neonatal aki

Neonatal AKI

Drew Maxted

What is different?

Nephrons formed from 5 weeks

Continues until 32-34 weeks gestation

Growth is maturity, not new nephrons

What is different?

0

5

10

15

20

25

Birth 24 hours 1 week 6 weeks Adult

Proportion of cardiac output from birth

D Selewski et al. Neonatal Acute Kidney Injury. Pediatrics 2015Vol136:2

M Starr and J Flynn. Neonatal hypertension: cases, causes, and clinical approach. Pediatric Nephrology (2019) 34:787–799

What is different?

Al-Dahhan et al. Sodium homeostasis in term and preterm neonates. ADC 1983,58:335-342

I Saxena et al. Urinary Protein Creatinine Ratio in Normal Zero to Three-Day-Old Indian Neonates. JCDR Mar201610:03

What is different?

R Vieux et al. Glomerular filtration rate reference values in very preterm infants. Pediatrics 2010;125:e1186–e1192

Definition


Definition

D Askenazi, N Ambalavanan & S Goldstein. Acute kidney injury in critically ill newborns: What do we know? What do we need to learn? Pediatr Nephrol (2009) 24:265–274

Definition

Aetiology

• Maternal risk factors: • NSAID use • ACEi and others

• Neonatal risk factors: • Small • Earlier gestations • Sick (HIE and sepsis)

Aetiology


Incidence


Treatment • Prevention:

• Often difficult (and out of our control) • However, can try and prevent secondary damage

• Some use agents to improve renal blood flow (e.g. dopamine) • Diuretics (to help prevent overload/RRT

• Some evidence can do harm, but outweigh risk/complexity of RRT

• Avoid nephrotoxic drugs, treat sepsis and hypotension/hypovalaemia

• Indications for RRT: • Refractory electrolyte abnormality • Refractory uraemia • Uncontrollable acidosis • Fluid overload

• Related to nutrition

Treatment

Outcomes - mortality

• 150 babies • 95% AKI babies <1.5kg • 69.2% mortality vs no AKI (13.5%)

• 2022 babies • 79 died in hospital • 9.7% mortality vs no AKI (1.4%)

• 398 babies • 82 died in NICU • 83% of these had AKI

Outcomes - CKD

• Autopsy of preterm babies

• Preterm babies had less glomeruli than term babies • And correlated with gestational age

• Less glomeruli in those with AKI than those without

• Poorer glomerulogensis in those preterm, than those born later

• Compensatory mechanisms such as glomerular hypertrophy etc.… may lead to hyperfiltration

Outcomes - CKD

S Chaturvedi, K Ng & C Mammen. The path to chronic kidney disease following acute kidney injury: a neonatal perspective. Pediatr Nephrol (2017) 32:227–241

Outcomes - CKD

Outcomes - CKD

Albuminuria: OR = 1.81 (1.19 – 2.77) ESRD: OR = 1.58 (1.33 – 1.88) Low eGFR: OR = 1.79 (1.31 – 2.45)

Outcomes - CKD

Outcomes - CKD

• Autopsy of preterm babies

• Retrospective, 20 patients <1kg

• 24% mortality in this age group, in renal failure mortality 49%

• Felt correlation existed between proteinuria and ESRD

• 11 GFR >90

• 9 GFR 7-70 (mean 29)

Outcomes - CKD

S Chaturvedi, K Ng & C Mammen. The path to chronic kidney disease following acute kidney injury: a neonatal perspective. Pediatr Nephrol (2017) 32:227–241

Outcomes - Dialysis

• 34 babies on CRRT (CVVHDF), 44% <36, median 2.8kg

• Preterm main indication = NEC, term = inborn errors metabolism

• Preterm, 12/15 died

• Poorer prognosis in preterm vs term

Outcomes - Dialysis

• 18 infants, median 3 months • 11 survived (61%) • 5 transplanted

• 10 infants, mean weight 825g • 2 survived • (normal renal function)

• 52 newborn infants • Mean duration 8.7 days • 12 survived (23%)

Outcomes - Dialysis

C Gimpel et al. Perinatal Diagnosis, Management, and Follow-up of Cystic Renal Diseases. JAMA Pediatr. doi:10.1001/jamapediatrics.2017.3938

Outcomes - Dialysis

• 1723 infants <12 months and starting PD • CAKUT commonest cause • 2 eras 1990-1999 and 2000-2014 (KDOKI guidance) • 61.5% transplanted • 21% died

• 32% neonates and 28% older children earlier cohort • 22% neonates and 14% older in later cohort

• Primary cause of death cardiorespiratory failure (25.8%)

Outcomes - Dialysis

Outcomes - Dialysis

• 264 patients, 32 countries • 242 PD

• 141 <7 days old at initiation • At 2yrs 45 died

• 2 yr survival = 81.2% • Main cause of death infection (35.6%) • 29% anuric when starting RRT • 45 patients transplanted within 2yrs of birth • Of those transplanted:

• 5yr patient and graft survival 84.2%

Outcomes - Dialysis

Outcomes - Dialysis

• UK renal registry data (from oral presentation) • Patients under 2 years of age

• PD:

• 81 patients • Started at median 124 days old • 50% had gastrostomy • 59% needed surgery for hernia/hydrocele • 18% of dialysis duration as inpatient • 50% transplanted, 18% died, 31% continue on dialysis

• HD:

• 21 patients • Started at 309 days • 19% of dialysis duration as inpatient • 55% transplanted, 25% died, 20% continue dialysis

So what do I do?

• Hard to define who has AKI and how bad

• Plenty of risk factors for most babies in NICU

• Unsure how bad it can be long term (if survive to discharge)

• So who do I follow up?!

