Sample Topic

Feline | Canine

Chronic Kidney Disease

Summary

  • Characterized by permanent loss of functional nephrons with or without a decrease in the glomerular filtration rate (GFR); often progressive even if initiating event no longer persists
  • By definition, kidney damage has to be present for a minimum of 3 months to be considered chronic kidney disease
  • May be complicated by concurrent prerenal or postrenal factors, or acute kidney injury
  • Disease may be stable for months to years
  • Staging of disease using International Renal Interest Society (IRIS) guidelines is recommended to help guide therapy and monitor response to treatment
  • The goals of therapy are to slow disease progression, alleviate the clinical signs, and provide appropriate nutritional support
  • Long-term prognosis in dogs is generally guarded to poor; depends on IRIS stage
  • Prognosis is more variable in cats
  • Consultation with a veterinary internal medicine specialist may be considered for severe or refractory cases

Causes and Risk Factors

Causes

Risk Factors

  • Prevalence increases with age
  • Familial predisposition
  • A recent study (Level 2) found that prior periodontal disease or cystitis, anesthesia or documented dehydration within the past year, or being a neutered male increased the risk of developing chronic kidney disease in cats
  • The following factors may cause progression of chronic kidney disease:
    • Volume depletion
    • Urinary obstruction
    • Urinary infection
    • Exposure to nephrotoxic drugs
    • Use of nonsteroidal anti-inflammatory drugs, angiotensin-converting enzyme inhibitors, angiotensin-II receptor blockers, or radiocontrast agents
    • Uncontrolled systemic hypertension
    • Comorbid conditions (e.g., cardiac disease)

Signalment

  • Often affects older dogs and cats, but may occur at any age
  • No sex predilection
  • Familial diseases impact specific breeds:
    • Amyloidosis
      • Dogs: Shar-Peis, Beagles, English Foxhounds
      • Cats: Abbysinians, Siamese, Oriental Shorthairs
    • Dysplasia
      • Golden Retrievers, Shih Tzus, Lhasa Apsos, Soft Coated Wheaten Terriers, and Miniature Schnauzers
    • Fanconi syndrome
      • Basenjis
    • Glomerulopathy
      • English Cocker Spaniels, Soft Coated Wheaten Terriers, Samoyeds, Dalmations, Rottweilers, Beagles, Bull Terriers, Doberman Pinschers
    • Polycystic kidney disease
      • Dogs: Cairn Terriers, Bull Terriers, West Highland White Terriers
      • Cats: Persians, Himalayans

Differential Diagnosis

  • Azotemia
    • Prerenal causes (e.g., dehydration)
    • Postrenal causes (e.g., urinary obstruction)
    • Acute kidney injury
      • Ischemia
      • Nephrotoxins
      • Drugs
      • Infection
      • Immune-mediated disease
    • Hypoadrenocorticism
    • Neoplasia

Diagnosis and Screening

General Points

  • A diagnosis of chronic kidney disease (CKD) is based on disease duration (> 3 months), clinical signs, and supportive laboratory findings
  • Serum creatinine is the most commonly used surrogate marker of kidney function; however, it may be influenced by prerenal and postrenal factors
  • Serum creatinine should always be interpreted in light of urine specific gravity and clinical status
  • Elimination or control of the inciting cause should be addressed; this will not alter existing renal damage but may minimize further renal injury
  • Decompensation of stable CKD may occur with concurrent illness ("acute-on-chronic" kidney disease)
  • Renal biopsies are typically only indicated if hereditary disease is suspected or if the results will influence prognosis or treatment; may be most useful in patients with proteinuric disease
  • All patients with chronic kidney disease should be screened for systemic hypertension
  • The International Renal Interest Society (IRIS) staging system should be applied to patients with stable chronic kidney disease
    • Prerenal, postrenal, and acute kidney injury factors should be managed prior to staging
    • Only creatinine measurements obtained when the patient is fasted and well-hydrated should be used for staging; a minimum of 2 measurements should be obtained

      IRIS stage

      Creatinine (mg/dl)

