Chronic kidney disease is a progressive condition that results in significant morbidity and mortality.

Because of the important role the kidneys play in maintaining homeostasis, chronic kidney disease can affect almost every body system. Early recognition and intervention are essential to slowing disease progression, maintaining quality of life, and improving outcomes. Family physicians have the opportunity to screen at-risk patients, identify affected patients, and ameliorate the impact of chronic kidney disease by initiating early therapy and monitoring disease progression. Aggressive blood pressure control, with a goal of 130/80 mm Hg or less, is recommended in patients with chronic kidney disease. Angiotensin-converting enzyme inhibitors and angiotensin-II receptor antagonists are most effective because of their unique ability to decrease proteinuria. Hyperglycemia should be treated; the goal is an A1C concentration below 7 percent. In patients with dyslipidemia, statin therapy is appropriate to reduce the risk of cardiovascular disease. Anemia should be treated, with a target hemoglobin concentration of 11 to 12 g per dL (110 to 120 g per L). Hyperparathyroid disease requires dietary phosphate restrictions, antacid use, and vitamin D supplementation; if medical therapy fails, referral for surgery is necessary. Counseling on adequate nutrition should be provided, and smoking cessation must be encouraged at each office visit.

The National Kidney Foundation (NKF) defines chronic kidney disease as kidney damage or a glomerular filtration rate (GFR) of less than 60 mL per minute per 1.73 m (body surface area) for three months or more. This GFR rate corresponds with a serum creatinine concentration higher than 1.5 mg per dL (132.6 mol per L) in men and higher than 1.3 mg per dL (114.9 mol per L) in women. Chronic kidney disease also can be defined by the presence of urinary albumin in an excretion rate higher than 300 mg per 24 hours or in a ratio of more than 200 mg of albumin to 1 g of creatinine
1 2 1 2,3 3

Chronic kidney disease currently affects as many as 20 million Americans.3 The incidence and prevalence of the disease have doubled in the past decade, most likely because improved treatments for hypertension, diabetes mellitus, and coronary disease have increased longevity in affected patients and, therefore, their likelihood of developing chronic kidney disease. Estimated medical and other economic costs of chronic kidney disease are expected to approach $28 billion annually by 2010, with an additional $90 billion in annual costs related to associated increased cardiovascular disease, infections, and hospitalizations.3 Causes of chronic kidney disease include diabetes mellitus, hypertension, ischemia, infection, obstruction, toxins, and autoimmune and infiltrative diseases. Although it is important to identify the cause(s) of chronic kidney disease so that specific therapy can be instituted, the disease often progresses despite appropriate treatment. As kidney function deteriorates, patients develop complications related to fluid overload, electrolyte and acid-base imbalances, and the build-up of nitrogenous waste. To survive, some patients eventually need hemodialysis or kidney transplantation. This article reviews the current recommendations and therapeutic strategies for preventing or delaying the progression of chronic kidney disease and the development of complications such as hypertension, hyperglycemia, hyperlipidemia, anemia, and renal osteodystrophy. Recommendations for nutrition and smoking cessation also are discussed.

CLASSIFICATION OF SEVERITY AND MONITORING OF DISEASE PROGRESSION

The GFR is used to assess the degree of kidney-function impairment and to monitor disease progression and treatment response. GFR is a measure of the overall filtration rate of all nephrons. In persons 30 years or younger, the normal GFR is approximately 125 mL per minute per 1.73 m2; after the age of 30 years, GFR declines by 1 mL per minute per 1.73 m2 per year. Estimation of the GFR no longer requires a 24-hour urine collection for creatinine clearance but can be accomplished with similar accuracy using a mathematic formula.1 The most commonly used formulas for estimating GFR in patients with stable chronic kidney disease are the Modification of Diet in Renal Disease (MDRD) equation and the Cockcroft-Gault equation Proteinuria is another marker of kidney injury. It is measured in a timed (overnight or 24-hour) urine collection or in an untimed (spot) urine sample by calculating the ratio of protein or albumin to creatinine(Table 1).1,4,5 The NKF Kidney Disease Outcome Quality Initiative (K/DOQI) stratifies chronic kidney disease into five stages based on the GFR and metabolic consequences (Table 3).1 The NKF suggests actions to slow disease progression.1

++++++++++++++++++
Chronic kidney failure occurs when disease or disorder damages the kidneys so that they are no longer capable of adequately removing fluids and wastes from the body or of maintaining the proper level of certain kidney-regulated chemicals in the bloodstream

Description
Chronic kidney failure, also known as chronic renal failure, affects over 250,000 Americans annually. It is caused by a number of diseases and inherited disorders, but the progression of chronic kidney failure is always the same. The kidneys, which serve as the body's natural filtration system, gradually lose their ability to remove fluids and waste products (urea) from the bloodstream. They also fail to regulate certain chemicals in the bloodstream, and deposit protein into the urine. Chronic kidney failure is irreversible, and will eventually lead to total kidney failure, also known as end-stage renal disease (ESRD). Without proper treatment intervention to remove wastes and fluids from the bloodstream, ESRD is fatal.