So what do I do?

S Maqsood et al. Outcome of extremely low birth weight infants with a history of neonatal acute kidney injury. Pediatr Nephrol (2017) 32:1035–1043

C Abitbol et al. Long-term follow-up of extremely low birth weight infants with neonatal renal failure. Pediatr Nephrol (2003) 18:887–893

So what do I do? • Pragmatic approach!

• All neonates being routinely followed up, even if not for AKI should have:

• BP, urine dip • Consider creatinine if any hint of AKI during NICU

• Nephrology/SPIN

• Needed dialysis • Nearly needed dialysis/had a lot of AKI • CKD or proteinuria or hypertension

• But what about my 33/40 who had a creatinine of 85, now normal and nothing else?

References 1. R Vieux et al. Glomerular filtration rate reference values in very preterm infants. Pediatrics 2010;125:e1186–e1192 2. D Selewski et al. Neonatal Acute Kidney Injury. Pediatrics 2015Vol136:2 3. J Al-Dahhan et al. Sodium homeostasis in term and preterm neonates. ADC 1983,58:335-342 4. I Saxena et al. Urinary Protein Creatinine Ratio in Normal Zero to Three-Day-Old Indian Neonates. JCDR Mar201610:03 5. Hentschel R, Lödige B, Bulla M. Renal insufficiency in the neonatal period. Clin Nephrol. 1996;46(1):54. 6. https://www.uptodate.com/contents/neonatal-acute-kidney-injury-pathogenesis-etiology-clinical-presentation-and-

diagnosis?source=history_widget 7. SM Sutherland et al. Fluid overload and mortality in children receiving continuous renal replacement therapy: the

prospective pediatric continuous renal replacement therapy registry. Am J Kidney Dis. 2010; 55(2):316–325 8. D Askenazi, N Ambalavanan & S Goldstein. Acute kidney injury in critically ill newborns: What do we know? What do we need

to learn? Pediatr Nephrol (2009) 24:265–274 9. MM Rodriguez et al. Histomorphometric analysis of postnatal glomerulogenesis in extremely preterm infants. Pediatr Dev

Pathol. 2004 Jan-Feb;7(1):17-25. 10. F Fang et al. Subclinical acute kidney injury is associated with adverse outcomes in critically ill neonates and children. Critical

Care (2018) 22:256 11. S Pozzoli, M Simonini and P Manunta. Predicting acute kidney injury: current status and future challenges. J Nephrol (2018)

31:209–223 12. A Bruel et al. Renal outcome in children born preterm with neonatal acute renal failure: IRENEO—a prospective controlled

study. Pediatr Nephrol (2016) 31:2365–2373 13. S Chaturvedi, K Ng & C Mammen. The path to chronic kidney disease following acute kidney injury: a neonatal perspective.

Pediatr Nephrol (2017) 32:227–241 14. C Abitbol et al. Long-term follow-up of extremely low birth weight infants with neonatal renal failure. Pediatr Nephrol (2003)

18:887–893M Kirkley et al. Acute kidney injury in neonatal encephalopathy: an evaluation of the AWAKEN database. Pediatric Nephrology (2019) 34:169–176

15. S Maqsood et al. Outcome of extremely low birth weight infants with a history of neonatal acute kidney injury. Pediatr Nephrol (2017) 32:1035–1043

References 16. C Gimpel et al. Perinatal Diagnosis, Management, and Follow-up of Cystic Renal Diseases. JAMA Pediatr.

doi:10.1001/jamapediatrics.2017.3938 17. S Lee & H Cho. Fluid overload and outcomes in neonates receiving continuous renal replacement therapy. Pediatr Nephrol

(2016) 31:2145–2152 18. M Coulthard et al. Haemodialysing babies weighing <8 kg with the Newcastle infant dialysis and ultrafiltration system (Nidus):

comparison with peritoneal and conventional haemodialysis. Pediatr Nephrol 2014; 29(10): 1873–1881. 19. S White et al. Is Low Birth Weight an Antecedent of CKD in Later Life? A Systematic Review of Observational Studies. Am J

Kidney Dis 54:248-261 20. C Crump et al. Preterm birth and risk of chronic kidney disease from childhood into mid-adulthood: national cohort study.

BMJ 2019;365:l1346 21. S Pollack et al. Long-term hemodialysis therapy in neonates and infants with end-stage renal disease: a 16-year experience

and outcome. Pediatr Nephrol (2016) 31:305–313 22. V Stojanovic ́ et al. PERITONEAL DIALYSIS IN VERY LOW BIRTH WEIGHT NEONATES. Peritoneal Dialysis International, Vol. 37,

pp. 389–396 23. A Kara et al. Acute peritoneal dialysis in neonatal intensive care unit: An 8-year experience of a referral hospital. Pediatrics

and Neonatology (2018) 59, 375e379 24. K Sanderson et al. Outcomes of infants receiving chronic peritoneal dialysis: an analysis of the USRDS registry. Pediatric

Nephrology (2019) 34:155–162 25. K Stralen et al. Survival and clinical outcomes of children starting renal replacement therapy in the neonatal period. Kidney

International (2014) 86, 168–174 26. M Starr and J Flynn. Neonatal hypertension: cases, causes, and clinical approach. Pediatric Nephrology (2019) 34:787–799 27. Vesna Stojanovic ́. Acute kidney injury in preterm infants admitted to a neonatal intensive care unit. Pediatr Nephrol (2014)

29:2213–2220 28. J Jetton et al. Incidence and outcomes of neonatal acute kidney injury (AWAKEN): a multicentre, multinational, observational

cohort study. Lancet Child Adolesc Health. 2017 November ; 1(3): 184–194

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