Kidney disease

Question 1

Urine collection

Answer 1

terile
○ Via urinary catheter
○ Under sedation (male)
○ Possibly just stocks (mare)?

Non-sterile - via free catch
○ Stand in a box with concrete for a few hours then put in a nice fresh bed and they will want to wee

The difference is the chance of contamination with bacteria

Question 2

pH of equine urine

Answer 2

Usually alkaline due to the forage they eat

Question 3

Isosthenuria

Answer 3

1.008-1.014

Question 4

Hyposthenuria

Answer 4

More dilute
<1.008

Question 5

Hypersthenuric

Answer 5

More concentrated
>1.014

Question 6

Microscopy of equine urine

Answer 6

Calcium crystals are common (Ca in forage high and renal excretion usually excessive)

Not a cause of concern

Casts can be seen, but not predictable even in fresh samples

Can sample single ureteral samples if suspect single kidney affected

Can check fractional excretion of electrolytes (compare serum to urine)

Question 7

Polydipsia in horses

Answer 7

Polydipsia: >100ml/kg/day intake
○ >70ml/kg/day poss more relevant
○ Maintenance: 4-60ml/kg/day

Question 8

Polyuria

Answer 8

> 50ml/kg/day
Hard to measure

Question 9

Most common cause of polydipsia in horses

Answer 9

Psychogenic PD

Or less likely PPID

Or CKD

Question 10

Creatinine in kidney disease

Answer 10

byproduct of muscle activity continually produced

Concentration proportional to glomerular filtration rate

Becomes increased once approx. 75% function of kidney gone

Question 11

Urea in kidney disease

Answer 11

nitrogenous waste product from liver

Not very sensitive

Affected by diet, prolonged exercise etc.

Question 12

SMDA in kidney disease

Answer 12

symmetric dimethylarginine

Endogenous arginine released into bloodstream during usual protein catabolism - excreted unchanged form in urine unless in kidney failure

Question 13

Blood biochemistry in AKI

Answer 13

Hyponatraemia, hypochloraemia, hypocalcaemia, hypokalaemia, hyperkalaemia, and hyperphosphataemia all reported

Question 14

Blood biochemistry in CKD

Answer 14

Hypercalcaemia (67%), hyponatraemia (65%), hyperkalaemia (56%), hypophosphataemia (47%), and hypochloraemia (46%)

Question 15

Hypercalcaemia in CKD

Answer 15

Intestinal absorption high from forage

Lack of excretion with CKD

Also have hypoalbuminaemia from renal losses so this can mask total calcium top as protein-bound will drop

Also increased as part of a paraneoplastic syndrome - could be lymphoma

Question 16

Acute kidney injury

Answer 16

Reduction in glomerular filtration rate

Failure to excrete nitrogenous waste

Cannot maintain acid-base

Failure to maintain fluid homeostasis

Question 17

AKI classification

Answer 17

Pre-renal
○ Poor perfusion of the kidney so cannot do its job

Renal - intrinsic
○ Which area affected - tubular etc.

Post-renal
○ Obstruction
○ Rupture of urinary tract distal to the kidneys (ureter/bladder/urethra)

Question 18

Oligouria

Answer 18

Reduction in production of urine

Question 19

Anuria

Answer 19

Lack of production of urine

Question 20

Signs of AKI

Answer 20

Many have no overt signs

Vague - dull, inappetant

Oliguric more likely than anuria

Think about AKI if severe profound conjunctival oedema with little inflammation

Question 21

Pre-renal AKI

Answer 21

Hypoperfusion of the kidneys

Often reversible

Secondary to severe water loss or blood loss
○ Colic
○ Colitis
○ Substantial haemorrhage

Slight azotaemia may be present - if borderline creatinine monitor it or check SDMA

