Equine Renal Flashcards
Acute Renal Failure (AKI)
Usually secondary to some other disease process — Aminoglycoside antimicrobial therapy — NSAID toxicity — Acute enterocolitis — Pleuropneumonia - DIC — Purpura hemorrhagica — Etc
3 General categories of AKI
- Prerenal - as an adaptive response to severe volume depletion and
hypotension, with structurally intact nephrons - Intrinsic - in response to cytotoxic, ischemic, or inflammatory insults to the kidney, with structural and functional damage
- Postrenal - from obstruction to the passage of urine
While this classification is useful in establishing a differential diagnosis,
many pathophysiologic features are shared among the different
categories
Presentation of AKI
Patients who develop AKI can be oliguric or nonoliguric, have a rapid or slow rise in
creatinine levels, and may have qualitative differences in urine solute concentrations and cellular content. (Approximately 50-60% of all causes of AKI are
nonoliguric.)
Anuria is defined as a urine output of less than 100 mL/d (human) and, if abrupt in onset, suggests bilateral obstruction or catastrophic injury to both kidneys.
This lack of a uniform clinical presentation reflects the variable nature of the injury
Etiology
The driving force for glomerular filtration is the pressure
gradient from the glomerulus to the Bowman space.
Glomerular pressure is primarily dependent on renal blood flow (RBF) and is controlled by combined resistances of renal afferent and efferent arterioles.
Regardless of the cause of acute kidney injury (AKI), reductions in RBF represent a common pathologic
pathway for decreasing GFR. The etiology of AKI consists of 3 main mechanisms
Etiology
Prerenal failure - Defined by conditions with normal tubular and
glomerular function; GFR is depressed by compromised renal perfusion
Intrinsic renal failure - Includes diseases of the kidney itself,
predominantly affecting the glomerulus or tubule, which are associated
with release of renal afferent vasoconstrictors; ischemic renal injury is the most common cause of intrinsic renal failure.
Postobstructive renal failure - Initially causes an increase in tubular
pressure, decreasing the filtration driving force; this pressure gradient
soon equalizes, and maintenance of a depressed GFR is then dependent
on renal efferent vasoconstriction
Etiology
Depressed RBF eventually leads to ischemia and cell
death. This may happen before frank systemic hypotension is present and is referred to as normotensive ischemic AKI.
The initial ischemic insult triggers a cascade of events that
includes production of oxygen free radicals, cytokines and
enzymes, endothelial activation and leukocyte adhesion,
activation of coagulation, and initiation of apoptosis.
These events continue to cause cell injury even after
restoration of RBF
Etiology
Tubular cellular damage results in disruption of tight
junctions between cells, allowing back leak of glomerular
filtrate and further depressing effective GFR. In addition,
dying cells slough off into the tubules, forming obstructing
casts, which further decrease GFR and lead to oliguria.
During this period of depressed RBF, the kidneys are
particularly vulnerable to further insults. This is when iatrogenic renal injury is most common
Common iatrogenic combinations
— Preexisting renal disease with radiocontrast agents,
aminoglycosides, NSAlDs
— Nonsteroidal anti-inflammatory drugs (NSAlDs)
Hypovolemia with aminoglycosides***, heme pigments, or
radiologic contrast agents
Aminoglycoside Toxicity
Despite extensive study, the exact mechanisms of aminoglycoside nephrotoxicity
remain elusive.
After glomerular filtration, approximately 15% of a filtered load of an
aminoglycoside is reabsorbed into the kidney
The uptake of aminoglycosides into the proximal tubule (a key step in the
pathogenesis of kidney injury) is saturable, although the level of this effect
depends upon the aminoglycoside
After uptake, a number of cellular processes are activated, culminating in apoptosis. This contributes to loss of the renal tubular epithelium and thus
kidney dysfunction but, conversely, shedding and urinary excretion of apoptotic
bodies may excrete aminoglycosides
NSAID Toxicity
Renal effects of NSAlDs are based on their pharmacologic mechanism of
action.
These effects are relatively mild and rare in healthy individuals but can be
serious in patients whose renal function is prostaglandin-dependent
Patients with contracted effective intravascular fluid volume as a result of
congestive heart failure, cirrhosis, diuretic use, or restricted sodium intake, are more likely to experience NSAlD-related changes in renal function
Renal papillary necrosis is the least common but potentially most severe
NSAlD-related renal adverse effect, as it represents permanent renal parenchymal damage. This can be caused acutely by a massive overdose
of an NSAID in a dehydrated individual
Chronic renal papillary necrosis is associated with long-term use of
multiple high doses of a single analgesic or combinations of analgesics
PE, CS, complaints with AKI
Weight loss Dullness Poor performance Depression Odor Anorexia Polyuria Oliguria Pigmenturia Signs consistent with primary disease process Can be SILENT
Urinalysis for AKI
Urinalysis — Normal equine urinalysis: - Specific gravity 1.025-1.050 - Color: yellow to clear, thick, syrupy - pH: alkaline - Protein: negative to 1+ - Blood: negative — Renal tubular casts — Moderate proteinuria — +/- hematuria — Pigmenturia — Increased white blood cells — Increased uGGT, uGGT:Cr — Abnormal fractional excretion of electrolytes — Isosthenuria
Urine osmolality
- Normal 727-1456 mosm/L
— ARF decreases osmolality to
226-495 mosm/L
Serum chemistry analysis
— Azotemia: BUN> 20mg/dl, Cr>2.0
— Hyponatremia, hypochloremia, hyperkalemia
— Fractional excretion of electrolytes
• {(Una/Pna)/ (Ucr/Pcr)} x 100
Cr Cr
• Na usually < 1.0%AKI Diagnostics
US
Rads
Nuclear scintigraphy
Renal biopsy
Pathophysiology of AKI
• Acute tubular necrosis
— Aminoglycoside toxicity
— Pigment nephropathy
• Acute interstitial nephritis
— ? delayed hypersensitivity
• Acute glomerulonephritis
— Ag:Ab complex deposition?
