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Background

Chronic kidney disease (CKD) and renal failure (RF) have been recognized as significant medical problems for most of the last 2 centuries and, until relatively recently, were uniformly fatal. Scientific and technologic improvements during the second half of the 20th century provided renal replacement therapy as a life-sustaining option for many individuals who otherwise may have died. The impact of these medical advancements has been remarkable. Chronic kidney disease is characterized by an irreversible deterioration of renal function that gradually progresses to end-stage renal disease (ESRD). Chronic kidney disease has emerged as a serious public health problem. Data from the United States Renal Data System (USRDS) show that incidence of kidney failure is rising among adults and is commonly associated with poor outcomes and high cost.[1] Moreover, in the past 2 decades, the incidence of the chronic kidney disease in children has steadily increased, with poor and ethnic minority children disproportionately affected.[1] The major health consequences of chronic kidney disease include not only progression to kidney failure but also an increased risk of cardiovascular disease. Evidence-based clinical practice guidelines support early recognition and treatment of chronic kidney diseaserelated complications to improve growth and development and, ultimately, the quality of life in children with this chronic condition. Appropriate pediatric care may reduce the prevalence of this complex and expensive condition.

Definition of chronic renal disease


The definition and classification of chronic renal disease may help identify affected individuals, possibly resulting in the early institution of effective therapy. To achieve this goal, the Kidney Disease Outcomes Quality Initiative (KDOQI) working group of the National Kidney Foundation (NKF) defined chronic kidney disease as "evidence of structural or functional kidney abnormalities (abnormal urinalysis, imaging studies, or histology) that persist for at least 3 months, with or without a decreased glomerular filtration rate (GFR), as defined by a GFR of less than 60 mL/min per 1.73 m2."[2, 3, 4] Note, however, that the above definition is not applicable to children younger than 2 years, because they normally have a low GFR, even when corrected for body surface area. In these patients, calculated GFR based on serum creatinine can be compared with normative ageappropriate values to detect renal impairment. See also Chronic Renal Failure, Renal Failure, Chronic and Dialysis Complications,Dermatologic Manifestations of Renal Disease, Renal Transplantation (Medical), and Perioperative Management of the Patient With Chronic Renal Failure.

Etiology and Pathophysiology


The chief causes of chronic kidney disease (CKD) in children include the following:

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Obstructive uropathy Hypoplastic or dysplastic kidneys Reflux nephropathy Focal segmental glomerulosclerosis as a variant of childhood nephritic syndrome Polycystic kidney disease, autosomal-recessive and autosomal-dominant varieties

Despite the diverse etiologies, once chronic kidney disease develops, the subsequent response of the failing kidney is similar. The kidney initially adapts to damage by increasing the filtration rate in the remaining normal nephrons, a process called adaptive hyperfiltration. As a result, patients with mild chronic kidney disease often have a normal or near-normal serum creatinine concentration. Additional homeostatic mechanisms (most frequently occurring within the renal tubules) permit the serum concentrations of sodium, potassium, calcium, and phosphorous and total body water to also remain within the reference range, particularly among those with mild to moderate stages of chronic kidney disease. Adaptive hyperfiltration, although initially beneficial, appears to result in long-term damage to the glomeruli of the remaining nephrons, which is manifested by pathologic proteinuria and progressive kidney insufficiency. This irreversibility appears to be responsible for the development of end-stage kidney failure among persons in whom the original illness is either inactive or cured. Although the underlying problem that initiated chronic kidney disease often cannot be treated primarily, extensive studies in experimental animals and preliminary studies in humans suggest that progression in chronic renal disease may be largely due to secondary factors that are unrelated to the activity of the initial disease. These include anemia, osteodystrophy, systemic and intraglomerular hypertension, glomerular hypertrophy, proteinuria, metabolic acidosis, hyperlipidemia, tubulointerstitial disease, systemic inflammation, and altered prostanoid metabolism. This common sequence of events in diverse types of chronic kidney disease is the basis for the common management plan for children with chronic kidney disease, irrespective of the etiology.

