Polycystic kidney disease overview
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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief: M. Khurram Afzal, MD [2], Serge Korjian, Yazan Daaboul
Overview
Autosomal dominant polycystic kidney disease (ADPKD), previously known as adult polycystic kidney disease, is a systemic disorder characterized primarily by multiple, bilateral renal cysts, cysts in other organs namely the liver and pancreas, and cardiovascular abnormalities including intracranial aneurysms and mitral valve prolapse. ADPKD is one of the most common inherited disorders worldwide almost 15 times more common than cystic fibrosis in the general population. It accounts for up to 3-5% of ESRD cases yearly. Classically, ADPKD presents with hypertension and varying degrees of renal insufficiency. Around half of the patients diagnosed with ADPKD will reach end-stage renal disease (ESRD) by the age of 60 years. Still, disease manifestation and severity is highly variable among patients even those within the same family.
Historical Perspective
King Stephen Bathory of Poland died from polycystic kidney disease in 1586. His death began the journey of the discovery of polycystic kidney disease as a disease process. In 1888, Fe´lix Lejars first used the term polycystic kidney. In the late 18th century, Dr. Matthew Baillie noted that these cysts were vesicular and not hydatid, and named them false hydatids of kidney. In 1994, PKD1 gene mutation on chromosome 16, was first implicated in the pathogenesis of ADPKD patients.
Classification
There is no established system for the classification of polycystic kidney disease. There are 2 types of polycystic kidney disease, autosomal dominant polycystic kidney disease (ADPKD) and autosomal recessive polycystic kidney disease (ARPKD). ADPKD has two major types ADPKD1 due to PDK1 mutation, and ADPKD2 due to PDK2 mutation. A third subtype can be considered in patients without any documented mutation. Autosomal recessive polycystic kidney disease (ARPKD) was previously known as infantile polycystic kidney disease and occurs mainly in children.
Pathophysiology
The pathogenesis of ADPKD is related to the protein products of the PKD1 and PKD2 genes known collectively as polycystins. These proteins are primarily involved in ciliary function in the renal tubular cells and defects in their function leads to intracellular cAMP accumulation and mTOR overactivity causing cell proliferation, fluid secretion, and abnormal extracellular matrix and intercellular interactions the main processes that lead to cyst formation.
Causes
Polycystic kidney disease is a genetic disorder. Autosomal dominant polycystic kidney disease (ADPKD) is an autosomal dominant disorder due to the heterozygous inheritance of PKD1 (chromosome 16) or PKD2 (chromosome 4) gene mutations. Despite the disease being monogenic, phenotype is variable possibly due to a two-hit process, haploinsufficiency, or environmental factors. Autosomal recessive polycystic kidney disease (ARPKD) is caused by a mutation in the PKHD1 gene.
Differentiating Polycystic Kidney Disease from Other Diseases
Autosomal dominant and autosomal recessive polycystic kidney disease must be differentiated from other diseases that cause renal cysts, such as simple renal cysts, medullary sponge kidney, tuberous sclerosis complex, von hippel-lindau disease.
Epidemiology and Demographics
The prevalence of autosomal dominant polycystic kidney disease (ADPKD) is approximately 100 - 250 per 100,000 individuals in the United States. The prevalence of ADPKD varies in different countries. The prevalence of autosomal recessive polycystic kidney disease (ARPKD) is approximately 5 per 100,000 children in the United States. The incidence increases with age for ADPKD. ARPKD commonly affects infants and children. Males and females are equally affected by ADPKD.
Risk Factors
There are no established risk factors for polycystic kidney disease. Since both autosomal dominant and autosomal recessive forms are genetic disorders, to review the genetic causes of polycystic kidney disease click here.
Screening
According to the Unified criteria for ultrasonographic diagnosis, screening for polycystic kidney disease by ultrasonography is recommended in at risk patients with family history of polycystic kidney disease. According to the kidney disease improving global outcomes (KDIGO), screening for polycystic kidney disease in children less than 18 years of age is not recommended. Serum creatinine, urinalysis and regular blood pressure measurements can also be implemented to test in these patients.
Natural History, Complications, and Prognosis
The earliest clinical signs of disease in patients with ADPKD include impaired renal concentrating capacity and hypertension. Other signs include flank pain, nephrolithiasis and urinary tract infections. In general half of the patients diagnosed with ADPKD will progress to ESRD by age 60. PDK1 mutants usually progress faster than PDK2 mutants. Factors associated with worse renal outcome include early age at diagnosis, male gender, uncontrolled hypertension, left ventricular hypertrophy, and cystic liver. Extra-renal manifestations in ADPKD include hepatic cysts usually more prevalent in women and with advancing age and declining renal function. Cysts can also be seen in the seminal vesicles, pancreas, and arachnoid membrane. Furthermore, the development of intracranial aneurysms can be a lethal complication in ADPKD patients whose risk is closely linked to the family history of aneurysms. Mitral valve prolapse is also a common cardiac manifestation seen in 25% of patients. Most cases of ARPKD present in the neonatal period with some disease findings detected on prenatal ultrasound. Most feared and common complication of ARPKD is pulmonary hypoplasia. Half of ARPKD patients usually progress to ESRD by age of 10. The prognosis of ARPKD improves in patients who survive the first few months of life. Survival at 15 years for patients of ARPKD ranges from 50% - 80%.