      Patient History

      At risk

      Dogs: < 1.4
      Cats: < 1.6

      Asymptomatic but at increased risk due to exposure to nephrotoxic drugs or infectious agents, advanced age, or familial predisposition

      1

      Dogs: < 1.4
      Cats: < 1.6

      Non-azotemic but other urinary abnormality present (e.g., low urine specific gravity, abnormal renal imaging, or proteinuria of renal origin)

      2

      Dogs: 1.4 - 2.0
      Cats:1.6 - 2.8

      Mild azotemia; clinical signs may be mild or absent

      3

      Dogs: 2.1 - 5.0
      Cats: 2.9 - 5.0

      Moderate azotemia; clinical signs often present

      4

      > 5.0

      Severe azotemia; increased risk of a uremic crisis



  • Substaging can be considered based on the presence of proteinuria and systemic hypertension

    Urine protein to creatinine ratio (UPC)

    IRIS Substage

    < 0.2

    Nonproteinuric (NP)

    Dogs: 0.2 – 0.5, Cats: 0.2 – 0.4

    Borderline proteinuric (BP)

    Dogs: > 0.5, Cats: > 0.4

    Proteinuric (P)



    Systolic pressure (mm Hg)

    Diastolic pressure (mm Hg)

    Risk of end-organ damage

    Arterial pressure substage

    < 150

    < 95

    None or minimal

    Normotension

    150-159

    95-99

    Low

    Borderline hypertension

    160-179

    100-119

    Moderate

    Hypertension

    > 179

    > 119

    High

    Severe hypertension

  • Patients may have changes to their staging following therapy in which case a "T" can be added to their most current stage designation
  • The presence (C) or absence (NC) of end-organ damage can also be included in the designation
  • As an example:
    • Prior to therapy, a cat with a creatinine of 3.0 mg/dl, a UPC of 0.3, and a systolic pressure of 200 mm Hg would be classified as IRIS CKD Stage 3-BP-Severe hypertension
    • Following successful antihypertensive therapy, the same cat with a creatinine of 3.2, a UPC of 0.3, and a systolic blood pressure of 155 mm Hg would be classified as IRIS CKD Stage 3-BP-borderline hypertension (T)

Signs and History

  • Polyuria and polydipsia
  • Weight loss
  • Lethargy
  • Poor appetite
  • Vomiting
  • Diarrhea

Physical Exam

  • Variable hydration
  • Poor general body condition
  • Hypertension
  • Retinal detachment or bleeding secondary to systemic hypertension; seen most often in cats
  • Oral ulcerations and/or stomatitis
  • Muscle wasting
  • Cervical ventroflexion may be seen in cats with severe hypokalemia
  • Renal osteodystrophy (primarily manifested as jaw fractures, loose teeth, or distortion of the maxilla) may be seen in patients with renal secondary hyperparathyroidism; most often occurs in young patients

Laboratory Tests

  • Routine laboratory tests
    • Ideally, all samples should be collected prior to initiation of therapy

    • Complete blood count with differential
      • Non-regenerative anemia is common

    • Biochemistry panel
      • Elevated blood urea nitrogen (BUN)
      • Elevated creatinine
      • Hyperphosphatemia
      • Hyperkalemia or hypokalemia
      • Metabolic acidosis
      • Hypoalbuminemia
      • Hypercalcemia or hypocalcemia

    • Urinalysis
      • Isosthenuria; some cats may demonstrate a decrease in urine concentrating ability before the development of overt azotemia
      • Proteinuria
      • Glucosuria

  • Symmetric dimethylarginine (SDMA) level
    • Elevated levels may be seen in patients with early renal disease, often before elevations in creatinine are noted
    • Should not be used alone as a screening test for chronic kidney disease
    • Persistent elevations in SDMA > 14 µg/dl suggests reduced renal function; dogs and cats with an SDMA > 14 µg/dl and with creatinine values < 1.4 or < 1.6 mg/dl, respectively, should be classified as IRIS CKD Stage 1

