Sanjay S. Kasturi, MD
BASICS
DESCRIPTION
• An infectious process that involves the renal pelvis and parenchyma.
– Most often ascending infection from the lower urinary tract.
– It is most often a result of bacterial infection, but fungi, parasites, and viruses may be involved.
• Classified as uncomplicated or complicated (ie, associated with obstruction, anatomic anomaly, or stones) making treatment more difficult.
EPIDEMIOLOGY
Incidence
• Estimated at 15–17 cases per 10,000 females and 3–4 cases per 10,000 males (1).
• At least 250,000 cases of pyelonephritis are diagnosed annually in the United States.
• Highest among young women, then infants, then the elderly.
RISK FACTORS
• Anatomic or functional abnormalities: Incomplete emptying of the bladder→urine is more prone to infection
– Vesicoureteral reflux, neurogenic bladder, BOO
• Foreign body: Acts as a nidus for bacterial colonization and infection
– Calculous disease, medullary sponge kidney
– Indwelling catheters
• Medical conditions: Diabetes mellitus, immunosuppression, alcohol abuse
• Social: Poor perineal hygiene (soiling)
– Variables in sexual behavior (new or multiple partners) and use of spermicide
– Previous episodes of pyelonephritis
Genetics
Related to vesicoureteral reflux
PATHOPHYSIOLOGY
• Women are at increased risk because the female urethra is shorter and in close proximity to the anus, allowing enteric organisms to more easily colonize the urinary tract
• Most common organism are gram-negative rods:
– Escherichia coli accounts for the majority of cases (80% in women, 70% in men)
– Klebsiella pneumoniae is the 2nd most common organism (5–10%)
• Bacteria enter urinary tract:
– Ascending infection: Urethra and bladder
– Results from colonization of the vaginal introitus with fecal flora in females
– Lymphatic and hematogenous dissemination to the kidneys is uncommon
• Bacteria adhere to the urothelium, with subsequent invasion and inflammatory response
– Adhesins and fimbriae: Allow bacteria to adhere to urothelium
– Lipopolysaccharides: Have toxic and inflammatory effects
– Hemolysins: Allow for bacterial invasion by damaging cells
– Aerobacter: Enables bacteria to compete for iron, necessary for aerobic metabolism and reproduction
ASSOCIATED CONDITIONS
See “Risk Factors”
GENERAL PREVENTION
• Eliminate anatomic/functional abnormalities
• Patients with recurrent infections may require low-dose prophylactic antibiotics
• Proper indwelling catheter management
DIAGNOSIS
HISTORY
• Fevers, chills, malaise, nausea, vomiting (2)
• Flank or abdominal pain
• Dysuria, urgency or frequency, gross hematuria
• Prior episodes of UTIs
• History of renal calculi or urinary tract abnormalities
• History of vaginal discharge and irritation makes a urinary source less likely
• History of diabetes, immunosuppression, or alcoholism; recent instrumentation
• Children may present with failure to thrive
PHYSICAL EXAM
• Vital signs for signs of sepsis
• CVA tenderness
• Abdominal distention with decreased bowel sounds may be present
• Pelvic exam in women may help differentiate from gynecologic disease
DIAGNOSTIC TESTS & INTERPRETATION
Lab
• CBC: Leukocytosis with neutrophil predominance (90%)
• Serum chemistry: Renal failure uncommon unless obstruction or sepsis present
• Blood culture: 12% of hospitalized pyelonephritis patients will have bacteremia
• Pregnancy test in women
• Urinalysis: Pyuria >5–10 WBCs/HPF:
– WBC casts indicate renal source of infection
– Hematuria and bacteria may be present
– Leukocyte esterase often positive, but nitrite may not be positive with staph or enterococci
• Gram stain urine may rapidly identify organism
• Urine culture: Positive with >100,000 bacteria/mL and identifies causative organism; 10,000 bacteria/mL suggests acute pyelonephritis in patients with catheterized urine samples
• Newer data suggests that urinary cultures may be negative especially if patients were started on antibiotics prior to presentation
Imaging
• In uncomplicated acute pyelonephritis, imaging studies are unnecessary; however, the combination of fever and flank pain especially with elevated WBC count requires imaging to rule out ureteral obstruction, which, with fever and infection, is a surgical emergency (3)
• Failure to respond to appropriate therapy within 72 hr requires radiographic evaluation to rule out obstruction, abscess, or other abnormalities
• Pediatric patients are at risk of scarring and should undergo imaging
• Abdominal x-ray (KUB): Evaluate for renal or ureteral calculi
– Intraparenchymal gas: Emphysematous pyelonephritis
– Renal shadow may be enlarged and poorly defined secondary to parenchymal edema
• IVP/ExU: 75% of patients with uncomplicated acute pyelonephritis will have a normal ExU
– ExU shows an enlarged kidney (>15 cm in length or 1.5 cm greater than the unaffected side with decreased nephrogram and delayed excretion)
– Cortical striations may be seen
– Focal enlargement of the kidney is consistent with focal bacterial nephritis, or acute lobar nephronia may be confused with tumor or abscess
– Nonobstructive dilation of the renal pelvis and ureter may be present (endotoxins impair ureteral peristalsis)
• US: Renal enlargement with hypoechoic parenchyma and loss or corticomedullary differentiation
– Noninvasive; no ionizing radiation
• CT: Noncontrast CT of the abdomen reveals an enlarged kidney with decreased attenuation of parenchyma, and perinephric fat stranding
– Contrast administration shows delayed enhancement with delayed excretion
• Radionuclide scan: Cortical agents (eg, DMSA) reveal decreased activity in the affected kidney; Useful to identify areas of scarring
Diagnostic Procedures/Surgery
Determine postvoid residual if indicated.
