NEONATAL ACUTE KIDNEY INJURY

Dr N K SinghNeonatal & Pediatric IntensivistSpecialist Pediatric NephrologyVPIMS, Lucknow

Case

What Next?

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

Outline

1. Why term AKI?2. Why neonatal AKI separately?3. Neonatal renal physiology : it’s clinical implication4. Is it different from Pediatric/Adult AKI ?5. Etiology6. Clinical features7. Management8. Long term follow up9. Evidence

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

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

Incidence

Neonatal Renal Physiology

Nephrogenesis

BEGINS ENDS

Glomerulogenesis

Chikkannaiah P et al. Indian Journal of Pathology and Microbiology 2012

Glomerulogenesis in Preterm Infants

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

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 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”

Renal Function in Preterm Infants

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

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 ORS. Creat ↑ ≥ 1.5 -1.9 X ref. value within 7days

<0.5ml/kg/hr for 6 -12hrs

2 S. Creat ↑ ≥ 2.0 – 2.9 X ref. value <0.5ml/kg/hr for >12hrs

3 S. Creat ↑ ≥ 3.0 X ref. value OR S. Creat >2.5mg% ORReceipt of DIALYSIS

<0.3ml/kg/hr for >24hrsOR

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

Prerenal factors – 85% Intrinsic renal Post renal

Common Causes of Neonatal AKI

Table 25.2 pediatric nephrology

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

Diagnostic Evaluation

Meticulous Urine Output measurement Serum Creatinine, Urea Indices – not useful in patients with nonoliguric

AKI & those receiving diuretics Biomarkers - role ??

Management

No specific therapy to prevent or treat AKI (mainly supportive)

Fluid & electrolytes Drugs – Frusemide, Dopamine, Fenoldapam,

Theophylline, Rasburicase Dyselectrolytemia Hypertension Nutrition RRT

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

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

Low Dose Dopamine No improvement in survival, shortened hospital

stay or limit dialysis No neonatal study

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

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

Rasburicase

Recombinant urate oxidase Safe & efficacious in treating elevated uric acid

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

Other Drugs

Dose needs to be modified as per creatinine clearance

1st dose / loading dose needn’t be modified, subsequent doses should be

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

Follow Up

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

Case

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

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

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

1. SRNS2. AKI of unknown origin3. RPGN4. HSP, SLE, IgA Nephropathy5. Inherited nephropathy – Alport’s syndrome6. Renal allograft dysfunction7. Detection of CNI toxicity