This slide set summarizes key study characteristics and scientific contributions of CKiD. Chronic...

This slide set summarizes key study characteristics and scientific contributions of CKiD.

Chronic Kidney Disease in Children (CKiD) Dossier

March 2015

Prepared by:CKiD Data Management and Analysis Center (KIDMAC)

Phone: 410-614-4751E-mail: [email protected]

Web: http://statepi.jhsph.edu/ckid/

CKiD Participating Sites

CKiD Study Structure

•Clinical Coordinating Centers

- Midwest (Warady)

- East Coast (Furth)

•Data Management and Analysis Center

- KIDMAC (Muñoz)

•Central Laboratory- University of Rochester (Schwartz)

Sponsorship: NIDDK, NICHD, NHLBI

Central Laboratories and Repositories

•Central Biochemistry Laboratory (George Schwartz, MD)

•ABPM Coordinating Center (Joshua Samuels, MD)

•Cardiovascular Imaging Core Research Laboratory (Peace Madueme , MD)

• NIDDK Biosample Repository (NIDDK BR) at Fisher BioServices – Rockville, MD

• NIH Genetics Initiative at Rutgers University Cell and DNA Repository – New Brunswick, NJ

SubcommitteesSteering

ProgressionSusan Furth, Co-ChairRobert Mak, Co-Chair

George Schwartz, Co-Chair

NeurocognitiveStephen Hooper, Co-ChairArlene Gerson, Co-Chair

Bradley Warady, Co-Chair

CardiovascularMark Mitnesfes, Co-ChairJoseph Flynn, Co-Chair

GrowthFrederick Kaskel, Co-ChairLarry Greenbaum, Co-Chair

DataAlvaro Muñoz, Co-ChairCraig Wong, Co-Chair

LaboratoryGeorge Schwartz, Chair

TrainingJackie Ndirangu, Co-Chair

Julie Starr, Co-Chair

OSMB

CKiD Study Design•O

bservational Cohort Study- 5 year study

initially, 10 year renewal (Oct 2003 – Jul

2008, Aug 2008 – Jul 2013, Aug 2013 – Jul 2018)

- Cohort 1 enrollment: Apr 2005 - Oct 2007

- Cohort 2 enrollment: Feb 2011 – March 2014

•Cohort 1: Children age 1 to 16 with mild to moderate kidney dysfunction

sGFR: 30 – 90 ml/min|1.73m2

•Cohort 2: Children age 1 to 16 with mildly impaired kidney function

eGFR: 45 – 90 ml/min|1.73m2

CKiD Study Goals

•Recruit & retain children with CKD

•Define risk factors for CKD progression

•Define effects of CKD progression on:

- Neurocognitive development/function

- Prevalence of CVD risk factors

- Growth failure

Exclusion Criteria•R

enal, other solid organ, bone marrow or stem cell transplantation•D

ialysis treatment within the past three months•C

ancer/leukemia or HIV diagnosis/treatment within last calendar year •C

urrent pregnancy or pregnancy within past year•I

nability to complete major data collection procedures (e.g.,

hypersensitivity to Iohexol, other contrast media or iodine)•C

urrent enrollment in a randomized clinical trial in which the specific treatment is unknown•P

lans to move out of area of any participating CKiD site (Families can be transferred to another CKiD site if they move)

•History of structural heart disease

•Genetic syndromes involving the central nervous system

(e.g., Down syndrome)

•Profound developmental delay due to severe anoxic brain injury

Year 3Year 2

CKiD Measurements According to Time-on-Study

Enrollment

Year 1 Year 4Odd Years from Year

5 on

GFR (Iohexol) (2 pt)

Echo, ABPM, Carotid IMTa, Lipids

CRP, iPTH, Vitamin D, FGF-23

Measurements

Kidney: Renal Panel*, CBC*, proteinuria, albuminuria, Cystatin C

CV: Standardized BP*

Growth: Height*, Weight*, FFQ, Tanner Stage*, Waist & Hip Circumference*

*Locally performed tests

PedsQOL, Cognitive, Behavior Tests

aSubcohort

Even Years from Year

6 on

See Year

3

See

Year

4

CKiD II

891= 586 + 305V1a Visits with at least one

measurement of GFR

Cohorts 1 & 2 as of March 2015

275 (31%) = 128+147Glomerular

616 (69%) = 458+158Non-Glomerular

60+12a (25%)EVENT

68+135 EVENT-Free

131+3b (22%)EVENT

327+155EVENT-Free

a 60 = 16 Transplant + 43 Dialysis + 1 Death a 12 = 1 Transplant + 10 Dialysis + 1 Death

b 131 = 61 Transplant + 68 Dialysis + 2 Death b 3 = 3 Transplant + 0 Dialysis + 0 Death

2006

Publications

Glomerular Filtration Rate via Plasma Iohexol

Disappearance: Pilot Study for Chronic Kidney Disease

in Children

Schwartz, Furth, … , Muñoz Kidney Int 2006;69:2070-7.

Iohexol Disappearance Curves from the Blood

(Schwartz, Furth, … , Muñoz . Kidney Int 2006;69:2070-7.)

Minutes from Iohexol Infusion

Iohe

xol i

n m

g/m

l (lo

g sc

ale)

slow component


Iohe

xol m

inus

slo

w c

ompo

nent

in m

g/m

l (lo

g sc

ale)

fast component

0 100 200 300

0.0

0.1

0.2

0.3

0.4

0.5

0.6

Iohe

xol i

n m

g/m

l

slow + fast

slow


GFR (9 pts)

Two Component GFR comparing 9 Points against 4 Points


GFR

(4 p

ts)

s.d.(GFR4)/s.d.(GFR9)BiasCorrelation

= 0.99 (p= 0.195) = 0.04 (p= 0.882) = 0.999

0 50 100 150 200 0 50 100 150 200

GFR

(4 p

ts) –

GFR

(9 p

ts)

.

Mean of GFR (4 pts) and GFR (9 pts)

One Component GFR versus GFR from the Two-Compartment Model

(Schwartz, Furth, … , Muñoz . Kidney Int 2006;69:2070-7.) GFR based on slow component only

GFR

(9 p

ts)

GFR (9 pts) = 0.9950 x GFR (A) – 0.001159 x [GFR (A)]2

0 50 100 150 200 250

200

250

150

100

50

0


GFR

(2 p

ts)

GFR

(2 p

ts) –

GFR

(9 p

ts)

s.d.(GFR2)/s.d.(GFR9)BiasCorrelation

= 0.97 (p= 0.357) = -1.21 (p= 0.266) = 0.986

GFR (9 pts) Mean of GFR (2 pts) and GFR (9 pts)

0 50 100 150 200 0 50 100 150 200

.GFR Based on Nine Points and

One Component GFR Based on 2 Points

.GFR Based on Nine Points versus Estimated

GFR from Schwartz Formula

(Schwartz, Furth, … , Muñoz . Kidney Int 2006;69:2070-7.) GFR (9 pts) Mean of eGFR

and GFR (9 pts)

eGFR

– G

FR (9

pts

)

s.d.(eGFR)/s.d.(GFR9)BiasCorrelation

= 1.17 (p= 0.038) = 12.22 (p=<0.001) = 0.934

0 50 100 150 200 0 50 100 150 200

eGFR

.

GFR Based on Nine Points vs. Standard Urine Iohexol Clearance

(Schwartz, Furth, … , Muñoz . Kidney Int 2006;69:2070-7.) GFR (9 pts)

urin

eGFR

Mean of urineGFR and GFR(9 pts)

urin

eGFR

– G

FR (9

pts

)

s.d.(urineGFR)/s.d.(GFR9)BiasCorrelation

= 1.19 (p= 0.171) = -13.95 (p= 0.008)= 0.77

0 50 100 150 200 50 100 150 2000

Design and Methods of the Chronic Kidney Disease in

Children (CKiD) Prospective Cohort Study

Furth, Cole, … , WaradyClin J Am Soc Nephrol 2006;1:1006-15.