Epidemiology
United States statistics
Based on data from the North American Pediatric Renal Transplant Cooperative Study (NAPRTCS) chronic renal insufficiency (CRI) database, 5651 patients aged 2-17 years were entered into this voluntary listing and had an estimated glomerular filtration rate (eGFR) of less than 75 mL/min per 1.73 m2.[5] In the past 2 decades, the incidence of the disease has steadily increased among all ethnic groups.

International statistics
Globally, the prevalence of chronic kidney disease (CKD) stage II or lower in children is reported to be approximately 18.5-58.3 per million children. Disease prevalence is much lower than that in adults; in a study from India, children constituted 5.3% of all patients with chronic

kidney disease seen in a referral hospital.[6] Data from the ItalKid study reported a mean incidence of 12.1 cases per year per million in the age-related population (age range, 8.8-13.9 y) and a prevalence of 74.7 per million in this population.[7] However, underreporting due to lack of recognition may suggest an even higher prevalence in children.

Sexual, racial, and age differences in incidence


In the United States, the incidence and rate of progression to end-stage renal disease (ESRD) are equal in both sexes, although obstructive uropathies are more common in males. ESRD rates in black individuals are 2.7 times higher than in white individuals, which may be due to genetic susceptibility; other factors may include socioeconomic problems and limited access to medical care. Such factors may result in the delivery of excessive numbers of low birth weight (LBW) babies, partially accounting for the observed increased incidence of ESRD, because chronic kidney disease is more common with increasing prematurity and survivorship. Choi et al found that rates of ESRD among black patients exceeded those among white patients at all levels of baseline eGFR.[8] Similarly, mortality rates among black patients were equal to or higher than those among white patients at all levels of eGFR. Risk of ESRD among black patients was highest at an eGFR of 45-59 mL/min/1.73 m2, as was the risk of mortality.[8] The frequency of chronic kidney disease increases with age and is much more common in adults than children. Among children, chronic kidney disease is more common in children older than 6 years than in those younger than 6 years. The percentages in the NAPRTCS cohort were 19% in children aged 0-1 years; 17% in those aged 6-12 years; 33% in children aged 2-5 years; and 31% in those older than 12 years.[5]

Prognosis
Once chronic kidney disease (CKD) occurs, progression to end-stage renal disease (ESRD) appears certain. However, the rate of progression depends on the underlying diagnosis, on the successful implementation of secondary preventive measures, and on the individual patient. About 70% of children with chronic kidney disease develop ESRD by age 20 years. Children with ESRD have a 10-year survival rate of about 80% and an age-specific mortality rate of about 30 times that seen in children without ESRD. The most common cause of death in these children is cardiovascular disease, followed by infection. Of the deaths due to cardiovascular causes, 25% were attributed to cardiac arrest (cause uncertain), 16% to stroke, 14% to myocardial ischemia, 12% to pulmonary edema, 11% to hyperkalemia, and 22% to other cardiovascular causes, including arrhythmia. Data from the Australia and New Zealand (ANZ) registry revealed that the risk of death was associated with the year in which renal replacement therapy was initiated, the age of patients at the start of that therapy, and the type of dialysis used.[9] Once the estimated glomerular filtration rate (eGFR) declines to less than 30 mL/min per 1.73 m2 and the child has stage IV chronic kidney disease, the child and the family should be prepared for renal replacement therapy. The family should be provided with information related to preemptive

kidney transplantation, peritoneal dialysis, and hemodialysis. When preemptive transplantation is not an option, the choice between the 2 forms of dialysis is generally dictated by technical, social, and compliance issues, as well as family preference. Peritoneal dialysis is much more common in infants and younger children. Patients on long-term dialysis have a high incidence of morbidity and mortality. Preemptive renal transplantation should be the goal of management in these children.

