Abstract
The current study aimed to examine whether the levels of TNF receptors 1 and 2 (TNFR1 and TNFR2) in serum and urine were associated with other markers of kidney injury and renal histological findings, including TNFR expression, in IgA nephropathy (IgAN). The levels of the parameters of interest were measured by immunoassay in 106 biopsy-proven IgAN patients using samples obtained immediately before renal biopsy and in 34 healthy subjects. Renal histological findings were evaluated using immunohistochemistry. The levels of serum TNFRs were higher in IgAN patients than in healthy subjects. The levels of both TNFRs in serum or urine were strongly correlated with each other (r > 0.9). Serum TNFR levels were positively correlated with the urinary protein to creatinine ratio (UPCR) and four markers of tubular damage of interest (N-acetyl-β-D-glucosaminidase [NAG], β2 microglobulin [β2m], liver-type fatty acid-binding protein [L-FABP], and kidney injury molecule-1 [KIM-1]) and negatively correlated with estimated glomerular filtration rate (eGFR). Patients in the highest tertile of serum TNFR levels showed more severe renal interstitial fibrosis than did those in the lowest or second tertiles. The tubulointerstitial TNFR2-, but not TNFR1-, positive area was significantly correlated with the serum levels of TNFRs and eGFR. Stepwise multiple regression analysis revealed that elevated serum TNFR1 or TNFR2 levels were a significant determinant of renal interstitial fibrosis after adjusting for eGFR, UPCR, and other markers of tubular damage. In conclusion, elevated serum TNFR levels were significantly associated with the severity of renal interstitial fibrosis in IgAN patients. However, the source of TNFRs in serum and urine remains unclear.
Highlights
IgA nephropathy (IgAN) is the most common form of glomerulonephritis worldwide, and it presents with various histological and clinical phenotypes [1,2,3]
DBP was significantly higher in healthy subjects, the values were within the normal range. estimated glomerular filtration rate (eGFR) and the urinary protein to creatinine ratio (UPCR) were lower and higher, respectively, in IgAN patients, as expected
Elevated serum TNF receptors (TNFRs) levels were associated with renal interstitial fibrosis in IgAN patients
Summary
IgA nephropathy (IgAN) is the most common form of glomerulonephritis worldwide, and it presents with various histological and clinical phenotypes [1,2,3]. A number of studies have reported that the levels of circulating TNF pathway-related molecules, such as TNFα and TNF receptors (TNFRs), are significantly higher in chronic kidney disease (CKD) patients, and that these levels are closely correlated with changes in the estimated glomerular filtration rate (GFR) [8,9]. These biomarkers are associated with lower GFR and higher albuminuria even in a community-based setting [10,11]. We measured the levels of TNFRs in IgAN patients using serum and urine samples obtained immediately before renal biopsy and examined renal histological findings, including TNFR expression
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