Statistical Power for Decline in GFR at 5% Two-Sided Significance Level with N= 540 and Overall Rate of GFR Decline of

5 ml/min per 1.73 m2 per Year.

(Furth, Cole, … , Warady. Clin J Am Soc Nephrol 2006;1:1006-15.)

Slope of exposed group/Slope of unexposed groupRelative Risk

Pow

er (%

)

100

80

60

40

20

0

1.1 1.2 1.3 1.4 1.5

40% exposed30% exposed20% exposed

2008

Publications

Hemoglobin Decline in Children with Chronic Kidney Disease:

Baseline Results from the Chronic Kidney Disease in Children Prospective Cohort Study

Fadrowski, Pierce, … , Furth Clin J Am Soc Nephrol 2008;3:457-62.

Hemoglobin versus GFR in Children with CKD

(Fadrowski, Pierce, … , Furth. Clin J Am Soc Nephrol 2008;3:457-62.)

Hem

oglo

bin

(g/d

L)

Glomerular Filtration Rate (mL/min|1.73m2)

2009

Publications

Association of Proteinuria with Race, Cause of Chronic Kidney

Disease, and Glomerular Filtration Rate in the Chronic Kidney Disease in Children Study

Wong, Pierce, … , SchwartzClin J Am Soc Nephrol 2009;4:812-9.

Urine Protein: Creatinine Ratios (Up/c) by Iohexol-Measured GFR (iGFR)

(Wong, Pierce, … , Schwartz. Clin J Am Soc Nephrol 2009;4:812-9.)Iohexol GFR, mL/min|1.73m2 (log scale)

Up/

c (lo

g sc

ale)

Non-Glomerular CKD, N= 328 Glomerular CKD, N= 91 Nephrotic Proteinuria

Significant Proteinuria

Norm

al

New Equations to Estimate GFR in Children with Chronic Kidney

Disease

Schwartz, Muñoz, … , Furth J Am Soc Nephrol 2009;20:629-37.

(Commentary by Lemley, KV in Nature Reviews Nephrology

2009;5:310-1)

Analysis of Log-Transformed Height/Scr and iGFR

(Schwartz, Muñoz, … , Furth. J Am Soc Nephrol 2009;20:629-37.)

Height (meters)/Scr

R-square= 65.0%iGFR= 41.2 (ht/Scr)0.775

Y= log(iGFR), X= log(height[meters]/Scr)

iGFR

Analysis of Log-Transformed 1.8/Cystatin C and iGFR


1.8/cystatin C

R-square= 43.7%iGFR= 41.9 (1.8/cystatin C)0.777

Y= log(iGFR), X= log(1.8/cystatin C)

iGFR

Analysis of Log-Transformed 30/BUN and iGFR


30/BUN

R-square= 39.0%iGFR= 39.8 (30/BUN)0.510

Y= log(iGFR), X= log(30/BUN)

iGFR

Bland-Altman Plot of Observed iGFR and Model III eGFR in a Testing Data Set of 168 Individuals in the CKiD Study


Average of eGFR and iGFR (39.4 +/- 14.4)

eGFR

- iG

FR (-

2.23

+/-

7.6

0)

Validation of Creatinine Assays Utilizing HPLC and IDMS

Traceable Standards in Sera of Children

Schwartz, Kwong, … , MuñozPediatr Nephrol 2009;24:113-9.

(Schwartz, Kwong, …, Muñoz. Pediatr Nephrol 2009;24:113-9.)

Comparison of Siemens Advia Enzymatic Assay against HPLC

Enzymatic Scr HPLC Scr

Correlation= 0.98N= 201

5

4

3

2

1.5

1

0.5

Bland-Altman Plot Comparing Siemens Advia Enzymatic Assay against High Performance Liquid Chromatography

(Schwartz, Kwong, …, Muñoz. Pediatr Nephrol 2009;24:113-9.)Mean of Enzymatic Scr and HPLC Scr

Enzy

mati

c Sc

r/H

PLC

Scr

s.d.(Enzymatic Scr)/ s.d.(HPLC Scr) = 0.992 (p= 0.523 for equality of s.d.s)Bias (Enzymatic Scr/ HPLC Scr) = 1.07 (p< 0.001 for no bias)Correlation = 0.984

Bias = 0.15 s.d of mean

Comparison of Siemens Advia Enzymatic Assay Against HPLC at Low Levels of Creatinine



Correlation= 0.83N= 50

0.1

0.25

0.5

1

Comparison of Siemens Advia Enzymatic Assay Against High-Performance Liquid Chromatography (HPLC)



0.1

0.25

543

2

1.5

.5

1

Urinary Incontinence in the CKiD Cohort and Health Related

Quality of Life

Dodson, Cohn, … , Furth J Urol 2009;182:2007-14.

Child Reported PedsQL by Continence Group

TotalScore

SocialFunctioning

SchoolFunctioning

PhysicalFunctioning

EmotionalFunctioning

TT BW nTT TT BW nTT TT BW nTT TT BW nTTTT BW nTT

Continence Status

Peds

QL:

Chi

ld S

elf-

Repo

rt

0

20

40

60

80

100

(Dodson, Cohn, … , Furth. J Urol 2009;182:2007-14.)

PhysicalFunctioning

SchoolFunctioning

TotalScore

SocialFunctioning

EmotionalFunctioning

TT BW nTT TT BW nTT TT BW nTT TT BW nTTTT BW nTT

Continence Status

Peds

QL:

Par

ent P

roxy

-Rep

ort

0

20

40

60

80

100

(Dodson, Cohn, … , Furth. J Urol 2009;182:2007-14.)

Parent Proxy Reported PedsQL by Continence Group

Longitudinal Formulas to Estimate Glomerular Filtration

Rate in Children with CKD

Abraham, Schwartz, … , Muñoz Clin J Am Soc Nephrol

2009;4:1724-30.

T ra ining data

iG F R at vis it 1

iGF

R a

t vi

sit

2

20 30 40 60 80 100

20

30

40

50

60

80

100 iG F R [2] to e G F R [2] (e rro r<30% ),M o de l IViG F R [2] to e G F R [2] (e rro r>30% ),M o de l IVR e gre s s io n line , M o de l I

Training Data, N= 220

(Abraham, Schwartz, … , Muñoz. Clin J Am Soc Nephrol 2009;4:1724-30.)

iGFR

at V

isit

2

iGFR at Visit 1

V alidation data

iG F R at vis it 1

iGF

R a

t vi

sit

2

20 30 40 60 80 100

20

30

40

50

60

80

100 iG F R [2] to e G F R [2] (e rro r<30% ),M o de l IViG F R [2] to e G F R [2] (e rro r>30% ),M o de l IV

Validation Data, N= 109

(Abraham, Schwartz, … , Muñoz. Clin J Am Soc Nephrol 2009;4:1724-30.)

iGFR

at V

isit

2

iGFR at Visit 1

2010

Publications

Optimizing Iohexol Plasma Disappearance Curves to Measure the Glomerular

Filtration Rate in Children with Chronic Kidney Disease

Schwartz, Abraham, … , MuñozKidney Int 2010;77:65-71.

100

150

Iohexol-Based GFR as a Function of Time of Sampling for the Slow Curve

(Schwartz , Abraham, … , Muñoz. Kidney Int 2010;77:65-71.)

