PYELONEPHRITIS
Pyelonephritis refers to an infection of the urinary
tract that involves the renal pelvis and parenchyma. The condition is more
common in women, for whom annual incidence is 12 to 13 per 10,000, than in men,
for whom the incidence is 2 to 3 per 10,000 men. It can lead to severe and
life-threatening systemic infections (urosepsis) and, if chronic, permanent
scarring of renal tissue. It can also be complicated by hemorrhage, abscess
formation, and gas formation.
PATHOPHYSIOLOGY
Ascension of pathogens from the lower tract is the
most common mechanism of infection, and in many cases cystitis precedes
pyelonephritis. The responsible pathogens, and their relative frequencies, are
the same as in cystitis (see Plate 5-1). Many of the risk factors are also
similar.
In rarer cases, the kidney may be hematogenously
seeded in the setting of bacteremia, usually with gram positive organisms (i.e., Staphylococcus aureus).
As with cystitis, the risk of pyelonephritis depends
on both host and bacterial factors. In young women, frequency of sexual
activity has been associated with a higher incidence of pyelonephritis,
presumably because of increased contamination of the lower urinary tract with
enteric flora. Diabetics are three times more likely than non-diabetics to
develop pyelonephritis during a lower tract infection because of numerous
factors. Pregnant women are also at increased risk because of relaxation of
smooth muscle around the ureters, which facilitates ascension of infected urine
from the lower tract as well as deficiencies in certain aspects of the normal
immune response. Patients with nephrolithiasis may have stones that become
seeded with bacteria, which make the bacteria very difficult to clear.
Individuals with vesicoureteral reflux (VUR) have
multiple factors that render them susceptible to pyelonephritis. First, the
retrograde flow of urine from the bladder into the ureters facilitates bacterial
ascension. Second, high-grade reflux into the ureters during voiding can cause
incomplete bladder emptying and urinary stasis. Third, chronic reflux may cause
upper tract scarring, which alters local antiadherence mechanisms. Fourth,
those with reflux are more likely to undergo catheterization and
instrumentation, which promote colonization of the urinary tract. Finally, lower
tract infections may themselves increase the degree of reflux because of the
increased intracystic pressure associated with inflammation. Thus individuals with vesicoureteral reflux (VUR) often
experience chronic pyelonephritis during childhood, which can lead to renal
scarring if severe and untreated.
Several factors determine whether a given pathogen is
likely to establish upper tract infection. E. coli with type 1 and P
fimbriae, for example, are more capable of adhering to the urothelium, which
facilitates ascension to the renal parenchyma. These mechanisms are
particularly important for pathogens causing pyelonephritis in anatomically
normal urinary tracts.
As bacteria infect the upper tract, an inflammatory
response occurs in the renal interstitium, where large numbers of leukocytes
(predominantly neutrophils in the acute phase) may be seen. Tubular injury,
suppurative necrosis, and abscess formation may occur. Even with extensive
inflammation, however, the glomeruli and local vasculature generally remain
intact. Neutrophils and proteinaceous material are flushed out in the urine as casts. Grossly, the kidney appears enlarged, with
multiple, discrete, small surface abscesses.
PRESENTATION AND DIAGNOSIS
In addition to the symptoms associated with cystitis
(see Plate 5-2), which may or may not be present, acute pyelonephritis features
high fever, anorexia, nausea/ vomiting, costovertebral angle tenderness, and
flank, abdominal, or pelvic pain. Patients with severe disease may have
concurrent septic shock and multiorgan failure. Older patients may have altered
mental status. Acute kidney injury does not usually occur in pyelonephritis
unless there is concomitant obstruction or shock.
As in cystitis, urinalysis should be positive for
leukocyte esterase, indicating the presence of white blood cells, and nitrites,
indicating the presence of bacteria. Proteinuria (of up to 2 g/day) may also be
noted. On urine microscopy, white blood cell casts may be seen in addition to
white blood cells and bacteria.
A complete blood count with differential may reveal
leukocytosis with neutrophilia. In some cases, serum chemistries may reveal
azotemia or electrolyte abnormalities secondary to dehydration.
Urine culture and at least two sets of blood cultures
should be obtained before initiation of antibiotic therapy to determine if
there is concurrent bacteremia.
