CHRONIC KIDNEY DISEASE

1
CHRONIC KIDNEY DISEASE

• Reinaldo Rosario MD, FASN
• Renal Electrolyte Hypertension Consultants
  (REHC)

2
NATURAL HISTORY OF RENAL DISEASE

• Initial injury to the kidney
• Adaptive hyperfiltration
• Long-term damage to the remaining nephrons
  proteinuria and progressive renal insufficiency
• Advanced renal disease dysfunction volume
  overload, hyperkalemia, metabolic acidosis, HTN,
  anemia and bone disease
• End Stage Renal Disease (ESRD)

3
CKD - DEFINITION

• Evidence of structural or functional kidney
  abnormalities that persists for at least 3
  months, with or without a decreased GFR.
• GFR lt60 mL/min/1.73m² for 3 months, with or
  without kidney damage
• Prevalence 4.7 or 8.3 million
• NKF. Am J Kidney Dis. 200239(supp1)S1

4
STAGES OF CHRONIC KIDNEY DISEASE
5
PREVALENCE OF CKD

• NKF. Am J Kidney Dis. 200239(supp 1)S1

6
ESRD

• As of Dec. 31 2006 506,256 dialysis pts
• In 2006 alone, 110,854 pts entered the ESRD
  program
• Medicare expenditure - 22.7 billion in 2006
• Projected number of ESRD pts by 2010 651,330
  and Medicare cost in excess of 28 billion
  dollars

• U.S. Renal Data System USRDS 2006

7
ESRD

• Annual mortality rate for all ESRD pts on
  treatment is 20-fold higher than the general
  population
• At age 45 life expectancy
  - General population
  
• 34.7 years
• - ESRD
• 6.2 years on dialysis / 19.5 years
• with a functioning kidney graft

• U.S. Renal Data System USRDS 2002

8
CAUSES OF DEATH IN ESRD

• U.S. Renal Data System USRDS 2002

9
MULTIPLE RISK FACTORS FOR CKD

• Diabetes
• Hypertension
• Autoimmune disease
• Systemic infections
• Exposure to drugs associated with acute decline
  in kidney function
• Recovery from acute kidney failure

• Older age
• Family history of kidney disease
• Reduced kidney mass
• Racial/ethnic background
• Smoking

• NKF. Am J Kidney Dis. 200239S46
• Pinto-Sietsma. Ann Intern Med. 2000133585

10
EVALUATING PATIENTS AT RISK FOR CKD

• Evaluating risk factors and identifying GFR
  declines are essential to the prompt and
  appropriate management of CKD
• GFR or age/weight-sensitive eGFR
• Blood pressure
• Glucose
• Urinalysis
• Microalbuminuria/proteinuria

11
COMORBIDITIES AND COMPLICATIONS OF CKD

• Anemia
• Hypertension
• Cardiovascular disease
• Diabetes
• Osteodystrophy

• Malnutrition
• Metabolic acidosis
• Dyslipidemia
• Deficits in functioning and well-being

• Zabetakis. Am J Kidney Dis. 200036(suppl 3)S31
• NKF. Am J Kidney Dis. 200239S17

12
DELAYED DIAGNOSIS OF CKD LEADS TO UNDERUSE OF
INTERVENTIONS

• Lack of interventions to treat HTN, CVD, DM,
  anemia, and malnutrition
• Under use and delayed consultations with
  nephrologists, cardiovascular specialists, or
  dietitians
• Lack of patient education
• Lack of a permanent vascular access at initiation
  of hemodialysis

13
OPTIMAL CKD PATIENT CARE

• Early detection of CKD
• Delay Prevent
  Treat Prepare
• progression complications
  comorbidities or RRT
• ACE inhibitors Anemia
  Cardiac disease Educate
  patient
• BP control Malnutrition
  Vascular disease Select RRT
  modality
• Blood sugar Osteodystrophy
  Diabetes Create
  access
• control and initiate
• Acidosis dialysis
  in a
• Protein timely fashion
• restriction?
  
• Pereira. Kidney International.
  200057351

14
MANAGEMENT OF PATIENTS WITH CKD

• Blood pressure control
• Diabetes control
• Cardiovascular disease management
• Anemia management
• Iron management
• Vitamin D and vital bone protection
• Eating well and exercise
• Access planning

15
CARDIOVASCULAR RISK AND GFR

• Go AS. N Engl J Med 20043511300

16
CARDIOVASCULAR MORTALITY AND HYPERTENSION

• Lewington S . Lancet 2002 360 1903-13.

