Question 1 of 10

    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.

    Presentation

    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.

    Liver, Gall & Pancreas
    Hepatomegaly
    • However, in rare cases the condition may be complicated with massive hepatomegaly leading to compression of the surrounding organs, or acute complications [ 2 ].[omicsonline.org]
    • 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[emedicine.medscape.com]
    • Symptoms that can occur include enlargement of the liver (hepatomegaly), pain in the lower portion of the back, an abnormal early feeling of fullness (early satiety), shortness of breath especially upon exertion (dyspnea), and backflow of the contents[rarediseases.org]
    • (If other organs are cystic there may be palpable hepatomegaly and even splenomegaly.)[patient.info]
    • The liver is the second most frequently affected organ, with hepatic cysts that cause hepatomegaly and abdominal pain although they may exceptionally cause hepatic dysfunction. [2] Cysts may also occur occasionally in the pancreas, ovaries, and choroid[sjkdt.org]
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  • Entire body system
    Anemia
    • They may initially order a complete blood count to look for anemia or signs of infection and a urinalysis to look for blood, bacteria, or protein in your urine.[healthline.com]
    • Anemia is less common than in other types of chronic kidney disease , presumably because erythropoietin production is preserved.[merckmanuals.com]
    • Serial hemoglobin levels may be needed to assure that the patient does not have significant anemia requiring transfusion.[journals.lww.com]
    • Laboratory examinations revealed hypokalemia and anemia due to iron deficiency ( Table I ).[spandidos-publications.com]
    • 2000 and incidence of 1:3000-1:8000 in a global scale. [5] [6] [7] [8] [9] Signs and symptoms [ edit ] Acute loin pain Haematuria Ballotable kidneys Sub arachnoid hemorrhage(berry aneurysm) Hypertension Associated liver cyst Uremia due to renal failure Anemia[en.wikipedia.org]
    Fever
    • Fever is common with acute pyelonephritis, and rupture of cysts into the retroperitoneal space may cause a fever that can last for weeks.[merckmanuals.com]
    • You have a fever.[drugs.com]
    • Symptoms: Hematuria (50%) Flank pain and fever (cyst rupture oder cyst infection) Nephrolithiasis Gastrointestinal symptoms due to large kidneys Arterial hypertension (80%) Renal failure and symptoms of uremia usually not before the age of 40 years Manifestations[urology-textbook.com]
    • These may include fever, right upper quadrant pain (from liver cysts), and headache (from unruptured cerebral aneurysm or uncontrolled hypertension).[journals.lww.com]
    • Cyst infections are associated with fever and back or abdominal pain.[rarediseases.org]
    Flank Mass
    • Clinical presentation is variable and includes 1 : dull flank pain of variable severity and time course: most common abdominal or flank masses haematuria hypertension: usually develops at the same time as renal failure renal functional impairment to renal[radiopaedia.org]
    • masses: In advanced ADPKD Nodular hepatomegaly: In severe polycystic liver disease Rarely, symptoms related to renal failure (eg, pallor, uremic fetor, dry skin, edema) Testing Routine laboratory studies include the following: Serum chemistry profile[emedicine.medscape.com]
    Infertility
    • Cysts affecting the seminal vesicles can potentially cause infertility.[rarediseases.org]
    • Male infertility is rare but can be due to cysts in the seminal vesicles and defective sperm motility.[patient.info]
    • Patients may also experience symptoms due to extra-renal involvement that include the liver and pancreas, cardiac valvular disease, intracranial aneurysms and diverticulosis as well as infertility related to seminal vesical cysts.[renalandurologynews.com]
    • Rarely, hepatic cyst infection can develop and requires antibiotic treatment or drainage. 16 Seminal vesicle cysts may cause male infertility. 16 Hypertension Many patients with ADPKD have hypertension that typically occurs early in the disease and is[journals.lww.com]
