Chronic Renal failure



Chronic Renal failure

Chronic renal failure (CRF) is the progressive loss of kidney function. The kidneys attempt to compensate for renal damage by hyperfiltration (excessive straining of the blood) within the remaining functional nephrons (filtering units that consist of a glomerulus and corresponding tubule). Over time, hyperfiltration causes further loss of function.

Chronic loss of function causes generalized wasting (shrinking in size) and progressive scarring within all parts of the kidneys. In time, overall scarring obscures the site of the initial damage. Yet, it is not until over 70% of the normal combined function of both kidneys is lost that most patients begin to experience symptoms of kidney failure.

Types

Chronic renal failure (CRF) can be classified by the site (location) of primary damage:

• Pre-renal CRF

• Post-renal CRF (obstructive uropathy)

• Renal CRF

CRF Causes

The cause for CRF sometimes can be determined by a detailed medical history, a comprehensive physical examination, and laboratory studies. More often than not, determining the cause of CRF is difficult if not impossible. Even a kidney biopsy may be inconclusive, because all forms of kidney failure eventually progress to diffuse scarring and look the same on kidney biopsy. The most common causes for CRF are diabetes and high blood pressure (hypertension.)

Kidney disorders, including chronic renal failure, are common in patients who have multiple myeloma (cancer that begins in a type of white blood cell called plasma cells). Several different factors are related to renal disease associated with multiple myeloma. Myeloma cells produce large numbers of proteins in the urine (called proteinuria). These proteins often form deposits in the kidneys (condition called amyloidosis) and cause kidney failure. In addition, multiple myeloma increases the risk for hypercalcemia (high levels of calcium in the blood) and anemia (low levels of red blood cells) and results in high blood levels of uric acid, which also increase the risk for chronic renal failure.

Pre-Renal CRF

Some medical conditions cause continuous hypoperfusion (low blood flow) of the kidneys, leading to kidney atrophy (shrinking), loss of nephron function, and chronic renal failure (CRF). These conditions include poor cardiac function, chronic liver failure, and atherosclerosis ("hardening") of the renal arteries. Each of these conditions can induce ischemic nephropathy.

Post-Renal CRF

Interference with the normal flow of urine can produce backpressure within the kidneys, can damage nephrons, and lead to obstructive uropathy, a disease of the urinary tract. Abnormalities that may hamper urine flow and cause post-renal CRF include the following:

• Bladder outlet obstruction due to an enlarged prostate gland or bladder stone

• Neurogenic bladder, an overdistended bladder caused by impaired communicator nerve fibers from the bladder to the spinal cord

• Kidney stones in both ureters, the tubes that pass urine from each kidney to the bladder

• Obstruction of the tubules,the end channels of the renal nephrons

• Retroperitoneal fibrosis, the formation of fiberlike tissue behind the peritoneum, the membrane that lines the abdominal cavity

• Vesicoureteral reflux (VUR), the backward flow of urine from the bladder into a ureter

Renal CRF

Chronic renal failure caused by changes within the kidneys, is called renal CRF, and is broadly categorized as follows:

• Diabetic nephropathy, kidney disease associated with diabetes; the most common cause of CRF

• Hypertension nephrosclerosis, a condition that occurs with increased frequency in African Americans; the second leading cause of CRF

• Chronic glomerular nephritis, a condition caused by diseases that affect the glomeruli and bring about progressive dysfunction

• Chronic interstitial nephritis, a condition caused by disorders that ultimately lead to progressive scarring of the interstitium

• Renal vascular CRF, large vessel abnormalities such as renal artery stenosis (narrowing of the large arteries that supply the kidneys)

CRF Signs and Symptoms

Chronic renal failure (CRF) usually produces symptoms when renal function — which is measured as the glomerular filtration rate (GFR) — falls below 30 milliliters per minute (< 30 mL/min). This is approximately 30% of the normal value.

When the glomerular filtration rate (GFR) slows to below 30 mL/min, signs of uremia (high blood level of protein by-products, such as urea) may become noticeable. When the GFR falls below 15 mL/min most people become increasingly symptomatic.

