NEONATAL ACUTE KIDNEY INJURY

Obasohan E.

Dept. of Paediatrics

University College Hospital, Ibadan

6/09/2022
 OBJECTIVES
• Definition and Epidemiology

• Nephrogenesis and its implication in AKI

• Perculiarities of Renal function in neonates

• Aetiology

• Pathogenesis, pathophysiology and Clinical features

• Investigation and treatment

• Prognosis and conclusion

 DEFINITION

• Acute kidney injury (AKI), formerly called acute renal failure, is a clinical
syndrome in which a sudden deterioration in renal function results in the
inability of the kidneys to maintain fluid and electrolyte homeostasis.

• To be more specific, it is defined as a sudden fall in glomerular filtrate rate,

which manifest as an abrupt and sustained rise in urea and creatinine. In
many cases, this is accompanied by oliguria. In a few case, there maybe
non-oliguric renal failure.
 DEFINITION contd.
• There are challenges with making the diagnosis early because of varying
definition and biomarkers used. The neonatal KDIGO by expert consensus
has become popular over the last decade

• While serum creatinine has been the gold standard to estimate clearance,
there has been challenges with its ability to accurately and timely detect AKI
especially in the neonatal population

• The nRIFLE was initially used in diagnosis but KDIGO is now the gold
standard for diagnosis and staging.
 DEFINITION contd.
• According to the Kidney Disease Improving Global Outcomes (KDIGO),
AKI is defined as any of the following:

 Increase in serum creatinine by 0.3mg/dL or more within 48 hours

OR

 Increase in serum creatinine to 1.5 times baseline or more within the

last 7 days

OR

 Urine output less than 0.5 mL/kg/h for 6 hours

 EPIDEMIOLOGY

• The prevalence of AKI is high. It is estimated to occur in 24% of neonates

admitted the hospital (T. L Gomella, Neonatology: Management, 2003)

• Incidence of AKI in neonates vary from different studies, but consistently

highest after cardiac surgery for congenital heart disease.

• The incidence of AKI secondary to systemic disease is higher than that of

primary kidney disease.
 EPIDEMIOLOGY contd.
• Assessment of worldwide Acute Kidney injury
Epidemiology in Neonates (AWAKEN): Multicentre,
• Incidence and outcomes of multinational, observational cohort study
neonatal acute kidney
injury

• Largest study on neonatal

AKI. Involved 24 NICUs in
India, USA, Canada and
Australia. 2, 022 neonates
were recruited

• Inclusion criteria
1. IV fluids ≥ 48 hours;
2. UO < 1ml/kg/hr on days
Jetton et al, AWAKEN, Lancet; Child and Adolescent health, 2017
2-7
 RENAL ANATOMY AND PHYSIOSIOLOGY
• The development of kidney begins in the fourth week of intrauterine life
from intraembryonic (intermediate) mesoderm which give rise to the
nephrogenic cord

• The nephrogenic cord forms three successive kidneys: pronephros,

mesonephros, and metanephros—succeeding each other in time and space
such that last to develop is retained as permanent kidney.

• Each permanent kidney develops from two distinct sources:

1. Metanephric blastema (metanephros): forms the excretory system

2. ureteric bud (from the mesonephric duct): forms the collecting system.

• The permanent kidneys develop in the sacral region and ascend to T12 to L3
RENAL ANATOMY AND PHYSIOSIOLOGY
formation of permanent kidneys
Formation of nephrogenic cord
RENAL ANATOMY AND PHYSIOSIOLOGY
Ascent of the kidneys
Why does the
kidney ascend ?

