Alport Syndrome and Thin Basement Membrane Nephropathy: Causes, Symptoms, Diagnosis & Treatment

Alport Syndrome and Thin Basement Membrane Nephropathy: Causes, Symptoms, Diagnosis & Treatment

pediagenosis    September 07, 2026   

HEREDITARY NEPHRITIS (ALPORT SYNDROME)/THIN BASEMENT MEMBRANE NEPHROPATHY

Hereditary nephritis (HN, also known as Alport syndrome) and thin basement membrane nephropathy (TBMN) are both inherited disorders that feature structural defects in type IV collagen, an integral component of the glomerular basement membrane. Both conditions present in childhood with persistent microscopic hematuria.

HN is rare, affecting 1 in 50,000 individuals, and often progresses to end stage renal disease (ESRD). TBMN, in contrast, affects 1 in 20 to 100 individuals and typically does not have a progressive course.

Extracorporeal Shock Wave Lithotripsy (ESWL): Procedure, Indications, Risks, Recovery & Success Rate

Extracorporeal Shock Wave Lithotripsy (ESWL): Procedure, Indications, Risks, Recovery & Success Rate

pediagenosis    July 28, 2026    Comment   

Plate 10-12

EXTRACORPOREAL SHOCK WAVE LITHOTRIPSY

Extracorporeal shock wave lithotripsy (ESWL) is a noninvasive procedure for the treatment of nephrolithiasis. In this procedure, acoustic shock waves are generated external to the patient and focused on the renal stones, which are fragmented into small pieces that can be spontaneously passed in the urine. The skin and surrounding renal parenchyma receive a much smaller dose of energy and therefore remain largely unharmed.

Renal Pelvis, Ureter, And Bladder

Renal Pelvis, Ureter, And Bladder

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Renal Pelvis, Ureter, And Bladder

Renal Pelvis

The entire urine collecting system is lined by a sheet of transitional epithelium known as urothelium. In the renal pelvis, the urothelial cells are two or three layers thick. The most superficial cells are larger than the others and send projections down over the lateral surfaces of the cells beneath them, sometimes having an umbrella-like appearance. These “umbrella cells” have abundant eosinophilic cytoplasm and may be binucleate. Underneath the umbrella cells are smaller intermediate cells and basal cells.

MEMBRANOPROLIFERATIVE GLOMERULONEPHRITIS

MEMBRANOPROLIFERATIVE GLOMERULONEPHRITIS

pediagenosis    September 30, 2023   

MEMBRANOPROLIFERATIVE GLOMERULONEPHRITIS

Membranoproliferative glomerulonephritis (MPGN) is a pattern of glomerular disease that can occur either as an idiopathic, primary phenomenon or secondary to numerous systemic conditions. It is a rare disorder, and its incidence appears to be decreasing, particularly in the developed world.

SIMPLE CYSTS

SIMPLE CYSTS

pediagenosis    January 29, 2023    Comment   

SIMPLE CYSTS

Renal cysts sometimes  occur as part of an  inherited disease, such as polycystic kidney disease (see Plate 2-15), nephronophthisis/medullary cystic kidney disease (see Plate 2-18), tuberous sclerosis, or von Hippel-Lindau syndrome. In clinical practice, however, most renal cysts are sporadic and incidentally discovered during abdominal imaging performed for some other indication. Such cysts, known as “simple cysts,” are very common among adults over the age of 50 and rarely cause symptoms.

RENAL DYSPLASIA

RENAL DYSPLASIA

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RENAL DYSPLASIA

Renal dysplasia refers to abnormal differentiation and organization of the renal parenchyma. The epidemiology is not known, since many patients with mild dysplasia are asymptomatic. Most cases appear to be sporadic.

RENAL HYPOPLASIA

RENAL HYPOPLASIA

pediagenosis    January 29, 2023    Comment   

RENAL HYPOPLASIA

A normal kidney contains approximately 600,000 to 1,400,000 nephrons. Renal hypoplasia occurs when a kidney possesses such a significant reduction in its nephron endowment that it weighs less than half of the standardized mean. Renal hypoplasia can occur in association with otherwise normal renal development; in combination with renal dysplasia (i.e., hypodysplasia), in which case the renal parenchyma appears undifferentiated and disorganized; or as a secondary effect of conditions that cause renal atrophy or involution, such as chronic reflux nephropathy secondary to vesicoureteral reflux.

