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PYELONEPHRITIS


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.


RISK FACTORS AND MAJOR FINDINGS OF PYELONEPHRITIS

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.

PATHOLOGY OF ACUTE PYELONEPHRITIS

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.