Chronic Renal Disease and Failure (CRD, CRF, CKD)
Chronic renal failure is defined as primary kidney disease that has
persisted for months to years and is characterized by a progressive
destruction of nephrons. It is hypothesized that regardless of the inciting
cause, after a critical level of renal dysfunction has been reached, that
renal damage will be self perpetuating.
There are several similar terms used to describe this state including
chronic renal disease, chronic renal failure, chronic kidney disease,
chronic renal insufficiency and others.
In the normal animal, not all nephrons are
being fully perfused at any one time. The "resting, non-working nephrons"
are the renal reserve and are called upon when the kidneys must perform
"extra work" or are "called into the work force" as nephrons are lost to
disease.
As CRD progresses, more and more nephrons are lost to disease and the
renal reserve diminishes until all remaining nephrons are working, all of
the time. The remaining nephrons hypertrophy and
increase their workload in attempt to maintain homeostasis for the animal
and the patient is asymptomatic. The workload per individual nephron is
called the "single nephron GFR" (SNGFR). The SNGFR in disease is greater
than in health but collectively the overall GFR of all the nephrons of both
kidneys is reduced simply because fewer nephrons exist. The increase in
SNGFR is also called hyperfiltration.
The adaptive mechanism of increased workload per nephron (hyperfiltration)
is initially beneficial and initially prevents development of clinical signs
but with time, the adaptive mechanisms may contribute to clinical signs and
to progression of renal damage.
As renal disease progresses, the remaining nephrons show a narrower range
of response to changes in the environment. The nephrons attempt to respond
appropriately to changes in the environment but cannot abruptly respond as
they were able to do in a state of health. For example, if the animal has a
sudden increase in the intake of sodium in the diet, the nephrons will
attempt to eliminate more sodium in the urine in order to keep body levels
of sodium constant. The nephrons may not be able to respond completely to
the change in sodium intake and sodium retension may occur. Conversely if
the sodium intake in the diet is gradually increased, over days to weeks,
then the remaining nephrons have time to adapt and will excrete excess
sodium to maintain constant blood levels.
Eventually the increased workload on surviving nephrons reaches a point
where they can no longer maintain homeostasis and the signs of renal failure
become apparent. When total nephron mass is reduced to 1/3 of normal, there
is an impaired ability to concentrate and dilute urine. When total nephron
mass is reduced to 1/4 of normal azotemia develops.
The
causes of CRF
are diverse but often by the time a diagnosis of CRF is made, the inciting
cause is no longer evident. Some potential causes of CRF include:
- congenital malformation of the kidneys
- chronic pyelonephritis
- systemic hypertension
- nephrolithiasis +/-
See reference
- renal ischemia due to vascular disease such as the vasculitis of
systemic lupus erythematosis
- immunologic injury such as that caused by immune complex disease
- progression of ARF
Often the renal biopsy of patients with CRF discloses nonspecific changes
that are called end stage renal disease (ESRD) which is advanced,
generalized, progressive irreversible renal disease with no inciting cause
evident or chronic interstitial nephritis (CIN) which likewise indicates
irreversibility and unknown cause.
An attempt has been made by the International Renal Interest Society to
stage dogs and cats with chronic kidney disease.
Staging of chronic kidney disease (CKD) is undertaken to facilitate
appropriate treatment and monitoring of the patient. Staging is based on
fasting plasma creatinine, assessed on at least two occasions in the stable
patient. The patient is then sub-staged based on
proteinuria and systemic blood pressure. See the
IRIS site for full details on staging. The table below is from the IRIS
web site.
| Stage |
|
Serum Creatinine |
| |
Dogs |
Cats |
| 1 |
non-azotemic. Some other
renal abnormality present e.g. inadequate concentrating ability
without identifiable non-renal cause; abnormal renal palpation
and/or abnormal renal imaging findings; proteinuria of renal origin;
abnormal renal biopsy results |
<1.4
mg/dl |
<1.6 mg/dl |
| 2 |
mild renal azotemia,
Clinical signs usually mild or absent
|
1.4
- 2 mg/dl |
1.6 - 2.8
mg/dl |
| 3 |
moderate renal azotemia,
Many systemic clinical signs may be present
|
2.1
- 5 mg/dl |
2.9 - 5
mg/dl |
| 4 |
severe renal azotemia,
Many extra-renal clinical signs present
|
>5 mg/dl |
>5 mg/dl |
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Because the kidneys perform so many diverse
functions the clinical signs of uremia are polysystemic.
