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Basics ⬇

Basics

Definition

Kidney disease encompasses functional or structural lesions in one or both kidneys as detected by blood or urine tests, imaging studies, or kidney biopsy. Chronic kidney disease has been present for >3 months. This definition includes all cases previously described by the terms renal insufficiency or renal failure, as well as less advanced forms of kidney disease. Patients are categorized into stages along a continuum of progressive CKD (IRIS CKD stages 1–4) based on two or more serum creatinine values obtained over several weeks when the patient is fasted and well hydrated. The IRIS system uses the term “kidney” rather than “renal” because it is more universally recognized by pet owners.

Pathophysiology

More than approximately 75% reduction in renal function results in impaired urine-concentrating ability (leading to PU/PD) and retention of nitrogenous waste products of protein catabolism (leading to azotemia). More advanced CKD results in uremia. Decreased erythropoietin and calcitriol production by the kidneys results in hypoproliferative anemia and renal secondary hyperparathyroidism, respectively.

Systems Affected

  • Cardiovascular-hypertension; uremic pericarditis; cardiomegaly.
  • Endocrine/Metabolic-renal secondary hyperparathyroidism, activation of the renin-angiotensin-aldosterone system, erythropoietin deficiency.
  • Gastrointestinal-uremic stomatitis, uremic halitosis, enhanced dental calculus, nausea, vomiting, anorexia, gastrointestinal bleeding, diarrhea (may be hemorrhagic).
  • Hemic/Lymphatic/Immune-anemia; hemorrhagic diathesis.
  • Musculoskeletal-renal osteodystophy; sarcopenia.
  • Neuromuscular-seizures and other neurologic signs due to hypertension and/or uremia; muscle tremors, muscle wasting.
  • Ophthalmic-retinal detachment, hemorrhage or edema due to hypertension.
  • Reproductive-impaired reproductive capacity.
  • Respiratory-uremic pneumonitis.
  • Skin/Exocrine-calcinosis cutis.

Genetics

  • Inherited in the following breeds (mode of inheritance, known or suspected, indicated in parentheses):
    • Abyssinian cats (autosomal dominant with incomplete penetrance)
    • Persian cats (autosomal dominant)
    • Bull terrier (autosomal dominant)
    • Cairn terrier (autosomal recessive)
    • German shepherd (autosomal dominant)
    • Samoyed (X-linked dominant)
    • English cocker spaniel (autosomal recessive)
    • Renal dysplasia (mode of inherence unresolved): shih tzu, Lhasa apso, golden retriever, Norwegian elkhound, chow chow, standard poodle, soft-coated Wheaten terrier, Alaskan malamute, miniature schnauzer, Dutch kooiker, and sporadically in many other breeds).

Incidence/Prevalence

  • 9 cases per 1,000 dogs examined and 16 cases per 1,000 cats examined.
  • Prevalence increases with age-age >15 years, reportedly 57 cases per 1,000 dogs examined and 153 cases per 1,000 cats examined.

Geographic Distribution

Worldwide

Signalment

Species

Dog and cat

Breed Predilections

See “Genetics”

Mean Age and Range

Mean age at diagnosis is approximately 7 years in dogs and 9 years in cats. Animals of any age can be affected, but prevalence increases with increasing age.

Predominant Sex

None

General Comments

Clinical signs are related to the stage of CKD and the presence of complications such as proteinuria and hypertension. Cats and dogs with CKD stages 1 and 2 may be asymptomatic; overt clinical signs typically become apparent in stages 3 and 4. An animal with stable CKD (particularly stages 3 and 4) may decompensate, resulting in a uremic crisis.

Historical Findings

  • PU/PD (less frequent in cats than dogs); litter box more wet; less color to urine
  • Anorexia
  • Lethargy
  • Vomiting
  • Weight loss
  • Nocturia
  • Constipation
  • Diarrhea
  • Acute blindness-due to hypertension
  • Seizures or coma-late
  • Cats may have ptyalism and muscle weakness with cervical ventroflexion (because of hypokalemic myopathy).