    Weight Loss
    • A wide variety of symptoms may be associated with end stage renal disease including fatigue, weakness, weight loss, difficulty breathing, nausea, vomiting, and cognitive problems such as difficulties concentrating or thinking clearly.[rarediseases.org]
    • Cyst size and number increase with age. [2] Although hepatic failure is uncommon, symptoms related to a massively enlarged cystic liver include loss of appetite, weight loss, esophageal reflux, and abdominal discomfort, which interfere with the activities[sjkdt.org]
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  • neurologic
    Headache
    • Evaluating Headaches See your doctor if you have severe or recurring headaches — especially if they feel different from other headaches you've had.[ucsfhealth.org]
    • You have a very bad headache, or you have frequent headaches.[drugs.com]
    • Headaches also can be caused by high blood pressure.[medicinenet.com]
    • The most common symptoms are pain in the back and the sides and headaches.[rarediseases.info.nih.gov]
    • Subarachnoid haemorrhage Symptoms of a subarachnoid haemorrhage include: a sudden and severe headache, which has been described as a 'thunderclap headache' - it is similar to a sudden hit on the head and causes a blinding pain that is unlike anything[hse.ie]
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  • Immune System
    Splenomegaly
    • (If other organs are cystic there may be palpable hepatomegaly and even splenomegaly.)[patient.info]
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  • gastrointestinal
    Abdominal Mass
    • The patient underwent abdominal and pelvic CT scanning with contrast for evaluation of an abdominal mass, which showed innumerable cystic lesions in both kidneys, suggestive of polycystic disease (Figure) .[patientcareonline.com]
    • […] of life. 2 Worldwide, about 12.5 million people have ADPKD, and it accounts for about 10% of cases of end-stage renal disease. 1,3,4 ADPKD has a variety of clinical presentations, including (in decreasing order of frequency) hypertension, flank pain, abdominal[mdedge.com]
    • The most common abnormalities related to the kidneys are arterial hypertension, abdominal mass, urinary tract infection (UTI), lumbar or abdominal pain, hematuria, nephrolithiasis, and renal failure.[sjkdt.org]
    Abdominal Pain
    • Abdominal pain is a common symptom in ADKPD.[hindawi.com]
    • Cyst infections are associated with fever and back or abdominal pain.[rarediseases.org]
    • pain, hypertension, urinary tract infection or urolithiasis Associated with von Meyenburg complexes in liver (97%, Mod Pathol 1996;9:233 ); hepatic cysts (40% - 88%); berry aneurysms (10% - 30%, cause death in 4% - 10%); mitral valve prolapse (20%);[pathologyoutlines.com]
    • Symptoms and signs include flank and abdominal pain, hematuria, and hypertension.[merckmanuals.com]
    • The age at diagnosis was higher, and there was a high prevalence of hypertension, nocturia, abdominal pain, nephrolithiasis, UTI, and renal dysfunction in Indian ADPKD patients.[sjkdt.org]
    Increased Abdominal Girth
    • Physical findings include increased blood pressure on average by 30 years of age, including 20% of affected children, increased abdominal girth, and ventral and inguinal hernias and auscultory abnormalities related to cardiac valve diseases such as mitral[renalandurologynews.com]
    Nausea
    • A wide variety of symptoms may be associated with end stage renal disease including fatigue, weakness, weight loss, difficulty breathing, nausea, vomiting, and cognitive problems such as difficulties concentrating or thinking clearly.[rarediseases.org]
    • If that happens, you may have: Fatigue The need to pee often Irregular periods Nausea Shortness of breath Swollen ankles , hands, and feet Erectile dysfunction Getting a Diagnosis If your doctor thinks there’s a problem with your kidneys, she may want[webmd.com]
    • Symptoms and signs of unruptured cerebral aneurysm can be absent or may include headache, nausea and vomiting, and cranial nerve deficits; these manifestations warrant immediate intervention (see Vascular Lesions in the Brain ).[merckmanuals.com]
