Glomerulonephritis in Cats (Felis) | Vetlexicon
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Glomerulonephritis

ISSN 2398-2950


Introduction

  • Cause: deposition orin situ formation of antigen-antibody complexes in the basement membranes of glomerular capillaries in the kidneys. 
  • Signs: ususally no clinical signs until advanced. Proteinuria leads to hypoalbuminemia and sometimes to ascites or edema. Severe glomerular damage leads to loss of nephrons and eventually to renal failure (causing polydipsia/polyuria, inappetence, vomiting).
  • Diagnosis: urine analysis, serum chemistry profile, histopathologic examination of kidney biopsy.
  • Treatment: detect and eliminate the underlying source of antigen, if possible. Special diet, angiotensin-converting enzyme (ACE) inhibition, +/- low-dose aspirin (with great care), +/- immunosuppressant/immunomodulator therapy.
  • Prognosis: variable. Some cases progress rapidly despite therapy, others remain stable for prolonged periods. Many undetected cases probably go on to develop renal failure and are diagnosed at that stage. If complicated by thromboembolism, eg pulmonary or caudal aortic, prognosis is poor.

Presenting signs

  • Often no clinical signs present.
  • Sometimes signs of an underlying infectious, inflammatory or neoplastic disorder are present.
  • Non-specific signs of malaise, eg lethargy, depression, weight loss.
  • Ascites, pleural effusion or subcutaneous edema, eg of distal limbs.
  • Polydipsia/polyuria if nephron loss is severe enough to cause renal insufficiency or failure.

Acute presentation

  • Acute dyspnea or sudden death if pulmonary thromboembolism Thromboembolism: aorta  develops. 
  • Cold, pulseless, paralyzed hind limbs with nail-bed cyanoisis if aortic 'saddle' thrombosis develops.
  • Signs of uremia if acute or chronic renal failure Kidney: acute renal failure Kidney: chronic kidney disease develops. Acute signs of uremia include:
    • Profound depression.
    • Anorexia.
    • Vomiting.
    • Halitosis.
    • Oral and gastric mucosal ulceration.

Special risks

  • Failure to recognize that GN is present in a particular patient can increase the risks below.
  • Anesthesia of GN-affected cats Anesthesia: in renal insufficiency may lead to acute renal failure.
  • Treatment of GN-affected cats with potentially nephrotoxic drugs may cause acute renal failure.

Pathogenesis

Etiology

Predisposing factors

General

  • An inflammtory, infectious, or neoplastic source of antigens that can contribute to immune complex formation.
  • A familial predisposition to form immune complexes in the glomeruli (not confirmed in cats).
  • Altered, ie increased, intestinal permeability may allow entry of antigens and play a role in some cats.

Pathophysiology

  • Antigen-antibody (Ag-Ab) complexes deposit or form at the glomerulus capillary basment membranes    →     complement activation   →   cell membrane damage   →   leukocyte attraction and platelet aggregation    →   glomerular injury   →    leakage of proteins, especially albumin, through the glomerular filter   →    proteinuria   →    (if severe) hypoalbuminemia Hypoproteinemia, weight loss, ascites, peripheral edema and hypercholesterolemia.
  • Cellular proliferation, mesangial cell contraction and glomerular obliteration   →   decreased glomerular filtration through affected glomeruli   →   increased glomerular filtration through other, less damaged nephrons   →   'hyperfiltration' and glomerulosclerosis of remaining nephrons   →   (if sufficiently severe) chronic renal failure.
  • Loss of antithrombin III, platelet hyperactivity, and (sometimes) thrombocytosis     →   hypercoagulable state   →    thromboembolic disorders (lungs, caudal aorta).

Timecourse

  • Variable. Disease may progress rapidly or remain stable for years.

Diagnosis

Presenting problems

  • Sometimes an incidental finding on a routine health screen.
  • Sometimes signs related to the underlying source of antigens are the reason for presentation.
  • Lethargy.
  • Weight loss Weight loss.
  • Polyuria/polydipsia (if renal insufficiency develops).
  • Vomiting Vomiting, anorexia (if uremia Uremia develops).

Client history

  • Often no abnormalities are reported.
  • Sometimes the history relates to the underlying source of antigens.
  • Lethargy.
  • Weight loss.
  • Muscle wasting.
  • Abdominal enlargement (if ascites present).
  • Polyuria/polydipsia (if complicated by renal insufficiency).
  • Acute dyspnea (if thromboembolism present).
  • Vomiting (if uremic).

Clinical signs

  • Often there are no clinical signs.
  • Sometimes signs are related to the underlying source of antigens.
  • Weight loss, muscle wasting.
  • Poor hair coat.
  • Ascites.
  • Abnormal kidney size (large or small), shape (lumpy), or texture (swollen, turgid).
  • Signs of uremia Uremia.
  • Dyspnea, cyanosis (if complicated by pulmonary thromboembolism).
  • Hindlimb paralysis, cyanosis, absence of femoral pulses (if complicated by aortic 'saddle' thrombosis).
  • Hyphema or retinal detachment in some cats (if GN complicated by severe systemic hypertension Hypertension).

