Hepatic and urinary Flashcards

Question

Interventions for hepatic disease-Antimicrobials

Answer 1

Use only when history, physical exam and further diagnostics are suggestive of an infectious aetiology A good example of when they are indicated: Leptospirosis (take urine/blood sample for PCR test before starting antimicrobials to avoid false negatives). Penicillins or doxycycline.

Answer 2

Indications Biopsy evidence of ongoing inflammation, e.g lymphocytic cholangitis in cats. No fibrosis or early/mild fibrosis Infectious causes ruled out as far as possible. Contraindications Known of suspected infectious cause Advanced, bridging fibrosis or non-inflammatory fibrosis (no benefit and increased risk portal hypertension (PH)) Ascites (in animals with liver disease this is usually caused by portal hypertension. CS can precipitate GI ulceration and HE, and increase water retention). HE (CS lead to protein catabolism and production of ammonia, worsening HE) Acute hepatitis (usually infectious or toxic aetiology, and high risk GI ulceration)

Answer 3

PH occurs due to increased resistance in the portal circulation and/or increased portal venous flow. Causes can be pre-hepatic, hepatic or post-hepatic Portal pressure is rarely measured directly (definitely not in first opinion practice!), and the diagnosis is inferred from the development of complications of hepatic disease, including multiple acquired PSS, ascites and HE.

Answer 4

Pre-surgical considerations- Anaemia Hypoproteinaemia Hepatic encephalopathy Extended coagulation times Ascites Dehydration Prophylactic antibiotics A large ventral midline abdominal incision from xiphoid cartilage caudally. The falciform ligament should be removed. Balfour abdominal retractors An assistant can retract caudally on stay sutures placed in the greater curvature of the stomach to facilitate manipulation of the liver. Common first opinion hepatic surgeries: biopsy; partial lobectomy

Answer 5

For peripheral lesions: - place a loop of absorbable suture around the tip of the liver lobe and tie tightly (remember surgeons knot). Empty suture packet can be used as a cutting board. Resect approx. 5mm distal to the suture, place in formalin and obtain C & S sample from hepatic tissue. For focal lesions: punch biopsy. Haemorrhage can be really well with e.g lysosypt (a collagen haemostat) which is left in place. Place biopsy sample in formalin and C & S as above. Both techniques: ensure haemostasis before routine abdominal closure.

Answer 6

Portosystemic shunts Definitive diagnosis? Imaging? Anesthetic and surgical training, e.g biliary surgery Biopsy – percutaneous ultrasound guided, laparascopic Inpatient care provision in first opinion practice– registered veterinary nurses, OOH arrangements etc.

Answer 7

SEPTIOCEMIA!! Viral infection- Rotavirus Coronavirus/adenovirus (Uncommon, usually seen in immunocompromised foals) Bacterial infection- Clostridium difficile Clostridium perfringens Escherichia coli (rare) Salmonella Fungal Infection - Candida/Mucor spp. (Rare: usually seen in immunocompromised foals) Protozoal infection- Cryptosporidium spp

Answer 8

Foal heat diarrhoea Nutritional causes (such as errors in feeding or lactose intolerance) Perinatal asphyxia syndrome/ HIE Necrotising enterocolitis

Answer 9

Nutritional causes (such as errors in feeding or lactose intolerance) Luminal irritants (such as sand enteritis) Gastric ulceration

Answer 10

Viral infection- Rotavirus Coronavirus/adenovirus (Uncommon, usually seen in immunocompromised foals) Bacterial infection- Clostridium difficile Clostridium perfringens Escherichia coli (rare) Salmonella Lawsonia intracellularis Rhodococcus equi ( rare: more commonly respiratory disease) Fungal Infection - Candida/Mucor spp. (Rare, usually seen in immunocompromised foals) Protozoal infection- Cryptosporidium spp Parasitic infection - strongyloides westeri (uncommon)

Answer 11

Viral infection- Rotavirus Coronavirus/adenovirus (Uncommon, usually seen in immunocompromised foals) Bacterial infection- Clostridium difficile Clostridium perfringens Escherichia coli (rare) Salmonella Fungal Infection- Candida/Mucor spp. (Rare: usually seen in immunocompromised foals) Protozoal infection- Cryptosporidium spp Parasitic infection- strongyloides westeri (uncommon)

Answer 12

Nutritional causes (such as errors in feeding or lactose intolerance) Luminal irritants (such as sand enteritis Gastric ulceration

Answer 13

Self-limiting condition in foals aged 5 days to 15 days No signs of systemic disease, and continue to suckle well Aetiology remains speculative Changes in mares' milk around time of first oestrus?? Unlikely as occurs in orphan foals too. Maturational changes in bacterial intestinal flora considered the most likely cause

Answer 14

Risk factors, dystocia, inadequate oxygenation following delivery Hypothesis: hypoxic injury of the gastrointestinal tract may lead to ischaemic damage to the enterocytes. May lead to diarrhoea, gastrointestinal reflux, intolerance of enteral feeding or abdominal distension

Answer 15

Pathophysiology: Multifactorial. complex interaction of immaturity, gastrointestinal mucosal injury, enteral milk feeding and bacterial invasion Severe weakness, inability to stand, colic, ileus, gastric reflux, intolerance to enteral feeding, shock signs. Even with intensive care, the prognosis is poor.

Answer 16

Ingestion of abnormal material e.g. sand Incorrect formulation of milk replacer (orphan foals)

Answer 17

D++ may be seen in association with gastric ulceration in foals. Concurrent clinical signs bruxism, ptyalism, dorsal recumbency, colic, ill thrift, poor hair coat and lethargy

Answer 18

Most commonly detected infectious agent in foals. Incubation period 1-4 days Clinical disease: ranges from mild self-limiting diarrhoea to profuse watery diarrhoea with significant dehydration and electrolyte derangements. Milder disease in older foals Most common 5-35 days of age. Virus infects the epithelial tips of the villi of the small intestine, resulting in cell lysis, blunting of villous tips and decreased production of lactase. Leads to lactose intolerance and prolonged diarrhoea. Faecal-oral transmission. Highly contagious. Can persist in the environment for several months. Infected foals shed virus for up to 10 days. Vaccination of pregnant mares may reduce outbreaks.

Answer 19

Clostridium difficile and Clostridium perfringens (both can rarely be found in normal foals) As with adults' development of disease is associated with toxin producing strains of the bacteria. Sporadic cases and “outbreaks” can occur. Risk factors: previous use of antimicrobials, stressors e.g., hospitalisation, travel and weaning. Can result in severe haemorrhagic enterocolitis in foals, with rapid progression and high mortality rates Clostridium difficile is commonly associated with diarrhoea in humans

Answer 20

Well recognised pathogens associated with diarrhoea and septicaemia in foals Clinical signs include moderate to severe diarrhoea, pyrexia, depression and inappetence. Foals with salmonellosis should be monitored closely for evidence of sepsis and for signs of localised infections such as uveitis, synovitis and osteomyelitis. Unlike in adult horses all neonatal foals with enteric salmonellosis should be treated with systemic antimicrobials Zoonotic

Answer 21

Infection via accidental oral ingestion, main reservoir of infection wildlife. Faecal shedding for 7‐17 days in infected foals 1-2 weeks organism survival in environment Primarily affects weanling and yearling horses between August and February Clinical signs: include lethargy, weight loss, pyrexia, diarrhoea and peripheral oedema. Marked hypoproteinaemia and hypalbuminaemia, and ultrasonographic evidence of small intestinal thickening Off label use of pig vaccine has been shown to be protective against clinical disease.

Answer 22

Primarily a respiratory pathogen, can cause extra-pulmonary disease including enterocolitis, abdominal abscessation, peritonitis and hepatitis

Answer 23

S westeri infects foals early in its life (transmission of larvae via ingestion of the mare’s milk), but its role in diarrhoea is questionable. Cryptosporidium parvum has been identified in the faeces of foals with diarrhoea, primarily in those less than 1 month of age. Contagious and zoonotic.

