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Preventing and Managing Chronic Kidney
Disease in Children
Constantinos J. Stefanidis, MD, PhD
“P & A Kyriakou” Children’s Hospital, Athens, Greece
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CKD
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Defining CKD
Preventing CKD progression
Managing complications
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Defining CKD
Kidney Disease Outcomes Quality Initiative (KDOQI)
working group of the National Kidney Foundation (NKF)
defined chronic kidney disease as:
• evidence of structural or functional kidney
abnormalities (abnormal urinalysis, imaging studies,
or histology)
• that persist for at least 3 months
• with or without a decreased glomerular filtration rate
(GFR <60 mL/min per 1.73 m2)
K/DOQI clinical practice guidelines for CKD Am J Kidney Dis. 2002
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Glomerular
capillaries
Bowman’s capsule
Glomerulus
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Glomerular filtration rate (GFR)
Bowman’s
capsule
Glomerular
capillaries
GFR
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170 L / 24hrs/1.73 m2
120 mL/min/1.73 m2
Glomerular filtration rate (GFR)
GFR
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170 L / 24hrs/1.73 m2
120 mL/min/1.73 m2
1.5 L /24hrs/1.73 m2
Glomerular filtration rate (GFR)
GFR
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NKF-K/DOQI Classification of the Stages of CKD
Stage
GFR /1.73 m2
1
≥90
Kidney damage* with
normal or increased GFR
2
60–89
Kidney damage with
mild reduction of GFR
Description
K/DOQI clinical practice guidelines for CKD Am J Kidney Dis. 2002
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NKF-K/DOQI Classification of the Stages of CKD
Stage
GFR /1.73 m2
1
≥90
Kidney damage with
normal or increased GFR
2
60–89
Kidney damage with
mild reduction of GFR
3
30–59
moderate reduction of GFR
4
15–29
severe reduction of GFR
5
<15
(or dialysis)
Kidney failure
Description
K/DOQI clinical practice guidelines for CKD Am J Kidney Dis. 2002
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Defining kidney damage in CKD
1. Urine sediment abnormalities
2. Electrolyte and other abnormalities due to tubular
disorders.
3. Imaging abnormalities. Patients with significant
structural abnormalities persisting for > 3 months.
4. Pathologic abnormalities in kidney tissue obtained by
biopsy.
5. History of kidney transplantation.
KDIGO 2012 Clinical Practice Guideline Kidney Intern 2013`
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Defining CKD: determine the cause
In any child with GFR<60 ml/min/1.73m2 or more than 1 SD below expected for their age and sex
or with markers of kidney damage
Consider:
• a complete review of their past history
• previous measurement or estimate of renal function
KDIGO 2012 Clinical Practice Guideline Kidney Intern 2013
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Defining CKD: determine the cause
In any child with GFR<60 ml/min/1.73m2 or more than 1 SD below expected for their age and sex
or with markers of kidney damage
Consider:
• a complete review of their past history
• previous measurement or estimate of renal function
• prenatal history, drug exposures of fetus or mother
• genetic conditions, coincident organ abnormalities
KDIGO 2012 Clinical Practice Guideline Kidney Intern 2013
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Defining CKD: determine the cause
In any child with GFR<60 ml/min/1.73m2 or more than 1 SD below expected for their age and sex
or with markers of kidney damage
Consider:
• a complete review of their past history
• previous measurement or estimate of renal function
• prenatal history, drug exposures of fetus or mother
• genetic conditions, coincident organ abnormalities
• physical examination
• fetal and post-natal laboratory measures
(amniotic fluid, pre- and post-natal imaging, placenta)
KDIGO 2012 Clinical Practice Guideline Kidney Intern 2013
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Stages of CKD (KDIGO 2012)
KDIGO 2012 Clinical Practice Guideline Kidney Intern 2013`
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Stages of CKD (KDIGO 2012)
KDIGO 2012 Clinical Practice Guideline Kidney Intern 2013`
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Defining CKD in children < 2 years
K/DOQI clinical practice guidelines for CKD Am J Kidney Dis. Feb 2002
This definition is not applicable to children < 2 years,
because they normally have a low GFR.
The criteria for duration >3 months does not apply to
newborns or infants <3 months of age.
