Moving Forward With Biologics in Lupus Nephritis.

The majority of patients with systemic lupus erythematosus develop lupus nephritis (LN) which significantly contributes to increased risks of hospitalizations, ESRD, and death. Unfortunately, treatments for LN have not changed over the past 15 years. Despite continued efforts to elucidate the pathogenesis of LN, no new drugs have yet replaced the standard-of-care regimens of cyclophosphamide or mycophenolate mofetil plus high-dose corticosteroids.

Targeted inhibition of Axl receptor tyrosine kinase ameliorates anti-GBM-induced lupus-like nephritis.

Glomerulonephritis (GN) is a typical lesion in autoantibody and immune complex disorders, including SLE. Because the Gas6/Axl pathway has been implicated in the pathogenesis of many types of GN, targeting this pathway might ameliorate GN. Consequently, we have studied the efficacy and mechanism of R428, a potent selective Axl inhibitor, in the prevention of experimental anti-GBM nephritis.

Monocyte and plasma expression of TAM ligand and receptor in renal failure: Links to unregulated immunity and chronic inflammation.

Chronic inflammation is increased in patients with chronic kidney disease (CKD) and contributes to cardiovascular morbidity and mortality. Specific immune mechanisms and pathways that drive and maintain chronic inflammation in CKD are not well described. The TAM ligands (Gas6 and protein S) and receptors (Axl and Mer) have been recently recognized as playing a prominent role in immune regulation.

Chronic kidney disease alters vascular smooth muscle cell phenotype.

Vascular access dysfunction associated with arteriovenous grafts and fistulas contributes to the morbidity and mortality of chronic kidney disease (CKD) patients receiving hemodialysis. We hypothesized that the uremic conditions associated with CKD promote a pathophysiological vascular smooth muscle cell (VSMC) phenotype that contributes to neointimal hyperplasia. We analyzed the effect of culturing human VSMC with uremic serum.

Impact of Donor Specific HLA Antibody Monitoring After Kidney Transplantation.

Kidney transplantation (KT) recipients with donor specific HLA antibodies (DSA) encounter higher rates of acute rejection and inferior allograft survival. We report our single center experience with prospective DSA monitoring and provide details of treatments utilized to overcome the potential impact of DSA in a cohort of predominantly African American adult KT recipients. Seventy-five flow crossmatch negative KT recipients underwent periodic screening for DSA utilizing the single antigen bead assay at 3, 6, 9, and 12 months post-transplant.

Biomarkers in renal transplantation.

Identifying surrogate markers of renal allograft outcome and biomarkers of acute and chronic graft injury is a critical issue for the transplant community. Measurement of serum creatinine and biopsy remain the current gold standards for the evaluation of renal allografts. These tests have significant limitations in predicting which patients are destined for immune tolerance or immune-mediated graft loss, and aiding in the management of long-term immunosuppression.