Purpose and Goal: CNEP # 2061

  • Understand why neonates are at high risk for acute kidney injury.
  • Learn about the complications of acute kidney injury in the neonate.

None of the planners, faculty or content specialists has any conflict of interest or will be presenting any off-label product use. This presentation has no commercial support or sponsorship, nor is it co-sponsored.

Requirements for successful completion:

  • Successfully complete the post-test
  • Complete the evaluation form

Date

  • April 2017 – April 2019

Learning Objectives

  • Describe the risk factors for acute kidney injury in the neonate.
  • Describe the main causes of acute kidney injury in the neonate.
  • State two approaches for the management of acute kidney injury.

Introduction

  • Acute kidney injury is common in the NICU
  • Studies have shown it is not an incidental finding
  • Premature infants are at highest risk of injury
  • Kidney injury can lead to poor outcomes
    • Increased morbidity
    • Increased mortality
    • Chronic kidney disease
     

Acute Kidney Injury in the NICU

  • Acute kidney injury is also known as AKI
  • AKI used to be known as acute renal failure
  • AKI is a sudden impairment in kidney function
  • Impairment leads to an inability to maintain:
    • Water balance
    • Electrolyte balance
    • Acid base regulation
    • Waste product elimination
     
  • AKI is clinically complex
    • With multiple causes
    • With multiple clinical manifestations
     
  • AKI has traditionally been defined as:
    • A decrease in urine output
    • An increase in serum creatinine
     
  • Other biomarkers are being studied
    • Urine lipocalin
    • Serum cystatin C
     

Pathophysiology of Acute Kidney Injury

  • Kidney development is complete by 35 weeks gestation
  • Kidney development continues after birth
    • But only for a short time
    • Regardless of gestational age
     
  • Completed development results in:
    • 0.6 - 1.2 million nephrons
    • Adequate renal filtration rates
     
  • Infant born < 35 weeks frequently lack adequate nephrons
    • Placing them at higher risk for AKI
    • Placing them at risk of chronic kidney impairment
     
  • Several changes occur in the neonatal period
    • Renal blood flow increases from 2 to 10%
    • Autoregulation of blood flow is inconsistent
      • Set at a lower range of blood pressures
      • Impairs the ability to regulate fluid volumes
      • Inconsistent regulation → inconsistent function
       
     
  • Urine concentrating ability is poor
    • Poor concentrating ability →  risk of fluid loss
    • Poor concentrating ability → ↓ reabsorption
    • Poor concentrating ability →  electrolyte imbalances
     

Incidence of Acute Kidney Injury

  • The incidence of AKI varies widely
    • Depending on the definition used
    • Depending on specific NICU populations
     
  • It has been reported to affect 8 - 35% of neonates
    • More common in premature neonates
    • Especially with interrupted renal development
     
  • Low birthweight infants are at 70% increased risk
  • Highest risk factors for AKI include:
    • Sepsis
    • Prematurity
    • Perinatal hypoxia
    • Low birth weight
    • Congenital heart disease
    • ECMO support
    • Renal anomalies
     
  • Risk increases with the number of risk factors present

Etiology of Acute Kidney Injury

  • There are 3 types of renal failure that lead to AKI
    • Pre-renal failure
      • Due to inadequate renal blood flow
      • Occurs in 85% of AKI
       
     
  • Post-renal failure
    • Due to intrarenal pathology
    • Occurs in 11% of AKI
     
  • Intrinsic renal failure
    • Due to obstruction of the urinary tract
    • Occurs in 3% of AKI
     
  • Causes of pre-renal failure
    • Hypovolemia
    • Hypotension
    • Hypoxemia
    • Heart failure
    • Dehydration
    • Septicemia
    • Hypoalbuminemia
    • Perinatal Asphyxia
      • Most common cause overall
      • Up to 61% will develop AKI
       
     
  • Respiratory distress syndrome
  • Congenital Heart disease
  • Cardiac surgery
  • Polycythemia
  • Pharmacologic agents
    • Indomethacin
    • Captopril
    • Vasodilators
    • Aminoglycosides
      • Gentamicin
       
    • Amphotericin
    • Radiocontrast agents
     
  • Causes of post-renal failure
    • Posterior urethral valves
    • Bilateral obstructive uropathy
    • Neurogenic bladder
     
  • Causes of intrinsic failure
  • Acute tubular necrosis
  • Corticomedullary necrosis
    • Renal venous thrombosis
    • Renal arterial thrombosis
    • Acute pyelonephritis
    • Disseminated vascular coagulation
    • Isoimmune hemolytic disease
    • Congenital renal anomalies
    • Systemic infections
    • Intrauterine infections
      • Candidiasis
      • Toxoplasmosis
       
