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

2000 ◽  
Vol 36 (2) ◽  
pp. 378-391 ◽  
Author(s):  
Jennifer C. Hood ◽  
Judy Savige ◽  
Anthony E. Seymour ◽  
John Dowling ◽  
Paul Martinello ◽  
...  
Keyword(s):  
Autosomal Dominant ◽  
Basement Membranes ◽  
Hereditary Nephritis ◽  
Ultrastructural Appearance

scholarly journals Prevalence of clinical, pathological and molecular features of glomerular basement membrane nephropathy caused by COL4A3 or COL4A4 mutations: a systematic review

2020 ◽  
Vol 13 (6) ◽  
pp. 1025-1036 ◽  
Author(s):  
Andreas Matthaiou ◽  
Tsielestina Poulli ◽  
Constantinos Deltas
Keyword(s):  
Basement Membrane ◽  
Alport Syndrome ◽  
Autosomal Dominant ◽  
Wide Spectrum ◽  
Age At Onset ◽  
Histological Finding ◽  
Basement Membranes ◽  
Thin Basement Membrane Nephropathy ◽  
Molecular Features ◽  
Thin Basement Membrane Disease

Abstract Background Patients heterozygous for COL4A3 or COL4A4 mutations show a wide spectrum of disease, extending from familial isolated microscopic haematuria, as a result of thin basement membranes (TBMs), to autosomal dominant Alport syndrome (ADAS) and end-stage renal disease (ESRD). Many patients are mentioned in the literature under the descriptive diagnosis of TBM nephropathy (TBMN), in which case it actually describes a histological finding that represents the carriers of autosomal recessive Alport syndrome (ARAS), a severe glomerulopathy, as most patients reach ESRD at a mean age of 25 years. Methods We performed a systematic literature review for patients with heterozygous COL4A3/A4 mutations with the aim of recording the spectrum and frequency of pathological features. We searched three databases (PubMed, Embase and Scopus) using the keywords ‘Autosomal Dominant Alport Syndrome’ OR ‘Thin Basement Membrane Disease’ OR ‘Thin Basement Membrane Nephropathy’. We identified 48 publications reporting on 777 patients from 258 families. Results In total, 29% of the patients developed chronic kidney disease (CKD) and 15.1% reached ESRD at a mean age of 52.8 years. Extrarenal features and typical Alport syndrome (AS) findings had a low prevalence in patients as follows: hearing loss, 16%; ocular lesions, 3%; basement membrane thickening, 18.4%; and podocyte foot process effacement, 6.9%. Data for 76 patients from 54 families emphasize extensive inter- and intrafamilial heterogeneity, with age at onset of ESRD ranging between 21 and 84 years (mean 52.8). Conclusions The analysis enabled a comparison of the clinical course of patients with typical ARAS or X-linked AS with those with heterozygous COL4A mutations diagnosed with TBMN or ADAS. Despite the consequence of a potential ascertainment bias, an important outcome is that TBM poses a global high risk of developing severe CKD, over a long follow-up, with a variable spectrum of other findings. The results are useful to practicing nephrologists for better evaluation of patients.

scholarly journals Bull terrier hereditary nephritis: A model for autosomal dominant Alport syndrome

1995 ◽  
Vol 47 (3) ◽  
pp. 758-765 ◽  
Author(s):  
Jennifer C. Hood ◽  
Judy Savige ◽  
Anne Hendtlass ◽  
Mary M. Kleppel ◽  
Clive R. Huxtable ◽  
...  
Keyword(s):  
Alport Syndrome ◽  
Autosomal Dominant ◽  
Hereditary Nephritis

scholarly journals Alport’s syndrome and benign familial haematuria: Light and electron microscopic studies of the kidney

2008 ◽  
Vol 136 (Suppl. 4) ◽  
pp. 275-281
Author(s):  
Jovan Dimitrijevic ◽  
Vera Todorovic ◽  
Anastasija Aleksic ◽  
Dijana Jovanovic ◽  
Dijana Pilcevic ◽  
...  
Keyword(s):  
Electron Microscopy ◽  
Light Microscopy ◽  
Light And Electron Microscopy ◽  
Definitive Diagnosis ◽  
Basement Membranes ◽  
Tissue Slices ◽  
Electron Microscopic ◽  
Tissue Samples ◽  
Hereditary Nephritis ◽  
Hereditary Nephropathy

