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Kidney disease in diabetes: From mechanisms to clinical presentation and treatment strategies

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Original languageEnglish
Article number154890
JournalMetabolism: clinical and experimental
Volume124
DOIs
PublishedNov 2021

Bibliographical note

Funding Information: CAR is supported by a Clinical research fellowship from Kidney Research UK (Kidney Research UK, TF_001_20171120). LG has been supported by Medical Research Council UK project grant MR/T032251/1 , British Heart Foundation Project Grant PG/16/41/32138 , Diabetes Research and Wellness Foundation (start-up grant). We also acknowledge support from National Institute for Health and Research, Biomedical Research Centre award to Guy's and St Thomas Foundation Trust in partnership with King's College London . Publisher Copyright: © 2021 Elsevier Inc. Copyright: Copyright 2021 Elsevier B.V., All rights reserved.

King's Authors

Abstract

Metabolic and haemodynamic perturbations and their interaction drive the development of diabetic kidney disease (DKD) and its progression towards end stage renal disease (ESRD). Increased mitochondrial oxidative stress has been proposed as the central mechanism in the pathophysiology of DKD, but other mechanisms have been implicated. In parallel to increased oxidative stress, inflammation, cell apoptosis and tissue fibrosis drive the relentless progressive loss of kidney function affecting both the glomerular filtration barrier and the renal tubulointerstitium. Alteration of glomerular capillary autoregulation is at the basis of glomerular hypertension, an important pathogenetic mechanism for DKD. Clinical presentation of DKD can vary. Its classical presentation, often seen in patients with type 1 diabetes (T1DM), features hyperfiltration and albuminuria followed by progressive fall in renal function. Patients can often also present with atypical features characterised by progressive reduction in renal function without albuminuria, others in conjunction with non-diabetes related pathologies making the diagnosis, at times, challenging. Metabolic, lipid and blood pressure control with lifestyle interventions are crucial in reducing the progressive renal function decline seen in DKD. The prevention and management of DKD (and parallel cardiovascular disease) is a huge global challenge and therapies that target haemodynamic perturbations, such as inhibitors of the renin-angiotensin-aldosterone system (RAAS) and SGLT2 inhibitors, have been most successful.

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