N= 27 (Pilot Study)

Sampling Interval (hours)

Iohe

xol G

FR (m

l/m

in p

er 1

.73

m2 )

75

50

40

30

20

4 5 6

Relationship between GFRs based on the Slow Component only (x-axis) and the Four-Point GFR (double exponential, y-axis)

(Schwartz , Abraham, … , Muñoz. Kidney Int 2010;77:65-71.) GFR based on Slow Component Only

GFR

Bas

ed o

n Sl

ow

and

Fast

Com

pone

nts

1.0019 x slowGFR – 0.001258 x slowGFR2

90

75

Comparison of GFR2 to 4-Point GFR4 Studies in Visit 2 of the CKiD Study

(Schwartz , Abraham, … , Muñoz. Kidney Int 2010;77:65-71.) Correlation= 0.999

GFR

(ml/

min

per

1.7

3 m

2 )N= 362 (Validation data set)

2.5%5%

10%

25%

50%

75%

90%95%97.5%

GFR2 GFR4

105

60

45

30

15

7

Linear Regression of GFR2 on GFR4 Showing a Very Close Agreement and a Very High Correlation


GFR

2 (m

l/m

in p

er 1

.73

m2 )

N= 362 (Validation data set)

GFR4 (ml/min per 1.73 m2)

Bland-Altman Analysis of GFR2 Versus Four-Point GFR Showing an Insignificant Bias of -0.002


N= 362 (Validation data set)

Geometric Mean of GFR2 and GFR4

GFR

2/G

FR4

Dyslipidemia in Children with Chronic Kidney Disease: A

Report of the Chronic Kidney Disease in Children (CKiD)

Study

Saland, Pierce, … , FurthKidney Int 2010 Dec;78:1154-63.

P-value for slope <0.01

Relation of Lipid Measurements to GFR

(Saland, Pierce, … , Furth. Kidney Int 2010 Dec;78:1154-63.)

Triglycerides HDL-C

non- HDL-CGFR, ml/min/1.73m2 GFR, ml/min/1.73m2

GFR, ml/min/1.73m2

HD

L-C,

mg/

dL

non-

HD

L, m

g/dL

Trig

lyce

rides

, mg/

dL




0

10

20

30

40

50

60

70

> = 50 [40-50] [30-40] < 30

3 markers 2 markers 1 marker

Prevalence of Dyslipidemia by GFRP

erce

nt

(%) 38%

(53/141) 31% (26/83)

53% (46/87)

65% (52/80)

iGFR, mL/min/1.73m2

0

10

20

30

40

50

60

70

80

Normal Mild Moderate Nephrotic

3 markers 2 markers 1 marker


Prevalence of Dyslipidemia by Up/cP

erce

nt

(%)

35% (36/103)

44% (71/160) 46% (33/72)

73% (32/44)

Proteinuria (Up/c)

Sleep and Fatigue Symptoms in Children and Adolescents with CKD: A Cross-Sectional

Analysis from the Chronic Kidney Disease in Children

(CKiD) StudyRoumelioti, Wentz, … , Unruh

Am J Kidney Dis 2010;55:269-80.

overall >=50 40-<50 30-<40 <30

mGFR, ml/min/1.73 m²

Pe

rce

nt

0

20

40

60

80

100

Often or Almost Always Sometimes Almost Never Never

Child Report of Trouble Sleeping

N= 245 83 54 62 46

(A)

overall >=50 40-<5030-<40 <30mGFR, ml/min/1.73 m²

Pe

rce

nt

0

20

40

60

80

100

Parent Report of Trouble Sleeping

N= 244 78 58 62 46

(B)

overall >=50 40-<50 30-<40 <30


Pe

rce

nt

0

20

40

60

80

100

N= 244 83 53 62 46

Child Report of Low Energy

(C)

overall >=50 40-<50 30-<40 <30


Pe

rce

nt

0

20

40

60

80

100

N= 243 77 58 62 46

Parent Report of Low Energy

(D)

Distribution of Child and Parent Reports of Trouble Sleeping and Low Energy by Measured GFR Level

(Roumelioti, Wentz, … , Unruh. Am J Kidney Dis 2010; 55: 269-280.)

overall >=50 40-<5030-<40 <30


Pe

rce

nt

0

20

40

60

80

100

Moderate or Severe Mild No Symptoms

Weakness

N= 281 91 63 64 63

(A)

overall >=50 40-<50 30-<40 <30


Pe

rce

nt

0

20

40

60

80

100

Waking Up Early

N= 280 91 63 63 63

(B)

overall >=50 40-<5030-<40 <30


Pe

rce

nt

0

20

40

60

80

100

Falling Asleep During Day

N= 278 89 63 63 63

(C)

overall >=50 40-<50 30-<40 <30


Pe

rce

nt

0

20

40

60

80

100

Decreased Alertness

N= 280 90 63 64 63

(D)(Roumelioti, Wentz, … , Unruh. Am J Kidney Dis 2010; 55: 269-280.)

Distribution of Child Report of Weakness, Waking up Early, Falling Asleep During the Day, and Decreased Alertness

Adjusted Estimated QOL Scores by Child and Parent for Trouble Sleeping and Low Energy


Child ReportTrouble Sleeping

Parent ReportTrouble Sleeping

Child ReportLow Energy

Parent ReportLow Energy

Child

Ove

rall

QO

L

Child

Ove

rall

QO

L

Pare

nt O

vera

ll Q

OL

Pare

nt O

vera

ll Q

OL

Never Almost Never Sometimes Often or Almost Always N= 91 48 40 23 N= 91 56 42 16 N= 70 62 46 23 N= 66 48 62 28

Adjusted Estimated QOL Scores by Parent and/or Child Report of Symptom Severity for Weakness, Waking up too Early, Falling Asleep

During the Day, and Decreased Alertness


Weakness Waking up Early Falling Asleep During Day

Decreased Alertness

Child

Ove

rall

QO

L

N= 132 26 28 N= 155 25 5 N= 131 38 16 N= 164 11 10

No Symptoms Mild Symptoms Severe/Moderate Symptoms

Masked Hypertension Associates with Left

Ventricular Hypertrophy in Children with CKD

Mitsnefes, Flynn, … , WaradyJ Am Soc Nephrol 2010;21:137-44.

Distribution of LVMI by Iohexol GFR (n= 363), overall p = 0.449

(Mitsnefes, Flynn, … , Warady. J Am Soc Nephrol 2010;21:137-44.)

20

40

60

50

30

10

LVM

Inde

x (g

/m2.

7 )

Iohexol GFR, ml/min/1.73m2

iGFR ≥ 50N= 123

iGFR 40-49N= 83

iGFR 30-39N= 81

iGFR < 30N= 76

LVH by Casual, Sleep, and Wake Systolic Blood Pressures


0

10

20

30

40

50

Normal HT0

10

20

30

40

50

Normal HT

0

10

20

30

40

50

Normal HT

LVH

, %

Casual SBP Sleep SBP Wake SBP

NormalN= 304

HypertensionN= 43

NormalN= 145

HypertensionN= 86

HypertensionN= 81

P= 0.005P= 0.006P= 0.002

NormalN= 140


LVH by Casual, Sleep, and Wake Diastolic Blood Pressures

0

10

20

30

40

50

Normal HT0

10

20

30

40

50

Normal HT

0

10

20

30

40

50

Normal HT

Casual DBP Sleep DBP Wake DBP

HypertensionN= 37

HypertensionN= 95

HypertensionN= 69

P= 0.004P= 0.070P= 0.070

LVH

, %

NormalN= 311

NormalN= 131

NormalN= 157

LVH by Casual and Ambulatory BP Status (n= 198)


0

10

20

30

40

50

P = 0.039

P = 0.097

Overall P = 0.003

LVH

, %

NormotensiveN= 83

White CoatHypertension

N= 4

MaskedHypertension

N= 76

ConfirmedHypertension

N= 35

Health-Related Quality of Life of Children with Mild to Moderate Chronic Kidney

Disease

Gerson, Wentz, … , FurthPediatrics 2010;125:349-57.

Percentage of CKD Group with Poor Quality of Life

(Gerson, Wentz, … , Furth. Pediatrics 2010;125:349-57.)