Patient Education
Children with chronic kidney disease and their families should receive education about the importance of compliance with secondary preventative measures, natural disease progression, prescribed medications (highlighting their potential benefits and adverse effects), diet, and types of long-term renal replacement modalities. Information related to preemptive kidney transplantation, peritoneal dialysis, and hemodialysis should be provided to the family once the child's estimated glomerular filtration rate (eGFR) declines to less than 30 mL/min per 1.73 m2 and the child has stage IV chronic kidney disease.

porphyria cutanea tarda or the bullous disease of dialysis. All nails show the distal brown-red and proximal white coloring of half-and-half nails. Hands of a transfusion-dependent patient on long-

term hemodialysis. Several uremia-related cutaneous disorders are visible. The pigmentary alteration results from retained urochromes and hemosiderin deposition. The large bullae are consistent with either porphyria cutanea tarda or t

History and Physical Examination


Chronic kidney disease (CKD) is asymptomatic in its earliest stages (stage I and stage II), although urinalysis findings or blood pressure may be abnormal. As chronic kidney disease progresses to more advanced stages, signs and symptoms greatly increase. Polydipsia and nocturia (secondary to a reduced capacity to concentrate the urine) may be one of the earliest symptoms that indicate a diagnosis of chronic kidney disease in an otherwise healthylooking child who has tubulointerstitial kidney disease. The signs and symptoms in advanced chronic kidney disease may include the following:
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Volume overload Hyperkalemia Metabolic acidosis Hypertension Anemia Bone disease (termed osteodystrophy) Cardiovascular disease Anorexia, nausea, vomiting

The absolute serum levels of blood urea nitrogen (BUN) or creatinine do not directly correlate with the development of these symptoms; however, estimated glomerular filtration rate (eGFR) seems to be associated with a stronger correlation. The physical findings vary depending on the severity of kidney failure and can range from an absence of any physical findings to the presence of one or more of the following:
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Anemia Short stature Hypertension Osteodystrophy Cardiac abnormalities (eg, left ventricular hypertrophy [LVH], pericarditis) Peripheral neuropathy Central nervous system (CNS) abnormalities (eg, ranging from loss of concentration and lethargy to seizures, coma)

Approximately 50-100% of patients with end-stage renal disease (ESRD) also have at least one dermatologic condition. In addition, uremia and conditions associated with renal replacement therapy often give rise to numerous and, often, relatively unique cutaneous disorders. These dermatologic manifestations of renal disease may be divided into 3 general associated with ESRD, uremia, or renal transplantation. Discussion of the common cutaneous disorders in renal

disease is beyond the scope of this article; see Dermatologic Manifestations of Renal Disease

Normal Kidneys and Their Function The kidneys are a pair of bean-shaped organs that lie on either side of the spine in the lower middle of the back. Each kidney weighs about pound and contains approximately one million filtering units called nephrons. Each nephron is made of a glomerulus and a tubule. The glomerulus is a miniature filtering or sieving device while the tubule is a tiny tube like structure attached to the glomerulus. The kidneys are connected to the urinary bladder by tubes called ureters. Urine is stored in the urinary bladder until the bladder is emptied by urinating. The bladder is connected to the outside of the body by another tube like structure called the urethra.

The main function of the kidneys is to remove waste products and excess water from the blood. The kidneys process about 200 liters of blood every day and produce about two liters of urine. The waste products are generated from normal metabolic processes including the breakdown of active tissues, ingested foods, and other substances. The kidneys allow consumption of a variety of foods, drugs, vitamins and supplements, additives, and excess fluids without worry that toxic by-products will build up to harmful levels. The kidney also plays a major role in regulating levels of various minerals such as calcium, sodium, and potassium in the blood.

As the first step in filtration, blood is delivered into the glomeruli by microscopic leaky blood vessels called capillaries. Here, blood is filtered of waste products and fluid while red blood cells, proteins, and large molecules are retained in the capillaries. In addition to wastes, some useful substances are also filtered out. The filtrate collects in a sac called Bowman's capsule. The tubules are the next step in the filtration process. The tubules are lined with highly functional cells which process the filtrate, reabsorbing water and chemicals useful to the body while secreting some additional waste products into the tubule.

The kidneys also produce certain hormones that have important functions in the body, including the following:
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Active form of vitamin D (calcitriol or 1,25 dihydroxy-vitamin D), which regulates absorption of calcium and phosphorus from foods, promoting formation of strong bone. Erythropoietin (EPO), which stimulates the bone marrow to produce red blood cells. Renin, which regulates blood volume and blood pressure.

