Thin‐membrane nephropathy — a common cause of glomerular haematuria

Perry, Gregory J. P.; George, C. R. P.; Field, Michael J.; Collett, Paul; Kalowski, Steven; Wyndham, Roger; Newland, R. C.; Lin, Betty; Kneale, Kennett L.; Lawrence, J. R.

doi:10.5694/j.1326-5377.1989.tb139637.x

Cited by 23 publications

(9 citation statements)

References 19 publications

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“…TBMN has been reported in Caucasians, Chinese, Indians, and Africans [19,28]. The median age at presentation is 7 years in children [1][2][3][4][5][6], and 37 years in adults [7][8][9][10][11][12][13][14][15][16][17], and hematuria from TBMN has been reported in infants as young as 1 year, and in an 86-year-old [7]. The majority of studies (71%) suggest that TBMN is more common in females than males (median male: female ratio ϭ 1.6) [1-5, 9-11, 13-16].…”

Section: Epidemiology Of Tbmnmentioning

confidence: 99%

“…Some series of adults included occasional children. The number of studies in which individual clinical features were noted are provided in parentheses (1)(2)(3)(4)(5)(6)(7)(8)(9)(10)(11)(12)(13)(14)(15)(16)(17).…”

Section: Epidemiology Of Tbmnmentioning

confidence: 99%

“…Thus, persistent hematuria in both children and adults appears to originate from the glomerulus more often than from elsewhere in the urinary tract. Furthermore, many series of children [25][26][27] and adults [13,[28][29][30] with persistent hematuria have demonstrated that TBMN is the most common histologic diagnosis despite nephrologists' reluctance to biopsy patients with normal renal function.…”

Section: Epidemiology Of Tbmnmentioning

confidence: 99%

“…Most individuals with thin basement membrane nephropathy (TBMN) have persistent dysmorphic hematuria, minimal proteinuria (Յ500 mg/day) and normal renal function [1][2][3][4][5][6][7][8][9][10][11][12][13][14][15][16][17]. On ultrastructural examination, their renal biopsies have a uniformly thinned glomerular basement membrane (GBM) without the long stretches of lamellation or thickening seen in Alport syndrome.…”

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confidence: 99%

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Thin basement membrane nephropathy

Savige

Rana

Tonna

et al. 2003

Kidney International

216

215

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Thin basement membrane nephropathy. Thin basement membrane nephropathy (TBMN) is the most common cause of persistent glomerular bleeding in children and adults, and occurs in at least 1% of the population. Most affected individuals have, in addition to the hematuria, minimal proteinuria, normal renal function, a uniformly thinned glomerular basement membrane (GBM) and a family history of hematuria. Their clinical course is usually benign. However, some adults with TBMN have proteinuria >500 mg/day or renal impairment. This is more likely in hospital-based series of biopsied patients than in the uninvestigated, but affected, family members. The cause of renal impairment in TBMN is usually not known, but may be due to secondary focal segmental glomerulosclerosis (FSGS) or immunoglobulin A (IgA) glomerulonephritis, to misdiagnosed IgA disease or X-linked Alport syndrome, or because of coincidental disease. About 40% families with TBMN have hematuria that segregates with the COL4A3/COL4A4 locus, and many COL4A3 and COL4A4 mutations have now been described. These genes are also affected in autosomal-recessive Alport syndrome, and at least some cases of TBMN represent the carrier state for this condition. Families with TBMN in whom hematuria does not segregate with the COL4A3/COL4A4 locus can be explained by de novo mutations, incomplete penetrance of hematuria, coincidental hematuria in family members without COL4A3 or COL4A4 mutations, and by a novel gene locus for TBMN. A renal biopsy is warranted in TBMN only if there are atypical features, or if IgA disease or X-linked Alport syndrome cannot be excluded clinically. In IgA disease, there is usually no family history of hematuria. X-linked Alport syndrome is much less common than TBMN and can often be identified in family members by its typical clinical features (including retinopathy), a lamellated GBM without the collagen alpha3(IV), alpha4(IV), and alpha5(IV) chains, and by gene linkage studies or the demonstration of a COL4A5 mutation. Technical difficulties in the demonstration and interpretation of COL4A3 and COL4A4 mutations mean that mutation detection is not used routinely in the diagnosis of TBMN.

