11. 10,000 patients 60+ years old
getting yearly evaluations for
up to 18 years.
They ran the simulation 1,000
times
Modeled laboratory reporting of creatinine versus
MDRD and its effect on death, dialysis and cost
effectiveness
12. eGFR performed better than a simple creatinine:
29 cases of ESRD prevented
13 premature deaths avoided
13. eGFR performed better than a simple creatinine:
29 cases of ESRD prevented
13 premature deaths avoided
However, it also over diagnosed chronic kidney
disease:
11,348 times
14. eGFR performed better than a simple creatinine:
29 cases of ESRD prevented
13 premature deaths avoided
However, it also over diagnosed chronic kidney
disease:
11,348 times
The conclusion was that the high rate of false
positives with eGFR reporting prevented the test
from being cost effective.
15. eGFR performed better than a simple creatinine:
29 cases of ESRD prevented
13 premature deaths avoided
However, it also over diagnosed chronic kidney
disease:
11,348 times
The conclusion was that the high rate of false
positives with eGFR reporting prevented the test
from being cost effective.
16. 2002 National Kidney Foundation Spring Clinical Meeting
K/DOQI Clinical Practice Guidelines
for Chronic Kidney Disease:
Evaluation, Classification, and Stratification
17. GFR = 170 x sCr -0.999 x Urea -0.170 x Alb +0.318 x Age -0.176 x (0.762 if female) x
(1.18 if African-American)
18. GFR=186 x sCr -1.154 x Age -0.203 x (0.742 if female) x (1.212 African-American)
Levey AS, Greene T, Kusek JW, Beck GJ: A simplified equation to predict glomerular filtration
rate from serum creatinine. J Am Soc Nephrol 11:A0828, 2000 (abstract)
36. 10 year study: Jan 1994 through Dec 2003
58,086 people in the city
37. 10 year study: Jan 1994 through Dec 2003
58,086 people in the city
6,863 had an eGFR 30-59
38. 10 year study: Jan 1994 through Dec 2003
58,086 people in the city
3,074 (5%) had 2nd eGFR 30-59 three
mo. after the initial measurement
39. Patients outcomes. Mean follow-up: 50 months
2%
31% 66%
No Endpoint
Died
Renal Failure
Eriksen, Ingebretsen. The progression of CKD: a 10-yr population-based study. Kidney Int (2006) vol. 69 (2) p. 375-82
40. 1.00 Renal Failure Death
0.84
0.75
0.49
0.50
0.25 0.17
0.07 0.04 0.03
0
<70 70-79 >79
Age
C U M U L AT I V E 1 0 Y E A R I N C I D E N C E O F R E N A L
FA I L U R E A N D D E AT H I N C K D S TA G E 3
Eriksen, Ingebretsen. Kidney Int (2006) vol. 69 (2) p. 375-82
48. Even though older people
were less likely to have
stable renal function
and had faster loss of
renal function they had a
lower risk of
renal failure
Eriksen, Ingebretsen. Kidney Int (2006) vol. 69 (2) p. 375-82
49.
50. All patients with a eGFR ≤60 in the year following
October 1, 2000 who had an additional eGFR ≤ 60 in
the previous 3 months.
Creatinine and outcomes were tracked for up to four
years (until 9/30/04).
O'Hare et al. Age affects outcomes in chronic kidney disease. J Am Soc Nephrol (2007) vol. 18 (10) pp. 2758-65
51. 209,622 veterans with CKD 3, 4 or 5.
Mean age 73, 47% over 75
97% male
Allen Park Veterans Administration Hospital, 1949
52. Incidence of death per 100 person-years
30
CKD 4 25.4
25
CKD 3b
20 CKD 3a
16.5
15.4
15 13.3
11.7
9.9
10 7.6 7.1 6.9
6.1 5.6
4.4 4.3
5 2.9 2.8 2.9
1.8
0
18 to 44 45 to 54 55 to 64 65 to 74 75 to 84 85 to 100
Age category
53. Incidence of dialysis or transplant per 100 person-years
25
20.3
20 CKD 4
17.2
15.0 CKD 3b
15
CKD 3a
9.3
10
6.2 6.3
5 3.6
2.2 2.7
1.3
0.3 0.6 0.3 0.2 0.6
0.1 0.2
0.1
0
18 to 44 45 to 54 55 to 64 65 to 74 75 to 84 85 to 100
Age category
69. The geriatric CKD patient
is just an innocent
bystander in the growing
pains of defining and
classifying CKD.
