Chronic kidney failure

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Classification according to ICD-10
N18.1 Chronic kidney disease, stage 1 - kidney damage with normal or increased glomerular filtration rate (GFR 90 ml / min or higher)
N18.2 Chronic kidney disease, stage 2 - kidney damage with a slightly reduced glomerular filtration rate (GFR 60 to below 90 ml / min)
N18.3 Chronic kidney disease, stage 3 - kidney damage with moderately reduced glomerular filtration rate (GFR 30 to below 60 ml / min)
N18.4 Chronic kidney disease, stage 4 - kidney damage with greatly reduced glomerular filtration rate (GFR 15 to below 30 ml / min)
N18.5 Chronic kidney disease, stage 5 - chronic uremia, terminal kidney disease
N18.9 Chronic renal failure, unspecified
ICD-10 online (WHO version 2019)
Chronic kidney disease: course, consequences, measures

When chronic kidney failure (also chronic renal insufficiency , chronic renal disease or chronic kidney disease ; in the literature also English Chronic Kidney Disease , CKD ) is it is a slow, progressive over months or years loss of kidney function. In the narrower sense of the current guidelines , the term chronic kidney failure describes the terminal or end stage of chronic kidney disease, which is characterized by a kidney performance of 15% of the norm or below (corresponding to a glomerular filtration rate of less than 15 ml / min / 1.73 m²) and the need for renal replacement therapy in the form of dialysis treatment or kidney transplantation . This article covers all stages of chronic kidney disease including the terminal stage.

Key Facts About Chronic Kidney Disease

  • The measure of kidney function is the glomerular filtration rate . Chronic kidney disease occurs when the glomerular filtration rate has fallen below a certain value (60 ml / min / 1.73 m²) or when protein is excreted in the urine . These malfunctions must have existed for at least three months.
  • More than 500 million people worldwide suffer from chronic kidney disease, which corresponds to one in ten adults.
  • The most common causes worldwide are inflammation and infection of the kidneys, narrowing of the lower urinary tract and congenital kidney diseases . In the industrialized nations, type 2 diabetes mellitus and high blood pressure due to lack of exercise and malnutrition are the most common causes. In developing countries, the incidence of kidney diseases due to diabetes and high blood pressure is increasing sharply.
  • Chronic kidney disease is determined by a simple blood and urine test. The concentration of the marker substance creatinine is determined in the blood , from which the kidney function is calculated ( MDRD formula ). The protein concentration is measured in the urine .
  • The consequences of undetected kidney disease are progressive loss of kidney function, possibly leading to the need for dialysis and transplantation , as well as cardiovascular complications. People with chronic kidney disease are at least 10 times more likely to die prematurely from cardiovascular disease ( coronary artery disease , heart failure , circulatory disorders of the brain and arteries ).

More than 80% of people who receive kidney replacement therapy live in industrialized nations. In developing countries, this treatment is largely unaffordable. In countries like India and Pakistan, fewer than 10% of those in need of treatment are receiving kidney replacement therapy. Kidney replacement therapy is usually not offered in many African countries, which means that many people simply die. The economic burden is particularly severe for developing countries because chronic kidney diseases occur there at an earlier age.

  • Chronic kidney disease is usually not recognized in the early stages, especially in developing countries. However, early detection enables treatment before complications arise.
  • People at increased risk should take part in early detection, especially
    • Patients with diabetes or high blood pressure,
    • Overweight people ,
    • Smoker ,
    • over 50-year-olds,
    • if you have a family history of diabetes, high blood pressure or kidney diseases.
  • Treatment should be started at an early stage. Be recommended
    • Control of body weight,
    • regular physical activity,
    • Smoking cessation,
    • medicinal lowering of blood pressure,
    • Correction of increased blood sugar, increased blood lipids and anemia.
  • Early treatment can slow the loss of kidney function and delay the onset of cardiovascular complications.

Source: Statement on World Kidney Day 2007, International Society for Nephrology, International Umbrella Association of Kidney Foundations.

Functions of the kidney

In addition to removing metabolic toxins from the body, a healthy kidney has a number of other vital tasks.

  1. Regulation of the fluid balance by controlling the excretion of water.
  2. Regulation of the electrolyte balance by controlling the concentration of ions such as sodium , potassium , calcium and phosphate in the body fluids.
  3. Regulation of the acid-base balance by controlling the acid excretion.
  4. Removal of drugs and toxins from the body.
  5. Release of hormones into the blood that cause the
    1. Blood pressure (renin),
    2. the formation of red blood cells ( erythropoietin (EPO)) and the
    3. Regulate bone metabolism (vitamin D 3 ).

In people with chronic kidney disease, one or more of these kidney functions are impaired.

Definition and classification

definition

Chronic kidney disease is defined by

  • Deviations in the structure or function of the kidneys from the norm that
  • exist for more than three months and
  • Have an impact on health.

The classification of chronic kidney disease is based on

  • Cause of kidney damage,
  • glomerular filtration rate and
  • Albumin excretion.

According to the definition of the KDIGO , chronic kidney disease is present if there are deviations from the normal structure or function of the kidneys with negative effects on the state of health for more than 3 months.

Chronic kidney disease is classified by specifying the underlying disease , the glomerular filtration rate and the albumin excretion .

Underlying disease

Chronic kidney disease can lead to both primary diseases of the kidney and systemic diseases which result in secondary diseases of the kidneys. Examples of primary kidney diseases are glomerulonephritis (inflammation of the kidney corpuscles ) or tubulo-interstitial nephritis (inflammation of the kidney tubules and kidney connective tissue ). Examples of secondary kidney damage and at the same time the most common kidney diseases in industrialized nations are diabetic nephropathy (kidney damage in diabetes mellitus ) and nephrosclerosis (kidney damage in high blood pressure ). Also systemic inflammatory diseases (eg. As lupus erythematosus ), or genetic disorders (eg. As polycystic kidney disease ) can cause chronic kidney disease. In contrast, simple kidney cysts are structural deviations from the norm. However, they have no effect on the state of health and therefore do not justify a diagnosis of chronic kidney disease.

Glomerular Filtration Rate

The glomerular filtration rate (GFR) is the most important measure of the excretory function of the kidneys. It can be calculated from a blood value, for example from the creatinine concentration, with the help of approximate formulas. Creatinine is a waste product from muscle metabolism. The creatinine concentration can easily be determined in the blood . If the excretory function of the kidneys decreases, the creatinine concentration in the blood increases. In young, healthy adults, the glomerular filtration rate is approx. 125 ml / min / 1.73 m². Chronic kidney disease is when the glomerular filtration rate has fallen below 60 ml / min / 1.73 m².

Albumin excretion

Damage to the blood-urinary barrier in the kidney corpuscles leads to the transfer of proteins from the blood into the urine . Albumin is a plasma protein that can be detected in traces in the urine of healthy people. For this purpose, the albumin concentration in the urine is determined and related to the creatinine concentration in the urine measured at the same time. In chronic kidney disease, albumin excretion often increases. Chronic kidney disease is when the albumin-creatinine ratio in the urine is more than 30 mg / g. This abnormally increased excretion of albumin is known as albuminuria . Albuminuria can precede the reduction in glomerular filtration rate in the course of chronic kidney disease.

CGA classification

The CGA-classification of chronic kidney disease is based on underlying disease ( C ofa ), g lomerulärer filtration rate and A lbuminurie. The glomerular filtration rate is divided into six categories (G1–5), and albuminuria into three (A1–3).

Chronic kidney disease

Glomerular Filtration Rate (GFR) Categories

and albumin excretion

KDIGO 2012

Albuminuria categories
A1 A2 A3
Normal to slightly increased Moderately increased Greatly increased
<30 mg / g 30-300 mg / g > 300 mg / g
GFR categories

(ml / min / 1.73 m²)

G1 Normal or high ≥90 55.6 1.9 0.4
G2 Mildly restricted 60-89 32.9 2.2 0.3
G3a Mild to moderately restricted 45-59 3.6 0.8 0.2
G3b Moderately to severely restricted 30-44 1.0 0.4 0.2
G4 Severely restricted 15-29 0.2 0.1 0.1
G5 Kidney failure <15 0.0 0.0 0.1
Green: low risk; if there are no additional abnormalities in the structure or function of the kidneys that are relevant to the disease, there is no evidence of chronic kidney disease.
Yellow: moderately increased risk.
Orange: high risk.
Red: Very high risk.

