Renal Hypodysplasia - Abnormally Small and Malformed Kidneys

Introduction

Renal hypodysplasia or aplasia is an autosomal dominant disorder that begins in utero. It is characterized by congenitally small and malformed kidneys with reduced renal mass and nephron number with the presence of dysplastic features. It belongs to a group of renal diseases that are perinatally lethal. Renal hypodysplasia was initially thought to be secondary to scarring that is associated with reflux or reflux nephropathy, but now it is considered as primary dysplasia that is associated with reflux.

What Is the Difference Between Agenesis, Aplasia, Hypodysplasia, Hypoplasia, and Dysplasia?

• Agenesis: It refers to developmental failure in which the organ fails to develop during embryonic growth and development because of the absence of primordial tissue. It indicates the complete absence of an organ.

• Aplasia: It indicates that the organ, tissue, or body part did not develop normally, and it is malformed.

• Hypodysplasia: It is also called aplasia. It is used to describe kidneys that are abnormally small and malformed.

• Hypoplasia: It refers to the developmental arrest in which an organ or a part of it remains below the normal size or it is immature.

• Dysplasia: It refers to the presence of abnormal cells within a tissue. It indicates abnormal growth or development of a tissue or organ. It usually precedes the development of cancer.

What Is Renal Hypodysplasia?

Renal hypodysplasia or aplasia is an autosomal dominant disorder that is characterized by the presence of abnormally small and malformed kidneys. It belongs to a group of perinatally lethal renal disorders such as bilateral renal aplasia, unilateral renal agenesis with contralateral dysplasia, and severe obstructive uropathy. A renal aplasia is a severe form of congenital anomalies of the kidney and urinary tract, which usually causes death in utero or during the perinatal period. Bilateral renal agenesis is a fatal condition, and death occurs in utero or in the perinatal period. However, unilateral agenesis is compatible with life with mild manifestations like vesicoureteral reflux.

What Causes Renal Hypodysplasia?

Renal hypodysplasia or aplasia is caused by mutations in the FGF20 gene on chromosome 8p22. It has been documented that bilateral renal agenesis or aplasia coexists with unilateral renal aplasia, renal dysplasia, and renal aplasia with renal dysplasia exists in families.

Exposure to the following environmental factors in the fetal and neonatal period contributes to renal hypodysplasia:

• Maternal vitamin A deficiency.

• Intrauterine growth restriction.

• Maternal low folic acid intake.

• Maternal hyperglycemia and diabetes.

• Maternal use of cocaine and excessive alcohol consumption.

• Maternal intake of angiotensin-converting enzyme inhibitors or angiotensin receptor blockers.

How Does Renal Hypodysplasia Occur?

The direct precursor of the mature kidney is the human metanephros. The human metanephros begins to form in the fifth week of gestation. During the fifth week of gestation, the ureteric bud branches from the mesonephric duct, and the renal mesenchyme condenses around the developing bud to form nephrons, while the bud forms the ureter and collecting ducts. Abnormalities in these events result in a spectrum of disorders which is known as congenital anomalies of the kidney and urinary tract (CAKUT).

Approximately 40 percent of children with chronic renal insufficiency or end-stage or end-stage renal failure have congenital anomalies of the kidney and urinary tract. Some of these renal malformations are associated with obstruction in the lower tract, which is caused by posterior urethral valve disease that is common in males. Renal dysplasia and hypoplasia are two common variants of CAKUT.

What Are the Clinical Features of Renal Hypodysplasia?

The clinical features and symptoms related to renal hypodysplasia include the following:

• Unilateral or bilateral renal agenesis (complete absence of one or both the kidneys).

• Renal dysplasia (a kidney that is not developed fully in the womb).

• Duplicated ureter (two ureters areformed on the same kidney).

• Ureteral agenesis (congenital absence of the urethra).

• Hydronephrosis (swelling of the kidney due to the build up of urine).

• Vesicoureteral reflux (urine flows backward to the kidneys).

• Ectopic kidneys (kidney’s are located in an abnormal position in the urinary tract).

• Horseshoe kidney (two kidneys are fused together).

• Pulmonary hypoplasia (incomplete development of the lung tissue).

The presence of bilateral renal agenesis in the developing fetus results in oligohydraminos, and the affected babies have a characteristic facial phenotype at birth. This is called potter facies. Potter facies is seen in newborns with bilateral renal agenesis or other renal abnormalities like renal aplasia, hypoplasia, dysplasia, or multicystic kidney disease. This typical facial phenotype is characterized by the presence of wide-set eyes, a receding chin, a flattened nose, and large, low-set ears that are deficient in cartilage. This characteristic facies occurs due to the decrease in the volume of amniotic fluid and consequent restriction in fetal movement.

Neonates with renal hypodysplasia may present with pneumothorax, feeding difficulties, urinary sodium loss, metabolic acidosis, and impaired renal function. During the first year of life, the infants experience persistent anorexia with vomiting and poor growth. After the first year, patients experience poor growth, proteinuria, polyuria, polydipsia, and renal failure.

What Are the Pathological Features of Renal Hypodysplasia?

The patients with renal hypodysplasia show features of both renal hypoplasia and dysplasia. It includes the following features on histopathological examination:

• The presence of dysplastic elements in the renal parenchyma, such as primitive tubules surrounded by undifferentiated stroma, smooth muscle, and metaplastic cartilage with cystic tubule dilations. Dysplasia can affect a segment of the kidney or the entire kidney.

• The presence of smaller kidneys that weighs less than 50 percent of the normal weight.

• A decrease in the number of nephrons. The total number of nephrons is reduced by 20 to 25 percent.

• The glomeruli in the kidneys are hypertrophic, and they are twice the normal size of the glomeruli.

• The affected tubules are hypertrophic. They are larger and longer than normal tubules.

• Electron microscopy reveals the presence of irregular thickening and fusion of epithelial cell foot processes. Thickening of Bowman’s capsule and abnormalities of the glomerular basement membrane is also seen.

How Is Renal Hypodysplasia Diagnosed?

The diagnosis of renal hypodysplasia is based on ultrasound examination during pregnancy and genetic testing for patients with a familial history of renal hypodysplasia.

• Ultrasound Imaging: It is performed during or after the third month of gestation helps in the diagnosis of renal hypodysplasia. It is diagnosed by using fetal renal measurements. Postnatally, patients with a unilateral abnormality and normal contralateral kidney have normal kidney function. Patients with bilateral renal impairment do not survive or may present with end-stage renal disease.

How Is Renal Hypodysplasia Treated?

• Individuals with unilateral hypodysplasia are monitored with follow-up ultrasounds to determine the growth of the normal contralateral kidney that exhibits compensatory hypertrophy.

• Individuals with bilateral renal hypodysplasia require supportive therapy to maintain fluid and electrolyte balance and growth promotion.

• The drugs like angiotensin-converting enzyme inhibitors are given to slow the progression to end-stage kidney disease.

• For individuals, who have progressed to end-stage renal disease, renal transplantation is recommended. There is no specific treatment protocol for renal hypodysplasia. It is mainly aimed at supportive management with growth promotion.

Conclusion

Renal hypodysplasia is a rare autosomal dominant disorder. It can be detected by antenatal ultrasound screening after the third month of gestation. Patients with a unilateral abnormality and normal contralateral kidney have normal kidney function. Patients with bilateral renal impairment do not survive or may present with end-stage renal disease. The main aim of treatment is to offer supportive therapy and to aid in growth promotion. Renal transplantation is recommended for patients who have progressed to end-stage renal disease.