70. Geriatric CKD patients
have a higher risk of dying
than progressing to
dialysis but they still
represent the age group
with the highest incidence
and second highest
prevalence of ESRD.
83. In previous analysis the patients
were compared to younger patients
or patients without kidney disease
This cannot answer the question:
To dialyze or
not to dialyze
84.
85. 112 patients No diabetes, active
cancer, nephrotic range
70+ years old proteinuria
GFR 5-7 mL/min
Brunori et al. Am J Kidney Dis (2007) vol. 49 (5) pp. 569-80
86. 112 patients No diabetes, active
cancer, nephrotic range
70+ years old proteinuria
GFR 5-7 mL/min
Very low protein diet dialysis
Brunori et al. Am J Kidney Dis (2007) vol. 49 (5) pp. 569-80
87. VERY LOW PROTEIN
0.3 g protein per kilogram (RDA is 0.8)
Supplemented with keto-analogs of amino acids
and 4 essential amino acids
Initiate dialysis if they develop:
symptomatic uremia
volume overload
uncontrollable hypertension
hyperkalemia
Brunori et al. Am J Kidney Dis (2007) vol. 49 (5) pp. 569-80
88. 40 of 56 patients (71%) of patients randomized to diet
initiated dialysis per protocol, median of 9.8 months
after randomization.
Mortality was equal in the two groups:
31 deaths in the dialysis group
28 in the diet group
Brunori et al. Am J Kidney Dis (2007) vol. 49 (5) pp. 569-80
94. 200 consecutive patients
GFR less than 45 mL/min twice, 3 months apart
Age >65
GFR falls below 45 mL/min after Jan 1, 2004
Retrospective chart review
Endpoints: death, ESRD, hospitalizations
95. 199 patients
117 women, 82 men
150 Caucasians, 48 African Americans, 1 Asian
Average age 75.5 (65-96)
Follow-up:
Average 3.2 years
639 patient years
96. GFR Co-morbidities
Average 30 mL/min DM 88 patients
Minimum 10 mL/min HTN 194 patients
Maximum 45 mL/min CAD 90 patients
CVA 21 patients
Ca 62 patients
97. OUTCOMES
Died prior to dialysis: 18
End-stage renal disease: 20
10%
Transplant 1 9%
Hemodialysis 18
Peritoneal dialysis 1
81%
ESRD Death No endpoint
98. Delta GFR vs follow up
40
30
Average progression 1.1 mL/min per year
20
loss of GFR (ml/min/yr)
10
0
0 1 2 3 4 5 6 7 8 9 10
-10
-20
-30
-40
100. 25 OH D
Ca Phos iPTH 25 OH D
Checked
ESRD 8.9 4.0 159.9 10% 10.5
Death 9.1 3.7 146.5 22% 23.5
Alive 9.3 3.5 95.6 29% 23.2
Only 2, 4, and 47 patients had 25 OH vitamin D checked
101. 60
ESRD Death Alive
45
30
15
DM
CAD 0
CVA
PVD
Ca
102. DIALYSIS ACCESS
All of the ESRD patients received access except the
one preemptively transplanted
Quinton
Of the 18 who started hemodialysis: 6%
Fistula
7 fistulas Pcath 39%
33%
4 grafts
Graft
6 permacaths
22%
1 Temporary quinton
103. DIALYSIS ACCESS
None of the 18 patients who died received an access
Of the 161 who are alive and not ESRD, only 3
received an access
All received AVF
March of 2007, most recent visit March 2009
December 2006, most recent visit March 2009
May 2007, most recent visit March 2008
104. SUMMARY
Our data is fresh and has yet to be vetted by the
skeptical eye of the biostatistician
ESRD appears more common with
lower eGFR
higher PTH
faster progression
105. GERIATRIC CKD
Half of patients over 69 have CKD
Two-thirds of them have CKD stage 3 or higher
Patients are more likely to die than develop to ESRD
Despite this it is the fastest growing age demographic
with ESRD
Notas do Editor
Occasionally studies are published which embarrass the specialty
The story the specialty has been telling, either through editorials or practice guidelines or by the standard of care is suddenly exposed to be more opinion than science by unblinking eye of the RCT
ACCORD Study showed higher mortality with tight insulin control
ENHANCE showed that lowering LDL with Zetia did not prevent atherosclerosis
ILLUMINATE showed that raising HDL did not yield the benefits found with naturally high HDL
COURAGE showed that PTCA was not helpful for stable coronary disease
CHOIR
ATN
HEMO
Occasionally studies are published which embarrass the specialty