20

40

50

30

10

0

Falli

ng 1

SD

Bel

ow M

ean,

%

QOL Variables

ParentOverall

ParentPhysical

ParentSchool

ParentSocial

ParentEmotional

ChildOverall

ChildPhysical

ChildSchool

ChildSocial

ChildEmotional

Inference for Mutually Exclusive Competing Events

through a Mixture of Generalized Gamma

Distributions

Checkley, Brower, Muñoz Epidemiology 2010;21:557-65.

(Checkley, Brower, Muñoz. Epidemiology 2010;21:557-65.)

12 ml/kg: UAB: 60% GG(2.19, 1.13, 0.09) Death: 40% GG(2.40, 1.03, 0.18) 6 ml/kg: UAB: 69% GG(2.20, 1.07, 0.34) Death: 31% GG(2.61, 1.02, 0.45)

Days after Randomization

Perc

ent

12 ml/kg, Unassisted Breathing6 ml/kg, Unassisted Breathing12 ml/kg, Death6 ml/kg, Death

.Assisted Breathing

Death

Unassisted Breathing


Perc

ent

Times to Unassisted Breathingp-value= 0.477

Probability of Unassisted Breathingp-value= 0.005


Probability of Death

8.6

8.0

10.4

11.3

Times to Deathp-value= 0.718

.

.

.

.

60%31%

40%

69%

UAB: [0.69x (1-Surv of GG(2.20,1.07,0.34))] / [0.60x(1-Surv of GG(2.19,1.13,0.09))] Death: [0.31x(1-Surv of GG(2.61,1.02,0.45))] / [0.40x(1-Surv of GG(2.40,1.03,0.18))]


Unassisted Breathing (UAB)

Death


Rela

tive

Cum

ulati

ve In

cide

nce

of U

AB a

nd D

eath

of t

he 6

ml/

kg to

12

ml/

kg S

trat

egie

s 2/1

3/2

5/4

11/101

10/11

4/5

2/3

1/2

5 10 15 20 25


Death

Unassisted Breathing

.Assisted Breathing


Perc

ent

Liberal: UAB: 68% GG(2.22, 0.81, -0.01) Death: 32% GG(2.71, 1.23, 0.35)Conservative: UAB: 72% GG(1.80, 0.74, -0.44) Death: 28% GG(2.47, 1.34, 0.16)

Probability of Death


Times to Deathp-value = 0.693

Times to Unassisted Breathingp-value < 0.001

Probability of Unassisted Breathingp-value = 0.202

9.2

6.7

13.0

11.0

.32%

.

.

.

68%28%72%


Unassisted breathing (UAB)

Death


Rela

tive

Cum

ulati

ve In

cide

nce

of U

AB a

nd D

eath

of

the

Cons

erva

tive

to L

iber

al S

trat

egie

s UAB: [0.72x(1-Surv of GG(1.80,0.74,-0.44))] / [0.68x(1-Surv of GG(2.22,0.81,-0.01))] Death: [0.28x(1-Surv of GG(2.47,1.34,0.16))] / [0.32x(1-Surv of GG(2.71,1.23,0.35))]

Days after randomization

5 10 15 20 25

1/2

2/3

4/5

10/11

1

11/10

5/4

3/2

2/1

RC

I of U

AB

an

d d

ea

th o

f the

co

nse

rva

tive

to li

be

ral s

tra

teg

y

Hemoglobin Differences by Race in Children with CKD

Atkinson, Pierce, … , Furth, Am J Kidney Dis 2010;55:1009-17.

(Editorial by Filler G, Huang SS, Sharma AP, pages 981-3)

mGFR, ml/min/1.73m² (log scale)

Hb

, g

/dL

15 20 30 40 50 60 70 90 110

8

10

12

14

16

18 White (n=338) A-A (n=91)

(Atkinson, Pierce, … , Furth. Am J Kidney Dis 2010;55:1009-17.)

Hemoglobin (Hb) Level versus Log-TransformedIohexol-Measured GFR (mGFR) by Race

Hem

oglo

bin,

g/d

L

.mGFR, ml/min/1.73m2 (log scale)

(Atkinson, Pierce, … , Furth. Am J Kidney Dis 2010;55:1009-17.)

Percentile Plots Show Distribution of Hb levels for Children not Using ESAs (n= 364) Versus those Using ESAs (n= 65) by Race

Hem

oglo

bin,

g/d

L

.Race/ESA use

Univariate Race-Specific Generalized Gamma (GG)-Derived Probability Density Curves of Hb Levels with

Left-Censoring for Current ESA Users

(Atkinson, Pierce, … , Furth. Am J Kidney Dis 2010;55:1009-17.) Hemoglobin, g/dL

Prob

abili

ty D

ensi

ty

Relative Percentile Plot of HB Levels for 81 African American versus 315 White Children

(Atkinson, Pierce, … , Furth. Am J Kidney Dis 2010;55:1009-17.) p (%)

Rela

tive

Perc

entil

es o

f Hb,

A-A

v. W

hite

2011

Publications

Casual Blood Pressure and Neurocognitive Function in

Children with Chronic Kidney Disease: A Report of the

Children with Chronic Kidney Disease Cohort Study

Lande, Gerson, … , FlynnCJASN 2011;6:1831-7.

Adjusted Performance IQ by Blood Pressure Index

(Lande, Gerson, … , Flynn. CJASN 2011;6:1831-7.)

Adju

sted

Per

form

ance

IQ

Systolic BP Index

Adju

sted

Per

form

ance

IQ

Diastolic BP Index0.7 0.8 0.9 1.0 1.1 1.2 1.3 1.21.00.80.60.4

60

80

100

120

140

60

80

100

120

140

Serum Adiponectin Complexes and

Cardiovascular Risk in Children with Chronic Kidney

Disease

Lo, Salisbury, … , MitsnefesPediatr Nephrol 2011;26:2009-17.

Adiponectin Complex Distribution in Serum of a Child with Chronic Kidney Disease (CKD)

(Lo, Salisbury, … , Mitsnefes. Pediatr Nephrol 2011;26:2009-17.)

Distribution of Adiponectin Complexes According to Gender, (Median (IQR))


0

20

40

60

Per

cen

t

HMW LMW Trimer

All P> 0.15

Girls Boys Girls Boys Girls Boys

Distribution of Adiponectin Complexes According to Race, (Median (IQR))


0

20

40

60

Per

cen

t

HMW LMW Trimer

All P> 0.15

AA Non-AA AA Non-AA AA Non-AA

Distribution of Adiponectin Complexes According to Pubertal Status, (Median (IQR))


0

20

40

60

Per

cen

t

HMW LMW Trimer

P= 0.005

Pre-Puberty

Puberty

Pre-Puberty

Puberty

Pre-Puberty

Puberty

P= 0.018 P= 0.030

Distribution of Adiponectin Complexes According to Obesity Status, (Median (IQR))


0

20

40

60

Per

cen

t

HMW LMW Trimer

P< 0.001

Non-Obese

Obese

P= 0.320 P= 0.010

Non-Obese

Obese

Non-Obese

Obese

Distribution of HMW/LMW by Iohexol GFR (n=105), Overall p=0.049, (Median (IQR))


Iohexol-GFR, ml/min/1.73m2

HM

W/L

MW

Rati

o

< 30 30-59 ≥ 60

0

1

2

3

4

5

6

7

The Association between Abnormal Birth History and

Growth in Children with CKD

Greenbaum, Muñoz, … , Warady Clin J Am Soc Nephrol 2011; 6:14-21.

Histograms of Age-Sex-Specific Height and Weight Z-Scores with a Density Function from a Gaussian Distribution Superimposed

(Greenbaum, Muñoz, … , Warady. Clin J Am Soc Nephrol 2011;6:14-21.)

