Congenital Renal Abnormalities

Renal Embryology

The kidney develops in the pelvis Pelvis The pelvis consists of the bony pelvic girdle, the muscular and ligamentous pelvic floor, and the pelvic cavity, which contains viscera, vessels, and multiple nerves and muscles. The pelvic girdle, composed of 2 “hip” bones and the sacrum, is a ring-like bony structure of the axial skeleton that links the vertebral column with the lower extremities. Pelvis: Anatomy and migrates cranially. Three separate renal systems form in sequence, giving rise to the kidney, in association with the urinary tract Urinary tract The urinary tract is located in the abdomen and pelvis and consists of the kidneys, ureters, urinary bladder, and urethra. The structures permit the excretion of urine from the body. Urine flows from the kidneys through the ureters to the urinary bladder and out through the urethra. Urinary Tract: Anatomy and urogenital system:

• Pronephros Pronephros The primordial kidney that develops from the intermediate mesoderm in the embryos of vertebrates, and is succeeded by the mesonephros. In higher vertebrates and humans, the pronephros is a vestigial and transient structure. Development of the Urogenital System:
  • Non-functional vestigial renal structure found in the cervical area
  • Appears in the 3rd week
  • Disappears by the 4th week
• Mesonephros Mesonephros One of a pair of excretory organs (mesonephroi) which grows caudally to the first pair (pronephroi) during development. Mesonephroi are the permanent kidneys in adult amphibians and fish. In higher vertebrates, proneprhoi and most of mesonephroi degenerate with the appearance of metanephroi. The remaining ducts become wolffian ducts. Development of the Urogenital System:
  • 4th week: Excretory units, composed of capillaries Capillaries Capillaries are the primary structures in the circulatory system that allow the exchange of gas, nutrients, and other materials between the blood and the extracellular fluid (ECF). Capillaries are the smallest of the blood vessels. Because a capillary diameter is so small, only 1 RBC may pass through at a time. Capillaries: Histology, the Bowman’s capsule Capsule An envelope of loose gel surrounding a bacterial cell which is associated with the virulence of pathogenic bacteria. Some capsules have a well-defined border, whereas others form a slime layer that trails off into the medium. Most capsules consist of relatively simple polysaccharides but there are some bacteria whose capsules are made of polypeptides. Bacteroides, and the collecting tubule connected to the Wolffian ducts Wolffian ducts A pair of excretory ducts of the middle kidneys of an embryo, also called mesonephric ducts. In higher vertebrates, wolffian ducts persist in the male forming vas deferens, but atrophy into vestigial structures in the female. Primary Amenorrhea, form. 
  • Derived from the intermediate mesoderm Intermediate mesoderm Development of the Urogenital System in the upper thoracic to the lumbar area
  • Functional for some time in utero
  • Mostly disappears; a small portion remains part of the final renal system:
    • Fuses with the cloaca Cloaca A dilated cavity extended caudally from the hindgut. In adult birds, reptiles, amphibians, and many fishes but few mammals, cloaca is a common chamber into which the digestive, urinary and reproductive tracts discharge their contents. In most mammals, cloaca gives rise to large intestine; urinary bladder; and genitalia. Development of the Abdominal Organs to create the bladder Bladder A musculomembranous sac along the urinary tract. Urine flows from the kidneys into the bladder via the ureters, and is held there until urination. Pyelonephritis and Perinephric Abscess
    • In boys, gives rise to a portion of the genital system
• Metanephros Metanephros Development of the Urogenital System:
  • 5th week: develops caudally in relation to the mesonephros Mesonephros One of a pair of excretory organs (mesonephroi) which grows caudally to the first pair (pronephroi) during development. Mesonephroi are the permanent kidneys in adult amphibians and fish. In higher vertebrates, proneprhoi and most of mesonephroi degenerate with the appearance of metanephroi. The remaining ducts become wolffian ducts. Development of the Urogenital System 
  • Renal parenchyma differentiates from the mesoderm Mesoderm The middle germ layer of an embryo derived from three paired mesenchymal aggregates along the neural tube. Gastrulation and Neurulation similarly to the mesonephros Mesonephros One of a pair of excretory organs (mesonephroi) which grows caudally to the first pair (pronephroi) during development. Mesonephroi are the permanent kidneys in adult amphibians and fish. In higher vertebrates, proneprhoi and most of mesonephroi degenerate with the appearance of metanephroi. The remaining ducts become wolffian ducts. Development of the Urogenital System.
  • The collecting duct Collecting duct Straight tubes commencing in the radiate part of the kidney cortex where they receive the curved ends of the distal convoluted tubules. In the medulla the collecting tubules of each pyramid converge to join a central tube (duct of bellini) which opens on the summit of the papilla. Renal Cell Carcinoma system:
    • Initially appears as a stalk and bud (blastema) derived from the mesonephric duct Mesonephric duct A pair of excretory ducts of the middle kidneys of an embryo, also called mesonephric ducts. In higher vertebrates, wolffian ducts persist in the male forming vas deferens, but atrophy into vestigial structures in the female. Kidneys: Anatomy close to the cloaca Cloaca A dilated cavity extended caudally from the hindgut. In adult birds, reptiles, amphibians, and many fishes but few mammals, cloaca is a common chamber into which the digestive, urinary and reproductive tracts discharge their contents. In most mammals, cloaca gives rise to large intestine; urinary bladder; and genitalia. Development of the Abdominal Organs
    • Later forms the ureter,  renal pelvis Renal pelvis Kidneys: Anatomy, and calyces and merges with the metanephric tissue, creating the collecting tubules Collecting tubules Straight tubes commencing in the radiate part of the kidney cortex where they receive the curved ends of the distal convoluted tubules. In the medulla the collecting tubules of each pyramid converge to join a central tube (duct of Bellini) which opens on the summit of the papilla. Kidneys: Anatomy
    • Tips TIPS A type of surgical portasystemic shunt to reduce portal hypertension with associated complications of esophageal varices and ascites. It is performed percutaneously through the jugular vein and involves the creation of an intrahepatic shunt between the hepatic vein and portal vein. The channel is maintained by a metallic stent. The procedure can be performed in patients who have failed sclerotherapy and is an additional option to the surgical techniques of portocaval, mesocaval, and splenorenal shunts. It takes one to three hours to perform. Cirrhosis of the collecting tubules Collecting tubules Straight tubes commencing in the radiate part of the kidney cortex where they receive the curved ends of the distal convoluted tubules. In the medulla the collecting tubules of each pyramid converge to join a central tube (duct of Bellini) which opens on the summit of the papilla. Kidneys: Anatomy interact with the metanephric tissue → nephrons.
    • 20th week: Entire collecting system has been formed.
    • 32nd–36th weeks: All nephrotic units have formed, but continue to mature after birth.
• Renal ascent:
  • Caused by growth of lumbar and sacral regions 
  • Blood supply is from arteries Arteries Arteries are tubular collections of cells that transport oxygenated blood and nutrients from the heart to the tissues of the body. The blood passes through the arteries in order of decreasing luminal diameter, starting in the largest artery (the aorta) and ending in the small arterioles. Arteries are classified into 3 types: large elastic arteries, medium muscular arteries, and small arteries and arterioles. Arteries: Histology coming off the aorta Aorta The main trunk of the systemic arteries. Mediastinum and Great Vessels: Anatomy.
  • As the kidney arises, new arteries Arteries Arteries are tubular collections of cells that transport oxygenated blood and nutrients from the heart to the tissues of the body. The blood passes through the arteries in order of decreasing luminal diameter, starting in the largest artery (the aorta) and ending in the small arterioles. Arteries are classified into 3 types: large elastic arteries, medium muscular arteries, and small arteries and arterioles. Arteries: Histology arise, while old arteries Arteries Arteries are tubular collections of cells that transport oxygenated blood and nutrients from the heart to the tissues of the body. The blood passes through the arteries in order of decreasing luminal diameter, starting in the largest artery (the aorta) and ending in the small arterioles. Arteries are classified into 3 types: large elastic arteries, medium muscular arteries, and small arteries and arterioles. Arteries: Histology disappear.
  • 9th week: Left kidney is at the level of T11–L2. Right kidney is at the level of T12–L2/3.

