2. Introduction
Acute kidney injury (AKI)
Common condition in the NICU
Mild renal dysfunction to complete
anuric kidney failure.
Characterized by a sudden decline in
kidney function over hours to days,
resulting in derangements in fluid,
electrolyte, and acid–base balance.
2
3. NORMAL NEONATAL RENAL FUNCTION
• The neonate is more vulnerable to AKI
– functional and developmental immaturity of the neonatal
kidney that affects glomerular filtration and tubular
function (eg, concentrating ability),
– hemodynamic changes that occur at delivery, and
– risk of hypovolemia due to large insensible water
losses.
3
4. Glomerular filtration rate
• It is challenging to ascertain normal neonatal glomerular filtration
rate (GFR) due to variability based on gestational age (GA) and
postnatal physiological changes and the difficulty of performing
accurate clearance measurements .
• Although measurement of inulin clearance is the gold standard to
determine GFR, it is difficult to use as it requires an intravenous
priming dose followed by continuous infusion
• As a result, neonatal GFR values are based on creatinine clearance
measurements.
• At birth, GFR is lower with lower GA. Very preterm infants (GA less
than 32 weeks) have a reduced GFR because renal embryogenesis
is not completed until 35 weeks gestation.
4
5. • Average GFR based on creatinine clearance
measurements at birth or within the first three
days of life vary by GA:
– •27 weeks gestation: 13.4 mL/min per 1.73 m2
– •28 weeks gestation: 16.2 mL/min per 1.73 m2
– •29 weeks gestation: 19.1 mL/min per 1.73 m2
– •30 weeks gestation: 21.9 mL/min per 1.73 m2
– •31 weeks gestation: 24.9 mL/min per 1.73 m2
– •Term infants: 26 mL/min per 1.73 m2
5
6.
7. Serum creatinine
• Clinically, serum creatinine (SCr) values are the most
convenient method to estimate GFR.
• SCr normally varies with gestational and postnatal age.
• SCr at birth is equal to the concentration in the mother
(approximately 1 mg/dL [88 micromol/L]).
• In term infants, SCr declines rapidly in the first or two
weeks of life to nadir values (SCr 0.2 to 0.4 mg/dL [18
to 35 micromol/L]), which remain stable through the first
year of life , whereas in preterm infants, the decline is
slower and nadir values are reached over the first one to
two months.
7
8. • In VPT infants (GA <32 weeks), SCr may
increase after birth, most likely due to low GFR
and tubular reabsorption of creatinine, followed
by a slower decline over two months .
• SCr values for VPT over the first months of life
are inversely related to decreasing GA.
• As a result, SCr levels remain higher in VPT
compared with term infants in the first months of
life
8
9. Time of first void and urine volume
• Although the time of the first void is variable, at least 50 percent of
newborns void by eight hours of age and nearly all before 24 hours.
• Urine output is not affected by gestational or postnatal age during
the first week of life, averaging 3 to 4 mL/kg per hour .
• Similar to older patients, neonatal AKI may be oliguric (urine volume
less than 1 mL/kg per hour) or nonoliguric, depending upon the
severity of the reduction in GFR and the degree of tubular
reabsorption.
9
10. Tubular function
• Urinary concentration —
– Urine concentrating ability is limited in the newborn compared
with the older individuals.
– The maximum urine concentration that can be achieved
increases from 400 mosmol/kg in the first few days after birth to
1200 mosmol/kg at one year of age.
– The reasons for poor urine concentrating ability in infants include
• low corticomedullary solute gradient,
• decreased formation of cyclic adenosine monophosphate (cAMP) in
response to antidiuretic hormone (ADH),
• a short loop of Henle, and interference by prostaglandins
10
11. • Sodium reabsorption —
– lower in neonates compared with older individuals
and is affected by gestational and postnatal age.
– In particular, tubular function is immature in VPT
infants (GA <32 weeks) with decreasing sodium
reabsorption as GA decreases .
– As a result, the use of fractional excretion of sodium
to differentiate between prerenal and intrinsic AKI
has limited utility in VPT infants.
