Urinary and endocrine Flashcards
What is PUPD?
> 50ml/kg/day - polyuria
100ml/kg/day intake dogs, >50ml/kg/day intake cats - polydipsia
One can drive the other - primary polydipsia or primary polyuria
Primary polydipsia - causes
Difficult to prove - often idiopathic
Altered thirst
- Centrally mediated disease - primary (neoplasia), secondary (changes to osmolarity or endocrine effects), compensating for losses other than urinary - GI, third space
Concentrated blood - osmolarity - drink to compensate
Physiological
- Salt toxicity - sea water
- Exercise
- High environmental temperature
Primary polyuria
Broadly - intrinsic renal problem, or extrinsic effect on kidneys
ADH (anti diuretic hormone) - increases aquaporin density and increased reabsorption from tubules
Osmotic diuresis - if urine contains solutes above normal values (e.g. glucose in diabetes mellitus) this ‘draws’ water into the tubules increasing output
Medullary solute washout – i.e. loss of solutes from the medulla, also leads to a concentration gradient and osmotic water loss. Can be overloaded on fluids to cause this
Interstitial tonicity reduction – protein restricted diets; reduced concentration gradients across the interstitium.
Increased GFR – e.g. hypertension will lead to increased filtration in excess of the kidneys resorptive capability - GFR dictated by perfusion - increased tension increases filtration
Causes of primary polyuria - ADH related
No ADH production (hypothalamus) or release (pituitary) – Central Diabetes Insipidus
Reduced ADH sensitivity/response
- Primary Nephrogenic Diabetes Insipidus (rare) – kidneys cannot respond to ADH
- Secondary NDI – primarily endocrine/inflammatory but can be other poorly known interactions – extrinsic cause to lack of ADH response by kidneys
- Hyperadrenocorticism (Cushings)
- Hypoadrenocorticism (Addisons)
- Hyperthyroidism
- Hyperaldosteronism (Conns)
- Liver Disease
- Pyelonephritis
- Pyometra
- Hypokalaemia
- Hypercalcaemia (think of all the various causes e.g. hyperPTH, neoplasia)
- Erythrocytosis
- Lepto
- Acromegaly (Excess GH – 25% of Diabetic Mellitus cats!)
- Neoplasia – Leiomyosarcoma, Haemangiosarcoma (unknown mechanism)
- Drugs e.g. steroids
Causes of primary polyuria - Glucose related
Osmotic Diuresis
- Glucose
- Diabetes Mellitus
- Primary renal glycosuria
- Fanconi’s syndrome (Basenjis (10% of Basenjis), small breed dogs, secondary to dodgy jerky ingestion!) (Proximal tubular disease and loss of glucose, but amino acids, bicarb, electrolytes, lactate, etc.)
Primary polyuria - sodium related
Osmotic diuresis
Sodium
- Post obstructive diuresis (blocked cats – multifactorial, glomerular/renal damage e.g. ADH response is probably also reduced)
- High salt diet
- Addisons
- Diuretics
- Spironolactone
- Furosemide (loop diuretic – also lose potassium!)
Primary polyuria - reduced medullary/interstitial tonicity - causes
Reduced medullary/interstitial tonicity
- Low protein diet
- Medullary washout (e.g. prolonged PUPD, prolonged aggressive fluid therapy)
Primary polyuria causes - unknown or mixed
Mixed/unknown cause
- Chronic Renal Failure
- Don’t forget, this could be present from youth in congenital defects e.g. renal dysplasia
- Acute Kidney Injury
- Phaeochromocytoma (Catecholamine producing tumour of the adrenal gland i.e. adrenaline) – hypertension – driving GFR – to PU
How to approach PUPD
History and signalment
Clinical exam
Age - congenital in young
Breed - fanconi
Species - Hyper T4 and CKD in older cats
Toxin, drugs, medications
Vaccination - lepto
Diet
Clinical exam
- BCS - chronic or acute
- Dehydration - primary polyuria
- Neurological disease - central lesion
- Other signs - endocrinopathies - dermatological (cushings), or waxing waning GI (addisons)
- Jaundice - hepatopathy, increased GI loss in diarrhoea driving thirst, enlarged abdomen - third space loss
USG - normal and appropriate levels
> 1.030 with normal hydration - normal or primary polydispia with intermittent polyuria not at time of sample
1.030 with dehydration - check for glucosuria, consistent with diabetes mellitus, fanconi, and renal tubular glycosuria
<1.030 with normal hydration - consider primary polydipsia, but consistently present
<1.030 with dehydration - primary polyuria and intrinsic renal disease or extrinsic affected renal function
<1.006 - hyposthenuric - diabetes insipidus, primary polydipsia, hypercalcaemia, hyperadrenocorticism (cushings)
1.008 -1.012 is normal osmolarity of blood - so not concentrating at all if here
1.006 - active dilution - kidneys working - primary PD, diabetes insipidus - no ADH
What to ask if thinking Primary PD
History - is it physiological, toxin exposure, GI losses
Rule out third space loss - POCUS - will drink more to compensate
Haem and biochem - consider hyper T4 in cats and liver disease, electrolyte imbalance
Central disease - neuro assessment
Primary PU - what to do
Causes
Primary Polyuria suspected?
