Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0851184 (thinning)
 11,252 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

In children with renal hematuria the Alport syndrome could be diagnosed more frequently, if electronmicroscopic examination of the patients renal biopsy and a positive family history were obtained. In 16 children with renal hematuria, Alport syndrome was suspected by renal biopsy, physical examination or family history. Electronmicroscopic examination of the biopsy specimens of all 16 children revealed thinning together with a thickening and lamellation of the glomerular basement membrane (GBM), considered to be characteristic for Alport syndrome. In 11 of the children nephropathy, inner ear deafness or ocular changes were identified in 31 family members. In these families genetic information on the risk for other children is possible; furthermore ineffective medications such as steroids and cytotoxic drugs can be avoided, once the diagnosis has been established. In 5 children with characteristic renal lesions family history revealed no further support of Alport syndrome. In these cases with presence of characteristic lesions of GMB without positive family history the diagnosis Alport syndrome cannot be established with certainty, further examinations are necessary.
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PMID:[Significance of family studies and kidney biopsies in children with renal hematuria]. 401 Jun 78

Previous reviews of hematuria in children and adolescents have included patients with proteinuria and other renal functional abnormalities such as hypertension and reduced GFR. We report the clinico-pathological correlations in 76 pediatric patients, aged 3 to 19 years, who underwent a renal biopsy because of isolated hematuria during the 10-year period, 1972 to 1981. All specimens were examined by light and electron microscopy and immunofluorescence techniques. The overall prevalence of abnormal renal histology was 56%. The vast majority (41 of 43) of the abnormal biopsy specimens could be classified into four distinct histological categories: (1) Alport syndrome (N = 9); (2) IgA nephropathy (N = 8); (3) thinning of the glomerular basement membrane (N = 17); (4) vascular C3 staining (N = 7). The children were divided into three clinical subgroups (1) isolated microscopic hematuria ( IMH ), N = 42; (2) IMH plus a family history of hematuria in a first degree relative, N = 15; and (3) IMH plus at least one episode of gross hematuria, N = 19. A significant graded increase in the likelihood of obtaining an abnormal renal biopsy was demonstrated (X2 = 10, P less than 0.007) from groups one to three. Sex, age at onset, or duration of hematuria were not associated with an increased proportion of histopathologic abnormalities. These findings indicate that the yield of a renal biopsy in children with isolated hematuria can be predicted accurately from specific clinical characteristics.
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PMID:Isolated hematuria in children: indications for a renal biopsy. 672 31

In 32 patients from 27 families affected with hereditary neophropathy (Alport syndrome) the glomerular basement membranes were examined electron microscopically and the percentage of characteristically split and thin basement membrane portions was determined. The clinical course was more severe in males which corresponded with a higher rate of basement membrane alterations: on an average in males 61% split and 6% thin but only 18% split and 21% thin in females. The splitting lesion increased with age in males but not so in females. There were also indications for a possible positive correlation of the splitting lesion and the grade of proteinuria. Compared with the splitting lesion basement membrane thinning seemed to be of minor importance.
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PMID:Hereditary nephropathy (Alport syndrome): correlation of clinical data with glomerular basement membrane alterations. 739 44

A 14-year-old female with microscopic hematuria was admitted for a renal biopsy. She had a family history of renal disease without deafness. The findings of light microscopy and conventional immunofluorescence were normal. Electron microscopy showed a diffuse thinning of the glomerular basement membrane (GBM) with its mild splitting. Irregular thickening of GBM and glomerular small dense particles was not observed. Thin basement membrane syndrome was suspected from these findings. However, it was difficult to differentiate from Alport syndrome. Immunofluorescence analysis using the monoclonal antibody to the 28-kilodalton monomers of the noncollagenous domain of type IV collagen verified the diagnosis of heterozygous Alport syndrome.
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PMID:Alport syndrome diagnosed by immunofluorescence using a new monoclonal antibody. 849 40

