It was time for her second trimester scan.  A first time expectant mother waited anxiously at the antenatal clinic. She had not felt her baby’s kicks as frequently as before.  There was no history of draining per vaginum. USG showed inadequate amniotic fluid and arrested development of the fetus. She was referred to a high risk perinatologist and a follow up scan showed absence of both the kidneys, a condition known as bilateral renal agenesis. The couple was given a choice – either to terminate the pregnancy or continue it knowing fully well that the baby might be still born or survive only for a couple of hours after birth. 

How did too little fluid lead to such a grave diagnosis?

This is an example of oligohydramnios (inadequate amniotic fluid) complicating pregnancy. The kidneys in the adult human being serve dual purpose – they cleanse the body off waste products like urea and they maintain the water and electrolyte balance of the body fluids. However these functions in the fetal life are taken care of by the placenta.

The main function of fetal kidneys is to produce urine.

By 20th week of gestation, urine is the main source of amniotic fluid. When the kidneys fail to develop, there’s severe paucity of amniotic fluid. That brings us to the basic question - how do the kidneys develop?

The intra-embryonic mesoderm on either side of the midline is divided into three distinct regions-

1. Paraxial mesoderm
2. Intermediate mesoderm and
3. Lateral plate mesoderm

The fate of paraxial and lateral plate mesoderm will be discussed in other articles. The intermediate mesoderm gives rise to the kidneys, ureter, adrenal gland and the reproductive system. 

During the 4th week of gestation, the intermediate mesoderm gives rise to a vertical tube extending from the cranial to the caudal end of the fetus. This is known as the mesonephric duct (also known as the Wolffian duct). The mesonephric ducts is the pillar around which the entire urinary system develops. The lower end of the mesonephric ducts from either side fuses with the cloaca and forms the posterior wall of the urinary bladder (cloaca is a part of the hindgut). The upper end of the mesonephric duct in the cranial region induces the mesoderm adjacent to it to from small bud like structures known as Pronephros.  The Pronephros is the most primitive type of kidney. While it functions as the adult kidney in some primitive fishes, it disappears in human fetus by the 25th day. Following this, the mesonephric duct in the thoracic and lumbar region of the embryo induce the formation of mesonephric buds. Small tubules develop from these buds, known as mesonephric tubules, and fuse with the mesonephric duct. The mesonephric buds produces small amounts of urine till the 10thweek of intrauterine life, thus establishing the first ever pathway for passage of urine. However, the mesonephric buds regress too! The mesonephric duct ceases to function too. In females, the duct disappears while in males it transforms into ducts for the genital system. 

The definitive kidney or the metanephros begins to develop around the 28th day. The mesonephric duct towards the lower end gives off a branch called the ureteric bud. Ureteric bud induces transformation in the intermediate mesoderm at the sacral region of the embryo. This region is called metanephric mesenchyme. The ureteric bud penetrates the metanephric mesenchyme and bifurcates multiple times. The definitive nephron develops from the metanephric mesenchyme, while the rest of the collecting portion of the kidney, namely the collecting duct, major and minor calyces, and the ureters develop entirely from the ureteric bud. 

The earliest gene expressed in the intermediate mesoderm is the Pax2 gene, which induces the genesis of kidneys.

Any mutation in this gene can lead to either complete absence (bilateral renal agenesis) or hypoplastic kidneys. Absence of both the kidneys leads to severe paucity of amniotic fluid. Hence the amniotic cavity fails to expand and provide the necessary space for the embryo to grow. This constraint in space leads to poorly developed limbs, wrinkled skin and an abnormal facial appearance – classically described as Potter sequence. Lack of space also prevents the growth and expansion of the thoracic cavity and lungs. Pulmonary hypoplasia is the reason why fetus with bilateral renal agenesis fails to survive. 

This is one of the scenarios emphasizing the need for vigilant antenatal scans. That’s how a subtle clue such as insufficient amniotic fluid can help us identify a bigger looming problem!