What part of the kidneys is especially susceptible to toxicants? WHy?
- because it receives 90% of the renal blood flow and contains the large endothelial surface area of the glomerular capillaries
What cells within the renal cortex are most frequently affected by ischemia and toxicant induced injury? Why?
- epithelial cells of the proximal tubule and thick ascending loop of Henle
- because of their transport functions and high metabolic rates
- Toxicants disrupt the metabolic pathways that generate ATP
- ischemia can rapidly deplete cellular A T P stores
-with the resulting loss of energy, the sodium-potassium pump (Na/K) fails, leading to cell swelling and death.
Why can tubular epithelial cells exposed to increasingly higher concentrations of toxicants.?
- resorb water and electrolytes from the glomerular filtrate
- Toxicants that are either secreted or resorbed by tubular epithelial cells (e.g., gentamicin) may accumulate in high concentrations within these cells
What effect might the countercur- rent multiplier system have regarding toxins?
may concentrate toxins in the medulla
How might biotransformation that occurs in the kidneys lead to ARF?
- the formation of a more toxic metabolite may occur
- ex: oxidation of ethylene glycol to glycolate and oxalate
Describe how lepto can lead to ARF?
1. acute interstitial nephritis → organisms colonize and proliferate within renal tubular epithelial cells
2. renal vasculitis and the development of swelling that further compromises renal blood flow
How does melamine contribute to ARF?
chemical reaction between melamine and cyanuric acid produces insoluble crystals that form in the distal renal tubules of affected animals, compromising renal function.
What is the clinical presentation of ARF in animals that have ingested melamine?
- variable and ranges from severe A R F to mild azotemia associated with urine- concentrating deficits to no clinical signs
- Crystalluria (round, yellow crystals with radiant striations that may resemble urate crystals) is observed in many cases
Give examples of how ARF may develop due to diagnostic or therpeutic treatments?
1. anesthesia and sx → hypotension and decreased renal perfusion
2. NSAIDs or vasodilators
3. prolonged anesthesia with inadequate fluid therapy in older dogs and cats with preexisting, subclinical renal insufficiency → renal ischemia and ARF in the hospital setting
4. tx with potential nephrotoxic drugs ( aminoglycosides)
What is the min MAP needed for kidneys to maintain adequate renal perfusion pressure by autoregulation?
Why must renal blood flow and perfusion be maintained?
needed for glomerular filtration and cellular delivery of oxygen and nutrients to occur
What is the common result of ischemic or toxicant-induced tubular cell swelling, injury, and death?
nephron dysfunction leading to a decreased glomerular filtration rate
How do the following result in dysfunction and reduced glomerular filtration at the individual nephron level:
1. tubular obstruction
2. tubular backleak
3. renal arteriolar vasoconstriction,
4. decreased glomerular capillary permeability
1. a. cellular debris within the tubule
1. b. interstitial edema may compress and obstruct renal tubules
2. occurs because of a loss of tubular cell integrity, allowing the filtrate to cross from the tubular lumen into the renal interstitium and subsequently the renal vasculature → facilitated by tubular obstruction because of the increased intratubular pressures proximal to the obstruction
3. afferent glomerular arteriole constriction occurs due to decreased resorption of solute and water by damaged proximal tubule segments results in the increased delivery of solutes and fluid to the distal nephron and macula densa in many nephrons,
4. leads to a reduction in glomerular filtration. For example, aminoglycosides decrease both the number and size of fenestrae in glomerular capillary endo- thelial cells, thereby decreasing the surface area available for ultrafiltration.
What are possible mediators of the vasoconstriction?
natriuretic factor, the renin- angiotensin system, and thromboxane
What are 3 phases of acute tubular damage leading to ARF? ( What are 3 phases through which ARF proceeds throuh)
What is the initiation phase?
What is the significance of the initiation period?
a. Spans the time from initiation of renal damage to the onset of azotemia (hrs to days)
b. Clinical signs may not be obvious;
- therapeutic measures to reduce the renal insult have the potential to prevent the development of established ARF
- In the initiation phase, individual tubules are damaged but overall renal function remains adequate
What could you look for to help ID Acute tubular damage, occurring before the development of ARF?
renal tubular epithelial cells and casts in the urine sediment
What characterizes the maintenance phase?
by the development of tubular lesions and nephron dysfunction
i.e., renal azotemia and urine- concentrating deficits
What impact does therapy have if initiated during the maintenance phase?