  • Urine culture and sensitivity testing
    • Urine culture and sensitivity testing should be considered as part of the initial work-up, for identification and management of concurrent upper or lower urinary tract infection

  • Other laboratory tests
    • In elderly cats (> 10 yrs), consider screening for hyperthyroidism
    • Ionized calcium and parathyroid hormone levels may be measured in patients with altered calcium metabolism or evidence of renal osteodystrophy
    • Testing for infection with feline leukemia virus Infection and feline immunodeficiency virus should be considered in cats with risk of exposure; retroviral infection may predispose patients to bacterial infections
    • Testing for leptospirosis, a potential cause of azotemia, should be considered in dogs with risk of exposure
    • Testing for tick-borne pathogens should be considered in patients with evidence of renal proteinuria; may predispose to glomerular disease

Imaging

  • Abdominal radiography
    • Kidneys may be normal or small in size
    • One kidney may be small and the other enlarged due to compensatory hypertrophy
    • Presence of uroliths or mineralization may be identified

  • Abdominal ultrasonography
    • Useful in assessing changes in shape and echogenicity
    • May identify pyelectasia, cysts, masses, obstruction, or other complicating factors

Other Diagnostic Tests

  • Indirect blood pressure measurement
    • All patients with chronic kidney disease should be screened for systemic hypertension
    • Doppler method for obtaining blood pressure measurement is preferred in cats; Doppler or oscillometric methods may be used in dogs
      • Cuff width should be approximately 40% of the circumference of the limb at the point of placement
      • The limb being used should be at the level of the heart
      • The final pressure recorded should be an average of 3 to 5 independent readings
    • Pressure measurements should be obtained when the patient is calm and acclimated to their surroundings
    • Results should be interpreted in light of clinical findings and underlying medical conditions
    • Elevated measurements in a patient with no clinical signs or evidence of end-organ damage should be reevaluated in 1 week
    • Serial measurements should be performed on the same limb with the same cuff size and positioning to ensure consistent readings

Screening Recommendations

  • Evaluation of body weight, blood pressure, and body condition score should be performed every 6 months in cats > 7 years of age; in addition, a complete blood count, serum biochemistry panel, and urinalysis should be performed at least yearly

Treatment

General Points

  • The goals of therapy are to slow disease progression, alleviate the clinical signs, and provide appropriate nutritional support
  • Any nephrotoxic drugs should be immediately discontinued
  • Any concurrent urinary tract problems or comorbid conditions should be specifically addressed
  • Medical management will require individualized treatment based on the patient's clinical status and laboratory findings; serial assessment and modification will be required
  • There is insufficient evidence to support the use of calcitriol in cats for chronic kidney disease
  • Consultation with a veterinary internal medicine specialist may be considered for severe or refractory cases

Medications

  • Management of hypertension
    • Should be considered when systolic pressure is consistently ≥ 160 mm Hg or if there is evidence of target-organ damage
    • For cats:
      • Amlodipine 0.625 mg PO every 24 hours; this can be increased to a maximum dose of 0.5 mg/kg PO every 24 hours as needed to control hypertension
      • An angiotensin-converting enzyme inhibitor (ACEI) may be added in patients who do not respond to amlodipine alone; however, do not use an ACEI in patients who are dehydrated
    • For dogs:
      • Enalapril or benazepril 0.5 to 1.0 mg/kg PO every 24 hours
        • Should not be used in patients with clinical evidence of dehydration
      • Amlodipine 0.2 to 0.4 mg/kg PO every 24 hours
        • Can be added to enalapril or benazepril therapy for patients with refractory hypertension
        • Dose can be increased as needed to 0.75 mg/kg/day; can be divided and given every 12 hours
      • The addition of hydralazine may be considered as a third-line choice for patients with refractory hypertension