Physical Examination Findings

  • Small, irregular kidneys, or enlarged kidneys secondary to polycystic kidney disease or lymphoma
  • Dehydration
  • Cachexia
  • Lethargy, weakness
  • Mucous membrane pallor
  • Oral ulceration
  • Uremic halitosis
  • Constipation
  • Hypertensive retinopathy
  • Renal osteodystrophy (may manifest as bone pain, particularly in the skull)
  • Reduced body temperature

Causes

  • Origin unknown in most cases due to late diagnosis.
  • Include familial and congenital renal disease, nephrotoxins, hypercalcemia, hypokalemic nephropathy, glomerulopathies, amyloidosis, pyelonephritis, polycystic kidney disease, nephroliths, chronic urinary obstruction, drugs, lymphoma, leptospirosis (following acute renal failure), and FIP.

Risk Factors

Age, proteinuria, hypercalcemia, hypokalemia (cats), hypertension, urinary tract infection.

Diagnosis ⬆ ⬇

Diagnosis

Differential Diagnosis

  • See Polyuria and Polydipsia chapter for differential diagnosis.
  • Azotemia-includes causes of prerenal and post-renal azotemia, acute renal failure, and hypoadrenocorticism.
  • Prerenal azotemia-azotemia with urine specific gravity >1.030 in dogs and >1.035 in cats; Rapid reduction in azotemia after correcting fluid volume/perfusion issues indicates prerenal azotemia. Prerenal azotemia commonly occurs concurrent with primary renal azotemia when gastrointestinal signs of uremia are present.
  • Post-renal azotemia-azotemia with obstruction or rupture of the excretory system; rapid correction of azotemia following elimination of obstruction or resolution of leakage from the urinary tract supports post-renal azotemia.
  • Acute renal failure-differentiated by normal to large renal size, cylindruria, lack of indications of chronicity, (absence of small kidneys, hypoproliferative anemia and renal osteodystrophy), and a history of recent nephrotoxin exposure or hypotensive episode.
  • Hypoadrenocorticism-characterized by hyponatremia and hyperkalemia with resting cortisol value <1 µg/dL or decreased adrenal response to ACTH stimulation.

CBC/Biochemistry/Urinalysis

  • Hypoproliferative anemia
  • High BUN and creatinine
  • Hyperphosphatemia
  • Metabolic acidosis (normal or high anion gap)
  • Hypokalemia or hyperkalemia
  • Hypercalcemia or hypocalcemia
  • Urine specific gravity <1.030 in dogs and <1.035 in cats
  • Proteinuria

Other Laboratory Tests

  • Urinary protein:creatinine ratio to assess proteinuria
  • Microalbuminuria assay to screen for early evidence of glomerular injury

Imaging

  • Abdominal radiographs may demonstrate small kidneys, or large kidneys secondary to polycystic kidney disease or lymphoma.
  • Ultrasound demonstrates small kidneys and hyperechoic renal parenchyma with less apparent distinction between the cortex and medulla in some animals. Animals with lymphoma often have renomegaly with hypoechoic renal parenchyma.
  • See also Congenital and Developmental Renal Diseases; Pyelonephritis; Nephrolithiasis; Hydronephrosis; Polycystic Kidney Disease.

Diagnostic Procedures

  • Blood pressure measurement to detect hypertension.
  • Measurement of glomerular filtration rate may be useful for detection of loss of kidney function before the onset of azotemia.
  • Renal biopsy is not indicated in patients with small kidneys; it may be indicated in proteinuric patients with normal to large kidneys.

