This document provides an overview of acute kidney injury (AKI) in neonates. It discusses the definition, incidence, pathophysiology, risk factors, clinical features, management and outcomes of AKI. The presentation covers neonatal renal physiology, the classification of AKI, common causes of pre-renal, intrinsic renal and post-renal AKI. It also describes the challenges in diagnosing AKI in neonates and the approach to evaluating a neonate with suspected AKI, including relevant laboratory and imaging tests.

1. Welcome To Seminar
Dr. Tareq
(Resident phase – B)
Dr. Agomoni Chaki
(Resident Phase – A)

2. Acute Kidney Injury (AKI) in
newborn

3. • Definition
• Incidence
• Neonatal renal physiology
• Pathophysiology of AKI
• Etiology
• Risk factor

4. Presentation Outline
• Definition
• Incidence
• Neonatal renal physiology
• Pathophysiology of AKI
• Etiology
• Complications
• Risk factor
• Clinical features
• Management
• Outcome of AKI
• Long term follow up

5. Definition
• Acute Kidney Injury (AKI), formerly referred to as
Acute renal failure, is defined as an abrupt reduction
in kidney function measured by a rapid decline in
glomerular filtration rate.
• AKI is an important contributing factor to the
morbidity & mortality of critically ill neonates.

6. Cont…
• AKI results in the disturbance of the following renal
physiological function :
- Impairment of nitrogenous waste
product excretion
- Loss of water & electrolyte regulation
- Loss of acid-base regulation

7. Definition
• Serum creatinine more than 1.5 mg/dl , regardless
of age or urine output, with normal maternal renal
function.
• T L Gomella, Neonatology: Management, Procedures, On-
Call problems, Diseases, and Drugs. 7th ed. Sydney. McGraw
Hill; 2003

8. Classification
RIFLE
stage RIFLE RIFLE and AKIN AKIN
AKIN
stage
Serum creatinine
increase from baseline
(GFR decrease)
Urine output
criteria
Serum creatinine
increase (or fold increase from
baseline)
Risk S. creatinine 1.5-fold
(GFR decrease > 25 %)
<0.5 ml/kg/h over
>6 h
>0.3 mg/dl [>26.4
m mol/l] ³ 1.5 to 2-fold
(150–200%)
1
Injury 2-fold (>50 %) <0.5 ml/kg/h for
>12 h
>2 to 3-fold
(>200–300 %)
2
Failure 3-fold (>75 %) <0.3 ml/kg/h for
>24 h
or anuria > 12 h
>4 mg/dl (>354 mmol/l) or >3-
fold (300%) or acute increase
of at least 0.5 mg/dl [44m
mol/l] or initiation of acute
RRT
3
Loss Persistent failure > 4
weeks
NA
End
stage
End-stage renal disease
> 3 months
NA

10. Incidence of AKI In Neonate
• The prevalence of hospital AKI is high. [24% of
hospital admitted neonates] - T L Gomella,
Neonatology: Management,2003
• Incidence of AKI in NICU varies from 8-20%
according to various studies, but it may be
increased up to 50% after cardiac surgery for
congenital heart disease.
• The incidence of AKI secondary to systemic illness
is higher than that of primary renal disease .

11. Hospital No. of
Pt
AKI M/F Pre-
renal
Renal Post-
renal
RRT
(IPD)
Death
BSMMU 921 11
(1.2%)
8/3 33.5% 51.0% 15.5% 18.2% 1(9.1%)
CMH 680 18
(2.9%)
13/5 34.0% 54.7% 11.3% 16.6% 3(16.6%)
DMCH 2163 501
(23.2%)
294/207 66.0% 32.0% 2.0% 2.4% 130
(26.0%)
Incidence, etiology and outcome of AKI in
neonate, 2013-14 in 3 NICU of DHAKA City
Prof. Habibur Rahman, Chairman, Department of Pediatric Nephrology, presented in an
International Conference

12. Neonatal Renal Physiology

13. Renal Function in Preterm Infants
 Greatest handicap - <30 wks , <1500 gms
 Sepsis, hypoxia, hypotension, PDA, mechanical
ventilation, acidosis, catabolism – additional burden
on kidney
 Indomethacin, high dose dopamine → further reduce
GFR
 Dexamethasone → catabolic effect → Increased
levels of urea

14. Functions of the Kidney
• Water balance
• Electrolyte balance
• Plasma volume
• Acid – base balance
• Osmolarity balance
• Excretion
• Hormone secretion

