Search PubMed⌕ Search

SEARCH · Search PubMed

Results for “Nephritis, Hereditary”

Search indexed PubMed citations on genomics, clinical trials, systematic reviews and public health. Explore titles, authors and supplied subject terms, then open the PubMed record.

Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.

At least 19 recordsLinked to original sources
PubMed1987

Nonfamilial hematuria associated with glomerular basement membrane alterations characteristic of hereditary nephritis: comparison with hereditary nephritis.

Characteristic ultrastructural alterations of the glomerular basement membrane (GBM) have been reported in hereditary nephritis and in children without a family history of renal disease. The clinical features, renal biopsy findings, and subsequent course were studied retrospectively in 48 children with such GBM changes to compare findings in those with and without a family history of nephritis and to determine the significance of the GBM changes in patients with nonfamilial disease. All 48 patients had hematuria. For 30, there was hematuria in at least one other member of the family (familial hematuria group); for 18, there was no familial incidence. There were no differences between the two groups with regard to clinical and pathologic findings. At the latest follow-up six boys with familial hematuria and three boys with nonfamilial hematuria had reduced renal function, and nine boys with familial hematuria and four boys and one girl with nonfamilial hematuria had neurosensory deafness. Our study results show that children with these GBM changes, with or without a family history of hematuria, tend to have a progressive course, with frequent occurrence of neurosensory deafness, and that the prognosis is more severe in boys. These observations suggest that such GBM changes in patients with nonfamilial hematuria may represent new mutations for hereditary nephritis.

Basement Membrane↗
PubMed1983

Catabolites of the third component of complement in urines of hereditary nephritis patients.

Hereditary nephritis protein (HNP), an unusual urine protein from patients with hereditary nephritis (Alport Syndrome), was purified 120-fold to homogeneity. A slightly larger protein, pro-HNP, was similarly purified and was found to be a precursor of HNP. Both pro-HNP and HNP showed immunological identity to the third component of human complement, C3, and to its catabolite C3c. Pro-HNP had a molecular weight of 143,000 and, in equimolar ratio, polypeptide chains or fragments of molecular weights 75,000, 40,000, and 28,000. The largest and smallest chains contained carbohydrate. HNP had a molecular weight of 141,000 and fragments of molecular weights 60,000, 38,000, 26,000, and 17,000 in equimolar ratio; the two smallest fragments contained carbohydrate. Plasmin digestion of pro-HNP showed that the 75,000-Da chain, identical with the intact beta-chain of C3, broke down to the 60,000- and 17,000-Da fragments of HNP. In both pro-HNP and HNP, the polypeptide chains were linked by disulfide bonds, with the exception of the 17,000-Da fragment of HNP. This fragment was readily dissociated from the rest of the HNP molecule in the presence of sodium dodecyl sulfate. Amino acid analyses showed that both pro-HNP and HNP contained approximately 22 half-cystine residues per molecule. Extinction coefficients, epsilon 1% 1cm, at 280 nm were calculated to be 8.5 and 8.8 for pro-HNP and HNP, respectively.

Amino Acids↗
PubMed1989

Abnormalities in the NC1 domain of collagen type IV in GBM in canine hereditary nephritis.

Samoyed hereditary glomerulopathy (SHG) in dogs serves as a model for human X-linked hereditary nephritis (HN). We previously showed that glomerular capillaries of affected males did not stain by immunofluorescence (IF) using serum from a patient with Goodpasture's syndrome. Our goal in the present study was to determine whether the NC1 domain of the collagen type IV molecule, which contains Goodpasture antigen (GPA), could be demonstrated in these dogs, and to assess its immunological reactivity. By SDS-PAGE, NC1 in collagenase digests of glomerular basement membranes (GBM) of unaffected and carrier female dogs in the family with SHG showed 24 kilodalton (kD), 26 kD and 28 kD monomer, and 46 kD and 47 kD dimer components, but the 24 kD monomer was diminished in the affected males. By IF, a rabbit antibody to NCl stained glomerular capillaries of unaffected, affected male, and carrier female dogs. In contrast, a human anti-GBM plasmapheresis fluid (PPF) stained glomerular capillaries of only the unaffected and carrier female dogs. By RIA, both antibodies reacted strongly with NCl in collagenase digests of GBM of the unaffected and carrier female dogs, but showed reduced reactivity with NCl of affected males. By Western blotting, both antibodies bound to dimers and 24 kD and 26 kD monomers of the NCl domain in collagenase digests of GBM of unaffected and carrier female dogs. However, in affected males, the rabbit anti-NCl antibody did not bind to the 24 kD monomer, while the human anti-GBM PPF showed weak binding to the 24 kD and 26 kD monomers.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1994

Canine X chromosome-linked hereditary nephritis: a genetic model for human X-linked hereditary nephritis resulting from a single base mutation in the gene encoding the alpha 5 chain of collagen type IV.

