Renal Agenesis and Hypoplastic Lung Syndrome
Vol 2. No. 10 


Ande L. Karimu MD PhD.

Resident Ob-Gyn
Yale New Haven Hospital

Renal agenesis and hypoplastic lung syndrome are congenital malformations of the neonates involving the kidneys and the lungs respectively i.e. the newborns are born with these disorders. The etiology of these malformations is probably multifactorial i.e. there are both inherited and environmental factors in the causation of the malformations. Oftentime both conditions co-exist as part of multiple congenital malformations.

 

Renal Agenesis

Renal agenesis is the complete absence of the kidney(s). The kidneys are the organs that filter the blood of waste products, eliminating them as urine.

There are two kidneys in the human under normal circumstances. Absence of the kidney could be unilateral or bilateral. If it is unilateral, it means only one kidney is absent. However, if it is bilateral, it means both kidneys are absent. Unilateral absence of the kidneys is compatible with life whereas bilateral absence of the kidneys is incompatible with life.

 

Development of the Kidneys

The kidneys are parts of the urinary system. Other members of the system include the ureters, bladder and the urethra. The urinary system develops in close association with the genital organs.

The kidneys are developed in three main stages called the pronephros, mesonephros and the metanephros (nephros means kidneys). The pronephros are non functional and soon degenerate being replaced by the mesonephros which function for a short time before they are in turn replaced by the metanephros, the definitive kidneys.

The permanent kidneys i.e. the metanephros begin to develop in the fifth week of intrauterine life. Urine formation begins about the end of the first trimester i.e. the 12th week and continues for the rest of the pregnancy. The urine produced by the fetus is secreted into the amniotic cavity and forms part of the amniotic fluid. In the fetus, the placenta is the main organ of excretion, therefore, the kidneys don’t need to become functional for excretory purposes during intrauterine life. However, the kidneys must be ready to assume their excretory functions at birth.

Earlier in pregnancy, the kidneys are located in the pelvis but by the ninth week of pregnancy the kidneys have attained their adult’s positions in the abdomen. This variation in positions is due to the differential increase in the growth of the abdomen. For this reason, it is often observed that the kidneys have various sources of blood supply during development which gradually degenerate as the kidneys ascend to the abdominal cavity. Not surprising, the adult kidneys sometimes have abberant blood supply due to its migratory developmental nature.

From the foregoing discussion, it becomes apparent that complete absence of the kidneys (bilateral renal agenesis) results when the metanephric buds fail to develop while unilateral renal agenesis will result from ipsilateral (one sided) metanephric bud absence.

 

Clinical Features

During prenatal life renal agenesis could be diagnosed with ultrasound examination both by the observation of oligohydramnios i.e. reduced amniotic fluid volume and absence of the kidney(s). In most centers in USA targeted ultrasound for detailed anatomical survey of the fetus is carried out around the 18th -20th week of gestation. At this time, based on the reduced fluid volume clinical suspicion is high, thus scheduled detailed anatomical survey will reveal the absence of the kidney(s). It is pertinent to note however, that ultrasound examination may not always reveal the absence of kidneys due to oligohydramnios. Moreover, adrenal tissues may be confused with renal tissue. In this situation, serial evaluation over a period of 4-6 hours to confirm absence of urine production as demonstrated by failure to visualize the fetal bladder may be very useful in establishing with certainty the diagnosis.

Suffice to say that absence of one kidney is compatible with life with the other kidney enlarging to compensate for the absent one. It is for this reason that as adults we could donate one kidney and still carry on effectively with the remaining kidney. In the unlikely event of an absent kidney not diagnosed before birth, it may be diagnosed in adulthood as an incidental finding during imaging studies of the abdomen for some other reasons.

With regards to bilateral renal agenesis, the fetus is usually stillbirth in more than 40% of cases while the majority of infants born alive usually die within 4 hours of life. The characteristic features of the infants described as Potter’s facies include: redundant and dehydrated skin, wide set eyes, prominent fold arising at the inner canthus of each eye, parrot beak nose, receding chin, large low set ears with deficient auricular cartilages, absent urine output and non palpable kidneys. Death shortly after birth is attributed to either pulmonary hypoplasia or renal failure. Other congenital anomalies associated with bilateral renal agenesis include absence of the urinary bladder, bilateral pulmonary hypoplasia, genital organs abnormalities such as absence of the vas deferens and the seminal vesicles in the males and the uterus and upper vagina in the females, anal atresia, absence of the rectum and the sigmoid colon, esophageal and duodenal atresia, single umbilical artery and major abnormalities of the lower limbs.

Management of Renal Agenesis

As earlier on mentioned, unilateral renal agenesis is compatible with life with the only available kidney enlarging to compensate for the absent pair. On the other hand, complete absence of the kidneys is not compatible with life. The fetus usually die in utero or shortly after birth. The best management approach therefore is taking preventive measures as much as is possible to prevent congenital malformations from occurring. For instance a pregnant woman with uncontrolled diabetes mellitus is proned to having a baby with congenital malformations including renal agenesis. Therefore adequate control of diabetes in pregnancy will reduce the likelihood of developing this malformation.

