SHAGUN CHOPRA M. D.

DI RECTOR OF DI ALYSI S &TRANSPLANT

NMCSD
ASSI STANT PROFESSOR OF MEDI CI NE UCSD
ASSI STANT PROFESSOR OF MEDI CI NE
USUHS
Chronic Kidney Disease
The Recognized Epidemic
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?
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)..
ESRD prevalence counts and prevalence
rates in the U.S. Graphic from USRDS
2010 Annual Report
Medicare expenditures on ESRD, not
adjusted for inflation. Graphic from
USRDS 2010 Annual Report
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?
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 >60. 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.
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. 2007;298:2038-2047; 3. Available at: http://www.kidney.org/news/newsroom/newsprint.cfm?id=51. Accessed April 18, 2008.
Stage of CKD
GFR
(mL/min/1.73m
2
)
n
1 90* 3,600,000
2 60-89* 6,500,000
3 30-59* 15,500,000
4 15-29* 700,000
5 < 15* 341,000*
CKD & CVD
DM, HTN
Anemia
Coronary Calcification Cax Po4
<55
Worsening HTN
Nephrotic syndrome
Hyperlipidemia
Management of CKD
Etiology of CKD/Progression
Anemia
Access
Adequacy
BP
Bone Mineral disorder
Cardiovascular Risk
Diet/Nutrition
Medication Reconciliation
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
:1+proteinuria-3.1%, 2+ 15.7%, GFR 60-30 2.4%,
GFR <30 41% over a 10 year period.

Management of CKD
Etiology of CKD/Progression
Anemia
Access
Adequacy
BP
Bone Mineral disorder
Cardiovascular Risk
Diet/Nutrition
Medication Reconciliation
TREAT
Management of CKD
Etiology of CKD/Progression
Anemia
Access
Adequacy
BP
Bone Mineral disorder
Cardiovascular Risk
Diet/Nutrition
Medication Reconciliation
Access
GFR <25ml/min or rapid progression consider
placement of hemodialysis access.
Transplant referral at GFR<30 and placement on
transplant list at <20.
AVF
AVG
Tunneled Catheter
Periotenal dialysis
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.
?GFR<15ml/min per NKF are indications to
consider the risks and benefits to initiating
dialysis.
European Best Practice guidelines state
GFR<6ml/min and consider at 8-10

Management of CKD
Etiology of CKD/Progression
Anemia
Access
Adequacy
BP
Bone Mineral disorder
Cardiovascular Risk
Diet/Nutrition
Medication Reconciliation
Safety
NEJM 2006, Efficacy and Safety of Benazepril for
advanced renal insuff
Benazepril vs placebo and both groups had
BP<130/80. Both groups had 1.5gm proteinuria
and GFR 25ml/min.
Benazepril reduced protenuria and lowered
progression to ESRD and adverse events (hyperk)
same.
BP
MDRD trial subgroup evaluated aggressive BP lowering
<125/75 vs <130/80: in 585 patients mean GFR<40ml/min
Decline in GFR was lowest in <1gm 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
>3gm had the fastest rate of progression but a substantial
benefit- 10.2 to 6.5ml/min per year.
Similar trends in another group with GRF<19ml/min
Management of CKD
Etiology of CKD/Progression
Anemia
Access
Adequacy
BP
Bone Mineral disorder
Cardiovascular Risk
Diet/Nutrition
Medication Reconciliation
Progression to Renal Failure
Normal
Diffuse
Nodular
Hyperplasia
Adenomatous
Hyperplasia
Early
Nodular
VDR expression
CaSR expression
Partial 1,25(OH)
2
D
resistance
1-Hydroxylase
Alteration of Parathyroid Gland Function
Progressive loss
of kidney function
National Kidney Foundation. K/DOQI clinical practice guidelines for bone metabolism and
disease in chronic kidney disease. Am J Kidney Dis. 2003;42(Suppl 3):S1-S201. Murayama A
et al. Endocrinology. 1999;140:2224-2231. Satomura K et al. Kidney Int. 1988;34:712716
CaSR=calcium sensing receptor
As hyperparathyroidism increases, the parathyroid
gland becomes more and more resistant to vitamin D

58
Block: Calcification and All-Cause Mortality
in CKD Patients New to Dialysis
*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. 2007;71(5):438-441.
Adjusted Survival
by Baseline CAC
Score
a
0 6 12 18 24 30 36 42 48 54 60 66
0.00
0.25
0.50
0.75
1.00
Months
S
u
r
v
i
v
a
l

D
i
s
t
r
i
b
u
t
i
o
n

F
u
n
c
t
i
o
n

P=0.002
CAC=0
CAC 1-400
CAC >400
(n=127)
N=127
A Preplanned Secondary Analysis of a Randomized Trial
in 127 Patients New to Hemodialysis
59
Shantouf: Calcification and All-Cause Mortality in
Maintenance Hemodialysis Patients
Adapted with permission from Shantouf RS, et al. Am J Nephrol. 2010;31(5):419-425.
Event rates increased from 11.1% to 41.7% as CAC increased across groups.
E
v
e
n
t
-
F
r
e
e

S
u
r
v
i
v
a
l

(
%
)

0 12 24 36 48 60 72
Follow-up (months)
100
80
60
40
20
0
CAC 0
CAC 1-100
CAC 101-400
CAC 400+
Event Rate: 11.1% (2/18)
Event Rate: 18.7% (9/48)
Event Rate: 32.1% (9/28)
Event Rate: 41.7% (30/72)
A Cohort Study of 166 Maintenance Hemodialysis Patients
PTH Testing: K/DOQI Guidelines
National Kidney Foundation. K/DOQI clinical practice guidelines for bone
metabolism and disease in chronic kidney disease. Am J Kidney Dis. 2003;42(Suppl
3):S1-S201
CKD Stage
GFR
(mL/min/1.73m
2
)
3
4
5
30-59
15-29
<15 or dialysis
Every 12 months
Every 3 months
Every 3 months
Measurement of
PTH
PTH Goals: K/DOQI Guidelines
National Kidney Foundation. K/DOQI clinical practice guidelines for bone
metabolism and disease in chronic kidney disease. Am J Kidney Dis. 2003;42(Suppl
3):S1-S201
CKD Stage
GFR
(mL/min/1.73m
2
)
3
4
5
30-59
15-29
<15 or dialysis
35-70
70-110
150-300
Target intact PTH
(pg/mL)
Management of CKD
Etiology of CKD/Progression
Anemia
Access
Adequacy
BP
Bone Mineral disorder
Cardiovascular Risk
Diet/Nutrition
Medication Reconciliation
Diet
Protein Restriction
Controversial
Theory High proteinhyperfiltration increased
glomerular hypertrophy glomerulosclerosis
Stage 4 slower progression on protein restriction.
Stage 5 though worried about malnutrition
Diet/Nutrition
Protein< 1.0 g/Kg in stage 4,5 of anmial protein
Sodium <2gm/dy
Metabolic acidosis maintain >22
Phosphorus <800mg/dy
Potassium40-70meq/dy
Lipids- LDL<100
Smoking Cessation
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

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


Percentage of the U.S. Population
with 2 Risk Factors
Risk Factors=High BP, High Cholesterol, Diabetes,

Obesity, Smoking
1991 2003
30%
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; 25:305.
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; 25:305.
Source: SEARCH for Diabetes in Youth
Study.NHW=Non-Hispanic whites;
AA=African Americans; H=Hispanics;
API=Asians/Pacific c Islanders;
AI=American Indians