Cyst kidney

from Wikipedia, the free encyclopedia
Classification according to ICD-10
Q61.1 Polycystic kidney, autosomal recessive
infantile type
Q61.2 Polycystic kidney, autosomal dominant
adult type
Q61.3 Polycystic kidney, unspecified
ICD-10 online (WHO version 2019)
Polycystic Kidney Preparation
In comparison, healthy kidneys (from lamb )
Section through an adult polycystic kidney

Polycystic kidney disease , also known as polycystic kidney designated ( English kidney disease polycystic , PCD are a group of serious, mostly) hereditary -related diseases of the kidney . Due to the formation of a multitude ( ancient Greek πολύς polys 'much') of fluid-filled chambers or vesicles, the so-called cysts , the kidneys are considerably restricted in their filtering function . A kidney cyst , on the other hand, is a single oneCyst mentioned in an examination as a generally harmless chance finding .

Genetically determined kidney cysts are the most common life-threatening hereditary disease in humans and one of the main causes of chronic kidney failure . A cure is only possible through a kidney transplant .

Symptoms

Section through a child's polycystic kidney (ARPKD)

The first symptoms that may indicate cystic kidneys are high blood pressure , bloody urine ( hematuria ), repeated urinary tract infections , an increase in the size of the abdomen, and pain in the abdomen. As long as the kidneys can compensate for any functional restrictions, there are often no symptoms. About a third of patients remain symptom- free, even up to the point of end-stage renal failure (ESRF). This makes an early diagnosis much more difficult. The increasing destruction of the kidney tissue leads to more and more complaints in various organs due to the retained waste products and the water. These include decreased performance and malaise, the yellowing and itching of the skin due to the stored urine toxins, sleep and concentration disorders, headaches, calf cramps, nausea, vomiting, diarrhea and taste disorders. High blood pressure, cardiac arrhythmias or inflammation, and breathing problems also occur. In addition, there is anemia (due to the reduction in the erythropoietin produced by the kidney, which is used for blood formation), coagulation disorders, increased susceptibility to infections, cerebral bleeding and bone softening (since the kidney is also involved in the vitamin D metabolism).

Patients with polycystic kidneys often complain of pain in the side flank of their back or abdomen . The pain can be temporary or permanent, dull and excruciating. The pain is probably due to the extensive cyst growth. In addition, the surrounding organs are displaced by the extreme expansion of the kidney capsule ( Capsula fibrosa renalis ).

The pain can be relieved briefly by puncturing the cyst, for example percutaneously , i.e. through the skin, or minimally invasively by laparoscopic decortication of the cysts. Due to the formation of new cysts, these measures are not sustainable, so that the corresponding interventions have to be repeated. The treatment also does not change the course of the disease.

In around 30 to 50% of patients, the initial diagnosis of “polycystic kidneys” is made from bloody urine ( hematuria ). The cause of the bleeding is usually a crack in the cyst. The bleeding itself is largely harmless and stops by itself. Due to the impaired kidney function, patients with cystic kidneys excrete increased amounts of endogenous proteins in the urine . If the body excretes 30 to 300  milligrams of albumin per day , it is called microalbuminuria . If even larger amounts of albumin are excreted, this is called macroalbuminuria . If proteins larger than albumin can be detected in the urine, proteinuria is present. The latter can be easily detected with test strips that are held in the urine. Microalbuminuria is much more difficult to detect. Protein and microalbuminuria are an indication of impaired kidney function. Polycystic kidneys are just one of several possible conditions that can lead to this dysfunction.

An arterial hypertension ( "hypertension") is located in front of patients with polycystic kidney at 50 to 75%. The blood pressure of those affected is often already significantly increased before a decline in kidney function ( glomerular filtration rate , GFR).

Diagnosis

Cyst kidneys on both sides (outlined in yellow) in a magnetic resonance imaging

The diagnosis is usually made by sonography ("ultrasound") or other imaging methods , such as magnetic resonance imaging . With ultrasonography, cysts down to a size of 5 mm can be diagnosed with modern devices. The early detection rate in 20-year-old patients is around 90%. The computer tomography while providing a higher resolution with better image quality, but it is mainly because of the radiation exposure not for patient screening used, but only for special diagnostic problems.