    • ., early satiety , nausea and vomiting, and abdominal discomfort), from their enlarged kidneys. [42] [43] [44] In such cases, nephrectomy can be required due to intractable symptoms or when, in the course of preparing for renal transplantation , the native[en.wikipedia.org]
    • ., nausea and vomiting, lethargy, photophobia, focal signs, seizure, transient ischemic attack, loss of consciousness) Family history of intracranial aneurysm or intracranial hemorrhage High-risk occupation (e.g., airline pilot) New-onset severe headache[aafp.org]
    Vomiting
    • As the condition progresses, you may also have one or more of the following symptoms: severe headaches vision problems, such as blurred vision, or seeing flashing lights before your eyes pain in your upper abdomen (just below your ribs) vomiting excessive[hse.ie]
    • A wide variety of symptoms may be associated with end stage renal disease including fatigue, weakness, weight loss, difficulty breathing, nausea, vomiting, and cognitive problems such as difficulties concentrating or thinking clearly.[rarediseases.org]
    • Symptoms and signs of unruptured cerebral aneurysm can be absent or may include headache, nausea and vomiting, and cranial nerve deficits; these manifestations warrant immediate intervention (see Vascular Lesions in the Brain ).[merckmanuals.com]
    • ., early satiety , nausea and vomiting, and abdominal discomfort), from their enlarged kidneys. [42] [43] [44] In such cases, nephrectomy can be required due to intractable symptoms or when, in the course of preparing for renal transplantation , the native[en.wikipedia.org]
    • ., nausea and vomiting, lethargy, photophobia, focal signs, seizure, transient ischemic attack, loss of consciousness) Family history of intracranial aneurysm or intracranial hemorrhage High-risk occupation (e.g., airline pilot) New-onset severe headache[aafp.org]
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  • musculoskeletal
    Back Pain
    • In those who go on to become symptomatic, this occurs by the end of the second decade in life, where flank pain, abdominal and lower back pain due to cystic enlargement and symptoms of infection are the most common complaints. [almostadoctor.co.uk]
    • Additional symptoms that can occur in individuals with ADPKD include blood in the urine (hematuria), abdominal or lower back pain, the development of kidney stones (nephrolithiasis), chronic urinary traction infections, and cyst infections.[rarediseases.org]
    • Symptoms include low-grade flank, abdominal, and lower back pain due to cystic enlargement and symptoms of infection.[merckmanuals.com]
    • Symptoms tend to result from mass effect (eg, dyspnoea, early satiety, gastro-oesophageal reflux, low back pain, ascites, oesophageal varices, obstructive jaundice) or from cyst complications (eg, haemorrhage, infection, torsion or rupture).[patient.info]
    • However, symptoms resulting from significant liver enlargement can include shortness of breath, early satiety or loss of appetite, abdominal discomfort, esophageal reflux, lower extremity edema, low back pain, and rarely inferior vena cava compression[aafp.org]
    Low Back Pain
    • Symptoms tend to result from mass effect (eg, dyspnoea, early satiety, gastro-oesophageal reflux, low back pain, ascites, oesophageal varices, obstructive jaundice) or from cyst complications (eg, haemorrhage, infection, torsion or rupture).[patient.info]
    • However, symptoms resulting from significant liver enlargement can include shortness of breath, early satiety or loss of appetite, abdominal discomfort, esophageal reflux, lower extremity edema, low back pain, and rarely inferior vena cava compression[aafp.org]
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  • cardiovascular
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  • urogenital
    Dysuria
    • Pyuria is common even without bacterial infection; thus diagnosis of infection should be based on culture results and clinical findings (eg, dysuria, fever, flank pain) as well as urinalysis.[merckmanuals.com]
    Flank Pain