Pathologic Findings
• Gross: Edematous kidney with multiple foci of inflammation
• Microscopic: Focal areas of destruction of renal architecture with lymphocytic infiltrations
DIFFERENTIAL DIAGNOSIS
• Any intra-abdominal inflammatory process
– Appendicitis, cholecystitis, diverticulitis, pancreatitis, peptic ulcer disease
• Gynecologic conditions:
– Pelvic inflammatory disease, ectopic pregnancy, ruptured ovarian cysts
• Urologic conditions:
– Renal colic with fever
– Renal and perinephric abscesses
• Lower lobe pneumonia
• Musculoskelet al pain
TREATMENT
GENERAL MEASURES
• Supportive care consists of hydration, antipyretics, and analgesics
• Empiric antibiotics that are active against the possible causative organisms and achieve adequate levels in the renal parenchyma and urine are used
MEDICATION
First Line
• Outpatient therapy: In uncomplicated acute pyelonephritis, those who are reliable, tolerate oral intake, and do not have signs of sepsis do not require hospitalization (4,5)
– Oral fluoroquinolones (ciprofloxacin 500 mg PO BID, or levofloxacin 750 mg/d PO) are adequate for empiric treatment. Levofloxacin is approved for a 5-day regimen
– An alternative: Trimethoprim–sulfamethoxazole
– Traditionally, continue therapy for 10–14 days. Recent data shows a 7-day course of ciprofloxacin is not inferior to a 14-day 1 in women with uncomplicated acute pyelonephritis
– Recent data suggests increased quinolone resistance as well as susceptibility to TMP-SMZ
• Inpatient therapy: If signs of sepsis, bacteremia, or cannot tolerate oral medications
– Also recommended for children, the elderly, pregnant patients, diabetics, and the immunocompromised and with complicated pyelonephritis
– Parenteral antibiotic therapy uncomplicated
Ampicillin (2 g IV q6h) and gentamicin (1.5 mg/kg IV q8h) is traditional treatment; OR
Ceftriaxone (1 g/d IV) empirically; OR
IV fluoroquinolones ciprofloxacin 400 mg q12h or levofloxacin 750 mg q24h; aztreonam is also an acceptable alternative
– Most patients continue to have fever or flank pain for several days after appropriate therapy has been started.
– IV therapy continued until the patient is afebrile or cultures indicate another appropriate antibiotic.
– When able to tolerate oral intake, switch to an oral antibiotic as for oral therapy above.
– Pregnant patients: Place on suppression therapy (eg, nitrofurantoin 100 mg/d PO, cephalexin 250 mg/d PO) after treatment until delivery, due to a relapse rate of up to 60% in nonsuppressed patients.
– Patients with a delayed response to therapy should be treated with a longer course of antibiotics (14–21 days), even without evidence of complicated disease.
• Complicated pyelonephritis: Assess for underlying urologic abnormalities (obstruction, stones, etc.) (6)
– Parenteral antibiotic therapy in complicated cases:
Piperacillin–tazobactam 3.375 g q6h, ticarcillin–clavulanate 3.1 g q6h, cefepime 1 g q12h
Alternates include meropenem, and imipenem. Dose-adjust with renal failure.
