Chronic renal failure

1. Chronic renal failure
Stephen P. DiBartola, DVM
Department of Veterinary Clinical Sciences
College of Veterinary Medicine
Ohio State University
Columbus, OH 43210
The Nephronauts

2. Chronic renal failure (CRF)
• Occurs when compensatory mechanisms
of the diseased kidneys are no longer able
to maintain the EXCRETORY,
REGULATORY, and ENDOCRINE functions
of the kidneys
• Resultant retention of nitrogenous
solutes, derangements of fluid, electrolyte
and acid-base balance, and failure of
hormone production constitute CRF

3. Causes of CRF in dogs
• Chronic tubulointerstitial nephritis of unknown cause
• Chronic pyelonephritis
• Chronic glomerulonephritis
• Amyloidosis
• Familial renal diseases
• Hypercalcemic nephropathy
• Chronic obstruction (hydronephrosis)
• Sequel to acute renal disease (e.g., leptospirosis)
CRF may affect 0.5 to 1.0% of the geriatric canine population

4. Causes of CRF in cats
• Chronic tubulointerstitial nephritis of unknown cause
• Chronic pyelonephritis
• Chronic glomerulonephritis
• Amyloidosis (familial in Abyssinians)
• Polycystic kidney disease (familial in Persians)
• Chronic obstruction (hydronephrosis)
• Sequel to acute renal disease
• Neoplasia (e.g. renal lymphoma)
• Granulomatous interstitial nephritis due to FIP
CRF may affect 1.0 to 3.0% of the geriatric feline population

5. Causes of CRF in large animals
• Horse
• Chronic
glomerulonephritis
• Chronic interstitial
nephritis of
unknown cause
• Chronic
pyelonephritis
• Amyloidosis
• Cow
• Chronic pyelonephritis
• Chronic interstitital
nephritis of unknown
cause
• Amyloidosis
• Renal infarction due to
sepsis
• Renal vein thrombosis
• Leptospirosis
• Renal lymphoma

6. Differentiation of CRF from ARF
• Renal size
• History of previous PU/PD
• Non-regenerative anemia
• Weight loss and poor haircoat
• Parathyroid gland size on ultrasound
• Carbamylated hemoglobin
• Hypothermia
• Hyperkalemia

7. Uremia as an intoxication
• No single compound likely to explain
the diversity of uremic symptoms
• Urea, guanidine compounds,
polyamines, aliphatic amines,
indoles, myoinositol, trace elements,
“middle molecules”
• PTH is the best characterized uremic
toxin

8. Concept of hyperfiltration
• Total GFR = 
SNGFR
• In progressive renal
disease, decline in
total GFR is offset
by increased
SNGFR in remnant
nephrons

9. Concept of hyperfiltration
• After an acute reduction
in renal mass, total GFR
increases 40-60% over a
period of several months
• Example: GFR falls from
40 to 20 ml/min after
uninephrectomy but 2
months later is 30 ml/min

10. Concept of hyperfiltration
• SNGFR = Kf(PGC-PT-GC)
• Increase in SNGFR occurs
due to alterations in
determinants of GFR: Kf
and PGC
• These changes helpful in
the short term but
maladaptive in the long run
Better check
notes on GFR
and RBF!

11. Proteinuria and glomerular sclerosis in
remnant nephrons are adverse effects of
hyperfiltration that may lead to progression of
renal disease

12. Concept of hyperfiltration
• In RATS, dietary protein restriction
reduces hyperfiltration and abrogates the
maladaptive response
• In DOGS, this may NOT be true
• 17% protein diet failed to prevent
hyperfiltration in dogs with 94% renal
ablation (Brown 1991)
• 8% protein diet caused malnutrition and
increased mortality in dogs with 92% renal
ablation (Polzin 1982)

13. Factors contributing to the progressive
nature of renal disease
• Species differences and extent of reduction in
renal mass
• Functional and morphologic changes in
remnant kidney
• Time followed
• Dietary factors
• Systemic complications of renal insufficiency
• Therapeutic interventions

14. Progession of renal disease: Species
differencres and extent of reduction in
renal mass
• Experimental rats: 75-80% reduction in renal
mass results in progression
• Dogs
• Clinical cases: Yes
• Experimental: 85-95% reduction in renal mass
• Cats
• Clinical cases: Yes
• Experimental: Cats with 83% reduction in renal
mass did not progress over 12 months

