You are here

Home » Content

İNCE GLOMERÜLER BAZAL MEMBRAN İÇEREN NEFROPATÎLER

NEPHROPATHIES WITH THIN GLOMERULAR BASEMENT MEMBRANE

Journal Name:

  • Türk Nefroloji, Diyaliz ve Transplantasyon Dergisi

Publication Year:

  • 2003
Author NameUniversity of AuthorFaculty of Author
Bookmark/Search this post with
Abstract (Original Language): 
Makroskopik hematüri hastaları, mikroskopik hematim ise hekimleri alarma geçirir. Ağır proteinüri, eritrosit silendirlerinin varlığı ya da idrarda bulunan eritrositlerin küçük ve dismorfik olması renal nedenleri düşündürür. Üriner sistemin ultrason, intravenöz ürografi ve sistoskopiyle incelenmesiyle kanama nedeninin saptanamaması halinde de yine böbrek patolojileri akla gelir (1). Çocukluk çağında başlayan glomeruler kökenli izole hematüri nedenleri arasında en sık rastlananları Alport sendromu, IgA nefropatisi ve benign familial hematüridir (2). Alport sendromu hematüri, sensörinöral işitme kaybı, göz bulguları ve glomeruler bazal membranda yapısal defektlerle karakterize progresif bir herediter nefropatidir. Çoğunlukla X'e bağlı kalıtılmakla birlikte, otozomal formları da bildirilmiştir (3). Alport sendromundaki temel defekt kollajen IV genindeki pek çok mutasyondan biridir ve bu mutasyon böbrek, lens veya cochleanın bazal membranında fenotipik ve fonksiyonel değişikliklere neden olur (4,5). Tip IV kollajen laminin, nidojen (entaktin) ve proteoglikanlarla beraber bazal membranı oluşturan başlıca elemandır. Bazal membranlar büyüyen hücreler için fiziksel destek sağlarlar ve doku kompartmanları arasında yarı geçirgen moleküler bir elektriki ve fiziksel bir bariyer görevi görürler. Elektron mikroskobuyla incelendiğinde bazal membranların amorf yapıda iki tabakadan oluştuğu görülür: lamına lucida ve lamina densa. Glomeruler bazal membran gibi bazı bazal membranların ise her iki tarafında da hücreler vardır ve endotelyal ve epitelyal bazal membranların birleşmesi sonucu oluşurlar. Bu şekilde ortada lamina densa ve her iki tarafında lamina lucidanın bulunduğu üç tabakalı yapı oluşur (6). Alport sendromunda renal biyopsi materyaline ait elektron mikroskobik incelemede lamina densada ayrılma ve glomeruler bazal membranda sıklıkla değişik derecelerde kalınlaşma (4) daha az oranda da incelme saptanır. Kollajen IV al ve a2 olmak üzere iki ana, ct3, a4, a5 ve a6 olmak üzere de dört adet daha az görülen isoformdan oluşur. Kollajen IV'ün bu 6 isoformu 3 ayrı kromozom üzerinde 6 gen tarafından kodlanır: C0L4A1 ve COL4A2 13. kromozomda, COL4A3 ve COL4A4 2. kromozomda ve COL4A5 ve COL4A6 X kromozomundadır (4,5). Mutasyonlar X'e bağlı kalıtılan formda COL4A5'te, otozomal resesif ve dominant tipte ise COL4A3 veya COL4A4 geninde saptanmıştır (7,8). Glomeruler bazal membrandaki karakteristik özelliklerin ileri yaşlarda gelişebileceği öne sürülmektedir (6). İncelme otozomal resesif formdaki gibi kalıcı tek bulgu olabildiği gibi (9), glomeruler bazal membrandaki değişikliğin başlangıç bulgusu da olabilir (10). Alport sendromlu bir erkek hastanın 9 ve 18 yaşlarında yapılan böbrek biyopsilerinden ilkinde glomeruler bazal membranda yaygın incelme varken ikincisinde karakteristik kalınlaşma ve ayrılma gözlenmiştir (10). Klinik tanı hematüri, proteinüri veya progresif kronik böbrek yetmezliğine ilişkin aile hikayesi ve sıklıkla eşlik eden yüksek tonda sensörinöral işitme kaybı ve/veya oküler anomalilerle konur (11). Oküler bulgulardan anterior lentikonusun %10-30'unda görüldüğü ve patognomonik olduğu bildirilmiştir (8). Klasik olarak erkeklerde hematüri ve sağırlık erken yaşta görülür ve ikinci dekatta böbrek yetmezliği gelişir. Kızlarda hastalığın erkeklere göre daha hafif seyrettiği bilinir (7). Leiomiyomatozis, hematolojik anomaliler ve mental retardasyonla birlikteliği bildirilmiştir (12). İmmünohistokimyasal olarak glomeruler bazal membrandaki kollajen IV isoformları çeşitli antijenlere karşı oluşan antikorların saptanmasıyla gösterilebilir. X'e bağlı kalıtılan Alport sendromunda mutant gen nedeniyle glomeruler bazal membranda olması gereken a5 antijeni saptanamamaktadır (13). Glomeruler bazal membranda X'e bağlı kalıtılan formda a5'in , otozomal resesif formda ise a3 veya a4'ün saptanamaması Alport sendromu için spesifiktir ancak sensitif değildir (8). Bu nedenle kollajen a3-a5'in pozitif saptanması Alport sendromu tanısından uzaklaştırmaz (14).
FULL TEXT (PDF): 
PDF icon pdf_tndt_452.pdf
  • 4
196-205
  • Turkish