- The kidneys excrete toxins (urea, creatinine and other nitrogen
containing wastes) from the body via glomerular filtration and tubular
secretion.
- The kidneys regulate body fluids, minerals and electrolytes via
glomerular filtration, tubular secretion and tubular reabsorption.
- The kidneys synthesize hormones and chemicals (erythropoietin,
active vitamin D) which have local and systemic effects.
Acid-base balance in CRF:
The diet yields acids that are normally renally eliminated in order to
maintain acid-base balance. Additionally the kidney must reabsorb
bicarbonate that is filtered by the glomeruli. Both the mechanisms for
excreting acid and preserving bicarbonate may be impaired resulting in
systemic acidosis. One method the kidneys use to eliminate acid is to use
ammonia (NH3) to trap hydrogen ions
as ammonium ions (NH4+). When
nephrons fail, the remaining nephrons increase production of NH3.
Increased concentrations of both NH3
and NH4+ stimulate
inflammation of renal tissues by cytokines. To some extent acidosis is
buffered by mobilization of minerals from the bone which contributes to
development of renal osteodystrophy. Chronic acidosis also disrupts
potassium homeostasis and may contribute to hypokalemia
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Water balance:
CRF patients often have a negative water balance (another way of saying
they are often dehydrated). The polyuria and gastrointestinal losses from
vomiting and diarrhea must be matched by increased water intake (polydipsia)
in order to remain normally hydrated. As CRF progresses, the patients become
systemically depressed and may drink less or may attempt to drink but
drinking water may incite vomiting.
The following discussion describes a single nephron but the concept can
be extrapolated to the entire population of nephrons. The blood flow to the
nephron is via the afferent arteriole. The afferent arteriole supplies blood
to the capillary loops that make up the glomerulus. In a state of health ~
1/4 to 1/3 of the plasma which enters the capillary loops in the glomerulus
enter the tubular lumen as glomerular filtrate. The is called the filtration
fraction:
filtration fraction = renal blood flow/ glomerular filtration
The blood which does NOT form glomerular filtrate leaves the glomerulus
in the efferent arteriole which continues into the medulla of the kidney as
the vasa recta capillaries which run parallel to the tubular portions of the
nephrons. In health, solute (primarily urea and sodium) are deposited in the
interstitium of the kidney (the black dots in the schematic). These solutes
make the interstitium hypertonic so that there is a "stimulus" for water to
leave the tubular lumen and enter the interstitium. In health the water will
enter the vasa recta capillaries as they leave the kidney resulting in
return of water to circulation.
As the overall GFR decreases, a greater amount of blood leaves the
glomerulus in the efferent arteriole resulting in increased blood flow in
the vasa recta capillaries. As blood flow increases, solute (urea and
sodium) are "washed" out of the interstitium so that it is no longer
hypertonic and there is less "stimulus" for water to leave the tubule and
enter the interstitium for subsequent reabsorption. This is called medullary
washout.
Additionally the increased amount of solute handled by a smaller number
of nephrons osmotically results in more fluid loss.
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Secondary hyperparathyroidism and renal osteodystrophy
Bone lesions occur as a consequence of long term elevation of parathyroid
hormone and as a consequence of bone buffering of metabolic acidosis.
Parathyroid hormone (PTH) is secreted by chief cells of the parathyroid
gland.
The effect of PTH on bone is to mobilize both calcium and phosphorus. The
full effect of PTH's action on bone requires the presence of vitamin D.
The effect of PTH on the gi tract is to increase the uptake of both
calcium and phosphorus. The full effect of PTH's action on the gi tract
requires the presence of vitamin D.
The effect of PTH on the kidney is more "discriminating". PTH increases
tubular Ca reabsorption (decreased excretion) and decreases tubular
phosphorus reabsorption (increased excretion).
PTH also stimulates the activation of vitamin D by the kidney to the
active form, (1,25 dihydroxycholecalciferol).
