What is the best approach for managing a patient with impaired renal function and a history of kidney disease, diabetes, or other conditions affecting kidney function?

Management of Chronic Kidney Disease in Diabetes

For patients with diabetes and impaired renal function, immediately initiate an SGLT2 inhibitor (if eGFR ≥20 mL/min/1.73 m²) combined with optimized glucose control (HbA1c <7%), blood pressure management (target <130 mmHg systolic), and ACE inhibitor or ARB therapy based on albuminuria status. 1, 2

Initial Assessment and Risk Stratification

Screen annually with both eGFR and spot urine albumin-to-creatinine ratio (UACR) in all patients with type 2 diabetes and in type 1 diabetes patients with disease duration ≥5 years. 1

• Confirm abnormal UACR results with 2 of 3 specimens collected over 3-6 months due to biological variability (>20% between measurements) 1, 2
• Calculate eGFR using serum creatinine with the CKD-EPI equation 1, 2
• Avoid UACR testing within 24 hours of exercise, during infection, fever, heart failure, marked hyperglycemia, menstruation, or marked hypertension as these falsely elevate results 1

Glucose Control Strategy

Target HbA1c <7.0% (53 mmol/mol) for most patients to reduce microvascular complications including diabetic kidney disease progression. 2

• For advanced CKD (eGFR <30 mL/min/1.73 m²) not on dialysis, individualize HbA1c targets between 6.5-8.0% due to hypoglycemia risk and shortened erythrocyte lifespan affecting HbA1c accuracy 2
• Metformin is contraindicated when eGFR <30 mL/min/1.73 m² and initiation is not recommended when eGFR is 30-45 mL/min/1.73 m² 3
• Obtain eGFR at least annually in all patients on metformin; assess more frequently in elderly patients at risk for renal impairment 3

Blood Pressure Management

Target systolic blood pressure to 130 mmHg and <130 mmHg if tolerated, but not <120 mmHg. 2

• Optimize blood pressure control and reduce blood pressure variability to slow CKD progression 1

Renin-Angiotensin System Blockade

For patients with UACR 30-299 mg/g (moderately elevated albuminuria), initiate either an ACE inhibitor or ARB. 1

For patients with UACR ≥300 mg/g (severely elevated albuminuria), strongly recommend either an ACE inhibitor or ARB. 1

• Do NOT use ACE inhibitors or ARBs for primary prevention in patients with normal blood pressure, normal UACR (<30 mg/g), and normal eGFR 1
• Never combine ACE inhibitors with ARBs simultaneously—dual renin-angiotensin system blockade increases risks of hypotension, hyperkalemia, and acute kidney injury without additional benefit 2
• Monitor serum creatinine and potassium levels periodically when using ACE inhibitors, ARBs, or diuretics 1

Critical Pitfall: Managing Creatinine Rise

Do NOT discontinue ACE inhibitor/ARB therapy for creatinine increases ≤30% above baseline in the absence of volume depletion. 1, 2, 4

• Expect an early rise in serum creatinine of approximately 25% above baseline (to ~1.7 mg/dL) after initiating ACE inhibitor/ARB therapy in patients with preexisting chronic renal insufficiency 4
• This rise occurs acutely (15% from baseline) during the first 2 weeks and more gradually (additional 10%) during weeks 3-4, then stabilizes after 4 weeks with normal salt and fluid intake 4
• This early modest creatinine rise is associated with long-term slowing of renal disease progression—discontinuing therapy eliminates nephroprotection 2, 4
• Only discontinue if creatinine rises >30% over baseline during the first 2 months or if hyperkalemia (serum potassium ≥5.6 mmol/L) develops 4

SGLT2 Inhibitor Therapy (First-Line Nephroprotective Agent)

For patients with type 2 diabetes and eGFR ≥20 mL/min/1.73 m², initiate an SGLT2 inhibitor (empagliflozin, canagliflozin, or dapagliflozin) to reduce CKD progression and cardiovascular events. 1, 2

