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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
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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).
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