Chronic kidney disease Flashcards
Another term for CKD
- Chronic Renal Failure (CRF)
What is CKD?
- Long-standing, irreversible damage to the kidneys that impairs their function.
- Self-perpetuating - Progressive over time at variable rate.
Is CKD common in cats & dogs?
- Common in dogs
- very common in cats (30-80% prevalence reported in geriatric cats)
Causes of CKD
Can have underlying cause e.g.
- Polycystic Kidney Disease
- pyelonephritis
- toxins
- glomerulonephritis
- neoplasia
- amyloidosis
- FIP
Often no cause identified
- age related degeneration
Common presenting signs
- PU/PD
- Anorexia
- Weight loss
- Vomiting and diarrhoea
- Dehydration
- Pallor
- Mucosal ulcers
- Uraemic breath
Breed predispositions
- Dogs- Westie, Boxer, Shar Pei, Bull Terrier, Cocker Spaniel, CKCS
- Cats-Persian, Abyssinian, Siamese, Ragdoll, Burmese, Russian Blue, Maine Coon
Age predispositions
- Can be juvenile if underlying familial disease, e.g. Polycystic Kidney Disease
- Older animals if not- age associated disease processes
Co-morbidities - Conditions likely to cause renal insult
- e.g. Hyperthyroidism, hypercalcemia, heart diseases, periodontal disease, cystitis, urolithiasis, diabetes etc
- Previous Acute Kidney Injury
- Nephrotoxic Drugs- NSAID, aminoglycosides, sulphonamides, polymyxins, chemotherapeutics
CKD pathphysiology
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.
* Reduced renal function > reduced Erythropoietin (EPO) production > non-regenerative anaemia
* Reduced metabolism and excretion of parathyroid hormone > renal hyperparathyroidism (osteodystrophy)
What is uraemic crisis?
- Build-up of urea and other toxins usually excreted in kidneys to intolerable levels
What does uraemic crisis occur due to?
- End stage Chronic Kidney Disease
- Acute Kidney Injury
- Acute on Chronic –AKI (e.g. ischemic or toxic insult) exacerbating existing CKD
Uraemic crisis - CS
- Vomiting/nausea
- Anorexia
- Lethargy
- Depression
- Oralulcers
- Melena (GI ulcers)
- Anaemia
- Weakness
- Hypothermia
- Muscle tremors
- Seizures
Uraemic crisis tx
Work out if AKI, CKD or acute on chronic and treat as needed but in addition:
* IVFT- Hartmann’s
– Replace dehydration + ongoing losses
– Care if AKI not to over perfuse- measure urine
* If can measure blood gases- assess for acidosis
– Bicarb if pH <7.2 or serum bicarb < 12
* Treat nausea/GI ulceration
– Omeprazole +/- H2 Blockers +/- sucralfate
– Antiemetics e.g. maropitant
– Pain relief – opioid
* Nutritional support- Important
– Appetite stimulants- Mirtazapine
– Feeding tubes (Nasogastric)
– Beware food aversion-DO NOT
introduce renal diet in hospital
Acute vs chronic (age, duration, hx, exam, harm/biochem, urine)
AKI & CKD can both present with uraemic crisis, but differentiation is very important as treatment and prognosis very different.
Age:
CKD - Often older
ARF - Any
Duration:
CKD - >3 months
ARF - <48 hours
Common history:
CKD - Weeks/ months of weight loss, reduced appetite PU/PD. Possible historic of renal insult
ARF - Sudden onset. Possible access to nephrotoxins (toxins or drugs) or evidence of urinary obstruction.
Exam:
CKD - BCS and coat quality reduced. Kidneys small and hard (enlarged possible dependant on cause e.g. PKD)
ARF - Good BCS, kidneys possibly enlarged and painful. Possibly v small bladder.
Haem/biochem:
CKD - K+ normal /decreased, relatively well for severity of azotaemia, non-regenerative anaemia
ARF - K+ increased, Metabolic acidosis, V unwell for severity of azotaemia, Haematology often normal
Urine:
CKD - USG <1.035 (inappropriately dilute), sediment usually not active though possible if UTI. Possible proteinuria.