Causes and symptoms

Kidney failure is triggered by disease or a hereditary disorder in the kidneys. Both kidneys are typically affected. The four most common causes of chronic kidney failure include: y Diabetes. Diabetes mellitus (DM), both insulin dependant (IDDM) and non-insulin dependant (NIDDM), occurs when the body cannot produce and/or use insulin, the hormone necessary for the body to process glucose. Long-term diabetes may cause the glomeruli, the filtering units located in the nephrons of the kidneys, to gradually lose functioning. Glomerulonephritis. Glomerulonephritis is a chronic inflammation of the glomeruli, or filtering units of the kidney. Certain types of glomerulonephritis are treatable, and may only cause a temporary disruption of kidney functioning. Hypertension. High blood pressure is unique in that it is both a cause and a major symptom of kidney failure. The kidneys can become stressed and ultimately sustain permanent damage from blood pushing through them at an excessive level of pressure over a long period of time.

Polycystic kidney disease. Polycystic kidney disease is an inherited disorder that causes cysts to be formed on the nephrons, or functioning units, of the kidneys. The cysts hamper the regular functioning of the kidney.

Other possible causes of chronic kidney failure include kidney cancer, obstructions such as kidney stones, pyelonephritis, reflux nephropathy, systemic lupus erythematosus, amyloidosis, sickle cell anemia, Alport syndrome, and oxalosis. Initially, symptoms of chronic kidney failure develop slowly. Even individuals with mild to moderate kidney failure may show few symtpoms in spite of increased urea in their blood. Among the symptoms that may be present at this point are frequent urination during the night and high blood pressure. Most symptoms of chronic kidney failure are not apparent until kidney disease has progressed significantly. Common symptoms include: y Anemia. The kidneys are responsible for the production of erythropoietin (EPO), a hormone which stimulates red cell production. If kidney disease causes shrinking of the kidney, this red blood cell production is hampered. Bad breath or a bad taste in mouth. Urea, or waste products, in the saliva may cause an ammonia-like taste in the mouth. Bone and joint problems. The kidneys produce vitamin D, which aids in the absorption of calcium and keeps bones strong. For patients with kidney failure, bones may become brittle, and in the case of children, normal growth may be stunted. Joint pain may also occur as a result of unchecked phosphate levels in the blood. Edema. Puffiness or swelling around the eyes, arms, hands, and feet. Frequent urination. Foamy or bloody urine. Protein in the urine may cause it to foam significantly. Blood in the urine may indicate bleeding from diseased or obstructed kidneys, bladder, or ureters. Headaches. High blood pressure may trigger headaches. Hypertension, or high blood pressure. The retention of fluids and wastes causes blood volume to increase, which in turn, causes blood pressure to rise. Increased fatigue. Toxic substances in the blood and the presence of anemia may cause feelings of exhaustion. Itching. Phosphorus, which is typically eliminated in the urine, accumulates in the blood of patients with kidney failure. This heightened phosphorus level may cause itching of the skin. Lower back pain. Pain where the kidneys are located, in the small of the back below the ribs. Nausea, loss of appetite, and vomiting. Urea in the gastric juices may cause upset stomach. This can lead to malnutrition and weight loss.

y y

y y y y y y y y y

Diagnosis
Kidney failure is typically diagnosed and treated by a nephrologist, a doctor that specializes in treating the kidneys. The patient that is suspected of having chronic kidney failure will undergo an extensive blood work-up. A blood test will assess the levels of creatinine, blood urea nitrogen (BUN), uric acid, phosphate, sodium, and potassium in the blood. Urine samples will also be collected, usually over a 24-hour period, to assess protein loss. Uncovering the cause of kidney failure is critical to proper treatment. A full assessment of the kidneys is necessary to determine if the underlying disease is treatable and if the kidney failure is chronic or acute. An x ray, MRI, computed tomography scan, ultrasound, renal biopsy, and/or arteriogram of the kidneys may be employed to determine the cause of kidney failure and level of remaining kidney function. X rays and ultrasound of the bladder and/or ureters may also be taken.