Question 22

Hypovolaemia vs dehydration

Answer 22

Hypovolaemia - loss of water from the circulation

Dehydration - loss of body water

Can occur together if losses have been going on long enough

Question 23

Haemorrhagic shock

Answer 23

Loss of circulatory volume due to whole blood loss

External bleeding
○ Easy to see!
○ Usually controlled but not always

Internal bleeding
○ Hard to estimate whether controlled

Question 24

Internal cause of haemorrhage

Answer 24

Haemoabdomen (idiopathic or peri-parturient)

Haemothorax (trauma)

Loss from internal organs
○ Intestinal blood loss (masses/diarrhoea with mucosal loss)
○ Renal or urethral blood loss
○ Pulmonary haemorrhage (associated with exercise)

Drug related
○ Phenylephrine administration (major or minor vessel bleed)

Question 25

Haemoabdomen on ultrasound

Answer 25

Internal haemorrhage ○ Hyperechoic swirls ○ Effusion ○ Ventral abdomen

Question 26

How to recognise haemorrhagic shock

Answer 26

Similar to acute colic Marked hypovolaemia results in tachycardia and tachypnoea Pale mucous membranes Prolonged capillary refill times Profuse sweating Depression or anxiety Reluctance to move Weakness

Question 27

Haematological and biochemical changes in haemorrhagic shock

Answer 27

Poor general tissue perfusion ○ Lactate concentration increased Poor renal perfusion ○ Pre-renal azotaemia - elevated creatinine and urea ○ Small volume of concentrated urine produced or may be anuric - this is one reason why we check USG in our inpatients after surgery or medical treatment for colic

Question 28

Pre-renal azotaemia

Answer 28

With hypovolaemic shock from colic, or colitis, the reduction in circulating volume is SLOWER than moderate or life-threatening haemorrhage This precipitous drop in blood pressure and circulating volume affects kidneys early on, so azotaemia recognised alongside only moderate signs of shock otherwise If you find an elevated creatinine, in a dull, vaguely unwell horse, check for internal haemorrhage

Question 29

Haematological and biochemical changes in pre-renal azotaemia

Answer 29

Total protein concentration - drops slowly over 12-24hrs Packed cell volume (PCV) - splenic contraction ruins any value in assessing PCV in most cases of haemorrhagic shock for approx. 24hrs

Question 30

Splenic reserves

Answer 30

Catecholamine release due to tissue hypoxia results in splenic contraction Spleen holds a vast reserve supply of RBC This provides advantageous good oxygen carrying capacity when exercising/running from a predator Will counteract the natural loss of RBC from haemorrhage so that the PCV will not drop reliably for at least 24hr after major haemorrhage Do not let a 'normal' PCV mislead you into ruling out haemorrhage

Question 31

Causes of acute tubular necrosis

Answer 31

Ischaemia - sustained or severe hypoperfusion of the kidney 'nephrotoxins' ○ Aminoglycosides ○ Tetracyclines ○ NSAIDs ○ Pigments (myoglobin/haemoglobin) ○ Bisphosphonates ○ Plants § Oak/acorn

Question 32

NSAIDs causing AKI

Answer 32

Most common sick horses receiving IV NSAIDs Also possible, though rarer, if oral doses of NSAIDs Might see haematuria COX-2 selectivity makes no real difference (COX-2 is expressed in the kidneys) So consider giving NSAIDs when dehydration corrected FIRST Consider language used ○ "Adverse reaction" or "adverse event" ○ Do not use the terminology "toxicosis" or overdose or hypersensitivity ○ Because this is not correct, misleading and infers blame which would be misplaced

Question 33

Aminoglycosides causing AKI

Answer 33

Concentration dependent antimicrobials A small percentage of every dose accumulates in the proximal tubular epithelial cells - localised into vacuoles Impaired organelle function -> tubular epithelial cell death ○ Accumulation when shorter intervals between doses Other risk factors ○ Hypovolaemia ○ Co-administration of other potentially nephrotoxic drugs ○ Concurrent pigmentiuria Increased dosing intervals are protective Trough concentration is important Therapeutic drug monitoring - trough probably more important to check than peak levels

Question 34

Bisphonates causing AKI

Answer 34

Reduce osteoclastic activity in bone Tiludronate/tiludronic acid (Tildren, Equidronate) Clodronate/clodronic acid (Osphos) NSAIDs should not be used concurrently with TILDREN. Concurrent use of NSAIDs with TILDREN may increase the risk of renal toxicity and acute renal failure Adequate access to drinking water should be provided when using the product.