The numbers in the fields indicate the percentage of the adult US population; there are no comparable figures for Germany.

Glomerular filtration rate and albuminuria are independent prognostic parameters; In other words, as the glomerular filtration rate decreases and the albumin excretion increases, the risk increases that chronic kidney disease will take an unfavorable course and that complications will occur, particularly in the area of ​​the cardiovascular system.

Causes of Chronic Kidney Failure

The most common causes of chronic kidney failure are diabetes and high blood pressure. In Germany, between 1994 and 2007, the QuaSi-Niere project (quality assurance in renal replacement therapy) collected statistical data from patients who were being treated with chronic renal replacement therapy (dialysis or kidney transplantation). Since 1997, the causes that have led to chronic kidney failure in these patients have been recorded annually. Significant shifts were observed in the period under review.

Percentage distribution of diagnoses at the start of renal replacement therapy in Germany
year 1996 1997 1999 2000 2001 2002 2003 2004 2005
Type 2 diabetes mellitus 24 29 30th 31 32 32 33 31 32
Nephrosclerosis (high pressure) 14th 16 16 15th 17th 18th 20th 22nd 23
Glomerulonephritis 16 15th 14th 15th 14th 14th 14th 12 13
Interstitial nephritis 13 11 11 10 9 9 8th 8th 8th
unknown genesis 11 9 10 9 10 9 9 9 8th
Cystic kidneys 6th 6th 6th 6th 6th 5 5 5 4th
Systemic diseases * 4th 4th 4th 4th 3 4th 4th 4th 4th
various 4th 4th 3 4th 4th 4th 4th 4th 4th
Type 1 diabetes mellitus 7th 6th 6th 5 4th 4th 3 3 3
congenital diseases 1 1 1 1 1 1 1 1 1
*) The following are summarized under systemic diseases with kidney involvement:

Lupus nephritis , Goodpasture syndrome , monoclonal gammopathies , amyloidosis , vasculitides ( microscopic polyangiitis , granulomatosis with polyangiitis , Churg-Strauss syndrome ), antiphospholipid syndrome , hemolytic uremic syndrome , thrombotic thrombocytopenic .

The table shows: Congenital kidney diseases, glomerulonephritis , interstitial nephritis and systemic diseases are only rarely the cause of renal insufficiency requiring dialysis; their proportion is decreasing due to ever better treatment options. Kidney damage from type 2 diabetes mellitus and high blood pressure , on the other hand, is increasing. In people with metabolic syndrome , a combination of obesity , lipid metabolism disorders , impaired glucose utilization and high blood pressure, the risk of chronic kidney disease is significantly higher.

A rare cause of chronic kidney failure is only partial growth of a donor heart that has been implanted in a small child ; The relatively small heart in old age causes cardiac and thus renal insufficiency in the sense of a cardiorenal syndrome . Excessive fluoride exposure is also seen as a risk factor .

Epidemiology and economic significance

stage GFR Prevalence (USA)
1 > 89 1.8%
2 60-89 3.2%
3 30-59 7.7%
4th 15-29 0.4%

The prevalence of chronic kidney disease in the United States was 10% in adults from 1988 to 1994 and increased to 13.1% in 1999–2004. In 1999–2004, the prevalence of stages 1 and 2 was 3% among 20 to 39-year-olds, and that of stages 3 and 4 was 0.7%. With increasing age, the prevalence of chronic kidney disease increased massively and was 10% in stages 1 and 2 in those over 70, and 38% in stages 3 and 4 (Fig.). In addition to age, diabetes and high blood pressure are the most important risk factors for chronic kidney disease. In the group of 20 to 59 year olds, the prevalence of chronic kidney disease was 8.2% if neither diabetes nor high blood pressure was present; 15.2% if there was only hypertension; 33.8% if only diabetes was present; and 43% in patients with both diabetes and hypertension.

In stage 3, only 12% of men and 6% of women were aware that they had kidney disease; in stage 4, only 42% of those affected knew about their disease.

In Germany , the QuaSi kidney indicates a prevalence of 769 dialysis patients and 288 kidney transplants per million population in 2005, which corresponds to 63,427 dialysis patients and 23,724 kidney transplants. Since 1995 the number of dialysis patients has risen by 53% and that of kidney transplant recipients by 78%. This increase only occurred in the over 65 age group. In the under 65 age group, the incidence and prevalence of chronic kidney replacement therapy have remained stable. There are no figures in Germany on the prevalence of stages 1–4 of chronic kidney disease.

Due to the high rate of cardiovascular complications and the need for expensive kidney replacement procedures (dialysis and kidney transplantation) in stage 5, chronic kidney failure results in high costs for the healthcare system. If one assumes that dialysis treatment costs around 50,000–60,000 euros per patient per year, in 2005 over 3 billion euros were spent on dialysis treatment in Germany alone. There are no figures on the follow-up costs for stages 1–4. Due to demographic change , there will be a considerable increase in the number of elderly people with kidney disease in the coming years, who will suffer from a large number of serious concomitant and secondary diseases and will present the health systems with considerable challenges.

Natural course, secondary diseases and complications

The normal value of the glomerular filtration rate (GFR) depends on age, gender and height. In young adults, the normal GFR is between 120 and 130 ml / min / 1.73 m². In women, the GFR is around 8% lower than in men. From the age of 20 to 30, the GFR decreases by approx. 1 ml / min / 1.73 m² annually. At the age of 70, the normal value of the GFR averages around 70 ml / min / 1.73 m² with a wide range of fluctuations.

In most people with chronic kidney disease, kidney function decreases over time. The majority of people with chronic kidney disease are older people with early stages of kidney impairment. Only 2-3% of these people will develop end-stage kidney failure. The course of chronic kidney disease depends

  1. from the GFR at the time of diagnosis and
  2. of the decrease in the GFR over time, the progression. The measure of progression is the annual decrease in the GFR, expressed in ml / min / 1.73 m² / year.

The progression of a kidney disease is usually relatively constant for an individual patient over time, but can vary greatly between different patients. A slowly progressive course can extend over decades; a rapidly progressive course can lead within months to the end stage of renal failure requiring dialysis.

The progression depends

  1. From the underlying disease: In diabetic nephropathy, glomerulonephritis, cystic kidney disease, and kidney disease in transplant recipients, the progression is faster than in kidney disease due to hypertension and interstitial nephritis.
  2. of factors that cannot be influenced: In people with black skin color, poor kidney function at the time of diagnosis, men and the elderly, the progression is faster.
  3. Factors that can be influenced: A more rapid progression is found with high protein excretion in the urine (proteinuria), low albumin in the serum, high blood pressure, poor blood sugar control in diabetics and smokers.
  4. The influence of elevated blood lipids and anemia on progression is not clear.
GFR Cardiovascula-

Complications

mortality
> 60 2.11 0.76
45-59 3.65 1.08
30-44 11.29 4.76
15-29 21.80 11.36
<15 36.60 14.14
ml / min / 1.73 m² per 100 person-years

As the kidney function becomes increasingly restricted, sequelae occur in several organ systems:

  1. High blood pressure. About 55–75% of all people with impaired kidney function suffer from high blood pressure. Pre-existing high blood pressure can be the cause of impaired kidney function. The restricted kidney function also leads to high blood pressure, causes are fluid overload, activation of the renin-angiotensin-aldosterone system , activation of the sympathetic nervous system , calcification of the arterial vascular system including the renal vessels and metabolic disorders with a number of other factors ( prostaglandins , Bradykinins , endothelin , nitric oxide ). High blood pressure is an important cause of the considerably increased cardiovascular risk in kidney patients.
  2. Disorders of bone metabolism. The causes are changes in the vitamin D metabolism, a reduced absorption of calcium via the intestine and a reduced excretion of phosphate via the kidneys. The consequences are reduced calcium and vitamin D levels in the blood, increased levels of phosphate and parathyroid hormone , increased bone remodeling and soft tissue calcifications, which also affect the coronary vessels and heart valves .
  3. Blood formation disorders. Decreased production of the hormone erythropoietin by the kidney leads to anemia due to a decrease in the number of red blood cells in the bone marrow .
  4. Electrolyte disorders . With advanced renal impairment, the potassium level in the blood may rise as a result of reduced excretion. In extreme cases, this can lead to fatal cardiac arrhythmias .
  5. Disorders of the acid-base balance. The reduced excretion of protons leads to acidosis of the blood ( acidosis ). The acidosis leads to a loss of bone substance.
  6. Overwatering. A reduced excretion of water can lead to increased water retention in tissues ( edema ) and in the lungs .
  7. Occurrence of further physical and mental functional impairments such as decreased mental performance and increased risk of age- related macular degeneration .
  8. Disorders of the immune system: With increasing renal impairment, the risk of developing pneumonia or dying from it increases up to 15 times, the response rates after vaccination against hepatitis B and pneumococci decrease. In contrast, the response to a vaccination against influenza is also good in dialysis patients.