INTRODUCTION. Hereditary nephropathy is clinically characterized by the familial occurrence in successive generations of progressive haematuric nephritis and neural hearing loss. Hereditary nephropathy of Alport?s syndrome (AS) and benign familial (recurrent) haematuria (BFH) are morphologically characterized by specific and diagnostically important thickening and splitting of lamina densa of the glomerular basement membranes. Those lesions can be recognized only by electron microscopy. Hereditary nephritis is usually present clinically with haematuria, and new mutations without a family history of haematuria. It is therefore important to differentiate hereditary nephritis from BFH and no familial haematuria. Thus, electron microscopy is essential in diagnosis of haematuria. OBJECTIVE. The aim of this study was to describe, by light microscopy, constellation of renal alterations by which hereditary nephropathy can be recognized with high probability as well as to compare the diagnostic validity of the findings observed by light and electron microscopy in AS and BFH. METHOD. We examined 48 renal biopsies of the patients with hereditary nephoropathies by light and electron microscopy. Tissue samples were fixed in buffered paraformaldehyde and embedded in paraffin for long-term preservation. For the electron microscopy analysis, the following fixation in 4% glutaraldehyde tissue was postfixed in 1% osmium tetroxide. Thereafter, the following dehydration procedure tissue slices were embedded in epon. RESULTS. Our results demonstrated that the interstitial foam cells, foetal-like glomeruli, minimal glomerular abnormalities with stain less intense in basement membranes, mild irregular mesangial widening, focal thickening of Bowman?s capsule, foci of dilatation tubules, tubular ectasia and atrophy, erythrocyte tubules casts were present in hereditary nephritis. Additionally, light microscopic biopsy findings in patients with BFH were either normal or revealed minor changes (e.g. increased mesangial matrix). All biopsies were reevaluated by electron microscopy and ultrastructural findings confirmed the diagnosis of hereditary nephropathies. CONCLUSION. The findings observed by light microscopy represent an important step that leads to a definitive diagnosis of AS and BFH. The definitive diagnosis, however, depends on electron microscopy.

Hereditary endotheliopathy with retinopathy, nephropathy, and stroke(HERNS)

Neurology ◽  
1997 ◽  
Vol 49 (5) ◽  
pp. 1322-1330 ◽  
Author(s):  
J. Jen ◽  
A. H. Cohen ◽  
Q. Yue ◽  
J. T. Stout ◽  
H. V. Vinters ◽  
...  
Keyword(s):  
Autosomal Dominant ◽  
Basement Membranes ◽  
American Family ◽  
Psychiatric Disturbance ◽  
Systemic Involvement ◽  
Ultrastructural Studies ◽  
The Third ◽  
Fourth Decade ◽  
The Brain ◽  
Renal Abnormalities

We describe a Chinese American family with a hereditary syndrome consisting of retinopathy, nephropathy, and stroke, affecting 11 members spanning three generations. Ophthalmologic evaluations revealed macular edema with capillary dropout and perifoveal microangiopathic telangiectases. Several members had renal abnormalities with proteinuria and hematuria. Initial manifestations were visual impairment and renal dysfunction; neurologic deficits occurred in the third or fourth decade of life. Symptoms included migraine-like headache, psychiatric disturbance, dysarthria, hemiparesis, and apraxia. Neuroimaging consistently demonstrated contrast-enhancing subcortical lesions with surrounding edema. Ultrastructural studies showed distinctive multilaminated vascular basement membranes in the brain and in other tissues, including the kidney, stomach, appendix, omentum, and skin. Genetic analysis ruled out linkage to the CADASIL locus on chromosome 19. Distinct from CADASIL, hereditary endotheliopathy with retinopathy, nephropathy, and stroke (HERNS) is an autosomal dominant multi-infarct syndrome with systemic involvement.

scholarly journals Familial Juvenile Hyperuricemic Nephropathy and Autosomal Dominant Medullary Cystic Kidney Disease Type 2: Two Facets of the Same Disease?

2001 ◽  
Vol 12 (11) ◽  
pp. 2348-2357 ◽  
Author(s):  
KARIN DAHAN ◽  
ARNO FUCHSHUBER ◽  
STAVROULA ADAMIS ◽  
MICHÈLE SMAERS ◽  
SABINE KROISS ◽  
...  
Keyword(s):  
Kidney Disease ◽  
Autosomal Dominant ◽  
Disease Type ◽  
Basement Membranes ◽  
Cystic Kidney Disease ◽  
Cystic Kidney ◽  
Autosomal Dominant Disorder ◽  
Medullary Cystic Kidney Disease ◽  
Familial Juvenile Hyperuricemic Nephropathy

Abstract. Familial juvenile hyperuricemic nephropathy (FJHN) is an autosomal dominant disorder heralded by hyperuricemia during childhood; it is characterized by chronic interstitial nephritis, with marked thickening of tubular basement membranes, and leads to progressive renal failure during adulthood. A gene for FJHN in two Czech families was recently mapped to chromosome 16p11.2, close to the MCKD2 locus, which is responsible for a variant of autosomal dominant medullary cystic kidney disease observed in an Italian family. In a large Belgian family with FJHN, a tight linkage between the disorder and the marker D16S3060, located within the MCKD2 locus on chromosome 16p12 (maximal two-point logarithmic odds score of 3.74 at a recombination fraction of θ = 0), was observed in this study. The candidate region was further narrowed to a 1.3-Mb interval between D16S501 and D16S3036. Together with the striking clinical and pathologic resemblance between previously reported medullary cystic kidney disease type 2 and FJHN occurring in the Belgian family (including the presence of medullary cysts), this study suggests that these two disorders are facets of the same disease.

scholarly journals The Genetics, Current Research, and Future Treatment of Alport Syndrome

