Find information on thousands of medical conditions and prescription drugs.

Polycystic kidney disease

Polycystic kidney disease (PKD) is a progressive, genetic disorder of the kidneys. It occurs in humans and other animals. PKD is characterized by the presence of multiple cysts (polycystic) in both kidneys. The disease can also damage the liver, pancreas and rarely the heart and brain. The two major forms of polycystic kidney disease are distinguished by their patterns of inheritance. more...

Bubonic plague
Pacman syndrome
Paget's disease of bone
Paget's disease of the...
Palmoplantar Keratoderma
Pancreas divisum
Pancreatic cancer
Panic disorder
Paramyotonia congenita
Parkinson's disease
Parkinson's disease
Paroxysmal nocturnal...
Patau syndrome
Patent ductus arteriosus
Pelizaeus-Merzbacher disease
Pelvic inflammatory disease
Pelvic lipomatosis
Pendred syndrome
Periarteritis nodosa
Perinatal infections
Periodontal disease
Peripartum cardiomyopathy
Peripheral neuropathy
Periventricular leukomalacia
Pernicious anemia
Persistent sexual arousal...
Pes planus
Peutz-Jeghers syndrome
Peyronie disease
Pfeiffer syndrome
Photosensitive epilepsy
Pica (disorder)
Pickardt syndrome
Pili multigemini
Pilonidal cyst
Pityriasis lichenoides...
Pityriasis lichenoides et...
Pityriasis rubra pilaris
Placental abruption
Pleural effusion
Plummer-Vinson syndrome
Pneumocystis jiroveci...
Pneumonia, eosinophilic
POEMS syndrome
Poland syndrome
Polyarteritis nodosa
Polycystic kidney disease
Polycystic ovarian syndrome
Polycythemia vera
Polymyalgia rheumatica
Polyostotic fibrous...
Pompe's disease
Popliteal pterygium syndrome
Porphyria cutanea tarda
Portal hypertension
Portal vein thrombosis
Post Polio syndrome
Post-traumatic stress...
Postural hypotension
Poxviridae disease
Prader-Willi syndrome
Precocious puberty
Premature aging
Premenstrual dysphoric...
Primary biliary cirrhosis
Primary ciliary dyskinesia
Primary hyperparathyroidism
Primary lateral sclerosis
Primary progressive aphasia
Primary pulmonary...
Primary sclerosing...
Prinzmetal's variant angina
Proconvertin deficiency,...
Progressive external...
Progressive multifocal...
Progressive supranuclear...
Protein S deficiency
Protein-energy malnutrition
Proteus syndrome
Prune belly syndrome
Pseudomyxoma peritonei
Pseudotumor cerebri
Pseudoxanthoma elasticum
Psychogenic polydipsia
Psychophysiologic Disorders
Pubic lice
Puerperal fever
Pulmonary alveolar...
Pulmonary hypertension
Pulmonary sequestration
Pulmonary valve stenosis
Pulmonic stenosis
Pure red cell aplasia
Purpura, Schoenlein-Henoch
Purpura, thrombotic...
Pyoderma gangrenosum
Pyruvate kinase deficiency

Autosomal dominant polycystic kidney disease (ADPKD) is generally a late onset disorder characterized by progressive cyst development and bilaterally enlarged kidneys with multiple cysts. Kidney manifestations in this disorder include renal function abnormalities, hypertension, renal pain, and renal insufficiency. Approximately 50% of patients with ADPKD have end-stage renal disease (ESRD) by age 60 years. ADPKD is, however, a systemic disease with cysts in other organs such as the liver, seminal vesicles, pancreas, and arachnoid mater and non-cystic abnormalities such as intracranial aneurysms and dolichoectasias, dilatation of the aortic root and dissection of the thoracic aorta, mitral valve prolapse, and abdominal wall hernias.

Initial human symptoms are hypertension, fatigue and mild pain and urinary tract infections. The disease often leads to chronic renal failure and may result in total loss of kidney function, known as end stage renal disease (ESRD) which requires some form of renal replacement therapy (e.g. dialysis).

Autosomal recessive polycystic kidney disease (ARPKD) is much rarer that ADPKD and is often lethal. The signs and symptoms of the condition are usually apparent at birth or in early infancy.


The disease exists both in an autosomal recessive and an autosomal dominant form. The autosomal dominant form, called ADPKD (autosomal dominant PKD or "Adult-onset PKD") is much more common but less severe. In 85% of patients, ADPKD is caused by mutations in the gene PKD1 (chromosomal locus 16p13.3-p13.1); in 15% of patients mutations in PKD2 (chromosomal locus 4q21-q23) are causative.

The recessive form, called ARPKD (autosomal recessive polycystic kidney disease) is the less common variant, mutations in the PKHD1 (chromosomal locus 6p12.2) cause ARPKD.