Many families with X-chromosome linked hereditary nephritis (HN) have mutations in the gene on the X chromosome that codes for the alpha 5 chain of collagen type IV. Canine X-linked HN is an animal model for human X-linked HN. To study the alpha 5(IV) gene in this model, we used the nucleotide sequence published for the human alpha 5(IV) cDNA to construct sets of primers covering approximately 95% of the complete cDNA. cDNA from both affected and normal dog kidneys was amplified by PCR in nine overlapping regions. The nucleotide sequence encoding the noncollagenous domain NC1 hybridized to the human X chromosome and was 93% identical at the DNA level and 97% identical at the protein level to the human alpha 5(IV) NC1 domain, confirming that the canine alpha 5(IV) cDNA had been amplified. Sequence analysis of the alpha 5(IV) cDNA detected a single nucleotide substitution, G-->T, in affected dogs, changing a codon for a conserved glycine residue (GGA) to a stop codon (TGA). When genomic DNA was amplified, the same abnormality was found in exon 35. Using the canine NC1 domain cDNA as a probe for Northern analysis, two transcripts of approximately 8.6 kb and approximately 6.7 kb were identified in both normal and affected male dog kidney RNA. However, the abundance of both transcripts was decreased by a factor of approximately 10 in the affected dog. These results establish at the molecular level that canine X-linked HN is a model for human X-linked HN. This model provides an opportunity to determine the efficacy of new therapies and to investigate the role of the alpha 5(IV) chain in type IV collagen assembly.

Amino Acid Sequence↗
PubMed1992

Production of anti-NC1 antibody by affected male dogs with X-linked hereditary nephritis: a probe for assessing the NC1 domain of collagen type IV in dogs and humans with hereditary nephritis.

Some patients with hereditary nephritis (HN) who have received a renal transplant have been shown to form antibody with specificity for the NC1 domain of collagen type IV, a major constituent of glomerular basement membranes (GBM). We attempted to duplicate this phenomenon in a family of dogs with X-linked HN, a model for human X-linked HN, by immunizing affected male dogs with normal dog NC1 domain. A collagenase digest was prepared from normal dog GBM, the NC1 domain was separated into dimer (approximately 50 kDa) and monomer (24 kDa and 26 kDa) components by SDS-PAGE, and injected into two affected male dogs. Antisera obtained from both dogs contained antibody which reacted with the NC1 domain of dog and human GBM by a plate-binding radioimmunoassay, bound to the dimer and 26 kDa monomer bands by Western blotting, and staining dog and human GBM by immunofluorescence (IF). The affected male dog antiserum reacted equally by radioimmunoassay with the NC1 domain isolated from GBM of unaffected, affected male, and carrier female dogs in the family with X-linked HN, and bound by Western blotting to dimers and the 26 kDa monomer band of the NC1 domain of GBM in each group of dogs. However, the affected male dog antiserum differentiated these dogs by IF; it produced global staining of GBM of unaffected dogs, failed to stain GBM of affected male dogs, and produced segmental staining of GBM of carrier female dogs. Absorption of the affected male dog antiserum with normal dog NC1 domain eliminated the staining of dog GBM by IF, whereas staining persisted after absorption with affected male dog NC1 domain. The abnormal staining patterns of GBM seen by IF in the affected male and carrier female dogs and the results of the absorption studies imply an abnormality of one or more determinants in the 26 kDa monomer band of the NC1 domain of their GBM. Amino acid sequencing of this band identified the alpha 1(IV) chain of collagen type IV, a finding that has implications for the pathogenesis of canine X-linked HN. Absent and segmental staining respectively were also seen by IF in GBM of a male and female patient with HN, using the affected male dog antiserum. Thus, the results obtained in affected male and carrier female dogs with X-linked HN may also be relevant to patients with this disease.

Amino Acid Sequence↗
PubMed2000

Ultrastructural appearance of renal and other basement membranes in the Bull terrier model of autosomal dominant hereditary nephritis.

Bull terrier hereditary nephritis may represent a model for autosomal dominant Alport's syndrome because affected dogs have the typically lamellated glomerular basement membrane (GBM) and father-to-son disease transmission occurs. This study examined the ultrastructural appearance of the renal and extrarenal basement membranes and their composition in affected Bull terriers. Affected stillborn animals and puppies had subepithelial frilling and vacuolation of the GBM. In adult dogs, lamellation was common, and subepithelial frilling and vacuolation were less prominent. Foot-process effacement and mesangial matrix expansion occurred frequently. Basement membranes in the glomeruli, tubules, and Bowman's capsule were significantly thickened and often mineralized. Immunohistochemical examination showed alpha 1(IV) and alpha 2(IV) collagen chains in all renal basement membranes; alpha 3(IV), alpha 4(IV), and alpha 5(IV) chains in the GBM, distal tubular basement membrane, and Bowman's capsule; and the alpha 6(IV) chain in Bowman's capsule. Conversely, the basement membranes from the affected Bull terrier cornea, lens capsule, retina, skin, lung, and muscle had a normal ultrastructural appearance and were not thickened compared with membranes in normal age-matched dogs. The distribution of basement membrane abnormalities in Bull terrier hereditary nephritis may occur because the defective protein is present exclusively or more abundantly in the kidney and is structurally more important in the kidney or because of local intrarenal stresses.