Two physiologic
reasons

1. It faces space
crunch in the
smaller pelvic
cavity

2. In search of
better blood
supply
 TIMELINE IN NEPHROGENESIS
Timeline Event
Beginning of 4th week Beginning of nephrogenesis
5th week Metanephros begin to develop
6th week Glomerular filtration begins
20th week The entire collecting system is formed.
34-36 weeks Formation of nephron is complete (range of 200 000
to 2 million per kidney)
1st decade Tubular growth and elongation is complete
18-20 years Increase in GFR ceases.
Some 98% of full-term infants void in the first 30 hours of life, with as many as 25% doing so in
the delivery room. A delay in urination can be normal and should not cause immediate
concern in the absence of an enlarged bladder, abdominal mass, or other indications of renal
disease. Failure to urinate in the first 48 hours should prompt further investigation
 KIDNEY FUNCTION ESTIMATION

• Kidney function is best measured as the glomerular filtration rate

• True measurement of the GFR is expensive and time consuming, the GFR is
commonly estimated (eGFR) by the clearance of endogenous creatinine.

• The “bedside” Schwartz formula is the most widely used pediatric formula
and is based on the serum creatinine (Scr), patient height, and an empirical
constant:
eGFR
 PERCULIARITIES OF RENAL FUNCTION IN NEONATES
A. GFR changes with age: The increase in GFR after birth is caused by

 reduction in intrarenal vascular resistance

 redistribution of intrarenal blood flow to the cortex, where more nephrons

are located.
• During the first week of postnatal life, an infant’s GFR passes through three
distinct phases to maintain fluid and electrolyte homeostasis.
Pre-diuretic phase Diuretic phase Post diuretic phase
• first 24-36 hours of life. • GFR increases rapidly • Typically begins around
• Transient ↑ GFR followed by a • Infant experiences day 4 to 5 of life
return to the baseline diuresis and natriuresis • The GFR begins to increase
• Minimal urine output regardless regardless of salt and slowly with salt and water
of salt and water intake water intake excretion varying
according to intake
 PERCULIARITIES OF RENAL FUNCTION IN NEONATES contd
B. Other perculiarities:
 During the first 48-72 hours of life, serum creatinine still reflects maternal
level and these values may decline at varying rate over days depending on
the gestational age

 Immaturity of the renal tubules: In preterm babies, there is an increased

level of serum creatinine due to back secretion into the circulation by the
immature kidney tubules

 Most of the evolving biomarkers use creatinine as reference standard.

 Serum creatinine may not change until 25-50% of the kidney function has
already been lost.
 PERCULIARITIES OF RENAL FUNCTION IN NEONATES contd

Varying normal Serum Creatinine level and GFR with gestational age

Jetton et al, AWAKEN, Lancet; Child and Adolescent health, 2017

PERCULIARITIES OF RENAL FUNCTION IN NEONATES contd
NOVEL BIOMARKERS
 PERCULIARITIES OF RENAL FUNCTION IN NEONATES contd
NOVEL BIOMARKER (study in Nigeria)
Study Author and year Findings
The role of urine NGAL as early K. U Obikwu, P. Urine NGAL detected more neonates
marker of AKI in sick neonates Opara, I.C with AKI in the first 48 hours before
admitted into the special care Anochie there was a rise in serum creatinine
baby unit of University of Port between the 3rd and 5th day, giving an
Harcourt Teaching hospital UPTH, 2021 incidence of NAKI of 38.3% and
23.5% using urine NGAL and serum
creatinine respectively

Determination of glomerular Olayinka Rasheed values of serum cystatin C and eGFR

filtration rate using cystatin C in Ibrahim et al. appeared low compared with most
healthy Nigerian newborns studies done out of Africa
UITH, 2017 It also varied with gestational age and
anthropometry
WHY NEONATES ARE SUSCEPTIBLE TO ACUTE KIDNEY INJURY

Other susceptibilities:
• Increased risk of
hypovolemia: no control
over intake, increased
evaporative loss,

• Immaturity of the renal

tubules

• Frequent use of
potentially nephrotoxic
drugs: aminoglycosides,
NSAIDS, etc
 CLASSIFICATION OF AKI IN NEONATES

• Based on the urine output: it can be of 3 types

1. Anuric: absence of urine by 24-48 hours of age

2. Oliguric: urine output < 1ml/kg/hr
3. Non-oliguric: urine outpu > 1ml/kg/hr

• Based on the site of origin of the insult:

