CKD therapy to improve outcomes of immune-mediated glomerular diseases

Abstract

The management of IgA nephropathy, membranous nephropathy, lupus nephritis, ANCA-associated vasculitis, C3 glomerulonephritis, autoimmune podocytopathies and other immune-mediated glomerular disorders is focused on two major treatment goals, namely preventing overall mortality and the loss of kidney function. As minimizing irreversible kidney damage best serves both goals, the management of immune-mediated kidney disorders must focus on the two central pathomechanisms of kidney function decline, i.e. controlling the underlying immune disease process, e.g. with immunotherapies, and controlling the non-immune mechanisms of chronic kidney disease (CKD) progression. Here we review the pathophysiology of these non-immune mechanisms of CKD progression and discuss non-drug and drug interventions to attenuate CKD progression in immune-mediated kidney disorders. Non-pharmacological interventions include reducing salt intake, normalizing body weight, avoiding superimposed kidney injuries, smoking cessation, and regular physical activity. Approved drug interventions include inhibitors of the renin-angiotensin-aldosterone system and of the sodium-glucose-transporter-2. Numerous additional drugs to improve CKD care are currently being tested in clinical trials. Here we discuss about how and when to use these drugs in the different clinical scenarios of immune-mediated kidney diseases.

Management of adult patients with podocytopathies: an update from the ERA Immunonephrology Working Group

“…Renin angiotensin system (RAS) blockade with angiotensin-converting enzyme inhibitors or angiotensin receptor blockers is an established treatment strategy that reduces proteinuria and slow eGFR decline, as these agents decrease intraglomerular pressure, thereby reducing glomerular hyperfiltration [ 54 ]. Also, RAS blockers have anti-inflammatory and antifibrotic properties [ 55 ].…”

Treatment of IgA Nephropathy: A Rapidly Evolving Field

“…24,25 Optimal supportive care consists of lifestyle modifications with smoking cessation, dietary sodium and protein restriction, weight control and exercise, statins in patients with hypercholesterolemia, BP control, and proteinuria reduction with maximally tolerated RAASi. 111 Its value was epitomized by the observation that more than a third of patients who underwent optimization of supportive care and RAASi during the run-in phase of the STOP-IgA nephropathy trial had substantial reductions in proteinuria such that they were ineligible for subsequent randomization. 45 The initial approach to all patients with IgA nephropathy (except special populations, see below) therefore consists of optimization of supportive care for at least 3 months, with the understanding that the 3-month period starts when target BP has been achieved (Figure 3).…”