RETROCAVAL URETER

RETROCAVAL URETER

pediagenosis    May 09, 2021    Comment   

RETROCAVAL URETER

The normal right ureter runs lateral to the inferior vena cava (IVC). A retrocaval (also known as circumcaval) ureter is a congenital anomaly in which the right ureter passes posterior to the IVC, emerges between the IVC and aorta, and then recrosses the iliac vessels anteriorly before inserting into the bladder. The portion of the ureter lying posterior to the IVC becomes obstructed, leading to dilation of the more proximal parts of the urine collecting system. This obstruction can become symptomatic during childhood or, more commonly, adulthood. The exact incidence of retrocaval ureter is uncertain but is likely 1 : 1000 to 1 : 1500, with males affected more often than females.

Embryology

A retrocaval ureter reflects abnormal development not of the ureter, but rather of the IVC. In the fourth week of gestation, the cardinal system of veins drains the body of the developing embryo. This system is divided into the two major branches: the anterior cardinal veins, which drain the superior portion of the embryo; and the posterior cardinal veins, which drain the inferior portion of the embryo. These join to form a common cardinal vein, which drains into the sinus venosus. Meanwhile, the vitelline veins, the precursors of the portal system, drain blood from the yolk sac to the sinus venosus. Finally, the umbilical veins carry oxygenated blood from the placenta to the embryo.

VESICOURETERAL REFLUX

VESICOURETERAL REFLUX

pediagenosis    May 09, 2021    Comment   

VESICOURETERAL REFLUX

Vesicoureteral reflux (VUR) is defined as the retrograde flow of urine from the bladder into the ureter and, in many cases, the renal pelvicalyceal system. This condition is considered problematic because it facilitates propulsion of bacteria toward the kidneys, which can cause recurrent pyelonephritis, renal scarring, and eventual renal dysfunction.

VUR is generally diagnosed during childhood. The overall incidence has been difficult to estimate because the condition is often undetected and frequently resolves with age. It has been reported, however, that 70% of infants who have urinary tract infections (UTIs) also have reflux. Although VUR is more common in male infants, it is more common in females after the first year of life.

Pathogenesis

Normal ureteral continence relies on a valve mechanism formed as the ureter courses between the bladder mucosa and detrusor muscle before terminating at the ureteric orifice. When the bladder contracts, compression of the intramural segment of each ureter prevents the retrograde flow of urine.

URETERAL DUPLICATION

URETERAL DUPLICATION

pediagenosis    May 09, 2021    Comment   

URETERAL DUPLICATION

As shown in Plate 2-1, the ureteric buds appear toward the caudal ends of the mesonephric ducts at 5 weeks of gestation. Each bud grows into its adjacent mass of metanephric mesenchyme, the precursor of the kidney, to form a ureter, a pelvicalyceal system, and collecting ducts.

Ureteral duplication results from abnormalities of the ureteric bud. It is one of the most common congenital malformations of the urinary tract, with an incidence of approximately 1 in 125. Duplication is more often unilateral than bilateral, and more often incomplete than complete. There does not appear to be any predilection for a particular side.

Complete Ureteral Duplication

In complete ureteral duplication, the kidney is drained by two distinct renal pelves, each of which leads to a ureter with its own insertion into the bladder. This anomaly occurs when a single mesonephric duct sprouts two ureteric buds, each of which induces a separate portion of the adjacent metanephric mesenchyme. The more cranial of the two ureteric buds becomes the collecting system of the upper pole, while the more caudal of the ureteric buds becomes the collecting system of the lower pole. Because of the manner in which the mesonephric ducts exstrophy into the bladder; however, the upper pole ureter terminates at an orifice located inferior and medial to that of the lower pole ureter. In many cases, the upper pole ureter has an ectopic site of termination, reflecting an especially cranial position of the ureteric bud from which it originated. The consistent pattern of ureteral crossing seen in a duplicated system, where the ureter serving the upper pole terminates inferior to the ureter serving the lower pole, is known as the Weigert-Meyer law.