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Section: Epidemiology Of Tbmnmentioning

confidence: 99%

Section: Epidemiology Of Tbmnmentioning

confidence: 99%

Section: Epidemiology Of Tbmnmentioning

confidence: 99%

mentioning

confidence: 99%

See 2 more Smart Citations

Thin basement membrane nephropathy

Savige

Rana

Tonna

et al. 2003

Kidney International

216

215

View full text Add to dashboard Cite

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“…The diagnosis of TBMN is made clinically when there is persistent glomerular hematuria, minimal proteinuria (500 mg/d), normal renal function(mostly), and no other obvious extrarenal abnormalities 12 . About 40% families with TBMN have hematuria that segregates with the mutations in COL4A3/COL4A4 locus and about two thirds of individuals with TBMN have at least one other family member with hematuria in autosomal dominant inheritance pattern 13 .…”

Section: Discussionmentioning

confidence: 99%

A Novel COL4A4 Mutation Identified in a Chinese Family with Thin Basement Membrane Nephropathy

Guo

Dong

et al. 2016

Sci Rep

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Thin basement membrane nephropathy (TBMN) is often attributable to mutations in the COL4A3 or COL4A4 genes that encode the α3 and α4 chains of type IV collagen, respectively, a major structural protein in the glomerular basement membrane. The aim of this study was to explore a new disease-related genetic mutation associated with the clinical phenotype observed in a Chinese Han family with autosomal dominant TBMN. We conducted a clinical and genetic study comprising seven members of this TBMN family. Mutation screening for COL4A3 and COL4A4 was carried out by direct sequencing. The RNA sequences associated with both proteins were also analyzed with reverse transcription PCR and TA cloning. The result showed that every affected patient had a novel heterozygous splicing mutation in COL4A4 (c.1459 + 1G > A), which led to the elimination of the entire exon 21 from the COL4A4 cDNA and resulted in the direct splicing of exons 20 and 22. This in turn caused a frameshift mutation after exon 20 in the open reading frame of COL4A4. In conclusion, we describe a novel splicing mutation in COL4A4 that results in TBMN. This analysis increases our understanding of TBMN phenotype-genotype correlations, which should facilitate more accurate diagnosis and prenatal diagnosis of TBMN.

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Value of urinary excretion of microalbumin in predicting glomerular lesions in children with isolated microscopic hematuria

Assadi

2005

Pediatr Nephrol

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Urinary microalbumin excretion was assessed in 76 children with asymptomatic microscopic hematuria in whom the presence of proteinuria, hypertension, reduced renal function, hypercalciuria, urinary tract infection or structural abnormality of the urinary tract had been excluded. All children underwent a percutaneous kidney biopsy to determine whether microalbumin excretion can be used as a marker to predict the source of hematuria. Microalbumin excretion was considered normal if the urinary ratio of microalbumin to creatinine (MA/Cr ug/mg) was < or =30. Twenty-two (29%) had microalbuminuria (MA/Cr 96+/-30 microg/mg) and 54 (71%) had normal albumin excretion (MA/Cr 13+/-2 microg/mg). Of those with normoalbuminuria, 38 (70%) had normal renal tissue, 15 (28%) thin glomerular basement membrane (TGBM) disease and 1 (2%) IgA nephropathy. In contrast, 20 (91%) of those with microalbuminuria had IgA nephropathy and 2 (9%) had TGBM disease. The mean urinary MA/Cr ratio for all IgA children was 89+/-32 microg/mg higher compared with a value for the children with TGBM disease (14 +/-3 microg/mg, P <0.001) or children whose renal biopsy appeared normal (11+/-2 microg/mg, P <0.001). Statistical analysis revealed no significant differences between the mean MA/Cr ug/mg ratio for children with TGBM disease and those with normal glomerular findings. Fourteen of the 20 children with IgA nephropathy who also had microalbuminuria were treated with an angiotensin-converting enzyme (ACE) inhibitor. Over a mean follow-up of 51 months, none developed overt proteinuia; hematuria resolved and microalbuminuria returned to normal in eight (57%) during therapy with the ACE-inhibitor. In contrast, hematuria persisted and prtoteinuria developed in the other untreated children. None of the children with TGBM disease developed overt proteinuria after a mean of 51 months. Hematuria was persistent in children with TGBM disease, but often resolved in those whose biopsies were completely normal. These data suggest that determination of urinary microalbumin excretion is warranted in the routine examination of children with isolated microscopic hematuria. Routine screening for microalbuminuria may help to identify a subgroup of patients with IgA nephropathy who are at high risk for progressive kidney disease and need more intensive therapy and closer follow-up.

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Thin‐membrane nephropathy — a common cause of glomerular haematuria

Cited by 23 publications

References 19 publications

Thin basement membrane nephropathy

Thin basement membrane nephropathy

A Novel COL4A4 Mutation Identified in a Chinese Family with Thin Basement Membrane Nephropathy

Value of urinary excretion of microalbumin in predicting glomerular lesions in children with isolated microscopic hematuria

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