Uremic symptoms can affect every organ system, most noticeably the following:

• Neurological system–cognitive impairment, personality change, asterixis (motor disturbance that affects groups of muscles), seizures (rare)

• Gastrointestinal system–nausea, vomiting, food distaste (often described as bland, metallic, "like cardboard")

• Blood-forming system–anemia due to erythropoetin deficiency, easy bruising and bleeding due to abnormal platelets

• Pulmonary system–fluid in the lungs, with breathing difficulties

• Cardiovascular system –chest pain due to inflammation of the sac surrounding the heart (pericarditis) and pericardial effusion (fluid accumulation around the heart)

• Skin –generalized itching

CRF Diagnosis

Chronic renal failure (CRF) is diagnosed by the observation of a combination of symptoms and elevated blood urea nitrogen (BUN) and creatinine (Cr) levels. The following abnormalities found in the blood may signal CRF:

• Anemia (low red blood cell count)

• High level of parathyroid hormone

• Hypocalcemia (low blood level of calcium)

• Hyperphosphatemia (high blood level of phosphate)

• Hyperkalemia (high blood level of potassium)

• Hyponatremia (low blood level of sodium)

• Low blood level of bicarbonate

• Low plasma pH (blood acidity)

Whether renal failure is acute or chronic usually can be distinguished by comparing prior test results (e.g., from the past several months or years). It is difficult to make the distinction without previous test results.

Ultrasound may show that the kidneys are small in size and echogenic (a sign of renal scarring), signs that supports a diagnosis of CRF. For unclear reasons patients with diabetic nephropathy often have preservation of kidney size despite CRF. They do however, typically have increased echogenicity.

Treatment

Once CRF has been diagnosed, the physician attempts to determine the cause and, if possible, plan a specific treatment. Nonspecific treatments are implemented to delay or possibly arrest the progressive loss of kidney function.

Control hypertension (high blood pressure)—Target systolic blood pressure (BP) is 120 to 135 mm Hg; target diastolic BP is 70 to 80 mm Hg. Antihypertensive medication from the ACE class is preferable because of protective effects on the kidneys.

Restrict dietary protein—Dietary protein is broken down into amino acids and absorbed from the stomach into the blood. The amino acids are taken from the bloodstream and used to build muscle and perform other essential functions. Excess amino acids are further broken down into carbohydrates and nitrogen-containing waste that is eliminated by the kidneys. Amino acid disposal further burdens the kidneys, and is believed to speed the progression of CRF. This process is like forcing a damaged machine to work harder, causing it to break down sooner than expected.

Affected patients must be cautious not to overdo protein restriction, because it can lead to malnutrition and muscle wasting. Moderate protein restriction for a CRF patient is about 0.6 to 0.8 gm/kg/day, which is effectively achieved by following the advice of a dietician.

Manage pre-end-stage renal disease (pre-ESRD)—Treatment for pre-ESRD should begin once the glomerular filtration rate (GFR) falls below 30 milliliters per minute (< 30 mL/min). Pre-ESRD management includes the identification and treatment of anemia (low red blood cell count). When the GFR drops below 30 mL/min, anemia often develops because the kidneys produce an inadequate amount of erythropoetin (EPO). This hormone is made by the kidneys and travels to the bone marrow, where it stimulates red blood cell production. Anemic patients are candidates for EPO (Procrit®) injections to maintain their hematocrit (volume percent of red blood cells in whole blood) between 30% and 36%.

Identify and Treat Secondary Hyperparathyroidism—With the loss of kidney function, phosphate accumulates in the blood. Excess phosphate in the blood reduces levels of blood calcium, and low blood calcium levels trigger the parathyroid gland (located in the neck) to release more parathyroid hormone (PTH). PTH then dissolves bone tissue to release stored calcium and raise the level of calcium in the blood. This chronic cycle of events is called secondary hyperthyroidism.

The net result of this condition is the development of metabolic bone disease (renal osteodystrophy). These patients are at risk for bone fractures, bone and muscle pain, which can sometimes be accompanied by severe itching, and cardiovascular complications. Severe itching is thought to be in part due to the elevated circulating PTH level itself.

