Chronic renal failure

Stephen P. DiBartola, DVM Department of Veterinary Clinical Sciences College of Veterinary Medicine Ohio State University Columbus, OH 43210

The Nephronauts

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

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

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

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

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

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

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

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

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!

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

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)

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

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

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

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

Progression of renal disease: Diet

Protein Phosphorus Calories Lipids

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)

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

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

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

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

Progression of renal disease: Systemic complications of renal insufficiency

Systemic hypertension Urinary tract infection Fluid, electrolyte, and acid-base abnormalities

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

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

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

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

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

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

Different responses for different solutes

No regulation (A) Complete regulation (C) Limited regulation (B)

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

BUN, creatinine (no regulation)

Azotemia does not develop until 75% or more of the nephron population has become nonfunctional

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

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

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

If GFR is decreased, how can polyuria develop?

Normal Diseased

Number of nephrons Total GFR (ml/min) SNGFR (nl/min) Urine output (ml/day) Urine output (ml/min) Urine output per nephron (nl/min) % Filtered water reabsorbed % Filtered water excreted

1,000,000 40 40 333 0.23 0.23 99.4 0.6

250,000 15 60 1,000 0.69 2.76 95.4 4.6

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

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)

Ca+2 balance in CRF: Complete regulation

Normal calcium balance depends on interactions of PTH, calcitriol, and calcitonin acting on kidney, gut, and bone

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

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

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

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)

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

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

Renal secondary hyperparathyroidism

Renal secondary hyperparathyroidism

Renal secondary hyperparathyroidism

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

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)

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

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

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-

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

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)

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)

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

Gastrointestinal disturbances in CRF Oral lesions

Foul odor Stomatitis Erosions and ulcers Tongue tip necrosis (fibrinoid necrosis and focal ischemia)

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

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

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

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

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

Hypertension in CRF Clinical Manifestations

Ocular
Blindness Retinal detachment Retinal hemorrhages Retinal vascular toruosity

Cardiovascular
LV enlargement Medial hypertrophy of arteries Murmurs and gallops

Clinical history in CRF

Findings are non-specific Polyuria and polydipsia Vomiting (dogs) Anorexia Weight loss Lethargy

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)

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

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

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?

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)

Conservative medical management of CRF: Protein restriction?

Relieve uremic symptomatology and improve patient well-being Can hyperfiltration be reduced?

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

Commercial diets for CRF management (dry matter basis)

Dog
Protein Phosphorus Sodium 15-17%

Cat
25-28%

0.2-0.3% 0.5-0.6% 0.2-0.3% 0.2-0.3%

Conservative medical management of CRF: Monitoring patient response

Stable body weight Stable serum albumin concentration Decreased BUN concentration Stable serum creatinine concentration

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

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)

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

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)

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

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

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

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

Conservative medical management of CRF: Phosphorus restriction

Aluminum hydroxide
Effective phosphorus binder Risk of aluminum intoxication? Becoming difficult to find in stores

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

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

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

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)

Medical Management of CRF:

H2 Receptor Blockers

Famotidine
Once per day dosing 1 mg/kg

Medical Management of CRF:

Endocrine replacement therapy

Erythropoietin Calcitriol

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!

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

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

Medical Management of CRF

Erythropoietin: Adverse Effects

Antibody formation Vomiting Seizures Hypertension Uveitis Hypersensitivity-like mucocutaneous reaction

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

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)

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

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

Medical Management of CRF

Hormonal Replacement: Calcitriol
Extremely low dosage required: 2.5 to 3.5 ng/kg/day Requires reformulation by compounding pharmacy
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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

Medical Management of CRF:

Anabolic steroids Equivocal effectiveness in dogs with CRF Several products
Methyltestosterone Stanozolol Oxymetholone Nandrolone decanoate

Medical Management of CRF:

Anabolic 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

Medical Management of CRF:

Blood Pressure Assessment

Oscillometric or Doppler methodology acceptable in dogs Doppler methodology more reliable in cats

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

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 dont think hes waving at you

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

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)

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

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

Medical Management of CRF:

Treatment of Hypertension

Other anti-hypertensive agents

Hydralazine (arterial vasodilator) Prazosin (1 adrenergic blocker) Propranolol (nonspecific blocker)

Medical Management of CRF: Avoid stress

Manage on outpatient basis whenever possible Consider SQ fluids at home by owner

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

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