15. Progression of renal disease: Functional
and morphologic changes in remnant
renal tissue
• Hyperfiltration increases movement of
proteins across glomerular capillaries into
Bowman’s space and mesangium
• Increased protein traffic is toxic to the
kidney
• End result may be glomerular sclerosis
and tubulointerstitial nephritis

16. Progression of renal disease:
Time followed
• Dogs with 75% renal mass reduction fed 19, 27
and 56% protein (1% Pi) and followed 4 years
did NOT show evidence of progression
• 3/10 dogs with 88% renal mass reduction fed
26% protein (0.9% Pi) progressed over 21-24
months
• 10/12 dogs with 94% renal mass reduction fed
17% protein (1.5% Pi) progressed over 24
months

17. Progression of renal disease: Diet
• Protein
• Phosphorus
• Calories
• Lipids

18. Diet and progression of renal
disease: Protein restriction
• Role of low protein diet in slowing
progression of renal disease is
controversial
• Prevention of hyperfiltration by low
protein diet may not be feasible in dogs
without inducing malnutrition
• Low protein diets may have other
beneficial effects (limitation of
proteinuria)

19. Diet and progression of renal
disease: Phosphorus restriction
• Slows progression of renal
disease
• Prevents or reverses renal
secondary hyperparathyroidism
• Limits renal interstitial
mineralization, inflammation and
fibrosis

20. Diet and progression of renal
disease: Caloric restriction
• Extremely low protein diets are
unpalatable and experimental rats
with remnant kidney consumed less
food
• One study showed improvement in
proteinuria and renal morphologic
changes when calories (but not
protein) were restricted

21. Diet and progression of renal
disease: Lipids
• -6 PUFA may hasten progression of
renal disease whereas -3 PUFA are
renoprotective
• -3 PUFA promote production of
“good” prostaglandins and limit
production of “bad” prostaglandins

22. Beneficial effects of -3 PUFA in
renal disease
• Decreased cholesterol and
triglycerides
• Decreased urinary eicosinoid
excretion
• Decreased proteinuria
• Preservation of GFR
• Less severe renal morphologic
changes

23. Progression of renal disease:
Systemic complications of renal
insufficiency
• Systemic hypertension
• Urinary tract infection
• Fluid, electrolyte, and acid-base
abnormalities

24. Progression of renal disease:
Therapeutic interventions
• ACE inhibitors (e.g. enalapril)
• Decrease proteinuria
• Decrease blood pressure
• Limit glomerular sclerosis
• Slow progression
• Low protein diet
• Decrease proteinuria
• Limit uremic symptomatology
• May not limit hyperfiltration

25. Concept of external balance
Solute input
from diet
Solute output
in urine
The challenge to the diseased kidneys is to maintain external
solute balance in the face of progressively declining GFR

26. Intact nephron hypothesis (Bricker)
• “In the presence of a
heterogeneity of morphologic
changes in the nephrons of
diseased kidneys, there is a
relative homogeneity of
glomerulotubular balance”

27. Maintenance of glomerulotubular
balance in progressive renal disease
• For any given solute, the diseased
kidneys maintain GT balance as GFR
declines by:
• DECREASING the FRACTION of the
filtered load of that solute that is
REABSORBED and
• INCREASING the FRACTION of the
filtered load of that solute that is
EXCRETED

28. “Trade off” hypothesis (Bricker)
• “The biological price to be paid for
maintaining external solute
balance for a given solute as renal
disease progresses is the
induction of one or more
abnormalities of the uremic state”

29. “Trade off” hypothesis
• Renal secondary hyperparathyroidism
(maintenance of normal calcium and
phosphorus balance at the expense of bone
mineral) is the most well-characterized
example of the “trade off” hypothesis
• This “mal”-adaptive process can be
prevented by PROPORTIONAL REDUCTION
in the intake of phosphorus

30. Different responses for
different solutes
• No regulation (A)
• Complete
regulation (C)
• Limited
regulation (B)

31. Different responses for different solutes
• NO REGULATION Solutes handled by GFR
alone (e.g. urea, creatinine)
• Plasma concentration reflects GFR
• COMPLETE REGULATION Some solutes
handled by GFR and a combination of tubular
reabsorption and secretion (e.g. Na+, K+)
• Normal plasma concentration maintained until
GFR < 5% of normal
• LIMITED REGULATION Some solutes handled
by GFR and a combination of tubular
reabsorption and secretion (e.g. Pi, H+)
• Normal plasma concentration maintained until
GFR < 15-20% of normal