Age Factors↗
PubMed1991

Recent developments in hereditary nephritis (Alport's syndrome).

Hereditary nephritis with deafness, or Alport's syndrome, is a familial disorder characterized by progressive renal insufficiency, sensorineural hearing loss and ocular abnormalities. The Alport's nephropathy appears to result from a primary biochemical defect of the glomerular basement membrane, specifically an alteration of type IV collagen. The cardinal clinical manifestation of Alport's is chronic hematuria. End-stage renal disease develops in most affected males, while affected females generally experience a benign renal course. The diagnosis depends on characteristic electron microscopy findings of a variably thickened and thinned glomerular basement membrane with lamellation and basket weaving. Alport's is a genetically heterogeneous disorder with several modes of inheritance. A review of the literature with discussion of the clinical and basic science aspects of hereditary nephritis is presented.

Adolescent↗
PubMed1975

[Dysembryogenesis in hereditary nephritis].

In 75 children with hereditary nephritis, in 27 ones with hematuric form of acquired nephritis and in 55 parents dysplastic symptoms were investigated. A high differential and diagnostic value of disembriogenetic stigmata for hereditary nephritis is demonstrated. It is considered that connective tissue stigmata are one of the symptoms of hereditary nephritis. Some genetic and ontogenetic aspects of displastic symptoms formation in this case are discussed.

Adolescent↗
PubMed1979

Blood coagulation and hereditary nephritis.

Nineteen patients with hereditary nephritis - members of six families - were studied for haemostasis on 11 occasions by the use of four capillary tests, 14 different blood coagulation tests and two different platelet function tests. Systemic capillaropathy was demonstrable in 8 out of 15 cases of the non-uraemic, and in all the 5 cases of the uraemic group. No completely normal blood coagulation was found in any of the cases and the coagulation disorders were never of exclusively haemorrhagic pattern. On the evidence of the complex studies, hypercoagulability as well as hyper-hypocoagulability were found in the uraemic and non-uraemic groups alike. Reduction in plasma fibrinolytic activity, elevation of the fibrinogen level and a shift of the thrombelastogram in the direction of thrombosis were demonstrable in the majority of the cases.

Adolescent↗
PubMed2006

Hereditary nephritis mimicking immune complex-mediated glomerulonephritis.

The defining ultrastructural features of hereditary nephritis are "basket weave" lamellation or thinning of glomerular basement membranes. Electron-dense deposits are not seen and immunofluorescence (IF) is generally negative. In this study, we report 5 cases of hereditary nephritis in which substantial amounts of glomerular electron-dense deposits were identified on electron microscopy, with corresponding positive IF staining in 4 cases, suggesting immune complex-mediated glomerulonephritis. However, no case had histological evidence of glomerular endocapillary or extracapillary proliferation or leukocyte infiltration typical of active glomerulonephritis. Four cases were diagnosed at outside institutions simply as forms of glomerulonephritis without considering the possibility of hereditary nephritis and were sent for consultation in contemplation of possible immunosuppressive therapy. All patients had negative serologies and no known underlying infectious or autoimmune disease; 4 patients had family history of hematuria or renal disease. The glomerular electron-dense deposits were predominantly mesangial (4 cases) and intramembranous (4 cases), as well as subepithelial (2 cases) or subendothelial (1 case). Corresponding IF positivity for immune reactants was identified in 4 cases, and IgG was the predominant immunoglobulin deposited. A characteristic feature was the tendency for deposits to form between the complex layers of glomerular basement membrane material, favoring a process of nonspecific entrapment of immune reactants within the thickened, lamellated basement membrane. In all cases, a diagnosis of hereditary nephritis was confirmed by demonstration of the characteristic loss of immunoreactivity for the alpha5 subunit of collagen IV (4 cases) or Goodpasture's antigen (1 case) in renal or epidermal basement membranes. These cases expand the spectrum of unusual pathological findings in hereditary nephritis and emphasize the potential for hereditary nephritis to mimic immune complex glomerulonephritis.

Adolescent↗
PubMed1994

Coexpression of May-Hegglin anomaly and hereditary nephritis in a family.