The proband was a 14-year-old girl with hematuria and proteinuria. Many members of her maternal pedigree had hematuria and proteinuria. Her mother, younger brother (age 12 years) and younger sister (age 9 years) had microscopic hematuria and proteinuria with normal renal function. Her mother had nephrotic syndrome during pregnancy and a renal biopsy was performed. Light microscopic findings of the renal biopsy specimen revealed mild mesangial proliferation and irregularity of glomerular basement membrane. The pedigree showed no chronic renal failure and no deafness. The proband had experienced microscopic hematuria and occasionally macroscopic hematuria since 3 years of age. Proteinuria increased steadily and at the age of 14 years, she had nephrotic syndrome and renal dysfunction (creatinine clearance of 57.9 ml/min/1.48 m2). Renal biopsy was performed and light microscopic findings showed segmental mesangial cell proliferation and numerous interstitial foam cells without significant findings by immunofluorescent study. Electron microscopic examination showed splitting into many layers and thinning of the glomerular basement membrane. She had no complaint of hearing. However, audiological studies detected bilateral low-tone (from 125 Hz to 1000 Hz) sensorineural hearing difficulty, ranging from 30 to 40 dB. High scores on the short increment sensitivity index (SISI) test suggested inner ear hearing difficulty. Audiogram of her brother revealed also low-tone sensorineural hearing loss. Hereditary nephritis with the characteristic lesion of the glomerular basement membrane and sensorineural hearing difficulty has been known as Alport syndrome. Alport syndrome associated with familial low-tone hearing difficulty has not been reported previously.
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PMID:Hereditary nephritis associated with low-tone sensorineural hearing difficulty: a case report. 869 14

Benign familial hematuria (BFH) is characterized by autosomal dominant inheritance, thinning of the glomerular basement membrane (GBM) and normal renal function. It is frequent in patients with persistent microscopic hematuria, but cannot be clinically differentiated from the initial stages of Alport syndrome, a severe GBM disorder which progresses to renal failure. We present here linkage of benign familial hematuria with the COL4A3 and COL4A4 genes at 2q35-37 (Zmax = 3.58 at theta = 0.0). Subsequently, a glycine to glutamic acid substitution was identified in the collagenous region of the COL4A4 gene. We conclude that type IV collagen defects cause both benign hematuria and Alport syndrome. Furthermore, our data suggest that BFH patients can be carriers of autosomal recessive Alport syndrome.
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PMID:Benign familial hematuria due to mutation of the type IV collagen alpha4 gene. 878 73

A mouse model for the autosomal form of Alport syndrome was produced. These mice develop a progressive glomerulonephritis with microhematuria and proteinuria, consistent with the human disease. End-stage renal disease develops at approximately 14 weeks of age. TEM analysis of the glomerular basement membranes (GBM) during development of renal pathology revealed focal multilaminated thickening and thinning beginning in the external capillary loops at 4 weeks and spreading throughout the GBM by 8 weeks. By 14 weeks, half of the glomeruli were fibrotic with collapsed capillaries. Immunofluorescence analysis of the GBM showed the absence of type IV collagen alpha-3, alpha-4, and alpha-5 chains and a persistence of alpha-1 and alpha-2 chains (these chains normally localize to the mesangial matrix). Northern blot analysis using probes specific for the collagen chains illustrate the absence of COL4A3 in the knockout, whereas mRNAs for the remaining chains are unchanged. An accumulation of fibronectin, heparan sulfate proteoglycan, laminin-1, and entactin was observed in the GBM of the affected animals. The temporal and spatial pattern of accumulation was consistent with that for thickening of the GBM as observed by TEM. Thus, expression of these basement membrane-associated proteins may be involved in the progression of Alport renal disease pathogenesis. The levels of mRNAs encoding the basement membrane-associated proteins at 7 weeks were unchanged.
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PMID:Collagen COL4A3 knockout: a mouse model for autosomal Alport syndrome. 895 99

