F.M. Lai

Tacrolimus for the treatment of systemic lupus erythematosus with pure class V nephritis

OBJECTIVES The treatment of pure membranous (class V) lupus nephropathy remains unsatisfactory. We studied the efficacy and safety of tacrolimus in the treatment of membranous nephritis secondary to SLE. METHODS We recruited 18 consecutive SLE patients (tacrolimus group) with recently confirmed biopsy-proven class V lupus nephritis. They were treated with a tailing dose of oral prednisolone and tacrolimus 0.1-0.2 mg/kg/day for 6 months, followed by maintenance prednisolone and AZA. The rate of resolution of proteinuria and SLEDAI were compared with 19 historical controls treated with oral cyclophosphamide or AZA (control group). All patients were followed for 12 months. RESULTS Baseline clinical characteristics were comparable between the groups. For the tacrolimus group, the complete and partial remission rates were 27.8 and 50.0%, respectively at 12 weeks; for the control group, they were 15.8 and 47.4%, respectively (overall chi-square test, P = 0.5). However, tacrolimus group had faster resolution of proteinuria than the control group by the general linear model with repeated measures (P = 0.032). At 12 weeks, proteinuria was reduced by 76.2 +/- 17.0% for the tacrolimus group and 47.1 +/- 51.1% for the control group (P = 0.028). Serial change in renal function and SLEDAI score did not differ between the groups. During the study period, four patients of the tacrolimus group, and 11 of the control group, developed lupus flare (P = 0.027). There was no serious adverse effect in the tacrolimus group. CONCLUSIONS A 6-month course of tacrolimus is a safe and effective treatment of pure class V (membranous) lupus nephritis. As compared with conventional cytotoxic treatment, tacrolimus possibly results in a faster resolution of proteinuria, and a lower risk of lupus flare within 1 yr. The long-term effect and optimal regimen of tacrolimus require further study.

Effective treatment of high-grade lymphoproliferative disorder after renal transplantation using autologous lymphocyte activated killer cell therapy.

Posttransplantation lymphoproliferative disorders (PTLD) is not uncommon and can occur in 2% to 5% of solid organ recipients on immunosuppression. Epstein-Barr virus (EBV) infection or reactivation and intensive anti-T lymphocyte treatment are important pathogenetic factors for a large proportion of these disorders. Nonclonal lesions with polymorphous histology have a potential for regressing when the immunosuppressants are reduced or stopped. Clonal tumors with a monomorphous histology carry a poor prognosis, and the mortality rate for monoclonal lymphoma has been reported as high as 80%. We report a renal transplant recipient who developed high-grade monoclonal lymphoma only 4 months after a live-donor transplantation. The tumor was EBV positive. Reduction of immunosuppressants resulted in minimal regression of the tumor. The patient was treated with adoptive immunotherapy using ex vivo generation of autologous lymphocyte activated killer (LAK) cells. She had leukapheresis, and autologous peripheral blood mononuclear cells were obtained and cultured in interleukin-2 (IL-2)-rich medium for 9 to 10 days. The IL-2-activated LAK cells were reinfused into the patient without any systemic administration of IL-2. The patient experienced no side effects during the infusion. There was no rejection episode, and the renal function of the patient remained stable after treatment. Computed tomography scan performed 2 months after the infusion showed marked regression of the lesions in the liver and spleen. Five months later, magnetic resonance imaging showed complete resolution of the tumor lesions. Ultrasonography 13 months after the LAK cell infusion showed no lesion. The allograft function was not affected after treatment. Adoptive immunotherapy using IL-2-activated autologous LAK cells was effective in treating this renal transplant patient with EBV-positive high-grade lymphoma. The patients kidney allograft functioned well without any rejection.

Histological appraisal of lupus nephritis

Abstract The importance of renal biopsy in systemic lupus erythematosus (SLE) patients with nephritis resides not only in the diagnosis, but mostly in its role in guiding and assessing therapy. The potential benefits of treatment in lupus nephritis include a dramatic clinical improvement and a direct impact on renal survival. However, these benefits can be achieved only if they are carefully weighed against the complex, prolonged, and potentially toxic treatment regimens. This review on lupus nephritis emphasizes on the histological appraisal of lupus nephritis, which may demonstrate some variations among institutions, but should be clearly defined if one expects to have more useful information for the routine management of patients, as well as in clinical trials.

Early IgA nephropathy: paradigm evolving from a clinical concept into a histological measure

Abstract The designation of “early” IgA nephropathy is often used in patients with normal renal function, no or mild proteinuria, and absence of other features, but the term is in fact poorly defined judging from the varying norms adopted. Even with stringent clinical criteria used to characterize clinical early IgA nephropathy, these may not be correlated with the prediction of disease outcome, nor with the severity of renal lesions. Due to such limitations, the clinical reference to early IgA nephropathy represents more a concept than an accurate measure. The histological definition of “early” IgA nephropathy appears to be different as the grading of biopsy permits one to segregate by semiquantitation patients with early renal lesion and very low risk of progression. This review puts the emphasis on the morphologic definition of early IgA nephropathy based on objective criteria, and on its practical consequences. The clinical implications include a better patient selection in therapy, and the potential to enhance results of treatment as well as for the appraisal of clinical trials. We also suggest that all patients suspected for IgA nephropathy, including those in early clinical stage should undergo renal biopsy because the information yielded are critical to the management and therapy.