Figure 1. Hindlimb edema characteristic of nephrotic syndrome
Systems. Pathologic proteinuria is evidence of urinary tract disease. However, proteinuria often occurs consequent to diseases in other organ systems, including extrarenal chronic inflammatory, infectious, or neoplastic processes or altered renal hemodynamics.
Genetic Implications. Proteinuria may occur as a sign of congenital glomerulopathies (in cocker spaniels, bull terriers, dalmatians, Doberman pinschers, beagles, rottweilers, Pembroke Welsh corgis, Newfoundlands, and bull mastiffs), hereditary immune-mediated glomerulonephritis (soft-coated wheaten terriers, Bernese mountain dogs, and Brittany spaniels), familial reactive systemic amyloidosis (shar-peis, beagles, English foxhounds, and Abyssinian cats), and renal dysplasia (shih tzus, Lhasa apsos, golden retrievers, standard poodles, miniature schnauzers, Alaskan malamutes, soft-coated wheaten terriers, chow chows, and Dutch Kooikers).
Incidence/Prevalence. Incidence and prevalence poorly documented. Prevalence of microalbuminuria in clinically healthy dogs and cats estimated at 19% to 25% and about 15%, respectively.
- Prerenal proteinuria is most often due to hemoglobinuria, myoglobinuria, or Bence Jones proteinuria.
- Functional renal proteinuria occurs with pyrexia, extremes of heat and cold, strenuous exertion, seizure, and stress.
- Pathologic glomerular renal proteinuria results from glomerular lesions impairing glomerular filtration of proteins.
- Pathologic tubular renal proteinuria results from tubular diseases that impair tubular uptake of small proteins. Pathologic interstitial renal proteinuria results from infectious or noninfectious inflammatory diseases of the renal interstitium.
- Postrenal proteinuria occurs due to urinary tract infections (occurring anywhere in the urinary tract including the kidneys), uroliths, urinary neoplasia, or urinary trauma.
- Chronic inflammatory, infectious, or neoplastic diseases
- Systemic hypertension
- Chronic kidney disease
- Acute kidney injury
- Hematuria and pyuria
- Multiple myeloma
- Extremes of heat or cold
The glomerulus is a high-pressure capillary tuft that allows production of a nearly protein-free filtrate. Proteins cross to the tubular fluid in inverse proportion to their size and negative charge. Proteins with a molecular weight of less than 20,000 Daltons pass easily across the glomerular capillary wall. Conversely, albumin, with a molecular weight of approximately 65,000 Daltons and a negative charge, is restricted.
Smaller proteins may pass through the glomerulus but are normally reabsorbed by the renal tubules before excretion. Tubular proteinuria occurs when tubulointerstitial disease prevents the proximal tubule from reabsorbing low-molecular-weight proteins normally present in the glomerular ultrafiltrate.
Glomerular capillary walls -- consisting of endothelial cells, the glomerular basement membrane, and visceral epithelial cells -- form a barrier to passage of some plasma proteins. In glomerular proteinuria, disturbances of the permselectivity function of this barrier in regard to size or electrical charge of molecules lead to leakage of albumin and larger plasma proteins into the glomerular ultrafiltrate. Immune mechanisms are central to the pathogenesis of most types of glomerulonephritis. In such cases, immunoglobulins and complement factors can be demonstrated on glomerular structures. Antibody-mediated glomerular injury may result from deposition of circulating immune complexes in the glomerular capillary wall or binding of antibodies directed against antigens present in the glomerular wall (in situ immune complexes).