Disorders of the Renal Parenchyma

Introduction

Renal embryologic disorders affecting the size, the shape, or the structure of kidney parenchyma (renal dysgenesis):

• Renal agenesis Agenesis Teratogenic Birth Defects: absence of renal tissue due to a disruption during embryologic renal development
• Renal hypoplasia Hypoplasia Hypoplastic Left Heart Syndrome (HLHS): small kidneys Kidneys The kidneys are a pair of bean-shaped organs located retroperitoneally against the posterior wall of the abdomen on either side of the spine. As part of the urinary tract, the kidneys are responsible for blood filtration and excretion of water-soluble waste in the urine. Kidneys: Anatomy with a decreased number of functioning nephrons
• Renal dysplasia Dysplasia Cellular Adaptation: focal or diffuse abnormalities of the nephron Nephron The functional units of the kidney, consisting of the glomerulus and the attached tubule. Kidneys: Anatomy architecture; can be:
  • Non-cystic (simple renal dysplasia Dysplasia Cellular Adaptation)
  • Cystic Cystic Fibrocystic Change dysplasia Dysplasia Cellular Adaptation: characterized by the formation of cysts Cysts Any fluid-filled closed cavity or sac that is lined by an epithelium. Cysts can be of normal, abnormal, non-neoplastic, or neoplastic tissues. Fibrocystic Change
    • Multicystic dysplastic kidneys Kidneys The kidneys are a pair of bean-shaped organs located retroperitoneally against the posterior wall of the abdomen on either side of the spine. As part of the urinary tract, the kidneys are responsible for blood filtration and excretion of water-soluble waste in the urine. Kidneys: Anatomy (MCDK): cystic Cystic Fibrocystic Change dysplasia Dysplasia Cellular Adaptation involving the entire kidney
    • Autosomal recessive polycystic kidney disease Autosomal Recessive Polycystic Kidney Disease Polycystic kidney disease (PKD) is an inherited genetic disorder leading to the development of numerous fluid-filled cysts in the kidneys. Autosomal recessive polycystic kidney disease is primarily characterized by cystic dilatations of the renal collecting ducts and intrahepatic bile duct dilatation with hepatic fibrosis. Autosomal Recessive Polycystic Kidney Disease (ARPKD) ( ARPKD ARPKD Polycystic kidney disease (PKD) is an inherited genetic disorder leading to the development of numerous fluid-filled cysts in the kidneys. Autosomal recessive polycystic kidney disease is primarily characterized by cystic dilatations of the renal collecting ducts and intrahepatic bile duct dilatation with hepatic fibrosis. Autosomal Recessive Polycystic Kidney Disease (ARPKD))