Answer 24

Thorough history and clinical examination Further laboratory testing is dependent on the age of the foal and severity of the clinical signs Baseline clinical pathology: Haematology Proteins Inflammatory markers Serum Electrolytes Renal enzymes/urinalysis (SG If less than 1.010 foal is hydrating itself)- foal being able to urinate in the first place is important in itself Plasma Lactate IgG (in young foals)

Answer 25

Faecal testing is important from a biosecurity point of view. Tests based on the most likely agent given the age of foal Many commercial labs offer “diarrhoea panels” but you should be happy about the most appropriate tests given the context of each case. In many foals with diarrhoea, more than one pathogen can be involved. A positive test does not always confirm that the particular agent is the underlying cause of the diarrhoea, as several pathogens can be found in healthy foals as well. Additional diagnostics – hospital setting Abdominal ultrasonography: Assess intestinal wall thickness, intestinal motility, stomach size, volume and appearance of peritoneal fluid in addition to umbilical structures in younger foals (important focus of infection) Abdominal radiography Sand /gas

Answer 26

In foals with evidence of hypovolaemia fluids are required. Enteral (very mild cases with no reflux) Intravenous (most cases): The rate, volume and type of fluid administered depends on the degree of hypovolaemia, cardiovascular status and plasma protein concentration Foals are not tolerant of large sodium loads, so hypertonic saline contraindicated For initial resuscitation in almost all cases a balanced crystalloid (such as lactated ringers) is appropriate. Common approach 10–20 ml/Kg over 20–30 minutes, and then repeat as indicated by response to therapy (normalisation of tachycardia, improved mentation, passing urine etc.) However, foals are not tolerant of excessive fluid volumes so care must be taken to avoid fluid overload. Frequent reassessment should be performed and used to guide fluid therapy (PCV/TP/Urine SG/ clinical signs) colloids- Synthetic colloids not advised: have been associated with the development of coagulopathies, renal failure and an ultimately worse outcome in humans Hyperimmune plasma (our best option) provides plasma proteins but also immunoglobulins. Essential in foals with failure of passive transfer, but any sick foal can rapidly consume immunoglobulins even if initially adequate concentrations. Electrolytes Electrolyte imbalances and acid-base disturbances are common Correction crucial for recovery and is typically performed via intravenous fluid therapy In more mild cases oral supplementation may be sufficient.

Answer 27

Foals under 2 weeks Clostridial infection Salmonella Lawsonia Choice of specific antibiotics and dose important Consideration should be given to hydration status and renal function prior to starting any potentially nephrotoxic antimicrobials

Answer 28

amikacin (25–30 mg/kg every 24 hours, i.v. or i.m.) and ampicillin (20 mg/kg every 6–8 hours, i.v. or i.m.) or ceftiofur (5–10 mg/kg, every 6–12 hours, i.v. or i.m.)

Answer 29

Metronidazole (dose varies with age)

Answer 30

oxytetracycline (5-10mg/kg i.v, every 12 hours). Or macrolide antimicrobials. (***Care re colitis in older animals with macrolides)

Answer 31

Analgesia Foals with D++ may show colic signs associated with inflammation / distension NSAIDs such as meloxicam/ flunixin (care re renal effects and effects on epithelial health) Butorphanol 0.01-0.04mg/kg i.v. Buscopan (N-butylscopolamonium bromide) 0.3mg/kg i.v.

Answer 32

Prophylactic use of anti-ulcer medication is controversial in neonates/ less so older foals Use of proton pump inhibitors has been associated with the development of diarrhoea in hospitalised foals (Furr et al, 2012) Sucralfate 20-40mg/kg po every 6 hour is an alternative option in neonates

Answer 33

Intestinal binding agents - Di-tri-octahedral smectite (Bio-Sponge; Platinum Performance) binds clostridial toxin Lactase- In cases where lactose intolerance is suspected (1 tablet 6-8 times daily) Probiotics - Not recommended. Have been shown to be associated with diarrhoea Nursing care - Hygiene and cleanliness Hindquarters and tail Mare's udder (strip out)

Answer 34

If an infectious aetiology is suspected strict biosecurity measures need to be put in place Protect other horses and humans (clostridia / salmonella = zoonosis) Isolate affected animals Separate stable equipment / ideally a separate muck heap Wear PPE (overalls/ boot covers and gloves) Foot dip/ sanitise hands prior to leaving (alcohol gel not effective vs clostridial spores) Foot dips – Bleach or Virkon Gross contamination with organic material deactivates bleach – will need to be changed Cleaning and disinfection (after disease) Remove bedding /wash walls and floor to remove organic material. Detergents are used to emulsify fats and loosen organic matter Clostridial spores and salmonella resistant to cleaning but this will reduce contamination dramatically

Answer 35

Any ‘sudden’ structural OR functional damage to the kidneys as defined by the IRIS criteria the progression of AKI can either result in: Complete Resolution Chronic Kidney Disease (CKD) Death or Euthanasia Can be- Ischaemic Infectious Toxic Obstructive

Answer 36

Any structural OR functional damage to the kidneys that has been present, and stable, for at least three months

Answer 37

Any episode of AKI that is superimposed on top of pre-existing CKD Can be in cases of ‘known’ CKD – i.e., come in for a ‘uraemic crisis’- Not uncommon in cats with CKD where for one reason or another, they become more uraemic/stop drinking and become dehydrated/anorexic. Often, a short period of hospitalisation with sufficient fluid therapy (typically in the optimisation phase) rehydrates them an improves appetite and can usually be discharge home soon after. As discussed in CKD lectures some clients wil opt for subcutaneous fluid adminstraiton at home or placement of an oesophagosotmy tube Sometimes can present as the first recognition of any kidney disease and can be difficult to differentiate from ‘just’ an AKI The two main methods of assessing for the presence of ‘acute on chronic’ kidney disease are: Body condition score/Muscle condition score (evidence of chronic pathology) Ultrasonography of the kidney demonstrating chronic changes Suspected higher incidence of pyelonephritis in acute on chronic cases – urine culture! Overall suspected ‘poorer’ prognosis than AKI

Answer 38

An increase in Creatinine and/or urea above their reference intervals

Answer 39

The clinical signs as a result of azotaemia (e.g. nausea/anorexia)

Answer 40

A rarely used term where AKI or CKD has progressed to the stage that the kidneys are unable to maintain ‘normal’ homeostasis with regards to hydration, electrolyte, or acid-base abnormalities.

Answer 41

An ‘acute on chronic’ flair-up resulting in increased uraemic toxins and signs of clinical illness

Answer 42

The classic situation is progressive renal inflammation in the background that slowly ‘burns away’ at the kidney and there is a steady decline in nephrons. This happens ‘in the background’ and it is not until roughly 75% of nephrons are lost when creatinine starts to increase. It is not until even further than that when signs of uraemia start to develop and the animal is presented as being unwell. Although interventions can be started there is usually on-going progressive decrease in renal function and progressive worsening of CKD. This progressed to a point where the animal either dies or is euthanised Often will be absent of clinical signs in the background until a significant number of nephrons lost and then clinical signs develop This will never reverse We can also have the situation where a health kidney experiences an episode of AKI (for varying causes) which causes a sudden reduction in kidney function. If this AKI does not fully resolve it can progress to CKD and in most cases (but not all) will then continue on the ‘classic’ CKD trajectory of on-going renal inflammation and a progressive decline towards an end-stage kidney

Answer 43

We can also have other causes of renal disease that are classed as ‘CKD’. For example, if an animal has a tumour on the kidney (strictly speaking – for 3 months) then it is still classed as CKD. Overtime, this tumour will progress and result in an end-stage kidney (or death due to the metastasis etc.)