17
PREVALENCE OF HYPERTENSION IN CKD

• 1795 patients with kidney diseases were screened
• GFR range 13-55 mL/min/1.73m²
• ? BP in 83 of patients (n1494)

• Buckalew. Am J Kidney Dis 199628811.

18
BLOOD PRESSURE IS POORLY CONTROLLED IN CKD

• Coresh. Arch Intern Med. 20011611207

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Aggressive Blood Pressure GoalsConsensus Across
Treatment Guidelines
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BLOOD PRESSURE CONTROL IN CKD GOALS

• NKF. Am J Kidney Dis. 20023a(suppl 1)S1

21
?GFR ?BP MEDS

• Nephsap. American Society of Nephrology 2005
  4101

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BP CONTROL INTERVENTIONS

• ACE inhibitors
• Angiotensin-receptor blockers (ARBs)
• Calcium channel blockers (CCBs)
• Diuretics
• Low-sodium diet
• Combination therapy

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DIABETES MELLITUS PREDICTIONS

• In the next 10 years there will be a 50 increase
  in the number of diabetics.
• 25 to 40 of these individuals will develop
  kidney disease.
• Obesity, poor dietary habits, lack of physical
  activity, family history are risks.

29
THE EPIDEMIC OF DIABETES

• Prevalence increased by 40 1990-99.
• Estimated increase by 165 2000-2050.
• Individuals born in 2000 risk developing
  diabetes 32.8 males, 38.5 females. Hispanic
  lifetime risk 45.4 males, 52.5 females.

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Adults With Diagnosed Diabetes
1990
No dataavailable
Less than 4
46
Above 6
Includes women with a history of gestational
diabetes.
Mokdad AH et al. Diabetes Care.
200023(9)1278-1283.
31
Adults With Diagnosed Diabetes
2000
46
Above 6
Includes women with a history of gestational
diabetes.
Mokdad AH et al. JAMA. 2001286(10)1195-1200.
32
DIABETIC KIDNEY DISEASE SIGNIFICANCE

• Accounts for 40-50 total kidney failure in the
  United States
• 40-50 of TYPE 1 Patients and 40 of TYPE 2
  Patients will develop clinical diabetic kidney
  disease.
• Diabetes affects certain ethnic groups more
  frequently than caucasians native americans 7x,
  hispanics and latinos 4-5x, african americans 4x.

33
ANEMIA IN PATIENTS WITH CKD

• N 5222
• CKD
• SCr 1.5-6.0 mg/d(women)
• SCr 2.0-6.0 mg/dL (men)

• McClellan, NKF. 2002

34
Severe Anemia is Common at the Start of Dialysis

• Obrador. Kidney Int. 2001 601875

35
ANEMIA SIGNIFICANTLY IMPACTS CKD PATIENTS

• Macdougall. Semin Oncol. 199825(suppl 7)40

36
EVALUATION OF ANEMIA

• Hemoglobin and/or hematocrit
• Red-blood-cell indices
• Reticulocyte count
• Iron parameters
• Test for occult-blood in stool

• NKF. Am J Kidney Dis. 200137S192

37
TREATMENT OF ANEMIA

• Iron supplementation (IV/PO)
• Erythropoiesis stimulating agents

38
IRON DEFICIENCY IN CKD

• Preexisting Iron Deficiency
• Poor nutrition
• Blood loss

• Iron deficiency with erythropoiesis-stimulating
  agents
• Increased iron needs

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ASSESSMENT OF IRON STATUS

• Frequently used tests
• Serum ferritin
• Transferrin saturation

• Target
• 100 ng/mL
• gt20

• Additional measurements
• Reticulocyte Hb content
• Hypochromic RBCs
• Erythrocyte ferritin

• NKF. Am J Kidney Dis. 200137(suppl 1)S182
• Macdougall. Curr Opin Hematol. 19996121
• Goodnough. Blood. 200096823

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POSSIBLE INADEQUACY OF ORAL IRON

• Low intestinal absorption of oral iron, even in
  healthy persons
• Poor patient adherence
• Intravenous iron has improved anemia in CKD and
  ESRD when oral iron has failed

• NKF. Am J Kidney Dis. 200137 (suppl 1)S182
• Silverberg. Kidney Int. 199955(suppl 69)S79

41
Anemia and LVH
Prevalence of LVH ( Patients)

• CrCl

Mean Hb (g/dL) 14.1 13.2
12.5 11.4

• Levin. Nephrol Dial Transplant, 200116 Suppl 2)
  7.

