Dr. Matthew Becker

Mentor: Dr. Manish Suneja

Evidence-Based Management of Diabetic Kidney Disease

I. Objectives

A) Discuss the screening and diagnosis of diabetic kidney disease (DKD)

B) Review the physiologic progression of diabetes

C) Discuss evidence-based management – glycemic control, blood pressure control, and the RAAS system

D) When to consult nephrology

II. Screening and diagnosing DKD

A) Definition

i) Urine albumin to creatinine ratio (UACR) > 30mg/g.

ii) GFR < 60mL/min/1.733m^2

B) Screening and diagnosis

i) Yearly assessment of GFR and albuminuria via spot UACR

ii) If albuminuria present, confirmatory test within 6 months

iii) Microalbuminuria – 30mg/g < UACR < 300mg/g

iv) Macroalbuminuria – UACR > 300mg/g

II. Physiologic progression of type 2 diabetes

i) Approximately 25% of patients develop microalbuminuria within 10 years

ii) Approximately 5% of patients develop macroalbuminuria within 10 years

iii) All-cause mortality increases as DKD progresses – CV causes are most common

III. Evidence-based management of DKD

A) Glycemic Control

i) The Diabetes Control and Complications Trial (1993): tighter glycemic control (A1C < 6.0%) lead to 39% decrease rate of microalbuminuria and 54% decrease rate in macroalbuminuria over 6.5 year follow up in Type one diabetics.

ii) ADVANCE (2008) and VADT (2009) Trials: no elevated CVD risk in patients with strict glycemic control.

a. INCREASED risk hypoglycemia without cardiovascular benefit.

iii) Goal A1C: <7.0 for type 1 diabetics, same for type 2 but less evidence

B) Metformin

i) No effect on preventing DKD; confers glycemic and mortality benefits

ii) May initiate with GFR >45, may continue with GFR between 30-45.

C) SGLT2 Inhibitors

i) Now standard of care (along with RAAS inhibitors) for patients with:

a. Type 2 diabetes, mild to moderate CKD, UACR > 300mg/g

ii) Watch out for urinary tract infections, increased risk of DKA

D) GLP-1 Agonists

i) 2nd line compared to SGLT2 inhibitors; decrease risk of new macroalbuminuria. Also decrease in incidents of GFR reduction, decreased risk of kidney failure

E) Blood Pressure Control

i) Current guidelines – target BP 130/80

ii) 1st line Tx – ACE/ARB. 2nd/3rd line – diuretic + CCB. 4th line – Spironolactone

F) RAAS Inhibition

i) 30% rise in serum creatinine expected after starting. Check K+ and creatinine within 2 weeks

ii) Indications – Diabetic patients who are normotensive with UACR > 30mg/g and risk of progression of DKD

IV. When to consult nephrology

i) When GFR < 30

ii) When the cause of CKD is in doubt

iii) When there are management challenges – resistant HTN, rapidly declining GFR

V. Take-away Points

i) Diabetes is the most common cause of chronic kidney disease.

ii) DKD is characterized by worsening kidney function, albuminuria, and increase in all-cause mortality and cardiovascular disease.

iii) Effective management of diabetic kidney disease includes glycemic control, BP control and blockade of RAAS.

iv) SGLT2 inhibitors and to a lesser extent GLP-1 agonists are appropriate for treating diabetics with chronic kidney disease, as well as non-diabetics with kidney disease.

Works Cited

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Advance Collaborative Group. Intensive Blood Glucose Control and Vascular Outcomes in Patients with Type 2 Diabetes. N Engl J Med 2008;358(24):2560–72.

Alicic RZ, Rooney MT, Tuttle KR. Diabetic Kidney Disease: Challenges, Progress, and Possibilities. Clin J Am Soc Nephrol. 2017 Dec 7;12(12):2032-2045. doi: 10.2215/CJN.11491116. Epub 2017 May 18.

American Diabetes Association. Standards of Medical Care in Diabetes—2019 Abridged for Primary Care Providers. Clin Diabetes 2019;37(1):11–34.

Bonner R, Albajrami O, Hudspeth J, Upadhyay A. Diabetic Kidney Disease. Prim Care. 2020 Dec;47(4):645-659. doi: 10.1016/j.pop.2020.08.004. Epub 2020 Sep 23.

Duckworth W, Abraira C, Moritz T, et al. Glucose control and vascular complications in veterans with type 2 diabetes. N Engl J Med 2009;360(2):129–39.

Erik J.M. van Bommel, Marcel H.A. Muskiet, Lennart Tonneijck, Mark H.H. Kramer, Max Nieuwdorp and Daniel H. van Raalte CJASN April 2017, 12 (4) 700-710.

Perkovic V, Jardine MJ, Neal B, et al. Canagliflozin and renal outcomes in type 2 diabetes and nephropathy. N Engl J Med 2019;380(24):2295–306.

The ACCORD Study Group. Effects of Intensive Glucose Lowering in Type 2 Diabetes. N Engl J Med 2008;358(24):2545–59.

The DCCT Research Group. The Effect of Intensive Treatment of Diabetes on theDevelopment and Progression of Long-Term Complications in Insulin-Dependent Diabetes Mellitus. N Engl J Med 1993;329(14):977–86.

Ussher, John & Drucker, Daniel. (2012). Cardiovascular Biology of the Incretin System. Endocrine reviews. 33. 187-215. 10.1210/er.2011-1052.

Wright JT, Williamson JD, Whelton PK, et al. A randomized trial of intensive versus standard blood-pressure control. N Engl J Med 2015;373(22):2103–16.