15. Nephron
• Primary unit of the kidney
is the nephron
• 1 million nephrons per
kidney
• Composed of a glomerulus
and a tubule

16. Renal blood flow

17. Renal Blood Flow
• RBF - At birth (2.5 -4%)
-24 hours ( 6%)
-1 week (10%)
-6 week (15-20%)
-Adult (20-25%)
• The eventual increase in renal blood flow at birth
due to - increase renal perfusion pressure
-increase systemic arteriolar resistance
-decrease renal vascular resistance due to
neurohumoral change

18. Glomerular Filtration Rate
GFR represents the most recognized measures of
kidney function
Glomerular filtration begins by 9-12 weeks of
gestation
GFR – 30 ml/min/1.73 m2 ( Term baby )
- 10-15 ml/min/1.73 m2 ( Preterm )
- 100-120ml/min/1.73m2 (1 year)

19. Calculation of GFR
• GFR : k X length / serum creatinine (mg/dl)
k = Empirically derived constant length
to muscle mass.
k = 0.34 in preterm
k = 0.45 in term

21. Serum Creatinine
• S. Creatinine – High at birth ( Maternal values )
- In PT – may rise in first few days
because of passive reabsorption of creatinine
through immature renal tubule.

23. Tubular Function

24. Tubular Function
• Proximal
– Most of reabsorption
occurs here
– Fluid is isotonic with
plasma
– 66-70% of sodium
presented is
reabsorbed
– Glucose and amino
acids are completely
reabsorbed

25. Tubular Function
• Loop of Henle
– Descending tubule –
permeable to water,
impermeable to
sodium
– Ascending tubule –
actively reabsorbs
sodium,
impermeable to
water

26. Tubular Function
• Distal Tubule &
Collecting System
– Early DT – impermeable
to water
– Late DT & Collecting
system
–Water
reabsorption occur
under the influence of
ADH
-Aldosterone
acts here to enhance Na
reabsorption and K
secretion

27. Pathophysiology of AKI

28. Classification of AKI
Based on the urine output, it can be of 3 types:
1. Anuric (Absence of urine output by 24-48
hours of age)
2. Oliguric (Urine output of <1ml/kg)
3. Non oliguric (>1ml/kg)
Non oliguric
Based on the site of origin of insult it can be of 3
types:
1. Pre renal (75- 80%)
2. Intrinsic renal (10-15%)
3. Post renal (5%)

29. Why Newborn more susceptible to
Acute Kidney Injury ?
• Developmental immaturity – immature renal
function
• Hemodynamic changes (ie, hypotension and
hypoxia) at birth – renal failure
• An increased risk of hypovolemia because of
large insensible water losses.
• Limited urine concentrating ability

30. Etiology

31. Pre- Renal
• Loss of effective blood volume
• Absolute loss
-Hemorrhage
-Dehydration
• Relative loss ↑ Capillary leak
-Sepsis
-Shock
-NEC
-RDS
-Hypoalbuminemia
-ECMO
• Renal hypoperfusion
Alteration in
plasma flow
Catecholamie
surge
Prostaglandn
& RAAS
activation
Dilation of
afferent
arteriole /
constriction
of efferent

32. Pre- Renal
• Congestive heart failure
• Pharmacologic agents
Indomethacin
Ibuprofen
ACE inhibitors
• Hypoxia

33. Intrinsic or Renal Parenchymal
• Sustained hypoperfusion leading to
ATN
• Congenital anomalies
Agenesis
Hypoplasia/ Dysplasia
Polycystic kidney disease
• Thromboembolic Disease
Bilateral Renal vein thrombosis
Bilateral renal arterial
thrombosis
• Nephrotoxins
Aminoglycosides
Radiographic contrast media
maternal use of captopril or
indomethacin
Increased transcapillary
hydrostatic pressure
Failure of
autoregulation +-
renal immaturity
Tubular damage
systemic inflammatory
response

34. Intrinsic or Renal Parenchymal
• Infection
-congenital syphilis
- Toxoplasmosis
-Candidiasis
-Pyelonephritis

35. Post Renal
• Urethral obstruction
- PUV (posterior Urethral Valve)
• Ureterocele
• ureteropelvic/ ureterovesical obstruction
• Extrinsic tumor
• Neurogenic bladder
• megacystitis/ megaureter syndrome

36. Common Nephrotoxic Substances
• Antibiotic : Aminoglycosides , cephalosporins ,
sulfonamides , tetracycline , imipenem , beta-
lactam antibiotic.
• Antifungal : Fluconazole , amphotericine B.
• Antiviral : Acyclovir , ribavirin
• ACE inhibitors , I/V Ig , Frusemide, NSAID.