The biopsy , in which a small amount of kidney and liver tissue is removed, is used in childhood to differentiate between ARPKD and ADPKD ( early-onset ). This means that morphological changes in the basement membrane can be detected at a very early stage. The diagnosis of ARPKD is made by determining congenital liver fibrosis .

According to Osathanondh and Potter , the cyst kidneys are pathologically and anatomically divided into the following types:

Type Infestation Kidney size Cyst size Glomeruli Bile duct cysts Survival time
I. both sides enlarged to greatly enlarged evenly wide (12 mm) normal available Neonatal period
II double-sided, one-sided or partially enlarged or reduced different sized diminished and abnormal unavailable Adulthood
III mostly bilateral enlarged different sizes, sometimes very far glomerular cysts occasionally, but then only in circumscribed areas Adulthood
IV both sides scaled down small, subcapsular Glomeruli diminished, glomular cysts unavailable Adulthood

However, the types defined in this way often do not allow a clear classification in practice . In addition to the pathoanatomical description of the kidneys and liver, the family history ( anamnesis ) therefore plays an important role. For hereditary cases of kidney cysts, the genetically based terms autosomal - dominant and autosomal- recessive are usually used.

By identifying potentially affected genes, a non-invasive demonstrative molecular genetic diagnosis is possible. In many cases, this procedure can replace invasive biopsy diagnostics and enable etiological classification. This classification in turn opens up possibilities for differential therapeutic options for treating the disease. The sensitivity for a really positive result is around 95%. A correlation between genotype and phenotype is only possible to a limited extent. Mutation analysis is difficult for the PKD1 gene due to its size (46 coding exons and 14.2 kb of the transcript ). In addition, the first 33 exons of PKD1 in three homologous copies of the affected chromosome 16 on gene locus p13.1 (HG-A ≈21 kb, HG-B ≈17 kb and HG-C ≈8.5 kb; HG = homologous gene). This makes specific multiplication by means of the polymerase chain reaction (PCR) considerably more difficult .

A particular problem arises from molecular genetic diagnostics. On the one hand, the early diagnosis of the patient's genetic disposition enables prophylactic measures and early supportive therapy. On the other hand, relatives and patients may be confronted with the likelihood of a life-threatening disease breaking out in several decades as early as childhood. The risks and benefits must therefore be carefully weighed before a diagnosis.

In patients with a familial disposition ( predisposition ), the diagnosis can be made by sonography from the age of 20 if at least two kidney cysts can be detected per kidney. Missing cysts, however, rule out the disease in those over 30 years of age.

Pathogenesis

The origin and development of cyst kidneys , the pathogenesis , is based on a cystic degeneration of the so-called tubules (urinary tubules ) in the kidneys. In the autosomal dominant inherited PKD, this leads to increasing kidney enlargement over the course of decades. This can lead to a functional impairment or even a complete loss of the kidney's filtering function. Both kidneys are equally affected. Several hundred cysts, which are bulky in their appearance, can develop per organ. As a result, the mass and volume of the kidneys can increase considerably. While a healthy kidney has an average mass of 160  g , polycystic kidneys can reach up to 8  kg with a volume of up to 40 × 25 × 20 cm³ (= 20 liters) (healthy kidney: 12 × 6 × 3 cm³ = 0.216 liters). Despite the significantly increased space requirement of the organ, functional disorders of the neighboring organs only occur relatively rarely.

The cysts are found on both the renal medulla ( medulla renis ) and the renal cortex ( cortex renalis ). In principle, any area of ​​a nephron can develop a cyst. However, the glomeruli and the loop of Henle are primarily affected . The cysts are filled with what is known as tubular urine . The diameter of a single cyst can vary widely from a few millimeters to over 100 mm. Large cysts can contain several hundred milliliters of tubular urine. The inside of the cyst consists of a single-layer squamous epithelium or single-layer isoprismatic (cubic) epithelium . As the disease progresses, both the number and size of cysts present can increase.

etiology

Polycystic changes in the kidneys are a condition that occurs in a number of diseases. They can arise sporadically as a deviation from the normal development of the kidneys or can be acquired in adult life ( acquired cystic kidneys ). The far more common cause ( etiology ) for this disease are inherited defects in certain genes ( hereditary cystic kidneys ). By far the largest share is taken by the autosomal dominant polycystic kidney disease ( English autosomal dominant polycystic kidney disease , ADPKD ). This disease is the most common hereditary cause of chronic kidney failure : around 7% of all dialysis patients suffer from it.

