1. Acute kidney injury: definition,
biomarkers, epidemiology, early
diagnosis.
Renal replacement therapy in children
Dmitry Zverev (Moscow, Russia)

2. Definition

“Sudden loss of renal function resulting in the loss of the
kidneys’ ability to regulate electrolyte and fluid
homeostasis”

3. Diagnostic criteria for AKI
 urine output

Serum creatinine levels


increase in serum creatinine (>50% above
baseline level) and, in most cases, a concomitant
reduction
in urine output (less than 0.5–1 ml/kg per hour)

4. Pediatric Modified RIFLEdefinition
Pediatric Modified RIFLE Criteria
CrCl
Risk GFR decrease by 25%
Injury GFR decrease by 50%
Failure
GFR decrease by 75% or
2
GFR<35ml/min/1.73m
Loss
Urine output
<0.5ml/kg/hour for8 hours
<0.5ml/kg/hour for16 hours
Persistent ARF > 4 weeks
End
stage
<0.3 ml/kg/hour for24 hours or
anuric for 12 hours
End Stage Renal Disease (>3 months)
Ackan-Arikan et al: Kid Int 2007

5. Calculating GFR
using Schwartz formula
GFR = height (cm) X К/sCr (mg/dl)
К - constant
k = 0.33 premature neonates
k = 0.45 neonates and infants, under 1 y.o.
k = 0.55 children, under 13 y.o.
and girls, over 13 y.o
k = 0.70 boys, over 13 y.o.
•
•
mg/dl х 88 = mkmol/l
mkmol/l х 0,0113= mg/dl

6. GFR in children
age
GFR
1 - 2 days
20.8 ± 5.0
4 - 14 days
36.8 ± 7.2
15 – 19 days
46.9 ± 12.5
1 – 3 months
60.4 ± 17.4
4 – 6 months
87.4 ± 22.3
7 – 12 months
96.2 ± 12.2
1 – 2 years
105.2 ± 17.3
3 – 8 years
111.2 ± 18.5
9 – 12 years
116.6 ± 18.1
13 – 15 years
117.2 ± 16.1
G.Schwarts. Glomerular filtration rate measurement and estimation in kidney disease.
Pediatric Nephrol (2007) 22:1839-1848

7. Creatinine disadvantages
as AKI marker
 Plasma Creatinine – measure of function (not
injury)
 More than 50% nephrons must be compromised for
SCr level changes to be evident
 Therefore, SCr is at best a late marker of significant
renal dysfunction

8. Characteristics of an Ideal Biomarker
1. Biomarker have to be an active substance that is
immediately excreted by the damaged cells of the
kidneys
2. Has a high sensitivity and specificity
3. Be available for direct determination in urine or
blood
4. Have an acceptable "price - quality"

9. Biomarkers of AKI
(Devarajan P: Emerging urinary biomarkers in the diagnosis of acute kidney injury. Expert Opin
Med Diagn 2008, 2:387-398.)





neutrophil gelatinase-associated lipocalin (NGAL)
cystatin С (CysC)
kidney injury molecule-1 (KIM-1)
interleukin 18 (IL-18),
liver-type fatty acid-binding protein(L-FABP)

10. NGAL(Neutrophil gelatinase-associated
lipocalin)


a 25-kD protein of the lipocalin superfamily, is expressed by
kidney tubules epithelium
First time as a marker of AKI was described in 2003
[Mishra J. et al]
The role of NGAL as a biomarker of kidney damage is
confirmed by experimental studies on various models of
critical states [Haase-Fielitz A., Bellomo R., Devarajanet P. 2009]
 Critically ill patients in ICUs have NGAL level ≥155 nmol/l,
indicating AKI (sensitivity 82%, specificity 97%) [Constantin J.M. et

al.2010 De Geus H.R., 2011 . Haase-Fielitz 2009 ]

11. Cystatin C
Cystatin С (protease inhibitor)
is filtrated in glomerulus in the kidneys,
completely reabsorbed and isn’t secreted in the tubules
 Consequently it is a marker of glomerular filtration
rate (GFR)
 If kidney function and glomerular filtration rate decline, the
blood levels of cystatin C rise
 Cystatin C levels in AKI become higher on 24-48 hours
earlier than creatinine levels
 Disadvantages: high cost


