Chronic Kidney Disease

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Chronic Kidney Disease

• Amret T. Hawfield, M.D.,
• Section on Nephrology

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Outline

• Review methods of measuring kidney function
• Define the stages of kidney disease
• Review the medical complications of chronic
  kidney disease and their treatment
• Anemia
• Secondary hyperparathyroidism
• Metabolic acidosis
• Malnutrition
• Natural history and management of Diabetic
  Nephropathy

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• Measurement of Kidney Function

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Measuring kidney function

• Serum creatinine
• Estimation equations for GFR
• MDRD formula (full and short equations)
• Cockcroft and Gault equation
• 24 hour urine collection of urea and creatinine
• Gold Standard
• Radioactive 125I-iothalamate, inulin

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• Can have normal creatinine and abnormal GFR
• Change in GFR larger when creatinine lower
• Creatinine depends on clearance and generation

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Cockcroft and Gault Equation

• (140 - age years) body weight kg
• Serum creatinine mg/dl 72
• Limitations
• Can use only in steady state
• Assumes ambulatory patient with normal muscle
  mass
• Overestimates renal function if
• Wheelchair bound
• Minimal ambulation due to comorbid medical
  conditions
• Amputee

GFR (ml/min)
0.85 in females
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Cockcroft and Gault Equation

• GFR in two patients with a SCr of 1.0 mg/dl
• 30 YO M weighing 72 kg
• CCr (140 - 30) (72) 110 ml/min
• (72) (1)
• 75 YO F weighing 50 kg
• CCr (140 - 75) (50) 0.85 38 ml/min
• (72) (1)

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Comparison of estimated GFR with measured GFR
(MDRD Study)
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MDRD equation

• MDRD GFR / 1.73m2 170 Scr - 0.999 Age -
  0.176
• 0.762 if female 1.180 if black BUN -
  0.170
• Serum albumin 0.318
• www.kidney.org/professionals/KDOQI/gfr_calculator.
  cfm

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24 Hour Urine Collection

• Use in place of estimating equations for GFR if
  the patient has decreased muscle mass
• Wheelchair bound
• Chronic disease that limit mobility
• Creatinine is filtered and secreted by the kidney
• Urine creatinine levels overestimate true GFR
• Urea is filtered and reabsorbed by the kidney
• Urine urea levels underestimate true GFR
• Therefore, use the average of urea and creatinine
  clearances to determine GFR in patients with
  moderate to severe CRI
• Cx(Ux x V)/Px expressed in ml/min/1.73 m2

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• Stages of CKD

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Definition and Stages of Chronic Kidney Disease
(CKD)
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Assessment of proteinuria

• Under most circumstances, untimed (spot) urine
  samples should be used to detect and monitor
  proteinuria
• First morning specimens are preferred, but random
  specimens are acceptable
• Patients with a positive dipstick test should
  undergo confirmation of proteinuria by a
  qualitative measurement
• Patients with two or more positive quantitative
  urine test spaced at least 1 week apart should be
  diagnosed as having persistent proteinuria and
  should undergo further evaluation and management
• K/DOQI guideline 5 Am J Kidney Dis 39S26, 2002

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Markers of chronic kidney diseaseother than
proteinuria

• In patients with kidney disease and in individual
  patients at increased risk of developing kidney
  disease
• Urine sediment exam or dipstick for red blood
  cells and white blood cells
• In select patients, imaging studies of the
  kidneys should be performed
• For example, ultrasound to diagnose polycystic
  kidney disease
• K/DOQI guideline 6 Am J Kidney Dis 39S26-27,
  2002

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Prevalence of Stages of CKD andLevels of Kidney
Function in the U.S.
NHANES III 1988 1994
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Incidence and Prevalence of End-Stage Renal
Disease in the US
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• Complications of CKD

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Medical complications of CKD (NHANES III)
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Number of CKD complications (NHANES III)
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Prevalence of HTN by GFR (NHANES III)
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• Hypertension in CKD

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Pathophysiology of Hypertension in CKD

• Some patients have HTN that leads to CKD
• Hypertensive nephrosclerosis
• More patients have HTN because of CKD
• Sodium retention
• Increased activity of the renin-angiotensin
  system (probably due to regional ischemia induced
  by scarring) despite normovolemia
• Enhanced activity of the sympathetic nervous
  system
• Secondary hyperparathyroidism raises the
  intracellular calcium concentration, which can
  lead to vasoconstriction and hypertension
• Treatment with erythropoietin
• Impaired nitric oxide synthesis and
  endothelium-mediated vasodilatation has been
  demonstrated in patients with uremia

