Shagun Chopra m.D.

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Chronic Kidney DiseaseThe Recognized Epidemic

• Shagun Chopra m.D.
• Director of dialysis Transplant NMcsd
• Assistant professor of medicine ucsd
• Assistant professor of medicine usuhs

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Outline

• ESRD
• What is CKD?
• Epidemiology of CKD?
• What does CKD predict?
• What can I do for my CKD patient?
• Where are we going with CKD?

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The number of individuals initiating treatment
for end-stage renal disease (ESRD) in the United
States, according to cause and calendar year,
1980 to 1999 (RenDER system of the United States
Renal Data System (USRDS) (http//www.usrds.org)..
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ESRD prevalence counts and prevalence rates in
the U.S. Graphic from USRDS 2010 Annual Report
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Medicare expenditures on ESRD, not adjusted for
inflation. Graphic from USRDS 2010 Annual Report
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ESRD

• Why is the life expectancy so poor?
• Why doesnt a drug change survival in the
  dialysis patient?
• Why is the CV risk so high?
• Is it too late?
• When should we start?

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Measurement of GFR

• Inulin clearance- Gold standard
• Cockroft-Gault 1976. Measures CrClr. Studied in
  249 indiv. No AA. Overestimates due to secretion
  as well in edematous, hypoalbuminemic and
  nephrotic states
• MDRD-1999. 1628 CKD patients. 6 DM. Underest if
  gt60. Overestimates in malnourished, vegetarian
  diet and nephrotic states.
• Cystatin C. made by nucleated cells. Altered by
  inflammatory states, leukocytosis, age, gender,
  diabetes etc. Not FDA approved.

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CKD Is Common 27 Million Americans Have CKD
Prevalent dialysis patients. 1. US Renal Data
System. USRDS 2007 Annual Data Report Atlas of
Chronic Kidney Disease and End-Stage Renal
Disease in the United States. 2007 2. Coresh J,
et al. JAMA. 20072982038-2047 3. Available at
http//www.kidney.org/news/newsroom/newsprint.cfm?
id51. Accessed April 18, 2008.
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CKD CVD
DM, HTN Anemia Coronary Calcification Cax Po4
lt55 Worsening HTN Nephrotic syndrome Hyperlipidemi
a
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Management of CKD
Etiology of CKD/Progression Anemia Access Adequacy
BP Bone Mineral disorder Cardiovascular
Risk Diet/Nutrition Medication Reconciliation
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Etiology/Progression

• In the MDRD study Rate of Progression of CKD
  varies based on
• Underlying disease, proteinuria, Stage of CKD,
  comorbidities and treatments.
• Retrospective analysis of MRFIT data showed that
  1proteinuria-3.1, 2 15.7, GFR 60-30 2.4,
  GFR lt30 41 over a 10 year period.

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Management of CKD
Etiology of CKD/Progression Anemia Access Adequacy
BP Bone Mineral disorder Cardiovascular
Risk Diet/Nutrition Medication Reconciliation
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TREAT
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Management of CKD
Etiology of CKD/Progression Anemia Access Adequacy
BP Bone Mineral disorder Cardiovascular
Risk Diet/Nutrition Medication Reconciliation
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Access

• GFR lt25ml/min or rapid progression consider
  placement of hemodialysis access.
• Transplant referral at GFRlt30 and placement on
  transplant list at lt20.
• AVF
• AVG
• Tunneled Catheter
• Periotenal dialysis

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Adequacy

• Is the GFR adequate to avoid volume overload,
  uremic sxs- nausea, malnutrition, pericarditis,
  lethargy, hyperk, acidosis. Most common reasons
  to start- malnutrition and volume overload.
• ?GFRlt15ml/min per NKF are indications to consider
  the risks and benefits to initiating dialysis.
• European Best Practice guidelines state
  GFRlt6ml/min and consider at 8-10

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Management of CKD
Etiology of CKD/Progression Anemia Access Adequacy
BP Bone Mineral disorder Cardiovascular
Risk Diet/Nutrition Medication Reconciliation
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Safety

• NEJM 2006, Efficacy and Safety of Benazepril for
  advanced renal insuff
• Benazepril vs placebo and both groups had
  BPlt130/80. Both groups had 1.5gm proteinuria and
  GFR 25ml/min.
• Benazepril reduced protenuria and lowered
  progression to ESRD and adverse events (hyperk)
  same.