Renal agenesis Agenesis Teratogenic Birth Defects

• Pathophysiology:
  • Interruption of the embryologic development of the ureteric bud, or metanephric blastema Metanephric blastema Wilms Tumor 
  • True renal agenesis Agenesis Teratogenic Birth Defects includes an absent ipsilateral ureter and bladder Bladder A musculomembranous sac along the urinary tract. Urine flows from the kidneys into the bladder via the ureters, and is held there until urination. Pyelonephritis and Perinephric Abscess hemitrigone.
  • Bilateral renal agenesis Agenesis Teratogenic Birth Defects is incompatible with life.
• Epidemiology:
  • Incidence Incidence The number of new cases of a given disease during a given period in a specified population. It also is used for the rate at which new events occur in a defined population. It is differentiated from prevalence, which refers to all cases in the population at a given time. Measures of Disease Frequency of unilateral renal agenesis Agenesis Teratogenic Birth Defects: ~1 in 500–1,000 births
  • ↑ in infants with a single umbilical artery Umbilical artery Specialized arterial vessels in the umbilical cord. They carry waste and deoxygenated blood from the fetus to the mother via the placenta. In humans, there are usually two umbilical arteries but sometimes one. Prenatal and Postnatal Physiology of the Neonate.
  • Boys ＞ girls
  • Common associations include:
    • Boys: absent ipsilateral vas deferens Vas Deferens The excretory duct of the testes that carries spermatozoa. It rises from the scrotum and joins the seminal vesicles to form the ejaculatory duct. Testicles: Anatomy
    • Girls: Müllerian duct Müllerian duct A pair of ducts near the wolffian ducts in a developing embryo. In the male embryo, they degenerate with the appearance of testicular anti-mullerian hormone. In the absence of anti-mullerian hormone, mullerian ducts give rise to the female reproductive tract, including the oviducts; uterus; cervix; and vagina. Uterus, Cervix, and Fallopian Tubes: Anatomy abnormalities 
• Etiology:
  • Genetic predisposition (e.g., mutations in genes Genes A category of nucleic acid sequences that function as units of heredity and which code for the basic instructions for the development, reproduction, and maintenance of organisms. DNA Types and Structure responsible for renal development, RET and GDNF)
  • Syndrome association:
    • Associated with vertebral anomalies, anal atresia Anal Atresia Esophageal Atresia and Tracheoesophageal Fistula, and cardiac Cardiac Total Anomalous Pulmonary Venous Return (TAPVR) anomalies (VACTERL)
    • Mayer-Rokitanski-Kuster-Hauser: vaginal aplasia Aplasia Cranial Nerve Palsies, uterine abnormalities
    • DiGeorge’s syndrome: palate Palate The palate is the structure that forms the roof of the mouth and floor of the nasal cavity. This structure is divided into soft and hard palates. Palate: Anatomy defects, cardiac Cardiac Total Anomalous Pulmonary Venous Return (TAPVR) abnormalities, absent thymus Thymus A single, unpaired primary lymphoid organ situated in the mediastinum, extending superiorly into the neck to the lower edge of the thyroid gland and inferiorly to the fourth costal cartilage. It is necessary for normal development of immunologic function early in life. By puberty, it begins to involute and much of the tissue is replaced by fat. Lymphatic Drainage System: Anatomy
  • Associated maternal risk factors:
    • Maternal diabetes Diabetes Diabetes mellitus (DM) is a metabolic disease characterized by hyperglycemia and dysfunction of the regulation of glucose metabolism by insulin. Type 1 DM is diagnosed mostly in children and young adults as the result of autoimmune destruction of β cells in the pancreas and the resulting lack of insulin. Type 2 DM has a significant association with obesity and is characterized by insulin resistance. Diabetes Mellitus
    • Maternal obesity Obesity Obesity is a condition associated with excess body weight, specifically with the deposition of excessive adipose tissue. Obesity is considered a global epidemic. Major influences come from the western diet and sedentary lifestyles, but the exact mechanisms likely include a mixture of genetic and environmental factors. Obesity
    • Young maternal age
    • Maternal smoking Smoking Willful or deliberate act of inhaling and exhaling smoke from burning substances or agents held by hand. Interstitial Lung Diseases
    • Maternal ethanol Ethanol A clear, colorless liquid rapidly absorbed from the gastrointestinal tract and distributed throughout the body. It has bactericidal activity and is used often as a topical disinfectant. It is widely used as a solvent and preservative in pharmaceutical preparations as well as serving as the primary ingredient in alcoholic beverages. Ethanol Metabolism consumption during pregnancy Pregnancy The status during which female mammals carry their developing young (embryos or fetuses) in utero before birth, beginning from fertilization to birth. Pregnancy: Diagnosis, Physiology, and Care
    • Teratogen exposure Exposure ABCDE Assessment (e.g., retinoic acid, cocaine Cocaine An alkaloid ester extracted from the leaves of plants including coca. It is a local anesthetic and vasoconstrictor and is clinically used for that purpose, particularly in the eye, ear, nose, and throat. It also has powerful central nervous system effects similar to the amphetamines and is a drug of abuse. Cocaine, like amphetamines, acts by multiple mechanisms on brain catecholaminergic neurons; the mechanism of its reinforcing effects is thought to involve inhibition of dopamine uptake. Local Anesthetics)
• Clinical presentation Presentation The position or orientation of the fetus at near term or during obstetric labor, determined by its relation to the spine of the mother and the birth canal. The normal position is a vertical, cephalic presentation with the fetal vertex flexed on the neck. Normal and Abnormal Labor: 
  • Prenatal:
    • Routine-monitoring ultrasound findings include oligohydramnios Oligohydramnios Oligohydramnios refers to amniotic fluid volume less than expected for the current gestational age. Oligohydramnios is diagnosed by ultrasound and defined as an amniotic fluid index (AFI) of ‰¤ 5 cm or a single deep pocket (SDP) of < 2 cm in the 2nd or 3rd trimester. Oligohydramnios and an absent bladder Bladder A musculomembranous sac along the urinary tract. Urine flows from the kidneys into the bladder via the ureters, and is held there until urination. Pyelonephritis and Perinephric Abscess and kidney.
    • Genetic testing Genetic Testing Detection of a mutation; genotype; karyotype; or specific alleles associated with genetic traits, heritable diseases, or predisposition to a disease, or that may lead to the disease in descendants. It includes prenatal genetic testing. Myotonic Dystrophies in cases with a high prenatal index of suspicion
    • Left kidney is more often absent.
  • Postnatal:
    • Often discovered during evaluation for other anomalies 
    • Incidental discovery on ultrasound
