Acute Pyelonephritis

Mariya Belyayeva; Jordan M. Jeong.

Author Information

Last Update: February 28, 2019.

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Introduction
Acute pyelonephritis is a bacterial infection causing inflammation of the kidneys and is one of
the most common diseases of the kidney. Pyelonephritis occurs as a complication of an
ascending urinary tract infection (UTI) which spreads from the bladder to the kidneys and their
collecting systems. Symptoms usually include fever, flank pain, nausea, vomiting, burning on
urination, increased frequency, and urgency. The 2 most common symptoms are usually fever
and flank pain. Acute pyelonephritis can be divided into uncomplicated and complicated.
Complicated pyelonephritis includes pregnant patients, patients with uncontrolled diabetes,
kidney transplants, urinary anatomical abnormalities, acute or chronic kidney failure, as well as
immunocompromised patients and those with hospital-acquired bacterial infections. It is
important to make a distinction between complicated and uncomplicated pyelonephritis, as
patient management and disposition depend on it.
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Etiology
The main cause of acute pyelonephritis is gram-negative bacteria, the most common
being Escherichia coli. Other gram-negative bacteria which cause acute pyelonephritis
include Proteus, Klebsiella, and Enterobacter. In most patients, the infecting organism will come
from their fecal flora. Bacteria can reach the kidneys in 2 ways: hematogenous spread and
through ascending infection from the lower urinary tract. Hematogenous spread is less common
and usually occurs in patients with ureteral obstructions or immunocompromised and debilitated
patients. Most patients will get acute pyelonephritis through ascending infection. Ascending
infection happens through several steps. Bacteria will first attach to urethral mucosal epithelial
cells and will then travel to the bladder via the urethra either through either instrumentation or
urinary tract infections which occur more frequently in females. UTIs are more common in
females than in males due to shorter urethras, hormonal changes, and close distance to the anus.
Urinary tract obstruction caused by something such as a kidney stone can also lead to acute
pyelonephritis. An outflow obstruction of urine can lead to incomplete emptying and urinary
stasis which causes bacteria to multiply without being flushed out. A less common cause of acute
pyelonephritis is vesicoureteral reflux, which is a congenital condition where urine flows
backward from the bladder into the kidneys.
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Epidemiology
Acute pyelonephritis in the United States is found at a rate of 15 to 17 cases per 10,000 females
and 3 to 4 cases per 10,000 males annually. Young sexually active women are the patients that
are most often affected by acute pyelonephritis. Groups with extremes of age such as the elderly
and infants are also at risk due to abnormalities in anatomy and changes in hormones. Pregnant
women can also be at risk, and 20% to 30% will develop acute pyelonephritis, usually during the
second and early third trimester. Acute pyelonephritis has no racial predisposition. [1]
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Pathophysiology
E. coli is the most common bacteria causing acute pyelonephritis due to its unique ability to
adhere to and colonize the urinary tract and kidneys. E.coli has adhesive molecules called P-
fimbriae which interact with receptors on the surface of uroepithelial cells. Kidneys infected
with E. coli can lead to an acute inflammatory response which can cause scarring of the renal
parenchyma. Though the mechanism in which renal scarring occurs is still poorly understood, it
has been hypothesized that the adhesion of bacteria to the renal cells disrupts the protective
barriers, which lead to localized infection, hypoxia, ischemia, and clotting in an attempt to
contain the infection. Inflammatory cytokines, bacterial toxins, and other reactive processes
further lead to complete pyelonephritis and in many cases systemic symptoms of sepsis and
shock.
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Histopathology
Histopathology will usually reveal necrosis or putrid abscess formation within the renal
parenchyma. The renal tissues are infiltrated with neutrophils, macrophages and plasma cells.
However, the architecture is not completely disorganized.
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History and Physical