12. Kidney injury molecule-1 (KIM-1)
 Transmembrane protein
 Not detected in blood and urine normally
 Expression is markedly up-regulated in the
damaged proximal tubules
 Disadvantages:
• doesn’t make prediction
• high cost

13. Interleukin 18 (IL-18)
 Proinflammatory cytokine, produced by the
distal tubules, collecting tubules of the
kidneys
 Urinary IL-18 is a useful biomarker of AKI
 IL-18 secretion distinctly increases in AKI
 Disadvantages:
• low sensitivity
• low specificity

14.  Nowadays biomarkers can’t provide the
stratification of ungraded AKI
 Validation of these biomarker studies needs
to be performed in different critically ill
populations

15. The incidence of AKI requiring RRT
Prevalence on 100 thousand.
227 cases for 84-91 years (Yorkshire UK)
19.7
17.2
4
5.9
1.5
adults
Children
Newborn
s
1-4 years
5-15 years
Adapted from Acute kidney injury in critically ill newborns: what do we know? What do we need
to learn?
Askenazi DJ, Goldstein SL. Pediatr Nephrol. 2009 Feb;24(2):265-74. Epub 2008 Dec
10.

16. Etiology of AKI
Prerenal
(renal hypoperfusion)
Renal (intrinsic)
Postrenal
Glomerulonephritis
Low
intravascular volume
Hemorrhage/bleeding
Severe dehydration
Third-space losses
Decreased effective
circulating volume
Cardiac dysfunction
Renal artery obstruction
Sepsis
rapidly progressive,
immune-mediated diseases
HUS
Cortical necrosis,
renal vein/artery thrombosis,
DIC
 Acute interstitial nephritis:
Infection/pyelonephritis
Acute tubular necrosis:
hypoxic/ischemic injury,
drug-induced
Tumor lysis syndrome
Urethral
obstruction:
posterior urethral
valves in neonates;
Obstruction
kidney urinary tract:
(ureteral–pelvic unction,
ureteral stenosis,
uretero–vesical unction),
stones, mass

17. Management of AKI
 should
be monitoring and laboratory
controlling
 require special methods of intensive therapy
in the ICU
 an optimal microclimate around the child
 conducted simultaneously with the diagnostic
activities

18. Management of AKI

At the beginning rapid volume replacement should be
undertaken at the same time for final diagnosis
(Crystalloid solution 20 ml/kg normal saline or 5% glucose
for 20-30 minutes)

fresh frozen plasma could be used as a starting solution in
sepsis, peritonitis and severe surgical pathology (it has
a long-lasting effect on hemodynamics and stays in the
circulatory longer)

19. Management of AKI
No diuresis ensues after
fluid administra-tion
Normal cardiac output
(normal renal perfusion)
Renal intrinsic injury
Dialysis
(attempt fast) improvement of renal perfusion (by dopamine, a
rapid increase in blood volume, colloids transfusion) may lead to
rupture of blood vessels in the germinal matrix and
intraventricular hemorrhage development


20. AKI etiology in children
and mortality
DGKB St.Vladimir (2002-12гг.)
AKI etiology
HUS and TTP
MODS
GN, systemic diseases
AKI in newborns
AKI of various etiology
Amount of
children
n = 326
219 (67,8%)
Mortality
n =53(16,3%)
11(5%)
24(7,4%)
14 (58,3%)
25
2
38(12,7%)
23 (60%)
19
3

21. AKI etiology in children
AKI etiology
DGKB St.Vladimir
Moscow
hospitals
years
2002-10
2012
2012
Children with
AKI
276
50
200
HUS
188(68%)
29(58%)
31(15,5%)
MODS, шок, sepsis,
cardiosurgery, HF
50
13
169

22. The main cause of AKI
Preschool age
School age
HUS
GN, shock, TTP

23. Hemolytic uremic syndrome
Is defined by a triad of symptoms:
- Hemolytic anemia
- Thrombocytopenia
- Azotemia

24. Pathological basis of HUS - thrombotic
microangiopathy affecting:
KIDNEYS
brain
lungs
bowel
liver
heart

25. Typical HUS
Escherichia Coli
O157:H7
O111:H8
O103:H2
O121
O145
O26
O113
Shiga like
toxin, type 1
Shiga like
toxin, type 2
B
B
B
AB
B
Shigella dysenteria
Serotype 1
Shiga-toxin, тип 1
Brooks J.T. et al., (2004)
Sonntag A.K. et al., (2004)
Noris and Remuzzi,, JASN, 16:1035 (2005)

