mycophenolic-acid and Pneumocystis-Infections

Management of patients with lupus nephritis can be complex and challenging. We suggest that there are some widely held misconceptions about lupus, and unfortunately, these underpin the treatment of many patients. There is little evidence to support the common assumption that intravenous pulse cyclophosphamide is the best treatment for lupus nephritis. Although there is much focus on which immunosuppressive agent to use, too little attention is paid to the proper dose and duration of corticosteroids and concomitant therapy with antimalarial agents. Many clinicians reflexively perform kidney biopsies when these biopsies may be high risk and not influence therapy. There is little emphasis on or awareness of nonadherence to therapy, which is an underappreciated cause of treatment resistance. Resolution of proteinuria and hematuria can take a long time, and immunotherapy should not be intensified based on urine sediment alone. Furthermore, the intensity of the immunosuppression must be considered in the context of lupus nephritis class and duration of kidney damage. Finally, clinicians are aware of the risks of pregnancy in the face of active lupus, but assume that their patients also are aware of this and forget to discuss this with them. With a combined experience of more than 50 years in managing children and adults with lupus, we offer our impression of recurrent mistakes in the management of lupus in general, with a focus on treatment of lupus nephritis.

Topics: Adult; Antimalarials; Azathioprine; Bone Density; Cyclophosphamide; Female; Glucocorticoids; Humans; Immunosuppressive Agents; Kidney; Lupus Erythematosus, Systemic; Lupus Nephritis; Mycophenolic Acid; Patient Compliance; Pneumocystis carinii; Pneumocystis Infections; Pregnancy; Pregnancy Complications; Renal Dialysis

To investigate the potential influence of variants in genes involved in the calcineurin pathway on the efficacy and toxicity of calcineurin inhibitors in renal transplantation.. Twenty-three polymorphisms in thirteen genes were tested in 381 renal transplant recipients receiving ciclosporin (n = 221) or tacrolimus (n = 160) and mycophenolate mofetil. Data were collected prospectively over the first year post-transplantation.. Multivariate survival analyses revealed no genetic associations with biopsy proven acute graft rejection and serious infections. Donor-recipient Cytomegalovirus mismatch was the only variable associated with serious infection.. This large exploratory study casts doubts on the potential interest of genetic biomarkers related to CNI pharmacodynamics but associations with other phenotypes in transplantation deserve further studies.

Topics: Adult; Calcineurin; Cyclosporine; Cytomegalovirus Infections; Female; Genetic Association Studies; Graft Rejection; Humans; Immunosuppressive Agents; Kidney Transplantation; Male; Middle Aged; Mycophenolic Acid; Pneumocystis carinii; Pneumocystis Infections; Polymorphism, Single Nucleotide; Prospective Studies; Risk; Signal Transduction; Tacrolimus

To highlight the rare but life-threatening infective consequences of immunosuppression or biologic treatment for sight-threatening uveitis.. Retrospective case series of four immunosuppressed patients with uveitis complicated by sepsis.. The affected patients were all treated using prednisolone 10 mg/day or greater, together with oral immunosuppression (2 mycophenolate mofetil, 1 azathioprine + ciclosporin, 1 methotrexate) and, in one case, infliximab. All patients survived following intensive treatment.. Life-threatening infection is a rare but important risk in immunosuppressed patients with uveitis. Complete protection is not possible and prophylaxis regimens are of unproven efficacy. Patients should understand the risks before agreeing to a course of treatment.

Topics: Adult; Aged; Azathioprine; Bacteremia; Cyclosporine; Drug Therapy, Combination; Female; Humans; Immunosuppression Therapy; Immunosuppressive Agents; Klebsiella Infections; Male; Methotrexate; Middle Aged; Mycophenolic Acid; Pneumocystis Infections; Prednisolone; Retrospective Studies; Uveitis