Cystic Diseases of the Kidney, Obstructive Uropathy, Renal Stones and Tumors

Hereditary, developmental, and acquired disorders

What are the three categories of renal cystic diseases mentioned in the sources?

ESRD

Adult polycystic kidney disease is a major cause of what chronic condition?

Malignant tumors

Renal cysts can occasionally be confused with what other type of growth?

Autosomal dominant

What is the inheritance pattern of adult polycystic kidney disease?

Polycystin-1

What is the 460-kD integral membrane protein encoded by the PKD1 gene?

PKD1

Which gene mutation accounts for about 85 percent of adult polycystic kidney disease cases?

16p13.3

On which chromosome is the PKD1 gene located?

PKD2

Which gene is located on chromosome 4q21 and accounts for about 15 percent of polycystic cases?

Polycystin-2

What is the product of the PKD2 gene?

Ca2+ permeable cation channel

What is the primary function of polycystin-2?

Somatic cells of the kidney

In ADPKD, the second nonfunctional allele of the involved genes is acquired where?

Fourth or fifth decade

Renal function in ADPKD is typically retained until what age?

Bilateral

Is adult polycystic kidney disease typically unilateral or bilateral?

Multicystic dysplasia

What condition do unilateral cases of reported ADPKD likely represent?

Primary cilium

What nonmotile 2 to 3 micrometer long hairlike organelle is central to the favored hypothesis of cyst formation?

Mechanosensor

What is the functional role of the apical cilia in the kidney tubule?

Cilia centrosome complex

What complex is placed at the center of the pathogenesis of polycystic disease?

Fluid flow

Cilia can induce a flux of which ion in cultured kidney epithelial cells?

Ca2+

A loss of the polycystin complex leads to a disruption of the intracellular levels of which ion?

Cellular proliferation, apoptosis, and secretory functions

Disruption of calcium signaling impacts which three downstream cellular events?

Epithelial cells lining the cysts

The increase in calcium is thought to stimulate proliferation and secretion from which cells?

Interstitial fibrosis

Inflammation and altered interactions with the ECM contribute to cyst formation and what other chronic change?

4 kg

What is the maximum weight reported for a single ADPKD kidney in the sources?

3 to 4 cm

What is the maximum diameter of cysts typically seen on the external surface of an ADPKD kidney?

Functioning nephrons

What does microscopic examination reveal dispersed between ADPKD cysts?

Renal insufficiency

Many ADPKD patients remain asymptomatic until what clinical finding announces the disease?

Renal colic

The excretion of blood clots in polycystic patients can cause what type of pain?

Insidious onset of hematuria

Besides pain, how does ADPKD occasionally begin?

Proteinuria and polyuria

Name two features of progressive chronic kidney disease seen in ADPKD patients.

Rarely more than 2 g/day

What is the typical limit for proteinuria in ADPKD?

PKD2

Mutations in which gene tend to be associated with an older age at onset and later development of renal failure?

Blacks, males, and hypertension

Name three factors that accelerate the progression of ADPKD.

Berry aneurysms

What intracranial vascular anomaly is found in 4 to 10 percent of individuals with ADPKD?

Circle of Willis

Where do intracranial berry aneurysms typically arise?

Polycystic liver disease

What extrarenal congenital anomaly is found in about 40 percent of ADPKD patients?

Biliary epithelium

From which structures are the cysts in polycystic liver disease derived?

Mitral valve prolapse

What cardiac valvular anomaly occurs in 20 to 25 percent of polycystic patients?

Radiologic imaging

How is the diagnosis of polycystic kidney disease made?

Coronary or hypertensive heart disease

What causes death in about 40 percent of adult ADPKD patients?

Ruptured berry aneurysm

What vascular catastrophe accounts for 15 percent of deaths in ADPKD patients?

Autosomal recessive

What is the inheritance pattern of childhood polycystic kidney disease?

Perinatal, neonatal, infantile, and juvenile

What are the four subcategories of ARPKD?

Renal failure

Infants with ARPKD might succumb rapidly to what condition?

PKHD1

Which gene mutation causes most cases of autosomal recessive polycystic kidney disease?

6p21-p23

Where does the PKHD1 gene map on the chromosome?

Fibrocystin

What is the 447-kD integral membrane protein encoded by PKHD1?

Primary cilium

Like polycystins, fibrocystin is localized to which cellular structure?

Compound heterozygotes

The vast majority of ARPKD patients inherit a different mutant allele from each parent, making them what?

Spongelike

What is the characteristic gross appearance of the cut section of an ARPKD kidney?

