acute kidney injury in neonate

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