Answer 44

Similar to neoplasia, we can also see this with polycystic kidney disease (typically persian cats) where cysts develop due to a mutation in the gene PKD1. Over time (often years!) these cysts increase in number and size resulting in reduced renal function and progression towards end-stage CKD. As these are present for a period of 3m+ they are a cause of CKD

Answer 45

We can also see this with Juvenile Onset Chronic Kidney disease (previously known as renal dysplasia). In JOCKD, there is a presumed congenital abnormality to the kidneys that contributes to on-going progressive deterioration in kidney function. As this is present for more than 3 months duration it is classed as CKD. Over time, this can often result in progressive renal dysfunction towards end-stage CKD

Answer 46

One of the causes of CKD is glomerular disease (disease pertaining to the glomeruli of the nephrons) which is more commonly seen in dogs cf. cats (see glomerular disease/proteinuria lectures). As the glomeruli leak excess protein into the renal tubules this results in inflammation and a progressive decline in renal function. Again, as this has been present for more than 3 months it is classed as CKD. e.g- Immune Complex Mediated Non-Immune Complex Mediated Amyloidosis

Answer 47

Any structural or functional change to the kidneys that is present for at least 3 months is classed as ‘chronic kidney disease’ Markers of glomerular filtration (GFR) are typically used to assess the presence and severity (creatinine/urea/SDMA) Urinalysis changes are also included (e.g., proteinuria) Imaging changes are also included (e.g., structural changes) Improvement in renal function is NOT generally seen in chronic kidney disease* The vast majority of cause of CKD are NOT reversible. Although we may see an improvement in creatinine, this is often the result of reduced muscle mass or fluid therapy rather than a true improvement in renal function. In the majority of cases of CKD, renal function will continue to decrease over time towards an end-stagfe kidney. There are, however, a notable number of cases where this does not occur and CKD is present, but stable for long periods of time. For a diagnosis of CKD, the changes must have been present, and ideally stable, for at least three months Until that point they are still technically classed as AKI Some changes will essentially lead to a diagnosis of CKD on discovery: 1- Evidence of chronic kidney disease on ultrasound or other imaging modalities 2- Evidence of renal neoplasia or PCKD on imaging 3- Azotaemia alongside poor BCS/MCS Otherwise, causes should be investigated and then reassessed at the three-month mark to assign a CKD stage

Answer 48

GFR can be accurately assessed using methods such as Iohexol or Inulin clearance – rarely performed in practice Proxy-biomarkers are more commonly used that approximate GFR Creatinine – produced in the muscles and filtered by the kidneys Urea – produced in the liver and excreted by the kidneys (non-specific) SDMA – produced by the majority of the cells in the body and filtered by the kidneys (less-affected by assay interference) ALL are affected by pre, intra, and post-renal factors Although the concentration of urea in the plasma can be reflective of GFR – it is heavily influenced by other factors such as hydration status, recent consumption of a meal,. Pyrexia, and gastrointestinal bleeding among others. Consequently, I do not put much emphasis on UREA – focus more on creatinine.,

Answer 49

Creatinine is the main GFR marker to assess renal function Produced in the muscles and filtered by the kidneys Does not tend to increase until ~75% of functional nephrons lost Also affected by muscle mass, hydration status, and hyperthyroidism Can be notably ‘falsely’ reduced in animals with loss of muscle mass Part of the IRIS staging system Best used for monitoring progression of CKD

Answer 50

S-Dimethyl Arginine (SDMA) is produced by the majority of the cells in the body and filtered by the kidneys Will typically increase prior to creatinine during the course of CKD Minimally affected by external factors (not affected by muscle mass) Better used to diagnose CKD – less suited to on-going monitoring (cf. creatinine) There is very little merit in measuring SDMA when creatinine is increased* The exception being to more accurately assess the IRIS stage when there is marked muscle loss which may falsely reduce the creatinine concentration. SDMA will be less affected by muscle mass so will likely be more representative of true decreased in renal function

Answer 51

As there is a progressive decline in nephrons (and thus GFR/renal function) there is a lag period before picking this up on blood work. In theory, if we did iohexhol/inulin clearance (more of a research technique) we would pick this up much sooner (?although it is unclear whether this has a clinical benefit?). However, in clinical practice this is rarely available. Generally speaking, SDMA is typically the first biomarker to increase outside of its reference interval and this typically precedes creatinine by a number of months. Following this we see a decrease in USG (loss of concentrating ability) – HOWEVER it must be remembered that a number of animals (especially cats) are able to maintain their urine concentrating ability despite a marked reduction in renal function. Finally, when around 75% of nephrons are lost, this is when creatinine starts to increase outside of its reference interval (however it tends to progressively increase within the reference interval far before this – but this is very difficult to pick up)

Answer 52

USG- Decreased urine concentrating ability is often seen in CKD- a number of animals (especially cats) can have a normal USG despite reduced renal function so it is not an overly accurate assessment UP:C- Reflecting tubular and/or glomerular damage (see glomerular disease/proteinuria lectures) Phosphate- Dysregulated in CKD and part of the IRIS staging system Blood pressure – Increased in the majority of animals with CKD and needs addressing PCV/HCT – Can be decreased in advanced CKD and may need addressing pH – Metabolic acidaemia often present in advanced CKD FGF-23 – a novel biomarker

Answer 53

International Renal Interest Society (IRIS) have produced a staging system for CKD Typically based on creatinine concentration, but more recently SDMA has been incorporated Also takes into account phosphate, proteinuria, and hypertension Provide management advice for different CKD stages Stage I CKD – Evidence of chronic changes to the kidney when creatinine is within the RI Stage II+ CKD – As above, but with increasing creatinine concentrations outside the RI THE IRIS CUT-OFFS ARE NOT REFERENCE INTERVALS The diagnosis of CKD is based on YOUR LABORATORIES RI and then staged based on the IRIS CKD cut-offs! Cases typically fall into two categories 1- Animals presenting due to clinical signs of uraemia 2- Incidentally discovered increased filtration markers (creatinine/SDMA) on routine/pre-anaesthetic blood-work Clinical signs do not tend to be present until IRIS stage III/IV (unless other comorbidities or acute on chronic are present) however signs can be seen at earlier stages, especially in smaller dogs* Most common presentation is an older cat (often 10 years plus) with progressive loss of condition, dehydration, and hyporexia-anorexia. The approach is the same in both categories, in both species Clinical signs can also be seen unexpectedly in animals with lower IRIS stages when the degree of muscle mass has ‘falsely’ lowered creatinine concentrations (note, SDMA would not typically be expected to result in reduced muscle mass) The majority of cats over the age of 15 will have some degree of chronic kidney disease. Consequently, the older feline cat with CKD is probably the most common presentation of CKD you will see in practice and consequently the lecture will focus mainly on this although the approach is similar in the dog. As there are a wide number of causes of CKD in dogs and cats there is inevitable a wide range of presentations!

Answer 54

Varying clinical signs depending on the severity of azotaemia (and thus uraemia) Typically, uraemia will lead to signs of nausea and hyporexia-anorexia This results in reduced water intake  dehydration (and perpetuation) The reduced calorie intake results in muscle and condition loss May also notice a ‘uraemic’ smell to the breath and/or oral ulceration May also have small or irregular kidneys on palpation Note – CKD also includes conditions that can be non-azotaemic (e.g. glomerular disease, or renal tubular dysfunction) that may have a completely different spectrum of clinical signs The oral ulceration can often be vague ‘redness’/discolouration at the edges of the tongue

Answer 55

As discussed, in some cases the presentation will be such that it is almost unequivocally CKD although the changes have not been documented for 3 months. So very much the initial investigations in the case are going to be very similar to the investigations of AKI (see AKI lectures) Again, in cases where CKD is highly likely, some of the ongoing management is likely to be started prior to this three-month point initial investigations should be focued in esablishing type of ckd- Investigate specific or ‘treatable’ causes- radiograph/ ultrasound should also establish- Baseline Creatinine, Phosphate, Calcium, Haematology ± SDMA Urinalysis, UP:C, urine culture Doppler Blood pressure As these cases technically present as an AKI – then investigations into underlying or specific causes should be performed – see AKI lecture Marked proteinuria (~≥2.0) should prompt investigations into underlying glomerular disease Imaging (abdominal radiographs and ultrasound) to assess likelihood of CKD, alongside specific causes (neoplasia, PCKD, ureteroliths etc.) A positive urine culture on presentation (using tissue breakpoints) should be treated as pyelonephritis Baseline bloodwork should be performed to look for causes/comorbidities but will need to be rechecked at three months to assigns IRIS stage SDMA if creatinine is not within the reference interval or if severe muscle wastage and concern of ab ility of creatinine to accurately reflect IRIS stage. Please note, although SDMA is better able to determine the IRIS stage in the presence of marked muscle wastage – the difference in treatment recommendations between IRIS stage is minimal and it could be considered academic to focus so heavily on SDMA (cf. creatinine) in these circumstances Animal presents with presumed CKD-> Baseline creatinine or SDMA (based on laboratory cut-offs)-> Investigations into presumed CKD-> Monitor for three-months ± treatment-> Assign IRIS CKD Stage based on IRIS cut-offs

