 |
||||||||||||||||||||||||||||
 |
||||||||||||||||||||||||||||
| ||||||||||||||||||||||||||||
The two kidneys filter approximately 650 mL of plasma every minute. This means that 37,000 grams of albumin pass through the glomeruli each day. Only 1.3 grams, or 0.004%, of the total albumin leaks through the glomeruli, which is an amazing efficiency for any filtration system. Ninety nine percent of the leaked albumin is degraded to fragments by the renal proximal tubules, resulting in a daily urinary excretion of only ~15 mg of albumin. Diabetic renal disease is the single most common cause of end stage renal disease in the United States. Approximately 40% of patients with type 1 and 20% with type 2 diabetes develop nephropathy. The earliest clinical evidence of nephropathy is the appearance of microalbuminuria. In healthy individuals, urinary protein excretion is less than 150 mg per day and albumin excretion is less than 30 mg per day. Microalbuminuria is defined as an increase in urinary albumin excretion at a level below that reliably detected by urine dipsticks (30 -299 mg/day or 20 -199 ug/minute). Microalbuminuria typically does not occur in type 1 diabetes until more than 5 years after onset. If not treated, approximately 80% of type 1 diabetics with sustained microalbuminuria progress to overt nephropathy within 10 to 15 years. Overt nephropathy is defined as albuminuria detectable by routine urinalysis. Once overt nephropathy develops, morphologic diabetic renal lesions are well established and progression to end stage renal disease is inevitable. The natural history of renal disease in type 2 diabetes is less certain. Microalbuminuria is often present at the time of diagnosis, because hyperglycemia has already been present for several years. Without specific clinical intervention, 20 to 40% of type 2 patients with microalbuminuria progress to overt nephropathy, but only 20% of patients with overt nephropathy progress to end stage renal disease within 20 years. In addition to its relationship with diabetic nephropathy, microalbuminuria is also a strong risk factor for early cardiovascular morbidity and mortality. The American Diabetes Association recommends the following test scheme. Routine urinalysis should be performed yearly in adults. If the urine dipstick is positive for protein, the albumin level is already greater than 300 mg/L and a follow-up quantitative urine protein is recommended. If routine urinalysis is negative for protein, microalbumin should be ordered. Screening of type 1 diabetics for microalbumin should begin at puberty or after 5 years duration. Screening of type 2 diabetics should begin at the time of diagnosis, because of the difficulty in dating the onset of diabetes. All initial positive results should be confirmed on a second sample collected on a different day, since there is significant day to day variability in urinary albumin excretion rates. If the first two results are discrepant, a third sample should be collected. If two of the three results are positive, early diabetic nephropathy is likely. Repeat testing of initial positive results is necessary because an individual's urinary albumin excretion rate can vary as much as 47%. Multiple factors can affect albumin excretion including diurnal variation, posture, strenuous physical activity, short term hyperglycemia, urinary tract infection, aminoglycoside antibiotics, acute febrile illnesses, heart failure, and hypertension. Three types of urine samples can be collected for microalbumin testing: 24 hour, 10 hour, and random collection. Twenty-four or 10 hour collections are the most sensitive methods for detecting microalbuminuria, but are inconvenient for patients and prone to collection errors. An acceptable alternative is measurement of the albumin to creatinine ratio in a random or first void urine sample. The following table provides interpretive guidelines.
Increased albumin excretion, or microalbuminuria, is defined as an albumin excretion rate (AER) of more than 20 ug/min as measured on a timed urine collection. This is the equivalent of albumin excretion of more than 30 mg per 24 hours. The albumin to creatinine ratio is calculated with the folllowing formula: ug albumin/mg creatinine = microalbumin (mg/dL) x 1000 creatinine (mg/dL) The factor of 1000 is used to convert from milligrams albumin to micrograms. The units for albumin and creatinine measurements on random or timed specimens vary in clinical practice. They can be expressed as either micrograms of albumin per milligram of creatinine or milligram of albumin per gram of creatinine. Some laboratories use a different ACR reference range for males and females : < 17 ug/mg for males and < 25 ug/mg for females. Urine samples contaminated with blood should not be submitted since albumin levels will be falsely elevated. If same day testing is not possible, urine can be stored refrigerated for two weeks without albumin degradation. |
||||||||||||||||||||||||||||
| ||||||||||||||||||||||||||||
|
||
