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The kidneys
Published in Martin Andrew Crook, Clinical Biochemistry & Metabolic Medicine, 2013
This comprises reduced eGFR, oedema, hypertension and proteinuria with significant haematuria. It is usually associated with systemic disease such as post-infectious glomerulonephritis, e.g. post-streptococcal or immunoglobulin A (IgA) nephropathy, ANCA-associated vasculitis, e.g. Wegener’s granulomatosis or microscopic polyarteritis, or antiglomerular basement membrane disease (Goodpasture’s disease).
Mechanisms of Chronic Glomerular Injury
Published in Robin S. Goldstein, Mechanisms of Injury in Renal Disease and Toxicity, 2020
Systemic hypertension occurs often in both experimental and clinical glomerular disease, and may play a major role in the progression of glomerulosclerosis, even after the inciting injurious event has resolved.11 Baldwin and Neugarten12 have extensively reviewed the potential impact of systemic hypertension on progressive glomerulopathy. Basically, they contend that many nephritic disorders are accompanied by a reduction in afferent arteriolar resistance (RA). An elevated systemic blood pressure could then be transmitted to the glomerular microcirculation, resulting in an increment in the glomerular capillary hydrostatic pressure (PGC), leading to further hemodynamically mediated injury.12 There are many clinical examples of hypertension occurring early in the course of glomerular disease long before the volume-overloaded state of severe chronic renal insufficiency contributes to the hypertension.13,14 In order to more reliably explore this mechanism, investigators have turned to experimental models of glomerular injury. Neugarten et al.15 demonstrated in nephrotoxic serum nephritis, a rat model for antiglomerular basement membrane disease, that the superimposition of two kidney/one clip hypertension aggravated the underlying glomerular disease as manifested by increments in proteinuria and the percentage of glomeruli demonstrating glomerular proliferation and glomerulosclerosis as compared to normotensive controls with the same underlying glomerulopathy. As a corollary to this, control of systemic hypertension should ameliorate this progression to glomerulosclerosis. Neugarten et al.16 superimposed hypertension on nephrotoxic serum nephritis by subjecting the rats to a unilateral nephrectomy and allowing them to drink only 0.9% sodium chloride. One group of these hypertensive nephritic rats was then treated with a combination of reserpine/hydralazine/hydrochlorothiazide in the drinking water which resulted in significant reductions in systolic blood pressure and amelioration of the progressive glomerulopathy. Micropuncture studies revealed that the untreated hypertensive nephritic rats had significantly elevated values for PGC, single nephron glomerular filtration rate (SNGFR), and glomerular capillary plasma flow rate (QA), while treatment of the systemic hypertension normalized all of these parameters. The authors concluded that the decreased severity of vascular and glomerular injury in the nephritic animals was due to treatment of the systemic hypertension with a resultant decrease in glomerular hydraulic stress.
The benefits and risks of escalation versus early highly effective treatment in patients with multiple sclerosis
Published in Expert Review of Neurotherapeutics, 2023
Annalisa Morgan, Emma Tallantyre, Daniel Ontaneda
Alemtuzumab is associated with the development of novel autoimmune conditions, including a risk of thyroid disease, immune thrombocytopenia, antiglomerular basement membrane disease, and hepatitis [3,4]. All DMTs, even low-moderate efficacy therapies, are associated with a theoretical elevated malignancy risk in comparison to the general population given their effect on immunosurveillance, which is an integral component of the body’s defense against malignancy [81,82]. Less long-term data is available regarding the malignancy risk associated with newer high efficacy therapies. Some studies have reported alemtuzumab and ocrelizumab to have an increased risk of malignancy compared to interferon/placebo [3,20]. However, a caveat to this is that while ocrelizumab was associated with a higher risk of breast cancer when compared to a pooled group of patients who received interferon beta-1a or placebo, this was still a lower risk than the general population, and recent long term registries have not shown this increased risk compared to the general population [20,83]. It is also important to note that if medications need to be stopped due to the occurrence of malignancy or other adverse effects, there is still a risk of ongoing or rebound disease activity, particularly with natiluzimab [5,84].
For Massachusetts Eye and Ear Special Issue: Updates on Therapies for Multiple Sclerosis for the Ophthalmologist
Published in Seminars in Ophthalmology, 2019
Tatiana Bakaeva, Sashank Prasad
Treatment with alemtuzumab is associated with various autoimmune conditions including autoimmune thyroid disease, immune-mediated thrombocytopenia, and antiglomerular basement membrane disease. Though incompletely understood, it has been proposed that these associations are due to immune reconstitution in the months following treatment. Fewer than 2% of patients treated for MS develop alemtuzumab-associated thyroid eye disease, which has a 10- to 20-fold higher incidence. The symptoms typically begin months to years following treatment and range from mild symptoms of eyelid retraction and ocular surface irritation to severe symptoms of restrictive orbital myopathy and compressive optic neuropathy. Management is the same as for nonalemtuzumab-associated thyroid eye disease.46