Merck Manual

Please confirm that you are a health care professional

honeypot link

Autosomal Dominant Polycystic Kidney Disease(ADPKD)

By

Enrica Fung

, MD, MPH, Loma Linda University School of Medicine

Last full review/revision Apr 2021| Content last modified Apr 2021
Click here for Patient Education
Topic Resources

Polycystic kidney disease (PKD) is a hereditary disorder of renal cyst formation causing gradual enlargement of both kidneys, sometimes with progression to renal failure. Almost all forms are caused by a familial genetic mutation. Symptoms and signs include flank and abdominal pain, hematuria, and hypertension. Diagnosis is by CT or ultrasonography. Treatment is symptomatic before renal failure and with dialysis or transplantation afterward.

Etiology of ADPKD

Inheritance of polycystic kidney disease (PKD) is

  • Autosomal dominant

  • Recessive

  • Sporadic (rare)

Autosomal dominant polycystic kidney disease (ADPKD) has an incidence of 1/1000 and accounts for about 5% of patients with end-stage renal disease (ESRD) requiring renal replacement therapy Overview of Renal Replacement Therapy Renal replacement therapy (RRT) replaces nonendocrine kidney function in patients with renal failure and is occasionally used for some forms of poisoning. Techniques include continuous hemofiltration... read more . Clinical manifestations are rare before adulthood, but penetrance is essentially complete; all patients 80 years have some signs.

In 86 to 96% of cases, ADPKD is caused by mutations in the PKD1 gene on chromosome 16, which codes for the protein polycystin 1; most other cases are caused by mutations in the PKD2 gene on chromosome 4, which codes for polycystin 2. A few familial cases are unrelated to either locus.

Pathophysiology of ADPKD

Polycystin 1 may regulate tubular epithelial cell adhesion and differentiation; polycystin 2 may function as an ion channel, with mutations causing fluid secretion into cysts. Mutations in these proteins may alter the function of renal cilia, which enable tubular cells to sense flow rates. A leading hypothesis proposes that tubular cell proliferation and differentiation are linked to flow rate and that ciliary dysfunction may thus lead to cystic transformation.

Early in the disorder, tubules dilate and slowly fill with glomerular filtrate. Eventually, the tubules separate from the functioning nephron and fill with secreted rather than filtered fluid, forming cysts. Hemorrhage into cysts may occur, causing hematuria. Patients are also at higher risk of acute pyelonephritis Introduction to Urinary Tract Infections (UTIs) Urinary tract infections (UTIs) can be divided into upper tract infections, which involve the kidneys (pyelonephritis), and lower tract infections, which involve the bladder (cystitis), urethra... read more , cyst infections, and urinary calculi Acute pyelonephritis Bacterial urinary tract infections (UTIs) can involve the urethra, prostate, bladder, or kidneys. Symptoms may be absent or include urinary frequency, urgency, dysuria, lower abdominal pain... read more (in 20%). Vascular sclerosis and interstitial fibrosis eventually develop via unknown mechanisms and typically affect < 10% of tubules; nonetheless, renal failure Acute Kidney Injury (AKI) Acute kidney injury is a rapid decrease in renal function over days to weeks, causing an accumulation of nitrogenous products in the blood (azotemia) with or without reduction in amount of urine... read more develops in about 35 to 45% of patients by age 60.

Extrarenal manifestations are common:

Symptoms and Signs of ADPKD

Autosomal dominant polycystic kidney disease usually causes no symptoms initially; one half of patients remain asymptomatic, never develop renal insufficiency or failure, and are never diagnosed. Most patients who develop symptoms do so by the end of their 20s.

Symptoms include low-grade flank, abdominal, and lower back pain due to cystic enlargement and symptoms of infection. Acute pain, when it occurs, is usually due to hemorrhage into cysts or passage of a calculus. Fever is common with acute pyelonephritis Introduction to Urinary Tract Infections (UTIs) Urinary tract infections (UTIs) can be divided into upper tract infections, which involve the kidneys (pyelonephritis), and lower tract infections, which involve the bladder (cystitis), urethra... read more , and rupture of cysts into the retroperitoneal space may cause a fever that can last for weeks. Hepatic cysts Hepatic Cysts Isolated hepatic cysts are commonly detected incidentally on abdominal ultrasonography or CT (1). These cysts are usually asymptomatic and have no clinical significance. The rare congenital... read more may cause right upper quadrant pain if they enlarge or become infected.

Symptoms and signs of unruptured cerebral aneurysm Brain Aneurysms Brain aneurysms are focal dilations in the cerebral arteries. In the US, brain aneurysms occur in 3 to 5% of people. Brain aneurysms can occur at any age but are most common among people aged... read more Brain Aneurysms can be absent or may include headache, nausea and vomiting, and cranial nerve deficits; these manifestations warrant immediate intervention.

