Sunday, July 24, 2011
More Notes from July 2011 St. Louis AVMA Conference-Kidney Disease
These are papers from the July 2011 St. Louis AVMA conference. I’ve edited them to delete some of the vet only jargon and for space considerations. If you see (…) that means that information has been deleted due to these considerations. The ones listed here include HCM, and other heart related papers, treatments, papers on x-rays and echos, thrombosis, kidney disease, idiopathic cystitis, pain management, anesthesia and cardiac disease, supplements and other hazards for pets, and some other basic information I hope is helpful.
AN UPDATE ON THE RECOGNITION, PREVENTION, AND MANAGEMENT
OF ACUTE KIDNEY DISEASE IN DOGS AND CATS
Richard E. Goldstein DVM, Dip. ACVIM, Dip. ECVIM-CA
Cornell University, College of Veterinary Medicine
Azotemia refers to a state where there is an increase in non-protein associated
nitrogen in the blood. Both increases in urea and creatinine are commonly
assessed when determining if a patient is azotemic. This is different than uremia
which refers to a clinical syndrome caused by renal failure. Azotemia does not
have to be a primary kidney disorder. It may be pre-renal, caused by
dehydration or decreased perfusion, renal, or post renal caused by a urinary
obstruction or a ruptured renal pelvis, ureter, bladder or urethra.
Acute kidney disease (AKD) is characterized by a rapid onset of renal
insufficiency, reduction in glomerular filtration rate (GFR) and renal plasma flow.
It results in an acute uremic syndrome with potential severe hematological and
systemic effects. In some patients this syndrome is accompanied by insufficient
quantities of urination (oliguria or anuria), although this is not pathognomonic,
and likely true for less than half of the patients seen. The excretory failure is
identified by rapid (hours to days) increases in BUN, serum creatinine and
phosphate, and variable hyperkalemia and metabolic acidosis. Urine
concentration capability is impaired. Acute renal failure is a tenuously reversible
state, which must be treated aggressively. Failure to initiate therapy may result
in irreversible parenchymal damage and death.
Stages of AKD:
1. The initial phase lasts from the onset of the ischemic insult until the
development of azotemia and oliguria if it develops. This is the stage where the
kidney is damaged and is characterized by acute cell injury leading to decreasing
urine concentration capability, sloughing of casts and cellular debris and finally
azotemia. If aggressive therapy is implemented in this stage there may be a
complete and rapid return to norma l function.
2. The maintenance phase is characterized by increasing azotemia loss of
concentrating ability and in some cases oliguria, along with increasing
percentages of cell death. Intervention in this phase may result in complete
resolution and return to normal function although the improvement will take
longer than in the previous phase. Without treatment this phase will end in death
if the damage is extensive enough.
3. The recovery phase includes recovery of the vascular blood supply but still
with tubular dysfunction resulting in diuresis and polyuria. Our therapeutic goal
is to convert our patients in the maintenance phase to the recovery stage and
allow time for renal healing. This phase can last many days. The degree of return
of function depends on the severity of the tubular injury sustained in the prior two
…Several mechanisms are thought to be
involved in each case of renal insult. There are 6 major sites of impairment:
Afferent arteriole vasoconstriction disrupts glomerular flow. This frequently
happens as a result of decreased systemic blood pressure, hypovolemia and
Mesangial cell contraction causes a reduction in glomerular filtration surface
area. This is commonly a result of ischemia, humural agents or toxins.
Vasodilation of the efferent arteriole causes decreased glomerular capillary
pressure and GFR. This is most commonly a result of pharmacological blocking
of the production angiotensin II with an ACE inhibitor. Reduced tubular
reabsorption of NaCl causes excessive Na delivery to the distal tubule (macula
densa) and causing tubular glomerular feedback and increased afferent
vasoconstriction. Damage to the tubular epithelial cells disrupts the integrity of
the tubular lining and may result in tubular backleak, reducing excretory capacity
and the effective GFR. Tubular damage can also cause tubular flow obstruction
by sloughing cellular casts and debris, reducing GFR by reducing glomerular
filtration gradient. The intracellular results of ischemia are ATP depletion,
increased intracellular calcium concentrations, increased free radical production
causing cellular dysfunction and if severe cell death.
Recognizing patients at risk for developing acute renal failure is a crucial role of
the clinician. Many cases of acute renal failure are preventable and occur in the
hospital setting or in a patient receiving veterinary care.
These are just some of the potential risk factors for acute renal failure:
Preexisting diseases: renal insufficiency, pancreatitis, hepatic insufficiency,
diabetes mellitus, heart disease, trauma.
Clinical conditions: volume depletion, electrolyte abnormalities (na+, ca2+, k+),
hypoalbuminemia, hyper or hypotension, fever, sepsis, anesthesia, surgery, radio
contrast media, nsaids, nephrotoxic drugs.
Intrinsic renal disease (partial list): infectious
fip, pyelonephritis, sepsis, glomerular disease, sle, vascular (thrombotic),
urinary outflow obstruction, urethral obstruction, ureteral obstruction, toxic – huge
list, ethylene glycol, cisplatin, amphotericin b, pigmenturia, neoplasia, lymphoma,
Clinical Presentation : The clinical presentation of patients with acute renal failure
varies based on the cause, severity, previous therapy and associated diseases
predisposing to the renal injury. Consistent and characteristic signs of ARF
include the sudden onset and rapidly progressive development of listlessness,
depression, anorexia, vomiting and diarrhea…Obtaining a thorough history especially of any possible
exposure to nephrotoxins or medications is crucial for accurate diagnosis and
Physical examination commonly demonstrates dehydration (prior excessive fluid
therapy makes overhydration a common presentation at referral centers),
hypothermia, oral ulceration, “uremic breath”, scleral injection, tachycardia or
bradycardia, tachypnea, abdominal pain, rarely seizures and enlarged and
painful kidneys on abdominal palpation. Melena resulting from GI bleeding is a
common finding on rectal palpation.