  • Management of proteinuria
    • For cats, medications for proteinuria are recommended for:
      • International Renal Interest Society (IRIS) CKD stages 1 or greater and with a urine protein creatinine (UPC) ratio > 1.0
      • IRIS CKD stages 2 to 4 and UPC ratio > 0.4
    • For dogs, medications for proteinuria are recommended for:
      • IRIS CKD stages 1 or greater and with a UPC ratio > 2.0
      • IRIS CKD stages 2 to 4 and a UPC ratio > 0.5
    • If serum albumin is < 2.0 mg/dl consider aspirin therapy:
      • For dogs: 1.0 to 5.0 mg/kg PO every 24 hours
      • For cats: 1 mg/kg PO every 72 hours

    • Angiotensin-converting enzyme inhibitors (ACEIs)
      • Enalapril or benazepril 0.25 to 0.5 mg/kg PO every 24 hours
        • Should not be used in patients with clinical evidence of dehydration
        • Increase by 0.25 to 0.5 mg/kg as needed (maximum daily dose of 2 mg/kg); can be divided and given every 12 hours

    • Angiotensin receptor blockers (ARBs)
      • Losartan 0.25 to 0.5 mg/kg PO every 24 hours
        • Can be added to ACEI therapy for dogs with unresponsive proteinuria; efficacy has not been well established in cats
        • Increase by 0.25 to 0.5 mg/kg as needed (maximum daily dose of 2 mg/kg); can be divided and given every 12 hours
      • In Europe, alternative option approved in cats is telmisartan
        • Telmisartan 1 mg/kg PO every 24 hours

    • Calcium channel blockers
      • Amlodipine 0.625 mg PO every 24 hours
        • Can be considered in cats that are have concurrent hypertension; amlodipine alone may lower urine protein creatinine ratio
        • Should not be used for this purpose in dogs

  • Management of anemia
    • Should be considered only for patients in which anemia is having a clinical effect, or if the packed cell volume (PCV) is persistently < 20%
    • Therapy may cause an increase in systolic blood pressure
    • Anabolic steroids have no proven benefit in the treatment of anemia
    • Iron supplementation should be considered for patients receiving erythropoietic agents:
      • Dogs: 10 to 20 mg/kg IM once, then monthly while on therapy
      • Cats: 50 mg/cat IM once, then monthly while on therapy
    • Erythropoietin 75 to 100 units/kg SC three times per week until target hematocrit is attained (25% to 35%); then decrease to once or twice weekly
      • Patients may develop antibodies to this agent which may result in refractory anemia and transfusion dependency
      • Contraindicated in patients with uncontrolled systemic hypertension
    • Darbepoetin 1 μg/kg SC once per week until target hematocrit is attained (25% to 35%); then decrease to every other week
      • This dose has been extrapolated from human medicine; the optimal dose for dogs and cats is not known
      • A study (Level 3) suggested that a dosing interval greater than q21d was ineffective for maintaining a response to treatment; a dosage of 0.8 μg/kg SC weekly appeared to be more effective than 0.5 μg/kg SC weekly
      • Thought to be less immunogenic than erythropoietin, but this has not been proven
      • May be cost prohibitive

  • Management of secondary renal hyperparathyroidism in dogs
    • Calcitriol 2.0 to 2.5 ng/kg PO every 24 hours
      • Once phosphorous levels are normalized, calcitriol may be considered for dogs with International Renal Interest Society (IRIS) CKD stage 3 or 4 disease
      • Should be administered in the evening on an empty stomach
      • Will require monitoring of ionized calcium and parathyroid hormone levels
      • Calcitriol is not recommended for cats with chronic kidney disease

  • Management of hypokalemia
    • Often seen in cats with chronic kidney disease; supplementation should be considered for cats with a serum K < 3.5 mmol/L (3.5 mEq/L)
    • Potassium gluconate 1 to 2 mEq(mmol)/kg PO every 24 hours
    • Potassium citrate 40 to 60 mg/kg PO divided into 2 to 3 doses
      • Can be used instead of potassium gluconate for patients who also require alkalinization therapy for metabolic acidosis; efficacy is unclear