Answer 56

Nutrition and maintaining hydration Managing Hyperphosphataemia Managing Proteinuria Managing Hypertension Other management considerations When we have reached the three month mark and have confirmed CKD (any stage) we begin management* It is important to note that, for the vast majority of cause of CKD – There is NO treatment Management is aimed at slowing on-going deterioration and maintaining/improving quality of life Most animals will continue to have a progressive decrease in renal function although a proportion will remain stable for long periods of time Again, it is exceptionally rare to see an improved in renal function Outlined in IRIS CKD guidelines

Answer 57

There are two main aspects as to the nutritional management of CKD: 1- Maintaining calorie intake 2- Transition on to a renal diet Hyporexia-Anorexia is common in IRIS stage III/IV and modifications are typically required to ensure adequate calorie intake Protein-energy wasting can result in worsening uraemia and poorer quality of life Maintaining hydration should be encouraged alongside Renal diets have been shown to improve survival of dogs and cats with CKD by 2-3 times Consequently, mainstay of management of CKD in both species However, it is generally considered more important that an animal maintains calorie intake rather than insufficient calorie intake from a renal diet “The wrong calories are better than no calories” Dry and Wet products available (wet preferred) Range of different products on the market including ‘combination’ diets Recent introduction of ‘early’ renal diets Although the exact features differ between renal diet, they typically share the following features Moderately restricted, high-quality protein source – Reduction in proteinuria and uraemic toxins High Calorie Density- Improve calorie intake Low phosphate- Reduction of plasma phosphate concentrations Fortification with Omega 3 Fatty acids- Maintenance of lean body mass and possible anti-inflammatory effects ± Potassium supplementation- Hypokalaemia can be seen in late stage CKD ± Bicarbonate supplementation – Metabolic acidosis can be seen in late stage CKD It can often take time to find a renal diet that the animal will eat Slow transitioning (especially in cats) can help with transition- in some cases you may need to transition over ‘1 kibble at a time’ over a period of weeks to months Adding water to dry food may improve uptake Clients will often add cooked meat to the diet – proactively advise against this In theory, starting a renal diet prior to development of uraemia may help improve acceptance Use of medical management may be beneficial In advanced stages, assisted enteral feeding may be required

Answer 58

Medical management can be used when ‘conservative’ approaches have failed Mirtazapine has been the mainstay in cats for management of anorexia and nausea (poorer effect in dogs) Dose reduction is recommended in CKD: - 2mg/CAT/PO q24-48hr Transdermal product available with a ‘smoother’ profile and fewer adverse effects - not as good for appitie Capromorelin is an excellent appetite stimulant with long-term safety studies- blood prssure lowers. dog version needs to be imported - 2-3mg/KG/PO q24hr Ondansetron has good anti-nausea properties that may help appetite but is not an appetite stimulant (see AKI lectures) Vitamin B12 supplementation can be considered- often low kidney cases Gastroprotectants should ONLY be used if high suspicion of gastrointestinal bleeding- previously gastroprotectants have been routinely recommended in dogs and cats with CKD due to a suspicion of uraemic gastric ulceration. However, more recent studies suggest that the incidence of such lesions is uncommon and thus routine gastroprotectants are not recommended

Answer 59

In advanced stages, animals with CKD are at risk of dehydration Plentiful and accessible water provision should be provided at all times Animals with advanced CKD may need intermittent periods of hospitalisation for IV rehydration Placement of oesophagostomy feeding tube or owner-provided subcutaneous fluids can also be considered Recent release renal-friendly water flavour-enhancer that increases water intake in cats- Note, the only research for this product is by the company who made the product and only investigated the product in healthy cats. Avoid using tuna-water or chicken broth as this has high inorganic phosphate concentrations that has been shown to be detrimental to the kidneys

Answer 60

Recent introduction of ‘early’ renal diets Lower degrees of phosphate and protein restriction Limited research currently but suggested benefit for: 1- Animals in IRIS Stage I (± early stage II CKD) 2- Animals in IRIS Stage I/II with increased FGF-23 concentrations that indicate inadequate phosphate restriction 3- Animals that have developed hypercalcaemia after starting a ‘standard’ renal diet Early renal diets should be avoided in presence of proteinuria above the IRIS reference intervals

Answer 61

Phosphate concentrations on presentation correlate with survival Reduction in phosphate concentrations may improve outcome in CKD Note, the target phosphate concentration is LOWER than the normal phosphate reference interval Dietary phosphate restriction is trialled first. If after six weeks the target concentration is not achieved, phosphate binders are indicated FGF-23 concentrations MAY help identify animals that require additional phosphate reduction in excess of the IRIS guidelines The ideal plasma phosphate concentration in CKD is 0.9-1.5mmol/l however after IRIS stage II this can be increasingly difficult to achieve. Consequently, more ‘realistic’ targets are provided for increasing IRIS stages If after six weeks of a renal diet phosphate targets are not achieved, phosphate binders are indicated Phosphate binders MUST be given with food- cant bind the phosphate of the food if not given at the same time Two main types: 1- Aluminium based – E.g. Alu-caps - Risk of aluminium toxicity – monitor for microcytosis and neurological signs 2- Calcium based – E.g. Pronefra, Ipakitine - Avoid in hypercalcaemia Newer human products likely to reach veterinary market (lanthanum, sevelamer etc.) Re-check after 4-6 weeks Note- although aluminium phosphate binders used to be the mainstay of treatment for hyperphosphataemia in CKD – they seem to be becoming less available from veterinary medicine wholesalers

Answer 62

reduce phosphate to manage ckd If after six weeks of a renal diet phosphate targets are not achieved, phosphate binders are indicated Phosphate binders MUST be given with food- must interact with the food to bind the phosphate Two main types: 1- Aluminium based – E.g. Alu-caps - Risk of aluminium toxicity – monitor for microcytosis and neurological signs 2- Calcium based – E.g. Pronefra, Ipakitine - Avoid in hypercalcaemia Newer human products likely to reach veterinary market (lanthanum, sevelamer etc.) Re-check after 4-6 weeks

Answer 63

Proteinuria is commonly seen in CKD and can be glomerular and/or tubular in origin Proteinuria on presentation is correlated with survival and treatment of proteinuria is likely to improve outcome Identification and management of proteinuria is covered in the proteinuria/glomerular disease lectures Proteinuria should be checked for persistence (confirmed twice in a six-week period) before treatment is initiated Pre-renal and post-renal inflammation should also be ruled out IRIS Proteinuria targets and treatments differ between dogs and cats - Dogs: <0.5 (or 50% reduction in UP:C) - Cats: <0.4 (or 50% reduction in UP:C) Mainstay of treatment is RAAS inhibitors alongside renal diet In dogs, an angiotensin receptor blocker (ARB) is recommended first line In cats, an ARB OR an ace-inhibitor (ACEi) is recommended first line Dose escalated until targets are reached OR adverse effects outweigh the benefits Blood-pressure, creatinine, and electrolytes should be checked 7-14 days after initiation or change in dose of RAAS inhibitors CARE in advanced CKD as may markedly worsen uraemia* Benazepril (ACEi) - 0.5mg/kg/PO q12hr Telmisartan (ARB) - 1mg/kg/PO q24hr RAAS inhibitors (ACEi/ARBs) MUST be discontinued in dehydrated/unwell animals – THIS MUST BE COMMUNICATED TO CLIENTS!

Answer 64

In dogs, an angiotensin receptor blocker (ARB) is recommended first line In cats, an ARB OR an ace-inhibitor (ACEi) is recommended first line Dose escalated until targets are reached OR adverse effects outweigh the benefits Blood-pressure, creatinine, and electrolytes should be checked 7-14 days after initiation or change in dose of RAAS inhibitors Benazepril (ACEi) - 0.5mg/kg/PO q12hr Telmisartan (ARB) - 1mg/kg/PO q24hr RAAS inhibitors (ACEi/ARBs) MUST be discontinued in dehydrated/unwell animals – THIS MUST BE COMMUNICATED TO CLIENTS!

