eMedicine Specialties > Radiology > Genitourinary
Autosomal Dominant Polycystic Kidney Disease
Updated: Dec 23, 2008
Introduction
Plain radiograph of the kidney, ureters, and bladder in a 50-year-old woman with adult-type polycystic kidney disease. The kidneys are enlarged with multiple, curvilinear, and ringlike calcifications arising from the renal cyst. The surgical clip from renal transplant is seen projected over the left iliac wing.
Excretory 30-minute urographic image in a patient with polycystic kidney disease. The kidneys are enlarged with an elongated, splayed, and distorted collecting system resulting from the presence of innumerable cysts. Note bilateral avascular necrosis of the femoral heads.
Sonogram of the right kidney in a patient with adult-type polycystic kidney disease. The scan shows numerous cysts of varying sizes, with a large cyst in the upper pole.
Background
Adult polycystic kidney disease, which affects approximately 1 in 1000 people, is transmitted as an autosomal dominant trait. Cysts arise from the nephrons and collecting tubules; microdissection reveals that the cysts communicate directly with the nephrons and collecting tubules. Islands of normal parenchymal renal tissue are interspaced between the cysts.
Patients present with hypertension and progressive renal failure after their third decade of life. Autosomal dominant polycystic kidney disease (ADPKD) is uncommon in children and is rarely seen in neonates. From 29% to 73% of patients with the disorder have associated hepatic cysts, 9% have associated pancreatic cysts, and 5% have associated splenic cysts; pulmonary cysts occur but are uncommon. These extrarenal manifestations are not found in neonates and children.1,2,3,4,5,6,7,8
For excellent patient education resources, visit eMedicine's Kidneys and Urinary System Center. Also, see eMedicine's patient education article Blood in the Urine.
Related eMedicine topics:
Cystic Diseases of the Kidney (Urology)
Polycystic Kidney Disease
Polycystic Kidney Disease (Pediatrics)
Pathophysiology
Autosomal dominant polycystic kidney disease is an inherited condition comprising at least 3 phenotypically indistinguishable but genetically distinct entities.9,10 The specific form that develops depends on which of 3 genes— PKD1, PKD2, or PKD3 —becomes mutated.11,12 In 90% of patients, the affected gene is located on chromosome arm 16p; in 10% of patients, the disease arises from a spontaneous mutation.13 ADPKD is transmitted as an autosomal dominant trait, with almost 100% penetrance if patients live long enough. Because of the condition's variable expressivity and the incidence of spontaneous mutation, nearly 50% of patients have no family history of the disease. Defective polycystins appear to contribute to cyst formation by affecting epithelial cell maturation, resulting in the development of cysts of varying sizes in the cortex and medulla.14,15,6 An association with tuberous sclerosis complex has been described.16
Histologically, ADPKD is characterized by an abnormal rate of tubule divisions, with hypoplasia of portions of tubules left behind as the ureteral bud advances. Cystic dilatation occurs in the Bowman capsule, loop of Henle, and proximal convoluted tubule, interspersed with normal renal tissue. Thus, in contrast to fluid from simple renal cysts, which is biochemically similar to plasma, the biochemical features of the fluid content of ADPKD cysts are closer to those of urine, particularly in samples that are taken from distal nephrogenic cysts. Cysts in ADPKD are lined with flattened or cuboidal epithelium. Stromal changes are those of renal failure and are nonspecific; dystrophic calcification is common.17
With minimal disease, the kidneys are smooth and of normal size; the cysts are discovered only on cut pathologic specimens. As the size of cysts increases, the kidneys enlarge, often asymmetrically, and may become bosselated and lose their reniform shape. The age of patients at onset of cyst formation varies; 54% of cysts appear by the first decade of life, 72% by the second decade, and 86% by the third decade.18 By the age of 80 years, evidence of cyst formation exists in all persons who have the gene.19
True unilateral ADPKD is rare. (Most genetic diseases involving paired organs are bilateral.) Segmental ADPKD also is uncommon; some investigators, in fact, doubt the existence of the segmental form and suggest that it should not be considered a forme fruste of ADPKD. Segmental disease is neither inherited nor associated with renal failure. Rarely, ADPKD may be detected in utero, usually in the third trimester, although the earliest diagnosis recorded was at 14 weeks' gestation.
With small cysts, ADPKD can be confused with autosomal recessive polycystic kidney disease (ARPKD) because the kidneys may be enlarged and echogenic. Sometimes, the cortical cysts are large enough to be found on ultrasonographic images, which can confirm the diagnosis when cysts are demonstrated in the fetus of a parent with the disease.
