Familial nephropathy differing from minimal change nephropathy and focal glomerulosclerosis

Branten, A. J. W.; Born, Jacob van den; Jansen, J.; Assmann, K.J.M.; Wetzels, Jack F.M.; Dijkman, with the technical assistance of Henry B.P.M.

doi:10.1046/j.1523-1755.2001.059002693.x

Cited by 30 publications

(23 citation statements)

References 34 publications

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“…These results are compatible with the entity referred to as "no change disease" previously described in experimental models and in cases of human nephrotic syndrome (25)(26)(27).…”

Section: Renal Phenotyping Of P0 ϫ/ϫ Micesupporting

confidence: 91%

“…Even if most proteinuric renal diseases are associated with massive loss of podocyte foot processes, there are indeed human and experimental models of nephrotic-range proteinuria in which this podocyte abnormality is absent. In human, a familial form of nephrotic syndrome without podocyte alteration has been previously reported (25), and a sporadic case of massive proteinuria with only segmental effacement of foot processes affecting 20 to 30% of capillary loops has been observed (26). In the rat, injection of mAb 5-1-6 directed against nephrin induces massive proteinuria without any foot process damage (27).…”

Section: Discussionmentioning

confidence: 99%

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Glomerular Permeability Is Altered by Loss of P0, a Myelin Protein Expressed in Glomerular Epithelial Cells

Plaisier¹,

Mougenot²,

Verpont³

et al. 2005

Journal of the American Society of Nephrology

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The myelin protein 0 (MPZ or P0) is a transmembrane glycoprotein that represents the most abundant myelin component. Mutations in the P0 gene are associated with one form of autosomal dominant demyelinating peripheral neuropathy, Charcot-Marie-Tooth disease type 1B (CMT1B). Because CMT1 may be associated with renal involvement, mostly focal segmental glomerulosclerosis, we hypothesized that P0 could be expressed in the kidney. P0 mRNA was detected by reverse transcriptase-PCR in the human and mouse renal cortex. P0 transcripts were identified by in situ hybridization at different stages of the mouse kidney development, especially in embryonic structures that give rise to the glomerulus. P0 protein was also detected by Western blot in human and rat glomerular extracts and in a human podocyte cell line using a monoclonal anti-P0 antibody. Immunofluorescence studies on human kidney sections showed that the podocytes were intensely labeled. Immunogold electron microscopy disclosed a predominant staining of the membranes of intracellular vesicles in podocytes. P0 was also detected in the podocyte cell membrane, including at the foot processes. P0؊/؊ mice exhibited mild growth retardation and demyelinating neuropathy similar to the one observed in patients with CMT1B. They also presented mild albuminuria, without significant ultrastructural change of the glomerular basement membrane or the podocytes. These results demonstrate that P0, the major myelin protein, is also expressed during nephrogenesis and in mature kidney, mostly in podocytes. They suggest that P0 gene mutations might be involved in renal diseases.

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“…These results are compatible with the entity referred to as "no change disease" previously described in experimental models and in cases of human nephrotic syndrome (25)(26)(27).…”

Section: Renal Phenotyping Of P0 ϫ/ϫ Micesupporting

confidence: 91%

Section: Discussionmentioning

confidence: 99%

Glomerular Permeability Is Altered by Loss of P0, a Myelin Protein Expressed in Glomerular Epithelial Cells

Plaisier¹,

Mougenot²,

Verpont³

et al. 2005

Journal of the American Society of Nephrology

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“…14 Renal biopsies from patients with minimal change nephropathy show absent or markedly reduced glomerular basement membrane staining with an antibody against heparan sulfate side chains but normal staining for the agrin core protein of heparan sulfate proteoglycans. 15 Recently, it has been demonstrated that relapsing steroid-sensitive nephrotic syndrome in children is associated with elevated urinary heparanase activity, 16 implicating loss of heparan sulfate in the pathogenesis of the nephrotic syndrome in these patients. Heparanase is expressed by peripheral T lymphocytes, providing a link between the immune abnormalities and glomerular basement membrane changes observed in minimal change nephropathy.…”

