Pyelonephritis

• Definition:
Pyelonephritis is an inflammatory condition affecting the renal
tubules, interstitium, and renal pelvis. It is one of the most common
diseases of the kidney.
Types of Pyelonephritis:
• Acute Pyelonephritis:
• Typically caused by bacterial infection.
• Often associated with urinary tract infections (UTIs).
• Leads to suppurative inflammation of the kidney.
• Chronic Pyelonephritis:
• More complex; repeated bacterial infections are involved.
• Commonly associated with:
• Vesicoureteral reflux (VUR)
• Urinary tract obstruction
Etiology and Pathogenesis
• Causative Organisms:
• >85% of UTIs are caused by gram-negative bacilli from the intestinal
flora.
• Most common: Escherichia coli
• Others: Proteus, Klebsiella, Enterobacter
• Also possible: Streptococcus faecalis, Staphylococci, fungi, and mycobacteria.
• Immunocompromised patients (e.g., transplant recipients):
• May develop renal infections due to viruses like polyomavirus, CMV,
or adenovirus.
Pathways of Infection
• Hematogenous Spread (Less Common)
• Bacteria spread via bloodstream to kidneys.
• Common in:
• Septicemia
• Localized infections (e.g., infective endocarditis)
• Patients with ureteral obstruction or immunosuppression
• Typical organisms: Staphylococcus, E. coli, fungi, viruses
• Ascending Infection (Most Common)
• Begins from distal urethra and ascends to the kidneys.
• Associated with:
• Instrumentation (e.g., catheterization)
• Anatomical or functional anomalies
 Mechanism of Ascending Infection
• A. Colonization
• Colonization of distal urethra and vaginal introitus by coliforms (especially in females)
• Influenced by:
• Bacterial adhesins (P-fimbriae) binding to urothelial receptors
• B. Entry to Bladder
• Occurs during:
• Urethral instrumentation
• Catheterization (especially long-term)
• Females are more vulnerable due to:
• Shorter urethra
• Lack of antibacterial prostatic secretions
• Hormonal influences
• Sexual trauma
Predisposing Factors for Kidney Involvement

• 1. Urinary Tract Obstruction & Urine Stasis

• Causes: BPH, tumors, stones, diabetes, neurogenic bladder
• Consequences:
• Incomplete emptying → residual urine → bacterial multiplication
• 2. Vesicoureteral Reflux (VUR)
• Dysfunctional ureterovesical junction allows retrograde urine flow
• Causes:
• Congenital shortening/absence of intravesical ureter
• Acquired from bladder infections
• Estimated incidence: 1–2% in normal children
• In adults: Caused by bladder atony (e.g., spinal cord injury)
• 3. Intrarenal Reflux
• Mechanism: Refluxed urine enters renal papillae and parenchyma
• Most common at:
• Upper and lower poles of kidney (flattened or concave papillae)
• Diagnosis: Voiding cystourethrography (VCUG)
• Shows reflux in ~30% of infants/children with UTI
• Without VUR → infection usually limited to bladder (no pyelonephritis)
Acute Pyelonephritis
• A suppurative inflammation of the kidney caused by:
• Bacteria (most common)
• Occasionally viruses (e.g., polyomavirus)
• Routes:
• Hematogenous (less common)
• Ascending infection (via ureter with VUR) – most common
MORPHOLOGY
• Hallmark Features
• Patchy interstitial suppurative inflammation
• Intratubular aggregates of neutrophils
• Neutrophilic tubulitis
• Tubular injury
• 🧪 Spread of Infection:
• Initially confined to tubules, using the tubular lumen as a conduit.
• Later, infection extends into the interstitium, causing abscesses and tubular destruction.
• Glomeruli are relatively resistant, but:
• Extensive infection or fungal pyelonephritis (e.g., Candida) can destroy glomeruli.
• Fungal infections → granulomatous interstitial inflammation.
Complications of Acute Pyelonephritis

