acute kidney injury in neonate
TRANSCRIPT
Welcome To Seminar
Dr. Tareq
(Resident phase – B)
Dr. Agomoni Chaki
(Resident Phase – A)
Acute Kidney Injury (AKI) in newborn
• Definition
• Incidence
• Neonatal renal physiology
• Pathophysiology of AKI
• Etiology
• Risk factor
Presentation Outline
• Definition• Incidence• Neonatal renal physiology• Pathophysiology of AKI• Etiology• Complications• Risk factor• Clinical features• Management• Outcome of AKI• Long term follow up
Definition
• Acute Kidney Injury (AKI), formerly referred to as Acute renal failure, is defined as an abrupt reduction in kidney function measured by a rapid decline in glomerular filtration rate.
• AKI is an important contributing factor to the morbidity & mortality of critically ill neonates.
Cont…
• AKI results in the disturbance of the following renal physiological function :
- Impairment of nitrogenous waste product excretion
- Loss of water & electrolyte regulation
- Loss of acid-base regulation
Definition
• Serum creatinine more than 1.5 mg/dl , regardless of age or urine output, with normal maternal renal function.
• T L Gomella, Neonatology: Management, Procedures, On-Call problems, Diseases, and Drugs. 7th ed. Sydney. McGraw Hill; 2003
Classification
RIFLEstage RIFLE RIFLE and AKIN AKIN
AKINstage
Serum creatinineincrease from baseline(GFR decrease)
Urine outputcriteria
Serum creatinineincrease (or fold increase frombaseline)
Risk S. creatinine 1.5-fold(GFR decrease > 25 %)
<0.5 ml/kg/h over>6 h
>0.3 mg/dl [>26.4m mol/l] ³ 1.5 to 2-fold(150–200%)
1
Injury 2-fold (>50 %) <0.5 ml/kg/h for>12 h
>2 to 3-fold(>200–300 %)
2
Failure 3-fold (>75 %) <0.3 ml/kg/h for>24 hor anuria > 12 h
>4 mg/dl (>354 mmol/l) or >3-fold (300%) or acute increaseof at least 0.5 mg/dl [44mmol/l] or initiation of acuteRRT
3
Loss Persistent failure > 4weeks
NA
Endstage
End-stage renal disease> 3 months
NA
Incidence of AKI In Neonate
• The prevalence of hospital AKI is high. [24% ofhospital admitted neonates] - T L Gomella,Neonatology: Management,2003
• Incidence of AKI in NICU varies from 8-20%according to various studies, but it may beincreased up to 50% after cardiac surgery forcongenital heart disease.
• The incidence of AKI secondary to systemic illnessis higher than that of primary renal disease .
Hospital No. of Pt
AKI M/F Pre-renal
Renal Post-renal
RRT(IPD)
Death
BSMMU 921 11(1.2%)
8/3 33.5% 51.0% 15.5% 18.2% 1(9.1%)
CMH 680 18(2.9%)
13/5 34.0% 54.7% 11.3% 16.6% 3(16.6%)
DMCH 2163 501(23.2%)
294/207 66.0% 32.0% 2.0% 2.4% 130(26.0%)
Incidence, etiology and outcome of AKI in neonate, 2013-14 in 3 NICU of DHAKA City
Prof. Habibur Rahman, Chairman, Department of Pediatric Nephrology, presented in an International Conference
Neonatal Renal Physiology
Renal Function in Preterm Infants
Greatest handicap - <30 wks , <1500 gms
Sepsis, hypoxia, hypotension, PDA, mechanicalventilation, acidosis, catabolism – additional burdenon kidney
Indomethacin, high dose dopamine → further reduceGFR
Dexamethasone → catabolic effect → Increasedlevels of urea
Functions of the Kidney
• Water balance
• Electrolyte balance
• Plasma volume
• Acid – base balance
• Osmolarity balance
• Excretion
• Hormone secretion
Nephron
• Primary unit of the kidney
is the nephron
• 1 million nephrons per
kidney
• Composed of a glomerulus
and a tubule
Renal blood flow
Renal Blood Flow
• RBF - At birth (2.5 -4%)
-24 hours ( 6%)
-1 week (10%)
-6 week (15-20%)
-Adult (20-25%)
• The eventual increase in renal blood flow at birth due to - increase renal perfusion pressure
-increase systemic arteriolar resistance
-decrease renal vascular resistance due to neurohumoral change
Glomerular Filtration Rate
GFR represents the most recognized measures ofkidney function
Glomerular filtration begins by 9-12 weeks ofgestation
GFR – 30 ml/min/1.73 m2 ( Term baby )
- 10-15 ml/min/1.73 m2 ( Preterm )
- 100-120ml/min/1.73m2 (1 year)
Calculation of GFR
• GFR : k X length / serum creatinine (mg/dl)
k = Empirically derived constant length to muscle mass.