  • Management of hyperphosphatemia
    • Aluminum hydroxide or aluminum carbonate or lanthanum carbonate 30 to 60 mg/kg PO every 24 hours, divided and given with meals
      • Development of microcytosis or generalized muscle weakness may indicate aluminum toxicity
    • Calcium acetate 60 to 90 mg/kg PO every 24 hours, divided and given with meals
      • Should not be used in patients with hypercalcemia

  • Management of metabolic acidosis
    • Should be considered only after patient has been on a renal diet for several weeks and is well hydrated
    • May be considered if serum bicarbonate level is < 16 mmol/L for cats or < 18 mmol/L in dogs
    • Sodium bicarbonate 8 to 12 mg/kg PO every 8 to 12 hours, or
    • Potassium citrate 40 to 60 mg/kg PO divided into 2 to 3 doses

  • Management of vomiting, anorexia, and nausea
    • The following agents may be used alone or in combination, depending on patient status and clinical response:
      • Famotidine 0.5 to 1 mg/kg PO or IV every 24 hours
      • Omeprazole 0.5 to 1 mg/kg PO every 24 hours
      • Pantoprazole 0.7 to 1 mg/kg IV every 24 hours
      • Maropitant 1 mg/kg SC or IV every 24 hours, or 2 mg/kg PO every 24 hours, for up to 5 consecutive days
      • Ondansetron 0.1 to 1 mg/kg IV, SC, IM, or PO every 8 to 12 hours; oral doses are more effective towards the high end of the dose range
      • Mirtazapine
        • Dogs: 0.6 to 1 mg/kg PO every 12 hours
        • Cats: 1.87 mg/cat PO every 48 hours

Surgical Interventions

  • May be required in the event of obstructive urinary disease or to obtain appropriate biopsy samples

Other Therapies

  • Fluid therapy
    • If necessary, depending on the patient's level of hydration and clinical signs, intravenous fluids should be administered; see acute kidney injury monograph
    • For patients with stable disease, intermittent administration of subcutaneous fluids may be considered; due to size and fluid requirements, cats and small dogs will benefit more from this therapy than larger dogs

  • Nutritional support
    • An established renal diet should be considered for all patients with stage 2 or greater kidney disease; these diets offer reduced protein, phosphorous, and sodium content as well as increased calories, fiber, fatty acids, and antioxidants
    • A canned diet should be offered to increase water intake
    • Transition to a renal-specific diet should not be attempted while the pet is ill or during hospitalization
    • Acidifying diets should be avoided as they may promote hypokalemia
    • Placement of an esophagostomy tube can be considered for patients with a consistently poor appetite or as a means of providing appropriate hydration

Follow-up

General Points

  • Staging should be re-evaluated every time the patient is examined so the designation reflects the most current effects of treatment

Therapeutic Follow-up

  • A physical examination (including weight and blood pressure measurements) as well as a biochemistry panel, including blood urea nitrogen, creatinine, and electrolytes, should be evaluated every 2 weeks until response to therapy is established
  • Additionally, patients with proteinuria should have a urine protein creatinine ratio (UPC) reevaluated 2 to 4 weeks after initiating anti-proteinuria therapy or any time there is a change in dosing; once stable, UPC should be evaluated again in 4 to 6 weeks, then every 3 to 4 months
  • In patients receiving erythropoietic agents, a hematocrit or packed cell volume (PCV) and systolic blood pressure should be evaluated weekly until target level is reached
  • Serum calcium and phosphorous levels should be measured every 4 to 6 weeks until stable, then every 3 months
  • Once hypertension is stabilized, blood pressure should be re-evaluated every 3 months; systolic blood pressure < 120 mm Hg indicates hypotension and a reduction in antihypertensive drugs is indicated

Prognosis

  • Long-term prognosis in dogs is generally guarded to poor and will depend on International Renal Interest Society (IRIS) stage