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Chronic kidney disease Chronic kidney disease occurs when one suffers from gradual and usually permanent loss of kidney function over time. This happens gradually, usually months to years. Chronic kidney disease is divided into five stages of increasing severity (see Table 1 below). The term "renal" refers to the kidney, so another name for kidney failure is "renal failure." Mild kidney disease is often called renal insufficiency. With loss of kidney function, there is an accumulation of water; waste; and toxic substances, in the body, that are normally excreted by the kidney. Loss of kidney function also causes other problems such as anemia, high blood pressure, acidosis (excessive acidity of body fluids), disorders of cholesterol and fatty acids, and bone disease. Stage 5 chronic kidney disease is also referred to as kidney failure, end-stage kidney disease, or end-stage renal disease, wherein there is total or near-total loss of kidney function. There is dangerous accumulation of water, waste, and toxic substances, and most individuals in this stage of kidney disease need dialysis or transplantation to stay alive. Unlike chronic kidney disease, acute kidney failure develops rapidly, over days or weeks.
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Acute kidney failure usually develops in response to a disorder that directly affects the kidney, its blood supply, or urine flow from it. Acute kidney failure is often reversible, with complete recovery of kidney function. Some patients are left with residual damage and can have a progressive decline in kidney function in the future.

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Others may develop irreversible kidney failure after an acute injury and remain dialysisdependent.

Table 1. Stages of Chronic Kidney Disease Stage 1 2 3 4 5 Description Slight kidney damage with normal or increased filtration Mild decrease in kidney function Moderate decrease in kidney function Severe decrease in kidney function Kidney failure GFR* mL/min/1.73m2 More than 90 60-89 30-59 15-29 Less than 15 (or dialysis)

*GFR is glomerular filtration rate, a measure of the kidney's function.

Chronic Kidney Disease Causes


Although chronic kidney disease sometimes results from primary diseases of the kidneys themselves, the major causes are diabetes and high blood pressure.
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Type 1 and type 2 diabetes mellitus cause a condition called diabetic nephropathy, which is the leading cause of kidney disease in the United States. High blood pressure (hypertension), if not controlled, can damage the kidneys over time. Glomerulonephritis is the inflammation and damage of the filtration system of the kidneys, which can cause kidney failure. Postinfectious conditions and lupus are among the many causes of glomerulonephritis. Polycystic kidney disease is an example of a hereditary cause of chronic kidney disease wherein both kidneys have multiple cysts. Use of analgesics such as acetaminophen (Tylenol) and ibuprofen (Motrin, Advil) regularly over long durations of time can cause analgesic nephropathy, another cause of kidney disease. Certain other medications can also damage the kidneys. Clogging and hardening of the arteries (atherosclerosis) leading to the kidneys causes a condition called ischemic nephropathy, which is another cause of progressive kidney damage. Obstruction of the flow of urine by stones, an enlarged prostate, strictures (narrowings), or cancers may also cause kidney disease.

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Other causes of chronic kidney disease include HIV infection, sickle cell disease, heroin abuse, amyloidosis, kidney stones, chronic kidney infections, and certain cancers.

If you have any of the following conditions, you are at higher-than-normal risk of developing chronic kidney disease. Your kidney functions may need to be monitored regularly.
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Diabetes mellitus type 1 or 2 High blood pressure High cholesterol Heart disease Liver disease Amyloidosis Sickle cell disease Systemic Lupus erythematosus Vascular diseases such as arteritis, vasculitis, or fibromuscular dysplasia Vesicoureteral reflux (a urinary tract problem in which urine travels the wrong way back toward the kidney) Require regular use of anti-inflammatory medications A family history of kidney disease

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Chronic Kidney Disease Symptoms


The kidneys are remarkable in their ability to compensate for problems in their function. That is why chronic kidney disease may progress without symptoms for a long time until only very minimal kidney function is left. Because the kidneys perform so many functions for the body, kidney disease can affect the body in a large number of different ways. Symptoms vary greatly. Several different body systems may be affected. Notably, most patients have no decrease in urine output even with very advanced chronic kidney disease. Effects and symptoms of chronic kidney disease include;
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need to urinate frequently, especially at night (nocturia); swelling of the legs and puffiness around the eyes (fluid retention);