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JNC 7 Compelling Indications for treatment of
hypertension
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BP management in CKD

• First line
• GFR gt 20 ACEI/ARB
• Tolerate 30 increase in crt or increase of 1.0
  if gt 2.0 t baseline
• Second line
• GFR gt 40 thiazide GFR lt 40 loop
• Loop twice daily (early afternoon second dose)
  may need to add metolazone
• Third Line
• NDHPCCB (dilt, verapamil)
• If low HR consider CCB such as norvasc
• Also limit Sodium intake to lt 2300 mg daily (lt
  100mEq)
• May make diuretics and ACEI/ARB ineffective
• Avoid NSAID and sympathomimetics (sudafed,
  cocaine)
• Goal lt 130/80

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• Anemia

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Prevalence of anemia in CKD patients
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Characteristics of Anemia of CKD

• Normochromic, normocytic red blood cells
• Reticulocyte count lt 50 of normal for degree of
  anemia
• Absolute or relative erythropoietin deficiency
• EPO produced primarily in the kidney (90) in
  pericapillary endothelial cells
• EPO production directly related to the deficit in
  tissue oxygenation
• Acts on the progenitor cells of the bone marrow
• Shortened red blood cell survival
• Blood loss due to uremic platelet dysfunction
• Uremic inhibitors of erythropoiesis
• ACEI

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Treatment of Anemia of CKD

• Rule out other causes of anemia
• Blood loss, folate or vitamin B12 deficiency,
  aluminum toxicity, low bone turnover states
• Do not have to measure EPO level
• Correct iron deficiency
• HD ferritin gt 200 T sat gt 20
• CKD and PD ferritin gt 100 T sat gt 20
• Caution with IV iron when ferritin gt 500
• K/DOQI guideline 8 Am J Kidney Dis 39S29, 2002,
  Hemoglobin target Update September 2007

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Iron other facts

• Vitamin C (250 mg per iron pill) should be
  co-administered with iron in achlorhydric pt(H2,
  ppi, after gastric surgery)
• Take thyroid hormone separate from iron
• IV iron contraindicated during active infection

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ESA therapy

• Begin EPO therapy at 50 100 U/kg/week
• Aranesp 0.45 mcg/kg/week (40 300 mcg SQ q 2 4
  weeks)
• Monitor hemoglobin every two weeks until both
  hemoglobin and EPO dose are stable, then monitor
  hemoglobin monthly
• Goal Hemoglobin 11 12
• Increased risk of blood clots, stroke, heart
  attacks with Hgb gt 13
• Hgb elevations of 1 2 g/dL/month generally
  tolerated well

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• Nutrition

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Relationship between serum albumin levels and GFR
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Treatment of poor nutritional status in CKD
patients

• Protein energy malnutrition develops during the
  course of kidney disease and is associated with
  adverse outcomes
• Low protein and calorie intake is a important
  cause of malnutrition in chronic kidney disease
• Patients with GFR lt 60 ml/min/1.73m2 should
  undergo assessment of dietary protein and energy
  intake and nutritional status
• Patients with decreased dietary intake or
  malnutrition should undergo dietary modification,
  counseling or specialized nutrition therapy
  (covered by Medicare)
• K/DOQI guideline 9 Am J Kidney Dis 39S29, 2002

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Fluid and electrolyte abnormalities in CKD

• Volume overload
• Metabolic acidosis
• Hyperkalemia
• Secondary hyperparathyroidism

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Vitamin D Metabolism Normal Physiology
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• Bone Metabolism
• Vitamin D Deficiency
• Secondary Hyperparathyroidism
• Renal Osteodystrophy
• (Adynamic Bone Disease-gt Osteitis Fibrosa
  Cystica)

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Secondary Hyperparathyroidism
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Secondary Hyperparathyroidism Pathophysiology
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Clearance of serum phosphorus by GFR level
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Clinical consequences of secondary
hyperparathyroidism

• Bone disease
• Soft tissue calcification
• Coronary arteries
• Heart valves
• Other major arteries can lead to amputations
• Proximal myopathy
• Pruritus
• Skin ulceration and soft tissue necrosis
  (calciphylaxis or calcific uremic arteriolopathy)

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Calciphylaxis
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Monitoring of Ca, Phos and PTH
www.kidney.org KDOQI guidelines
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Treatment of secondary hyperparathyroidism

