The Thickness of the Glomerular Basement Membrane in Congenital Nephrotic Syndrome of the Finnish Type

Autio–Harmainen, Helena; Rapola, Juhani

doi:10.1159/000182978

Cited by 18 publications

(4 citation statements)

References 7 publications

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“…The disease specifically affects the kidney and is characterized by massive proteinuria already in utero. Electron microscopic examination of NPHS1 patient kidneys reveals thinner lamina densa of the GBM than in controls, but no structural abnormality of the GBM has been detected (22,23). In kidneys of patients with NPHS1, the podocyte foot processes are absent, and no slit diaphragms have been described in the podocyte cell-cell adhesions.…”

mentioning

confidence: 91%

Nephrin is specifically located at the slit diaphragm of glomerular podocytes

Ruotsalainen

Ljungberg

Wartiovaara

et al. 1999

Proc. Natl. Acad. Sci. U.S.A.

663

488

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We describe here the size and location of nephrin, the first protein to be identified at the glomerular podocyte slit diaphragm. In Western blots, nephrin antibodies generated against the two terminal extracellular Ig domains of recombinant human nephrin recognized a 180-kDa protein in lysates of human glomeruli and a 150-kDa protein in transfected COS-7 cell lysates. In immunof luorescence, antibodies to this transmembrane protein revealed reactivity in the glomerular basement membrane region, whereas the podocyte cell bodies remained negative. In immunogold-stained thin sections, nephrin label was found at the slit between podocyte foot processes. The congenital nephrotic syndrome of the Finnish type (NPHS1), a disease in which the nephrin gene is mutated, is characterized by massive proteinuria already in utero and lack of slit diaphragm and foot processes. These features, together with the now demonstrated localization of nephrin to the slit diaphragm area, suggests an essential role for this protein in the normal glomerular filtration barrier. A zipper-like model for nephrin assembly in the slit diaphragm is discussed, based on the present and previous data.

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mentioning

confidence: 91%

Nephrin is specifically located at the slit diaphragm of glomerular podocytes

Ruotsalainen

Ljungberg

Wartiovaara

et al. 1999

Proc. Natl. Acad. Sci. U.S.A.

663

488

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“…There have been a few reports documenting the electron microscopic data of the GBM of Finnish-type CNS or DMS. The width of the GBM, especially of the lamina densa in Finnish-type CNS, is 124-144 nm, which is thinner than the control for the same age (200 nm) [1,2]. The GBM of DMS is thickened and highly irregular, with a cloudy pattern of alteration, and the changes reminiscent of Alport syndrome [18,20] suggest a disturbance of GBM development [15].…”

Section: Discussionmentioning

confidence: 99%

Diffuse mesangial sclerosis associated with Kawasaki disease: an analysis of alpha chains (α1-α6) of human type IV collagen in the renal basement membrane

et al. 1997

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A case of diffuse mesangial sclerosis (DMS) associated with Kawasaki disease is reported. A previously healthy Japanese girl, aged 4 months, presented with clinical features of Kawasaki disease. At week 10 of the illness, she developed the nephrotic syndrome, which was refractory to steroid therapy. Renal biopsy demonstrated a diffuse mesangial proliferative glomerulonephritis with microcystic tubular dilatation and, ultrastructurally, marked thinning of the lamina densa in the glomerular basement membrane (GBM) and the tubular basement membrane (TBM) of the proximal tubule. She went into chronic renal failure and died at the age of 11 months. At autopsy, the kidney revealed DMS. Histologically, we found Finnish microcystic disease in its early stages in the biopsy. Using a newly developed monoclonal antibody, we analysed the alpha chains (alpha 1-alpha 6) of type IV collagen in the GBM and TBM. There was no defective constitution of alpha chains on the thin GBM, but the thin TBM of the microcystic proximal tubule showed a weak or discontinuous reactivity for alpha 1 and alpha 2 chains, suggesting faulty formation of the basement membrane. The sclerosing glomeruli of the DMS did not depend on collapse of the GBM, which was positive for alpha 3-alpha 5 chains, but mainly on the proliferation of mesangial matrix, which was positive for alpha 1 and alpha 2 chains.

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“…Nephrin—the product of the NPHS1 gene—was discovered when mutations in NPHS1 were found in patients with congenital nephrotic syndrome of the Finnish type [72]. Examination of kidney samples from patients with congenital nephrotic syndrome of the Finnish type shows thinning of the lamina densa layer of the GBM, yet otherwise insignificantly different from healthy, control kidneys [73]. An experiment utilizing a murine model, in which the Nphs1 gene is inactivated, presents histologic evidence of podocyte foot process effacement and absence of a slit diaphragm, along with proteinuria and the immediate death soon after parturition [70].…”

Section: Nephrinmentioning

confidence: 99%

A Compendium of Urinary Biomarkers Indicative of Glomerular Podocytopathy

Sekulic

2013

Pathology Research International

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It is well known that glomerular podocyte injury and loss are present in numerous nephropathies and that the pathophysiologic consecution of disease hinges upon the fate of the podocyte. While multiple factors play a hand in glomerulopathy progression, basic logic lends that if one monitors the podocyte's status, that may reflect the status of disease. Recent investigations have focused on what one can elucidate from the noninvasive collection of urine, and have proven that certain, specific biomarkers of podocytes can be readily identified via varying techniques. This paper has brought together all described urinary biomarkers of podocyte injury and is made to provide a concise summary of their utility and testing in laboratory and clinical theatres. While promising in the potential that they hold as tools for clinicians and investigators, the described biomarkers require further comprehensive vetting in the form of larger clinical trials and studies that would give their value true weight. These urinary biomarkers are put forth as novel indicators of glomerular disease presence, disease progression, and therapeutic efficacy that in some cases may be more advantageous than the established parameters/measures currently used in practice.

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The Thickness of the Glomerular Basement Membrane in Congenital Nephrotic Syndrome of the Finnish Type

Cited by 18 publications

References 7 publications

Nephrin is specifically located at the slit diaphragm of glomerular podocytes

Nephrin is specifically located at the slit diaphragm of glomerular podocytes

Diffuse mesangial sclerosis associated with Kawasaki disease: an analysis of alpha chains (α1-α6) of human type IV collagen in the renal basement membrane

A Compendium of Urinary Biomarkers Indicative of Glomerular Podocytopathy

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