ARF - USG usually 1.008-1.015 but can be any if bladder not emptied since onset. Urine casts/ proteinuria/ cell debris common. Possible glucosuria
Diagnosis - IRIS staging
Early stage (I or early II)- rarely picked up this soon:
* Abnormal renal imaging/ known insult OR
* Persistent elevation/ increasing Creatine/ SDMA OR
* Persistent renal proteinuria
Later stages (Late II- IV):
* Consistent clinical signs
* Azotaemia/ persistently elevated creatinine/ SDMA
AND
USG <1.035 (cats) or <1.030 (dogs) (this is important - doesn’t haven’t to be isosthenuric)
CKD - markers of GFR
- Serum creatinine
- SDMA (symmetric dimethylated arginine)
Current consensus: When staging- use either/both
Serum creatinine
- Product of muscle metabolism
- Produced at constant rate and excreted via kidney
- Muscle atrophy/cachexia can decrease
- Can increase after feeding- starved
sample - only increase when >75% of nephrons already lost
SDMA
- Produced by all nucleated cells at constant rate and cleared by kidneys
- Not affected by muscle mass
- Increases at 40% nephron loss
- BUT more expensive, less available and possibly less sensitive?
CKD tx
- Treat underlying cause if possible/known
- Slow progression by managing risk factors.
- Recommendations vary by stage/substage, but focus around monitoring/ controlling
– Proteinuria
– Hypertension and
– Hyperphosphatemia
As linked to progression and worse prognosis
Diet very important stage II onwards
Later stages - more emphasis on
* Treating 2ndary anaemia/acidosis/nausea
* Maintaining hydration
* Ensuring adequate nutrition
Why does hyperphosphataemia occur with CKD?
- Phosphate- filtered by Kidneys so builds up in CKD
- High phos > quicker progression of renal disease
What other condition can hyperphosphataemia cause?
- hyperparathyroidism > Metabolic Bone Disease
Hyperphosphataemia tx
Aim to keep to low end of ref range via
* Dietaryrestriction(renaldiet)
* +/-enteric phosphate binders (e.g. Aluminium hydroxide)
Monitor serum Phos monthly until stable then 3 monthly.
FGF23- new biomarker;
- Increases in cats who have phos within target range but are still at increased risk of hyperparathyroidism
- Once phos stable consider measuring FGF23 – if elevated further restrict phos (care interpreting if anaemia/inflammatory dx or pre-existing hyperCa2+)
Primary causes of hypertension
- Stress/environment
- Idiopathic (prevalence >12% in healthy cats >10 yrs)
Secondary causes of hypertension
- Iatrogenic (e.g. glucocorticoids)
- Systemic disease including CRF, Cushing’s, hyperT4, hypoT4, DM,
obesity, pheochromocytoma or primary hyperaldosteronism
Concern with hypertension
- end organ damage if sustained
Hypertension diagnosis
Based on repeated measurements of systolic blood pressure (SBP) – consistent technique and equipment
- Approx 20% of CKD patients have increased BP at diagnosis
- A further 10-20% will develop increased BP over time- monitor
Treat if SBP reliably and consistently >160 mm Hg and evidence of EOD (CKD = evidence)
- SBP <140mmHg = normotensive
- SBP 140-159mmHg = pre-hypertensive
- SBP 160-179mmHg = hypertensive
- SBP >180mmHg = severely hypertensive
Effect of hypertension on kidneys
- Faster decline of renal function
- Increased proteinuria
- More frequent
uremic crises - Higher mortality
Tx of renal hypertension
ACE inhibitors (ACEi):
* e.g. Benazepril, Enalapril
Angiotensin receptor blockers (ARB)
* e.g. Telmisartan, Spironolactone
Calcium Channel Blocker (CCB)
* e.g. Amlodipine
Hypertension tx aim & specific for dogs + cats
Aim to reduce to <150mmhg over a few weeks – quicker (hours) if severe ocular / CNS signs
Dogs – aim to interfere with RAAS activation . Should reduce BP and proteinuria
* Angiotensin receptor blockers (ARB) -1st choice
* ACE inhibitors (ACEi)
If needed can add in Calcium Channel Blocker (CCB)to ACEi or ARB
Cats- start with CCB as more effective at reducing BP unless also proteinuria
* Can add ARB or ACEi to CCB to increase effect if needed.
