Neonatal Acute Renal Failure From NNU, Aberdeen Maternity Hospital Teaching Session.

1. Neonatal Acute Kidney Injury
SUTIRTHA ROY
SPECIALTY DOCTOR IN NEONATOLOGY
NNU, ABERDEEN MATERNITY HOSPITAL

2. Objectives:
• Recent Advances in the of Evidence Based Definitions of Neonatal AKI
• Epidemiology, Risk factors, Classification and Outcomes of Neonatal AKI
• Advances in diagnosis, prevention and mitigation
• Outline of management

3. Generic Definitions of Neonatal AKI
 Consequence of a sudden decrease in glomerular filtration rate
 Subsequent retention of nitrogen waste products
 Disturbance in water, electrolyte and acid-base balance
Giuseppe Buonocore, Rodolfo Bracci, Michael Weindling, Editors.
Neonatology A Practical Approach to Neonatal Diseases, Second Edition. Springer 2018.

4. West of Scotland Definition for Paediatric AKI
• Oliguria - Urine Output: <300ml/m2/day or 0.5ml/kg/hr
• Anuria - Urine Output: <1ml/kg/day
• Hyperkalaemia: K >6.0 mmol/L on 2 separate occasions
• Clinical Fluid Overload
• Oedema
• Triple Rhythm
• Hypertension

5. Redefining Neonatal AKI: The Obvious Issues
• Current thresholds of changes in serum creatinine (SCr).
• The optimal definition of oliguria that defines AKI in neonates (UO).
• The incorporation of novel biomarkers into the definitions of AKI (nBM).
• Wide variability of parameters across the Gestational Age (GA).

6. Neonatal AKI: Recent Advances in Evidence Based Medicine
• Acute Kidney Injury Network AKIN Definition. Jetton JG et al 2012.
• Neonatal RIFLE. Zaccaria Ricci and Claudio Ronco 2013.
• Kidney Disease: Improving Global Outcomes KDIGO Definition.
Developed and modified for neonates. 2013.
• Assessment of Worldwide Acute Kidney Injury Epidemiology in
Neonates: AWAKEN Study Definition. Jetton JG et al 2016.

7. nRIFLE: The Uncertain Thresholds

8. Neonatal Acute Kidney Injury: Defining Criteria

11. Nuances of neonatal renal transition and physiology
• Neonatal kidneys are particularly susceptible to hypoperfusion
• Ischemia secondary to dynamic changes in postnatal renal blood flow
• Changes in the renin-angiotensin system and prostaglandins due to the
alteration in renal perfusion in early extra uterine life
• Sympathetic nervous system renal vascular tone in afferent and efferent
arterioles
• Upregulation of α2 receptors is associated with downregulation of β2
receptors

12. The glomerulus: Intrarenal Regulation of GFR

13. Nuances of perinatal renal transition and physiology
• In utero nephron development begins at 5 weeks’ gestation and continues to 34–36 weeks
of gestation.
• The majority of nephrogenesis occurs late in pregnancy with up to 60% of nephrogenesis
occurring in the third trimester.
• Each additional Kilogram increase in Birth Weight confers nearly 200,000 additional
nephrons.
• In healthy premature neonates, nephrogenesis continues after birth, but for only 40 days .
• Consequently, premature birth and Low Birth Weight both alter final nephron number and
development increasing the Risk for AKI and subsequent CKD.

14. Nuances of perinatal renal transition and physiology
• Glomerular filtration rate at birth is close to 20 mL/min per 1.73 m2 in term
neonates.
• Doubles within 2 weeks.
• Reaches 50 mL/min per 1.73 m2 at 4 weeks of life.
• In healthy premature neonates, nephrogenesis continues after birth, but for
only 40 days.
• Low birthweight infants have consequently a lower number of nephrons
than term infants.
• GFR is lower in low birthweight infants and increases more slowly than in
full-term neonates

15. Epidemiology
• Andreoli estimated the incidence of AKI (in a review of single-center studies that
used a serum creatinine cut-off of 1.5 mg/dL) in critically ill neonates at between 8%
and 24%, with mortality rates between 10% and 61%.
• Using more contemporary definitions (an absolute rise of 0.3 mg/dL or 50% rise
from lowest previous SCr), studies suggest an incidence of 19–40% in very low birth
weight infants and 38% in term neonates with perinatal asphyxia.

16. Epidemiology: Changing Perspectives
• In the largest study to date, the AWAKEN study, investigators evaluated
the incidence and impact of neonatal AKI in an international,
multicentric cohort study of 2022 neonates admitted to 24 NICUs over
a 3-month period.
• In this study, incidence of AKI was 30%, with variation by GA (22 to <29
weeks’: 48%; 29 to <36 weeks’: 18%; 36 weeks’: 37%).

