General renal and AKI Flashcards
Name 3 situations in which it may be useful to determine GFR
- Evaluation of renal function in patients where kidney disease is suspected, but no azotemia is present (PU/PD, low USG cases)
- Screening tool for patients where incipient renal disease is suspected (breed with known nephropathies)
- Patients undergoing administration of potentially nephrotoxic drugs
What are the key characteristics of markers used to measure GFR?
- Freely filtered at the glomerulus
- Not circulate bound to plasma proteins
- No undergo renal tubular absorption or secretion
- Not be nephrotoxic or alter GFR
Although exact values vary with method, what is typically considered a normal GFR for dogs? Cats?
- Dogs: 3.5-4.5 mL/min/kg
- Cats: 2.5-3.5 mL/min/kg
**May not be appropriate for dogs <10kg or >50kg
Is GFR higher or lower in puppies/kittens?
Higher
How is renal or urinary clearance used to evaluate GFR?
An amount of substance (endogenous or exogenous) is assayed in both the plasma and urine over a time period (usually 12-24 hours). Requires a urinary catheter to completely empty the bladder
What is the formula for urinary clearance?
Clearance (mL/min) = (Uv x Uc)/Pc
Uv = urine flow rate (mL/min)
Uc = urine concentration of the solute
Pc = plasma concentration of the solute
What is the gold standard method for determining GFR?
Urinary clearance of inulin
How is plasma clearance used to estimate GFR?
Timed plasma samples are collected to measure markers of plasma clearance - exogenous creatinine, iohexol, radiolabeled markers
Why is plasma clearance of inulin not used when urinary clearance is used?
40% of inulin is excreted via non-renal routes, so using plasma alone without urine is not appropriate
What equation is used to calculate plasma clearance?
Clearance = D/AUS
D = dose of the substance administered
AUC = area under the plasma concentration vs time curve
What surrogate marker of GFR is reabsorbed in the renal tubules and is resorbed more with slower tubular flow rates (such as in hypovolemic or dehydrated patients)?
BUN
What is the ideal timing for measurement of BUN/creatinine in dogs and cats?
8-12 hours of fasting - avoids the effects of dietary protein ingestion
What is the difference in creatinine between puppies and adult dogs? In kittens and cats?
- Dogs: creatinine gradually increases over the first year of life, then remains stable or mildly increases until 8-10 years
- Cats: kittens have relatively high creatinine at birth, but it is similar to an adult or slightly lower by 8 weeks of age
What dog breed and what cat breed have higher creatinine concentrations?
Greyhounds
Birmans
Describe the relationship between creatinine and GFR? Does this make creatinine a sensitive or insensitive marker of renal function?
Exponential relationship, so creatinine is an insensitive indicator of renal function (change in GFR results in only a small change in creatinine)
What is cystatin C?
Low molecular weight proteinase inhibitor that is produced at a constant rate and freely filtered through the glomerulus
How are proteins reabsorbed in the proximal tubule?
Through megalin and cubulin mediated endocytosis
What is lower limit of protein detection on colorimetric dipsticks?
30mg/dL
What is the sensitivity and specificity of urine protein dipsticks?
Sensitivity ~80% but specificity is very poor, especially in cats
What may cause false negative results on a urine protein dipstick?
- Bence Jones proteinuria
- Dilute urine
- Acidic urine
What may cause false positive results on a urine protein dipstick, especially in cats?
- Alkaline urine
- Highly concentrated urine
- Pyuria/hematuria
What is microalbuminuria?
Concentration of albumin in the urine that is >1 mg/dL but lower than 30mg/dL
How can microalbuminuria be detected?
Species specific ELISA or point of care semi-quantitative tests
What patients should be screened for microalbuminuria?
- When a low level of proteinuria may be indicative of the onset of hereditary disease
- When there is concern for a false negative UPC
- Monitoring of known microalbuminuria
A UPC >0.4 in the cat and >0.5 in the dog corresponds to what albumin concentration in the urine?
> 30mg/dL
A UPC greater than what number is strongly suggestive of glomerular disease?
> 2.0
A spot UPC correlates well with urine protein quantification over what period of time?
24 hours
What degree of hematuria must be present to influence UPC?
Gross hematuria = >250 RBC/hpf
When should a renal biopsy be considered?
