Acute Pyelonephritis

Definition

• Robbins & Kumar Basic Pathology

Pathogenesis & Routes of Infection

• Enteric bacteria colonize the distal urethra and perineum
• Bacteria ascend to the bladder (facilitated by instrumentation, catheterization, or sexual intercourse)
• An incompetent vesicoureteral valve allows reflux up the ureter
• Intrarenal reflux then seeds the renal parenchyma
• Women are disproportionately affected due to the short urethra and proximity of the urethral meatus to the rectum

• Secondary to bacteremia, sepsis, or endocarditis
• Common agents: Staphylococcus, E. coli
• Produces multifocal cortical abscesses
• Robbins & Kumar Basic Pathology; Campbell Walsh Wein Urology

Predisposing Factors

Microbiology

• E. coli - by far the most common (~80%), possesses special virulence factors (P pili, K antigens, endotoxin, type 1 fimbriae)
• Proteus, Klebsiella, Enterobacter, Pseudomonas - in complicated cases, recurrent UTIs, hospitalized patients, catheterized patients
• Enterococcus faecalis, S. epidermidis, S. aureus - gram-positives (less common)

• Campbell Walsh Wein Urology

Morphology (Pathology)

• Pyonephrosis - when obstruction prevents pus drainage, filling the renal pelvis and calyces
• Perinephric abscess - extension through the renal capsule into perinephric fat
• Papillary necrosis - ischemic/suppurative necrosis of papillae; seen in diabetics, patients with urinary obstruction, and sickle cell anemia
• Robbins & Kumar Basic Pathology

Clinical Presentation

• Classic triad: Abrupt onset of fever (≥38.0°C/100.3°F), chills, and unilateral or bilateral flank pain / costovertebral angle (CVA) tenderness
• Lower urinary tract symptoms (dysuria, frequency, urgency) may or may not be present
• Nausea, vomiting, and diarrhea can simulate a GI presentation
• Asymptomatic progression is possible, especially in immunocompromised patients
• Acute renal failure is rare but can occur

Note: PID is frequently misdiagnosed as acute pyelonephritis. A pelvic exam is warranted when STI risk factors are present.

• Campbell Walsh Wein Urology; Textbook of Family Medicine 9e

Diagnosis

Urinalysis

• Pyuria - numerous WBCs, often in clumps
• WBC casts - nearly pathognomonic when combined with fever and flank pain
• Bacteriuria (rods or cocci chains on microscopy)
• Mild proteinuria and hematuria are common

Urine Culture

• Always obtain before starting antibiotics
• Guides therapy if initial empiric treatment fails
• Nitrite dipstick lacks sensitivity and does not identify the organism

Blood Tests

• Leukocytosis with neutrophilia
• Elevated CRP and ESR
• Elevated creatinine if renal failure is present

Blood Cultures

• Positive in ~25% of cases
• Not routinely required for uncomplicated pyelonephritis in women
• Should be obtained in: men, pregnant women, those with systemic toxicity, hospitalized patients

Imaging

• Ultrasound - focal parenchymal swelling, increased or decreased echogenicity; useful to exclude obstruction/stones
• CT (contrast) - gold standard for complicated cases; shows focal swelling with diminished, inhomogeneous contrast enhancement; can detect abscesses, gas, and obstruction
• MRI - focal swelling and restricted diffusion on DWI
• Campbell Walsh Wein Urology

Management

Classification for Management

Antibiotic Regimens (per IDSA / Campbell Walsh Wein)

• Fluoroquinolones: first-line only if local resistance is <10%
• TMP-SMX: use only if the causative organism is known susceptible; otherwise, precede with one-time IV ceftriaxone 1 g

• Transition to oral therapy once afebrile and clinically stable
• Total duration: 10-14 days for hospitalized patients

• Parenteral: ampicillin + gentamicin, or aztreonam
• Oral: cephalexin 500 mg q6h for 10-14 days (fluoroquinolones and TMP-SMX avoided in pregnancy)

Indications for Hospitalization

• Severe sepsis
• Inability to tolerate oral fluids/medications
• Diagnostic uncertainty
• Failure to improve on outpatient therapy within 48-72 hours
• Pregnancy with significant illness

Subsequent / Follow-up Management

• Even with successful treatment, fever and flank pain may persist for several days
• Urine culture: repeat 4 days on therapy, and 10 days after completing antibiotics
• If no improvement within 72 hours: re-culture, adjust antibiotics, obtain imaging (CT preferred)
• If obstruction or abscess found: drainage via ureteral stent or percutaneous nephrostomy

Differential Diagnosis

• Acute appendicitis (right-sided; normal urinalysis)
• Acute diverticulitis
• Pancreatitis
• Ovarian pathology / PID
• Herpes zoster (dermatomal pain without urinary symptoms)
• Renal colic (colicky pain, hematuria, no fever typically)

Complications

• Renal abscess / perinephric abscess
• Pyonephrosis (obstructed infected kidney)
• Papillary necrosis (diabetics, sickle cell, obstruction)
• Gram-negative sepsis / septic shock
• Chronic pyelonephritis and renal scarring (especially with VUR in children)
• Acute kidney injury (rare; more common with bilateral involvement or solitary kidney)

Special Populations

• Children: VUR is the major predisposing factor; renal scarring (reflux nephropathy) is a key long-term concern
• Pregnant women: Carries risk of preterm labor and maternal sepsis; all cases warrant hospitalization
• Diabetics: Higher risk of emphysematous pyelonephritis, fungal infection, and papillary necrosis
• Immunocompromised: May present atypically or asymptomatically; higher risk of complicated course