GFR > 1 SD below the mean (> -1 SDS): normal
GFR < 1 SD below the mean: moderately reduced GFR
GFR < 2 SD below the mean: severely reduced GFR
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GFR in children < 2 years
Piepsz A, et al. Eur J Nucl Med Mol Imaging, 2006
http://cjasn.asnjournals.org/content/4/11/1832.full
moderately
Reduced GFR
severely Age months
Mean Mean -1SD Mean -2SD
<1 50 40 30
1.1 to 3.5 60 50 35
3.6 - 8 70 60 45
8.1 - 12 80 65 50
12.1 - 24 90 75 55
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Glomerular filtration rate (GFR)
• Estimated GFR (eGFR)
• Creatinine clearance (CCr)
• Isotopic measurement (iGFR)
• Inulin clearance
• Ιohexol clearance and urinary protein
Chronic Kidney Disease in Children (CKiD) trial
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Equations to Estimate GFR in Children with CKD
Updated Schwartz “bedside” formula:
eGFR = 0.41 x height (cm) / Scr (mg/dl)
25% reduction from the previous formula
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2653687/
GJ Schwartz et al, CJ Am Soc Nephrol. 2009
eGFR = 36.5 x height (cm) / Scr (μmol/L)
enzymatic creatinine determinations
Chronic Kidney Disease in Children (CKiD) trial
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Equations to Estimate GFR in Children with CKD
Updated Schwartz bedsite formula:
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2653687/
GJ Schwartz et al,J Am Soc Nephrol. 2009
K = 0.41
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Cystatin C to estimate GFR in Children with CKD
The sensitivity of s-CysC for detecting impaired GFR in
pediatric patients seems superior to that of plasma
creatinine, especially in selected populations of children
with low muscle mass.
To answer the question of superiority of s-CysC in the
‘creatinine-blind’ area, studies excluding children with low
GFR values need to be performed.
Andersen TB et al., Pediatr Nephrol 2009
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Preventing CKD progression
Managing complications
Defining CKD
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Prevention of CKD progression
KDIGO 2012 Clinical Practice Guideline Kidney Intern 2013
We recommend that in children with CKD, BP-lowering
treatment is started when BP is consistently above the
90th percentile for age, sex, and height. (1C)
We suggest that in children with CKD (particularly those
with proteinuria), BP is lowered to consistently
achieve systolic and diastolic readings less than or
equal to the 50th percentile for age, sex, and height,
(2D)
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Prevention of CKD progression
KDIGO 2012 Clinical Practice Guideline Kidney Intern 2013
We suggest that an ARB or ACE-I be used in children
with CKD in whom treatment with BP-lowering drugs is
indicated, irrespective of the level of proteinuria. (2D)
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Prevalence of CKD complications
KDIGO 2012 Clinical Practice Guideline Kidney Intern 2013
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ESCAPE trial
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ESCAPE trial
385 children of age 3-18 years GFR 15-80 ml/min/1.73m2
Patients were randomly assigned to:
Intensified BP control
(with a target 24-hour mean arterial pressure <50th percentile)
or
Conventional BP control
(mean arterial pressure in the 50th to 95th percentile)
Ramipril 6 mg/m2/day
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ESCAPE trial
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ESCAPE trial
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Age (years)
0 2 4 6 8 10 12 14 16
0
10
20
30
40
50
60
70
80
Renal hypoplasia-dysplasia
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CKD and risk of AKI
KDIGO 2012 Clinical Practice Guideline Kidney Intern 2013
We recommend that all people with CKD are considered
to be at increased risk of AKI. (1A)
People with CKD, should be followed for management
when undergoing investigation and procedures that are
likely to increase the risk of AKI. (Not Graded)
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Preventing CKD progression
Managing complications
Defining CKD
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How does CKD present?
