What is the recommended approach for diagnosing and managing diabetic nephropathy, including targets for glycemic control, blood pressure, albuminuria, medication selection, and monitoring?

Diabetic Nephropathy: Diagnosis and Management

The cornerstone of diabetic nephropathy management is annual screening for microalbuminuria starting at diagnosis in type 2 diabetes (or after 5 years in type 1 diabetes), combined with aggressive optimization of both glycemic control (HbA1c <7%) and blood pressure control, with ACE inhibitors or ARBs as first-line agents when albuminuria is present. 1

Screening and Diagnosis

Who to Screen and When

• Type 1 diabetes: Begin annual microalbuminuria screening after 5 years of disease duration 1
• Type 2 diabetes: Begin annual microalbuminuria screening immediately at diagnosis 1
• Measure serum creatinine at least annually in all adults with diabetes to estimate GFR and stage chronic kidney disease 1

How to Screen

• Use a spot urine albumin-to-creatinine ratio as the preferred method—this is more practical than 24-hour or timed collections 1, 2
• Confirm abnormal results with 2 out of 3 specimens collected over 3-6 months, as transient elevations occur with exercise, infection, fever, marked hyperglycemia, or uncontrolled hypertension 1, 2

Albuminuria Categories

• Normal: <30 mg/g creatinine 1
• Microalbuminuria: 30-299 mg/g creatinine 1
• Macroalbuminuria (overt nephropathy): ≥300 mg/g creatinine 1

Glycemic Control Targets

Target HbA1c <7% (53 mmol/mol) to reduce the risk and slow progression of nephropathy. 1, 2 This represents A-level evidence from landmark trials including UKPDS 33, which demonstrated that intensive glucose control reduces microvascular complications 1

Blood Pressure Management

Blood Pressure Targets

• Standard target: <140/90 mmHg for most patients with diabetic nephropathy 1, 3
• More intensive target: Systolic <130 mmHg (but never <120 mmHg) if tolerated, particularly in those with additional cardiovascular risk 2, 3
• Optimizing blood pressure control represents A-level evidence for slowing nephropathy progression 1

Medication Selection Algorithm

First-line agents when albuminuria is present:

For Type 1 Diabetes

• ACE inhibitors are first-line for hypertensive and normotensive patients with any degree of albuminuria, as they delay nephropathy progression 1

For Type 2 Diabetes

• ACE inhibitors or ARBs for hypertensive patients with microalbuminuria—both delay progression to macroalbuminuria 1
• ARBs have specific A-level evidence in type 2 diabetes with hypertension, macroalbuminuria, and renal insufficiency (serum creatinine >1.5 mg/dl) 1
• If one class is not tolerated, substitute the other 1

Newer Agents (Based on Most Recent Evidence)

• SGLT2 inhibitors (empagliflozin, canagliflozin, or dapagliflozin) should be initiated immediately in patients with diabetic hyperfiltration (eGFR >120 mL/min/1.73 m²) or when eGFR is 30-90 mL/min/1.73 m² with albuminuria, as they reduce progression of kidney disease and cardiovascular events 2, 3
• GLP-1 receptor agonists (liraglutide or semaglutide) provide additional cardiovascular and renal protection at eGFR >30 mL/min/1.73 m² 2

Alternative Agents

• Non-dihydropyridine calcium channel blockers, β-blockers, or diuretics can be used in patients unable to tolerate ACE inhibitors or ARBs 1
• Dihydropyridine calcium channel blockers are less effective than ACE inhibitors/ARBs for slowing nephropathy and should be restricted to additional therapy, not initial monotherapy 1

Monitoring Requirements

Monitoring Potassium and Creatinine

• Monitor serum potassium and creatinine when using ACE inhibitors, ARBs, or diuretics to detect hyperkalemia and acute changes in renal function 1
• Do not discontinue ACE inhibitors/ARBs for modest creatinine increases (<30%) without evidence of volume depletion—this represents expected hemodynamic changes 2

Surveillance Schedule Based on Disease Stage

• Normal albuminuria with hyperfiltration: Re-evaluate eGFR and albumin-to-creatinine ratio every 6 months 2
• Microalbuminuria (30-299 mg/g): Re-evaluate every 6 months 2
• Macroalbuminuria (≥300 mg/g): Re-evaluate every 3-4 months 2
• Stage 2 CKD (GFR 60-89): Annual creatinine/eGFR and at least yearly urine albumin-to-creatinine ratio 3
• All patients: Yearly measurement of creatinine, urinary albumin excretion, and potassium 1

Dietary Protein Restriction

Limit protein intake to 0.8 g/kg/day (based on ideal body weight) once overt nephropathy develops. 1, 2 This represents the adult Recommended Dietary Allowance and approximately 10% of daily calories 1

• Further restriction to 0.6 g/kg/day may be useful in selected patients once GFR begins to decline, though nutritional deficiency and muscle weakness are risks 1
• Protein-restricted meal plans should be designed by a registered dietitian familiar with diabetes management 1
• Do not reduce protein below 0.8 g/kg/day routinely, as this does not improve glycemic measures, cardiovascular outcomes, or GFR decline 2

Nephrology Referral Criteria

Refer to a nephrologist when:

• eGFR falls to <60 mL/min/1.73 m² (some guidelines suggest <80 mL/min/1.73 m²) 1
• eGFR <30 mL/min/1.73 m² (mandatory referral) 1, 3
• Uncertainty about the etiology of kidney disease (heavy proteinuria, active urine sediment, absence of retinopathy, rapid GFR decline) 1, 3
• Difficulties managing hypertension or hyperkalemia 1
• Rapid GFR decline (>5 mL/min/1.73 m²/year) 3
• Type 1 diabetes duration <10 years with persistent albuminuria (suggests non-diabetic kidney disease) 1

Early referral reduces cost, improves quality of care, and delays dialysis 1

Additional Management Considerations

Other Complications of Progressive Renal Disease

• Implement sodium and phosphate restriction and use phosphate binders when indicated for complications like osteodystrophy 1
• Monitor electrolytes, bicarbonate, hemoglobin, calcium, phosphorus, and parathyroid hormone at appropriate intervals based on GFR stage 1
• Ensure vitamin D sufficiency and consider bone density testing when eGFR 45-60 mL/min/1.73 m² 1

Contrast Media Precautions

• Radiocontrast media are particularly nephrotoxic in diabetic nephropathy 1
• Carefully hydrate azotemic patients before any contrast procedures that cannot be avoided 1

Critical Pitfalls to Avoid

• Never delay ACE inhibitor/ARB therapy in patients with albuminuria waiting for blood pressure to rise—these agents provide nephroprotection independent of blood pressure effects 1
• Do not combine ACE inhibitors and ARBs—dual renin-angiotensin-aldosterone system blockade has demonstrated harm 4
• Target ≥30% reduction in albumin-to-creatinine ratio as a therapeutic goal when albuminuria ≥300 mg/g is present, as this degree of reduction slows CKD progression 2
• Monitor closely for hyperkalemia in older patients and those with advanced renal insufficiency when using ACE inhibitors or ARBs 1