• Use SGLT2 inhibitors regardless of albuminuria status when eGFR ≥20 mL/min/1.73 m² 1, 2
• SGLT2 inhibitors are recommended for patients with UACR ≥200 mg/g creatinine (Grade A evidence) 1
• SGLT2 inhibitors are also recommended for patients with UACR ranging from normal to 200 mg/g creatinine (Grade B evidence) 1

Additional Nephroprotective Agents

Consider adding a nonsteroidal mineralocorticoid receptor antagonist (finerenone) if eGFR ≥25 mL/min/1.73 m² in patients with albuminuria who are at increased cardiovascular risk or unable to use SGLT2 inhibitors. 1, 2

• Finerenone reduces both CKD progression and cardiovascular events 1
• Monitor potassium levels closely; finerenone requires baseline potassium ≤4.8 mmol/L 1

Consider GLP-1 receptor agonists (liraglutide or semaglutide) if eGFR >30 mL/min/1.73 m² for additional cardiovascular and renal protection. 2

Monitoring Frequency Based on Disease Severity

For eGFR ≥60 mL/min/1.73 m² with normal UACR: Monitor eGFR and UACR annually. 2

For eGFR 45-59 mL/min/1.73 m² or UACR 30-299 mg/g: Monitor every 6 months. 2

For eGFR 30-44 mL/min/1.73 m² or UACR ≥300 mg/g: Monitor every 3-4 months. 2

For eGFR <30 mL/min/1.73 m²: Monitor every 1-3 months and refer to nephrology. 1, 2

• When eGFR <60 mL/min/1.73 m², evaluate and manage potential CKD complications including anemia, secondary hyperparathyroidism, and metabolic bone disease 1

Albuminuria Reduction as Treatment Target

For patients with UACR ≥300 mg/g, aim for ≥30% reduction in UACR as this degree of reduction slows CKD progression. 1, 2

• Continue monitoring UACR to assess response to therapy and disease progression 1

Dietary Protein Restriction

For non-dialysis-dependent stage 3 or higher CKD, limit dietary protein intake to 0.8 g/kg/day based on ideal body weight. 1, 2

• Do NOT restrict protein below 0.8 g/kg/day as it does not improve glycemic measures, cardiovascular outcomes, or GFR decline 1, 2
• For patients on dialysis, increase protein intake to 1.0-1.2 g/kg/day since protein energy wasting is a major problem 1

Nephrology Referral Criteria

Refer to nephrology when eGFR <30 mL/min/1.73 m² or when there are continuously increasing UACR levels and/or continuously decreasing eGFR. 1

Promptly refer for uncertainty about kidney disease etiology, difficult management issues (anemia, secondary hyperparathyroidism, resistant hypertension, electrolyte disturbances), or rapidly progressing kidney disease. 1

• Consultation when stage 4 CKD develops (eGFR <30 mL/min/1.73 m²) reduces cost, improves quality of care, and delays dialysis 1

Special Considerations for Metformin Safety

Stop metformin at the time of or prior to iodinated contrast imaging procedures in patients with eGFR 30-60 mL/min/1.73 m², history of hepatic impairment, alcoholism, heart failure, or when intra-arterial contrast will be administered. 3

• Re-evaluate eGFR 48 hours after imaging and restart metformin only if renal function is stable 3
• Temporarily discontinue metformin during surgical procedures or when patients have restricted food and fluid intake 3
• Measure hematologic parameters annually and vitamin B12 every 2-3 years in patients on metformin 3

Key Clinical Pitfalls to Avoid

• Never discontinue renin-angiotensin system blockade for mild to moderate creatinine increases (≤30%) without evidence of volume depletion 1, 2, 4
• Never combine ACE inhibitors with ARBs—this increases harm without benefit 2
• Never withhold ACE inhibitor/ARB therapy in patients with significant albuminuria (≥300 mg/g) due to fear of creatinine rise 4
• Never delay SGLT2 inhibitor initiation in eligible patients (eGFR ≥20 mL/min/1.73 m²)—these agents provide both cardiovascular and renal protection 1, 2