Pyelonephritis

This is infection within the renal pelvis, usually accompanied by infection within the renal parenchyma.¹ The source of sepsis is often ascending infection from the bladder but haematogenous spread can also occur. The usual organisms are the same as for lower urinary tract infection (e.g. Escherichia coli, Klebsiella spp; Proteus spp; Enterococcus spp.). Repeated attacks of acute pyelonephritis can lead to chronic pyelonephritis.

Incidence

Acute pyelonephritis can occur at any age. In neonates it is 1.5 times more common in boys and tends to be associated with abnormalities of the renal tract. Uncircumcised boys tend to have a higher incidence than circumcised boys.² Beyond that age girls have a 10-fold higher incidence. In adult life it reflects the incidence of urinary tract infection (UTI) in that it is much more common in young women. Over 65 the incidence in men rises to match that of women.

Risk factors¹

These include:

• Structural renal abnormalities
• Calculi and urinary tract catheterisation
• Stents or drainage procedures
• Pregnancy
• Diabetes
• Primary biliary cirrhosis
• Immunocompromised patients
• Neuropathic bladder

Presentation³

Onset is usually rapid with symptoms appearing over a day or two. There is unilateral or bilateral loin pain, suprapubic or back pain. Fever is variable but can be high enough to produce rigors. Malaise, nausea, vomiting, anorexia and occasionally diarrhoea occur. There may or may not be accompanying lower urinary tract symptoms with frequency, dysuria, gross haematuria or hesitancy. Gross haematuria occurs in 30 to 40% of young women. The patient looks ill and there is commonly pain on firm palpation of one or both kidneys and moderate suprapubic tenderness without guarding.

Presentation in children, especially when small, can be much less specific and culture of urine should be a routine investigation in pyrexial and unwell infants.⁴

Differential diagnosis

• Abdominal abscess
• Abdominal aortic aneurysm
• Appendicitis
• Causes of acute abdomen
• Causes of loin pain
• Diverticulitis
• Ectopic pregnancy
• Endometritis
• Epididymitis
• Interstitial cystitis
• Nephrocalcinosis
• Nephrolithiasis
• Oophoritis
• Papillary necrosis
• Pelvic inflammatory disease
• Prostatitis
• Renal corticomedullary abscess
• Renal vein thrombosis
• Salpingitis
• Sexually transmitted infections
• Ureteropelvic junction obstruction
• Urethritis
• Vesicoureteral reflux
• Vesicovaginal and ureterovaginal fistula

Investigations^3,5

• Urinalysis: the urine is often cloudy with an offensive smell. It may be positive on dipstick urinalysis for blood, protein, leucocyte esterase and nitrite. A mid-stream specimen of urine (MSU) should be sent off for microscopy and culture, although there is often poor correlation between symptoms and bacteriuria. A catheter specimen will be acceptable if a catheter is in situ and special arrangements may be needed for collecting a sample from a child (e.g. peroneal bag, suprapubic aspiration). Microscopy of urine shows pyuria.
• Inflammatory markers: C-reactive protein (CRP), erythrocyte sedimentation rate (ESR), plasma viscosity are raised. One study found that if a dimercaptosuccinic acid scintigraphy (DMSA scan) is not available (see below), it is reasonable to treat a febrile UTI as acute pyelonephritis if the CRP is >66.4 mg/L in a patient with >2 days of fever or if the CRP is >27.3 mg/L in a patient febrile for ≤2 days.⁶
• Full blood count: this shows elevated white cell count with neutrophilia.
• Blood cultures: these are positive in approximately 12-20% of patients with pyelonephritis.
• Imaging:
  • Ultrasound is first-line in all patients with recurrent pyelonephritis and may help to identify obstruction or stones.
  • Contrast-enhanced helical/spiral CT scan (CECT) is the best investigation in adults where diagnosis is in doubt or deterioration occurs.
  • DMSA scan is preferred in children where making the diagnosis is often more difficult.⁷
• The Fairley test: this is used to determine whether infection is confined to the bladder or has spread to the kidneys. Perform a bladder washout with neomycin and fibrinolytic enzymes. Then take urine culture immediately and at 10, 20 and 30 minutes. With isolated bladder infection, bacteriuria returns slowly. With kidney infection, bacteriuria appears rapidly. This test is not often used and tends to be limited to those with neurogenic bladder. Even then, it is thought to be fairly limited, although the washout itself may be beneficial from a therapeutic point of view.⁸