REFERENCES

References: 

1. Editorials. Thin membrane nephropathy-how thin is thin? The Lancet 1990; 336: 469-470.
2. Piqueras Al, White RHR, Raafat F et al: Renal biopsy diagnosis in children with hematuria. Pediatr Nephrol 1998; 12: 386-391.
3. Tryggvason K, Zhou J, Hostikka SL et al. Molecular genetics of Alport syndrome. Kidney
Int 1993;43:38-44.
4. Kashtan CE, Michael AF: Alport syndrome.
Kidney International 1996; 50: 1445-1463
5. Meleg-Smith S, Magliato S, Cheles M, et al. X-
Linked Alport Syndrome in Females. Human
Pathology 1998; 29 (4): 404-408.
6. Smeets HJM, Knoers VVAM, van de Heuvel LPWJ et al. Hereditary disorders of the glomerular basement membrane. Pediatr Nephrol 1996; 10:
779-788.
7. Jefferson JA, Lemmink HH, Hughes AE et al. Autosomal dominant Alport syndrome linked to type IV collagen alpha 3 and 4 genes. Nephrol
Dial Transplant 1997; 12: 1595- 1599.
8. Pirson Y: Making the diagnosis of Alport's
syndrome. Kidney Int 1999; 56: 760-775.
9. Gubler MC, Knebelmann B, Beziau A et al. Autosomal recessive Alport syndrome: Immunohistochemical study of type IV collagen
chain distribution. Kidney Int 1995; 47: 1142¬1147.
10. Cangiotti AM, Sessa A, Meroni M et al. Evolution of glomerular basement membrane lesions in a male patient with Alport syndrome: ultrastructural and morphometric study. Nephrol Dial Transplant
1996; 11: 1829-1834.
11. Flinter FA, Cameron JS, Chantler C et al. Genetics of classic Alport's syndrome Lancet 1988; 2: 1005-1007.
12. Kashtan CE. Alport syndromes: phenotypic heterogeneity of progressive hereditary nephritis.
Pediatr Nephrol 2000; 14: 502-512.
13. Nakanishi K, Yoshikawa N, Lijima K et al: Immunohistochemical study of al-5 chains of type IV collagen in hereditary nephritis. Kidney Int
1994; 46: 1413-1421.
14. Liapis H, Gökden N, Hmiel P et al. Histopathology, ultrastructure, and clinical phenotypes in thin glomeruler basement membrane disease variants. Human Pathology
2002; 33: 836-845.
15. Nieuwhof CM, deHeer F, deLeeuw P et al. Thin GBM nephropathy premature glomeruler obsolence is associated with hypertension and late onset renal failure. Kidney Int 1997; 51: 1596¬1601.
16. Turco AE, Renieri A, DeMarchi M. Alport syndrome- is there a genotype - phenotype relationship? Nephrol Dial Transplant 1997; 12: 1551-1552.
17. Monnens LAH. Thin glomerular basement
membrane disease. Kidney Int 2001; 60: 799-800.
18. Piccini M, Casari G, Zhou J et al. Evidence for genetic heterogeneity in bening familial hematuria. Am J Nephrol 1999;" 19: 464-467.
19. Savige J, Rana K, Tonna S, Buzza M, Dagher H. Thin basement membrane nephropathy. Kidney Int
2003; 64: 1169-1178.
20. Netzer KO, Seibold S, Weber M. Thin basement
membrane-do we have a window for understanding the moleculer pathogenesis? Nephrol Dial Transplant 1999; 14: 1060- 1061.
21. Hebert LA, Betts JA, Sedmak DD et al. Loin pain-hematuria syndrome associated with thin