Height Z-Scores

Mean= -0.68SD= 1.16N= 1,393

Mean= -0.09SD= 1.27N= 1,383

Weight Z-Scores

Diff

eren

ce in

Hei

ght Z

-sco

re (a

bnor

mal

- no

rmal

)Multivariate CKD Diagnosis-Specific Repeated Measures

Analyses of Abnormal Birth History Exposures on Age-Sex-Specific Height Z-Scores


*Z-score expected for females, white race, 11 years of age, >90% of life with CKD,

mid-parental height of 1.71 meters and NORMAL birth history

2.0

1.5

1.0

0.5

0

-0.5-1.0-1.5

GlomerularNon-Glomerular

p= 0.124

p= 0.364

p= 0.813

p= 0.639

LBW Premature SGA ICU-1.04* -1.01* -1.27* -1.03* -1.05* -1.05* -1.13* -1.01*

Multivariate CKD Diagnosis-Specific Repeated Measures Analyses of Abnormal Birth History Exposures on

Age-Sex-Specific Weight Z-Scores


*Z-score expected for females, white race, 11 years of age, >90% of life with CKD,

mid-parental height of 1.71 meters and NORMAL birth history

Diff

eren

ce in

Wei

ght Z

-sco

re (a

bnor

mal

- no

rmal

)

GlomerularNon-Glomerular

-2.0

1.5

1.0

0.5

0

-0.5-1.0-1.5

LBW Premature SGA ICU-0.57* -0.24* -0.80* -0.41* -0.53* -0.42* -0.88* -0.31*

p= 0.246

p= 0.029

p= 0.172

p= 0.172

Extracellular Volume and Disease Progression in Children with Chronic

Kidney Disease

Abraham, Muñoz, … , SchwartzClin J Am Soc Nephrol 2011;6:741-7.

(Abraham, Muñoz, … , Schwartz. Clin J Am Soc Nephrol 2011;6:741-7.)

Distribution of Weight-Normalized ECV by Age and Tanner Stage

AGE (Years)

TANNER STAGE

EC

V (

L)/

WT

(kg

)E

CV

(L

)/W

T(k

g)

N= 756

N= 788

ECV versus BSA Illustrating the Correlation Between the Two Measures of Body Size, N= 790

ECV

(L)

BSA (m2)(Abraham, Muñoz, … , Schwartz. Clin J Am Soc Nephrol 2011;6:741-7.)

Distribution of Weight-Normalized ECV by Systolic Blood Pressure Categories, N= 756

96

SBP %tile >= 95SBP %tile >= 95SYSTOLIC BP PERCENTILE

ECV

(L)/

WT(

kg)

0.1

0.2

0.3

0.4

N= 660

97.5%

90%75%

50%

25%

10%

2.5%

(Abraham, Muñoz, … , Schwartz. Clin J Am Soc Nephrol 2011;6:741-7.)

Methods for Characterizing Differences in Longitudinal

GFR Changes Between Children with Glomerular

and Non-Glomerular Chronic Kidney Disease

Pierce, Cox, … , MuñozAm J Epidemiol 2011;174:604-12.

Generalized Gamma Model

(Pierce, Cox, … , Muñoz. Am J Epidemiol 2011;174:604-12.)

Mixed Model

Annualized GFR Ratio

0 0

0.050.10

0.25

0.50

0.75

0.90

0.95

Cum

ulati

ve P

roba

bilit

y

0.05

0.10

0.50

0.75

0.900.95

Cum

ulati

ve P

roba

bilit

y

0.25

1

Annualized GFR Ratio

1

Generalized Gamma - Modeled Relative Percentiles of Annualized GFR Ratio, Glomerular vs. Non-Glomerular CKD Children

Rela

tive

Perc

entil

es o

f G

lom

erul

ar to

Non

-Glo

mer

ular

Dx

P (%)(Pierce, Cox, … , Muñoz. Am J Epidemiol 2011;174:604-12.)

Baseline GFR ≤ 45 ml/min| 1.73m2

Baseline GFR > 45 ml/min| 1.73m2

Cum

ulati

ve P

roba

bilit

y

0

0.050.10

0.50

0.75

0.90

0.95

0.25

Cum

ulati

ve P

roba

bilit

y

1

Annualized GFR Ratio Annualized GFR Ratio

0

0.050.10

0.50

0.75

0.900.95

0.25

1

(Pierce, Cox, … , Muñoz. Am J Epidemiol 2011;174:604-12.)

Baseline GFR Level-Specific Generalized Gamma Modeled Relative Percentiles of Annualized GFR Ratio,

Glomerular vs. Non-Glomerular CKD ChildrenRe

lativ

e Pe

rcen

tiles

of

Glo

mer

ular

to N

on-G

lom

erul

ar D

x

P (%)(Pierce, Cox, … , Muñoz. Am J Epidemiol 2011;174:604-12.)

Universal GFR Determination Based on Two Time Points During Plasma

Iohexol Disappearance

Ng, Schwartz, … , MuñozKidney Int 2011;80:423-30.

(Ng, Schwartz, … , Muñoz. Kidney Int 2011;80:423-30.)

Relationship of Fast Area on BSA

R2= 56%Fast Area= 6.46 x BSA

-1.023

BSA (m2)

Fast

Are

a (m

g m

in/m

l)

No Residual Dependence of Fast Area on Slow Area once BSA is Accounted for

R2= 0.2%

Slow Area (mg min/ml)

log(

fast

are

a) –

[log

(6.4

6) –

1.0

23 lo

g (B

SA)]


Solid line = 0.12 x (GFR0,2 / 100)R2 = 75%

Dashed line = Nonparametric spline

GFR0,2 (GFR based on slow component only; ml/min|1.73m2)

Fast

Are

a /

Slow

Are

a =

(GFR

0,2 /

GFR

2,2)

– 1

Congruency Between CKiD and MACS

( )( )


Agreement Between GFR and Observed GFR

2,2 2,2 2,2 2,2CKiD MACS

GFR

(ml/

min

per

1.7

3m2 )


Metabolic Abnormalities, CVD Risk Factors and GFR

Decline in Children with CKD

Furth, Abraham, … , WaradyCJASN 2011;6:2132-2140.

Distribution of the Annual Percent Decline in GFR Presented by Non-Glomerular and Glomerular Diagnosis

(Furth, Abraham, … , Warady. CJASN 2011;6:2132-2140.)

FSGS HUS Other G ObstructUropathy

A/Hypo/Dysplastic

RefluxNeph

Polycyst(ARPKD)

Other NG

Annu

al P

erce

ntag

e Ch

ange

Urological Disorders in Chronic Kidney Disease in

Children (CKiD) Cohort: Clinical Characteristics and

Estimation of Glomerular Filtration Rate

Dodson, Jerry-Fluker, Ng, … , FurthJ of Urol 2011;186:1460-6.

Agreement Plots and Correlation of CKiD Bedside Equation Estimated GFR to Measured Iohexol GFR for

Children with Urological Diagnoses

(Dodson, Jerry-Fluker, … , Furth. J of Urol 2011;186:1460-6.)

n= 326

ml/

min

| 1.

73m

2

Bland-Altman Plot Comparing the CKiD Bedside GFR Equation with the iGFR Measurement

Beds

ide

GFR

– iG

FR (m

ean=

-0.5

+/-

11.

0)

Average of Bedside GFR and iGFR (mean= 46.3 +/- 16.5)(Dodson, Jerry-Fluker, … , Furth. J of Urol 2011;186:1460-6.)

Agreement Plots and Correlation of CKiD Bedside Equation Estimated GFR to Measured Iohexol GFR for Children not used in Original Equation Development, n= 119

ml/

min

| 1.

73m

2

(Dodson, Jerry-Fluker, … , Furth. J of Urol 2011;186:1460-6.)

