Polycystic Kidney Disease

Updated: Dec 16, 2021
  • Author: Roser Torra, MD, PhD; Chief Editor: Vecihi Batuman, MD, FASN  more...
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Practice Essentials

Polycystic kidney disease is an inherited disease that involves bilateral renal cysts (see the image below). The condition is broadly divided into 2 forms: autosomal dominant polycystic kidney disease (ADPKD) and autosomal recessive polycystic kidney disease (ARPKD). This article focuses on ADPKD; for full discussion of ARPKD, see Pediatric Polycystic Kidney Disease. However, note that although ADPKD was previously known as adult polycystic kidney disease and ARPKD was previously known as infantile polycystic kidney disease, those descriptions are not accurate, and that nomenclature is no longer used.

Polycystic kidney. Polycystic kidney.

ADPKD is one of the most common inherited disorders in humans and the most frequent genetic cause of kidney failure in adults, accounting for 6-8% of patients on dialysis in the United States. It is a multisystemic and progressive disorder characterized by cyst formation and enlargement in the kidney and other organs (eg, liver, pancreas, spleen). [1] Clinical manifestations usually begin in the third to fourth decade of life, but cysts may be detectable in childhood and in utero. [2] Up to 50% of patients with ADPKD require renal replacement therapy by 60 years of age.

ARPKD is characterized by cystic dilatation of renal collecting ducts associated with hepatic abnormalities of varying degrees, including biliary dysgenesis and periportal fibrosis. The disorder is usually diagnosed in infants and children, although hepatic involvement may not manifest in neonates (50-60%).

Just as polycystic kidney disease may invove the liver, autosomal dominant polycystic liver disease (ADPLD) may involve cysts in the kidneys, although if present, they are few in number. However, like patients with ADPKD, patients with ADPLP also present with abdominal pain, as the liver cysts enlarge and cause hepatomegaly. [3]  

Signs and symptoms

Pain—in the abdomen, flank, or back—is the most common initial complaint, and it is almost universally present in patients with ADPKD. Dull aching and an uncomfortable sensation of heaviness may result from a large polycystic liver.

The pain can be caused by any of the following:

  • Enlargement of one or more cysts
  • Bleeding: May be confined inside the cyst or lead to gross hematuria with passage of clots or a perinephric hematoma
  • UTI (eg, acute pyelonephritis, infected cysts, perinephric abscess)
  • Nephrolithiasis and renal colic
  • Rarely, a coincidental hypernephroma

See Presentation for more detail.


Examination in patients with ADPKD may demonstrate the following:

  • Hypertension: One of the most common early manifestations of ADPKD, [4, 5] in which increased diastolic BP is the rule; clinical course in ADPKD is usually more severe early on, then becomes less problematic as the kidney insufficiency progresses
  • Palpable, bilateral flank masses: In advanced ADPKD
  • Nodular hepatomegaly: In severe polycystic liver disease
  • Rarely, symptoms related to kidney failure (eg, pallor, uremic fetor, dry skin, edema)


Routine laboratory studies include the following:

  • Serum chemistry profile, including calcium and phosphorus
  • CBC count
  • Urinalysis
  • Urine culture
  • Uric acid determination
  • Intact parathyroid hormone assay

Genetic testing may be performed, in which the major indication is for genetic screening in young adults with negative ultrasonographic findings who are being considered as potential kidney donors. [6]


Staging of kidney failure is by glomerular filtration rate (GFR), as follows:

  • Stage 1: GFR above 90 mL/min
  • Stage 2: GFR 60-90 mL/min
  • Stage 3: GFR 30-60 mL/min
  • Stage 4: GFR 15-30 mL/min
  • Stage 5: GFR below 15 mL/min

Imaging studies

Radiologic studies used in the evaluation of ADPKD include the following:

  • Ultrasonography: Technique of choice for patients with ADPKD and for screening patients' family members; useful for exploring abdominal extrarenal features of ADPKD (eg, liver cysts, pancreatic cysts)
  • CT scanning: Not routine; useful in doubtful pediatric cases or in complicated cases (eg, kidney stone, suspected tumor)
  • MRI: Not routine; helpful in distinguishing renal cell carcinoma from simple cysts; criterion standard to help determine renal volume for clinical trials when testing drugs for ADPKD; best imaging tool for monitoring kidney size after treatment, as an indication of disease progress.
  • Magnetic resonance angiography (MRA): Not routine; preferred imaging technique for diagnosing ADPKD-related intracranial aneurysms

Ultrasonographic diagnostic criteria for ADPKD1 are as follows [7] :

  • At least 2 cysts in 1 kidney or 1 cyst in each kidney in an at-risk patient younger than 30 years
  • At least 2 cysts in each kidney in an at-risk patient aged 30-59 years
  • At least 4 cysts in each kidney for an at-risk patient aged 60 years or older

Ultrasonographic diagnostic criteria for ADPKD in patients with a family history but unknown genotype are as follows [8] :

  • Three or more (unilateral or bilateral) renal cysts in patients aged 15-39 years
  • Two or more cysts in each kidney in patients aged 30-59 years

Fewer than 2 renal cysts in the findings provides a negative predictive value of 100% and can be considered sufficient for ruling out disease in at-risk individuals older than 40 years.