37. Complications of AKI
• Fluid overload – heart failure , pulmonary
edema
• Hypertension
• Hyponatremia
• Hyperkalemia
• Metabolic acidosis
• hyperphosphatemia

38. Common Risk Factors
• Very low birth weight (less than 1500 g)
• Low 5-minute APGAR score
• Maternal drug administration (NSAIDs and antibiotics)
• Intubation at birth
• Respiratory distress syndrome
• Patent ductus arteriosus
• Dehydration, sepsis
• Neonatal medication administration (NSAIDs, antibiotics like
aminoglycosides, cephalosporin, sulphonamide, diuretics,
etc.)
• Zübarioğlu et al.Neonatal Kidney Injury. JAREM 2013; 3: 53-9

39. Welcome
To
2nd Part of Seminar

40. Diagnosis Of AKI
History
 Prenatal : - H/O Maternal DM.
- Maternal amniotic fluid volume.
- Maternal drug history.
 Natal : Any risk for AKI.
Decrease or absent urine output
Seizure.
 Family history

41. Diagnosis Of AKI
Examination
• Hydration status
• Vital signs
• Dysmorphic features
• Potter facies
• Abdominal distention
• Prune belly
• Meningomyelocele

42. Laboratory studies
1. S. Creatinine
2. BUN (15-20 mg/dl suggests renal insufficiency)
3. Urinary Indices
4. Urine analysis (Urine R/E)
5. CBC and platelet count
6. S. Electrolytes ( ↓Na, ↑K)
7. Radiological studies
-USG
-X-Ray
-Radionuclide scan

43. Challenges to S Creatinine Based
Definition
–S Cr indicates function not injury
–25-50% functional loss is needed to raise
SCr
–SCr is affected by age, sex, medications,
bilirubin and muscle mass, Hydration status
• Cannot distinguish pre renal, renal & post
renal cause
• First few weeks S cr reflect maternal kidney
function
Helmut Schiffl et al, Paediatric Nephrology2013;28:837-842
Frusemide ,

44. Urinary indices
Urinary indices Prerenal Post renal
Urine osmolality(
mosm/kg water)
>400 <400
Urine sodium
(mEq/L)
<20 >40
Urine/ plasma
osmolality ratio
>1.5 <0.8-1.2
FENa (%) <2.5 >2.5
RFI <3 >3
Blood urea to
creatinine ratio
>20:1 <20:1

45. Calculation of renal indices
• GFR : k X length / serum creatinine (mg/dl)
k = Empirically derived constant length to muscle mass.
k = 0.34 in preterm
k = 0.45 in term
• FENa : (Urine Na x serum cr./serum Na x urine cr. ) x 100
• RFI : Urine Na x serum creatinine / urine creatinine

46. Some Additional Tests
 Biomarkers:
1. Serum & urinary Cystatin C level
2. Plasma & urinary neutrophil gelatinase associated lipocalin
(NGAL) levels
3. Serum & urinary Interleukin (IL) -18 levels
4. Urinary albumin to creatinine ratio (ACR)

48. Approach To a Neonate With
Suspected AKI

49. Neonate with suspected AKI
Measure serum creatinine and urine output
Serum
biochemical
Markers
(Na, K, Ca, PO4, Urea,
Creatinine, blood
gases,
total blood count)
Urine
evaluation
(urinanalysis, urine
culture,
spot urine Na,
Creatinine,
osmolality)
Radiologic
evaluation
(Renal USG, Doppler
USG,
voiding
cystourethrogram,
radionuclide
scintigraphy

50. •Maintenance of fluid and electrolyte balance
•Avoidance of life-threatening complications
•Adequate nutritional support
•Treatment of the underlying cause
Pre Renal
-Fluid boluses
-Correct renal
hypoperfusio
n
Renal
-Remove
underlying
cause
Post Renal
-Eliminate
obstruction

51. Management
• Medical management
• Renal replacement therapy

52. Management
Medical Management
Supportive
Management
Definitive
Management:
-Rx of underlying condition
--post renal : relief of
obstruction