Diagnosis
Diagnostic Study of Choice
The diagnostic study of choice for polycystic kidney disease is ultrasound. Findings on an ultrasound diagnostic of polycystic kidney disease include, atleast three unilateral or bilateral cysts in patients 15 - 39 years old, atleast two cysts in each kidney in patients 40 - 59 years old, atleast four cysts in each kidney in patients 60 years of age or older.
History and Symptoms
The hallmark of polycystic kidney disease is flank or back pain. A positive family history of renal failure, cystic diseases, intracranial aneurysms is suggestive of polycystic kidney disease. The most common symptoms of polycystic kidney disease include hematuria, polyuria, nocturia and hypertension.
Physical Examination
Patients with polycystic kidney disease usually are in discomfort. Physical examination of patients with polycystic kidney disease is usually remarkable for hypertension, jaundice, pallor, icteric sclera, palpable nodular hepatomegaly, palpable flank mass.
Laboratory Findings
Common laboratory findings in polycystic kidney disease are urinary abnormalities including reduction in concentration capacity, hypocitraturia, hematuria, and proteinuria. Hyperuricemia is also a common finding and is a risk factor for disease progression and ESRD.
Electrocardiogram
There are no ECG findings associated with polycystic kidney disease.
X-ray
An x-ray KUB may be helpful in the diagnosis of polycystic kidney disease. Findings on an x-ray suggestive of polycystic kidney disease include, enlarged kidneys, multiple ring like calcifications arising from the renal cyst, elongated and splayed calyces due to the cyst.
Ultrasound
Ultrasound may be helpful in the diagnosis of polycystic kidney disease. Findings on an ultrasound diagnostic of polycystic kidney disease include, atleast three unilateral or bilateral cysts in patients 15 - 39 years old, atleast two cysts in each kidney in patients 40 - 59 years old, atleast four cysts in each kidney in patients 60 years of age or older.
CT scan
Although ultrasonography is the modality of choice for diagnosing ADPKD mainly due to the low cost and lack of radiation exposure, computed tomography and magnetic resonance imaging have higher resolutions and increased sensitivity for renal cysts less than 1 cm in diameter. Findings on CT scan include, numerous renal cysts of varying size and shape with little intervening parenchyma with water attenuation and very thin wall, reduction in sinus fat due to expansion of the cortex, occasional complex cysts with hyperdense appearance, with possible septations or calcifications, multiple homogeneous and hypoattenuating cystic lesions in the liver in patients with liver involvement.
MRI
Magnetic resonance imaging can be used to identify cysts smaller than 1 cm and to differentiate complex from simple cysts without contrast or radiation exposure. Renal MRI may be helpful in the diagnosis of polycystic kidney disease. Findings on MRI diagnostic of polycystic kidney disease include, T2 weighted images show enlarged kidneys with multiple cysts, normal parenchyma is absent, presence of fluid/fluid interface, wall thickening, hypointense signals in T2-weighted and DWI images, and hyperintense signals in T1-weighted images.
Other Imaging Findings
There are no other imaging findings associated with polycystic kidney disease.
Other Diagnostic Studies
Other diagnostic studies for polycystic kidney disease include, genetic testing, which demonstrates, frame insertions / deletions, non-canonical splice site alterations, combined missense changes.
Treatment
Medical Therapy
Patients with polycystic kidney disease are treated with lisinopril or telmisartan for control of hypertension, tolvaptan for slowing disease progression, hydration, analgesia and bed rest. The treatment is targeted more towards managing symptoms and disease complications rather than slowing cyst formation.
Interventions
Dialysis is not the first-line treatment option for patients with polycystic kidney disease. Dialysis is usually reserved for patients with either end stage renal disease (ESRD) or renal failure.
Surgery
Surgery is not the first-line treatment option for patients with polycystic kidney disease. Surgery is usually reserved for patients with either end stage renal disease (ESRD), recurrent UTI, chronic pain, renal cell carcinoma, chronic hematuria requiring transfusions. Surgical options are either nephrectomy or renal transplantation.
Primary Prevention
Since polycystic kidney disease is a genetic disorder. There are no established measures for the primary prevention of polycystic kidney disease.
Secondary Prevention
There are no established measures for the secondary prevention of polycystic kidney disease.