Indications for MRA are as follows [9, 10] :

  • Family history of stroke or intracranial aneurysms
  • Development of symptoms suggesting an intracranial aneurysm
  • Job or hobby in which a loss of consciousness may be lethal
  • Past history of intracranial aneurysms

See Workup for more detail.


Management of ADPKD includes the following:

  • Control blood pressure: Drugs of choice are ACEIs (eg, captopril, enalapril, lisinopril) or ARBs (eg, valsartan, telmisartan, losartan, irbesartan, candesartan, olmesartan)
  • Control abnormalities related to kidney failure: Drugs to maintain electrolyte levels (eg, calcium carbonate, calcium acetate, sevelamer, lanthanum carbonate, calcitriol [possibly], diuretics, blood pressure medications)
  • Treat UTIs
  • Treat cyst infections: Gyrase inhibitors (eg, ciprofloxacin, chloramphenicol, clindamycin, levofloxacin); dihydrofolic acid inhibitors (TMX/SMP)
  • Treat hematuria: Possibly analgesic plus copious oral hydration
  • Reduce abdominal pain produced by enlarged kidneys
  • Prevent cardiac valve infection in patients with intrinsic valve disease
  • Reduce kidney function decline in adults at risk of rapidly progressive ADPKD (tolvaptan)

Surgical intervention in ADPKD includes the following:

  • Surgical drainage: Usually in conjunction with ultrasonographically guided puncture; in cases of infected kidney/liver cysts not responding to conventional antibiotics
  • Open or fiberoptic-guided surgery: For excision/drainage of the outer walls of cysts to ablate symptoms
  • Nephrectomy: Last resort for pain control in patients with inaccessible cysts in the renal medullae; bilateral nephrectomy in patients with severe hepatic involvement
  • Partial hepatectomy: To manage massive hepatomegaly
  • Liver transplantation: In cases of portal hypertension due to polycystic liver or hepatomegaly with nonresectable areas

Patients with ADPKD who progress to end-stage renal disease may require the following procedures:

  • Hemodialysis
  • Peritoneal dialysis
  • Kidney transplantation

See Treatment and Medication for more detail.



The main feature of ADPKD is a bilateral progressive increase in the number of cysts, which may lead to end-stage renal disease. Hepatic cysts, cerebral aneurysms, and cardiac valvular abnormalities also may occur. [11, 12]

Although ADPKD is a systemic disease, it shows a focal expression because less than 1% of nephrons become cystic. In ADPKD, each epithelial cell within a renal tubule harbors a germ-line mutation, yet only a tiny fraction of the tubules develop renal cysts.

It is currently held that the cells are protected by the allele inherited from the parent without ADPKD. When this allele is inactivated by a somatic event (mutation or otherwise) within a solitary renal tubule cell, the cell divides repeatedly until a cyst develops, with an aberrant growth program causing endless expansion. The severity of ADPKD is thought to be a direct consequence of the number of times and the frequency with which this cystogenic process occurs within the kidneys over the life of the patient. However, it is hard to understand how this hypothesis would apply in neonatal cases.

The hyperplastic cells cause an out-pocketing of the tubule wall, with the formation of a saccular cyst that fills with fluid derived from glomerular filtrate that enters from the afferent tubule segment. Progressive expansion eventually causes most of the emerging cysts to separate from the parent tubule, leaving an isolated sac that fills with fluid by transepithelial secretion. This isolated cyst expands relentlessly as a result of continued proliferation of the mural epithelium together with the transepithelial secretion of sodium chloride and water into the lumen.

The expanding fluid-filled tumor masses elicit secondary and tertiary changes within the renal interstitium evinced by thickening and lamination of the tubule basement membranes, infiltration of macrophages, and neovascularization. Fibrosis within the interstitium begins early in the course of the disease.

Cellular proliferation and fluid secretion may be accelerated by cyclic adenosine monophosphate (cAMP) and growth factors, such as epidermal growth factor (EGF). In summary, cysts function as autonomous structures and are responsible for progressive kidney enlargement in ADPKD.

