Chronic kidney disease

• Chronic kidney disease (CKD) - overview


  Also referred to as chronic renal failure (CRF)

  Long-standing, irreversible damage to the kidneys, that impairs their function.

  Self-perpetuating - progressive over time at a variable rate.

  Common in dogs, very common in cats.

  Can have underlying cause e.g. Polycystic kidney disease, pyelonephritis, toxins, glomerulonephritis, neoplasia, amyloidosis, FIP

  Often no cause identified - age related degeneration
• Chronic kidney disease (CKD) - common presenting signs

  PUPUD

  Anorexia

  Weight loss

  Vomiting and diarrhoea

  Dehydration

  Pallor

  Mucosal ulcers

  Uraemic breath.
• Chronic kidney disease (CKD) - breed predispositions

  Dogs:

  • Westie, Boxer, Shar Pei, Bull Terrier, Cocker spaniel, CKCS

  Cats:

  • Persian, Abyssian, Siamese, Ragdoll, Burmese, Russian blue, Main coon
• Chronic kidney disease (CKD) - age pre-dispositions

  Can be juvenile if there is underlying familial disease, e.g. Polycystic kidney disease. Most common though is older animals (age associated disease processes).
• Chronic kidney disease (CKD) - co-morbidities

  Conditions likely to cause renal insult:

  • Hyperthyroidism, Hypercalcaemia, heart diseases, periodontal disease, cystitis, urolithiasis, diabetes.
  • Previous acute kidney injury
  • Nephrotoxic drugs - NSAID, aminoglycosides (gentamycin), sulphonamides, polymyxins, chemotherapeutics.
• Chronic kidney disease (CKD) - pathophysiology

  Nephron damage progressive and irreversible.

  Nephron loss > other nephrons GFRs increased to compensate > glomerular capillary wall damage and more plasma protein filtration > further glomerular and tubulointerstitial damage.

  Nephron loss > reduced total GFR > build-up of products normally excreted (e.g. urea) > uraemic crisis.
• Chronic kidney disease (CKD) - uraemic crisis overview

  Build-up of urea and other toxins usually excreted in kidneys to intolerable levels.

  Due to:

  • End stage chronic kidney disease
  • Acute kidney injury
  • Acute on chronic - AKI (e.g. ischemic or toxic insult) exacerbating existing CKD.
• Chronic kidney disease (CKD) - uraemic crisis clinical signs

  Vomiting/ nausea

  Anorexia

  Lethargy

  Depression

  Oral ulcers

  Melena (GI ulcers)

  Anaemia

  Weakness

  Hypothermia

  Muscle tremors

  Seizures

  Death.
• Chronic kidney disease (CKD) - treatment

  IVFT - Hartmann’s

  • Replace dehydration + ongoing losses
  • Care if AKI not to over perfuse - measure urine.

  If can measure blood gases - assess for acidosis.

  • Bicarbonate if pH <7.2 or serum bicarbonate <12

  Treat nausea/GI ulceration

  • Omeprazole +/- H2 Blockers +/- sucralfate
  • Antiemtics e.g. maropitant
  • Pain relief - opioid (NSAIDs are nephrotoxic)
• Chronic kidney disease (CKD) - nutritional support

  Appetite stimulants - Mirtazapine

  Feeding tubes (nasogastric)

  Beware food aversion - DO NOT introduce renal diet in hospital.
• Chronic kidney disease (CKD) - IRIS staging

  Early staging (I or early II) - rarely picked up this soon.

  • Abnormal renal imaging/ known insult OR
  • Persistent elevation/ increasing Creatinine/SDMA OR
  • Persistent renal proteinuria

  Later stages (Late II-IV)

  • Consistent clinical signs
  • Azotaemia/ persistently elevated creatinine /SDMA
  • USG<1.035 (cats) or <1.030 (dogs)
• Chronic kidney disease (CKD) - markers of GFR - serum creatinine


  Product of muscle metabolism

  Produced at constant rare and excreted via kidney

  Muscle atrophy/cachexia can decrease.

  Can increase after feeding - starved sample

  Only increases when more than 75% of nephrons already lost!
• Chronic kidney disease (CKD) - markers of GFR - SDMA


  Symmetric dimethylated arginine

  Produced by all uncleated cells at constant rate and cleared by kidneys.