– In addition, the value used to differentiate between
prerenal and intrinsic disease is higher in term or late
term infants.
11
12. • Bicarbonate reabsorption —
– Neonates have a lower threshold for proximal renal
tubular bicarbonate reabsorption, resulting in smaller
proportion of reabsorbed filtered bicarbonate than in
older children and adults.
– As a result, infants have a lower normal
serum/plasma bicarbonate (HCO3-) than older
children and adults (20 versus 24 mEq/L).
• Acid excretion —
– The maximum net acid excretion by the distal
nephron is limited in newborn infants, especially
preterm infants. 12
13. INCIDENCE
• Neonatal AKI is a common occurrence, occurring in
30% of critically ill neonates
• The incidence of AKI varied by gestational age
group, occurring in
– 48% of infants 22-29 weeks’ gestation,
– 18% of infants 29-36 weeks’gestation, and
– 37% of infants ≥36 weeks’ gestation.
13
14. Neonates are at particularly high risk
– low GFR in the frst week of life,
– immaturity of renal tubules,
– increased susceptibility of the kidney to impaired
perfusion,
– high exposure to nephrotoxic agents including
indomethacin and aminoglycosides,
– frequent use of umbilical access catheters with
potential for thrombosis
14
15. • heightened risk of developing AKI among
– term and near-term neonates with perinatal
asphyxia,
– very low birth weight and extremely low birth
weight infants,
– infants requiring cardiac surgery or ECMO support
15
16. • Difficult in establishing a standardized
definition of AKI in neonates because of
– Maturational difference in kidney function at
different gestational ages,
– Overall low GFR of neonates
– Serum Cr reflects maternal Cr for days to a week
after birth.
16
17. • the neonatal modifed KDIGO (Kidney Disease: Improving Global
Outcomes) criteria.
– These criteria define neonatal AKI in infants under 120 days of age
– Increase in serum Cr ≥0.3 mg/ dL or 50% or more from the previous lowest
value and/or urine output <0.5 mL/kg/hr.
17
19. Clinical signs
• Oliguria,
•Systemic hypertension,
•Cardiac arrhythmia,
•Evidence of fluid overload or
volume depletion,
•Decreased activity,
•Seizure, Vomiting, and Anorexia.
19
20. Laboratory findings
• elevated serum creatinine and blood urea nitrogen,
• hyperkalemia,
• metabolic acidosis,
• hypocalcemia,
• hyperphosphatemia, and
• a prolonged half-life for medications excreted by the
kidney (e.g., aminoglycosides, vancomycin,
theophylline).
20
21. Biomarkers
• may show promise in the earlier detection of
neonatal AKI, potentially identifying earlier
stages of kidney injury, which occur prior to
the elevation of serum creatinine
– neutrophil gelatinaseassociated lipocalin (NGAL)
– urinary interleukin-18
– cystatin C
21
22. • The causes of neonatal AKI are multiple and can be
divided into
– prerenal,
– renal
– postrenal
22
24. Prerenal Azotemia
– most common type of AKI in the neonate
– Account for up to 85% of all cases.
– characterized by inadequate renal perfusion,
which if promptly treated, is followed by
improvements in renal function and urine
output.
24
25. Most common causes
– Hypotension,
– Volume depletion,
– Hemorrhage,
– Septic shock,
– Necrotizing
enterocolitis,
– Patent ductus
arteriosus,
– Congestive heart
failure.
• medications that reduce
renal blood flow,
– Indomethacin or
– Ibuprofen
– ACE inhibitors, and
– phenylephrine eye drops,
25
27. Intrinsic (Renal) Acute Kidney Injury
• The most common cause of intrinsic AKI in
neonates
– acute tubular necrosis (ATN).
• Risk factors for ATN include a
– prolonged prerenal state,
– perinatal asphyxia,
– sepsis,
– neonatal cardiac surgery,
– need for ECMO support, and
– nephrotoxic drug administration (acyclovir, aminoglycoside antibiotics,
amphotericin B, ACE inhibitors, NSAIDs, radiocontrast agents, and
vancomycin).
