Thin basement membrane nephropathy (benign familial hematuria)

INTRODUCTION

Thin basement membrane nephropathy (TBMN, also called thin basement membrane disease and benign familial hematuria) is a relatively common disorder [1]. The only finding on renal biopsy is diffuse thinning of the glomerular basement membranes requiring electron microscopy for the diagnosis [1-4].

This disorder is often familial, with a family history of hematuria being noted in 30 to 50 percent of cases. TBMN seems to account for most cases of what has been called benign familial hematuria. Several mutations of the type IV collagen genes COL4A3 and COL4A4 have been identified in patients with thin basement membrane nephropathy, but such mutations are not present in all families [5].

Thin basement membrane nephropathy will be discussed in this topic review. Alport syndrome is presented separately. (See "Genetics, pathogenesis, and pathology of hereditary nephritis (Alport syndrome)".)

EPIDEMIOLOGY

Studies on kidneys used for renal transplantation suggest that the frequency of thin basement membranes in the general population may be as high as 5 to 9 percent [6,7]. However, thin basement membrane disease is clinically diagnosed is less than 1 percent of the population [8].

PATHOGENESIS

It had been suspected that the genetic defect in thin basement membrane nephropathy would be similar to that in hereditary nephritis (Alport syndrome), since patients with the latter group of disorders also have thin basement membranes early in the course of the disease [9]. This hypothesis has been confirmed in families in which thin basement membrane nephropathy was due to heterozygous defects in COL4A3 or COL4A4, the genes that encode for the alpha-3 and alpha-4 chains of type IV collagen [8,10-15]. The entire group of disorders encompassing TBMN and Alport syndrome has been called the Type IV Collagen Nephropathies.

             