32. BUN, creatinine (no regulation)
• Azotemia does
not develop
until 75% or
more of the
nephron
population has
become non-
functional

33. Water balance (complete regulation)
• Ability to produce concentrated urine
and to excrete a water load both are
impaired in CRF
• Clinical manifestations: PU/PD
• Increased solute load per residual
functioning nephron (osmotic diuresis)
is the MOST important factor
contributing to the concentrating defect

34. Impaired concentrating ability
• Develops when 67% of nephron
population becomes non-functional
• Corresponds to USG 1.007-1.015 or
UOsm 300-600 mOsm/kg
• Some cats retain considerable
concentrating ability even after
development of azotemia

35. Why does polyuria develop?
• Consider a 10 kg dog producing 333
ml urine per day with average UOsm of
1,500 mOsm/kg (i.e. solute load of
500 mOsm/day)
• With CRF, this dog might have a fixed
UOsm of 500 mOsm/kg and would
require a urine volume of 1,000 ml to
excrete the same 500 mOsm of solute

36. Normal Diseased
Number of nephrons 1,000,000 250,000
Total GFR (ml/min) 40 15
SNGFR (nl/min) 40 60
Urine output (ml/day) 333 1,000
Urine output (ml/min) 0.23 0.69
Urine output per nephron (nl/min) 0.23 2.76
% Filtered water reabsorbed 99.4 95.4
% Filtered water excreted 0.6 4.6
If GFR is decreased, how can polyuria develop?

37. Na+ balance in CRF: Complete regulation
• As GFR declines, fractional reabsorption of
Na+ decreases (fractional excretion
increases)
• Natriuretic substances probably play a role
(e.g. ANP)
• Less flexibility in Na+ handling
• Ability to excrete an acute Na+ load impaired
• Ability to conserve Na+ impaired
• Changes in Na+ intake should be made
gradually in CRF patients

38. K+ balance in CRF: Complete regulation
• As GFR declines, fractional reabsorption of
K+ decreases (fractional excretion
increases)
• Aldosterone contributes but is not essential
• Less flexibility in K+ handling
• Reduced ability to tolerate a K+ load
• May have reduced ability to conserve K+
(hypokalemia occurs in 10-30% of dogs and
cats with CRF)

39. Ca+2 balance in CRF: Complete regulation
Normal calcium balance depends on
interactions of PTH, calcitriol, and calcitonin
acting on kidney, gut, and bone

40. Ca+2 balance in CRF: Complete regulation
• Kidney is normal
site of conversion
of 25-OH
cholecalciferol to
1,25-(OH)2
cholecalciferol
(calcitriol) by 1
hydroxylase

41. Ca+2 balance in CRF
• Total serum Ca+2 concentration
usually is normal but ionized
hypocalcemia occurs in 40% of CRF
dogs
• “Mass Law” effect due to increased Pi
• Decreased production of calcitriol by
kidneys due to hyperphosphatemia
and/or parenchymal renal disease
• Impaired gut absorption of calcium

42. Ca+2 balance in CRF
• Hypercalcemia occurs in 5-10% of dogs
with CRF
• Ionized Ca+2 may be normal or low
• May be difficult to determine which came
first: renal failure or hypercalcemia
• Hypercalcemia (and hypophosphatemia)
develops in some horses with CRF

43. Phosphorus balance in CRF:
Limited regulation
• Ca+2 and Pi balance maintained by
progressive increase in PTH (renal
secondary hyperparathyroidism)
• Leads to bone demineralization and
possibly other toxic effects (“Trade
off” hypothesis)

44. Phosphorus balance in CRF:
Limited regulation
• Hyperparathyroidism is a consistent
finding in progressive renal disease
• PTH decreases the TMax for Pi reabsorption
• Compensation is maximal when GFR
decreases to 15-20% of normal. After this
point, Pi balance can only be maintained
by development of hyperphosphatemia

45. Renal secondary hyperparathyroidism
Classical theory
• Decreased GFR causes
 Pi
• Mass Law effect results
in  Ca+2
•  Ca+2 stimulates PTH
secretion
• Increased PTH causes
increased renal
excretion of Pi and
mobilization of Ca+2
from bone

