What is the pathophysiology of pyelonephritis (infection of the renal pelvis and kidney)?

From the Guidelines

Pyelonephritis is a bacterial infection of the kidney and renal pelvis that typically occurs when bacteria from the lower urinary tract ascend to the kidneys, with Escherichia coli (E. coli) being the most common causative organism, accounting for about 80% of cases 1. The infection begins when uropathogens colonize the urethra and bladder, then travel up the ureters to reach the kidneys. These bacteria possess virulence factors like adhesins, which allow them to attach to urinary epithelium, and toxins that damage renal tissue. Once in the kidney, bacteria trigger an inflammatory response with neutrophil infiltration, causing tissue damage and abscess formation. This inflammation leads to the classic symptoms of fever, flank pain, and costovertebral angle tenderness. Risk factors include female anatomy (shorter urethra), urinary tract abnormalities, kidney stones, diabetes, pregnancy, and immunosuppression.

Pathophysiology

• Bacterial ascent from the lower urinary tract to the kidneys
• Colonization of the urethra and bladder by uropathogens
• Attachment to urinary epithelium via adhesins
• Damage to renal tissue by toxins
• Inflammatory response with neutrophil infiltration
• Tissue damage and abscess formation

Diagnosis

• Urinalysis, including assessment of white and red blood cells and nitrite 1
• Urine culture and antimicrobial susceptibility testing
• Evaluation of the upper urinary tract via ultrasound to rule out urinary tract obstruction or renal stone disease
• Additional investigations, such as a contrast-enhanced computed tomography scan, or excretory urography, if the patient remains febrile after 72 h of treatment, or immediately if there is a deterioration in clinical status 1

Treatment

• Fluoroquinolones and cephalosporins are the only antimicrobial agents that can be recommended for oral empiric treatment of uncomplicated pyelonephritis 1
• Intravenous antimicrobial regimen, such as a fluoroquinolone, an aminoglycoside, or an extended-spectrum cephalosporin or penicillin, for patients with uncomplicated pyelonephritis requiring hospitalization 1
• Carbapenems and novel broad-spectrum antimicrobial agents should only be considered in patients with early culture results indicating the presence of multidrug-resistant organisms 1

From the Research

Pathophysiology of Pyelonephritis

The pathophysiology of pyelonephritis involves a bacterial infection of the renal parenchyma, most commonly caused by Escherichia coli 2. The infection typically ascends from the lower urinary tract to the kidneys, where it causes inflammation and damage to the renal tissue.

Causative Pathogens

The most common pathogens responsible for pyelonephritis are:

• Escherichia coli (E. coli) 3, 4, 2, 5, 6
• Klebsiella pneumoniae 3

Antibiotic Resistance

There is a growing concern about antibiotic resistance in the treatment of pyelonephritis, with high resistance rates detected for:

• Cotrimoxazole (55%) 3
• Ciprofloxacin (48%) 3, 6
• Ceftriaxone (34.4%) 3

Treatment Options

Treatment options for pyelonephritis include:

• Extended-spectrum cephalosporins (e.g., ceftriaxone) 3, 4, 5
• Fluoroquinolones (e.g., ciprofloxacin, levofloxacin) 3, 4, 2, 6
• Aminoglycosides (e.g., gentamicin) 2

Clinical Outcomes

Clinical outcomes of patients with pyelonephritis treated with different antibiotics have been compared, with results showing:

• Ceftriaxone was more effective than levofloxacin in terms of microbiological response 3
• No statistically significant difference in clinical cure rates between ceftriaxone and levofloxacin 3, 5
• Ciprofloxacin was effective as an initial empirical antibiotic for treatment of uncomplicated acute pyelonephritis, even in regions with high prevalence of fluoroquinolone resistance 6