From stage 3 the risk of acute kidney failure is increased, especially if diabetes, high blood pressure or increased protein excretion are also present.

KDOQI stage Onset of dialysis mortality
2 1.1% 19.5%
3 1.3% 24.3%
4th 19.9% 45.7%
within 5 years

In stage 5 of chronic kidney failure, there are increasing complications of urine poisoning ( uremia ): weight loss and malnutrition due to loss of appetite, nausea and vomiting, fluid overload, tendency to bleed, pericardial inflammation , depression , decrease in physical performance, damage to the peripheral nervous system , infertility and increased susceptibility to infections. The urine-like bad breath ( Foetor uraemicus ) is noticeable .

The main cause of death for all patients with chronic kidney failure are cardiovascular diseases such as coronary artery disease , left ventricular hypertrophy , vascular calcifications and cardiac insufficiency . The second most common cause of death in dialysis patients is infection. Older patients in particular are much more likely to die from complications of the cardiovascular system than they are to dialysis (Fig.). The mortality rate (mortality) is markedly increased even at a low renal function and increases with increasing renal impairment exponentially on. Irrespective of the degree of renal impairment, mortality also increases with increasing urine protein excretion (proteinuria) . Prevention of diseases of the cardiovascular system is therefore of particular importance in all stages of chronic kidney disease.

The increased incidence and death rate from cardiovascular diseases in patients with chronic kidney disease is only partially explained by the increased occurrence of traditional cardiovascular risk factors ( cardiovascular risk factors). In addition, non-traditional risk factors associated with impaired kidney function or its treatment arise in chronic kidney disease.

Traditional risk factors Non-traditional risk factors
Biochemical factors

Pathological processes

Factors promoting heart muscle thickening

Graft-specific factors

Symptoms of chronic kidney failure

In stages 1–4, chronic kidney disease usually proceeds without any symptoms. Excreting high levels of protein in the urine can cause the urine to foam and water retention. A very high excretion of red blood cells ( macrohematuria ) can manifest itself in a brown discoloration of the urine and usually indicates diseases of the lower urinary tract, more rarely bleeding in cystic kidneys or IgA nephropathy . Pain in the kidney region indicates problems with the spine and intervertebral discs, kidney stones , inflammation of the renal pelvis , acute complications of cystic kidney disease and, very rarely, acute glomerulonephritis . Chronic kidney disease, on the other hand, is usually painless.

In advanced stage 4 and stage 5 there is an increasing reduction in physical and mental performance, loss of appetite, vomiting and nausea, water retention, shortness of breath and skin changes . Seizures may occur if the kidney function is far advanced .

therapy

Treatment goals for chronic kidney disease are

  • in risk groups, the prevention and in particular the early detection and consistent treatment of diabetes and high blood pressure,
  • in stage 1 and 2
    • the early detection of kidney disease and
    • the treatment of the various underlying diseases
  • in stages 2 to 4
    • the prevention and treatment of cardiovascular complications and
    • the inhibition of progression
  • in stage 3 to 5 the treatment of complications and secondary diseases
  • in stage 5 dialysis and kidney transplantation, or supportive therapy if a kidney replacement procedure is not possible.

Prevention of chronic kidney failure

Preventing chronic kidney disease may reduce the number of potential dialysis patients and reduce morbidity and mortality from cardiovascular complications.

early detection

Chronic kidney disease progresses without symptoms in the early stages. For this reason, screening tests were carried out in several countries, such as the USA (NHANES III), Australia (AusDiab Study), Japan (Okinawa Screening Program), the Netherlands (PREVEND Study), Iceland, India and Singapore. The detection of protein and albumin in the urine and the determination of creatinine in the blood were used as early detection examinations. Legally prescribed early detection measures in Japan have reduced the incidence of progressive inflammatory kidney disease ( progressive glomerulonephritis ) in young adults ; the mean age at the time of onset of dialysis has increased significantly in Japan over the same period.

Change of lifestyle

High blood pressure and diabetes are the most common causes of chronic kidney failure. Assured general measures for prevention are:

  • Reduction of obesity,
  • regular physical activity,
  • Reduction of table salt consumption,
  • Diet with plenty of fruits and vegetables and little saturated fat,
  • No nicotine and
  • Reduction in alcohol consumption.

Contrary to popular belief, while drinking plenty of fluids may reduce the risk of kidney stones, it does not improve kidney function. There is even evidence that drinking large amounts of fluids can accelerate the progression of chronic kidney disease.

Medicinal measures

Early detection and consistent drug treatment of diabetes and high blood pressure can prevent the development of chronic kidney disease.

Progression inhibition

Chronic kidney diseases tend to deteriorate continuously. The aim of treatment is therefore to inhibit progression, i.e. H. to reduce the annual loss of kidney function.

Patients with chronic kidney disease should avoid drugs that can be harmful to the kidney, such as: B.

A drug-based lowering of the blood pressure inhibits the progression, blood pressure values ​​below 130/80 mmHg are given as the goal of blood pressure treatment. There are indications that this intensive reduction in blood pressure (compared to a standard target blood pressure of 140/90 mmHg) only benefits those patients who also have significant proteinuria (urine protein excretion); so far, however, only data on Americans of black African origin are available. In most cases, several high-pressure medications are required in combination to achieve an intensive reduction in blood pressure.

In patients with diabetic nephropathy or excessive protein excretion in the urine, ACE inhibitors or AT1 antagonists , two related classes of antihypertensive drugs, can inhibit progression to a particular degree. The aim of treatment is to reduce urine protein excretion to values ​​below 500–1000 mg per day. To achieve this, a target blood pressure lower than 130/80 mmHg may have to be aimed for. If the proteinuria cannot be reduced sufficiently, ACE inhibitors and AT1 antagonists are also used in combination or in very high doses, possibly even combined with aldosterone antagonists . Since these drugs have often only been approved for the treatment of high blood pressure, the treatment is often a so-called off-label use , that is, the use of drugs outside of the actual approval. This type of combination treatment may only be used in diseases with high proteinuria and must be closely monitored; in the routine treatment of high blood pressure, the combination of ACE inhibitors and AT1 antagonists does not provide any additional benefit and is even associated with increased complication rates.

The protein intake with food (see Diet in Renal Insufficiency ) should be moderately restricted. It is recommended to consume 0.8–1 g of protein per kilogram of body weight per day. Strictly restricting protein intake does not bring any additional benefit.

There is evidence that lowering blood lipids with drugs and treating hyperacidity with baking soda can inhibit progression.

For all measures, the earlier it is started in the course of a kidney disease, the greater the chance of success.

Treatment of secondary diseases

Definitions of the KDIGO

(Kidney Disease Improving Global Outcomes)

Mineral and bone metabolism disorder

with chronic kidney disease:

Systemic disruption of mineral and bone metabolism

chronic kidney disease that is manifested by

1. Changes in calcium, phosphate, or parathyroid hormone

Vitamin D metabolism and / or

2. Changes in sales, volume, or growth

Strength of the bone and / or

3. Soft tissue or vascular calcifications.
Renal osteodystrophy:
Changes in bone structure ( morphology )

in chronic kidney disease, which is proven by

quantitative histological examination of a

Bone sample ( histomorphometry of a bone biopsy ).

