acute kidney injury in newborn

1. NEONATAL
ACUTE KIDNEY INJURY
PRESENTER-Dr K HARISH REDDY

2. Acute kidney injury (AKI) is characterized by a sudden impairment in kidney
function, which may result in dysregulation of
• Fluid Balance
• Acid–base
• Electrolytes and
• Nitrogenous waste products.
No universal consensus definition.
Serum Creatinine >1.5mg/dl used in many studies

3. • Acute renal failure  Acute kidney injury
• Injury – highlights the spectrum of organ and differentiates the damaged organ
from the organ with dysfunction.
• KDIGO(2012) defines - AKI when there is a rise in SCr of 0.3 mg/dL over 48
hours or a decrease in urine output (UOP) occurs

4. • NIDDK (2013)
• Serum Creatinine-based AKI definitions do not detect kidney damage; instead
they document changes in kidney function.
• It has significant shortcomings, including:
• SCr does not change until 25%–50% of the kidney function has been lost, and
thus it may take 48–72 hours for SCr levels to rise after an insult .
• At a lower glomerular filtration rate (GFR), SCr will overestimate renal function
due to tubular secretion.
• SCr varies by muscle mass, hydration status, sex, age, and gender.
• Different measurement methods produce different values, and medications and
bilirubin can affect SCr measured by the Jaffee method.

5. In neonates:
• SCr measurements in the first few days of life reflect the mother’s levels;
thereafter, the distribution of normal SCr values varies greatly, dependent on level
of prematurity and age.
• Normal nephronogenesis in the healthy fetus continues until 34 weeks of gestation
when the number of nephrons, approximates that of an adult

6. RELATION OF CREATININE WITH GESTATION
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7. CLASSIFICATION SYSTEMS
• pRIFLE  KDIGO  AKIN  modified KDIGO

9. p-RIFLE CRITERIA

10. ACUTE KIDNEY INJURY NETWORK (AKIN)

11. STAGE Change in serum creatinine Urine output over 24 hours
0 No change or rise <0.3 mg/dl within 48hrs >1 mL/kg/h
1 Rise in S Cr by 0.3 mg/dl within 48 hrs or
Rise in S Cr 150-200% of lowest previous value within
7 days
≤ 1 mL/kg/h
2 Rise in S Cr 200-300% of lowest previous value < 0.5 mL/kg/h
3 Rise in S Cr 300% of lowest previous value or 2.5
mg/dl or receipt of dialysis
< 0.3 mL/kg/h
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Modified KDIGO classification

12. INCIDENCE
• The exact incidence of neonatal AKI is difficult to quantify because infants
commonly have nonoliguric renal failure and may therefore may not be screened
with Serum Cr for AKI..
• AWAKEN study – overall incidence – 29.9%.

13. ETIOLOGY

14. • PRERENAL AZOTEMIA
Decrease in RBF
Renal autoregulation – activation of RAAS system
- increase in sympathetic tone
- increase in vasopressin
Preservation of GFR

15. • Correction of cause – restoration of renal function.
• Severe / prolonged – renal parenchymal damage occurs even if renal
perfusion is restored.

16. • INTRINISIC KIDNEY INJURY
• Renal hypoperfusion for prolonged period – common cause.
• Nephrotoxic medications and sepsis – can cause with hypo /
hyperdynamic blood flow.
• Damage – not immediately reversible.
• Severity – mild tubular dysfuction to ATN to renal infarction and
corticomedullary necrosis with irreversible damage.

17. • Ischemic kidney injury and prerenal azotemia – continuum
• phases –
Prerenal phase – if restoration of RBF occurs – GFR returns to normal.
Intiation phase – insult + associated events + fall in GFR
Maintainence phase – tubular dysfunction + low GFR
Recovery phase – gradual restoration of GFR and tubular
functions.may take months.

18. • Histologic hallmark - damage to epithelial tubular cells with characteristic bleb
formation and loss of brush border in the apical portion of the cell cytoskeleton
disruption and loss of tight junctions between cells.
• If injury is severe enough, apoptosis and necrosis will occur with resultant
desquamation of cells, which lead to tubular obstruction.
• Severe cases – can damage renal vascular endothelial cells.
• When endothelial cell damage occurs  activation of vasocontriction,impaired
vasodilation, and impaired leukocyte adhesion  capillary obstruction and
distorted peritubular capillary morphology.
• Capillary obstruction and impaired morphology lead to a cycle of increasing
ischemia and vascular inflammation

