What is the recommended diagnostic and therapeutic approach for diabetic nephropathy in a patient with type 1 or type 2 diabetes?

Diabetic Nephropathy: Diagnostic and Therapeutic Approach

Screening Protocol

Begin annual screening for diabetic nephropathy 5 years after diagnosis in type 1 diabetes and immediately at diagnosis in type 2 diabetes using spot urine albumin-to-creatinine ratio (UACR) and estimated glomerular filtration rate (eGFR). 1

Required Laboratory Tests

• Spot urine albumin-to-creatinine ratio (UACR): Use first morning void to minimize diurnal variation and orthostatic effects 1
• Serum creatinine with eGFR calculation: Use the 2021 CKD-EPI equation without race 1
• Do not rely on standard hospital protein assays as they lack sensitivity for microalbuminuria detection 2

Diagnostic Thresholds

UACR categories 1:

• Normal: <30 mg/g creatinine
• Moderately increased albuminuria (microalbuminuria): 30-299 mg/g creatinine
• Severely increased albuminuria (macroalbuminuria): ≥300 mg/g creatinine

eGFR categories 1:

• Normal or high: ≥90 mL/min/1.73 m²
• Mildly decreased: 60-89 mL/min/1.73 m²
• Moderately decreased: 30-59 mL/min/1.73 m²
• Severely decreased: 15-29 mL/min/1.73 m²
• Kidney failure: <15 mL/min/1.73 m²

Confirmation Requirements

Obtain 2 out of 3 abnormal specimens over a 3-6 month period before diagnosing diabetic nephropathy due to 40-50% day-to-day variability in albumin excretion 3, 1

Exclude transient causes before repeat testing 3, 1:

• Exercise within 24 hours
• Acute infection or fever
• Congestive heart failure
• Marked hyperglycemia
• Urinary tract infection
• Marked hypertension

Treatment Algorithm

Stage 1: Microalbuminuria (UACR 30-299 mg/g)

Initiate ACE inhibitor or ARB therapy immediately, even if normotensive, to prevent progression to macroalbuminuria 3

• Type 1 diabetes with hypertension and any albuminuria: ACE inhibitors delay nephropathy progression 4
• Type 2 diabetes with hypertension and microalbuminuria: Both ACE inhibitors and ARBs delay progression to macroalbuminuria 4
• Target blood pressure: ≤130/80 mmHg 3
• Titrate to maximum approved dose for greater antiproteinuric effect 2
• If one class is not tolerated, substitute the other 4

Stage 2: Macroalbuminuria (UACR ≥300 mg/g)

For type 2 diabetes with macroalbuminuria and renal insufficiency (serum creatinine >1.5 mg/dL), ARBs are specifically proven to delay nephropathy progression 4, 5

• The RENAAL study demonstrated losartan reduced the composite endpoint of doubling serum creatinine, ESRD, or death by 16% (p=0.022), reduced doubling of serum creatinine by 25% (p=0.006), and reduced ESRD by 29% (p=0.002) 5
• Continue blood pressure target ≤130/80 mmHg 3

Glycemic Control

Target HbA1c <7% through intensive diabetes management to delay onset and slow progression of nephropathy 4, 3

Additional Renoprotective Measures

• Protein restriction: 0.8 g/kg body weight/day in early chronic kidney disease stages 4, 3
• SGLT2 inhibitors: Add as first-line therapy for renoprotection 2
• GLP-1 receptor agonists: Consider for cardiovascular and kidney protection 2
• Lipid control, smoking cessation, dietary salt restriction, weight reduction, and increased physical activity 6

Monitoring Frequency

Adjust monitoring based on disease severity 1:

• Low-risk (eGFR ≥60, UACR <30): Annual monitoring
• Moderate-risk (eGFR 45-59 or UACR 30-299): Monitor 2-4 times per year
• High-risk (eGFR <45 or UACR ≥300): Monitor 3-4 times per year

Measure serum creatinine and calculate eGFR at least every 3-4 months in patients with established nephropathy 3

Nephrology Referral Thresholds

Refer to nephrology when eGFR falls below 60 mL/min/1.73 m² or if difficulties managing hypertension or hyperkalemia occur 4, 3

Urgent referral when eGFR <30 mL/min/1.73 m² as early referral reduces cost, improves quality of care, and delays dialysis 4, 3

Critical Prognostic Information

• Without intervention, 80% of type 1 diabetes patients with microalbuminuria progress to overt nephropathy over 10-15 years 2
• Without intervention, 20-40% of type 2 diabetes patients with microalbuminuria progress to overt nephropathy 2
• 10-year all-cause mortality increases from 11.5% in diabetes without kidney disease to 31% with diabetic kidney disease 2
• Albuminuria indicates greatly increased cardiovascular morbidity and mortality, not just kidney disease 2