k = 0.34 in preterm
k = 0.45 in term
Serum Creatinine
• S. Creatinine – High at birth ( Maternal values )
- In PT – may rise in first few days because of passive reabsorption of creatinine through immature renal tubule.
Tubular Function
Tubular Function
• Proximal
– Most of reabsorption occurs here
– Fluid is isotonic with plasma
– 66-70% of sodium presented is reabsorbed
– Glucose and amino acids are completely reabsorbed
Tubular Function
• Loop of Henle
– Descending tubule –permeable to water, impermeable to sodium
– Ascending tubule –actively reabsorbs sodium, impermeable to water
Tubular Function
• Distal Tubule & Collecting System– Early DT – impermeable
to water– Late DT & Collecting
system–Water
reabsorption occur under the influence of ADH
-Aldosterone acts here to enhance Na reabsorption and K secretion
Pathophysiology of AKI
Classification of AKI
Based on the urine output, it can be of 3 types:1. Anuric (Absence of urine output by 24-48
hours of age)2. Oliguric (Urine output of <1ml/kg)3. Non oliguric (>1ml/kg)
Non oliguricBased on the site of origin of insult it can be of 3
types:1. Pre renal (75- 80%)2. Intrinsic renal (10-15%)3. Post renal (5%)
Why Newborn more susceptible to Acute Kidney Injury ?
• Developmental immaturity – immature renal function
• Hemodynamic changes (ie, hypotension and hypoxia) at birth – renal failure
• An increased risk of hypovolemia because of large insensible water losses.
• Limited urine concentrating ability
Etiology
Pre- Renal
• Loss of effective blood volume • Absolute loss
-Hemorrhage-Dehydration
• Relative loss ↑ Capillary leak-Sepsis-Shock-NEC-RDS -Hypoalbuminemia-ECMO
• Renal hypoperfusion
Alteration in plasma flow
Catecholamiesurge
Prostaglandn& RAAS
activation
Dilation of afferent
arteriole / constriction of efferent
Pre- Renal
• Congestive heart failure
• Pharmacologic agents
Indomethacin
Ibuprofen
ACE inhibitors
• Hypoxia
Intrinsic or Renal Parenchymal
• Sustained hypoperfusion leading to ATN
• Congenital anomaliesAgenesisHypoplasia/ DysplasiaPolycystic kidney disease
• Thromboembolic DiseaseBilateral Renal vein thrombosisBilateral renal arterial
thrombosis• Nephrotoxins
AminoglycosidesRadiographic contrast mediamaternal use of captopril or
indomethacin
Increased transcapillaryhydrostatic pressure
Failure of autoregulation +-renal immaturity
Tubular damage
systemic inflammatory response
Intrinsic or Renal Parenchymal
• Infection
-congenital syphilis
- Toxoplasmosis
-Candidiasis
-Pyelonephritis
Post Renal
• Urethral obstruction
- PUV (posterior Urethral Valve)
• Ureterocele
• ureteropelvic/ ureterovesical obstruction
• Extrinsic tumor
• Neurogenic bladder
• megacystitis/ megaureter syndrome
Common Nephrotoxic Substances
• Antibiotic : Aminoglycosides , cephalosporins , sulfonamides , tetracycline , imipenem , beta-lactam antibiotic.
• Antifungal : Fluconazole , amphotericine B.
• Antiviral : Acyclovir , ribavirin
• ACE inhibitors , I/V Ig , Frusemide, NSAID.