In addition, various other - much rarer - hereditary diseases cause cystic kidneys. Acquired cystic kidneys can also develop - especially in dialysis patients. Since the vast majority of cyst kidneys are caused by ADPKD, the term “cyst kidney” is often used synonymously for ADPKD.

Hereditary cystic kidneys

The majority of polycystic kidney diseases are hereditary ( hereditary ). A large number of different genes can be affected and thus trigger the disease. The syndromes listed below represent a selection of the most important hereditary polycystic kidney diseases. Some of the diseases are included in the so-called NPH-MCKD complex .

Overview of Hereditary Polycystic Kidney Disease
gene Chromosome
gene locus
protein illness Incidence Age ∗)
Autosomal dominant          
PKD1 16 p13.3 Polycystin-1 ADPKD 1: 500-1000 approx. 50
PKD2 4 q21-q23 Polycystine-2 ADPKD 1: 3500-7000 approx. 70
VHL 3 p26-p25 VHL30 Von-Hippel-Lindau 1: 35,000 20-30
TSC1 9 q34 Hamartin Tuberous sclerosis 1: 10,000 (both together) 30-40
TSC2 16 p13.3 Tuberine Tuberous sclerosis    
? 1 q21   Medullary cystic kidney disease type 1 1 to 9: 1,000,000 (type 1 + 2) 62
UMOD 16 p12.3 Uromodulin Medullary cystic kidney disease type 2   32
Autosomal recessive          
PKHD1 6 p21.2-p12 Fibrocystin ARPKD 1: 20,000 <20
NPHP1 2 q13 Nephrocystine-1 Nephronophthisis (juvenile) approx. 1: 100,000 (all NPHP) 13
NPHP2 9 q22-q31 Inverse Nephronophthisis (infantile)   <1
NPHP3 3 q22.1 Nephrocystine-3 Nephronophthisis (adolescent)   19th
NPHP4 1 p36.22 Nephroretinin Nephronophthisis   21st
NPHP5   Nephrocystine 5 Nephronophthisis   13
NPHP6   Nephrocystine 6 Nephronophthisis    
GLIS2 16 p13.3 GLI-Similar Protein 2 Nephronophthisis    
BBS1 11 q13.1 BBS1 protein Bardet-Biedl syndrome 1: 140,000 (all BBS)  
BBS2 16 q21 BBS2 protein Bardet-Biedl syndrome    
ARL6 3 p13-p12 BBS3 protein
ADP-ribosylation factor-like protein 6
Bardet-Biedl syndrome    
BBS4 15 q22.3-q23 BBS4 protein Bardet-Biedl syndrome    
BBS5 2 q31.1 BBS5 protein Bardet-Biedl syndrome    
MKKS 20 p12 BBS6 protein McKusick-Kaufman syndrome    
BBS7 4 q27 BBS7 protein Bardet-Biedl syndrome    
TTC8 14 q31.3 BBS8 protein Tetratricopeptide Repeat Domain 8    
BBS9 7 p14 PTHB1 Bardet-Biedl syndrome    
BBS10 12 q21.2 BBS10 protein Bardet-Biedl syndrome    
TRIM32 9 q33.1 Zinc finger protein HT2A Tripartite motif-containing 32    
BBS12 4 q27 BBS12 protein Bardet-Biedl syndrome    
X-linked dominant          
CXORF5 X p22.3-p22.2 OFD1 Oro-facio-digital syndrome type 1 1: 250,000  
Unknown inheritance          
? ?   Medullary cyst kidney 1: 5000 40-50
? ?   Multicystic kidney dysplasia   <10 and 50-60
∗) middle age to end stage renal failure

Autosomal dominant polycystic kidney disease

Native CT Scan of ADPKD: Polycystic Liver and Polycystic Kidneys (Post Transplant)

The autosomal dominant polycystic kidney disease (ADPKD), also known as Potter type III cystic kidney degeneration , is the most common life-threatening hereditary disease in humans. There are approximately 5 million people affected by ADPKD worldwide. The incidence is 1: 500 to 1: 1000. For example, in the United States, it is two times more common than multiple sclerosis and ten times more common than sickle cell anemia . Men and women are equally affected. Race and origin are also irrelevant. The symptoms are usually observed only in adulthood. The inheritance of ADPKD is autosomal dominant ( monogenic ) with complete penetrance . Due to the autosomal dominant inheritance, half of the children inherit the mutated gene from their parents on the statistical average and will develop ADPKD themselves. About 50% of all mutation carriers suffer from progressive renal insufficiency. At an average age of 58 years, kidney replacement therapy is indicated in half of ADPKD patients .

