Leflunomide plus low-dose prednisone in patients with progressive IgA nephropathy: a multicenter, prospective, randomized, open-labeled, and controlled trial.

BACKGROUND: Immunoglobulin A nephropathy (IgAN) is the most common cause of glomerulonephritis worldwide, and the optimal approach to its treatment remains a significant challenge. METHODS: We did a prospective, randomized, open-labeled, multicenter, controlled trial, comprised of 3-month run-in, 12-month treatment, and 12-month follow-up phases. After 3-month run-in phase, patients with biopsy-confirmed IgAN at risk of progression were randomly allocated to LEF plus low-dose prednisone (LEF + prednisone group) or conventionally accepted-dose prednisone [prednisone(alone) group] Our primary outcome was 24-h urine protein excretion (UPE) and secondary outcomes were serum albumin (sALB), serum creatinine (Scr), and eGFR. Safety was evaluated in all patients who received the trial medications. RESULTS: One hundred and eight patients [59 in LEF + prednisone group, 49 in prednisone (alone) group]were enrolled and finished their treatment and follow-up periods. There is no significant difference in the baseline level between the two groups. Compared with baseline, both groups showed a significant decrease in 24-h UPE (p < 0.01) and increase in sALB (p < 0.01), with stable Scr and eGFR throughout the 12-month treatment period. What's more, these effects were sustained through the 12-month follow-up period. However, there was no difference in 24-h UPE, sALB, Scr, and eGFR between the two groups (p > 0.05). At 12 months, a difference in overall response rate, relapsing rate, and incidence of adverse events between the two groups was not significant. CONCLUSIONS: The efficacy and safety of LEF plus low-dose prednisone and conventionally accepted-dose prednisone in the treatment of progressive IgAN are comparable.

Pilot 24 month study to compare mycophenolate mofetil and tacrolimus in the treatment of membranous lupus nephritis with nephrotic syndrome.

AIM: This pilot study compared mycophenolate mofetil (MMF) and tacrolimus (Tac) in the treatment of severe membranous lupus nephritis (MLN). METHOD: This was a 24 month prospective, randomized, open-label multi-centre exploratory study on Chinese patients with biopsy-proven pure Class V MLN with nephrotic syndrome. Patients were randomized to treatment with either MMF or Tac, both in combination with prednisolone and the efficacy and tolerability outcomes were examined. RESULTS: Sixteen patients were included, seven in the MMF and nine in the Tac treatment arm. At 24 months the complete response, partial response and overall response rates were 57.1% vs. 11.1% (P = 0.049), 14.3% vs. 44.4% (P = 0.197) and 71.4% vs. 55.6% (P = 0.515) in the MMF and Tac groups, respectively. The two groups had similar reduction of proteinuria and longitudinal profiles of serum albumin and creatinine levels. Serum creatinine remained stable in both groups, except in two patients who had a transient increase associated with high Tac blood levels. Adverse events in the MMF group included herpes zoster in one patient and reversible leucopenia in another, while in the Tac group four patients had severe infections and one developed new onset diabetes. No relapse occurred during the study period. CONCLUSION: Both MMF and Tac when combined with corticosteroids are effective treatment options for severe MLN.

Serum major-histocompatibility-complex class I-related chain A antibody detection for the evaluation of graft dysfunction in renal allograft recipients.

BACKGROUND: In addition to the well-known antibodies against human leukocyte antigens (HLA)-induced kidney-graft rejection, polymorphic major-histocompatibility-complex (MHC) class I-related chain A (MICA) antigens can elicit antibodies and have been suggested to play a role in the antibody-mediated allograft rejection (AMR). We carried out a prospective study of MICA antibodies in post-renal transplant patients to determine the association between MICA antibodies, C4d staining, histological features, and graft outcome. METHODS: We tested 52 patients who had biopsy results due to graft dysfunction. The MICA antibodies in concurrent sera were determined by Luminex. All patients were followed up for one year after renal biopsy. The influence of antibody production on the function of graft was analyzed. RESULTS: Antibodies against MICA were positive in 15 out of the 52 patients (28.9%). The presence of MICA antibodies was associated with renal-allograft deterioration. During one-year follow-up, the estimated glomerular filtration rate (eGFR) decreased (24.0 ± 3.4)% among recipients with anti-MICA antibodies. However, among recipients without anti-MICA antibodies, the eGFR has declined only (8.4 ± 3.0)% (P = 0.017). The association between C4d staining, histological features and MICA antibody production was found no significant difference. CONCLUSION: Besides anti-HLA antibodies, the presence of post-transplant MICA antibody is associated with poor graft outcome and increases the risk of graft failure.