Patients with secondary hyperthyroidism should limit their intake of foods that are high in phosphate (e.g., dairy products, colas). Many patients must take medication with meals that binds the phosphate (phosphate-binders) and prevents it from being absorbed into the blood and allows it to be excreted in the stool (feces). In general, calcium based salts (e.g., TUMS, Oscal)have been the phosphate-binders prescribed. A new organic based phophate-binder called renagel has recently become available and, although it is more expensive, it has many advantages over the calcium based phosphate-binders.

Most patients also require a potent vitamin D supplement (e.g., calcitrol, hexitrol), which helps to suppress excess PTH production. The final metabolic step in the synthesis of vitamin D occurs normally in the kidney and there is often a deficiency of this vitamin in these patients.

Cinacalcet hydrochloride (e.g., Sensipar™) may be used alone or in combination with Vitamin D supplements or phosphate-binders to treat patients with secondary hyperparathyroidism who are on dialysis. Sensipar tablets should be taken with food and the dosage varies, depending on calcium and phosphate levels in the blood. Side effects include nausea, vomiting, and diarrhea.

Preparation for renal replacement therapy (RRT)

Early preparation is important. The health care team educates the patient about the different procedures involved in RRT, which include the following:

• Hemodialysis—removal of toxic elements from the blood, which is filtered through a membrane while circulated outside of the body

• Peritoneal dialysis—filtration through the lining membrane of the abdominal cavity; fluid is instilled into the peritoneal space, then drained

• kidney transplantation

It is important to place an arteriovenous fistula (AVF)—a passage between an artery and a vein that provides a suitable blood vessel for repeated dialysis—at least 3 months prior to beginning hemodialysis, because an AVF requires 3 months to mature before it can be used.

The health care team can address the patient's fears and anxieties about treatment and can clarify the financial, emotional, and social concerns of RRT.

Prognosis

CRF is often insidious in its onset and progression. The rate of progression is variable but usually renal function steadily declines resulting in end-stage renal disease (ESRD).

Acute glomerulonephritis

(AGN) is active inflammation in the glomeruli. Each kidney is composed of about 1 million microscopic filtering "screens" known as glomeruli that selectively remove uremic waste products. The inflammatory process usually begins with an infection or injury (e.g., burn, trauma), then the protective immune system fights off the infection, scar tissue forms, and the process is complete.

There are many diseases that cause an active inflammation within the glomeruli. Some of these diseases are systemic (i.e., other parts of the body are involved at the same time) and some occur solely in the glomeruli. When there is active inflammation within the kidney, scar tissue may replace normal, functional kidney tissue and cause irreversible renal impairment.

The severity and extent of glomerular damage—focal (confined) or diffuse (widespread)—determines how the disease is manifested. Glomerular damage can appear as subacute renal failure, progressive chronic renal failure (CRF); or simply a urinary abnormality such as hematuria (blood in the urine) or proteinuria (excess protein in the urine).

Causes

In diffuse glomerulonephritis (GN), all of the glomeruli are aggressively attacked, leading to acute renal failure (ARF). Disorders that attack several organs and cause diffuse GN are referred to as secondary causes. Secondary causes of diffuse GN include the following:

• Cryoglobulinemia

• Goodpasteur’s syndrome (membranous antiglomerular basement membrane disease)

• Lupus nephritis

• Schönlein-Henoch purpura

• Vasculitis (e.g., Wegener's granulomatosis, periarteritis nodosa)

Primary diseases that solely affect the kidneys and cause AGN, include the following:

• Immunoglobulin A nephropathy (IgA nephropathy, Berger’s disease)

• Membranoproliferative nephritis (type of kidney inflammation)

• Postinfectious GN (GN that results after an infection)

Signs and Symptoms

Patients who have secondary causes of AGN often exhibit these symptoms:

• Cough with blood-tinged sputum

• Fever

• Joint or muscle pain

• Rash

Diagnosis

Patients with acute glomerulonephritis (AGN) have an active urinary sediment. This means that signs of active kidney inflammation can be detected when the urine is examined under the microscope. Such signs include red blood cells, white blood cells, proteinuria (blood proteins in the urine), and "casts" of cells that have leaked through the glomeruli and have reached the tubule, where they develop into cylindrical forms.A kidney biopsy is essential to establish a diagnosis of AGN, determine the cause, and create an effective treatment plan.