Dependent on the history; rule out major life threatening disease first e.g. pyometra, addisons, acute kidney injury, diabetes mellitus progressing to diabetic ketoacidosis, haemangiosarcoma
Triage - (POCUS, Elecs, BG, UG, U/C/K+)
Intrinsic renal disease
- Further urinalysis including UPCR, urine sediment exam (e.g. casts in tubular disease), culture and sensitivity (e.g. pyelonephritis).
- Biochemistry – Urea, Creatinine, symmetric dimethylarginine (SDMA)
- Further imaging +/- renal biopsy.
Extrinsic disease
- Further urinalysis including urine glucose and culture and sensitivity (ascending infections common in diabetes mellitus, hyperadrenocorticism and hyperthyroidism)
- Haematology and biochemistry
- Ideally ionised calcium for hypercalcaemia
- Further imaging +/- FNA/Biopsy
- Physiological assessment e.g. inappropriate hypertension in phaeochromocytoma
Azotaemia - what is it and what does it mean
Elevated urea and creatinine
Pre-renal - fluid loss - haemoconcentration and reduced renal blood flow - reduced perfusion so just not reaching to filter out enough -HYPOVOLAEMIA
- Addisons - marked pre-renal azotaemia similar to renal disease
- Phosphorus is likely to be high - GFR dependant
- PUPD may be present depending on cause
- Rapidly fluid responsive
Post-renal - obstruction or uroabdomen
- PUPD not really a feature - until after removing obstruction
- POCUS
- Dangerous! - Hyperkalaemia can develop rapidly
Renal
- AKI or chronic renal failure - intrinsic
- USG poorly concentrated - functional loss. But NOT dilute
- Cats can develop glomerular disease without issues of concentration and maintain normal USG
- Phosphorus likely to be high (GFR dependant)
In AKI - phosphorus increased marked
In CKD - phosphorus increase more moderate and consistent with creatinine elevation
Dangerous - Hyperkalaemia can develop in AKI (oliguria or anuria)
Albumin and UPCR - protein losing nephropathy
Non regenerative anaemia - CKD - reduced EPO production
Azotaemia - what is it and what does it mean
Elevated urea and creatinine
Pre-renal - fluid loss - haemoconcentration and reduced renal blood flow - reduced perfusion so just not reaching to filter out enough -HYPOVOLAEMIA
- Addisons - marked pre-renal azotaemia similar to renal disease
- Phosphorus is likely to be high - GFR dependant
- PUPD may be present depending on cause
- Rapidly fluid responsive
Post-renal - obstruction or uroabdomen
- PUPD not really a feature - until after removing obstruction
- POCUS
- Dangerous! - Hyperkalaemia can develop rapidly
Renal
- AKI or chronic renal failure - intrinsic
- USG poorly concentrated - functional loss. But NOT dilute
- Cats can develop glomerular disease without issues of concentration and maintain normal USG
- Phosphorus likely to be high (GFR dependant)
In AKI - phosphorus increased marked
In CKD - phosphorus increase more moderate and consistent with creatinine elevation
Dangerous - Hyperkalaemia can develop in AKI
AKI - acute kidney injury
Haemodynamic
It could be argued this isn’t a true AKI i.e. it’s simply reduced renal blood
supply.