Secondary hyperparathyroidism (increased levels of PTH) is the price paid
(the trade-off) for maintenance of phosphorus and subsequently calcium
levels.
Progressive nephron destruction results in a decrease in total GFR which
results in a transient increase in serum phosphorus. Increased phosphorus
causes reduction in serum ionized calcium by simple mass action (as P
increases Ca decreases). Reduction of ionized calcium is the stimulus for
the chief cells of the parathyroid gland to increase PTH production. PTH
leads to increased kidney reabsorption and intestinal reuptake of Ca, and a
return of serum P and Ca to normal. A new steady state is reached with
higher serum levels of PTH.
As GFR steadily falls with progressive disease, PTH levels continue to
rise. Serum Ca levels are usually normal until terminal states. The response
of the parathyroid glands is appropriate as it is properly responding to the
stimulus of low Ca.
With time, some patients will develop autonomously
functioning parathyroid glands which do not respond to the return of serum
Ca to normal and continue secreting PTH resulting in hypercalcemia. Some
call this
tertiary hyperparathyroidism which is not common in dogs
and cats as they usually don't live as long with renal disease as do people
who can be maintained by dialysis and transplantation.
As functional renal mass declines to 10-15% or normal, active vitamin D
is no longer produced, thus reducing intestinal Ca uptake and mobilization
of Ca from bone resulting in a low serum Ca and further stimulation of PTH
release
Clinical signs that may be attributable to PTH include:
- soft tissue calcification which can manifest as pruritus
- metabolic bone disease (renal osteodystrophy)
- anemia due to marrow fibrosis as a consequence of cortical bone
remodeling encroaching upon the marrow cavity. PTH also increases the
fragility of RBC making them more susceptible to lysis
- neuromuscular disturbances. PTH has been shown to cause disturbances
in the electrical activity in neurons and muscle cells leading to mental
dullness/lethargy and muscle weakness
- decreased reabsorption of amino acids
- anorexia. PTH causes a state of partial insulin resistance. Blood
glucose levels are mildly increased which gives the animal the sensation
of not being hungry.
- PTH impairs both cellular and humeral immunity which predisposes CRF
patients to infections.
- PTH can contribute to the progression of renal dysfunction.
The bony changes of renal osteodystrophy can be subtle or striking. As
bone mineral is reabsorbed under the influence of PTH, fibrous tissue may be
deposited in an attempt to "strengthen" the bone weakened by loss of
mineral. The most marked gross changes in bone structure occur in young
dogs.The bones may become more flexible due to loss
of mineral: "rubber jaw"
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Anemia of CRF is nonregenerative, normocytic
and normochromic. It is caused by deficiency of erythropoietin releasing
factor, erythroblast inhibition, reduced survival of RBC, iron deficiency
(blood loss, impaired absorption), myelofibrosis, chronic infection, or loss
due to coagulation abnormalities.
Coagulation abnormalities
arise from abnormal function of normal numbers of platelets which is called
thrombocytopathia.
Sodium handling
by diseased kidneys: The kidneys still try to maintain sodium balance by
excreting excess or conserving in states of limited intake. Each nephron
must excrete more sodium to maintain balance and there is a narrower range
of response which leads to an inability of the chronically diseased kidney
to adapt to rapid changes in sodium intake (increases or decreases).
Blood pressure: Renal failure
patients are often hypertensive. Hypertension is defined as a systolic
pressure > 180 mmHg (dog) > 200 mmHg (cat) and a diastolic pressure > 95
mmHg (dog) > 145 mmHg (cat).
Blood pressure can be
measured by indirect techniques using oscillometric
or Doppler methods from the cranial tibial/dorsal pedal artery, metacarpal
artery or the coccygeal artery. Indirect readings are comparable to direct
measurements obtained by arterial puncture.
Blood pressure monitoring equipment is not uniformly reliable in dog sand
cats. Several readings should be obtained to confirm consistency of the
measured values.
Blood pressure can be measured using a Doppler blood pressure unit which
measures systolic
pressure only or an oscillometric blood pressure unit with inflatable cuffs.
The cuff size must be appropriate for the size of the patient or the
readings will be inaccurate.