Disturbance of mineral and bone metabolism

Pathogenesis

From stage 3 of chronic kidney disease, the excretion of phosphate in the urine decreases . This leads to an increase in the level of phosphate in the blood ( hyperphosphataemia ). In response to this, the parathyroid gland releases more parathyroid hormone into the blood ( hyperparathyroidism ); the osteoblasts of the bone produce more fibroblast growth factor 23 (FGF-23) . In the kidneys, the activation of 25 (OH) vitamin D 3 to form calcitriol decreases, the calcitriol level in the blood decreases, the calcium absorption in the intestine decreases, the calcium level in the blood decreases, which in turn stimulates the release of parathyroid hormone . In the healthy kidney, the increase in parathyroid hormone would cause an increased excretion of phosphate and an increased recovery (reabsorption) of calcium from the filtrate of the kidney corpuscle (primary urine) ; FGF-23 would also stimulate phosphate excretion. The result would be a decrease in the phosphate level and an increase in the calcium in the blood. The damaged kidney cannot respond adequately to parathyroid hormone and FGF-23, and there is no increase in phosphate excretion or calcium reabsorption. However, the increased parathyroid hormone level leads to the release of calcium and phosphate from the bones, bone remodeling increases, the bone substance decreases, the risk of bone fractures increases. As the kidney function continues to decline, the blood phosphate level rises, and calcium phosphate is actively deposited in the soft tissues. The result is calcification of vessels and soft tissue, circulatory disorders, cardiovascular complications and reduced life expectancy. This combination of bone metabolism disorder and vascular calcification has recently been referred to as disorder of mineral and bone metabolism in chronic kidney disease or CKD-MBD (Chronic Kidney Disease-Mineral and Bone Disorder) .

Diagnosis

The KDIGO guidelines specify examination intervals and target values ​​that depend on the stage of the disease. For regular determinations of calcium, phosphate, parathyroid hormone and alkaline phosphatase , a determination of the 25 (OH) vitamin D 3 level can be considered. The control should be started in adults from stage 3.

Mineral and bone metabolism disorders in chronic kidney disease on the one hand and osteoporosis in healthy people on the other hand are different clinical pictures that must not be confused. In contrast to the general population, there is no relationship between bone density and the risk of bone fractures in patients with chronic kidney disease . The routine determination of bone density ( osteodensitometry ) is therefore not recommended in the presence of chronic kidney disease .

For the diagnosis of vascular calcification, a conventional side (lateral) is abdomen - X-ray for detection or exclusion of vascular calcification and an echocardiography for detection or exclusion of heart valve calcification recommended.

The histological examination of a tissue sample of the bone ( bone biopsy ) is recommended in the case of unexplained fractures, persistent bone pain, unexplained increase in calcium (hypercalcaemia) , unexplained increase in phosphate (hyperphosphataemia) or decrease (hypophosphataemia) , suspected aluminum overload and prior to therapy with bisphosphonates.

therapy

The aim is to keep calcium and phosphate levels in the normal range. In dialysis patients, however, it is often not possible to achieve normal phosphate levels, but efforts are made to lower elevated phosphate levels towards the normal range.

In the case of increased phosphate levels, the phosphate intake through food has so far been restricted. However, a recent study could not prove the value of a low-phosphate diet.

The drug treatment of increased phosphate levels is carried out with substances that bind phosphate in the intestine and thus inhibit its absorption into the body. Calcium and aluminum salts, sevelamer (a polymer) and lanthanum carbonate are currently used as phosphate binders . Calcium-free phosphate binders are preferred for increased calcium values, arterial calcification of the arteries, reduced bone turnover (adynamic bone) and / or reduced parathyroid hormone , the supply of calcium-containing phosphate binders is restricted, as is the administration of calcitriol and active vitamin D derivatives. Aluminum can also accumulate in the bones and lead to disease of the bone. Long-term treatment with phosphate binders containing aluminum is therefore avoided; the aluminum level must be checked regularly.

Vitamin D deficiency
Vitamin D deficiency 25 (OH) D 3 (calcidiol) <10 ng / ml (25 nmol / l)
Vitamin D Insufficiency 25 (OH) D 3 (calcidiol) 10–30 ng / ml (25–80 nmol / l)

The KDIGO guidelines suggest correcting a vitamin D deficiency (vitamin D deficiency, vitamin D insufficiency) by administering a vitamin D preparation, but warn that "the real effect can differ considerably from the estimated effect ".

The optimal parathyroid hormone range is unknown. If an elevated parathyroid hormone does not respond to treatment with diet, phosphate binders, calcium and / or vitamin D, or even increases further, active vitamin D metabolites are used. With these substances (alfacalcidol, calcitriol) the metabolic step of vitamin D activation, which normally takes place in the kidneys, has already taken place. As a side effect, however, the absorption of calcium and phosphate via the intestine is stimulated. Active vitamin D derivatives (e.g. paricalcitol) have recently been used, which inhibit parathyroid hormone secretion from the parathyroid gland particularly strongly and have less of an effect on the intestine. If the concentration of calcium and phosphate increases too much during vitamin D therapy, vitamin D must be reduced. Too strong an inhibition of the parathyroid hormone secretion should also be avoided, as this leads to reduced bone remodeling (adynamic bone disease) and favors soft tissue calcification.

With increasing kidney function impairment, the bone metabolism changes. So the sensitivity of the bone to parathyroid hormone decreases. For this reason, attempts are made in dialysis patients to keep the parathyroid hormone values ​​in a range between approximately two times and nine times the upper normal range of the determination method used.

Cinacalcet has been approved for the treatment of elevated parathyroid hormone levels in dialysis patients since 2004. Cinacalcet binds to the calcium receptor of the parathyroid gland, simulates an increased calcium level and thus inhibits parathyroid hormone secretion. Despite these measures, it is sometimes not possible to prevent the parathyroid hormone from rising. In this case, the parathyroid glands must be surgically removed.

Treatment with bisphosphonates should be avoided if the parathyroid hormone is elevated and / or in stages 3–5; in cases of doubt, a bone biopsy should be performed prior to bisphosphonate treatment. After a successful kidney transplant and treatment with steroids , however, bone density measurement (osteodensitometry) and treatment with bisphosphonates, possibly in combination with vitamin D and active vitamin D metabolites, can be useful.

Over-acidification of the blood also leads to a loss of bone substance. The treatment is carried out with alkali salts such as citrate or bicarbonate . The administration of bicarbonate may also slow down the loss of kidney function and improve the nutritional status.

Renal anemia

Ferritin target range
KDOQI stage Ferritin target range
3 and 4 100-500 ng / ml
5 200-500 ng / ml

As the kidney function progresses, the production of the messenger substance erythropoietin decreases . Erythropoietin is made in the kidneys and controls the production of red blood cells in the bone marrow . The concentration of the red blood pigment ( hemoglobin ) therefore decreases with increasing kidney function impairment. The result is anemia (renal anemia) with a decrease in physical performance.

Regular determinations of hemoglobin, ferritin, and transferrin saturation are required for the diagnosis and treatment of renal anemia . During the initial examination, a complete blood count including the reticulocytes should be made. A determination of the erythropoietin level is not required. Anemia is present when the hemoglobin concentration in the blood has fallen below 12.0 g / dl in women and below 13.5 g / dl in men.

Hemoglobin target range
KDOQI stage Hb target range
3 to 5 11.0-12.0 g / dL

By giving iron, preferably intravenously in dialysis patients , ferritin levels and transferrin saturation are raised to the highly normal range. Usually, however, additional erythropoietin must be given to raise the hemoglobin to the target range. The target ranges for ferritin and hemoglobin do not correspond to the normal ranges. The desired ferritin levels are higher than the normal values, the desired hemoglobin concentration is slightly below the normal range. An increase of the hemoglobin value in the normal range is no benefit, but leads to increased incidence of hypertension , stroke and shunt - thrombosis ; possibly accept mortality , heart - circulation -Komplikationen and progression to renal impairment. The cause of the increased complication rates with higher hemoglobin target values ​​is unknown. A direct effect of hemoglobin, e.g. B. by increased viscosity of the blood, a side effect of erythropoietin, a side effect of iron, the increased blood pressure during erythropoietin treatment or the consequence of a decreased response to erythropoietin.

