Kidney: chronic kidney disease

• Gradual, progressive loss of renal tissue   →   inability of kidney to perform normal functions of waste excretion, fluid/electrolyte/acid-base homeostasis and endocrine functions.
• Cause: in younger animals usually either congenital or familial; in older animals usually acquired.
• Signs: initially polyuria/polydipsia   →   uremia (vomiting, anorexia, oral ulceration) if >75% of renal tissue not functioning.
• Diagnosis: biochemistry, urinalysis, histopathology.
• Treatment: dietary managment +/- phosphate binding agents; ACE inhibitor; IV fluid therapy; H-2 blockers, +/- erythropoietin.
• Prognosis: guarded - early detection and management of chronic renal failure will ameliorate the signs of uremia and may, in some cases, slow down the progression of disease.
  Print off the owner factsheet Kidney disease in your cat  Kidney disease in your cat to give to your client. 

• Polyuria/polydipsia.

• Signs of uremia Uremia:
  • Anorexia.
  • Oral ulceration.
  • Lethargy.
  • Diarrhea.

• Tongue tip necrosis.
• Uremic encephalopathy/neuropathy (muscle twitching, convulsions).
• Uremic pericarditis.
• Uremic pneumonitis.
• Anemia.

• Acute decompensation of chronic renal disease can cause an uremic crisis (severe uremia, dehydration, collapse).

• Depends on etiology (generally >7 years).

• Young animals 0-4 years for juvenile renal diseases.
• Usually older animals for acquired disease.

• Often depend on underlying cause which may be breed specific.

• Abyssinian Abyssinian secondary to amyloidosis.
• Maine Coon Maine Coon.
• Siamese Siamese.
• Persian Persian longhair (secondary to polycystic kidney disease Kidney: autosomal dominant polycystic kidney disease).

• Russian Blue Russian Blue.
• Burmese Burmese.
• Balinese Balinese.
• Japanese Bobtail Japanese bobtail.

• Rex Cornish Rex  Devon Rex.

• Anesthesia since many anesthetic agents excreted through kidneys Anesthesia: in renal insufficiency and hypotension during anesthesia may contribute.
  Warn owner of risks associated with anesthesia.
• Increased risk of decompensation with heat stress or dehydration.
  Warn owner of risks of heat stress and/or dehydration.

Young animals

• Juvenile renal diseases; renal cortical hypoplasia, renal dysplasia, hereditary nephritis, glomerulopathy, polycystic disease, familial amyloidosis, etc.

Older animals

• Chronic pyelonephritis Pyelonephritis.
• Chronic glomerulonephritis Glomerulonephritis.
• Hypertension Hypertension.
• Infectious causes (FIP Feline infectious peritonitis).
• Polycystic renal disease Kidney: autosomal dominant polycystic kidney disease.
• Renal pseudocyst.
• Renal amyloidosis Amyloidosis.
• Neoplasia (lymphoma Lymphoma).
• Chronic interstitial nephritis.
• Hypercalcemia Hypercalcemia: overview.
• Following acute renal failure Kidney: acute renal failure.
• Chronic generalized nephropathy.
• Nephrolithiasis/ureterolithiasis Nephrolithiasis.

• Damage to one component of nephron   →   generalized nephron failure   →   scarring and compensatory changes   →   chronic generalized nephropathy.
• 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 a shortened RBC lifespan   →   normochromic, normocytic, non-regenerative anemia.
• Hyperphosphatemia, due to inability to excrete phosphate   →   hyperparathyroidism   →   osteodystrophy and nephrocalcinosis which increases renal damage.
• Lack of active vitamin D3   →   initiates and exacerbates hyperparathyroidism.

• Some animals can be managed for a long period, while others may decompensate and deteriorate rapidly (acute-on-chronic disease).

• Polyuria/polydipsia.
• Anorexia.
• Weight loss  Weight loss.
• Vomiting Vomiting /diarrhea.

• Polyuria/polydipsia.

• Anorexia.
• Weight loss.

• Lethargy.
• Vomiting Vomiting.
• Diarrhea.
• Halitosis.

• Tongue-tip necrosis.
• Neurological signs, muscle weakness, muscle tremors.

• Dehydration.
• Oral ulceration (especially buccal mucosae, adjacent to teeth) and stomatitis              .
• Small kidneys on abdominal palpation.
• Weight loss/thin.

• Pale mucous membranes   .
• Hypertension Hypertension (retinal hemorrhage   or detachment   ).

• Hyperemic mucous membranes (sign of uremia).
• Tongue-tip necrosis.
• Osteodystrophy/'rubber jaw'. 'Rubber jaw' is uncommon in the cat. Bone pain may be present.