1. pre-renal (75-85%)
2. Intrinsic renal (10-15%)
3. Post renal (5%)
 AETIO-PATHOGENESIS OF AKI IN NEONATES
PRE-RENAL (85% of AKI) RENAL (10-15%) POST-RENAL (3-5%)
↓circulating volume There is renal Obstruction to urine flow
parenchymal damage
↓ renal perfusion Impaired removal of fluid
a) The most common cause and other waste.
↓ GFR is ATN. The Risk include
Note:no parenchyma damage i. Prolonged pre-renal a) Posterior urethral valve
a) Excessive fluid loss ii. Perinatal asphyxia b) PUJ obstruction
evaporative loss, NG-tube loss, iii. Need for ECMO c) Vesicoureteric junction
haemorrhage, diuretics iv. Others: Acyclovir, obstruction
b) Decreased cardiac output vancomycin, NSAIDS, d) Meatal stenosis
sepsis, NEC, CHDs aminoglycosides e) Extrinsic compression of
c) Hypoalbuminemic state b) Other causes: renal the bladder: sacroccygeal
Hypoproteinaemia hypoplasia, ARPKD, renal teratoma
d) Drugs ↓ RBF: NSAIDS, ACE-I venous thrombosis, etc f) Others: calculi, fungal balls
 PATHOPHYSIOLOGY
Ischaemia Tubular damage
Nephrotoxins

1 2 3 4
Vasoconstriction Obstruction Tubular Interstitial
Renin-angiotensin by casts backleak
Endothelin
↓PG12 , ↓NO ↑Intratubular ↓ tubular
pressure Fluid flow
5
Direct glomerular effect ↓ GFR Oliguria
 CLINICAL FEATURES
PRE-RENAL
• Usually features of
diminished circulating
volume or volume depletion:
1. Dry mucous membrane
2. Tachycardia
3. Sunken fontanelles
4. Loss of skin tugor
• History of causes: asphyxia,
cardiac failure, shock,
hypotension, dehydration
INTRINSIC RENAL POST-RENAL
• More likely to present with • Obstructive
features of volume overload / symptoms
Hypervolemia:
1. Peripheral oedema 1. A poor urinary output
2. Pulmonary oedema (rales)
3. Hypertension, 2. Poor urinary stream,
4. Haematuria etc
3. A palpable bladder is
• History/features of highly suggestive of
underlying causes: renal bladder outflow
agenesis, sepsis, DIC, obstruction.
nephrotoxins, etc
4. Bilaterally ballotable
kidneys.

Features of complications: seizures, respiratory distress, apnoea,

 EVALUATION OF AKI IN NEONATES
A. History B. Physical examination

C: Laboratory evaluation
 Electrolytes: blood urea nitrogen↑, creatinine ↑, sodium↓, potassium↑,
bicarbonate↓, calcium↓, phosphorus↑, albumin, and uric acid.
 Other investigations: urinalysis, Urine mcs, urinary indices, Blood culture, FBC
 Imaging: abdominal ultrasound:
EVALUATION OF AKI IN NEONATES contd.
POTTER SYNDROME
 EVALUATION OF AKI IN NEONATES Contd.
Diagnostic indices PRE-RENAL AKI RENAL AKI

Urine Specific gravity >1.020 <1.010

Urine Osmolality >350 Osm/kg (>500 <300 mOsm/kg (≤350 in older
mOsm/kg in other age grp) age group)
Urinary sodium (UNa) Low (<20mEq/L) High (>50mEq/L) > 40 in others
Fractional excretion of Na < 2% (<1% in other age grp) >10% (>2% other age group)
Urine plasma creatinine ratio >40 <20
Urine plasma urea ratio >8 <3
Urine microscopy Usually normal Many RBCs, granular casts and
red cell cast
BUN/Cr ratio (mg/mg) > 30 < 20
 EVALUATION OF AKI IN NEONATES contd.
IMAGING: ultrasound

