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.
Post-renal AKI
Ureteric obstruction
— stone disease, tumor, fibrosis, ligation during pelvic surgery
Bladder neck obstruction
— benign prostatic hypertrophy [BPH], cancer of the prostate
[CA prostate or prostatic CA], neurogenic bladder, tricyclic antidepressants, ganglion blockers, bladder tumor, stone
disease, hemorrhage/clot
Urethral obstruction
— strictures, tumor, phimosis
Intra-abdominal hypertension Renal vein thrombosis
Diseases causing urinary obstruction from the level of the renal tubules to the urethra include:
— Tubular obstruction from crystals (eg, uric acid, calcium oxalate,
acyclovir, sulfonamide, methotrexate, myeloma light chains)
— Ureteral obstruction - Retroperitoneal tumor, retroperitoneal
fibrosis (methysergide, propranolol, hydralazine), urolithiasis, or
papillary necrosis
— Urethral obstruction - Benign prostatic hypertrophy; prostate,
cervical, bladder, colorectal carcinoma; bladder hematoma; bladder stone; obstructed Foley catheter; neurogenic bladder; or stricture
ARF Tx
Monitoring: — Therapeutic drug monitoring — Blood pressure — Central venous pressure — Urinalysis — Electrolytes — Creatinine — Etc
ARF prognosis
- Depends on underlying event. Length of time
present - Severe ischemic failure, AIN carry worst prognosis
- ATN prognosis good if basement membrane
intact - Patients recover but may not be able to fully
concentrate urine
Chronic Renal Failure
Infrequently recognized in horses
Primarily a problem in older patients
Many older patients have renal lesions: large renal reserve prevents clinical signs
— Requires 2/3 to % of functional parenchyma be lost
Underlying causes can be congenital or acquired
CRF PE, CS, complaints
Gradual weight loss Poor performance Pendent edema PU/PD Excessive dental tartar Oral ulcerations Stunted growth Abdominal pain
Causes of CRF
Two broad classes of causation:
— Primary glomerular disease
• Glomerulnephropathy, glomerulopathy, renal glomerular hypoplasia, amyloidosis
— Tubulointerstitial disease
• Incomplete recovery from ARF, pyelonephritis, nephrolitiasis,
hydronephrosis, renal dysplasia, papillary necrosis (rare)
Chronic interstitial nephritis in most common cause
— Chronic interstitial nephritis in most common cause: ATN Drug induced Obstruction NSAID toxicity Pigmenturia Ischemic causes Nephrolitiasis
Diagnostics of CRF
As for ARF but include: - BUN:Cr usually > 10 with CRF — Red cell parameters: CRF patients frequently anemic — Albumin: < 2.5 gm/dl — More electrolyte abnormalities — Blood gas parameter: acidosis common — Hypercholesterolemia/ hyperlipidemia — Rectal exam and US to evaluate renal size
CRF Tx
Treat any acute component as ARF Supportive care, IV fluid support Adequate feed, decrease protein Unlimited water access Oral Naa Or NaHC03 Avoid NSAlDs and steroids Remove calculi if present Pyelonephritis: antimicrobial therapy All efforts are palliative
Prognosis for CRF
GRAVE
Causes of Hematuria
Pyelonephritis Cystitis Idiopathic renal Urolithiasis Sabulous bladder Urethral rent Blister beetle toxicosis Trauma
UTI PE, CS
Lower Urinary Tract - Altered urine flow - Urine scalding - Dysuria - pollakuria - Gross hematuria - Calculi at end of urination Upper urinary tract - Fever - Weight loss - Signs of systemic illness - Other like LUTI
Diagnostics of UTI
Urinalysis — > 20 organisms/hpf, > 10 WBC/hpf in mid-stream catch or catheterized sample Ultrasound Chemistry screen Hematology with fibrinogen Urine culture
Pathogenesis of UTI
Neurologic disorders
— EPM, EHV-I, cauda equine neuritis, botulism
Urolithiasis
Foaling trauma
Poor perineal conformation
Common organisms:
— E. coli, Proteus spp, Klebsiella spp, Pseudomonas spp.