ECTOPIC URETER

ECTOPIC URETER

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ECTOPIC URETER

An ectopic ureter terminates caudal to the normal position in the trigone. Although a ureter that terminates cranial to the normal position is clearly abnormal, and is often associated with vesicoureteral reflux (see Plate 2-21), the term “ectopic” is generally not applied.

In males, the most common sites of ureteral ectopia are the prostatic urethra and seminal glands (vesicles), whereas in females, the most common sites are the urethra and vagina. The incidence of ectopic ureter is not known with precision, although one series estimated it at 1 in 1900. The condition is at least twice as common in females than in males, for unknown reasons.

Pathogenesis

As described on page 30, the ureteric buds appear toward the caudal ends of the mesonephric ducts during the fifth week of gestation. Each ureteric bud grows into the adjacent mass of metanephric mesenchyme, the precursor of the kidney, to form a ureter, a pyelocalyceal system, and collecting ducts.

URETEROCELE

URETEROCELE

pediagenosis    May 09, 2021    Comment   

URETEROCELE

A ureterocele is a cystic dilation of the terminal ureter that balloons into the bladder. About 80% of ureteroceles are associated with ureteral duplication, occurring in the ureter that drains the upper pole (see Plate 2-23). About 10% of ureteroceles are bilateral.

A ureterocele is known as “intravesical” if it extends only into the bladder, and “ectopic” if it reaches the bladder neck or urethra. The orifice is termed “stenotic” if a pinpoint opening is seen and “sphincteric” if it lies distal to the bladder neck. If the orifice possesses both of these characteristics, it is known as “sphincterostenotic.”

The overall incidence of ureteroceles is difficult to estimate because many small ureteroceles are not identified. The clinical incidence of ureterocele, however, appears to range from 1 in 5000 to 1 in 12,000. In contrast, one autopsy series reported the incidence to be as high as 1 in 500. For unknown reasons, there is a female : male ratio of 4 : 1, and most cases occur in whites.

Pathogenesis

The embryologic basis for ureteroceles is unknown, but several theories have been proposed. One is that ureteroceles result from incomplete breakdown of the Chwalla membrane, a normally transient structure that divides the ureter from the bladder. Although this theory explains ureteroceles with stenotic orifices, it does not explain those with patent orifices. Another theory is that the terminal ureter is lined with an inadequate number of smooth muscle cells, which causes it to become dilated.

URETERAL DUPLICATION

URETERAL DUPLICATION

pediagenosis    May 09, 2021    Comment   

PRUNE BELLY SYNDROME

The prune belly syndrome (PBS, also known as Eagle-Barrett or triad syndrome) is a rare, congenital disorder that occurs almost exclusively in males. Its major features include deficient abdominal wall musculature, bilateral cryptorchidism, and urinary tract anomalies that include renal dysplasia, hydronephrosis, and dilation of the ureters and bladder.

PBS occurs in approximately 3.5 per 100,000 live male births. Blacks are at increased risk and Hispanics are at decreased risk when compared with the overall population. There are rare reports of females born with deficient abdominal wall musculature and urinary tract anomalies, although their ovaries are generally normal.

Appearance of abdominal wall in prune belly syndrome

Pathogenesis

The pathogenesis of PBS remains poorly understood. One theory argues that early obstruction of the bladder outlet causes dilation of the bladder, ureters, and then renal pelves. Such dilation is posited to cause an increase in intraabdominal pressure that results in atrophy of the abdominal wall musculature and inhibition of normal testicular descent. This hypothesis, however, is challenged by the fact that many patients with PBS do not have an anatomic outlet obstruction, and that many patients who do have such obstructions (such as those with posterior urethral valves) do not have PBS.