    • A recent study (Level 3) in dogs found that a higher body condition score (BCS ≥ 4/9) at the time of diagnosis was associated with improved survival
    • Two studies (Level 2) have reported that dogs with urine protein creatinine ratio ≥ 1 or systolic blood pressure ≥ 180 mm Hg at the time of diagnosis had increased risk of a uremic crisis and death
  • Cats tend to live longer with chronic kidney disease than dogs, although the presence of proteinuria is still a poor prognostic indicator

    • One study (Level 3) demonstrated a median survival of 1151 days for cats with IRIS CKD stage 2B and 778 days for cats with IRIS CKD stage 3

Evidence

Guidelines and Consensus Statements

  • Sparkes AH, Caney S, Chalhoub S, et al. ISFM Consensus Guidelines on the Diagnosis and Management of Feline Chronic Kidney Disease. J Fel Med Surg. 2016 Mar;18(3):219-39. Level C (IND) Article
  • International Renal Interest Society Staging of CKD (Modified 2015). Level C (IND) Article
  • International Renal Interest Society: Treatment Recommendations for CKD. (Modified 2015). Level C (IND) Article

Systematic Reviews/Meta-analyses

  • None available

Randomized, Controlled Trials (RCTs)

  • Sent U, Gossl R, Elliott J, et al. Comparison of efficacy of long-term oral treatment with telmisartan and benazepril in cats with chronic kidney disease. J Vet Intern Med. 2015 Nov-Dec;29(6):1479-87. Epub 2015 Oct 16. Level 2 (IND) Article
  • Ross SJ, Osborne CA, Kirk CA, et al. Clinical evaluation of dietary modification for treatment of spontaneous chronic kidney disease in cats. J Am Vet Med Assoc. 2006 Sep 15;229(6):949-57. Level 2 (IND) Abstract
  • Jacob F, Polzin DJ, Osborne CA, et al. Clinical evaluation of dietary modification for treatment of spontaneous chronic renal failure in dogs. J Am Vet Med Assoc. 2002 Apr 15;220(8):1163-70. Level 2 (IND) Abstract

Other Studies or Reviews

  • Bijsmans ES, Jepson RE, Chang YM, et al. Changes in systolic blood pressure over time in healthy cats and cats with chronic kidney disease. J Vet Intern Med. 2015 May;29(3):855-61. Level 2 (IND) Article
  • Greene JP, Lefebvre SL, Wang M, et al. Risk factors associated with the development of chronic kidney disease in cats evaluated at primary care veterinary hospitals. J Am Vet Med Assoc. 2014 Feb 1;244(3):320-7. Level 2 Abstract
  • Jacob F, Polzin DJ, Osborne CA, et al. Evaluation of the association between initial proteinuria and morbidity rate or death in dogs with naturally occurring chronic renal failure. J Am Vet Med Assoc. 2005 Feb 1;226(3):393-400. Level 2 (IND) Abstract
  • Jacob F, Polzin DJ, Osborne CA, et al. Association between initial systolic blood pressure and risk of developing a uremic crisis or of dying in dogs with chronic renal failure. J Am Vet Med Assoc. 2003 Feb 1;222(3):322-9. Level 2 (IND) Abstract

