Managing a child with CRI CKD4

1
Managing a child with CRI (CKD4)

• Constantinos Stefanidis

P. A. Kyriakou Childrens Hospital Athens,
Greece
2
20 months old girl

• 1st UTI at the age of 13 months
• fever 3 days
• U/C E. coli gt105/ml
• VCUG VUR Gr. IV RL
• US dilatation of pelvis
• S. Creatinine 1.3 mg/dl (114 µmol/L)
• Length 69 cm
• Weight 8 kg (Birth Wt 2.4 kg)
• BP 75/53mmHg

3

• 2nd UTI at the age of 17 months
• fever 1 day
• U/C E. coli gt105/ml
• At the age of 20 months
• US dilatation of pelvis, high echogenity
• S. Creatinine 1.6 mg/dl (141 µmol/L)
• Length 73 cm
• Weight 9 kg

BP 108/65 mmHg
4
https//web.emmes.com/study/ped/resources/htwtcalc
.htm
5
https//web.emmes.com/study/ped/resources/htwtcalc
.htm
6
This child has hypertension ?
BP 108/65 mmHg
7
BP 108/65 mmHg
Hypertension
http//www.nhlbi.nih.gov/guidelines/hypertension/c
hild_tbl.pdf
Fourth Report on the Diagnosis, Evaluation, and
Treatment of High Blood Pressure in Children and
Adolescents
8
BP 108/65 mmHg
Hypertension
http//www.nhlbi.nih.gov/guidelines/hypertension/c
hild_tbl.pdf
Fourth Report on the Diagnosis, Evaluation, and
Treatment of High Blood Pressure in Children and
Adolescents
9

• U Pr/Cr 1
• Hgb 8.8 g/dL (HCt 27)
• K 4.3 mEq/L Na 136 mEq/L
• Ca 9.2 mg/dl P 5.5 mg/dl
• pH 7.32 HCO3 18 mEq/L

Proteinuria
Anemia
Metabolic Acidosis
10
Kidney length (mm)
Height (cm)
11
What is the diagnosis ?
VUR with renal hypoplasia
12
This child has CKD ?
13
Estimated Ccr
Ccr k L/Pcr where k 0.55
Schwartz GJ, Haycock GB, Edelmann CM Pediatrics
1976
in adolescent boys k 0.7 in full-term infants
during the first year of life k 0.45 in
pre-term infants during the first year of life k
0.35
Schwartz GJ, Feld LG, Langford J Pediatr. 1984
14
Criteria for the Definition of CKD
1. Kidney damage for 3 months, with or without
decreased GFR, manifested by 1 or more of the
following features Abnormalities in the
composition of the blood or urine
Abnormalities in imaging tests Abnormalities
on kidney biopsy
2. GFR lt60 mL/min/1.73 m2 for 3 months, with or
without the other signs of kidney damage
described above.
Hogg RJ et al, Pediatrics. 2003
15
NKF-K/DOQI Classification of the Stages of CKD
Hogg RJ et al, Pediatrics. 2003
16
Prevelence of CKD
17
North American Pediatric Renal Transplant
Cooperative Study
4666 children
28
50-75
40
25-49
27
1024
5
lt10
Seikaly MG et al. Pediatr Nephrol 2003
18
Chronic Kidney Disease

• Prevalence of CKD in adult population 10.2
• US data Coresh et al., AJKD 2003
• Worldwide 1.800.000 people on RRT
• RRT patients in US 350.000
• Xue et al., J Am Soc Nephrol 2001

19
Can we predict the progression of CKD ?
20
Estimated kidney survival in children with CRF by
age
1197 patients
Overall population (n 1197) patients with
baseline creatinine clearance lt25 mL/min (n
315) 2550 mL/min (n 419) 5175 mL/min (n
463).
Ardissino, G. et al. Pediatrics 2003111382-387
21
Remuzzi et al., J Clin Invest 16, 2006
22
Can we slow down the progression of CKD ?
23

• Reduced prevalence of RRT
• Better patient survival, reduced CVD mortality
• Better quality of live
• Reduction of health care costs

