Download Neonatal Acute Kidney Injury - Lucknow Academy of Pediatrics

NEONATAL ACUTE KIDNEY INJURY
Dr N K Singh
Neonatal & Pediatric Intensivist
Specialist Pediatric Nephrology
VPIMS, Lucknow
Case
Term, LSCS, B.wt – 3 kg
Bag & mask resuscitation
Started on O2 by hood → CPAP
Referred on D3 with severe RD, shock, edema
Wt – 3.290 kg
↓UO
HR – 180/min, RR – 80/min, Spo2 – 70% on 4-6 L/min, CRT>4 sec
Hb – 10.3 gm%, TLC – 26250/mm3,
P86L10E2M2, Plts – 35,000/mm3
S Creat – 1.8mg%, Urea – 53 mg%, Na-123
meq/L, K-4.37 meq/L Ca-6.4/0.8 mg/dl
What Next?
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Bolus ? Volume ? Repeat ?
Inj Frusemide – Bolus / Continuous infusion?
Low dose Dopamine ?
Any other drug for AKI ?
RRT ?
Outline
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Why term AKI?
Why neonatal AKI separately?
Neonatal renal physiology : it’s clinical implication
Is it different from Pediatric/Adult AKI ?
Etiology
Clinical features
Management
Long term follow up
Evidence
AKI
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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
Why Neonatal AKI Separately
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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
Incidence
Neonatal Renal Physiology
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Nephrogenesis
BEGINS
ENDS
Glomerulogenesis
Chikkannaiah P et al. Indian Journal of Pathology and Microbiology 2012
Glomerulogenesis in Preterm Infants
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Radial glomerular count (RGC) is decreased
RGC less in AKI pt survivors
Those surviving >40 days without AKI – Increased
glomerular size - ? Hyperfiltration
Nephrogenesis continues, but altered postnatally
& ceases after 40 days
Nephron Endowment
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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
Carmody and Charlton et al.Pediatrics:June2013, vol.131,No.6
Brenner’s Hypothesis
Renal Blood Flow & Glomerular
Filtration Rate
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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
Fetal GFR ᾳ Body Mass & GA
Growth = “Third Kidney”
As neonates grow rapidly, protein &
nutrients are incorporated into tissues
Decreased demand on the kidney
THIRD KIDNEY
Renal Function in Preterm Infants
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Greatest handicap - <30 wks POG, <1500 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
Tubular Function in VLBW Babies
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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
Proposed Neonatal AKI Classification
Stage
S. Creatinine
Urine output
0
No change in S. creat / ↑ < 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
<0.5ml/kg/hr for 6 -12hrs
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S. Creat ↑ ≥ 2.0 – 2.9 X ref. value
<0.5ml/kg/hr for >12hrs
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S. Creat ↑ ≥ 3.0 X ref. value OR
S. Creat >2.5mg% OR
Receipt of DIALYSIS
<0.3ml/kg/hr for >24hrs
OR
Anuria for > 12hrs
• 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
2012;24(2):191-6
Etiology
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Prerenal factors – 85%
Intrinsic renal
Post renal
Common Causes of Neonatal AKI
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Table 25.2 pediatric nephrology
Clinical Features
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Oliguria, non-oliguric
failure
Edema
Vomitting, poor
feeding
Seizures
Hypertension
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Microscopic
hematuria – in ATN
Proteinuria
Hyperkalemia
Hyponatremia
Post renal – abdominal mass, HTN,
oligoanuria/polyuria, urinary ascites,septicemia,
metabolic acidosis
Diagnostic Evaluation
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Meticulous Urine Output measurement
Serum Creatinine, Urea
Indices – not useful in patients with nonoliguric AKI
& those receiving diuretics
Biomarkers - role ??
Management
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No specific therapy to prevent or treat AKI (mainly
supportive)
Fluid & electrolytes
Drugs – Frusemide, Dopamine, Fenoldapam,
Theophylline, Rasburicase
Dyselectrolytemia
Hypertension
Nutrition
RRT
Fluid & Electrolytes
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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
Loop Diuretics
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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
Low Dose Dopamine
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No improvement in survival, shortened hospital
stay or limit dialysis
No neonatal study
Fenoldapam
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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
Theophylline
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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
Rasburicase
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Recombinant urate oxidase
Safe & efficacious in treating elevated uric acid
Renal Replacement Therapy
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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
Other Drugs
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Dose needs to be modified as per creatinine
clearance
1st dose / loading dose needn’t be modified,
subsequent doses should be
Outcome
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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
Follow Up
A Prospective & Observational Study On AKI In Critically
ill Neonates
Prajal Agarwal, Niranjan Kr Singh, P. K. Mishra
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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
Case
Term, LSCS, B.wt – 3 kg
Bag & mask resuscitation
Started on O2 by hood → CPAP
Referred on D3 with severe RD, shock, edema
Wt – 3.290 kg
↓UO
HR – 180/min, RR – 80/min, Spo2 – 70% on 4-6 L/min, CRT>4 sec
Hb – 10.3 gm%, TLC – 26250/mm3,
P86L10E2M2, Plts – 35,000/mm3
S Creat – 1.8mg%, Urea – 53 mg%, Na-123
meq/L, K-4.37 meq/L Ca-6.4/0.8 mg/dl
Summary
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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
Panel discussion
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.
Antenatal USG & Kidney
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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
Renal biopsy – Indications
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SRNS
AKI of unknown origin
RPGN
HSP, SLE, IgA Nephropathy
Inherited nephropathy – Alport’s syndrome
Renal allograft dysfunction
Detection of CNI toxicity