• The role of routine post-natal abdominal ultrasound for newborns in a resource-poor setting: a longitudinal
study. A tinuke M Agunloye, Adejumoke I Ayede and Samuel I Omokhodion
 STAGING OF AKI IN NEONATES
Neonatal Modified Kidney Disease Improving Global Outcomes
(KDIGO) criteria for Aki
Stage Serum creatinine (SCr) Urine output
0 No change in SCr or rise <0.3mg/dl ≥ 0.5 ml/kg/hr
1 SCr rises ≥ 0.3mg/dl within 48 hours < 0.5 ml/kg/hr for
OR 6-12 hours
SCr rises by ≥ 1.5-1.9 times
baseline/reference SCr within 7
days

2 SCr rises ≥2-2.9 times the baseline < 0.5 ml/kg/hr for ≥
12 hours.
3 SCr rises ≥ 3.0 times the baseline OR < 0.3ml/kg/hr for ≥
SCr > 2.5 mg/dl or receipt of dialysis 24 hours or anuric
for 12 hrs
 TREATMENT
• TREATMENT GOALS
1. Maintenance of electrolyte balance

2. Maintenance of fluid balance

3. Treatment of cause of AKI

4. Adequate nutrition

5. Treatment of emerging complications

6. Prevention of further nephrotoxicity – : Remove nephrotoxins etc

• Management is multidisciplinary: neonatologist, nephrologist, nurses,
urologist etc
 TREATMENT contd
• In the case of established oliguric AKI:

 a urinary catheter should be placed to exclude lower urinary tract obstruction

 If there is no improvement and there is hypovolaemia, fluid (normal saline) at

10ml /kg should be administered over 30 minutes to 1 hour to exclude
prerenal AKI.

 If the patient is now normovolaemic and remains oliguric, Vasopressor (low

dose dopamine) may be tried especially if MAP is low.

• 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
 TREATMENT contd.
• For intrinsic AKI:
 The goal of medical management of intrinsic AKI is to provide supportive care
until there is spontaneous improvement in renal function

 To prevent symptomatic fluid overload, intake should be restricted to

insensible losses (500 mL/m2 per day, or 30 mL/kg per day) plus urine output
and other measured losses.

 Adjust medications by dose, interval, or both according to GFR

 Potassium and phosphorus should be restricted neonates with hyperkalemia

and hyperphosphatemia. NaHCO3 for severe metabolic acidosis
• Surgical consultation for obstructive uropathy
• Kidney support therapy, antibiotics for sepsis.
 TREATMENT contd.
• Renal Replacement Therapy:

 is needed when maximum medical management fails to maintain acceptable

fluid and electrolyte levels.

 Options include: Peritoneal dialysis, intermittent haemodialysis and CRRT

 Indications for dialysis:

INDICATIONS FOR DIALYSIS
1. Intractable hyperkaelemia 6. Volume overload / pulmonary oedema
2. Severe metabolic acidosis 7. Features of uremia: seizures, gastritis
3. severe calcium phosphate imbalance 8. Inability to provide adequate nutrition
4. Presence of dialyzable toxin
5. Severely elevated BUN and creatinine
 TREATMENT contd: RENAL REPLACEMENT THERAPY
PERITONEAL
Principle Infusion of a pyrogen-free
solution into the peritoneal cavity
where it is drained in subsequent
cycles. Principles here include
diffusion, convection and osmotic
ultrafiltration.
IT IS A COMMONLY USED RRT IN
NEONATES.
Types: Intermittent and continuous
equilibrated peritoneal dialysis
Advantage No need for vascular access and
anticoagulation, less difficlut
Disadvant- Bacterial peritonitis, gut
ages perforation, slower removal of
solutes,
HAEMODIALYSIS
Dissolved particles from one fluid
compartment move to the other by
diffusion along a concentration
gradient on opposite sides of a
semipermeable membrane.
Vascular access are large vessels
subclavian or femoral vein to permit
the rapid flow rates required.
Intermittent haemodialysis dialysis
Rapid removal of solutes.
Hypotension, need for anticoagulation
and disequilibrium syndrome
CRRT
Extracorporeal therapy in which
solutes are removed from the
patient by convection over an
extended period of time.
No blood pumps are used, the
arteriovenous pressure gradient
represents the driving force that
moves the blood throughout the
extracorporeal circuit.
Continuous arterovenous,
venovenous haemofiltration and
Continuous veno-venous
haemodiafiltration
Best option for the
haemodynamically unstable
Need for anticoagulation,
expensive.
 MONITORING ORDER FOR AKI
1. Strict fluid input- output chart