As a systemic disease in ADPKD, other organs - in most cases the liver - are often affected by cyst formation. Depending on the author, up to 75% of those affected by ADPKD have liver cysts.

genetics

Autosomal dominant inheritance
Examples of point mutations

So far, mutations in two different genes have been identified as the cause of the disease in ADPKD patients: the genes PKD1 and PKD2 . In humans, PKD1 is located on chromosome 16 locus 16p13.3-p13.12. It codes for the protein polycystin-1 . In patients with significant mutations in PKD1, renal insufficiency reaches its end stage at an average age of 50 years, so renal replacement therapy is indicated. Patients with mutations in PKD2, which is located on chromosome 4 gene locus q21-q23 and encodes polycystin-2, reach this stage considerably later, at an average age of 70 years ( late onset ). About 85% of patients with ADPKD carry one or more mutations in PKD1. The remaining 15% are due to mutations in PKD2.

At the cellular level, ADPKD is a recessive mechanism. The first condition for the disease is a germline mutation in one of the PKD1 or PKD2 alleles . Second, a somatic mutation , a so-called second hit, has to take place so that the cyst formation is initiated. This loss of heterozygosity ( loss of heterocygosity , LOH) found in ADPKD obviously takes forever. The initial somatic mutation can be on the other gene. In this case, called transheterozygosity , the germline mutation is on PKD1 and the somatic mutation on PKD2, or vice versa. In animal models it was found that germline mutations affecting both alleles of a PKD gene are perinatally fatal. With the second hit , the affected cell loses the ability to inhibit proliferation and thus becomes the starting point for the formation of a new cyst. An important indication of the correctness of the second hit theory are experiments with knockout mice in which PKD1 or PKD2 were switched off ( gene deletion ). Only homozygous animals become ill , while heterozygous animals develop almost normally. The second hit theory also explains why only about 1% of all nephrons in ADPKD form cysts, even though all cells carry the inherited mutation.

From 1995 onwards, a third gene, called PKD3, was suspected to be another possible cause of ADPKD. Mutations that were not caused by PKD1 or PKD2 were later observed in four other families with cystic kidneys from different countries. The existence of this gene is now being questioned.

Frequency of the different types of mutations in ADPKD
gene Loci Exons Mutation type Frequency (%)
PKD1 16p13.3 46 (14.1 kb) Nonsense 33
Frameshift 28
In-frame 6th
Splicing 14th
Missense 19th
PKD2 4q21-q23 15 (5 kb) Nonsense 37
Frameshift 39
Splicing 17th
Missense 6th
Deletion 1

Molecular causes and cyst formation

Schematic representation of PKD1 and PKD2 on a cell

The proteins polycystin-1 and polycystin-2 encoded by the affected genes and the fibrocystin encoded by the PKHD1 gene are located at the base of the primary cilium of the cells of the renal tubule (renal tubule cells) . The primary cilium is a hair-thin cell extension, of which each cell only develops one. According to current knowledge, a malfunction of the primary cilium plays a decisive role in the formation of cysts in all diseases leading to cyst kidneys. The primary ciliates of the tubular cells protrude into the tubular lumen, where they probably serve to perceive the flow of fluid. In addition, the primary cilium is involved in the spatial alignment of the mitotic spindle during cell division . The two polycystines form a calcium- regulating ion channel that is permeable to calcium ions. The polycystine complex plays an important role in the primary cilium with several signaling pathways and mechano-sensory functions. The physiological function of this cell organelle is still largely not understood.

The origin of the cysts can be in any section of a nephron - from the glomerulum to the collecting ducts ( tubulus renalis colligens ). When the cysts reach a diameter of more than 0.2 mm, they no longer have any connection to the kidney tubules ( tubules ).