In the absence of acute kidney injury or urinary tract
obstruction, radiologic studies do not need to be pursued at the outset. In patients who fail to defervesce after 48 to 72
hours of treatment with appropriate antibiotics, however, a renal ultrasound or
computed tomography (CT) scan of the abdomen and pelvis may be performed. In
uncomplicated pyelonephritis, ultrasonography is usually normal, whereas a CT
scan may reveal perinephric stranding and patchy areas of diminished,
inhomogeneous enhancement. The presence of an abscess, gas collection, or
obstruction indicates complicated pyelonephritis.
TREATMENT
Patients with pyelonephritis should be admitted for
intravenous antibiotics if their symptoms are severe or they are unable to
comply with oral treatment. For example, a toxic-appearing patient with high
fevers, shaking chills, and rigors should be admitted. Patients who are
pregnant or immunocompromised should also be admitted. Otherwise, patients can
often be managed in an outpatient setting.
For patients being treated on an outpatient basis,
fluoroquinolones are appropriate empiric treatment. In patients with drug
allergies or a high likelihood of infection with resistant agents, oral
third-generation cephalosporins, such as cefpodoxime, may also be considered.
Patients should be advised to maintain adequate fluid intake and follow up
closely until symptoms resolve.
For patients who require hospitalization and
intravenous antibiotics, appropriate empiric therapies include ceftriaxone (a third generation
cephalosporin) or, in areas of low resistance, fluoroquinolones. Fluid
resuscitation is also critical. The antibiotic regimen can be refined once
culture results clarify the organism’s sensitivities. Empiric treatment should
be more aggressive for patients with urosepsis or a high risk of being
colonized with drug-resistant organisms, such as residents of long-term care
facilities or those with a history of frequent hospitalizations. In such cases,
initial treatment should employ a broad spectrum antibiotic, such as piperacillin-tazobactam,
ampicillin-sulbactam, or cefepime. Pending culture results, clinicians may wish
to add a second agent with additional gram-negative coverage, such as an
aminoglycoside or fluoroquinolone. The double coverage strategy provides the
highest chances of providing an agent that is active against the causative
organism; however, patients should be carefully monitored for renal toxicity
and other adverse effects,
especially if they are elderly.
In hospitalized patients, pyelonephritis should be
treated for 7 to 14 days, depending on severity. It is advisable to obtain a
repeat urine culture 5 to 9 days after the completion of treatment, since a
subset of patients will experience relapse, possibly without symptoms. Patients
with positive repeat cultures should undergo an additional 2 to 4 weeks of
treatment and may require evaluation for the presence of an infectious focus,
such as an abscess or an infected stone.
PROGNOSIS
The prognosis of uncomplicated pyelonephritis is
excellent unless urosepsis occurs, in which case mortality rates are substantially
higher. Moreover, in patients with chronic renal disease or renal scars from
childhood pyelonephritis, acute pyelonephritis may lead to further
deterioration of renal function. Poor prognosis is also associated with older
age, underlying comorbidities, and infection with resistant gram negative pathogens.
COMPLICATED PYELONEPHRITIS
Emphysematous pyelonephritis (EPN) is an uncommon but life-threatening necrotizing infection that causes
gas formation in the collecting system and renal parenchyma. It is most common
in diabetic patients with poor glycemic control.
EPN can occur secondary to E. coli or Klebsiella
spp. Less commonly, Proteus, Pseudomonas, and Clostridium species
may be responsible. Gas accumulation occurs in tissues with rapid catabolism
where efficient transport of the end products is not present. In diabetes, heavy
glycosylation of peripheral vessel walls can produce this effect because of
poor circulation.
In addition to the typical symptoms of pyelonephritis
described above, patients with EPN can have shock, altered sensorium, thrombocytopenia, and dyspnea.
X-ray and CT scans may be notable for the presence of extraluminal gas in the
renal tissue and perirenal space.
Nephrectomy is generally the treatment of choice;
however, it may not be possible in the setting of decreased renal function,
thrombocytopenia, hemodynamic instability, or altered mental status. In these
situations, a conservative approach may be pursued, including percutaneous
drainage and antibiotic therapy. Xanthogranulomatous pyelonephritis is
another rare form of complicated pyelonephritis, in which the kidney undergoes
wide destruction, with the damaged parenchyma replaced by lipid laden macrophages in granulomatous tissue.
