What are the primary kidney protective agents in diabetes?

Kidney Protective Agents in Diabetes

SGLT2 inhibitors are the primary kidney protective agents for patients with type 2 diabetes and chronic kidney disease, recommended as first-line therapy for patients with eGFR ≥20 mL/min/1.73 m². 1

Primary Kidney Protection: SGLT2 Inhibitors

SGLT2 inhibitors should be initiated for all diabetic patients with CKD regardless of glucose control needs, as their kidney protective effects operate independently of glycemic management. 1

Key benefits include:

• Reduce incident or worsening nephropathy by 39% 1
• Reduce risk of doubling serum creatinine by 44% compared to placebo 1
• Decrease oxidative stress in the kidney by >50%, reduce intraglomerular pressure, decrease albuminuria, and slow GFR loss through non-glycemic mechanisms 1
• Can be initiated and continued down to eGFR ≥20 mL/min/1.73 m², expanding use to advanced CKD stages 1

Specific agents with proven efficacy include empagliflozin and canagliflozin. 1

Secondary Kidney Protection: RAS Blockade

ACE Inhibitors or ARBs

ACE inhibitors or ARBs are recommended for all patients with albuminuria ≥30 mg/24h and should be titrated to maximum tolerated doses. 1

The treatment algorithm based on albuminuria level:

For albuminuria 30-299 mg/24h (with hypertension):

• Either ACE inhibitors or ARBs reduce progression to higher albuminuria levels and slow CKD progression 1

For albuminuria ≥300 mg/24h:

• ACE inhibitors or ARBs are first-line therapy 1
• Reduce progression to end-stage kidney disease in both type 1 and type 2 diabetes 1

Critical monitoring requirements:

• Check serum creatinine and potassium within 2-4 weeks of initiation or dose changes 1
• Continue therapy even if creatinine increases up to 30% without hyperkalemia, as this reflects hemodynamic changes rather than kidney injury 1

Important caveat: Combination therapy with ACE inhibitor plus ARB is NOT recommended, as it increases adverse events (hyperkalemia, acute kidney injury) without additional clinical benefit. 2

Tertiary Kidney Protection: Additional Agents

Finerenone (Nonsteroidal MRA)

• Add finerenone to RAS blockade when additional protection is needed 1
• Reduces both CKD progression and cardiovascular events 1

GLP-1 Receptor Agonists

• Use when cardiovascular risk is the predominant concern 1
• Reduce CVD events and may slow CKD progression 1
• Safe across all stages of renal impairment 3

Essential Supportive Measures

Blood pressure control:

• Target <130/80 mmHg for all diabetic patients to reduce CVD mortality and slow CKD progression 1

Glucose control:

• Intensive glucose control to achieve near-normoglycemia delays onset and progression of albuminuria 1

Lifestyle modifications:

• Smoking cessation strongly recommended 1
• Weight loss reduces albuminuria 1
• Dietary sodium restriction to <2,300 mg/day 1

Common Pitfalls to Avoid

• Do not discontinue ACE inhibitors/ARBs for creatinine increases <30% without hyperkalemia—this is expected hemodynamic effect 1
• Do not combine ACE inhibitor with ARB—increases harm without benefit 2
• Do not withhold SGLT2 inhibitors based solely on glucose levels—their kidney protection is independent of glycemic control 1
• Do not stop SGLT2 inhibitors until eGFR falls below 20 mL/min/1.73 m²—newer guidelines expanded their use to advanced CKD 1