    • CT: Abdominal CT: imaging of renal cysts, e.g. if flank pain has to be evaluated.[urology-textbook.com]
    • In this paper we describe an 11-year-old child with ADPKD who was presented with bloody urine and flank pain.[hindawi.com]
    • In those who go on to become symptomatic, this occurs by the end of the second decade in life, where flank pain, abdominal and lower back pain due to cystic enlargement and symptoms of infection are the most common complaints. [almostadoctor.co.uk]
    • Clinical presentation is variable and includes 1 : dull flank pain of variable severity and time course: most common abdominal or flank masses haematuria hypertension: usually develops at the same time as renal failure renal functional impairment to renal[radiopaedia.org]
    • Flank pain secondary to renal hemorrhage, calculi, or urinary tract infection is the most common symptom. 4 ADPKD is also associated with cerebral aneurysms, hepatic cysts, mitral and aortic valve prolapse, colonic diverticular disease, pancreatic cysts[patientcareonline.com]
    Hematuria
    • Hemorrhage into cysts may occur, causing hematuria.[merckmanuals.com]
    • Occasionally, hematuria can persist for weeks.[journals.lww.com]
    • Hematuria affects approximately 40 percent of individuals.[rarediseases.org]
    • Patients with recurrent episodes of gross hematuria have the largest kidneys and progress more quickly to kidney failure. [16] Gross or microscopic hematuria was reported in 21.6% patients in our study.[sjkdt.org]
    • Clinical profiles of gross hematuria in autosomal dominant polycystic kidney disease.[aafp.org]
    Kidney Failure
    • When kidney function starts to decline, treatment is aimed at slowing down the progression to kidney failure.[genome.gov]
    • It is the fourth leading cause of kidney failure and more than 50 percent of people with ADPKD will develop kidney failure by age 50.[pkdcure.org]
    • It causes about 5% of all kidney failure.[kidney.org]
    • PKD is the fourth leading cause of kidney failure.[healthline.com]
    Macroscopic Hematuria
    • Urinalysis detects mild proteinuria and microscopic or macroscopic hematuria.[merckmanuals.com]
    • […] filtration rate declines at an average of 4.4 to 5.9 mL per minute per year. 8 Clinical Manifestations and Management Many patients with ADPKD are asymptomatic, and only a few patients will present early with symptoms such as abdominal or flank pain, macroscopic[aafp.org]
    Nocturia
    • An impaired concentrating ability leads to nocturia.[sjkdt.org]
    • Damage to the kidneys in ADPKD may be slowly progressive and can cause a variety of symptoms including weakness and fatigue, changes in appetite, puffiness or swelling, back pain, poor digestion, nausea and vomiting and nocturia (night-time urination)[rarediseases.org]
    • Complications associated with renal disease Impaired urine concentrating capacity is a common early presentation with problems associated with excessive water and salt loss such as nocturia.[patient.info]
    • Patients describe thirst, urinary frequency, nocturia and abdominal pain as their most significant concerns.[renalandurologynews.com]
    Polyuria
    • Tolvaptan appears to slow increase in renal volume and decline in renal function, but it can cause adverse effects via free water diuresis (eg, thirst, polydipsia, polyuria) that can make adherence difficult.[merckmanuals.com]
    • Side effects related to increased urine output including polyuria and polydipsia were found in the tolvaptan treated participants and a slight increase in prevalence of increased liver transaminases were found.[renalandurologynews.com]
    • A defect in urine concentrating ability with onset in childhood is common in patients with ADPKD, [2] many of whom also report polydipsia and polyuria at an early stage of the disease.[sjkdt.org]
    Uremic Fetor
    • fetor, dry skin, edema) Testing Routine laboratory studies include the following: Serum chemistry profile, including calcium and phosphorus CBC count from cysts Urinalysis Urine culture Uric acid determination Intact PTH assay Genetic testing may be[emedicine.medscape.com]
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  • Workup

