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Chronic renal failure

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Title: 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 Bowmans 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
    lt 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
    lt 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
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
Ca2 balance in CRF Complete regulation
Normal calcium balance depends on interactions of
PTH, calcitriol, and calcitonin acting on kidney,
gut, and bone
40
Ca2 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
Ca2 balance in CRF
  • Total serum Ca2 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
Ca2 balance in CRF
  • Hypercalcemia occurs in 5-10 of dogs with CRF
  • Ionized Ca2 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
  • Ca2 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 hyperparathyroidismClassical
theory
  • Decreased GFR causes ? Pi
  • Mass Law effect results in ? Ca2
  • ? Ca2 stimulates PTH secretion
  • Increased PTH causes increased renal excretion of
    Pi and mobilization of Ca2 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 Ca2 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 CRFOral lesions
  • Foul odor
  • Stomatitis
  • Erosions and ulcers
  • Tongue tip necrosis (fibrinoid necrosis and focal
    ischemia)

58
Gastrointestinal disturbances in CRFGastric
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 (lt 5 of normal)
  • Primary intrarenal mechanism for Na retention in
    glomerular disease

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

64
Clinical history in CRFFindings 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 Ca2
  • 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)
  • Dont pass judgement on animal until several days
    of conscientious fluid therapy

Isnt 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)
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- lt 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 Ca2 or Al3
  • Constipation is common side effect
  • Al3 containing phosphorus binders are not
    considered safe in humans with CRF due to Al3
    retention
  • Risk of Al3 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 Ca2 or Al3
  • 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 CRFHormonal 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 CRFHormonal Replacement
Erythropoietin
  • Consider in symptomatic dogs and cats with PCV lt
    20
  • Starting dosage 100 U/kg SQ 3X per week
  • Supplement with FeSO4
  • When PCV gt 30 decrease to 2X per week

91
Medical Management of CRFHormonal 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 CRFErythropoietin Adverse
Effects
  • Antibody formation
  • Vomiting
  • Seizures
  • Hypertension
  • Uveitis
  • Hypersensitivity-like mucocutaneous reaction

93
Medical Management of CRFErythropoietin 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 ME ratio while receiving EPO
  • Discontinue EPO if antibody formation suspected
  • Prolonged transfusion dependence may result

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

95
Medical Management of CRFHormonal 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 CRFHormonal Replacement
Calcitriol
  • Used only after hyperphosphatemia controlled
  • (Ca ? Pi lt 60-70)
  • Watch for hypercalcemia (especially with Ca2
    containing Pi binders)
  • Rapidly lowers serum PTH concentration

97
Medical Management of CRFHormonal 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 CRFHormonal 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 CRFAnabolic steroids
  • Equivocal effectiveness in dogs with CRF
  • Several products
  • Methyltestosterone
  • Stanozolol
  • Oxymetholone
  • Nandrolone decanoate

100
Medical Management of CRFAnabolic steroids
  • 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

101
Medical Management of CRFBlood 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 13134, 1999
103
Medical Management of CRFBlood Pressure
Assessment
  • Patient, trained technician
  • Quiet, undisturbed environment
  • Sufficient time for acclimation
  • Correct cuff size
  • Several sequential measurements
  • Average sequential readings

I dont think hes waving at you
104
Medical Management of CRFHypertension To treat
or not?
  • BP consistently
  • gt 170 mm Hg
  • High BP and fundic lesions
  • Retinal hemorrhage
  • Vascular tortuosity
  • Retinal edema
  • Intra-retinal transudate
  • Retinal detachment

105
Medical Management of CRFTreatment 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 CRFTreatment 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 CRFTreatment 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 CRFTreatment of
Hypertension
  • Other anti-hypertensive agents
  • Hydralazine (arterial vasodilator)
  • Prazosin (?1 adrenergic blocker)
  • Propranolol (nonspecific ? blocker)

109
Medical Management of CRFAvoid stress
  • Manage on outpatient basis whenever possible
  • Consider SQ fluids at home by owner

110
Medical Management of CRFWhy 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 CRFFindings 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
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