Slowing down of CKD Progression
24
Proteinuria
Hypertension
Progression of CKD
Ca-Phosphate PTH
Anemia
Genetic background
Underlying renal disease
25
European Study Group on CRF Progression in
Childhood
Blood Pressure
Proteinuria
Protein intake
Study Period (years)
Study Period (years)
Study Period (years)
Wingen et al. Lancet 1997 3491117
26
European Study Group on CRF Progression in
Childhood
Blood Pressure
Proteinuria
Protein intake
Study Period (years)
Study Period (years)
Study Period (years)
Wingen et al. Lancet 1997 3491117
27
European Study Group on CRF Progression in
Childhood
Blood Pressure
Proteinuria
Protein intake
Study Period (years)
Study Period (years)
Study Period (years)
Wingen et al. Lancet 1997 3491117
28
Hypertension
Mitsnefes M et al. J Am Soc Nephrol. 2003
29
Is it possible to slow down the progression of
CKD ?
30
Renoprotection by ACE-inhibition
Combined antiproteinuric and antihypertensive
treatment by ACE-inhibition to slow
deterioration of GFR
31
ESCAPE trial
Antihypertensive and antiproteinuric efficacy of
ramipril in children with chronic renal
failure. Wuhl E, Mehls O, Schaefer F ESCAPE
Trial Group. Kidney Int 2004
32
ESCAPE trial

• 397 children of age 3-18 years
• GFR 15-80 ml/min/1.73m2
• 24hrs MAP gt 50th percentile
• Ramipril 6 mg/m2

33
ESCAPE trial
34
ESCAPE trial
35
Antihypertensive and Renoprotective Effect of
Ramipril Independent of Underlying Renal Disease
Effect of ramipril treatment by renal function
(K/DOQI CKD Stage 2-5)






Mean SEM
Mean SEM




Stage 2 3 4 5
Stage 2 3 4 5
ESCAPE
36
Antihypertensive and Renoprotective Effect of
Ramipril Independent of Underlying Renal Disease
Effect of ramipril treatment by renal function
(K/DOQI CKD Stage 2-5)






Mean SEM
Mean SEM




Stage 2 3 4 5
Stage 2 3 4 5
ESCAPE
37
Frequency of anemia in CKD5 ?
38
North American Pediatric Renal Transplant
Cooperative Study
1,942 patients (017 years)
of children with CKD
Hematocrit
33
gt33
30-33
27-30
lt27
Warady BA  and Ho M Pediatr Nephrol 2003
39
Why anemia is a problem in children with CKD ?
40
A baseline hematocrit of lt33 was associated with
more hospitalization
Anemia was associated with a 52 higher risk of
death
Cardiopulmonary disease was the primary reported
cause of death
Warady BA  and Ho M Pediatr Nephrol 2003
41
Should we treat the anemia of this child ?
Hgb 8.8 g/dL (HCt 27)
42
The management of anemia
Guidelines by an ad hoc European
committee Cornelis H. Schröder and The European
Pediatric Peritoneal Dialysis Working Group
After the work-up has been completed, iron
and/or erythropoietin therapy should be initiated
to obtain a target Hgb of at least 11 g/dl (Hct
33)
Start with EPO of 50100 U/kg SC x 2-3 per week.
Maintenance recommendations 300 U/kg/week
(weight of lt20 kg) 120 U/kg/week (weight of
gt30 kg )
Schröder CH et al.Pediatr Nephrol 2003
43
Transferrin saturation gt 20 Serum ferritin
concentration gt 100 ng/ml Iron supplements
23 mg/kg body weight per day in two to three
divided doses either 1 or 2 h after food.
Schröder CH et al.Pediatr Nephrol 2003
44
Darbepoetin alfa
124 pediatric patients
CKD 4 and 5
Warady BA  et al. Pediatr Nephrol 2006
45
Darbepoetin alfa
rHuEPO
Darboepoetin alfa
2 3 times /week
1 dose /week
1 dose /week
1 dose /2 weeks
Cumulative dose of Darboep./week with
conversion 100 U rHuEPO 0.42 mcg of Darboep.
Mean dose of rHuEpo 194 U/ kg/ week
Mean dose of Darboep. 0.9 mcg/ kg/ week
Warady BA  et al. Pediatr Nephrol 2006
46
Erythropoietin resistance
Schröder CH et al.Pediatr Nephrol 2003
47
How is the growth of this child ?
48
Length
http//www.cdc.gov/nchs/data/ad/ad314.pdf
49
Weight
http//www.cdc.gov/nchs/data/ad/ad314.pdf
50