ANOMALIES OF THE URACHUS

ANOMALIES OF THE URACHUS

pediagenosis    April 27, 2021    Comment   

ANOMALIES OF THE URACHUS

As described on page 32, the urorectal septum partitions the cloaca into the primitive urogenital sinus and the rectum. The urogenital sinus, which gives rise to the bladder, is initially continuous with the allantois, a tube that extends into the connecting stalk (see Plate 2-4 for an illustration). As the bladder matures and descends into the pelvis, however, the allantois narrows to form a thick, epithelial-lined tube known as the urachus. Normally the urachus regresses into a fibrous cord, known as the median umbilical ligament. For uncertain reasons, however, this normal regression process sometimes fails, resulting in a persistent urachus that is either partially or completely patent. Because many urachal anomalies are undiagnosed, their overall incidence is unknown.

Presentation And Diagnosis

An entirely patent urachus, which permits drainage of urine from the bladder to the umbilicus, accounts for about half of urachal anomalies. It typically presents during the neonatal period as dribbling of fluid from the umbilicus. The fluid leakage may increase in response to bladder contraction during either purposeful voiding or other increases in intraabdominal pressure, such as during crying or straining. Umbilical edema and delayed healing of the umbilical stump may also be noted. The diagnosis can be confirmed with either sonographic evaluation of the bladder or with more invasive studies, such as a retrograde fistulogram or voiding cystourethrogram (VCUG).

BLADDER DUPLICATION AND SEPTATION

BLADDER DUPLICATION AND SEPTATION

pediagenosis    April 27, 2021    Comment   

BLADDER DUPLICATION AND SEPTATION

Bladder duplication and septation are very rare congenital abnormalities, with only a small number of cases reported in the scientific literature. In either duplication or septation, division of the bladder may be complete or incomplete, and it may occur in the coronal or sagittal plane.

In duplication, each half of the divided bladder receives its own ureter and possesses its own full thickness wall. In incomplete duplication, the two halves typically unite above the level of the bladder neck and then drain together into a single urethra. In complete duplication, the two halves remain separate to the level of the bladder neck and can even drain into two independent urethras, each with its own external meatus. In some cases, however, one of the bladder halves lacks a urethral component, resulting in outlet obstruction and ipsilateral renal abnormalities.

In septation, a fibromuscular wall divides the bladder into separate compartments. In contrast to duplication, septation produces two compartments that share a common wall. Like duplication, septation can be incomplete or complete, depending on how far the wall extends toward the bladder neck. Septation, however, is not associated with duplication of the urethra, and thus both compartments must be in open communication with the urethra. In some cases, however, fusion of the septum with the bladder neck causes one compartment to lose access to the urethra, resulting in obstruction.

Bladder duplication and septation are frequently associated with other anomalies, especially in the genitourinary system. For example, vesicoureteral reflux may be seen on one or both sides, resulting in hydronephrosis if severe. Likewise, one or both of the bladder components may lack a normal continence mechanism. If there is complete duplication of the bladder, concurrent duplication of the external genitalia may be seen as well. Less often, duplication may also occur in the lower gastrointestinal tract or spine.

Pathogenesis

The embryologic basis for these various anomalies is unknown. It is possible that complete duplication of the bladder and adjacent organ systems reflects partial twinning of the embryonic tail early in gestation. In contrast, isolated defects of the bladder may reflect abnormalities during cloacal septation (see Plate 2-4).

POSTERIOR URETHRAL VALVES

POSTERIOR URETHRAL VALVES

pediagenosis    April 27, 2021    Comment   

POSTERIOR URETHRAL VALVES

Posterior urethral valves (PUVs) are abnormal mucosal folds in the distal urethra that arise during fetal development and interfere with the normal outflow of urine. They are the most common cause of congenital urinary tract obstruction, occurring in 1 in 8000 to 1 in 25,000 live births, and are seen only in males. Even if treated early on, the obstruction associated with PUVs frequently causes severe, often permanent urinary tract abnormalities.