Answer 65

Hypertension can occur at any CKD stage and at any time- non-azotaemic animals can still be hypertensive due to renal disease (e.g. glomerular disease). Hypertension can contribute to on-going deterioration in renal function and can also lead to target organ damage (cardiac, ophthalmic, neurological etc.) Important to aim to get reliable blood pressure measurements (although not possible in all animals) Treatment depends on species Aim is to reduce blood pressure to <160mmHg see ACVIM Hypertension Guidelines 2018 for what to do and how often to measure blood prssure

Answer 66

( in order of choice) ACEi – e.g. benazepril (0.5mg/kg/PO q12hr)* Increased dose of ACEi Addition of amlodipine (0.1-0.25mg/kg/PO q24hr) Combination ACEi/amlodipine The current recommendation for treating hypertension in dogs is to use an ACEi as first line treatment (cf. proteinuria which is an ARB). ARBs have a similar anti-hypertensive effect to ACEis in dogs so they can be considered as an alternative and is in-line with the ACVIM hypertension guidelines. Furthermore, it is not uncommon to have a dog where an accurate blood pressure cannot be acquired for varying reasons. However, if the animal is proteinuric, there is merit for starting an ARB and thus also likely addressing blood pressure at the same time

Answer 67

( in order of choice) Amlodipine (0.1-0.25mg/kg/PO q24hr) OR ARB (telmisartan – 2mg/kg/ PO q24hr) Increase dose of amlodipine Combination therapy Remember to monitor blood pressure, creatinine, and electrolytes 7-14 days after initiation/dose change

Answer 68

Anaemia can be seen in advanced CKD and can contribute to malaise Rule out ‘other’ causes of anaemia (e.g., gastrointestinal bleeding) Treat when PCV is <0.20l/l (20%) or convincing related clinical signs Treatment is Erythropoietin and iron supplementation (some cases may require transfusion) Anabolic steroids (e.g., Laurabolin) are of no proven benefit and may be detrimental

Answer 69

Drugs with potential nephrotoxicity should be discontinued and avoided In advanced stages of CKD, drug-dose reductions should be considered (outside expected new-graduate competency) Complex situation with NSAIDs NSAIDs can be directly and indirectly nephrotoxic However, some studies suggest a benefit in feline CKD-However, this remains controversial. One study even suggested a benefit in feline CKD however this is likely not to be the case and NSAIDs should not be used for this justification The pros and cons should be weighed up carefully alongside close monitoring. Consider less nephrotoxic alternatives

Answer 70

On initial presentation of CKD (technically AKI), positive urine cultures should be treated as pyelonephritis Tissue break-points should be applied to determine culture and sensitivity Marbofloxacin 2mg/kg/PO q24hr for 14 days (or based on C+S) Future positive urine cultures should be treated if: - Signs suggestive of LUTD (treat as UTI)- amoxycillan - Signs suggestive of pyelonephritis (treat as pyelonephritis) - Sudden increase in creatinine (treat as pyelonephritis) - Pyrexia or neutrophilia that cannot be attributed to another cause (treat as pyelonephritis) Otherwise, do not treat asymptomatic positive urine cultures

Answer 71

Marbofloxacin 2mg/kg/PO q24hr for 14 days (or based on C+S)

Answer 72

Hypokalaemia can be seen in advanced CKD, especially in cats Contributes to lethargy, anorexia, and muscle weakness Oral supplementation with potassium gluconate or potassium citrate Hypercalcaemia (total or ionised) can develop in a number of animals with CKD over time – this can be complex to investigate/treat – get specialist advice Acidaemia – metabolic acidosis can develop in advanced CKD contributing to muscle wastage/anorexia – consider potassium citrate/sodium bicarbonate- Neither of these are palatable and can be difficult to administer (consider giving with food or in a gelatine capsule

Answer 73

After diagnosis of CKD, frequency of monitoring is determined by IRIS stage Rechecks involve (on a starved sample): Clinical examination (BCS/MCS/Hydration) Creatinine (± Urea) Phosphate Electrolytes UP:C (± culture) Doppler Blood pressure PCV ± Acid-base ± Ionised Calcium ± FGF-23 Some of these will be performed more frequently depending on medication dose changes/additions shuld be monitored acording to iris stage- 1- 6 monthly 2- 3-6 monthly 3- 1-3 monthly 4- 1-2 monthly

Answer 74

Somewhat dependent on underlying cause and whether glomerular component In ‘idiopathic’ CKD, when consuming a renal diet, very rough prognoses are given Acute on Chronic CKD likely has a worse prognosis and ‘speeds up’ deterioration Some animals will have stable creatinine for long-periods of time (do not give clients false hopes!)- some stay in stge 2 for whole lives Severity of manifestations of CKD generally becomes pronounced from IRIS stage III+, but can be seen at earlier stages prognosis acording to iris stage cats- 1- unknown 2- 2-3 years 3- 1-2 years 4- 1-3 months dogs- 1- >1year 2- 1-1.5 years 3- 3-7 months 4- 1-2 months

Answer 75

In animals that are not able to maintain their normal renal homeostasis despite medical management then dialysis or renal transplantation is indicated Although dialysis is available in the UK at one centre (RVC) this is only available for AKI Renal transplantation available in the US and owners must adopt the donor cat Veterinary renal transplantation is currently against the law in the UK

Answer 76

SDMA is a biomarker of glomerular filtration and typically increases prior to creatinine Furthermore, less influenced by factors such as muscle mass Best placed to diagnose CKD but creatinine is a better marker of progression Increased SDMA but normal creatinine – treat as IRIS Stage I CKD* There is generally no benefit for measuring SDMA when creatinine is increased However, may allow more accurate staging of CKD in presence of reduced muscle mass - ?clinical relevance?

Answer 77

A new renal biomarker has recently been released for use in cats – FGF-23 FGF-23 is involved in mineral-bone disease in CKD Increases prior to parathyroid hormone and is able to comment on adequacy of phosphate restriction – ‘going that bit further’ Indications: Assessment of adequacy of phosphate restriction when in target range Need for early renal diet in IRIS Stage I/II CKD Guidance for interpretation provided by IDEXX

Answer 78

Machine learning approach to the prediction of the development of CKD in cats* Offers prediction of likelihood of cat developing CKD over next two years Highly specific – if predicts that the cat will develop CKD there is a high chance it will Very poorly sensitive – if predicts that the cat will NOT develop CKD there is still a high chance it can do Predictive ability improves the ‘closer’ to the development of clinically recognisable CKD This is likely to be a growing field in veterinary medicine although should be interpreted cautiously – difficult to recommend routinely currently N.b., the study that looked at the accuracy of this prediction algorithm was performed by the company who own the laboratory that provide the test- furthermore, based on an American rather than UK feline population

Answer 79

Relative reduction in urine output

Answer 80

where there is damage directly to the kidney

Answer 81

results from a decrease in perfusion to the kidneys -> reduction in GFR -> an increase in SDMA/Creatinine/Urea If severe enough/present for long enough can lead to intrinsic AKI Due to either: 1- Reduced afferent perfusion- Hypotension, hypovolaemia, shock etc. 2- Increased efferent venous congestion- Cirrhotic liver disease, Right sided heart failure, fluid overload Both tend to have normal-milder increases in creatinine (~140-300μmol/L) that is rarely hyperkalaemia/oliguria/anuric and tends to rapidly respond to treatment of underlying cause However, can result in a secondary INTRINSIC AKI that can present more severely

Answer 82

results from obstruction of the urinary tract -> increased tubular pressures -> reduction in GFR -> an increase in SDMA/Creatinine/Urea N.b. urinary tract rupture can also be classed as Post-renal AKI but the azotaemia occurs via different mechanisms If severe enough/present for long enough can lead to intrinsic AKI Due to: Urethral obstruction Ureteral obstruction Urinary tract rupture Cases of post-renal AKI are much more likely to be hyperkalaemic Presence of hyperkalaemia should be a red-flag for searching for obstructive causes! See obstructive nephropathy lecture which also covers treatment of hyperkalaemia

Answer 83

reduced perfusion to the kidneys leading to intrinsic AKI. Any cause of hypotension or shock (e.g., anaesthesia, sepsis, blood-loss, severe diarrhoea etc.)

