Kidney Development: Pronephros & Mesonephros

Introduction

• Embryological and anatomical components are closely connected
• Both systems develop from a common mesodermal ridge, known as the intermediate mesoderm
• Development occurs along the posterior wall of the abdominal cavity
• Excretory ducts initially enter a shared cavity called the cloaca

Development Sequence

• Three overlapping kidney systems form in a cranial to caudal sequence during intrauterine life in humans
• The three systems that form are the pronephros, mesonephros, and metanephros

Pronephros

• It is rudimentary and nonfunctional
• During the fourth week, it is represented by 7 to 10 solid cell groups in the cervical region
• These groups create vestigial excretory units called nephrotomes
• Nephrotomes regress shortly after forming
• By the end of the fourth week, all indications of the pronephric system disappears

Mesonephros

• The second system functions briefly during early fetal period
• The mesonephros and mesonephric ducts derive from intermediate mesoderm, specifically from upper thoracic to upper lumbar (L3) segments
• The first excretory tubules of the mesonephros emerges during regression of the pronephric system
• Tubules lengthen quickly into an S-shaped loop, acquiring a tuft of capillaries that forms a glomerulus at its medial extremity

Metanephros: The Definitive Kidney

• The third urinary system, the metanephros, forms permanent kidneys, emerging in the fifth week
• Tubules around the glomerulus form Bowman's capsule; together, forming a renal corpuscle
• Tubules enter the longitudinal collecting duct, also known as the mesonephric or wolffian duct, on the lateral side

Collecting System

• Excretory units develop from metanephric mesoderm
• The collecting ducts of the permanent kidney develop from the ureteric bud
• The ureteric bud is an outgrowth of the mesonephric duct located near its entrance to the cloaca
• The ureteric bud penetrates the metanephric tissue, molding over its distal end as a cap

Metanephros Tubule Formation

• The ureteric bud dilates, forming the primitive renal pelvis and splitting into cranial/caudal portions, which will become the major calyces
• Each calyx generates two new buds that penetrate the metanephric tissue
• Buds further subdivide to form 12 or more generations of tubules
• As this occurs, more tubules form at the periphery until the end of the 5th month

Renal Development

• Collecting tubules of the fifth and successive generations elongate and converge on the minor calyx
• Convergence forms the renal pyramid
• The ureteric bud develops into the ureter, the renal pelvis, the major/minor calyces, and approximately 1-3 million collecting tubules

Excretory System Formation

• Each newly formed collecting tubule is hooded at its distal end by a metanephric tissue cap
• Stimulated by the tubule, cells in the tissue cap form renal vesicles, which gives rise to small S-shaped tubules
• Capillaries grow into the pocket at one end of the S-shaped tubule and differentiate into glomeruli
• Tubules and glomeruli structure that form are called nephrons, or excretory units
• The proximal end of each nephron forms Bowman’s capsule, indented by a glomerulus

Kidney Development & Function

• The distal end forms an open connection with the collecting tubules, establishing a passageway from Bowman's capsule to the collecting unit
• Continuous lengthening of the excretory tubule results in the formation of the proximal convoluted tubule, loop of Henle, and distal convoluted tubule
• The kidney develops from metanephric mesoderm, that provides excretory units and the ureteric bud, that gives rise to the collecting system
• Urine is passed into the amniotic cavity, mixes with the amniotic fluid, and fluid gets swallowed by the fetus and is recycled through the kidneys
• During fetal life, the placenta is responsible for excretion of waste products so the kidneys are not responsible for excretion of waste products

Kidney Position

• The kidney initially residing in the pelvic region and later shifts to a more cranial position in the abdomen
• The ascent of the kidney is caused by diminished body curvature and body growth in the lumbar and sacral regions

Blood Supply

• In the pelvis, the metanephros is supplied by a pelvic branch of the aorta
• With its ascent into the abdomen, it becomes vascularized by arteries originating from the aorta at continuously higher levels
• The lower vessels degenerate, but may remain

Bladder and Urethra

• From the fourth to seventh weeks of development, the cloaca divides into the urogenital sinus anteriorly and the anal canal posteriorly
• The urorectal septum, made of mesoderm, separates the primitive anal canal and the urogenital sinus

Urogenital Sinus

• Three Sections: an upper & largest part, the urinary bladder, a pelvic part that gives rise to the prostatic and membranous parts of the urethra in males, and a phallic part
• The urinary bladder initially continuous with the allantois
• The allantois lumen becomes obliterated a thick fibrous cord, the urachus, and connects the apex of the bladder with the umbilicus
• In adults, it is known as the median umbilical ligament
• The phallic section is flattened from side to side
• The genital tubercle grows and the sinus gets pulled ventrally

Bladder Development

• The caudal portions of the mesonephric ducts are absorbed into the wall of the urinary bladder during cloaca differentiation
• Ureters initially outgrowths from the mesonephric ducts, enter the bladder separately
• As the kidneys ascend, the ureter orifices reposition cranially -The mesonephric ducts move closer together to enter the prostatic urethra
• The mesonephric ducts and ureters both originating in the mesoderm results in the bladder mucosa being formed in by of the ducts
• The lining also becomes mesodermal, specifically the trigone of the bladder
• In time the mesodermal lining of the trigone replaced by endodermal epithelium resulting in the inner bladder lining becoming completely lined with endodermal epithelium

Urethra Development

• The epithelium of the urethra originates from the endoderm in both sexes
• The surrounding connective and smooth muscle comes from splanchnic mesoderm
• The prostatic urethra begins to proliferate at the end of the third month
• The proliferation results in sprouts, penetrating the surrounding mesenchyme
• In males, these buds form the prostate gland
• In females, the cranial part of the urethra gives rise to the urethral and paraurethral glands

Wilms' Tumor

• Wilms’ tumor is a kidney cancer usually affects children under 5
• This can occur in the fetus
• It is due to mutations in the WT1 gene on 11p13, and it may be associated with other abnormalities and syndromes

Renal Agenesis and Dysplasia

• Renal dysplasias and agenesis causes severe malformations
• Severe malformations require dialysis and transplantation
• Multicystic dysplastic kidney represents abnormalities in which multiple ducts are surrounded by undifferentiated cells, so there are numerous
• Nephrons fail to develop and the ureteric bud fails to branch, which causes the collecting ducts to never form

Kidney Position Abnormalities

• Pelvic kidney pertains that the kidney remains in the pelvis near the common iliac artery
• Occasionally the kidneys are pushed closer, leading the lower poles to fuse; forming horseshoe kidney

Bladder Defects

• If the lumen of the intraembryonic portion of the allantois persists, the resultant urachal fistula causes urine drainage from the umbilicus
• A local area of allantois persistence causes cyst dilation, that forms a urachal cyst
• If the vessel lumen persists in the upper part, it forms a urachal sinus
• This sinus is usually continuous with the urinary bladder

Exstrophy of the Bladder

• Exstrophy is a ventral body wall defect resulting in an internal mucosa exposure
• Epispadias is a consistent trait, extending an open urinary tract along the dorsal penis to the umbilicus
• Mesodermal migration is lacking between the umbilicus/genital tubercle, followed by ectoderm rupture