Polycystic kidney disease (PKD or PCKD, also known as polycystic kidney syndrome) is a
genetic disorder in which the
renal tubules become structurally abnormal, resulting in the development and growth of multiple
cysts within the kidney. These cysts may begin to develop in utero, in infancy, in childhood, or in adulthood. Cysts are non-functioning tubules filled with fluid pumped into them, which range in size from microscopic to enormous, crushing adjacent normal tubules and eventually rendering them non-functional as well.
PKD is caused by abnormal genes that produce a specific abnormal protein; this protein has an adverse effect on tubule development. PKD is a general term for two types, each having their own pathology and genetic cause:
autosomal dominant polycystic kidney disease
Autosomal dominant polycystic kidney disease (ADPKD) is one of the most common, life-threatening inherited human disorders and the most common hereditary kidney disease. It is associated with large interfamilial and intrafamilial variability, whi ...
(ADPKD) and
autosomal recessive polycystic kidney disease (ARPKD). The abnormal gene exists in all cells in the body; as a result, cysts may occur in the
liver,
seminal vesicles, and
pancreas. This genetic defect can also cause aortic root
aneurysms, and aneurysms in the
circle of Willis cerebral arteries, which if they rupture, can cause a
subarachnoid hemorrhage
Subarachnoid hemorrhage (SAH) is bleeding into the subarachnoid space—the area between the arachnoid membrane and the pia mater surrounding the brain. Symptoms may include a severe headache of rapid onset, vomiting, decreased level of consci ...
.
Diagnosis may be suspected from one, some, or all of the following: new onset flank pain or red urine; a positive family history; palpation of enlarged kidneys on physical exam; an incidental finding on abdominal
sonogram; or an incidental finding of abnormal kidney function on routine lab work (
BUN,
serum creatinine, or
eGFR). Definitive diagnosis is made by abdominal
CT exam.
Complications include hypertension due to the activation of the
renin–angiotensin–aldosterone system (RAAS), frequent cyst infections, urinary bleeding, and declining renal function. Hypertension is treated with
angiotensin converting enzyme inhibitors
Angiotensin-converting-enzyme inhibitors (ACE inhibitors) are a class of medication used primarily for the treatment of high blood pressure and heart failure. They work by causing relaxation of blood vessels as well as a decrease in blood volum ...
(
ACEI
Angiotensin-converting-enzyme inhibitors (ACE inhibitors) are a class of medication used primarily for the treatment of high blood pressure and heart failure. They work by causing relaxation of blood vessels as well as a decrease in blood vol ...
s) or
angiotensin receptor blockers (ARBs). Infections are treated with antibiotics. Declining renal function is treated with
renal replacement therapy
Renal replacement therapy (RRT) is therapy that replaces the normal blood-filtering function of the kidneys. It is used when the kidneys are not working well, which is called kidney failure and includes acute kidney injury and chronic kidney dis ...
(RRT):
dialysis Dialysis may refer to:
*Dialysis (chemistry), a process of separating molecules in solution
**Electrodialysis, used to transport salt ions from one solution to another through an ion-exchange membrane under the influence of an applied electric pote ...
and/or
transplantation. Management from the time of the suspected or definitive diagnosis is by a board-certified
nephrologist.
Signs and symptoms
Signs and symptoms include high blood pressure, headaches, abdominal pain,
blood in the urine, and
excessive urination.
Other symptoms include pain in the back, and cyst formation (renal and other organs).
Cause
PKD is caused by abnormal genes which produce a specific abnormal protein which has an adverse effect on tubule development. PKD is a general term for two types, each having their own pathology and genetic cause:
autosomal dominant polycystic kidney disease
Autosomal dominant polycystic kidney disease (ADPKD) is one of the most common, life-threatening inherited human disorders and the most common hereditary kidney disease. It is associated with large interfamilial and intrafamilial variability, whi ...
(ADPKD) and
autosomal recessive polycystic kidney disease (ARPKD).
Autosomal dominant

Autosomal dominant polycystic kidney disease (ADPKD) is the most common of all the inherited cystic kidney diseases
with an incidence of 1:500 live births.
Studies show that 10% of
end-stage kidney disease (ESKD) patients being treated with
dialysis Dialysis may refer to:
*Dialysis (chemistry), a process of separating molecules in solution
**Electrodialysis, used to transport salt ions from one solution to another through an ion-exchange membrane under the influence of an applied electric pote ...
in Europe and the U.S. were initially diagnosed and treated for ADPKD.
Genetic mutations in any of the three
genes
In biology, the word gene (from , ; "...Wilhelm Johannsen coined the word gene to describe the Mendelian units of heredity..." meaning ''generation'' or ''birth'' or ''gender'') can have several different meanings. The Mendelian gene is a ba ...