The story the specialty has been telling, either through editorials or practice guidelines or by the standard of care is suddenly exposed to be more opinion than science by unblinking eye of the RCT
ACCORD Study showed higher mortality with tight insulin control
ENHANCE showed that lowering LDL with Zetia did not prevent atherosclerosis
ILLUMINATE showed that raising HDL did not yield the benefits found with naturally high HDL
COURAGE showed that PTCA was not helpful for stable coronary disease
CHOIR
ATN
HEMO
Occasionally studies are published which embarrass the specialty
The story the specialty has been telling, either through editorials or practice guidelines or by the standard of care is suddenly exposed to be more opinion than science by unblinking eye of the RCT
ACCORD Study showed higher mortality with tight insulin control
ENHANCE showed that lowering LDL with Zetia did not prevent atherosclerosis
ILLUMINATE showed that raising HDL did not yield the benefits found with naturally high HDL
COURAGE showed that PTCA was not helpful for stable coronary disease
CHOIR
ATN
HEMO
Occasionally studies are published which embarrass the specialty
The story the specialty has been telling, either through editorials or practice guidelines or by the standard of care is suddenly exposed to be more opinion than science by unblinking eye of the RCT
ACCORD Study showed higher mortality with tight insulin control
ENHANCE showed that lowering LDL with Zetia did not prevent atherosclerosis
ILLUMINATE showed that raising HDL did not yield the benefits found with naturally high HDL
COURAGE showed that PTCA was not helpful for stable coronary disease
CHOIR
ATN
HEMO
Occasionally studies are published which embarrass the specialty
The story the specialty has been telling, either through editorials or practice guidelines or by the standard of care is suddenly exposed to be more opinion than science by unblinking eye of the RCT
ACCORD Study showed higher mortality with tight insulin control
ENHANCE showed that lowering LDL with Zetia did not prevent atherosclerosis
ILLUMINATE showed that raising HDL did not yield the benefits found with naturally high HDL
COURAGE showed that PTCA was not helpful for stable coronary disease
CHOIR
ATN
HEMO
Occasionally studies are published which embarrass the specialty
The story the specialty has been telling, either through editorials or practice guidelines or by the standard of care is suddenly exposed to be more opinion than science by unblinking eye of the RCT
ACCORD Study showed higher mortality with tight insulin control
ENHANCE showed that lowering LDL with Zetia did not prevent atherosclerosis
ILLUMINATE showed that raising HDL did not yield the benefits found with naturally high HDL
COURAGE showed that PTCA was not helpful for stable coronary disease
CHOIR
ATN
HEMO
Markov chain Monte Carlo analysis
1000 simulations of 10,000 patients
between 10 and 180 million patient years
defined the stages of ckd 1-5
defined how in clinical practice we measure GFR
except we don’t us this formula which requires three pieces of biochemical data
we use this formula which requires only 1, interestingly only published in abstract form.
lead to an almost immediate push back, re: healthy patients, tranplanters.
if you use standard cr use this formula
this study really quieted the outrage because instead of focusing on whether the MDRD accurately measured GFR Go showed that it accurately predicted outcomes:
•Death from any cause
•Any CV event
•Any hospitalization
this study really quieted the outrage because instead of focusing on whether the MDRD accurately measured GFR Go showed that it accurately predicted outcomes:
•Death from any cause
•Any CV event
•Any hospitalization
this study really quieted the outrage because instead of focusing on whether the MDRD accurately measured GFR Go showed that it accurately predicted outcomes:
•Death from any cause
•Any CV event
•Any hospitalization
Coresh
National Health and Nutrition Survey
direct consequence of defining CKD by GFR are these conclusions: half of the elderly have ckd!