* If also proteinuria then start with an ARB (Telmisartan).
Consider low salt diet- increased effects of ACEis and ARBs in dogs and cats.
Monitoring hypertension
Wait 3-4 weeks between changes (unless emergency) but recheck sooner (after 1-2 weeks if CRF stable or 3-4 days if unstable/ late stage)
Check for-
* Evidence of worsening EOD on exam
* Marked increase in azotaemia
* Evidence syncope/hypotension (SBP <120mmHg)
Antihypertensives should reduce proteinuria if present
* Aim for >50% reduction in UPCR
Once stable and BP <150mmHg can check BP Q4 months
Why does CKD cause proteinuria?
Nephron loss > other nephrons GFRs increased to compensate> glomerular capillary wall damage and more plasma protein filtration > further glomerular and tubulointerstitial damage
Proteinuria diagnosis
If urine dipstick positive assess via Urine Protein Creatinine Ratio (UPCR)
– UPCR >0.5 (dog) or >0.4 (cat) –Likely caused by glomerular leakage, IF no inflammation/haematuria
(UPCR >3.5 = more likely primary glomerular disease)
Proteinuria tx
- RAAS inhibitor (ACEI or ARB) and feed a clinical renal diet
Other causes of chronic renal disease
While CKD can occur as a result of aging changes and fibrosis there are conditions which can predispose CKD development.
Renal examples:
- Glomerular disease
- Fanconi’s syndrome
- Polycystic Kidney Disease
- Pyelonephritis
- Nephrotoxin exposure
- Neoplasia
Extrarenal examples:
-Hypertension
-Cardiac disease
- Hyperthyroidism
-Diabetes
- Urolithiasis/ obstruction Cystitis
- Neoplasia
- Hypercalcaemia
What is pyelonephritis?
- bacterial infection of the renal pelvis and parenchyma
Pyelonephritis prevalence
Uncommon in cats and dogs with normal urinary tracts but
* 5-8% prevalence if CKD
* Increased prevalence in other conditions e.g. AKI/ urolithiasis/ obstruction
Can pyelonephritis worsen/cause underlying kidney dz?
- yes
Pyelonephritis diagnosis
- Compatible clinical signs (fever, abdo pain, pu/pd)
- Haematology - neutrophilia with left shift
- Ultrasound - renal pelvis dilatation with hyperechoic mucosa, altered cortex/ medulla echogenicity.
- NOT pyelocentesis as high risk- culture urine sample
Antibiotics and CRF
Up to 33% dogs and 25% cats with CKD +ive urine culture – subclinical
Only treat if clinical signs of cystitis/ pyelonephritis (point of debate)
Treatment of UTIs/ pyelonephritis with antibiotics
Choose renally excreted drugs e.g. amoxycillin/ amoxyclav -higher conc in urine
* E.coli can be resistant so culture if recurrence/ pyelonephritis
Other options
* TMPS- beware many adverse effects
* Fluoroquinolones?- NOT Enrofloxacin in cats
* 3rd Gen Cephalosporins (e.g. cefotaxime)?
Note - fluoroquinolone & 3rd Gen cephalosporins are protected, so only use if confirmed pyelonephritis
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 function at high
doses
Benign primary neoplasia of the kidneys
Adenomas, lipomas, fibromas, and papillomas- usually incidental
Malignant primary neoplasia of the kidneys
- usually unilateral so rarely signs of CKD
Is primary renal neoplasia common?
- no
Are the kidneys a common site of metastatic spread?
- yes
- consider CKD signs if bilateral or underlying issue
Renal carcinoma
- Usually at one pole and well demarcated
- Mets early to other kidney/ lungs/ liver/ adrenals
- Less common- Transitional cell carcinomas, renal sarcomas
Multicentric- Can result in CKD
Renal 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
What is polycystic kidney disease (PKD)?
- 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.
PKD signalment
- Breeds- Persians (34%), Exotic Shorthair, Himalayan, British/American Shorthair, Burmilla, Ragdoll, Maine Coon
- Average age clinical signs 7 yrs
PKD exam & diagnosis
- Exam- as CRF but large irregular kidneys
- Diagnosis -ultrasound -hypo/anechoic spherical cavities
Advise for PKD
Advise all Persians / exotic short haired screened before breeding even if parents ultrasound negative.
