Urinary excretion of soluble tumour necrosis factor receptor 1 as a marker of increased risk of progressive kidney function deterioration in patients with primary chronic glomerulonephritis

Abstract

The effects of tumor necrosis factor α (TNF α), a potent proinflammatory cytokine, in the kidneys are mediated by two membrane receptors (TNFR), TNFR1 and TNFR2. The expression of both TNF and TNFRs increases in several kidney diseases and is associated with the shedding of the receptors out of the cell membranes. In an experimental model of glomerulonephritis (GN), elevated concentrations of TNFRs in serum and TNFRs excretion in urine were demonstrated. The aim of this study was evaluation of urinary excretion of TNFR1 and its relationship with the clinical markers of kidney injury in patients with GN. The value of basal urinary TNFR1 excretion as a prognostic indicator of the progression of kidney function impairment was also assessed. Fifty-five patients with newly diagnosed, biopsy-proven primary GN were included in the study. In all patients, and in 20 healthy subjects, UTNFR1 was measured using an ELISA . In the patients, risk factors of the progression of impairment of kidney function (reduced eCcr, nephrotic syndrome, hypertension and intensity of morphological lesions in the kidneys) were evaluated. The appropriate treatment was then introduced and the patients were in follow-up for 4 years. The progression of kidney function impairment was defined as a reduction of eCcr > 5 mL/min/1.73 m2 /year during follow-up. The association of basal TNFR1 excretion with the progression was evaluated. Urinary excretion of TNFR1 in the patients with GN (4039.2 ± 3801.5 pg/mgCr) was greater than in the healthy subjects (1358.9 ± 927.8 pg/mgCr, P < 0,00002). A significant negative correlation between TNFR1 excretion and eCcr (Sr=0.464, P < 0.01) and a positive correlation between TNFR1 excretion and proteinuria (Sr = 0,463, P < 0.01) were found. In 13 patients, a marked reduction of eCcr was observed during follow-up. Logistic regression analysis revealed that TNFR1 excretion > 3863.3 pg/mgCr predicts progression of renal function impairment along with advanced interstitial fibrosis in the kidney biopsy specimens at presentation. Markedly elevated urinary TNFR1 excretion may be considered as a good marker of an activated TNFα-pathway in patients with newly diagnosed GN and as a potentially modifiable risk factor of progressive kidney function impairment.