Acute pyelonephritis will classically present as a triad of fever, flank pain, and nausea or
vomiting, but not all symptoms have to be present. Symptoms will usually develop within
several hours or over the course of a day. Symptoms of cystitis such as dysuria and hematuria
will be present in women usually. In children, common symptoms of acute pyelonephritis can be
absent. Symptoms such as failure to thrive, fever and feeding difficulty are most common in
neonates and children under 2 years old. Elderly patients may present with altered mental status,
fever, deterioration, and damage to other organ systems. On physical examination, the patient's
general appearance will be variable. Some patients will appear ill and uncomfortable, while
others may appear healthy. Patients will usually not appear toxic. When a patient is febrile, fever
may be high, often over 103 F. Costovertebral angle tenderness is commonly unilateral over the
affected kidney, but in some cases, bilateral costovertebral angle tenderness may be present.
Suprapubic tenderness during the abdominal examination will vary from mild to moderate with
or without rebound tenderness.
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Evaluation
A good history and physical is the mainstay of evaluating acute pyelonephritis, but laboratory
and imaging studies can be helpful. A urinary specimen should be obtained for a urinalysis. On
urinalysis, one should look for pyuria as it the most common finding in patients with acute
pyelonephritis. Nitrite production will indicate that the causative bacteria is E.coli. Proteinuria
and microscopic hematuria may be present as well on urinalysis. If hematuria is present, then
other causes may be considered such as kidney stones. All patients with suspected acute
pyelonephritis should also have urine cultures sent for proper antibiotic management. Blood
work such as a complete blood cell count (CBC) is sent to look for an elevation in white blood
cells. The complete metabolic panel can be used to search for aberrations in creatinine and BUN
to assess kidney function. The imagining study of choice for acute pyelonephritis is
abdominal/pelvic CT with contrast. Imaging studies will usually not be required for the diagnosis
of acute pyelonephritis but are indicated for patients with a renal transplant, patients in septic
shock, those patients with poorly controlled diabetes, complicated UTIs, immunocompromised
patients, or those with toxicity persisting for longer than 72 hours. Ultrasonography can be used
to detect pyelonephritis, but a negative study does not exclude acute pyelonephritis. Regardless,
ultrasound can still be a useful study when evaluating for acute pyelonephritis because it can be
done bedside, has no radiation exposure and may reveal renal abnormalities, which can prompt
further testing or definitive treatment.
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Treatment / Management
Acute pyelonephritis can be managed as either outpatient or inpatient. Healthy, young, non-
pregnant women who present with uncomplicated pyelonephritis can be treated as outpatients.
Inpatient treatment is usually required for those who are very young, elderly,
immunocompromised, those with poorly controlled diabetes, renal transplant, patients, patients
with structural abnormalities of the urinary tract, pregnant patients, or those who cannot tolerate
oral intake. The mainstay of treatment of acute pyelonephritis is antibiotics, analgesics, and
antipyretics. Nonsteroidal anti-inflammatory drugs (NSAIDs) work well to treat both pain and
fever associated with acute pyelonephritis. The initial selection of antibiotics will be empiric and
should be based on the local antibiotic resistance. Antibiotic therapy should then be adjusted
based on the results of the urine culture. Most uncomplicated cases of acute pyelonephritis will
be caused by E. coli for which patients can be treated with oral cephalosporins or TMP-SMX for
14 days. Complicated cases of acute pyelonephritis require intravenous (IV) antibiotic treatment
until there are clinical improvements. Examples of IV antibiotics include piperacillin-
tazobactam, fluoroquinolones, meropenem, and cefepime. For patients who have allergies to
penicillin, vancomycin can be used. Follow up for non-admitted patients for resolution of
symptoms should be in 1 to 2 days. Follow up urine culture results should be obtained only in
patients who had a complicated course and are usually not needed in healthy, non-pregnant
women. Any patient that had a complicated UTI should be sent for follow up imaging to identify
any abnormalities that predispose the patient to further infections.
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Differential Diagnosis
When diagnosing acute pyelonephritis, keeping the differential broad is a wise idea. Physicians
should consider other disorders as well when patients present with fever, flank pain, and
costovertebral angle tenderness. Because symptoms can be variable (unilateral, bilateral,
radiating, sharp, dull) and because pyelonephritis can progress to sepsis and shock the
differential diagnoses associated with pyelonephritis can be extensive. Common mimics of acute
pyelonephritis can include but is not limited to:
 Appendicitis
 Abdominal abscess
 Nephrolithiasis
 Cholecystitis
 Urinary tract obstruction
 Pelvic inflammatory disease
 Pancreatitis
 Ectopic pregnancy [2]
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Prognosis
Overall the majority of cases of pyelonephritis are managed in an outpatient setting with most
patients improving with oral antibiotics. Usually, young women are among those most likely to
be treated as outpatients.[1] Despite pyelonephritis improving in most cases, there is still
significant morbidity and mortality that can be associated with severe cases of this disease.
Overall mortality has been reported around 10% to 20% in some studies with a recent study from
Hong Kong finding a mortality rate closer to 7.4%. More importantly, this study found that old
age (older than 65 years), male gender, impaired renal function, or presence of disseminated
intravascular coagulation were associated with increased mortality. With the proper recognition
of the underlying etiology and prompt intervention with adequate treatment, even patients with
severe pyelonephritis generally have a good outcome. [3]
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Complications
Acute pyelonephritis can have several complications such as renal or perinephric abscess
formation, sepsis, renal vein thrombosis, papillary necrosis, or acute renal failure, with one of the
more serious complications being emphysematous pyelonephritis (EPN).[4] Emphysematous
pyelonephritis is a necrotizing infection of the kidney usually caused by E. coli or Klebsiella
pneumoniae and is a severe complication of acute pyelonephritis. EPN is usually seen in the
setting of diabetes and occurs more frequently in women. The diagnosis can be made with
ultrasound, but CT is typically necessary. Overall the mortality rate is estimated to be
approximately 38% with better outcomes associated with patients who receive both medical and
surgical management versus medical management alone. [5]
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Consultations
Most cases of acute pyelonephritis are uncomplicated and do not require consultations. More
complicated cases of acute pyelonephritis may require consults such as urology, obstetrics and
gynecology, and infectious disease. Urology is usually consulted for patients with urethral
obstruction, urogenital abnormalities or first episode of pyelonephritis in an infant. Obstetrics
and gynecology would be consulted for a pregnant patient with acute pyelonephritis. Infectious
disease can be consulted for patients that are immunocompromised, have resistant pathogens or
blood cultures that are positive for more than 48 hours.
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Deterrence and Patient Education