Hypertension may play a role in the self perpetuation of renal failure.
Hypertension can also cause cardiac disease, CNS dysfunction and retinal
detachment leading to blindness.
Factors which contribute to hypertension include:
- failure to excrete salt and fluid
- stiffening of venous capacitance vessels
- altered adrenergic activity
- activation of renin-angiotensin-aldosterone system
- suppression of renodepressor prostaglandins
Other ionic disturbances may be present including an
increase in magnesium which can cause drowsiness and increased neuromuscular
excitability.
Potassium is variable depending on urine output, dietary intake and
gastrointestinal losses but is usually normal or low in polyuric CRF. Cats
may develop a painful myopathy as a result of hypokalemia. Amlodipine may
promote hypokalemia in cats with kidney disease.
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Diagnosis of CRD and CRF
The history is often nonspecific including signs such as polyuria &
polydipsia, nocturia/incontinence, gastrointestinal signs, anorexia, or
depression.
On physical examination, dehydration, weight loss, pale
mucous membranes, oral ulcers, palpably small kidneys, pathologic fractures
or loose teeth may be seen. Oral ulcers are due to the breakdown of urea
present in saliva to ammonia by oral bacteria. Hypertensive animals may
present with acute blindness caused by retinal detachment.
Hematology often discloses nonregenerative, normochromic
normocytic anemia and normal or a stress leukogram. CRF patients may have
impaired phagocytic function of neutrophils which may lead to infection and
leukocytosis. Anemia may be masked by hemoconcentration (dehydration).
Platelets are normal in number but abnormal in function which can lead to
bruising at the venipuncture site or other abnormal bleeding.
Biochemical changes include
- increased BUN
- increased creatinine
- increased phosphorus
- Na+ and Cl- usually normal but total body
concentration may be increased or decreased
- Ca is usually normal until terminal stage (may be low terminally)
unless hypercalcemia caused the renal disease in which case calcium will
be increased
Urinalysis will disclose a specific gravity between
1.007-1.017 (Isosthenuria). Proteinuria is variable and is most often seen
in patients with congenital CRD and those in which glomerular disease is the
cause of CRF. The urine sediment is usually normal. Microalbuminuria will be
presented in the section on proteinuria.
Radiology may show a decrease in kidney size, with
irregular contours. If the animal is in poor body condition, the absence of
abdominal fat may make visualization of the kidneys difficult.
Contrast studies of
the kidneys are NOT indicated. Decreased bone density may be appreciated
on the radiographs.
Renal function
tests are not necessary if the patient is azotemic.
Renal biopsy is often low yield in patients with CRF and is
not necessary to make a diagnosis. Renal biopsy is of value to make a
diagnosis of
congenital renal disease.
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Treatment of CRF
The uremic crisis should be managed similar to the
patient with ARF.
Any prerenal influences should be corrected with fluid therapy. Prerenal
insults may precipitate a uremic crisis in a previously compensated CRF
patient.
Specific therapy of causative disorders may slow or stop the development
of renal lesions including correction of hypercalcemia causing
hypercalcemic
nephropathy, antibiotics to eliminate bacterial infection, antifungals
to eliminate mycotic infections, removal of obstructions (e.g., uroliths or
neoplasms), or correction of abnormal renal perfusion that caused ischemia.
Diuretics are not indicated in the CRF patient unless they are oliguric,
and then only once the patient is rehydrated. Intensive diuresis protocols
using osmotic diuretics may be used if the patient becomes oliguric. See the
ARF section for
more specific information.
Conservative medical management is formulated to reduce
the clinical signs of uremia and to maintain fluid, electrolyte, acid-base,
endocrine, and nutrient balance by providing unlimited access to water,
decreasing the quantity of metabolic wastes to be excreted by the kidneys
and to provide metabolites that the kidneys cannot effectively conserve or
produce. This regime is conservative with respect to the cost and effort
required compared to more aggressive forms of therapy such as aggressive
fluid therapy or dialysis. Conservative
medical management is indicated when the clinical signs of renal dysfunction
are not severe enough to warrant more intensive forms of therapy and after
successful treatment of the uremic crisis by more intensive measures. The
initial response to conservative therapy may be relatively slow, taking
weeks to months to see a response.
