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.



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,

adenocarcinoma, hypercalcemia.

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

Fluid balance

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

Managing hypovolemia

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


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