Implications of blood soluble and cell surface tumor necrosis factor receptors in childhood nephrotic syndrome

We investigated whether leukocyte cell surface TNF receptors (cTNFR) and plasma soluble TNF receptors (sTNFR) could serve as predictors of childhood steroid-resistant nephrotic syndrome (SRNS) during the early stage of diagnosis. We recruited 39 nephrotic children for studies correlating plasma sTNFR and leukocyte cTNFR with disease activity and therapeutic response. We found that patients with idiopathic childhood nephrotic syndrome (NS) had higher pretreatment plasma sTNFR1 (P<0.001) and sTNFR2 levels (P<0.001) than controls without NS. In contrast, cTNFR1 (P<0.001) and cTNFR2 (P=0.014) expression on granulocytes but not lymphocytes was lower in patients than controls. Patients with SRNS, similar to steroid-sensitive nephrotic syndrome (SSNS), had higher sTNFR1 and sTNFR2 levels pre treatment. However, patients with SRNS revealed higher expression of cTNFR1 (P<0.001) and cTNFR2 (P=0.023) than those with SSNS. After 4 weeks of steroid treatment, plasma sTNFR1 and sTNFR2 levels returned to normal in both patients with SRNS and SSNS. Post treatment, the decreased cTNFR1 and cTNFR2 expression on granulocytes in patients with SSNS returned to normal, while patients with SRNS revealed no change before and after treatment. This study suggests that a higher plasma sTNFR level associated with lower cTNFR expression reflects NS disease activity, whereas a higher initial granulocyte cTNFR expression tends to predict steroid resistance. TNFR may play a pathophysiological role in childhood NS.