What is the recommended treatment for a patient with diabetes who has persistent albuminuria (≥30 mg/g creatinine) and an estimated glomerular filtration rate below 60 mL/min/1.73 m² consistent with diabetic nephropathy?

Treatment of Diabetic Nephropathy with Persistent Albuminuria and Reduced eGFR

For a patient with diabetes, persistent albuminuria ≥30 mg/g creatinine, and eGFR <60 mL/min/1.73 m², you must initiate an ACE inhibitor or ARB immediately, add an SGLT2 inhibitor if eGFR ≥30 mL/min/1.73 m² (especially if albuminuria ≥300 mg/g), optimize glucose control to HbA1c <7% for most patients, and target blood pressure <130/80 mmHg. 1

Immediate Pharmacologic Interventions

Renin-Angiotensin System Blockade (First-Line, Mandatory)

• Start an ACE inhibitor or ARB immediately for all patients with eGFR <60 mL/min/1.73 m² and/or albuminuria ≥30 mg/g creatinine, regardless of blood pressure level. 1, 2
• This recommendation is strongly supported (Grade A evidence) when albuminuria is ≥300 mg/g and eGFR <60 mL/min/1.73 m². 1, 2
• For moderately increased albuminuria (30-299 mg/g), ACE inhibitor or ARB carries Grade B evidence but is still recommended. 1, 2
• Do not discontinue the ACE inhibitor/ARB if serum creatinine increases by <30% in the absence of volume depletion—this represents beneficial hemodynamic changes, not kidney injury. 1, 2

SGLT2 Inhibitor (Second-Line, Strongly Recommended)

• Add an SGLT2 inhibitor with proven kidney or cardiovascular benefit if eGFR ≥30 mL/min/1.73 m² and albuminuria >300 mg/g creatinine (Grade A evidence). 1
• The 2022 ADA/KDIGO consensus strongly recommends SGLT2 inhibitors for patients with T2D, CKD, and eGFR ≥20 mL/min/1.73 m²—once initiated, continue even as eGFR declines below 30. 1
• SGLT2 inhibitors provide additional cardiovascular risk reduction when eGFR and albuminuria are >30 mL/min/1.73 m² or >300 mg/g, respectively. 1

GLP-1 Receptor Agonist (Third-Line)

• Consider adding a GLP-1 receptor agonist with proven cardiovascular benefit if the patient does not meet individualized glycemic targets with metformin and/or SGLT2 inhibitor, or cannot use these medications. 1
• GLP-1 receptor agonists reduce renal endpoints (primarily albuminuria progression) and cardiovascular events in patients with CKD at increased cardiovascular risk. 1

Nonsteroidal Mineralocorticoid Receptor Antagonist (Emerging Therapy)

• Add a nonsteroidal MRA if eGFR ≥25 mL/min/1.73 m², normal serum potassium, and albuminuria (ACR ≥30 mg/g) for additional kidney and cardiovascular benefit. 1

Glycemic Control Optimization

• Target HbA1c <7% for most patients to reduce risk and slow progression of diabetic kidney disease (Grade A evidence). 1, 3
• Intensive diabetes management delays onset of microalbuminuria and progression from micro- to macroalbuminuria. 1
• Adjust glycemic targets based on individual patient factors including hypoglycemia risk, life expectancy, and comorbidities. 1

Blood Pressure Management

• Target blood pressure <130/80 mmHg for patients with diabetes and CKD, particularly when albuminuria is present. 1, 3
• Blood pressure optimization is Grade A evidence for reducing risk and slowing CKD progression. 1
• Most patients will require 2 or more antihypertensive agents to achieve target. 3
• The ACE inhibitor or ARB serves dual purposes: renoprotection and blood pressure control. 1, 2

Dietary Protein Restriction

• Limit dietary protein intake to approximately 0.8 g/kg body weight per day (the recommended daily allowance) for non-dialysis-dependent CKD. 1, 2
• Higher protein intake should be considered only for patients on dialysis due to malnutrition risk. 1, 2

Monitoring Strategy

Initial Monitoring After Starting ACE Inhibitor/ARB

• Check serum creatinine and potassium within 2-4 weeks of initiating or titrating ACE inhibitor/ARB therapy. 1, 4
• Accept up to 30% increase in creatinine as expected hemodynamic effect. 1, 2, 4

Ongoing Surveillance

• Monitor UACR and eGFR every 6 months (twice annually) for patients with albuminuria >30 mg/g and/or eGFR <60 mL/min/1.73 m². 1, 3
• Some experts recommend monitoring every 3-4 months if established diabetic kidney disease with declining function. 3
• Monitor serum creatinine and potassium periodically when using ACE inhibitors, ARBs, or diuretics. 1

Nephrology Referral Criteria

• Refer to nephrology when eGFR falls to <30 mL/min/1.73 m² for consideration of renal replacement therapy planning. 1, 2
• Consider earlier referral (eGFR <60 mL/min/1.73 m²) if difficulties occur in managing hypertension or hyperkalemia. 1
• Early referral reduces cost, improves quality of care, and delays dialysis initiation. 1

Critical Pitfalls to Avoid

• Do not wait for blood pressure elevation before starting ACE inhibitor/ARB—the presence of albuminuria mandates therapy regardless of blood pressure. 2, 4
• Do not discontinue ACE inhibitor/ARB for creatinine increases <30% unless volume depletion is present. 1, 2
• Do not use ACE inhibitors or ARBs for primary prevention in patients with normal blood pressure, normal UACR (<30 mg/g), and normal eGFR—they are not indicated. 2
• Confirm persistent albuminuria—two of three specimens collected within 3-6 months should be abnormal before confirming diagnosis, as exercise, infection, fever, heart failure, marked hyperglycemia, menstruation, and marked hypertension can temporarily elevate UACR. 1, 2, 3
• Avoid NSAIDs in patients with any degree of kidney dysfunction, as they accelerate CKD progression. 3
• Avoid therapeutic inertia—most patients with diabetes and CKD require multiple interventions simultaneously to optimize outcomes. 1

Evidence Strength Considerations

The strongest evidence comes from the 2022 ADA/KDIGO consensus report 1 and 2021 ADA Standards of Care 1, which represent the most recent and comprehensive guidelines. The addition of SGLT2 inhibitors represents a major advancement since earlier guidelines 1, with robust evidence for kidney and cardiovascular protection. The synergistic relationship between reduced eGFR and albuminuria creates exponentially higher risk—patients with both eGFR <30 mL/min/1.73 m² and macroalbuminuria have >1,000-fold higher risk of ESRD progression compared to those with normal parameters. 5