How long does this stage usually persist?
- life saving but they usually do little to diminish the severity of existing renal lesions, improve function, or hasten recovery
- Even with removal of the inciting cause and re-establishment of renal blood flow improvement there is often no noticeable improvement in renal function
- This stage usually persists for days to weeks.
What is the volume of urine produced during the maintenance phase?
- Patients with severe damage to the kidneys will be anuric or oliguric; those with less severe damage will have normal urine production or more likely be polyuric.
- It is not uncommon for patients to die in this phase.
- Hemodialysis can be lifesaving for patients in this phase to buy time for recovery
What is the recovery phase?
How long might the recovery phase take?
renal lesions are repaired and function improves
may take up to 6-8 weeks or longer
When might tubular damage be reversible ( or when is repair only possible)?
What happens to the remaining surviving nephrons?
- if the tubular basement membrane is intact and viable epithelial cells are present
- the remaining surviving nephrons will undergo hypertrophy to compensate for the loss of irreversibly injured nephrons that will be replaced by scar tissue.
Can new nephrons be produced?
What might happen to other surviving nephrons? How is this beneficial?
- no and irreversibly damaged nephrons cannot be repaired
- the functional hypertrophy of surviving nephrons may adequately compensate for the decrease in nephron numbers
- Even if renal functional recovery is incomplete, adequate function may be reestablished.
What are CS of ARF?
- often nonspecific :
• occasionally, uremic breath or oral ulcers
What CS would increase your suspicion of ARF?
• uremic breath
• oral ulcers or tongue tip necrosis,
• bilaterally enlarged and possibly painful kidneys
What volume of urine production may be present?
- Oliguria (< 0.5 ml/kg/hr)
- less frequently, anuria (< 0.1 ml/kg/hr)
- nonoliguric forms of ARF where the patient's urine production is normal or increased fortunately occur
How do most patients with ARF usually appear on PE?
- in good body condition
- they may be hypothermic
- may have an increased respiratory rate secondary to a resulting metabolic acidosis
When is a dx of ARF suspected?
if azotemia develops acutely and is associated with persistent isosthenuria or minimally concentrated urine.
What conditions might mimic renal failure?
What will help you to resolve the azotemia in these cases?
- prerenal dehydration and azotemia superimposed on an inability to concentrate urine
• Addison's disease
• overzealous use of furosemide)
- IVFT, volume replacement
What are some unique CS of ARF related to this quick onset of CS?
What is an active urine sediment in this case?
1. enlarged or swollen kidneys
3. good body condition
4. active urine sediment (e.g., granular casts, renal epithelial cells)
5. relatively severe hyperkalemia and metabolic acidosis (especially in the face of oliguria)
Compare CS of ARF to those of CRF?
tend to be severe compared with those seen in an animal with C K D and similar magnitude of azotemia
Describe US findings in animals with ARF?
usually nonspecific, with diffusely normal to slightly hypoechoic renal cortices
Describe the renal cortices in animals with calcium oxalate nephrosis associated with ethylene glycol ingestion?
- renal cortices may be markedly hyperechoic
- a medullary rim sign seen, however, this is not pathognomonic
What might renal biopsy show in some animals with ARF?
proximal tubular cell degeneration, ranging from ( varying degrees) :
• cloudy swelling → necrosis, with edema and mononuclear and polymorphonuclear leukocyte infiltration in the interstitium.
What pathology is Ethylene glycol and melamine-associated nephrotoxicity frequently associated with?
Can you tell toxicant-induced ARF from ARF caused by ischemia by histo?
no in all cases, but histologic findings are often helpful in establishing a prognosis.
What does tubular regeneration look like on histo?
- flattened, basophilic epithelial cells with irregular nuclear size
- mitotic figures
- high nuclear/cytoplasmic ratios
What is generally good prognostic findings on histo?
1. evidence of tubular regeneration
2. finding an intact tubular basement membrane
**** may be observed as early as three days after the insult
What are poor prognostic signs for ARF?
1. large numbers of granular casts
2. extensive tubular necrosis
3. interstitial mineralization
4. fibrosis with disrupted tubular basement membranes
Overall, what are you using to help decide the overall prognosis for ARF?
1. histo findings
2. degree of functional impairment
3. response to therapy *** probably most important
What are risk factors for the development of ARF?
