Fetal Kidney Development

• Fetal kidneys are a primary source of amniotic fluid
• Amniotic fluid pressure enables bronchiole expansion for lung development; no kidneys results in no lungs

Conception to 2 Years Old

• Neonatal kidney physiology is immature compared to adults
• By age 2, the kidney is fully developed
• Extra caution is required to protect the kidney up to age 2 because it is still developing

Nephron Embryology

• GDNF is a chemoattractant for guiding the ureteric bud
  • Binds to the RET receptor on the Wolffian duct, starting ureteric bud outgrowth
  • Causes branching morphogenesis
• WT1 activates GDNF expression and prevents nephrogenic mesenchyme apoptosis
• WT1 ensuring GDNF output and sustained GDNF-RET signaling drives ureteric bud formation
• Nephrogenesis starts at 3 weeks
• Urine production begins at 9-11 weeks
• Full kidney development, but not maturation, is achieved at 36 weeks

Role of Fetal Kidneys

• Regulates blood pressure, not initially the heart
• Regulates amniotic fluid levels
• Absent kidneys means absent amniotic fluid; results in a deformed child

Development of Fetal Kidneys

• Angiotensin II is a key vasoconstrictive mediator needed for nephron development
• Pregnant mothers/children under 2 should not take ACE inhibitors or aldosterone

Fetal Water Flow

• Fetal kidneys are a primary source of amniotic fluid
• Adequate amniotic fluid creates enough pressure for lung bronchiole expansion

Neonatal Period Kidney Function

• Includes Renal Blood Flow (RBF) and Glomerular Filtration Rate (GFR)
• Includes Sodium and Water Reabsorption, Potassium Secretion
• Also includes Calcium and Phosphate Handling
• Deals with Body Water Compartments

RBF And GFR

• RBF is low at birth, increasing with age due to increased perfusion pressure
• RBF increases due to decreased vascular resistance and better autoregulation
• Effective Renal Plasma Flow (ERPF) is low at birth
• Low glomerular hydrostatic pressure results in low GFR at birth
• Low GFR is due to low systemic blood pressure, low RBF, and high renal vascular resistance
• High levels of angiotensin II contribute to high renal vascular resistance
• Low GFR is important to conserve energy
• Low GFR supports fluid/electrolyte reabsorption to prevent postrenal adaptation to stressors
• Babies with low GFR/RBF risk fluid overload and electrolyte imbalance
• Treatment involves fluid restriction, fluid composition considerations, and monitoring

Kidney Sodium Handling

• Causes large urinary sodium losses despite high aldosterone levels
• High levels of plasma ANP are present after birth
• Full-term infants on intravenous fluids must excrete a solute load of about 15 mosm/kg/day in the urine
• Babies generally experience negative sodium balance and lose sodium
• Sodium supplementation is initiated with adequate diuresis, reduced serum sodium, or 5-6% weight loss
• Delaying sodium supplements helps with normal postnatal adaptation
• Low principal cell secretory capacity and ROMK channel absence contribute
• Increased tubular flow rate does not affect potassium secretion
• Delaying potassium supplementation occurs until kidneys can excrete it

Neonatal Acid-Base Balance

• Neonates have metabolic acidosis due to higher metabolism and acid production
• Respiratory and kidney function cannot properly regulate acid-base balance
• Buffers may be insufficient preterm and sick newborns

Handling Of Acids And Bases

• Proximal tubules have limited bicarbonate reabsorption, leading to increased urinary loss
• Distal tubules/collecting ducts have immature bicarbonate reabsorption and proton secretion
• Reduced hydrogen ion excretion contributes to acidosis
• Limited ammonium production and excretion reduces acid buffering
• Neonates are more susceptible to metabolic acidosis due to weak renal buffering
• Improving renal acid-base regulation occurs by 1-2 years old

Hormonal Actions

• RAAS function is less responsive in neonates
• Possibly results in low renin secretion affecting angiotensin II and aldosterone production
• Reduced sodium balance and blood pressure regulation impacts fluid and electrolyte imbalances
• Immature Antidiuretic Hormone (ADH) response limits urine concentration ability
• Higher risk for dehydration and impaired fluid balance occur, especially during stress/illness
• Tubuloglomerular Feedback (TGF) is less developed in neonates
• Reduced TGF impacts the ability to adjust GFR to changes in sodium or fluid

Urine Concentration

• Neonates void frequently to remove excess fluid from inside the womb
• Effective urine concentration requires functioning loops of Henle Functional urine concetration also requires good medullary blood flow through vasa recta and ADH/Vasopressin
• Acceptable osmolality range is 300-400 mOsm/kg/day
• Impaired urine concentration aids in physiologic ECF volume contraction

Fluid Balance

• Neonatal kidney is relatively unresponsive to serum vasopressin/ADH concentrations
• Ability to concentrate urine and preserve water depends on medullary interstitium hypertonicity
• Reduced in neonates due to low urea/sodium concentrations and immature/shorter loops of Henle
• Reduced in neonates due to poorly differentiated thin ascending loops and low aquaporin expression

Tubular Function

• Positive phosphate balance is vital for newborns' skeletal growth due to efficient reabsorption in the proximal tubule/intestine
• Phosphate conservation is important because breast milk has less phosphorus than formula
• Phosphate retention is supported by growth hormone
• High phosphate levels leads to low calcium levels
• Low calcium levels are common, particularly in preterm infants

ECF Volume

• Fetuses have high extracellular fluid in the womb
• Feto-maternal osmotic gradient favors water transport from mother to fetus

Total Body Water Components

• Physiological postnatal diuresis removes ECF excess due to low concentration/sodium reabsorption defects
• Aldosterone deficiency heightens urination and results in physiologic weight loss by removing ECF
• Most neonates urinate within 12 hours, and 95% of preterm and term infants urinate within 24 hours
• No urine output after 48 hours must be investigated
• Infants are practically bags of water so be careful controlling fluid intake
• Avoid ACE inhibitors
• Be careful controlling fluid intake volume, because there are several conditions with abnormalities like: -hyperkalemia -acidemia -hyperphosphatemia
• By year 2 kidney function reaches adult level