46. Renal secondary hyperparathyroidism

47. Renal secondary hyperparathyroidism

48. Renal secondary hyperparathyroidism
Renal secondary
hyperparathyroidism
can be prevented or
reversed by a
proportional reduction
in phosphorus intake

49. Renal secondary hyperparathyroidism
Alternative hypothesis: Role of calcitriol
• Phosphate retention inhibits 1 hydroxylase
and reduces renal production of calcitriol
• Ionized hypocalcemia due to decreased GI
absorption of Ca+2 stimulates PTH synthesis
• Decreased numbers of calcitriol receptors in
parathyroid glands (less negative feedback)
• Decreased DNA binding of calcitriol-VDR
complex in parathyroid glands (less negative
feedback)

50. Renal secondary hyperparathyroidism
• “Early” in course of progressive
renal disease, phosphate restriction
reduces inhibition of 1 hydroxylase
and increases calcitriol synthesis
• “Late” in course of progressive renal
disease, insufficient functional renal
mass prevents production of
adequate amounts of calcitriol and
replacement therapy is necessary

51. Renal secondary hyperparathyroidism:
Phosphorus restriction
• Blunts or reverses renal secondary
hyperparathyroidism
• Slows progression of renal disease
• Improves renal function (some
species)
• Minimizes renal interstitial
mineralization, inflammation and
fibrosis

52. Acid-base regulation: Limited
regulation
• Limitation of renal NH4
+ production is main
cause of metabolic acidosis in CRF
• Total NH4
+ excretion decreases in progressive
renal disease but NH4
+ excretion per remnant
nephron increases 3 to 5 fold
• This adaptation is maximal when GFR
decreases to 10-20% of normal and acid-base
balance then must be maintained by reduction
in serum HCO3
-

53. Acid-base regulation: Limited
regulation
• Metabolic acidosis of CRF usually
mild due to large reservoir of buffer
(bone CaCO3)
• Normochloremic (high anion gap)
acidosis “late” in course of
progressive renal disease due to
accumulation of “unmeasured” PO4
and SO4 anions

54. Anemia of CRF
• Non-regenerative (normochromic,
normocytic)
• Variable in magnitude and correlated
with severity of CRF (as estimated by
serum creatinine)
• Serum EPO concentrations are low to
normal (inappropriate for PCV)

55. Anemia of CRF: Contributory
factors
• Main cause is inadequate production of EPO
by diseased kidneys
• Uremic toxins reduce lifespan of circulating
RBC and may impair erythropoiesis
• Platelet dysfunction promotes ongoing blood
loss (e.g. GI tract)
• Increased RBC 2,3-DPGA decreases Hb
affinity for O2 and enhances O2 deliver to
tissues (compensatory effect)

56. Hemostasis in CRF
• Abnormal platelet function (e.g.
aggregation) but numbers normal
• GI blood loss most common
• Best to check buccal mucosal
bleeding time to assess risk of
hemorrhage
• Guanidines and PTH suspected to
contribute to platelet dysfunction

57. Gastrointestinal disturbances in CRF
Oral lesions
• Foul odor
• Stomatitis
• Erosions and
ulcers
• Tongue tip
necrosis (fibrinoid
necrosis and focal
ischemia)

58. Gastrointestinal disturbances in CRF
Gastric lesions
• Back diffusion of acid
• Bleeding due to
platelet dysfunction
• Bacterial NH4
+
production from urea
• Ischemia due to
vascular lesions
• Increased gastrin

59. Metabolic complications of CRF
• Hyperglycemia due to peripheral insulin
resistance
• Catabolic effect of increased glucagon
• Increased gastric acid due to excess gastrin
• Altered metabolism of thyroid hormones
(“euthyroid sick syndrome”)
• Increased mineralocorticoids may contribute to
hypertension
• Impaired erythropoietin and calictriol
production

60. Less commonly recognized
disturbances in CRF
• Defective cell-mediated immunity
• Uremic encephalopathy (related
more to rate of onset than severity
of uremia)
• Uremic neuropathy
• Uremic pneumonitis

61. Hypertension in CRF
• Prevalence
uncertain
• Up to 67% of dogs
and cats with CRF
• Up to 80% of dogs
with glomerular
disease

62. Hypertension in CRF
Mechanisms
• Renal ischemia with activation of the
renin-angiotensin system
• Sympathetic nervous system stimulation
• Impaired Na+ excretion and ECFV
expansion when GFR very low (< 5% of
normal)
• Primary intrarenal mechanism for Na+
retention in glomerular disease