1. Preexisting renal disease or renal insufficiency
3. Decreased cardiac output
8. Liver disease
9. Electrolyte abnormalities
10. Concurrent diuretics with potentially nephrotoxic drugs ( ie: aminoglycosides)
11. Concurrent use of potentially nephrotoxic drugs such as
aminoglycosides, nonsteroidal antiinflammatory drugs,
and intravenous radiographic contrast agents
12. Decreased dietary protein
11. Diabetes mellitus
What will you try and do before an animal in hospital recieves therapy?
- decide if they are at risk of ARF due to an underyling condition
-assess the risk:benefit ratio in individual cases in which an elective anesthetic procedure is considered or treatment with potentially nephrotoxic drugs is indicated.
- try an eliminate predisoposing factors if possible ie: IVFT
What are the major categories of risk factors regarding ARF?
- disorders affecting renal perfusion
- preexisting renal disease
- electrolyte disturbances
- treatment with nephrotoxic drugs
- dietary influences.
How does poor renal perfusion affect the kidneys?
increases the risk of nephrotoxic and ischemic damage to the kidney
What can cause renal hypoperfusion?
1. ↓ cardiac output
2. ↓ plasma oncotic pressure
3. ↑ blood viscosity
4. systemic vaso- dilation
What other impacts does volume depletion have other then decreased renal perfusion?
1. decreased volume of distribution of nephrotoxic drugs
2. a decreased flow of tubular fluid.
What is the impact of decreased tubular fluid flow?
potentiates tubular resorp- tion, which can increase the intratubular concentration of nephrotoxicants.
Explain how Preexisting renal disease and advanced age may lead to ARF?
1. may increase the potential for nephrotoxicity → ie: pharma- cokinetics of potentially nephrotoxic drugs may be altered in the face of decreased renal function.
2. reduced urine-concentrating ability and thus a decreased ability to compensate for dehydration
3. compromised production of vasodilatory prostaglandins dt preexisting dz → get unbalanced vasoconstriction → decreased renal perfusion
When might reduced dietary potassium be a problem?
- when giving drugs like gentamycin
- exacerbates gentamicin-induced nephrotoxicity, possibly because potassium-depleted cells are more suscep- tible to necrosis.
Should you still be concerned about a patient that has serum potassium concentrations in the normal range but has had prolonged anorexia, vomiting, or diarrhea?
- because it is intracelluar and theses conditions will result in whole body K depletion
What drug combination is associated with an increased risk of ARF in dogs?
furosemide and gentamicin
How does furosemide most likely lead to ARF with coadministration of an AG?
- potentiates gentamicin-induced neph- rotoxicity by:
1. causing dehydration
2. reducing the volume of distribution of gentamicin
3. increasing its renal cortical uptake.
Does IVFT necessarily help to prevent the affects seen with both furosemide and AG?
What other substances has this been seen with when furosemide is given?
- not necessarily
- minimizes but does not negate the additive effect of furosemide on gentamicin-induced neph- rotoxicity in the dog
- furosemide facilitates the tubular uptake of gentamicin independent of hemodynamic changes
- enhance radiocontrast agent and cisplatin- induced nephrotoxicity in human beings
What conditions are we more likely to see the potentional for adverse effects on renal fucntion?
- in situations associated with high renin concentration:
• sodium or volume depletion,
• congestive heart failure,CKD)
What effect to hi renin states have?
What role do prostaglandins play in such state?
- stimulate the production of angiotensin and aldosterone → which can, in turn, decrease renal blood flow and GFR
- renal prostaglandins counteract this decrease in renal blood flow and GFR
What happens to the protective effects of PG in patients with CKD and those undergoing treatment with NSAIDs?
What NSAIDS do dogs appear to be particularly senstitive to?
ibuprofen and naproxen, which, in addition to ARF, may cause gastrointestinal tract ulceration.
Are there some NSAIDS that are okay to use in dogs? Explain?
- At one time, COX 2-specific inhibitors were thought to have less effect on renal blood flow
- research shows that COX 2 enzymes are present or expressed in the canine kidney → so any NSAID, regardless of its COX specificity or sparing properties, has the potential to produce adverse renal effects
Why might dogs be more senstitive to COX 2 selective drugs?
dogs express higher basal levels of C O X 2 in the kidney than some other species
What might be the relationship between ACE I and NSAIDS use?
have increased risk of renal toxicity when treated with NSAIDs because some of the beneficial effects of ACEI are derived from kinin-stimulated production of prostaglandins.