Collecting ducts

The uniform lining of cuboidal cells in ARPKD cysts reflects their origin from which structure?

Congenital hepatic fibrosis

What hepatic injury is characterized by periportal fibrosis and biliary ductule proliferation in ARPKD patients who survive infancy?

Portal hypertension and splenomegaly

Congenital hepatic fibrosis can lead to which two clinical concerns in older children?

Inversin

What protein mediates left-right patterning during embryogenesis and is associated with ARPKD?

Medullary sponge kidney

What term describes multiple cystic dilations of the medullary collecting ducts?

Radio-graphically

How is medullary sponge kidney usually discovered?

Normal

What is the status of renal function in a typical medullary sponge kidney patient?

Nephronophthisis

Which medullary cystic disease is almost always associated with renal dysfunction?

Corticomedullary junction

Where are cysts concentrated in the nephronophthisis disease complex?

Distal tubules

Initial injury in nephronophthisis probably involves which structures?

Cortical tubulointerstitial damage

What is the specific cause of renal insufficiency in nephronophthisis?

Familial juvenile nephronophthisis

What is the most common variant of the nephronophthisis complex?

Renal-retinal dysplasia

What variant of nephronophthisis is accompanied by ocular lesions?

Autosomal recessive

What is the inheritance pattern for familial forms of nephronophthisis?

Polyuria and polydipsia

What are the first two presenting symptoms in children with nephronophthisis?

Concentrating ability

Polyuria in nephronophthisis reflects a defect in which renal function?

5 to 10 years

What is the expected timeline for progression to ESRD in nephronophthisis?

NPHP1 to NPHP11

Which gene loci encode proteins called nephrocystins?

Ciliopathy

What general term describes diseases caused by mutations in genes related to cilia or basal bodies?

Contracted granular surfaces

In gross morphology, what is the surface appearance of a kidney with nephronophthisis?

Multicystic renal dysplasia

Which sporadic disorder involves irregular, multicystic kidneys and islands of undifferentiated mesenchyme?

Islands of cartilage

What specific histological feature is characteristic of multicystic renal dysplasia?

Ureteropelvic obstruction

Most cases of renal dysplasia are associated with what type of urinary tract anomaly?

Surgical removal

What is the treatment for unilateral multicystic renal dysplasia?

Prolonged dialysis

Acquired renal cystic disease occurs in patients with ESRD who have undergone what?

Calcium oxalate crystals

What crystals are often found in the lining of acquired renal cysts?

100-fold

Acquired renal cystic disease increases the risk of renal cell carcinoma by how much?

Cortical

Simple cysts most commonly involve which part of the kidney?

1 to 5 cm

What is the typical size range for simple cysts?

Avascular

What radiographic signal do simple cysts give during imaging studies?

Hydronephrosis

What term describes permanent renal atrophy caused by unrelieved urinary tract obstruction?

Posterior urethral valves

Name a common congenital cause of urinary tract obstruction.

Calculi, BPH, and tumors

List three common acquired causes of obstructive uropathy.

Functional or neurogenic disorders

What type of urinary obstruction results from spinal cord damage or diabetic nephropathy?

Diffusion into renal interstitium

Why does glomerular filtration persist for some time even with complete obstruction?

Impaired concentrating ability

What is the initial tubular functional alteration caused by obstruction?

Postobstructive diuresis

What massive event can occur after the relief of a complete urinary tract obstruction?

Unilateral

Are 80 percent of kidney stones unilateral or bilateral?

Supersaturation

What is the most important determinant for the formation of renal calculi?

Calcium oxalate or phosphate

About 70 percent of renal stones are composed of which chemicals?

Struvite stones

Which stone type makes up about 15 percent of cases and is associated with infection?

Magnesium ammonium phosphate

What is the chemical composition of struvite stones?

Urea-splitting bacteria

Struvite stones form after infections by what type of bacteria?

Proteus and staphylococci

Name two bacteria capable of splitting urea into ammonia.

Alkaline

Urea splitting results in what type of urine pH?

Staghorn calculi

What term describes large stones that create a cast of the pelvic and calyceal system?

Uric acid stones

Which stone type is common in patients with gout or leukemias?

Below 5.5

A tendency to excrete urine with what pH level predisposes to uric acid stones?

Radiolucent

What is the radiographic appearance of uric acid stones compared to calcium stones?

Cystine stones

Which stone type is caused by genetic defects in renal amino acid reabsorption?

Nephrocalcin

What glycoprotein is an inhibitor of crystal formation in urine?