Autosomal Dominant Polycystic Kidney Disease

Autosomal dominant polycystic kidney disease (ADPKD) is a genetic condition characterized by bilateral renal cysts and fibrosis, which leads to a progressive loss of renal function and various associated symptoms.


Most individuals who are affected by ADPKD are diagnosed after a complication has occurred [15] [16]. With reference to complications affecting the urinary system, two of the most commonly observed manifestations are recurrent urinary tract infections or episodes of pyelonephritis. Hematuria is a frequent complication, caused by traumatization of the kidneys due to clots or stones, and is usually self-limited to a microscopic degree. The stones that develop are more commonly uric acid stones. Due to the progressive enlargement of the renal cystic lesions, the kidneys themselves also continue to expand, in terms of their dimensional space. They may be palpable if the size augmentation is considerable; if the cysts affect other organs as well, palpable viscera may be detected (splenomegaly, hepatomegaly). Hypertension is another common complication of ADPKD and is associated only with renal failure, but also with left ventricular hypertrophy (LVH). Patients often report pain felt at the lower part of the back, between the lower ribs and pelvis: hematuria, urinary tract infections or renal stones can be held accountable for such a symptom when it arises acutely and subsidies. Chronicity of the painful sensation is usually a result of the presence of the cysts or other, yet unidentified factors.

The autosomal dominant polycystic renal disease is not a condition that is limited to the kidneys. Multiple complications affect organs other than the kidneys and may, eventually, constitute the cause of death. Aneurysms are a common manifestation related to ADPKD and can be found in the cerebral vascular network, but also in the aorta or coronary artery, with dissections being a possible complication. Cardiovascular defects are frequent co-existent pathologies and include mitral valve prolapse and aortic insufficiency. The liver can also be affected, with cystic lesions developing in the hepatic parenchyma as well, but this type of complication usually causes no symptomatology; possible sequelae, however, include haemorrhage, rupture, and torsion. The pancreas is also sensitive to cystic development, with pancreatitis being a rare, but possible manifestation. Lastly, cysts located in the seminal vesicles can lead to infertility in male patients.


Even though cystic lesions can independently arise as the age progresses, criteria have been determined for the diagnosis of ADPKD, depending on the age. Ultrasonography or magnetic resonance imaging are useful tools for the detection of cysts, whether renal, hepatic or pancreatic, and can be employed to detect the condition in individuals at risk who have not surpassed the age of 40 years old. Patients who possess two or more risk factors for ADPKD and are younger than 40 years old are considered disease-free when the number of cysts in the kidneys does not exceed 5 [17].

Genetic testing for both PKD1 and PKD2 genetic mutations is currently available. Tests aiming at the detection of a PKD1 mutation, however, are hardly cost-effective due to the extreme complexity and large size of the gene [18] [19].


Autosomal dominant polycystic kidney disease cannot be cured, but can be symptomatically managed, depending on the complications:

  • Hypertension: Dietary adaptations and antihypertensive agents, such as ACE inhibitors or angiotensin receptor blockers
  • Back pain: Pain-relievers (nonopioid), narcotic analgesics or nerve blockade
  • Urinary tract infections: Depending on the pathogen, possible antibiotic treatments encompass trimethoprim-sulfamethoxazole, fluoroquinolones, clindamycin and metronidazole
  • Cystic lesions: Sclerosis, aspiration or fenestration

In general, patients are carefully monitored with frequent follow-ups, due to the need to slow the progression to end-stage renal disease down. Management of the elevated blood pressure, hyperlipidemia, control of acidosis and restricted protein intake are paramount towards this cause. Further complications, such as ruptured cerebral aneurysms or cardiac abnormalities, are also managed symptomatically.

Patients who have reached ESRD require renal transplantation [20] [21] [22] [23] [24], with living kidney donation viewed as the best option [25]. Should there not be a transplantation option, hemodialysis or peritoneal dialysis can also be useful, although with poorer long-term effects.


ADPKD is a condition with a generally poor prognosis, as the majority of the patients are ultimately lead to end-stage renal disease if they reach the age of 65. Kidney failure has been diagnosed even in pediatric patients, whereas a minority may be affected by the disease and be unaware of it. In general, renal cysts continue to grow in size and eventually lead to renal insufficiency and failure; the size of the kidneys is inversely proportional to the level of GFR [8] [9].

Furthermore, the genotype of the affected individual plays an important role in a prognostic sense, as patients who are diagnosed with ADPKD 1 exhibit severer symptomatology and usually reach end-stage renal disease (ESRD) at the age of 53 [10] [11]. On the other hand, ADPKD2 individuals are diagnosed with renal failure at an average age of 68, even though the symptoms grossly remain the same. Various other risk factors have been incriminated for severer ADPKD, with the complete list being the following:

Most patients affected by autosomal dominant polycystic kidney disease succumb due to cardiovascular events. Another frequent cause of death is infections, usually systemic, cerebral aneurysms or uremia [14].