TreatmentThe

goal of treatment is to stop the ongoing inflammation and lessen the degree of scarring that ensues. Depending on the diagnosis, there are different treatment strategies. Often the treatment warrants a regimen of immunosuppressive drugs to limit the immune system’s activity. This decreases the degree of inflammation and subsequent irreversible scarring.

Acute Interstitial Nephritis

The interstitium is the tissue that surrounds and imbeds the glomeruli (microscopic "filtering screens") and tubules (long tubes that connect with each glomerulus and channel urine) within the kidneys. Acute interstitial nephritis (AIN) is rapidly developing inflammation that occurs within the interstitium. It can produce a variety of clinical symptoms, depending upon the severity and extent of kidney involvement.

Causes

Most AIN is caused by an acute allergic reaction to a medication, including antibiotics and nonsteroidal anti-inflammatory drugs (NSAIDs) such as:

• Ibuprofen

• Cephatholin

• Cimetidine

• Cyclosporine

• Methicillin

• Penicillins

AIN is also linked with certain infections and diseases such as Legionella pneumophila, collagen vascular diseases (e.g., sarcoidosis), streptococcal infections, and transplant rejection.

Signs and Symptoms

Indicators of AIN include a recent history of infection or the start of a new medication. Symptoms often include fever, rash, and generalized aches and pains.

Diagnosis

The definitive diagnosis of AIN requires a kidney biopsy, which reveals inflammation of the renal interstitium. Urinalysis (analysis of the urine) often reveals eosinophils—specialized white blood cells that are seen in allergic reactions. Often one can detect increased eosinophils in the blood in patients with AIN. AIN sometimes is diagnosed by means of a gallium scan (nuclear medicine imaging method; a radiologist injects the patient with gallium-67, which will accumulate in areas of infection or malignancy and can be viewed with a special camera).

Treatment

All medication(s) believed to be responsible for the inflammation must be discontinued. If there is significant renal impairment, treatment with steroids typically is required for 2 to 3 months. Stronger immunosuppressive agents may be needed if there is no response to the steroids. Each case of AIN must be reviewed by a nephrologist (kidney specialist).

Acute Tubular Necrosis

Each glomerulus (microscopic "filtering screen") has a tubule that transports urine to the ureters (see anatomy) and metabolically alters the urine and its chemicals. Because the tubules are exceedingly metabolically active, they are very dependent on the oxygen that supplies the tubular cells. They are often described as being nearly oxygen starved because they work so hard. Close to 200 liters of fluid is filtered across the glomeruli, and the tubules reabsorb 99% (198 liters) of the fluid in a selective manner.

Acute tubular necrosis (ATN) is the death of tubular cells, which may result when tubular cells do not get enough oxygen (ischemic ATN) or when they have been exposed to a toxic drug or molecule (nephrotoxic ATN). Fortunately, new tubular cells usually replace those that have died. Indeed, the tubular cells of the kidneys undergo a continuous cycle of cell death and renewal, much like the cells of the skin.

Causes

In the hospital setting, ATN is the most common cause of acute renal failure (ARF). Hospital patients often have acute medical problems that limit the oxygen supplied to the tubules or that cause tubular hypoperfusion (decreased blood flow).

Certain medical and surgical situations are associated with a high risk for developing ischemic ATN:

• Hypotension (low blood pressure)

• Obstetric (birth-related) complications

• Obstructive jaundice (yellow-tinged skin caused by blocked flow of bile

• Prolonged prerenal state

• Sepsis (infection in the blood or tissues)

• Surgery (e.g., open heart surgery, repair of abdominal aortic aneurysm)

Some medications and clinical materials can cause nephrotoxic ATN:

• Aminoglycosides (antibacterial antibiotics such as streptomycin and gentamicin)

• Amphotericin B (antibiotic used to treat some forms of meningitis and systemic fungal infections)

• Cisplatin (anticancer agent used to treat late-stage ovarian and testicular cancers)

• Radioisotopic contrast media (agent used in certain imaging studies)

Exposure to certain molecules also may cause nephrotoxic ATN. For example, when a person suffers significant muscle trauma, such as during a crush injury, the muscle enzyme creatinine phosphokinase (CPK) leaks into the blood. Myoglobulin is the protein that leaks into the blood and ultimately causes ATN. Measurement of CPK is a marker of myoglobulin released by muscle cells. If enough CPK spills into the blood and is filtered through the glomeruli, it can damage the tubules, causing nephrotoxic ATN.