Approximately 85-90% of patients with ADPKD have an abnormality on the short arm of chromosome 16 (ie, ADPKD type 1 [ADPKD1]). A second defect, termed ADPKD type 2 (ADPKD2), is responsible for 10-15% of ADPKD cases and is found on the long arm of chromosome 4. A third candidate gene, GANAB (Glucosidase II Alpha Subunit), accounting for a very low number of ADPKD cases, has also been described. [13]  Additional cases caused by ALG9, DNAJB11 or LRP5  have been reported. [14, 15, 16]

PKD1 and PKD2 are expressed in most organs and tissues of the human body. The proteins that are encoded by PKD1 and PKD2, polycystin 1 and polycystin 2, seem to function together to regulate the morphologic configuration of epithelial cells. The polycystins are expressed in development as early as the blastocyst stage and are expressed in a broad array of terminally differentiated tissues. The functions of the polycystins have been scrutinized to the greatest extent in epithelial tissues of the kidneys and liver and in vascular smooth muscle (see Etiology).

A decrease in urine-concentrating ability is an early manifestation of ADPKD. The cause is not known. Plasma vasopressin levels are increased; this increase may represent the body's attempt to compensate for the reduced concentrating capacity of the kidneys and could contribute to the development of renal cysts, hypertension, and kidney insufficiency. [17]


Renal cysts in ADPKD are associated with excessive angiogenesis evinced by fragile vessels stretched across their distended walls. When traumatized, these vessels may leak blood into the cyst, causing it to expand rapidly, resulting in excruciating pain. If bleeding continues, then the cyst may rupture into the collecting system, causing gross hematuria. Alternatively, the cyst may rupture into the subcapsular compartment and eventually dissect through the renal capsule to fill the retroperitoneal space.



ADPKD is a hereditary disorder. The pattern of inheritance is autosomal dominant. Because the disorder occurs equally in males and females, each offspring has a 50% chance of inheriting the responsible mutation and, hence, the disease.

ADPKD is a genetically heterogeneous condition that involves at least 2 genes. PKD1 is located on 16p13.3 and accounts for most ADPKD cases. PKD2 is located on 4q21-q22 and accounts for 15% of ADPKD cases. Other genes identified in the etiology of ADPKD include GANAB, ALG9, DNAJB11 and LRP5. [3]

Polycystin 1 and 2

PKD1 codes for a 4304–amino acid protein (polycystin 1). The function of polycystin 1 is not yet fully defined, but this protein interacts with polycystin 2 and is involved in cell cycle regulation and intracellular calcium transport. Polycystin 1 localizes in the primary cilia of renal epithelial cells, which function as mechanosensors and chemosensors.

PKD2 codes for a 968–amino acid protein (polycystin 2) that is structurally similar to polycystin 1 and co-localizes to the primary cilia of renal epithelial cells. It is a member of the family of voltage-activated calcium channels.

Polycystin 1 and polycystin 2 are highly conserved ubiquitous transmembrane proteins. In the kidney, they are located in the epithelial cells of the renal tubules—in particular, in the primary cilia at the luminal side of the tubules, as well as in other areas of the renal cell epithelium.

Polycystin 1 is a large protein with a long extracellular N-terminal region, 11 transmembrane domains, and a short intracellular C-terminal tail. Polycystin 2 is structurally related to the transient receptor potential (TRP) channel family, and it is known to function as a nonselective cation channel permeable to Ca2+.

Polycystin 1 and polycystin 2 form heteromeric complexes and colocalize in the primary cilium of renal epithelial cells. The primary cilium is a long, nonmotile tubular structure located in the apical surface of the epithelial cells in the renal tubules. Its function was unknown for a long time. However, studies now indicate that the primary cilium may be a mechanoreceptor that senses changes in apical fluid flow and that transduces them into an intracellular Ca2+ signaling response.

This model involves the participation of polycystin 1 as a mechanical sensor of ciliary bending induced by luminal fluid flow. Bending of the cilium would cause a conformational change in polycystin 1 that would, in turn, activate the polycystin 2–associated Ca2+ channel, increasing the intracellular Ca2+ concentration and triggering intracellular signaling pathways leading to normal kidney development. [18]

There is a genotype-phenotype correlation for PKD1, with truncating mutations causing a more severe phenotype than non-truncating ones. [19]

ADPKD1 is more severe than ADPKD2. The mean age of ESRD for patients with ADPKD1 is 53 years. The mean age of ESRD for patients with ADPKD2 is 74 years.

