New Biologics for Glomerular Disease on the Horizon

Abstract

The major advances achieved in immunology and cellular biology have led to the development of biotherapies that specifically target different mediators and pathways involved in the physiopathology of renal diseases. After the major breakthroughs obtained with B-cell depletion in autoantibody-mediated glomerulopathies, several other immunomodulation strategies are being tested in autoimmune glomerulonephritides, such as blockade of B-cell costimulation and activation, inhibition of complement pathways or modification of the T-B-lymphocyte crosstalk. Other drugs, inhibiting proinflammatory cytokines, are being developed in order to control the inflammatory response initiating and amplifying the kidney tissue injury observed in different systemic diseases. Finally, several promising therapeutic agents target specific renal cells such as podocytes or fibroblasts, blocking the common final steps of the deleterious pathological process underlying various types of nephropathy. Although several of these drugs are still under evaluation in phase 2/3 clinical trials, biotherapies have undoubtedly opened a new era in the treatment of glomerular disease.

Maternal and fetal outcomes of pregnancy in chronic kidney disease: diagnostic challenges, surveillance and treatment throughout the spectrum of kidney disease

“…rituximab in membranous glomerulonephritis and SLE, belimumab in SLE). [105][106][107] Biologic agents are derivatives of IgG, differing in structure, half-life, and placental passage. Placental transfer of IgG is limited during organogenesis, but increases gradually and exponentially from the beginning of the second trimester until term (Table 1).…”

Multi-Target Drugs for Kidney Diseases

“…Biologics such as monoclonal antibodies and nanobodies that act on single target are advancing kidney diseases with improvements in bioavailability and tissue targeting. 69,70 Likewise, RNA-based short interfering RNAs and long coding RNAs are advancing to treat kidney diseases.…”

“…Developing biologics and RNA-based drugs with multi-target activities for kidney and glomerular diseases could have kidney and cell targeting advantages; however, several challenges remain that would need to be overcome. 69,70,71,72 Consequently, there is ample avenues to be investigated in developing multi-target therapies for kidney diseases.…”

Conventional induction and maintenance treatment of Antineutrophil cytoplasmic antibodies-associated vasculitis – still of value for our patients?

“…Hopefully we will have the chance to use an increasing number of biologics that are currently tested in clinical studies in different glomerulonephritides including AAV [75], for instance other strategies aimed at B-cell depletion, B-cell modulation, blockade of B-cell co-stimulation and activation, inhibition of complement activation and inhibition of proinflammatory cytokines.…”