Conservative medical management of CRF includes:
- unlimited access to water
- avoidance of stress and increased renal work ( changes in the
environment, nephrotoxic antibiotics, corticosteroids)
- avoidance or correction of circumstances which cause dehydration and
prerenal azotemia (e.g. unnecessary surgical episodes, vomiting,
diarrhea)
- modification of dietary protein intake
- phosphorus restriction
- control of blood pressure
- water soluble vitamins
- normalization of acid base status
- correction of anemia
Several of the above treatments/managements are integrated into
commercial diets marketed for patients with renal failure. Diets
recommended for dogs and cats with renal failure, compared to maintenance
diets, typically have reduced protein, phosphorus, and sodium; and increased
B-vitamins and calories. The diets are designed to maintain a neutral pH.
Feline renal failure diets are often supplemented with potassium and dog
renal failure diets may have increased omega-3 fatty acids (PUFA). Some
renal failure diets may have additional fiber to enhance GI excretion of
nitrogenous wastes.
It is generally agreed that feeding renal failure diets to dogs and cats
with renal disease improves their quality of live and may minimize the
progression of the disease resulting in a longer life span. The components
of renal failure diets are discussed individually below but clinical trials
that evaluate the impact of dietary changes on quality and quantity of life
typically use commercial diets that differ in their composition of protein,
phosphorus, sodium and lipids compared to maintenance diets so that positive
effects are not attributable to a single component of the diet but rather to
a "diet effect".
A randomized, double masked, clinical study in 38 dogs with spontaneous
stage 3 or 4 kidney disease, half of which were fed a renal failure diet and
the other half a maintenance diet, published in
JAVMA in 2002, demonstrated improved quality and increased quantity of
life in the group fed the renal failure diet.
- The median interval before development of a uremic crisis was twice
as long in the group fed the renal diet
- Dogs fed the renal diet survived at least 13 months longer (average
593 vs 188 days)
- Owners of dogs fed the renal diet reported significantly higher
quality of life scores for their dogs
The results of a
study of cats with naturally occurring stable chronic renal failure fed
a diet restricted in phosphorus and protein compared to cats with CRF fed a
maintenance diet reported a median survival of 633 days for 29 cats fed the
renal diet compared to 264 days for 21 cats fed a regular diet. The groups
were not randomly determined but based on cat & owners willingness to change
to the renal diet.
In a study published in
JAVMA in 2006, 45 client-owned cats with spontaneous stage 2 or 3 CKD
were randomly assigned to an adult maintenance diet (23 cats) or a renal
diet (22 cats) and evaluated for up to 24 months. Findings included:
- Significant differences: BUN lower and blood bicarbonate higher in
the renal diet group
- No Significant differences
body weight
PCV
urine protein-to-creatinine ratio
creatinine
potassium
calcium
parathyroid hormone concentrations.
- 26% of cats fed the maintenance diet had uremic episodes (26%),
compared with 0% cats fed the renal diet
- At the conclusion of the study, 5 (21.7%) cats in the maintenance
diet group had died from renal causes and there were no renal-related
deaths in the renal diet group.
- There were no significant differences in quality of life as
perceived by owners responding to a questionnaire.
- Owners impressions of cats willingness to consume the diets did not
differ between groups
Specific components of therapy/management
Modification of dietary protein intake: It is generally
agreed that reducing dietary protein intake can ameliorate some of the
clinical signs of uremia. The controversial aspects of protein modification
include when to restrict protein, how much protein is needed, and will
protein restriction delay the progression of renal disease? Some studies in
rats, humans and dogs demonstrate that high protein diets result in
glomerular hyperfiltration that in turn contributes to progression of
deterioration in renal function suggesting that protein restriction in
patients with CRD may ameliorate glomerular hyperfiltration and delay
disease progression. There is not evidence that proves
protein restriction delays progression of renal disease in dogs or cats.
The optimal dietary protein requirements for dogs and cats with CRF are
not established. Renal failure diets contain reduced amounts of protein of
high biologic value compared to maintenance diets.