26. Infection sources
Escherichia coli O157:H7
- meat
- dairy products
- fruit juices
- potable water
-
pets
- water in open-air reservoirs and swimming pools

27. Typical HUS occurrence
North America
2-3 cases per 100000 children
under 5 years old,
Argentina
10 times higher
Moscow – 4 cases
Moscow region 4-5 cases
per 100000 children under 5 years old

28. Pediatric nephrology (2008)23:1749-1760

29. The earlier dialysisthe better prognosis of
HUS

30. HUS outcomes
 Mortality during the acute phase
2-6%
 ESRF development
1-2%
 Development ESRF during first 5 years
5-7%
 Development ESRF during 10-15 years
10-15% more

31. Thrombotic thrombocytopenic purpura
 TTP is characterized by microangiopathic
hemolysis and platelet aggregation in hyaline
thrombi, with no activation of the coagulation
system
 This leads to partial occlusion of blood vessels
associated with excessive proliferation of
endothelial cells
 Kidney, brain, heart, pancreas, spleen, and
adrenals endothelium are suffered

32. Thrombotic thrombocytopenic purpura
 The reason of familial and aquired idiopatic TTP is
insufficient destruction of unusually large
multimers of von Willebrand factor, which are
destroyed by metalloproteinase ADAMTS-13
 lack of protease activity caused by either its serious
shortage or production of autoantibodies

33. Management of TTP
 Plasmapheresis became the treatment of choice for
TTP in mid-80s
 Supply of ADAMTS-13 and removal of anti-
ADAMTS-13 autoantibodies and unusually large
multimers of von Willebrand factor make provision
the effect of plasmapheresis
 Pulse therapy with Metipred

34. The mechanism of AKI in GN
Edema of interstitial tissue, increasing of
hydrostatic pressure in the proximal tubule and
the Bowman's capsule, which leads to
reduction of filtrational pressure and
glomerular filtration
 protein mass and blood clots occlude tubules
 fast-growing proliferation of glomerular
capillary loops with compression and/or
tubulointerstitial changes
 vasoactive substances and cytokines release
from monocytes and other cells


35. Management of GN with AKI
 RRT when indicated
 Symptomatic therapy (treatment of
neurological, cardiovascular and respiratory
disorders)
 Pathogenetic therapy of GN in the early
stages of the disease (corticosteroids,
alkylating agents, plasmapheresis)

36. Indications for emergency dialysis


ANURIA > 1 day
Complicated OLIGURIA:
•
•
•
•
•
•
•
hyperhydration with pulmonary edema and/or
respiratory failure, uncontrolled hypertension
disorders of the central nervous system
heart failure
hyperkalaemia > 7.5 mmol/l
decompensated metabolic acidosis
increase of creatinine level > 120 mkmol/day
ensuring adequate child nutrition and infusion
therapy

37. HD? PD? CVVHDF?

38. Hemodialysis in children
(basic practical guidelines
European Pediatric Dialysis Working Group, 2005)
1. Department of HD should be located in a children's
hospital with multi-disciplinary experts available
2. Water quality: adequate biochemical composition,
the absence of microbiological contamination
3. A hemodialysis machine:
volume control UF, a
single needle
connected option
4. Hemodiafiltration option for maximum
efficiency

39. Hemodialysis
Advantages
The high speed of purification and UF
The ability to adjust the composition of the dialysate
Disadvantages
•Difficulties of vascular access to ensure an adequate
blood flow in child weighing < 5 kg
•Large extracorporeal volume
•Hypotension episodes during UF
•Cardiovascular insufficiency
•Risk of bleeding assosiated
with systemic anticoagulation
•Fluid limitation between dialysis;
•Disequilibrium syndrome

40. Peritoneal dialysis
1. Dialysis solution
2,3. Containers
measuring cylinders
4. Peritoneal catheter
5. Container for the drained solution
6. Clip
Begins from 10 ml/kg
Exposition 0,5 – 1 hour