In order for the cysts to form, the number of cells inside the cyst wall must increase. This happens through excessive proliferation of the epithelial cells of the kidneys. The protein mTor ( mammalian target of rapamycin ) is upregulated . Fluid must also accumulate in the cyst lumen due to increased secretion and / or decreased drainage. This transepithelial fluid secretion is dependent on the secondary active chloride ion secretion. The secretion of chloride ions is regulated by the CFTR ( cystic fibrosis transmembrane conductance regulator ) or by a calcium-dependent chloride channel. Both are located in the apical cell membrane .

Course and prognosis

The course of ADPKD is slowly progressive (progressive). Even before the onset of renal insufficiency, a disturbance in urine concentration (water reabsorption) can be detected in the affected patients. In the early stages of the disease, kidney function is not restricted by the formation of cysts. The performance only decreases from a kidney size of 1000 cm³. If the kidney volume is above 1500 cm³, the glomerular filtration rate is reduced annually by about 4 to 5 ml · min −1 . On average, the volume of the kidneys increases by over 5% per year in patients with a kidney volume above 750 cm³. The first symptoms of the disease are usually noticed between the ages of 30 and 40 years. In general, however, there is a wide range of variation - often within a family.

In almost all cases, the disease leads to end-stage renal failure (ultimate kidney failure). Women reach this stage an average of six years later than men.

Further survival is then only guaranteed through kidney replacement therapy, i.e. dialysis or kidney transplantation. It is not yet fully understood why polycystic kidneys ultimately lead to terminal kidney disease. The mechanism cannot be explained by the pressure atrophy of the parenchyma alone. Surgical interventions such as punctures do not delay the course of the disease. From histological examinations it can be concluded that hypertension is an important factor in the progression of renal insufficiency.

In addition to genetics, the patient's environment and lifestyle also have an impact on the course of ADPKD. In women, for example, it was found that multiple deliveries and other estrogenic factors significantly worsen the course of the disease. The accelerated growth of the cysts compared to women and the earlier reaching of terminal kidney failure in men are also attributed to hormonal influences. Also, the tobacco smoking influences - especially among men - the progression of ADPKD negative. One possible explanation here are the known negative effects of smoking on the blood vessels .

Life expectancy

Comparison of the survival rate of patients with ADPKD (blue: mutations in PKD1; red: mutations in PKD2; green: control group without ADPKD)

In a study, 333 patients from 31 families with PKD1 and 291 patients with PKD2 from 31 families were compared with a 398-strong, geographically identical control group. PKD1 patients reached a mean age of 53.0 years (± 1.8 years; 95% probability). PKD2 patients, on the other hand, came to an average of 69.1 years (± 2.2 years; 95%), while the persons from the control group were 78.0 years (± 4.2 years; 95%) (see adjacent graphic).

Causes of death

In a retrospective study, the cause of death of 129 patients with ADPKD was analyzed. After that, 36% died of heart disease and 24% of infections . 94% of the infections were sepsis (blood poisoning). At the autopsies , cardiac hypertrophy was found in 89% of all patients and coronary artery disease in 81% . A neurological event resulted in death in 12% of the patients and a rupture of a brain aneurysm in 6%. Cerebral hemorrhage caused by hypertension was the cause of death in 5% and an ischemic stroke in 1% of patients. No patient died of kidney cancer .

Autosomal recessive polycystic kidney disease

Autosomal recessive inheritance

Autosomal recessive polycystic kidney disease ( ARPKD ), also known as spongy kidney or Potter I kidney , manifests itself in childhood. The prevalence of this disease in newborns is in the range of 1: 6,000 to 1: 40,000, with an average of 1: 20,000. The disease is therefore relatively rare. The penetrance is complete. Around every seventieth person is a carrier of the mutation (see diagram of autosomal recessive inheritance). Mutations in the PKHD1 gene - which in humans is located on chromosome 6 , gene locus p21.1-p12 - can lead to the formation of cystic kidneys. The protein fibrocystin encoded by PKHD1 is found together with polycystin-2 in the basal body of the primary cilia . In the apical domain of polarized epithelial cells, it is apparently involved in the formation of the tubules and / or the maintenance of the architecture of the lumen of the collecting tube . Accordingly, in ARPKD, the collecting ducts are essentially affected by the cyst formation. Autosomal recessive polycystic kidney disease is associated with congenital liver fibrosis.

ARPKD manifests itself in patients at a very young age ( early onset ). The age range is 0 to 20 years. The mean life expectancy of the affected children is six years. A distinction is made between perinatal (28th week of pregnancy up to seven days after birth), neonatal (newborn), infantile (childlike) and juvenile (adolescent) form. The lower the age at the onset, the worse the prognosis .