UTI Tx
• Treat any associated ARF/CRF
• Antimicrobial therapy based on urine culture and sensitivity
— TMS, penicillin, ceftiofur sodium
Parasites of UTIs
Uncommon Strongylus vulgaris Halicephalobus gingivalis (deletrix) Dioctophyma renale Klossiella equi
Urethral Rents
Urethral rents that occur on the convex surface of the urethra at the level of the ischial arch cause hematuria in geldings and hemospermia in stallions.
Urethral rents communicate with the corpus spongiosum penis (CSP).
Hemorrhage through the rent into the urethral lumen occurs
when pressure within the CSP increases at the end of urination
or during ejaculation.
The 5-10-mm rent is identified endoscopically on the convex surface of the urethra, near the level of the ischial arch.
Urethral rents often heal without treatment.
Urolithiasis
Urinary calculi or stones may form in any part of the equine
urinary tract, but the most common site is the bladder (cystic).
Calculi are formed by material dissolved in the urine (solutes) being precipitated upon a collection of bladder or other cells, such as tubular epithelial, renal papillary or red
or white blood cells.
Usually only one calculus occurs at a time, often composed
of calcium carbonate.
Urolithiasis
The factors favoring this precipitation are not well understood but include urine pH; alkalinity increases the formation of carbonate calculi; and the concentration of
urine solutes.
— This can be affected by diet, water intake and loss.
— If the diet or water has a high mineral content, urine solute
content increase.
— A high-concentrate, low-roughage ratio may allow the
deposited solute to cement together more easily
Urolithiasis
All breeds and both sexes are equally likely to develop
calculi, athough in mares they become very large before
symptoms appear.
— These are similar to those seen in cases of cystitis, which
often is present at the same time.
— Affected individuals urinate more frequently, with straining
and dribbling of urine.
— Less commonly there may be mild recurrent colic, loss of
condition and stilted gait.
Occasionally a calculus passes into the male urethra,
causing acute obstruction of urine flow.
Urolithiasis Dx
Diagnosis of cystic calculi involves: — Urine analysis (the changes are similar to those of cystitis) — Rectal examination — Passage of urinary catheter — Ultrasound of the bladder — Urinary tract endoscopy
Urolithiasis Tx
Surgical removal of the calculus is the only effective
method of treatment.
The approach and type of surgery is determined by
the size of the stone and the sex of the patient.
Some cases may also require treatment for
concurrent cystitis.
— Pyridium!
Urinary acidification may be attempted but is often unrewarding.
What is sabulous bladder?
Inflammation of the bladder with an accumulation of calcium carbonate sludge at the bottom
Incontinence
Incontinent horses due to neurologic dysfunction
dribble urine because effective detrusor contraction is
absent and bladder contents are not subject to muscle
contraction and forced ejection from the body, as occurs in a normal state. The neurologic circuitry that mediates the micturition reflex is complex, and examples of disease processes that can interfere with various segments of the reflex loop include herpes
myelitis, polyneuritis equi (cauda equine syndrome), and equine protozoal myeloencephalitis.
Cystitis sediment
Bladders that become paralyzed because of these pathologic processes often show deposition of a
sandy, crystalloid sediment, a condition called sabulous cystitis, instead of formed uroliths. Bladder paralysis permits settling of deposits onto the bladder floor, where the material’s weight prevents it from
being extruded during dribbling of urine from the incontinent bladder. The sediment contributes to
inflammation and irritation of the mucosal lining,
exacerbating cystitis and most likely, the discomfort of the horse
Treatment of cystitis sediment
Treatment of the condition involves lavage of the bladder
lumen with isotonic solutions to remove the sediment load,
administration of systemic antibiotics chosen with regard
for culture results and sensitivity testing of a catheterized
urine sample, anti-inflammatories, and urine acidification.