• Evaluate for vitamin D deficiency (vit D25)
• Control serum phosphate levels
• Dietary protein restriction
• Phosphate binders
• Control metabolic acidosis
• Dietary protein restriction
• Bicarbonate therapy
• Suppress PTH levels
• Active oral vitamin D sterol supplementation
• Calcitriol
• Doxercalciferol (Hectorol)
• Paricalcitol (Zemplar)
• Calcimimetic
• Cinacalcet (Sensipar)
• Subtotal parathyroidectomy
• K/DOQI guideline 10 Am J Kidney Dis 39S29, 2002

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Phosphate binders

• Bind phosphate to a cation in the intestinal
  lumen
• Insoluble complex is excreted in the feces
• Therefore, patient MUST take binders with meals
  in order for binders to be effective!
• Avoid more than 2 gm total Calcium Daily
• Binder types
• Calcium Calcium carbonate (Oscal, Tums)
• Calcium acetate (Phos-Lo)
• Calcium citrate (Citrical)
• Aluminum Aluminum hydroxide (Alu-Tab, Amphogel)
• Aluminum carbonate (Basagel)
• Lanthanum Lanthanum carbonate (Fosrenol)
• Polymers Sevelamer (Renagel, Renvela)

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• Metabolic Acidosis

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Metabolic Acidosis

• Early failure of Bicarb reclamation in PT, later
  failure of H excretion distally

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Summary Management of CKD

• Control BP lt 130/80 and control proteinuria
• ACEI, ARB
• Diuretic
• Diltiazem, verapamil
• Control Protein intake but avoid malnutrition
• 2 - 3 gm Sodium diet
• Control cholesterol
• Smoking cessation
• Reduce obesity
• Correct severe anemia
• Avoid NSAIDs, fleets, IV contrast and gadolinium
• Use NaHCO3 to correct acidosis
• Control high phos and PTH

Caution with Crestor pravastatin and
atorvastatin do not require dose adjustment
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• Diabetic Kidney Disease

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AJKD Atlas of USRDS Data from 2006 published
January 2007
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Diabetic nephropathy

• Most common etiology of ESRD in the United States
• Characterized by persistent albuminuria
  (gt300mg/24 hour) on atleast 2 occasions separated
  by 3 6 months
• This is equivalent to 500 mg/24 hours
• Usually develop HTN, progressive proteinuria and
  decline in GFR

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Cumulative Incidence of Diabetic Nephropathy
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Annual Incidence of Diabetic Nephropathy
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Renal Management of Type I DM

• Similar approach can be used for type 2 DM
• For reference
• Low protein diet controversial and depends on pt
  nutritional status
• NO METFORMIN

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Prevention of Progressive Diabetic Nephropathy

• Intensive control of blood sugar
• Annual screening for microalbuminuria in patients
  with IDDM for more than 5 years and/or a family
  history of renal disease or hypertension
• Angiotensin-converting enzyme inhibitor (ACE-I)
  or angiotensin receptor blocker (ARB) therapy for
  blood pressure control and reduction of
  proteinuria
• Close monitoring of serum creatinine and
  potassium levels after starting ACE-I or ARB
  therapy
• ACE-I and ARB therapy is contraindicated in the
  presence of pregnancy

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Prevention of Progressive Diabetic Nephropathy

• Blood Sugar control (KDOQI recommends Hgb A1c lt
  7.0)
• Screen for microalbuminuria
• ACEI/ARB
• Monitor creatinine and potassium
• ACE-I and ARB therapy is contraindicated in the
  presence of pregnancy
• Control BP lt 130/80, 125/75 if proteinuria gt 1 gm
• Cessation of smoking
• Consider Dietary protein restriction 0.8g/kg/day
• Lipid control

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Chronic kidney disease Summary (1 of 2)

• Present in about 10 of adults
• Increased risk in elderly, diabetics
• Use estimated GFR, not serum creatinine level, to
  determine kidney function
• Numerous complications of CKD
• Hypertension
• Anemia
• Mineral metabolism derangements
• Acid-base and electrolyte abnormalities

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Chronic kidney disease Summary (2 of 2)

• Treatment of these complications can slow the
  progression of kidney disease and reduce the rate
  of non-renal complications
• HTN ACE and ARBs in patients with glomerular
  diseases can slow loss of kidney function
• Anemia Correction can prevent left ventricular
  hypertrophy and may decrease the risk of
  cardiovascular events
• Secondary hyperparathyroidism Correction can
  decrease risk of cardiovascular disease (vascular
  calcification and inflammation) and bone disease

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Vitamin D Deficiency/Insufficiency