• Post-renal acute renal failure
Tx for AKI
- Focus on reversing or treating the inciting cause
- Prevention is important
- Restore and maintain intravascular fluid volume
- Maintain glomerular filtration and urine
production - Monitor closely
Endothelin and nitric oxide (ET and NO)
Vasoconstrictor and vasodilator
Should be balanced
Restoration of renal blood flow and associated complications
• Recovery from AKI is first dependent upon restoration of RBF.
— Early RBF normalization predicts better prognosis for
recovery of renal function.
• In prerenal failure, restoration of circulating blood volume is
usually sufficient.
• Rapid relief of urinary obstruction in postrenal failure results in a prompt decrease of vasoconstriction.
With intrinsic renal failure, removal of tubular toxins and
initiation of therapy for glomerular diseases decreases renal
afferent vasoconstriction
AKI Tx
• IV fluids @ 40-80 ml/kg/day until Cr decreases dramatically
• Decrease fluid rate to 1-20 ml/kg/day until Cr
normal
• Persistent oliguria: 10-12 hrs after initiating fluid therapy:
— Dopamine CRI: ‘renal dose’ 3ug/kg/min
— Diuretic agents:
• Mannitol: osmotic diuretic ONCE filtered: no longer recommended
• Furosemide: loop diuretic
Furosemide and AKI
Maintenance of volume homeostasis and correction of
biochemical abnormalities remain the primary goals of
treatment. Furosemide can be used to correct volume overload when the patients are still responsive; this often requires high intravenous (IV) doses.
• Furosemide plays no role in converting an oliguric AKI to
a nonoliguric AKI or in increasing urine output when a patient is not hypervolemic
Furosemide in AKI
• However, the response to furosemide can be taken as a good prognostic sign. At this stage, the kidneys remain vulnerable to the toxic effects of various chemicals.
All nephrotoxic agents (eg, radiocontrast agents, antibiotics with nephrotoxic potential, heavy metal
preparations, cancer chemotherapeutic agents, NSAlDs)
are either avoided or used with extreme caution.
• Similarly, all medications cleared by renal excretion should
be avoided or their doses should be adjusted appropriately
GFR recovery
Once RBF is restored, the remaining functional nephrons
increase their filtration and eventually hypertrophy.
GFR recovery is dependent upon the size of this remnant
nephron pool.
— If the number of remaining nephrons is below some critical
value, continued hyperfiltration results in progressive
glomerular sclerosis, eventually leading to increased nephron
loss.
— A vicious cycle ensues; continued nephron loss causes more
hyperfiltration until complete renal failure results.
— This has been termed the hyperfiltration theory of renal
failure and explains the scenario in which progressive renal
failure is frequently observed after apparent recovery from AKI
Intrinsic AKI
Structural injury in the kidney is the hallmark of intrinsic AKI, and
the most common form is ATN, either ischemic or cytotoxic. Frank
necrosis is not prominent in most human cases of AT N and tends to be patchy.
Less obvious injury includes loss of brush borders, flattening of
the epithelium, detachment of cells, formation of intratubular casts, and dilatation of the lumen
Although these changes are observed predominantly in proximal tubules, injury to the distal nephron can also be demonstrated.
In addition, the distal nephron may become obstructed by
desquamated cells and cellular debris.
Acute tubular necrosis (ATN)
A physiologic hallmark of ATN is a failure to maximally dilute
or concentrate urine (isosthenuria). This defect is not responsive to pharmacologic doses of vasopressin.
The injured kidney fails to generate and maintain a high
medullary solute gradient, because the accumulation of
solute in the medulla depends on normal distal nephron
function.
— (Failure to excrete concentrated urine even in the presence of oliguria is a helpful diagnostic clue in distinguishing prerenal from intrinsic renal disease; in prerenal azotemia, urine osmolality is
typically more than 500 mOsm/kg, whereas in intrinsic renal disease, urine osmolality is less than 300 mOsm/kg.)
Post-renal AKI
Mechanical obstruction of the urinary collecting system,
including the renal pelvis, ureters, bladder, or urethra, results in obstructive uropathy or postrenal AKI.
If the site of obstruction is unilateral, then a rise in the serum creatinine level may not be apparent due to
contralateral renal function. Although the serum creatinine level may remain low with unilateral obstruction, a significant loss of GFR occurs, and
patients with partial obstruction may develop progressive loss of GFR if the obstruction is not relieved. Causes of obstruction include stone disease; stricture; and intraluminal, extraluminal, or intramural tumors.
