This document summarizes research on chronic kidney disease in children. It includes: 1) Mortality rates are much higher for children on dialysis compared to the general pediatric population, especially for certain demographic groups. 2) Common causes of chronic kidney disease in children include congenital abnormalities, genetic disorders, and diabetes. 3) Growth failure is a major complication and is associated with protein and calorie malnutrition as well as metabolic bone disease. 4) Treatment involves optimizing nutrition, managing acidosis and mineral disorders, and considering growth hormone therapy.

1. Isidro B. Salusky, M.D.
Distinguished Professor of Pediatrics
Chief, Division of Pediatric Nephrology
Director, Clinical Translational Research Center
Associate Dean of Clinical Research
David Geffen School of Medicine at UCLA

4. Mitsnefes MM JASN 23:578, 2012

5. % Annual mortality
100
Dialysis Population
10
1
GP Male
GP Female
GP Black
GP White
Dialysis Male
Dialysis Female
Dialysis Black
Dialysis White
0.1
0.01
0
25-34
35-44
45-54
55-64
65-74
75-84
>85
Age (yr)
NKF Task Force on Cardiovascular Disease. Am J Kidney Dis. 1998;32(suppl 3):S115.Sarnak MJ,
Levey AS. Am J Kidney Dis. 2000;35(suppl 1):S117-S131.

6. •
•
•
•
•
•
•
Homozygous hypercholesterolemia
Kawasaki disease
Diabetes type I and II
Chronic kidney disease
Congenital heart disease/ Pediatric heart transplant
Chronic inflammatory disease (SLE & RA)
Childhood cancer
Kavey REW et al. Circulation 114:2710, 2006

7. –Protein and Calorie Malnutrition
–Acidosis/Electrolyte Abnormalities
–Primary kidney disease
–Anemia
–Renal bone diseases
–Hormonal Factors
–Immunosuppressive Medications

8. GFR
Description
(mL/min/1.73 m2)
1
Kidney damage with
normal or GFR
90
2
Kidney damage with
mild GFR
60-89
3
Moderate
30-59
4
Severe
5
Kidney failure
Stage
GFR
GFR
15-29
15 or dialysis
K/DOQI: Evaluation, classification and stratification. AJKD 39: 2001

9. n=366
Wong H et al. KI 70:585, 2006

10. SAs
s of Anemia in CKD Patients (1 of 3)
• Renal insufficiency = EPO deficient state
Kidney
ency
Decreased
erythropoietin
production
production
etin
n of uremic
Erythroid
progenitor cells
Inhibition of
erythropoiesis
Bone
Bone
marrow

11. • EPO resistance
– Iron deficiency
– Hyperparathyroidism
– High dose ACE
inhibition
– Aluminum toxicity
– Antibodies to ESA
–
–
–
–
–
–
Inflammation
Folate/B12 deficiency
Hemoglobinopathies
Hemolysis
Chronic Blood Loss
Chronic infection

12. • Erythropoietin Stimulating factors (ESA)
• Iron
• Diagnose and treat underlying cause of
Epogen resistance

13. Borzych-Buzalka D et al. JASN 24:665, 2013

14. NAPRTCS 2011

15. • Loss of appetite-may manifest early in the
course of kidney disease
• Spontaneous food intake decreases with
worsening kidney failure
• Calorie Malnutrition-seen during the first
years of life
• Protein Malnutrition-not frequently seen in
children with kidney failure

16. • Adequate caloric intake
– Infants-growth rates during this period are
correlated with calorie intake
• Nasogastric (NG) or Gastrostomy (G) Tube Feeding
– Older children- intake should not be less than 80%
of the Recommended Daily Allowance (RDA)
• Therapy with recombinant human growth
hormone

17. Rees L et al. JASN 22:2302, 2011

18. (n=153)
Rees L et al. JASN 22:2302, 2011

19. Rees L et al. JASN 22:2303, 2011

20. • North America: Oligo-anuric, high glucose exposure and
treatment with RhGH
• Europe: Biocompatible PD fluids
• Turkish: Lower serum albumin levels, higher serum P levels and use of
amino-acids containing solutions
• Latin America: Persistent residual renal function, higher use of
phosphate binders and lowest rate of NaCl supplementation
Rees L et al. JASN 22:2302, 2011

21. • Many congenital kidney diseases lead to
loss of electrolytes and decreased ability of
the kidneys to concentrate urine
• Infants with kidney failure due to renal
dysplasia-high urinary losses of sodium
• Metabolic acidosis- kidney function below
50%
• The specific effect of bicarbonate therapy
on growth in CKD remains to be defined
• Correction prior to treatment with rhGH