The traditional classification system describes two major types of valves, which vary both in morphology and relative frequency. Type I valves, said to account for more than 95% of cases, begin as a mucosal ridge from the seminal colliculus, which extends distally and divides into two flaps that fuse with the walls of the membranous urethra. There is typically incomplete fusion of the flaps with the anterior wall of the urethra, and there is a small opening in the membrane near the posterior wall of the urethra, adjacent to the seminal colliculus. Type III valves, in contrast, are said to account for about 5% of cases and resemble disklike membranes that span the entire circumference of the membranous urethra and contain a small central opening. (Type II valves, extending from the seminal colliculus toward the bladder neck, are no longer thought to be actual valves but rather bladder neck hypertrophy, which accompanies any distal urethral obstruction.) More recent work, however, suggests that in fact all PUVs are membranous, originally resembling type III valves, and that type I valves are actually an artifact of urethral instrumentation, which divides the single membrane into two flaps.

Pathogenesis

The male urethra is divided into four portions, the precursors of which become evident early in development. The segments include the prostatic urethra, which extends from the bladder neck to the urogenital diaphragm; the membranous urethra, which traverses the diaphragm; the bulbous urethra, which extends from the urogenital diaphragm to the penoscrotal junction; and the spongy (penile) urethra, which continues through the penile shaft until the urethral meatus.

BASIC FUNCTIONS AND HOMEOSTASIS

BASIC FUNCTIONS AND HOMEOSTASIS

pediagenosis    April 27, 2021    Comment   

BASIC FUNCTIONS AND HOMEOSTASIS

Blood enters the kidneys in a series of branching vessels that give rise to afferent arterioles. Each afferent arteriole leads to a tuft of glomerular capillaries. Plasma and small, non–protein bound solutes are filtered across the walls of the glomerular capillaries into Bowman’s space, the initial portion of the nephron. From there, the filtrate is conveyed through the remaining segments of the nephron which include the proximal tubule, thin limb, distal tubule, and collecting duct before being excreted in the final urine.

In the various segments of the renal tubules, there is extensive exchange of material with the surrounding capillaries. Such exchange is known as “reabsorption” if materials are transferred from the tubular lumen to the capillaries and/or interstitium, and as “secretion” if they are transferred in the opposite direction.

By continuously adjusting the contents of blood, the kidneys make critical contributions to the maintenance of fluid and salt homeostasis, as well as to the excretion of unwanted chemicals and waste products. In addition, the kidneys contribute to the regulation of arterial pressure, acid-base status, erythropoiesis, and vitamin D synthesis.

Mechanisms Of Homeostasis

To maintain homeostasis, the kidneys must adjust their retention or excretion of fluid and filtered solutes so that, in cooperation with other excretory organs (lungs, skin, bowel), overall output equals intake.

RENAL HANDLING OF SODIUM AND CHLORIDE

RENAL HANDLING OF SODIUM AND CHLORIDE

pediagenosis    April 27, 2021    Comment   

RENAL HANDLING OF SODIUM AND CHLORIDE

Sodium and chloride are both predominantly extracellular ions. In plasma, the sodium concentration is maintained between 135 to 145 mmol/L, whereas the chloride concentration is maintained between 98 to 108 mmol/L.

Both sodium and chloride are freely filtered at the glomerulus and almost completely (approximately 99%) reabsorbed. 60% of the filtered load is reabsorbed in the proximal tubule; 30% is reabsorbed in the thick ascending limb; 7% is reabsorbed in the distal convoluted tubule; and 2% to 3% is reabsorbed in the connecting tubule and collecting duct.

 

NEPHRON SITES OF SODIUM REABSORPTION

Mechanisms Of Transport

In all portions of the nephron, basolateral Na⁺/K⁺ ATPases pump sodium from the tubular epithelial cells into the interstitium. As a result, intracellular sodium concentrations remain low, establishing a gradient for transcellular reabsorption.

RENAL HANDLING OF POTASSIUM

RENAL HANDLING OF POTASSIUM

pediagenosis    April 13, 2021    Comment   

RENAL HANDLING OF POTASSIUM

Potassium is a primarily intracellular ion, with skeletal muscle alone containing more than 75% of the body’s total load. Less than 2% of this load is found in the extracellular fluid. The normal plasma concentration is between 3.5 and 5.0 mmol/L.