Blood transfers are required only in rare cases and are avoided whenever possible.

Prevention of complications

Patients with chronic kidney disease are primarily at risk from cardiovascular diseases such as coronary artery disease , heart failure , stroke and arterial disease . In contrast, the risk of becoming dependent on dialysis in the course of the disease is significantly lower. Stage 5 kidney disease is a cardiovascular risk factor that is as serious as having had a heart attack ; mortality from cardiovascular complications is about 10-20 times higher than that of the general population. If there is also diabetes mellitus, the mortality is around 40% higher than in stage 5 kidney patients without diabetes.

In the presence of chronic kidney disease, the blood lipids total cholesterol , LDL cholesterol, HDL cholesterol and triglycerides should be determined. If the LDL cholesterol is high and cannot be reduced sufficiently through a change in diet and increased physical activity, it is recommended to use a statin to lower it with medication , in accordance with the guidelines that apply to the normal population. For stage 5 of chronic kidney disease, the K / DOQI guidelines recommend a particularly aggressive lowering of LDL cholesterol to values ​​below 100 mg / dl (2.6 mmol / l), in the presence of diabetes some authors even set target values ​​below 70 mg / dl (1.82 mmol / l) recommended.

Post-hoc analyzes of studies on the lowering of blood lipids using drugs confirm the beneficial influence of a lowering of LDL cholesterol on the occurrence of cardiovascular complications in stage 3 of kidney disease. A large, placebo-controlled multicenter study showed that in chronic kidney disease, lowering LDL cholesterol with drugs using simvastatin and ezetimibe reduces the frequency of heart attacks, strokes and circulatory disorders that require treatment.

On the other hand, lowering the LDL cholesterol with drugs could no longer reduce cardiovascular complications in dialysis patients . Cohort studies on patients with chronic kidney disease and hemodialysis patients even showed better survival with higher total and LDL cholesterol. This relationship between risk factor and course, which is reversed compared to the normal population, is also known as reverse epidemiology .

These discrepant findings have recently been interpreted to mean that in stage 5 the changes in the cardiovascular system are so advanced that they no longer respond well to a drug-based lowering of LDL cholesterol. In addition, low cholesterol levels can be the result of malnutrition that is common in kidney patients and a chronic inflammatory constellation. Consequently, the American Heart Association recommends classifying the early stages of chronic kidney disease in the highest cardiovascular risk level and striving for a particularly aggressive lowering of cholesterol.

So far there are no data showing an additional beneficial effect in chronic kidney disease if the triglycerides or HDL cholesterol are influenced by drugs in addition to LDL cholesterol.

Renal replacement therapy

In stage 4 of chronic kidney disease (GFR <30 ml / min / 1.73 m²), the patient, family member and doctor should decide which kidney replacement method should be used in the event of a further loss of kidney function. The choices are:

  1. Hemodialysis (blood washing),
  2. Peritoneal dialysis ( peritoneal dialysis ),
  3. Kidney transplantation (possibly pre-emptively, i.e. before the start of dialysis treatment if a suitable donor is available),
  4. Conservative therapy (drug and supportive therapy if dialysis treatment or kidney transplantation is not desired by the patient).

In stage 5 of chronic kidney disease (GFR <15 ml / min / 1.73 m²) a kidney replacement procedure is started. An early start of renal replacement therapy (i.e. with an eGFR 10-14 ml / min / 1.73 m²) has no advantage over starting dialysis later (eGFR 5-7 ml / min / 1.73 m²). Without renal replacement therapy, the further course of the disease leads to death in the uremia . In very old and frail people, dialysis treatment in stage 5 extends life by about two years, but the initiation of renal replacement therapy can also lead to a significant deterioration in the general condition; in such cases conservative treatment may be an acceptable alternative.

Guidelines

In 1997, the National Kidney Foundation started the Dialysis Outcomes Quality Initiative (DOQI). The aim of this project was to improve the care of dialysis patients. It emerged evidence-based guidelines for hemodialysis, peritoneal dialysis (peritoneal dialysis), for vascular access and the nutrition of dialysis patients. In 1999 the National Kidney Foundation decided to extend the quality initiative to the early stages of chronic kidney disease (Kidney Disease Outcomes Quality Initiative or K / DOQI). In 2002 the first K / DOQI guideline appeared. This guideline stipulated diagnostic measures (evaluation), defined the currently used staging (classification) and suggested measures for assessing the risk of disease deterioration and the occurrence of complications (stratification).

There are currently twelve guidelines published:

  1. Hemodialysis
  2. Peritoneal dialysis
  3. Vascular access
  4. Anemia management
  5. nutrition
  6. Evaluation, classification and stratification of chronic kidney disease
  7. Lipid metabolism disorder
  8. Bone metabolism disorders
  9. Bone metabolism disorders in children
  10. High blood pressure and blood pressure treatment
  11. Cardiovascular diseases in dialysis patients
  12. Diabetes and chronic kidney disease.

The Kidney Disease: Improving Global Outcomes (KDIGO) is a global non-profit foundation with the aim of improving the care of chronic kidney patients and their treatment outcomes worldwide. KDIGO has published the following guidelines:

  1. Prevention, diagnosis, evaluation and treatment of hepatitis C in chronic kidney disease.
  2. Diagnosis, evaluation, prevention and treatment of disorders of mineral and bone metabolism in chronic kidney disease.
  3. Care of the kidney transplant patient.

The European Renal Association has published guidelines on anemia management, hemodialysis and kidney transplantation.

The Canadian Society of Nephrology guidelines address principles of treating the terminal stage of renal disease, GP-to-nephrologist referral, hemodialysis, peritoneal dialysis, vascular access, dialysis initiation, and anemia management.

The British guidelines of the Royal College of Physicians in collaboration with the British Kidney Association were published in 2005 and updated in 2008. Measures for the detection and management of kidney disease and criteria for referral to specialist are suggested.

The guidelines of the Nephrological Society of Australia and New Zealand have been published since 2000. They include the diagnosis, prevention and treatment of chronic kidney disease, dialysis and kidney transplantation.

The database of the Working Group of the Scientific Medical Societies in Germany contains guidelines on diabetic nephropathy, uremic polyneuropathy and kidney transplantation from a urological point of view. A German S3 guideline on the outpatient care of patients with chronic kidney disease who does not require dialysis was published by the German Society for General Medicine and Family Medicine in 2019 .

Self-help organizations

As an independent organization, the German Kidney Foundation, founded in 1997, has placed information and education, early detection and prevention of chronic kidney disease in the focus of its activities. In 2013 she started a corresponding program with “Strong kidneys”, and since spring 2016 she has been working with 30 company health insurers under the motto “Tatort Kidney”.

In Germany there are a large number of local self-help groups that work in particular for dialysis patients and kidney transplant recipients.

Many of these groups are part of the "Bundesverband Niere - Selbsthilfe Kidney - Prevention, Dialysis, Transplantation - e. V. “merged. The goals of the association include a.

  • promoting willingness to donate organs in public,
  • the prevention of kidney disease,
  • the commitment to quality management in renal replacement therapy,
  • safeguarding the interests of the members of its affiliated member associations.

The Federal Association of Kidneys publishes the journal The Kidney Patient.

The “network of people with chronic kidney disease and their relatives c / o home dialysis patients (HDP) e. V. “aims to promote home dialysis procedures such as peritoneum dialysis or home hemodialysis.

The "PKD Familiare Zystennieren e. V. “is aimed at patients with cyst kidney and their family members and is part of an international network of cyst kidney patients .

The goals of the self-help group are self-help - prevention - research, etc. a.

  • medical education with the help of doctors,
  • Conversations with those affected and their family members,
  • personal exchange of experiences,
  • Help with occurring problems,
  • Specialist lectures on topics related to illness,
  • common leisure activities,
  • Contact point for parents with sick children.

The association “Young Kidney Diseases Germany e. V. “represents the interests of young people with kidney disease. It is specifically aimed at adolescents and young adults affected by kidney disease. Among other things, the association offers events, seminars and trips that are also suitable for people with kidney disease who suffer from dialysis, and provides advice and support with problems in the social, professional and school environment.

