How can a patient with suspected kidney disease have a normal albumin (Albumin)/creatinine (Creatinine) ratio?

Normal Albumin/Creatinine Ratio in Suspected Kidney Disease

A normal albumin/creatinine ratio is possible in a patient with suspected kidney disease because not all kidney diseases cause albuminuria, especially in early stages, and there is significant day-to-day variability in urinary albumin excretion that may result in false-negative readings.

Understanding Normal Albumin/Creatinine Ratio in Kidney Disease

Definition of Normal Albumin/Creatinine Ratio

• Normal urinary albumin-to-creatinine ratio (UACR) is defined as <30 mg/g creatinine 1
• This corresponds to <3 mg/mmol in international units 1

Reasons for Normal UACR in Kidney Disease

Non-Albuminuric Kidney Disease

• Some forms of kidney disease may not initially present with albuminuria 1
• Kidney damage can manifest through other markers besides albuminuria, such as structural abnormalities or decreased GFR 1
• In type 2 diabetes, kidney disease can sometimes present without significant albuminuria, as confirmed by kidney biopsy 1

Early Stage Disease

• Early kidney damage may not yet have progressed to the point of detectable albuminuria 1
• Chronic kidney disease is defined by abnormalities present for >3 months, and early changes might not affect albumin excretion 1

High Biological Variability

• UACR has high biological variability of >20% between measurements 1
• Recent research shows that within-individual variability of UACR can be as high as 48.8% coefficient of variation 2
• A repeated UACR measurement can be as low as 0.26 times the first measurement due to this variability 2

Factors Affecting UACR Measurement

• Exercise within 24 hours before testing can affect results 1
• Infection, fever, congestive heart failure, marked hyperglycemia, menstruation, and marked hypertension may elevate UACR independently of kidney damage 1
• Some medications like ACE inhibitors, angiotensin receptor blockers, and SGLT2 inhibitors can reduce albuminuria 2

Clinical Implications and Recommendations

Diagnostic Approach

• Due to high variability, two of three specimens of UACR collected within a 3-6 month period should be abnormal before considering a patient to have high albuminuria 1
• First-morning spot collections are best for children and adolescents to avoid confounding effect of orthostatic proteinuria 1
• Patients should refrain from vigorous exercise for 24 hours before sample collection 1

When to Consider Additional Testing

• If kidney disease is still suspected despite normal UACR, evaluate estimated glomerular filtration rate (eGFR) as another marker of kidney function 1
• Consider referral to a nephrologist for uncertainty about the etiology of kidney disease, especially if clinical suspicion is high despite normal UACR 1
• Kidney biopsy may be necessary in some cases to confirm diagnosis when standard markers are inconclusive 1

Monitoring Recommendations

• For patients with diabetes, annual screening for albuminuria is recommended regardless of previous normal results 1
• Consider using the mean of multiple collections to improve diagnostic accuracy, as this narrows the range of diagnostic uncertainty 2
• Recent research suggests that even UACR values >10 mg/g (still within normal range) could predict future CKD progression in patients with type 2 diabetes 3

Common Pitfalls to Avoid

• Single Measurement Reliance: Avoid making clinical decisions based on a single normal UACR result due to high day-to-day variability 2
• Ignoring Other Markers: Don't rule out kidney disease solely based on normal UACR; consider other markers of kidney damage 1
• Timing Issues: Avoid collecting samples after exercise or during conditions that can temporarily affect results 1
• Delayed Follow-up: Even with normal UACR, regular monitoring is essential in high-risk patients (diabetes, hypertension) 1