How might the amount of protein fed relate to ARF?
- quantity of protein fed before a nephrotoxic insult can significantly affect the degree of renal damage and dysfunction
- High- dietary-protein (27.3%) conditioning 21 days before and continuing during gentamicin administration was found to reduce nephrotoxicity, enhance gentamicin clearance, and result in a larger volume of distribution com- pared with the findings in dogs fed medium (13.7%) or low levels of protein (9.4%)
What is the significant to you regarding the effects of protein in diet and insults?
realize that anorectic animals may be at increased risk for A R F as a result of decreased protein intake
Why should you ensure adequate IVFT in patients with a pyometria?
- ARF is common in dogs with pyometra and Escherichia coli endotoxin-induced urine- concentrating defects
- If fluid therapy is inadequate during anesthesia for ovariohysterectomy or during the recovery period, dehydration and decreased renal perfusion may result in ARF
What parameters are a good way to monitor renal function during anesthesia?
1. blood pressure
2. urine production and outout
What are some possible early indicators of renal tubular damage in animals receiving potentially nephrotoxic drugs?
- Increased urinary excretion of protein, glucose (normoglycemic glucosuria), or casts and/or renal tubular epitheial cells
What is an alternative to standard clinicopathologic tests to detect early nephrotoxicity?
- quantification of urine enzymes (enzymuria)
- most serum enzymes are not filtered by the glomerulus because of their large molecular weight
- may also be an indication of renal tubular leakage or necrosis
What enzymes originate from specific cellular organelles and thus can serve as markers for damage to a specific site?
GGT → proximal tubular brush border
NAG → is a lysosomal enzyme
*** need baselines in both before
When does enzymuria occur in relation to the other markers of renal dz?
- generally several days before azotemia and decreased urine-concentrating ability associated with nephrotoxic proximal tubular injury
- urine G G T : creatinine and N A G : creatinine ratios have been shown to accurately reflect 24-hour urine GGT and NAG excretion in dogs, if determined before the onset of azotemia
What levels of enzymes are suggestive of clinically relevant tubular damage?
Twofold to threefold increases in the GGT/creatinine or NAG/creatinine ratio
What are the goalst for tx of ARF?
1. eliminate renal hemodynamic disorders
2. alleviate water and solute imbalances to give the nephrons additional time to repair and hypertrophy.
What indicates a positive response to therapy?
1. a decrease in the serum creatinine concentration
2. an increase in urine production
How does diuresis help?
- decreasing serum:
• urea nitrogen
• potassium concentrations
- by lessening the likelihood of overhydration.
What is the actually reason for the increased urine production?
decreased tubular resorption of filtrate
GFR and renal blood flow may improve in response to diuresis, they are frequently unchanged,
Why are most animals with ARF dehydrated?
gastroin- testinal fluid loss (e.g., vomiting) superimposed on their inability to concentrate urine.
Why do we want to replace their volume deficits?
1. correct the prerenal component of the ARF
2. help protect against any additional ischemic renal tubular damage
What should you consider doing next once their volume deficits are corrected?
- decrease resorption of solutes
- facilitate excretion of solutes that are reabsorbed and secreted by renal tubular cells (e.g., urea nitrogen and potassium).
How would you help to promote solute exretion?
diuresis → Increasing tubular flow rates and volumes will hinder reabsorption and favor secretion of solutes.
How should fluids for diuresis be given? Why?
- Jugular catheters or other central venous lines are ideal because they facilitate frequent blood sampling and infusion of hypertonic solutions (e.g., mannitol) and allow access for central venous pressure ( C V P ) measurement.
How could you assess for the possibility of a subse- quent volume overload?
- give a fluid bolus challenge of 20 ml/kg body weight given intravenously over 10 minutes
- C V P should not increase by more than 2 cm of water if the patient's cardiovascular func- tion is normal
What is the purpose for replacing volume deficits over the first 4 to 6 hours rather than over the normal 12 to 24 hours?
to rapidly improve renal perfusion and decrease the likelihood of continued ischemic damage.
What fluids are ideal for hyperkalemic patients?
For normokalemic patients?
For if hyperkalemic and hypernatremic patientes?