Treatment
Chronic kidney failure is an irreversible condition. Hemodialysis, peritoneal dialysis, or kidney transplantationmust be employed to replace the lost function of the kidneys. In addition, dietary changes

and treatment to relieve specific symptoms such as anemia and high blood pressure are critical to the treatment process. Hemodialysis Hemodialysis is the most frequently prescribed type of dialysis treatment in the United States. Most hemodialysis patients require treatment three times a week, for an average of three to four hours per dialysis "run" depending on the type of dialyzer used and their current physical condition. The treatment involves circulating the patient's blood outside of the body through an extracorporeal circuit (ECC), or dialysis circuit. The dialysis circuit consists of plastic blood tubing, a two-compartment filter known as a dialyzer, or artificial kidney, and a dialysis machine that monitors and maintains blood flow and administers dialysate, a chemical bath used to draw waste products out of the blood. The patient's blood leaves and enters the body through two needles inserted into the patient's vein, called an access site, and is pushed through the blood compartment of the dialyzer. Once inside of the dialyzer, excess fluids and toxins are pulled out of the bloodstream and into the dialysate compartment, where they are carried out of the body. At the same time, electrolytes and other chemicals in the dialysate solution move from the dialysate into the bloodstream. The purified, chemically-balanced blood is then returned to the body. Peritoneal dialysis In peritoneal dialysis (PD), the patient's peritoneum, or lining of the abdomen, acts as a blood filter. A catheter is surgically inserted into the patient's abdomen. During treatment, the catheter is used to fill the abdominal cavity with dialysate. Waste products and excess fluids move from the patient's blood-stream into the dialysate solution. After a waiting period of six to 24 hours, depending on the treatment method used, the waste-filled dialysate is drained from the abdomen, and replaced with clean dialysate. There are three types of peritoneal dialysis, which vary by treatment time and administration method: Continuous Ambulatory Peritoneal Dialysis (CAPD), Continuous Cyclic Peritoneal Dialysis (CCPD), and Intermittent Peritoneal Dialysis (IPD). Kidney transplantation Kidney transplantation involves surgically attaching a functioning kidney, or graft, from a brain dead organ donor (a cadaver transplant), or from a living donor, to a patient with ESRD. Patients with chronic renal disease who need a transplant and don't have a living donor register with UNOS (United Network for Organ Sharing), the federal organ procurement agency, to be placed on a waiting list for a cadaver kidney transplant. Kidney availability is based on the patient's health status. When the new kidney is transplanted, the patient's existing, diseased kidneys may or may not be removed, depending on the circumstances surrounding the kidney failure. A regimen of immunosuppressive, or anti-rejection medication, is required after transplantation surgery. Dietary management A diet low in sodium, potassium, and phosphorous, three substances that the kidneys regulate, is critical in managing kidney disease. Other dietary restrictions, such as a reduction in protein, may be prescribed depending on the cause of kidney failure and the type of dialysis treatment employed. Patients with chronic kidney failure also need to limit their fluid intake. Medications and dietary supplements Kidney failure patients with hypertension typically take medication to control their high blood pressure. Epoetin alfa, or EPO (Epogen), a hormone therapy, and intravenous or oral iron supplements are used to manage anemia. A multivitamin may be prescribed to replace vitamins lost during dialysis treatments. Vitamin D, which promotes the absorption of calcium, along with calcium supplements, may also be prescribed. Since 1973, Medicare has picked up 80% of ESRD treatment costs, including the costs of dialysis and transplantation and of some medications. To qualify for benefits, a patient must be insured or eligible for benefits under Social Security, or be a spouse or child of an eligible American. Private insurance and state Medicaid programs often cover the remaining 20% of treatment costs.

Key terms
End-stage renal disease (ESRD) Total kidney failure; chronic kidney failure is diagnosed as ESRD when kidney function falls to 5-10% of capacity. Nephrotic syndrome Characterized by protein loss in the urine, low protein levels in the blood, and fluid retention. Ureters The two ducts that pass urine from each kidney to the bladder.

Prognosis
Early diagnosis and treatment of kidney failure is critical to improving length and quality of life in chronic kidney failure patients. Patient outcome varies by the cause of chronic kidney failure and the method chosen to treat it. Overall, patients with chronic kidney disease leading to ESRD have a shortened lifespan. According to the United States Renal Data System (USRDS), the lifespan of an ESRD patient is 18-47% of the lifespan of the age-sex-race matched general population. ESRD patients on dialysis have a lifespan that is 16-37% of the general population. The demand for kidneys to transplant continues to exceed supply. In 1996, over 34,000 Americans were on the UNOS waiting list for a kidney transplant, but only 11,330 living donor and cadaver transplants were actually performed. Cadaver kidney transplants have a 50% chance of functioning nine years, and living donor kidneys that have two matching antigen pairs have a 50% chance of functioning for 24 years. However, some transplant grafts have functioned for over 30 years.

http://medical-dictionary.thefreedictionary.com/Chronic+kidney+disease http://www.aafp.org/afp/2004/1115/p1921.html