27
28. • The pathophysiology of ATN is complex and appears to
involve
– Interrelationships among renal tubular cellular injury
– Hypoxia, and Altered glomerular fltration and
hemodynamics.
• Other causes of intrinsic AKI in the newborn include
– renal dysplasia,
– autosomal recessive polycystic kidney disease, and
– renal arterial or venous thrombosis
28
29. Obstructive (Postrenal) Acute Kidney Injury
• posterior urethral valves,
• bilateral ureteropelvic or ureterovesical junction obstruction,
• obstructive urolithiasis
• neurogenic bladder.
• compression of the ureters or bladder
– Extrinsic compression - a congenital tumor such as a sacrococcygeal
teratoma
– Intrinsic obstruction - renal calculi or fungus balls.
29
30. • TREATMENT-
– relief of the urinary tract obstruction may yield
improvement in urine output and GFR,
• COMPLICATION-
– CKD because of variable degrees of
associated renal dysplasia.
30
31. Evaluation
History
• prenatal ultrasound
abnormalities,
• perinatal asphyxia,
• the pre- or postnatal
administration of potentially
nephrotoxic drugs, and
• a family history of renal
disease.
physical examination
• signs of volume depletion
• volume overload, the
• abdomen, genitalia, and a
search for other congenital
anomalies or
• signs of the oligohydramnios
(Potter) sequence.
31
32. Evaluation
• Levels of electrolytes
– calcium,
– phosphorus,
• blood urea nitrogen, creatinine (Cr)
• albumin
• uric acid
• urinalysis, urine culture, and urine sodium
and creatinine
32
33. prerenal from intrinsic AKI
• FENa (%) ( = × UNa PCr) (PNa U × × Cr) %
100
– Neonates with a FENa > 3.0% generally have intrinsic AKI,
– a FENa < 2.5% have prerenal AKI.
• Baseline normal FENa values in preterm neonates may
be as high as 6% at birth so the FENa measurement
may be less helpful in distinguishing intrinsic versus
prerenal AKI in that population.
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36. Medical Management
• Established oliguric AKI,
– a urinary catheter should be placed to exclude
lower urinary tract obstruction.
– If there is no improvement in urine output after
bladder drainage is established,
– a fluid challenge of 10-20 mL/kg should be
administered over 1-2 hours to exclude
prerenal AKI.
36
37. • Consider to use of vasopressor support such as
dopamine to ensure that the infant has a mean arterial
pressure adequate to provide renal perfusion.
• A lack of improvement in urine output and serum
creatinine following adequate bladder drainage, fluid
resuscitation, and establishment of an adequate mean
arterial pressure suggests intrinsic AKI.
37
38. • The goal of medical management of intrinsic AKI is to
– provide supportive care until there is spontaneous improvement
in renal function.
• After adequate resuscitation, intake should be restricted to
insensible losses (500 mL/m2 perday, or 30 mL/kg per day)
plus urine output and other measured losses to prevent
symptomatic fluid overload.
• Daily to twice daily weights and careful intake and output
measurements are essential to follow volume status.
• Nephrotoxic drugs should be discontinued to reduce the
risk of additional renal injury.
38
39. • Medications should be adjusted by dose, interval, or both
according to the degree of renal dysfunction.
• Potassium and phosphorus should be restricted in those
neonates with hyperkalemia, hyperphosphatemia,
oliguria, and/or rapidly worsening renal function.
• Metabolic acidosis may require treatment with
intravenous or oral sodium bicarbonate.
• Loop diuretics may prove helpful in augmenting the
urinary flow rate but should be withheld if there is no
response or in the case of anuria.
39
40. • Renal Replacement Therapy
– rarely needed in neonates with AKI
– In general, only neonates > 1.5-2 kg in size may be because of
• limited ability to place and maintain dialysis access in smaller
infants.
– When maximum medical management fails to maintain
acceptable fluid and electrolyte levels.
– The two purposes of renal replacement therapy are
• ultrafltration (removal of water) and
• dialysis (removal of solutes).
