Background and purpose: Rhein, an anthraquinone compound isolated from rhubarb, has been proved effective in treatment of experimental diabetic nephropathy (DN). To explore the mechanism of its therapeutic effect on DN, rhein was tested for its effect on the hexosamine pathway. Experimental approach: The influence of rhein on cellular hypertrophy, fibronectin synthesis, glucose uptake, glutamine: fructose 6-phosphate aminotransferase (GFAT) activity, UDP-N-acetylglucosamine (UDP-GlcNAc) level and TGF-b1 and p21 expression was evaluated in MCGT1 cells, a GLUT1 transgenic rat mesangial cell line. GFAT activity in normal rat mesangial cells in high glucose concentrations and in vitro was also measured. Key results: Significantly increased fibronectin synthesis, cellular hypertrophy, much higher GFAT activity and UDP-GlcNAc level and increased TGF-b1 and p21 expression were found in MCGT1 cells cultured in normal glucose concentration. Rhein treatment decreased all these features of MCGT1 cells but did not exert a direct effect on GFAT enzymatic activity. Conclusions and implications:There was over-activity of the hexosamine pathway in MCGT1 cells, which may explain the higher expression of TGF-b1 and p21, the cellular hypertrophy and the increased expression of extracellular matrix (ECM) components in the cells. By inhibiting the increased activity the hexosamine pathway, rhein decreased TGF-b1 and p21 expression and thus contributed to the decreased cellular hypertrophy and ECM synthesis. Inhibition of the hexosamine pathway may be one of the mechanism through which rhein exerts its therapeutic role in diabetic nephropathy.

C4d deposition in peritubular capillaries (PTC) has been used as a marker of antibody-mediated rejection (AMR). However, PTC C4d deposition is not described in patients with lupus nephritis (LN). C4d deposition in PTC was detected in 455 patients with biopsy proven LN in the present study. Renal tissues from 21 cases of acute AMR served as controls. C4d deposition in PTC was found in 31 patients (6.81%) with LN. Patients with PTC C4d positive showed higher SLEDAI score and higher frequency of hypocomplementemia as compared to C4d negative. The prevalence of ANA, anti-dsDNA, anti-Sm and ACA were higher in C4d positive group, and most of these patients showed the diffuse proliferative glomerular lesion. In contrast with acute AMR, the staining pattern of C4d was granular deposition and the detection of C4d along PTC was accompanied by deposition of IgG and C1q or C3. Electron dense deposition on PTC was observed in most of LN patients. In conclusion, C4d deposition in PTC could be found in a small part of patients with LN. Our study suggested for the first time that C4d positive deposition were close relation with the higher disease activity of LN, and that immune complex formation might be involved in PTC C4d deposition in LN patients, Such PTC C4d deposition is distinct from that of AMR.

This prospective study investigated the efficiency of the tacrolimus (Tac) combined with mycophenolate mofetil (MMF) alone without immunoadsorption (IA) or plasmapheresis (PPH) as treatment for early (within 2 weeks) acute humoral rejection (AHR) in non-sensitized renal allograft recipients. Of 160 patients enrolled in this prospective study, 11 patients had histologically and clinically confirmed early steroid-resistant acute rejection with an antibody response and received Tac-MMF therapy. No other aggressive rescue methods such as IA, PPH were used, according to the study design. Patients (n=11) were followed for 13.8+/-3.5 months; nine were females. The complement-dependent cytotoxicity crossmatch was negative before transplantation in all patients and only positive for panel-reactive antibody in one patient. Most of the rejection episodes were mixed with cellular rejection (four patients met Banff IIA criteria, five patients met Banff IIB, one patient met Banff IB, and one patient met Banff borderline). After 16.19+/-6.16 days of treatment, all rejection episodes were successfully reversed and all graft functions were stable, with a mean serum creatinine level of 1.12+/-0.32 mg/dl during follow-up. No patient suffered from severe infectious complications (except one case of urinary infection). Our investigation suggests that Tac combined with MMF alone is adequate to reverse early mixed cellular and humoral C4d-positive rejection in non-sensitized renal allograft recipients.