glomerular basemnt membrane disease and hemorrhage into renal tubules. Kidney Int 1996;
49: 168-173.
203
22. Buzza M, Wilson D, Savige J. Segregation of hematuria in thin membrane disease with haplotypes at loci for Alport syndrome. Kidney Int 200l; 59: 16 70-16 76.
23. Cosio FG, Falkenhain ME, Sedmak DD. Association of thin glomerular basement membrane with other glomerulopathies. Kidney Int 1994;46:471-474.
24. Praga M, Martinez MA, Andres A et al. Association of thin basement membrane nephropathy with hypercalciuria, hyperuricosuria and nephrolithiasis. Kidney Int 1998; 54: 915¬920.
25. Ozen S, Ertoy D, Heidet L et al. Benine familial hematuria associated with a novel 1COL4A4 mutation. Pediatr Nephrol 2001; 16: 874-877.
26. Collar JE, Ladva S, Cairns TDH et al. Red cell traverse through thin glomerular basement membranes. Kidney Int 2001; 59: 2069-2072.
27. Frasca GM, Onetti-Muda A, Renieri A. Thin
flomerular basement membrane disease. J Nephrol 000; 13: 15-19.
28. Nishi S, Ueno M, Karasawa R et al. Morphometric study of glomerular basement membrane and proximal tubular basement membrane in adult thin basement membrane disease. Clin Exp Nephrol
1999;3:290-295.
29. Tiebosch ATMG, Frederic PM, van Breda
Vriesman PJC et al. Thin basement membrane nephropathy in adults with persistent hematuria. N Engl J Med 1989; 320: 14-18.
30. SuhKS, Kim JO, Kang GH. Thin glomerular basement membrane disease: Light microscopic and electron microscopic studies. JKMS 1997; 12:
234-239.
31. Morita M, White RHR, Raafat F et al. Glomerular basement membrane thickness in children. Pediatr Nephrol 1988; 2: 190-195. ( Abstract
32. Ramage IJ, Howatson AG, McColl JH et al.
Glomerular basement membrane thickness in children: A stereologic assessment. Kidney
International 2002; 62: 895-900.
33. Das AK, Pickett TM, Tungekar MF. Glomerular
basement membrane thickness-a comparison of two methods of measurement in patients with unexplained haematuria. Nephrol Dial Transplant
1996; 11: 1256-1260.
34. Colville D, Savige J, Branley P et al. Ocular abnormalities in tnin basement membrane disease.
British Journal of Ophthalmology 1997; 81: 373¬377.
35. Cohen JJ, Harrington Jt, Madias NE. Molecular
fenetics of hereditary nephritis. Kidney Int 1992; 2 : 783-792.
36. Coppo R, Gianoglio B, Porcellini MG et al for the Group of Renal Immunopathology of the Italian Society of Pediatric Nephrology and Group of Renal Immunopathology of the Italian Society of Nephrology. Frequency of renal diseases and clinical indications for renal biopsy in children (Report of the Italian National Registry of Renal Biopsies in Children) Nephrol Dial Transplant
1998; 13:293-297.
37. Dische FE, Anderson VE, Keane SJ et al. Incidence of thin membrane nephropathy: morphometric investigation of a population
sample. J Clin Pathol 1990; 43 (6): 457-460. (Abstract)
38. Gauthier B, Trachtman H, Frank R, Valderrama E. Familial thin basement membrane nephropathy in children with asymtomatic microhematuria. Nephron 1989; 51: 502 - 508.