  Not affected by muscle mass.

  Increases at 40% nephron loss.

  But more expensive, less available and possible less sensitive.
• Chronic kidney disease (CKD) - treatment

  Treat underlying cause of possible/ known.

  Slow progression by managing risk factors.

  Recommednations vary by stage/substage but focus around monitoring/controling.

  • Proteinuria
  • Hypertension
  • Hyperphosphateamia

  As linked to progression and worse prognosis
• Chronic kidney disease (CKD) - diet

  Very important in stage II onwards

  • Treatinf secondary anaemia/ acidosis/ nausea
  • Maintaining hydration
  • Ensuring adequate nutrition.
• Chronic kidney disease (CKD) - treating stage 1

  use nephrotoxic drugs with caution.

  Correct pre-renal and post-renal abnormalities.

  Fresh water available at all times

  Monitor trends in creatinine and SDMA to document stability or progression.

  Investigate for and treat underlying disease and/or complications.

  Treat hypertension if systolic blood pressure persistently >160 or evidence of end-organ damage.

  Treat persistent proteinuria with renal therapeutic diet and medication.
• Chronic kidney disease (CKD) - treating stage 2

  Same as stage 1.

  Renal therapeutic diet.

  Treat hypokalaemia in cats

  Treat hypokalaemia in cats.

  Treat inappetence and nausea if present.
• Chronic kidney disease (CKD) - treating stage 3


  Same as stage 3.

  Keep phosphorus.

  Consider feeding tube for nutritional and hydration support and ease of medicating.
• Chronic kidney disease (CKD) - hyperphophatemia

  Phosphate - filtered by kidney so builds up in CKD

  High phosphate > quicker progression of renal disease.

  Can also > hyperparathyroidism > metabolic bone disease.

  Aim to jeep to low end of reference range:

  • Dietary restriction (renal diet).
  • +/- enteric phosphate binders (e.g. Aluminium hydroxide)

  Monitor serum phosphate monthly until stable then 3 monthly.
• Chronic kidney disease (CKD) - hypertension causes

  Primary:

  • Stress/ environment
  • Idiopathic (prevalence >12% in healthy cats >10 years).

  Secondary:

  • Iatrogenic (e.g. glucocorticoids)
  • Systemic disease inclduing CRF, Cushing’s, hyperT4, hypoT4, DM, obesity, pheochromocytome or primary hyperaldosteronism.
• Chronic kidney disease (CKD) - hypertension and CRF diagnosis

  Based on repeated measurements of systolic blood pressure (SBP)

  • Consistent technique and equipment.

  Approximately 20% of CKD Pateints have increased blood pressure at diagnosis.

  A further 10-20% will develop increased blood pressure over time.
• Chronic kidney disease (CKD) - effects of hypertension on kidneys

  Faster decline of renal function.

  Increased proteinuria.

  More frequent uraemic crises

  Higher mortality.
• Chronic kidney disease (CKD) - treatment of renal hypertension


  ACE inhibitors (ACEi) - Benazepril, Enalapril.

  Angiotensin receptor blockers (ARB) - Telmisrtan, Spironolactone

  Calcium channel blocker (CCB) - more in cats - Amlodipine
• Chronic kidney disease - monitoring hypertension and CRF


  Wait 3-4 weeks between changes (unless emergency) but recheck (after 1-2 weeks if CRF stable or 3-4 days in unstable/late stage).

  Check for:

  • Evidence of worsening EOD on exam.
  • Marked increase in azotemia
  • Evidence syncope/hypotension

  Antihypertensives should reduce proteinuria if present
• Other causes of chronic renal disease - renal causes

  Glomerular disease

  Fanconi’s syndrome

  Polycystic Kidney disease

  Pyelonephritis

  Nephrotoxin exposure

  Neoplasia
• Other causes of chronic renal disease - extra-renal causes

  Hypertension

  Cardiac disease

  Hyperthyroidism

  Diabetes

  Urolithiasis/ obstruction

  Cystitis

  Neoplasia

  Hypercalcaemia.
• Definition of pyelonephritis

  Bacterial infection of the renal pelvis and parenchyma. Uncommon in cats an dogs with normal urinary tracts but:

  • 5-8% prevalence if CKD.
  • Increased prevalence in other conditions e.g. AKI/urolithiasis/obstruction.