The protein source
determines the biologic value and usability of the protein. Proteins with
high biologic value can be readily converted to body proteins with minimal
waste production. Animal proteins have a higher biologic value than
vegetable proteins. Eggs have the highest biologic value.
The goal of alteration of dietary protein is to achieve the best
compromise between control of clinical manifestations of uremia and
prevention of malnutrition. Dietary protein intake must be individualized to
meet patient needs. The potential advantages of protein restriction include
reduction of nitrogen containing wastes, possibly slower progression of
kidney disease, and lower phosphorus intake which may slow the development
of renal osteodystrophy.
Potential disadvantages of protein restriction include protein
malnutrition characterized by weight loss, reduction in muscle mass, reduced
PCV, and reduced albumin. Protein restricted diets are less palatable than
higher protein diets. Dogs with CRD that are still eating are more likely to
accept a change in diet to a protein restricted diet than are dogs who are
very ill and refusing most foods. Protein restricted diets are more
expensive than higher protein diets.
Adequate calories from fat and carbohydrate sources must be supplied to
prevent the ingested protein from being catabolized for energy therefore
commercial renal failure diets are higher in fat than maintenance diets.
Water soluble vitamins like B and C are lost through
diuresis and may need to be supplemented. Commercial diets sold for patients
with renal disease contain increased amounts of water soluble vitamins so
additional vitamins do not need to be given.
Potassium: Lack of appetite and loss via polyuria may
result in hypokalemia requiring potassium supplementation. Cats are more
likely to be hypokalemic than are dogs. Potassium gluconate or citrate
administered orally are most commonly used in hypokalemic patients.
Potassium chloride is acidifying and not recommended. Feline renal diets
contain higher levels of potassium & additional supplementation is probably
not needed unless the cat shows signs of myopathy.
Phosphorus restriction may delay the progression of
renal failure and will minimize hyperparathyroidism. Protein restricted
diets are also restricted in phosphorus. If phosphorus remains increased
while feeding a protein restricted diet, phosphate binding agents which bind
phosphorus in intestinal tract can be administered. Allow about 2 weeks of
feeding just the phosphate restricted diet to determine its impact on blood
phosphorus concentration before adding phosphate binders. Samples to analyze
serum phosphorus should be obtained after a 12 hour fast. Phosphate binding
agents include aluminum carbonate, aluminum hydroxide, aluminum oxide,
calcium citrate, calcium acetate and calcium carbonate. Phosphate binding
agents are given with meals (or mixed with food) and are dosed to effect to
normal serum phosphorus levels. Side effects may include hypophosphatemia,
constipation, and aluminum toxicity. Aluminum toxicity causes
encephalopathies and bone disease in humans, neither of which have been
documented in cats or dogs. Calcium containing phosphate binding agents
(acetate, carbonate, citrate) should not be used until serum phosphorus is
reduced to < 6 mg/dl. Monitor blood calcium and phosphorus concentrations at
10 to 14 day intervals while determining the necessary dose, then at 4 to 6
week intervals when serum phosphorus has normalized.
Sevelamer hydrochloride (Renagel) is a cationic polymer that binds P. It
has potential to induce vitamin-K deficiency so prothrombin time should be
monitored.
Calcium levels may be controlled by controlling
hyperphosphatemia. Active vitamin D or calcium supplements may be given if
hypocalcemia persists but only when hyperphosphatemia has been controlled.
When Ca x P product exceeds 70, calcium-phosphate salts will precipitate in
soft tissues including the kidneys.
Suppression of PTH levels:
Elevated levels of PTH may play a role in the genesis of many of the
clinical signs of CRF patients and may also contribute to the progressive
nature of chronic renal dysfunction. The administration of low doses of 1,
25 dihydroxycholecalciferol (calcitriol) will suppress PTH secretion by the
parathyroid glands with reversal of some of the clinical manifestations and
possibly a resultant slowing of the rate of progression of renal
dysfunction.
References on calcitriol & treatment of CRF
A study performed at the University of Minnesota and reported in the
2006 Hills & WVC symposiums did not show low dose calcitriol to alter
mortality or improve appetite, activity or quality of life.