The vast majority of the patients affected by ADPKD exhibit mutations in a single gene, the PKD1 found on chromosome 16, with its exact location being 16p13.3. Variations of the PKD2 gene (4q22.1) have also been observed, although in a minority of the patients. The type of mutation that is present varies between missense, truncating, nontruncating mutations, deletions and atypical splicing [3].


Nearly 10% of all individuals requiring renal replacement therapy are ADPKD patients; the disorder is believed to affect approximately 5.5 million on a worldwide scale [4]. It is thought that 1 out of 1000 people carry an ADPKD-associated mutation, with most patients being affected by an abnormal PKD1 gene, at a rate of 85% [5]. The condition does lead to more profound symptomatology and complications in male patients when compared to females, but the discrepancy is not significant.

Sex distribution
Age distribution


ADPKD is primarily characterized by cystic lesions that are found on both kidneys and follow an expanding course; other features may include cerebral aneurysms and defective cardiac valves [6] [7].

With regard to the kidneys, the cysts are initially formed on the wall of the tubule and contain liquid material that reaches the location from glomerular filtrate that enters via the afferent segment. The cysts increase their dimensions continually, a fact which leads to their ultimately being detached from the tubule; upon their separation, a sac is left behind that continues to fill with transepithelial secretions, which also grows at a continuous rate. This change in the structure and architecture of the renal parenchyma causes fibrosis and lamination of the basement membranes of the tubules, neovascularization and a secondary infiltration by white blood cells, particularly macrophages.

The condition is a consequence of abnormalities in the PKD1 or PKD2 genes, which produce polycystin 1 and 2 respectively. The two genes are expressed in almost every organ of the body. Cyclic adenosine monophosphate (cAMP) as well as growth factors such as EGF definitely influence cellular growth and fluid production in a positive manner.


Given that each offspring of an affected individual has 50% chance of inheriting the PKD1 or PKD2 mutation, prenatal testing should be encouraged. [26] [27].


Autosomal dominant polycystic kidney disease (ADPKD) is a monogenetic disorder that features bilateral renal cysts, nephrolithiasis, hypertension and gradually developing renal failure, induced by the expansion of the cysts and fibrosis [1] [2].

It affects approximately 5 million people internationally and occurs as a result of modifications of a single gene, PKD1 or PKD2. Although the clinical picture of the patients encompasses the same characteristics irrespective of the type of mutation, it is known that the PKD1 genotype entails severer symptomatology and a poorer prognosis. Most patients with such a mutation are expected to be in need of renal replacement therapy at an age of 10 years prior to those affected by the PKD2 mutation.

It has been estimated that nearly 10% of all individuals requiring renal replacement therapy do so because of complications of this particular disorder. The kidneys are the main target of ADPKD; cystic lesions follow a continually expanding course, altering the architecture of the parenchyma and interfering with the organ's functions: complications of ADPKD include nephrolithiasis, hematuria, recurrent urinary tract infections or pyelonephritis, hypertension and osphyalgia. The liver, spleen, brain and heart may also be affected, as the disease is not necessarily limited to the kidneys. Sequelae affecting other organs are multiple, such as hepatosplenomegaly, cerebral aneurysms that are susceptible to rupturing, heart valvular defects and others.

Autosomal dominant polycystic kidney disease is a condition that can only be symptomatically treated and is expected, in the majority of the cases, to lead to end-stage renal disease and renal replacement therapy. Kidney transplantation is the optimum choice, if this stage has been reached.

Patient Information

Autosomal dominant polycystic kidney disease (ADPKD) is a genetic condition, which causes cysts to form in the kidneys and in other organs such as the liver or pancreas. It is caused by mutations in one of the two genes, PKD1 or PKD2, which are expressed in almost every organ. ADPKD is inherited through the autosomal pattern, which means, that every individual who possesses even one defective gene will be affected by the condition.

ADPKD is a genetic condition; therefore the cause is a genetic mutation. However, those affected with a PKD1 mutation experience severer symptoms. Other risk factors for severer manifestations of ADPKD include hypertension, multiple pregnancies, African descent, the PKD1 mutation, excessively enlarged kidneys, many episodes of pyelonephritis and others.

The condition is usually diagnosed when complications arise. Possible complications are urinary tract infections and kidney infections that recur, kidney stones, hypertension even when the kidneys function properly, blood in the urine, enlarged kidneys that may be palpable, back pain and, ultimately, kidney failure. Other complications can affect the liver (cysts), the brain (aneurysms) or the heart (valve abnormalities). The condition is diagnosed usually based on the number of cysts present, in combination with the risk factors each individual possesses. Ultrasonographic scans or magnetic resonance imaging scans are used to detect cysts. Genetic testing is also available if parents with ADPKD are planning to have offspring.

ADPKD cannot be cured, as it is a genetic disease. However, its symptoms can be managed and its progression can, in many cases, be delayed. Patients receive antihypertensive medication for hypertension, pain-relievers for the loin pain, antibiotics for the infections and various treatments for the cysts themselves. Brain aneurysms and heart defects are treated primarily surgically. At the final stages of the disease, if renal failure is diagnosed, the patient will require transplantation; if it is not an option, they may be treated with hemodialysis.


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