Lavage can be achieved through a catheter. Placement of an indwelling catheter for a brief initial period helps lower urine stasis and maintains the bladder in a fairly
decompressed state, abating further detrusor damage.
Adding acetic acid to decrease luminal pH during lavage is
advocated.
Pharmacological intervention in cystitis sediment/ sabulous bladder
The parasympathomimetic drug bethanechol augments contractility of the detrusor smooth muscle.
- Bethanechol (20-40 mg or 0.07 mg/kg SQ q 8 hours, 80 mg PO q 8
hours do not give I.V. or I.M.) is not currently available as a
proprietary formulation but can be obtained from compounding
pharmacies.
- Phenoxybenzamine, (0.2-0.7 mg/kg PO, q 6-8 hrs) is an
adrenergic antagonist, and may be given to help relax the
distal urethral sphincter in cases where the condition is determinedly due to upper motor neuron damage.
Phenazopyridine
(4 mg/kg PO q 8-12 hours), an azo dye compound that acts
to confer relief from irritation or spasm of the urinary tract
mucosa via local anesthetic activity, may also be
administered in the initial management of the cystitis
caused by the sedimentary accumulation.
This compound discolors urine.
— Owners should be warned that it will stain skin and textiles which
inadvertently come into contact with the substance.
• In humans with urinary tract inflammation the agent
alleviates symptoms of dysuria, frequency, burning, and the
sensation of urgency.
Estrogen
Mares in which urinary incontinence is from
hypoestrogenism may enjoy a better prognosis for response to treatment. Successful management of the condition in such mares has been observed in association with administration
of estradiol cypionate or benzoate (5-10 _ g/kg I.M. q 48 hours).
PU/PD
Rare, indicates a failure of normal homeostatic
mechanisms controlling water balance
Can be caused by either increased water intake or increased urine production
Establishing if a horse is really PU/PD can be a challenge
Rule out:
— Diarrhea
— Acute Renal Failure
— Horse on High Salt Diet
Causes of PU/PD
Psychogenic polydipsia Thirst Compulsive salt or glucose consumption Diabetes mellitus Diabetes insipidus Hyperadrenocorticism Sepsis/endotoxemia Iatrogenic Primary renal insufficiency
Diagnostics for PU/PD
History Clinical Examination Clinical Pathology Renal function tests Water deprivation test Modified water deprivation test ADH (vasopressin) stimulation test
Nephrogenic DI
Decreased sensitivity of collecting ducts to vasopressin Rare in horses Hyposthenuria in the face of dehydration Positive response to vasopressin
Psychogenic polydipsia
Psychogenic water
(common) or salt (rare) consumption
Drink 2-3 times that of others horses in same
environment
Respond to water
deprivation by concentrating
urine
Syndrome of Inappropriate ADH Secretion (SIADH)
Most common in neonates
Associated with perinatal asphyxial syndrome
Very concentrated urine
Hyponatremia secondary to increased water
retention, ‘dilutional’
Excessive weight gain
Usually resolves, treatment is appropriate fluid
restriction
Urinary incontinence
Causes: — Neurological diseases — Intramural bladder/urethral disease — Hormonal — Ectopic ureter — Bladder tumor — Adhesions — Urolithiasis — Sorghum toxicity - Etc
Urinary Incontinence Tx
Depends on underlying problem
Upper motor neuron:
— Phenoxybenzamine
— Bethanacol
Lower motor neuron:
— Phenylpropanolamine
Older mares:
— Estradiol
Urinary Incontinence Prognosis
Poor to guarded
May fully recover from EHV-I, botulism with time
Urinary Tract Tumors
Bladder: — Squamous cell carcinoma, transitional cell carcinoma (RARE) Kidney: — Renal cell carcinoma, lymphosarcoma