39. Mafalda N, Joiner C, Kim H, Nathaniel D et al.
Thin basement membrane disease and heavy proteinuria: a report of seven cases. Laboratory
Investigation 1998; 78 (1): 148
40. Sasatomi Y, Kiyoshi Y, Takebayashi S. Does thin basement membrane disease prolong the urinary abnormality in minimal change IgA nephropathy?
Clin Exp Nephrol 1999; 3: 181-185.
41. Kawasaki Y, Suzuki J, Nozawa R et al. Thin basement membrane disease with membranoproliferative glomerulonephritis in a 13 year old girl. Pediatrics Int 2002; 44r 321-323.
42. Abt AB, Carroll LE, Mohler JH. Thin basement
membrane disease and acute renal failure secondary to gross hematuria and tubular necrosis. American Journal of Kidney Diseasaes 2000; 35
(3): 533-36.
43. Baranowska-Daca E, Choi Y-J, Barrios R et al. Nonlupus nephritides in patients with Systemic Lupus erythematosus: A comrenensive clinicopathologic study and review of the literature. Human Pathology 2001; 32 (10): 1125¬1135.
44. Moghal NE, Milford DV, White RHR et al.
Coexistence of thin membrane and Alport nephropathies in families with haematuria. Pediatr
Nephrol 1999; 13:778-781.
45. Hayashi H, Karasawa R, Inn H et al. An electron microscopic study of glomeruli in Japanese patients with non-insulin dependent diabetes
mellitus. Kidney Int 1992; 41: 749-757.
46. Marquez B, Stavrou F, Zouvani I, Anastasiades E, Patsias C et al. Thin glomerular basement membranes in patients with hematuria and minimal change disease. Ultrastruct Pathol 1999;
23 (3): 149-56. (abstract)
47. Caestecker MP, Hall CL, Maclver AG. Atypical
antiglomerular basement membrane disease associated with thin membrane nephropathy.
Nephrol Dial Transplant 1990;5: 909-913.
48. Lanteri M, Wilson D, Savige J. Clinical features in two patients with IgA glomerulonephritis and thin basement membrane disease. Nephrol Dial
Transplant 1996; 11: 791-793.
49. Sheth RT, Hawkins EP, Brewer ED. Vascular Ç3 deposits on renal biopsy in pediatric patients with hematuria. Pediatr Nephrol 2000; 14: 797-801.
50. Van der Loop FT, Heidet L, Timmer ED et al. Autosomal dominant Alport syndrome caused by a COL4A3 splice site mutation. Kidney Int 2000;
58: 1870-1875.
51. Kagawa M, Kishiro Y, Naito I et al. Epitope-defined monoclonal antibodies against type IV collagen for diagnosis of Alport's syndrome.
Nephrol Dial Transplant 1997; 12: 1238-1241.
52. Kalia A, Travis L, Brouhard B. The association of idiopathic hypercalciuria and asymptomatic gross hematuria in children. J Pediatr 1981; 99 (5): 716¬719.
53. Roy S III, Stapleton FB, Noe HN, Jerkins G:
Hematuria preceding renal calculus formation in children with hypercalciuria. J Pediatr 1981; 99:
712-715.
54. Stapleton FB, Roy III S, Noe NH, Jerkins G.
204
Hypercalciuria in children with hematuria. N Eng J Med 1984; 310 (21): 1345-1348.