Anything that affects renal blood flow locally or systemic hypotension will
contribute to this, common causes being hypovolaemia, anaesthesia, use of
NSAIDS (prostaglandin inhibition).
This produces a pre-renal azotaemia due to reduced clearance that is
rapidly resolved by correcting the underlying cause (often fluid therapy to
restore renal perfusion).
If this is not corrected – progression to intrinsic renal damage occurs –
ischaemia and hypoxia
AKI - Intrinsic renal disease - true renal damage - ischaemic/hypoxic/toxic
Causes
Ischaemic – lack of blood supply - hypoxia
- Hypovolaemia, distributive, obstructive, cardiogenic shock
- Deep / prolonged anaesthesia – blood pressure - iatrogenic
- Thrombosis / DIC
- Hyperviscosity / polycythaemia
- NSAIDs
Primary renal disease
Infectious - UTI (e.coli, gram negative) - pyelonephritis
- Lepto - zoonotic
Immune mediated - glomerulonephritis, SLE
Neoplasia - lymphoma
Secondary disease
Infectious - FIP, leishmania
Malignant hypertension
Hepatorenal syndrome in cirrhosis - rare
Sepsis - endothelial glycocalyx damage, vascular leak, microcirculatory disruption
Nephrotoxins
- NSAIDs
- Ethylene glycol
- Lillies - cats
- Vitamin D toxicity
- Aminoglycoside antibiotics
AKI - intrinsic - 4 disease phases
Phase 1 – Asymptomatic phase of the initial insult, towards the end of this phase Azotaemia begins to develop and urine output drops.
Phase 2 – hypoxia and inflammatory responses propagate renal damage, particularly proximal tubule and loop of Henle (highly metabolic cells).
Phase 3 – can last up to three weeks, urine output may be increased or decreased.
Phase 4 – recovery phase, can last weeks to months. During this period, sodium may be lost and severe polyuria – this can result in hypovolaemia, causing recurrent damage through hypoxia.
Stage 1 and 2 often missed
Phase 3 - damage already done - support animal into phase 4 to recovery - can last for a long time
Post-renal AKI
Pressure buildup back into kidneys - GFR pressure and pressure in system - no filtration - AKI
Urinary obstruction
- Ureteral obstruction
- Ureterolithiasis is becoming more common in cats
- Iatrogenic post spey
- Urethral obstruction (blocked bladder)
- Prolonged obstruction will lead to intrinsic renal damage
Urinary leakage
- Ureteral, bladder or proximal urethra damage leading to uroabdomen
- Distal urethra leading to tissue leakage
- If a UTI is present, septic peritonitis can develop
Resolves with treatment of the underlying problem
Diagnosis of AKI
Identify ASAP
History - presence of predisposing factor - anaesthesia, toxin exposure
<1 week history - anorexia, vomiting, PUPD, lethargy, diarrhoea
Clinical exam
- Signs associated with fluid loss - dehydration, hypovolaemia
- Signs associated with concurrent illness - sepsis
Specific signs
- Renal pain - palpable enlargement
- Uremic halitosis and oral ulceration
- Jaundice - lepto
What will be seen on biochem with AKI
- Azotaemia
- Hyperphosphataemia (relatively marked)
- Hyperkalaemia – to a possibly dangerous level
- Hypokalaemia possible
- Hypocalcaemia
- Elevated hepatic parameters in Lepto
What will be seen on urinalysis with AKI
- Inappropriate USG
- Proteinuria
- Glucosuria
- Get a sample for culture and sensitivity
Imaging of AKI
POCUS ultrasound
Kidneys may appear normal or enlarged
Peri-renal free fluid may be seen with lepto in dogs or lymphoma in cats
Hydronephrosis - obstruction or pyelonephritis
Allows for FNA or biopsy
Radiography/CT
- Obstructions
- IV contrast
Leptospirosis
- Renal damage (99.6%)
- Hepatic damage (26%)
- Dyspnoea – Leptospira pulmonary haemorrhage syndrome (LPHS)
(76.7%) - DIC (18.2%)
- Therefore findings consistent with the above, and can include
thrombocytopaenia, anaemia, electrolyte disturbances. - Imaging may reveal interstitial/alveolar patterns, hepatomegaly,
splenomegaly, abdominal free fluid, mild lyphadenomegaly. - Lepto is zoonotic – so any dog with a possible AKI should be tested.