– After transitioning to species-specific antibiotics, PO continued for 14–21 days
• Pregnancy considerations:
– Ampicillin, amoxicillin and, PO cephalosporins have proven to be safe; amoxicillin/clavulanic acid (Augmentin) is recommended for resistant organisms; nitrofurantoin is safe for the fetus but potentially toxic to the mother; fluoroquinolones should be avoided in pregnancy
SURGERY/OTHER PROCEDURES
• Diversion with indwelling stent or percutaneous drain may be necessary in patients with urinary obstruction.
• If a renal abscess forms:
– 3–5 cm in size then place percutaneous drain
– >5 cm may require more than 1 percutaneous drain or surgical drainage
ONGOING CARE
PROGNOSIS
With 1st episode of acute pyelonephritis, 1-yr risk of a 2nd episode was 9.2% in females and 5.7% in males. With a 4th episode, the risk of a 5th infection was 50% for females and males.
COMPLICATIONS
• Short term:
– Septic shock
– Abscess formation (corticomedullary, perinephric)
– Papillary necrosis
• Long term: Renal scarring (20%)
• Children with developing kidneys are at significant risk of scarring from even 1 episode of acute pyelonephritis
• Diabetics are at significant risk of developing emphysematous pyelonephritis, a more fulminant process with a high mortality:
– Characterized by renal intraparenchymal gas and detectable on KUB
• Patients with calculi or urinary tract obstruction who have recurrent episodes of pyelonephritis may develop xanthogranulomatous pyelonephritis:
– Characterized by large nonfunctioning renal mass
– Stones are present in 80% of cases
• Pregnant patients are at high risk because of the physiologic changes of pregnancy to the urinary tract:
– Sepsis
– Adult respiratory distress syndrome
– Preterm delivery with low–birth-weight infants
FOLLOW-UP
Patient Monitoring
• Urine cultures 4–6 wk after completion of antibiotics to verify infection cleared
• 10–30% suffer a relapse and may be treated with a 2nd 14-day course of antibiotics
• Occasionally, a 6-wk course needed for cure
• Confirm hematuria clears if initially present
Patient Resources
http://kidney.niddk.nih.gov/kudiseases/pubs/pyelonephritis/
REFERENCES
1. Czaja CA, Scholes D, Hooton TM, et al. Population-based epidemiologic analysis of acute pyelonephritis. Clin Infect Dis. 2007;45:273–280.
2. Hooton TM, Stamm WE. Diagnosis and treatment of uncomplicated urinary tract infection. Infect Dis Clin North Am. 1997;11:551–581.
3. Piccoli GB, Consiglio V, Deagostini MC, et al. The clinical and imaging presentation of acute “non complicated” pyelonephritis: A new profile for an ancient disease. BMC Nephrol. 2011;12:68.
4. Warren JW, Abrutyn E, Hebel JR, et al. Guidelines for antimicrobial treatment of uncomplicated acute bacterial cystitis and acute pyelonephritis in children. Clin Infect Dis. 1999;29:745–758.
5. Sandberg T, Skoog G, Hermansson AB, et al. Ciprofloxacin for 7 days versus 14 days in women with acute pyelonephritis: A randomised, open-label and double-blind, placebo-controlled, non-inferiority trial. Lancet. 2012;380(9840):484–490.
6. Siegel J, Smith A, Moldwin R. Minimally invasive treatment of renal abscess. J Urol. 1996;155:52–55.
ADDITIONAL READING
Hooton TM. Clinical practice. Uncomplicated urinary tract infection. N Engl J Med. 2012;366(11):1028–1037.
See Also (Topic, Algorithm, Media)
• Pyelonephritis, Acute, Adult Image 
• Pyelonephritis, Chronic
• Pyelonephritis, Emphysematous
• Pyelonephritis, Xanthogranulomatous
• Urinary Tract Infection (UTI), Adult Female
• Urinary Tract Infection (UTI), Adult Male
• Urinary Tract Infection (UTI), Pediatric
CODES
ICD9
• 041.49 Other and unspecified Escherichia coli [E. coli]
• 590.10 Acute pyelonephritis without lesion of renal medullary necrosis
• 593.73 Other vesicoureteral reflux with reflux nephropathy NOS
ICD10
• B96.20 Unsp Escherichia coli as the cause of diseases classd elswhr
• N10 Acute tubulo-interstitial nephritis
• N13.729 Vesicoureter-reflux w reflux nephropathy w/o hydrourt, unsp
CLINICAL/SURGICAL PEARLS
• Urine cultures may be negative in patients especially if started on recent antibiotics.
• If fevers last for more than 72 hr after antibiotics, obtain at CT scan to rule obstruction, soft tissue infection, or abscess formation.