53. Supportive Management
• Fluid Challenge
• Replace insensible fluid loss
• Maintain fluid & electrolyte balance
• Maintain nutrition
• Restrict protein (<2 g/kg/day)
• Correction of – hyponatremia, hyperkalemia,
hypocalcemia, hyperphosphatemia, metabolic
acidosis
• Dopamine ( less than 5 µg/kg/min)
• Diuretics

54. Fluid Challenge
• Diagnostic fluid challenge: In the absence of
obvious sign of fluid overload or congestive
cardiac failure

55. AIIMS Protocol, 2014

57. Fluid Balance
• Limited to insensible losses
30 ml/kg/day (Term)
50-70 ml/kg/day (Preterm)
• Plus U.O. , GI losses
• IV antibiotics, feeds should be subtracted

58. Fluid Balance
• Fluid requirement should be revised based on
urine output, weight and assessment of
extracellular volume status, preferably every 8
hourly.
• The insensible water losses should be
replaced with 5-10% dextrose.

59. Nutrition
• The goal is to provide 100 kcal/kg/day
• Ensure adequate non protein caloric intake
• Restrict protein and amino acid to <2 g/kg/day

60. Correction of Electrolyte Imbalance
• Hyponatremia
 Babies can have hyponatremia in oliguric renal failure.
 Hyponatremia is due to dilution secondary to water
retention hence has to be corrected with fluid restriction.
 Babies with non-oliguric ARF may have urinary sodium
losses of up to 10 mEq/kg/day and these must be
replaced.
{Na required (mEq) = [Na desired – Na actual] x body
weight (kg) x 0.6}

61. Correction of Electrolyte Imbalance
• Hyperkalemia
It is one of the most dangerous complications
of AKI
Management of hyperkalemia:
- Stoppage of all potasium containing fluid and
drugs
- Medications

62. AIIMS- NICU Protocol, 2014

63. For hyperphosphatemia – Phosphate binder
can be used
For hypocalcemia – 10% Ca gluconate
Correction of Metabolic Acidosis

64. Loop Diuretics
• Diuretics have an important role in volume
management in AKI
• Do not prevent AKI or improve AKI outcomes
• Continuous vs intermittent dose – continuous
infusion yields comparable UO with a much
lower dose
• Commonly used- Frusemide 1-2 mg/kg/day

65. Low Dose Dopamine
• No improvement in survival, shortened
hospital stay or limit dialysis
• Dose- less than 5µg/kg/min
• No neonatal study
(Friedrich et al. 2005, analyzed 61 randomized or quazi-
randomized controlled trials of low dose dopamine and found
no improvement of survival, no decrease in dialysis
requirement, no improvement in renal function and
improvement in urine output only on the first day of therapy
in adults with ARF of any cause)

66. Renal Replacement Therapy
•Types of Renal Replacement Therapy
-Peritoneal dialysis
- CRRT
- Hemodialysis
•Indication:
Hyperkalemia
Hyponatremia
Acidosis
Hypocalcemia
Hyperphosphatemia
Uremic symptoms

67. Consequence of AKI
Brenner’s Hypothesis

68. Outcome
• Non oliguric renal failure has a better
prognosis
• Mortality ranges from 25 to 78% in oligo
anuric AKI
• Long term abnormalities in GFR and tubular
function are common

69. Causes of Poor Outcome
• very low birth weight
• BPD
• Antenatal steroid (????)
• High creatinin level, BUN and potassium
• Low serum sodium level
• Anuria
• Dialysis
• Mechanical ventilation
• Hypotension requiring ionotropic support
Bolat F et al. Acute kidney injury in a single neonatal intensive care unit in Turkey. World J
Pediatr 2013

70. Follow Up
–Regular follow up.
Growth, nutritional status, BP and RFT
Importance:
- ELBW→CKD ( within 1 yr)
Risk Factor:
random urinary PCR > 0.6,
serum creatinine >0.6 mg/dL
BMI > 85th percentile for age & sex

71. Follow Up

72. Practical Issues
 Is renal dose of all drugs are availabe?
 What to do when a patient has severe
hyponatremia along with AKI- how to
calculate fluid?

73. Key Message
Incidence of Neonatal AKI depends on
etiology and birth wt of baby
Pre renal etiology like sepsis , hypovolumia &
perinatal asphyxia are the commonest cause
Medical management is the important tool of
treatment
Outcome of Neonatal AKI is poor
Mortality rate ranges from 25-78%
Surviving Neonates needs regular follow up to
detect CKD

74. Thank You All