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Pyelonephritis is an ascending urinary tract infection that has reached thepyelum (pelvis) of the kidney (nephros in Greek). If the infection is severe, the term urosepsis is used interchangeably (sepsis being a systemic inflammatory response syndrome due to infection). It requires antibiotics as therapy, and treatment of any underlying causes to prevent recurrence. It is a form of nephritis. It can also be calledpyelitis. It presents with dysuria (painful voiding of urine), abdominal pain (radiating to the back on the affected side) and tenderness of the bladder area and the side of the involved kidney (costovertebral angle tenderness) which may be elicited by performing the kidney punch. In many cases there are systemic symptoms in the form of fever, rigors (violent shivering while the temperature rises), headache, and vomiting. In severe cases, delirium may be present. Severe cases of pyelonephritis lead to sepsis, a systemic response to infection characterized by fever, a raised heart rate, rapid breathing and decreased blood pressure (occasionally leading to septic shock). When pyelonephritis or other urinary tract infections lead to sepsis, it is termedurosepsis.

Diagnosis

The presence of nitrite and leukocytes (white blood cells) on a urine dipstick test in patients with typical symptoms are sufficient for the diagnosis of pyelonephritis, and are an indication for empirical treatment. Formal diagnosis is with culture of the urine; blood cultures may be needed if the source of the infection is initially doubtful. If a kidney stone is suspected (e.g. on the basis of characteristic colicky pain, disproportionate amount of blood in the urine), X-rays of the kidneys, ureters and bladder (KUB) may assist in identifying radioopaque stones. In patients with recurrent ascending urinary tract infections, it may be necessary to exclude an anatomical abnormality, such as vesicoureteral reflux (urine from the bladder flowing back into the ureter) or polycystic kidney disease. Investigations that are commonly used in this setting are ultrasound of the kidneys or voiding cystourethrography.

Causes

Most cases of community-acquired pyelonephritis are due to bowel organisms that enter the urinary tract. Common organisms areE. coli (70-80%) andEnterococcus faecalis. Hospital-acquired infections may be due to coliforms and enterococci, as well as other organisms uncommon in the community (e.g. Klebsiella spp.,Pseudomonas aeruginosa). Most cases of pyelonephritis start off as lower urinary tract infections, mainly cystitis and prostatitis. Risk is increased in the following situations:
  1. Mechanical: any structural abnormalities to the kidneys and the urinary tract, vesicoureteral reflux (VUR) especially in young children, calculi (kidney stones), urinary tract catheterisation, urinary tract stents or drainage procedures (e.g. nephrostomy), pregnancy, neurogenic bladder (e.g. due to spinal cord damage, spina bifida or multiple sclerosis) and prostate disease (e.g. benign prostatic hyperplasia) in men
  2. Constitutional: diabetes mellitus, immunocompromised states
  3. Behavioural: change in sexual partner within the last year, spermicide use
  4. Positive family history (close family members with frequent urinary tract infections)

Pathology

Acute pyelonephritis is anexudative purulent localized inflammation of the renal pelvis (collecting system) and kidney. The renal parenchyma presents in the interstitium abscesses (suppurative necrosis), consisting in purulent exudate (pus): neutrophils, fibrin, cell debris and central germ colonies (hematoxylinophils). Tubules are damaged by exudate and may contain neutrophil casts. In the early stages, glomeruli and vessels are normal. Gross pathology often reveals pathognomonic radiations of hemorrhage and suppuration through the renal pelvis to the renal cortex. Chronic infections can result in fibrosis and scarring. Xanthogranulomatous pyelonephritis is a form of chronic pyelonephritis associated with granulomatous abscess formation and severe kidney destruction.

Treatment

As practically all cases of pyelonephritis are due to bacterial infections, antibiotics are the mainstay of treatment. Mild cases may be treated with oral therapy, but generally intravenous antibiotics are required for the initial stages of treatment. The type of antibiotic depends on local practice, and may include fluoroquinolones (e.g. ciprofloxacin), beta-lactam antibiotics (e.g. amoxicillin or a cephalosporin), trimethoprim (or co-trimoxazole). Aminoglycosides are avoided due to their toxicity, but may be added for a short duration. All acute cases with spiking fevers and leukocytosis should be admitted to the hospital for IV fluids hydration and IV antibiotic treatment immediately. ciprofloxacin IV 400mg every 12 hours is the first line treatment of choice. Alternatively, ampicillin IV 2g every 6 hours plus gentamicin IV 1mg/kg every 8 hours also provide excellent coverage. If the patient is pregnant, ampicillin/gentamicin combination is the treatment of choice, as ciprofloxacin is contraindicated. During the course of antibiotic treatment, serial white blood count and temperature should be closely monitored. Typically, the IV antibiotics should be continued till the patient is afebrile for at least 24 to 48 hours, then equivalent oral antibiotic agents can be given for a total of 2-week duration of treatment. If the patient is unwell and septic, intravenous fluids may be administered to compensate for the reduced oral intake, insensible losses (due to the raised temperature) and vasodilation and to maximize urine output. In recurrent infections, additional investigations may identify an underlying abnormality. Occasionally, surgical intervention is necessary to reduce chances of recurrence. If no abnormality is identified, some studies suggest long-term preventative (prophylactic) treatment with antibiotics, either daily or after sexual intercourse. In children at risk of recurrent UTIs, meta-analysis of the present literature indicates that not enough studies have been performed to conclude prescription of long-term antibiotics have a net positive benefit. Ingestion of cranberry juice has been studied as a prophylactic measure; while studies are heterogeneous, many suggest a benefit. Some recommend other nutritional approaches to prevent recurrence of UTIs. Increasing fluid intake, consuming cranberry juice, blueberry juice, and fermented milk products containing probiotic bacteria, have been shown to inhibit adherence of bacteria to the epithelial cells of the urinary tract.

Epidemiology

Pyelonephritis is very common, with 12-13 cases annually per 10,000 population in women and 3-4 cases per 10,000 in men. Young women are most likely to be affected, traditionally reflecting sexual activity in that age group. Infants and the elderly are also at increased risk, reflecting anatomical abnormalities and hormonal status.