Answer 84

Pyelonephritis – Infection of the kidneys Pyonephrosis – Dilation of renal pelvis with pus Uncommon cause of AKI (<2%), but increased prevalence in acute on chronic kidney disease Most common infectious agent is Escherichia coli Also consider Leptospirosis and Borrelia burgdoferi* Risk factors include urinary tract obstruction, diabetes mellitus, renal and non-renal neoplasia. Borrelia burgdoferri (lyme nephritis) CAN cause a very severe glomerulonephritis. HOWEVER, this presentation of Lyme borreliosis appears to be much less common in the UK and Europe compared to America

Answer 85

Damage to the glomeruli

Answer 86

History - Mechanism of injury (MOI) likely to result in AKI (e.g. Toxin exposure or sepsis) Clinical signs- Uraemia, dehydration, or as a result of underlying MOI Biochemistry – New increases in creatinine or SDMA (care re: urea) Urinalysis- Proteinuria, glucosuria, cylinduria, reduced urine output after rehydration Imaging – Evidence of ischaemia or obstruction Generally speaking, in animals with AKI without uraemia (i.e. their severity of their azotaemia is not so marked as to result in clinical signs) Urea/BUN can be affected by a wide range of causes, many of which are not directly related to kidney function (e.g. pyrexia or dehydration) – so I personally would be extremely hesitant to diagnose an AKI based on urea alone (unless SDMA was increased or creatinine was increase within the reference interval although outside of the reference interval) However, overall, creatinine is going to be your main one for diagnosis AKI

Answer 87

includes animals with creatinine typically within the reference interval Non-azotaemic (absent signs of uraemia- Although the animal can have few to no signs of uraemia, there may be other non-uraemic signs present such as hypertension, glucosuria, etc. ), increase in creatinine (≥ 26.4 μmol/L) within the RI - oliguria/anuria - Imaging changes consistent with AKI - Urine changes consistent with AKI (proteinuria, cylinduria, glucosuria,etc.)

Answer 88

Increasing severity of azotaemia (typically above the reference interval) ± combinations of the above

Answer 89

“There is not much you can do to help AKI, but there is a lot you can do that is detrimental” Excluding cats with urethral obstruction, the majority of the cases of AKI you will see in primary care practice will not have an identifiable cause After ruling out causes of AKI that require specific treatments the treatment of the remaining causes of AKI is largely supportive The aim is to support the animal to see IF an adequate degree of renal recovery can occur by the three-month mark at which point it will undergo CKD staging The majority will not have an identifiable cause, most likely because the cause has ‘been and gone’ and you are left picking up the pieces. Animal Presents with AKI-> Rule out causes that require specific treatments -> Provide supportive care -> CKD stage at three-month mark Causes of AKI that MUST be investigated: urgent (within hours)- Obstructive AKI Infectious AKI Hypoadrenocorticism (D)- Please note, hypoadrenocorticism is NOT strictly a cause of intrinsic AKI but tends to cause a pre-renal AKI (but this can lead to an intrinsic AKI). However, the biochemical and electrolyte changes associated with hypoadrencorticism can very closely mimic AKI so when I am presented with an animal with AKI, I will always rule out hypoadrenocroticsm in DOGS because I have been caught out previously! less urgent (within days)- Neoplasia Glomerulonephritis their absence, treatment is supportive

Answer 90

urgent (within hours)- Obstructive AKI Infectious AKI Hypoadrenocorticism (D)- Please note, hypoadrenocorticism is NOT strictly a cause of intrinsic AKI but tends to cause a pre-renal AKI (but this can lead to an intrinsic AKI). However, the biochemical and electrolyte changes associated with hypoadrencorticism can very closely mimic AKI so when I am presented with an animal with AKI, I will always rule out hypoadrenocroticsm in DOGS because I have been caught out previously! less urgent (within days)- Neoplasia Glomerulonephritis

Answer 91

‘Traditionally’ we would suspect pyelonephritis in any animal that presents with an AKI and has a combination of: Pyrexia Neutrophilia often with left shift/toxic-changes Renal pain Renal pelvic/ureteral dilation and/or peri-renal hyperechogenicity or free-fluid* on ultrasound- peri-renal free fluid is relatively common in animals with leptospirosis More recently, studies have suggest that these ‘classic’ signs are not as common as first thought and can be more ‘subtle’ Consequently, currently recommend to treat every AKI case with a positive urine culture as pyelonephritis

Answer 92

Diagnosis of pyelonephritis: A positive urine culture from the renal pelvis is the ‘gold standard’ Cystocentesis urine sample is an adequate alternative (in non-obstructive AKI)- EVERY AKI case should have a urine culture with tissue breakpoints- It is important that you submit urine in both a plain tube, boric acid, and charcoal swab (as false negatives can occur during transport, even with same-day lab collection) – it is imperative that you ask the laboratory to perform culture and sensitivity testing with tissue breakpoints so that they can assess the susceptibility of bacteria within the renal tissue (otherwise the laboratory assumes that the concentration of the antibiotic is much higher due to urinary concentrating). * Primary decision making for immediate use of IV antimicrobials is based on sepsis criteria (see sepsis lectures) In absence of sepsis signs, base on clinical suspicion OR positive urine culture De-escalate antimicrobials if culture-negative N.b., different antimicrobial choices for Leptospirosis

Answer 93

Treatment of pyelonephritis: Based on meeting sepsis criteria: 25mg/kg/q6hr IV Amoxicillin clavulanate 5mg/kg IV once marbofloxacin (then 2mg/kg/24hr IV thereafter) AMOXICILLIN CLAVULANTE should NOT be used ALONE for pyelonephritis as it has POOR renal parenchymal penetration (even if the culture and sensitivity result suggest it is sensitive!). Marbofloxacin is given as a ‘one off’ loading dose of 5mg/kg IV and then continued as 2mg/kg/q24hr IV. The duration of treatment for sepsis depends somewhat on clinical improvement. When an animal has been diagnosed as pyelonephritis purely based on C+S (i.e, there were no sepsis signs to warrant treatment on initial presentation but the C+S results returned positive) then marbofloxacin (or other appropriate antimicrobial based on C+S) should be given for 14 days It is somewhat recommend to repeat urine cultures 1-2 weeks following cessation of antimicrobial treatment for pyelonephritis. HOWEVER, there is a possibility that this may just reflect ‘bacteriuria’ so unless the initially clinical suspicion was very high, this may not be overly necessary. Based on clinical suspicion/positive urine culture: 2mg/kg/q24hr IV/PO marbofloxacin for 14 days (or based on C+S) Pyonephrosis: As above, but requires urgent surgical drainage (referral procedure)

Answer 94

5mg/kg/q12hr PO Doxycycline for 14 days or 25mg/kg/q8hr IV Amoxcillin clavulanate until doxycycline course can be tolerated

Answer 95

HA is not generally considered a cause of AKI however does cause a marked pre-renal azotaemia Also often get hyperkalaemia and hyperphosphataemias Consequently, in every DOG with an AKI, I check basal cortisol to screen for HA A basal cortisol >55nmol/L* rules out HA If a very high suspicion, do an ACTH stimulation test and treat presumptively Please note this cut off has ONLY been validated on the immulite 2000 and Tosoh AIA360 analsyers – i.e. only if you send to an external laboratory. In-house analysers have NOT been validated for this cut-off point. However, if your basal cortisol is >100nmol/L, it is probably unlikely that the animal has HA

Answer 96

MOST cases of renal neoplasia will present as CKD. However, might be difficult to differentiate between first presentation of CKD and AKI Perform POCUS in every AKI case Renal lymphoma in cats can result in bilateral changes and relatively-normal architecture FNA of kidneys MAY detect renal neoplasia and should be considered in cases with a clinical suspicion and where clotting-ability permits it Please note, renal FNA is ONLY accurate for neoplasia (and even then is not that accurate) – renal biopsies are needed for all other conditions. Furthermore, renal biopsies require very special handling and MUST only be sent to the European (Italy) or American veterinary renal pathology services (DO NOT send renal biopsies to other laboratories). It is STRONGLY ADVISED to discuss the need for renal biopsies with an veterinary internal medicine specialist before considering them.