1. 0.9% NaCl
2. LRS or equivalent replacement fluid
3. Half strength saline (0.45 %) in 5 % dextrose
What is the fluid of choice for rehydration in most cases? **ask about this
When would you not use this fluid type? What should you use instead?
patient is hypernatremic, → 0.45% saline with 2.5% dextrose solution
What are you observing the patient for during this rapid fluid rehydration phase? Why?
What should you record before starting fluids?
- overhydration ( fluid overload)
- Overhydration in dogs and cats with oligoanuric ARF is a common complication that is extremely difficult to correct → not be able to excrete excess fluids
- BASELINE BODY WEIGHT before fluid therapy is initiated, reweigh patient at least 2X daily
How do you assess for fluid overload?
- body weight
- packed cell volume
- plasma total solids
What are CS of overhydration?
What condition usually develops before these CS?
• ↑ broncho- vesicular sounds or overt crackles and wheezes
• serous nasal discharge
- pulmonary edema
What are other parameters to measure during rehydration?
1. urine production
2. electrolyte and acid-base status assessed
*** need to know so that you can determine when maintenance therapy should be started
What should fluid admin match once the animal is rehydrated and urine production is re-established?
- fluid administration is matched to ongoing losses ("ins-and-outs" fluid therapy)
*** MEASURE URINE OUTPUT AND OTHER FLUID LOSSES (weight pee pads, measure volume of urine produced via urinary catheterization) so that fluid requirements can be properly assessed.
Do all animals have the same maintenance needs for fluid loss?
no → approximately two thirds of normal maintenance fluid needs are due to fluid loss in urine
- oliguric and nonoliguric patients can have large variations in their mainte- nance fluid needs
What are methods that can be used to collect and meaure urine volume?
1. Metabolism cages
2. urinary catheters → strict aseptic technique and closed collection systems must be used
3. manual collection
Which is prefered: intermittent urinary bladder catheterization or indwelling catheterization? Why?
intermittant due to risk of UTI
What is a way to measure urine production in cats?
litter pan before and after voiding is a useful, although less accurate
What might be a method for measuring output if indwelling urinary catheter or a metabolism cage is not available?
weighed in the same scale two or three times a day to assess fluid gain or loss.
What should you do if urine flow is not reestablished, and there are no signs of overhydration?
give another bolus of fluids over 4 to 5 hours equivalent to 5% dehydration to achieve mild volume expansion. If patient is hypernatremic or hyperkalemic give 0.45 % NaCl in 2.5 % dextrose.
What might you consider for therapy if urine production is still not reestablished or is subnormal (<0.3 - 1.0 ml/kg/hr),?
diuretic ± dopamine can be administered to promote diuresis
What condition can develop after several days of starting IVFT with solutions containing large amounts of NA+ or NaBicarb in patients with ARF ?
What could you use to tx the hypernatremia if it does develop?
0.45% NaCl with 2.5% dextrose fluids will usually correct the problem.
When might you consider a primary hypercalcemic disorder (e.g., neoplasia or vitamin D3 intoxication) as the cause of the ARF?
If moderate to severe hypercalcemia is observed
What is the preferred measurement for calcium levels in most cases?
ionized calcium concentration is preferable to measurement of the total calcium concentration
What are tx options for hypercalcemia?
1. rehydration with 0.9% NaCl fol- lowed by diuresis induced with furosemide
3. Intravenous bisphosphonates
How do GC help with hypercalcemia?
When should you only use these?
- lower calcium concentrations by decreasing intestinal absorption and facilitating excretion
- but their use may interfere with the diagnosis of the underlying disorder (e.g., lymphoma)
Why are we concerned about hyperkalemia?
- 6.5 to 7.0 mEq/L
- lead to :
• cardiac conduction disturbances
• these can be life threatening
What are some Electrocardiographic Findings seen with Hyperkalemia?
What if its severe?
• Decreased P-wave amplitude,
• Increased PR interval,
• Widened QRS complexes,
• Tall, spiked T waves
• atrial standstill
• ventricular tachycardia
• ventricular fibrillation
When do we treat hyperkalemia?
1. mild to mod → typically resolves with administration of potassium-free fluids (dilution) and improved urine flow (increased excretion)
2. severe ( (>7-8 mEq/ L), ECG changes
What are tx options for the more moderate? 2 severe hyperkalemia? 1
1. Sodium bicarbonate → correct metabolic acidosis and ↓ serum potassium concentration by exchanging intracellular hydrogen ions for potassium ( moderate)
2. Insulin/glucose → increase intracellular shifting of potassium → Regular insulin followed by glucose bolus ( moderate)
3. 10% calcium gluconate (severe)
*** are all short-lived → fluid and acid-base therapy to initiate and maintain a diuresis and maintain blood pH and bicarbonate within the normal range are important to maintain potassium excretion and normokalemia.