Diagnosis of ADPKD

  • Ultrasonography

  • Sometimes CT or MRI or genetic testing

The diagnosis of polycystic kidney disease is suspected in patients with the following:

  • A positive family history

  • Typical symptoms or signs

  • Cysts detected incidentally on imaging studies

Patients should be counseled before undergoing diagnostic testing, particularly if they are asymptomatic. For example, many authorities recommend against testing asymptomatic young patients because no disease-modifying treatment is effective at this age and diagnosis has potential negative effects on mood and on the ability to obtain life insurance on favorable terms.

Diagnosis is usually by imaging, showing extensive and bilateral cystic changes throughout the kidneys, which are typically enlarged and have a moth-eaten appearance due to cysts that displace functional tissue. These changes develop with age and are less often present or obvious in younger patients.

Ultrasonography is usually done first. If ultrasonography results are inconclusive, CT or MRI, which are both more sensitive (particularly when done using contrast), is done. MRI is especially useful for measuring cyst and kidney volume.

Urinalysis detects mild proteinuria and microscopic or macroscopic hematuria. Gross hematuria may be due to a dislodged calculus Urinary Calculi Urinary calculi are solid particles in the urinary system. They may cause pain, nausea, vomiting, hematuria, and, possibly, chills and fever due to secondary infection. Diagnosis is based on... read more or to hemorrhage from a ruptured cyst. Pyuria is common even without bacterial infection; thus diagnosis of infection should be based on culture results and clinical findings (eg, dysuria, fever, flank pain) as well as urinalysis. Initially, blood urea nitrogen (BUN) and creatinine are normal or only mildly elevated, but they slowly increase, especially when hypertension is present. Rarely, CBC detects polycythemia.

Patients with symptoms of cerebral aneurysm require high-resolution CT or magnetic resonance angiography. However, most experts do not recommend routine screening for cerebral aneurysm in asymptomatic patients. A reasonable approach is to screen patients with autosomal dominant polycystic kidney disease (ADPKD) who have a family history of hemorrhagic stroke Overview of Stroke Strokes are a heterogeneous group of disorders involving sudden, focal interruption of cerebral blood flow that causes neurologic deficit. Strokes can be Ischemic (80%), typically resulting... read more Overview of Stroke or cerebral aneurysm Subarachnoid Hemorrhage (SAH) Subarachnoid hemorrhage is sudden bleeding into the subarachnoid space. The most common cause of spontaneous bleeding is a ruptured aneurysm. Symptoms include sudden, severe headache, usually... read more Subarachnoid Hemorrhage (SAH) .

Genetic testing for polycystic kidney disease (PKD) mutations is currently reserved for any of the following:

  • Patients with suspected PKD and no known family history

  • Patients with inconclusive results on imaging

  • Younger patients (eg, age < 30, in whom imaging results are often inconclusive) in whom the diagnosis must be made (eg, a potential kidney donor)

Genetic counseling is recommended for 1st-degree relatives of patients with ADPKD.

Prognosis for ADPKD

Cyst and kidney volume measurements predict risk of progression to chronic kidney disease Chronic Kidney Disease Chronic kidney disease (CKD) is long-standing, progressive deterioration of renal function. Symptoms develop slowly and in advanced stages include anorexia, nausea, vomiting, stomatitis, dysgeusia... read more Chronic Kidney Disease and end-stage renal disease, often before changes in routine laboratory studies. For example, cyst size and kidney size predict 8-year risk of chronic kidney disease more accurately than age, degree of proteinuria, or serum blood urea nitrogen (BUN) or creatinine. Kidney size is the most important predictor for progression, particularly total kidney volume >1500 mL (1 Prognosis references Polycystic kidney disease (PKD) is a hereditary disorder of renal cyst formation causing gradual enlargement of both kidneys, sometimes with progression to renal failure. Almost all forms are... read more Prognosis references ).

Phosphaturic hormone fibroblast growth factor (FGF) 23 elevation was associated with increased kidney size and annualized rate of estimated glomerular filtration rate (eGFR) decline but interestingly did not enhance risk prediction for disease progression (2 Prognosis references Polycystic kidney disease (PKD) is a hereditary disorder of renal cyst formation causing gradual enlargement of both kidneys, sometimes with progression to renal failure. Almost all forms are... read more Prognosis references ).

ADPKD does not increase risk of renal cancer, but if patients with ADPKD develop renal cancer, it is more likely to be bilateral. Renal cancer rarely causes death. Patients usually die of heart disease (sometimes valvular), disseminated infection, or ruptured cerebral aneurysm.

