Introduction
Acute renal cortical necrosis (ACN) is an uncommon but often catastrophic cause of
acute kidney injury (AKI). Although the exact incidence of ACN is unknown, it is reported
to account for 1% to 2% of all cases of AKI in developed countries.
1
Commonly, ACN occurs as a result of catastrophic obstetric complications. We describe
an unusual case of AKI due to renal cortical necrosis attributed to N-methylamphetamine
(“crystal meth”) use.
Case Presentation
A 27-year-old Caucasian homeless woman presented to the emergency department with
symptoms of vomiting, poor oral intake, lower back pain, and decrease in urine output
of 2 days’ duration. The patient reported frequent use of nonsteroidal anti-inflammatory
drugs for the past 4 years. Her past medical history was significant for chronic hepatitis
C infection and a spontaneous second-trimester miscarriage. She denied any history
of clotting disorders or autoimmune disease. The patient had a history of i.v. drug
use for the past 10 years, and her previous toxicology screens had been positive for
cocaine, marijuana, and opiates. She reported frequent use of both oral and i.v. crystal
meth (methamphetamines) for the past 2 months. On examination, she was conscious and
oriented. She was afebrile with a heart rate of 63 bpm, respiratory rate of 16 breaths/min,
and blood pressure of 119/70 mm Hg. Her remaining physical examination findings were
unremarkable except for anasarca. Laboratory evaluation revealed serum creatinine
of 6.4 mg/dl and blood urea nitrogen of 34 mg/dl. No recent baseline creatinine value
was available, and she denied any past history of kidney disease. The rest of the
laboratory data were as follows: leukocyte count 13,700/μl, hemoglobin 11.9 g/dl,
platelets 96,000K/UL, bicarbonate 23 mEq/dl, and creatinine phosphokinase 108 IU/l.
Aspartate aminotransferase and alanine aminotransferase were mildly elevated at 219
IU/l and 82 IU/l, respectively. A pregnancy test result was negative. Urine examination
showed large blood, protein 100 mg/dl, 24 red blood cells per high-power field, and
no leukocytes. Renal ultrasound revealed normal sized kidneys without any hydronephrosis.
Blood culture results were negative. With differential diagnosis of acute glomerulonephritis
and acute interstitial nephritis, further a workup was performed. A component of prerenal
AKI was suspected, and treatment was initiated with isotonic i.v. fluids. However,
on day 2, the patient remained anuric with worsening renal function and refractory
hyperkalemia, following which emergent dialysis had to be initiated.
Serological workup showed mildly decreased complement C3 at 82 mg/dl (normal range,
88−206 mg/dl), normal complement C4, and positive rheumatoid factor at 23.9 IU/ml.
Antinuclear antibody and antineutrophil cytoplasmic antibody serology results were
negative. Both hepatitis B core antibody and hepatitis B surface antibody results
were positive, whereas hepatitis B surface antigen and hepatitis C RNA result were
negative. Serum cryoglobulin results were also negative. Anticardiolipin IgM was mildly
elevated at 21.1 IgM phospholipid units and lupus anticoagulant results were negative.
Kidney biopsy was performed on day 4. Sections for light microscopy had 19 glomeruli,
2 of which were globally sclerotic. Viable glomeruli were of normal overall size and
cellularity. There was widespread coagulative necrosis of the renal cortex (Figure 1).
There was also a sharp demarcation between areas of coagulative necrosis and the surrounding
inflamed but nonnecrotic tissue (Figure 2). No vasculitis or evidence of thrombotic
microangiopathy was seen in the viable kidney. Immunofluorescence staining was negative.
Toluidine blue−stained sections revealed extensive coagulative necrosis.
Figure 1
Necrotic tissue with ghost outlines of glomeruli and tubules with loss of cellular
detail (hematoxylin and eosin stain; original magnification ×200).
Figure 2
Sharp demarcation between eosinophilic necrotic parenchyma and inflamed but viable
tissue (hematoxylin and eosin stain; original magnification ×100).