42
LVH and CKD

• LVH is an independent risk predictor of cardiac
  death
• HTN, anemia and diabetes are modifiable
  predictors of LVH
• Blood pressure increase is associated with 3
  increase in LVH risk
• Hb decrease of 1 g/dL is associated with 6
  increase in LVH risk

• Greaves. Am J Kid Dis. 1994 24768
• Levin. Am J Kid Dis. 1996 27347.

43
Normal Hematocrit Trial

• Study Objective Whether normal Hct value should
  be the target level in dialysis patients
• Study Design 1233 HD patients with cardiac
  disease. Baseline Hct. 27- 33. Mean age 65
  years.
• Primary Endpoint time to death or first nonfatal
  myocardial infarction
• Methods Patients randomly assigned to achieve
  and maintain a Hct of 42 or 32 WITH EPO tx
• Results Study terminated early (29 months) due
  to increase mortality in the group targeted for
  normal Hct level.

• N Eng J Med 1998 339584

44
CHOIR Study (Correction of Hemoglobin and
Outcomes in Renal Insufficiency)

• Study Objective Whether a normal or near-normal
  Hb value should be the target level in
  pre-dialysis pts with CKD
• Study Design 1432 CKD patients (eGFR 15-50
  mL/min) with Hb lt 11g/dL
• Primary Endpoint Composite of death, myocardial
  infarction, stroke, and hospitalization for heart
  failure
• Methods Randomization to achieve target Hb of
  either 13.5 or 11.3g/dL
• Results Study terminated early(16 months) due to
  higher number of events in the high Hb group.

• Drueke, TB et al. N Engl J Med 20063552071

45
CREATE Study(Cardiovascular Risk Reduction by
Early Anemia Treatment with Epoietin Beta)

• Study Objective Whether a normal or near-normal
  Hb value should be the target level in
  pre-dialysis pts with CKD.
• Study Design 603 pts with GFRs between 15-35
  mL/min
• Primary Endpoint Composite of eight CV events
• Methods Randomization to normal Hb (13-15 g/dL)
  or subnormal (10.5 11.5 g/dL)
• Results At 3 years similar risk of experiencing
  the primary endpoint in bot groups ( HR of 0.78,
  95 CI 0.53-1.14)

• Singh, AK et al. N Engl J Med 2006 3552085

46
Ongoing and Future Studies

• TREAT study Randomized, placebo-controlled
  trial in Predialysis pts with DM type 2 to Hb 13
  or greater than9 g/dL.
• Primary endpoint is overall mortality and
  nonfatal CV events.
• NEPHRODIAB2 trial Prospective randomized
  open-label trial in CKD stage 3 and 4 with DM
  type 2. Randomization to Hb 13-14.9 g/dL or 11-12
  g/dL.
• Primary endpoint is decline in kidney function.
• Secondary outcomes include mortality

47
Anemia current recommendations

• Close monitoring of predialysis Hb levels
• Erythropoietic agents rather than blood
  transfusions
• Target Hb should generally be in the range of 11
  12 g/dL and should not exceed 13 g/dL.
• Supplemental iron

48
SECONDARY HYPERPARATHYROIDISM

• Most common form of renal osteodystrophy
• Prevalence
• 47 of 176 patients with ESRD had a PTH level
  more than three times the normal amount

• Mizumoto. Nephrol Dial Transplant. 199491751
• Billa. Perit Dial Int. 200020315

49
VITAMIN D DEFICIENCY AND PHOSPHATE RETENTION

• CKD
• Vitamin D Deficiency Phosphate Retention
• Hypocalcemia
• Hyperparathyroidism
• Osteodystrophy

• Liach. In Brenner. The Kidney. 19962187
• Schomig.Nephrol Dial Transplant. 200015(suppl
  5)18

50
Hyperphosphatemia

• Begins early in renal disease
• Intimately related to secondary
  hyperparathyroidism which contributes to release
  of calcium and phosphorus from bone
• Elevated Ca x PO4 promotes precipitation of such
  in arteries, joints, soft tissues and the vicera
• Ca x PO4 gt55 associated with increased mortality,
  similar to that observed with elevated PO4 level
  alone

• Menon, V. Am J Kidney Dis 2005 46455.