Diagnostic investigation

Urinalysis

  • Preferably obtain urine by cystocentesis Cystocentesis.
  • There should be no gross hematuria Hematuria, or evidence of urinary tract infection (pyuria, bacteruria, large amounts of cellular debris) on urine sediment examination Urinalysis: centrifuged sediment.
  • Proteinuria Urinalysis: protein may be detected on routine dipstick, or using another semi-quantitative method.
  • Urine protein creatinine ratio (UPC) is increased; usually³2, and often much higher.
  • Somtimes hyaline casts are seen on sediment examination.

Serum biochemistry

Hematology

  • Evidence of systemic inflammation or infection in some cases.
  • Normocytic, normochromic, non-regenerative anemia Anemia: blood loss in some cases; especially those with chronic inflammation or renal faillure.
  • Sometimes concurrent immune-mediated thrombocytopenia or anemia is present.

Radiography

  • Look for an underlying infectious, inflammatory or neoplastic process, particularly in the body cavities Radiography: abdomen.
  • Poor detail and contrast, due to ascites, may be present in some advanced cases.
  • A small pleural effusion may be present in a few advanced cases.
  • Kidneys may appear enlarged, small, irregular or (often) normal.

2-D Ultrasonography

  • See ultrasonography of the kidney Ultrasonography: kidney.
  • Look for an underlyling infectious, inflammatory or neoplastic process, particularly in the body cavities.
  • Normal or decreased cortico-medullary demarcation in the kidneys (non-specific).
  • Dilated renal pelvis if polydipsic/polyuric.

Abdominocentesis (if ascites present)

Histopathology

  • Renal biopsy and histopathological examination required for definitive diagnosis.
  • Ultrasound-guided needle biopsy Biopsy: ultrasound-guided is commonly done, several pieces may need to be taken if a small biopsy needle is used (consult your pathologist). Checking a coagulation profile, measuring arterial blood presure, and having fresh, frozen plasma on hand are usually recommended prior to needle biopsy.

Serology

  • Check for some potentially underlying, infectious diseases, eg FeLV, FIV (where appropriate).

Arterial blood pressure measurement

  • Systemic arterial hypertension commonly replicates GN.

Confirmation of diagnosis

Discriminatory diagnostic features

  • Heavy proteinuria +/- hyaline casts in the absence of other urine sediment abnormalities.
  • Hypoalbuminemia, hypercholesterolemia.

Definitive diagnostic features

  • Characteristic histopathologic findings on kidney biopsy Kidney: surgical approach. Most affected cats have membranous glomerulonephropathy.

Gross autopsy findings

  • May be no gross lesions.
  • Variable kidney size.
  • Chronic cases may have renal fibrosis causing firmness of renal parenchyma, perhaps with some scarring and alteration of renal outline.
  • Check for evidence of uremia/renal failure.

Histopathology findings

  • Membranous GN is most common in cats.
  • Proliferation of mesangial and glomerular capillary cells, with thickening of basement membranes.
  • There may be tuft atrophy, thickening of Bowman's capsule, tubular protein casts and interstitial fibrosis.

Differential diagnosis

  • Glomerular disease that is not GN, eg familial renal amyloidosis Amyloidosis in Abyssinian cats.
  • Bacterial urinary tract infection (can cause proteinuria, but sediment usually shows evidence of inflammation).
  • Severe liver disease (causes hypoalbuminemia, but not heavy proteinuria).
  • Severe gastrointestinal disease (protein-losing enteropathy Protein-losing enteropathy typically causes hypoalbuminemia and hypoglobulinemia, not just hypoalbuminemia).
  • In patients with acites, other causes of abdominal fluid accumulation (abdominal neoplasia, peritonitis Peritonitis, portal hypertension Hypertension, abdominal hemorrhage).
  • Hyperthyroidism Hyperthyroidism often causes mild proteinuria.

Treatment

Initial symptomatic treatment

  • It is important to detect and eliminate the underlying source of antigens, if possible.
  • Manage renal insufficiency/failure appropriately, if it has developed.
  • Manage systemic hypertension, if it is complicating the GN.

Diet

  • Feed a moderately protein-restricted, high-quality protein diet. Sodium restriction and n3 fatty acid supplementation.

ACE inhibition

  • ACE inhibitors ACE inhibitors: overview help reduce the degree of proteinuria and sloe disease progression. Monitor for developing or worsening azotemia and lower the dose of ACE inhibitor, if azotemia worsens substantially.
  • If sytemic hypertension is present, and is not controlled by ACE inhibition alone, use other antihypertenisve drugs, eg amlodipine Amlodipine, in conjunction with the ACE inhibitor.