Chronic kidney failure in veterinary medicine

In veterinary medicine, chronic kidney failure is most common in domestic cats and is one of the leading causes of death for this species (see Chronic kidney disease in cats ).

literature

  • Bertram Hartmann, David Czock, Frieder Keller: Drug therapy in patients with chronic kidney failure . In: Dtsch Arztebl Int . No. 107 (37) , 2010, pp. 647-656 ( aerzteblatt.de ).

Web links

Individual evidence

  1. ^ Kidney Disease: Common, Harmful, Treatable . World Kidney Day, a joint initiative of the International Society of Nephrology (ISN) and the International Federation of Kidney Foundations (IFKF).
  2. ↑ a b KDIGO 2012 Clinical Practice Guideline for the Evaluation and Management of Chronic Kidney Disease . In: Kidney Disease: Improving Global Outcomes [KDIGO] CKD Work Group (Ed.): Kidney Int . Suppl. 3, no. 1 , 2013, p. 1–150 ( KDIGO CKD 2012 [PDF]). KDIGO CKD 2012 ( Memento of the original from March 4, 2016 in the Internet Archive ) Info: The archive link was inserted automatically and has not yet been checked. Please check the original and archive link according to the instructions and then remove this notice.  @1@ 2Template: Webachiv / IABot / www.kdigo.org
  3. ↑ U. Frei, H.-J. Schober-Halstenberg: Renal replacement therapy in Germany. Federal Kidney Association , annual reports 1995 to 2005/2006, Berlin, Germany. The data were provided by QuaSi-Niere gGmbH. The author is solely responsible for the interpretation and further evaluation of this data.
  4. ↑ IM Wahba u. a .: Obesity and Obesity-Initiated Metabolic Syndrome: Mechanistic Links to Chronic Kidney Disease. In: Clin J Am Soc Nephrol . 2007 2, pp. 550-562.
  5. ↑ ndt Nephrology Dialysis Transplantation: fluoridation of drinking water and chronic kidney disease
  6. ↑ Figure: Prevalence of chronic kidney disease by age NHANES 1988–1994 and 1999–2004. JAMA , 2007, 298 (17), pp. 2038-2047.
  7. ↑ Allan J. Collins et al. a .: Who should be targeted for CKD screening? Impact of diabetes, hypertension, and cardiovascular disease . In: American Journal of Kidney Diseases . tape 53 , 3 Suppl 3, March 2009, ISSN  1523-6838 , p. S71-77 , doi : 10.1053 / j.ajkd.2008.07.057 , PMID 19231764 .
  8. Jump up ↑ Josef Coresh, Elizabeth Selvin, Lesley A. Stevens, Jane Manzi, John W. Kusek, Paul Eggers, Frederick Van Lente, Andrew S. Levey: Prevalence of chronic kidney disease in the United States . In: JAMA: The Journal of the American Medical Association . tape 298 , no. 17 , November 7, 2007, ISSN  1538-3598 , p. 2038-2047 , doi : 10.1001 / jama.298.17.2038 , PMID 17986697 .
  9. ↑ Mitchell Rosner, Emaad Abdel-Rahman, Mark E. Williams: Geriatric nephrology: responding to a growing challenge . In: Clinical Journal of the American Society of Nephrology . tape 5 , no. 5 , May 2010, ISSN  1555-905X , p. 936-942 , doi : 10.2215 / CJN.08731209 , PMID 20185600 .
  10. ↑ Gesine Weckmann, Jean-François Chenot, Sylvia Stracke: S3 guideline for the care of patients with chronic kidney disease that does not require dialysis in the general practitioner's practice . In: DEGAM guideline no. 22, AWMF register no. 053-048 . June 30, 2019 ( awmf.org [PDF; accessed May 12, 2020]).
  11. ↑ Gesine Weckmann, Jean-François Chenot, Sylvia Stracke: S3 guideline for the care of patients with chronic kidney disease that does not require dialysis in the general practitioner's practice . In: DEGAM guideline no. 22, AWMF register no. 053-048 . June 30, 2019 ( awmf.org [PDF; accessed May 12, 2020]).
  12. ↑ AS Go u. a .: Chronic Kidney Disease and the Risks of Death, Cardiovascular Events, and Hospitalization . In: N. Engl. J. Med. 351, 2004, pp. 1296-1305
  13. ↑ Manjula Kurella Tamura Virginia Wadley et al. a .: Kidney function and cognitive impairment in US adults: the Reasons for Geographic and Racial Differences in Stroke (REGARDS) Study . In: American Journal of Kidney Diseases: The Official Journal of the National Kidney Foundation . tape 52 , no. 2 , August 2008, ISSN  1523-6838 , p. 227-234 , doi : 10.1053 / j.ajkd.2008.05.004 , PMID 18585836 .
  14. ↑ Minesh Khatri et al. a .: CKD associates with cognitive decline . In: Journal of the American Society of Nephrology: JASN . tape 20 , no. November 11 , 2009, ISSN  1533-3450 , p. 2427-2432 , doi : 10.1681 / ASN.2008101090 , PMID 19729443 .
  15. ↑ Gerald Liew Paul Mitchell, Tien Yin Wong, Sudha K Iyengar, Jie Jin Wang: CKD increases the risk of age-related macular degeneration . In: Journal of the American Society of Nephrology: JASN . tape 19 , no. 4 , April 2008, ISSN  1533-3450 , p. 806-811 , doi : 10.1681 / ASN.2007080844 , PMID 18216312 .
  16. ^ Matthew T. James et al. a .: CKD and risk of hospitalization and death with pneumonia . In: American Journal of Kidney Diseases: The Official Journal of the National Kidney Foundation . tape 54 , no. 1 , July 2009, ISSN  1523-6838 , p. 24-32 , doi : 10.1053 / j.ajkd.2009.04.005 , PMID 19447535 .
  17. ↑ Annamaria Kausz, Dilip Pahari: The value of vaccination in chronic kidney disease . In: Seminars in Dialysis . tape 17 , no. 1 , February 2004, ISSN  0894-0959 , p. 9-11 , PMID 14717802 .
  18. ↑ CY Hsun et al. a .: The risk of acute renal failure in patients with chronic kidney disease . In: Kidney Int . No. 74 , 2008, p. 101-107 ( abstract ).
  19. ^ DS Keith et al. a .: Longitudinal Follow-up and Outcomes Among a Population With Chronic Kidney Disease in a Large Managed Care Organization. In: Arch Intern Med. 2004, 164, pp. 659-663.
  20. ^ Allan J. Collins, Robert N. Foley, David T. Gilbertson, Shu-Chen Chen: The state of chronic kidney disease, ESRD, and morbidity and mortality in the first year of dialysis . In: Clinical Journal of the American Society of Nephrology: CJASN . 4 Suppl 1, December 2009, ISSN  1555-905X , p. S5-11 , doi : 10.2215 / CJN.05980809 , PMID 19996006 .
  21. ↑ GFR threshold above which the probability of requiring dialysis exceeds the probability of dying before; by age group from Ann M. O'Hare u. a .: Age Affects Outcomes in Chronic Kidney Disease . In: J Am Soc Nephrol . tape 18 , no. 10 , October 1, 2007, p. 2758-2765 , doi : 10.1681 / ASN.2007040422 .
  22. ↑ M. Tonelli et al. a .: Chronic Kidney Disease and Mortality Risk: A Systematic Review J Am Soc Nephrol 2006 17: 2034-2047.
  23. ↑ Kunihiro Matsushita et al. a .: Association of estimated glomerular filtration rate and albuminuria with all-cause and cardiovascular mortality in general population cohorts: a collaborative meta-analysis . In: The Lancet . tape 375 , no. 9731 , June 12, 2010, ISSN  1474-547X , p. 2073-2081 , doi : 10.1016 / S0140-6736 (10) 60674-5 , PMID 20483451 .
  24. ^ MA Roberts et al. a .: Cardiovascular Biomarkers in CKD: Pathophysiology and Implications for Clinical Management of Cardiac Disease. In: American Journal of Kidney Diseases. 48 (2006), pp. 341-360.
