Update on diagnosis, pathophysiology, and management of diabetic kidney disease

Mai Sugahara; Wai Lun Will Pak; Tetsuhiro Tanaka; Sydney C. W. Tang; Masaomi Nangaku

doi:10.1111/nep.13860

journal article Feb 17, 2021

Update on diagnosis, pathophysiology, and management of diabetic kidney disease

Mai Sugahara

Nephrology Vol. 26 No. 6 pp. 491-500 · Wiley

View at Publisher Save 10.1111/nep.13860

Abstract

AbstractDiabetic kidney disease (DKD) is a chronic complication of diabetes mellitus which may eventually lead to end‐stage kidney disease (ESKD). Despite improvements in glycaemic control and blood pressure management with renin‐angiotensin‐aldosterone system (RAAS) blockade, the current therapy cannot completely halt DKD progression to ESKD in some patients. DKD is a heterogeneous disease entity in terms of its clinical manifestations, histopathology and the rate of progression, which makes it difficult to develop effective therapeutics. It was formerly considered that albuminuria preceded kidney function decline in DKD, but recent epidemiological studies revealed that a distinct group of patients presented kidney dysfunction without developing albuminuria. Other comorbidities, such as hypertension, obesity and gout, also affect the clinical course of DKD. The pathophysiology of DKD is complex and multifactorial, involving both metabolic and haemodynamic factors. These induce activation of intracellular signalling pathways, oxidative stress, hypoxia, dysregulated autophagy and epigenetic changes, which result in kidney inflammation and fibrosis. Recently, two groups of antidiabetic drugs, sodium‐glucose cotransporter 2 (SGLT2) inhibitors and glucagon‐like peptide‐1 (GLP‐1) receptor agonists, were demonstrated to provide renoprotection on top of their glucose‐lowering effects. Several other therapeutic agents are also being developed and evaluated in clinical trials.

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References

117

[1]

10.1016/j.jdiacomp.2017.12.003

[2]

10.1016/j.jdiacomp.2015.10.007

[3]

National Kidney Foundation "KDOQI clinical practice guidelines and clinical practice recommendations for diabetes and chronic kidney disease" Am J Kidney Dis. (2007) 10.1053/j.ajkd.2006.12.005

[4]

10.2337/diab.32.2.s64

[5]

Tang S (2019)

[6]

10.1046/j.1523-1755.2003.00712.x

[7]

10.1001/jama.2016.10924

[8]

10.2337/dc15-0184

[9]

10.1016/j.jdiacomp.2018.09.019

[10]

10.1016/j.jdiacomp.2012.09.010

[11]

Lee E "The incidence of cardiovascular events is comparable between normoalbuminuric and albuminuric diabetic patients with chronic kidney disease" Medicine (Baltimore) (2016)

[12]

10.2337/dc18-1320

[13]

10.1016/j.dsx.2017.05.016

[14]

10.1007/s00125-018-4691-2

[15]

10.1159/000333249

[16]

10.1016/j.numecd.2019.07.017

[17]

10.1016/s2213-8587(14)70155-x

[18]

10.2337/db05-1620

[19]

10.1053/j.ackd.2017.10.011

[20]

10.1007/s11892-019-1133-6

[21]

Global and regional diabetes prevalence estimates for 2019 and projections for 2030 and 2045: Results from the International Diabetes Federation Diabetes Atlas, 9th edition

Pouya Saeedi, Inga Petersohn, Paraskevi Salpea et al.

Diabetes Research and Clinical Practice 10.1016/j.diabres.2019.107843

[22]

Saran R "US renal data system. 2018 USRDS annual data report: epidemiology of kidney disease in the United States" Am J Kidney Dis. (2019)

[23]

10.1093/ndt/gfk014

[24]

10.2337/dc20-s011

[25]

Fiorentino M "Renal biopsy in patients with diabetes: a pooled meta‐analysis of 48 studies" Nephrol Dial Transplant (2017)

[26]

10.1681/asn.2016060666

[27]

Matoba K "Targeting redox imbalance as an approach for diabetic kidney disease" Biomedicine (2020)

[28]

10.1155/2016/7813072

[29]

10.1152/ajprenal.00181.2002

[30]

10.2337/diabetes.55.01.06.db05-0894

[31]

10.1089/ars.2016.6664

[32]

10.1007/s00125-003-1155-z

[33]

10.1097/rli.0b013e3181ec9b02

[34]

10.1038/sj.ki.5002567

[35]

10.1152/ajprenal.00049.2016

[36]

10.1016/j.kint.2020.02.041

[37]

10.1681/asn.2013090990

[38]

Chronic Hypoxia and Tubulointerstitial Injury

Masaomi Nangaku

Journal of the American Society of Nephrology 10.1681/asn.2005070757

[39]

10.1016/j.kint.2017.10.020

[40]

10.1093/ndt/gfy324

[41]

10.4093/dmj.2015.39.6.451

[42]

Impaired Podocyte Autophagy Exacerbates Proteinuria in Diabetic Nephropathy

Atsuko Tagawa, Mako Yasuda, Shinji Kume et al.

Diabetes 10.2337/db15-0473

[43]

10.1530/joe-14-0437

[44]

10.1172/jci44774

[45]

10.1016/j.bbrc.2009.04.136

[46]

10.1038/s41581-019-0135-6

[47]

10.1038/s41598-018-34612-3

[48]

10.1073/pnas.1603712113

[49]

10.1056/nejm199311113292004

[50]

Effects of Losartan on Renal and Cardiovascular Outcomes in Patients with Type 2 Diabetes and Nephropathy

Barry M. Brenner, Mark E. Cooper, Dick de Zeeuw et al.

New England Journal of Medicine 10.1056/nejmoa011161

Showing 50 of 117 references

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Metrics

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Citations

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References

Details

Published: Feb 17, 2021
Vol/Issue: 26(6)
Pages: 491-500
License: View

Authors

M

Mai Sugahara

Division of Nephrology and Endocrinology The University of Tokyo Graduate School of Medicine Japan

W

Wai Lun Will Pak

Renal Unit, Department of Medicine and Geriatrics United Christian Hospital Hong Kong

T

Tetsuhiro Tanaka

Division of Nephrology and Endocrinology The University of Tokyo Graduate School of Medicine Japan

S

Sydney C. W. Tang

Division of Nephrology, Department of Medicine The University of Hong Kong, Queen Mary Hospital Hong Kong

M

Masaomi Nangaku

Division of Nephrology and Endocrinology The University of Tokyo Graduate School of Medicine Japan

Cite This Article

Mai Sugahara, Wai Lun Will Pak, Tetsuhiro Tanaka, et al. (2021). Update on diagnosis, pathophysiology, and management of diabetic kidney disease. Nephrology, 26(6), 491-500. https://doi.org/10.1111/nep.13860

Update on diagnosis, pathophysiology, and management of diabetic kidney disease

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