diaphragms separating podocyte foot processes as filtration barriers (36,37,38). For instance, genes including NPHS-1 and NPHS-2, identified as responsible for nephrotic syndrome with the Mendelian hereditary trait, are expressed exclusively in slit diaphragms (39,40).…”

Section: Discussionmentioning

confidence: 99%

Heparan Sulfate of Perlecan Is Involved in Glomerular Filtration

Morita

Yoshimura²,

Inui³

et al. 2005

Journal of the American Society of Nephrology

View full text Add to dashboard Cite

show abstract

“…Glomerular injury leads to increased glomerular permeability to macromolecules, such that albumin and other large serum proteins are able to gain access to the mesangium and tubular fluid. In some morphologic studies, the magnitude of proteinuria or albuminuria is correlated with the magnitude of severity of glomerular and tubulointerstitial damage, as well as GFR decline (32,33). It is well established that proteinuria is part of the natural history of many CKD.…”

Section: Physiologic Basis For Proteinuria and Its Relationship To Kimentioning

confidence: 99%