The polycystic kidney disease (PKD) is a hereditary disorder with kidney cyst formation, which causes a gradual enlargement of both kidneys, sometimes with progression to renal failure. Almost all forms are due to a familial gene mutation. Symptoms and signs include flank and abdominal pain, hematuria, and hypertension. The diagnosis is made by CT or ultrasound. Treatment is before the occurrence of renal failure, then it consists of dialysis or kidney transplantation.
(See also Overview of cystic Nierenerkrankheiten.)
The polycystic kidney disease (PKD) is a hereditary disorder with kidney cyst formation, which causes a gradual enlargement of both kidneys, sometimes with progression to renal failure. Almost all forms are due to a familial gene mutation. Symptoms and signs include flank and abdominal pain, hematuria, and hypertension. The diagnosis is made by CT or ultrasound. Treatment is before the occurrence of renal failure, then it consists of dialysis or kidney transplantation. (See also Overview of cystic Nierenerkrankheiten.) Is etiology Inheritance of PKD Autosomal dominant recessive Sporadic (rare) The autosomal dominant polycystic kidney disease (ADPND) has an incidence of 1: 1000, affecting about 5% of all patients with ESRD renal replacement therapy need. The clinical manifestation before adulthood is rare, but the penetrance is substantially complete. All patients ? 80 years has symptoms. In contrast, the autosomal recessive polycystic renal dysplasia is rare. The incidence is 1: 10,000. They often results in childhood renal failure (kidney malformations: Autosomal recessive polycystic kidney disease). In 86-96% of cases ADPND is caused by a mutation in PKD1 gene on chromosome 16 encoding for the protein polycystin. 1 Most other cases are caused by a mutation of the gene PKD2 on chromosome 4, coding for polycystin. 2 A few familial cases are correlated with any of the loci. Pathophysiology Polycystin 1 can regulate cell adhesion and cell differentiation of tubulus epithelium. Polycystin 2 can be used as an ion channel function with mutations that cause fluid secretion in cysts. Mutations in these proteins can alter the function of renal cilia, which enables the tubular cells to register the flow rates. It is believed that tubular cell proliferation and differentiation are linked to the flow rate and that can lead to ciliary dysfunction cystic transformation. At the beginning of the disease, the tubules expand and fill slowly with glomerular filtrate. Finally, the tubules separated from functioning nephron, fill with more than secreted filtered liquid, thus forming cysts. Bleeding into cysts may occur and cause adrenal hematoma. Patients also have a higher risk of acute pyelonephritis, cystic infections and urinary stones (in 20%). A vascular sclerosis and interstitial fibrosis eventually develop over unknown mechanisms and generally relate to <10% of the tubules. Nevertheless, it is at 35-45% of patients at the age of 60 to kidney failure. Extrarenal manifestations are common: liver cysts most patients; usually this will not affect the liver function. Patients have frequently pancreas - and intestinal cysts Kolondivertikel and bars - and abdominal hernias. Valvular disorders (mostly mitral valve prolapse or aortic) are found by cardiac ultrasound in 25-30% of patients. Other valve disorders can be due to collagen abnormalities. The aortic regurgitation resulting from a Aortenwurzeldilatation caused by changes in the arterial wall (incl. Aortic aneurysm) is limited. Koronararterienaneurysmen also occur. Cerebral aneurysms are present in about 4% of young adults and up to 10% of elderly patients. The aneurysms rupture at 65-75% of patients, usually before age 50. Risk factors include aneurysms or -Rupturen in the family history, larger aneurysms and poorly controlled hypertension. Symptoms and complaints The autosomal dominant polycystic kidney disease usually causes no symptoms initially; half of the patients remain asymptomatic, never developed a renal or kidney failure and remains undiagnosed. Most patients who develop symptoms do so towards the end of the third decade of life. Symptoms are moderate flanks -, Abdominal - and lower back pain, caused by the cystic magnification, and symptoms of infection. Acute pain is usually caused by bleeding into the cyst or finish of a stone. Fever is common in acute pyelonephritis and a rupture of cysts in the retroperitoneal space can cause fever that may last for weeks. Liver cysts can cause pain in the right upper quadrant, if they enlarge or become infected. Cardiac valve disorders rarely cause symptoms, but sometimes heart failure and require valve replacement. Symptoms of a ruptured cerebral aneurysm can not missing or headache, nausea and vomiting, and cranial nerve deficits; these manifestations require immediate intervention (vascular lesions in the brain). The results are non-specific and include hematuria and hypertension (respectively 40-50%) and, proteinuria in 20% of patients in the subnephrotische limit (<3.5 g / 24 in adults) Anemia is rare as in other types of chronic kidney disease probably because the erythropoietin is obtained. In advanced cases, the kidneys are greatly enlarged and palpable and cause a feeling of fullness in the upper abdomen, and the flank. Diagnostic sonography Sometimes CT or MRI or genetic tests, the suspected diagnosis of polycystic kidney disease results in patients who have the following: A positive family history Typical symptoms or complaints cysts that happen to be diagnosed with imaging tests. Patients should be informed before carrying out diagnostic tests, particularly if they are asymptomatic. So many experts recommend not to carry out tests in asymptomatic young patients, because no disease-modifying treatment at this age is effective and the diagnosis of potentially negative effects on the preservation of health insurance to good conditions and has on mood. The diagnosis is usually done by imaging methods, the extensive and bilateral cystic changes on the whole kidneys, which are enlarged typically, and the cysts that replace the renal