Because of the abrupt onset of uremia, patients are often of good body condition,
good hair coats and normally pink or injected mucous membranes when
compared to the general poor condition of chronic renal failure patients on
presentation. When the acute disease comes “on top” of a chronic condition the
presentation becomes quite confusing.
Laboratory evaluation: The initial data base should include a CBC, biochemical
profile (including HCO3- or TCO2 or central venous blood gas), urinalysis (if
urine is obtainable) and urine culture….Chemistry panel: Azotemia is the biochemical hallmark of renal failure.
It is common for the azotemia to be marked in cases of acute renal failure (BUN
above 100mg/dl and creatinine above 6mg/dl…Serum phosphate is regulated primarily via urinary excretion and tubular reabsorption and is heavily dependent on glomerular filtration. In acute renal
changes increases in serum phosphate concentrations are often times marked,
more than with the same degree of azotemia in chronic disease. This is a
valuable tool in our battle to differentiate acute from chronic renal disease.
Additional electrolyte abnormalities include hyperkalemia…This is
a life threatening condition and necessitates rapid therapeutic measures when
present. Hypocalcemia is also a common finding in acute renal failure, it too can
be life threatening, although is usually not...Increases in additional values in the chemistry panel may be increased as well, if they are dependent on GFR. Pancreatic enzymes amylase, lipase and TLI
(trypsin like immunoreactivity) are all typically elevated. Although ARF and
pancreatitis can occur concurrently it is important to remember this fact and not
to suspect that every case of renal insufficiency also has biochemical evidence of
Urinalysis: Obtaining urine for analysis prior to initiation of fluid therapy is
extremely valuable in differentiating acute renal failure from pre-renal azotemia.
If there is no urine at that time it should be obtained as soon as possible after
initiation of therapy…
Imaging: On routine radiographs kidney size can be assessed although masses
and cysts may not be differentiated from renal parenchyma. Ultrasound
evaluation is superior for the evaluation of renal parenchyma and is indicated in
acute renal disease. Kidneys are generally normal to enlarged and may be
hyperechoic in certain disease states (ethylene glycol toxicity for example).
Uroliths and signs of urinary obstruction may be seen in radiographic or
ultrasonographic evaluations. Ultrasound also is necessary for percutaneous
renal aspirates or biopsies in most dogs but is not usually necessary in cats).
Additional studies such as contrast radiography, computer tomography and
nuclear scintigraphy are useful in some cases.
Renal aspirate & biopsy: Indicated in many cases of acute renal disease. The
information obtained from these procedures may be crucial in understanding the
etiology of the renal disease (neoplasia, inflammation, infection) as well as the
duration of the disease and the prognosis…
Consequences of ARF
The clinical presentation of dogs and cats in acute renal failure can be
complicated and require intense monitoring and a complex therapeutic regime.
Problems likely to occur should be anticipated and prevented. This type of
strategy will carry a much higher success rate than treating the problems as they
are identified. Most cases in acute renal failure will present initially in a state of
hypovolemia and dehydration, usually contributed to by anorexia, vomiting and
diarrhea. Rapidly worsening azotemia will be a consistent finding in serial blood
evaluations. Inappropriate and overzealous fluid therapy usually in the face of
oliguria/anuria will produce overhydration and hypervolemia. It is not uncommon
to receive the cases in this state in a secondary or tertiary referral center. At this
time they may have peripheral or pulmonary edema, ascites and or pleural
effusion. This overhydrated state will potentiate systemic hypertension which will
likely be present. In cases with underlying cardiac insufficiency fluid therapy may
cause “full blown” congestive heart failure.
Oliguria or anuria are present in up to 50% of ARF cases seen at veterinary
centers. Before making this clinical assumption one must try and rule out prerenal
causes of oliguria (as long as a normal animal is dehydrated urine output
should be minimal) as well as post renal causes such as obstruction or tear in the
urinary system. (DO NOT act upon oliguria until rehydration has been
When oliguria is present it is devastating and life threatening as it does not allow
for conservative medical management via diuresis and electrolyte therapies. The
solute retention increases the uremia, hyperkalemia results as well as worsening
acidosis and death. Inappropriate attempts at diuresis cause life threatening
overhydration. If oliguria or anuria are present in a hydrated animal despite fluid
therapy in a patient with ARF every attempt must be made to re-establish
adequate urine production. If this is not achieved then there is no chance of
improvement with continued conservative medical therapy.
Additional consequences of ARF
Neurological complications have been associated with, Uremic encephalopathy
-Weakness, lethargy, Seizures, Hypertension, Bleeding disorders, Platelet dysfunction
Vasculitis (Lepto..), DIC, GI disorders, Uremic ulcers, Vomiting, Hypergastrinemia
Electrolyte imbalances, Hyperkalemia, Hyperphosphatemia, Increased Phosphorous X calcium product
Hypocalcemia, Severe metabolic acidosis
Maintaining blood pressure
Use reno-protective agents – mannitol or Lasix and dopamine in animals
predisposed to ARF or doing any surgery on a patient predisposed.
Monitor hydration and urine production during surgery or in any sick animal…
Correct metabolic acidosis
Give a lot of bicarb!
Assess blood pressure and begin to correct severe hypertension.
Hypertension is common with acute and chronic renal disease. Systolic pressure should be
lowered to no more than 160mmHg. Drugs in common use today include
ACE inhibitors (Enalapril, Benazepril)
After Rehydration and mild volume expansion-Document urine production
And then - treat oliguria/anuria. Do not assess urine production prior to