55. Stapleton FB. Idiopathic hypercalciuria: Association with isolated hematuria and risk for urolithiasis in children. A report of the Southwest Pediatric Nephroloey Study Group. Kidney Int 1990;37:807-811.
56. Perrone HC, Ajzen H, Toporovski J et al. Metabolic disturbance as a cause of recurrent hematuria an children. Kidney Int 1991; 39: 707¬710.
57. Rizzoni G, Braggion F, Zacchello G. Evaluation of glomerular and nonglomerular hematuria by phase-contrast microscopy. The Journal of
Pediatrics 1983; 103: 370-374.
58. Praga M. New insights into familial microhematuria. Current Opinion in Nephrology
and Hypertension 1999; 8 (2): 173-177.
59.
Kavukç
u S, Soylu A, Türkmen MA et al. Hypercalciuria preceding Ig A nephropathy in a child with haematuria. Scand J Urol Nephrol 1999;
33:630: 1-3.
60. Tasic V, Korneti P, Ristoska N et al. Idiopathic hypercalciuria preceding igA nephritis in a child with recurrent hematuria. Pediatr Nephrol 2003;
18:394-396.
61. Tanaka H, Kim ST, Takasugi M et al. Isolated Hematuria in Adults: IgA Nephropathy is a predominant cause of hematuria compared with thin glomerular basement membrane nephropathy. Am J Nephrol 1996; 16: 412A116.
62. Piel CF, Biava CG, Goodman JR. Glomerular basement membrane attenuation in familial nephritis and bening hematuria. J Pediatr 1982;
101 (3): 358-365.
63. Floege J, Feehally J. IgA Nephropathy: Recent developments. Journal of the American Society of Nephrology 2000; 1L (12): 2395-403.
64. Galla JH. IgA nephropathy. Kidney Int 1995; 47: 377-387.
65. McCallum D, Smith L, Harley F, Yiu V. IgA
nephropathy and thin basement membrane disease in association with Crohn disease. Pediatr Nephrol 1997;11:637-640.
66. Julian
BA
, Quiggins PA, Thompson JS et al. Familial IgA Nephropathy. Evidence of an inherited mechanism of disease. N Eng J Med
1985;312:202-208.
67. Berthoux FC, Laurent B, Alamartine E et al. New subgroup of primary IgA nephritis with thin glomerular basement membrane: syndrome or association. Nephrol Dial Transplant 1996; ll: 558-561.
68. Yoshikawa N, Matsuyama S, Ito H et al. Non familial hematuria associated with glomerular basement membrane alterations characteristic of hereditary nephritis: Comparison with hereditary
nephritis. J Pediatr 1987; 111: 519-24.
69. Meglic A, Kuzman D, Jazbec J et al. Erythrocyte
deformability and microhematuria in children and
adolescents. Pediatr Nephrol 2003: 18: 127-132.
70. Savige J, Wang YY. Red blood cells and thin basement membrane disease. Kidney Int 2002; 61
(4): 1550.
71. Schurek HJ. Mechanism of glomerular proteinuria and hematuria. Kidney Int 1994; 46, Suppl 47: 12¬16.
72. Liapis H, Foster K, Miner JH. Red cell traverse through thin glomerular basement membrane. Kidney Int 200; 61: 762-763.
73. Jalalah S, Alzahrani IH, Furness PN. Glomerular changes in microscopic haematuria, studied by quantitative immunoelectron microscopy and in situ zymography. Nephrol Dial Transplant 2002;
17: 1586-1593.
205

Thank you for copying data from http://www.arastirmax.com