For healthy, young, premenstrual women, one of the best ways to avoid acute pyelonephritis is to
focus on prevention of one of the more common predisposing causes which are urinary tract
infections. While many factors may lead to urinary tract infections, a simple way to help in
prevention is to void before and immediately after intercourse as well as wiping from front to
back after urinating and defecating. This will help to stop the introduction of bacteria into the
urethra and subsequent ascending structures. Aside from behavioral interventions, there have
also been studies focusing on cranberry juice, probiotics, and low dose prophylactic antibiotics to
prevent UTIs.[6] To avoid recurrent acute pyelonephritis, patients must finish the entire course
of antibiotics and take them as directed. Avoiding dehydration also helps to prevent acute
pyelonephritis and improves kidney function.
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Pearls and Other Issues

 Complicated pyelonephritis includes pregnant patients, patients with uncontrolled
diabetes, transplant patients, those with urinary anatomical abnormalities, acute or
chronic kidney failure, as well as immunocompromised patients
 Acute pyelonephritis will classically present as a triad of fever, flank pain, and nausea or
vomiting, but not all symptoms have to be present.
 Ultrasonography can be used to detect pyelonephritis, but a negative study does not
exclude acute pyelonephritis.
 Most uncomplicated cases of acute pyelonephritis will be caused by E. coli for which
patients can be treated with oral cephalosporins or TMP-SMX for 14 days.
 Old age (older than 65 years), male gender, impaired renal function, or presence of
disseminated intravascular coagulation are associated with increased mortality.
  Acute pyelonephritis can have several complications such as renal or perinephric abscess
formation, sepsis, renal vein thrombosis, papillary necrosis, or acute renal failure, with
one of the more serious complications being emphysematous pyelonephritis.
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Enhancing Healthcare Team Outcomes

The treatment of acute pyelonephritis is usually done by a team of healthcare professionals that
include a nephrologist, infectious disease consultant, pain specialist, internist, urologist, and an
obstetrician if the patient is pregnant. Both the nurse and pharmacist play a critical role in the
monitoring of the patient, administration of antibiotics and monitoring for recovery. A dietary
consult should be called if the patient is diabetic but the key is hydration. Today, the emphasis is
on the prevention of the condition. Women should be educated about safe sex, contraceptive use,
and early treatment of cystitis. If reinfection occurs within 14 days of discharge, the urologist
should be consulted to investigate for an anatomical problem predisposing to the condition. The
pharmacist must follow the culture results and ensure that the patient is on the right drugs to
cover the organisms causes the infection. In addition, the pharmacists must ensure that the
patient is on no nephrotoxic agent that can exacerbate the renal damage. (Level V)
Outcomes
The key to outcomes in patients with acute pyelonephritis is prompt diagnosis and treatment.
Any delay in treatment can often lead to very high morbidity. Delays in proper management can
lead to longer hospital admissions, severe pain, and disability. Even after discharge, follow-up is
needed to ensure that full recovery has occurred. Pregnant females with acute pyelonephritis are
at a very high risk for premature delivery.
Further, the infection tends to be much more severe in diabetics compared to the general
population. The mortality rates are higher in the elderly who have other comorbidities.
Complications known to occur from acute pyelonephritis include sepsis, acute renal failure, renal
scarring, and renal transplant pyelonephritis. (Level V)