  25. ↑ UC Brewster et al. a .: Dermatological Disease in Patients With CKD . In: American Journal of Kidney Diseases . No. 51 , 2008, p. 331-344 ( Article ).
  26. ↑ AK Bello u. a .: Prevention of chronic kidney disease. A global challenge . In: Kidney International . 68, Supplement 98, 2005, pp. S11-S17 ( article ).
  27. ↑ E. Imai et al. a .: Kidney Disease Screening Program in Japan. History, Outcome, and Perspectives . In: Clin J Am Soc Nephrol . No. 2 , 2007, p. 1360-1366 ( abstract ).
  28. ↑ Stephan R. Orth, Stein I. Hallan: Smoking: A Risk Factor for Progression of Chronic Kidney Disease and for Cardiovascular Morbidity and Mortality in Renal Patients Absence of Evidence or Evidence of Absence? In: Clin J Am Soc Nephrol . No. 3 , 2008, p. 226-236 ( abstract ).
  29. ^ UO Wenzel u. a .: My Doctor Said I Should Drink a Lot! Recommendations for Fluid Intake in Patients with Chronic Kidney Disease . In: Clin J Am Soc Nephrol . No. 1 , 2006, p. 344-346 ( cjasn.asnjournals.org ).
  30. ↑ K / DOQI Clinical Practice Guidelines on Hypertension and Antihypertensive Agents in Chronic Kidney Disease. In: American Journal of Kidney Diseases. 2004; 43: 5 (Suppl 1), p. S1.
  31. ↑ Lawrence J. Appel et al. a .: Intensive blood-pressure control in hypertensive chronic kidney disease . In: The New England Journal of Medicine . tape 363 , no. 10 , September 2, 2010, ISSN  1533-4406 , p. 918-929 , doi : 10.1056 / NEJMoa0910975 , PMID 20818902 .
  32. ↑ DM Kent u. a .: Progression Risk, Urinary Protein Excretion, and Treatment Effects of Angiotensin-Converting Enzyme Inhibitors in Nondiabetic Kidney Disease . In: J Am Soc Nephrol. 2007, 18, pp. 1959-1965.
  33. ↑ M. MacKinnon et al. a .: Combination Therapy With an Angiotensin Receptor Blocker and an ACE Inhibitor in Proteinuric Renal Disease: A Systematic Review of the Efficacy and Safety Data . In: American Journal of Kidney Diseases. 2006, 48, pp. 8-20.
  34. ↑ Roland E. Schmieder u. a. Additional Antiproteinuric Effect of Ultrahigh Dose Candesartan: A Double-Blind, Randomized, Prospective Study . In: J Am Soc Nephrol. 2005, 16, pp. 3038-3045.
  35. ↑ Leszek Tylicki et al. a .: Triple pharmacological blockade of the renin-angiotensin-aldosterone system in nondiabetic CKD: an open-label crossover randomized controlled trial . In: American Journal of Kidney Diseases . tape 52 , no. 3 , September 2008, ISSN  1523-6838 , p. 486-493 , doi : 10.1053 / j.ajkd.2008.02.297 , PMID 18423812 .
  36. ↑ Fausta Catapano, Paolo Chiodini, Luca De Nicola, Roberto Minutolo, Pasquale Zamboli, Ciro Gallo, Giuseppe Conte Antiproteinuric response to dual blockade of the renin-angiotensin system in primary glomerulonephritis: meta-analysis and metaregression . In: American Journal of Kidney Diseases: The Official Journal of the National Kidney Foundation . tape 52 , no. 3 , September 2008, ISSN  1523-6838 , p. 475-85 , doi : 10.1053 / j.ajkd.2008.03.008 , PMID 18468748 .
  37. ^ Salim Yusuf et al. a .: Telmisartan, ramipril, or both in patients at high risk for vascular events . In: The New England Journal of Medicine . tape 358 , no. 15 , April 10, 2008, ISSN  1533-4406 , p. 1547-1559 , doi : 10.1056 / NEJMoa0801317 , PMID 18378520 .
  38. ↑ Bruno Cianciaruso et al. a .: Effect of a low- versus moderate-protein diet on progression of CKD: follow-up of a randomized controlled trial . In: American Journal of Kidney Diseases: The Official Journal of the National Kidney Foundation . tape 54 , no. 6 , December 2009, ISSN  1523-6838 , p. 1052-1061 , doi : 10.1053 / j.ajkd.2009.07.021 , PMID 19800722 .
  39. ↑ J. Shepherd et al. a .: Effect of Intensive Lipid Lowering with Atorvastatin on Renal Function in Patients with Coronary Heart Disease: The Treating to New Targets (TNT) Study . In: Clin J Am Soc Nephrol . No. 2 , 2007, p. 1131-1139 ( abstract ).
  40. ↑ a b Ione de Brito-Ashurst, Mira Varagunam, Martin J. Raftery, Muhammad M. Yaqoob: Bicarbonate supplementation slows progression of CKD and improves nutritional status . In: Journal of the American Society of Nephrology: JASN . tape 20 , no. 9 , September 2009, ISSN  1533-3450 , p. 2075-2084 , doi : 10.1681 / ASN.2008111205 , PMID 19608703 .
  41. ↑ a b c KDIGO clinical practice guideline for the diagnosis, evaluation, prevention, and treatment of chronic kidney disease - mineral and bone disorder (CKD - ​​MBD). In: Improving Global Outcomes [KDIGO] CKD-MBD Work Group (Ed.): Kidney International . 76 (Suppl 113), 2009, p. S1 – S130 ( kdigo.org [PDF]). German translation (PDF; 164 kB)
  42. ^ Steven M. Brunelli: The Association between Prescribed Dietary Phosphate Restriction and Mortality among Hemodialysis Patients . In: CJASN . December 2010, 2011 ( article ).
  43. ↑ KDOQI Clinical Practice Guidelines for Bone Metabolism and Disease in Chronic Kidney Disease ( Memento of February 14, 2015 in the Internet Archive ). In: American Journal of Kidney Diseases. 2003: 42 Supplement 3.
  44. ↑ KDOQI Clinical Practice Guidelines and Clinical Practice Recommendations for Anemia in Chronic Kidney Disease. In: American Journal of Kidney Diseases. 2006: 47 Supplement S3
  45. ↑ KDOQI Clinical Practice Guideline and Clinical Practice Recommendations for Anemia in Chronic Kidney Disease: 2007 Update of Hemoglobin Target. In: American Journal of Kidney Diseases. 2007: 50, pp. 522-528.
  46. ↑ TB Drüeke u. a .: Normalization of hemoglobin level in patients with chronic kidney disease and anemia. In: N Engl J Med. 2006; 355, pp. 2071-2084.
  47. ↑ AK Singh et al. a .: Correction of anemia with epoetin alfa in chronic kidney disease. In: N Engl J Med. 2006; 355, pp. 2085-2098.
  48. ↑ Marc A. Pfeffer u. a .: A trial of darbepoetin alfa in type 2 diabetes and chronic kidney disease . In: The New England Journal of Medicine . tape 361 , no. 21 , November 19, 2009, ISSN  1533-4406 , p. 2019-2032 , doi : 10.1056 / NEJMoa0907845 , PMID 19880844 .
  49. ↑ Suetonia C. Palmer et al. a .: Meta-analysis: erythropoiesis-stimulating agents in patients with chronic kidney disease . In: Annals of Internal Medicine . tape 153 , no. 1 , July 6, 2010, ISSN  1539-3704 , p. 23-33 , doi : 10.7326 / 0003-4819-153-1-201007060-00252 , PMID 20439566 .
  50. ↑ S. Fishbane, A. Besarab: Mechanism of Increased Mortality Risk with erythropoietin treatment to Higher hemoglobin targets . In: Clin J Am Soc Nephrol . No. 2 , 2007, p. 1274-1282 ( abstract ).
  51. ↑ Anna Kottgen u. a .: Reduced Kidney Function as a Risk Factor for Incident Heart Failure: The Atherosclerosis Risk in Communities (ARIC) Study . In: J Am Soc Nephrol . No. 18 , 2007, p. 1307-1315 ( Article ).
