ProteinuriaR80

Proteinuria is defined as the excretion of > 150mg protein/24h day with the urine or a deviation from the physiological protein pattern. Proteinuria is not an independent disease but a clinical symptom caused by damage to the kidneys or capillary system. From a clinical perspective, proteinuria must be evaluated as a significant risk factor for both renal failure and cardiovascular events. Therefore, it must always be clarified with regard to a triggering underlying disease.

Note. Low protein excretion in urine is physiological.

Depending on the composition and quantity of the urine proteins, a distinction is made between

• Benign proteinuria: Benign proteinuria occurs especially in young people after physical exertion, emotional stress and hypothermia. About 20% of pregnant women also have passive proteinuria during pregnancy. These benign proteinurias are physiologic and are distinguished from pathologic forms by a normal protein concentration in the morning urine (< 300 mg/l).
• Pathological proteinuria: Pathological proteinurias are further differentiated according to their underlying disorder:
  • Prerenal proteinuria
  • Glomerular proteinuria
  • Glomerular unselective proteinuria
  • Glomerular selective proteinuria
  • Tubular proteinuria
  • Postrenal proteinuria

Different forms of proteinuria:

Functional proteinuria: Occurrence e.g. during stress, physical exertion, cold, fever. Usually only mild proteinuria (<1g/24h).

Orthostatic proteinuria (position-dependent proteinuria): Occurrence only in upright position.

Intermittent proteinuria: Idiopathic transient proteinuria (in women, mild proteinuria due to fluorine is possible).

To determine proteinuria, the amount of protein in the collective urine is determined. The normal protein excretion in urine is between 60 and 150 mg within 24 hours. A excretion of > 150 mg protein/day is therefore by definition called proteinuria.

• Microalbuminuria = albumin excretion of 30-300 mg/24 h or 20-200 mg/L (urine). Due to varying albumin excretion, 3 check-ups over a period of 6-8 weeks are recommended for confirmation
• Macroalbuminuria = albumin excretion >300 mg/24 h or >200 mg/L (urine)

Albumin-creatinine ratio: As a screening test, the albumin-creatinine ratio (normal <30mg/g) in urine can be determined.

Urine test strip: A negative test field for proteins on the urine test strip does not exclude proteinuria (only detect the macroalbumin range > 200mg/l). Furthermore, L-chains are not detected in monoclonal proteinuria (Bence-Jones protein). In the case of urinary tract infections, the diagnosis cannot be reliably assessed either.

Electrophoretic separation of urine proteins (disk electrophoresis): The molecular weight-related separation of urine proteins allows a differentiated, quantitative and qualitative determination of the lead proteins in urine. The following protein patterns can be distinguished:

• Glomerular proteinuria: protein excretion due to a pathological function of the glomeruli. Characteristic is the occurrence of large molecular weight proteins
• Selective glomerular proteinuria: Only certain large proteins are found in the urine, such as albumin and transferrin, which are found in diseases with a loss of selection of the glomerular filter (e.g. minimal change glomerulonephritis)
• Non-selective glomerular proteinuria: All types of proteins can be detected in urine (markers are albumin and IgG). Occurs in diseases with severe damage to the glomerulus, so that there is permeability for all blood components (e.g. rapid-progressive glomerulonephritis)
• Tubular proteinuria: protein excretion due to impairment of the renal tubules: disturbed reabsorption of physiologically occurring small molecular weight proteins (lead protein is the low-molecular weight beta2 protein, this is glomerularly filtered and reabsorbed tubularly; in the case of disturbances in tubular reabsorption, it appears excessive in the urine even without simultaneous detection of large proteins)
• Glomerular-tubular mixed proteinuria: In diseases involving glomeruli + renal tubules, signs of both tubular and glomerular proteinuria can be detected.
• Prerenal proteinuria (overflow proteinuria): occurrence of proteins of prerenal origin in the urine. If these proteins are present in increased amounts, the tubular reabsorption capacity is exceeded. They appear in the urine.
• Bence-Jones proteinuria (e.g. light chain or Bence-Jones proteins in multiple myeloma).
• Haemoglobinuria (for haemolysis)
• Myoglobinuria (with rhabdomyolysis)
• Postrenal proteinuria: Occurrence of proteins that are produced in the tubule system (e.g. Tamm-Horsfall protein) or in the further course of the disease or that enter the urine. This situation arises in the case of injuries or inflammation (cystitis, urethritis) of the urinary tract

According to the recommendations for classification and graduation of toxicities, a proteinuria is graduated as follows:

• Grade 0: none
• Grade 1: >3 g/l
• Grade 2:3.1-10g/l
• Grade 3:>10g/l
• Grade 4: nephrotic syndrome