Advances and Researches in Idiopathic Nephrotic Syndrome Biomarkers

In 1985, through co-culture using PBMC of patients with recurrent primary small change nephropathy (IMLNS) and normal rat glomerular, Garin found that 35sulfate absorption of glomerular was improved and proteinuria was induced. These suggested that the PBMC of patients with relapsed IMLNS may release a factor leading to this result [4] and the muddy pine can reduce 35sulfate absorption of glomerular basement membrane [5]. On this basis, he also observed the synergistic effect of monocytes and lymphocytes. Using co-culture of rat glomerular with PBMC, monocytes and lymphocyte supernatant of MCNS patients, respectively, he suggested that monocytes may play a role of stimulating and amplifying cytokines [6]. Yoshizawa stimulated PBMC of MCNS patients using concanavalin A and injected supernatant into rats. Rats were induced proteinuria and renal pathological changes similar to MCNS. But the other types kidney disease can not produce this result [7]. Maruyama found that the rats were induced proteinuria and reduced basement membrane anion sites by injecting T-cell culture supernatant of MCNS patients into the rat left renal artery [8]. Heslan thought that vascular permeability factor (VPF) was the product of T cells [9], which can change glomerular permeability and lead to proteinuria. Koyamal prepared four hybridomas derived from T lymphocytes of MCNS patients to secret glomerular permeability factor (GPF), which was injected into the rat resulting in significant proteinuria [10]. Wang’s study showed that using PBMC supernatant of the active hormone-sensitive nephrotic syndrome (NS) patients to fill the rat kidney, they found glomerular polyanions were decreased and ultrastructural changed like MCNS [11]. Filling PBMC supernatant of MCNS and FSGS patients into the normal renal artery can induce proteinuria and polyanion reduction [12]. In 2006, Garin EH divided PBMC supernatant of IMLNS patients into three parts by liquid chromatography: bovine serum albumin, β-amylase and ferritin. These were injected into rats, respectively. Only β-amylase induced podocyte fusion in rats, which may play an important role in IMLNS pathogenesis [13]. The role of humoral immunity in INS pathogenesis is not fully clear. T cell dysfunction has been confirmed by various evidence, but the reliability of the experimental methods need to be improved. Recent studies have shown that the infiltration of monocytes/macrophages in renal tissue was related to the increased expression of adhesion molecules like ICAM-1 [14]. CD25+ lymphocytes were also observed in the renal interstitium of animals with NS induced by doxorubicin [15]. Although there are presence reports of macrophages also in glomerulus of animals with NS [14], most studies have not detected glomerular macrophage infiltration [16-18].