51
Why growth retardation is a problem in children
with CKD ?
52
Psychosocial problems

• Children with CRF and extreme short stature are
  at risk that this disability may affect their
• physical
• psychological
• social well-being

Henning P Arch Dis Child (1988) Law CM. Arch
Dis Child (1987)
53
Growth retardation Hospitalizations Risk
ratio per patient/year Severe (z lt
-3) 1.65 1.50 Moderate (z lt
-2) 1.59 1.51 Normal growth 1.05 1.0
Death rate Risk
ratio Severe 16.2 3.2 Moderate 11.5 2.
1 Normal growth 5.6 1.0
Furth SL et al., Pediatri Nephrol 2002
54
North American Pediatric Renal Transplant
Cooperative Study
Seikaly MG et al Pediatr Nephrol 2006
55
Why children with CKD have growth retardation?
56
Etiology of growth failure in CKD
? Growth
Disordered GH metabolism
57
The 3 phases of growth in CKD
2 SDS
180 160 140 120 100 80 60
Mean
- 2 SDS
Height (cm)
Sex hormones
GH (and thyroid hormones)
2 4 6 8 10
12 14 16 18
Age (years)
58
Management of growth retardation

• Aggressive nutritional intervention should be
  planed (especially when the weight for height
  sdslt -2)
• Anemia with recombinant human erythropoietin and
  iron administration should be corrected
• Renal osteodystrophy should be treated
  appropriately
• Sodium losses of children with hypoplastic
  kidneys should be replaced
• Metabolic acidosis (HCO3 lt 20 mEq/L) should be
  corrected to reduce protein catabolism

59
Committee on Dietary Allowances (1989)
Recommended dietary allowances. National Academy
of Science, Washington D.C.
60
Prediction of protein intake
Protein intake (Urea-N excretion x 15.4)-0.8
(g/kg/day)
(g/kg/day)
Calculation of mean urea-N excretion from at
least 4 consecutive measurements is reliable,
provided the patients don't suffer from caloric
malnutrition or severe acidosis.
A.-M. Wingen, C. Fabian-Bach, and O. Mehls Clin
Nephrol (1993)
61
Age, years
0.5 1.5 2.5 3.5 4.5 5.5
6.5 7.5 8.5 9.5 10.5 11.5
12.5
0 -1.0 -2.0 -3.0 -4.0
5
2
7
20
10
Height SDS
19
18
15
27
40
24
34
42
43
44
59
55
47

• Retrospective analysis
• 81 children
• CRF in the first 6 months of life
• GFR lt 20 ml/min/1.73m2
• 81 enterally fed for 0.1 to 6.8 years

68
62
75
71
75
78
63
Kari et al. Kidney Int 2000
62
Age, years
0.5 1.5 2.5 3.5 4.5 5.5
6.5 7.5 8.5 9.5 10.5 11.5
12.5
0 -1.0 -2.0 -3.0 -4.0
5
2
7
20
10
Height SDS
19
18
15
27
40
24
34
42
43
44
59
55
47

• Retrospective analysis
• 81 children
• CRF in the first 6 months of life
• GFR lt 20 ml/min/1.73m2
• 81 enterally fed for 0.1 to 6.8 years

68
62
75
71
75
78
63
Kari et al. Kidney Int 2000
63
Age, years
0.5 1.5 2.5 3.5 4.5 5.5
6.5 7.5 8.5 9.5 10.5 11.5
12.5
0 -1.0 -2.0 -3.0 -4.0
5
2
7
20
10
Height SDS
19
18
15
27
40
24
34
42
43
44
59
55
47

• Retrospective analysis
• 81 children
• CRF in the first 6 months of life
• GFR lt 20 ml/min/1.73m2
• 81 enterally fed for 0.1 to 6.8 years