Asymptomatic Disease
Especially early despite the
accumulation of harmful metabolites
Incidental finding of urine abnormalities or
raised creatinine
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Complications of CKD
Polyuria
Nocturia
Oedema
LVH
Hypertension
Seizures
Confursion
Coma
CKD-MBD
Muscle weackness
Bone pain
Fractures
Anemia
Pallor
GI tract
Anorexia
Nausea
Vomiting
Diarrhea
Endocrine
Amenorrhoea
Growth failure
Malnutrition
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Complications of CKD: Poor growth
Polyuria
Nocturia
Sodium loss
CKD-MBD
Muscle weackness
Bone pain
Fractures
Anemia
Pallor
Endocrine
Amenorrhoea
Growth failure
GI tract
Anorexia
Nausea
Vomiting
Diarrhea
Malnutrition
Metabolic acidosis
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0
-1.0
-2.0
-3.0
-4.0
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
Age, years
63
75 78
75 71
68 62
59 55 47
44 43 42
40
34
27 24
20 19 18 15
10 7
5
2
Kari et al. Kidney Int 2000
Heig
ht
SD
S
Retrospective analysis from GOS
81 children <6 months of life
GFR < 20 ml/min/1.73m2
81%: enterally fed for 0.1 to 6.8 years
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0
-1.0
-2.0
-3.0
-4.0
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
Age, years
63
75 78
75 71
68 62
59 55 47
44 43 42
40
34
27 24
20 19 18 15
10 7
5
2
Kari et al. Kidney Int 2000
Heig
ht
SD
S
Retrospective analysis from GOS
81 children <6 months of life
GFR < 20 ml/min/1.73m2
81%: enterally fed for 0.1 to 6.8 years
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0
-1.0
-2.0
-3.0
-4.0
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
Age, years
63
75 78
75 71
68 62
59 55 47
44 43 42
40
34
27 24
20 19 18 15
10 7
5
2
Kari et al. Kidney Int 2000
Heig
ht
SD
S
Retrospective analysis from GOS
81 children <6 months of life
GFR < 20 ml/min/1.73m2
81%: enterally fed for 0.1 to 6.8 years
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Growth failure in Children with Chronic Kidney Disease (4C)
Doyon et al. PLOSone 2015
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Prevalence of CKD complications
KDIGO 2012 Clinical Practice Guideline Kidney Intern 2013
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Salt intake
KDIGO 2012 Clinical Practice Guideline Kidney Intern 2013
We recommend restriction of sodium intake for children
with CKD who have hypertension or prehypertension
(1C)
We recommend supplemental free water and sodium s
for children with CKD and polyuria to avoid chronic
intravascular depletion and to promote optimal growth.
(1C)
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Metabolic acidosis
KDIGO 2012 Clinical Practice Guideline Kidney Intern 2013
We suggest that in people with CKD and serum
bicarbonate concentrations < 22mmol/l treatment with
oral bicarbonate supplementation be given to maintain
serum bicarbonate within the normal range, unless
contraindicated. (2B)
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Prevalence of CKD complications
KDIGO 2012 Clinical Practice Guideline Kidney Intern 2013
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Metabolic acidosis and statural growth
Doyon et al. PLOSone 2015
The Cardiovascular Comorbidity in Children with Chronic Kidney Disease (4C)
There was a negative effects of metabolic acidosis on
height SDS.
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Chronic Kidney Disease – Mineral Bone Disorder (CKD – MBD)
A systemic disorder of bone and
mineral metabolism due to CKD
manifested by either one or a
combination of the following:
– Abnormalities of Ca, P, PTH,
or vit. D metabolism
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Chronic Kidney Disease – Mineral Bone Disorder (CKD – MBD)
A systemic disorder of bone and
mineral metabolism due to CKD
manifested by either one or a
combination of the following:
– Abnormalities of Ca, P, PTH,
or vit. D metabolism
– Abnormalities in bone
turnover, mineralization,
volume, linear growth, or
strength
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Chronic Kidney Disease – Mineral Bone Disorder (CKD – MBD)
A systemic disorder of bone and
mineral metabolism due to CKD
manifested by either one or a
combination of the following:
– Abnormalities of Ca, P, PTH,
or vit. D metabolism
– Abnormalities in bone
turnover, mineralization,
volume, linear growth, or
strength
– Vascular or other soft tissue
calcification
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Calcitriol, PTH and stages of CKD
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The Cardiovascular Comorbidity in Children with Chronic Kidney Disease (4C)
Doyon et al. PLOSone 2015
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Normal 25-OH D3 Attenuate Renal Failure Progression in Children with CKD
Shroff R JASN 2015 EPUB
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CKD – behavioral and learning problems
http://www.niddk.nih.gov/health-information/health-topics/kidney-disease/facing-the-
challenges-of-chronic-kidney-disease-in-children/Pages/facts.aspx`
Children with (CKD) may have a negative self-image
and may have relationship problems with family
members.
The condition can lead to behavior problems and
make participating in school and extracurricular
activities more difficult.
Children with CKD may have trouble concentrating
CKD can cause learning problems
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Multiprofessional team
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Take home messages
Early diagnosis and treatment of kidney damage
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Take home messages
Early diagnosis and treatment of renal damage
Effective management to slow progression of CKD
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Take home messages
Early diagnosis and treatment of renal damage.
Effective management to slow progression of CKD.
Appropriate treatment of complications
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CKD
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CKD