Consult the medical resource doctors trust

UpToDate is one of the most respected evidence-based medical information resources in the world, used by over 400,000 doctors and thousands of patients to find answers to medical questions.

  • Content written by a faculty of over 4,000 physicians from leading medical institutions
  • Unbiased: free of advertising or pharmaceutical funding
  • Evidence-based treatment recommendations
  • Continuously updated to incorporate new medical findings

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].

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 [8]. 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 [9-15]. The entire group of disorders encompassing TBMN and Alport syndrome have been called the Type IV Collagen Nephropathies.

» To continue reading this article you need to login or subscribe.

Ready to join over 400,000 satisfied users? Subscribe to read this article and others like it.
Last literature review version 18.2: May 2010
This topic last updated: June 4, 2008
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 (click here) ©2010 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, M, Sedmak, DD. Association of thin glomerular basement membrane nephropathy with other glomerulopathies. Kidney Int 1994; 46:471.
  8. Rumpelt, HJ. Hereditary nephropathy (Alport's syndrome): Correlation of clinical data with glomerular basement membrane alterations. Clin Nephrol 1980; 13:203.
  9. Lemmink, HH, Nillesen, WN, Mochizuki, T, et al. Benign familial hematuria due to a mutation of the type IV collagen alpha-4 gene. J Clin Invest 1996; 98:1114.
  10. 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.
  11. Badenas, C, Praga, M, Tazon, B, et al. Mutations in the COL4A4 and COL4A3 genes cause familial benign hematuria. J Am Soc Nephrol 2002; 13:1248.
  12. Buzza, M, Dagher, H, Wang, YY, et al. Mutations in the COL4A4 gene in thin basement membrane disease. Kidney Int 2003; 63:447.
  13. 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.
  14. Savige, J, Rana, K, Tonna, S, Buzza, M. Thin basement membrane nephropathy. Kidney Int 2003; 64:1169.
  15. Frasca, 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 a3(IV) and a4(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, Tazon-Vega, B, Ars, E, Ballarin, J. Collagen type IV ({alpha}3-{alpha}4) 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, Martinez, MA, Andres, 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, Tornroth, 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, et al. 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, Urhara, 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, Hernandez, E, et al. Familial microscopic hematuria caused by hypercalciuria and hyperuricosuria. Am J Kidney Dis 2000; 35:141.
Thin basement membrane nephropathy (benign familial hematuria) Chronic menorrhagia or anovulatory uterine bleeding Clinical manifestations and diagnosis of calcium pyrophosphate crystal deposition disease Patient information: Depression treatment options for adolescents Bone and joint complications in sickle cell disease Diagnosis and management of placenta accreta Patient information: Type 2 diabetes mellitus and diet Patient information: Tamoxifen and raloxifene for the prevention of breast cancer Patient information: Helicobacter pylori infection and treatment Patient information: Gastroesophageal reflux disease in adults