42. PD in infants with
extremely low birth weight

43. Advantages of PD






Continuing process of blood purification and UF;
Implantation of peritoneal catheter and PD conducting is a
simple procedure, possible in hospital
PD does not have a marked influence on hemodynamics, it
can be used in patients with hypotension and even in
patients with multiple organ failure
Isn’t required providing of vascular access, anticoagulation
therapy
PD solution - a source of extra calories
Low cost of treatment

44. Disadvantages of PD
 low nitrogenous wastes, blood electrolytes
clearance, small rate of UF
 PD conducting is impossible in patients with
purulent peritonitis, in the early postoperative
period after laparotomy, with leaking abdominal
 cautious and limited using of PD in patients with
concomitant respiratory failure

45. Surgical complications during PD
1. Catheter setting and operation
dialysate draining (14,1%),
drainage disruption(4.5%),
internal organs wounding, bleeding
2. Infectious
Peritonitis -80%, inflammation in the catheter area
3. Concomitant diseases of the abdominal cavity
(diaphragmatic, inguinal and umbilical hernia)

46. Continious methods of RRT
CVVHDF - extracorporeal
blood purification technique
due to convective transport of
substances through the highly
permeable membrane, with the
replacement of UF with a
special solution


47. Parametres of CVVHDF
The rate of blood flow 4-8 ml/kg/min
•
Neonates 20-40 ml/min
Infants 40-80 ml/min
The volume of extraCorporeal circuit
55-72ml
Hemofilter membrane
area – 0.2 м²

48. Parametres of CVVHDF
Substitution rate:
35-50 ml/kg/hr
The flow rate of the dialysis
solution:
equal to or greater than 1.5
times the rate of substitution
Heparinization:
•Bolus - 20-30 U/kg
•Continuous infusion 10-30 U/kg/hr

49. Vascular access
Two way catheter
under 6 kg - 6,5 Fr
from 6 to 15 kg - 8 Fr
more than 15 kg - 11 Fr
The implantation method
 puncture
 venesection

50. The puncture site
Subcutaneous
vein
Jugular vein
Femoral vein

51. Dynamics of blood creatinine in patients with
AKI using
PD, HD and CVVHDF
C
r
e
a
t
i
n
i
n
600
HD
ГД
550
ПД
PD
500
ПВВГДФ
CVVGDF
450
400
350
300
250
200
150
100
0
mkmol/l
1
2
3
4
5
6
Сутки dialysis
The day of диализа
7
8
9

52. Urea, mmol/l
Dynamics of blood urea in patients with
AKIusing
PD, HD and CVVHDF
The day of dialysis
CVVHDF
PD
HD

53. Advantages of CVVHDF







provides continuous purification and UF;
better control of azotemia
does not require a large flow of blood
little effect on hemodynamics
can be used in critically ill patients with heart failure, severe
edema, cerebral edema;
UF rate can be calculated, assigned and adjusted according
to the hourly needs of the patient;
does not require water treatment and specially trained
staff

54. Disadvantages of CVVHDF
 Heparinization necessity
 Central venous catheterization
 Fairly sophisticated equipment
 High cost of the procedure
 The procedure is conducted by nondialysis staff
who has many other responsibilities

55. Factors affecting the type of the dialysis
selection
 age and anthropometric data
 hemodynamic
 the presence of respiratory failure
 degree of safety consciousness and the presence of
seizures
 the primary purpose of correction by the RRT
 the severity of fluid overload
 the severity of azotemia and electrolyte imbalance

56. The algorithm of RRT method selection
in children with AKI
AKI
HD
PD
Fluid overload
Neurological
symptoms
Hypotension
Hypertension
CVVGDF
CVVGDF
Age

57. Starting type of a dialysis in treatment of
children with AKI
1991-2004
 HD
2006-09
48.5% 15%
 PD
51.5%
25%
 CVVGDF 60%
2010-12
0,9%
19,6%
79,5%

58. The cost of consumables
per 1 day of AKI treatment (USD)
Acute PD in
child
Acute PD in
adult
Acute HD
CVVGDF

59. CONCLUSIONS
 CRRT – a choice method at patients with sepsis,
the overhydratation, the expressed metabolic
and electrolytic violations.
 PD – a choice method at stable patients with
AKI, at a hemorrhagic syndrome, impossibility of
ensuring vascular access, and also basic therapy
at long AKI
 HD – a choice method at children of advanced
age.