Signs and Symptoms

Acute tubular necrosis (ATN) typically does not produce specific signs or symptoms.

Diagnosis

Diagnosis often is supported by a positive history of risk factors. Yet the physician must rule out other reasons for acute renal failure, such as prerenal, postrenal, and renal ARF. Distinguishing ATN from prerenal ARF can be extremely difficult. Urine chemistry and microscopic examination of the urine help to confirm the diagnosis. ATN does not rapidly improve following the administration of large-volume intravenous fluid.

Treatment

Management relies on aggressive treatment of the factors that precipitated ATN. One exception is the treatment of ATN associated with the breakdown of muscle fibers caused by a crush injury. Aggressive, forced diuresis (i.e., an increased excretion of urine) may improve the condition.

Patients at high risk for developing ARF from contrast induced ATN should be treated with intravenous (IV) fluids prior to contrast exposure to prevent the ATN. There has been a recent report suggesting that pretreatment of these patients with a medication called mucomyst may also help to prevent ARF in patients undergoing IV contrast exposure.

Prognosis

Because tubular cells have the capacity to replace themselves, the overall prognosis for ATN is quite good if the cause is corrected. Once the precipitating factor has been treated and removed, ATN usually resolves within 7 to 21 days. On occasion, the kidneys may not completely recover or (rarely) may never recover, despite the resolution of other medical problems. This situation usually indicates that there is preexisting, unidentified renal dysfunction.

Anemia

Anemia is characterized by an insufficient number of red blood cells (RBCs). RBCs carry oxygen from the lungs to tissues throughout the body. All cells require oxygen to function.

Red blood cells originate in bone marrow as erythroblasts (a "blast" is a primitive cell that develops into a mature cell). Hemoglobin (Hb), a protein that binds to oxygen, is the main component of red blood cells. Once RBCs become filled with hemoglobin they enter the bloodstream as erythrocytes. Healthy hemoglobin holds the oxygen molecules with a precise degree of force. If it binds oxygen molecules in the lungs too loosely, it cannot hold onto them and carry them away. If it binds them too tightly, it cannot release them to tissues.

Red blood cell production is stimulated by the hormone erythropoietin (EPO), which is produced in the kidneys. If the kidneys fail to produce adequate EPO, anemia develops.

Blood Transfusion

Hospitals use blood supplied by blood banks (companies that collect, prepare, and store blood for medical and emergency uses). Blood banks type blood and test the compatibility of donor and recipient blood before transfusion (called cross-matching). Blood types are A, B, AB, and O. Whether the type is positive or negative depends on whether the Rh factor is present on the person's red blood cells.

All types can receive O negative blood, but may not be compatible with other types:

• Recipients with A+ blood type can receive A+, A-, O+ and O- blood types

• Recipients with B+ blood type can receive B+, B-, O+ and O- blood types

• Recipients with AB+ blood type can receive AB+, AB-, O+ and O- blood types.

• Recipients with O+ blood type can receive O+ and O- blood types

• Recipients with A- blood type can receive A- and O- blood types

• Recipients with B- blood type can receive B- and O- blood types

• Recipients with AB- blood type can receive AB- and O- blood types.

• Recipients with O- blood type can receive O- blood type.

Blood products commonly transfused in intensive care units (ICUs) include

• red blood cells (RBCs) – contain hemoglobin, which carries oxygen to all tissues;

• plasma – straw-colored fluid that carries the blood cells, enzymes, and hormones throughout the body; and

• platelets – cell-like bodies that control bleeding.