- Persistent, substantial proteinuria: UPC >3.5
- Proteinuria that is unresponsive to anti-proteinuric treatment
- Progressive increase in proteinuria or decline in renal function despite therapy
- Patients with AKI undergoing dialysis to see if a regenerative response is occurring and its worth continuing
When performing a renal biopsy, how many samples should be obtained?
At least two 10mm long cores of cortical tissue
Satisfactory renal biopsies were obtained in what percent of dogs and cats undergoing this procedure?
87%
For performance of transmission electron microscopy, samples should be placed in what medium?
Glutaraldehyde
Transmission electron microscopy is needed to diagnose what percent of immune mediated glomerulonephritis cases, which would have been missed on histopathology?
27%
What percent of dogs and cats experience complications due to renal biopsy? How often does hemorrhage occur?
Complication rate: dogs 13%, cats 19%
Hemorrhage: dogs 10%, cats 17%
What are factors associated with increased risk of renal biopsy?
Small size (<5 kg), severe azotemia (creat >5), hemostasis disorders
How does ADH cause water absorption in the late distal tubule and collecting duct?
Insertion of aquaporin 2 water channels
What controls the release of ADH?
Plasma osmolarity and blood volume
ADH driven water absorption is dependent on what medullary system?
The counter current multiplier system
What transporters absorb glucose in the proximal tubule
SGLT2»_space; SGLT1
What is the renal threshold for glucose absorption in the dog? In the cat?
Dogs: >180 mg/dL
Cats: >300mg/dL
What drugs can cause a false positive on a urine glucose dipstick?
If using a glucose oxidase reaction: ciprofloxacin
If using a copper sulfate reagent: penicillin and cephalosporin
What urine crystals may be seen with ethylene glycol toxicosis?
Calcium monohydrate crystals
Where are casts formed in the kidney?
Ascending loop of Henle and collecting duct (where flow rates are the slowest)
What type of cast is this and what is it composed of?
Hyaline cast
Proteinaceous material
What patients commonly have hyaline casts?
- May be found in patients after extreme exercise or fever
- Most common in patients with proteinuria
What type of cast is this and what is it composed of?
Epithelial casts
Formed when epithelial cells become trapped within mucoprotein (hyaline casts)
When do epithelial casts form?
After direct tubular cell damage (ex. gentamicin toxicosis)
What type of cast is this and what is it composed of?
Fine granular cast
Formed from partial degradation of the cellular components of a cast
What are granular casts indicative of?
Indicative of ischemic or nephrotoxic renal tubular insult
What type of cast is this and what is it composed of?
Waxy cast
Formed when there is complete degradation of cellular components in the cast
When are waxy casts formed?
Protracted periods of tubular stasis
What are erythrocyte casts indicative of?
Marked renal hemorrhage (idiopathic renal hematuria, post-renal biopsy)
What is an IRIS grade I AKI?
Creatine <1.6 (nonazotemic) but documented evidence of an AKI on bloodwork/imaging, increase in creatinine >0.3 within 48 hours or oliguria/anuria
What is an IRIS grade II AKI?
Creat 1.7-2.5 (mild AKI)
What is an IRIS grade III AKI?
Creat 2.6-5
What is an IRIS grade IV AKI?
Creat 5.1-10
What is an IRIS grade V AKI?
Creat >10
What is volume responsive or hemodynamic azotemia?
- Azotemia caused by any process that decreases renal blood flow (dehydration, hypovolemia, etc).
- Characterized by increased BUN/creatinine with an increased USG
- Rapidly reversible with correction of underlying condition (fluids, BP management, etc)
What regions of the renal tubule are more pre-disposed to toxic and ischemic damage? Why?
Proximal tubule and loop of Henle
- Receive 90% of renal blood flow
- Metabolically the most active
How does hypoxia result in cell death?
Leads to a decrease in ATP which impairs the Na+/K+ ATPase pump => cellular swelling and death
How can the fractional excretion of sodium be used to differentiate pre-renal from renal azotemia?
With hemodynamic/volume responsive azotemia, kidneys conserve sodium well
With intrinsic renal damage, sodium excretion will be higher
How do aminoglycosides lead to AKI?
Ionize to cationic complexes, which bind to anionic sites on epithelial cells. They are then internalized by pinocytosis, leading to 10x the concentration in renal cortical cells compared to the plasma => tubular damage
What factors increase the risk of aminoglycoside toxicosis?