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high blood pressure; fatigue and weakness (from anemia or accumulation of waste products in the body); loss of appetite, nausea and vomiting; itching, easy bruising, and pale skin (from anemia); shortness of breath from fluid accumulation in the lungs; headaches, numbness in the feet or hands (peripheral neuropathy), disturbed sleep, altered mental status (encephalopathy from the accumulation of waste products or uremic poisons), and restless legs syndrome; chest pain due to pericarditis (inflammation around the heart); bleeding (due to poor blood clotting); bone pain and fractures; and decreased sexual interest and erectile dysfunction

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hen to Seek Medical Care


Several signs and symptoms may suggest complications of chronic kidney disease. Call your health care practitioner if you notice any of the following symptoms:
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Change in energy level or strength Increased water retention (puffiness or swelling) in the legs, around the eyes, or in other parts of the body Shortness of breath or change from normal breathing Nausea or vomiting Lightheadedness Severe bone or joint pain Easy bruising Itching

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If you have diabetes, high blood pressure, or kidney problems, see your health care practitioner right away if you know or suspect that you are pregnant.

See your health care practitioner as recommended for monitoring and treatment of chronic conditions such as diabetes, high blood pressure, and high cholesterol. The following signs and symptoms represent the possibility of a severe complication of chronic kidney disease and warrant a visit to the nearest hospital emergency department.
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Change in level of consciousness - extreme sleepiness or difficult to awaken Fainting Chest pain Difficulty breathing Severe nausea and vomiting Severe bleeding (from any source) Severe weakness

Chronic Kidney Disease Diagnosis


Chronic kidney disease usually causes no symptoms in its early stages. Only lab tests can detect any developing problems. Anyone at increased risk for chronic kidney disease should be routinely tested for development of this disease.
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Urine, blood, and imaging tests (X-rays) are used to detect kidney disease, as well as to follow its progress. All of these tests have limitations. They are often used together to develop a picture of the nature and extent of the kidney disease. In general, this testing can be performed on an outpatient basis.

Urine Tests Urinalysis: Analysis of the urine affords enormous insight into the function of the kidneys. The first step in urinalysis is doing a dipstick test. The dipstick has reagents that check the urine for the presence of various normal and abnormal constituents including protein. Then, the urine is examined under a microscope to look for red and white blood cells, and the presence of casts and crystals (solids). Only minimal quantities of albumin (protein) are present in urine normally. A positive result on a dipstick test for protein is abnormal. More sensitive than a dipstick test for protein is a laboratory estimation of the urine albumin (protein) and creatinine in the urine. The ratio of albumin (protein) and creatinine in the urine provides a good estimate of albumin (protein) excretion per day.

Twenty-four hour urine tests: This test requires you to collect all of your urine for 24 consecutive hours. The urine may be analyzed for protein and waste products (urea nitrogen, and creatinine). The presence of protein in the urine indicates kidney damage. The amount of creatinine and urea excreted in the urine can be used to calculate the level of kidney function and the glomerular filtration rate (GFR). Glomerular filtration rate (GFR): The GFR is a standard means of expressing overall kidney function. As kidney disease progresses, GFR falls. The normal GFR is about 100-140 mL/min in men and 85-115 mL/min in women. It decreases in most people with age. The GFR may be calculated from the amount of waste products in the 24-hour urine or by using special markers administered intravenously. An estimation of the GFR (eGFR) can be calculated from the patient's routine blood tests. Patients are divided into five stages of chronic kidney disease based on their GFR (see Table 1 above). Blood Tests Creatinine and urea (BUN) in the blood: Blood urea nitrogen and serum creatinine are the most commonly used blood tests to screen for, and monitor renal disease. Creatinine is a product of normal muscle breakdown. Urea is the waste product of breakdown of protein. The level of these substances rises in the blood as kidney function worsens. Estimated GFR (eGFR): The laboratory or your physician may calculate an estimated GFR using the information from your blood work. It is important to be aware of your estimated GFR and stage of chronic kidney disease. Your physician uses your stage of kidney disease to recommend additional testing and suggestions on management. Electrolyte levels and acid-base balance: Kidney dysfunction causes imbalances in electrolytes, especially potassium, phosphorus, and calcium. High potassium (hyperkalemia) is a particular concern. The acid-base balance of the blood is usually disrupted as well. Decreased production of the active form of vitamin D can cause low levels of calcium in the blood. Inability to excrete phosphorus by failing kidneys causes its levels in the blood to rise. Testicular or ovarian hormone levels may also be abnormal. Blood cell counts: Because kidney disease disrupts blood cell production and shortens the survival of red cells, the red blood cell count and hemoglobin may be low (anemia). Some patients may also have iron deficiency due to blood loss in their gastrointestinal system. Other nutritional deficiencies may also impair the production of red cells. Other tests Ultrasound: Ultrasound is often used in the diagnosis of kidney disease. An ultrasound is a noninvasive type of imaging test. In general, kidneys are shrunken in size in chronic kidney disease, although they may be normal or even large in size in cases caused by adult polycystic kidney disease, diabetic nephropathy, and amyloidosis. Ultrasound may also be used to diagnose