A very small number of families with polycystic kidney disease do not have apparent mutations in any of the three known genes. An unidentified gene or genes may also be responsible for this disease.

Polycystic kidney disease is one of the most common inherited disorders caused by mutations in a single gene. It affects about 500,000 people in the United States. The autosomal dominant form of the disease is much more common than the autosomal recessive form. Autosomal dominant polycystic kidney disease affects 1 in 400-1,000 people, while the autosomal recessive type is estimated to occur in 1 in 20,000-40,000 people.


Recent studies in fundamental cell biology of cilia/flagella using experimental model organisms like the green algae Chlamydomonas, the round worm Caenorhabditis elegans and the mouse Mus musculus have shed light on how PKD develops in patients. All cilia and flagella are constructed and maintained, including localizing of protiens inserted into ciliary and flagellar membranes, by the process of intraflagellar transport. Environmental sensing and cellular signaling pathways initiated from proteins inserted into ciliary/flagellar membranes are thought to be critical for normal renal cell development and functioning. Membrane protiens which function in developmental and physiological environmental sensing and intracellular signalling are sorted to and localized to the cilia in renal epithelial cells by intraflagellar transport. These epithelial cells line the lumen of the urinary collecting ducts and sense the flow of urine. Failure in flow-sensing signaling results in programed cell death or apoptosis of these renal epithelial cells producing the characteristc multiple cysts of PKD. PKD may result from mutations of signaling and environmantal sensing protiens, or failure in intraflagellar transport. Two PKD genes, PKD1 and PKD2, encode membrane proteins which localize to a non-motile cilium on the renal tube cell. Polycystin-2 encoded by PKD2 gene is a calcium channel which allows extracellular calcium ions to enter the cell. Polycystin-1, encoded by PKD1 gene, is thought to be associated with polycystin-2 protein and regulate its channel activity. The calcium ions are important cellular messengers which, in turn, trigger complicated biochemical pathways which lead to cell proliferation and differentiation. Malfunctions of polycystin-1 or polycystin-2 proteins, defects in the assembly of the cilium on the renal tube cell, failures in targeting these two proteins to the cilium, and deregulations of calcium signaling all likely cause the occurrence of PKD.


[List your site here Free!]

Polycystic kidney disease: guidelines for family physicians - Editorial
From American Family Physician, 2/15/96 by V.E. Torres

Few diseases can cause as much distortion of an organ as autosomal dominant polycystic kidney disease (ADPKD). Many physicians have an enduring impression from the sight at surgery or at autopsy of massively enlarged polycystic kidneys or a huge cystic liver, with the parenchyma entirely replaced by cysts of variable sizes and colors ranging from pale yellow to black.

These massively enlarged organs represent the end of the spectrum of a common disease that in recent years has been diagnosed earlier and more frequently than in the past. Too often in the past, physicians approached ADPKD with undue pessimism and therapeutic nihilism, and patients trying to cope with the diagnosis were left in despair or denial. With the increased recognition of milder and earlier cases of ADPKD and advances in molecular biology, molecular genetics and medical technology, these attitudes toward ADPKD are no longer justified.

Family physicians should be able to counsel patients and their families so that this disease does not become an unreasonable burden. The article in this issue on ADPKD(1) provides useful information on the course of this disease. Five basic points for physicians will help in the management of ADPKD:

* Understand the genetic heterogeneity and marked phenotypic variability of ADPKD. The ADPKD1 gene on chromosome 16p13.3 is responsible for most cases of the disease. The ADPKD2 gene on chromosome 4 q13-q23 is responsible for a milder form of the disease. Because linkage studies were initially performed in families of patients in dialysis units, the relative prevalence of ADPKD2 has been underestimated. ADPKD2 probably accounts for at least 10 percent to 20 percent of families with ADPKD. In addition, evidence points to a third gene (ADPKD3), as well as to another gene that causes polycystic liver disease without renal involvement.

Until recently, only the ADPKD1 gene had been identified and completely sequenced. It is a very large gene and encodes a protein (polycystin), the function of which is now the focus of intensive research. The large size of the gene increases the likelihood of mutation events and may explain the high prevalence of ADPKD. The mutations so far identified are highly heterogeneous, which makes the diagnosis of the disease by direct mutation analysis difficult. For now, diagnostic genetic testing depends on linkage analysis in families with at least six relatives with an established diagnosis, of which at least two are affected.

The high phenotypic variability of ADPKD reflects the genetic heterogeneity, different mutations in the same gene, different genetic background and environmental factors. The marked effects of different genetic backgrounds and environmental factors have been clearly demonstrated in models of inherited polycystic disease in rodents.