Management³

• Support: rest, adequate fluid intake and analgesia are important.
• Hospital admission: many patients can be managed in the community providing they are otherwise healthy. Guidelines generally recommend admission for pregnant women, although the few randomised trials which exist suggest that outpatient treatment is safe.⁸ Indications for admission include:
  • Severe vomiting
  • Co-morbidity such as diabetes
  • Signs of sepsis (e.g. tachypnoea, tachycardia, hypotension)
  • Dehydration
  • Severe pain or debility
  • Failure of response to treatment in primary care
  • Urinary tract obstruction
  • Oliguria or anuria
  • Suspected complications (see below)
  • Uncertain diagnosis
  • Social issues
  • Non-concordance with treatment
  • Inadequate access to follow-up
  • Relapse of symptoms as soon as antibiotics stopped
• Antibiotics:¹ start empirical antibiotic treatment whilst awaiting culture and sensitivity. For adults, the Health Protection Agency recommends ciprofloxacin for seven days (adult dose 250-500 mg PO bd) or co-amoxiclav for 14 days (adult dose 500 mg bd PO or 250 mg PO 8-hrly). Local protocols may suggest other antibiotics and should be followed, as resistance patterns may vary.
  There is a theoretical concern that children who are not treated with early intravenous antibiotics could develop renal scarring. A Cochrane review found that children with acute pyelonephritis can be treated effectively with oral cefixime or with short courses (2-4 days) of intravenous (IV) therapy followed by oral therapy.⁹ If IV therapy is chosen, a broad spectrum cephalosporin is used and single daily dosing with aminoglycosides added if there is no improvement. One study found that early switching from IV to oral therapy did not compromise recovery in patients hospitalised with acute pyelonephritis.¹⁰ There is no consensus regarding duration of treatment and one meta-analysis comparing short-course (7- to 14-day) with long-course (14- to 42-day) treatment with the same antibiotic regimens found no difference in effectiveness or tolerability.¹¹ Further research is required on this issue, as well as trials to establish which antibiotics would be appropriate for initial therapy.
• Surgery: this may be required to drain renal or periphrenic abscesses, or to relieve obstructions causing the infection (e.g. stones).

Complications

These occur more often in patients with diabetes mellitus, chronic renal failure, sickle cell disease, renal transplant (especially first 3 months), AIDS and other immunocompromised states. They include:

• Septicaemia
• Perinephric abscess (more common if urinary tract abnormality)
• Renal abscess, including emphysematous pyelonephritis (rare, life-threatening form with tissue necrosis and accumulation of gas in renal parenchyma, perinephric space and collecting systems - particularly occurs in obese, elderly diabetic women with urinary tract obstruction)
• Acute papillary necrosis is more likely in the elderly and those with diabetes (suggested by associated symptoms of renal colic)
• Pregnancy - tends to produce a more complicated course with significant risk of premature labour
• Pyelonephritis more likely to scar the kidney of a growing child

Prognosis³

Premature labour can occur in pregnant women. Most other patients have an uncomplicated recovery, providing there are no significant co-morbidities.

Prevention

Consider prophylactic treatment in women with at least 3 symptomatic infections a year. Trimethoprim is widely used.³ One study in infants with primary urinary tract infection found that intravenous antibiotic for 1 week followed by 3 weeks of the same oral antibiotic provided good prophylaxis against uncomplicated pyelonephritis.¹²

This produces characteristic scarring on kidney and occurs after recurrent or persistent infections.

Risk factors

• Any structural renal tract anomalies, obstruction or calculi
• Children with vesicoureteral reflux

Presentation

• Fever
• Malaise
• Loin pain
• Nausea
• Vomiting
• Dysuria
• Hypertension
• Failure to thrive

Investigations

• Urine microscopy, culture and sensitivity: this may be helpful in identifying the organism involved but negative urine culture does not exclude diagnosis.
• Imaging:
  • Intravenous pyelogram (IVP) may show small kidneys, ureteric and caliceal dilatation/blunting with cortical scarring.
  • Voiding cystourethrogram (VCUG) may help to identify reflux.
  • Ultrasound and KUB X-ray may show stones but are not sensitive for reflux nephropathy.
  • Technetium-99 DMSA scan may show renal scars.¹⁴

Management¹³

• Blood pressure should be controlled to slow the progression of renal failure. Ideally angiotensin-converting enzyme (ACE) inhibitors should be used.
• Supervening UTI may require lengthier courses of antibiotics than are normally given.
• Underlying vesicoureteral reflux diagnosed in children should be treated with antibiotics prophylactically until puberty or until the reflux resolves (see Prevention).
• Surgical reimplantation of the ureters may be needed in severe cases but in most cases surgical management is not superior to medical.
• Renal failure may eventually require renal transplantation.¹⁵

Complications¹³

• Progressive renal scarring with reflux nephropathy and renal failure
• Secondary hypertension
• Pyonephrosis
• Focal glomerulosclerosis
• Urea splitting organisms can lead to staghorn calculi - usual culprit is Proteus spp.

Prognosis¹⁴

2% of children with vesicoureteral reflux develop renal failure and 5-6% can have long-term complications such as hypertension. One study found that 15% of a patient sample requiring a transplant had a preceding diagnosis of chronic pyelonephritis.¹⁵

Prevention¹⁴

• On the assumption that most pyelonephritis is caused by ascending infection its prevention is based on preventing UTI. If children have structural abnormalities of the renal tract they require assessment with a view to correction.
• In those at risk, long-term antibiotics may be of benefit and there is evidence that drinking cranberry juice may reduce susceptibility to UTI.¹⁶
• Women should be encouraged to void after sexual intercourse.
• A Cochrane review concluded that treatment of asymptomatic bacteriuria of pregnancy with antibiotics does reduce the risk of pyelonephritis.¹⁷