63. Hypertension in CRF
Clinical Manifestations
• Ocular
• Blindness
• Retinal detachment
• Retinal hemorrhages
• Retinal vascular toruosity
• Cardiovascular
• LV enlargement
• Medial hypertrophy of
arteries
• Murmurs and gallops

64. Clinical history in CRF
Findings are non-specific
• Polyuria and polydipsia
• Vomiting (dogs)
• Anorexia
• Weight loss
• Lethargy

65. Physical findings in CRF
• Weight loss
• Poor haircoat
• Oral lesions (most common in dogs)
• Pallor of mucous membranes
• Dehydration
• Osteodystrophy (young growing dog
with familial renal disease)
• Ascites or edema (consider glomerular
disease)

66. Laboratory findings in CRF
• Nonregenerative anemia, lymphopenia
• Isosthenuria (67% loss of nephrons)
• Azotemia (75% loss of nephrons)
• Hyperphosphatemia (85% loss of
nephrons)
• Decreased serum HCO3
-
• Variable serum Ca+2
• Mild hyperglycemia

67. Laboratory findings in CRF:
Urinalysis
• Isosthenuria (cats may retain
considerable concentrating ability)
• Persistent proteinuria with inactive
sediment, hypoalbuminemia, and
hypercholesterolemia suggest
glomerular disease
• Pyuria and bacteriuria suggest UTI
but do not localize it

68. Management of CRF: General
principles
• Search for reversible
causes (e.g.
pyelonephritis,
obstruction,
hypercalcemia)
• Don’t pass judgement
on animal until
several days of
conscientious fluid
therapy
Isn’t that
bandage a
little tight?

69. Conservative medical management of CRF
• Free access to water at all times!
• Protein and calories
• Sodium chloride
• Alkali and potassium and replacement
• Phosphorus restriction
• H2 receptor blockers
• Hormone replacement (erythropoietin, calcitriol)
• Anabolic steroids
• Blood pressure control
• Avoid stress (SQ fluids at home by the owner)

70. Conservative medical management
of CRF: Protein restriction?
• Relieve uremic
symptomatology
and improve
patient well-being
• Can hyperfiltration
be reduced?

71. Conservative medical management
of CRF: Protein restriction
• Introduce when patient has persistent mild to
moderate azotemia in the hydrated state
• Feeding moderately protein-restricted diets is
preferable to extremely high or low protein
diets
• Dogs require minimum of 5% of calories from
protein
• Cats require minimum of 20% of calories from
protein

72. Commercial diets for CRF
management (dry matter basis)
0.2-0.3%
0.2-0.3%
Sodium
0.5-0.6%
0.2-0.3%
Phosphorus
25-28%
15-17%
Protein
Cat
Dog

73. Conservative medical management of
CRF: Monitoring patient response
• Stable body weight
• Stable serum albumin
concentration
• Decreased BUN concentration
• Stable serum creatinine
concentration

74. Conservative medical management
of CRF: Non-protein calories
• Adequate non-protein calories to
maintain body condition should
be provided by carbohydrate and
fat
• -3 PUFA may be renoprotective
whereas -6 PUFA may hasten
progression of renal disease

75. Conservative medical management
of CRF: Sodium chloride
• Reasons for sodium restriction
• Documented hypertension
• Glomerular disease (primary intrarenal
mechanism for sodium retention)
• Make changes slowly (CRF patients
are less flexible in adjusting to
changes in dietary sodium)

76. Conservative medical management of
CRF: Alkali and potassium replacement
• Severe metabolic acidosis (serum
HCO3
- < 12 mEq/L) can be treated
with NaHCO3, K+ gluconate or K+
citrate
• Hypokalemia may occur in 10-30%
of dogs and cats with CRF and may
be treated with K+ gluconate or K+
citrate

77. Conservative medical management
of CRF: Phosphorus restriction
• Reversal or blunting of renal
secondary hyperparathyroidism
• Prevention of soft tissue
mineralization (including kidneys)
• Improvement in renal
tubulointerstitial lesions
• Improvement in renal function (rats)

78. Conservative medical management
of CRF: Phosphorus restriction
• Modified-protein diets for dogs and
cats with CRF also are low in
phosphorus
• Initially try dietary phosphorus
restriction alone
• If inadequate, add phosphorus
binders

