Advanced glycation end product is implicated in amyloid-related kidney complications.
BACKGROUND
Kidney failure is a common complication in familial amyloidotic polyneuropathy (FAP). It has been suggested that advanced glycation end products (AGEs) play an important role in the development and pathogenesis of FAP.


METHODS
To evaluate the impact of AGEs on FAP patients' kidney dysfunction, we measured AGE in serum and urine of 28 FAP patients and 18 healthy controls by AGE-specific enzyme-linked immunosorbent assay (ELISA). Immunohistochemistry utilizing antibodies to AGE and the receptor for AGE (RAGE) were used on kidney tissue from 3 FAP patients and 3 diabetic patients to disclose a correlation between amyloid deposits and AGE-RAGE.


RESULTS
The glomeruli of FAP patients were heavily deposited with amyloid and the glomerular size was enlarged. The space between Bowman's capsule and glomerulus was totally covered by the enlarged glomerulus. AGE and RAGE were deposited in glomeruli and tubuli and correlated with amyloid deposits. Decreased AGE levels in the liver-transplanted FAP patients' serum compared with that of non-transplanted patients were noted, and AGE concentration in serum tended to be higher in non-transplanted FAP patients compared with normal control subjects. There were no differences in the AGE urine levels in FAP patients compared with controls. No correlation could be found between AGE in urine and serum compared with serum albumin, serum creatinine and creatinine clearance.


CONCLUSIONS
The accumulation of AGE, RAGE and amyloid in the kidney of FAP patients suggests that these molecules play an important role in the origin and pathogenesis of renal failure in FAP patients.
Matsunaga
N
N
Department of Medicine, Gastroenterology and Hepatology Section, University Hospital of Umeå, Sweden.
Anan
I
I
Rosenberg
P
P
Nagai
R
R
Lundström
O
O
Horiuchi
S
S
Ando
Y
Y
Suhr
O B
OB
D028227:Amyloid Neuropathies, Familial / Q000150:complications / Q000378:metabolism* / Q000473:pathology*; D000686:Amyloidosis / Q000150:complications / Q000378:metabolism / Q000473:pathology; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D017127:Glycation End Products, Advanced / Q000378:metabolism*; D006801:Humans; D007668:Kidney / Q000378:metabolism / Q000473:pathology; D007677:Kidney Function Tests; D008297:Male; D008875:Middle Aged; D011228:Prealbumin / Q000378:metabolism; D000067759:Receptor for Advanced Glycation End Products; D011971:Receptors, Immunologic / Q000378:metabolism; D051437:Renal Insufficiency / Q000209:etiology / Q000378:metabolism* / Q000473:pathology*
D017127:Glycation End Products, Advanced; D011228:Prealbumin; D000067759:Receptor for Advanced Glycation End Products; D011971:Receptors, Immunologic