What are the causes of albuminuria (presence of albumin in the urine) in an adult patient with a history of hypertension, diabetes, or other cardiovascular risk factors, and normal range urea and creatinine levels, indicating normal kidney function?

Causes of Albuminuria with Normal Urea and Creatinine

Albuminuria with normal urea and creatinine represents early kidney damage or systemic vascular disease before significant loss of glomerular filtration rate occurs, most commonly caused by diabetes, hypertension, or cardiovascular disease. 1, 2

Primary Causes

Diabetic Kidney Disease

• Diabetes is the leading cause of albuminuria with preserved kidney function, presenting as early glomerular damage before eGFR decline 1
• In type 2 diabetes, albuminuria may appear at diagnosis or without retinopathy, unlike type 1 diabetes where retinopathy typically precedes kidney involvement 1
• The mechanism involves glomerular hyperfiltration and endothelial dysfunction that allows albumin leakage before measurable creatinine elevation 2, 3

Hypertensive Nephropathy

• Hypertension causes glomerular capillary damage and increased permeability to albumin even when eGFR remains ≥60 mL/min/1.73 m² 1, 4
• High-normal albuminuria (even 9.4-15 mg/g) in hypertensive patients associates with concentric left ventricular hypertrophy, increased body weight, and insulin resistance 4
• Hyperfiltration in early hypertensive kidney disease can maintain normal creatinine while albumin leaks through damaged glomeruli 4

Cardiovascular and Systemic Vascular Disease

• Albuminuria reflects widespread endothelial dysfunction affecting both kidney microvasculature and systemic vessels 3, 5
• It serves as a biomarker for coronary artery disease, stroke risk, heart failure, and arrhythmias independent of kidney function 5
• Myocardial capillary disease and arterial stiffness produce albuminuria before renal function decline 5

Secondary and Transient Causes

Metabolic Factors

• Marked hyperglycemia temporarily elevates albumin excretion without permanent kidney damage 1
• Insulin resistance and metabolic syndrome associate with high-normal albuminuria even in normalbuminuric ranges 4

Hemodynamic Factors

• Congestive heart failure increases glomerular capillary pressure, causing transient albuminuria 1
• Marked hypertension (hypertensive urgency/emergency) temporarily increases albumin leakage 1

Transient Physiologic Causes

• Vigorous exercise within 24 hours before testing 1, 6
• Fever or acute infection 1
• Menstruation 1

Critical Diagnostic Approach

Confirmation Requirements

• Obtain 2 out of 3 urine albumin-to-creatinine ratio measurements over 3-6 months showing ≥30 mg/g to confirm persistent albuminuria 1, 2, 6
• Use first morning urine samples to minimize variability 2
• Calculate eGFR using CKD-EPI equation to confirm preserved kidney function (≥60 mL/min/1.73 m²) 1, 2

Exclude Transient Causes

• Avoid testing within 24 hours of exercise 1, 6
• Defer testing during acute illness, fever, or menstruation 1
• Reassess after treating acute heart failure or severe hypertension 1

Common Pitfalls

• Do not assume normal kidney function based solely on urea and creatinine—always calculate eGFR, as creatinine may remain normal until 50% of kidney function is lost 2
• Do not dismiss single elevated albumin measurement—biological variability exceeds 20%, requiring multiple confirmatory tests 1
• In type 2 diabetes, absence of retinopathy does not exclude diabetic kidney disease, unlike type 1 diabetes 1
• High-normal albuminuria (even <30 mg/g) carries cardiovascular risk and may warrant closer monitoring 4

When to Refer to Nephrology

• Rapidly increasing albuminuria despite treatment 2
• Presence of hematuria or cellular casts suggesting glomerulonephritis 2
• Uncertainty about etiology (e.g., absence of diabetes/hypertension, atypical presentation) 1, 2
• Development of nephrotic-range proteinuria 2
• Rapid decline in eGFR even if still >60 mL/min/1.73 m² 1