Prognosis references

Treatment of ADPKD

  • Control of complications (eg, hypertension, infection, renal failure)

  • Supportive measures

Strict control of hypertension Treatment Hypertension is sustained elevation of resting systolic blood pressure (≥ 130 mm Hg), diastolic blood pressure (≥ 80 mm Hg), or both. Hypertension with no known cause (primary; formerly, essential... read more Treatment is essential. Typically an ACE inhibitor or angiotensin receptor blocker is used. In addition to controlling BP, these drugs help block angiotensin and aldosterone, growth factors that contribute to renal scarring and loss of renal function. Urinary tract infections Introduction to Urinary Tract Infections (UTIs) Urinary tract infections (UTIs) can be divided into upper tract infections, which involve the kidneys (pyelonephritis), and lower tract infections, which involve the bladder (cystitis), urethra... read more (UTIs) should be treated promptly. Percutaneous aspiration of cysts may help relieve severe pain due to hemorrhage or compression but has no effect on long-term outcome. Nephrectomy is an option to relieve severe symptoms due to massive kidney enlargement (eg, pain, hematuria) or recurrent UTIs.

Supportive measures include increased fluid intake (particularly water) to suppress vasopressin release, even if only partially, in patients who are able to safely excrete the load.

Mammalian target of rapamycin (mTOR) inhibitors may slow the increase in kidney volume but not the decline in renal function; thus, they are not typically used in routine practice.

Tolvaptan, a vasopressin receptor 2 antagonist, is a drug that may benefit patients with ADPKD (1, 2) Treatment references Polycystic kidney disease (PKD) is a hereditary disorder of renal cyst formation causing gradual enlargement of both kidneys, sometimes with progression to renal failure. Almost all forms are... read more Treatment references . Tolvaptan appears to slow increase in renal volume and decline in renal function, but it can cause adverse effects via free water diuresis (eg, thirst, polydipsia, polyuria) that can make adherence difficult. Tolvaptan has been reported to cause severe liver failure and is hence contraindicated in patients with significant liver impairment or injury. Tolvaptan may be especially beneficial for patients at higher risk for rapid progression of kidney disease. Expert consultation is recommended before starting tolvaptan due to its potential adverse effects. Tolvaptan has not been studied in children and is not recommended in those <18 years of age.

Treatment references

  • 1. Torres VE, Chapman AB, Devuyst O: Tolvaptan in patients with autosomal dominant polycystic kidney disease. N Engl J Med 367(25):2407-2418, 2012. doi: 10.1056/NEJMoa1205511

  • 2. Torres VE, Chapman AB, Devuyst O: Tolvaptan in later-stage autosomal dominant polycystic kidney disease. N Engl J Med 16;377(20):1930-1942, 2017. doi: 10.1056/NEJMoa1710030

  • 3. Cadnapaphornchai MA, George DM, McFann K, et al: Effect of pravastatin on total kidney volume, left ventricular mass index, and microalbuminuria in pediatric autosomal dominant polycystic kidney disease. Clin J Am Soc Nephrol 9(5):889-896, 2014.

Key Points

  • Autosomal dominant polycystic kidney disease occurs in about 1/1000 people.

  • About half of patients have no manifestations, but in others symptoms of back or abdominal pain, hematuria and/or hypertension develop gradually, usually beginning before age 30; 35 to 45% develop renal failure by age 60.

  • Extrarenal manifestations are common and include cerebral and coronary artery aneurysms, cardiac valve disease, and cysts in the liver, pancreas, and intestines.

  • Diagnose PKD based on imaging studies and clinical findings, reserving genetic testing for patients with no family history, with inconclusive results on imaging, or who are young and in whom the diagnosis will affect management.

  • Do not routinely screen asymptomatic patients for ADPKD or asymptomatic patients who have ADPKD for cerebral aneurysms.

  • Arrange genetic counseling for 1st-degree relatives of patients with ADPKD.

  • Give ACE inhibitors or angiotensin receptor blockers for hypertension and to help prevent renal scarring and dysfunction; treat other complications as they arise, and consider use of tolvaptan.

Click here for Patient Education
NOTE: This is the Professional Version. CONSUMERS: Click here for the Consumer Version
Professionals also read
Test your knowledge
Metabolic Nephropathies
Several metabolic disturbances can cause tubulointerstitial nephritis. Acute urate nephropathy is not a true form of acute tubulointerstitial nephritis but rather an intraluminal obstructive uropathy. The most common cause of this type of nephropathy is which of the following?
Download the Manuals App iOS ANDROID
Download the Manuals App iOS ANDROID
Download the Manuals App iOS ANDROID
Download the Manuals App iOS ANDROID
Download the Manuals App iOS ANDROID
Download the Manuals App iOS ANDROID

Also of Interest

Download the Manuals App iOS ANDROID
Download the Manuals App iOS ANDROID
Download the Manuals App iOS ANDROID
TOP