Why should you monitor BG during insline admin?
- several hours after administration of insulin because hypoglycemia may occur.
What is the role of the 10% calciumgluconate?
counteract the cardiotoxic effects of hyperkalemia without lowering the serum potassium and can be used in emergency situations.
How is the metabolic acidosis treated?
- usually resovles on its own with the IVT
- tx with bicarb ( choice) if blood pH < 7.15 or total C O 2 / C O 3 H is less than 12 mEq/L
What are AE of too much bicarb tx?
1. ionized hypocalcemia
2. paradoxical cerebral spinal fluid (CSF) acidosis → hyperventilation abates and CO2 diffuses into the CSF
3. and/or cerebral edema
4. metabolic alkalosis
What are ways to reduce Accumulation of Nitrogenous Wastes and Uremic Toxins?
1. ideally by re-establishing urine production for elimination → IVFT diuresis
3. diuretic + dopamine combo ( rare to see major benefits
What are the diuretics of choice if you choose to to use them in animals with ARF?
furosemide and mannitol
How does furosemide work?
- loop diuretic
- blocks the reabsorption of chloride and sodium in the thick ascending limb of Henle, resulting in natriuresis and osmotic diuresis
- Some animals will respond to furosemide, but not mannitol or visa versa
How can mannitol help?
How often can you repeat if urine production occurs with mannitol?
- As an osmotic agent, give slow over 20 min
- preferred for initial diuretic therapy
- mannitol may decrease tubular cell swelling, increase tubular flow, and help prevent tubular obstruction or collapse
- If urine production occurs then the dose of mannitol can be repeated every 4 hours, or as a constant rate infusion (CRI) (1-2 mg/kg/min).
What tx for osmotic diuresis is superior in healthy cats?
mannitol when used as an adjunct to fluid therapy, are superior to those of furosemide and dopamine combination.
In what patients is mannitol contraindicated in? 3 Why?
1. overhydrated patient → the resultant increase in intravascular volume may precipitate pulmonary edema
2. pulmonary edema
3. congestive heart failure
a catecholamine, capable of stimulating dopaminergic receptors in the renal vasculature and inducing vasodilation in dogs (not cats).
Why might dopamine be used?
- potential of increasing renal blood flow and GFR
- Only a low dose CRI (0.5 - 3.0 ug/kg/min) will induce renal vasodilation
- in people, there is growing evidence that dopamine treatment has no benefit; however, there are species differences with respect to distribution of dopamine receptors
What is Diltiazem?
What should you monitor patients for with this drug?
Is what specific case of ARF might this drug be used?
- antiendothelin effects leads to increased renal blood flow
- May also have some other renoprotective effects (via decreased tubular cell death)
- Monitor patient for hypotension
- benefit in ARF induced by Leptospirosis in dogs.
What are indications for tapering IVFT?
How long might it be before you see some of these indications?
(1) signifi- cant decreases in B U N and phosphorus concentrations
(2) control of vomiting and diarrhea
(3) improved mood and renewed
interest in eating and drinking.
- may be 4 -10 d
When would you d/c tapering?
- patient loses weight
- increases in packed cell volume, total protein, and B U N and/or creatinine concentrations
** restart previous maintenance for at least 48 hrs
When would you consider Peritoneal or hemodialysis?
1. severe, persistent uremia, acidosis, or hyperka- lemia
2. tx overhydration
3. cases of toxicants to hasten elimination
**** Warn owners that dialysis is very expensive and time consuming
When might you consider a renal biopsy?
- diagnosis is in doubt
- if the patient does not respond to therapy within 3 to 5 days
- if dialysis is considered.
What is the long term Px for cats and dogs with ARF?
What do you need to do first in order to establish an accurate Px?
- fair to good if survives the period of renal tubular regeneration and compensation
- guarded to poor if with well established ARF
- aggressive therapy
What carries a poor px with ARF?