the presence of urinary obstruction, kidney stones and also to assess the blood flow into the kidneys. Biopsy: A sample of the kidney tissue (biopsy) is sometimes required in cases in which the cause of the kidney disease is unclear. Usually, a biopsy can be collected with local anesthesia by introducing a needle through the skin into the kidney. This is usually done as an outpatient procedure, though some institutions may require an overnight hospital stay.

Chronic Kidney Disease Treatment Self-Care at Home


Chronic kidney disease is a disease that must be managed in close consultation with your health care practitioner. Self-treatment is not appropriate.
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There are, however, several important dietary rules you can follow to help slow the progression of your kidney disease and decrease the likelihood of complications. This is a complex process and must be individualized, generally with the help of your health care practitioner and a registered dietitian.

The following are general dietary guidelines:


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Protein restriction: Decreasing protein intake may slow the progression of chronic kidney disease. A dietitian can help you determine the appropriate amount of protein for you. Salt restriction: Limit to 4-6 grams a day to avoid fluid retention and help control high blood pressure. Fluid intake: Excessive water intake does not help prevent kidney disease. In fact, your doctor may recommend restriction of water intake. Potassium restriction: This is necessary in advanced kidney disease because the kidneys are unable to remove potassium. High levels of potassium can cause abnormal heart rhythms. Examples of foods high in potassium include bananas, oranges, nuts, and potatoes. Phosphorus restriction: Decreasing phosphorus intake is recommended to protect bones. Eggs, beans, cola drinks, and dairy products are examples of foods high in phosphorus.

Other important measures that you can take include:


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carefully follow prescribed regimens to control your blood pressure and/or diabetes; stop smoking; and

lose excess weight.

In chronic kidney disease, several medications can be toxic to the kidneys and may need to be avoided or given in adjusted doses. Among over-the-counter medications, the following need to be avoided or used with caution:
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Certain analgesics: Aspirin; nonsteroidal antiinflammatory drugs (NSAIDs, such as ibuprofen [Motrin, for example]) Fleets or phosphosoda enemas because of their high content of phosphorus Laxatives and antacids containing magnesium and aluminum such as magnesium hydroxide (Milk of Magnesia) and famotidine (Mylanta) Ulcer medication H2-receptor antagonists: cimetidine (Tagamet), ranitidine (Zantac), (decreased dosage with kidney disease) Decongestants such as pseudoephedrine (Sudafed) especially if you have high blood pressure Alka Seltzer, since this contains large amounts of salt Herbal medications

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If you have a condition such as diabetes, high blood pressure, or high cholesterol underlying your chronic kidney disease, take all medications as directed and see your health care practitioner as recommended for follow-up and monitoring.

Medical Treatment
There is no cure for chronic kidney disease. The four goals of therapy are to: 1. slow the progression of disease; 2. treat underlying causes and contributing factors; 3. treat complications of disease; and 4. replace lost kidney function. Strategies for slowing progression and treating conditions underlying chronic kidney disease include the following:
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Control of blood glucose: Maintaining good control of diabetes is critical. People with diabetes who do not control their blood glucose have a much higher risk of all complications of diabetes, including chronic kidney disease.