    • May have recurrent urinary tract infections Urinary tract infections Urinary tract infections (UTIs) represent a wide spectrum of diseases, from self-limiting simple cystitis to severe pyelonephritis that can result in sepsis and death. Urinary tract infections are most commonly caused by Escherichia coli, but may also be caused by other bacteria and fungi. Urinary tract infections (UTIs) (UTIs) or hypertension Hypertension Hypertension, or high blood pressure, is a common disease that manifests as elevated systemic arterial pressures. Hypertension is most often asymptomatic and is found incidentally as part of a routine physical examination or during triage for an unrelated medical encounter. Hypertension
    • Pulmonary hypoplasia Hypoplasia Hypoplastic Left Heart Syndrome (HLHS) due to a lack of amniotic fluid Amniotic fluid A clear, yellowish liquid that envelopes the fetus inside the sac of amnion. In the first trimester, it is likely a transudate of maternal or fetal plasma. In the second trimester, amniotic fluid derives primarily from fetal lung and kidney. Cells or substances in this fluid can be removed for prenatal diagnostic tests (amniocentesis). Placenta, Umbilical Cord, and Amniotic Cavity production may be a sign.
  • Potter’s syndrome: 
    • Bilateral renal agenesis Agenesis Teratogenic Birth Defects, pulmonary hypoplasia Hypoplasia Hypoplastic Left Heart Syndrome (HLHS) resulting from oligohydramnios Oligohydramnios Oligohydramnios refers to amniotic fluid volume less than expected for the current gestational age. Oligohydramnios is diagnosed by ultrasound and defined as an amniotic fluid index (AFI) of ‰¤ 5 cm or a single deep pocket (SDP) of < 2 cm in the 2nd or 3rd trimester. Oligohydramnios 
    • Facial abnormalities: widely separated eyes, prominent epicanthal folds, broad and compressed nose Nose The nose is the human body’s primary organ of smell and functions as part of the upper respiratory system. The nose may be best known for inhaling oxygen and exhaling carbon dioxide, but it also contributes to other important functions, such as tasting. The anatomy of the nose can be divided into the external nose and the nasal cavity. Nose and Nasal Cavity: Anatomy, and low-set ears Low-set ears DiGeorge Syndrome 
    • Other abnormalities: club foot Foot The foot is the terminal portion of the lower limb, whose primary function is to bear weight and facilitate locomotion. The foot comprises 26 bones, including the tarsal bones, metatarsal bones, and phalanges. The bones of the foot form longitudinal and transverse arches and are supported by various muscles, ligaments, and tendons. Foot: Anatomy, leg Leg The lower leg, or just “leg” in anatomical terms, is the part of the lower limb between the knee and the ankle joint. The bony structure is composed of the tibia and fibula bones, and the muscles of the leg are grouped into the anterior, lateral, and posterior compartments by extensions of fascia. Leg: Anatomy bowing, diaphragmatic hernia Hernia Protrusion of tissue, structure, or part of an organ through the bone, muscular tissue, or the membrane by which it is normally contained. Hernia may involve tissues such as the abdominal wall or the respiratory diaphragm. Hernias may be internal, external, congenital, or acquired. Abdominal Hernias, eye anomalies (e.g., cataract Cataract Partial or complete opacity on or in the lens or capsule of one or both eyes, impairing vision or causing blindness. The many kinds of cataract are classified by their morphology (size, shape, location) or etiology (cause and time of occurrence). Neurofibromatosis Type 2, lens Lens A transparent, biconvex structure of the eye, enclosed in a capsule and situated behind the iris and in front of the vitreous humor (vitreous body). It is slightly overlapped at its margin by the ciliary processes. Adaptation by the ciliary body is crucial for ocular accommodation. Eye: Anatomy prolapse), cardiovascular abnormalities (e.g., ventricular septal defect Ventricular Septal Defect Tetralogy of Fallot, patent ductus arteriosus Patent ductus arteriosus The ductus arteriosus (DA) allows blood to bypass pulmonary circulation. After birth, the DA remains open for up to 72 hours and then constricts and involutes, becoming the ligamentum arteriosum. Failure of this process to occur results in patent ductus arteriosus (PDA), a condition that causes up to 10% of congenital heart defects. Patent Ductus Arteriosus (PDA), tetralogy of Fallot Tetralogy of Fallot Tetralogy of Fallot is the most common cyanotic congenital heart disease. The disease is the confluence of 4 pathologic cardiac features: overriding aorta, ventricular septal defect, right ventricular outflow obstruction, and right ventricular hypertrophy. Tetralogy of Fallot)
    • Potter’s syndrome may also be associated with cystic Cystic Fibrocystic Change renal dysplasia Dysplasia Cellular Adaptation, obstructive uropathy, ARPKD ARPKD Polycystic kidney disease (PKD) is an inherited genetic disorder leading to the development of numerous fluid-filled cysts in the kidneys. Autosomal recessive polycystic kidney disease is primarily characterized by cystic dilatations of the renal collecting ducts and intrahepatic bile duct dilatation with hepatic fibrosis. Autosomal Recessive Polycystic Kidney Disease (ARPKD), renal hypoplasia Hypoplasia Hypoplastic Left Heart Syndrome (HLHS), and medullary dysplasia Dysplasia Cellular Adaptation.  
• Management: 
  • Children with a solitary kidney have a high risk for chronic kidney disease Chronic Kidney Disease Chronic kidney disease (CKD) is kidney impairment that lasts for ≥ 3 months, implying that it is irreversible. Hypertension and diabetes are the most common causes; however, there are a multitude of other etiologies. In the early to moderate stages, CKD is usually asymptomatic and is primarily diagnosed by laboratory abnormalities. Chronic Kidney Disease ( CKD CKD Chronic kidney disease (CKD) is kidney impairment that lasts for ≥ 3 months, implying that it is irreversible. Hypertension and diabetes are the most common causes; however, there are a multitude of other etiologies. In the early to moderate stages, CKD is usually asymptomatic and is primarily diagnosed by laboratory abnormalities. Chronic Kidney Disease):
    • Monitor the contralateral kidney for hypertrophy Hypertrophy General increase in bulk of a part or organ due to cell enlargement and accumulation of fluids and secretions, not due to tumor formation, nor to an increase in the number of cells (hyperplasia). Cellular Adaptation.
    • Long-term follow-up for hypertension Hypertension Hypertension, or high blood pressure, is a common disease that manifests as elevated systemic arterial pressures. Hypertension is most often asymptomatic and is found incidentally as part of a routine physical examination or during triage for an unrelated medical encounter. Hypertension and proteinuria Proteinuria The presence of proteins in the urine, an indicator of kidney diseases. Nephrotic Syndrome in Children
    • Kidney function testing
  • Avoiding contact sports is controversial.

