• Definition: an abnormally increased concentration of protein (often albumin) in urine.
• Causes: proteinuria may be prerenal, renal (which may be either glomerular or tubular), or postrenal. Glomerular proteinuria is the most important kind. In prerenal proteinuria, the kidneys are presented with an abnormally increased concentration of small proteins in the blood, which are smaller than the effective glomerular filtration barrier and exceeds the ability of the renal tubules to reabsorb it. This protein may, for example, be free hemoglobin, myoglobin or, in patients with lymphoma or multiple myeloma, immunoglobulin light chains (Bence-Jones protein). In glomerular proteinuria, the glomeruli are damaged and an abnormally large amount of protein leaks through an excessively permeable glomerular filter into the urinary space. For example, in glomerulonephritis, antigen-antibody complexes may be deposited, or may form, in the glomerular capillary basement membranes, damaging them. Damage to the filtration barrier leads to glomerular proteinuria, sometimes very severe. Glomerular amyloidosis is another important cause of severe glomerular proteinuria. Damaged renal tubules may fail to reabsorb filtered protein, leading to tubular proteinuria. In postrenal proteinuria, tissue damage or inflammation beyond the kidney tubules is responsible for the increased urinary protein concentration. For example, bacterial urinary tract infection (upper or lower) can lead to passage of proteinaceous inflammatory exudate in the urine. Transient proteinuria is poorly described in cats but occurs in humans associated with fever or exercise, which is usually mild and may be reversible with treatment of the underlying cause.
• Severity: proteinuria may be overt (detectable using conventional urine dipsticks) or less severe. Massive (or heavy) proteinuria may lead to the nephrotic syndrome (the combination of heavy proteinuria and consequent hypoalbuminemia, hypercholesterolemia and edema or ascites).
• Signs: prerenal proteinuria may be associated with discolored urine (if the protein is hemoglobin or myoglobin) and clinical signs of the underlying disease (eg myeloma, lymphoma). Postrenal proteinuria is usually associated with abnormally increased frequency of urination, straining, and, again, discolored urine (typically pink or red). Often glomerular proteinuria causes no clinical signs until it is severe. Then it may lead to hypoalbuminemia and sometimes to subcutaneous edema (eg of the distal limbs). Progressive loss of damaged glomeruli may eventually lead to renal failure (with polydipsia/polyuria, inappetence, and vomiting).
• Diagnosis: urine analysis, including sediment examination, urine protein quantitation usin the urine protein : creatinine ratio (UPCR), serum chemistry profile, and ideally histopathologic examination of a kidney biopsy. In prerenal proteinuria, there will be an excessive amount of a protein in the blood. In postrenal proteinuria, there will usually be evidence in the urine sediment of urinary tract inflammation or hemorrhage. In glomerular proteinuria, there will be excessive albumin in the urine, which may be extreme.
• Treatment: categorize the proteinuria and then eliminate the underlying cause, if possible. Glomerular proteinuria may be managed using a renal diet, antiplatelet drugs, inhibition of the renin-angiotensin-aldosterone system (RAAS) ± immunosuppressive therapy in certain cases.
• Prognosis: very variable depending upon the underlying cause and the severity. Some cases with glomerular proteinuria progress rapidly despite therapy, others remain stable for prolonged periods. If complicated by thromboembolism (eg pulmonary or caudal aortic) or stage 3 or 4 chronic kidney disease.

Presenting signs

• Cats with prerenal proteinuria may have pigmenturia (often red or brown because of the presence of hemoglobin Hemoglobinuria or myoglobin Myoglobinuria) or other signs related to the underlying cause (eg bone pain, radiographically-evident lucent bone lesions, lymphadenopathy).
• Patients with postrenal proteinuria may have kidney pain (due to pyelonephritis Pyelonephritis), discolored urine Discolored urine, increased frequency of urination, straining to urinate, or other signs of urinary tract inflammation Feline lower urinary tract disease (FLUTD).
• Patients with glomerular proteinuria often have no clinical signs unless urinary protein loss is severe. Non-specific signs of malaise (eg lethargy, depression, weight loss) may develop. Peripheral (eg distal limb) subcutaneous edema will develop if hypoalbuminemia Hypoproteinemia becomes sufficiently severe. Ascites and/or pleural effusion Pleural effusion may develop. Polydipsia / polyuria Polyuria/polydipsia (PU/PD) can develop if glomerular injury is sufficiently severe to cause progressive nephron loss.
• Signs of an underlying infectious, inflammatory or neoplastic disorder may be evident in patients with glomerulonephritis Glomerulonephritis (although often not).

Acute presentation

• Acute dyspnea or sudden death if pulmonary thromboembolism complicates severe glomerular proteinuria.
• Cold, pulseless, paralyzed hind limbs with nail-bed cyanosis if caudal aortic (saddle) thrombosis Thromboembolism: aorta develops.
• Signs of uremia Uremia if severe renal failure Kidney: chronic kidney disease ensues. Signs of uremia include profound depression, anorexia Anorexia, vomiting Vomiting, halitosis, weight loss, and oral and gastric mucosal ulceration.

Age predisposition

• Any age.
• Membranous glomerulopathy (syn. membranous glomerulonephropathy, membranous nephropathy), a major cause of glomerular proteinuria in cats, is 6 times more common in males than in females and is more common in young cats (mean 3.6 years; range 1-7 years)
• Cats with familial amyloidosis Amyloidosis are usually less than 5 years old when they are first diagnosed. Often they are presented in renal failure, rather than because of heavy proteinuria (this is because amyloid deposits are predominantly in the renal medulla rather than the glomeruli).
• Glomerulonephropathy can develop at any age, but is more frequently diagnosed in middle-aged to older animals.
• Most of the causes of prerenal and postrenal proteinuria are also more common in middle-aged to older animals.

Breed/Species predisposition

• Renal amyloidosis (not always associated with heavy proteinuria):
  • Abyssinian Abyssinian.
  • Siamese Siamese.
  • Oriental shorthair Oriental shorthair.

Special risks

• Anesthesia of cats with unrecognized glomerular proteinuria may lead to acute kidney injury.
• Arterial thromboembolism may complicate severe glomerular proteinuria. This is because severe glomerular proteinuria leads to a hypercoagulable state. This state results partly from urinary loss of antithrombin-3 and partly because platelet activity may be increased in hypoproteinemic patients.