- SNAP Lepto antibody test (needs antibodies to have been generated,
so early false negatives) - External lab – PCR or MAT (microscopic agglutination test)
Treatment of AKI
Treat any concurrent/underlying/causative disease
Fluid therapy
Maintain volume status and renal perfusion, but avoid overload - close monitoring
Monitor in and out and bodyweight
Match losses - in severe PU may need high fluid rates but if losses are less then titrate down to avoid volume overload as damaged kidneys cant get rid of it - dont go over target weight and reassess target weight daily
Treatment of oliguria/anuria
Oliguria - <1ml/kg/hr in the hydrated and perfused patient
Anuria – little to no urine in the hydrated and perfused patient
Loop diuretics e.g. furosemide – no good evidence for improved outcomes in AKI, however may be justified to prevent fluid overload and allow increased volumes of e.g. nutrition (tube feeding). Furosemide is nephrotoxic in the poorly hydrated patient.
Osmotic diuresis – mannitol – no good evidence for improved outcomes despite many theoretical benefits, may also cause AKI itself.
Dopamine – increases afferent renal blood flow, but not GFR, no evidence for improving outcomes.
Fenoldopam – increases urine output, no evidence for improved outcomes yet.
Ca2+ channel antagonists – diltiazem – afferent renal vasodilation; some none significant findings supporting improved resolution of azotaemia and urine output, other study showing no significant increase in GFR or UO.
Renal Replacement Therapy – Dialysis
Indicated for the non-responsive patient to fluid therapy or acute poisoning e.g. lilly/ethylene glycol toxicity in cats.
Peritoneal dialysis – the first opinion option.
- Peritoneal catheter is placed
- Dialysate solution (glucose containing) is infused, left anywhere from 20 minutes to a few hours, to allow for diffusion, then drained.
- Repeated as needed
- Complications are moderate, including causing a septic abdomen.
- Moderately improved outcomes.
Haemodialysis – the referral option.
- Requires dialysis machine and specific training
- Improved outcomes
Treating AKI complications
Suspected urinary tract infection – Amoxy-Clav is a good first line choice for e.coli, Doxycycline for Lepto.
Metabolic acidosis – Hartmann’s (Careful if considering sodium bicarbonate, could worsen hypernatraemia if present, and if lung function is impaired can paradoxically cause CNS acidosis)
Tachyarrythmias – ECG for VTACH and consider lidocaine
Hyperkalaemia – Glucose, insulin, bicarbonate or beta agonist.
Hypertension – not uncommon and further damages the kidneys – amlodipine. Avoid ACE inhibitors which reduce afferent renal blood flow.
Nutrition – catabolic disease; feeding tube
CKD - chronic kidney disease - common presenting signs
PUPD
Anorexia
Weight loss
Dehydration
Pallor
Vomiting and diarrhoea
Mucosal ulcers
Uraemic breath
Breed predispositions to CKD
Dogs
- Westie
- Boxer
- Shar pei
- Bull terrier
- Cocker spaniel
- CKCS
Cats
- Persian
- Abyssinian
- Siamese
- Ragdoll
- Burmese
- Russian blue
- Maine coon
Age
- Can be juvenile if underlying familial disease - Polycystic kidney disease
Older animals if not - age assocaited disease processes
Comorbidities
- Hyperthyroid, hypercalcaemia, heart disease, periodontal disease, cystitis, urolithiasis, diabetes
Previous AKI
Nephrotoxic drugs - NSAIDs, aminoglycosides, sulphonamides, polymyxins, chemotherapeutics
Pathophysiology - CKD
Nephron damage - progressive and irreversible
Other nephron GFR increased to compensate - capillary wall damage, more plasma protein filtration, further glomerular and tubulointerstitial damage
Nephron loss - reduced total GFR, build up of products normally excreted (urea), uraemic crisis
Reduced renal function, reduced EPO production - non regenerative anaemia
Reduced metabolism and excretion of parathyroid hormone - renal hyperparathyroidism - osteodystrophy
IRIS staging - CKD
Early stage - I or II - rarely picked up this soon
- Abnormal renal imaging/known insult or
- Persistant elevation/increasing creatinine/SDMA or