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Treatment of metabolic acidosis
Metabolic acidosis occurs commonly in animals in uremic crisis, but
less so in animals with stable renal disease. Consider treatment for
animals with plasma bicarbonate values < 15 mmol/L on repeat evaluation.
Serum total CO2 measurements are
not as accurate as bicarbonate values.
Treatment options include diet change, sodium bicarbonate or potassium
citrate. Renal failure diets are slightly alkalinizing.
When treating acidosis, the goal is to increase serum bicarbonate to
normal.
Potassium citrate is a good choice as it supplements potassium in
addition to its alkalinizing effect.
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Sodium: Diseased kidneys are less efficient at
regulating sodium and plasma volume. Diseased kidneys cannot adapt rapidly
to abrupt changes in sodium intake. Make changes in sodium intake gradually
over several weeks. Excessive sodium intake in cats with kidney disease may
worsen renal function without causing an increase in blood pressure.
Treatment of hypertension: An attempt should be made to
confirm hypertension by measuring blood
pressure. Unless the animal is displaying signs of organ injury (such as
acute blindness from retinal detachment), treatment is not an emergency. It
may take weeks to months to reduce hypertension to below 160/100 mmHg.
Hypertension may be treated with several classes of drugs but the drugs
most commonly used are:
-
ACE inhibitor vasodilator drugs: enalapril or benazepril
- calcium channel blocking drugs: amlodipine
The effectiveness of treatment should be assessed through serial
measurements of blood pressure. Hypertension and proteinuria are risk
factors for progression of CKD in humans and studies at University of
Minnesota have shown they are also risk factors for uremic crises and
increased mortality in dogs with stage 3 & 4 kidney disease.
The ACE
inhibitor enalapril was administered to dogs with induced kidney disease
and resulted in reduced systemic and glomerular hypertension with a
reduction in proteinuria. It is suggested to consider administration of an
ACE inhibitor to dogs with CKD when systolic blood pressures remain above
160 mmHg and when UPC ratios exceed 1. ACE inhibitors may reduce proteinuria
even when the patient does not have systemic hypertension.
Anabolic agents may promote anabolism (positive nitrogen
balance) for patients in a positive caloric balance. They may also increase
renal production of erythropoietin, stimulate bone marrow stem cells along
RBC lines, increase production of RBC 2,3 DPG with a shift of the
oxygen-hemoglobin dissociation curve to the right to facilitate release of
oxygen from hemoglobin to tissues, enhance Ca deposition in bones, and
stimulate appetite. In fact, anabolic agents are usually ineffective
in accomplishing any of the benefits ascribed to them. Anabolic agents
include testosterone, stanozolol (Winstral V), oxymetholone, and nandrolone
decanoate.
Treatment of anemia: When the PCV is ~20 in cats and ~
25% in dogs, anemia contributes to the clinical signs. Anemia can be treated
by blood transfusion or the administration of recombinant human
erythropoietin. Erythropoietin is very effective in increasing PCV but has
the potential for adverse side effects including:
-
antibody formation which suppresses endogenous erythropoietin production
but is reversible with cessation of use
-
hypertension
-
seizures
Erythropoietin is administered subcutaneously at a starting dose of 50 to
150 U/kg three times weekly (100 U/kg is the most commonly used starting
dose). When PCV is ~33% in dogs or ~30% in cats the dose is reduced to twice
weekly. A maintenance dose of 50 to 100 U/kg one to three times weekly is
usually required. Low doses, 50 U/kg three times weekly should be used
initially in patients with hypertension. Use with caution in hypertensive
animals.
Both recombinant canine and feline erythropoietin are currently
undergoing trials.
Clinical efficacy and safety of recombinant canine erythropoietin in
dogs with anemia of chronic renal failure and dogs with recombinant
human erythropoietin-induced red cell aplasia.
"Recombinant cEPO stimulated erythrocyte production in dogs with
nonregenerative anemia secondary to chronic renal failure without
causing the profound erythroid hypoplasia that can occur in rhEPO-treated
dogs. Unfortunately, rcEPO was not as effective in restoring erythrocyte
production in dogs that had previously developed rhEPO-induced red cell
aplasia."
Periodic blood transfusions may be necessary in patients in which EPO
cannot or is not used.