Renal hypoplasia Hypoplasia Hypoplastic Left Heart Syndrome (HLHS)

• Pathophysiology:
  • Small kidneys Kidneys The kidneys are a pair of bean-shaped organs located retroperitoneally against the posterior wall of the abdomen on either side of the spine. As part of the urinary tract, the kidneys are responsible for blood filtration and excretion of water-soluble waste in the urine. Kidneys: Anatomy (＜50% than expected for age) 
  • Fewer-than-normal nephrons and calyces
  • Large glomeruli and tubules ( hypertrophy Hypertrophy General increase in bulk of a part or organ due to cell enlargement and accumulation of fluids and secretions, not due to tumor formation, nor to an increase in the number of cells (hyperplasia). Cellular Adaptation to compensate)
  • Over time, patients Patients Individuals participating in the health care system for the purpose of receiving therapeutic, diagnostic, or preventive procedures. Clinician–Patient Relationship develop end-stage renal disease (ESRD).
• Epidemiology:
  • Incidence Incidence The number of new cases of a given disease during a given period in a specified population. It also is used for the rate at which new events occur in a defined population. It is differentiated from prevalence, which refers to all cases in the population at a given time. Measures of Disease Frequency of 1 in 400 live births
• Etiology:
  • Vascular abnormalities: 
    • Renal hypoperfusion in utero leads to hypoplasia Hypoplasia Hypoplastic Left Heart Syndrome (HLHS).
  • Genetic disorders: 
    • Over 200 associated syndromes
    • Mutation Mutation Genetic mutations are errors in DNA that can cause protein misfolding and dysfunction. There are various types of mutations, including chromosomal, point, frameshift, and expansion mutations. Types of Mutations in key regulatory genes Genes A category of nucleic acid sequences that function as units of heredity and which code for the basic instructions for the development, reproduction, and maintenance of organisms. DNA Types and Structure in renal development
• Clinical presentation Presentation The position or orientation of the fetus at near term or during obstetric labor, determined by its relation to the spine of the mother and the birth canal. The normal position is a vertical, cephalic presentation with the fetal vertex flexed on the neck. Normal and Abnormal Labor:
  • Unilateral: 
    • Diagnosed incidentally during evaluation for hypertension Hypertension Hypertension, or high blood pressure, is a common disease that manifests as elevated systemic arterial pressures. Hypertension is most often asymptomatic and is found incidentally as part of a routine physical examination or during triage for an unrelated medical encounter. Hypertension or urinary complaints
    • Neonates may present with failure to thrive Failure to Thrive Failure to thrive (FTT), or faltering growth, describes suboptimal weight gain and growth in children. The majority of cases are due to inadequate caloric intake; however, genetic, infectious, and oncological etiologies are also common. Failure to Thrive.
  • Bilateral:
    • History of polyuria Polyuria Urination of a large volume of urine with an increase in urinary frequency, commonly seen in diabetes. Renal Potassium Regulation, polydipsia Polydipsia Excessive thirst manifested by excessive fluid intake. It is characteristic of many diseases such as diabetes mellitus; diabetes insipidus; and nephrogenic diabetes insipidus. The condition may be psychogenic in origin. Diabetes Insipidus, and/or urinary abnormalities 
    • Development of ESRD in the 1st decade of life
• Diagnosis: 
  • Prenatal: 
    • Found through routine screening Screening Preoperative Care ultrasound by 3 months’ gestation
  • Postnatal: 
    • Renal ultrasound of suspected cases
    • Can be further confirmed by histology but rarely performed
• Management:
  • Unilateral:
    • Periodic follow-up by ultrasound and urinalysis Urinalysis Examination of urine by chemical, physical, or microscopic means. Routine urinalysis usually includes performing chemical screening tests, determining specific gravity, observing any unusual color or odor, screening for bacteriuria, and examining the sediment microscopically. Urinary Tract Infections (UTIs) in Children to monitor compensatory hypertrophy Hypertrophy General increase in bulk of a part or organ due to cell enlargement and accumulation of fluids and secretions, not due to tumor formation, nor to an increase in the number of cells (hyperplasia). Cellular Adaptation of the unaffected kidney
  • Bilateral:
    • May require human growth hormone Human growth hormone A 191-amino acid polypeptide hormone secreted by the human adenohypophysis, also known as gh or somatotropin. Synthetic growth hormone, termed somatropin, has replaced the natural form in therapeutic usage such as treatment of dwarfism in children with growth hormone deficiency. Idiopathic Intracranial Hypertension (rHGH) to allow appropriate growth
    • Angiotensin-converting enzyme (ACE) inhibitors to slow the progression to ESRD
    • Renal transplant for patients Patients Individuals participating in the health care system for the purpose of receiving therapeutic, diagnostic, or preventive procedures. Clinician–Patient Relationship with advanced disease

