Neonatal Acute Kidney Injury

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Neonatal Acute Kidney Injury

• Dr N K Singh
• Neonatal Pediatric Intensivist
• Specialist Pediatric Nephrology
• VPIMS, Lucknow

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Case
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What Next?

• Bolus ? Volume ? Repeat ?
• Inj Frusemide Bolus / Continuous infusion?
• Low dose Dopamine ?
• Any other drug for AKI ?
• RRT ?

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Outline

1. Why term AKI?
2. Why neonatal AKI separately?
3. Neonatal renal physiology its clinical
   implication
4. Is it different from Pediatric/Adult AKI ?
5. Etiology
6. Clinical features
7. Management
8. Long term follow up
9. Evidence

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AKI

• Acute renal failure or Acute renal insufficiency
  ill defined,
• difficult to analyze information compare
  data
• To have a Standard Objective criteria
• Renal dysfunction is detected early preventive
  measures can be taken
• 2000 Acute Dialysis Quality Initiative (ADQI)
  proposed RIFLE criteria
• pRIFLE
• 2007 - Acute Kidney Injury Network (AKIN) revised
  criteria
• Validated in no. of adult studied
• Pediatric Neonatal studies coming up

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Why Neonatal AKI Separately

• Pediatric population is not a small adult
• Neonate is not a small pediatric patient
• Renal physiology is different in ELBW VLBW as
  compared to Term babies

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Incidence
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Neonatal Renal Physiology

• Nephrogenesis

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Glomerulogenesis
Chikkannaiah P et al. Indian Journal of Pathology
and Microbiology 2012
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Glomerulogenesis in Preterm Infants

• Radial glomerular count (RGC) is decreased
• RGC less in AKI pt survivors
• Those surviving gt40 days without AKI Increased
  glomerular size - ? Hyperfiltration
• Nephrogenesis continues, but altered postnatally
  ceases after 40 days

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Nephron Endowment

• Average of 900,000 nephrons per kidney
• Factors a/w decreased no. of nephrons
• LBW related to prematurity/IUGR
• Poor maternal nutrition
• Tobacco exposure
• Hyperglycemia
• Corticosteroids, NSAIDS, ACE inhibitors

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Carmody and Charlton et al.PediatricsJune2013,
vol.131,No.6
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Brenners Hypothesis
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Renal Blood Flow Glomerular Filtration Rate

• RBF Fetus (2-4), Newborn (15-18), Adult
  (20-25)
• Glomerular filtration begins by 9-12 weeks of
  gestation
• GFR 15-20 ml/min/1.73 m2 ( Term baby )
• - 10-15 ml/min/1.73 m2 ( Preterm )
• - 35-45 ml/min/1.73 m2 (End of 2
  weeks )
• - 75-80 ml/min/1.73 m2 ( End of 8
  weeks )
• S. Creatinine High at birth ( Maternal values )
• - In PT may rise in
  first few days bec of
• passive creatinine
  reabsorption through
• leaky immature
  tubules 0.5-0.6 mg/dl
• by end of 2nd week

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Fetal GFR ? Body Mass GA
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Growth Third Kidney
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Renal Function in Preterm Infants

• Greatest handicap - lt30 wks POG, lt1500 gms
• Rapid postnatal increase in GFR is not seen in
  VLBW baby
• 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

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Tubular Function in VLBW Babies

• Urinary Na loss ? High ? Serious hyponatremia
• Decreased concentrating ability careful
  balancing of fluid electrolyte intake
• Renal excretion of Calcium is more ?
  Hypocalcemia, Nephrocalcinosis
• Hypercalciuria is ?by Frusemide
• Renal threshold for HCO3 is low ? Acidosis

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Proposed Neonatal AKI Classification
Stage S. Creatinine Urine output
0 No change in S. creat / ? lt 0.3mg 0.5ml/kg/hr
1 S. Creat ? 0.3mg within 48hrs OR S. Creat ? 1.5 -1.9 X ref. value within 7days lt0.5ml/kg/hr for 6 -12hrs
2 S. Creat ? 2.0 2.9 X ref. value lt0.5ml/kg/hr for gt12hrs
3 S. Creat ? 3.0 X ref. value OR S. Creat gt2.5mg OR Receipt of DIALYSIS lt0.3ml/kg/hr for gt24hrs OR Anuria for gt 12hrs
Baseline S. creat is defined as the lowest previous S. Creat value Baseline S. creat is defined as the lowest previous S. Creat value Baseline S. creat is defined as the lowest previous S. Creat value
Modified from JettonJG, Askenazi DJ.Update on acute kidney injury in the neonate. Curr Opin Pediatr 201224(2)191-6 Modified from JettonJG, Askenazi DJ.Update on acute kidney injury in the neonate. Curr Opin Pediatr 201224(2)191-6 Modified from JettonJG, Askenazi DJ.Update on acute kidney injury in the neonate. Curr Opin Pediatr 201224(2)191-6
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Etiology

• Prerenal factors 85
• Intrinsic renal
• Post renal

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Common Causes of Neonatal AKI

• Table 25.2 pediatric nephrology

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Clinical Features

• Oliguria, non-oliguric failure
• Edema
• Vomitting, poor feeding
• Seizures
• Hypertension

• Microscopic hematuria in ATN
• Proteinuria
• Hyperkalemia
• Hyponatremia

Post renal abdominal mass, HTN,
oligoanuria/polyuria, urinary ascites,septicemia,
metabolic acidosis
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Diagnostic Evaluation

• Meticulous Urine Output measurement
• Serum Creatinine, Urea
• Indices not useful in patients with nonoliguric
  AKI those receiving diuretics
• Biomarkers - role ??