2017 ◽  
Vol 6 (1) ◽  
pp. 1-7
Author(s):  
Elise Alexandra Kikis ◽  
Emily Holland Williams
Keyword(s):  
Basement Membrane ◽  
End Stage Renal Disease ◽  
Alport Syndrome ◽  
Autosomal Recessive ◽  
Type Iv Collagen ◽  
Autosomal Dominant ◽  
Basement Membranes ◽  
Type Iv ◽  
Stage Renal Disease ◽  
End Stage

Alport syndrome is a type IV collagen disease that affects the glomerular basement membrane of approximately one in every 5000 people. The disease was first described by A. Cecil Alport in 1927 as “a dominantly inherited hereditary nephritis.” The three genotypes of the disease are X-linked dominant, autosomal recessive, and autosomal dominant. The X-linked dominant genotype is the most common, accounting for 80% of all cases of Alport syndrome, affecting mainly men. The autosomal recessive and autosomal dominant types affect men and women equally. Alport syndrome is caused by mutations on the COL4A3, COL4A4, and COL4A5 genes, which code the ?3, ?4, and ?5 (IV) chains that make up type IV collagen molecules, an important component of basement membranes. Thus, Alport syndrome results in malformed basement membranes, with symptoms including renal impairment, hematuria, bilateral sensorineural hearing loss, and an abnormal structure of the glomerular basement membrane. Alport syndrome also often progresses to end-stage renal disease, especially in men with X-linked Alport syndrome. At this point, there is no cure for Alport syndrome. However, there are many successful treatments for its symptoms. Angiotensin-converting enzyme (ACE) inhibitors are often given to patients in the early stages of Alport syndrome. For patients with end-stage renal disease, dialysis or kidney transplants are considered the best course of action.

scholarly journals Autosomal dominant form of type IV collagen nephropathy exists among patients with hereditary nephritis difficult to diagnose clinicopathologically

Nephrology ◽  
2018 ◽  
Vol 23 (10) ◽  
pp. 940-947 ◽  
Author(s):  
Aya Imafuku ◽  
Kandai Nozu ◽  
Naoki Sawa ◽  
Eiko Hasegawa ◽  
Rikako Hiramatsu ◽  
...  
Keyword(s):  
Type Iv Collagen ◽  
Autosomal Dominant ◽  
Dominant Form ◽  
Hereditary Nephritis ◽  
Type Iv ◽  
Autosomal Dominant Form

scholarly journals Significance of kidney biopsy in autosomal dominant tubulointerstitial kidney disease-UMOD: is kidney biopsy truly nonspecific?

2021 ◽  
Vol 22 (1) ◽  
Author(s):  
Tamehito Onoe ◽  
Satoshi Hara ◽  
Kazunori Yamada ◽  
Takeshi Zoshima ◽  
Ichiro Mizushima ◽  
...  
Keyword(s):  
Kidney Disease ◽  
Autosomal Dominant ◽  
Kidney Biopsy ◽  
Interstitial Fibrosis ◽  
Hereditary Disease ◽  
Basement Membranes ◽  
Pathological Findings ◽  
Tubular Atrophy ◽  
Pas Staining ◽  
Conventional Methods

Abstract Background Autosomal dominant tubulointerstitial kidney disease (ADTKD) is a rare hereditary disease caused by a variety of genetic mutations. Carriers of a mutation in the responsible genes are at risk of reaching end-stage kidney disease typically in middle age. The frequency of this disease is assumed to be underestimated because of a lack of disease-specific signs. Pathological findings obtained from kidney of uromodulin related ADTKD (ADTKD-UMOD) patients are regarded as non-specific and less-informative for its diagnosis. This research was undertaken to evaluate the significance of kidney biopsy in ADTKD-UMOD patients. Methods Thirteen patients from 10 families with nine identified uromodulin (UMOD) gene mutations who underwent kidney biopsy in the past were studied. Their kidney tissues were stained with anti-UMOD antibody in addition to conventional methods such as PAS staining. When positive, the numbers of tubules with visible UMOD protein accumulations were calculated based on the total numbers of UMOD expressing tubules. Pathological findings such as tubulointerstitial fibrosis, atrophy, inflammation and glomerulosclerosis were also evaluated and analyzed. Results Interstitial fibrosis and tubular atrophy were present in all 13 patients. Most atrophic tubules with thickening and lamellation of tubular basement membranes showed negative UMOD staining. In all but two patients with C94F mutations, massive accumulation of UMOD proteins was observed in the renal endoplasmic reticulum. UMOD accumulations were also detectable by PAS staining as polymorphic unstructured materials in the 11 patients at frequencies of 2.6–53.4%. 80.4% of the UMOD accumulations were surrounded by halos. The detection rate of UMOD accumulations positively correlated with eGFR. Glomerulosclerosis was detected in 11/13 patients, with a frequency of 20.0 to 61.1%, while no cystic dilatations of glomeruli were detected. Conclusions Massively accumulated UMOD proteins in ADTKD-UMOD kidneys are detectable not only by immunostaining using anti-UMOD antibody but also by conventional methods such as PAS staining, although their detection is not easy. These findings can provide important clues to the diagnosis of ADTKD-UMOD. Kidney biopsy in ADTKD-UMOD may be more informative than assumed previously.

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