Pathologic Findings

  • Gross-small kidneys with a lumpy or granular surface; renal capsule frequently adheres to the renal parenchyma.
  • Histopathologic-variable. Patients with proteinuric stage 1 CKD may have changes consistent with various forms of glomerulopathy. Depending on the cause for kidney disease, complete evaluation of biopsy material from these patients may require light, immunofluorescent, and electron microscopy. In patients with more advanced CKD, nonspecific changes including interstitial fibrosis and foci of interstitial mononuclear cells; chronic generalized nephropathy or “end-stage kidneys.”
  • Findings may be specific for diseases causing CKD in some patients with less advanced disease.

Treatment ⬆ ⬇

Treatment

Appropriate Health Care

Patients with compensated CKD may be managed as outpatients; patients in uremic crisis should generally be managed as inpatients.

Nursing Care

  • Patients in uremic crisis-correct fluid and electrolyte deficits with intravenous fluid therapy (e.g., lactated Ringer's solution). Generally provide 25% of calculated fluid deficit in the first hour. Thereafter, serially monitor perfusion (capillary refill time, pulse pressure, heart rate, and temperature of feet), blood pressure and urine output to assess adequacy of fluid therapy. If perfusion has not improved, additional fluid should cautiously be administered. Provide the remaining fluid deficit over the next 12–24 hours.; Avoid excessive fluid administration.
  • Subcutaneous fluid therapy (q24–48h) may benefit patients (especially cats) with moderate-to-severe CKD. Continue therapy only if clinical improvement is noted.

Activity

Unrestricted

Diet

  • Diets designed for dogs and cats with CKD delay the onset of uremic crisis and extend survival in dogs and cats with CKD stages 2–4. They are a standard of care for these patients.
  • Foods containing reduced protein and n-3 fatty acids may be beneficial for proteinuric patients with stage 1 CKD.
  • Important components of renal foods include: reduced protein, phosphorus, sodium and net acid content and supplementation of n-3 fatty acids and antioxidants.
  • Free access to fresh water at all times.

Client Education

  • Dogs and many cats-CKD typically progresses to terminal kidney failure over months to years.
  • CKD may not be progressive in some cats.
  • Higher levels of proteinuria associated with shorter survival times. This effect may be mitigated by therapy for proteinuria.
  • Heritability of familial renal diseases.

Surgical Considerations

  • Avoid hypotension during anesthesia to prevent additional renal injury.
  • Renal transplantation has been successfully performed in cats with CKD.

Medications ⬆ ⬇

Medications

Drug(s) Of Choice

Uremic Crisis

  • Famotidine (0.5–1 mg/kg PO, IM, IV q12–24h) to minimize nausea and vomiting (primarily dogs).
  • Antiemetics (maropitant 1 mg/kg q24h up to 5 days; or ondansetron 0.1–0.2 mg/kg slow IV q12h) to minimize vomiting and impaired appetite due to nausea.
  • Potassium chloride in IV fluids or potassium gluconate PO (2–6 mEq/cat/day) as needed to correct hypokalemia.
  • Sodium bicarbonate to correct metabolic acidosis (IV to raise blood pH >7.1).

Compensated CKD

  • Famotidine (dogs, 0.5–1 mg/kg PO q24h) to minimize uremic gastritis and possible nausea and inappetence.
  • Antiemetic (maropitant) and potassium gluconate as above.
  • Intestinal phosphate binders (e.g., aluminum carbonate, 30–100 mg/kg/day PO with meals) as needed to correct hyperphosphatemia (see Hyperparathyroidism, Renal Secondary).
  • Calcitriol (start at 2 ng/kg PO q 24h and monitor effect on PTH and ionized calcium-avoid inducing hypercalcemia) (see Hyperparathyroidism, Renal Secondary).
  • Darbepoetin (see Anemia of Chronic Kidney Disease).
  • Amlodipine (dogs, 0.1–0.6 mg/kg PO q24h; cats, 0.625–1.25mg/cat PO q24h) or ACE inhibitors (e.g., enalapril or benazepril, 0.5 mg/kg PO q24h) as needed for hypertension. Amlodipine is more effective than ACE inhibitors in cats with CKD-induced hypertension. If refractory to monotherapy, consider combination of amlodipine and ACE inhibitor with frequent monitoring of blood pressure.
  • ACE inhibitor (benazepril or enalapril) for proteinuria (start at 0.5 mg/kg PO q24 h; may increase to 1 mg/kg PO q12h if needed to reduce proteinuria).