 

Hypoplastic Lung Syndrome

This is simply underdevelopment of the lungs. It commonly results from abnormal development of the diaphragm, a muscular structure which separates the thoracic (chest) from the abdominal cavity.

It also may occur as part of multiple congenital anomalies affecting a fetus including: renal agenesis, urinary tract outflow obstruction, extra-amniotic fetal development, thoracic dystrophies. Other associations include intrauterine central nervous system damage sufficient to decrease fetal breathing movement, trisomy 21, erythroblastosis fetalis otherwise called fetal isoimmunization and certain drugs e.g.ACE inhibitors. As earlier mentioned, abnormal development of the diaphragm is the more common cause and this is amenable to surgical correction soon after birth. I will therefore describe in more detail development of the diaphragm and how its malformation may result in hypoplastic lung syndrome.

 

Development of the Diaphragm

The diaphragm develops from four structures including the septum transversum, pleuroperitoneal membranes, dorsal mesentery of the esophagus and the body wall.

The septum transversum is that part of the embryonic mesoderm which separates the ventrally located pericardial cavity from the dorsally located gut. It forms the definitive central tendon of the diaphragm. The central tendon is a trifoliate aponeurotic structure which fuses with the pericardium of the heart.

The pleuroperitoneal membranes separate the pleural and the peritoneal cavities. The pleural cavity contains the lungs while the peritoneal cavity contains the abdominal organs. By the sixth week of intrauterine life the pleuroperitoneal membranes usually fuse with the dorsal mesentery of the esophagus and the septum transversum thus effectively demarcating the pleural and the peritoneal cavities (i.e. the chest and the abdomen). In fetal life, the pleuroperitoneal membranes represent a large portion of the diaphragm, however, they represent a small part of the definitive diaphragm.

The dorsal mesentery of the esophagus is a double layer of peritoneum which forms the median portion of the diaphragm. Two slips of muscles called the right and left crura arise from the lumbar vertebrae to grow into the dorsal mesentery around the ninth to twelfth week of intrauterine life.

The body wall is the most peripheral part of the diaphragm. The developing fetal lung and pleural cavities usually invade the body wall. At this time the body wall divides into two layers with the inner layer forming the definitive peripheral rim of the diaphragm.

During development of the diaphragm, the septum transversum the first indication of the developing diaphragm lies in the cervical (neck) region opposite the third to the fifth cervical somites. During the fifth week of development, the muscle cells from these somites migrate into the developing diaphragm, taking their nerves (phrenic nerves) with them from the cervical region. As the diaphragm migrates to its final location in the thorax the phrenic nerve accompanies it, thus traversing a long course of almost 30 centimeters.

 

Congenital Diaphragmatic Hernia.

This is a relatively common congenital malformation of the diaphragm occurring in 1:2000 newborn infants. It results from a defect in the posterolateral region of the diaphragm. Congenital posterolateral defect of the diaphragm is due to non fusion of the pleuroperitoneal membranes with the septum transversum and the dorsal mesentery of the esophagus. It is usually unilateral, occurring commonly on the left side. The reason for the left sided preponderance is due to the early closure of the right pleuroperitoneal membrane secondary to the presence of the bulky embryonic liver on the right side. Normally, the pleuroperitoneal membranes fuse with the other diaphragmatic components by the seventh week of intrauterine life. If a pleuroperitoneal membrane is unfused by the time the intestine return from the umbilical cord to the abdomen around the tenth week of intrauterine life, the intestine usually pass into the thorax. The spleen and stomach may also herniate into the thorax. At birth, the thoracic intestines usually dilate with swallowed air, compromising the functions of the heart and lungs. The mediastinum and its contents including the heart is usually displaced to the right while the lungs are hypoplastic i.e. underdeveloped. Normally during pregnancy the lungs are filled with fluids which helps to maintain the lung volumes. However, with compression from intraabdominal organs the lungs are not able to accumulate enough fluid to maintain the requisite volumes hence their underdevelopment.

 

Diagnosis of Diaphragmatic Hernia


At birth the newborn infant will demonstrate evidence of respiratory distress syndrome viz dyspnea, tachypnea, cyanosis, tachycardia etc. The lungs may be dull to percussion due to non expansion after birth and air entry to the lungs will be remarkably reduced on auscultation. Imaging studies of the chest and abdomen will reveal the presence of abdominal organs in the thoracic cavity.

Clinical Management

The immediate goal is to return the abdominal organs to their definitive positions in the abdomen and closure of the diaphragmatic defects. Once the hernia is reduced, the affected lungs usually expand with aeration and ultimately achieve their normal size.

Conclusion

The etiology of congenital anomalies is usually multifactorial i.e.both genetic and environmental factors play a role. Some of the causative factors are amenable to control by the way of preventive measures. Some good examples are the recommended intake of folic acid in pregnancy to reduce the likelihood of malformations of the brain and tight glucose control to ameliorate possible renal malformation. Others include avoidance of certain medications such as ACE inhibitors during pregnancy and avoidance of over the counter medications of unproven safety. Until such a time that we are able to determine with certainty the etiology of congenital anomalies, the best that can be done is mainly preventive. In any case, it is said that prevention is better than cure and certainly cheaper in the present managed health care environment.

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