* Distinguish ADPKD from other renal cystic diseases. The diagnosis of ADPKD in patients with a family history of the disease and a compatible phenotype is straightforward. The ultrasonographic diagnostic criteria for individuals known to be at 50 percent risk for the disease have been recently revised: two cysts, either unilateral or bilateral, for individuals less than 30 years old; two cysts in each kidney for those 30 to 59 years of age, and at least four cysts in each kidney for those over the age of 60 years. The early, but rare, clinical presentation of ADPKD in the first year of life, with large echogenic kidneys without distinct macroscopic cysts, is an exception to these criteria.

In the absence of a family history of this disease or in the presence of atypical phenotypes, other renal cystic diseases and benign simple cysts should be considered in the differential diagnosis. Renal cystic diseases that are occasionally confused with ADPKD include those associated with malformation or disruption syndromes, autosomal recessive polycystic kidney disease, tuberous sclerosis complex, von Hippel-Lindau's disease, orofaciodigital syndrome type 1, localized renal cystic disease and acquired renal cystic disease. Acquired renal cysts have been observed in conditions such as renal insufficiency, ischemia, chronic hypokalemia and renal tubular acidosis.

* Know why, when and how to screen family members for the presence of the disease. Only individuals who have been properly informed about the advantages and disadvantages of screening should be offered presymptomatic screening for ADPKD and they should receive appropriate follow-up counseling if ADPKD is diagnosed. Presymptomatic screening can be performed by ultrasound examination, which may not be conclusive before the age of 20 years, or by genetic linkage analysis, which is possible only in large families with detailed medical histories. Screening by ultrasound examination is adequate in most cases.

Prenatal diagnosis by chorionic villus sampling and DNA linkage analysis is rarely performed, since termination of pregnancy is usually not considered an acceptable option by ADPKD patients. Blood pressure monitoring and abdominal palpation to exclude large kidneys should be performed in children at risk for ADPKD, but presymptomatic screening is not in their best interest.

Young adults may benefit from presymptomatic screening. If they are not affected, they will be reassured, and if they are affected, they may benefit from specialized counseling for family planning and from the identification and management of such treatable complications as hypertension. The disadvantages of presymptomatic screening relate to insurability and employability. Recommendations will change when more effective therapies for the disease become available.

* Detect and treat conditions that may affect the outcome of ADPKD. Hypertension is a common, early and often nondiagnosed manifestation of ADPKD and may lead to early organ damage. Left ventricular hypertrophy by echocardiographic criteria develops in young adults and is an independent risk factor for premature death. Hypertension increases the morbidity and mortality caused by extrarenal manifestations of ADPKD, such as valvular heart disease, intracranial aneurysms and aortic dissections. Hypertensive cerebral hemorrhage may be more frequent than aneurysmal cerebral hemorrhage in ADPKD. The development of renal insufficiency is accompanied by severe intrarenal arterial and arteriolar sclerosis, possibly due in part to hypertension.

Existing hypertension is the most important risk factor for fetal and maternal complications during pregnancy. An early diagnosis and aggressive treatment of hypertension in ADPKD is imperative. Attention should also be paid to correction of other cardiovascular risk factors (e.g., smoking and hyperlipidemia, which have also been associated with a poor renal prognosis).

* Promptly identify problems that require specialized evaluation and treatment. Patients with flank pain, episodes of hematuria or any impairment of renal function should be evaluated by a nephrologist. Localized abdominal pain, fever and constitutional symptoms may indicate the presence of a cyst infection or, rarely, an associated malignancy. The risk of a subarachnoid hemorrhage in a patient with ADPKD is small and does not justify widespread screening for intracranial aneurysms. However, a sudden, severe and localized headache may signal aneurysmal leak. Selective presymptomatic screening for aneurysms may be warranted in subsets of patients with a higher risk.

Patients with severe polycystic liver disease should be cautioned against becoming pregnant, using oral contraceptives or taking postmenopausal estrogens. The rare patients with chronic pain due to distortion of the kidneys by large cysts and patients with severe, highly symptomatic polycystic liver disease may benefit from percutaneous cyst aspiration, alcohol sclerosis or surgical interventions. The type of treatment indicated in each case depends on the number, size and distribution of the cysts. Surgical interventions such as laparoscopic fenestration of polycystic kidneys or combined hepatic resection and cyst fenestration are difficult procedures, with significant morbidity, and should only be performed by surgeons experienced in these procedures.

Importantly, ADPKD should not be viewed as a congenital disease with a fate already determined at birth. It is an inherited disease with a highly variable and potentially modifiable clinical course. It is treatable and to some extent, its complications are preventable. The remarkable research accomplishments of the past decade have raised the hopes of physicians and patients and have planted the seeds for finding even better treatments in the near future.

(1) Beebe DK. Autosomal dominant polycystic kidney disease. Am Fam Physician 1996;53:925-35.

COPYRIGHT 1996 American Academy of Family Physicians
COPYRIGHT 2004 Gale Group

Return to Polycystic kidney disease
Home Contact Resources Exchange Links ebay