Prolonged use (>5 days)
Preexisting renal disease
Dehydration
Metabolic acidosis
Hypokalemia, hypocalcemia, hypomagnesemia
Diuretics
How should aminoglycoside use be monitored?
Daily urinalysis looking for proteins or casts - occur prior to azotemia with early AKI
Giving expired tetracyclines can cause what?
Fanconi like syndrome due to accumulation of metabolites that interfere with proximal tubule oxidative enzymes
What is the function of prostaglandins in the kidney?
Cause afferent arteriolar vasodilation to maintain renal blood flow in situations where it may be decreased
Which COX isoform is expressed in the kidneys?
Both COX1 and COX2 - COX2 selective inhibitors are not safer and can still cause AKI
A sick animal may lose what percent of body weight per day due to anorexia?
0.5% to 1% - weight change in excess of this is due to fluid status
GFR must be less than what percent of normal for BUN/Creatinine to become elevated?
<75% of normal
What is normal urine production in a healthy animal?
1-2mL/kg/hour
What is the “shock dose” of fluids? How is it given?
Dogs: 60-90 mL/kg
Cats: 45-60 mL/kg
Give 25% over 5-15 minutes, monitor response
How much fluid is lost in “insensible losses” per day (respiration, etc)?
22mL/kg/day
Why are high chloride fluids (0.9% NaCl) associated with a higher risk of AKI?
Higher amount of chloride in the distal tubule causes the macula densa to induce renal afferent arteriolar constriction
Administration of diuretics does not improve renal function or the outcome of AKI. However, when can it be useful?
The ability to respond to diuretics may be a marker of less severe renal injury and a better prognosis - if dialysis is not available, may be the only way to treat fluid overload but it’s not great
What is the mechanism of action of mannitol?
Osmotic diuretic that causes extracellular volume expansion
- Also inhibits renin, leading to inhibition of renal Na+ reabsorption
- Increases tubule flow, which may help remove casts/debris causing obstruction
What is the mechanism of action of furosemide?
Inhibit the Na+2/Cl/K pump in the luminal cell membrane of the loops of Henle
Name 5 indications for renal replacement therapy
- Inadequate urine production
- Life threatening fluid overload
- Hyperkalemia or other life threatening electrolyte disturbances
- Progressive azotemia
- Acute toxicosis with a substance that can be removed via dialysis
If you suspect a patient may be oliguric/anuric, what are 3 things to trouble shoot before considering dialysis?
- Is the urinary system patent? Rule out obstruction or rupture
- Is the patient volume underloaded, so the kidneys aren’t producing a lot of urine? Give fluids (3-5% over 2-6 hours if appear hydrated already)
- Is the blood pressure adequate to perfuse the kidneys? >80mmHg systolic needed
What is dialysis disequilibrium?
Rapid decline in blood osmolality cause by rapid removal of osmoles (urea, etc) by dialysis. Leads to CNS signs (seizures, mentation changes)
What ECG changes can be seen with hyperkalemia?
Bradycardia, tall spiked T waves, shorted QT interval, wide QRS complex, small or absent P waves
What percent of dogs with AKI are hypertensive during hospitalization?
80%
Severe (>180) in 56%
What should the goal of antihypertensive therapy be in hospital?
<180 mmHg
What is the mortality rate for AKI?
Roughly 50%, depends on the cause and study
What factors increase the risk for mortality due to an AKI, according to a PLOS One meta analysis?
- Dialyzed animals
- Infectious etiology (19% mortality vs 59% for non-infectious causes)
In a group of 100 dogs with acute on chronic kidney disease, what were the most common etiologies?
Unknown - 45%
Inflammatory - 30%
Pyelonephritis - 15%
Ischemia - 7%
In a group of 100 dogs with acute on chronic kidney disease, what was the median hospitalization time and mortality rate?
5 days
35% mortality
In a group of 100 dogs with acute on chronic kidney disease, that factors were associated with outcome?
Respiratory rate
Creatinine kinase
Serum creatinine concentration on presentation (IRIS AKI grade)
In a group of 100 dogs with acute on chronic kidney disease, what was the MST of the survivors? Was it associated with etiology of the AKI?
105 days
Not associated with etiology
AKI occurs in what percent of dogs with sepsis?