68
62
75
71
75
78
63
Kari et al. Kidney Int 2000
64
Indications for growth hormone therapy
Standard deviation score (SDS) for height lt -2
or /and SDS for height velocity lt -2 SDS
At least two separate height measurements during
the previous year are necessary to assess height
velocity
rhGH should be prescribed once assurance has been
made that provision of energy, protein, and
micronutrients is adequate and that metabolic
acidosis, hyperphosphataemia, and secondary
hyperparathyroidism have been managed
65
Growth hormone therapy
30 children lt 2.5 years with CRF Placebo vs rhGH
treatment for 2 years
Fine RN et al. Pediatr Nephrol 1995
66
Growth hormone therapy
Final height sds
Initial height sds
-1,6
-3,1
RhGH administration
Haffner DJ et al, N Engl J Med 2000
67
How to improve outcome
1. Organize a CKD 4 Clinic
2. Early referrals
3. Early management
68
CKD 4 Clinic

• Organized from a pediatric RRT program
• Educational material, organized education
• Multiprofessional team

69
Multiprofessional team
70
How to improve outcome
1. Organize a CKD 4 Clinic
2. Early referrals
3. Early management
71
Nephrology Dialysis Transplantation 2006
21(4)957-961
72
Early referrals

• Data of 180 children on CPD
• in the years 2002 and 2003 in 13 dialysis centres

Early referrals (ER) when they entered the
dialysis programme at least 1 month after the
first referral to a nephrologist. 79 Late
referrals (LRs) when the dialysis was introduced
within 1 month from the first visit. 21
Jander A et al. Nephrology Dialysis
Transplantation 2006 21(4)957-961
73
Early referrals
Jander A et al. Nephrology Dialysis
Transplantation 2006 21(4)957-961
74
Early referrals
Jander A et al. Nephrology Dialysis
Transplantation 2006 21(4)957-961
75
Early referrals

• Percentage of subjects with
• Body mass index (BMI) lt 10th percentile
• ER patients 22
• LR 37 (Plt0.001)
• PD as the first method of dialysis
• ER patients 59
• LR 46

Jander A et al. Nephrology Dialysis
Transplantation 2006 21(4)957-961
76
CKD 4
CKD 5
Pre-emptive
Transplantation
Dialysis
HD
CPD
77
Residual renal function and growth

• The native KCr had a significant positive
  correlation with delta height SDS.

Chadha V et al., Perit Dial Int 2001
78
Residual renal function and growth
0
-0,5
RRF 0
-1
-1,29 (N10)
Height SDS
-1,37 (N10)
-1,44 (N8)
-1,5
-1,66 (N6)
-2
-2,5
-3
0
1
2
3
Dialysis period (years)
Stefanidis CJ et al., Pediatr Nephrol 2006
79
When to start dialysis or premptive
transplantation?

• European
• Paediatric
• Dialysis
• Working
• Group
• Watson AR
• Schroder C
• Fischbach M
• Schaefer F
• Edefonti A
• Stefanidis C
• Ronnholm K
• Zurowska A

FI
UK
PL
NL
DE
FR
IT
GR
Pediatr Nephrol 2000 6, 5C38.
80
Choice of ESRF Therapy in Eight European Centres
Retrospective study April 1996 - March 1999

• 189 patients (109 male)
• Mean age 9.1 yrs (range 0.01-19.3 yrs)
• 51 (27) lt 5 yrs of age
• 138 (73) gt 5 yrs of age

81
Choice of ESRF Therapy in Eight European Centres
Commencing dialysis

• Consensus
• CKD5 (GFR 10 - 14 ml/min/1.73m2)
• GFR (KUr KCr )/2
• Reality

Mean GFR 8.6 4.5 ml/min/1.73m2 Mean HEIGHT SDS
- 1.3 1.6 Mean WEIGHT SDS - 1.2 1.7
82
Early referral
Early RRT
Appropriate Management
83
Chronic Kidney Disease 4

• Nutrition and growth
• Hypertension Proteinuria
• Renal osteodystrophy
• Anemia
• Infection urinary tract problems
• Sodium losses metabolic acidosis
• Psychosocial care

84
CKD 4