- having a prolonged time for recovery in animals with moderate to severe renal damage → may require many weeks for renal repair
What are the most important prognostic indicators during early ARF? 3
1. severity of the initial azotemia/uremia
2. response to fluid therapy
3. assessment of renal histopathologic lesions
What are other factors that might affect Px? 5
1. Urine output: nonoliguric ARF has a better prognosis that oliguric/anuric ARF.
2. Cause - ARF secondary to infectious and hemodynamic causes tends to have a better prognosis than if induced by a toxin.
3. Other organ failure or disease states (e.g., sepsis, CHF)
4. Age: older animals are more likely to have underlying renal disease or other systemic diseases.
5. Access to hemodialysis.
- clinical syndrome characterized by the sudden onset (within hours to days) of hemodynamic, filtration, and excretory failure of the kidneys
What is the result of failure of te kidneys to maintain their HD, filtration and excretory functions?
1. accumulation of metabolic toxins (BUN, creatinine, phosphorous, etc.)
2. disruption of fluid, electrolyte, and acid-base homeostasis
What are some other causes of acute uremia?
- prerenal azotemia
- postrenal azotemia
- combinations of these.
How is ARF different from CRF?
- reversible if diagnosed early and aggressively treated, ARF has the potential to be reversable
- any delay Delay in implementing therapy, can result in irreversible renal damage or death
What are the most common causes of ARF?
- but the etiology is often multifactorial.
What are 2 categories for causes of ARF?
2. intrinsic renal parenchymal diseases,
3. postrenal disorders.
What are some risk factors that predispose dogs and Cats to ARF?
- Preexisting renal disease or renal insufficiency
- Dehydration and hypovolemia from any cause
- DIC and vasculitis
- Decreased cardiac output
- Diabetes mellitus
- Concurrent use of nephrotoxic drugs with diuretics
- Advanced age
- Use of multiple nephrotoxic drugs in the same patient
- Systemic hypertension
- Prolonged anesthesia with inadequate fluid therapy
- Heat stroke
Prerenal - hemodynamic disorders causes of ARF?
1. shock, hypovolemia → Hemorrhage, septic Shock, cardiogenic shock, heat stroke, severe 3rd degree burns
2. systemic dz ( pancreatitis, peritonitis (acute abdomen), DIC, hypoadrenocorticism
3. Renal vascular/hypoperfusion
Anatomical - renal artery occlusion
Functional - Drugs - NSAIDS, ACE inhibitors, anesthetic drugs, hepatorenal syndrome
Intrinsic Renal Parenchymal Disorders
1. Renal vein occlusion
Leptospirosis, Pyelonephritis, FIP, Leishmaniasis, Fungal, Lyme dz, etc
3. Renal Disorders
MODS, Glomerulonephritis, Hemolytic uremic syndrome, SLE, trauma,
Renal neoplasia, Renal transplant rejection (graft vs host), acute interstitial nephritis
- Antimicrobial agents
- Chemotherapy drugs: methotrexate, cisplatin, doxorubicin in cats,
- Others: Radiocontrast agents, NSAIDS, ACE Inhibitors
- Heavy metals: Hg, Pb, etc
- Toxins: Ethylene glycol
- Plants: some lilies (cats), mycotoxins
- Endogenous toxins
- Miscellaneous: streptokinase, acetaminophen, snake venom, Bee venom, grapes (dogs)
What are ex of Am agents that are neprhotoxic?
- aminoglycosides, idiopathic rxns to ALL other classes
- Antifungal drugs: amphotericin B`
What are examples of endogenous products that are nephrotoxic?
hemoglobin, myoglobin, hypercalcemia
What are ex of postrenal disorders that can cause ARF?
1. Partial or complete obstruction of the urethra or bladder by uroliths, mucous plugs, blood clots, strictures, or an intra or extraluminal mass
2. Bilateral ureteral obstruction or unilateral ureteral obstruction with a single kidney
3. Bilateral renal pelvis obstruction or unilateral renal pelvis obstruction with a single kidney
What are . Factors that make the Kidney Vulnerable to Ischemic and Toxic Injury?
1. large amount of blood flow to the kidneys ( more toxins brought forward)
2. renal cortex: 90% renal blood flow, large metabolically active endothelial surface area (i.e., glomerular capillaries, proximal tubules).
What cells in the kidneys are especially vunlnerable to ischemic and toxic injury? Why?
• Renal tubular epithelial cells, especially in the proximal tubules and ascending thick Loop of Henle → high metabolic rates
What causes of azotemia are you trying to R/O in cases of ARF?
