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Microalbuminuria is a term used to indicate that there is a small increase in the excretion of serum albumin in the urine.

The NycoCard U-Albumin test is a 3-minute point-of-care test for the measurement of albumin in urine. The Afinion ACR test provides a simple, fast and reliable point of care test for determination of albumin, creatinine and albumin/creatinine ratio (ACR) in human urine with the ratio helpful to normalise urine concentration and thus the interpretation of urinary albumin levels.

Some renal physiology
The kidney normally performs a number of essential functions:

It participates in the maintenance of the constant extracellular environment that is required for adequate functioning of the cells. This is achieved by excretion of some of the waste products of metabolism (such as urea, creatinine and uric acid) and by specifically adjusting the urinary excretion of water and electrolytes to match net intake and endogenous production. The kidney is able to regulate individually the excretion of water and solutes such as sodium, potassium and hydrogen, largely by changes in tubular reabsorption or secretion.

It secretes hormones that participate in the regulation of systemic and renal haemodynamics (renin, angiotensin II, prostaglandins and bradykinin), red blood cell production (erythropoietin), and calcium, phosphorus and bone metabolism (1,25-dihydroxy vitamin D3 or calcitriol).

It performs such miscellaneous functions as catabolism of peptide hormones and synthesis of glucose (gluconeogenesis) in the fasting condition.

Most of the water and solutes in the ultrafiltrate are reabsorbed in the tubules. By selective absorption and secretion by the tubular cells the body rids itself of waste products, such as urea, regulates electrolyte metabolism, whilst reabsorbing glucose, amino acids and other nutrients. Filtered proteins are reabsorbed to a certain extent. When the filtered amount exceeds the absorptive capacity, protein excretion will be increased. A small increase in albumin excretion (microalbuminuria) is a first sign of diabetic renal disease.

The basic unit of the kidney is the nephron, with each kidney in humans containing approximately 1.0 to 1.3 million nephrons. Each nephron consists of a glomerulus, which is a tuft of capillaries interposed between two arterioles (the afferent and efferent arterioles), and a series of tubules lined by a continuous ephithelial layer. The glomeruli are located in the outer part of the kidney, called the cortex, whereas the tubules are present in both the cortex and the inner part of the kidney, the medulla.

The initial step in the excretory function of the nephron is the formation of an ultrafiltrate of plasma across the glomerulus. This fluid then passes through the tubules and is modified in two ways: by reabsorption and by secretion. Reabsorption refers to the removal of a substance from the filtrate, whereas secretion refers to the addition of a substance to the filtrate.

The rate of glomerular filtration averages 135 to 180 L/day in normal adults. Since this represents a volume that is more than 10 times that of the extracellular fluid and approximately 60 times that of the plasma, it is evident that almost all of this fluid must be returned to the systemic circulation. This process is called tubular reabsorption.

The composition of the urine differs from that of the relatively constant extracellular fluid in two important ways. First, the quantity of solutes and water in the urine is highly variable, being dependent upon the intake of these substances. A normal subject, for example, appropriately excretes more Na+ on a high-salt diet than on a low-salt diet. In both instances, the steady state and therefore the extracellular volume are maintained as output equals intake. Similarly, the urine volume is greater after a water load than after water restriction, resulting in stable plasma Na+ concentration. This relation to intake means that there are no absolute "normal" values for urinary solute or water excretion. We can only describe a normal range, which merely reflects the range of dietary intake, for example, 100 to 250 mEq/day for Na+.

Proteins in the urine either come from plasma proteins or from the tubular cells. With normal kidney function adults excrete up to 150 mg protein/day, somewhat more in adolescents. The albumin excretion is low, rarely more than 30 mg/24 hours of 20 µgram/minute. Some other plasma proteins are filtered and excreted, the rest derives from the tubular cells, or in case of disease, in the urinary tract for ureters, bladder or urethra. If blood is mixed with the urine, kidney or urinary tract disease, or from menstrual blood, the concentration levels of plasma proteins in the urine will increase markedly.

Increased albumin excretion in the urine is the first sign of diabetic kidney disease, nephropathy. The commonly used urine dipsticks are a relatively insensitive marker for albuminuria, becoming positive first when albumin concentration in urine exceeds 200 to 250 mg/L. Use is therefore made of a specific and much more sensitive assay for albumin.