PKD1,
PKD2
Polycystin-2 is a protein that in humans is encoded by the ''PKD2'' gene.
This gene encodes a member of the polycystin protein family, called TRPP2, previously known as polycystin-2, PC2 or APKD2. TRPP2 contains multiple transmembrane domains, a ...
, and
PKD3 have similar phenotypical presentations.
* Gene PKD1 is located on
chromosome 16 and codes for a protein involved in regulation of cell cycle and intracellular calcium transport in epithelial cells, and is responsible for 85% of the cases of ADPKD.
* Gene PKD2 is identified, using genetic linkage study, on chromosome 4. A group of voltage-linked
cation channel
Ion channels are pore-forming membrane proteins that allow ions to pass through the channel pore. Their functions include establishing a resting membrane potential, shaping action potentials and other electrical signals by Gating (electrophysiol ...
s, with inward selectivity for K>Na>>Ca and outward selectivity for Ca2+ ≈ Ba2+ > Na+ ≈ K+, are coded for by PKD2 on
chromosome 4.
* PKD3 recently appeared in research papers as a postulated third gene.
Fewer than 10% of cases of ADPKD appear in non-ADPKD families. Cyst formation begins
in utero from any point along the
nephron, although fewer than 5% of nephrons are thought to be involved. As the cysts accumulate fluid, they enlarge, separate entirely from the nephron, compress the neighboring kidney
parenchyma
Parenchyma () is the bulk of functional substance in an animal organ or structure such as a tumour. In zoology it is the name for the tissue that fills the interior of flatworms.
Etymology
The term ''parenchyma'' is New Latin from the word π ...
, and progressively compromise
kidney function.
Autosomal recessive
Autosomal recessive polycystic kidney disease (ARPKD) (OMIM #263200) is the less common of the two types of PKD, with an incidence of 1:20,000 live births and is typically identified in the first few weeks after birth. Unfortunately, the kidneys are often
underdeveloped
Underdevelopment, in the context of international development, reflects a broad condition or phenomena defined and critiqued by theorists in fields such as economics, development studies, and postcolonial studies. Used primarily to distinguish st ...
resulting in a 30% death rate in newborns with ARPKD.
PKHD1 is involved.
Mechanism

Both autosomal dominant and autosomal recessive polycystic kidney disease cyst formation are tied to abnormal
cilia
The cilium, plural cilia (), is a membrane-bound organelle found on most types of eukaryotic cell, and certain microorganisms known as ciliates. Cilia are absent in bacteria and archaea. The cilium has the shape of a slender threadlike projecti ...
-mediated signaling. The
polycystin-1
Polycystin 1 (often abbreviated to PC1) is a protein that in humans is encoded by the ''PKD1'' gene. Mutations of ''PKD1'' are associated with most cases of autosomal dominant polycystic kidney disease, a severe hereditary disorder of the kidneys ...
and
polycystin-2
Polycystin-2 is a protein that in humans is encoded by the ''PKD2'' gene.
This gene encodes a member of the polycystin protein family, called TRPP2, previously known as polycystin-2, PC2 or APKD2. TRPP2 contains multiple transmembrane domains, a ...
proteins appear to be involved in both autosomal dominant and recessive polycystic kidney disease due to defects in both proteins.
Both proteins have communication with calcium channel proteins, and causes reduction in resting (intracellular) calcium and endoplasmic reticulum storage of calcium.
The disease is characterized by a ‘second hit’ phenomenon, in which a mutated dominant allele is inherited from a parent, with cyst formation occurring only after the normal, wild-type gene sustains a subsequent second genetic ‘hit’, resulting in renal tubular cyst formation and disease progression.
PKD results from defects in the
primary cilium, an immotile, hair-like cellular organelle present on the surface of most cells in the body, anchored in the cell body by the basal body.
In the kidney, primary cilia have been found to be present on most cells of the nephron, projecting from the apical surface of the renal epithelium into the tubule lumen. The cilia were believed to bend in the urine flow, leading to changes in signalling, however this has since been shown to be an experimental error (the bending of cilia was an artifact of focal plane compensation, and also the actual effect on micturition by severe hypertension and cardiac arrest) and that bending of cilia does not contribute to alterations in Ca flux. While it is not known how defects in the primary cilium lead to cyst development, it is thought to possibly be related to disruption of one of the many signaling pathways regulated by the primary cilium, including intracellular calcium, Wnt/β-catenin, cyclic adenosine monophosphate (cAMP), or planar cell polarity (PCP). Function of the primary cilium is impaired, resulting in disruption of a number of intracellular signaling cascades which produce differentiation of cystic epithelium, increased cell division, increased apoptosis, and loss of resorptive capacity.
