Kidney Function in Neonates

1. Introduction

Neonatal renal function is characterized by physiological immaturity compared to older children and adults.
The primary goal is maintaining fluid and electrolyte homeostasis during the transition from the aquatic intrauterine environment to extrauterine life.
Adaptation occurs in three distinct phases of fluid balance.

Phase I: Transition (Diuretic Phase)

Duration: First week of life (ends with maximum weight loss).
Physiology: Characterized by the contraction of the extracellular fluid (ECF) compartment.
Mechanism: Natriuresis (sodium loss) and diuresis result in physiological weight loss.
Weight Loss: Term neonates lose 7–10%; preterm neonates lose 10–15% of birth weight.

Phase II: Intermediate Phase

Characteristics: Insensible water loss reduces as the skin barrier matures.
Renal Status: Urine volume falls ( $< 2$ ml/kg/hr) and sodium excretion becomes low.
Clinical: Weight stabilizes.

Phase III: Stable Growth

Characteristics: Continuous weight gain with a positive net balance for water and sodium to support tissue growth.

Status at Birth: Physiologically low GFR due to high renal vascular resistance and low perfusion pressure.
Postnatal Rise: GFR increases rapidly in the first 2 weeks, then steadily rises to reach adult values by 1–2 years.
Assessment (Serum Creatinine):
- First 48 hours: Reflects maternal creatinine; not a reliable marker of neonatal intrinsic function.
- Preterm Pattern: Creatinine may rise transiently in the first 4 days (due to tubular reabsorption) before declining.
- Estimation: GFR is estimated using the Schwartz Formula: $e G F R (m l / m i n / 1.73 m^{2}) = \frac{k \times L e n g t h (c m)}{S e r u m C r e a t i n i n e (m g / d l)}$
  - $k = 0.33$ for preterm infants $< 1$ year
  - $k = 0.45$ for term infants $< 1$ year

Neonates have a limited capacity to both concentrate and dilute urine.

Concentrating Defect:
- Due to the anatomical shortness of the Loop of Henle and distal nephron immaturity.
- Max Osmolality:
  - Preterm: $\approx 600$ mOsm/L
  - Term: $\approx 800$ mOsm/L
  - (Adults can concentrate up to 1200 mOsm/L).
Diluting Defect:
- Due to low GFR, limiting the volume of fluid delivered to diluting segments.
- Min Osmolality: Lower limit $\approx 50$ mOsm/L.

Obligatory Sodium Loss: Neonatal kidneys have a limited capacity to conserve sodium under stress (risk of hyponatremia).
Mechanism:
- Tubular immaturity (limited reabsorption).
- Reduced responsiveness to aldosterone.
Fractional Excretion of Sodium (FENa):
- Normal FENa is higher in neonates than adults ( $< 1 %$ ).
- Term: FENa up to $2.5 - 3 %$ is considered physiological.
- Preterm (<32 weeks): FENa can be as high as $6 - 8 %$ .
Implication: Sodium supplementation is often required in VLBW infants after the initial diuretic phase (after first week) to prevent hyponatremia and poor growth.

Bicarbonate Threshold: Lower renal threshold for bicarbonate reabsorption ( $19 - 21$ mEq/L).
Acid Excretion: Limited capacity to excrete hydrogen ions and ammonium.
Result: Propensity for mild metabolic acidosis, especially during illness or high protein load.

Parameter	Normal Range / Definition
Urine Output	$1 - 3$ ml/kg/hour (Oliguria: $< 1$ ml/kg/hr after 24h)
Specific Gravity	$1.005 - 1.012$
Urine Osmolality	$100 - 400$ mOsm/L (Physiological range)
Serum Creatinine	High at birth, declines to $0.3 - 0.4$ mg/dl by 3–4 weeks
Voiding	~93% void in first 24h; 100% by 48h

Fluid Therapy: Neonates cannot handle large rapid fluid boluses (risk of overload) or severe restriction (risk of dehydration/AKI).
Drug Clearance: Nephrotoxic drugs (e.g., Aminoglycosides) require extended dosing intervals due to low GFR.
Renal Reserve: Reduced renal functional reserve makes neonates highly susceptible to Acute Kidney Injury (AKI) during stress, asphyxia, or sepsis.