Complications of AKI
• Fluid overload – heart failure , pulmonary edema
• Hypertension
• Hyponatremia
• Hyperkalemia
• Metabolic acidosis
• hyperphosphatemia
Common Risk Factors• Very low birth weight (less than 1500 g)
• Low 5-minute APGAR score
• Maternal drug administration (NSAIDs and antibiotics)
• Intubation at birth
• Respiratory distress syndrome
• Patent ductus arteriosus
• Dehydration, sepsis
• Neonatal medication administration (NSAIDs, antibiotics likeaminoglycosides, cephalosporin, sulphonamide, diuretics,etc.)
• Zübarioğlu et al.Neonatal Kidney Injury. JAREM 2013; 3: 53-9
Welcome
To
2nd Part of Seminar
Diagnosis Of AKI
History Prenatal : - H/O Maternal DM.
- Maternal amniotic fluid volume.
- Maternal drug history.
Natal : Any risk for AKI.
Decrease or absent urine output
Seizure.
Family history
Diagnosis Of AKI
Examination
• Hydration status
• Vital signs
• Dysmorphic features
• Potter facies
• Abdominal distention
• Prune belly
• Meningomyelocele
Laboratory studies1. S. Creatinine
2. BUN (15-20 mg/dl suggests renal insufficiency)
3. Urinary Indices
4. Urine analysis (Urine R/E)
5. CBC and platelet count
6. S. Electrolytes ( ↓Na, ↑K)
7. Radiological studies
-USG
-X-Ray
-Radionuclide scan
Challenges to S Creatinine Based Definition
– S Cr indicates function not injury
–25-50% functional loss is needed to raise SCr
– SCr is affected by age, sex, medications, bilirubin and muscle mass, Hydration status
• Cannot distinguish pre renal, renal & post renal cause
• First few weeks S cr reflect maternal kidney functionHelmut Schiffl et al, Paediatric Nephrology2013;28:837-842
Frusemide ,
Urinary indicesUrinary indices Prerenal Post renal
Urine osmolality( mosm/kg water)
>400 <400
Urine sodium (mEq/L)
<20 >40
Urine/ plasma osmolality ratio
>1.5 <0.8-1.2
FENa (%) <2.5 >2.5
RFI <3 >3
Blood urea to creatinine ratio
>20:1 <20:1
Calculation of renal indices
• GFR : k X length / serum creatinine (mg/dl)
k = Empirically derived constant length to muscle mass.
k = 0.34 in preterm
k = 0.45 in term
• FENa : (Urine Na x serum cr./serum Na x urine cr. ) x 100
• RFI : Urine Na x serum creatinine / urine creatinine
Some Additional Tests
Biomarkers:
1. Serum & urinary Cystatin C level
2. Plasma & urinary neutrophil gelatinase associated lipocalin(NGAL) levels
3. Serum & urinary Interleukin (IL) -18 levels
4. Urinary albumin to creatinine ratio (ACR)
Approach To a Neonate With Suspected AKI
Neonate with suspected AKI
Measure serum creatinine and urine output
Serum biochemical
Markers(Na, K, Ca, PO4, Urea,
Creatinine, blood gases,
total blood count)
Urine evaluation
(urinanalysis, urine culture,
spot urine Na, Creatinine,osmolality)
Radiologic evaluation
(Renal USG, Doppler USG,
voiding cystourethrogram,
radionuclide scintigraphy
•Maintenance of fluid and electrolyte balance•Avoidance of life-threatening complications
•Adequate nutritional support•Treatment of the underlying cause
Pre Renal-Fluid boluses-Correct renal hypoperfusio
n
Renal-Remove
underlying cause
Post Renal-Eliminate
obstruction
Management
• Medical management
• Renal replacement therapy
Management
Medical Management
Supportive Management
Definitive Management:
-Rx of underlying condition--post renal : relief ofobstruction
Supportive Management
• Fluid Challenge
• Replace insensible fluid loss
• Maintain fluid & electrolyte balance
• Maintain nutrition
• Restrict protein (<2 g/kg/day)
• Correction of – hyponatremia, hyperkalemia,hypocalcemia, hyperphosphatemia, metabolicacidosis
• Dopamine ( less than 5 µg/kg/min)
• Diuretics
Fluid Challenge
• Diagnostic fluid challenge: In the absence of obvious sign of fluid overload or congestive cardiac failure
AIIMS Protocol, 2014
Fluid Balance
• Limited to insensible losses
30 ml/kg/day (Term)
50-70 ml/kg/day (Preterm)
• Plus U.O. , GI losses
• IV antibiotics, feeds should be subtracted
Fluid Balance
• Fluid requirement should be revised based onurine output, weight and assessment ofextracellular volume status, preferably every 8hourly.