NPH-MCKD complex

The NPH-MCKD complex ( nephronophthisis-medullary cystic kidney disease ) is a group of genetic diseases of the kidney that lead to a cyst kidney. In the case of nephronophthisis, inheritance is autosomal recessive, while it is autosomal dominant in both forms of medullary cystic kidney disease. The common clinical picture of the diseases is the formation of cystic kidneys at the cortical-medullary border (corticomedullary border). All diseases of the NPH-MCKD complex lead to terminal kidney failure in certain age ranges, depending on the affected gene.

Bardet-Biedl syndrome

Bardet-Biedl syndrome (BBS) is a very rare oligogenetic hereditary disease with an autosomal dominant inheritance. The cause of the disease are mutations in the BBS genes 1 to 12. In addition to the formation of polycystic kidneys, there is degeneration of the retina , childhood obesity , intellectual disabilities , malformations of the urinary and sexual apparatus and polydactyly (multiple fingers).

Tuberous sclerosis

Individual kidney cysts are common in autosomal dominant inherited tuberous sclerosis. Polycystic kidney disease is also less common. This is mostly due to larger deletions affecting both the TSC2 gene, which is affected in tuberous sclerosis, and the PKD1 gene; both genes are located in close proximity on chromosome 16 .

Oro-facio-digital syndrome type 1 (OFD 1)

X-linked dominant inheritance

The oro-facio-digital syndrome type 1, also called Papillon-Leage-Psaume syndrome, is a very rare X-linked dominantly inherited disease. The prevalence in newborns is around 1: 250,000. The disease has a variety of symptoms, particularly of the face and mouth, and a tendency to have polycystic kidneys seen in many patients. The latter are usually diagnosed very late when the kidney failure is well advanced.

The disease is prenatally fatal for males .

With orofazio -digital syndrome type 2 , OFD2 or Mohr syndrome , no changes are observed in the kidneys.

Acquired cystic kidneys

A special form of Endstadiumniere, as polycystic secondary transform or as acquired cystic kidney (engl. Acquired cystic kidney disease , ACKD ) is referred to, to 50% of all patients developing at 40 after long-term dialysis. She is a very serious complication in ESRD ( English end-stage renal disease, ESRD ). In the case of transplant recipients , both their own kidneys and the transplant can be affected. The cause of the development of the acquired dialysis-related cyst kidneys is usually a long-term dialysis for analgesic nephropathy . Cysts on the kidneys are very common in patients with end-stage renal disease. The frequency and size of the cysts increase with the duration of dialysis. Both sexes are equally affected by the disease, regardless of the age of the patient. The likelihood that kidney cancer will develop as a further complication is significantly increased - especially in male patients.

therapy

Sirolimus (rapamycin)

There is currently only one drug approved for the treatment of polycystic kidney disease ( tolvaptan , see below). About 50% of all ADPKD patients - the majority of those with polycystic kidney disease - will require renal replacement therapy during their lifetime. A cure is only possible through a kidney transplant .

Adjuvant measures

The adjustment of the arterial blood pressure, usually with the help of ACE inhibitors , is of particular importance as an adjuvant measure in the case of polycystic kidneys. In addition, there are a number of recommendations for patients with cystic kidneys, which also do not allow a cure, but make the progression of the disease more favorable for the patient.

Since caffeine is suspected of accelerating cyst growth, patients should avoid drinks containing caffeine as much as possible. A low-salt diet helps lower blood pressure, which is associated with impaired excretion of sodium ions. Nonsteroidal anti-inflammatory drugs , mixed analgesics , certain antibiotics and other drugs that are toxic to the kidneys should be avoided as far as possible. On the other hand, cyst infections are treated as early as possible with antibiotics that can penetrate the cyst or bile .

Renal replacement therapy

A Gambro AK200 hemodialysis machine

Only kidney replacement therapy, i.e. dialysis or kidney transplantation, ensures the survival of the patient in terminal kidney failure. In most cases, dialysis is carried out in the form of hemodialysis , since the oversized kidneys - and often the liver - make the abdominal cavity very narrow and peritoneal dialysis is therefore not possible. If possible, kidney transplantation is preferable to dialysis. It enables the restoration of physical performance, quality of life and the social integration of patients. It also significantly improves life expectancy compared to dialysis. The long waiting times for donor kidneys are problematic due to the low number of available donor kidneys.

