Diabetes Management in Patients with CKD
SUMMARY:
Diabetes is a major risk factor for the development of CKD, with an estimated 40% of people with diabetes developing CKD during their lifetimes. Patients with both conditions are at increased risk of cardiovascular events, kidney disease progression, and increased mortality. Optimal management of diabetes in CKD is crucial to prevent or delay the development of CKD complications. The ADA and KDIGO have published a consensus guideline in 2022 on the treatment of diabetes in patients with kidney disease to assist with improving care.
- Screening and Diagnosis
- Treatment
- Glycemic Agents
- Adjunctive Therapy
- Lifestyle Changes
- Blood Pressure Management
- Lipid Management
- Follow-Up
Screening and Diagnosis
- CKD is defined as
- eGFR <60 mL/min/1.73 m2 | Albuminuria (ACR ≥ 30 mg/g) | Other evidence kidney damage (e.g., hematuria or structural abnormalities)
- Abnormalities must be persistent for or at least 3 months
- Screening for CKD should be done in all patients with diabetes
- Type 1 diabetes: Screen for CKD at least 5 years after diagnosis, then annually
- Type 2 diabetes: Screen for CKD at diagnosis, then annually
- Urine tests: Annual screening for albuminuria
- Spot urine albumin-to-creatinine ratio (ACR): Early morning spot testing is ideal and positive results should be confirmed with repeat testing in 3 to 6 months
- 24-hour urine collection
- Blood tests: At least annual assessment of GFR
- Serum creatinine
- Cystatin C: When used to calculate eGFR increases precision and reduces racial and
ethnic bias found in eGFR calculations
- Consider a cause of CKD other than DM if
- Patient has other systemic diseases that can lead to CKD (e.g., kidney stones, vasculitis)
- If patient lacks concomitant retinopathy
- Red flags such as: Glomerular hematuria | Large and abrupt changes in eGFR or albuminuria | Abnormal serology tests
Treatment
- Pharmacologic therapy should be individualized based on each patient’s: Comorbidities | Medication tolerability | Kidney function
- Adjunctive treatment focuses on lifestyle changes and reducing CV risk with blood pressure and lipid management
- When possible, patients should be treated in a multidisciplinary healthcare setting including:
- Diabetes education specialists | Nephrologists | Primary care providers | Dietitians | Exercise specialists | Pharmacists | Dentists | Podiatrists | Mental health professionals
Glycemic Agents
- KDIGO recommends an individualized HbA1c target of <6.5% to <8.0% for patients with diabetes and CKD
- ADA recommends target of <7% in most non-pregnant adult patients with diabetes
- Higher goals of <8% is acceptable for patients with limited life expectancy or where risks outweigh benefits of stricter control
- Metformin
- Preferred first-line agent for glycemic control in most patients with CKD and DM2, except in those with eGFR < 30 mL/min/1.73 m2
- Dose should be reduced to 1,000mg daily for eGFR 30 to 44 mL/min/1.73 m2 and in some patients with eGFR 45 to 59 mL/min/1.73 m2 who are at high risk of lactic
acidosis (e.g., patients >65 years old|excessive alcohol intake|hepatic impairment) - Available in immediate and extended-release formulations
- Dose should be increased slowly to minimize GI side effects
- Can cause vitamin B12 deficiency and patients should be monitored for vitamin B 12 deficiency when treated with metformin for >4 years
- Insulin therapy or non-insulin glucose-lowering medications may be used in patients with advanced CKD or those who cannot tolerate metformin or fail to meet their glycemic goals. Appropriate dose adjustment based on eGFR is important for medications that increase risk of side effects with low eGFR or undergo elimination through the kidney. When needed, careful use and titration of insulin and sulfonylurea agents is recommended to avoid hypoglycemia (see Learn More – Primary Sources for dosages)
- Sodium-glucose cotransporter-2 inhibitors (SGLT2i)
- Includes: Dapagliflozin (Farxiga) | Canagliflozin (Invokana)
- Have been shown to reduce cardiovascular events and kidney disease progression in patients with DM2 and CKD
