Contributors: Phil Nicholls, Melissa Wallace, Rosanne Jepson

 Species: Canine   |   Classification: Diseases

Introduction Pathogenesis Diagnosis Treatment Outcomes Further Reading

Introduction

  • Cause: in younger animals consider congenital or familial renal disease. In older animals usually acquired, progressive tubulointerstitial nephritis. Results in an inability of the kidney to perform normal functions of waste excretion, fluid/electrolyte/acid-base homeostasis or endocrine function. Some kidney disease may be primarily associated with dysfunction, eg nephrogenic diabetes insipidus, renal tubular acidosis, cystinuria without obvious morphological abnormalities.
  • Signs: in early stages (International Renal Interest Society (IRIS) stage I-II) clinical signs may be mild or not detected. With progressive decline in renal function (IRIS stage II-IV) clinical signs can include polyuria/polydipsia and signs associated with uremia (nausea, vomiting, anorexia, oral ulceration, weight loss, constipation). Duration >3 months implies chronicity.
  • Treatment: management should be based on IRIS staging (Table 3) but may include phosphate restricted renal diet +/- dietary phosphate binders, gastroprotectants, anti-emetics, anti-proteinuric therapy, subcutaneous/intravenous fluid therapy, erythrocyte stimulating agent, calcitriol, anti-hypertensive therapy.
  • Prognosis: early detection of CKD permits management of associated pathophysiological adaptations, eg secondary renal hyperparathyroidism, proteinuria and systemic hypertension, which may slow progression of disease. Management of clinical signs of uremia may improve quality of life.
Print off the owner factsheet on Chronic kidney disease (CKD) to give to your client. Use the interactive tools from ROYAL CANIN® UK to explain dog anatomy and disease conditions to your client. Visit ROYAL CANIN Natom Explorer to find out more.​

Presenting Signs

  • Dependent on stage of CKD:
    • International renal interest society (IRIS) stage I-II CKD: clinical signs mild or not identified.
    • IRIS stage (II-IV) presenting signs may include polyuria/polydipsia, hyporexia/anorexia, weight loss, sarcopenia, vomiting/nausea, lethargy, constipation.
  • End-stage disease patients may present in uremic crisis Uremia with clinical signs as above in addition to collapse, dehydration, halitosis, oral ulceration, tongue tip necrosis, nausea, vomiting, hypothermia, muscle tremors, uremic encephalopathy.

Acute Presentation

  • Historical information should provide evidence of chronic disease > 3 months duration. However, acute decompensation of CKD may result in acute presentation with clinical presentation attributed to uremic crisis.

Age Predisposition

  • Young animals < 4 years for congenital/familial kidney disease.
  • Usually older dogs for acquired disease but may affect dogs of any age.

Breed Predisposition

  • Tubulointerstitial nephritis: no breed predisposition identified.
  • Familial or congenital kidney disease: see etiology below.

Special Risks

  • Increased risk with anesthesia Anesthesia: in renal insufficiency : consider requirement for fluid therapy.
  • Increased risk of decompensation with pre-renal causes, eg heat stress or dehydration.
  • Increased risk of occult urinary tract infection.
  • Increased risk of systemic hypertension Hypertension.
  • Increased risk of decompensation with use of nephrotoxic drugs:
    • Avoid use of nephrotoxic drugs if alternative possible.
    • Monitor renal function carefully if unavoidable.
  • Consider drug dose and frequency with renal excreted medications.

Pathogenesis

Etiology

Etiology 
Table 1: Etiology of acquired chronic kidney disease
Tubulointersitial nephritis 
Chronic nephrotoxin exposure 
Obstructive nephropathyNephrolithiasis, ureterolithiasis, spay granuloma,
transitional cell carcinoma of bladder affecting ureterovesicular junction
Drug associatedNSAID, antibiotics
Immune mediated 
Renal ischemia 
Proteinuric kidney diseaseAmyloidosis
Primary congenital/juvenile glomerulopathy
Secondary glomerulopathy, eg immune complex mediated
InfectiousBacterial - Leptospirosis, pyelonephritis, Lyme nephritis
Mycotic - Candida albicans, blastomycosis
Leishmaniasis
MetabolicHypercalcemia
Hypokalemia
NeoplasiaRenal lymphoma
Renal carcinoma
Nephroblastoma
 