Thin glomerular basement membrane (GBM) nephropathy, also called familial benign hematuria, is characterized by chronic hematuria and uniform thinning of the lamina densa of the glomerular basement membrane. It generally holds an excellent renal prognosis. Alport syndrome in early stages can also show attenuation of the GBM; conversely, renal insufficiency has been reported in familial benign hematuria. To discern early Alport syndrome from thin GBM nephropathy, we carried out a prospective epidemiological study in which 19 normotensive and non-azotemic adult patients with chronic microscopic (18 of 19) and macroscopic (1 of 19) hematuria and biopsy-proven thin GBM nephropathy were followed for a median of 12 years (range 9 to 15 years). Renal biopsies of thin GBM patients at entry showed an increased incidence of focal global glomerulosclerosis when compared to disease controls as IgA nephropathy (P = 0.047) and normal renal tissue (P = 0.0075). All renal biopsies showed the presence of the Goodpasture antigen when tested immunohistochemically. Presence of Alport syndrome was excluded clinically as none of the patients had complaints of hearing loss or abnormalities by audiography and ophthalmology. At the end of follow-up, the incidence of hypertension in thin GBM nephropathy (35%) exceeded that of healthy clinical controls (P = 0.048), and one hypertensive patient developed mild renal failure. In the normotensive patients, the glomerular filtration rate at follow-up as measured by inulin clearance was reduced in three out of seven; these were over 50 years of age. Although no family members were known to have renal disease at inclusion, within four families six elderly first degree relatives had developed unexplained renal insufficiency at the end of follow-up. Thus, thin GBM nephropathy predisposes to premature glomerular obsolescence, leading in time to increased incidences of hypertension and late onset renal insufficiency.
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PMID:Thin GBM nephropathy: premature glomerular obsolescence is associated with hypertension and late onset renal failure. 915 Apr 78

The cochleae from a COL4A3-deficient mouse line were examined for defects that might shed light on the molecular mechanism of otopathology observed in humans with Alport syndrome. At the light microscopic level no obvious defects were observed. Immunohistochemical analysis using antibodies specific for the basement membrane collagen chains revealed the absence of the COL4A3 and COL4A4 chains throughout the membranous labyrinth. The COL4A5 chain was absent from all cochlear basement membranes except those in the vessels of the stria vascularis. Expression of the COL4A1 and COL4A2 chains was unchanged in the mutant. Electron microscopic examination of the cochlear basement membranes revealed significant thinning of the basement membrane running from the spiral limbus, down the inner sulcus, across the basilar membrane and up to the spiral prominence. Basement membranes that normally ensheathe the root cells were not detectable. In contrast, the basement membranes surrounding the vessels of the stria vascularis were significantly thickened in the mutant. This was associated with endothelial cell swelling and a marked decrease in internal capillary diameter. In severe cases, pathology was observed in the marginal cells with a loss of basolateral infoldings. Immunohistochemical analysis of the strial vessels revealed an increase in entactin and collagen COL4A1 and COL4A2 chains. Auditory-evoked brainstem response measurements suggest a small increase in thresholds across all frequencies when successive measurements on individual mutant mice were examined between 6 and 8 postnatal weeks. Combined, these results illustrate changes in the basement membranes of the strial vessels that bear resemblance to Alport glomerular basement membrane pathology. A closer look at this compartment in human Alport biopsy specimen may be warranted.
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PMID:Ultrastructural, physiological, and molecular defects in the inner ear of a gene-knockout mouse model for autosomal Alport syndrome. 968 11

A detailed morphometric analysis of glomerular basement membrane (GBM) thickness was carried out on biopsies from 16 patients exhibiting normal histology and unremarkable immunofluorescence. Eleven of these patients presented with proteinuria, 8 in the nephrotic syndrome range, while 5 had hematuria as well. The remaining 5 patients presented with hematuria only. Eight patients had an initial diagnosis of minimal change disease, 4 were diagnosed as thin-membrane nephropathy, 2 had Alport syndrome, and the remaining 2 had hypertensive nephropathy. Quantitative morphometric analysis of GBM identified 3 subsets of patients. The first subset consisted of 6 patients: 5 adults, with an average GBM width of 361 +/- 34 nm, and 1 child. The second subset included 8 patients with thin GBMs and a mean thickness of 253 +/- 15 nm. The last subset comprised 2 patients with Alport syndrome showing marked variability in GBM thickness. This study has confirmed the presence of thin GBMs in hematurics, but has also revealed GBM thinning in 50% of patients with a diagnosis of minimal change disease.
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PMID:Thin glomerular basement membranes in patients with hematuria and minimal change disease. 1044 81


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