Recent Updates on Diabetic Nephropathy

Youn Kyung Kee; Seung Hyeok Han

doi:10.4093/jkd.2017.18.4.214

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Kee and Han: Recent Updates on Diabetic Nephropathy

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J Korean Diabetes 2017;18(4):214-228.

Published online: 10 January 2017

DOI: https://doi.org/10.4093/jkd.2017.18.4.214

Recent Updates on Diabetic Nephropathy

Youn Kyung Kee, Seung Hyeok Han

Department of Internal Medicine, Yonsei University College of Medicine, Seoul, Korea

Corresponding author: Seung Hyeok Han Department of Internal Medicine, Yonsei University College of Medicine, 50-1 Yonsei-ro, Seodaemun-gu, Seoul 03722, Korea, E-mail: HANSH@yuhs.ac

Received 16 October 2017 Accepted 26 October 2017

This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/4.0) which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.

Abstract

Diabetic nephropathy is a common complication of diabetes mellitus and is the leading cause of chronic kidney disease. Glycemic and blood pressure control constitute the main strategies of diabetic nephropathy prevention and treatment. However, despite current therapies, nephropathy progresses to renal failure and end-stage renal disease in many patients. Therefore, new therapeutic strategies targeting different pathophysiological mechanisms are needed. This review article briefly summarizes the standard therapy for diabetic nephropathy and also describes recent advances in potential renoprotective agents that could be used to prevent the development or progression of diabetic nephropathy.

Keywords: Diabetic nephropathy, Treatment

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Table 1.

Conventional treatment of diabetic nephropathy

Treatments	Goals
Blood glucose control	•HbA1c < 7.0% (ADA), HbA1c < 6.5% (KDIGO)
Blood pressure control	•< 140/90 mmHg with albuminuria (≤ 30 mg/g Cr)
Blood pressure control	•< 130/80 mmHg with albuminuria (> 30 mg/g Cr) with increased risk of CVD and CKD progression
Use of RAAS blockers	•Not recommended for patients without albuminuria (< 30 mg/g Cr) and those with normal eGFR (≥ 60 mL/min/1.73 m²) and normal blood pressure •Recommended for patients with hypertension and albuminuria (30∼299 mg/g Cr) and strongly recommended for those with severe albuminuria (≥ 300 mg/g Cr) and/or decreased eGFR (< 60 mL/min/1.73 m²)
Treatment of dyslipidemia	•Treatment with statins is recommended for all DN patients
Smoking cessation	•Recommended for all DN patients
Diet control	•Diet salt restriction to less than 5∼6 g/d •Diet protein restriction to 0.6∼0.8 g/kg/d in CKD 3 and 4
Treatment of metabolic acidosis	•Administer sodium bicarbonate (maintaining serum tCO2 at 22∼24 mEq/L)
Others	•Treatment of hyperuricemia •Management of hyperphosphatemia •Pentoxifylline •Vitam in D receptor agonists

ADA, American Diabetes Association; KDIGO, Kidney Disease Improving Global Outcomes guideline; Cr, creatinine; CVD, cardiovascular disease; CKD, chronic kidney disease; RAAS, renin-angiotensin-aldosterone system; eGFR, estimated glomerular filtration rate; DN, diabetic nephropathy.

Table 2.

Potential drugs for diabetic nephropathy under clinical trials

Drug	Target actions	Study type and status	Populatio (n)	on Duration	Results
Pirfenidone	Anti-fibrotic and antiinflammatory action	Randomized controlled phase-II study, completed	77	6 months	Improved eGFR
Pyridoxine	Inhibition of the formation of AGEs	Randomized controlled phase-III study, terminated	Terminated due to funding constraint		No results available
Bardoxolone	Inhibition of the proinflammatory factor, NF-κB	Randomized controlled phase-III study, terminated	Terminated due to increased risk of cardiovascular deaths and event		Improved eGFR and BP Reduction of albuminuria
GS-4997	Inhibition of the apoptosis signal-regulating kinase 1	Randomized controlled phase-II study, completed	334	48 weeks	No results available
CCX 140-B	Selective inhibition of the chemokine receptor 2	Randomized controlled phase-II study, completed	332	52 weeks	Reduction of albuminuria Decelerated eGFR decline
Bindarit	Inhibition of the activation of NF-κB	Randomized controlled phase-II study, completed	100	12 weeks	No results available
Colchicine	Anti-fibrotic and anti-inflammatory action	Randomized controlled phase-II study, ongoing	–		–
Baricitinib	Inhibition of JAK pathway	Randomized controlled phase-II study, completed	129	6 months	Reduction of albuminuria and inflammation markers without affecting renal function
Ruboxistaurin	Protein kinase C inhibitor	Randomized controlled phase-II study, completed	123	12 months	Reduction of albuminuria without affecting renal function
GLY-230	Inhibition of the glycosylation of plasmatic albumin	Randomized controlled phase-II study, completed	21	14 days	Reduction of albuminuria
Atrasentan	Inhibition of endothelin A receptor	Randomized controlled phase-II study, completed	211	12 weeks	Reduction of albuminuria without affecting renal function Fluid retention (weight gain and reduction in hemoglobin)

eGFR, estimated glomerular filtration rate; AGEs, advanced glycation end products; NF-κB, nuclear factor kappa B; BP, blood pressure.

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