Renal pathologyBreed associations
Table 2: Congenital or familial chronic kidney disease
Renal dysplasiaShih Tzu, Golden Retriever, Norwegian Elkhound,
Lhasa Apso, Chow chow, Standard poodle,
Soft Coated Wheaten Terrier, Alaskan malamute,
Miniature Schnauzer
GlomerulopathyEnglish Cocker Spaniel, Doberman Pinscher, English bull terrier,
Soft Coated Wheaten Terrier, Samoyed, Dalmation, Bullmastiff,
Newfoundland, Beagle, Bernese Mountain dog, Pembroke Welsh Corgi
AmyloidosisShar-pei, English Foxhound, Beagle
Polycystic kidney diseaseBull Terrier, West Highland White Terrier, Cairn Terrier
Reflux nephropathy with segmental hypoplasiaBoxer
TelangectasiaPembroke Welsh Corgi
Fanconi syndromeBasenji
Hereditary multifocal renal cystadenocarcinomaHereditary multifocal renal cystadenocarcinoma

Pathophysiology

  • Reduction of functional nephrons → loss of ability to concentrate urine and retention of waste products.
  • Hyperfiltration of remaining nephrons → self-perpetuating destruction of remaining nephrons.
  • Metabolic acidosis → renal ammoniagenesis → toxic and inflammatory effect on renal interstitium.
  • Uremia → erythropoietin deficiency and shortened RBC lifespan → normochromic, normocytic, non-regenerative anemia.
  • Hyperphosphatemia Hyperphosphatemia , due to inability to excrete phosphate → hyperparathyroidism → renal osteodystrophy and soft tissue mineralisation (including nephrocalcinosis which may potentiate renal damage).
  • Lack of active vitamin D3 (calcitriol) → initiates and exacerbates hyperparathyroidism.
  • Proteinuria Proteinuria → increased tubular reabsorption potential to promote tubulointerstitial inflammation → progression of tubulointerstitial nephritis.
  • Systemic hypertension → transfer of high systemic pressure to glomerular capillaries → development of glomerular hypertension, glomerular hyperfiltration and glomerulosclerosis → perpetuating renal damage.

Timecourse

  • Timecourse is variable and difficult to predict. Some animals can be managed for a long period, while others may show more rapid progression of disease.

Diagnosis

Presenting Problems

Client History

  • Chronic duration of clinical signs differentiates from acute kidney injury Kidney: acute kidney injury (AKI).
  • Historical information from clients may include:
    • Polyuria/polydipsia.
    • Hyporexia/anorexia.
    • Weight loss.
    • Lethargy.
    • Vomiting/nausea.
    • Constipation.
    • Halitosis.
  • Patients presenting with uremic crisis client history as above but in addition may include:
    • Weakness.
    • Muscle tremors.
    • Collapse.
    • Neurological signs.
    • Diarrhea.
    • Melena.
    • Hematochezia.

Clinical Signs

  • Polyuria/polydipsia.
  • Hyporexia/anorexia.
  • Weight loss.
  • Lethargy.
  • Vomiting/nausea.
  • Constipation.
  • Low body condition.
  • Sarcopenia/low muscle condition score.
  • Pale mucous membranes.
  • Halitosis.
  • Small irregular kidneys.
  • Enlargement of parathyroid glands.
  • Uremic crisis (as above) in addition to:
    • Weakness.
    • Collapse.
    • Muscle tremors.
    • Uremic stomatitis/oral ulceration/tongue tip necrosis/xerostomia.
    • Uremic pericarditis.
    • Uremic pneumonitis.
    • Uremic enterocolitis (melena, hematochezia, diarrhea).
    • Altered behavior/uremic or hypertensive encephalopathy.
    • Hypothermia.