    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].

    Test Results

    Laparoscopy
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  • Laboratory

    Serum
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  • Urine
    Pyuria
    • Pyuria is common even without bacterial infection; thus diagnosis of infection should be based on culture results and clinical findings (eg, dysuria, fever, flank pain) as well as urinalysis.[merckmanuals.com]
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  • Imaging

    X-ray
    Multiple Renal Cysts
    • renal cysts 2016 2017 2018 Billable/Specific Code POA Exempt specified as polycystic Q61.3 ICD-10-CM Diagnosis Code Q61.3 Polycystic kidney, unspecified 2016 2017 2018 Billable/Specific Code POA Exempt adult type Q61.2 kidney (acquired) N28.1 ICD-10-[icd10data.com]
    • ADPKD ACCOUNTS FOR 10% OF END-STAGE RENAL DISEASE ADPKD is a genetic condition characterized by multiple renal cysts. 1 Progressive enlargement of these cysts leads to a gradual decline in kidney function and eventually end-stage renal disease by the[mdedge.com]
    • Computed tomography indicated a right adrenal tumor and multiple renal cysts.[spandidos-publications.com]
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  • Treatment

    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.

    Prognosis

    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].

    Complications

    Acute Pyelonephritis
    • Patients are also at higher risk of acute pyelonephritis, cyst infections, and urinary calculi (in 20%).[merckmanuals.com]
    • Acute pyelonephritis and symptomatic cyst infection require admission for intravenous antibiotic therapy.[patient.info]
    • 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[emedicine.medscape.com]
    • The most frequent infections were cyst infections and acute pyelonephritis, with a determinant role in the progression of renal failure, probably in relation to the deterioration of kidney function secondary to episodes of haemodynamic instability derived[revistanefrologia.com]
    Aneurysm
    • No additional aneurysms were found by DSA.[stroke.ahajournals.org]
    • International study of unruptured intracranial aneurysms investigators.[joacp.org]
    • , and thoracic and abdominal aortic aneurysms. 5 Intracranial aneurysms (ruptured and incidentally detected aneurysms) occur in 5% of patients with ADPKD.[patientcareonline.com]
    • Coronary artery aneurysms occur.[merckmanuals.com]
    Aortic Aneurysm
    • Associated with von Meyenburg complexes in liver (97%, Mod Pathol 1996;9:233 ); hepatic cysts (40% - 88%); berry aneurysms (10% - 30%, cause death in 4% - 10%); mitral valve prolapse (20%); cysts in pancreas, lung, spleen, pineal gland and seminal vesicles; aortic[pathologyoutlines.com]
    • People who have ADPKD have renal cysts in both kidneys and may also develop cysts in other organs such as the liver and pancreas; abnormalities of blood vessels (vascular system) such as high blood pressure (hypertension) intracranial and aortic aneurysms[genome.gov]
    • Associated with colonic diverticula , aortic aneurysm , mitral valve prolapse .[librepathology.org]
    • […] hemorrhage, calculi, or urinary tract infection is the most common symptom. 4 ADPKD is also associated with cerebral aneurysms, hepatic cysts, mitral and aortic valve prolapse, colonic diverticular disease, pancreatic cysts, and thoracic and abdominal aortic[patientcareonline.com]
    Cerebral Aneurysm
    • Cerebral aneurysms are present in about 4% of young adults and up to 10% of elderly patients.[merckmanuals.com]
    • ADPKD can also be associated with extrarenal manifestations, mainly polycystic liver disease and cerebral aneurysms, which contribute to increased morbidity and mortality of these patients.[emjreviews.com]
    • Avoid instrumentation of the urinary tract, such as cystoscopy, which may dispose patients to infection. 24 Cerebral aneurysms Cerebral aneurysms are among the most deadly complications of ADPKD, occurring in 4% to 20% of patients and increasing in incidence[journals.lww.com]