  Can cause/worsen underlying kidney disease
• Diagnosis of pyelonephritis

  Compatible clinical signs (fever, abdominal pain, PUPD)

  Haemotology - Neutrophilia with left shift.

  Ultrasound - renal pelvis dilation with hyperechoic mucosa, altered cortex/ medulla echogenecity.

  NOT pyelocentesis as high risk - culture urine sample.
• Treatment of UTIs/ pyelonephritis

  Choose renally excreted drugs e.g. amoxicillin/amoxiclav as will have a higher concentration in urine.

  • E.coli (common UTI infection) can be resistant so culture if necessary.

  Other options:

  • TMPS (sheep) - beware as many adverse side effects, but is much cheaper.
  • Fluoroquinolones
  • 3rd gen cephalosporins
  • Only used if confirmed pyelonephritis that is resistant to other drugs.
• Nephrotoxic antibiotics

  Avoid when treating any infection in patient with CKD.

  Aminoglycosides - can cause acute tubular necrosis.

  Enrofloxacin - can cause renal damage in cats with reduced renal functions.
• Renal neoplasia - benign primaries

  Renal primary neoplasia is very common.

  Benign primaries:

  • Adenomas, lipomas, fibromas, and papillomas - usually incidental.
• Renal neoplasia - malignant primaries

  Common site of metastatic spread possibly > CKD signs if bilateral or underlying issue.

  Usually unilateral so rarely signs of CKD.

  Carcinoma:

  • Usually at one pole and well demarcated.
  • Mets early to other kidney/lungs/liver/adrenals
  • Less common - transitional cell carcinomas, renal sarcomas.
• Renal neoplasia - multicentric

  Can result in CKD.

  Lymphoma - renal lesions found in up to 50% of dogs and cats with lymphoma.

  • Can be found only in kidneys (particularly in cats)
  • Usually multifocal or diffuse, interstitial and bilateral > large, irregular kidneys.
• Chronic kidney disease - polycystic kidney disease (PKD) overview

  Autosomal dominant hereditary condition.

  Fluid filled cysts present from birth in the kidney and possibly other organs (e.g. liver and pancreas). Size and number gradually increase with age > CRF.

  Average age clinical signs 7 years.

  Exam as CRF but large irregular kidneys.
• Chronic kidney disease - polycystic kidney disease (PKD) diagnosis and advise

  Diagnose with ultrasound. Hypo/anechoic spherical cavities.

  Advise - all Persians/ exotic short haired screened before breeding even if parents ultrasound is negative.

  • Ultrasound (from around 10 months).
  • Genetic testing preferred (any age) - PCR for mutated PKD1 gene.
• Chronic kidney disease - Fanconi’s syndrome causes

  Disease of proximal tubule > reduced resorption of solutes - dogs - loss of glucose, Na+, K+, phosphorous, bicarbonate, albumin, and amino acids.

  Causes:

  • Idiopathic
  • Hereditary - gradual onset - mostly Basenjis (genetic marker)
  • Gentamycin nephrotoxicosis (discontinue)
  • Chicken jerky treats (discontinue)
• Chronic kidney disease - Fanconi’s syndrome signs

  PUPD and weight loss +/- signs of uraemia.

  Diagnosis:

  • Increased urinary fractional excretion of glucose, Na+, K+, phosphorous and bicarbonate in urine despite normal plasma concentration.
• Chronic kidney disease - Fanconi’s syndrome treatment


  Supplement oral NaCl (5-10mg/kg/day, PO), K+ (potassium citrate 10-30mg/kg/day,PO), an bicarbonate if serum concentration is low.
• Chronic kidney disease - glomerular disease overview


  Can be secondary to advanced CKD or primary and cause/ worsen CKD. Glomerular damage > low molecular weight proteins (notably albumin and antithrombin) pass into urine - protein losing nephropathy.

  Signs consistent with CKD/ureamia or can be non-specific weight loss/ lethargy.
• Chronic kidney disease - glomerular disease diagnosis

  Haemotology/biochemistry

  • Likely as for CRF but may not be azotaemia
  • Likely hypoproteinaemia

  Urinalysis

  • Proteinuria
  • May still be able to concentrate urine
  • Hyaline casts common as protein lines tubules.