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

Carlo Alberto Ricciardi; Luigi Gnudi

doi:10.1016/j.metabol.2021.154890

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

Carlo Alberto Ricciardi, Luigi Gnudi^*

^*Corresponding author for this work

Research output: Contribution to journal › Review article › peer-review

86 Citations (Scopus)

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.

Original language	English
Article number	154890
Journal	Metabolism: clinical and experimental
Volume	124
DOIs	https://doi.org/10.1016/j.metabol.2021.154890
Publication status	Published - Nov 2021

Keywords

Albuminuria
Diabetes
End-stage renal disease
Hypertension
Kidney

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

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10.1016/j.metabol.2021.154890

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title = "Kidney disease in diabetes: From mechanisms to clinical presentation and treatment strategies",

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.",

keywords = "Albuminuria, Diabetes, End-stage renal disease, Hypertension, Kidney",

author = "Ricciardi, {Carlo Alberto} and Luigi Gnudi",

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: {\textcopyright} 2021 Elsevier Inc. Copyright: Copyright 2021 Elsevier B.V., All rights reserved.",

year = "2021",

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doi = "10.1016/j.metabol.2021.154890",

language = "English",

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T2 - From mechanisms to clinical presentation and treatment strategies

AU - Ricciardi, Carlo Alberto

AU - Gnudi, Luigi

N1 - 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.

PY - 2021/11

Y1 - 2021/11

N2 - 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.

AB - 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.

KW - Albuminuria

KW - Diabetes

KW - End-stage renal disease

KW - Hypertension

KW - Kidney

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DO - 10.1016/j.metabol.2021.154890

M3 - Review article

AN - SCOPUS:85116069380

SN - 0026-0495

VL - 124

JO - Metabolism: clinical and experimental

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M1 - 154890

ER -

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

Abstract

Keywords

UN SDGs

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