What causes albuminuria?

Causes of Albuminuria

Albuminuria is primarily caused by diabetes, hypertension, and various forms of kidney disease, with diabetes being the single leading cause of persistent albuminuria and end-stage renal disease. 1

Definition and Classification

• Albuminuria is defined as increased urinary albumin excretion and is categorized based on severity:

  • Normal albuminuria: <30 mg/24h or <30 mg/g creatinine 1
  • Moderately elevated albuminuria (formerly microalbuminuria): 30-300 mg/24h or 30-300 mg/g creatinine 1
  • Severely elevated albuminuria (formerly macroalbuminuria): >300 mg/24h or >300 mg/g creatinine 1

• Albuminuria should be confirmed with at least 2 specimens collected within a 3-6 month period due to high biological variability 1

Primary Causes

Diabetes

• Occurs in 20-40% of patients with diabetes 1

• In type 1 diabetes:

  • Typically develops after 10 years of diabetes duration (most commonly 5-15 years after diagnosis) 1
  • Rare to develop diabetic kidney disease without retinopathy 1
  • About 13-19% of patients with normal albumin levels develop microalbuminuria over time 1

• In type 2 diabetes:

  • May be present at diagnosis due to undetected diabetes for years 1
  • About 20-40% develop renal failure without specific interventions 1
  • Can occur without retinopathy, unlike type 1 diabetes 1
  • In patients with type 2 diabetes and albuminuria but without retinopathy, approximately 69% have diabetic glomerulopathy, while 31% have either normal glomerular structure (18%) or non-diabetic glomerulopathies like glomerulonephritis (13%) 2

Hypertension

• Present in up to 23% of patients with hypertension 3
• In type 1 diabetes, hypertension usually results from underlying diabetic nephropathy 1
• In type 2 diabetes, hypertension is often present at diagnosis in about one-third of patients 1
• Both systolic and diastolic hypertension accelerate progression of diabetic nephropathy 1

Other Causes and Risk Factors

• Hemolytic disorders causing increased red blood cell breakdown 4
• Glomerulonephritis and other primary kidney diseases 2
• Cardiovascular disease 5, 6
• Metabolic syndrome components including prediabetes and dyslipidemia 3
• Systemic vascular disease affecting myocardial capillaries and arterial stiffness 5

Transient Causes of Elevated Albuminuria

• Exercise within 24 hours 1
• Infection or fever 1
• Congestive heart failure 1
• Marked hyperglycemia 1
• Marked hypertension 1
• Pregnancy 1
• Urinary tract infection 1
• Hematuria 1

Pathophysiological Mechanisms

• Albuminuria reflects widespread endothelial dysfunction 6
• Elevated albuminuria causes tubulointerstitial damage through activation of proinflammatory mediators, leading to progressive decline in renal function 7
• Albuminuria is a marker of systemic microvascular and macrovascular damage 3
• In diabetic kidney disease, albuminuria typically precedes decline in glomerular filtration rate (GFR) 1

Clinical Significance

• Albuminuria is an independent predictor of cardiovascular risk 5, 3
• Associated with increased risk of coronary artery disease, stroke, heart failure, and arrhythmias 5
• Persistent albuminuria in the range of 30-299 mg/24h is an early stage of diabetic nephropathy in type 1 diabetes 1
• Patients with persistent albuminuria who progress to levels ≥300 mg/24h are likely to progress to end-stage renal disease 1
• Spontaneous regression of microalbuminuria occurs in up to 40% of patients with type 1 diabetes 1
• About 30-40% of patients with microalbuminuria remain at that level and do not progress to higher levels over 5-10 years of follow-up 1

Screening Recommendations

• Annual screening for albuminuria in type 1 diabetic patients with diabetes duration ≥5 years 1
• Annual screening for albuminuria in all type 2 diabetic patients starting at diagnosis 1
• Consider screening in non-diabetic patients with cardiovascular risk factors 3