40
41. The indications for the initiation of renal
replacement therapy
• hyperkalemia,
• hyponatremia with symptomatic volume
overload,
• acidosis,
• hypocalcemia, hyperphosphatemia,
• uremic symptoms, and an inability to
provide adequate nutrition because of the
need for fluid restriction in the face of
oliguria 41
43. • Peritoneal dialysis
– most commonly used renal replacement
modality in the neonatal population, because
it is technically less difficult and does not
require vascular access or anticoagulation.
– For this procedure, hyperosmolar dialysate
is repeatedly infused into and drained out of
the peritoneal cavity through a surgically
placed catheter, accomplishing ultrafltration
and dialysis.
43
44. • Contraindications to peritoneal dialysis
include
– recent abdominal surgery,
– necrotizing enterocolitis,
– pleuroperitoneal leakage, and
– ventriculoperitoneal shunting
44
46. • Continuous renal replacement therapy
(CRRT) is
– becoming a more frequently used therapeutic
modality in neonates and infants with AKI.
– For this procedure, the patient’s blood is
continuously circulated through a pump driven
extracorporeal circuit containing a highly
permeable hemoflter.
– In continuous venovenous hemofltration
46
47. • The chief advantage of CRRT is the ability to carefully control fluid
removal, which makes this modality especially useful in the neonate
with hemodynamic instability.
• The main disadvantages are the need to achieve and maintain
central vascular access and the need for continuous anticoagulation.
47
48. • Intermittent hemodialysis
– less commonly used but technically feasible
mode of renal replacement therapy in the
neonatal population.
– Hemodialysis involves intermittent 3- to 4-
hour treatments in which fluid and solutes are
rapidly removed from the infant using an
extracorporeal dialyzer, with clearance
achieved by the use of countercurrent
dialysate.
48
49. • the chief advantage of hemodialysis is the ability to
rapidly remove solutes and fluid, a characteristic that
makes this modality the therapy of choice in neonatal
hyperammonemia.
• The main disadvantages are the requirement for central
vascular access, usually a double lumen 7 French
catheter, and the hemodynamic instability and osmolar
shifts that may occur with rapid solute and fluid shifts.
49
50. • Providing adequate renal replacement therapy
may be limited by the challenges in placing
and/or maintaining intravascular or peritoneal
dialysis access in the very small premature
neonate.
• If dialysis access cannot be established, care of
the infant with AKI is limited to maximal
supportive medical management, with
meticulous attention to fluid, electrolyte, and
acid–base balance.
50
51. Prognosis
• higher mortality rates and lengths of
hospitalization
– presence of AKI is independently
– higher stages of AKI
• high rates of chronic kidney disease (CKD) in
survivors of neonatal AKI.
– Associated inadequate nephron development
• Prematurity and
• Low birth weight
51
53. • Special attention
– history of AKI stages 2 and 3
– treatment with dialysis,
– signifcant prematurity,
– IUGR
– underlying renal anomalies.
53
54. Prevention of AKI
maintenance of an adequate circulatory volume,
careful fluid and electrolyte management, and
prompt diagnosis and treatment of hemodynamic or respiratory
abnormalities.
Nephrotoxic medications such as acyclovir, aminoglycoside
antibiotics, amphotericin B, ACE inhibitors, NSAIDs, radiocontrast
agents, and vancomycin should be avoided if possible in neonates
at high risk for AKI.
54
55. Prophylactic theophylline (5 mg/kg IV) given within the
frst hour of life has been recommended to reduce the
incidence of AKI in asphyxiated neonates, although its
use must be weighed against potentially harmful
neurologic side effects.
• Therapeutic hypothermia protocols currently used for
treatment of infants with perinatal asphyxia may have a
benefcial effect in reducing the incidence of neonatal
AKI.
55
A consensus defnition for neonatal AKI was recently established and termed
Three stages of neonatal AKI are defIned by relative changes in serum Cr from baseline
monitored at least daily or more frequently if signifcant metabolic abnormalities are present.
where U = urinary, P = plasma
Early identifcation of CKD allows implementation of strategies to slow the loss of kidney function, including healthy lifestyle, careful management of BP, reduction of proteinuria, hydration, and avoidance of nephrotoxin exposure.