The genetic heterogeneity of ADKPD, and the possible contribution of modifier genes, may explain the wide clinical variability in this disease, both within and between families. [16]



Worldwide, ADPKD affects approximately 4 to 7 million individuals and accounts for 7-15% of patients on renal replacement therapy. [20] In North America and Europe, ADPKD is responsible for 6-10% of ESRD cases. Approximately one per 800-1000 population carries a mutation for this condition. Approximately 85-90% of patients with ADPKD have ADPKD1; most of the remaining patients have ADPKD2. [21]

ADPKD is slightly more severe in males than in females, but the difference is not statistically significant.

Symptoms generally increase with age. Children very rarely present with kidney failure from ADPKD.



The prognosis in patients with ADPKD covers a wide spectrum. Kidney failure has been reported in children; conversely, individuals with ADPKD may live a normal lifespan without knowing that they have the disease. More typically, however, ADPKD causes progressive kidney dysfunction, resulting in grossly enlarged kidneys and kidney failure by the fourth to sixth decade of life. There is an inverse association between the size of polycystic kidneys and the level of glomerular filtration. [22, 23]

An early study estimated that approximately 70% of patients with ADPKD would develop kidney insufficiency if they survived to age 65 years. Currently, half of all patients with ADPKD require renal replacement therapy by age 60 years. Risk factors for progression include the following:

  • PKD1 genotype
  • Large kidneys
  • Several episodes of gross hematuria [24]
  • Severe and frequent kidney infections
  • Hypertension
  • Multiple pregnancies
  • Black racial background [21]
  • Male sex

The presence of more than one risk factor increases the risk of progression to end-stage renal disease (ESRD).

Although the 2 forms of ADPKD, ADPKD1 and ADPKD2, share similar clinical features, renal prognosis is strikingly different. [25, 26] ADPKD2 is a milder disease, based on the age of onset of ESRD. The median age of renal survival for individuals with ADPKD1 is 56 years, compared with 68 years in those with ADPKD2. Nevertheless, even though ADPKD2 is milder than ADPKD1, it has an overall impact on survival and shortens life expectancy.

Cardiovascular pathology and infections account for approximately 90% of deaths in patients treated with hemodialysis or peritoneal dialysis and after kidney transplantation. A rare cause of mortality is in ADPKD is subarachnoid hemorrhage from intracranial aneurysms. [27]

In a retrospective, observational study of 88 patients with ADPKD who died between 1981 and 1999, Rahman et al determined that almost half of the patients died of cardiovascular problems. [28] The median age of death was 60.5 years. Causes of death included the following:

  • Cardiovascular problems - 46.6% of patients
  • Infection - 15.9% of patients, with 42% of these deaths resulting from septicemia
  • Central nervous system disorders - 11.36% of patients, with 60% of these deaths caused by cerebrovascular events
  • Uremia - 2.2% of patients
  • Other, miscellaneous causes - 11.36%

The Mayo Clinic calculator for ADPKD is a useful tool for predicting disease progression. Recommendations for assessing rapid progression of ADPKD have been provided by European experts. [29]

The PROPKD score predicts risk of progression to ESRD in patients with ADPKD. The score is calculated on the basis of the following factors [30] :

  • Male sex: 1 point
  • Hypertension before 35 years of age: 2 points
  • First urologic event before 35 years of age: 2 points
  • PKD2 mutation: 0 points
  • Nontruncating PKD1 mutation: 2 points
  • Truncating PKD1 mutation: 4 points

Risk categories, on the basis of point totals, are as follows:

  • 0-3 points: low risk; median age for ESRD onset 70.6 years
  • 4-6 points: intermediate risk; median age for ESRD onset 56.9 years
  • 7-9 points: high risk; median age for ESRD onset 49 years

A PROPKD score of 3 or less eliminates evolution to ESRD before 60 years of age with a negative predictive value of 81.4%. A score higher than 6 forecasts ESRD onset before 60 years of age with a positive predictive value of 90.9%. [30]

A study by Sato et al in 55 Japanese patients with ADPKD determined that high serum phosphate levels were independently associated with poor renal prognosis. Risk rose with every 1-mg/dL increase (hazard ratio, 6.78; 95% confidence index, 1.94–34.02; P = 0.002). [31]


Patient Education

Ensure that patients are aware that this disease is hereditary and that their children have a 50% chance of acquiring the disease. Patients should also understand that although several treatments are being tested, this disease currently has no cure. Only interventions that slow the progression of kidney disease (eg, adequate blood pressure control) are of benefit. Hopefully, effective specific therapy will be available in a few years.

Prenatal diagnosis is available through DNA linkage studies, if enough family members cooperate, or through a mutation search. Suggest that family members who are not screened for ADPKD have annual blood pressure checks and urine screenings for hematuria.