Section: Hereditary Multiple Exostosesmentioning

confidence: 99%

Familial Nephropathy and Multiple Exostoses With Exostosin-1 (EXT1) Gene Mutation

Roberts

Gleadle

2008

Journal of the American Society of Nephrology

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“…Variants of minimal-change nephritic syndrome with proteinuria are not associated with podocyte foot process effacement (44). Branten et al (45) report that a familial form of nephrotic syndrome occurs in the absence of podocyte foot process effacements. Additionally, several other anecdotal reports with human biopsies that support the notion that proteinuria can occur without podocyte foot process effacement exist.…”

mentioning

confidence: 99%

Proteinuria with and without Renal Glomerular Podocyte Effacement

Kalluri

2006

Journal of the American Society of Nephrology

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Renal biopsies of patients with proteinuria and kidney disease most often are associated with podocyte foot process effacement. For several decades, nephrologists have wondered whether proteinuria is a result of podocyte foot process effacement or the cause of it. In the past few years, the author's laboratory has addressed this issue using different mouse models of proteinuria. Although in most cases, podocyte effacement is associated with proteinuria and glomerular disease, in three different mouse models, it was demonstrated that proteinuria can be observed without podocyte foot process effacement. The first model is generated by injection of antibodies to vascular endothelial growth factor or soluble vascular endothelial growth factor receptor 1. The second model is a mouse with deletion of type IV collagen ␣3 chain in the glomerular basement membrane. The third model was generated by genetic deletion of a slit diaphragm protein known as nephrin. Collectively, these experiments and the supporting evidence from several human studies demonstrate that severe defects in either the glomerular basement membrane or the glomerular endothelium can lead to proteinuria without foot process effacement.J Am Soc Nephrol 17: 2383 -2389, 2006 . doi: 10.1681 I n the process of blood filtration, the two kidneys in the human body clear approximately 125 ml of filtrate that enters the renal tubular system via the glomeruli every minute, or approximately 180 L of plasma filtrate every day. In a normal physiologic setting, it is thought at any given time, the filtrate volume represents approximately 20% of the total plasma that enters the glomeruli, and the other 80% of the plasma bypasses the renal tubular system and enters the efferent arterioles directly. Of 125 ml of filtrate that enters the renal tubular system per minute, 124 ml is reclaimed by tubular resorption, tubular secretion, and concentration. The urine that enters the ureters is very different in its molecular composition and is only a very small fraction of the total plasma being filtered, which in a given day can accumulate to approximately 1.5 L in the bladder. During a 24-h period, approximately 1.5 g of salt also is filtered by the renal system.Renal glomerular filtration apparatus is composed of three different components: The fenestrated endothelium, the glomerular basement membrane (GBM), and the epithelial cells with characteristic foot processes, known as podocytes (1-9). Filtration through this barrier depends on the charge and the size of the molecules present in the blood. In addition, it depends on the net filtration pressure in the glomerular tuft. The entire blood volume of a human passes through the kidneys approximately every 5 min. In a normal physiologic setting, the arterial capillaries of the glomerular tuft are under a hydrostatic pressure of approximately 45 mmHg (this pressure is higher than that found in other capillaries) and facilitated by the juxtaglomerular apparatus autoregulation, which constricts or dilates the afferent arterioles i...

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Familial nephropathy differing from minimal change nephropathy and focal glomerulosclerosis

Abstract: We propose that this family represents a new familial nephropathy. The molecular basis of the permeability defect remains to be identified.

Cited by 30 publications

References 34 publications

Glomerular Permeability Is Altered by Loss of P0, a Myelin Protein Expressed in Glomerular Epithelial Cells

Glomerular Permeability Is Altered by Loss of P0, a Myelin Protein Expressed in Glomerular Epithelial Cells

Familial Nephropathy and Multiple Exostoses With Exostosin-1 (EXT1) Gene Mutation

Proteinuria with and without Renal Glomerular Podocyte Effacement

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