Diagnostic Investigation

Serum biochemistry

Urinalysis

  • Specific gravity Urinalysis: specific gravity , dipstick Urinalysis: dipstick analysis , sediment examination:
    • Inadequate urine concentrating ability (specific gravity <1.030) with documented azotemia confirms renal origin.
  • Urine culture preferably from sterile sample, eg cystocentesis Cystocentesis /catheter.
  • Urine protein to creatinine ratio (UP/C) Renal function assessment :
    • Should be performed only after documentation of inactive sediment and negative urine culture Urinalysis: bacteriology.
    • Consider pooled urine samples (equivolume of urine collected from 3 morning samples) for patients with UP/C >2.

Hematology

Radiography

  • See abdominal radiography Radiography: abdomen :
    • Assessment of kidney (size, shape, location, number), uroliths or masses affecting kidney ureter, bladder and urinary bladder (size, shape, presence of uroliths).
    • Common findings:
      • Small and irregular kidneys Kidney small - radiograph.
      • Evidence of constipation.
      • Bone demineralisation consistent with renal secondary hyperparathyroidism Renal secondary hyperparathyroidism. May be most apparent in mandible "rubber jaw".
      • Soft tissue mineralisation particularly affecting stomach, kidneys, aorta.

2-D Ultrasonography

Biopsy

Gross Autopsy Findings

  • Kidneys are small, pale, irregular in outline, firm to cut, may be calcified.
  • Gross signs of uremia Uremia may be present.

Histopathology Findings

  • Findings dependent on underlying etiology.
  • Common findings in tubulointerstitial nephritis include:
    • Tubulointerstitial lymphoplasmacytic inflammation.
    • Fibrosis.
    • Mineralization.
    • Tubular atrophy.
    • Glomerular hypertrophy.
    • Glomerulosclerosis.

Differential Diagnosis

  • See etiology of CKD.
  • Differentials for polyuria/polydipsia.

Treatment

Initial Symptomatic Treatment

  • IV fluid therapy Fluid therapy (after taking blood and urine samples) if animal is dehydrated and/or presents in uremic crisis.