17. Risk Factors:
• Prematurity and Low Birth Weight
• Hypoxic Ischemic Encephalopathy
• Congenital Heart Disease
• Necrotizing Enterocolitis
• Nephrotoxic Medications
• Extracorporeal Life Support
Coleman et al.2022

18. Classification of Neonatal AKI
Based on Urine Output:
Gouyon J B, Guignard J P. 2000
• Oliguric:
Thirty percent of normal newborns void soon after birth; 92% will void within the first 24 hours and 99% by 48 hours.
Oliguria is observed in the majority of neonates presenting with ARF nearly two third.
• Nonoliguric:
One fourth to one third of neonates with ARF may have nonoliguric failure and the renal failure can only be
recognized by the finding of elevated urea and serum creatinine concentrations.
Based on Site of the Insult:
Hentschel R et al. 1996
• Prerenal/ Functional (75- 80%)
• Intrinsic/ Renal (10-15%)
• Postrenal (5%)

19. Aetiologies of Acute Renal Failure in Neonates
• Prerenal
• Hypovolemia or renal hypoperfusion
• Asphyxia
• Respiratory distress syndrome (RDS)
• Dehydration
• Hemorrhage (maternal antepartum, twin-to-twin transfusion, intraventricular
bleeding, haemolytic disease)
• Sepsis
• Cardiac disease (patent ductus arteriosus, aortic coarctation)
• Polycythaemia (hyperviscosity)

20. Aetiologies of Acute Renal Failure in Neonates
Renal
 Acute tubular necrosis (ATN)
 Persistent prerenal disturbances
 Nephrotoxins (nephrotoxic antibiotics, e.g., aminoglycosides, contrast agents, angiotensin-
converting enzyme [ACE] inhibitors and angiotensin II AT1 receptor blockers)
 Myoglobinuria, haemoglobinuria, hyperuricemia
 Vascular disorders (renal vein thrombosis, renal artery thrombosis, aortic thrombosis,
disseminated intravascular coagulation)
 Congenital renal anomaly (dysplasia, hypoplasia, polycystic kidney, agenesis)
 Pyelonephritis
 Transient acute renal failure of the neonate
 Maternal aetiology (gentamicin, indomethacin, ACE inhibitors, paraproteinemia)

21. Aetiologies of Acute Renal Failure in Neonates
• Postrenal
• Congenital anomaly (ureteral/urethral obstruction, neurogenic bladder, magacystis-
megaureter)
• Obstruction secondary to circumcision
• Renal candidiasis
• Calculi
• Neurogenic bladder

22. Overlapping Pathways in the Pathogenesis of Neonatal AKI

23. Diagnostics and the Dilemma of Neonatal AKI
• Azotaemia refers to the retention of nitrogenous waste products.
• Detected by the elevated levels of Creatinine and Plasma Urea.
• Serum Creatinine (SCr): the most widely used surrogate marker for eGFR.
• SCr is currently the “gold-standard” of biomarkers to identify AKI.
• BUT SCr serves as a measure of renal function, rather than injury.
• Furthermore, SCr is a delayed (up to 48–72 h) marker of Renal Function,
may not change until 25–50% of the kidney function has been lost.

24. Diagnostics and the Dilemma of Neonatal AKI
• Plasma Urea:
• Plasma urea is a poor marker of renal function.
• It is influenced by multiple factors:
Protein intake, Urine Output, Gastrointestinal Bleeding, Hypercatabolic state.

25. Renal Indices for Neonatal AKI
Fractional Excretion of Sodium (FENa):

26. Renal Indices for Neonatal AKI

27. Parameters to Differentiate Functional/Prerenal from
Intrinsic /Renal Failure
Parameters Prerenal Intrinsic Renal
Urinary Na <20mEq/L >50mEq/L
RFI Low <1 High >4
FENa <1 >3

28. Novel Biomarkers for Neonatal AKI
• Neutrophil gelatinase associated lipocalin (NGAL)
• Plasma Cystatin C (CysC)
• Interleukin-18 (IL-18)
• Kidney injury molecule-1 (KIM-1)
• Osteopontin (OPN)
• Beta-2 microglobulin (B2mG)

29. Clinical Assessment of AKI: West of Scotland Guidelines
• Patient Weight – Required Daily
• Urine Output
• Blood Pressure
• Hydration Status
• Blood Biochemistry and FBC
• Cardiorespiratory Examination
• Neurological Examination
• Musculoskeletal Examination
• Bruising/Bleeding
• Drug History Investigations

30. Laboratory Evaluation
 U&E’s, LFT’s and CRP
 Uric acid
 Magnesium
 Glucose
 Osmolality
 FBC ± Blood film
 Coagulation Screen
 LDH
 FENa
 Urinalysis
 Urinary Sodium, Osmolality
 Microscopy for casts
 Culture and sensitivity
 Renal Ultrasound

31. Management Outline of neonatal AKI

32. Medications Requiring Dose Adjustment with Compromised GFR

33. Management Outline of neonatal AKI
• Fluid Management
• Correction of Dyselectrolytaemia: Hyperkalaemia,
Hypo/hypernatraemia,
• Correction of acid-base disorders
• Nutrition
• Hypertension

34. THANK YOU
Questions?