Prevalence and Correlates of Multiple Cardiovascular Risk Factors in Children with CKD

Wilson, Schneider, … , MitsnefesCJASN 2011; 6:2759-65.

Distribution of the Number of Cardiovascular Risk Factors (CVRF) by Category of Age-Gender Specific Body Mass Index (BMI) Percentile, n= 250

(Wilson, Schneider, … , Mitsnefes. CJASN 2011; 6:2759-65.)

Lean

Overweight ObeseBMI Percentile (age-sex specific)

Perc

ent

Prevalence of Hypertension, Dyslipidemia, and Abnormal Glucose Metabolism by Category of Age-Gender Specific Body Mass Index (BMI) Percentile, n= 250

(Wilson, Schneider, … , Mitsnefes. CJASN 2011; 6:2759-65.)

Lean

Overweight ObeseBMI Percentile (age-sex specific)

Perc

ent

HNF1B and PAX2 Mutations are a Common Cause of Renal

Hypodysplasia in the CKiD Cohort

Thomas, Sanna-Cherci, … , GharaviPediatr Nephrol 2011; 26:897-903.

Chromatograms of Novel Pathogenic Mutations

(Thomas, Sanna-Cherci, … , Gharavi. Pediatr Nephrol 2011; 26:897-903.)

A

B

C

A G G R Y352fsX352

CKiD Sample (sequencing forward)

CKiD Sample (sequencing reverse)

Wild Type

Q L G V F V N G24E

CKiD Sample

Wild Type

CKiD Sample

Wild Type

P S T| Exon

Frameshift Mutation

MIssenseMutation

Splice SiteMutation

2012

Publications

Reliability of Resting Blood Pressure Measurement and

Classification Using an Oscillometric Device in

Children with Chronic Kidney Disease

Flynn, Pierce, … , WaradyJ Pediatr 2012; 160:434-440.

(Editorial by McBryde, KD)

auscultatory SBP, mm Hg

osc

illo

me

tric

SB

P, m

mH

g

60 80 100 120 140 160 180

60

80

10

01

20

14

01

60

18

0

mean of auscultatory SBP and oscillometric SBP

SB

P, o

scill

om

etr

ic-a

usc

ulta

tory

80 100 120 140 160

-40

-20

02

04

0

0.25

-0.25

0.5

-0.5

1

-1

Scatterplot and Bland-Altman of the SBP Oscillometric Measures against their Respective Auscultatory Measures

Mean of Auscultatory SBP and Oscillometric SBPAuscultatory SBP, mm Hg

SB

P,

Osc

illo

met

ric

- A

us

cult

ato

ry

Osc

illo

met

ric

SB

P,

mm

Hg

s.d.(oscill)/s.d.(ausc)= 1.019 (P=.72 for eq. of s.d.s)Bias (oscill-ausc) = 8.658 (P<.01 for no bias)Correlation = 0.624

Bias= 76% of s.d. of mean

(Flynn, Pierce, … , Warady. J Pediatr 2012; 160:434-440.)

auscultatory DBP, mm Hg

osc

illo

me

tric

DB

P, m

mH

g

20 40 60 80 100 120

20

40

60

80

10

01

20

mean of auscultatory DBP and oscillometric DBP

DB

P, o

scill

om

etr

ic-a

usc

ulta

tory

40 50 60 70 80 90 100

-40

-20

02

04

0

0.25

-0.25

0.5

-0.5

1

-1

Scatterplot and Bland-Altman of the DBP Oscillometric Measures against their Respective Auscultatory Measures

(Flynn, Pierce, … , Warady. J Pediatr 2012; 160:434-440.)

Mean of Auscultatory DBP and Oscillometric DBPAuscultatory DBP, mm Hg

SB

P,

Osc

illo

met

ric

- A

us

cult

ato

ry

Osc

illo

met

ric

DB

P,

mm

Hg

s.d.(oscill)/s.d.(ausc) = 0.929 (P=.201 for eq. of s.d.s)Bias (oscill-ausc) = 5.709 (P<.01 for no bias)Correlation = 0.491

Bias= 60% of s.d. of mean

Correlates of Resistin in Children with Chronic Kidney Disease: The Chronic Kidney Disease in Children Cohort

Nehus, Furth, … , MitsnefesJ Pediatr 2012; 161:276-280.

Correlation of Resistin and iGFR levels in Children with CKD

(Nehus, Furth, … , Mitsnefes. J Pediatr 2012; 161:276-280.)

1

2

3

4

5L

og

Tra

nsf

orm

ed R

esis

tin

, n

g/m

L

0 10 20 30 40 50 60 70 80 90 100 110 120 130 140 150 160

iGFR, mL/min/1.73m2

Correlation of Resistin and IL-6 levels in Children with CKDL

og

Tra

nsf

orm

ed R

esis

tin

, n

g/m

L

Log Transformed IL-6, pg/mL-1

0.5

0 1 2

0.6

0.7

0.8

0.9

1.0

1.1

1.2

1.3

1.4

1.5

1.6

1.7

1.8

1.9

2.0


Correlation of Resistin and HOMA-IR Values in Children with CKD L

og

Tra

nsf

orm

ed R

esis

tin

, n

g/m

L

Log Transformed HOMA-IR, mU/L-3 -2 -1 0 1 2 3 4

1

2

3

5

4


Improved GFR Estimating Equations in Children with

Chronic Kidney Disease Using Immunonephelometric

Determination of Cystatin C

Schwartz, Schneider, … , MuñozKidney Int 2012; 82:445-453.

(Commentary by Delanye P and Ebert N in Nat Rev Nephrol 2012; 8:503-504.)

Cystatin C Measured using the DAKO Turbidimetric Method vs. the Siemens Healthcare Nephelometric Method

(Schwartz, Schneider, … , Muñoz. Kidney Int 2012; 82:445-453.)

Dako(turbidimetric)

Siemens Healthcare(nephelometric)

r = 0.77

Cys

tati

n C

, m

g/L

0.75

1

2

3

4

5

6 N = 495

Log-Transformed Iohexol-Measured GFR (iGFR) vs. the Cystatin C-based Equation using Siemens Healthcare Measurements

10

20

30

40

5060708090

100110

iGF

R [

mL

/min

per

1.7

3m2 ]

1/2 2/3 1 3/2 2 5/21.8/Cystatin C (Siemens Healthcare [nephelometric] [mg/L])

N= 965R-square= 76.1%

eGFR= 40.6 [1.8/Cystatin C]0.93


10

20

30

40

5060708090

100110

iGF

R [

mL

/min

per

1.7

3m2 ]

1/4 1/3 1/2 1 2 3Height [m] / Serum Creatinine [mg/dL]

N= 965R-square= 77.1%

eGFR= 42.3 [height / serum creatinine]0.79

.

Log-Transformed Iohexol-Measured GFR (iGFR) vs. the Cystatin C-based Equation using Siemens Healthcare Measurements


Comparisons of Height/Serum Creatinine-based and Cystatin C-based eGFR against iGFR

Ht/Scr-basedeGFR

Iohexol-basedGFR

Cystatin C-basedeGFR

r = 0.872r = 0.878

10

20

40

80

100N= 965

Glo

mer

ula

r F

iltr

atio

n R

ate

[mL

/min

per

1.7

3m2 ]


Association Between Common Iron Store Markers and

Hemoglobin in Children with Chronic Kidney Disease

Atkinson, Pierce, … , FurthPediatr Nephrol 2012;27:2275-2283.

Distribution of Iron Biomarker Values by Stage of CKD in 304 Iron- and Erythropoiesis Stimulating Agent-naïve Enrolled in the CKiD Study

(Atkinson, Pierce, … , Furth. Pediatr Nephrol 2012;27:2275-2283.