Renal dysplasia Dysplasia Cellular Adaptation

• Epidemiology:
  • 2–4 per 1,000 births
  • Boys-to-girls ratio:
    • Bilateral 1.3:1
    • Unilateral 2:1
• Classification:
  • Simple renal dysplasia Dysplasia Cellular Adaptation
  • Cystic Cystic Fibrocystic Change renal dysplasia Dysplasia Cellular Adaptation
• Etiology: 
  • Primarily due to the incorrect differentiation of renal tissue caused by:
    • Embryonic ureteral buds arise in incorrect locations, leading to the incorrect differentiation of renal tissue.
    • Obstructive uropathy in gestation
• Clinical presentation Presentation The position or orientation of the fetus at near term or during obstetric labor, determined by its relation to the spine of the mother and the birth canal. The normal position is a vertical, cephalic presentation with the fetal vertex flexed on the neck. Normal and Abnormal Labor:
  • Unilateral: 
    • Diagnosed incidentally during evaluation for another dysmorphism
  • Bilateral:
    • Found to have renal failure Renal failure Conditions in which the kidneys perform below the normal level in the ability to remove wastes, concentrate urine, and maintain electrolyte balance; blood pressure; and calcium metabolism. Renal insufficiency can be classified by the degree of kidney damage (as measured by the level of proteinuria) and reduction in glomerular filtration rate. Crush Syndrome at birth or will develop renal failure Renal failure Conditions in which the kidneys perform below the normal level in the ability to remove wastes, concentrate urine, and maintain electrolyte balance; blood pressure; and calcium metabolism. Renal insufficiency can be classified by the degree of kidney damage (as measured by the level of proteinuria) and reduction in glomerular filtration rate. Crush Syndrome soon after
    • Associated urinary abnormalities lead to frequent UTI UTI Urinary tract infections (UTIs) represent a wide spectrum of diseases, from self-limiting simple cystitis to severe pyelonephritis that can result in sepsis and death. Urinary tract infections are most commonly caused by Escherichia coli, but may also be caused by other bacteria and fungi. Urinary tract infections (UTIs), hematuria Hematuria Presence of blood in the urine. Renal Cell Carcinoma, and abdominal pain Abdominal Pain Acute Abdomen.
• Diagnosis: 
  • Prenatal: 
    • Found through routine screening Screening Preoperative Care ultrasound by 3 months’ gestation
  • Postnatal: 
    • Renal ultrasound of suspected cases 
• Management:
  • At risk for CKD CKD Chronic kidney disease (CKD) is kidney impairment that lasts for ≥ 3 months, implying that it is irreversible. Hypertension and diabetes are the most common causes; however, there are a multitude of other etiologies. In the early to moderate stages, CKD is usually asymptomatic and is primarily diagnosed by laboratory abnormalities. Chronic Kidney Disease:
    • Blood pressure should be closely monitored.
    • Yearly urinalysis Urinalysis Examination of urine by chemical, physical, or microscopic means. Routine urinalysis usually includes performing chemical screening tests, determining specific gravity, observing any unusual color or odor, screening for bacteriuria, and examining the sediment microscopically. Urinary Tract Infections (UTIs) in Children
    • Urine Urine Liquid by-product of excretion produced in the kidneys, temporarily stored in the bladder until discharge through the urethra. Bowen Disease and Erythroplasia of Queyrat function tests in patients Patients Individuals participating in the health care system for the purpose of receiving therapeutic, diagnostic, or preventive procedures. Clinician–Patient Relationship with proteinuria Proteinuria The presence of proteins in the urine, an indicator of kidney diseases. Nephrotic Syndrome in Children/ hypertension Hypertension Hypertension, or high blood pressure, is a common disease that manifests as elevated systemic arterial pressures. Hypertension is most often asymptomatic and is found incidentally as part of a routine physical examination or during triage for an unrelated medical encounter. Hypertension
• MCDK:
  • Most common cause of an abdominal mass Mass Three-dimensional lesion that occupies a space within the breast Imaging of the Breast in newborns
  • Usually unilateral (polycystic kidney disease is often bilateral)
  • Bilateral is incompatible with life.
  • May be diagnosed during prenatal ultrasound
  • May be asymptomatic and diagnosed incidentally on imaging
  • Complete cyst regression Regression Corneal Abrasions, Erosion, and Ulcers occurs by 7 years in half of cases.
  • Annual follow-up with ultrasound and blood pressure monitoring is recommended.

ARPKD ARPKD Polycystic kidney disease (PKD) is an inherited genetic disorder leading to the development of numerous fluid-filled cysts in the kidneys. Autosomal recessive polycystic kidney disease is primarily characterized by cystic dilatations of the renal collecting ducts and intrahepatic bile duct dilatation with hepatic fibrosis. Autosomal Recessive Polycystic Kidney Disease (ARPKD)