Contraindications

Avoid nephrotoxic drugs (aminoglycosides, cisplatin, amphotericin B) and corticosteroids.

Precautions

  • Drug dosage or dosing interval may need to be modified for some drugs eliminated by the kidneys.
  • Use ACE inhibitors with caution; monitor for worsening of azotemia.
  • Generally avoid NSAIDs.

Possible Interactions

Cimetidine or trimethoprim may cause artifactual increases in the serum creatinine concentration by reducing tubular secretion in dogs with CKD.

Alternative Drug(s)

  • Metoclopramide (0.2–0.4 mg PO or SC q6–8h) can be used in addition to H2-receptor antagonists to treat uremic vomiting.
  • Ranitidine (0.5–2 mg/kg PO or IV q12h) or cimetidine (5 mg/kg q8–12h for dogs; 2.5–5 mg/kg q8–12h for cats) may be used instead of famotidine.
  • Hemodialysis and renal transplantation are available at selected referral hospitals.

Follow-Up ⬆ ⬇

Follow-Up

Patient Monitoring

  • Dogs and cats with CKD-monitor at regular intervals; initially weekly for patients receiving calcitriol or erythropoietin; every 1–3 months for stable patients with CKD stages 3 and 4 (minimum: chemistry profile and PCV).
  • Proteinuric patients-monitor at least every 3–4 months (minimum: serum creatinine and urine protein:creatine ratio).

Prevention/Avoidance

  • Do not breed animals with familial renal disease.
  • Include urinalysis and serum creatinine in yearly examination for older dogs and cats.

Possible Complications

  • Systemic hypertension
  • Uremia
  • Anemia
  • Urinary tract infection
  • Nephrolithiasis and uretrolithiasis
  • Exuberant dental calculus

Expected Course and Prognosis

  • Short-term-depends on severity.
  • Long-term-guarded to poor in dogs (CKD tends to be progressive over months to years); poor to good in cats (CKD does not progress in some cats).

Miscellaneous ⬆

Miscellaneous

Associated Conditions

  • Hyperthyroidism in cats
  • Urinary tract infection
  • Systemic hypertension
  • Nephrolithiasis and ureterolithiasis

Age-Related Factors

Renal function may decrease with aging.

Zoonotic Potential

Leptospirosis

Pregnancy/Fertility/Breeding

Patients with mild CKD may maintain pregnancy; those with moderate-to-severe disease may be infertile or have spontaneous abortions; breeding of female patients not recommended.

Synonyms

  • Chronic kidney failure
  • Chronic renal disease
  • Chronic renal failure

Abbreviations

  • ACE = angiotensin-converting enzyme
  • ACTH = adrenocorticotropic hormone
  • CKD = chronic kidney disease
  • FIP = feline infectious peritonitis
  • IRIS = International Renal Interest Society
  • NSAID = nonsteroidal anti-inflammatory drug
  • PCV = packed cell volume
  • PU/PD = polyuria/polydipsia

Internet Resources

www.iris-kidney.com.

Author David J. Polzin

Consulting Editor Carl A. Osborne

Client Education Handout Available Online

Suggested Reading

Polzin DJ. Chronic kidney disease. In: Ettinger SJ, Feldman EC, eds., Textbook of Veterinary Internal Medicine, 7th ed. St. Louis: Elsevier, 2010, pp. 1990–2021.

Ross SJ, Polzin DJ, Osborne CA. Clinical progression of early chronic renal failure and implications for management. In: August JR, ed., Consultations in Feline Internal Medicine. St. Louis: Elsevier, 2006, pp. 389–398.