Standard Treatment

  • Options for standard treatment outlined below.
  • Treatment and management should reflect the individual patient.
    IRIS recommendations for stage specific therapy can be found at: http://www.iris-kidney.com:
    • Treat underlying cause if known (all IRIS stages).
    • Discontinue nephrotoxic medications (all IRIS stages).
    • Identify and treat any pre-renal or post-renal abnormalities (all IRIS stages).
    • Maintain adequate hydration (all IRIS stages).
    • IV fluid therapy to correct hypovolemia and dehydration.
    • Ensure adequate free access to water.
  • Antihypertensive therapy:
    • Should be started in patients with systolic blood pressure in ACVIM/IRIS substage moderate/severe risk category > 2 occasions 1-4 weeks apart or with evidence of hypertensive target organ damage, eg hypertensive retinopathy/choroidopathy on single occasion (Table 5); all IRIS stages):
  • Antiproteinuric therapy:
    • Requirement dependent on IRIS stage (Table 3).
    • Documentation of persistence of proteinuria ideally performed prior to starting anti-proteinuric therapy.
    • IRIS stage I/early stage II (non-azotemic):
      • UP/C >2.0: investigate underlying disease and treat with anti-proteinuric measures.
      • UP/C 1.0-2.0: thorough investigation for underlying disease and close monitoring.
      • UP/C 0.5-1.0: close monitoring.
    • IRIS stage II-IV (azotemic):
      • UP/C >0.5 Investigate underlying disease and treat with anti-proteinuric measures.
    • Antiproteinuric therapy options:
      • Angiotensin converting enzyme inhibitor (enalapril Enalapril , benazepril Benazepril ) + renal diet Dietetic diet: for chronic kidney disease (CKD).
        • Caution re decline in GFR and exacerbation of azotemia particularly in patients with IRIS stage III/IV disease.
      • Angiotensin receptor blocker (telmisartan, losartan) + renal diet:
        • Caution re decline in GFR and exacerbation of azotemia particularly in patients with IRIS stage III/IV disease.
      • Low dose aspirin therapy if serum/plasma albumin Blood biochemistry: albumin <20 g/l (2.0 g/dL).
  • Phosphate restricted renal diet (azotemic IRIS stage II-IV or as part of management of proteinuria for IRIS stage I-IV (see above)):
    • Concurrent benefits of commercial renal diet Dietetic diet: for chronic kidney disease (CKD) include:
      • Restricted high quality protein.
      • Moderate sodium restriction.
      • Potassium supplementation.
      • Polyunsaturated fatty acid supplementation.
      • Alkalinization.
      • Vitamin B and vitamin C supplementation.
  • Oral phosphate binders (aluminium hydroxide, calcium acetate, calcium carbonate+/- chitosan, lanthanum carbonate) (azotemic IRIS stage II-IV where dietary therapy alone is inadequate to attain IRIS phosphate target (Table 6)):
    • Caution re development of hypercalcemia with administration of calcium based phosphate binder.
    • MUST be administered with food.
  • Potassium supplementation (all IRIS stages with evidence of hypokalemia Hypokalemia ).
  • Calcitriol therapy (IRIS stage III-IV only when control of hyperphosphatemia has been achieved and adequate monitoring of serum phosphate, ionized calcium and PTH is available).
  • Address metabolic acidosis (blood bicarbonate Blood biochemistry: bicarbonate or total CO2 <18 mmol/l) once stabilized on renal diet (most likely to be identified in IRIS stage III/IV):
    • Oral sodium bicarbonate (or potassium citrate if hypokalemic) to effect.
    • Target bicarbonate/ total CO2 18-24 mmol/l.
  • Supportive therapy (all IRIS stages on an individual patient basis):
    • Gastroprotectant:
    • Anti-emetic:
    • Consider additional measures to prevent episodes of dehydration:
      • Subcutaneous fluid administration for chronic maintenance of hydration status.
      • Fluid therapy via esophageal feeding tube.
    • Erythrocyte stimulating agents:
      • Darbepoetin (modified human erythropoietin analogue - consider risk of anti-erythropoietin antibody and development of aplastic anemia).
    • Blood transfusion Blood: transfusion if clinical requirement with severe anemia.
    • Assisted nutrition:
      • Esophageal feeding tube placement.
      • Can be used for maintaining hydration status.
    • Treatment as necessary for urinary tract infections (ideally based on urine culture and sensitivity results).
IRIS StageSerum/plasma phosphate target
(mg/dl/ mmol/l)
Table 6: International Renal Interest Society targets for serum/plasma phophate
II>2.7 < 4.6 / >0.9 < 1.5
III<5.0 / <1.6
IV<6.0 / <1.9

Monitoring

  • Historical information: severity/progression of clinical signs.
  • Physical examination:
    • Hydration status (skin tent, mucous membranes, pulse rate and quality).
    • Body condition, muscle condition and body weight.
    • Presence of anemia (pale mucous membranes/heart rate/pulse quality/respiratory rate).
    • Clinical signs of uremia (oral ulceration, uremic stomatitis).
    • Hypokalemic myopathy Myopathies.
    • Constipation Constipation.
  • Serum biochemistry:
    • Azotemia & IRIS stage.
    • Hyperphosphatemia Hyperphosphatemia.
    • Hypokalaemia.
    • Acid-base status.
  • Packed cell volume Hematology: packed cell volume /total solids.
  • Complete blood count Hematology: complete blood count (CBC) for development of non-regenerative anemia Anemia: non-regenerative.
  • Systolic blood pressure +/- fundic examination for development of systemic hypertension.
  • Urinalysis (specific gravity, dipstick, sediment examination):
    • Development of urinary tract infection Cystitis.
    • Urine protein to creatinine ratio.

