Plasma albumin is normally filtered in very low amount by the glomerulus, and then more than 99% of it is reabsorbed by the cells of the proximal convoluted tubule. The term albuminuria refers to the loss of albumin by urine, regardless of the extent of the loss. Under stable physiological conditions and at rest, albuminuria is present only in trace amounts, i.e., in concentrations ≤10 mg/L. The most important physiological factors that can cause significant changes in albuminuria are sex, age, body mass index (BMI), and a high-protein diet. Other factors that cause albuminuria, independently of kidney function, are physical exercise over the 24 h prior to urine collection, fever, congestive heart failure, marked hyperglycemia, urinary tract infections, severe hypertension, menstrual period, and certain medications. Albuminuria is a prognostic index of progression of diabetic nephropathy in both type 1 and type 2 diabetes, according to the scheme shown in Table.1, broken down by various modes of expression of the outcome. In 80% of patients with type 1 diabetes and albuminuria, urinary albumin excretion increases at an annual rate of 10–20%, with development of clinical proteinuria within 10–15 years. After the onset of clinical proteinuria, most of these patients (>80%) manifest reductions in GFR until the development, in a relatively short time, of ESKD. 20–40% of patients with type 2 diabetes and albuminuria evolve to clinical proteinuria, but, in the 20 years following the onset of clinical proteinuria, only 20% of these patients evolve to ESKD. Finally, in patients with type 1 or 2 diabetes and albuminuria between 30 and 300 mg/g creatinine, the risk of cardiovascular disease is significantly increased: meta-analysis studies have shown that in type 2 diabetes, albuminuria doubles cardiovascular morbidity and mortality (OR 2; 95% CI 1.4–2.7) and more than doubles all other causes of death (OR 2.4; 95% CI 95%). According to the new recommendations of the American Diabetes Association (ADA) on the standards of care for diabetic patients, a significant albuminuria value must be found in at least two out of three samples over 3–6 months before a patient can be considered albuminuric. The threshold values defined by the scheme reported in Table.1 are very useful for defining the onset and the extent of progression of diabetic nephropathy; regarding CKD, it is defined by a constant value of albuminuria >30 mg/24 h or >30 mg/g of urinary creatinine in the extemporaneous sample, for more than 3 months. The choice of this threshold value is based, among other things, on the evidence that 30 mg corresponds to a value three times higher than the average value found in a healthy young adult (10 mg). Recent studies have shown that, in healthy adult populations, changes in urinary albumin excretion expressed in relation to urinary creatinine (albumin-to--creatinine ratio (ACR)) are significantly associated with the risk of ESKD and death. However, nowadays, albuminuria has assumed a more extensive clinical significance as a marker of cardiac and extracardiac organ damage and as an independent cardiovascular risk factor, and values <30 mg/24 h or <30 mg/g urinary creatinine should be clinically evaluated. Albuminuria is a marker of endothelial dam age: factors such as hyperglycemia and hypertension, as mentioned above, and dyslipidemia induce an increase in endothelial permeability, both in the renal and systemic compartments, mediated by different metabolic pathways, with passage of molecules from the vascular to the interstitial compartment, including albumin. This passage triggers the acute phase, and the consequent recall of immunocompetent cells and accumulation of cytokines and acute-phase proteins, and this process maintains and increases endothelial damage. The prevalence of albuminuria in essential hyper tension varies between 10% and 30% and increases with age and disease duration. Albuminuria is associated with signs of extracardiac vascular damage, such as increased carotid intima-media thickness, an expression of atherosclerosis, and increased pulse wave propagation velocity, an expression of arterial stiffness. In addition, albuminuria is associated with left ventricular hypertrophy and increased intrarenal vascular resistance. For these reasons, concentrations below 30 mg/day are significant, since they define the risk, which is a continuous variable and, therefore, changes considerably, for example, between an albuminuria value of 15 mg and one of 25 mg. As described above, in a CKD patient, albuminuria and eGFR define the cumulative risk of adverse outcome and progression to ESKD, as reported in Table 2. The determination of albuminuria requires great attention from the clinical laboratory, which is called to choose analytical methods with excellent quality specifications, especially those able to guarantee reliable measurements even in the range of concentrations below 30 mg. The choice of the type of sample is very important and is closely related to the expression of the results. Spot urine sample allows expressing albuminuria as albumin-to-creatinine ratio (ACR) (mg/g or mg/mmol of urinary creatinine); the timed collection (albumin excretion rate (AER)) allows expressing albuminuria as a share of daily excretion or in any case referred to as a time frame (mg for 24, 12, 6, or 3 h). There is a wide consensus on the recommendation to avoid expressing the results in relation to the urinary volume (mg/L) because too many variables contribute in this case to make the results not very reproducible. The “normalization” of results for urinary creatinine decreases the variability of albuminuria. In a 1989 study, it was shown that the intraindividual biological variability (coefficients of variation (CVs)) is lower in the first morning sample (36%) and further decreases (31%) when the result is expressed as an albuminuria/creatinuria ratio. In a more recent study, these results have been confirmed: the total variability of albuminuria is about 26% on the second morning urination when related to volume (mg/L) and drops to about 13% when related to urinary creatinine (mg/g creatinine). Several studies have confirmed that the best accuracy and reproducibility in the measurement of albuminuria is achieved by using the spot urine sample and expressing the result in relation to urinary creatinine, and, therefore, it is recommended that all laboratories follow this recommendation. Some recommendations for the determination and reporting of albuminuria are summarized in Table 3. However, factors related to reduced muscle mass, such as older age, female sex, and low body weight, result in reduced urinary excretion of creatinine, which, in turn, affects the ACR calculation at least partially, thus resulting in falsely increased results. Various remedies have been proposed to overcome this problem, including the development of equations to estimate urinary creatinine and their use as a correction factor to be multiplied by ACR. Finally, about the time of sample collection, it has been found that ACR measured in the extemporaneous random sample leads to an overestimation of the prevalence of albuminuria compared with ACR measured in the first morning urination. The clinical importance of albuminuria determination requires an effort to standardize analytical methods commonly used in routine practice. Although a candidate method has been developed as a reference method, all the elements of a “reference system” to standardize the determination of albuminuria, such as a reference material with a “target” value assigned by a reference method, are not yet available. Analytical issues related to the determination of albuminuria involve conformational differences of the molecule, which include the amount and types of bound substances and the degree of glycation. In urine, in addition, factors such as pH, ionic strength, and high concentrations of urea, glucose, and ascorbic acid contribute to albumin changes. Most of the routine methods for the determination of albuminuria are represented by immunoturbidimetric ones, but a further factor of variability among methods is just the type or mixture of antibodies used (polyclonal, monoclonal, mixed). This variability makes the methods nonhomogeneous, assigning different specifications and performance to each. Based on the data of biological variability, the analytical goal of inaccuracy, expressed as a coefficient of variation (CV, in percentage), should be <15%, a result confirmed by the external quality control schemes managed by various international bodies. There is also sufficient evidence to define stable albumin in urine samples up to 7 days between +2 and +8 °C, even if it is preferable to measure it on fresh samples or stored at −80 °C. Ultimately, the clinical importance of microalbuminuria requires the utmost commitment of the clinical laboratory in providing precise and accurate results, in the choice of sample type and mode of expression of results, and in the constant monitoring of analytical quality. These requirements are essential not only in the screening but also in the follow-up of patients with CKD, cardiovascular diseases, diabetes, and patients under therapeutic treatment, to improve the analytical reliability of a test so important in the definition of cardiovascular risk and mortality.