Transesophageal echocardiography showed that the patient’s ejection fraction was 55%
with no evidence of emboli, vegetation, or endocarditis. The patient’s further hospital
course was complicated by line-associated bacteremia, for which she was successfully
treated with i.v. antibiotics. She has remained dialysis dependent during 2 months
of follow-up.
Discussion
Acute renal cortical necrosis is a rare cause of AKI, with a reported incidence of
about 2.0% in developed countries. In contrast, in developing countries, the incidence
is higher, and about 6% to 7% of AKI cases are attributed to ACN. Pregnancy related
complications remain the most common cause of ACN. About 60% to 70% of ACN cases are
sequelae of obstetric complications such as septic abortion, puerperal sepsis, abruptio
placentae, postpartum hemorrhage, and eclampsia. The remaining 30% to 40% are attributed
to nonobstetric causes, with fulminant sepsis and hemolytic uremic syndrome being
the most common ones.
1
Other causes of nonobstetric ACN include snake bites, malaria, renal trauma, acute
pancreatitis, diabetic ketoacidosis, and hyperacute renal transplant rejection.2,
3 With improvement in obstetric health care, and a marked decline in septic abortion,
the incidence of obstetric ACN has decreased significantly. However, novel causes
of non-obstetric ACN have emerged in the literature, which include prescription drugs
(bisphosphonates, tranexamic acid)4, 5, 6 and drugs of abuse (synthetic cannabinoids).
7
Table 1 lists the known causes of ACN. To the best of our knowledge, this is the first
case report of N-methylamphetamine (crystal meth)−induced ACN as a non-obstetric cause
of AKI in a young white woman.
Table 1
Causes of acute renal cortical necrosis
Obstetric
Non-obstetric
Septic abortionPuerperal sepsisAbruptio placentaePostpartum hemorrhageEclampsia
Drugs
Nonsteroidal anti-inflammatory drugs
Tranexamic acid
Polyethylene glycol
Quinine
Bisphosphonates
Drugs of abuse
Synthetic cannabinoids
Alcohol
Diethylene glycol
Poisonings
Snake bite
Wasp sting
Organophosphorus poisoning
Laundry detergent ingestion
Infections
Malaria
Streptococcal pharyngitis
Sepsis
Acute gastroenteritis
Protein S deficiency following varicella
AIDS
Hemolytic uremic syndromeTrauma/hemorrhagic shockBurnsPancreatitisDiabetic ketoacidosisGlucose-6-phosphate
dehydrogenase deficiency with intravascular hemolysisHyperacute kidney transplant
rejectionSLE-associated antiphospholipid syndrome
SLE, systemic lupus erythematosus.
The typical histological feature of ACN is total ischemic necrosis of the affected
area of the renal cortex (glomerului, blood vessels, and tubules). Two types of cortical
necrosis are recognized on the basis of renal histology: (i) diffuse cortical necrosis,
and (ii) patchy cortical necrosis. Diffuse cortical necrosis is characterized by confluent
cortical destruction extending into columns of Bertin. There is preservation of a
thin rim of subcapsular and juxtamedullary tissue. Clinically, diffuse ACN results
in irreversible renal failure, leading to end-stage renal disease. The incomplete
or patchy variety involves 30% to 50% of the entire cortical tissue. The latter variety
can present with initial oliguria or even anuria, followed by a variable return of
renal function and a stable period of moderate renal insufficiency.
8
Renal function may improve until after the third year of onset.
9
Even though the pathophysiology of ACN is not clearly understood, the final common
pathway involves significantly diminished renal arterial perfusion. The initiating
event is the vasospasm of small vessels and endothelial injury due to liberation of
vasoactive substances such as endothelin-1. There is unique involvement of a part
of the renal vasculature, mainly the interlobular cortical arteries and afferent arterioles,
with sparing of vessels from the main renal arteries, arcuate arteries, and collateral
subcapsular vessels.