As ADPKD progresses, impaired renal function ensues. Hypertension precedes renal failure. Extrarenal manifestations include liver cysts in 29-73% of patients, pancreatic cysts in 9%, and splenic cysts in 5%. Cysts have also been reported in the thyroid, parathyroid, lung, brain, pituitary gland, pineal gland, ovary, uterus, testis, seminal vesicles, epididymis, bladder, and peritoneum. Aneurysms of cerebral arteries (berry aneurysms) have been found in 3-50% of patients. A variety of cardiac and aortic abnormalities have been associated with ADPKD, including aortic root dilatation, aortic regurgitation, bicuspid aortic valves, coarctation of the aorta, mitral regurgitation, and abdominal aortic aneurysm.20,21
Cysts vary in size from barely visible to several centimeters in diameter. They usually contain clear, straw-colored fluid, but hemorrhage into 1 or more cysts is common, which may change the fluid's gross, biochemical, and histologic character. Cysts can become infected, and aspiration of the fluid may reveal purulent contents. Incidence of renal cell carcinoma is only slightly increased in patients with ADPKD; a greater rise in incidence is associated with cystic disease of dialysis.
Approximately 50 cases of renal cell carcinoma have been reported in association with polycystic kidneys; some of the cases were associated with von Hippel–Lindau disease and tuberous sclerosis.22 No correlation exists between the severity of renal disease and the number of liver cysts. Liver function usually remains normal in ADPKD, but with longer survival of patients with ADPKD, liver function abnormalities may occur, particularly in individuals with portal hypertension. An association between ADPKD and congenital hepatic fibrosis has been described.23
Frequency
United States
One in 1000 people carry the trait for autosomal dominant polycystic kidney disease, making it the most common genetically linked renal disorder. There are 200,000-400,000 persons with ADPKD in the United States, with approximately 6000 new cases occurring each year. About 10-12% of patients receiving maintenance hemodialysis have ADPKD.
International
To the authors' knowledge, no accurate figures are available regarding the international incidence and prevalence of autosomal dominant polycystic kidney disease.
Mortality/Morbidity
- By 60 years of age, most patients with autosomal dominant polycystic kidney disease experience renal failure.
- Hypertension predates renal failure. Complications of hypertension secondary to ADPKD are similar to those of essential hypertension. Patients who are normotensive at presentation have a better prognosis in terms of survival.
- Infections, hemorrhage, cyst rupture, and renal calculus disease are recognized complications of ADPKD.
- Results of experimental studies have suggested that cystic kidneys become infected more easily than noncystic kidneys. The urinary tract is at particular risk of serious infections in ADPKD, which adds considerably to morbidity and mortality.
- Rarely, massive intracystic or retroperitoneal hemorrhage can occur; these require nephrectomy.
- Before the availability of renal dialysis and renal transplantation, most patients died within 10 years after the onset of symptoms.
- Liver and other extrarenal cysts seldom cause symptoms; however, with longer survival of patients with ADPKD, liver impairment may cause increased morbidity and mortality rates. Rare complications of hepatic cystic disease include cyst hemorrhage, infection, portal hypertension, biliary obstruction from cystic mass effect, and cholangiocarcinoma.
- The variety of cardiac and aortic problems associated with ADPKD may add to morbidity and mortality.
- Approximately 10% of patients with ADPKD die of a ruptured, intracranial berry aneurysm.
Race
No race predilection for autosomal dominant polycystic kidney disease exists.
Sex
No sex preponderance for autosomal dominant polycystic kidney disease exists.
Age
Patients of any age can be affected with autosomal dominant polycystic kidney disease, but the mean age at diagnosis is 43 years. In rare cases, renal cysts are incidentally discovered in people aged 70-90 years.
Presentation
Sonogram of the kidney in a patient with polycystic kidney disease shows numerous cysts of varying sizes.
Sonogram of the liver (same patient as in Image above) shows multiple cysts. Approximately 29-73% of patients with adult-type polycystic disease have cysts in the liver.
Excretory 5-minute urographic image in a young male patient with bilateral polycystic disease. The calyces are elongated and splayed because of the cysts, seen best on the right. Note the large size of both kidneys.
Aortogram (same patient as in Image above) demonstrates stretching of the intrarenal arterial branches, seen best in the upper pole of the right kidney.
Autosomal dominant polycystic kidney disease probably begins in utero in most patients, but symptoms are unusual until the fourth or fifth decade (although, with increasing use of cross-sectional imaging, ADPKD is also being discovered incidentally in asymptomatic patients between 70 and 90 years of age). The most common presentation is a palpable mass, hypertension, abdominal pain, and hematuria. Hypertension often predates renal failure.
