health conditions or disease processes. Nephropa-
thy is the main cause of END-STAGE RENAL DISEASE
(ESRD) and the leading reason for KIDNEY TRANS-
PLANTATION. Doctors diagnose more than 100,000
Americans with nephropathy every year. DIABETES
and HYPERTENSION (high BLOOD PRESSURE) are the
leading cause of nephropathy in the United States.
These conditions damage the delicate glomeruli,
the capillary networks that feed BLOODthrough
the nephrons, the filtering structures of the kid-
neys. Each kidney contains more than a million
nephrons and can tolerate the loss of about two
thirds of them before symptoms of kidney failure
become apparent. By such time, however, damage
to the kidneys is usually profound.
Nephropathy of diabetes Diabetes accounts for
45 percent of kidney failure among Americans.
The elevated GLUCOSE(sugar) levels in the blood
that occur with diabetes are particularly damaging
to the blood vessels and the nerves that serve
them. For reasons researchers do not understand,
African Americans, Hispanic Americans, and
Native Americans who have diabetes are signifi-
cantly more likely to develop nephropathy of dia-
betes (sometimes called diabetic nephropathy).
About 40 percent of people who have diabetes
develop some degree of nephropathy, half of
whom eventually progress to ESRD. Nephropathy
is more likely in type 1 diabetes.
Nephropathy of hypertension Hypertension
accounts for 25 percent of nephropathy among
Americans. Chronically elevated blood pressure
places considerable stress against the walls of the
glomeruli, causing microscopic ruptures and scar-
ring (fibrosis). As with nephropathy of diabetes,
nephropathy of hypertension (sometimes called
hypertensive nephropathy) is significantly more
likely to develop in African Americans, Hispanic
Americans, and Native Americans. The progres-
sion to ESRD can be rapid in poorly controlled or
untreated hypertension.
IgA nephropathy In IMMUNOGLOBULINA (IgA)
nephropathy, a dysfunction of the IMMUNE SYSTEM
results in deposits of gA, a protein, accumulating
within the tubules of the nephrons. The kidneys
have no process for removing these deposits,
which eventually clog the tubules and prevent
them from transporting filtrate. IgA nephropathy
typically is ongoing for 20 years or longer before
causing enough damage to result in symptoms.
Many people who have IgA nephropathy also
have a systemic autoimmune disorder such as SYS-
TEMIC LUPUS ERYTHEMATOSUS (SLE), RHEUMATOID
ARTHRITIS, orANKYLOSING SPONDYLITIS. Treating the
underlying autoimmune disorder often slows the
progression of the nephropathy.
Toxic nephropathy Many drugs and chemicals
are nephrotoxins, substances that damage the kid-
neys. Toxic nephropathy typically develops as a
result of chronic exposure though can occur with
limited though substantial exposure (such as DRUG
overdose). Common nephrotoxins include heavy
metals (such as lead and cadmium), organic sol-
vents (such as benzene), and certain ANTIBIOTIC
MEDICATIONS (notably gentamicin and strepto-
mycin, which are sometimes the only antibiotics
effective against life-threatening infections such as
bacterial MENINGITIS).
Worrisome culprits are the NONSTEROIDAL ANTI-
INFLAMMATORY DRUGS(NSAIDS). DEHYDRATIONin com-
bination with NSAID use, which occurs among
people who compete in ENDURANCEactivities, is a
particular risk. Long-term, daily use of other pain-
relief medications, notably codeine and combina-
tion products that contain CAFFEINE with
acetaminophen or aspirin, also can cause this form
of toxic nephropathy, commonly called analgesic
nephropathy. People who have conditions of
chronic PAIN are most susceptible to analgesic
nephropathy. People who have diabetes or conges-
tive HEART FAILURE, have other kidney disease,
engage in heavy ALCOHOLconsumption, or are age
70 or older also have increased risk for analgesic
nephropathy, in part because many people do not
understand the danger regular analgesic use poses
for the kidneys. These circumstances reduce kidney
function, increasing the likelihood that further
damage to the kidneys will result in kidney failure.Symptoms and Diagnostic Path
Nephropathy generally does not show symptoms
until damage to the kidneys is fairly advanced.
One of the earliest indications of nephropathy is
ALBUMINURIA, a consequence of protein leaking
from the glomeruli into the filtrate. Doctors often
detect albuminuria through urinalysis done as part
of a routine medical examination. When symp-
toms do appear, they often include210 The Urinary System