From the Guidelines
The workup for elevated albumin-to-creatinine ratio (ACR) should begin with confirmation of the abnormal result through repeat testing, ideally with a first-morning urine sample, as recommended by the most recent guidelines 1. Once confirmed, a comprehensive evaluation includes:
- A complete medical history focusing on diabetes duration, hypertension, and medication use
- A physical examination assessing blood pressure and signs of systemic diseases
- Laboratory tests, such as:
- Comprehensive metabolic panel
- Complete blood count
- Lipid profile
- HbA1c (if diabetic)
- Urine studies, including urinalysis with microscopy and a 24-hour urine collection for protein and creatinine
- Additional blood tests to consider are complement levels (C3, C4), antinuclear antibodies, anti-double stranded DNA, and serum and urine protein electrophoresis if a systemic cause is suspected
- Renal ultrasound should be performed to assess kidney size, structure, and rule out obstruction For patients with persistent significant proteinuria (ACR >300 mg/g), especially with hematuria or declining kidney function, referral to nephrology for possible kidney biopsy is warranted, as suggested by the 2022 standards of medical care in diabetes 1. Management focuses on:
- Treating underlying causes
- Implementing ACE inhibitors or ARBs (starting with low doses like lisinopril 5-10mg daily or losartan 25-50mg daily and titrating up)
- Optimizing blood pressure control to <130/80 mmHg
- Glycemic control in diabetics
- Lifestyle modifications, including sodium restriction, smoking cessation, and weight management Early detection and intervention are crucial, as elevated ACR indicates kidney damage and increased cardiovascular risk, and prompt referral to a nephrologist is recommended for uncertainty about the etiology of kidney disease, difficult management issues, and rapidly progressing kidney disease, as stated in the 2022 guidelines 1.
From the Research
Workup for Elevated ACR
Elevated Albumin-to-Creatinine Ratio (ACR) is a significant indicator of kidney disease and cardiovascular outcomes. The following steps can be taken for the workup of elevated ACR:
- Measure urine ACR and protein-to-creatinine ratio (PCR) to assess the severity of kidney disease 2, 3
- Estimate ACR from PCR using validated equations, such as Weaver's and Sumida's equations, for epidemiologic retrospective studies or research purposes 2, 3
- Assess kidney function using estimated glomerular filtration rate (eGFR) and serum creatinine levels 4, 5
- Evaluate the presence of albuminuria, which is a predictor of kidney disease progression and cardio-renal outcomes in patients with type 2 diabetes mellitus 4, 6
- Consider calculating estimated albumin excretion rate (eAER) using spot ACR and estimated creatinine excretion rate (eCER) for improved albuminuria assessment 5
Diagnostic Tests
The following diagnostic tests can be used to assess kidney function and albuminuria:
- Urine ACR and PCR measurements 2, 3
- eGFR calculation using serum creatinine levels 4, 5
- Serum creatinine and uric acid measurements 4
- eAER calculation using spot ACR and eCER 5
Clinical Implications
Elevated ACR is associated with an increased risk of kidney disease progression and cardio-renal outcomes. The following clinical implications should be considered:
- Patients with elevated ACR should be monitored regularly for kidney function decline and cardio-renal outcomes 4, 6
- Albuminuria is a predictor of kidney disease progression and cardio-renal outcomes in patients with type 2 diabetes mellitus 4, 6
- Estimating ACR from PCR can be useful in certain clinical and research applications where only PCR is available 2, 3