• 1. Papillary Necrosis
• Seen in:
• Diabetics
• Sickle cell disease
• Urinary tract obstruction
• Usually bilateral, but can be unilateral.
• Affects tips/distal 2/3 of renal pyramids
• Gross: Gray-white to yellow necrosis on cut surface.
• Microscopy: Ischemic coagulative necrosis with preserved tubular outlines; leukocyte response only at
viable tissue borders.
• 2. Pyonephrosis
• Occurs with complete/almost complete urinary obstruction, especially high in the tract.
• Suppurative exudate fills the renal pelvis, calyces, and ureter.
• 3. Perinephric Abscess
• Infection extends through the renal capsule into the perinephric tissue.
Risk Factors
• Urinary tract obstruction (congenital or acquired)
• Instrumentation (e.g., catheterization)
• Vesicoureteral reflux
• Pregnancy:
• 4–6% develop bacteriuria
• 20–40% of these progress to symptomatic UTI if untreated
• Gender & Age:
• Women: Common between infancy and ~40 years
• Men: Increased risk in elderly (due to BPH and instrumentation)
• Pre-existing renal lesions
• Diabetes mellitus:
• ↑ infection risk
• Neurogenic bladder
• Frequent instrumentation
• Immunosuppression or immunodeficiency
Symptoms
• Sudden onset of:
• Fever
• Malaise
• Costovertebral angle pain
• Irritative bladder symptoms:
• Dysuria
• Frequency
• Urgency
• Urine findings:
• Pyuria (↑ WBCs): Not specific for upper/lower tract infection
• Leukocyte casts (WBC casts): Specific for renal involvement
• Diagnosis: Quantitative urine culture
Parenteral Antibiotic Regimens for
Acute Uncomplicated Pyelonephritis
Drug Dose (mg) Interval
Ceftriaxone 1000–2000 mg Every 24 hours
Cefepime 1000–2000 mg Every 12 hours
Fluoroquinolones
• Ciprofloxacin † 200–400 mg Every 12 hours
• Levofloxacin † 250–750 mg Every 24 hours
Gentamicin† 3–5 mg/kg body weight Every 24 hours
• (low-dose option) 1 mg/kg body weight Every 8 hours
Ampicillin (+ gentamicin†) 1000 mg Every 6 hours

Trimethoprim-sulfamethoxazole† 160/800 mg Every 12 hours

Aztreonam 1000 mg Every 8–12 hours

Piperacillin-tazobactam 3375 mg Every 6–8 hours
Imipenem-cilastatin†,‡ 250–500 mg Every 6–8 hours
Meropenem‡ 500 mg Every 8 hours
Ertapenem‡ 1000 mg Every 24 hours
Ceftolozane/tazobactam 1500 mg Every 8 hours
Ceftazidime/avibactam 2500 mg Every 8 hours
Vancomycin§ 1000 mg Every 12 hours
Oral Antibiotic Regimens for
Acute Uncomplicated
Pyelonephritis
Drug
Fluoroquinolones
Dose (mg) Interval Comments

Use only when pathogen is known to be susceptible.

• Ciprofloxacin 500 mg Every 12 hours (q12h) Can be combined with a broad-spectrum agent
if Enterococcus coverage is needed. Avoid in
pregnancy, breastfeeding, and <18 years.

• Ciprofloxacin XR 1000 mg Every 24 hours (q24h) Same comments as above.

• Levofloxacin 250–750 mg Every 24 hours (q24h) Preferred for empiric treatment, but same precautions
as above.

Use only when pathogen is susceptible. If used in

Trimethoprim-sulfamethoxazole (TMP-SMX) 160/800 mg Every 12 hours (q12h) pregnancy (off-label), avoid during 1st trimester.

Cefpodoxime proxetil 200 mg Every 12 hours (q12h) Limited data; use only when pathogen is susceptible.

Limited data; use only when pathogen is known to be

Amoxicillin-clavulanate 500/125 to 875/125 mg Every 12 hours (q12h)
susceptible.