Anti-platelet therapy

  • Helps reduce the deleterious glomerular reponse to the presence of immune complexes.
  • Aspirin (low dose 0.5 mg/kg, PO BID). Start after recovery from kidney biopsy. Although this is a very low dose, observe animals with renal failure closely. Do not dose in the face of dehydration. 

Immunomodulation

Immunosuppressant therapy for GN is controversial and there is little evidence to support its use.

  • Glucocorticoids are not recommended because they can worsen proteinuria and promote thromboembolism. However, if immune-mediated polyarthritis, thrombocytopenia or hemolytic anemia complicate GN, a glucocorticoid may have to be used.
  • In one study, cyclosporine Ciclosporin was shown not to be effective in treatment of canine GN. There was no equivalent study for cats.

Managing edema or ascites

  • Paracentesis or thoracocentesis is rarely needed for management of ascites/pleural effusion Pleural effusion. Use if respiratory distress or excessive effort is evident.
  • Sodium restriction will help.
  • Furosemide Furosemide (1-2 mg/kg as needed) is sometimes used to control edema or ascites, but its use may exacerbate hypovolemia and promote azotemia and even uremia. It should be used with caution and careful monitoring, if at all.
  • Plasma transfusion, with careful monitoring, may be indicated in severely hypoproteinemic cases.

Prevention

Outcomes

Prognosis

  • Variable. Depends on response to therapy. Heavy proteinuria and presence of azotemia at the time of diagnosis of GN are usually considered negative prognostic indicators. However, some patients with heavy proteinuria make a full recivery, especially if an underlying source of antigen is detected and eliminated. Even if the source of antigen is not found, some animals respond well to therapy and may remain stable for years. Many cases eventually progress to chronic renal failure and need to be managed for that.
  • The prognosis is generally poor if thromboembolism develops.

Expected response to treatment

  • Improvement in clinical demeanor.
  • Diminishing proteinuria as assessed by monitoring serial urine protein creatinine ratios (improvement typically over days to weeks).
  • Control of systemic hypertension.

Reasons for treatment failure

  • Progression to chronic renal failure with uremia.
  • Progressive or uncontrolled proteinuria, hypoalbuminemia   →   intractable edema or fatal thromboembolism.
  • Uncontrolled hypertension   →   fatal cerebral vascular accident or other complications.

Further Reading

Publications

Refereed papers

  • Recent references from PubMed and VetMedResource.
  • Grauer G F (2007) Measurement, interpretation, and implications of proteinuria and albuminuria. Vet Clin North Am Sm Anim Pract 37 (2), 283-295 PubMed.
  • Elliott J & Syme H M (2006) Proteinuria in chronic kidney disease in cats-prognostic marker or therapeutic target? J Vet Intern Med 20 (5), 1052-1053 PubMed.
  • Kuwahara Y, Ohba Y, Kitoh K et al (2006) Association of laboratory data and death within one month in cats with chronic renal failure. JSAP 47 (8), 446-450 PubMed.
  • Langston C E & Reine N J (2006) Hyperthyroidism and the kidney. Clinical techniques in Small Animal Practice 21 (1), 17-21 PubMed.
  • Mardell E J & Sparkes A H (2006) Evaluation of a commercial in-house test kit for the semi-quantitative assessment of microalbuminemia in cats. J Fel Med Surg (4), 269-278 PubMed.
  • Syme H M, Markwell P J, Pfeiffer D et al (2006) Survival of cats with naturally occurring chronic renal failure is related to severity of proteinuria. J Vet Intern Med 20 (3), 528-535 PubMed.
  • Welles E G, Whatley E M, Hall A S et al (2006) Comparison of Multistix PRO dipsticks with other biochemical assays for determining urine protein (UP), urine creatinine (UC) and UP:UC ratio in dogs and cats. Vet Clin Pathol 35 (1), 31-36 PubMed.
  • White J D, Norris J M, Baral R M et al (2006) Naturally-occurring chronic renal disease in Australian cats: a prospective study of 184 cases. Aust Vet J 84 (6), 188-194 PubMed.
  • Lees G E, Brown S A, Elliott J et al (2005) Assessment and management of proteinuria in dogs and cats: 2004 ACVIM Forum Consensus Statement (small animal). J Vet Intern Med 19 (3), 377-385 PubMed.
  • Lees G E (2004) Early diagnosis of renal disease and renal failure. Vet Clin North Am Sm Anim Pract 34 (4), 867-885 PubMed.
  • Osbourne C A, Bartges J W, Polzin D J et al (1996) Percutaneous needle biopsy of the kidney. Inidcations, applications, technique, and complications. Vet Clin North Am Sm Anim Pract 26 (6), 1461-1504 PubMed.
  • Arthur J E, Lucke V M, Newby T J et al (1986) The long term prognosis of feline idiopathic membranous glomerulonephritis. JAAHA 22 (6), 731-737 VetMedResource.
  • Nash A S, Wright N G, Spencer A J et al (1979) Membranous nephropathy in the cat: a clinical and pathological study. Vet Rec 105 (4), 71-77 PubMed.