    • Valvular heart disorders – in 25-30% of patients Aortic regurgitation – may result from aortic root dilation due to arterial wall changes Coronary artery aneurysms Cerebral aneurysms – in approximately 4% of young adults and up to 10% of elderly patients[almostadoctor.co.uk]
    • Management of cerebral aneurysms in autosomal dominant polycystic kidney disease.[joacp.org]
    Cerebral Hemorrhages
    Chronic Pyelonephritis
    • (WC) Sign out Kidney, Right, Nephrectomy: - Polycystic kidney with chronic pyelonephritis and changes of chronic renal failure, consistent with polycystic kidney disease. - NEGATIVE for malignancy.[librepathology.org]
    Hydronephrosis
    • ) pancreatic cysts more common primary renal disease related cysts the renal parenchyma appears abnormal, reduced in volume with increased echogenicity on ultrasound 3 multiple 'incidental' renal cysts usually far fewer in number kidney not enlarged hydronephrosis[radiopaedia.org]
    • Q61.3 Polycystic kidney, unspecified Q61.5 Medullary cystic kidney Q61.8 Other cystic kidney diseases Q61.9 Cystic kidney disease, unspecified Q62 Congenital obstructive defects of renal pelvis and congenital malformations of ureter Q62.0 Congenital hydronephrosis[icd10data.com]
    Hypertension
    Left Ventricular Hypertrophy
    • FGF23 induces left ventricular hypertrophy.[mdedge.com]
    • Renal volume, renin-angiotensin-aldosterone system, hypertension, and left ventricular hypertrophy in patients with autosomal dominant polycystic kidney disease.[patientcareonline.com]
    • Although ACE inhibitors are known to reduce proteinuria, left ventricular hypertrophy, and slow renal decline in other kidney diseases, the specific use of ACE inhibitors has not been proven to slow progression of ADPKD.[journals.lww.com]
    • ventricular hypertrophy earlier in the disease course.[aafp.org]
    • Left ventricular hypertrophy can obstruct the flow of blood from the heart and can be associated with a variety of symptoms.[rarediseases.org]
    Liver Failure
    • Therefore they do not cause liver failure.[hse.ie]
    • Also, tolvaptan has been reported to cause severe liver failure, and data on long-term outcomes are not yet sufficient to confirm a favorable benefit/harm balance.[merckmanuals.com]
    • Hepatic cysts do not cause liver failure.[patient.info]
    Nephrolithiasis
    • However, nephrolithiasis is rare in childhood age group.[hindawi.com]
    • […] of nephrolithiasis compared to females (0.044).[sjkdt.org]
    • Nephrolithiasis About 25% of patients with ADPKD develop nephrolithiasis, often presenting with the usual flank pain and hematuria.[journals.lww.com]
    • Overall prognosis: Overall prognosis has become better due to better treatment options of complications like urinary tract infection, nephrolithiasis, hypertension or renal insufficiency.[urology-textbook.com]
    • Nephrolithiasis is twice as common in persons with ADPKD compared with the general population and is suggested by flank pain with or without hematuria.[aafp.org]
    Pancreatitis
    • Distant complications include: subarachnoid haemorrhage aortic dissection General imaging differential considerations include: von Hippel Lindau disease (vHL) pancreatic cysts more common primary renal disease related cysts the renal parenchyma appears[radiopaedia.org]
    • Other symptoms include liver and pancreatic cysts, urinary tract infections , abnormal heart valves, high blood pressure , kidney stones , brain aneurysms , and diverticulosis .[rarediseases.info.nih.gov]
    • There are a number of potential presenting features: Renal Failure Unexplained hypertension Recurrent loin pain Recurrent UTIs Enlarged kidneys Incidental finding of renal, liver or pancreatic cysts on USS Subarachnoid Haemorrhage Family history of ADPKD[newcastle-hospitals.org.uk]
    • Pancreatic cysts can, rarely, cause recurrent pancreatitis.[patient.info]
    • Pancreatic and intestinal cysts, colonic diverticula, and inguinal and abdominal wall hernias – occur in higher incidence in ADPKD patients.[almostadoctor.co.uk]
    Perinephric Abscess
    • abscess) Nephrolithiasis and renal colic Rarely, a coincidental hypernephroma See Presentation for more detail.[emedicine.medscape.com]
    Polycythemia
    Proteinuria