esrd prevelance increased from 209k to 472k from 1991 to 2004
incidence increased 43% in the 10 yrs following 1991
NHANES cross sectional analysis: 88-91, 91-94 (n=15,488) and then: 99-00, 01-02, 03-04 (n=13,233)
Coresh
National Health and Nutrition Survey
direct consequence of defining CKD by GFR are these conclusions: half of the elderly have ckd!
esrd prevelance increased from 209k to 472k from 1991 to 2004
incidence increased 43% in the 10 yrs following 1991
NHANES cross sectional analysis: 88-91, 91-94 (n=15,488) and then: 99-00, 01-02, 03-04 (n=13,233)
Coresh
National Health and Nutrition Survey
direct consequence of defining CKD by GFR are these conclusions: half of the elderly have ckd!
esrd prevelance increased from 209k to 472k from 1991 to 2004
incidence increased 43% in the 10 yrs following 1991
NHANES cross sectional analysis: 88-91, 91-94 (n=15,488) and then: 99-00, 01-02, 03-04 (n=13,233)
almost immediately following this the push back began
Hostetter former head of NIDDK
almost immediately following this the push back began
Hostetter former head of NIDDK
almost immediately following this the push back began
Hostetter former head of NIDDK
almost immediately following this the push back began
Hostetter former head of NIDDK
almost immediately following this the push back began
Hostetter former head of NIDDK
almost immediately following this the push back began
Hostetter former head of NIDDK
almost immediately following this the push back began
Hostetter former head of NIDDK
almost immediately following this the push back began
Hostetter former head of NIDDK
almost immediately following this the push back began
Hostetter former head of NIDDK
Cleveland Clinic and Mayo Clinic
Cleveland Clinic and Mayo Clinic
Cleveland Clinic and Mayo Clinic
Cleveland Clinic and Mayo Clinic
Cleveland Clinic and Mayo Clinic
Feldman’s Monte Carlo simulation used only patients over 60 and half of the analysis occurred in patients over 69
5% of city with stage 3 ckd compares to 7% on Coresh’s NHANES data
used 4 v MDRD eq (assumed all people were non-black)
5% of city with stage 3 ckd compares to 7% on Coresh’s NHANES data
used 4 v MDRD eq (assumed all people were non-black)
5% of city with stage 3 ckd compares to 7% on Coresh’s NHANES data
used 4 v MDRD eq (assumed all people were non-black)
5% of city with stage 3 ckd compares to 7% on Coresh’s NHANES data
used 4 v MDRD eq (assumed all people were non-black)
renal failure defined as RRT or GFR < 15
similar to Keith’s data from Kaiser Permenente that found 1% risk for CKD 3 at 5 years
loss of kidney function averaged 1 mL/min/yr, faster in the elderly
loss of kidney function averaged 1 mL/min/yr, faster in the elderly
clearly this apparent paradox or absurdity is due to the competing morbidity: death, even though they were losing kidney function they were still dying prior to needing the dialysis. this was made more explicit in an earlier study...
Found the risk of death of death out weighed the risk of ESRD in the elderly while the opposite was true among younger patients with CKD
Possibility in a prevalent cohort older patients with CKD are CKD survivors (slow or non-progressive disease)
CKD in the elderly is a marker for a variety of age-related co-existing conditions so it is a predictor of global health outcomes
Found the risk of death of death out weighed the risk of ESRD in the elderly while the opposite was true among younger patients with CKD
Possibility in a prevalent cohort older patients with CKD are CKD survivors (slow or non-progressive disease)
CKD in the elderly is a marker for a variety of age-related co-existing conditions so it is a predictor of global health outcomes
only 18.6% of patients ≥75 years compared with 62.5% of patients <65 years were diagnosed with an intrinsic renal disease such as diabetic nephropathy, glomerulonephritis, obstructive nephropathy, interstitial nephritis or polycystic kidney disease.
So the lack of a dx was associated with an improved prognosis, as we get better as delaying dialysis with ACEi/ARB/glycemic control we may get more at risk patients in the older age categories.
think about average attendence at an average MLB game That’s how many 75+ year olds we are putting on dialysis every year