• Epidemiology: 
  • Incidence Incidence The number of new cases of a given disease during a given period in a specified population. It also is used for the rate at which new events occur in a defined population. It is differentiated from prevalence, which refers to all cases in the population at a given time. Measures of Disease Frequency varies from 1:10,000 to 1:40,000 live births.
• Etiology:
  • An autosomal recessive Autosomal recessive Autosomal inheritance, both dominant and recessive, refers to the transmission of genes from the 22 autosomal chromosomes. Autosomal recessive diseases are only expressed when 2 copies of the recessive allele are inherited. Autosomal Recessive and Autosomal Dominant Inheritance disorder caused by the polycystic kidney and hepatic disease 1 ( PKHD1 PKHD1 Autosomal Recessive Polycystic Kidney Disease (ARPKD)) gene Gene A category of nucleic acid sequences that function as units of heredity and which code for the basic instructions for the development, reproduction, and maintenance of organisms. Basic Terms of Genetics 
  • Affects: kidneys Kidneys The kidneys are a pair of bean-shaped organs located retroperitoneally against the posterior wall of the abdomen on either side of the spine. As part of the urinary tract, the kidneys are responsible for blood filtration and excretion of water-soluble waste in the urine. Kidneys: Anatomy, lungs Lungs Lungs are the main organs of the respiratory system. Lungs are paired viscera located in the thoracic cavity and are composed of spongy tissue. The primary function of the lungs is to oxygenate blood and eliminate CO2. Lungs: Anatomy, and liver Liver The liver is the largest gland in the human body. The liver is found in the superior right quadrant of the abdomen and weighs approximately 1.5 kilograms. Its main functions are detoxification, metabolism, nutrient storage (e.g., iron and vitamins), synthesis of coagulation factors, formation of bile, filtration, and storage of blood. Liver: Anatomy; rarely, the brain Brain The part of central nervous system that is contained within the skull (cranium). Arising from the neural tube, the embryonic brain is comprised of three major parts including prosencephalon (the forebrain); mesencephalon (the midbrain); and rhombencephalon (the hindbrain). The developed brain consists of cerebrum; cerebellum; and other structures in the brain stem. Nervous System: Anatomy, Structure, and Classification
• Clinical presentation Presentation The position or orientation of the fetus at near term or during obstetric labor, determined by its relation to the spine of the mother and the birth canal. The normal position is a vertical, cephalic presentation with the fetal vertex flexed on the neck. Normal and Abnormal Labor:
  • Neonatal period or early infancy:
    • Typically presents with abdominal distension with bilateral flank masses 
    • Other associations: pulmonary hypoplasia Hypoplasia Hypoplastic Left Heart Syndrome (HLHS) and respiratory distress, spontaneous pneumothorax Pneumothorax A pneumothorax is a life-threatening condition in which air collects in the pleural space, causing partial or full collapse of the lung. A pneumothorax can be traumatic or spontaneous. Patients present with a sudden onset of sharp chest pain, dyspnea, and diminished breath sounds on exam. Pneumothorax, Potter’s syndrome, hypertension Hypertension Hypertension, or high blood pressure, is a common disease that manifests as elevated systemic arterial pressures. Hypertension is most often asymptomatic and is found incidentally as part of a routine physical examination or during triage for an unrelated medical encounter. Hypertension, impaired renal function, failure to thrive Failure to Thrive Failure to thrive (FTT), or faltering growth, describes suboptimal weight gain and growth in children. The majority of cases are due to inadequate caloric intake; however, genetic, infectious, and oncological etiologies are also common. Failure to Thrive, polyuria Polyuria Urination of a large volume of urine with an increase in urinary frequency, commonly seen in diabetes. Renal Potassium Regulation, polydipsia Polydipsia Excessive thirst manifested by excessive fluid intake. It is characteristic of many diseases such as diabetes mellitus; diabetes insipidus; and nephrogenic diabetes insipidus. The condition may be psychogenic in origin. Diabetes Insipidus, ESRD
  • Infants and children:
    • Typically has a mixed renal-hepatic presentation Presentation The position or orientation of the fetus at near term or during obstetric labor, determined by its relation to the spine of the mother and the birth canal. The normal position is a vertical, cephalic presentation with the fetal vertex flexed on the neck. Normal and Abnormal Labor
    • Often present with hepatosplenomegaly Hepatosplenomegaly Cytomegalovirus, signs of portal hypertension Portal hypertension Portal hypertension is increased pressure in the portal venous system. This increased pressure can lead to splanchnic vasodilation, collateral blood flow through portosystemic anastomoses, and increased hydrostatic pressure. There are a number of etiologies, including cirrhosis, right-sided congestive heart failure, schistosomiasis, portal vein thrombosis, hepatitis, and Budd-Chiari syndrome. Portal Hypertension (prominent periumbilical veins Veins Veins are tubular collections of cells, which transport deoxygenated blood and waste from the capillary beds back to the heart. Veins are classified into 3 types: small veins/venules, medium veins, and large veins. Each type contains 3 primary layers: tunica intima, tunica media, and tunica adventitia. Veins: Histology, thrombocytopenia Thrombocytopenia Thrombocytopenia occurs when the platelet count is < 150,000 per microliter. The normal range for platelets is usually 150,000-450,000/µL of whole blood. Thrombocytopenia can be a result of decreased production, increased destruction, or splenic sequestration of platelets. Patients are often asymptomatic until platelet counts are < 50,000/µL. Thrombocytopenia, and gastroesophageal varices), ascending cholangitis, choledochal cysts Cysts Any fluid-filled closed cavity or sac that is lined by an epithelium. Cysts can be of normal, abnormal, non-neoplastic, or neoplastic tissues. Fibrocystic Change
    • Renal manifestations may be absent or similar to those in the neonatal period.
• Diagnosis:
  • Prenatal ultrasound: 
    • Oligohydramnios Oligohydramnios Oligohydramnios refers to amniotic fluid volume less than expected for the current gestational age. Oligohydramnios is diagnosed by ultrasound and defined as an amniotic fluid index (AFI) of ‰¤ 5 cm or a single deep pocket (SDP) of < 2 cm in the 2nd or 3rd trimester. Oligohydramnios
    • Absence of urine Urine Liquid by-product of excretion produced in the kidneys, temporarily stored in the bladder until discharge through the urethra. Bowen Disease and Erythroplasia of Queyrat in the bladder Bladder A musculomembranous sac along the urinary tract. Urine flows from the kidneys into the bladder via the ureters, and is held there until urination. Pyelonephritis and Perinephric Abscess
  • Postnatal ultrasound:
    • Bilaterally enlarged, uniformly hyperechogenic kidneys Kidneys The kidneys are a pair of bean-shaped organs located retroperitoneally against the posterior wall of the abdomen on either side of the spine. As part of the urinary tract, the kidneys are responsible for blood filtration and excretion of water-soluble waste in the urine. Kidneys: Anatomy with poor corticomedullary differentiation and multiple cysts Cysts Any fluid-filled closed cavity or sac that is lined by an epithelium. Cysts can be of normal, abnormal, non-neoplastic, or neoplastic tissues. Fibrocystic Change
    • Hepatosplenomegaly Hepatosplenomegaly Cytomegalovirus with a hyperechoic Hyperechoic A structure that produces a high-amplitude echo (lighter grays and white) Ultrasound (Sonography) liver Liver The liver is the largest gland in the human body. The liver is found in the superior right quadrant of the abdomen and weighs approximately 1.5 kilograms. Its main functions are detoxification, metabolism, nutrient storage (e.g., iron and vitamins), synthesis of coagulation factors, formation of bile, filtration, and storage of blood. Liver: Anatomy and dilatation of the peripheral intrahepatic and main bile Bile An emulsifying agent produced in the liver and secreted into the duodenum. Its composition includes bile acids and salts; cholesterol; and electrolytes. It aids digestion of fats in the duodenum. Gallbladder and Biliary Tract: Anatomy ducts
  • Molecular genetic testing Genetic Testing Detection of a mutation; genotype; karyotype; or specific alleles associated with genetic traits, heritable diseases, or predisposition to a disease, or that may lead to the disease in descendants. It includes prenatal genetic testing. Myotonic Dystrophies confirms the diagnosis.
• Management:
  • Aggressive ventilatory support
  • Supportive treatment with the multidisciplinary team:
    • Antihypertensive medications ( ACE inhibitors ACE inhibitors Truncus Arteriosus)
    • Diuretics Diuretics Agents that promote the excretion of urine through their effects on kidney function. Heart Failure and Angina Medication for edema Edema Edema is a condition in which excess serous fluid accumulates in the body cavity or interstitial space of connective tissues. Edema is a symptom observed in several medical conditions. It can be categorized into 2 types, namely, peripheral (in the extremities) and internal (in an organ or body cavity). Edema
    • Osteopenia Osteopenia Osteoporosis management
    • Palliative unilateral/bilateral nephrectomy Nephrectomy Excision of kidney. Renal Cell Carcinoma
    • Dialysis Dialysis Renal replacement therapy refers to dialysis and/or kidney transplantation. Dialysis is a procedure by which toxins and excess water are removed from the circulation. Hemodialysis and peritoneal dialysis (PD) are the two types of dialysis, and their primary difference is the location of the filtration process (external to the body in hemodialysis versus inside the body for PD). Peritoneal Dialysis and Hemodialysis
    • Renal and/or hepatic transplantation
  • Pre-implantation genetic testing Genetic Testing Detection of a mutation; genotype; karyotype; or specific alleles associated with genetic traits, heritable diseases, or predisposition to a disease, or that may lead to the disease in descendants. It includes prenatal genetic testing. Myotonic Dystrophies with in vitro fertilization Fertilization To undergo fertilization, the sperm enters the uterus, travels towards the ampulla of the fallopian tube, and encounters the oocyte. The zona pellucida (the outer layer of the oocyte) deteriorates along with the zygote, which travels towards the uterus and eventually forms a blastocyst, allowing for implantation to occur. Fertilization and First Week in families with a history of ARPKD ARPKD Polycystic kidney disease (PKD) is an inherited genetic disorder leading to the development of numerous fluid-filled cysts in the kidneys. Autosomal recessive polycystic kidney disease is primarily characterized by cystic dilatations of the renal collecting ducts and intrahepatic bile duct dilatation with hepatic fibrosis. Autosomal Recessive Polycystic Kidney Disease (ARPKD)