Question 35

Pigment nephropathy

Answer 35

Myoglobin ○ Muscle injuries ○ Hypoglycin A toxicity ○ Exertional myopathy ○ PSSM Haemoglobin ○ Haemolysis - IMHA, neonatal isoerytholysis Might not have pigmenturia at the time of renal injury - don't guess - check bloods

Question 36

Haematuria

Answer 36

presence of blood in the urine RBC - whole blood - can be seen under the microscope Haemoglobin - massive IV haemolysis overspills via kidney to urine

Question 37

Pigmentiuria

Answer 37

change from the usual pigment of the urine Usually as a result of myoglobin Care if only seen in wood shavings bed - metabolites in urine oxidise and turn red

Question 38

Pigmentiuria - mechanisms of injury

Answer 38

Not well understood Could be tubular obstruction, oxidative stress, vasoconstriction? Be aware that dipstick 'positive' for haemoglobin could be (Arguably more likely to be) myoglobin

Question 39

Acute glomerular nephritis

Answer 39

Rare Nephrotic syndrome ○ Might have haematuria/oliguria Might see with other autoimmune diseases e.g. purpura haemorrhagica Diagnosis with biopsy Histopathology - demonstration of immune complexes

Question 40

Acute interstitial nephritis

Answer 40

Rare Rapid increase in urea and creatinine Biopsy - interstitial oedema and infiltrate Unknown aetiology Corticosteroids but a poor prognosis

Question 41

AKI diagnosis

Answer 41

Biochemistry ○ Low sodium, low chloride, azotaemia Urinalysis ○ USG - concentrated and small volumes ○ Casts Enzymuria (GGT:Creatinine ration in urine)

Question 42

Treatment of AKI

Answer 42

All about the primary risk factors - NSAIDs (not swap, just stop), haemorrhage - blood transfusion, treat colic or colitis Replace deficit, meet maintenance requirements and ongoing losses - IVFT BUT now need to 'flush obstruction'? Frusemide - might reduce metabolic demands on the cell (Na/K ATP ase pump is massive drain on energy in cells)

Question 43

Chronic kidney disease

Answer 43

Gradual loss of renal concentrating ability Retention of nitrogenous waste and other products Retention of Na and Ca Maybe acid base derrangements Vit D and erythropoietin might be affected

Question 44

Clinical signs of CKD

Answer 44

Weight loss Inappetance PUPD Oedema (due to hypoalbuminaemia) Lethargy/poor performance Rough retained hair coat Uraemic syndrome - halitosis, dental tartar, encephalopathy

Question 45

Congenital CKD

Answer 45

Young Often no history

Question 46

Acquired CKD

Answer 46

Insidious onset Probably don't know what the original cause was - it has been missed, subclinical etc. No one notices a problem until overt clinical signs of failure by which time irreversible change

Question 47

Glomerulonephritis

Answer 47

Immune-mediated ○ Deposition of immune complexes on the glomerulus basement membrane ○ Haematuria and proteinuria Was considered rare, but might be subclinical disease 53% of CKD in one study

Question 48

Diagnosis of CKD

Answer 48

Persistent isosthenuria ○ USG 1.008 - 1.014 Azotaemia - often really marked Mild anaemia Hypoalbuminaemia High potassium, low sodium and chloride, hypercalcaemia

Question 49

Treatment of CKD

Answer 49

Try to biopsy if they'll let you - referral not an 'in the barn' job Prognosis dreadful once thin due to low albumin Palatable diet Try to control calcium intake? Add Na bicarb

Question 50

Idiopathic renal haemorrhage

Answer 50

Spontaneous, severe haemorrhage Try to find out if another cause Might respond to steroids Could be unilateral and consider nephrectomy