A) Serum Iron B) Serum Ferritin C) TSAT

Se

rum

Iro

n,

µg

/dL

Se

rum

Fe

rrit

in,

ng

/dL

TS

AT

, %

GFR, ml/min|1.73m2 GFR, ml/min|1.73m2 GFR, ml/min|1.73m2

Percentile Plots of Hemoglobin Z-Score by KDOQI Recommended Thresholds for Ferritin in 304 Iron Supplement- and Erythropoiesis Stimulating agent-naïve Children

(Atkinson, Pierce, … , Furth. Pediatr Nephrol 2012;27:2275-2283.)

Serum Ferritin, ng/mL

Hem

og

lob

in,

z-sc

ore

Percentile Plots of Hemoglobin Z-Score by KDOQI Recommended Thresholds for TSAT in 304 Iron Supplement- and Erythropoiesis Stimulating agent-naïve Children


Transferrin Saturation, %

Hem

og

lob

in,

z-sc

ore

Regression tree analysis examining factors predictive of hemoglobinpercentile value in 304 iron supplement- and erythropoiesis

stimulating agent-naive children.


N=604th %ile[2, 9]

N=17531st %ile[22, 42]

N=6969th %ile[57, 79]

p = 0.11

p = 0.08

p = 0.11

p = 0.01

p = 0.14

p < 0.001

AllN=304

31th %ile(24, 38)

GFR < 60N=216

GFR ≥ 60N=88

GFR < 30N=34

GFR [30, 60)N=182

sFE < 50N=19

sFE ≥ 50N=69

sFE < 75N=20

sFE ≥ 75N=14

sFE [50, 75)N=25

sFE ≥ 75N=44

ferritin ≥ 100N=11

ferritin < 100N=171

sFE < 50N=33

sFE ≥ 50N=13

GFR [30, 45)N=15

GFR [45, 60)N=18

p < 0.001

p = 0.001

GFR: glomerular filtration rate (ml/min/1.73m2)sFE: serum iron (µg/dL)ferritin units = ng/mL

p = 0.11

Carotid Intima-Media Thickness in Children with Chronic Kidney Disease:

Results from the CKiD Study

Brady, Schneider, … , MitsnefesClin J Am Soc Nephrol 2012;7:1930-

1937.

Box-Percentile Plots Illustrating the Distribution of cIMT Measurements in 101 Children of the CKiD and in 97 Healthy Controls

0.25

0.30

0.35

0.40

0.45

0.50

0.55

0.60

0.65

CKiD Controls

Ca

rotid

art

ery

intim

a-m

ed

ial t

hic

kne

ss (

mm

)

N= 101 97

0.432

2.5%5%

10%

25%

50%

75%

90%

95%97.5%

0.413

2.5%5%10%

25%

50%

75%

90%

95%

97.5%

(Brady, Schneider, … , Mitsnefes. Clin J Am Soc Nephrol 2012;7:1930-1937.)

2013

Publications

Second Hand Smoke Exposure is Associated with Proteinuria in Children with

Chronic Kidney Disease

Omaloja, Jerry-Fluker, … , MitsnefesPediatr Nephrol 2013;28:1243-1251.

Distributions of Urine Cotinine Level by Proteinuria Category, with Proportions Classified as Exposed to Second Hand Smoke

(Omaloja, Jerry-Fluker, … , Mitsnefes. Pediatr Nephrol 2013;28:1243-1251.)

Proteinuria Category

Distributions of Urine Cotinine/Urine Creatinine Level by Proteinuria Category, with Proportions Classified as Exposed to Second Hand Smoke

Proteinuria Category

(Omaloja, Jerry-Fluker, … , Mitsnefes. Pediatr Nephrol 2013;28:1243-1251.)

Non-proportionality of Hazards in the Competing

Risks Framework

Muñoz, Abraham, … , WadaRisk Assessment: Evaluation of Predictions

Springer Verlag, 2013

Sub-Hazards and Relative Sub-Hazards for the Competing Risks Setting Defined by the True Model

(Muñoz, Abraham, … , Wada. Risk Assessment: Evaluation of Predictions; Springer Verlag, 2013)


Effect of Annual Income Above/Below $36,000 on the Competing Events of ESRD and Renal Transplantation in the CKiD Study


Effect of Nephrotic Proteinuria (uP/C >2) on the Competing Events of ESRD and Renal Transplantation in the CKiD Study

2014

Publications

Nonlinear Trajectory of GFR in Children to RRT

Zhong, Muñoz, … , AbrahamJ Am Soc Nephrol 2014; 25: 913-917.

Nonlinear GFR Decline before RRT can be Approximated with a Piece-Wise Log-Linear Model

(Zhong, Muñoz, … , Abraham. J Am Soc Nephrol 2014 Jan 2. [Epub ahead of print])

Disordered FGF23 and Mineral Metabolism in Children with CKD

Portale, Wolf, … , SaluskyClin J Am Soc Nephrol 2014;9:344-353.

Mineral and Hormone Values According to Estimated GFR at 10-ml/min per 1.73 m2 Intervals in Children with CKD

(Portale, Wolf, … , Salusky. Clin J Am Soc Nephrol 2014;9:344-353.)

(A) Median concentrations of serum corrected–calcium, phosphorus, and immunoreactive parathyroid

hormone (iPTH)

(B) Median concentrations of serum 25-hydroxyvitamin D (25OHD) (ng/ml), 1,25-

dihyroxyvitamin D [1,25(OH)2D] (pg/ml), and

plasma fibroblast growth factor 23 (FGF23)

Mean phosphorus z scores and median plasma FGF23 concentrations according to estimated GFR at 10-ml/min per 1.73 m2 intervals


*P< 0.05**P< 0.001

Prevalence of Hyperphosphatemia, Hyperparathyroidism, and Increased Plasma FGF23 According to GFR Groups


Ceramides and Cardiac Function in Children with Chronic Kidney

Disease

Mitsnefes, Scherer, … , WaradyPediatr Nephrol 2014;29:415-422.

Comparison of Total Ceramide Levels in Healthy Children and Children with Chronic Kidney Disease (CKD)

(Mitsnefes, Scherer, … , Warady. Pediatr Nephrol 2014;29:415-422.)

No

rmal

ized

Cer

amid

es (

To

tal)

Controls CKD

14

12

10

8

6

4

P< 0.001

Distribution of Ceramides in Healthy Controls and Children with Chronic Kidney Disease (CKD)


Per

cen

t

60

50

40

30

20

10

0

ControlsCKD

Comparison of Individual Ceramide Levels in Healthy Children and Children with Chronic Kidney Disease (CKD)


P< 0.001 for all pair comparisons except C18:1

ControlsCKD

No

rmal

ized

Cer

amid

e L

evel

Distribution of Lactosylceramides C16:0L and C24:0L in Healthy Controls and Children with Chronic Kidney Disease (CKD)


Per

cen

t

C24:0 Metabolites

Per

cen

t

*C15:0DH is 0.27% for controls and 0.41% for CKD

Controls CKD Controls CKD

C16:0 Metabolites

BP Control and Left Ventricular Hypertrophy Regression in

Children with CKD

Kupferman, Friedman, … , MitsnefesJ Am Soc Nephrol 2014;25:167-174.

Partial Residual Plot of Log(LVMI) versus (A) SBP and (B) DBP Z-Scores

(Kupferman, Friedman, … , Mitsnefes. J Am Soc Nephrol 2014;25:167-174. )

(BP Z-score was adjusted for age, sex, and height.)

The Effect of Abnormal Birth History on Ambulatory Blood

Pressure and Disease Progression in Children with

Chronic Kidney Disease

Flynn, Ng, … , GreenbaumJ Pediatr 2014; 165: 154-162.

Distribution of Propensity Scores, by Birth History Status and Matched Data with Weighting, based on Full Constrained Matching

(Flynn, Ng, … , Greenbaum. J Pediatr 2014; 165: 154-162.)