  52. ↑ Meng Lee et al. a .: Low glomerular filtration rate and risk of stroke: meta-analysis . In: BMJ (Clinical Research Ed.) . tape 341 , 2010, ISSN  1468-5833 , p. c4249 , PMID 20884696 .
  53. ↑ K / DOQI Clinical Practice Guidelines for Managing dyslipidemias in Chronic Kidney Disease . In: American Journal of Kidney Diseases. 2003, 41, Supplement S3
  54. ↑ ME Molitch: management of dyslipidemias in Patients with Diabetes and Chronic Kidney Disease . In: Clin J Am Soc Nephrol. 2006, 1, pp. 1090-1099.
  55. ^ Third Report of the Expert Panel on Detection, Evaluation, and Treatment of High Blood Cholesterol in Adults (Adult Treatment Panel III) . ( Memento of October 4, 2014 in the Internet Archive ) National Heart, Lung and Blood Institute
  56. ^ Joseph Nogueira, Matthew Weir: The Unique Character of Cardiovascular Disease in Chronic Kidney Disease and Its Implications for Treatment with Lipid-Lowering Drugs . In: Clin J Am Soc Nephrol . No. 2 , 2007, p. 766-785 ( Article ).
  57. ↑ Marcello Tonelli et al. a .: Effect of Pravastatin on Cardiovascular Events in People With Chronic Kidney Disease . In: Circulation . No. 110 , 2004, p. 1557-1563 ( Article ).
  58. ↑ Michael J. Koren u. a .: Focused Atorvastatin Therapy in Managed-Care Patients With Coronary Heart Disease and CKD . In: American Journal of Kidney Diseases . Vol. 53, Issue 5, 2009, pp. 741-750 ( abstract ).
  59. ↑ Colin Baigent et al. a .: The effects of lowering LDL cholesterol with simvastatin plus ezetimibe in patients with chronic kidney disease (Study of Heart and Renal Protection): a randomized placebo-controlled trial . In: Lancet . tape 377 , no. 9784 , June 25, 2011, ISSN  1474-547X , p. 2181-2192 , doi : 10.1016 / S0140-6736 (11) 60739-3 , PMID 21663949 .
  60. ↑ Christoph Wanner u. a .: Atorvastatin in patients with type 2 diabetes mellitus undergoing hemodialysis . In: The New England Journal of Medicine . tape 353 , no. 3 , July 21, 2005, ISSN  1533-4406 , p. 238-248 , doi : 10.1056 / NEJMoa043545 , PMID 16034009 .
  61. ↑ Bengt C. Fellström et al. a .: Rosuvastatin and cardiovascular events in patients undergoing hemodialysis . In: The New England Journal of Medicine . tape 360 , no. 14 , April 2, 2009, ISSN  1533-4406 , p. 1395-1407 , doi : 10.1056 / NEJMoa0810177 , PMID 19332456 .
  62. ↑ Bonnie CH Kwan u. a .: Lipoprotein Metabolism and Lipid Management in Chronic Kidney Disease . In: J Am Soc Nephrol . No. 18 , 2007, p. 1246-1261 ( Article ).
  63. ↑ RD Kilpatrick u. a .: Association between Serum Lipids and Survival in Hemodialysis Patients and Impact of Race . In: J Am Soc Nephrol . No. 18 , 2007, p. 293-303 ( Article ).
  64. ↑ CP Kovesdy et al. a .: Inverse Association between Lipid Levels and Mortality in Men with Chronic Kidney Disease Who Are Not Yet on Dialysis: Effects of Case Mix and the Malnutrition-Inflammation-Cachexia Syndrome . In: J Am Soc Nephrol . No. 18 , 2007, p. 304-311 ( Article ).
  65. ↑ MJ Sarnak et al. a .: Kidney Disease as a Risk Factor for Development of Cardiovascular Disease: A Statement From the American Heart Association Councils on Kidney in Cardiovascular Disease, High Blood Pressure Research, Clinical Cardiology, and Epidemiology and Prevention. In: Circulation. 2003; 108, pp. 2154-2169.
  66. ↑ Gursharan Dogra, Ashley Irish, Dick Chan, Gerald Watts: A randomized trial of the effect of statin and fibrate therapy on arterial function in CKD . In: American Journal of Kidney Diseases: The Official Journal of the National Kidney Foundation . tape 49 , no. 6 , June 2007, ISSN  1523-6838 , p. 776-785 , doi : 10.1053 / j.ajkd.2007.03.003 , PMID 17533020 .
  67. ↑ NKF K / DOQI GUIDELINES: Clinical Practice Guidelines and Clinical Practice Recommendations, 2006 Updates, Hemodialysis Adequacy, Peritoneal Dialysis Adequacy, Vascular Access. In: American Journal of Kidney Diseases. 2006: 48 Supplement S1 kidney.org ( Memento of the original dated February 11, 2007 in the Internet Archive ) Info: The archive link was inserted automatically and has not yet been checked. Please check the original and archive link according to the instructions and then remove this notice. @1@ 2Template: Webachiv / IABot / www.kidney.org
  68. ↑ Bruce A. Cooper et al. a .: A Randomized, Controlled Trial of Early versus Late Initiation of Dialysis . In: The New England Journal of Medicine . June 27, 2010, ISSN  1533-4406 , doi : 10.1056 / NEJMoa1000552 , PMID 20581422 .
  69. ↑ Seth Wright et al. a .: Timing of dialysis initiation and survival in ESRD . In: Clinical Journal of the American Society of Nephrology: CJASN . tape 5 , no. October 10 , 2010, ISSN  1555-905X , p. 1828-1835 , doi : 10.2215 / CJN.06230909 , PMID 20634325 .
  70. ↑ Rachel C. Carson, Maciej Juszczak, Andrew Davenport, Aine Burns: Is Maximum Conservative Management an Equivalent Treatment Option to Dialysis for Elderly Patients with Significant Comorbid Disease? In: Clin J Am Soc Nephrol . tape 4 , no. 10 , October 1, 2009, p. 1611-1619 , doi : 10.2215 / CJN.00510109 ( abstract [accessed February 6, 2010]).
  71. ↑ Manjula Kurella Tamura, Kenneth E. Covinsky, Glenn M. Chertow, Kristine Yaffe, C. Seth Landefeld, Charles E McCulloch: Functional status of elderly adults before and after initiation of dialysis . In: The New England Journal of Medicine . tape 361 , no. 16 , October 15, 2009, ISSN  1533-4406 , p. 1539-1547 , doi : 10.1056 / NEJMoa0904655 , PMID 19828531 .
  72. ↑ Vincenzo De Biase, Olga Tobaldini, Claudia Boaretti, Cataldo Abaterusso, Nicoletta Pertica, Carmelo Loschiavo, Gaetano Trabucco, Antonio Lupo, Giovanni Gambaro: Prolonged conservative treatment for frail elderly patients with end-stage renal disease: the Verona experience . In: Nephrology Dialysis Transplantation . tape 23 , no. 4 , April 2008, ISSN  1460-2385 , p. 1313-1317 , doi : 10.1093 / ndt / gfm772 , PMID 18029376 .
  73. ↑ kdigo.org - Kidney Disease: Improving Global Outcomes (KDIGO)
  74. ↑ KDIGO clinical practice guidelines for the prevention, diagnosis, evaluation, and treatment of hepatitis C in chronic kidney disease . In: Kidney International. Supplement . No. 109 , April 2008, ISSN  0098-6577 , p. S1-99 , doi : 10.1038 / ki.2008.81 , PMID 18382440 ( kdigo.org [PDF]).
  75. ↑ KDIGO clinical practice guideline for the care of kidney transplant recipients . In: American Journal of Transplantation . 9 Suppl 3, November 2009, ISSN  1600-6143 , p. S1–155 , doi : 10.1111 / j.1600-6143.2009.02834.x , PMID 19845597 ( kdigo.org [PDF]).
  76. ↑ Gesine Weckmann Gesine, Jean-François Chenot, Sylvia Stracke: S3 guideline for the care of patients with chronic kidney disease that does not require dialysis in the general practitioner's practice . In: DEGAM guideline no. 22, AWMF register no. 053-048 . June 30, 2019 ( awmf.org [PDF; accessed May 12, 2020]).
  77. ↑ Crime scene kidney , bkk-sued.de