     
  • Nephrotoxic drug exposure
    • Amphotericin
    • Aminoglycosides
      • Gentamicin
       
    • Radiocontrast agents
     

Clinical Presentation of Acute Kidney Injury

  • AKI should be suspected with:
    • Low or absent urine output
    • Elevated or rising serum creatinine
     
  • Absent urine output is defined as no urine in 48 hours
  • Low urine output is defined as urine <1 ml/kg/hr
  • An elevated creatinine is an indicator of:
    • Reduced kidney blood flow
    • Decreased kidney filtration rate
     
  • Creatinine levels > 1.5 mg/dl are the hallmark of AKI
  • Other lab abnormalities that may be present include:
    • Hyponatremia
    • Hyperkalemia
    • Hyperphosphatemia
    • Hypocalcemia
    • Metabolic acidosis
     

Diagnostic Evaluation of Acute Kidney Injury

  • There are 3 main areas of focus:
    • History and risk factors
    • Physical examination
    • Laboratory and radiology findings
     
  • History and risk factors
    • Maternal history
      • Fetal ultrasounds
      • Oligohydramnios
       
    •  Birth history
     
      • Resuscitation
      • Chest compressions
      • Vasoactive drug use
       
    • Clinical history
      • Nephrotoxic drug use
      • Gentamicin levels
       
    •  Physical examination
      •  Volume status is the focus
        • Signs of dehydration
          • Tachycardia
          • Hypotension
          • Sunken fontanel
          • Dry mucous membranes
           
        • Signs of fluid overload
          • Tachypnea
          • Dependent edema
          • Worsening oxygen requirement
          • Escalating ventilator support
           
        • Cumulative fluid balance should be estimated
          • Daily weight
          • Daily fluid input
          • Daily fluid output
           
         
       
    • Laboratory and radiology findings
      • Serial lab values should be monitored
        • Electrolytes
        • Calcium
        • Magnesium
        • Phosphorous
        • BUN and creatinine
        • Albumin
        • Blood gas
        • Complete blood count
        • Urinalysis
        • Random urine sodium
        • Random urine creatinine
        • Fractional excretion of sodium
         
      • Radiology studies should be obtained
        •  Chest xray
        • Bladder ultrasound
        • Renal ultrasound
        • Doppler flow of renal vessels
        • Voiding cystourethrogram
        • Radionuclide scintigraphy
         
       
     

Stages of Acute Kidney Injury

  • Traditionally, 4 stages of AKI have been identified
    • Stages are used to help predict outcomes
     
  • Stage 0
    • Creatinine normal
    • Creatinine ↑ < 0.3 mg dl
    • Urine output >0.5 ml kg hr
     
  • Stage 1
    • Creatinine >0.3 mg dl
    • Creatinine ↑ 1.5 – 1.9 times baseline
    • Urine output <1ml/kg/hr
     
  • Stage 2
    • Creatinine ↑  2 – 2.9 times baseline
    • Urine output <0.5 ml/kg/hr
     
  • Stage 3
    • Creatinine >2.5 mg/dl
    • Creatinine ↑ 3+ times baseline
    • Urine output <0.1 ml/kg/hr
    • Dialysis or renal replacement therapy required
     
  • Baseline is defined as the lowest previous value
  • Stages apply in infants without congenital renal anomalies

Diagnostic Challenges in Acute Kidney Injury

  • Creatinine is a marker of kidney function
    • NOT kidney injury
     
  • Creatinine initially reflects maternal levels
    • Maternal kidney function
    • NOT neonatal kidney function
     
  • Normal creatinine levels decline after birth
    • At varying rates
    • Over days to weeks
    • Depending on gestational age
     
  • Many neonates have higher creatinine levels
    • Regardless of maternal levels
    • Especially if born prematurely
     
  • Creatinine levels increase late after injury
    • 24 – 48 hours following injury
    • Not until 25 – 50% of kidney function is lost
     
  • Creatinine levels do not differentiate between causes
    • Pre-renal causes
    • Timing of the kidney insult
    • Nephrotoxic drug exposure
    • Ischemic acute tubular necrosis
     
  • Many premature neonates will have kidney injury
    • Without decreased urine output
    • Due to immature renal tubular function
      • Impaired filtration rates
       
     

Medical Management of Acute Kidney Injury

  • There are currently no specific therapies
    • For prevention of AKI
    • For treatment of AKI
     
  • The management of AKI is supportive
    • Close attention to at risk neonates
    • Close monitoring of kidney function
     
  • The keys to supportive management are:
    • Identify risk factors
    • Correct risk factors
    • Treat the cause, if identified
    • Minimize additional kidney injury
     