2. postrenal → Check for signs of lower urinary tract obstruction (especially if patient is anuric) or rupture
3. environmental exposure to toxins
4. medical exposure to drugs ( AG, ibuprofen)
Q: How would you rule out both of these possibilities?
Prerenal: check PCV for hemoconcentration and compare it to USG
When is the best time to take a USG in a sick animals? Why?
- urine sample to measure the USG prior to fluid therapy
- however, do not delay IV fluid therapy for this if the patient is sick and clinically dehydrated or you suspect ARF
- Fluid therapy induces diuresis, often leading to production of dilute urine; this can delay and frustrate attempts to localize azotemia
How can most prerenal causes of azotemia be ruled out?
What is an exception? Give some examples?
In such dz's, what should happen to the azotemia with IVFT?
- with a baseline UA
- those disorders where prerenal azotemia is superimposed on an inability to concentrate urine from another cause of PU/PD
- e.g., hypoadrenocorticism, hypercalcemia, etc → These can mimic ARF; the azotemia should promptly resolve with fluid therapy.
What might indicate renal tubular damage on lab work>
presence of increased granular and cellular casts, and possibly proteinuria and glucosuria (with normal serum glucose).
What is a strong suggestor of ethylene glycol posioning?
high numbers of calcium oxalate dihydrate or monohydrate crystals
In regards to mgt of ARF, what is the basic goal?
to buy time for the remaining nephrons to repair and hypertrophy → 2. Time is of the essence so work quickly. These patients need 24-hr intensive care
What are ways of trying to buy the remaining nephrons time?
1. Minimize further renal damage and correct the underlying disease.
2. Correct alterations in ECF volume.
3. Minimize hyperkalemia.
4. Correct acid/base disturbances.
5. Establish urine production to reduce accumulation of uremic toxins.
6. Good supportive care and nutritional management
How can you minimize further renal dameage?
1. d/c all potentially nephrotoxic drugs → consider measures to reduce their absorption if appropriate (induction of emesis, gastric lavage, cathartics, etc.).
2. Start specific antidotal therapy if applicable
3. ID and eliminate any prerenal or postrenal abnormalities that exist
What are ex of specific antidotal therapies?
1. alcohol dehydrogenase inhibitor 4-methylpyrazole for ethylene glycol toxicity
2. penicillin for Leptospirosis)
What nephrotoxicty is furosemide best avoided in?
promotes gentamicin-induced ARF; avoid in these cases and in other forms of toxicant ARF.
What are important aspects to consider for supportive care?
1. Control Vomiting and Combat Uremic Gastritis
2. Nutritional Support
How can you control vomiting?
1. Administer of H2 receptor blockers and a central acting antiemetics
2. Use lower doses (metoclopramide, H2 blockers) if renally excreted
Why is it important to pay attention to nutrition?
daily caloric requirements is very important for improving outcome
Why are animals inappetent?
gastric hyperacidity and vomiting - give antiemetics and H2-receptor blockers.
What might you consider for nutritional support if the patient is not vomiting? vomiting
enteral feeding techniques
Parenteral (IV) nutrition
How should you choose your Am?
Is Prophylactic antibiotic administration warranted for prevention of an iatrogenic UTI from urinary catheter placement?
- C & S
- no, ineffective and promotes colonization with a more resistant bacterial population.
What can dialysis be used for?
- to remove uremic toxins and levels of nitrogenous wastes in order to buy time for renal function to recover.
What impact does dialysis have on Px?
- hemodialysis has improved the outcome in dogs with ARF
- In a case series of 124 dogs with ARF who underwent dialysis, the overall survival rate was 41 %
- The underlying cause for the ARF was a major factor determining survival
1. What are some risk factors for ARF that you should monitor for in your patients in order to help prevent ARF developing?
2. List 3 reasons why the kidney is so susceptible to toxic injury?
Other than ethylene glycol name 2 drugs and 2 other endogenous or exogenous substances that are toxic to the kidneys?
5. Other than ARF what are other DDx for hyperkalemia in a patient?
How will you address hyperkalemia in a patient with ARF?
6. How will you treat a severe metabolic acidosis (pH = 6.9) in a patient with ARF?
What are the possible adverse effects of this treatment?
9. Other than a diuretic what other drugs can be used to promote renal blood flow in patients with ARF?