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Management

• No specific therapy to prevent or treat AKI
  (mainly supportive)
• Fluid electrolytes
• Drugs Frusemide, Dopamine, Fenoldapam,
  Theophylline, Rasburicase
• Dyselectrolytemia
• Hypertension
• Nutrition
• RRT

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Fluid Electrolytes

• Limited to insensible losses
• 30-40 ml/kg/day (Term)
• 50-100 ml/kg/day (Preterm)
• Plus U.O. , GI losses
• Electrolyte free
• IV antibiotics, feeds should be subtracted

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Loop Diuretics

• Do not prevent AKI or improve AKI outcomes
• Continuous vs intermittent dose continuous
  infusion yields comparable UO with a much lower
  dose
• Bumetanide a/w transient increase in S. Creat.
• Side effects ototoxicity, interstitial
  nephritis, osteopenia, nephrocalcinosis,
  hypotension, persistence of PDA

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Low Dose Dopamine

• No improvement in survival, shortened hospital
  stay or limit dialysis
• No neonatal study

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Fenoldapam

• Selective Dopamine 1 receptor agonist
• Renal splanchnic vasodilation increased renal
  blood flow GFR
• 2 prospective studies in neonates with
  cardiopulmonary bypass demonstrates that high
  dose fenoldapam (1 mcg/kg/min) may benefit in
  terms of AKI incidence, fluid balance or time to
  sternal closure

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Theophylline

• Nonspecific adenosine receptor antagonist
• 2 RCTs IV Theophylline given within an hour of
  perinatal asphyxia in term infants improves Cr
  clearance, S Cr levels fluid balance

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Rasburicase

• Recombinant urate oxidase
• Safe efficacious in treating elevated uric acid

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Renal Replacement Therapy

• PD/HD/CRRT
• Indications Volume overload
• - Inability to provide
  adequate
• nutrition
• - Hyperkalemia,
  Hyponatremia
• - Uremic symptoms etc.
• Early dialysis in presence of anuria, sepsis
  hypercatabolic state

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Other Drugs

• Dose needs to be modified as per creatinine
  clearance
• 1st dose / loading dose neednt be modified,
  subsequent doses should be

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Outcome

• Majority require only one dialysis over 48 hrs
• Those with sepsis, consumptive coagulopathy
  persistent anuria beyond 1 week need prolonged
  dialysis
• Renal biopsy
• Mortality in Oliguric AKI 30-50
• 40 of those who recover have residual renal
  damage structural, glomerular or tubular abn or
  hypertension

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Follow Up
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A Prospective Observational Study On AKI In
Critically ill Neonates Prajal Agarwal,
Niranjan Kr Singh, P. K. Mishra

• Total no. of subjects 78
• Prevalence of AKI 17.9
• Sepsis most common etiology, f/b perinatal
  asphyxia
• Most of the babies receiving 3 -5 antibiotics
• ? Late referral
• Inadequate neonatal care facilities at primary
  secondary care system lead to high prevalence of
  AKI

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Case
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Summary

• Perinatal renal physiology is dynamic
  complicated
• NICU population is at a high risk of AKI,
  complications of AKI future development of CKD
• Anticipating identifying AKI early meticulous
  supportive management are keys to improve
  outcome. Follow Up

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Panel discussion
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Renal teratogens
S No. Drug Teratogenicity
1 ACEI/ARB Renal insufficiency
2 Cyclosporin A low nephron no.
3 Mycophenolate mofetil Renal agenesis, renal ectopia
4 Cyclophosphamide HDN
5 Adriamycin HDN, Bladder agenesis
6 Dexamethasone Altered tubular transport, low nephron no.
7 NSAIDS Tubular alteration
8 Furosemide Renal concentrating defect
9 Antiepileptic drug MCKD
10 Aminoglycosides Tubular alteration, low nephron no.
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Antenatal USG Kidney

• 15 of all malformations
• 1-2/1000 live birth significant anomaly
• 1st trimester ARPKD, megacystis
• 2nd Tr- most malformations, eg. MCKD, agenesis,
  ectopia, duplication
• 3rd HDN, renal cysts, ADPKD
• BOO fetal therapy
• Isolated / chromosomal / syndromic
• Genitourinary

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Renal biopsy Indications

1. SRNS
2. AKI of unknown origin
3. RPGN
4. HSP, SLE, IgA Nephropathy
5. Inherited nephropathy Alports syndrome
6. Renal allograft dysfunction
7. Detection of CNI toxicity