  • Fiocchi EH, Cowgill LD, Brown DC, et al. The Use of Darbepoetin to Stimulate Erythropoiesis in the Treatment of Anemia of Chronic Kidney Disease in Dogs. J Vet Intern Med. 2017 Mar;31(2):476-85. Epub 2017 Mar 3. Level 3
  • Papich MG. Saunders Handbook of Veterinary Drugs: Small and Large Animal, 4th Edition. St Louis, MO: Elsevier; 2016. Level 3
  • Plumb’s Veterinary Drugs (online databse), Tulsa, OK: Brief Media; 2016. Accessed March 17, 2017. Level 3
  • Quimby JM. Update on medical management of clinical manifestations of chronic kidney disease. Vet Clin North Am Small Anim Pract. 2016;46:1163-81. Level 3 (IND)
  • Ross S. Utilization of feeding tubes in the management of feline chronic kidney disease. Vet Clin North Am Small Anim Pract. 2016 Aug 5. pii: S0195-5616(16)30050-X. doi: 10.1016/j.cvsm.2016.06.014. [Epub ahead of print]. Level 3
  • Vaden SL, Elliot J. Management of proteinuria in dogs and cats with chronic kidney disease. Vet Clin North Am Small Anim Pract. 2016 Jul 30. pii: S0195-5616(16)30045-6. doi: 10.1016/j.cvsm.2016.06.009. [Epub ahead of print]. Level 3 (IND)
  • Hall JA, Yerramilli M, Obare E, et al. Relationship between lean body mass and serum renal biomarkers in healthy dogs. J Vet Intern Med. 2015 May-Jun;29(3):808-14. Level 3 (IND)
  • Nabity MB, Lees GE, Boggess MM, et al. Symmetric dimethylarginine assay validation, stability, and evaluation as a marker for the early detection of chronic kidney disease in dogs. J Vet Intern Med. 2015 Jul-Aug;29(4):1036-44. Level 3 (IND)
  • McLeland SM, Lunn KF, Duncan CG, et al. Relationship among serum creatinine, serum gastrin, calcium-phosphorus product, and uremic gastropathy in cats with chronic kidney disease. J Vet Intern Med. 2014 May-Jun;28(3):827-37. Level 3
  • Hall JA, Yerramilli M, Obare E, et al. Comparison of serum concentrations of symmetric dimethylarginine and creatinine as kidney function biomarkers in cats with chronic kidney disease. J Vet Intern Med. 2014 Nov-Dec;28(6):1676-83. Level 3
  • Braff J, Obare E, Yerramilli M, et al. Relationship between serum symmetric dimethylarginine concentration and glomerular filtration rate in cats. J Vet Intern Med. 2014 Nov-Dec;28(6):1699-701. Level 3
  • Elliot J, Watson ADJ. Chronic kidney disease: International Renal Interest Society staging and management. In: Bonagura JD, Twedt D, ed’s. Kirk’s Current Veterinary Therapy XV. Philadelphia: Elsevier Saunders; 2014:857-63. Level 3
  • Grauer GF. Proteinuria/albuminuria: implications for management. In: Bonagura JD, Twedt D, ed's. Kirk's Current Veterinary Therapy XV. Philadelphia: Elsevier Saunders;2014:849-52. Level 3
  • O'Neill DG, Elliott J, Church DB, et al. Chronic kidney disease in dogs in UK veterinary practices: prevalence, risk factors, and survival. J Vet Intern Med. 2013 Jul-Aug;27(4):814-21. Level 3
  • Paepe D, Daminet S. Feline CKD: diagnosis, staging and screening – what is recommended? J Feline Med Surg. 2013 Sep;15 Suppl 1:15-27. Level 3
  • Polzin DJ. Evidence-based step-wise approach to managing chronic kidney disease in dogs. J Vet Emerg Crit Care (San Antonio). 2013 Mar-Apr;23(2):205-15. Level 3
  • Polzin DJ. Chronic kidney disease. In: Ettinger SJ, Feldman EC, ed.'s. Textbook of Veterinary Internal Medicine. 7th ed. St. Louis: Saunders Elsevier; 2010:1990-2021. Level 3
  • Chakrabarti S, Syme HM , Elliott J, et al.Clinicopathological variables predicting progression of azotemia in cats with chronic kidney disease. J Vet Intern Med. 2012 Mar-Apr;26(2):275-81.Level 3
  • Parker V, Freeman L. Association between body condition and survival in dogs with acquired chronic kidney disease. J Vet Intern Med. 2011 Nov-Dec;25(6):1306-11. Level 3
  • Boyd LM, Langston C, Thompson K, et al. Survival in cats with naturally occurring chronic kidney disease (2000-2002). J Vet Intern Med. 2008 Sep-Oct;22(5):1111-7. Level 3
  • Syme HM, Markwell PJ, Pfeiffer D, et al. Survival of cats with naturally occurring chronic renal failure is related to severity of proteinuria. J Vet Intern Med. 2006 May-Jun;20(3):528-35. Level 3 (IND)