Subsequent Management

Treatment

  • Continue renal phosphate restricted diet:
    • Target IRIS phosphate (Table 6).
  • Management of hyperphosphatemia:
    • Addition of oral phosphate binders when IRIS phosphate target exceeded despite feeding of renal phosphate restricted diet.
    • Target IRIS phosphate (Table 6).
  • Management of proteinuria:
    • Target IRIS borderline/non-proteinuric (UP/C <0.5) or 50% reduction from baseline UP/C (Table 4).
  • Management of systemic hypertension:
    • Target Minimal/Mild ACVIM hypertension guideline risk category (Table 5).
  • Consideration of erythrocyte stimulating agents (darbepoetin) with development of clinically significant anemia (typically when packed cell volume <18%).
  • Symptomatic therapy as indicated on individual patient basis with progression of clinical signs (see above).

Monitoring

  • Frequency dependent on IRIS stage/severity of azotemia, clinical signs and progression of CKD.
  • Once stable CKD established, typically monitoring q2-4 months adequate.
  • More frequent monitoring required in certain circumstances, eg advanced stage (IRIS stage III/IV), with evidence of progressive disease, during stabilization of systemic hypertension, adjustments to anti-proteinuric therapy, when controlling hyperphosphatemia or treating concurrent conditions, eg urinary tract infections.
  • Monitoring as above.

Outcomes

Prognosis

  • Poor:

    • If renal disease is advanced (IRIS stage IV) at diagnosis and underlying disease cannot be treated.
    • Presentation in uremic crisis, clinical signs persist and animal remains severely uremic, despite adequate rehydration (intensive therapy for 3-7 days).
  • Guarded:
    • If detected at a very early stage (IRIS stage I/II) and appropriate therapy is started, progression may be delayed.
    • Some animals may remain compensated for a long period on maintenance therapy.
    • If underlying renal disease can be treated prognosis may be improved, although some permanent damage may already have occurred.
    • If kidney function remains stable or is documented to be only slowly progressive with monitoring.
    • If level of uremia and symptoms decrease after appropriate fluid therapy.

Expected Response to Treatment

  • Improvement in clinical signs and quality of life with symptomatic therapy.
  • Improvement in biochemical/hematological parameters:
    • Control of hyperphosphatemia if present.
    • Control of hypokalemia if present.
    • Control of proteinuria if present.
    • Improvement in anemia if present with darbepoetin therapy/blood transfusion.
    • Azotemia may remain stable or demonstrate progression in spite of instituted management.
  • Control of systemic hypertension if present.

Reasons for Treatment Failure

  • Advanced or end stage kidney disease at diagnosis.
  • Progression of underlying disease.

Further Reading

Publications

Refereed papers

  • Recent references from PubMed and VetMedResource.
  • Brown S A (2013) Renal pathophysiology: Lessons learned from the canine remnant kidney model. J Vet Emerg Crit Care 23 (2), 115-121 PubMed.
  • O'Neill D G, Elliott J, Church D B, McGreevy P D, Thomson PC & Brodbelt D C (2013) Chronic kidney disease in dogs in UK veterinary practices: prevalence, risk factors, and survival. JVIM 27 (4), 814-821 PubMed.
  • Polzin D J (2013) Evidence-based step-wise approach to managing chronic kidney disease in dogs and cats. J Vet Emerg Crit Care 23 (2), 205-215 PubMed.
  • Bartges J W (2012) Chronic kidney diseases in dogs and cats. Vet Clin North Am Small Anim Pract 42 (4), 669-692 PubMed.
  • Littman M P (2011) Protein-losing nephropathy in small animals. Vet Clin North Am Small Anim Pract 41 (1), 31-62 PubMed.
  • Finco D R et al (1999) Progression of chronic renal disease in the dog. JVIM 13 (6), 516-28 PubMed.
  • Brown S A, Finco D R & Brown C A (1998) Is there a role for dietary polyunsaturated fatty acid supplementation in canine renal disease? J Nutr 128 (12 Suppl), 2765S-2767S PubMed.
  • Devaux C, Polzin D J & Osbourne C A (1996) What role does dietary protein restriction play in the management of chronic renal failure in dogs? Vet Clin North Am 26 (6), 1247-1267 PubMed.
  • Macdougall D F, Cook T, Steward A P & Cattell V (1986) Canine chronic renal disease - prevalence and types of glomerulonephritis in the dog. Kidney Int 29 (6), 1144-1151 PubMed.

Other Sources of Information