Academic journal article International Journal of Child Health and Human Development

Neonatal Nephrology

Academic journal article International Journal of Child Health and Human Development

Neonatal Nephrology

Article excerpt

Introduction

Kidneys are vital organs with a complex morphogenesis. Functional development of kidneys continues until 2 years of life after birth. Developmental abnormalities of the kidneys account for almost 50% of cases of end stage renal disease (ESRD) in the United States. The following is a brief review on development, physiologic changes and some common neonatal renal pathology.

Renal development

Mammalian kidneys follow a complex evolutionary process. In humans there are three stages in renal development. Pronephros and mesonephros are rudimentary kidneys that start rostrally and progress to metanephros caudally. The rudimentary kidneys disappear towards the end of the first trimester. Induction of the metanephros starts at 5 weeks of gestation and this involves ureteric bud invagination of the metanephric mesenchyme. Several important genes including PAX2, WT-1 and signaling pathway including Glial derived neurotrophic factors (GDNF) are involved in the initial cross talk between the ureteric bud and metanephric mesenchyme. Kidneys formed initially are in the pelvic region and ascend up to their abdominal location by about 10 weeks of gestation. Around the same time urine generation is initiated as well.

Nephrogenesis continues until 34 to 36 weeks of gestation. Babies born prematurely might continue to form new nephrons but different factors including IUGR, NICU mortality and morbidity might affect the ultimate total. The number of functioning nephrons (nephron endowment) varies significantly and follows a bell shaped curve in the normal population. The range for nephron endowment varies between 300,000 to 1 million in each kidney. There are many studies linking a reduced nephron endowment early in life with hypertension (1) and vulnerability to secondary renal insults in adulthood (2).

Physiology of the neonatal kidney

Fetal urine formation increases from 2 ml/hour at 20 weeks of gestation progressively up to 26 ml/hr by the end of 34 weeks contributing to the amniotic fluid (3). Babies with decreased amniotic fluid secondary to renal agenesis, exposure to angiotensin blockers or with bilateral renal obstruction will have the Potter (oligohydramnios) sequence. If the oligohydramnios is severe babies can be stillborn with characteristic facial features including flattened nose, prominent bilateral epicanthal folds and low set ears with wide pinnae. Most of these babies suffer from severe lung hypoplasia which contributes to mortality. There are skeletal malformations including prominent bilateral club feet and bowing of legs.

After birth multiple changes occur in renal physiology. Rapid increase in glomerular filtration rate (GFR) occurs with increase in mean arterial pressure and decreased renal vascular resistance. But when compared to adults GFR within the first week of life is only 40 ml/min/1.73m2 and reaches adult equivalent (120 ml/min/1.73m2) at 2 years of age. Serum creatinine which is a measure of GFR is elevated in the first days of life as it mainly reflects maternal creatinine levels and reaches newborn value of 0.4 ± 0.02 mg/dl at 2 weeks of life. The Schwartz formula is used in calculation of GFR from serum creatinine in children <18 years of age and for newborns the following applies: GFR (ml/min/1.73 m2) = K x Height in cm/Plasma creatinine. K = 0.45 (Newborn with normal weight)

Renal blood flow gradually increases from fetal life (2 to 4% of cardiac output) to ultimate adult value of 20 to 25% of cardiac output. Irrespective of decreased renal blood flow GFR is maintained with the help of marked vasoconstriction of the efferent arterioles. Angiotensin II, endothelin I and the sympathetic nervous system play a main role in this physiologic effect. A greater sensitivity to angiotensin converting enzyme inhibitors with a drop in GFR is elicited in the newborn secondary to the rapid decrease in angiotensin.

Total body water in the newborns account for 75 to 80% of their body weight with almost 40% making up the extracellular space. …

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