    • The quantification of proteinuria was always lower than 300mg/dL, which agrees with that already described 19 and there were no cases of nephrotic-range proteinuria.[revistanefrologia.com]
    • Urinalysis detects mild proteinuria and microscopic or macroscopic hematuria.[merckmanuals.com]
    • Urinalysis showed no dysmorphic red blood cells or significant proteinuria.[patientcareonline.com]
    • Haematuria , hypertension and proteinuria are common signs.[almostadoctor.co.uk]
    • Because patients with ADPKD rarely have proteinuria, their BP goal is less than 140/90 mm Hg, as well.[journals.lww.com]
    Pyelonephritis
    • Patients are also at higher risk of acute pyelonephritis, cyst infections, and urinary calculi (in 20%).[merckmanuals.com]
    • (WC) Sign out Kidney, Right, Nephrectomy: - Polycystic kidney with chronic pyelonephritis and changes of chronic renal failure, consistent with polycystic kidney disease. - NEGATIVE for malignancy.[librepathology.org]
    • UTI and pyelonephritis may be presenting features.[patient.info]
    • 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[emedicine.medscape.com]
    • Both urinary tract infections (cystitis and/or pyelonephritis) and renal cyst infections can occur independently or in combination.[journals.lww.com]
    Renal Cell Carcinoma
    • cell carcinomas , which typically manifest as atypical renal cysts 10 .[radiopaedia.org]
    • "Renal cell carcinoma in autosomal dominant polycystic kidney disease.".[librepathology.org]
    • "Prevalence of renal cell carcinoma in patients with autosomal dominant polycystic kidney disease and chronic renal failure.".[en.wikipedia.org]
    • Renal cell carcinoma in autosomal dominant polycystic kidney disease.[sjkdt.org]
    • Renal cell carcinoma is a rare cause of pain in ADPKD.[patient.info]
    Renal Colic
    Secondary Hypertension
    • Primary aldosteronism (PA) is an endocrine disease that causes secondary hypertension and increases the risk of cardiovascular disease.[spandidos-publications.com]
    Subarachnoid Hemorrhage
    • Cerebral hemorrhage: 9% of patients with ADPKD die of subarachnoid hemorrhage (aneurysm hemorrhage).[urology-textbook.com]
    • […] such as hypertension, hepatic cysts, and intracranial aneurysms (ICANs). 1 Compared with the general population, patients with ADPKD have an increased frequency of ICAN with estimates of prevalence ranging from 4% to 41% and the morbidity of aneurysmal subarachnoid[stroke.ahajournals.org]
    • hemorrhage (SAH). [4] Routine screening is recommended for patients with unruptured aneurysm admitted to undergo elective surgery if they have co-existing ADPKD and a family history of previous SAH. [5] Treatment options for intracranial aneurysm range[joacp.org]
    • Comparison of intracerebral hemorrhage and subarachnoid hemorrhage in patients with autosomal-dominant polycystic kidney disease.[link.springer.com]
    • A rare cause of mortality is in ADPKD is subarachnoid hemorrhage from intracranial aneurysms. [ 23 ] 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[emedicine.medscape.com]
    Urinary Tract Infection
    • . , DOI: 10.1152/ajprenal.00279.2017 Abstract Urinary tract infection (UTI) is a broad term referring to an infection of the kidneys, ureters, bladder and/or urethra.[ajprenal.physiology.org]
    • Urinary tract infections and kidney stones are also common.[webmd.com]
    • Urinary tract infections in polycystic kidney disease.[aafp.org]
    • Other symptoms include liver and pancreatic cysts, urinary tract infections , abnormal heart valves, high blood pressure , kidney stones , brain aneurysms , and diverticulosis .[rarediseases.info.nih.gov]
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  • Etiology

    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].

    Epidemiology

    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

    Pathophysiology

    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.

    Prevention

    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].

    Summary

    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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    References

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