Biochemistry

• Azotemia Azotemia.
• Increased [urea] and [creatinine] Blood biochemistry: urea  Blood biochemistry: creatinine.
• Hyperphosphatemia Hyperphosphatemia  Blood biochemistry: phosphate in later stage.
• Hypokalemia Hypokalemia  Blood biochemistry: potassium common often as a result of reduced intake due to anorexia/urine losses. Hyperkalemia may also be seen, particularly with more advacned stages.
• Signs of glomerular disease Glomerulonephritis (hypoproteinemia Hypoproteinemia, hypercholesterolemia Blood biochemistry: cholestero ).
• [Calcium] Blood biochemistry: total calcium usually normal although may see hypocalcemia terminally (10% cases).
• Metabolic acidosis in later stage Acid base imbalance.
• Occasionally hypercalcemia has been reported at (10-21% cats with CRF).
• Elevated [parathyroid hormone] PTH assay is common but this assay is expensive and clinical significance of monitoring levels is unproven at present. 

Urinalysis

• Isosthenuric urine SG <1.030 Urinalysis: specific gravity although some cats retain urine concentrating capacity (sometimes absent in primary glomerular diseases).
• Abnormal sediment Urinalysis: centrifuged sediment, eg proteinuria, bacteria, hematuria, casts.
• Proteinuria Proteinuria: urine protein: creatinine ratio (UPV) > 0.4.
• Culture Urinalysis: culture and sensitivity: may be positive in face of benign sediment due to inability to concentrate urine and mobilize white blood cells.

Hematology

• Normocytic Hematology: mean corpuscular volume, normochromic Hematology: mean corpuscular hemoglobin concentration, non-regenerative anemia Hematology: packed cell volume.
• Often stress leucogram Hematology: leucogram.
• Bleeding tendency, due to abnormalities in platelet function.

Radiography

• See abdominal radiography Radiography: abdomen.
• Small kidneys.
• Loss of lamina dura of the dental alveolus, giving the appearance of 'floating teeth'.
• Generalized osteopenia.
• Metastatic calcification of soft tissue.
• Rule out underlying causes.

2-D Ultrasonography

• See ultrasonography of the kidneys Ultrasonography: kidney for details on the technique.
• Small kidneys.
• Irregular in outline.
• Increase in echogenicity of renal cortex, blurring of corticomedullary junction.
• Increase in echogenicity at corticomedullary junction due to hypercalcemia.

Assessment of hypertension  

• Ocular examination Eye: examinatio : evidence of tortuous vessels, edema, retinal hemorrhage, retinal detachment.
• Doppler technique appropriate for measurement of systolic blood pressure Blood pressure: Doppler ultrasound Hypertension.
• Values > 160 mmHg with CKD are of concern.

Other

• Glomerular filtration rate (GFR).
• Creatinine clearance assay Creatinine clearance gives rough estimate
• Creatinine clearance = ([urine creatinine] x urine volume/([serum creatinine] in middle of test period x urine collection time in min x bodyweight in kg).
• Glomerular filtration estimation using radiolabelled markers Scintigraphy: renal for GFR has also been studied (normal 2.6 ml/min/kg).
• Fractional electrolyte excretion  Fractional electrolyte excretion increased in renal failure.
• Fractional excretion = ([urine electrolyte] x [serum electrolyte])/([plasma [creatinine] x [urine creatinine]) x 100
  Make sure units are standardized.

Histopathology

• Interstitial fibrosis in 'end-stage' renal disease.
• Nephrocalcinosis.
• Indications of underlying cause.
  Not recommended as provides little additional information and may cause further loss of renal function.

• Small, pale kidneys with irregular contour (normal     ).
• Poor body condition Body condition scores.

• Anemia.
• Oral ulceration/stomatitis.
• Gastroenteritis (uremic).

• Dystrophic calcification of soft tissues   .

• Renal interstitial fibrosis.
• Interstitial nephritis.

• Evidence of underlying renal pathology (pyelonephritis Pyelonephritis, glomerulonephritis, amyloidosis, hydronephrosis   , etc).

• Nephrocalcinosis.

Acute renal failure (ARF)

• ARF  Kidney: acute renal failure: normal to large kidneys, no history of polyuria/polydipsia.
• CKD: anemia, osteodystrophy.

Pre-renal azotemia  

• Caused by diseases that reduce perfusion of the kidneys and reduce GFR Pre-renal azotemia.
• Urine is usually concentrated > 1.040.

Post-renal azotemia

• Urinary tract obstruction Urethra: obstruction, urinary tract rupture Uremia.