Control of high blood pressure: This also slows progression of chronic kidney disease. It is recommended to keep your blood pressure below 130/80 mm Hg if you have kidney disease. It is often useful to monitor blood pressure at home. Blood pressure medications known as angiotensin converting enzyme (ACE) inhibitors or angiotensin receptor blockers (ARB) have special benefit in protecting the kidneys. Diet: Diet control is essential to slowing progression of chronic kidney disease and should be done in close consultation with your health care practitioner and a dietitian. For some general guidelines, see the Self-Care at Home section of this article.

The complications of chronic kidney disease may require medical treatment.


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Fluid retention can be treated with any of a number of diuretic medications, which remove excess water from the body. However, these drugs are not suitable for all patients. Anemia can be treated with erythropoiesis stimulating agents such as erythropoietin or darbepoetin (Aranesp, Aranesp Albumin Free, Aranesp SureClick). Erythropoiesis stimulating agents are a group of drugs that replace the deficiency of erythropoietin, which is normally produced by healthy kidneys. Often, patients treated with such drugs require iron supplements by mouth or sometimes even intravenously. Bone disease develops in kidney disease due to an inability to excrete phosphorus and a failure to form activated Vitamin D. In such circumstances, your physician may prescribe drugs binding phosphorus in the gut, and may prescribe active forms of vitamin D. Acidosis may develop with kidney disease. The acidosis may cause breakdown of proteins, inflammation, and bone disease. If the acidosis is significant, your doctor may use drugs such as sodium bicarbonate (baking soda) to correct the problem.

Renal Replacement Therapies


In end-stage kidney disease, kidney functions can be replaced only by dialysis or by kidney transplantation. The planning for dialysis and transplantation is usually started in Stage 4 of chronic kidney disease. Most patients are candidates for both hemodialysis and peritoneal dialysis (see below). There are few differences in outcomes between the two procedures. Your physician or an educator will discuss the appropriate options with you and help you make a decision that will match your personal and medical needs. It is best to choose your modality of dialysis after understanding both procedures and matching them to your lifestyle, daily activities, schedule, distance from the dialysis unit, support system, and personal preference. Your doctor will consider multiple factors when recommending the appropriate point to start dialysis, including your laboratory work and your actual or estimated glomerular filtration rate, nutritional status, fluid volume status, the presence of symptoms compatible with advanced kidney failure, and risk of future complications. Dialysis is usually started before individuals are very symptomatic or at risk for life-threatening complications.

Dialysis
There are two types of dialysis 1) hemodialysis (in-center or home) and 2) peritoneal dialysis. Before dialysis can be initiated, a dialysis access has to be created. Dialysis Access A vascular access is required for hemodialysis so that blood can be moved though the dialysis filter at rapid speeds to allow clearing of the wastes, toxins, and excess fluid. There are three different types of vascular accesses: arteriovenous fistula (AVF), arteriovenous graft, and central venous catheters. 1. Arteriovenous fistula (AVF): The preferred access for hemodialysis is an AVF, wherein an artery is directly joined to a vein. The vein takes two to four months to enlarge and mature before it can be used for dialysis. Once matured, two needles are placed into the vein for dialysis. One needle is used to draw blood and run through the dialysis machine. The second needle is to return the cleansed blood. AVFs are less likely to get infected or develop clots than any other types of dialysis access. 2. Arteriovenous graft: An arteriovenous graft is placed in those who have small veins or in whom a fistula has failed to develop. The graft is made of artificial material and the dialysis needles are inserted into the graft directly. 3. Central venous catheter: A catheter may be either temporary or permanent. These catheters are either placed in the neck or the groin into a large blood vessel. While these catheters provide an immediate access for dialysis, they are prone to infection and may also cause blood vessels to clot or narrow. Peritoneal access (for peritoneal dialysis): A catheter is implanted into the abdominal cavity (lined by the peritoneum) by a minor surgical procedure. This catheter is a thin tube made of a soft flexible material, usually silicone or polyurethane. The catheter usually has one or two cuffs that help hold it in place. The tip of the catheter may be straight or coiled and has multiple holes to allow egress and return of fluid. Though the catheter can be used immediately after implantation, it is usually recommended to delay peritoneal dialysis for at least 2 weeks so as to allow healing and decrease the risk of developing leaks.