Extracellular potassium is freely filtered at the glomerulus. A large fraction of the filtered load is consistently reabsorbed along the proximal tubule (66%) and loop of Henle (25%). In the distal tubule, however, there is a variable degree of reabsorption or secretion that depends on input from homeostatic feedback mechanisms. In this manner, the kidneys make a crucial contribution to plasma potassium concentration.

Transport Mechanisms

Proximal Tubule. In the proximal tubule, potassium is reabsorbed along a paracellular route. A chemical gradient is established as the reabsorption of sodium and water concentrates potassium in the tubular fluid. An electrical gradient is established as chloride is reabsorbed, which leaves a positive charge in the late part of the proximal tubule. There is some evidence that potassium also undergoes some transcellular reabsorption in this segment, but the details and relative importance of this pathway remain unknown.

RENAL HANDLING OF CALCIUM, PHOSPHATE, AND MAGNESIUM

RENAL HANDLING OF CALCIUM, PHOSPHATE, AND MAGNESIUM

pediagenosis    April 12, 2021    Comment   

RENAL HANDLING OF CALCIUM, PHOSPHATE, AND MAGNESIUM

Calcium

More than 98% of total body calcium is in bones, whereas the remainder is located in intracellular and extracellular fluid. Normal plasma concentrations, which range from 8.8 to 10.3 mg/dL, are maintained by the actions of PTH, 1,25-hydroxy vitamin D, and calcitonin on bones, the gastrointestinal tract, and the kidneys.

About half of the extracellular calcium load is in an active, ionized form, whereas the remainder complexes with albumin and other anions. The ionized calcium is freely filtered at the glomerulus, and normally almost all of it is reabsorbed.

In the proximal tubule, 50% to 60% of the filtered load is reabsorbed along a paracellular route. A chemical gradient is established as sodium and water are reabsorbed, concentrating calcium in the tubular fluid. Meanwhile, an electrical gradient is established by the paracellular reabsorption of chloride, which leaves a positive charge in the lumen. Specialized tight junction proteins, such as claudin-2, may form a cation-specific paracellular pathway.

In the thick ascending limb, 15% of the filtered load is reabsorbed along a paracellular route. An electrical gradient, formed secondary to K⁺ recycling, drives this process. Claudin-16, another tight junction protein, is an important component of this paracellular pathway, and mutations are associated with familial hypomagnesemia with hypocalciuria.

In the distal convoluted and connecting tubules, 10% to 15% of the filtered load is reabsorbed along a transcellular route. Calcium crosses the apical membrane through TRPV5 channels, binds to calbindin, then exits the basolateral membrane on the NCX1 Na⁺/Ca2⁺ exchanger and, to a lesser degree, a Ca2+ ATPase (PMCA).

The collecting duct makes an unknown, but likely minor, contribution to calcium reabsorption.

Hypocalcemia triggers release of PTH, which has numerous effects on renal function. In the proximal tubule, it inhibits the NHE-3 Na⁺/H⁺ exchanger, reducing the gradient for paracellular calcium reabsorption. (This seemingly paradoxical effect allows PTH to increase phosphate excretion, as discussed later.) In the distal nephron, however, it up-regulates the apical TRPV5 calcium channel, causing a net increase in calcium reabsorption. Meanwhile, hypercalcemia both suppresses PTH release and directly inhibits calcium reabsorption. In the thick ascending limb, for example, the increased load of reabsorbed calcium activates a basolateral calcium-sensing receptor (CaSR), which then inhibits NKCC2 transporters and ROM-K channels, reducing the electrical gradient for calcium reabsorption.

Finally, acidosis inhibits the TRPV5 calcium channel, whereas alkalosis has the opposite effect.

RENAL HANDLING OF CALCIUM AND PHOSPHATE

Phosphate

About 85% of total body phosphate is stored in bones, 14% in soft tissues, and 1% in extracellular fluid. Normal plasma concentrations, which range from 3 to 4.5 mg/dL, are maintained by the actions of PTH, 1,25-hydroxyvitamin D, and phosphatonins on the parathyroid glands, bones, gastrointestinal tract, and kidneys.