79. Conservative medical management of
CRF: Phosphorus restriction
• Ideally, monitor renal secondary
hyperparathyroidism by serial
measurement of serum PTH
• Evaluate serum phosphorus
concentration after 12 hour fast
• Aim for serum phosphorus
concentration of 2.5 to 5.0 mg/dL

80. Conservative medical management
of CRF: Phosphorus binders
• Most phosphorus binders contain
Ca+2 or Al+3
• Constipation is common side effect
• Al+3 containing phosphorus binders
are not considered safe in humans
with CRF due to Al+3 retention
• Risk of Al+3 intoxication in dogs and
cats is uncertain

81. Conservative medical management of
CRF: Phosphorus binders
• Aluminum hydroxide
• Aluminum carbonate
• Calcium acetate
• Calcium carbonate
90 mg/kg/day divided and
given with within 2 hours
of feeding
Slightly lower dosage of calcium acetate may be necessary due to
more efficient phosphate binding

82. Conservative medical management of
CRF: Phosphorus restriction
• Aluminum hydroxide
• Effective phosphorus
binder
• Risk of aluminum
intoxication?
• Becoming difficult to
find in stores

83. Conservative medical management of
CRF: Phosphorus restriction
• Calcium carbonate
• Effective phosphorus
binder
• Also provides
calcium
• Monitor carefully in
patients receiving
calcitriol due to risk
of hypercalcemia

84. Conservative medical management
of CRF: Phosphorus binders
• Sevelamer HCl (Renagel)
• Does not contain Ca+2 or Al+3
• 30-60 mg/kg/day divided and given with
food
• May cause GI adverse effects including
constipation
• At extremely high dosage may interfere
with GI absorption of folic acid, vitamin
D, and vitamin K
• Expensive

85. Medical Management of CRF:
Uremic Gastroenteritis
• Plasma gastrin concentrations are
high in dogs and cats with CRF
• Degree of hypergastrinemia
correlates with severity of CRF
• Potential clinical manifestations
• Anorexia
• Vomiting
• Gastrointestinal bleeding

86. Medical Management of CRF:
H2 Receptor Blockers
• Decrease gastric
acid secretion
• Cimetidine
(5 mg/kg q12h)
• Ranitidine
(2 mg/kg q12h)
• Famotidine
(1 mg/kg q24h)

87. Medical Management of CRF:
H2 Receptor Blockers
• Famotidine
• Once per day
dosing
• 1 mg/kg

88. Medical Management of CRF:
Endocrine replacement therapy
• Erythropoietin
• Calcitriol

89. Medical Management of CRF
Hormonal Replacement: Erythropoietin
• Effects in treated
dogs and cats
• Resolution of anemia
• Weight gain
• Improved appetite
• Improved haircoat
• Increased alertness
• Increased activity
Not approved for use in dogs and cats!

90. Medical Management of CRF
Hormonal Replacement: Erythropoietin
• Consider in symptomatic
dogs and cats with PCV
< 20%
• Starting dosage 100 U/kg
SQ 3X per week
• Supplement with FeSO4
• When PCV > 30%
decrease to 2X per week

91. Medical Management of CRF
Hormonal Replacement: Erythropoietin
• Monitor iron status with serum iron and
TIBC
• Monitor PCV weekly using same
technique (table top centrifuge or Coulter
counter) every time
• Target PCV range: 30 to 40%
• Depending on severity of anemia may take
3 to 4 weeks for PCV to enter target range

92. Medical Management of CRF
Erythropoietin: Adverse Effects
• Antibody formation
• Vomiting
• Seizures
• Hypertension
• Uveitis
• Hypersensitivity-like mucocutaneous
reaction

93. Medical Management of CRF
Erythropoietin: Adverse Effects
• High risk of antibody formation
• Occurs 30 to 160 days after starting treatment
• Progressive decrease in PCV and marked
increase in bone marrow M:E ratio while
receiving EPO
• Discontinue EPO if antibody formation
suspected
• Prolonged transfusion dependence may result

94. Medical Management of CRF
Erythropoietin: The future
• Recombinant canine and feline
erythropoietin (Cornell
University)
• Erythropoietin gene therapy in
cats (University of Florida, Ohio
State University)