2. Daily dipstick urinalysis

3. Daily weighing

4. Blood pressure - at least 2hrly on day 1, Modify interval subsequently as

appropriate. Pulse rate - at least 2hrly on day 1

5. Temperature - ,,

6. Daily E/U/Creatinine

7. Others: Continuous Spo2, Dressing over PD catheter, RPG, PCV, etc

 PREVENTION OF NEONATAL AKI
LEVELS OF
PREVENTION
General health • Health education
promotion • Environmental hygiene
Specific Protection • Strict fluid management- adequate breastfeeding,
incubator care for preterms,
• Antibiotics for bacterial sepsis
• Use potentially nephrotoxic drugs with caution

Early diagnosis and • Give fluid in hypovolaemia

prompt treatment • Elimination of nephrotoxins
• Single dose theophylline in asphyxiated babies.
• Catheterization: in asphyxia, obstructive uropathy.

Limitation of • Treatment of electrolyte derangement, optimal nutrition,

disability cardiovascular support, dialysis
Rehabilitation • Management of ESRD.
 PREVENTION OF NEONATAL AKI contd.
Methylxanthines in prevention of AKI

• Treating perinatal asphyxia with theophylline at birth helps to reduce the severity of renal dysfunction in term
neonates. Alok Raina et al, 2016 Oct
• Effectiveness of theophylline administration in neonates with perinatal asphyxia:meta-analysis. Ioannis Bellos,
Aakash Pandita, 2020
 PROGNOSIS AND CONCLUSION
• Research has demonstrated that AKI is not just a marker of severity of illness
in neonates but is also independently associated with poor outcomes.

• Infants with higher stages of AKI had higher mortality rates and lengths of
hospitalization when compared with infants with lower stages of AKI.

• Observational studies have demonstrated high rates of CKD in survivors of

neonatal AKI. The risk of CKD in survivors of neonatal AKI may be compounded
by the risks of prematurity and low birth weight, both of which are associated
with CKD because of associated inadequate nephron development

• Long-term nephrology follow-up care is important in neonates with a history o

AKI to monitor for evidence of CKD
 ACKNOWLEDGEMENT

• Dr. Tongo

• Dr. Ayede

• Dr. Alao

• Dr. Ademola

• Dr. Bayo
 REFERENCES
• Embryology of the renal and genitourinary system Intensive Revision Course of NPMCN 28th January, 2022. Dr.
Asinobi
• Perinatal Asphyxia Membership course by Dr. Tongo
• Acute peritoneal dialysis: impact of an opt-out model and adaptable methods in a hospital in Nigeria Michael
Abel Alao et al
• klaus and Fanaroff’s care of the high-risk neonate, seventh edition
• Textbook of Clinical Embryology Vishram Singh, ms.
• Nelson Textbook of Pediatrics, 21st edition.
• Renal Replacement therapy H.A Aikhionbare.
• Common Kidney Disorders in Children WACP Membership Revision course 11th August, 2021.
• The role of routine post-natal abdominal ultrasound for newborns in a resource-poor setting: a longitudinal
study. Atinuke M Agunloye, Adejumoke I Ayede, and Samuel I Omokhodion
• Neonatal Acute Kidney Injury, Dept of Neonatology, SGPGIMS, Lucknow https://
www.youtube.com/watch?v=JTej9ajJy7g
• Determination of glomerular filtration rate using cystatin C in healthy Nigerian newborns. Olayinka Rasheed
Ibrahim et al. UITH, 2017
• Neonatal acute kidney injury. Cassandra Coleman et al
• Acute kidney injury in neonates: From urine output to new biomarkers. Alexandra Braga Liborio et al.
THANKS