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MANAGEMENT OF VITAMIN D DEFICIENCY AND PHOSPHATE
RETENTION

• Vitamin D analogs
• Low phosphate diet (800 mg/day)
• Phosphate binders (calcium and non-calcium based)
• Calcium

• Coburn. J Am Soc Nephrol. 19989S71
• Schroeder. Nephrol Dial Transplant. 200015460
• Chertow. Clin Nephrol. 19995118

52
Phosphate Binders
53
ACID/BASE BALANCE

• Renal NH4
• Excretion
• 40 mEq/day
• Endogenous Renal Net Acid
• H Production Renal Excretion
• 70 mEq/day Excretion 70
  mEq/day
• 30 mEq/day
• Normal Acid/Base Balance
• HCO3 24 mEq/L

• Alpem. Am J Kidney Dis. 199729291

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CONSEQUENCES OF METABOLIC ACIDOSIS

• Abnormal renal handling of ions
• ? tubular-phosphate reabsorption
• ? filtered load of calcium and phosphate
• ? tubular-calcium reabsorption
• Increased resorption of bone
• Increased muscle catabolism

• Franch. J Am Soc Nephrol. 19989S78

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TREATMENT OF METABOLIC ACIDOSIS IN CKD

• Goal
• Serum HCO3- gt 20 mEq/L
• pH gt 7.35
• Agents
• Sodium bicarbonate tablets
• (650 mg 8 mEq HCO3-)
• Sodium citrate (Shohls solution)
• Dose of HCO3-
• 1.0 1.5 mEq/kg/day
• Dependent upon initial serum HCO3- and degree of
  renal insufficiency

• Dubose TD. Harrisons Principles of Internal
  Medicine. 1998277

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Recommendations in Metabolic Acidosis Treatment

• Alkali therapy to maintain plasma bicarbonate
  concentration above 22 meq/L (K/DOQI guideline
  recommendation)
• Sodium bicarbonate Agent of choice may cause
  bloating.
• Sodium Citrate Avoid when also taking
  aluminum-containing anti-acids since it markedly
  enhances aluminum absoption

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EATING WELL AND EXERCISE

• Protein malnutrition is common in CKD
• Consider dietary protein restriction
• Properly monitored by experienced dietitian
  and nephrologist
• May improve long-term survival of patients
• Exercise
• Improves physical functioning
• Improves cardiovascular health

• Bailey. Therapy in Nephrology and Hypertension.
  1998474

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EXERCISE

• ? Physical functioning
• ? Blood pressure control
• ? Muscle, bone strength
• ? Level of cholesterol and triglycerides
• Better sleep
• ? Control of body weight

• NKF. Staying fit with Kidney Disease

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VASCULAR ACCESS FOR HEMODIALYSIS

• Establish communication between nephrologist and
  PCP
• Preserve an arm no intravenous injections or
  blood draws
• Refer to surgeon for fistula when SCr gt4mg/dL,
  CrCl lt25 mL/min, or dialysis anticipated within 1
  year
• Fistula may take 3 to 4 months to mature

• NKF. Am J Kidney Dis. 200137(suppl 1)S147

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TEAM APPROACH ROLE OF PRIMARY PHYSICIAN AND
NEPHROLOGIST IN CKD

• Nephrologists
• Assist in development of care strategy
• Aid recommendation and implementation of patient
  care
• Provide role-specific patient education

• Primary Physician
• Screen and identify risk factors of CKD
• Provide ongoing management of patients with CKD
• Provide role-specific patient education

61
BENEFITS OF EARLY INTERVENTION IN THE MANAGEMENT
OF CKD

• Delayed progression of CKD
• Improved teamwork between physicians
• Decreased risk of cardiovascular complications
• Improved dialysis outcomes
• Better educated and prepared patients

• Pereira. Kidney Int. 200057351.