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.
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.
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. 
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.
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.
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.
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.
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.
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:
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. 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. 
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). 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. 
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.
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. 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.
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)
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)
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