Disorders of Renal Positioning

Renal ectopia and non-rotation

• Definition:
  • Renal ectopia: abnormal ascent of the kidneys Kidneys The kidneys are a pair of bean-shaped organs located retroperitoneally against the posterior wall of the abdomen on either side of the spine. As part of the urinary tract, the kidneys are responsible for blood filtration and excretion of water-soluble waste in the urine. Kidneys: Anatomy during embryonic development
  • Renal non-rotation: abnormal rotation Rotation Motion of an object in which either one or more points on a line are fixed. It is also the motion of a particle about a fixed point. X-rays of the kidneys Kidneys The kidneys are a pair of bean-shaped organs located retroperitoneally against the posterior wall of the abdomen on either side of the spine. As part of the urinary tract, the kidneys are responsible for blood filtration and excretion of water-soluble waste in the urine. Kidneys: Anatomy
• Epidemiology:
  • Incidence Incidence The number of new cases of a given disease during a given period in a specified population. It also is used for the rate at which new events occur in a defined population. It is differentiated from prevalence, which refers to all cases in the population at a given time. Measures of Disease Frequency of renal ectopia: 1 in 900 births
  • Incidence Incidence The number of new cases of a given disease during a given period in a specified population. It also is used for the rate at which new events occur in a defined population. It is differentiated from prevalence, which refers to all cases in the population at a given time. Measures of Disease Frequency of renal non-rotation: 1 in 2,000 autopsies
• Clinical presentation Presentation The position or orientation of the fetus at near term or during obstetric labor, determined by its relation to the spine of the mother and the birth canal. The normal position is a vertical, cephalic presentation with the fetal vertex flexed on the neck. Normal and Abnormal Labor:
  • Usually asymptomatic
  • May have a higher incidence Incidence The number of new cases of a given disease during a given period in a specified population. It also is used for the rate at which new events occur in a defined population. It is differentiated from prevalence, which refers to all cases in the population at a given time. Measures of Disease Frequency of UTI UTI Urinary tract infections (UTIs) represent a wide spectrum of diseases, from self-limiting simple cystitis to severe pyelonephritis that can result in sepsis and death. Urinary tract infections are most commonly caused by Escherichia coli, but may also be caused by other bacteria and fungi. Urinary tract infections (UTIs), urinary obstruction, or kidney stones Kidney stones Nephrolithiasis is the formation of a stone, or calculus, anywhere along the urinary tract caused by precipitations of solutes in the urine. The most common type of kidney stone is the calcium oxalate stone, but other types include calcium phosphate, struvite (ammonium magnesium phosphate), uric acid, and cystine stones. Nephrolithiasis
  • Ectopic kidney may be found in the pelvis Pelvis The pelvis consists of the bony pelvic girdle, the muscular and ligamentous pelvic floor, and the pelvic cavity, which contains viscera, vessels, and multiple nerves and muscles. The pelvic girdle, composed of 2 “hip” bones and the sacrum, is a ring-like bony structure of the axial skeleton that links the vertebral column with the lower extremities. Pelvis: Anatomy, the thorax, or the contralateral side. 
  • Blood supply is variable Variable Variables represent information about something that can change. The design of the measurement scales, or of the methods for obtaining information, will determine the data gathered and the characteristics of that data. As a result, a variable can be qualitative or quantitative, and may be further classified into subgroups. Types of Variables.
• Diagnosis:
  • Antenatal or postnatal renal ultrasound
  • Voiding cystourethrogram Voiding Cystourethrogram Urinary Tract Infections (UTIs) in Children (VCUG) and serial serum creatinine may be necessary if there is evidence of kidney injury.

Kidney fusion

• Definition: fusion of the lower poles of the kidney (horseshoe kidney)
• Epidemiology:
  • Incidence Incidence The number of new cases of a given disease during a given period in a specified population. It also is used for the rate at which new events occur in a defined population. It is differentiated from prevalence, which refers to all cases in the population at a given time. Measures of Disease Frequency of 1 in 400–500 births 
  • Associated with Turner’s syndrome
  • Wilms’ tumor Tumor Inflammation, stone disease, hydronephrosis Hydronephrosis Hydronephrosis is dilation of the renal collecting system as a result of the obstruction of urine outflow. Hydronephrosis can be unilateral or bilateral. Nephrolithiasis is the most common cause of hydronephrosis in young adults, while prostatic hyperplasia and neoplasm are seen in older patients. Hydronephrosis, and MCDK are more common in horseshoe kidneys Horseshoe Kidneys Imaging of the Urinary System.
• Clinical presentation Presentation The position or orientation of the fetus at near term or during obstetric labor, determined by its relation to the spine of the mother and the birth canal. The normal position is a vertical, cephalic presentation with the fetal vertex flexed on the neck. Normal and Abnormal Labor and management:
  • Hydronephrosis Hydronephrosis Hydronephrosis is dilation of the renal collecting system as a result of the obstruction of urine outflow. Hydronephrosis can be unilateral or bilateral. Nephrolithiasis is the most common cause of hydronephrosis in young adults, while prostatic hyperplasia and neoplasm are seen in older patients. Hydronephrosis is a common finding (80% of cases).
  • Many patients Patients Individuals participating in the health care system for the purpose of receiving therapeutic, diagnostic, or preventive procedures. Clinician–Patient Relationship are asymptomatic and require no treatment.