Etiology
Proteinuria can be transient or persistent. Transient proteinuria can be detected in several clinical scenarios, including after heavy physical exertion, in patients with fever, during urinary tract infection, and in patients with significant urologic hemorrhage. Proteinuria can also occur with the assumption of upright posture (orthostatic proteinuria). Transient and orthostatic proteinuria are of little clinical significance.[29][30]
Glomerular
The glomerulus forms a barrier to the filtration of large blood proteins into the urinary space. Disruption or loss of the glomerular basement membrane or podocyte foot process effacement allows protein to pass from glomerular capillary blood into the urine. Since albumin is the major protein in blood, glomerular proteinuria is defined by a predominance of albumin.
Proteinuria accompanied by hematuria is more likely to be caused by a glomerular etiology. Glomerular proteinuria is typically in the range of 1 to 20 g/day. Moderately increased albuminuria is also considered to be of glomerular etiology, although the absolute quantity does not meet the definition for overt proteinuria. Moderately increased albuminuria is seen in disease processes characterized by endothelial dysfunction (e.g., diabetic nephropathy) with resultant disruption of the glomerular endothelial lining.
Glomerular causes of proteinuria include:
Diabetic nephropathy
Minimal change disease
Focal segmental glomerulosclerosis
Membranous nephropathy
Membranoproliferative glomerulonephritis
IgA nephropathy
Systemic lupus erythematosus
Postinfectious glomerulonephritis
Hemolytic uremic syndrome
Thrombotic thrombocytopenic purpura
Scleroderma renal crisis
Medium- and small-vessel vasculitis
Amyloidosis
Light and heavy chain deposition diseases
Fibrillary/immunotactoid glomerulopathy
Proliferative glomerulonephritis with IgG deposition
Idiopathic nodular glomerulosclerosis
Fabry disease
Anti-glomerular basement membrane (anti-GBM) disease
In patients with glomerular disease, reduction in proteinuria is associated with a lower risk of disease progression.[21][31]
Tubular
Low-molecular-weight proteins are freely filtered at the glomerulus. In healthy people, the proximal renal tubules metabolize and reabsorb virtually all of this protein to prevent urinary loss. In the setting of tubular dysfunction, abnormal quantities of low-molecular-weight proteins (e.g., retinol-binding protein, alpha-2-microglobulin, beta-2-microglobulin) may escape metabolism and are excreted in the urine. Tubular proteinuria may accompany other markers of tubular dysfunction (e.g., glucosuria, phosphaturia, proximal renal tubular acidosis), and protein excretion is typically <1.5 to 2 g/day. With predominantly tubular proteinuria, the ratio of 24-hour albumin to beta-2-microglobulin excretion is generally in the range of 1 to 13, with the ratio in glomerular proteinuria being >1000.[32] Tubular proteinuria often coexists with glomerular proteinuria.
Tubular causes of proteinuria include:
Acute tubular injury
Interstitial nephritis
Urinary tract obstruction
Fanconi syndrome
Cystic kidney disease
Heavy metal poisoning
Hypercalciuria
Dent disease
Aristolochic acid nephropathy
Overflow
Production of abnormal quantities of protein that exceeds the reabsorptive capacity of the proximal tubules will result in proteinuria. The classic example is the overproduction of monoclonal light chains in a patient with multiple myeloma. The low-molecular-weight light chains are freely filtered at the glomerulus at a concentration surpassing the reabsorptive capacity of the renal tubules. These light chains are subsequently excreted in the urine. Similar to glomerular proteinuria, the total quantity of proteinuria can reach up to 20 g/day.
Overflow causes of proteinuria include:[33]
Light chain cast nephropathy
Rhabdomyolysis
Polymyositis
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