630
U N I T 7
Kidney and Urinary Tract Function
state of hydration, blood pressure, and the pH of the
urine. Elderly persons are particularly susceptible to
kidney damage caused by drugs and toxins. The dan-
gers of nephrotoxicity are increased when two or more
drugs capable of producing kidney damage are given at
the same time.
Drugs and other toxic substances can damage the kid-
neys by causing a decrease in renal blood flow, directly
damaging tubulointerstitial structures, producing hyper-
sensitivity reactions, or obstructing urine flow. Some
drugs, such as diuretics, high–molecular-weight radiocon-
trast media, the immunosuppressive drugs cyclosporine
and tacrolimus, and the nonsteroidal anti-inflammatory
drugs (NSAIDs), can cause acute kidney injury by
decreasing renal blood flow (discussed in Chapter 26).
Other drugs such as sulfonamides and vitamin C supple-
ments can form crystals that cause kidney damage by
obstructing urinary flow in the tubules.
Acute drug-related hypersensitivity reactions produce
tubulointerstitial nephritis, with damage to the tubules
and interstitium. This condition was observed initially
in persons who were sensitive to the sulfonamide drugs;
currently, it is observed most often with the use of meth-
icillin and other synthetic antibiotics, and with the use
of furosemide and the thiazide diuretics in persons sensi-
tive to these drugs. The condition begins approximately
15 days (range, 2 to 40 days) after exposure to the drug.
4
At the onset, there is fever, eosinophilia, hematuria, mild
proteinuria, and, in approximately one fourth of cases,
a rash. In approximately 50% of cases, signs and symp-
toms of acute renal failure develop. Withdrawal of the
drug commonly is followed by complete recovery, but
there may be permanent damage, usually in older per-
sons. Drug nephritis may not be recognized in its early
stage because it is relatively uncommon.
Chronic analgesic nephritis
, which is associated with
analgesic abuse, causes tubulointerstitial nephritis with
renal papillary necrosis. Prostaglandins (particularly PGI
2
and PGE
2
) are potent renal vasodilators that contribute to
the regulation of renal blood flow. The deleterious effects
of aspirin and other NSAIDs are thought to result from
their ability to decrease prostaglandin synthesis and thus
decrease renal blood flow. The susceptibility of the papil-
lae to damage is believed to be related to the establishment
of a renal gradient in which the papillary concentration
of the drug is higher than in the cortex. Persons particu-
larly at risk are the elderly because of age-related changes
in renal function, individuals who are dehydrated or have
a decrease in blood volume, and those with preexisting
kidney disease or renal insufficiency.
Chinese herbal drugs have also been implicated in
drug-related kidney damage. Early recognition of the
problem surfaced in the early 1990s with reports of an
unusually rapid and progressive form of renal failure
in women with a shared history of chronic ingestion
of slimming herbs, such as ephedra (ma huang), from
China as part of a weight loss program.
23
Growing evi-
dence from both clinical and animal models suggests
that this form of kidney damage is attributable, at least
in part, to the presence of aristolochic acid in the slim-
ming herb preparations.
Illicit drug use has also been implicated in a wide
spectrum of kidney diseases.
26
For example, acute renal
failure has been reported in persons presenting with
acute cocaine intoxication. The cause is probably mul-
tifactorial and involves direct vasoconstriction, altered
systemic hemodynamics, and myoglobin-induced renal
failure. The chronic inhalation of solvents (e.g., glue,
paint thinner), aerosols, gases, and nitrates has also
been associated with a variety of toxic kidney effects,
including acute and chronic renal failure. The tubular
manifestations of solvent abuse probably result from
the interference with intracellular metabolic processes
involved in membrane transport.
A
B
FIGURE 25-12.
Chronic pyelonephritis.
(A)
The cortical surface contains many
irregular depressed scars (reddish areas).
(B)
There is marked dilation of calyces caused
by inflammatory destruction of papillae,
with atrophy and scarring of the overlying
cortex. (From Jennette JC.The kidney. In:
Rubin R, Strayer DS, eds. Rubin’s Pathology:
Clinicopathologic Foundations of Medicine.
6th ed. Philadelphia, PA: Wolters Kluwer
Health | Lippincott Williams &Wilkins;
2012:797.)