Polycystic kidneys are - in contrast to the previous practice - only removed pretransplant in exceptional cases, for example when the kidney volume has reached a critical size.

Future therapeutic approaches

The treatment of patients with cystic kidneys incurs annual costs of over US $ 1 billion in the USA alone. This sum essentially results from the costs for the renal replacement therapy necessary in terminal kidney failure.

The proliferation and size increase of the thin-walled, fluid-filled cysts depend on two processes: proliferation of cells of the cyst epithelium and secretion of fluid into the cysts. Both processes are dependent on cAMP . cAMP stimulates the Ras / MAP kinase pathway and thus leads to abnormal cell growth. In addition, cAMP activates the CFTR - chloride channel , thus promoting fluid secretion into cysts. Therapeutic approaches currently being tested target both cAMP-dependent processes in order to slow down cyst formation and growth.

Research is also being carried out into the possible involvement of the protein C-Met and, associated with this, a therapy with C-Met inhibitors , which have shown promising results in animal experiments with mice .

Imaging procedures and investigation of new therapeutic approaches

The average age at diagnosis of ADPKD is currently 27 years. If renal impairment occurs, there is a rapid decrease in GFR of ≈5.9 ml / min per year. So far, no randomized study in this late stage of the disease has been able to demonstrate the beneficial effect of a treatment. Because of the long presymptomatic phase and the late onset of renal insufficiency , the primary endpoints that are usually investigated in studies on chronic kidney disease, such as time to dialysis treatment, doubling of serum creatinine or death, are only of limited use in studies on polycystic kidney disease. This is why the Consortium for Radiologic Imaging Studies of Polycystic Kidney Disease was created. (CRISP), whose task it is to examine imaging procedures that enable statements to be made about the course of the disease in the early stages. An important finding of the investigations of CRISP using magnetic resonance imaging is that the cysts in patients with ACPKD grow continuously and quantifiable and that the cyst growth correlates with the decrease in kidney function. That is, a larger increase in cyst size is associated with a faster decrease in kidney function.

HALT-Polycystic Kidney Disease (HALT-PKD) is a prospective study that is currently investigating the effects of a blockade of the renin-angiotensin-aldosterone system and / or strict blood pressure control in the early stages of the disease on cyst growth or in later stages of the disease had an impact on serum creatinine doubling, onset of dialysis, and on death.

Inhibition of cell proliferation

Model of the rapamycin-binding domain of mTOR (red) in a complex with rapamycin (pink) and FKBP12 (blue)

In recent years, with increasing molecular biological knowledge about the causes of PKD, new therapeutic approaches have been found. Some of these approaches are currently in clinical testing . Initially, however, it was more of an incidental finding: in some patients who had received a foreign kidney, a retrospective study found that the remaining polycystic kidney did not increase in volume, but that the cysts partially regressed somewhat. The number of patients in the first study (n = 4) was not statistically meaningful, but the effect could be statistically proven in various animal models . The obvious cause of this improvement was taking sirolimus (rapamycin), which was given to patients as an immunosuppressant . Patients with a donor kidney have to take immunosuppressants for the rest of their life in order to avoid rejection of the foreign organ by the body's own immune system . In human studies, treatment with the mTOR inhibitors sirolimus and everolimus slowed the increase in kidney volume, but not the progressive decrease in kidney function.

In addition to sirolimus and derivatives of this compound, research is also being carried out on other potential substances, some of which use other signaling pathways. Thus, for example, cAMP - antagonists somatostatin and vasopressin potential drug because elevated levels of cAMP stimulate the proliferation and secretion of cystic epithelial cells.

Triptolide is a small molecule isolated from a traditional Chinese drug ( Thunder God Vine ) that has anti-proliferative and pro- apoptotic properties. Triptolide promotes calcium release through a polycystin-2 dependent metabolic pathway and inhibits cyst formation and growth in animal models.

Inhibition of fluid secretion

Antidiuretic hormone (vasopressin) levels are increased in patients with polycystic kidney disease . The V2 vasopressin receptor in the distal tubule and collecting duct expressed . These are the places on the nephron where cyst formation takes place. Vasopressin stimulates the formation of cAMP in the distal tubule via the V2 receptor.

