What causes a high urine microalbumin (Microalbumin) to creatinine (Creatinine) ratio (UMCR)?

What Causes a High Urine Microalbumin-to-Creatinine Ratio

A high urine microalbumin-to-creatinine ratio (≥30 mg/g creatinine) is most commonly caused by diabetic kidney disease or hypertension-related kidney damage, but can also result from transient conditions including recent exercise, acute infections, fever, congestive heart failure, marked hyperglycemia, menstruation, or marked hypertension. 1

Pathologic (Chronic) Causes

Diabetic Kidney Disease

• Diabetic kidney disease is the leading cause of elevated UACR in patients with diabetes, occurring in 20-40% of diabetic patients and representing the most common cause of end-stage renal disease in the United States. 1
• In type 1 diabetes, kidney disease typically develops after 10 years of diabetes duration, while in type 2 diabetes it may be present at diagnosis. 1
• The presence of elevated UACR indicates generalized vascular dysfunction and endothelial damage beyond just kidney involvement. 2, 3

Hypertensive Nephropathy

• Essential hypertension is a common cause of microalbuminuria independent of diabetes, with elevated UACR indicating pressure-related albumin leakage through damaged glomeruli. 2
• Among nondiabetic patients with essential hypertension, microalbuminuria is associated with higher blood pressures, increased total cholesterol, and reduced HDL cholesterol. 4

Primary Glomerular Diseases

• Primary glomerular diseases can present with microalbuminuria before progressing to overt proteinuria. 2
• Consider this diagnosis when there is active urinary sediment (red or white blood cells or cellular casts), rapidly increasing albuminuria, rapidly decreasing eGFR, or absence of retinopathy in type 1 diabetes. 1

Renal Vascular Disease

• Renal vascular disease can cause microalbuminuria through ischemic nephropathy. 2

Transient (Reversible) Causes

These conditions can elevate UACR independently of kidney damage and should be ruled out before confirming chronic kidney disease: 1

Physiologic and Acute Conditions

• Exercise within 24 hours of urine collection causes temporary elevation in albumin excretion. 1, 2
• Acute infections and fever lead to transient microalbuminuria through inflammatory mechanisms. 1, 2
• Congestive heart failure causes increased venous pressure resulting in microalbuminuria. 1, 2
• Marked hyperglycemia, even without established diabetic nephropathy, can cause microalbuminuria. 1, 2
• Marked hypertension causes pressure-related albumin leakage. 1, 2
• Menstruation can cause false elevations in measured albumin. 1
• Urinary tract infections with associated inflammation can cause microalbuminuria. 2
• Hematuria and pyuria can cause false elevations in measured albumin. 2

Clinical Significance and Cardiovascular Risk

• Microalbuminuria is a powerful predictor of future cardiovascular events and death, even in treated patients, indicating generalized vascular dysfunction beyond renal involvement. 2, 3, 4
• The presence of elevated UACR correlates strongly with elevated C-reactive protein levels, abnormal vascular responsiveness to vasodilating stimuli, failure of nocturnal blood pressure drops, and insulin resistance. 2
• Microalbuminuria predicts increased cardiovascular morbidity and mortality independent of other risk factors. 2

Diagnostic Confirmation Requirements

A critical pitfall to avoid: single measurements can be misleading due to high biological variability of >20% between measurements. 1

• Two of three specimens of UACR collected within a 3-6 month period should be abnormal before confirming chronic albuminuria. 1, 2
• First morning void samples are preferred to minimize effects of orthostatic proteinuria. 2, 5
• Rule out transient causes (exercise, infections, fever, heart failure, marked hyperglycemia, menstruation, marked hypertension) before confirming chronic kidney disease. 1, 2

When to Suspect Alternative Diagnoses

Refer to nephrology for further evaluation including possible kidney biopsy when: 1

• Active urinary sediment (red or white blood cells or cellular casts) is present
• Rapidly increasing albuminuria or nephrotic syndrome develops
• Rapidly decreasing eGFR occurs
• Absence of retinopathy in type 1 diabetes (it is rare for type 1 diabetics to develop kidney disease without retinopathy)
• Uncertainty about the etiology of kidney disease exists

Common Pitfalls in Evaluation

• Standard dipstick tests are inadequate—specific assays for microalbumin are required. 2
• Failure to adjust for creatinine can lead to errors from variations in urine concentration. 2
• Not accounting for sex differences in creatinine excretion can lead to errors (men typically have higher urine creatinine excretion due to greater muscle mass). 2
• Confusing urine creatinine (which is merely a normalizing factor) with serum creatinine (which reflects kidney function). 2