Blood banks also test blood for anemia and pathogens (disease-causing bacteria and viruses), including hepatitis viruses B and C, human immunodeficiency virus (HIV), and Treponema pallidum (bacterium that causes syphilis).

Despite the many regulations in place to assure the safety of blood supplies, transfusions are not risk free. Possible complications of blood transfusions include

• allergic reaction (caused by an allergen in the donor blood) and

• hemolytic transfusion reaction (caused by incompatible blood).

Managing patients in ICU requires strategies to minimize blood loss and increase production of blood in bone marrow. Limiting laboratory testing and phlebotomy (drawing blood) are important components of blood management.

Other Treatment

Injectable EPO (e.g., PROCRIT®, EPOGEN®) is an alternative to blood transfusion to treat critically ill patients with anemia. Exogenous EPO is identical to the natural hormone in its role of stimulating the bone marrow to produce red blood cells. EPO has been used safely in many clinical settings, including chronic renal failure, oncology, and surgery. In the ICU, use of EPO has been shown to reduce the amount of blood transfused by almost 50%, at the same time significantly increasing hemoglobin levels.

Diabetic nephropathy

Diabetic nephropathy is kidney disease that develops as a result of diabetes mellitus (DM). DM, also called simply diabetes, affects approximately 5% of the U.S. population. This disease damages many organs, including the eyes, nerves, blood vessels, heart, and kidneys. DM is the most common cause of kidney failure in the United States and accounts for over one-third of all patients who are on dialysis.

Diabetes mellitus (DM)

Diabetes mellitus is a disorder in which the body is unable to metabolize carbohydrates (e.g., food starches, sugars, cellulose) properly. The disease is characterized by excessive amounts of sugar in the blood (hyperglycemia) and urine; inadequate production and/or utilization of insulin; and by thirst, hunger, and loss of weight.

Diabetics who require daily insulin shots to maintain life have insulin-dependent diabetes mellitus, or DM 1. In this type of diabetes, the pancreas secretes little or no insulin and the blood sugar level remains high, unless treated. DM 1 usually occurs in children and young adults and is often called juvenile onset diabetes. Onset of the disease is abrupt. The patient becomes very sick and requires immediate insulin therapy. Approximately 1 million people in the United States have DM 1.

Non-insulin-dependent diabetes, or DM 2, differs from DM 1 in that the main problem is a peripheral resistance to the action of the insulin. DM 2 usually occurs in adults over the age of 40 who are overweight and have a family history of the disease. Some patients can manage their diabetes with weight loss and changes in their diet. Others require medication, and many with DM 2 eventually require insulin. Onset is gradual, and patients may be sick for quite some time without knowing it. Nearly 95% of diabetics are diagnosed with DM 2.

Signs and Symptoms

Approximately 25% to 40% of patients with DM 1 ultimately develop diabetic nephropathy (DN), which progresses through about five predictable stages.

Stage 1 (very early diabetes)—Increased demand upon the kidneys is indicated by an above-normal glomerular filtration rate (GFR).

Stage 2 (developing diabetes)—The GFR remains elevated or has returned to normal, but glomerular damage has progressed to significant microalbuminuria (small but above-normal level of the protein albumin in the urine). Patients in stage 2 excrete more than 30 mg of albumin in the urine over a 24-hour period. Significant microalbuminuria will progress to end-stage renal disease (ESRD). Therefore, all diabetes patients should be screened for microalbuminuria on a routine (yearly) basis.

Stage 3 (overt, or dipstick-positive diabetes)—Glomerular damage has progressed to clinical albuminuria. The urine is "dipstick positive," containing more than 300 mg of albumin in a 24-hour period. Hypertension (high blood pressure) typically develops during stage 3.

Stage 4 (late-stage diabetes)—Glomerular damage continues, with increasing amounts of protein albumin in the urine. The kidneys' filtering ability has begun to decline steadily, and blood urea nitrogen (BUN) and creatinine (Cr) has begun to increase. The glomerular filtration rate (GFR) decreases about 10% annually. Almost all patients have hypertension at stage 4.

Stage 5 (end-stage renal disease, ESRD)—GFR has fallen to approximately 10 milliliters per minute ( ................
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