* Ultrasound (from 10 months)
* Genetic testing preferred (any age)- PCR for mutated PKD1 gene
What is Fanconi’s syndrome?
Disease of proximal tubule > reduced resorption of solutes -> loss of glucose, Na+, K+, phosphorus, bicarbonate, albumin, and amino acids
Causes of Fanconi’s syndrome
- Idiopathic
- Hereditary- gradual onset- mostly Basenjis (genetic marker)
- Gentamycin nephrotoxicosis (discontinue)
- Chicken Jerky treats(discontinue)
Signs of Fanconi’s syndrome
- PU/PD and wt loss +/- signs of uraemia
Fanconi’s syndrome diagnosis
- Increased urinary fractional excretion of glucose, Na+, K+, phosphorus & bicarbonate in urine despite normal plasma concs.
Fanconi’s syndrome tx
- remove cause if possible
- Supplement oral NaCl (5–10 mg/kg/day, PO), K+ (potassium citrate 10–30 mg/kg/day, PO), and bicarb (sodium bicarbonate 10–30 mg/kg/day, PO) if serum concentration is low
Glomerular disease
- 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 (PLN)
Glomerular disease - signs
- consistent with CKD/ uraemia or can be non-specific weigh loss/ lethargy
Glomerular disease diagnosis
Haematology/ Biochem
* 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
Primary glomerular disease signalment
CATS- less common than in dogs
DOGS- A leading from of renal disease, Most common in middle age
Primary glomerular disease - common causes in cats
- neoplasia
- systemic inflammatory diseases
- chronic FeLV/ FIV/ FIP
Primary glomerular disease - common primary forms in dogs
Immune complex glomerulonephritis
* immune complexes in the glomerular capillary wall, > inflammatory change
* Idiopathic (most) or associated with neoplasia, rickettsial diseases , SLE, heartworm, pyometra, chronic septicaemia or adenovirus.
Familial glomerulopathies
* in several breeds including Bernese Mountain Dogs, English
Cocker Spaniels, English Springer Spaniels, Doberman, Greyhounds and more
Amyloidosis (non-familial form)
*Chronic inflammation results in protein deposition in glomerulus
Glomerulosclerosis
* Currently poorly characterised but IDed at histology
Glomerular disease- investigations
Proteinuria is a hallmark of glomerular disease
- Assess proteinuria via Urine Protein Creatinine Ratio (UPCR)
– UPCR >0.5 (dog) or >0.4 (cat) –Likely caused by glomerular leakage, IF no inflammation/haematuria
– Higher UPCR = more likely primary glomerular disease- >3.5 investigate for Glomerular disease
Imaging findings may be non-specific, possible:
* Small kidneys
* Increased cortex echogenicity
* Loss of corticomedullary definition
Renal biopsy- definitive diagnosis
Indications for renal biopsy
Only if will alter patient management (generally not CKD) e.g.
* PLN – unexpected/doesn’t respond to treatment
* AKI- cause and prognosis
* Mass lesions
Contraindications for renal biopsy
- Late stage CKD
- Severe anaemia/ azotaemia
- Uncontrolled hypertension/ coagulopathy
- Severe hydronephrosis/ many large cysts
- Pyelonephritis/ perirenal abscesses
- NSAIDs in last 5 days
Requires GA & operator skill
Renal biopsy technique
- Ultrasound guided- preferred
- Laparoscopic/keyhole
- Surgical wedge biopsy- avoid specific areas * Blind/palpation?-care - cats only
Only sample CORTEX or bleeds/ infarctions/ fibrosis
Ideally cranial or caudal pole for best sample of glomeruli
Ask lab what to fix samples with for histo/ electron microscopy/ immunofluorescence
Renal biopsy after care
Severe haemorrhage post procedure possible
* IVFT 24 hours post to reduce chance renal pelvis clots
* Rest patient for 72 hrs and monitor PCV
What is nephrotic syndrome?