• IV fluid therapy Fluid therapy: overview (after taking blood and urine samples) if animal is dehydrated and/or uremic.
• If severe vomiting give metoclopramide Metoclopramide.
  Care with dose as metoclopramide is renally excreted.

• Avoid stressing animal.
• H2-receptor antagonists, ie cimetidine Cimetidine 2.5-5.0 mg/kg BID-TID, or ranitidine   Ranitidine 0.5-2 mg/kg BID PO or IV for poor appetite and/or vomiting.

• Gastrocytoprotective drugs, eg sucralfate  Sucralfate.
• Antibiotic  Therapeutics: antimicrobial drug  if evidence of urinary tract infection Feline lower urinary tract disease (FLUTD).
• ACE-inhibitors ACE inhibitors: overview have recently been investigated for their role in management of CKD in cats, as they reduce proteinuria.
• Clinical trials showed improved quality of life but did not significantly prolong survival in cats receiving benazepril Benazepril.
  May increase creatinine concentration at start of therapy.

Transplantation

• Renal transplantation has been successfully carried out at several centers in the US. Peri-operative mortality is of the order of 25% with 40-50% of cases surviving 3 years.
• Ethical issues regarding the donor cat have prevented this procedure being offered in the UK.

• Treat underlying cause where possible.

Fluid balance

• Unlimited access to water (unless vomiting persists).
• Intravenous fluid therapy Fluid therapy: overview to rehydrate and then promote diuresis of urea and creatinine in acute deterioration of CKD where pre-renal component present.
  Take blood and urine samples before giving fluid therapy.
• Once uremia controlled continue maintenance fluids and taper slowly.
  Care not to volume overload particularly if pre-existing heart disease.

Electrolyte balance

• Dietary phosphate restriction Dietetic diet: for chronic kidney disease (CKD) important.
• Restrict to 65-85 mg/kg/day.
• Aim to reduce serum phosphate levels to target values dependent on IRIS classification:
  • Stage II: 0.81-1.45 mmol/l (2.5-4.5 mg/dl).
  • Stage III: 0.81-1.61 mmol/l (2.5-5.0 mg/dl).
  • Stage IV: 0.81-1.94 mmol/l (2.5-6 mg/dl).
• If phosphate remains high after 4 weeks introduce oral phosphate binders, eg aluminum hydroxide   Aluminum antacid 30-180 mg/kg/day with meals, calcium carbonate (care with hypercalcemia) or lanthanum carbonate.

• Active vitamin D (calcitriol) to reduce secondary renal hyperparathyroidism, but beware of possibility of causing hypercalcemia.
  Use only if can demonstrate a beneficial clinical response.
• Potassium gluconate Potassium chloride / gluconate 2-6 mEq/cat/day PO in food for hyperkalemia.

Controlling azotemia

• Dietary protein restriction is controversial in the cat. Protein restriction is mainly employed to restrict dietary phosphate levels.
• Restrict to 21% of gross energy as protein. Adjust restriction according to requirement of individual cat.
• Peritoneal dialysis.

Management of anemia

• Anabolic steroids Nandrolone may increase protein anabolism, increase erythropoiesis (and may also help to improve cat's appetite).
• Anti-emetics (metocolopramide Metoclopramide, prochlorperazine).
• Blood transfusion Anemia: transfusion indicationsif very anemic. Only when PCV drops below 18% but depends on clinical signs. Consideration needs to be given to ethical use of a donor and the need for repeated transfusions.
• Erythropoietin Erythropoietin or darbopoietin injections in cases of severe non-regenerative anemia.

Hypertension

• Antihypertensive drugs (amlodipine Amlodipine, enalapril Enalapril) if systolic arterial pressure is >160 mmHg Hypertension.
• Hypertensio  Hypertension accelerates progression of chronic renal failure.

• Fluid therapy addresses any dehydration, which can be monitored by clinical examination and measurements of PCV and total protein, bodyweight and central venous pressure (if possible) Central venous pressure.
• Monitor urine output.
• BUN/creatinine: after adequate rehydration, the level of these parameters is indicative of the severity of the renal disease.

Treatment

• Allow free access to water at all times.
• Continue dietary therapy as before.
• Erythropoietin/darbopoietin injections in severely anemic patients: the frequency of injections depends on the response of the individual patient. Watch for signs of anti-erythropoietin antibodies (less likely with darbopoietin).
• If patient is uratemic, H2-receptor antagonists may be indicated, particularly if anorexic or vomiting.
• Phosphate restriction: needs to be adjusted for the individual patient using regular serum phosphate measurements - maintain phosphate at lower end of normal range or PTH normal.
• Avoid drugs which might decompensate cat, eg NSAIDs.