Renal failure ultimately occurs in most patients by age 60 years. Persons may present with fever, dysuria, and leukocytosis as a result of urinary tract infections. Renal and/or ureteric colic from calculi is a known complication. Hemorrhage, which can be intracystic or retroperitoneal, may present with hematuria, abdominal pain, and, rarely, massive hemorrhagic shock or anemia. Polycythemia is a rare, but known, association secondary to increased erythropoietin production. Rarely, intracystic hemorrhage within a liver cyst may cause acute abdominal pain, mimicking acute cholecystitis. Urinalysis may reveal proteinuria and hematuria.
Seminal tract cysts are seen in 43.5% of patients with ADPKD; however, this finding does not correlate with sperm abnormalities, which are also a frequent finding, especially asthenozoospermia. This semen abnormality is probably related to the abnormal function of polycystins. Thus, the reproductive aspects of patients with ADPKD need early evaluation before the ability to conceive is further impaired by uremia.24
Preferred Examination
Sonogram of the right kidney in a patient with adult-type polycystic kidney disease. The scan shows numerous cysts of varying sizes, with a large cyst in the upper pole.
Selective renal arteriogram (same patient as in Image above). A large filling defect is demonstrated in the upper pole of the right kidney, forming an acute angle with the normal renal cortex that results in a characteristic beak appearance.
Sonogram of the liver in a newborn with polycystic kidney disease shows numerous tiny cysts affecting both lobes of the liver.
Sonogram of the kidney in a newborn (same patient as in Image above) shows numerous cysts of varying sizes predominantly situated in the periphery.
Ultrasonography is the procedure of choice in the workup of patients with autosomal dominant polycystic kidney disease, and it is an ideal modality for screening patients' families. Plain radiographs offer limited information. Plain radiographic findings are normal in the early stages of ADPKD, but with enlargement of the kidneys, soft-tissue masses displace the intra-abdominal organs. In earlier studies in young children, intravenous urography and nephrotomography were shown to be slightly more sensitive than ultrasonography.
Computed tomography (CT) scanning is as sensitive as ultrasound in the detection of cystic disease, although problems may arise with smaller cysts. CT scanning appears to be more specific than sonography in differentiating an obstructed renal pelvis from a parapelvic cyst. It also seems to be superior to ultrasonographic images in helping assess retroperitoneal rupture of a cyst and perinephric extension of blood or pus from an infected cyst.25,26
Magnetic resonance imaging (MRI) is especially useful for examining patients who are allergic to iodinated contrast media and those with compromised renal function who are at risk for iodinated contrast – induced renal failure. MRI also has advantages for patients in whom hemorrhagic cysts are considered and is probably superior to other modalities in characterizing complicated cysts.
The role of angiography in the diagnosis of ADPKD is limited. Although angiography has a high degree of accuracy in diagnosing ADPKD, its specificity is low.
Radionuclide studies have a complementary role in the assessment of renal function in ADPKD. These studies do not have the added hazard of patient exposure to iodinated contrast material.
Limitations of Techniques
Nephromegaly, which can be detected on plain radiographs, may result from causes other than autosomal dominant polycystic kidney disease. Similarly, curvilinear calcification is not specific for ADPKD and may be found in other types of cysts, as well as in tumors and granulomas. Simple renal cysts with nongenetic origins may be similar to ADPKD lesions. Also, cysts associated with ADPKD cannot always be differentiated from multiple simple cysts and cysts associated with von Hippel – Lindau disease or tuberous sclerosis. Such findings apply to intravenous urography, ultrasonography, CT scanning, MRI, and angiography.
Differential Diagnoses
Autosomal Recessive Polycystic Kidney
Disease
Kidney, Lymphoma
Multilocular Cystic Nephroma
Tuberous Sclerosis
Von Hippel-Lindau Syndrome
Other Problems to Be Considered
Any cause of multiple intrarenal fluid collections
Hydrocalycosis, particularly if the renal pelvis is not dilated
Multiple hypoechoic and/or anechoic nodes (eg, lymphoma)
Acquired renal cystic disease
More on Autosomal Dominant Polycystic Kidney Disease |
 Overview: Autosomal Dominant Polycystic Kidney Disease |
| Imaging: Autosomal Dominant Polycystic Kidney Disease |
| Follow-up: Autosomal Dominant Polycystic Kidney Disease |
| Multimedia: Autosomal Dominant Polycystic Kidney Disease |
| References |
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Further Reading
Keywords
autosomal dominant polycystic kidney disease, Potter type III disease, adult polycystic kidney disease, kidney disease, polycystic kidney disease, renal cyst, ADPKD, ADPCKD, renal failure, hypertension, impaired renal function, PKD1, PKD2, PKD3
