Albuminuria as a Biomarker of the Renal Disease

Abstract

Albuminuria is an early and sensitive marker of kidney damage in diabetic patients, a good predictor of kidney outcome and cardiovascular disease. Screening for albuminuria is important to identify individuals at risk for renal outcome, i.e., developing end-stage renal disease, acute kidney injury, and progressive chronic kidney disease as well as cardiovascular disease and all-cause mortality in both general and high-risk population (diabetes, cardiovascular disease, hypertension, and older patients). Also, it is the most widely used clinical marker of diabetic nephropathy. The terminology of “early diabetic nephropathy” indicated diabetic subjects with albuminuria. In this early phase of diabetic nephropathy, the glomerular filtration rate is usually well preserved. In patients with several cardiovascular risks, albuminuria is predicting outcome, even below the level to be taken as normal. It seems that the pathophysiologic mechanisms linking albuminuria to cardiovascular and renal risk are generalized loss of vascular endothelial function in organs. Furthermore, albuminuria can be used as a target for treatment for primary and secondary prevention of renal and cardiovascular disease development. ACE inhibition in subjects with nondiabetic albuminuria may prevent future cardiovascular events. Measurement of albuminuria can help to determine whether or not the patient with hypertension should be treated, how aggressively they should be treated, and what medications we should treat them with.

Definitions

Acute kidney injury (AKI)

Acute kidney injury (AKI) is the sharp loss of kidney function, resulting in the retention of urea and other nitrogenous waste products and in the dysregulation of extracellular volume and electrolytes.

Albumin-to-creatinine ratio (ACR)

Expression of albuminuria from the ratio of albumin to creatinine in urine, determined in individual sample of urine.

Angiotensin-converting enzyme inhibitors

Are drugs that block the production of angiotensin II. The latter is a hormone that circulates in the blood and has many effects on the cardiovascular system; angiotensin II is a strong vasoconstrictor.

Angiotensin II receptor antagonists

Are the drugs that modulate the renin–angiotensin–aldosterone system by blocking angiotensin II receptors.

Chronic kidney disease (CKD)

Chronic kidney disease, also called chronic kidney failure, describes the gradual loss of kidney function. Its stages are based on the patient’s level of glomerular filtration rate (GFR) which is a measure of filtering capacity of the glomeruli.

Diabetic nephropathy

Is a slow progressive kidney disease that occurs in patients with diabetes.

End-stage renal disease (ESRD)

Means glomerular filtration rate below 15 ml/min/1.73 m².

Estimated glomerular filtration rate (eGFR)

Describes how much fluid filtered through the kidney. It is usually measured with creatinine clearance rate: it is the volume of plasma that is cleared of creatinine per unit time. Nowadays, glomerular filtration rate is estimated using different formulas based on creatinine or other markers such as cystatin C.

Framingham score for assessment of cardiovascular risk

It gives an estimate of the probability that a person will develop cardiovascular disease within a specified amount of time, usually 10–30 years. It also indicates who is most likely to benefit from prevention.

Glomeruli and tubule

Both represent part of the nephron, the basic structural and functional unit in the kidney.

Immunochemistry assays

(Immunonephelometry, immunoturbidimetry, radioimmunoassay, enzyme-linked immunosorbent assay) Are based on the interaction of the urinary albumin with anti-albumin antibodies in the reagents.

Insulin resistance

A decreased sensitivity to the action of insulin. Conditions in which the increased amount of insulin is inadequate to induce normal insulin responses in insulin-sensitive tissues (liver, skeletal muscles, adipose tissues).

Likelihood ratios

Tell us how much we should shift our suspicion for a particular test result. The “positive likelihood ratio” (LR+) tells us how much to increase the probability of disease if the test is positive, while the “negative likelihood ratio” (LR−) tells us how much to decrease it if the test is negative.

Nonsteroidal anti-inflammatory drugs

It is a group of medication with antipyretic, analgesic, and anti-inflammatory effects.

Progression of chronic kidney disease

Worsening of kidney function, usually slow, which is determined by measuring glomerular filtration rate and albuminuria and/or proteinuria.

Renal replacement therapy (RRT)

Refers to the three ways of replacing the lost kidney function: dialysis (hemo- or peritoneal) and kidney transplant.

Renin–angiotensin–aldosterone system

Is a hormone system that regulates blood pressure and water balance in the body.

Sensitivity vs. specificity

Sensitivity (the true positive rate) measures the proportion of actual positives which are correctly identified (the percentage of sick people who are correctly identified as having the condition). Specificity (the true negative rate) measures the proportion of negatives which are correctly identified (the percentage of healthy people who are correctly identified as not having the condition).

Type 1 diabetes mellitus

It is a type of glucose control disturbance that results from the autoimmune destruction of insulin-producing cells in the pancreas. There is absolute lack of insulin. Type 2 diabetes mellitus It is characterized by hyperglycemia due to insulin resistance and relative lack of insulin.

Urinary albumin excretion (UAE)

The presence of albumin in the urine as a consequence of high permeable glomerular membrane and inhibition of tubular cell reabsorption.