Presentation on acute kidney injury / renal failure in neonates

1. NEONATAL ACUTE KIDNEY INJURY
Obasohan E.
Dept. of Paediatrics
University College Hospital, Ibadan
6/09/2022

2. 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

3. 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.

4. 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.

5. 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

6. 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.

7. EPIDEMIOLOGY contd.
• Assessment of worldwide Acute Kidney injury
Epidemiology in Neonates (AWAKEN): Multicentre,
multinational, observational cohort study
Jetton et al, AWAKEN, Lancet; Child and Adolescent health, 2017
• Incidence and outcomes of
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
2-7

8. 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

9. RENAL ANATOMY AND PHYSIOSIOLOGY
Formation of nephrogenic cord
formation of permanent kidneys

10. 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
RENAL ANATOMY AND PHYSIOSIOLOGY

11. 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

12. 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 =
0.413 𝑥 ℎ𝑒𝑖𝑔ℎ𝑡 (𝑐𝑚)
𝑠𝑒𝑟𝑢𝑚 𝑐𝑟𝑒𝑎𝑡𝑖𝑛𝑖𝑛𝑒 (𝑚𝑔/𝑑𝑙

13. 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.
• Transient ↑ GFR followed by a
return to the baseline
• Minimal urine output regardless
of salt and water intake
• GFR increases rapidly
• Infant experiences
diuresis and natriuresis
regardless of salt and
water intake
• Typically begins around
day 4 to 5 of life
• The GFR begins to increase
slowly with salt and water
excretion varying
according to intake

14. 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.

15. 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

16. PERCULIARITIES OF RENAL FUNCTION IN NEONATES contd
NOVEL BIOMARKERS

17. PERCULIARITIES OF RENAL FUNCTION IN NEONATES contd
NOVEL BIOMARKER (study in Nigeria)
Study Author and year Findings
The role of urine NGAL as early
marker of AKI in sick neonates
admitted into the special care
baby unit of University of Port
Harcourt Teaching hospital
K. U Obikwu, P.
Opara, I.C
Anochie
UPTH, 2021
Urine NGAL detected more neonates
with AKI in the first 48 hours before
there was a rise in serum creatinine
between the 3rd and 5th day, giving an
incidence of NAKI of 38.3% and
23.5% using urine NGAL and serum
creatinine respectively
Determination of glomerular
filtration rate using cystatin C in
healthy Nigerian newborns
Olayinka Rasheed
Ibrahim et al.
UITH, 2017
values of serum cystatin C and eGFR
appeared low compared with most
studies done out of Africa
It also varied with gestational age and
anthropometry

18. 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

19. 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%)

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

21. PATHOPHYSIOLOGY
Ischaemia
Nephrotoxins
Tubular damage
1
Vasoconstriction
Renin-angiotensin
Endothelin
↓PG12 , ↓NO
2
Obstruction
by casts
3
Tubular
backleak
4
Interstitial
5
Direct glomerular effect ↓ GFR
↑Intratubular
pressure
↓ tubular
Fluid flow
Oliguria

22. PRE-RENAL INTRINSIC RENAL POST-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
• More likely to present with
features of volume overload /
Hypervolemia:
1. Peripheral oedema
2. Pulmonary oedema (rales)
3. Hypertension,
4. Haematuria etc
• History/features of
underlying causes: renal
agenesis, sepsis, DIC,
nephrotoxins, etc
• Obstructive
symptoms
1. A poor urinary output
2. Poor urinary stream,
3. A palpable bladder is
highly suggestive of
bladder outflow
obstruction.
4. Bilaterally ballotable
kidneys.
Features of complications: seizures, respiratory distress, apnoea,
CLINICAL FEATURES

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

24. EVALUATION OF AKI IN NEONATES contd.
POTTER SYNDROME

25. 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
mOsm/kg in other age grp)
<300 mOsm/kg (≤350 in older
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

26. 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

27. 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
OR
SCr rises by ≥ 1.5-1.9 times
baseline/reference SCr within 7
days
< 0.5 ml/kg/hr for
6-12 hours
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
SCr > 2.5 mg/dl or receipt of dialysis
< 0.3ml/kg/hr for ≥
24 hours or anuric
for 12 hrs

28. 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

29. 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

30. 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.

31. 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
2. Severe metabolic acidosis
3. severe calcium phosphate imbalance
4. Presence of dialyzable toxin
5. Severely elevated BUN and creatinine
6. Volume overload / pulmonary oedema
7. Features of uremia: seizures, gastritis
8. Inability to provide adequate nutrition

32. TREATMENT contd: RENAL REPLACEMENT THERAPY
PERITONEAL HAEMODIALYSIS CRRT
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.
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.
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.
Types: Intermittent and continuous
equilibrated peritoneal dialysis
Intermittent haemodialysis dialysis Continuous arterovenous,
venovenous haemofiltration and
Continuous veno-venous
haemodiafiltration
Advantage No need for vascular access and
anticoagulation, less difficlut
Rapid removal of solutes. Best option for the
haemodynamically unstable
Disadvant-
ages
Bacterial peritonitis, gut
perforation, slower removal of
solutes,
Hypotension, need for anticoagulation
and disequilibrium syndrome
Need for anticoagulation,
expensive.

33. 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
MONITORING ORDER FOR AKI

34. PREVENTION OF NEONATAL AKI
LEVELS OF
PREVENTION
General health
promotion
• Health education
• 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
prompt treatment
• Give fluid in hypovolaemia
• Elimination of nephrotoxins
• Single dose theophylline in asphyxiated babies.
• Catheterization: in asphyxia, obstructive uropathy.
Limitation of
disability
• Treatment of electrolyte derangement, optimal nutrition,
cardiovascular support, dialysis
Rehabilitation • Management of ESRD.

35. 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

36. 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
of AKI to monitor for evidence of CKD

37. ACKNOWLEDGEMENT
• Dr. Tongo
• Dr. Ayede
• Dr. Alao
• Dr. Ademola
• Dr. Bayo

38. 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.

39. THANKS