Medication Treatment Complexity and Adherence in

Children with CKD

Blydt-Hansen, Pierce, … , FurthClin J Am Soc Nephrol 2014;9:247-254.

Distribution of Number of CKD-Related Medication Groups by CKD Stage and CKD Diagnosis (N=558)

(Blydt-Hansen, Pierce, … , Furth. Clin J Am Soc Nephrol 2014;9:247-254.)CKD diagnosis & stage

Pe

rce

nt

0

20

40

60

80

100

NG G NG G NG G NG GII IIIa IIIb IV

0 1-2 3-4 5-6 >=7Number of medication groups:

N= 89 38 120 23 153 36 76 23

Cluster Plots Showing Primary Pair-Wise Associations and Subsequently Ranked Associations between Medication Groups, Restricted to 19 Groups of Medications for Management of CKD-Specific

Complications, Treatment of Underlying Kidney Disease, and Symptom Control

(Blydt-Hansen, Pierce, … , Furth. Clin J Am Soc Nephrol 2014;9:247-254.)

Nutritional Supplements

(n=12)

Alkali Therapy(n=163)

Growth Hormones

(n=65)

ESA(n=75)

Iron Supplements

(n=166)

PO4 Binders(n=114)

ActiveVitamin D(n=206)

OR=12.8; n=165 OR=11.8; n=183

OR=4.5; n=268

OR=4.6; n=343

OR=5.9; n=240

OR=5.1; n=189

Cluster 2: N=343 patients on 1+ medications in this cluster

Lipid Lowering Rx(n=17)

Diuretics(n=38)

Other BP Meds(n=106)

OR=8.7; n=49

OR=5.0; n=131


Corticosteroids(n=36)

Other immunosuppressants(n=42)

Antacids(n=54)

Vitamin D(n=17)

OR=67.5; n=53

OR=11.7; n=84

OR=4.22; n=93


Heart Rate and Blood Pressure Variability in Children with Chronic Kidney Disease: A

Report from the CKiD Study

Barletta, Flynn, … , FurthPediatr Nephrol 2014;29:1059-1065.

Comparison of blood pressure (BP) standard deviation (SD) and heart rate SD by sleep-wake periods and hypertensive condition

(Barletta, Flynn, … , Furth. Pediatr Nephrol 2014;29:1059-1065.)

Sys

toli

c B

P S

D

Dia

sto

lic

BP

SD

Hea

rt R

ate

SD

Sleep Sleep

Sleep Wake

WakeWake

Protein Energy Wasting in Children with Chronic Kidney

Disease

Abraham, Mak, … , FurthPediatr Nephrol 2014;29:1231-1238.

The Prevalence of Indicators of Protein-Energy Wasting (PEW) used to form the Three Definitions. The Prevalence is Presented

Stratified by CKD Stage and Overall

(Abraham, Mak, … , Furth. Pediatr Nephrol 2014;29:1231-1238.)

The Prevalence of Protein Energy Wasting (PEW) as Classified using the Three Definitions Adopted in this Study: Minimal PEW,

Standard PEW, and Modified PEW


The Unadjusted and Adjusted Incidence Rate Ratios for Hospitalization within the 2 years from Baseline Comparing the Three Protein-Energy Wasting (PEW) Definitions used in this Study


Adjusted

Unadjusted

Medication Adherence and Growth in Children with Chronic

Kidney Disease

Akchurin, Schneider, … , SkverskyClin J Am Soc Nephrol 2014;9:1519-1525.

Medication Use at the First Seven Visits of the CKiD Study

(Akchurin, Schneider, … , Skversky. Clin J Am Soc Nephrol 2014;9:1519-1525.

Prevalence of Non-Adherence by Medication Group at each of the First Seven Visits of the CKiD Study

Study Visit

Mis

sing

Med

icat

ion

in t

he p

revi

ous

7 da

ys (

%)

(Akchurin, Schneider, … , Skversky. Clin J Am Soc Nephrol 2014;9:1519-1525.

Hepcidin and Risk for Anemia in CKD: a Cross-Sectional and

Longitudinal Analysis in the CKiD Cohort

Atkinson, Kim, … , FurthPediatr Nephrol 2014 Nov 8 [Epublished ahead of print].

Scatterplots of Log-transformed Hepcidin vs. GFR (a), Hemoglobin (b), Ferritin (c), and Rank of log-transformed Hepcidin vs. Rank of Ferritin (d)

(Atkinson, Kim, … , Furth. Pediatr Nephrol 2014 Nov 8 [Epublished ahead of print])

ieGFR (mL/min/1.73m2)20 40 60 80 100

1.0

1.5

2.0

2.5

Lo

g(H

ep

cid

in)

(lo

g n

g/m

L)

(a) (b)

1.0

1.5

2.0

2.5

Lo

g(H

ep

cid

in)

(lo

g n

g/m

L)

(c)

1.0

1.5

2.0

2.5

Lo

g(H

ep

cid

in)

(lo

g n

g/m

L)

Ferritin (ng/mL)0 100 200 300 400 500

HGB (g/dL)10 12 14 16

Rank of Ferritin

Ra

nk

of

Lo

g(H

ep

cid

in) 60

50

40

30

20

10

00 10 20 30 40 50 60

(d)

Genome-Wide Association Studies in Nephrology: Using Known Associations for Data

Checks

Wuttke, Schaefer, … , KöttgenAm J Kidney Dis 2014 Nov 18 [Epublished ahead of print].

Effects of Serum Creatinine-based Estimated GFR Adjustment on Single-Nucleotide Polymorphism (SNP) Associations with

Serum Bilirubin Concentrations

(Wuttke, Schaefer, … , Köttgen. Am J Kidney Dis 2014 Nov 18 [Epub ahead of print])

Effects of Serum Creatinine-based Estimated GFR Adjustment on Single-Nucleotide Polymorphism (SNP) Associations with

Cystatin C Concentrations

(Wuttke, Schaefer, … , Köttgen. Am J Kidney Dis 2014 Nov 18 [Epub ahead of print])

2015

Publications

Progression of Pediatric CKD of Non-Glomerular Origin in the

CKiD Cohort

Fathallah-Shaykh, Flynn, … , WongClin J Am Soc Nephrol 2015 Jan 29

[Epublished ahead of print].

Changes in GFR by Baseline Urine Protein-to-Creatinine Ratio and Casual Blood Pressure Status for 522 Children with Nonglomerular CKD

(Fathallah-Shaykh, … , Wong. Clin J Am Soc Nephrol 2015 Jan 29[Epub ahead of print])

Baseline Urine Protein:Creatinine

GF

R C

han

ge,

mL

/min

|1.7

3m2 /

year

Predictors of Rapid Progression of Glomerular and Nonglomerular Kidney Disease in Children and

Adolescents: the Chronic Kidney Disease in Children (CKiD)

Cohort

Warady, Abraham, … , FurthAm Social J Kidney Dis 2015 Mar 12

[Epublished ahead of print].

Kaplan-Meier and Log-Normal Survival Curves for Composite Event of Baseline Urine Protein-Creatinine Ratio (UPC) for Glomerular and Nonglomerular Participants

(Warady, Abraham, … , Furth. Am Social J Kidney Dis 2015 Mar 12 [Epub ahead of print])

Kaplan-Meier Curves show the Predicted Standardized Times of the Composite Event Resulting from the Cross-Validation

(Warady, Abraham, … , Furth. Am Social J Kidney Dis 2015 Mar 12 [Epub ahead of print])W

Su

rviv

al F

un

ctio

n

Su

rviv

al F

un

ctio

n

W

Estimates of Survival Curves for the Composite Event based on Log-Normal Models of Participants with Different Constellations of Clinical Variables for Glomerular and Nonglomerular Participants

(Warady, Abraham, … , Furth. Am Social J Kidney Dis 2015 Mar 12 [Epub ahead of print])

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