What are the indications for checking the urine protein-to-creatinine (protein/creatinine) ratio, and what does an elevated ratio of 41 milligrams per millimole (mg/mmol) indicate in the setting of normal creatinine levels and glomerular filtration rate (GFR)?

From the Guidelines

Elevation of the urine protein/creatinine ratio to 41 mg/mmol in the setting of normal creatinine and GFR indicates significant proteinuria, suggesting early kidney damage or glomerular injury, and warrants further investigation with a complete kidney workup. The urine protein/creatinine ratio is a valuable tool for screening for kidney disease, monitoring known kidney conditions, evaluating preeclampsia in pregnant women, and assessing patients with diabetes, hypertension, or systemic diseases like lupus. According to the national kidney foundation practice guidelines for chronic kidney disease, evaluation, classification, and stratification 1, persistent proteinuria, as indicated by positive results on quantitative tests temporally spaced over 3 months, should undergo further evaluation for chronic kidney disease. Key points to consider in the interpretation of the urine protein/creatinine ratio include:

• The recommended cutoff value for an albumin–creatinine ratio is greater than 30 mg/g in men and women, with some studies suggesting sex-specific cutoff values 1.
• The standard dipstick for protein and the untimed urine measurements for total protein-creatinine ratio are useful for detecting proteinuria in adults not at increased risk for developing chronic kidney disease 1.
• Monitoring proteinuria in adults with chronic kidney disease should use the albumin–creatinine ratio or total protein-creatinine ratio if the albumin–creatinine ratio is high (>500 to 1000 mg/g) 1. Given the elevation of the urine protein/creatinine ratio to 41 mg/mmol, which exceeds the normal range, and the presence of normal creatinine and GFR, it is essential to investigate further to determine the underlying cause of the proteinuria, as it may indicate early kidney damage or glomerular injury. This finding warrants a comprehensive kidney evaluation, including a 24-hour urine collection, kidney ultrasound, and possibly referral to a nephrologist, to prevent progressive kidney function decline.

From the Research

Reasons for Checking Urine Protein/Creatinine Ratio

• To diagnose and monitor kidney damage or disease, such as diabetic nephropathy 2, 3
• To assess the risk of cardiovascular events in patients with kidney disease 2
• To monitor the effectiveness of treatment for kidney disease, such as angiotensin-converting enzyme inhibitors and angiotensin II receptor blockers 2, 3, 4

Elevation of Urine Protein/Creatinine Ratio to 41 mg/mmol

• May indicate kidney damage or disease, such as diabetic nephropathy, even in the presence of normal creatinine and GFR 2, 3
• Can be a sign of microalbuminuria, which is a characteristic of diabetic nephropathy 2
• May require further testing, such as immunofluorescence and electron microscopy studies, to differentiate diabetic nephropathy from other conditions that result in glomerulosclerosis 5

Normal Creatinine and GFR in the Presence of Elevated Urine Protein/Creatinine Ratio

• Does not necessarily rule out kidney damage or disease, as diabetic nephropathy can occur even with normal creatinine and GFR 2, 3
• May indicate early stages of kidney disease, which can be asymptomatic and only detectable through urine protein/creatinine ratio testing 2, 3