19. NEPHROTOXIC MEDICATIONS
Drug Mechanism
Indomethacin/NSAIDS • Potentiation of vasoconstrictive and sodium- and water-retaining effects of
AT II, NE, and vasopressin
Amphotericin B • Distal tubular toxicity, vasoconstriction, and decreased GFR
Aminoglycosides • Proximal tubule toxicity due to inhibition of lysosomal phospholipases
• Intrarenal vasoconstriction and local glomerular cell contraction
Acyclovir • Rapidly filtered and excreted
• Urinary precipitation and obstruction and damage
Radiocontrast agents • Renal tubular toxicity due to release of free radicals
• Intra renal vasoconstriction
Vancomycin • Mechanism: unclear, possibly: Prox tubule injury with generation of reactive
free radicals
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20. POSTRENAL AKI
• Common causes of obstructive kidney dysfunction in the newborn are congenital
malformations, including imperforate prepuce, urethral stricture, prune belly
syndrome, and posterior urethral valves.
• Other causes - neurogenic bladder, extrinsic compression (e.g., hematocolpos,
sacrococcygeal teratoma), and intrinsic obstruction from renal calculi or fungal
balls.

21. MANAGEMENT
APPROACH
LABS
PREVENTION
TREATMENT
COMPLICATIONS

22. HISTORY
• PRENATAL – Pregnancy H/O / USG abnormalities / oligohydrminos / family
H/O
• INTRPARTUM- Perinatal Asphyxia/APGAR Scores?
• POSTNATAL- Hypovolemia/Drugs/Cardiac conditions
• Other- Surgical conditions

23. EXAMINATION
• Signs of volume depletion
• Volume overload
• Abdominal/Genital examination
• Dysmorphism/Potter sequence
• Complications- Hypertension/Arrhythmias/Neurologic dysfunction

24. DIAGNOSIS
• Diagnosis is established as per modified KDIGO guidelines.
• RFT- S.Creatinine, BUN, Dyselectrolytemia.
• URINE -Granular casts, Proteiniuria, Haematuria.
• RADIOLOGICAL – CAKUT, Altered echogenicity, HDN, Doppler
abnormalities.

25. PRERENAL VS INTRINSIC

26. NOVEL MARKERS

27. FLUID CHALLENGE
Identify infants with prerenal AKI due to hypovolemia
• IV administration of 10-20ml/kg of isotonic saline given over 1-2 hours.
UOP <1ml/g/hr
• A positive response: urine output in anuric patient, an increase in urine
output >1ml/kg/hr in oliguric patient or improvement in serum
creatinine.
Prerenal AKI
Inj Furosemide 1 mg/kg
Intrinsic renal failure
UOP >1ml/kg/hr

29. PRESERVATION /PREVENTION
• Provide supportive care until there is spontaneous improvement in renal function.
• Nephrotoxic drugs should be discontinued if possible to reduce the risk of
additional renal injury.
• Maintaining adequate renal perfusion-Inotropes,hydrocortisone in preterms
• Assuring adequate oncotic pressure (keeping a serum albumin of 2.5 mg/dL or
higher)
• Interventions to eliminate the obstruction.

30. ROLE OF DOPAMINE
• Low-dose dopamine can increase renal perfusion in the sick preterm and term
infant with prerenal azotemia caused by hypoxemia, acidosis, or indomethacin
administration.
• STUDIES: compared with placebo, low-dose dopamine does not improve
survival, shorten hospital stay, or limit dialysis use.

31. MEDICAL MANAGEMENT
• Medications adjusted by dose, interval, or both according to the degree of renal
dysfunction.
• Potassium/phosphorus restricted in those neonates with hyperkalemia,
hyperphosphatemia, oliguria, and/or rapidly worsening renal function.

32. 1. Fluid balance
2. Diuretics
3. Hypertension
4. Electrolyte imbalances
5. Nutrition
6. Dialysis

33. FLUID MANAGEMENT
• Weight monitoring- twice a day.
• Restricted to insensible water loss (IWL) along with urinary loss.
• The urinary loss must be replaced volume for volume.
• Fluid requirement -revised 8-12 hourly based on
• urine output
• weight
• assessment of extracellular volume status.
• During the polyuric phase, hourly monitoring of urine output and serial
monitoring of serum electrolytes with appropriate replacement of sodium,
potassium and water are indicated to prevent dehydration, hyponatremia and
hypokalemia

34. DIURETICS
• Fluid overload is a proven independent risk factor associated with higher mortality
in late preterm neonates.
• Current evidence doesn’t support the use of loop diuretics to prevent AKI, except
in cases of fluid overload with oliguria/anuria.
• Use cautiously due to their ototoxic potential and the risk of nephrotoxicity,
osteopenia, nephrocalcinosis, hypotension and electrolyte imbalances.