12%
What are the histopathologic findings of sepsis induced AKI?
Mild to moderate tubular changes with little evidence of necrosis, despite marked reductions in kidney function. Makes it different from nephrotoxins or ischemia induced AKI, which cause extensive necrosis
What factors are thought to contribute to sepsis induced AKI?
Inflammation at the septic site leads to the release of DAMPs and ROS that then induce inflammation in distant organs
What is the tubuloglomerular feedback mechanism?
Tubular dysfunction results in a lack of NaCl reabsorption in the proximal tubule. This is detected in the macula densa in the distal tubule, leading to widespread vasoconstriction of the afferent arteriole and a drop in GFR => AKI
In a retrospective study of 86 dogs, what percent developed AKI within one week after receiving IV contrast?
7.6%
In a group of 100 cats with acute on chronic kidney disease, what were the suspected etiologies?
Unknown - 66%
Ureteral obstruction - 11%
Ischemia - 9%
Pyelonephritis - 8%
In a group of 100 cats with acute on chronic kidney disease, what was the survival to discharge rate? What variable was associated with mortality?
58% survived to discharge
Higher serum phosphorus associated with mortality
In a group of 100 cats with acute on chronic kidney disease, what was the MST of the survivors? What factor was associated with long term survival
MST = 66 days
Serum creatinine at presentation and at discharge associated with survival
In a retrospective study of 56 dogs, what percent developed AKI due to pit viper envenomation? What was associated with AKI?
29%
Dogs with AKI had higher shock index on presentation (tachycardic, hypotensive) and were more likely to need transfusions
What is fenoldopam and why might it help with AKI?
Dopamine 1 receptor agonist
Causes vasodilation in the peripheral arteries, increased GFR, and diuresis in the kidneys in healthy animals
Does fenoldopam actually improve outcomes in AKI?
No - safe, but did not improve anything in dogs presenting with AKI (JVECC study) or dogs with heatstroke (JVIM study)
In dogs that survive AKI, GFR gradually improved throughout hospitalization. What other change occurs that can be used as a marker of renal recovery?
Decreased fractional clearance of sodium occurs over time as dogs recover
What is the fractional excretion of electrolytes in dogs with intrinsic AKI vs volume responsive AKI?
Intrinsic AKI = higher FE of electrolytes, such as sodium (2.4% vs 0.24%)
What primary hemostatic abnormalities were observed in 10 dogs with AKI (grade III or worse) vs healthy controls?
- Decreased collagen-activated platelet aggregometry
- Type II von Willebrand disease-like phenotype - high vWF:Ag to vWF:CBA
What percent of dogs with AKI had evidence of hypertensive retinopathy?
16%
What percent of uremic dogs and cats are hypothermic?
38% of cats, 20% of dogs
Improved with dialysis
How is the pharmacokinetics of ampicillin different in azotemia dogs?
Peak concentration, half life, and AUC were all greater in azotemic dogs
Clearance was prolonged
Could potentially reduce to once daily
What was the most common pathogen isolated from dogs with histologic evidence of pyelonephritis?
E coli (37%)
What percent of dogs with renal lymphoma are azotemic? What percent display erythrocytosis?
Azotemia: 86%
Erythrocytosis: 51%
What is the prognosis with renal lymphoma?
- Only 47% respond to chemo
- MST overall 12 days
- For dogs responding to chemo, MST 47 days
What is the sensitivity and specificity for the diagnosis of renal neoplasia via FNA?
100% in a study of 12 cats
What ultrasonographic changes are more likely to yield positive cytology results on an FNA?
Subcapsular renal infiltrate, diffuse renal enlargement without pelvic dilation, infiltrative or nodular change
Is performing bacterial culture of urine obtained from pyelocentesis advantageous over a general urine culture?
No - same results
What is the diagnostic rate of a pyelogram for identifying ureteral obstruction?
94%
What ultrasonographic findings are noted in the kidneys of CKD cats and how to they correlate to IRIS staging?
Cortical thickness is decreased - negatively correlates with creatinine
Could potentially be used to monitor disease progression
In a retrospective study, what was the sensitivity/specificity of renal FNA in dogs?
Neoplastic lesions: 78% and 50%
Non-neoplastic lesions: 50% and 77%
Lymphoma: 100% sensitivity