Hemodialysis
Hemodialysis involves circulation of blood through a filter or dialyzer on a dialysis machine.
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The dialyzer has two fluid compartments and is configured with bundles of hollow fiber capillary tubes. Blood in the first compartment is pumped along one side of a semipermeable membrane, while dialysate (the fluid that is used to cleanse the blood) is pumped along the other side, in a separate compartment, in the opposite direction.

Concentration gradients of substances between blood and dialysate lead to desired changes in the blood composition, such as a reduction in waste products (urea nitrogen and creatinine); a correction of acid levels; and equilibration of various mineral levels. Excess water is also removed. The blood is then returned to the body.

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Hemodialysis may be done in a dialysis center or at home. In-center hemodialysis typically takes three to five hours and is performed three times a week. You will need to travel to a dialysis center for in-center hemodialysis. Some centers may offer the option of nocturnal (night-time) hemodialysis wherein the therapy is delivered while you sleep. Long nocturnal dialysis offers patients a better survival and an improvement in their quality of life. Home hemodialysis is possible in some situations. A care partner is needed to assist you with the dialysis treatments. A family member or close friend are the usual options, though occasionally people may hire a professional to assist with dialysis. Home hemodialysis may be performed as traditional three times a week treatments, long nocturnal (overnight) hemodialysis, or short daily hemodialysis. Daily hemodialysis and long nocturnal hemodialysis offer advantages in quality of life and better control of high blood pressure, anemia, and bone disease. Peritoneal dialysis Peritoneal dialysis utilizes the lining membrane (peritoneum) of the abdomen as a filter to clean blood and remove excess fluid. Peritoneal dialysis may be performed manually (continuous ambulatory peritoneal dialysis) or by using a machine to perform the dialysis at night (automated peritoneal dialysis).
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About 2 to 3 liters of dialysis fluid are infused into the abdominal cavity through the access catheter. This fluid contains substances that pull wastes and excess water out of neighboring tissues. The fluid is allowed to dwell for two to several hours before being drained, taking the unwanted wastes and water with it. The fluid typically needs to be exchanged four to five times a day. Peritoneal dialysis offers much more freedom compared to hemodialysis since patients do not need to come to a dialysis center for their treatment. You can carry out many of your usual activities while undergoing this treatment. This may be the preferable therapy for children.

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Most patients are candidates for both hemodialysis and peritoneal dialysis. There are little differences in outcomes between the two procedures. Your physician may recommend one kind of dialysis over the other based on your medical and surgical history. It is best to choose your

modality of dialysis after understanding both procedures and matching them to your lifestyle, daily activities, schedule, distance from the dialysis unit, support system, and personal preference.

Kidney Transplantation
Kidney transplantation offers the best outcomes and the best quality of life. Successful kidney transplants occur every day in the United States. Transplanted kidneys may come from living related donors, living unrelated donors, or people who have died of other causes (cadaveric donors). In people with type I diabetes, a combined kidney-pancreas transplant is often a better option. However, not everyone is a candidate for a kidney transplant. People need to undergo extensive testing to ensure their suitability for transplantation. Also, there is a shortage of organs for transplantation, requiring waiting times of months to years before getting a transplant. A person who needs a kidney transplant undergoes several tests to identify characteristics of his or her immune system. The recipient can accept only a kidney that comes from a donor who matches certain of his or her immunologic characteristics. The more similar the donor is in these characteristics, the greater the chance of long-term success of the transplant. Transplants from a living related donor generally have the best results. Transplant surgery is a major procedure and generally requires four to seven days in the hospital. All transplant recipients require lifelong immunosuppressant medications to prevent their bodies from rejecting the new kidney. Immunosuppressant medications require careful monitoring of blood levels and increase the risk of infection as well as some types of cancer.

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