Answer 97

Glomerular disease can present as both an AKI or CKD Some AKIs as a result of glomerular disease can be rapidly progressive The hallmark of glomerular disease is proteinuria and is typically ≥ 2.0 Every AKI should have urine protein:creatinine ratio (UP:C) performed However, UP:C can be temporarily increased in AKI for a range for of reasons so need to re-check twice in a six week period* 25-50% of cases of glomerular disease in dogs and cats may benefit from immunosuppression so important to check- discuss with internal medicine specialist Please note, glomerular disease can exist at UP:C magntiudes even as low as <0.5. However, those that typically result in AKI’s are often >2.0. We can also see high UP:C as a result of inflammation and UP:Cs can also be increase *pre and post-renal inflammation can result in temporarily increased UP:C hence why you need to re-check the proteinuria TWICE in a six week period. However, if you have progressive azotaemia, hypoalbuminaemia, or nephrotic syndrome – it is worth speaking to an internal medicine specialist as some cases may benefit from immunosuppressive medication.

Answer 98

Haematology and Biochemistry Cystocentesis urine for urinalysis, UP:C, culture and sensitivity POCUS ± FNA Doppler Blood Pressure ±Basal cortisol (dogs) ± Acid-base analysis ± Leptospirosis tests ± Investigations into comorbidities in ‘AKI’ Please note, glomerular disease can exist at UP:C magntiudes even as low as <0.5. However, those that typically result in AKI’s are often >2.0. We can also see high UP:C as a result of inflammation and UP:Cs can also be increase

Answer 99

Treatment of AKI: Once we have ruled out causes that require specific treatment (or alongside treatment) the remainder of treatment for AKI is supportive The overall aim is to support the animal until (/IF) it manages to achieved a sufficient amount of renal recovery to maintain the following aspects of homeostasis on its own: Water balance (hydration) Electrolyte balance Acid-base balance Nutrition We then wait to see what degree of renal function is left ‘when the dust settles’ (/IF) at the three-month mark where we assess its CKD stage.

Answer 100

Fluid therapy in AKI Fluid therapy is an important aspect of the treatment for AKI and involves ensuring that an animal’s water requirements are met to avoid dehydration However, a ‘Goldilocks’ approach is needed as animals with renal disease are highly susceptible to fluid overload When we get to a point where an animal with AKI is able to drink adequate amounts of water and not become dehydrated (i.e., maintain its own hydration), then fluid therapy MAY no longer be indicated Some causes of AKI (toxins) MAY warrant higher rates of fluid therapy Some post-renal obstructive causes of AKI MAY develop post-obstructive diuresis necessitating higher rates of fluid therapy (see obstruction lecture) Paying close attention to fluid therapy is most critical in oliguric/anuric animals Stage of fluid therapy: R- Resuscitation – Replacing intravascular deficits (rarely required in primary AKI- If AKI is the main presenting complaint, then it is uncommon for animals to require resuscitation of their intravascular volume (e.g., in a ‘primary’ intrinsic AKI) however in AKI is secondary to other cuass (e.g. sepsis) then intravascular resuscitation might be required. ) O – Optimisation – Rehydrating total body water deficits S- Stabilisation – Providing maintenance water requirements IF an animal is not able to do so itself E – Evacuation – De-escalation of fluid therapy

Answer 101

R- Resuscitation – Replacing intravascular deficits IF an animal presents with signs of reduced intravascular volume (e.g., Shock) then fluid boluses are required to improve this (see ECC lectures) Typically 5-10ml/kg boluses of Balanced Crystalloid (e.g. Lactated Ringer’s) over 15-20 minutes until end-points are met The use of 0.9% NaCl is discouraged This is rarely required in AKI

Answer 102

O- Optimisation – Repleting total body water deficits It is not uncommon for animals with an AKI to present as dehydrated The optimisation phase involves replacing these losses of 6-8 hours* Base on clinical assessment of hydration Typically using balanced crystalloid solution (e.g. Lactated Ringer’s) Frequent, re-assessments of hydration status to avoid overhydration**

Answer 103

S- Stabilisation – Continue to provide maintenance water requirements IF required At this stage, we are attempting to provide on-going water requirements if an animal is not able to maintain hydration through oral intake Typically, this is using maintenance fluid rates (1-2ml/kg/hr)- Please note, that the mtainenance fluid rates are AVERAGE WATER requirements for the animal for the day. In fact, an animals’ ACTUAL water requirement varies MASSIVELY, and is typically lower in animals that rae not eating. Consequently, and as per the rehydration (optimisation) phase, it is important to continually assess the animal for signs of overhydration 0.45% NaCl is preferred owing to its lower sodium concentration, otherwise Balanced electrolyte solution (E.g., lactated ringers) 26-30mmol/L KCl supplementation is also recommended in non-hyperkalaemic animals Frequently attempt to reduce the rate to avoid overhydration with frequent hydration assessments ?Need/accuracy? Of ‘ins-outs’ approach in non-oliguric/anuric animals?

Answer 104

E- Evacuation – De-escalation of fluid therapy When an animal is either drinking* on its own or expected to do so- A phrase that is often used in veterinary medicine is “fluids until eating” however there is very little rationale behind this statement as animals will quite commonly drink when they are not eating. Consequently, do not use/rely on the phase “fluids until eating” as there is no evidence behind this. Important to note that animals will often fail to drink until they are 0.5% dehydrated so may not drink whilst on IV fluids When deemed safe to do so, slowly decrease the fluid rate by 25% every 8-12 hours and assess for any evidence of overall dehydration or deterioration Ensure that the animal is then able to maintain its hydration status on oral intake alone Do not base fluid requirement on changes in creatinine concentrations

Answer 105

Oliguria – relative/partial reduction in urine output Anuria – complete reduction in urine output Can occur with ANY grade of AKI Presence of oliguria/anuria can only be assessed once an animal is in the maintenance phase of fluid therapy More likely to occur with causes that also cause hyperkalaemia MARKED risk of fluid overload in these animals Requires rapid recognition and strict fluid therapy assessment The ‘ins outs’ approach: Aim to balance total fluid input with total fluid lost Fluid in: Oral intake and IV Fluids Water in nutrition (especially if assisted enteral feeding) Medications, CRIs, IV-flushes etc. Fluid out: Insensible losses – respiration, salivation, faeces, wounds etc. Sensible losses – Urination/drains Volume of fluid lost (insensible + sensible) is replaced with TOTAL fluid in Insensible losses are ~0.75ml/kg/hr Sensible losses are calculated from urine output Often requires indwelling urinary catheter or weighing bedding/litter trays (1g = 1ml) However, this is a very rough estimate and if you start ‘overhydrated’ can lead to ‘chasing up’ fluid volume. For example: 10kg dog Insensible losses = 7.5ml/hour Sensible losses (urine) = dog has produced 40ml of urine in the last four hours = 10ml/hour Total losses – 17.5ml/hour Non-fluid ‘ins’: 2ml per hour from IV flushes, 5ml from CRIs, 10ml from O.tube feeds = 17ml/hour Therefore, IV fluid required to match ‘losses’ = 0.5ml hour (out – ins = 0.5ml) However, need to frequently monitor the animal for dehydration or fluid overload

Answer 106

Animals with an AKI are typically hyporexic-anorexic often as a result of uraemia -> nausea/vomiting Presence of oral ulceration (uraemic ulcers) may also contribute as well as concurrent illness Medical therapy (anti-nausea, appetite stimulants) may help address this If animal cannot consume at least 75% of its required calorie intake by 48 hours, will need assisted enteral feeding (see nutrition lectures)

Answer 107

Nausea typically results from build-up of uraemic toxins can be improved with anti-nausea medication Maropitant – very good anti-emetic, but poor anti-nausea - 1mg/kg IV q24hr or 2mg/kg PO q24hr Ondansetron – very good anti-nausea, but poor anti-emetic - 0.5-1mg/kg IV/PO q8hr (can be given with maropitant) - N.b., can risk serotonin syndrome if given alongside mirtazapine Gastroprotectants are NOT recommended unless there is convincing evidence of gastrointestinal bleeding

Answer 108

Appetite stimulants can help improve appetite Capromorelin – 3mg/kg PO q24hr - Excellent appetite stimulant with wide safety profile Mirtazapine – 2mg/CAT/PO q48hr - Excellent appetite stimulant in cats (poorer in dogs) with anti-nausea properties - Risk of serotonin syndrome if given alongside ondansetron - Both capromorelin and mirtazapne can be given together Vitamin B12 – (250μg/animal/SC or IM once) - Can be considered as an appetite stimulant There is some rationale to vitamin b12 given that it is a water soluble vitamin and diuresis may lead to lower concentrations. Currently, it also generally considered to be ‘safe’ to administer empirically as a ‘one off