tissue, moths show-like appearance. These changes develop with age and are less frequently present or obvious in younger patients. An ultrasound is usually done first. If the results of the ultrasound are inconclusive, a CT or MRI will be performed, the (when particular contrast agent) are both more sensitive. MRI is particularly useful for measuring the cyst and kidney volume. These measurements say the risk of progression to chronic kidney disease and end stage renal disease often ahead before changes in routine laboratory studies. For example, cyst size and renal size say the 8-year risk of chronic kidney disease requires more accurate than age, degree of proteinuria, BUN or serum creatinine or. Urinalysis, renal function tests and blood counts are performed, but the results are not specific. In urinalysis low proteinuria, and a microscopic or macroscopic hematuria be detected. A severe hematuria may be caused by a dislocated stone or by bleeding from a ruptured cyst. Pyuria is common even without bacterial infection; Therefore, the diagnosis of infection to culture results and clinical findings (eg. as dysuria, fever, flank pain) and urine analysis should be based. In the beginning, urea and creatinine are still normal or only slightly increased, but increase slowly, especially when co-existing hypertension. Rarely is a polycythemia in the blood. Patients with symptoms of cerebral aneurysm require high-resolution CT or magnetic resonance angiography. However, most experts recommend no routine screening for aneurysm in asymptomatic patients. It makes sense to the screening of patients with ADPND who have a family history of hemorrhagic stroke, or cerebral aneurysm. Genetic testing for PKD mutations are folgendne reserved for patients: patients with suspected PCD and with no known family history of patients with inconclusive results of imaging Younger patients (eg age <30, where imaging results are often ambiguous.), Where the (z. B. a potential living kidney donors) must be made diagnosis Genetic counseling is recommended for first-degree relatives of patients with ADPND. Forecast At the age of 75 years need 50-75% of patients with ADPND renal replacement therapy (dialysis or transplantation). On average, the glomerular filtration rate (GFR) is reduced by about 5 ml / min / year after the fourth decade of life. Among the predictors of a more rapid progression to renal failure include the following: Early age at diagnosis Male sex sickle cell trait PKD1 genotype Larger or rapidly growing kidney size macrohematuria hypertension blackness Increasing proteinuria ADPND not increase the kidney cancer risk, but if patients develop ADPND a renal carcinoma, this happens probably on both sides. Renal carcinomas rarely lead to death. Patients usually die from heart disease (sometimes valvular), disseminated infection or ruptured aneurysm. Therapy control of complications (eg. As high blood pressure, inflammation, renal failure) Supportive measures Strict control of blood pressure is necessary. Typically, an ACE inhibitor or angiotensin II receptor blocker is prescribed. In addition to controlling blood pressure, these drugs to block angiotensin and aldosterone, growth factors that contribute to renal scarring and loss of kidney function help. Urinary tract infections should be treated promptly. Percutaneous puncture of cysts can help relieve by hemorrhage or compression caused severe pain; but it has no effect on the long-term course. Nephrectomy is a way through massive kidney enlargement (z. B. pain, haematuria) to alleviate or recurrent urinary tract infection caused severe symptoms. Hemodialysis or peritoneal dialysis or kidney transplant are required in patients who develop chronic renal failure. A ADPND does not develop in the transplant. Among dialysis patients keep ADPND a higher Hb level than other patients with kidney failure. Mammalian target of rapamycin (mTOR) inhibitors can not slow down the increase in kidney volume, the decline in kidney function. Thus, they are not generally used in routine operation. Tolvaptan, a vasopressin receptor 2 antagonist, is a drug that can benefit from the ADPKD patients, but its use is not recommended. Tolvaptan appears to slow the increase in renal volume and the decline in renal function but may cause side effects about "free water diuresis" (z. B. thirst, polydipsia, polyuria) cause that can make compliance difficult. Also been reported tolvaptan that it causes severe liver failure, and data on long-term results are not yet sufficient to confirm a favorable benefit / harm balance. In children with autosomal dominant polycystic kidney disease, early administration of pravastatin, the progression of structural renal disease slow down (1). Treatment Note Cadnapaphornchai MA, George DM, McFann K, et al. autosomal dominant Effect of pravastatin on total kidney volume, left ventricular mass index, and microalbuminuria in pediatric polycystic kidney disease. Clin J Am Soc Nephrol 9 (5): 889-896, 2014. Key points Autosomal dominant polycystic kidney disease occurs in about 1/1000 people. About half of the patients have no manifestations, but in others, symptoms of back or abdominal pain, hematuria and / or hypertension develop gradually, usually starting before age 30; 35 to 45% develop kidney failure at the age of 60. Extrarenal phenomena are common and include cerebral and coronary aneurysms, heart valve disease and cysts in the liver, pancreas and intestines. Diagnose PKD based on imaging studies and clinical findings, they reserve genetic testing for patients with no family history of clear results in imaging or who are young, and in whom the diagnosis will affect the treatment. Do not perform routine screening in asymptomatic patients for ADPKD by or in asymptomatic patients who have ADPKD for cerebral aneurysms. Arrange genetic counseling for relatives first degree relatives of patients with ADPND. Enter prevent ACE inhibitors or angiotensin receptor blockers for high blood pressure and to renal dysfunction and scarring. Treat other complications as they arise, and drag the use of tolvaptan considered.