35. DYSELECTROLYTEMIA
• Hyponatremia
• Hyperkalemia
• Hypocalcemia
• Hyperphosphatemia

36. MANAGEMENT OF HYPERKALEMIA

37. HYPERTENSION
• Fluid overload in neonatal ARF can result in hypertension, which can be
controlled with fluid restriction and antihypertensive agents. The development of
severe hypertension in the setting of neonatal ARF should raise the suspicion for
renal artery or venous thrombosis.
• Commonly used antihypertensives in newborns are oral amlodipine (0.1-0.3
mg/kg/dose q 12-24 hourly), enalapril (0.1-0.4 mg/kg/day q 6-12 hourly, with
careful monitoring of potassium and renal functions) and intravenous diazoxide
(2-5 mg/kg/dose over 5 min q 4-24 hourly)

38. ACIDOSIS
• Mild metabolic acidosis is common in babies with ARF. If pH is <7.2 and
bicarbonate <18 mEq/L, sodium bicarbonate is given in a dose of 1-2 mEq/kg over
3-4 hrs.
• But monitoring for fluid overload, hypernatremia, intracranial hemorrhage and
hypocalcaemia is needed. Babies with persistent acidosis require dialysis.

39. NUTRITION
• The goal is to provide 100 kcal/kg/day as babies with ARF are catabolic. Proteins
or amino acids can be provided in a dose of 1-2 g/kg/day.
• If enteral feeding is possible, breast milk can be used, failing which, low
phosphate formula can be given. Caloric density can be increased by adding
medium chain triglycerides.
• In the baby is on parenteral nutrition, a central venous catheter may be needed to
infuse hypertonic glucose in order to prevent hypoglycemia

40. RENAL REPLACEMENT THERAPY
• Considered if maximum medical management fails to maintain acceptable fluid &
electrolyte levels.
• Does not prevent or treat AKI; used solely to support the infant who lacks
adequate kidney function.
• The two purposes of renal replacement therapy are -ultrafiltration (removal of
water) and -dialysis (removal of solutes).
• Neonates greater than 1.5 to 2 kg- considered for RRT because of limited ability
to place & maintain dialysis access in smaller infants.

41. INDICATIONS OF RRT
• Fluid overload> 10 %
• Persistent hyperkalaemia
• Severe hyperphosphatemia when accompanied with hypocalcaemia
• Severe metabolic acidosis unresponsive to medical treatment)
• BUN> 100-150mg/dl or lower but rapidly rising.

42. MODALITIES
• Peritoneal Dialysis (PD)
• Intermittent Haemodialysis (HD)
• Continuous renal replacement therapy (CRRT)

43. Modality Advantages Disadvantages
Peritoneal dialysis o Slow & continuous
o Less hemodynamic instability
o No need for vascular access
o No anticoagulation
o Slower
o Risk of infection
o Caution with intra-abdominal &
pulmonary diseases
o Less precision
Hemodialysis o Initial modality of choice in
hyperammonemia
o Rapid
o Vascular access
o Blood prime
o Risk of hemodynamic instability
o Anticoagulation
o Dialysis disequilibrium
Continuous RRT
(CVVH/CVVHD/CVVHDF)
o Slow continuous
o Less risk of hemodynamic
instability
o Removal of cytokines and toxins
o Vascular access
o Blood prime
o Hypotension initially
o Anticoagulation
o Costs and availability

44. OUTCOMES
• Prognosis of AKI in neonates is worse than in adults.
• Follow-up care as they are at-risk for chronic kidney disease (CKD) or elevated
blood pressure.
Prominent risk factors for progression of renal disease at 1 year of age:
• random urinary protein/creatinine ratio of greater than 0.6
• serum creatinine greater than 0.6 mg/Dl.
• tendency to obesity with a body mass index greater than the 85th percentile

45. • Most common cause of mortality in neonates due to AKI includes: infections >
prematurity > asphyxia.
• Non oliguric AKI has twice the better prognosis than oligo-anuric AKI.
• Prevention of AKI is better than cure due to adverse long term outcome.
• Management includes identification of etiology, prevent further renal injury and
renal support.
• Close attention to hemodynamic status and delicate balance in fluid management
is critical based on the phases of AKI.
• RRT should be considered early in the course of AKI.

46. THANK YOU