What is the appropriate workup for Proteinuria (presence of excess proteins in the urine)?

From the Guidelines

The workup for proteinuria should begin with quantification of protein excretion using urine albumin-to-creatinine ratio (ACR) as the preferred initial test, followed by urine protein-to-creatinine ratio, and then reagent strip urinalysis for total protein with automated reading, as recommended by the KDIGO 2012 guideline 1. The initial evaluation of proteinuria involves measuring the amount of protein in the urine, and the preferred method is to use a spot urine sample to measure the albumin-to-creatinine ratio (ACR) or the protein-to-creatinine ratio, as these methods are more convenient and accurate than a 24-hour urine collection 1. Some key points to consider in the workup of proteinuria include:

• Using an early morning urine sample is preferred for initial testing of proteinuria 1
• The KDIGO guideline recommends using the urine ACR as the first-line test, followed by the urine protein-to-creatinine ratio, and then reagent strip urinalysis for total protein with automated reading 1
• The National Kidney Foundation recommends a cutoff value for an albumin–creatinine ratio greater than 30 mg/g in men and women to detect proteinuria 1
• At very high levels of proteinuria (spot urine total protein to creatinine ratio 500 to 1,000 mg/g), measurement of total protein, instead of albumin, on a spot urine sample is acceptable 1 The workup for proteinuria should also include a comprehensive evaluation, including a complete medical history, physical examination, and laboratory tests, such as a complete blood count, comprehensive metabolic panel, serum albumin, lipid profile, and urinalysis with microscopic examination, as well as additional tests to detect underlying causes of proteinuria, such as serum and urine protein electrophoresis, complement levels, and serologies for hepatitis and HIV 1. Renal ultrasound should be performed to assess kidney size, structure, and rule out obstruction, and a kidney biopsy may be necessary if the cause of proteinuria remains unclear after initial evaluation, particularly for patients with nephrotic-range proteinuria, hematuria, reduced kidney function, or systemic disease 1. Early diagnosis and management of proteinuria are crucial to prevent progressive kidney damage and to initiate appropriate treatment, which may include angiotensin-converting enzyme inhibitors for non-specific proteinuria or immunosuppressive therapy for immune-mediated glomerular diseases 1.

From the Research

Assessment of Proteinuria

The assessment of proteinuria involves measuring the amount of protein in the urine, which can be an indicator of renal disease 2, 3. The following methods can be used to assess proteinuria:

• 24-hour urine collection: This method involves collecting a patient's urine over a 24-hour period to measure the total amount of protein excreted 2, 4.
• Protein-to-creatinine ratio (PCR): This method involves measuring the ratio of protein to creatinine in a spot urine sample, which can be used to estimate the amount of protein excreted over 24 hours 3, 4.
• Albumin-to-creatinine ratio (ACR): This method involves measuring the ratio of albumin to creatinine in a spot urine sample, which can be used to estimate the amount of albumin excreted over 24 hours 2, 5.

Interpretation of Results

The results of proteinuria assessments can be interpreted as follows:

• A PCR greater than 15 mg/mmol or an ACR greater than 3.5 mg/mmol may indicate pathological proteinuria 2.
• A 24-hour urine protein excretion of greater than 150 mg/day may indicate proteinuria 2.
• The correlation between PCR and 24-hour urine protein excretion is generally good, but may be affected by physical activity 4.
• The correlation between ACR and 24-hour urine albumin excretion is generally good, but may be affected by the level of proteinuria and physical activity 5.

Clinical Applications

The assessment of proteinuria has several clinical applications, including:

• Screening for renal disease in high-risk populations, such as diabetics, patients with heart disease, and patients with a family history of renal disease 2.
• Monitoring the progression of renal disease and the effectiveness of treatment 3, 5.
• Estimating the risk of cardiovascular mortality and total mortality in patients with proteinuria 2.

Comparison of Methods

The different methods for assessing proteinuria have been compared in several studies, with the following results:

• The PCR and ACR methods are generally considered to be reliable and convenient alternatives to 24-hour urine collection 3, 6.
• The estimated protein excretion rate (ePER) and estimated albumin excretion rate (eAER) may be superior to PCR and ACR for estimating daily proteinuria and albuminuria 5.
• The urine albumin-to-protein ratio (APR) may be useful for detecting tubular proteinuria, but should be compared with urine protein electrophoresis (PEP) 5.