Answer 109

Blood pressure: A notable proportion of animals with an AKI will be hypertensive on presentation and a greater proportion will develop this during hospitalisation Treatment of hypertension is complex as some anti-hypertensive medications may be considered nephrotoxic If systolic blood pressure >160mmHg AND/OR evidence of target organ damage*  treat In THESE cases* – amlodipine 0.05mg/kg/q24hr PO Otherwise, repeat BP assessment twice over next eight weeks (see CKD lecture) In the CKD lectures we discussed about using RAAS inhibitors (acei/arbs) to treat systemic hypertension. However, in AKI these are verging on contraindicated due to the risk of a precipitous drop in glomerular filtration rate and a risk of worsening renal damage. Consequently, in AKI only, treatment of hypertension is recommended with Amlodipine (however, if the animal progresses to CKD this should be re-evaluated and RAAS inhibitors re-considered). Target organ damage typically refers to: Ocular – retinal detachment or haemorrhage Neurological – vestibular signs or seizures Normally, we would treat high blood pressure in dogs with ACEi/ARBs. However, as these can drop GFR, especially at higher values of creatinine, they should be avoided in AKI until GFR has reduced/is more stable. Consequently, the first line treatment for hypertension in AKI is amlodipine in BOTH dogs and cats(second line is hydralazine) (note this part of the 2023 IRIS AKI consensus and differs from the ACVIM consensus on hypertension of any cause). Do not use Ace inhibitors or angiotensin receptor blockers in AKI cases as these MAY result in worsening renal function

Answer 110

Electrolyte abnormalities: Electrolyte abnormalities are not uncommon in AKI cases Hyperkalaemia – is more commonly seen in obstructive causes of AKI (see obstruction lectures) Hypokalaemia – can be seen on presentation or during hospitalisation - This should be treated with IV supplementation or oral supplementation (e.g., potassium citrate) Hyperphosphataemia – is almost always present in AKI, although its treatment in the ‘acute’ should only be started once enteral nutrition has been achieved (see CKD lectures)-Do not give phosphate binders on an empty-stomach Hypernatraemia – can be present on admit due to dehydration or can develop during hospitalisation following the use of ‘high sodium’ fluids (use 0.45% NaCl in maintenance phase to avoid this)

Answer 111

Nephrotoxic drugs should be discontinued and avoided in AKI ‘Classic’ examples include: - NSAIDs* - Amphotericin B - Aminoglycosides - Allopurinol (more insidious progression) - ACEis and ARBs (RAAS inhibitors) - ?Intravenous contrast agents? However, possibility for idiosyncratic reaction to ANY drug – consider any recently started medications as a potential cause of AKI and consider withdrawal/substituted? Consider dose changes for drugs that undergo renal excretion Please note, this is in contrast to CKD where NSAIDs can be considered in select cases ACEis and ARBs may not directly cause AKI but may decrease GFR with potentially marked exacerbation of uraemia Intravenous contrast agents have historically been considered to be nephrotoxic however more recent evidence suggests this is not the case

Answer 112

The aim of treatment of AKI is to get an animal to a point where (/IF) it can achieve an adequate degree of renal recovery that allows it to maintain overall homeostasis on its own (± medications) It will take on average 1-3 weeks before an improvement is seen- excluding TREATED pre-renal, post-renal (obstructive), pyelonephritis/leptospirosis causes of AKI. This does not mean that the animal will necessarily need to be in the hospital for this period of time, just do not overly expect to see rapid changes in creatinine – this will typically occur over the subsequent weeks! Do not expect to see an improvement in creatinine within the first week of hospitalisation (although if it does improve, the prognosis is likely favourable) Note changes in creatinine during hospitalisation may just be reflective of dilution from fluid therapy Creatinine concentration on presentation is poor predictor of survival Oliguria/Anuria is a negative prognostic indicator Overall survival is around 50% but highly dependent on cause of AKI IF can get animal to a point where can maintain its homeostasis at home, monitor over the subsequent three months (e.g., 1 week, 1 month, and 3 months) - Repeat assessments of creatinine, electrolytes, phosphate, blood pressure, UP:C At the three-month mark, if creatinine is stable, assign an IRIS CKD STAGE (see CKD lectures) Unfortunately, a proportion of animals will not make it to this point and will deteriorate in the meantime

Answer 113

Maintaining Hydration Maintaining Calorie Intake Assessing for, and treating systemic hypertension Addressing electrolyte and acid-base derangements Other Supportive care

Answer 114

There are a number of toxic causes (or potential causes) of AKI that you will commonly come across in primary care practice These include: Grapes/Raisins (dogs)- Grapes/Raisans have been seen to cause clinical signs in cats but these are usually gastrointestinal signs rather than acutekidney inury Lillies (cats) Ethylene glycol – almost invariably fatal by the time AKI develops NSAIDs Myoglobin/haemoglobin (see toxicology lectures) There is some theoretical evidence as to providing increased fluid rates in toxic causes of AKI - especially in haemoglobin/myoglobin Majority of textbooks will recommend increased fluid rates in toxic causes of AKI Consequently, based on the current (limited) veterinary research, it is likely professionally safer to follow these guidelines for suspected toxic causes of AKI However, continue to monitor for evidence of fluid overload or relative oliguria/anuria hesitant to go higher then 4-6ml/kg/hr and would much prefer to use lower-sodium fluid such as 0.45% NacL but monitoring for hyponatraemia – this recommendation may change over time

Answer 115

Leptospirosis is not an uncommon cause of AKI in dogs Typically seen in young, unvaccinated dogs However, can also be seen in those who have only received Bivalent L2 vaccine Presentation is very variable and likely serovar related Think leptospirosis in any dog with a cholestatic pattern on biochemistry and AKI (but do not always have hepatic component!) Not uncommon to be oliguric/anuric so be careful with fluids Gold standard test is paired, rising MAT antibody titres- However these will take time to return and need to be taken 2-4 weeks apart, consequently, treatment is nearly always initiated pending a diagnosis Marked cross-reaction with vaccine antibodies so in-house tests need to be interpreted cautiously- if an animal has been vaccinated against Leptospirossi within the last 6-12 months, the antibody tests will nearly always be the result of this (need to demonstrate a rising titre to confirm that this was cause of AKI) – this includes the point-of-care assays such as Witness or SNAPlepto Will often need to treat presumptively based on clinical suspicion: - 5mg/kg/q12hr PO Doxycycline for 14 days - but if oral medication cannot be tolerated - 25mg/kg/q6-8hr IV Amoxicillin clavulanate until doxycycline can be tolerated

Answer 116

“Flushing the kidneys out” - Traditionally, very high rates of fluids have been advised to attempt to ‘flush the toxins out’. Not only has this been shown to work, but both human and veterinary studies have shown that the resultant fluid overload to be severely detrimental – DO NOT DO IT! “Changes in creatinine reflect improvement in kidney function” - Although overall a decreasing trend of creatinine can suggest improvement in renal function, it can also just reflect ‘dilution’ by fluid therapy - This typically causes confusion when fluid therapy is reduced from a higher rate with a resultant mild increase in creatinine – this typically just reflects ‘reduced dilution’

Answer 117

In cases of AKI or CKD where the degree of renal dysfunction is so severe that medical treatment is unable to maintain homeostasis within ‘liveable’ parameters- dialysis is indicated. Dialysis acts as an ‘external kidney’ allowing time to see IF the native kidneys can improve to a degree that is compatible with life The typical indications can be remembered by the ‘vowels’: A- Acidaemia E- Electrolyte abnormalities (typically potassium) I- Intoxication (e.g., Ethylene glycol) O- Overload (fluid) U- Uraemia Currently (2023) only one centre in the UK offers dialysis (RVC) and only for AKI cases Not uncommon to require weeks of treatment and typically in the tens of thousands of pounds* May be prudent, professionally, to discuss options with clients in cases where dialysis is indicated Leptospirosis cases anecdotally improve a lot quicker and may be cheaper It is not uncommon for animals to be referred to the RVC where the clinical decision is that dialysis is not currently indicated and medical treatment is continued – do not promise that dialysis will be performed!

Hepatic and urinary Flashcards

(143 cards)