The normal rate of albumin excretion is less than 30 mg/day (20 µg/min) in a patient with diabetes is called microalbuminuria and is usually indicative of diabetic nephropathy (unless there is some coexistent renal disease). Values above 300 mg/day (200 µg/min) are considered to represent overt nephropathy.

Table 8: Determination of urine albumin excretion rate.

Method Need to measure Upper normal Incipient nephropathy Manifest nephropathy
24 hour albumin excretion 24 hour urine volume, albumin concentration <30 mg albumin/24 h <30-300 mg/24 h >300 mg/24 h
Timed albumin excretion Urine volume over specific time for collection, albumin concentration <20 µg/min 20-200 µg/min >300 µg/min
Albumin/creatinine ratio Albumin and creatinine concentration in random urine specimen <2.5 mg albumin/mmol creatinin or <30 mg albumin/g creatinine A test above upper normal indicates the need for timed urine collection. Dilute urine, e.g. due to high blood glucose levels, may give misleading results.
Albumin concentration Albumin concentration in random sample, best in first morning sample <20 mg/L  

 

The 24-h or timed urine collection is the gold standard for the detection om microalbuminuria (Table 8). However, many find it difficult to practice urine collection. In that case, spot testing is adequate to exclude increased albumin excretion. This may be particularly valuable in young patients unable to collect a 24-h or timed specimen. However, a test above the upper normal strongly indicates the need for proper urine collection.

Increased albuminuria, why is it important?
Microalbuminuria is the earliest clinical sign of diabetic nephropathy. In patients with Type 1 diabetes who have microalbuminuria not everyone will progress to renal failure. Most who develop microalbuminuria within the first ten years of Type 1 diabetes have progression to macroalbuminuria; in comparison, progression may occur in only about one-half of patients with later onset microalbuminuria.

Control of both hyperglycaemia and hypertension (particularly with ACE inhibitors) contributes to improvement in the course of the disease. Patients who progress are also more likely to have higher HbA1c values and a higher blood pressure than non-progressors.

Microalbuminuria is also associated with an increase in blood pressure. Patients with Type 1 diabetes are almost always normotensive if albumin excretion is normal or only slightly increased. The blood pressure usually begins to rise within the normal range in the third year after the onset of microalbuminuria; the incidence of overt hypertension is approximately 15-25% in all patients with microalbuminuria and much higher as the patient progresses to overt nephropathy.

I Type 2 diabetes, progression from microalbuminuria to overt nephropathy within a 10-year period occurs in 20-40% of Caucasian patients with Type 2 diabetes. Risk factors contributing to progression include hyperglycaemia, hypertension, and cigarette smoking.

A number of studies have demonstrated that microalbuminuria is also an important risk factor for cardiovascular disease and early cardiovascular mortality in Type 1 and Type 2 diabetes and also in essential hypertension. This increase in risk was independent of other cardiovascular risk factors. The apparent association between microalbuminuria and arteriosclerosis may result from generalised vascular wall dysfunction.

Microalbuminuria represents a stage of diabetic nephropathy at which treatment is often successful in preventing progressive renal disease. Even in the microalbuminuric phase, intensive combined therapy with optimal glycaemic control, ACE inhibition, combined with other antihypertensive drugs if necessary to achieve normotension, is advised to retard or stop the progression to overt nehpropathy and renal failure. Whether other antihypertensive drugs will be as effective as ACE inhibitors in preventing progressive proteinuria is unclear.

In addition, since increased urine albumin excretion is a risk factor for cardiovascular complications, intensive treatment of other risk factors is advised. The appearance of microalbuminuria both in Type 1 and Type 2 diabetes points to the need for improved glycaemic control, treatment with ACE-inhibitors, normalisation of blood pressure, ideal serum lipid levels with intensified dietary instruction and perhaps lipid-lowering drugs, and cessation of smoking.

How often should urine albumin excretion be measured?
In general, one a year is enough as long as increased excretion has not been found. Once a positive test has been found, it is necessary to do two more, to ensure that albumin excretion really is increased. Two out of three tests (either 24 hours' urine collection, or timed test with increased excretion per minute) are necessary to make the diagnosis of increased albumin excretion. In individuals with increased albumin excretion, the excretion rate should be followed by 3-4 tests per year to evaluate the effect of interventions.

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