Nephrotoxic injury is damage to one or both of the kidneys that results from exposure to a toxic material, usually through ingestion.
The kidneys are the primary organs of the urinary system, which purifies the blood by removing wastes from it and excreting them from the body in urine. Every day, the kidneys filter about 45 gal (180 l) of blood, about four times as much as the amount that passes through any other organ. Because of this high volume, the kidneys are more often exposed to toxic substances in the blood and are very vulnerable to injury from those sources.
Each kidney contains over one million structures called nephrons. Each nephron consists of two parts: the renal corpuscle and the renal tubule. The renal corpuscle is where the blood is filtered. It is made up of a network of capillaries (the glomerulus) and the structure that surrounds these capillaries (Bowman's capsule). Blood flows into the glomerulus, where the liquid part of the blood (plasma) passes through the walls of the capillaries and into Bowman's capsule (blood cells and some proteins are too big to pass through and therefore remain in the blood vessels). The plasma, now called filtrate, contains substances that the body needs, such as water, glucose, and other nutrients, as well as wastes, excess salts, and excess water. When the filtrate moves from Bowman's capsule into the renal tubules, about 99% of it is taken back up as the action of the tubules allows beneficial substances to be reabsorbed into the blood stream. The remaining filtrate is then passed to the bladder as urine.
When the kidneys are exposed to a toxic agent, either accidentally or intentionally (as in a suicide attempt), damage can occur in a number of different ways, depending upon the agent. One toxin may directly affect the glomerulus or the renal tubules, causing the cells of these structures to die. Another toxin may create other substances or conditions that result in the same cell death. Nephrotoxic injury can lead to acute renal failure, in which the kidneys suddenly lose their ability to function, or chronic renal failure, in which kidney function slowly deteriorates. If unchecked, renal failure can result in death.
Causes and symptoms
Several different substances can be toxic to the kidneys. These include:
- antibiotics, primarily aminoglycosides, sulphonamides, amphotericin B, polymyxin, neomycin, bacitracin, rifampin, trimethoprim, cephaloridine, methicillin, aminosalicylic acid, oxy- and chlorotetracyclines
- analgesics, including acetaminophen (Tylenol), all nonsteroidal anti-inflammatory drugs (e.g. aspirin, ibuprofen), all prostaglandin synthetase inhibitors
- contrast agents used in some diagnostic tests, such as sodium iodide
- heavy metals, such as lead, mercury, arsenic, and uranium
- anti-cancer drugs, such as cyclosporin, cisplatin, and cyclophosphamide
- methemoglobin-producing agents
- solvents and fuels, such as carbon tetrachloride, methanol, amyl alcohol, and ethylene glycol
- herbicides and pesticides
- overproduction of uric acid
Nephrotoxic injury is most commonly caused by drugs, primarily antibiotics, analgesics, and contrast agents. In some cases, such as with aminoglycosides and amphotericin B, the drug itself will damage the kidneys. In others, such as with methicillin, sulphonamides, and some contrast agents, the drug provokes an allergic reaction that destroys the kidneys. Some chemicals found in certain drugs and industrial agents damage the kidneys by converting the hemoglobin of red blood cells into methemoglobin, thereby interfering with the blood's transport of oxygen. In hospitals, the most common form of nephrotoxic injury is antibiotic nephropathy, which usually occurs when antibiotics are given to patients with already weakened kidneys. Analgesic nephropathy is another common form of nephrotoxic injury and occurs as a result of long-term abuse of analgesics, usually NSAIDs (e.g., ibuprofen). Analgesic nephropathy is most prevalent in women over 30. Lead nephropathy, arising from lead poisoning, and nephropathy, from ingestion of the solvent carbon tetrachloride, are also more common forms of nephrotoxic injury. Uric acid nephropathy is one form of nephropathy that is not caused by exposure to an external toxin; instead, it arises from the body's overproduction of uric acid, usually in persons with diseases of the lymph nodes or bone marrow.
Risk factors for nephrotoxic injury include:
- Age. The elderly are more likely to overdose on antibiotics or analgesics.
- Underlying kidney disease. Kidneys already weakened by conditions such as diabetes can be particularly susceptible to nephrotoxic injury.
- Severe dehydration.
- Prolonged exposure to heavy metals or solvents on the job or in the home.
- Presence of diseases that cause the overproduction of uric acid.
Symptoms of nephrotoxic injury are wide ranging and, in some cases, depend upon the type of toxin involved. In general, symptoms are similar to those of renal failure and include excess urea in the blood (azotemia), anemia, increased hydrogen ion concentration in the blood (acidosis), excess fluids in the body (overhydration), and high blood pressure (hypertension). Blood or pus may be present in the urine, as may uric acid crystals. A decrease in urinary output may also occur. If the toxin's effect on the kidneys remains unchecked, more serious symptoms of kidney failure may occur, including seizures and coma.
Damage to the kidneys is assessed through a combination of physical examination, blood tests, urine tests, and imaging procedures. Diagnosis of nephrotoxic injury as the underlying cause results from a thorough investigation of the patient's history. Information regarding preexisting conditions, current prescriptions, and environmental exposures to toxins aid the physician in determining what toxin, if any, has caused the kidneys to malfunction.
Treatment of nephrotoxic injury takes place in the hospital and focuses on removing the toxin from the patient's system, while maintaining kidney function. Removal methods are targeted to specific toxins and may include the use of diuretics or chelates to enhance excretion of the toxin in urine, or, in extreme cases, the direct removal of toxins from the blood via hemodialysis or passing the blood over an absorbent substance such as charcoal. Support of kidney function depends on the extent of damage to the organs and ranges from monitoring fluid levels to dialysis.
Bowman's capsule — The structure surrounding the glomerulus.
Chelate — A chemical that binds to heavy metals in the blood, thereby helping the body to excrete them in urine.
Contrast agent — Substance ingested so as to highlight anatomical structures in x-ray imaging tests.
Diuretic — A drug that promotes the excretion of urine.
Glomerulus — A network of capillaries located in the nephron where wastes are filtered from the blood.
Methemoglobin — A compound formed from hemoglobin by oxidation.
Nephron — Basic functional unit of the kidney.
Nephrotoxin — Substance that is poisonous to the kidneys.
Renal failure — Disorder characterized by the kidney's inability to filter wastes from the blood. It may be acute (occuring suddenly and usually reversable) or chronic (developing slowly over time as a result of permanent damage).
The outcome of nephrotoxic injury is determined by the cause and severity of the damage. In cases where damage has not progressed beyond acute renal failure, kidney function can be fully restored once the toxin is removed from the system and equilibrium restored. However, if permanent damage has resulted in chronic renal failure, lifelong dialysis or a kidney transplant may be required.
Exposure to nephrotoxins can be minimized several different ways. When taking antibiotics or analgesics, recommended dosages should be strictly followed. Also, elderly patients on these medications (for example, those taking aspirin for heart problems or NSAIDs for arthritis) should be closely monitored to prevent accidental overdose. Health care workers should be aware of any underlying conditions, such as diabetes or allergies to antibiotics, that may heighten the effect of a potential nephrotoxin. When using solvents or handling heavy metals, procedures regarding their safe use should be employed.
American Kidney Fund (AKF). Suite 1010, 6110 Executive Boulevard, Rockville, MD 20852. (800) 638-8299. http://184.108.40.206/Default.htm.
National Kidney Foundation. 30 East 33rd St., New York, NY 10016. (800) 622-9010. http://www.kidney.org.