In three generations of a family investigation for coexpression of May-Hegglin anomaly and hereditary nephritis was done by routine studies, as well as electron microscopy of renal tissue and blood cells, platelet aggregation studies, audiograms, and ophthalmologic evaluations. The propositus had typical May-Hegglin anomaly and a mild form of hereditary nephritis. One son had May-Hegglin anomaly and possible hereditary nephritis, and one daughter had May-Hegglin anomaly and probable hereditary nephritis. A grandson had May-Hegglin anomaly but no evidence of hereditary nephritis at age 23. The mild form of hereditary nephritis described here was atypical for Alport's syndrome, but together with similar reports, suggests that a combination of May-Hegglin anomaly and mild hereditary nephritis may be a distinct disorder.

Adult↗
PubMed1995

Bull terrier hereditary nephritis: a model for autosomal dominant Alport syndrome.

Bull terrier hereditary nephritis is inherited as an autosomal dominant disease and causes renal failure at variable ages in affected dogs. The aims of this study were to compare the clinical, ultrastructural and immunohistochemical features of bull terrier hereditary nephritis with the characteristics of the human forms of Alport syndrome. Many animals with bull terrier hereditary nephritis have hematuria, and some have anterior lenticonus. However, deafness is not associated with the renal disease, and affected dogs do not have the large platelets that are occasionally seen in patients with autosomal Alport syndrome. The glomerular capillary basement membrane (GCBM) in affected bull terriers has an identical ultrastructural appearance to that seen in X-linked Alport syndrome, with lamellations and intramembranous electron-dense deposits. However, both the Goodpasture and the Alport antigens, which represent parts of the alpha 3(IV) and alpha 5(IV) collagen chains, respectively, are present in the GCBM of affected dogs. Bull terrier hereditary nephritis represents an animal model for autosomal dominant Alport syndrome, and can be used to further examine how genetic mutations affect a basement membrane protein and the corresponding membrane structure.

Animals↗
PubMed1981

The glomerular basal lamina in hereditary nephritis.

Characteristic ultrastructural alterations of the glomerular basal lamina have been reported in hereditary nephritis. The basal lamina is irregularly thickened and the lamina densa shows replication with a "basket weave" pattern, enclosing electron-lucent lacunae which frequently contain small dense particles. However there is controversy regarding the specificity of this lesion in hereditary nephritis. To determine the specificity, 366 renal biopsies from 310 children were studied retrospectively. Twenty-four out of 27 patients with hereditary nephritis showed the characteristic changes of the basal lamina and they were widespread in 17. Two patients with recurrent haematuria but no family history of deafness or haematuria showed similar extensive changes and are regarded as new mutant cases of hereditary nephritis. Similar changes were seen in 17 of the 281 patients with other conditions but were always localized to a few capillary loops. We conclude that a widespread "basket weave" pattern appears to be confined to hereditary nephritis and is seen in the great majority of such cases.

Adolescent↗
PubMed1989

The glomerular basement membrane defect in Alport-type hereditary nephritis: absence of cationic antigenic components.

Alport-type hereditary nephritis is a familial disorder which results in progressive renal insufficiency and sensorineural hearing loss. It is thought to result from a biochemical defect affecting basement membranes. To study this further, non-collagenous components of type IV collagen were prepared from the glomerular basement membrane (GBM) by collagenase digestion from three male patients with hereditary nephritis. The normal Goodpasture antigenicity of the 28 and 26 kD monomers and 54 and 50 kD dimers which may be isolated from the GBM was absent on one-dimensional immunoblots. Two-dimensional electrophoresis and immunoblotting studies showed absence of Goodpasture antigenicity of these molecular weight components as well as all cationic monomeric and dimeric spots. It is concluded that the expression of the Goodpasture antigen is altered in basement membranes of hereditary nephritis patients. The altered antigenicity thus acts as a marker for the underlying abnormality.

Anti-Glomerular Basement Membrane Disease↗
PubMed1990

Hereditary nephritis in the bull terrier: evidence for inheritance by an autosomal dominant gene.

A high prevalence of renal failure has been reported in bull terriers in Australia. The pattern of inheritance was analysed in a family of 33 bull terriers in which 10 dogs had renal disease manifested by proteinuria, ultrastructural abnormalities in the glomerular basement membrane, renal failure, or 'end stage' kidneys. The presence of at least one affected parent for each affected offspring, the approximately equal male/female ratio and the apparent absence of 'generation-skipping', strongly supported an autosomal dominant mode of inheritance, assuming a fully penetrant single major gene locus. Further evidence was not compatible with either an autosomal recessive or X-linked inheritance pattern. This contrasts with the X-linked inheritance shown in Alport's-type human hereditary nephritis and hereditary glomerulopathy in the samoyeds. Hereditary nephritis in the bull terrier should be a useful model for non-Alport's-type human hereditary nephritis, which is also reported to have an autosomal dominant inheritance pattern.

Animals↗