10
Intravascular coagulation and microvascular injury have also been implicated in the
genesis of ACN.
1
In our patient, we attributed ACN to methamphetamine-induced vasospasm affecting the
renal vasculature. However, given the known effect of nonsteroidal anti-inflammatory
drugs in blocking the vasodilatory effects of prostaglandins in the afferent arteriole
(and thus reducing renal blood flow), nonsteroidal anti-inflammatory drug use may
have additionally contributed to the genesis of ACN. Alternative etiologies such as
thrombotic microangiopathy were ruled out.
Methamphetamine and related substances have become the second most frequently used
drugs of abuse in the world after cannabis, with approximately 33,900,000 users reported
worldwide in 2013.
11
Although the exact prevalence of adverse effects among methamphetamine users is unknown,
myriad cardiovascular and cerebrovascular complications have been described, including
malignant hypertension, arrhythmias, aortic dissection, myocardial infarction, stroke
(both ischemic and hemorrhagic), and cardiomyopathy.
12
Methamphetamine-induced ischemic colitis
13
and retinal vasculitis
14
have also been described.
These effects appear to be related to the stimulated release of neurotransmitters
including dopamine, serotonin, and/or noradrenaline. Noradrenaline acts via α1 receptors
in arterial vasculature to stimulate vasoconstriction,
15
and increases cardiac contractility and heart rate via β1 receptors.
16
Catecholamine excess with associated coronary vasospasm has been postulated to be
a cause of methamphetamine-associated cardiomyopathy. Other proposed mechanisms include
increases in reactive oxygen species, mitochondrial injury, and changes in myocardial
metabolism.
17
More recently, a study has demonstrated methamphetamine-induced release of endothelin
in mouse brain endothelial cells, suggesting an additional mechanism in which methamphetamine
can cause arterial vasoconstriction.
18
Endothelin, which is released from vascular endothelial cells, as a result of both
renal hypoperfusion and endothelial injury, may act as final common factor leading
to renal damage and subsequent ACN. In conclusion, it can be postulated that N-methylamphetamine
causes acute cortical renal necrosis via noradrenergic and endothelin-mediated renal
arterial vasoconstriction.
Renal biopsy is considered the gold standard in the diagnosis of ACN, but may be difficult
to perform due to clinical instability and underlying coagulopathy in patients. In
addition, biopsy may miss the diagnosis if ACN is patchy.
19
Noninvasive diagnostic modalities such as ultrasound, radionuclide scintigraphy, computed
tomography, magnetic resonance imaging, and renal arteriography may support the clinical
diagnosis of ACN by specific findings. Contrast-enhanced computed tomography demonstrates
the characteristic finding of a lack of renal cortical enhancement, and, in later
stages of ACN, cortical calcifications may be seen.
19
A double-line pattern of calcification resembling a tram-line has also been described.
20
Table 2 shows the teaching and interesting points of our case. Our case highlights
that renal cortical necrosis remains an important differential in the diagnosis of
acute kidney injury, especially with emergence of an epidemic of drug abuse. As in
this case, N-methylamphetamine may not be used in isolation, so the use of other drugs
may contribute to its effects. Although the patchy variety may be partially reversible,
the more common outcome is long-term dialysis dependence.
Table 2
Teaching points
• Acute renal cortical necrosis is a rare cause of acute kidney injury.
• Methamphetamines and other related drugs of abuse are emerging as an important cause
of non-obstetric acute renal cortical necrosis.
• The most common presentation of acute cortical necrosis is anuric acute kidney injury
that often requires initiation of renal replacement therapy.
• Renal biopsy is the gold standard for diagnosis of acute renal cortical necrosis.
• Although acute renal cortical necrosis is partially reversible in 20% to 40% of
cases, patients frequently require long-term renal replacement therapy.
• To the best of our knowledge, this is the first case illustrating N-methylamphetamine
as a cause of acute renal cortical necrosis, and clinicians should be aware of its
associated potential complications.
Disclosure
All the authors declared no competing interests.