Thin-Basement-Membrane Nephropathy in Adults with Persistent Hematuria

Abstract

Thin-basement-membrane nephropathy, also called benign recurrent hematuria, is characterized by diffuse thinning of the glomerular basement membrane and by hematuria. To determine the incidence of thin-basement-membrane nephropathy among patients with idiopathic hematuria, we conducted a prospective study in the nephrology units of three large hospitals in the Netherlands. Eighty normotensive adults without azotemia underwent renal biopsy because of recurrent macroscopic hematuria (n = 26) or persistent microscopic hematuria (n = 54). Idiopathic IgA nephropathy was found in 27 of the 80 patients. Light microscopical examination showed that 42 patients had normal renal tissue. The remaining 11 patients had mesangioproliferative glomerulonephritis (n = 5), interstitial nephritis (n = 3), or focal global glomerulosclerosis (n = 3). Tissue from the 42 patients whose renal biopsy specimens were normal when examined with light microscopy was analyzed morphometrically with electron microscopy to determine the thickness of the glomerular basement membrane. Two subsets of patients were identified by this analysis. In 18, thin-basement-membrane nephropathy was found (mean basement-membrane thickness [+/- SE], 191 +/- 28 nm; normal, 350 +/- 43 nm); all but one of these 18 patients had microscopic hematuria, which persisted during follow-up (median duration, 50 months). (Of the 54 patients who presented with microscopic hematuria, 17 [31 percent] had thin-basement-membrane nephropathy.) The thickness of the glomerular basement membrane was normal in the other 24 patients (361 +/- 69 nm); during follow-up, hematuria disappeared in all 13 of these patients who had macroscopic hematuria, and hematuria resolved in 5 of the 11 patients who had microscopic hematuria. We conclude that in patients with persistent microscopic hematuria, the incidence of thin-basement-membrane nephropathy is similar to that of idiopathic IgA nephropathy. Morphometric analysis of the thickness of the glomerular basement membrane should be included in the workup of adults with persistent microscopic hematuria that is not of urologic origin.

Chronic Renal Failure and Shortened Lifespan in COL4A3+/− Mice

“…The basis of these investigations was monitoring life expectancy and the clinical phenotype in heterozygous COL4A3 ϩ/Ϫ mice during a period of 3 yr. Eight-week-old COL4A3 ϩ/Ϫ mice developed dysmorphic microhematuria comparable to hematuria in humans with TBMN (18,33). Minimal to mild proteinuria is a common clinical feature of TBMN in adult humans (25), and this condition could be simulated in COL4A3 ϩ/Ϫ mice that were older than 3 mo.…”

“…Although TBMN is considered to have a good prognosis owing to a nonprogressive nephropathy, numerous hints in the literature suggest a reduced lifespan in affected individuals. First, the possibility that TBMN may not be benign in terms of ultimate prognosis has been considered before (13,14,18,30,25), and ESRD similar to that seen in AS was reported in adults with heterozygote COL4A3/A4 mutations (occasionally also referred to as "autosomal dominant Alport syndrome") (15,34 -37). It should be noted that it was suggested that the molecular type of COL4A3/A4 mutations and additional modifier genes are likely to influence the severity of the renal phenotype eventually (35,36,37).…”

“…A spate of new data have become available concerning individuals with thin basement membrane nephropathy (TBMN) showing heterozygous mutations in the COL4A3 and COL4A4 genes (4 -10). TBMN, or familial benign hematuria (11) first was described in 1926 (12) and is a very common hereditary disorder that clinically is characterized by persistent or recurrent hematuria that can be aggravated by increased BP in approximately 30% of patients (5,(13)(14)(15), proteinuria (15)(16)(17)(18)(19), hearing loss, and/or progression toward chronic renal failure (11,(13)(14)(15)17,20). The trait is inherited in an autosomal dominant pattern (8).…”

Thin Basement Membrane Nephropathy

“…The urinary blood cells are dysmorphic with irregular shape and size, indicating hematuria of glomerular origin (17,18). Occasionally, the hematuria has disappeared with time (3,47,50,58).…”

The Many Faces of Thin Basement Membrane Nephropathy; A Population Based Study

“…Normal GBM thickness has been estimated in several reports (Coleman, Haynes, Dimopoulos, Barratt, & Jarvis, 1986;Das, Pickett, & Tungekar, 1996;Dische et al, 1985;Haas, 2009;Jovanovic GB, 1990). Since there is a lack of a general consensus on diagnostic criteria, it is recommended that a GBM normal range should be established for each laboratory (Dische et al, 1985;Tiebosch et al, 1989). This normal range is a necessary pre-requisite that facilitates the subsequent accurate diagnosis of TBMN.…”