Diagnosis
Polycystic kidney disease can be ascertained via a
CT scan
A computed tomography scan (CT scan; formerly called computed axial tomography scan or CAT scan) is a medical imaging technique used to obtain detailed internal images of the body. The personnel that perform CT scans are called radiographers ...
of abdomen, as well as, an
MRI and
ultrasound of the same area. A physical exam/test can reveal enlarged
liver,
heart murmurs
Heart murmurs are unique heart sounds produced when blood flows across a heart valve or blood vessel. This occurs when turbulent blood flow creates a sound loud enough to hear with a stethoscope. Turbulent blood flow is not smooth. The sound dif ...
and elevated
blood pressure
Blood pressure (BP) is the pressure of circulating blood against the walls of blood vessels. Most of this pressure results from the heart pumping blood through the circulatory system. When used without qualification, the term "blood pressure" r ...
[
]
Natural history
Most cases progress to bilateral disease in adulthood.
Treatment
In 2018, Jynarque (Tolvaptan) was introduced as the first FDA-approved treatment for PKD. In a recent long-term study, patients using Tolvaptan had a 6.4% higher kidney function after 5 years compared to standard of care. In 2019, a team of researchers at UCSB found that a ketogenic diet might be able to halt, or even reverse progression in mice, and the results of a first human case series study are showing potential benefit. The results of a 3-month randomized, prospective dietary intervention clinical trial are pending. In addition, recent research indicates that mild to moderate calorie restriction or time-restricted feeding slow the progression of autosomal dominant polycystic kidney disease
Autosomal dominant polycystic kidney disease (ADPKD) is one of the most common, life-threatening inherited human disorders and the most common hereditary kidney disease. It is associated with large interfamilial and intrafamilial variability, whi ...
(ADPKD) in mice
Patient communities have been combining both ketogenic diets and time-restricted feeding with a low-oxalate diet to prevent the formation of stones and early reports show an average of 17% increase in kidney function after approximately one year on a ketogenic, time-restricted dietary regimen. If and when the disease progresses enough in a given case, the nephrologist or other practitioner and the patient will have to decide what form of renal replacement therapy
Renal replacement therapy (RRT) is therapy that replaces the normal blood-filtering function of the kidneys. It is used when the kidneys are not working well, which is called kidney failure and includes acute kidney injury and chronic kidney dis ...
will be used to treat end-stage kidney disease ( kidney failure, typically stage 4 or 5 of chronic kidney disease).
That will either be some form of dialysis Dialysis may refer to:
*Dialysis (chemistry), a process of separating molecules in solution
**Electrodialysis, used to transport salt ions from one solution to another through an ion-exchange membrane under the influence of an applied electric pote ...
, which can be done at least two different ways at varying frequencies and durations (whether it is done at home or in the clinic depends on the method used and the patient's stability and training) and eventually, if they are eligible because of the nature and severity of their condition and if a suitable match can be found, unilateral or bilateral kidney transplantation
Kidney transplant or renal transplant is the organ transplant of a kidney into a patient with end-stage kidney disease (ESRD). Kidney transplant is typically classified as deceased-donor (formerly known as cadaveric) or living-donor transplantati ...
.
A Cochrane Review study of autosomal dominant polycystic kidney disease made note of the fact that it is important at all times, while avoiding antibiotic resistance
Antimicrobial resistance (AMR) occurs when microbes evolve mechanisms that protect them from the effects of antimicrobials. All classes of microbes can evolve resistance. Fungi evolve antifungal resistance. Viruses evolve antiviral resistance. ...
, to control infections of the cysts in the kidneys, and if affected, the liver, when needed for a certain duration to combat infection, by using, " bacteriostatic and bacteriocidal
A bactericide or bacteriocide, sometimes abbreviated Bcidal, is a substance which kills bacteria. Bactericides are disinfectants, antiseptics, or antibiotics.
However, material surfaces can also have bactericidal properties based solely on thei ...
drugs".
Prognosis
ADPKD individuals might have a normal life; conversely, ARPKD can cause kidney dysfunction and can lead to kidney failure by the age of 40–60. ADPKD1 and ADPKD2 are very different, in that ADPKD2 is much milder.
Currently, there are no therapies proven effective to prevent the progression of ADPKD.
Epidemiology
PKD is one of the most common hereditary diseases in the United States, affecting more than 600,000 people. It is the cause of nearly 10% of all end-stage renal disease. It equally affects men, women, and all races. PKD occurs in some animals as well as humans.
See also
* Autosomal recessive polycystic kidney disease
References
Further reading
*
*
*
External links
{{DEFAULTSORT:Polycystic kidney disease
Kidney diseases
Ciliopathy
Congenital disorders of urinary system