95. Medical Management of CRF
Hormonal Replacement: Calcitriol
• Enhances
gastrointestinal
absorption of calcium
and corrects ionized
hypocalcemia
• Reduces PTH
secretion by
occupying calcitriol
receptors on
parathyroid glands

96. Medical Management of CRF
Hormonal Replacement: Calcitriol
• Used only after
hyperphosphatemia
controlled
(Ca  Pi < 60-70)
• Watch for hypercalcemia
(especially with Ca+2
containing Pi binders)
• Rapidly lowers serum
PTH concentration

97. Medical Management of CRF
Hormonal Replacement: Calcitriol
• Extremely low
dosage required:
2.5 to 3.5
ng/kg/day
• Requires
reformulation by
compounding
pharmacy
http://www.islandpharmacy.com/

98. Medical Management of CRF
Hormonal Replacement: Calcitriol
• Monitoring patients on calcitriol
• Clinical appearance may be
unreliable
• Follow serum PTH concentration
• Long-term benefit to animal
unknown

99. Medical Management of CRF:
Anabolic steroids
• Equivocal effectiveness in dogs with
CRF
• Several products
• Methyltestosterone
• Stanozolol
• Oxymetholone
• Nandrolone decanoate

100. • Cats may develop hepatotoxicity after
stanozolol administration
• Anorexia
• Increased ALT and ALP
• Hyperbilirubinemia
• Vitamin K-responsive coagulopathy
• Centrilobular hepatic lipidosis and cholestasis on
liver biopsy
Medical Management of CRF:
Anabolic steroids

101. Medical Management of CRF:
Blood Pressure Assessment
• Oscillometric or Doppler
methodology acceptable in dogs
• Doppler methodology more
reliable in cats

102. Medical Management of CRF
Hypertension: “White Coat Artifact”
• Makes it difficult to decide if a cat is truly
hypertensive
• Mean 24-hr systolic blood pressure by
radiotelemetry:
• Normal cats: 126 mm Hg
• CRF cats: 148 mm Hg
• During clinical examination:
• Normal cats: 143 mm Hg
• CRF cats: 170 mm Hg
Belew et al. J Vet Int Med 13:134, 1999

103. Medical Management of CRF:
Blood Pressure Assessment
• Patient, trained technician
• Quiet, undisturbed
environment
• Sufficient time for
acclimation
• Correct cuff size
• Several sequential
measurements
• Average sequential readings
I don’t think
he’s waving
at you

104. Medical Management of CRF
Hypertension: To treat or not?
• BP consistently
> 170 mm Hg
• High BP and fundic
lesions
• Retinal hemorrhage
• Vascular tortuosity
• Retinal edema
• Intra-retinal transudate
• Retinal detachment

105. Medical Management of CRF:
Treatment of Hypertension
• Dietary salt restriction
• Commercial pet foods designed for CRF
often also are sodium-restricted
• Diuretics
• Risk of dehydration and pre-renal
azotemia greater with loop diuretics
(e.g. furosemide) than with thiazides
(e.g. hydrochlorothiazide)

106. Medical Management of CRF:
Treatment of Hypertension
• Amlodipine
• 0.18 mg/kg in dogs
or 0.625 to 1.25 mg
per cat PO q24h
• Recheck BP one
week after starting
drug

107. Medical Management of CRF:
Treatment of Hypertension
• Enalapril
• 0.5 mg/kg q12h or
q24h
• Effect on blood
pressure may be
modest
• May have other
potentially
beneficial effects
on kidney

108. Medical Management of CRF:
Treatment of Hypertension
• Other anti-hypertensive agents
• Hydralazine (arterial vasodilator)
• Prazosin (1 adrenergic blocker)
• Propranolol (nonspecific 
blocker)

109. Medical Management of CRF:
Avoid stress
• Manage on
outpatient basis
whenever
possible
• Consider SQ
fluids at home by
owner

110. Medical Management of CRF:
Why is survival time so variable?
• Rate of progression
varies among
individuals
• Different individuals are
diagnosed at different
stages of disease
• Activity of underlying
disease may fluctuate
• Treatment may affect
progression
Slope of 1/SCr vs time is a ROUGH
indicator of progression

111. Medical Management of CRF:
Findings indicative of a poor prognosis
• Severe intractable anemia
• Advanced osteodystrophy
• Inability to maintain fluid
balance
• Progressive azotemia
despite treatment
• Progressive weight loss
• Severe endstage renal
lesions on biopsy