  • The goals for supportive management are:
    • Prevent fluid overload
    • Maintain electrolyte balance
    • Avoid nephrotoxic drug exposure
    • Maintain adequate kidney perfusion
     
  • First steps should include:
    • Placement of a urinary catheter
    • Fluid challenge if no signs of fluid overload
      • 10 ml/kg isotonic saline
      • Given slowly over 1-2 hours
       
    • Discontinuation of fluids containing potassium
    • Adjustment of drugs requiring renal excretion
     
  • Obstructions should be corrected quickly
    • Increased urine output may result
    • Close monitoring of electrolytes is critical
    • Electrolytes should be replaced as needed
     
  • Fluid losses should be replaced as needed
    • Insensible water losses
    • Chest tube losses
    • Gastrointestinal losses
     
  • Hyperkalemia can occur and is a critical finding
  • At high risk for occurrence
  • Can be life threatening
  • An EKG is helpful
    • Peaked T waves
    • Flattened P waves
    • Increased PR interval
    • Widened QRS complex
     
  • Calcium gluconate may be beneficial
  • Other drugs that might be beneficial include:
    • Albuterol
    • Sodium bicarbonate
    • Regular insulin
    • Kayexalate
     
  • Fluid management can be challenging
    • Large volumes may not be tolerated
    • Fluid overload may easily develop
    • Subsequent fluid restriction
      • Limits nutritional intake
      • May not avoid fluid overload
       
     
  • Several studies have evaluated other approaches
    • None have been shown to be beneficial
      • Dopamine
      • Diuretics
      • Theophylline
      • Fenoldopam
       
     
  • Dialysis or renal replacement therapy may be needed
    • Available modalities include:
      • Hemodialysis
      • Peritoneal dialysis
      • Hemofiltration
        • With dialysis
        • Without dialysis
         
       
    • Early renal replacement therapy is critical
      • Especially with hyperkalemia
       
    • Studies show poor outcomes with:
      • Higher fluid overload
      • End stage renal disease
       
     

Long Term Outcomes in Acute Renal Injury

  • Renal development continues after birth
    • But only for a short time
    • Can be interrupted by illness
    • Can be interrupted by preterm birth
     
  • Interrupted development or preterm birth can lead to:
    • Nephron sclerosis
    • Nephron hypertrophy
    • Loss of nephron function
    • Loss of function → poor outcomes
      • Proteinuria
      • Sodium retention
      • Systemic hypertension
      • Progressive chronic disease
       
     
  • The prognosis for AKI depends on:
    • Gestational age
    • The underlying cause
    • The severity of the cause
    • The reversibility of the cause
     
  • Mortality is as high as 60% with oliguric AKI
  • Mortality is as high as 86% in infants with:
    • Congenital heart disease
    • Urinary tract anomalies
     
  • Chronic kidney diseases develops in 70% of LBW infants
  • Chronic renal failure develops in 40% of infants with:
    • Asphyxia
    • Vascular thrombosis
    • Hypotension
     
  • Prognosis is excellent with non-oliguric AKI

Summary

  • AKI is sudden decrease in kidney function
  • It is measured by a rapid decline in normal filtration
    • Increasing creatinine levels
    • Decreasing urine output
     
  • It is an important contributing factor
    • In mortality
    • In morbidity
    • In poor outcomes
     
  • Neonates are at higher risk of injury
    • Due to functional kidney immaturity
    • Due to developmental kidney immaturity
     
  • Renal replacement therapy should be considered early
    • If fluid balance cannot be maintained
    • If electrolyte balance cannot be maintained
    • If adequate nutrition cannot be maintained
     

References

  1. Jetton, J.G. & Askenazi, D.J. 2014. Acute Kidney Injury in the Neonate. Clinics in Perinatology, 41 (2014), p. 487-502.
  2. Mattoo, T.K. 2015. Acute Kidney Injury (Acute Renal Failure) in the Newborn. Up-To-Date
  3. Okusa, M.D. & Rosner, M.H. 2016. Overview of the Management of Acute Kidney Injury (Acute Renal Failure). Up-To-Date
  4. Flynn, J.T. 2015. Etiology, Clinical Features, and Diagnosis of Neonatal Hypertension. Up-To-Date
  5. Chaturvedi, S. Ng, K.H, and Mammen, C. 2015. The Path to Chronic Kidney Disease Following Acute Kidney Injury: A Neonatal Perspective. Pediatric Nephrology, 2017 (32), p. 227-241.
  6. Davarajan, P. 2017. Prevention and Management of Acute Kidney Injury (Acute Renal Failure) in Children. Up-to-Date

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