- Recommended for eGFR > 20 mL/min/1.73 m2, but once initiated may be continued if eGFR falls below this
- Associated with an increased risk of genital mycotic infections and genital hygiene practices should be reviewed with patient
- Can cause DKA and patients should be educated on early signs and symptoms
- Glucagon-like peptide-1 receptor agonists (GLP-1 RA)
- Includes: Semaglutide (Ozempic) | Liarglutide (Victoza)
- Recommended for patients with DM2 and CKD who do not meet their glycemic target with metformin and/or an SGLT2i (or who are unable to use these drugs)
- Can assist with weight loss in addition to reducing CV risk
- Dose should be increased slowly to minimize GI side effects
- Nonsteroidal mineralocorticoid receptor antagonist (ns-MRA)
- Includes: Finerenone (Kerendia)
- Recommended for: eGFR > 25 mL/min/1.73 m2 |Normal serum potassium | Albuminuria and HTN despite maximum tolerated dose of renin-angiotensin system (RAS) inhibitor
- Has proven kidney and cardiovascular benefits
Adjunctive Therapy
- For patients with diabetes and CKD the focus is on risk reduction of CKD progression and cardiovascular events by focusing on: Blood pressure control | Kidney protective medications | Lifestyle interventions | Lipid management
Lifestyle changes
- Smoking cessation
- Regular exercise
- Recommend moderate to intense/vigorous physical activity with a cumulative duration of ≥ 150 min/week
- Weight loss for overweight and obese patients
- Glucagon-like peptide-1 receptor agonists (GLP-1 RA) can assist with this for patients who qualify
- Optimizing nutrition
- Diets high in vegetables, fruits, and whole grains
- Diets low in refined carbohydrates and sugar-sweetened beverages
- Target a dietary protein intake of 0.8 g/kg/day
- Patients benefit from diet education with dietitians and diabetes specialists
Blood Pressure Management
- ADA recommends BP goal of
- <130/80 mmHg for patients with HTN, DM and HIGH CV risk (e.g., 10-year ASCVD risk ≥15%)
- <140/90 mmHg for patients with HTN, DM and LOW CV risk (e.g., 10-year ASCVD risk <15%)
- Angiotensin-converting enzyme inhibitors (ACEi) or angiotensin II receptor blockers (ARB) are the preferred agents for DM1/2 with CKD
- For use in patients with diabetes and concomitant hypertension and proteinuria
- Should be used to reduce proteinuria and slow the progression of kidney disease
- Titrate to max tolerated dose
- In patients with DM who are unable to reach their BP targets on ACEi/ARB alone can add:
- Dihydropyridine CCB (e.g., Amlodipine (Norvasc) | Diuretics (e.g., Hydrochlorothiazide) | ns-MRA (e.g., Finerenone (Kerendia))
Lipid Management
- Statins
- For DM1 and DM2 patients with CKD
- Moderate intensity dosing (e.g., Simvastatin 20 to 40mg daily) for primary prevention
- High intensity for patients with known ASCVD or some patients with multiple ASCVD risk factors (e.g., Atorvastatin 40 to 80mg daily)
- Lipids may also be managed with non-statin therapies (e.g., Ezetimibe, PCSK9i) if indicated based on ASCVD risk and lipid panel
Follow-up
- Patients with CKD and diabetes should be monitored at least every 3 to 6 months with repeat assessment of eGFR, blood sugar levels, and risk factor assessments
- Annually check: Comprehensive foot examination | Dilated eye examination | Lipid profile
- Serum potassium and estimated GFR should be monitored closely in patients taking RAASi
- In patients taking SGLT2i, monitoring for eGFR decline and volume depletion is recommended
KEY POINTS:
- Annual screening for albuminuria and assessment of GFR are recommended in patients with CKD and diabetes
- Metformin is the preferred first-line agent for glycemic control in most patients with CKD, except in those with a GFR < 30 mL/min/1.73 m2
- Blood pressure should be controlled to <130/80 mmHg using RAASi unless contraindicated
- SGLT2i, GLP-1 RA, and ns-MRA are used for risk reduction in cardiovascular and kidney disease outcomes
- Regular monitoring and comprehensive care are essential for optimal management of CKD and diabetes
Primary Sources – Learn More
Medication Dose Adjustments for eGFR< 45 mL/min/1.73 m2
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