Renal tubular dysgenesis and tubulointerstitial nephritis antigen in juvenile nephronophthisis.
OBJECTIVE
The relationship between abnormalities of tubular architecture and tubulointerstitial nephritis antigen (TIN-ag) in juvenile nephronophthisis (J-NPH) was evaluated.


METHODS
Sixteen J-NPH patients were examined. Nephrocystin-1, TIN-ag, type IV collagen, Fas antigen and the C5b-9 complement complex were stained by immunohistochemical methods.


RESULTS
Renal tubules of patients with J-NPH showed morphological abnormalities of tubular basement membranes (TBM) and frequent apoptosis of tubular epithelial cells. Additionally, the C5b-9 complement complex was deposited within the TBM in the absence of immunoglobulin deposition, suggesting complement-dependent TBM injury. Localization of TIN-ag in the TBM of J-NPH patients disclosed a partial defect or discontinuity in 14 of the 16 patients, while type IV collagen immunoreactivity was relatively preserved. These findings suggest that tubulogenesis is disturbed during nephronogenesis in J-NPH patients because of a defect in nephrocystin, an NPHP gene product. TBM defects induce further morphological abnormalities such as cystic dilation of tubules; as tubular function impairment advances, the incomplete tubules may be injured by C5b-9 complement complexes, followed by apoptotic cell death.


CONCLUSIONS
TIN-ag, which is important in early nephrogenesis, lacks normal activity, and vulnerable and incomplete tubules with deficient TIN-ag expression are formed. Removal of these defective tubules by apoptosis combined with the C5b-9 complement complex could be the primary reason for progression to end-stage renal disease in J-NPH patients.
Department of Paediatrics, Kinki University School of Medicine, Osaka, Japan.
Keisuke
K
Sugimoto
Yutaka
Y
Takemura
Hidehiko
H
Yanagida
Shinsuke
S
Fujita
Tomoki
T
Miyazawa
Naoki
N
Sakata
Mitsuru
M
Okada
Tsukasa
T
Takemura
D001485:Basement Membrane / Q000473:pathology; D015815:Cell Adhesion Molecules / Q000032:analysis / Q000502:physiology*; D024141:Collagen Type IV / Q000032:analysis; D015938:Complement Membrane Attack Complex / Q000032:analysis; D006801:Humans; D052177:Kidney Diseases, Cystic / Q000150:complications / Q000151:congenital*; D007676:Kidney Failure, Chronic / Q000209:etiology*; D007684:Kidney Tubules / Q000002:abnormalities*; D019014:fas Receptor / Q000032:analysis
D015815:Cell Adhesion Molecules; D024141:Collagen Type IV; D015938:Complement Membrane Attack Complex; C085434:TINAG protein, human; D019014:fas Receptor