Abstract
BackgroundThe TNF-like weak inducer of apoptosis (TWEAK) contributes to kidney inflammation producing secretion by renal cells. The present study examined whether the level of TWEAK is associated with histologic findings in patients with IgA nephropathy (IgAN).MethodsThe levels of urinary TWEAK (uTWEAK) from 116 IgAN patients, 50 non-IgA kidney disease patients, and 50 healthy individuals were measured by ELISA. Histological findings of renal biopsy specimens of patients with IgAN were evaluated according to the Oxford classification and histological classification for IgAN in Japan. We investigated the expression of TWEAK/Fn14 in renal tissues of those patients and assessed the effect of TWEAK in glomerular mesangial cells and podocytes.ResultsThe levels of uTWEAK in the patients with IgAN and other renal diseases were significantly higher than in the healthy controls (P < 0.001). In the IgAN patients, the levels of uTWEAK correlated significantly with urinary protein excretion and extracapillary proliferation (r = 0.54, P < 0.001 and r = 0.32, P < 0.001, respectively). In a comparison of the levels of uTWEAK at diagnosis with that of follow-up, the levels of uTWEAK in patients with clinical and partial remission decreased significantly. We showed not only increased expression of both TWEAK and Fn14 in IgAN patients with glomerular crescents but also TWEAK-induced cell motility in podocytes.ConclusionsThe relationship between the levels of uTWEAK and clinicopathological findings observed in this study suggests that TWEAK/Fn14 system affects crescent formation and proteinuria in patients with IgAN.
Highlights
The TNF-like weak inducer of apoptosis (TWEAK) contributes to kidney inflammation producing secretion by renal cells
In the present study, we showed that the urine excretion of soluble TWEAK is associated with clinicopathological findings in patients with IgA nephropathy (IgAN)
We found that extracapillary proliferation was a significant independent factor that was associated with the levels of urinary TWEAK (uTWEAK)
Summary
The TNF-like weak inducer of apoptosis (TWEAK) contributes to kidney inflammation producing secretion by renal cells. The present study examined whether the level of TWEAK is associated with histologic findings in patients with IgA nephropathy (IgAN). The TNF-like weak inducer of apoptosis (TWEAK, TNFSF12), a TNF superfamily member, is synthesized as a type II transmembrane glycoprotein that circulates in plasma as a soluble form [1]. IgA nephropathy (IgAN) is the most common form of primary glomerulonephritis worldwide [10] and is one of the leading causes of end-stage renal disease (ESRD) [11]. Podocyte injury is a common denominator in many forms of human glomerular diseases [13] and is characteristic of proteinuric kidney diseases, including IgAN [14]. Podocyte loss from the glomerular basement membrane (GBM) in IgAN may cause the progression of proteinuria and glomerulosclerosis [15,16]
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