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Modification of dietary lipids:
There are several types of lipids derived from the diet:
- polyunsaturated plant origin lipids contain large amounts of omega 6
fatty acids
- polyunsaturated fish origin lipids contain large amounts of omega 3
fatty acids
- animal fats are primarily saturated and do not contain omega 3 or 6
fatty acids
The omega 3 and omega 6 fatty acids are degraded to different eicosanoids.
In a study of 15/16 nephrectomized dogs, those fed diets supplemented
with omega-3 PUFA had lower mortality, better renal function, fewer renal
lesions, less proteinuria, and lower cholesterol levels compared to dogs fed
diets high in saturated fats or omega-6 PUFA.
If feeding a renal failure diet supplemented with
omega-3 PUFA, additional supplementation is not needed.
Subcutaneous Fluids
Since cats and dogs with renal failure are polyuric and may not drink
enough to remain hydrated, some patients may benefit from intermittent SC
fluids. The decision to recommend subcutaneous fluids should be made on a
case-by-case basis as not all animals will tolerate sc fluids nor are all
owners willing or able to administer fluids. The most common fluids used are
normal saline or lactated Ringer's solution or a maintenance solution
containing 0.45% saline and 2.5% glucose supplemented with 20 mEq/L of
potassium chloride. A cat or small dog is given approximately 75 to 150 mls
daily or as needed. Risks include overhydration, hypernatremia,
irritation/or infection. See
http://www.vetmed.wsu.edu/ClientED/cat_fluids.aspx for sample
instructions for pet owners.
Proteinuria
Tolerability and efficacy of benazepril in cats
with chronic kidney disease.
JVIM Oct 2006
192 cats with CKD were recruited into a double-blind,
prospective, randomized clinical trial. Cats received daily placebo or
benazepril for up to 1,119 days. Most cats were fed a diet containing low
amounts of phosphate, protein, and sodium. Benazepril produced a significant
reduction in proteinuria, assessed by the urine protein-to-creatinine ratio.
There was no difference in renal survival time between the 2 groups when all
192 cats were compared.
Effects of the angiotensin converting enzyme
inhibitor benazepril in cats with induced renal insufficiency.
AJVR 2001
Administration of benazepril to cats with induced renal
failure was associated with a small but significant reduction in systemic
hypertension and an increase in whole kidney GFR. Benazepril may be an
effective treatment to slow the rate of progression of renal failure in cats
with renal disease.
Prognostic factors in cats with chronic kidney
disease.
JVIM Oct 2007
Renal survival time was defined as the time from initiation
of therapy to the need for parenteral fluid therapy, euthanasia, or death
related to renal failure. In a study population of 37 cats factors
associated with a shorter renal survival time
-
Increased plasma creatinine concentration
-
increased urine protein-to-creatinine ratio (UPC)
(proteinuria)
-
increased blood leukocyte count
-
Increased concentrations of plasma phosphate or urea
-
lower blood hemoglobin concentration or hematocrit
Anorexia
See ARF section for information on use of H2 blockers and
antiemetics to control nausea and vomiting. Warming food or adding odiferous
toppings may entice anorexic animals to eat. Trying different brands of
renal failure diets may entice some animals to eat. Some may prefer rotating
diets every few weeks.
Some animals will remain anorexic. Some owners may opt for
placement of a gastric feeding tube to provide nutritional support.
Complications and outcomes associated with use of gastrostomy tubes for
nutritional management of dogs with renal failure: 56 cases (1994-1999).
Drug modification
Because the kidneys are responsible for elimination of many
drugs, drug clearance is often reduced as renal function declines. This may
lead to drug toxicity. See table 260-1 in Ettinger's textbook of Internal
medicine for guidelines for dose modifications of common drugs in patients
with altered renal function.
1. An EXCELLENT reference written by
Carol and David
DiFiori, owners of a cat who died of CRF
2.
Canine Renal Disease. written by a lay person who has compiled a
comprehensive site of resources with an emphasis on congenital renal
diseases.
3.
Nutrition Support
Service Dr. Tony Buffington, the Ohio State University
4.
IRIS summary of treatment recommendations for dogs and cats 2006
Last Edited: May 05, 2008 4:51 PM