Monitoring

• Generally benefit from routine monitoring; frequency depends on stability.
• BUN/creatinine: intervals depend on individual patients (1-6 months).
• Level of anemia.
• Serum calcium and inorganic phosphate concentration. PTH if possible.
• Serum electrolytes.
• Urine - monitor for urinary tract infection.
• Blood pressure

• Poor: if symptoms persist and animal remains severely uremic, despite adequate rehydration (intensive therapy for 3 days).
• Chronic kidney disease cannot be cured.
• Some animals may remain compensated for a long period on maintenance therapy, particularly in early stages (I-II).

• Improvement in clinical signs.
• Decreased uremia within 2-3 days of fluid therapy.
• Decreased anemia.
• Decreased serum inorganic phosphate level.

• Renal failure is too severe.
• Underlying disease process progresses, despite therapy, which is typical.
• Lack of compliance from patient (unwilling to eat renal diets; uncooperative with oral medication).
• Lack of commitment from owners (time or financial pressures).

Refereed papers

• Recent references from PubMed and VetMedResource.
• Jepson R E, Brodbelt D, Vallance C et al (2009) Evaluation of predictors of the development of azotemia in cats. J Vet Intern Med 23 (4), 806-813 PubMed.
• Roudebush P, Polzin D J, Ross S J et al (2009) Therapies for Feline Chronic Kidney Disease. What is the evidence?​ J Feline Med Surg 11 (3), 195-210 PubMed.
• Syme H (2009) Proteinuria in cats: Prognostic marker or mediator? J Feline Med Surg 11 (3), 211-218 PubMed.
• Boyd L M, Langston C, Thompson K et al (2008) Survival in cats with naturally occurring chronic kidney disease (2000-2002). J Vet Intern Med 22 (5), 1111-1117 PubMed.
• King J N, Tasker S, Gunn-Moore D A et al (2007) Prognostic factors in cats with chronic kidney disease. J Vet Intern Med 21 (5), 906-916 PubMed.
• King J N, Gunn-Moore D A, Tasker S et al (2006) Tolerability and efficacy of benazepril in cats with chronic kidney disease. J Vet Intern Med 20 (5), 1054-1064 PubMed.
• Hostutler R A, DiBartola S P, Chew D J et al (2006) Comparison of the effects of daily and intermittent-dose calcitriol on serum parathyroid hormone and ionised calcium concentrations in normal cats and cats with chronic renal failure. J Vet Intern Med 20 (6), 1307-1313 PubMed.
• Ross S J, Osborne C A, Kirk C A et al (2006) Clinical evaluation of dietary modification for treatment of spontaneous chronic kidney disease in cats. J Am Vet Med Assoc 229 (6), 949-957 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.
• Elliott J, Rawlings J M, Markwell P J et al (2000) Survival of cats with naturally occurring chronic renal failure: effect of dietary management. JSAP 41 (6), 235-242 PubMed.
• Barber P J, Rawlings J M, Markwell P J et al (1999) Effect of dietary phosphate restriction on renal secondary hyperparathyroidism in the cat. JSAP 40 (2), 62-70 PubMed.
• Barber PJ & Elliott J (1998) Feline chronic renal failure- clinical findings in 80 cases diagnosed between 1992 and 1995. JSAP 39 (2), 78-85 PubMed.
• Barber P J & Elliott J (1998) Feline chronic renal failure- calcium homeostasis in 80 cases diagnosed between 1992 and 1995. JSAP 39 (3), 108-116 PubMed.

Other sources of information

• Sanderson S L (2009) Measuring glomerular filtration rate: practical use of clearance tests. In: Kirks Current Veterinary Therapy XIV, (ed) J Bonagura & D Twedt, Elsevier Saunders pp 868-871.
• Polzin D J, Osborne C A & Ross S (2009) Evidence-based management of chronic kidney. In: Kirks Current Veterinary Therapy XIV, (ed) J Bonagura & D Twedt, Elsevier Saunders pp 872-879.
• Elliott J & Watson A D J (2009) Chronic kidney disease: Staging and management. In: Kirks Current Veterinary Therapy XIV, (ed) J Bonagura & D Twedt, Elsevier Saunders pp 883-892
• Elliott J (2008) The role of phosphate in chronic kidney disease (CKD) progression: Part 1. UK Vet 13 (2), 23-28 VetMedResource.
• Elliott J (2008) The role of phosphate in chronic kidney disease (CKD) progression: Part 2. UK Vet 13 (2), 37-41 VetMedResource.
• International Renal Interest Society: www.iris-kidney.com