22. • Effects on bone remodeling and modeling
– Skeletal fracture and microfracture repair
– Bone deformities
– Growth retardation
• Relationship to:
– Osteopenia / osteoporosis
– Changes in bone mass over time during long-term dialysis
– Vascular calcifications
• Bone loss after renal transplantation and
cardiovascular disease

23. 100
Bone turnover
% of Subjects
80
PTH
60
40
20
0
2
3
CKD Stage
4
Wesseling-Perry K CJASN (2012) 7:146

24. 1000
200
GH
*
150
PTH (pg/ml)
BFR (um3/um2/y)
GH
100
50
GH
GH
750
*
500
250
0
0
Low/nl BFR
GH
High BFR
Low/nl BFR
High BFR
No GH
Bacchetta J et al CJASN 2013

25. Height < -2 SD
153 (61.9%)
Clinical manifestations of bone disease
91 (36.8%)
Deformities
63 (25.5%)
Pathological fractures
33 (13.4%)
Aseptic bone necrosis
32 (13.0%)
Mild disabling bone disease
26 (10.5%)
Severe disabling bone disease
18 (7.3%)
Invalidating bone disease (all)
44 (17.8%)
Groothoff JW KI 63 (2003) 266–275

26. Lumen
Intimal Atherosclerotic Plaque

28. From Passive Deposits to Active Processes

29. A systemic disorder of mineral and bone metabolism due to
CKD manifested by either one or a combination of the
following:
– Abnormalities of calcium, phosphorus, PTH, or vitamin D
metabolism
– Abnormalities in bone
turnover, mineralization, volume, linear growth, or strength
– Vascular or other soft tissue calcification
Moe et al Kidney International 2006

30. • Patients with Stage 5 CKD are at high risk for vascular
calcification
• Vascular calcifications are present in almost 50% of
patients with stage 4 CKD and new dialysis patients
• Vascular calcification can be quantified
• Vascular calcification is associated with modifiable risk
factors
– Ca intake from calcium-based binders
– S-P, S-Ca and Ca P product
• Vascular calcification results in arterial stiffening and
increased pulse pressure and adynamic bone disease

31. Therapeutic Options for the Treatment of
CKD-MBD
Phosphate Binders
Calcitriol
Paricalcitol
D2-D3
1,25(OH)D
Doxercalciferol
Ca-Salts
Sevelamer:
Ca free – Metal Free
Lanthanum Ca:
Ca free - Metal +
Ergocalciferol
Calcimimetic
Drugs
Cinacalcet

32. Treatment
Stage
Treatment Target Range
3
KDIGO: Upper Limit of Normal* (2C)
KDOQI: 35-70 pg/mL
4
KDIGO: Upper Limit of Normal* (2C)
KDOQI: 70-110 pg/mL
5
KDIGO: Upper Limit of Normal* (2C)
KDOQI: 150-300 pg/mL
5D
KDIGO: 2 to 9 times Upper Limit of Normal (2C)
KDOQI: 150-300 pg/mL
Europe Children: 2 to 3 x upper Limit of Normal
*In patients with CKD stages 3-5 not on dialysis, in whom serum PTH is progressively rising and remains
persistently above the upper limit of normal for the assay despite correction of modifiable factors, treatment with
calcitriol or vitamin D analogs is suggested. (2C)
1. Kidney Disease: Improving Global Outcomes (KDIGO) CKD-MBD Work Group. KDIGO clinical practice guideline
for the diagnosis, evaluation, prevention, and treatment of chronic kidney disease-mineral and bone disorder (CKD-MBD)
Kidney Int. 2009;76(suppl 113):S1-S130.
2. Adapted from National Kidney Foundation (NKF). KDOQI clinical practice guidelines for bone metabolism and disease in
chronic kidney disease. Am J Kidney Dis. 2003;42(4 suppl 3):S1-S201.

33. (n=3409)
(n= 4026)
Favors Non-Ca
Favors Ca
Jamal SA et al. Lancet, 2013

34. Months on Dialysis
0
0
12
24
Months post Transplantation
0
24
48
72
-0.5
-1
-1.5
-2
-2.5
-3
NAPRTCS 2010/2011

35. GH/IGF
System
Optimize
Growth and
Survival
Vascular
Calcification
Bone Health
Vitamin D/PTH/
FGF23 Axis