- Persistant renal proteinuria
Later stages II or IV
- Consistent clinical signs
- Azotaemia/persistently elevated creatinine/SDMA
AND USG <1.035 cats <1.030 dogs
- Dehydration and azotaemia with isosthenuria or <1.030 is inappropriate - should be more
Markers of GFR - creatinine and SDMA
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 increases with >75% 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 - earlier
More expensive test, less available, and less sensitive
Treatment for CKD
Treat underlying cause if possible/known
Slow progression by managing risk factors
Recommendations vary by stage - monitor and control
- Proteinuria, hypertension and hyperphosphataemia
Diet - very important from stage II onwards
later stage - treat secondary anaemia, acidosis, nausea, maintain hydration, ensure adequate nutrition
Uraemic crisis
Build up of urea and other toxins normally excreted in kidneys to intolerable levels
- Due to end stage CKD, AKI, acute on chronic AKI (ischaemic, toxic - exacerbating existing CKD)
Clinical signs
- Vomiting, nausea
- Anorexia
- Lethargy
- Depression
- Oral ulcers
- Melena - GI ulcers
- Anaemia
- Weakness
- Hypothermia
- Muscle tremours
- Seizures
Acute vs chronic kidney disease
Age, duration, common history, exam, biochem, urine
CKD
- Older
- >3 weeks
- Weight loss, reduced appetite, PUPD, renal insult - ongoing
- BCS and coat quality reduced, small hard kidneys, enlarged possible
- K+ normal/reduced, non regenerative anaemia
USG <1.035 - inappropriately dilute
Sediment usually not active though possible if UTI
Possible proteinuria
ARF
- Any age
- <48hours
- Sudden onset, nephrotoxin, urinary obstruction
- Good BCS, kidneys possibly enlarged and painful, possibly small bladder
- Increased K+, metabolic acidosis, very unwell for severity of azotaemia
- Haem often normal
- USG usually 1.008-1.015 but can be any if bladder not empty since onset
- Urine casts/proteinuria/cell debris, possible glucosuria
How to treat uraemic crisis
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 – care with dosage and excretion
Nutritional support- Important!
* Appetite stimulants- Mirtazapine
* Feeding tubes (Nasogastric)
* Beware food aversion-DO NOT introduce renal diet in hospital
Other causes of chronic renal disease
Renal diseases
- Glomerular disease
- fanconi
- Polycystic kidney disease
- Pyelonephritis
- Nephrotoxin exposure
- Neoplasia
Extrarenal issues
- Hypertension
- Cardiac disease
- Hyperthyroidism
- Diabetes
- Urolitiasis/obstruction
- Cystitis
- Neoplasia
- Hypercalcaemia
Hypertension and CRF
Primary Stress/environment
Idiopathic (prevalence >12% in healthy cats >10 yrs)
Secondary Iatrogenic (e.g. glucocorticoids)
Systemic disease including CRF, Cushing’s, hyperT4, hypoT4, DM, obesity, pheochromocytoma or primary hyperaldosteronism
Concern- end organ damage if sustained
Diagnosis
Based on repeated measurements of systolic blood pressure (SBP)
– consistent technique and equipment.
Beware white coat effect!
* Approx 20% of CKD patients have BP at diagnosis
* A further 10-20% will develop BP over time- monitor!
Treat if SBP reliably and consistently >160 mm Hg and evidence of EOD (CKD = evidence)
Hypertension
- Renal injury
- Renal sensory nerves stimulated
- Sympathetic pathways upregulated to improve renal perfusion
- Renin release
- Angiotensin > angiotensin I
- Angiotensin I > Angiotensin II
- Receptor binding > vasoconstriction and aldosterone release > More Na+ absorption - hypertension
Treat with ACE inhibitors - inhibit Angiotensin > angiotensin I -Enalapril
Or CCB - calcium channel blockers - amlodipine
CCB in cats first
ACE in dogs first
Low salt diet
Pyelonephritis
Bacterial invasion of renal pelvis and parenchyma
Diagnosis on
- Clinical signs - fever, abdo pain, PUPD
- Haematology - neutrophilia with left shift
- US - renal pelvis dilatation with hyperechoic mucosa, altered cortex, medulla echogenicity
NOT pyelocentesis as high risk - culture urine
Treat with renally excreted drugs - amoxicillin, amoxyclav
Avoid aminoglycosides - acute tubular necrosis
