Kidney Cystic Diseases

• Cystic diseases of the kidney are a heterogeneous group, comprising hereditary, developmental (but non-hereditary), and acquired disorders.
• Cystic diseases are common and may present diagnostic challenges for clinicians, radiologists, and pathologists.
• They are major causes of chronic renal failure (CRF) and can sometimes be mistaken for malignant tumors.

Simple Cysts

• Simple cysts are very common acquired lesions found in about 50% of people over 50 years old.
• They are typically incidental findings at autopsy and rarely produce clinical symptoms unless large.
• Cysts can be single or multiple and usually involve the cortex, commonly measuring 1-5cm in diameter.
• Simple cysts are translucent, lined by a gray, glistening, smooth membrane, and filled with clear fluid.
• Histologically, the membrane is composed of a single layer of cuboidal or flattened cuboidal epithelium, which may be atrophic
• Simple cysts may need differentiation from kidney tumors.

Dialysis-Associated Acquired Cysts

• Dialysis-associated acquired cysts manifest as multiple cortical and medullary cysts.
• The cysts occur in the kidneys of patients with end-stage renal disease undergoing long-term dialysis.
• After 5 years of dialysis, more than 75% of patients develop bilateral cystic kidneys.
• Cysts are initially lined by flat to cuboidal epithelium.
• Adenoma or adenocarcinoma may arise in the walls of cysts

Polycystic Kidney Diseases (PKD)

• Polycystic kidney diseases are a heterogenous group of congenital and acquired disorders
• PKD is characterized by distortion of the renal parenchyma by numerous cysts.
• Types of PKD include autosomal dominant, autosomal recessive, and nephronophthisis-medullary cystic disease complex.

Autosomal Dominant Polycystic Kidney Disease (ADPKD)

• ADPKD was previously called adult polycystic kidney disease.
• The term "adult" is inappropriate because ADPKD can manifest at any age.
• ADPKD is the most common monogenic renal disorder and is potentially fatal.
• It affects 1 in 400 to 1 in 1000 persons in the U.S.
• ADPKD accounts for 5-10% of cases of CRF
• About 50% of patients eventually develop end-stage renal failure.
• ADPKD is the 3rd leading cause of ESRD in the U.S., following diabetes and hypertension.

ADPKD Pathogenesis

• ADPKD is usually inherited as an autosomal dominant trait, and spontaneous mutations may occur.
• It is genetically heterogeneous.
• In 85% of cases, mutations are present in the PKD-1 gene on chromosome 16p.
• Defects in cell-cell interactions can cause alterations in growth, differentiation, and matrix production by epithelial cells, leading to cyst formation.
• The PKD-2 gene is implicated in 15% of cases; it resides on chromosome 4 and encodes polycystin-2.
• Polycystin-1 and 2 are believed to interact together by forming heterodimers.

ADPKD Morphology

• In ADPKD, kidneys are markedly enlarged bilaterally and may weigh up to 4500g.
• Both kidneys are usually similar in size, but about ¼ of patients have more than a 30% difference between the two kidneys.
• Asymmetric involvement is seen more often in children than adults.
• External contours are distorted by numerous cysts filled with straw-colored fluid.
• Cysts range from 0.5 to 5cm in diameter without intervening parenchyma.
• Microscopic examination reveals functioning nephrons dispersed between the cysts
• Cysts are typically filled with clear to yellow fluid unless hemorrhage has occurred.
• Cysts are present in both the cortex and medulla
• The distinction between cortex and medulla becomes obscured by advanced cystic transformation, though it persists at earlier stages.
• The calyces are often markedly distorted by the cysts.
• The pelvis may be normal or more tubular than usual.
• The ureter remains unaffected
• Microscopically, cysts are lined by cuboidal or columnar epithelium.
• They arise from any point along the nephron, and some contain glomeruli.
• Areas of normal renal parenchyma are found between the cysts.
• Hepatic cysts lined by cells resembling bile duct epithelium occur in 1/3 of patients, usually asymptomatically.
• Splenic cysts are seen in 10% of patients, and pancreatic cysts in 5%.
• About 1/5th of patients have an associated cerebral aneurysm.
• Fewer patients have cysts in the lungs
• Intracranial hemorrhage is a frequent cause of death.
• Mitral valve prolapse and other cardiac valvular abnormalities are seen in 20 to 25% of patients, mostly asymptomatically
• A large number of patients also develop colonic diverticula.
• Patients may survive for many years with azotemia slowly progressing into uremia.
• About 40% of adult patients die of coronary or hypertensive heart disease
• Other causes of mortality include infections (25%), ruptured berry aneurysm, hypertensive intercerebral hemorrhage (15%)

ADPKD Clinical Courses

• Symptoms are not typically seen until 4th decade.
• Common complaints include flank pain or a heavy dragging sensation.
• Other complaints include bilateral flank & abdominal masses and passage of blood clots in the urine
• Complications include hypertension (75%) and urinary infection.
• ADPKD is ultimately fatal, but the outlook is generally better than with most chronic renal diseases.
• The disease is relatively stable and progresses very slowly.
• Death usually occurs from uremia or hypertensive complications.

Autosomal Recessive Polycystic Kidney Disease (ARPKD)

• ARPKD was once called infantile polycystic kidney disease.
• The term "infantile" is no longer acceptable because the disease may not become clinically apparent until later in childhood; autosomal dominant polycystic disease may be present in infancy as well.
• Collecting ducts are the target
• The candidate gene is the PKHD1 gene on chromosome 6p
• Kidneys are typically enlarged relative to gestational age.
• The external surface of the kidney is smooth.
• The kidneys are grossly enlarged but retain their reniform shape.
• Involvement is variably bilateral and symmetrical.
• Kidneys may be so large as to impede delivery.
• Close inspection of the external surface reveals numerous, relatively round cysts up to several mm in diameter lying beneath the opaque capsule.
• A cut surface reveals elongated, fusiform cysts in the cortex arranged perpendicularly to the capsule, producing a radial pattern.
• The medulla also has cysts, which are more rounded than those in the cortex.
• The calyces are distorted, but the renal pelvis and ureter are unremarkable.
• The kidney has a sponge-like appearance.
• Cysts have a uniform lining of cuboidal cells.
• Cysts arise predominantly from collecting ducts, but some may be located in ascending limbs of the loop of Henle and proximal tubules.
• Almost all cases have multiple epithelium-lined cysts in the liver, accompanied by proliferation of portal bile ducts.
• Patients who survive infancy develop liver cirrhosis.
• ARPKD is much less frequent than the autosomal dominant variant.
• It is seen in 1:10,000 to 1:50,000 live births.
• Perinatal, neonatal, infantile, and juvenile subcategories have been identified, depending on the time of presentation and the presence of associated hepatic lesions.
• The first two subcategories (perinatal, neonatal) are most common.
• About 75% of those affected die in the perinatal period, often because the large kidneys compromise expansion of the lungs.
• Exceptional cases occur in older children and adults.