In the animal model, V2 receptor antagonists inhibit the formation of cAMP, the increase in size of the kidneys and the formation of cysts and protect kidney function.

The V2 receptor antagonist tolvaptan was shown to be safe and well tolerated in patients with ADPKD in phase II / III studies . A double-blind, placebo-controlled study was performed in patients with ADPKD, with normal kidney function and with a kidney volume greater than 750 ml. Tolvaptan can slow the progression of the disease. Tolvaptan has been approved for the treatment of ADPKD in Europe since May 2015.

Complications

Ureteral stone in a computed tomographic image (see red arrow)

Typical complications with cystic kidneys are increased blood pressure due to stimulation of the renin-angiotensin-aldosterone system and urinary tract infections .

Due to the shorter urinary tract, urinary tract infections particularly affect female patients. In most cases it is an infection of the urinary bladder caused by gram-negative and nosocomial germs. Urinary tract infections are treated symptomatically, preferably with lipophilic antibiotics . Extreme infections, such as pyonephrosis (a purulent hydronephrosis ), can lead to the removal of the affected kidney ( nephrectomy ).

While the incidence of kidney stones in the population is around 5%, these deposits affect 10 to 34% of patients with polycystic kidneys. One possible cause of the increased incidence of kidney stones is the low pH level in the urine of those affected.

Depending on the author and the study carried out, 25 to 75% of all ADPKD patients with cystic kidneys also have liver cysts . The number of liver cysts increases with the age of the patient. Women have larger and higher numbers of cysts on the liver. Due to the cysts, the liver can be considerably enlarged and literally permeated with cysts. In most cases, however, the function of the parenchymal cells is not impaired. For example, liver enzyme and bilirubin levels are normal. More extensive complications arise from the space required by the sometimes extremely enlarged liver. For example, the diaphragm may be elevated , individual sections of the intestine narrowed, which can make it difficult to transport food, and larger blood vessels, such as the inferior vena cava , may be obstructed .

ARPKD leads to fibrosis, cirrhosis , and increased pressure in the portal vein ( portal hypertension ) in the liver .

In other organs such as the pancreas , spleen, or ovaries , cysts are much less common in patients with polycystic kidneys.

A connection between polycystic kidneys and cerebral aneurysms was described as early as 1904 . The data on the prevalence vary between 4.5 and 22.5%. A possible tear (rupture) of the affected blood vessel is one of the most feared complications in cystic kidneys and is fatal in almost 50% of cases.

history

William Osler (1881)

The Paris surgeon Félix Lejars (1863-1932) first used the term polycystic kidneys in his dissertation in 1888 . The Canadian physician William Osler described it in 1915. Until the middle of the 20th century, only a few publications dealt with this clinical picture. In his dissertation in 1957, Dalgaard was the first to recognize the autosomal dominant inheritance of ADPKD. In 1985, Reeders and colleagues discovered the PKD1 gene locus on chromosome 16 in humans.

literature

Technical article

  • W. Kühn, G. Walz: Autosomal dominant polycystic kidney disease. In: Dtsch Arztebl. , 104, 2007, pp. A3022-A3028.
  • I. Ishikawa: Acquired renal cystic disease. In: The Cystic Kidney. Kluwer, 1990, ISBN 0-7923-0392-X , pp. 351-377.
  • JJ Grantham, PA Gabow: Polycystic Kidney Disease. In: Diseases of the Kidney. Little Brown, 1988, pp. 583-615.
  • Joachim Frey : Cystic kidneys and other congenital anomalies. In: Ludwig Heilmeyer (ed.): Textbook of internal medicine. Springer-Verlag, Berlin / Göttingen / Heidelberg 1955; 2nd edition ibid. 1961, p. 974 f.

Reference books

  • ML Watson (Ed.): Polycystic kidney disease. Oxford Univ. Press, 1996, ISBN 0-19-262578-0 .
  • HM Sass, P. Schröder (ed.): Patient education in the case of genetic risk. LIT Verlag, 2003, ISBN 3-8258-4987-2 , pp. 147-198.

Patient information

Popular science

Web links

Commons : Cyst Kidney  - Collection of pictures, videos and audio files
Wiktionary: cyst kidney  - explanations of meanings, word origins, synonyms, translations

Videos

Individual evidence

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This article was added to the list of excellent articles on November 15, 2008 in this version .