What’s on the web for family physicians – microalbuminuria in clinical practice

Alfred KY Tang 鄧權恩，Chung-ping Ho 何仲平

Microalbuminuria Overview
http://www.dialysis.com.hk/wp-content/uploads/proteinuria-as-a-clinical-tool.pdf

One of the most significant discoveries in nephrology is microalbuminuria in diabetic patients. It was known that in patients with incipient diabetic nephropathy, there was increased urine albumin excretion (UAE) at a concentration not yet detectable by the common urine dipstick. It was called ‘micro-albuminuria’. The term ‘micro’ referred to the low urine albumin concentration and not the molecular size, as the albumin detected are normal albumin molecules.

In quantitative terms, normal urine contains albumin of 20 mg/l and dipsticks can only detect albumin around 150 mg/l. A patient is said to have macro-albuminuria if urine albumin reached the concentration which can be detected by the dipstick. Albumin excretion between 20 –150 mg/l is thus called microalbuminuria. It is an early indicator of diabetic nephropathy as the risk of diabetic nephropathy increased 10 –20 times. It is amenable to treatment at this stage.

Apart from incipient diabetic nephropathy, the presence microalbuminuria also signaled the increased risk of cardiovascular disease.

Why We Use Microalbuminuria / Creatinine Ratio (ACR)
https://labtestsonline.org/understanding/analytes/microalbumin/tab/test/

To avoid the interference caused by the urine hydration, it is common to test for both the urine (micro) albumin and urine creatinine concentration and the result was expressed as a ratio. Under such circumstances, urine albumin: creatinine ratio > 2.5 mg/mmol in men, > 3.5 mg/mmol (30 mg/g) for women was regarded as microalbuminuria.

The American Diabetes Association (ADA) has stated a preference for the ACR for screening for albuminuria indicating early kidney disease. Since the amount of albumin in the urine can vary considerably, an elevated ACR should be repeated twice within 3 to 6 months to confirm the diagnosis. When collecting urine sample for ACR, an early morning sample is preferred and the patient should have refrained from heavy exercises for 24 hours. A repeat test should be done 3 to 6 months after the first positive test.

According to the ADA, microalbuminuria is defined as levels of urinary protein greater than or equal to 30 mg/ day, 20 µg/minute, or 30 to 299 µg creatinine/mg. Urinary excretion of abnormal quantities of protein for ≥ 3 months, with or without a decrease in glomerular filtration rate (GFR), is diagnostic of chronic kidney disease (CKD).

Screening for Microalbuminuria in Diabetic Patients
http://care.diabetesjournals.org/content/28/1/164

Screening for microalbuminuria should be performed yearly, starting 5 years after diagnosis in type 1 diabetes or earlier in the presence of puberty or poor metabolic control. In patients with type 2 diabetes, screening should be performed at diagnosis and yearly thereafter.

Early detection of diabetic nephropathy, interventions against major risk factors (hyperglycemia, hypertension, dyslipidaemia and smoking), and the use of angiotensinconverting enzyme (ACE) inhibitor and angiotensin receptor blocker (ARB) as renoprotective agents are effective in reducing the progression of renal disease. Every halving of albumin excretion is associated with an 18% reduction of cardiovascular events. Early intervention prevents the onset of overt nephropathy and subsequent progression to end-stage renal disease.

Microalbuminuria in Hypertensive Patients
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2658722/

Later discovery showed that microalbuminuria is an independent risk for stroke, myocardial infarction and congestive heart failure. Thus patients with hypertension should also have microalbuminuria checked.

Microalbuminuria correlates strongly with cardiovascular risk: albumin excretion rates as low as 4.8 microg/min are associated with increased risk of cardiovascular and cerebrovascular disease. Increased microalbuminuria indicates endothelial dysfunction or developing atherosclerosis leading to end-organ damage, major cardio or cerebrovascular events.

Low-grade micro-albuminuria is associated with an increase in cardiovascular events. As sensitive and reliable methods for assessment of UAE are getting more available, the screening for microalbuminuria should be comparable to that of blood pressure control and lipid screening in clinical importance. Early detection of microalbuminuria allow aggressive treatment to be delivered in time for the high risk patients to slow disease progression.

Microalbuminuria as a Measure of Endothelial Dysfunction and Bearing on Treatment
http://www.biochemia-medica.com/content/microalbuminuria-and-risk-cardiovascular-diseasespatients-diabetes-and-hypertension

Endothelial dysfunction is an important antecedent of microalbuminuria in diabetes and it provides an explanation for the association between microalbuminuria and vascular disease in diabetes, microalbuminuria is a measure of endothelial dysfunction. Impaired endothelial function and disturbed vascular remodeling may be related to activation of the renin-angiotensin system (RAS) occurring in kidney disease. ACE inhibitors or ARB may have beneficial effect on microalbuminuria by the action on the RAS in addition to blood pressure reduction.

Methods of Detection of Microalbuminuria
http://www.ajol.info/index.php/nhj/article/viewFile/90499/79917

The significance, risk factors and methods of detection of microalbuminuria are reviewed in the article. Microalbuminuria is a sensitive test for the detection of preclinical kidney dysfunction, and also a predictor of subsequent diabetic nephropathy and hypertension.

Microalbuminuria is an early maker of glomerular injury. Screening may be performed with a semiquantitative assay. If the screen is positive, UAE should be evaluated by a quantitative assay. If the confirmatory test is positive, treatment with an ACE inhibitor would retard the microalbuminuria and prevent progression to overt renal failure.

Management of Microalbuminuria
http://www.gpnotebook.co.uk/simplepage.cfm?ID=x20020429231048021840

Studies have shown that not only do ACE inhibitors result in a reduction in blood pressure, they can also reduce the level of albumin excretion and therefore delay the progression to renal disease. ACE inhibitors can be started with the usual precautions and titrate to full dose in all individuals with confirmed raised albumin excretion rate (> 2.5 mg/mmol for men, > 3.5 mg/mmol for women). An angiotensin II-receptor antagonist can be substituted for an ACE inhibitor for a person with an abnormal albumin: creatinine ratio if an ACE inhibitor is poorly tolerated.

Reduction of proteinuria by pharmacological therapy is used as a marker in the management of chronic kidney disease and many acute glomerular diseases and is associated with improved renal outcomes. For a person with an abnormal albumin: creatinine ratio, it is important to maintain his blood pressure below 130/80 mmHg

Clinical Guidelines on Chronic Kidney Disease Prevention and Management
http://www.racgp.org.au/your-practice/guidelines/ national-guide/chronic-kidney-disease-prevention-andmanagement/

CKD is classified into six stages depending on GFR as outlined in the article. Even mild reduction in GFR is associated with excess cardiovascular and stroke risk. While at any given level of kidney function, microalbuminuria or macroalbuminuria is associated with increased cardiovascular and stroke morbidity and mortality. The interventions concerned with preventing kidney disease, detecting and slowing the progression of established CKD, and reducing the associated risks of cardiovascular disease and stroke, are tabulated in the article. Patients with more advanced disease or significant comorbidities, or at risk in other ways, are likely to benefit from referral to a secondary care nephrology service. The Caring for Australians with Renal Impairment guidelines recommend referral of patients with:

• Stage 4 or 5 CKD of any cause
• Persisting albuminuria (ACR > 30 mg/mmol)
• Declining eGFR > 5 mL/min/1.73 m2 in 6 months (average of at least three measurements)
• CKD and elevated BP that is not at target despite at least three BP lowering medications
• Unexplained anaemia (< 100 g/L) with eGFR < 60 mL/min/1.73 m2