Patrick Hamilton

By Patrick Hamilton, Rhodri Harris and Sandip Mitra

Immunoadsorption is an extracorporeal technique used for the removal of antibodies and molecules from the blood. A large number of different adsorbents are now available allowing for the non-selective removal of all subclasses of immunoglobulins such as IgG or more selective removal of disease specific molecules such as lipoprotein(a) and CRP. This selectivity, coupled with its highly efficient removal of the molecule, along with a favourable side-effect profile, has made immunoadsorption an attractive option in a range of autoimmune diseases. Here we discuss the mechanism and technique of immunoadsorption and review the current evidence and indications for its use, particularly in relation to sepsis.

Part of the book: Aspects in Continuous Renal Replacement Therapy

By Patrick Hamilton, Durga Kanigicherla and Paul Brenchley

Membranous nephropathy is the most common cause of adult nephrotic syndrome worldwide with a significant health care burden. There has been a leap in our understanding of the disease mechanism over the last decade with a remarkably strong genetic component to the development of the disease and its strong association with high affinity antibody—in the form of anti-PLA2R autoantibody in the majority of cases, with a smaller proportion associated with anti-THSD7A autoantibody. New evidence is now providing confirmation of specific elements in the development of the disease pathogenesis, such as involvement of loss of peripheral tolerance. There is a striking correlation between disease activity and anti-PLA2R antibody levels, along with response to treatment; evidence points strongly to these antibodies being pathogenic. The development of membranous nephropathy therefore follows the well appreciated multi-hit step-wise path to autoimmune clinical disease. Given its strong genetic basis and putative pathogenic antibody the disease provides an invaluable model for understanding of autoimmunity. This chapter focuses on the most up to date knowledge of autoimmune membranous nephropathy and provides a paradigm for understanding the underlying disease mechanisms in autoimmunity.

Part of the book: Glomerulonephritis and Nephrotic Syndrome

By Omar Ragy, Patrick Hamilton and Durga Kanigicherla

Membranous nephropathy is one of the leading causes of nephrotic syndrome in adults. The disease manifests in different forms with varying severity and outcomes range from spontaneous remission to rapid disease progression. The effects of the disease are so far best understood using conventional histopathological morphology and clinical phenotype. Being an autoimmune condition subject to a multi-hit hypothesis, the notion of underlying genetic risks is being examined in recent times. Current evidence points to significant heterogeneity in the gene expression profiles in both the immune system and at the glomerular level, with potential implications for disease management. Further proteomic and transcriptomic analysis can instruct classification, prognostication, and treatment pathways. This chapter focuses on the links identified between primary membranous nephropathy and underlying gene polymorphism, and pathways using both proteomics and transcriptomic analysis. We discuss the potential impact this could have on future management to try to minimize the patient’s immunosuppression exposure and find the most effective targeted immunosuppressive therapy.

Part of the book: Urinary Tract Infection and Nephropathy