Table1. Levels of excretion of albuminuria referred to as impromptu and timed collection

Table2. Chronic kidney disease (CKD) staging and cumulative risk of clinical outcome by glomerular filtration rate (GFR) and albuminuria (ACR) categories

Table3. Recommendations for the laboratory evaluation of albuminuria

اخر الاخبار

اخبار العتبة العباسية المقدسة

تزامنًا مع حلول شهر ربيع الأول.. العتبة العباسية المقدسة ترفع مظاهر الحزن والسواد في المرقد الطاهر

بعد انتهاء شهري المحرم وصفر.. قسم الصيانة يباشر إدامة الثريات واستبدال مصابيح المرقد الطاهر

قسم الشؤون الخدمية يشرع بإدامة آليّات النظافة عقب انتهاء زيارة الأربعين

موكب عزاء الشعراء والرواديد ينظم مسيرة عزائية في ختام شهري الأحزان المحرم الحرام وصفر

المزيد

الآخبار الصحية

العنب.. فاكهة صغيرة بمفعول "خارق" للقلب والدماغ

دراسة تحدد "الحلقة المفقودة".. تسبب ارتفاع ضغط الدم

هذه الأطعمة تحمي دماغك من الشيخوخة وتزيد حدة الذكاء

خبراء يحذرون من مخاطر "الدهون المخفية" على القلب

المزيد

الآخبار التكنلوجية

الأرصاد الجوية تلجأ إلى الذكاء الاصطناعي.. لأي غرض؟

في منزلك.. "تعديل بسيط" يخفض ضغط الدم بشكل طبيعي

"ميزة جديدة" من إنستغرام تنافس تيك توك.. طال انتظارها

غوغل في مأزق.. بيانات 2.5 مليار مستخدم بقبضة القراصنة

المزيد

مواضيع ذات صلة

Water Balance

Proteinuria

rheumatoid factor (RF)

reticulocyte count (Retic count)

red blood cell indices (RBC indices, Blood indices)

NGAL

Biomarkers of Tubulo-Interstitial Injury

Low-Molecular-Weight Plasma Proteins

Immunofluorescence Assay (IFA)

Enzyme-Linked Fluorescent Assay (ELFA)

Diagnostic Evaluation of Lyme disease

red blood cell count (RBC count, Erythrocyte count)