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.
Chronic renal failure (CRF) can be classified by the site (location) of primary damage:
* Pre-renal CRF
* Post-renal CRF (obstructive uropathy)
* Renal CRF
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.
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.
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
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)
* Vasculitis, inflammation of the small blood vessels
* Cystic kidney disease, kidney disease distinguished by multiple cysts (lined cavities or sacs)
* Hereditary diseases of the kidney, such as Alport's syndrome (hereditary nephritis)
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
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.
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.
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).