Neonatal nephrology in a hurry

Dr Shuman Haq

Consultant Paediatric Nephrologist

Southampton Children’s Hospital

28 weeks g

estatio

n

30 weeks g

estatio

n

34 weeks g

estatio

n

40 weeks g

estatio

n

57%

5%

23%16%

Most nephrons form by..

A. 28 weeks gestation

B. 30 weeks gestation

C. 34 weeks gestation

D. 40 weeks gestation

10 days a

fter b

irth

20 days a

fter b

irth

30 days a

fter b

irth

40 days a

fter b

irth.

12%

38%36%

14%

In premature infants, nephrogenesis continues until..

A. 10 days after birth

B. 20 days after birth

C. 30 days after birth

D. 40 days after birth.

10 20 30 40

10%

30%33%

28%

What is the glomerular filtration rate (GFR) at birth in a term infant?

A. 10

B. 20

C. 30

D. 40

20 30 40 50

2%

39%

44%

15%

What is the GFR 4 weeks after term delivery?

A. 20

B. 30

C. 40

D. 50

Intra

uterin

e gro

wth

reta

...

Poor mate

rnal d

iet d

urin...

Antenata

l glu

coco

rtico

ids

Two o

f the above

All of t

he above

7%2%

73%

16%

2%

Final nephron number is affected by...

A. Intrauterine growth retardation

B. Poor maternal diet during pregnancy

C. Antenatal glucocorticoids

D. Two of the above

E. All of the above

Neonates and their kidneys

Children are not just small adults

Neonates are not just small children

Neonates and their kidneys

What happens in utero?

What happens after birth?

Why are their kidneys so vulnerable?

Foetal and infant origins of adult disease

Embryology

Nephrogenesis – starts at 5 weeks, complete by 34 weeks

Glomerular development - 9 weeks

Nephron number 750,000 per kidney (250,000 to 1,900,000)

If low Hypertension

Heart disease

Renal impairment

Renal function in utero

Placenta

Equilibration of plasma creatinine from 20 weeks gestation

Fetal urine 10 weeks

2-5 ml/hr at 22 weeks

25-40 ml/hr at term

Majority of amniotic fluid

Immediate postnatal period 1-3 ml/hr

Oligohydramnios

Renal causes

Renal agenesis

Urinary tract obstruction

Potter facies

Polyhydramnios

Renal causes

Diabetes insipidus

Bartter’s syndrome

Renal function in newborn

‘Deficient’ glomerular and tubular function

Adequate function to deal with normal physiological burden

Limited adaptive response to stress

Renal function in the newborn

Renal blood flow

Glomerular filtration rate

Fluid homeostasis

Acid-base balance

Renal blood flow

15-20% of cardiac output v 25% in adult

Mostly directed to juxtamedullary nephrons most mature sodium and water conservation

High renal vascular resistance

Blood flow distribution changes in days Favours outer cortical nephrons

Glomerular filtration rate

Birth Low systemic BP

High vascular resistance

Limited filtration surface

Low GFR

Rise in GFR over first 4 weeks

Neonatal fluid homeostasis

Birth TBW 75%, ECF 40%

Within days TBW , ECF , ICF

9 months TBW 62%, ECF 27%, ICF 35%

Neonatal fluid homeostasis

Term infants lose 5-10% body weight

ECF

Leaky capillaries

Urine concentrating ability

Low capacity

Dangers of water depletion

Maturation: 1-2 months

Premature infant

(28-30 weeks)

Term infant

3 days 3 days 2 weeks

Urine output

(ml/kg/hr)

0.6 – 3.1 1.0 – 3.1 1.0 - 5

Maximal urine osmolality

(mOsm/Kg H2O)

400-500 500-600 540-700

GFR

(ml/min/1.73 m2)

10 20 40

Acid-base balance

Extracellular and intracelluar buffers

From birth

Respiratory adaptation

From birth

Respiratory function

Neurology

Renal adaptation

Limited

Acid-base balance

Renal threshold for bicarbonate

Premature infants: 14 mmol/l

Term infant: 18-20 mmol/l

12 months adulthood: 24-26 mmol/l

Acid-base balance

Aggravated by

Asphyxia

Sepsis

Volume depletion

Drugs

Presentation of renal disease

Antenatal evaluation

Postnatal evaluation

Antenatal evaluation

Congenital abnormalities of the kidneys and urinary tract (CAKUT)

Liquor volume

Postnatal evaluation Eye abnormalities

Ear abnormalities

Branchial fistulae and cysts

Potter facies

Heart failure

Deficiency of abdominal musculature and cryptorchidism

Deformities of lumbar and sacral spine

Other skeletal anomalies

Imperforate anus

Bladder extrophy

Genital abnormalities

Oedema

Postnatal evaluation: urine output

Newborn oliguria <0.5ml/kg/hr

Polyuria >4ml/kg/hr

Urinary stream

Bedside postnatal evaluation

Proteinuria

Physiological

Vascular disorders

Congenital nephrotic syndrome

Infections

Nephrotoxins

Acute tubular necrosis

Bedside postnatal evaluation

Haematuria

Bleeding diathesis

Vascular disorders

Cystic diseases

Tumours

Trauma

Nephritis

Postnatal evaluation: lab tests

Creatinine

Gestational age

Body length

Body weight

Increases transiently in VLBW infants

Cystatin C

Congenital renal disease

CAKUT

Congenital nephrotic syndrome

Bartters’ syndrome

Nephrogenic diabetes insipidus

Acute kidney injury

Antenatal vascular damage

Maternal drugs

Twins

Primary renal and urological diseases

CAKUT

Congenital nephrotic syndrome

Acquired postnatal diseases

All the dangers of the neonatal unit!

Pre-renal acute kidney injury

Gastrointestinal losses

Haemorrhage

Sudden compartmental fluid shifts

Favourable prognosis

Intrinsic acute kidney injury

Acute vascular events

Renal venous thrombosis, renal artery stenosis

Acute interstitial nephritis

Congenital nephrotic syndrome

Poorest prognosis

Post-renal acute kidney injury

Urinary tract obstruction

Prognosis variable

Lab results in AKI

Dip the urine!

Proteinuria

Haematuria

Lab results in AKI

Pre-renal AKI Intrinsic AKI

Urine osmo > 400mosm/kg H2O Urine osmo < 400mosm/kg H2O

Urine Na < 40 mmol/l Urine Na > 40mmol/l

Urine/Plasma Osmolality >1.3 Urine/Plasma Osmolality <1.0

FeNa <2% FeNA >3.0%

The future for these children?

Low birth weight and pre-term birth linked with reduced nephron number

Proteinuria

Hypertension

Renal impairment

But who’s watching?

Neonates and their kidneys

Unique vulnerabilities

Effects on nephron mass

Who do we follow up?

How do we follow up?

An example of how seriously some take this...

Birth weight and nephron number working group

IUGR, Preterm, LBW, pre-eclampsia, gestational diabetes

Yearly to 2 yearly BP and urinalysis from 3 yr old

<32/40, VLBW, AKI

Screen from before 1 yr old

AKI, hypertension, proteinuria, cardiovascular disease, CAKUT, obesity, diabetes

Renal profile and urinary protein every 2 years

Baseline renal ultrasound scan

From 18 yrs old

BP, BMI, Urinalysis – every 2 yrs until 40 yrs old, yearly thereafter

Birth weight and nephron number working group

Education about lifestyle and avoidance of nephrotoxins

Avoid rapid catch-up growth to prevent obesity associated exacerbation of renal risk

Caution in potential living kidney donors