Uncommon result of Protein Losing Nephropathies (PLNs)
Pathognomonic for glomerular disease
Clinical findings of nephrotic syndrome
in addition to usual signs of renal disease)
* Pitting oedema /ascites/ pleural effusion
* Hypoalbuminaemia
* Hyperlipidaemia (TGs and cholesterol)
Why does PLN/nephrotic syndrome cause hyperlipidaemia, ascites/oedema & hypoalbuminaemia?
- Excessive protein loss via kidneys -> hypoalbuminaemia
- Hypoalbuminaemia -> Upregulation of cholesterol and triglyceride production & reduced plasma oncotic pressure
- Upregulation of cholesterol and triglyceride production -> hyperlipidaemia
- reduced plasma oncotic pressure + increased vascular permeability + altered renal tubule Na+ retention -> 3rd spacing of fluid (ascites/oedema)
Nephrotic syndrome tx
- Antiproteinurics
- Anticoagulants
- Fluid removal
Use of antiproteinurics for tx of nephrotic syndrome
- Slow nephron damage and increase plasma oncotic pressure
- ACE-inhibitors- e.g. Benazepril/ Enalapril
Use of anticoagulants for tx of nephrotic syndrome
- Risk of thromboembolism - as regulatory proteins (e.g.
antithrombin and protein S) lost along side albumin - Aspirin or Clopidogrel- minimize spontaneous platelet
aggregation.
Use of fluid removal for tx of nephrotic syndrome
- Only if severe impairment of resp/ heart/QoL as result
- Will reform as RAS upregulates and worsens hypovolaemia
- Abdominal/ pleural tap
- Diuretics- frusemide? Spironolactone (K+ sparing)
Glomerular disease- treatment
- If a cause of immune complex disease present – treat
- Manage Nephrotic syndrome if present
- Limit proteinuria
– ACEi (or ARBs) – reduce further interstitial fibrosis - If glomerular inflammation at biopsy and no known primary antigenic stimulus consider Immunosuppressives
– e.g. mycophenolate, azathioprine, cyclophosphamide, cyclosporine
– NB-Corticosteroids only beneficial in mild glomerulopathy and can worsen
proteinuria. - Monitor and manage CKD as per IRIS staging
CRF prognosis - dependent on
- Complications (e.g. high BP, glomerulonephritis)
- Patient age
- Duration and severity of signs
- Serum phosphorus
- Severity of proteinuria
- IRIS stage
- Primary disease process
- Owner commitment
- Ability to medicate/ feed
as required
CRF prognosis in cats
Mean days survival from diagnosis:
- Stage II =1151 days
- Stage III =679 days
- Stage IV =35 days
↓ if:
* Uncontrolled hypertension
* Persistent ↑ Serum Phosphorus
* Persistent Proteinuria
* Unable to medicate/
switch to renal diet.
* Can’t control
underlying issue
CRF prognosis in dogs
Median survival from diagnosis:
- Stage II = 200-400 days
- Stage III = 110 to 200 days
- Stage IV = 14 to 80 days
↓ if:
* Uncontrolled hypertension
* Persistent ↑ Serum Phosphorus
* Persistent Proteinuria
* Unable to medicate/
switch to renal diet.
* Can’t control
underlying issue.
Rabbits and CKD
- Same underlying disease processes as dogs and cats (but also can be due to E. Cuniculi)
Rabbits and CKD - CS
- PU/PD, weight loss (hide signs well)
- occasional haematuria (renal infarctions / 2ndary to hypercalciuria > uroliths)
Rabbits and CKD - diagnosis
Urinalysis
- (Don’t cysto if possible -free catch/ express)
- Inappropriate urine concentration (ref 1.003-1.035- should be >1.035 if dehydrated). - Proteinuria common in CRF
–possible in healthy animals/ inflammatory disease/contaminants
– interpret with USG and sediment and consider UPCR
Biochem
- hypercalcaemia and azotaemia (use lab reference ranges for rabbits).
- If severe also ^K+ and Phos.
Rabbits and CKD - tx
- Treat underlying causes if possible
- Discontinue nephrotoxic drugs
- Treatment as dogs/cats BUT dietary management different (see endocrine)
- 2ndary hypertension common- diagnose as dogs/cats and treat with ACEi