Tacrolimus combined with corticosteroids in treatment of nephrotic idiopathic membranous nephropathy: a multicenter randomized controlled trial.

BACKGROUND: Idiopathic membranous nephropathy (IMN), a common cause of nephrotic syndrome in adults, is usually treated with corticosteroids in combination with cyclophosphamide or cyclosporine. A recent placebo-controlled study suggested that tacrolimus monotherapy was effective in IMN. However, the effectiveness of tacrolimus versus classic regimen and its potential nephrotoxicity remain inconclusive. This study evaluated the efficacy and safety of tacrolimus plus prednisone in patients with nephrotic IMN. METHODS: Seventy-three patients with nephrotic IMN were recruited in this multicenter randomized controlled trial, 39 receiving tacrolimus and prednisone, while 34 receiving cyclophosphamide and prednisone. Tacrolimus was given at 0.1 mg/kg/d initially and adjusted to a blood trough level at 5 to 10 ng/mL for 6 months and then reduced to 2 to 5 ng/mL in the subsequent 3 months. RESULTS: Intention-to-treat analysis suggested that the remission rate at the end of the sixth month was significantly higher in tacrolimus group than that in cyclophosphamide group (85% versus 65%, P < 0.05). The decrease of proteinuria was significantly greater in tacrolimus group. At the end of the 12th month, the remission rates were comparable between these 2 groups. Patients treated with tacrolimus were more likely to develop glucose intolerance (or diabetes mellitus), infection, and hypertension. No obvious nephrotoxicity of calcineurin inhibitor was found in repeat renal biopsy. CONCLUSIONS: Tacrolimus plus corticosteroids is an alternative therapeutic regimen for nephrotic IMN. The short-term efficacy might be better than cyclophosphamide plus prednisone.

[Treatment of proliferative lupus nephritis with leflunomide and steroid: a prospective multi-center controlled clinical trial].

OBJECTIVE: Leflunomide (LEF) is a selective inhibitor of de novo pyrimidine synthesis, currently used in the treatment of rheumatoid arthritis. To evaluate the efficacy and safety of LEF in the treatment of proliferative lupus nephritis, a prospective multi-center controlled clinical trial was conducted. METHODS: Patients with biopsy-confirmed proliferative lupus nephritis were recruited. Patients of recent onset who had not used any immunosuppressive drug were given either oral LEF (group A) or IV cyclophosphamide (group B); relapsed patients who had received immunosuppressive therapy 3 months before were given LEF (group C). Efficacy and safety were evaluated at 6 months after treatment. RESULTS: Total 51 patients were enrolled, 4 patients withdrew due to adverse events. For those initial treated patients, total response rate were 80% in group A and 75% in group B, complete remission rate were 40% and 25% respectively, not statistically different. Renal parameters (proteinuria, serum albumin and serum creatinine) and systemic lupus erythematosus disease activity index (SLEDAI) improved similarly in both groups. For 14 relapsed patients, total response rate was 60% and complete remission rate was 6.7%. Major adverse events reported in LEF treated patients were infection and alopecia. Herpes zoster was the most often type among infectious events, and one case of severe lung infection was reported. CONCLUSION: LEF combined with steroid was effective in the induction therapy of proliferative lupus nephritis. LEF was generally well-tolerated, its efficacy in maintenance therapy and long-term safety remains to be clarified.