Subscribers log in here

To continue reading this article you must have access through your hospital or your group practice, log in to your personal subscription, or purchase a personal subscription. For more information, click below.
Literature review current through: Apr 2013. | This topic last updated: Mar 28, 2012.
The content on the UpToDate website is not intended nor recommended as a substitute for medical advice, diagnosis, or treatment. Always seek the advice of your own physician or other qualified health care professional regarding any medical questions or conditions. The use of this website is governed by the UpToDate Terms of Use ©2013 UpToDate, Inc.
References
Top
  1. Tryggvason K, Patrakka J. Thin basement membrane nephropathy. J Am Soc Nephrol 2006; 17:813.
  2. Aarons I, Smith PS, Davies RA, et al. Thin membrane nephropathy: a clinico-pathological study. Clin Nephrol 1989; 32:151.
  3. Tiebosch AT, Frederik PM, van Breda Vriesman PJ, et al. Thin-basement-membrane nephropathy in adults with persistent hematuria. N Engl J Med 1989; 320:14.
  4. Thin-membrane nephropathy--how thin is thin? Lancet 1990; 336:469.
  5. Rana K, Wang YY, Powell H, et al. Persistent familial hematuria in children and the locus for thin basement membrane nephropathy. Pediatr Nephrol 2005; 20:1729.
  6. Dische FE, Anderson VE, Keane SJ, et al. Incidence of thin membrane nephropathy: morphometric investigation of a population sample. J Clin Pathol 1990; 43:457.
  7. Cosio FG, Falkenhain ME, Sedmak DD. Association of thin glomerular basement membrane with other glomerulopathies. Kidney Int 1994; 46:471.
  8. Savige J, Rana K, Tonna S, et al. Thin basement membrane nephropathy. Kidney Int 2003; 64:1169.
  9. Rumpelt HJ. Hereditary nephropathy (Alport syndrome): correlation of clinical data with glomerular basement membrane alterations. Clin Nephrol 1980; 13:203.
  10. Lemmink HH, Nillesen WN, Mochizuki T, et al. Benign familial hematuria due to mutation of the type IV collagen alpha4 gene. J Clin Invest 1996; 98:1114.
  11. Buzza M, Wang YY, Dagher H, et al. COL4A4 mutation in thin basement membrane disease previously described in Alport syndrome. Kidney Int 2001; 60:480.
  12. Badenas C, Praga M, Tazón B, et al. Mutations in theCOL4A4 and COL4A3 genes cause familial benign hematuria. J Am Soc Nephrol 2002; 13:1248.
  13. Buzza M, Dagher H, Wang YY, et al. Mutations in the COL4A4 gene in thin basement membrane disease. Kidney Int 2003; 63:447.
  14. Hudson BG, Tryggvason K, Sundaramoorthy M, Neilson EG. Alport's syndrome, Goodpasture's syndrome, and type IV collagen. N Engl J Med 2003; 348:2543.
  15. Frascà GM, Onetti-Muda A, Mari F, et al. Thin glomerular basement membrane disease: clinical significance of a morphological diagnosis--a collaborative study of the Italian Renal Immunopathology Group. Nephrol Dial Transplant 2005; 20:545.
  16. Mochizuki T, Lemmink HH, Mariyama M, et al. Identification of mutations in the alpha 3(IV) and alpha 4(IV) collagen genes in autosomal recessive Alport syndrome. Nat Genet 1994; 8:77.
  17. Boye E, Mollet G, Forestier L, et al. Determination of the genomic structure of the COL4A4 gene and of novel mutations causing autosomal recessive Alport syndrome. Am J Hum Genet 1998; 63:1329.
  18. Heidet L, Arrondel C, Forestier L, et al. Structure of the human type IV collagen gene COL4A3 and mutations in autosomal Alport syndrome. J Am Soc Nephrol 2001; 12:97.
  19. Torra R, Tazón-Vega B, Ars E, Ballarín J. Collagen type IV (alpha3-alpha4) nephropathy: from isolated haematuria to renal failure. Nephrol Dial Transplant 2004; 19:2429.
  20. Saito A, Yamazaki H, Nakagawa Y, Arakawa M. Molecular genetics of renal diseases. Intern Med 1997; 36:81.
  21. Kashtan CE. Alport syndrome and thin glomerular basement membrane disease. J Am Soc Nephrol 1998; 9:1736.
  22. Buzza M, Wilson D, Savige J. Segregation of hematuria in thin basement membrane disease with haplotypes at the loci for Alport syndrome. Kidney Int 2001; 59:1670.
  23. Wang YY, Rana K, Tonna S, et al. COL4A3 mutations and their clinical consequences in thin basement membrane nephropathy (TBMN). Kidney Int 2004; 65:786.
  24. Collar JE, Ladva S, Cairns TD, Cattell V. Red cell traverse through thin glomerular basement membranes. Kidney Int 2001; 59:2069.
  25. Blumenthal SS, Fritsche C, Lemann J Jr. Establishing the diagnosis of benign familial hematuria. The importance of examining the urine sediment of family members. JAMA 1988; 259:2263.
  26. Schurek HJ. Mechanisms of glomerular proteinuria and hematuria. Kidney Int Suppl 1994; 47:S12.
  27. Hebert LA, Betts JA, Sedmak DD, et al. Loin pain-hematuria syndrome associated with thin glomerular basement membrane disease and hemorrhage into renal tubules. Kidney Int 1996; 49:168.
  28. Praga M, Martínez MA, Andrés A, et al. Association of thin basement membrane nephropathy with hypercalciuria, hyperuricosuria and nephrolithiasis. Kidney Int 1998; 54:915.
  29. Abt AB, Carroll LE, Mohler JH. Thin basement membrane disease and acute renal failure secondary to gross hematuria and tubular necrosis. Am J Kidney Dis 2000; 35:533.
  30. Auwardt R, Savige J, Wilson D. A comparison of the clinical and laboratory features of thin basement membrane disease (TBMD) and IgA glomerulonephritis (IgA GN). Clin Nephrol 1999; 52:1.
  31. Hall CL, Bradley R, Kerr A, et al. Clinical value of renal biopsy in patients with asymptomatic microscopic hematuria with and without low-grade proteinuria. Clin Nephrol 2004; 62:267.
  32. Pettersson E, Törnroth T, Wieslander J. Abnormally thin glomerular basement membrane and the Goodpasture epitope. Clin Nephrol 1990; 33:105.
  33. van Paassen P, van Breda Vriesman PJ, van Rie H, Tervaert JW. Signs and symptoms of thin basement membrane nephropathy: a prospective regional study on primary glomerular disease-The Limburg Renal Registry. Kidney Int 2004; 66:909.
  34. Iseki K, Miyasato F, Uehara H, et al. Outcome study of renal biopsy patients in Okinawa, Japan. Kidney Int 2004; 66:914.
  35. Nieuwhof CM, de Heer F, de Leeuw P, van Breda Vriesman PJ. Thin GBM nephropathy: premature glomerular obsolescence is associated with hypertension and late onset renal failure. Kidney Int 1997; 51:1596.
  36. Yoshioka K, Hino S, Takemura T, et al. Type IV collagen alpha 5 chain. Normal distribution and abnormalities in X-linked Alport syndrome revealed by monoclonal antibody. Am J Pathol 1994; 144:986.
  37. Chrystomou, A, Kincaid-Smith, P, Becker, G. Clinical features and prognosis of thin basement membrane disease (abstract). J Am Soc Nephrol 1993; 4:261.
  38. Knebelmann B, Breillat C, Forestier L, et al. Spectrum of mutations in the COL4A5 collagen gene in X-linked Alport syndrome. Am J Hum Genet 1996; 59:1221.
  39. Voskarides K, Damianou L, Neocleous V, et al. COL4A3/COL4A4 mutations producing focal segmental glomerulosclerosis and renal failure in thin basement membrane nephropathy. J Am Soc Nephrol 2007; 18:3004.
  40. Kashtan CE. The wages of thin. J Am Soc Nephrol 2007; 18:2800.
  41. Matsumae T, Fukusaki M, Sakata N, et al. Thin glomerular basement membrane in diabetic patients with urinary abnormalities. Clin Nephrol 1994; 42:221.
  42. Andres A, Praga M, Bello I, et al. Hematuria due to hypercalciuria and hyperuricosuria in adult patients. Kidney Int 1989; 36:96.
  43. Praga M, Alegre R, Hernández E, et al. Familial microscopic hematuria caused by hypercalciuria and hyperuricosuria. Am J Kidney Dis 2000; 35:141.