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