• The insensible water losses should bereplaced with 5-10% dextrose.
Nutrition
• The goal is to provide 100 kcal/kg/day
• Ensure adequate non protein caloric intake
• Restrict protein and amino acid to <2 g/kg/day
Correction of Electrolyte Imbalance
• Hyponatremia
Babies can have hyponatremia in oliguric renal failure.
Hyponatremia is due to dilution secondary to waterretention hence has to be corrected with fluid restriction.
Babies with non-oliguric ARF may have urinary sodiumlosses of up to 10 mEq/kg/day and these must bereplaced.
{Na required (mEq) = [Na desired – Na actual] x bodyweight (kg) x 0.6}
Correction of Electrolyte Imbalance
• Hyperkalemia
It is one of the most dangerous complicationsof AKI
Management of hyperkalemia:
- Stoppage of all potasium containing fluid anddrugs
- Medications
AIIMS- NICU Protocol, 2014
For hyperphosphatemia – Phosphate bindercan be used
For hypocalcemia – 10% Ca gluconateCorrection of Metabolic Acidosis
Loop Diuretics
• Diuretics have an important role in volumemanagement in AKI
• Do not prevent AKI or improve AKI outcomes
• Continuous vs intermittent dose – continuousinfusion yields comparable UO with a muchlower dose
• Commonly used- Frusemide 1-2 mg/kg/day
Low Dose Dopamine
• No improvement in survival, shortenedhospital stay or limit dialysis
• Dose- less than 5µg/kg/min
• No neonatal study(Friedrich et al. 2005, analyzed 61 randomized or quazi-randomized controlled trials of low dose dopamine and foundno improvement of survival, no decrease in dialysisrequirement, no improvement in renal function andimprovement in urine output only on the first day of therapyin adults with ARF of any cause)
Renal Replacement Therapy
•Types of Renal Replacement Therapy-Peritoneal dialysis- CRRT - Hemodialysis
•Indication:HyperkalemiaHyponatremiaAcidosisHypocalcemiaHyperphosphatemiaUremic symptoms
Consequence of AKI
Brenner’s Hypothesis
Outcome
• Non oliguric renal failure has a betterprognosis
• Mortality ranges from 25 to 78% in oligoanuric AKI
• Long term abnormalities in GFR and tubularfunction are common
Causes of Poor Outcome
• very low birth weight
• BPD
• Antenatal steroid (????)
• High creatinin level, BUN and potassium
• Low serum sodium level
• Anuria
• Dialysis
• Mechanical ventilation
• Hypotension requiring ionotropic support Bolat F et al. Acute kidney injury in a single neonatal intensive care unit in Turkey. World J
Pediatr 2013
Follow Up
–Regular follow up.
Growth, nutritional status, BP and RFT
Importance:
- ELBW→CKD ( within 1 yr)
Risk Factor:
random urinary PCR > 0.6,
serum creatinine >0.6 mg/dL
BMI > 85th percentile for age & sex
Follow Up
Practical Issues
Is renal dose of all drugs are availabe?
What to do when a patient has severehyponatremia along with AKI- how tocalculate fluid?
Key Message
Incidence of Neonatal AKI depends onetiology and birth wt of baby
Pre renal etiology like sepsis , hypovolumia &perinatal asphyxia are the commonest cause
Medical management is the important tool oftreatment
Outcome of Neonatal AKI is poor
Mortality rate ranges from 25-78%
Surviving Neonates needs regular follow up todetect CKD
Thank You All