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BP

• MDRD trial subgroup evaluated aggressive BP
  lowering lt125/75 vs lt130/80 in 585 patients mean
  GFRlt40ml/min
• Decline in GFR was lowest in lt1gm proteinuria but
  no benefit in aggressive BP arm
• Patients with 1-3gm proteinuria had more rapid
  progression and a modest benefit from a lower BP
• gt3gm had the fastest rate of progression but a
  substantial benefit- 10.2 to 6.5ml/min per year.
• Similar trends in another group with GRFlt19ml/min

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Management of CKD
Etiology of CKD/Progression Anemia Access Adequacy
BP Bone Mineral disorder Cardiovascular
Risk Diet/Nutrition Medication Reconciliation
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Alteration of Parathyroid Gland Function
As hyperparathyroidism increases, the parathyroid
gland becomes more and more resistant to vitamin D
Progressive lossof kidney function
Adenomatous Hyperplasia
? 1?-Hydroxylase
? VDR expression
Nodular Hyperplasia
? CaSR expression
Early Nodular
Partial 1,25(OH)2D resistance
Diffuse
Progression to Renal Failure
CaSRcalcium sensing receptor
National Kidney Foundation. K/DOQI clinical
practice guidelines for bone metabolism and
disease in chronic kidney disease. Am J Kidney
Dis. 200342(Suppl 3)S1-S201. Murayama A et al.
Endocrinology. 19991402224-2231. Satomura K et
al. Kidney Int. 198834712716
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Block Calcification and All-Cause Mortality in
CKD Patients New to Dialysis
A Preplanned Secondary Analysis of a Randomized
Trial in 127 Patients New to Hemodialysis
1.00
N127
0.75
CAC0
0.50
Survival Distribution Function
Adjusted Survival by Baseline CAC Scorea
CAC 1-400
0.25
CAC gt400
P0.002
0.00
(n127)
0
6
12
18
24
30
36
42
48
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60
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Months
CACS Coronary artery calcification
score aMultivariable adjusted (age, race, gender,
diabetes). P value represents significance across
all 3 groups. Adapted with permission from Block
GA et al. Kidney Int. 200771(5)438-441.
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Shantouf Calcification and All-Cause Mortality
in Maintenance Hemodialysis Patients
A Cohort Study of 166 Maintenance Hemodialysis
Patients
100 80 60 40 20 0
CAC 0
Event Rate 11.1 (2/18)
CAC 1-100
Event Rate 18.7 (9/48)
Event Rate 32.1 (9/28)
CAC 101-400
Event-Free Survival ()
CAC 400
Event Rate 41.7 (30/72)
0 12 24 36 48 60 72 Follow-up (months)
Event rates increased from 11.1 to 41.7 as CAC
increased across groups.
Adapted with permission from Shantouf RS, et al.
Am J Nephrol. 201031(5)419-425.
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PTH Testing K/DOQI Guidelines
GFR(mL/min/1.73m2)
Measurement of PTH
CKD Stage
3 4 5
30-59 15-29 lt15 or dialysis
Every 12 months Every 3 months Every 3 months
National Kidney Foundation. K/DOQI clinical
practice guidelines for bone metabolism and
disease in chronic kidney disease. Am J Kidney
Dis. 200342(Suppl 3)S1-S201
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PTH Goals K/DOQI Guidelines
GFR(mL/min/1.73m2)
Target intact PTH(pg/mL)
CKD Stage
3 4 5
30-59 15-29 lt15 or dialysis
35-70 70-110 150-300
National Kidney Foundation. K/DOQI clinical
practice guidelines for bone metabolism and
disease in chronic kidney disease. Am J Kidney
Dis. 200342(Suppl 3)S1-S201
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Management of CKD
Etiology of CKD/Progression Anemia Access Adequacy
BP Bone Mineral disorder Cardiovascular
Risk Diet/Nutrition Medication Reconciliation
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Diet

• Protein Restriction
• Controversial
• Theory High protein?hyperfiltration ? increased
  glomerular hypertrophy ? glomerulosclerosis
• Stage 4 slower progression on protein
  restriction.
• Stage 5 though worried about malnutrition

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Diet/Nutrition

• Proteinlt 1.0 g/Kg in stage 4,5 of anmial protein
• Sodium lt2gm/dy
• Metabolic acidosis maintain gt22
• Phosphorus lt800mg/dy
• Potassium40-70meq/dy
• Lipids- LDLlt100
• Smoking Cessation

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Early Referral

• Proteinuria, Stage 3 with proteinuria or rapid
  progression or unclear etiology of CKD, stage 4
  and 5.
• Multidisciplinary Approach
• CV risk reduction
• Preparation for renal replacement
• Preemptive transplant

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Management of CKD
Etiology of CKD/Progression Anemia Access Adequacy
BP Bone Mineral disorder Cardiovascular
Risk Diet/Nutrition Medication Reconciliation
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Percentage of the U.S. Population with ?2 Risk
Factors
Risk FactorsHigh BP, High Cholesterol,
Diabetes, Obesity, Smoking
1991
2003
?30
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Prevalence of hypertension in men according to
age and race/ethnicity in the United States from
the NHANES-III survey. Hypertension occurs
earlier and more frequently in African-American
men. Data from Burt, VL, Whelton, P, Roccella,
EJ, et al, Hypertension 1995 25305.
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Prevalence of hypertension in women according to
age and race/ethnicity in the United Statesr from
the NHANES-III survey. Hypetension occurs earlier
and more frequently in African-American women.
Data from Burt, VL, Whelton, P, Roccella, EJ, et
al, Hypertension 1995 25305.
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Source SEARCH for Diabetes in Youth
Study.NHWNon-Hispanic whites AAAfrican
Americans HHispanics APIAsians/Pacific c
Islanders AIAmerican Indians
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