Acute pyelonephritis is infection within the renal pelvis, usually accompanied by infection within the renal parenchyma. The source of the infection 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 (UTI) - eg, Escherichia coli, Klebsiella spp., Proteus spp., Enterococcus spp. Unusual organisms are occasionally seen - eg, mycobacteria, yeasts and fungi and opportunistic pathogens such as Corynebacterium urealyticum. Repeated attacks of acute pyelonephritis can lead to chronic pyelonephritis, which involves destruction and scarring of renal tissue due to repeated inflammation.
Acute pyelonephritis can occur at any age. Around 1% of boys and 3% of girls will have had acute pyelonephritis by the age of 7. Incidence is highest in women aged 15-29, followed by infants and older people.It is relatively uncommon in men. In neonates it is more common in boys and tends to be associated with abnormalities of the renal tract. Over the age of 65 the incidence in men rises to match that of women.
- Structural renal abnormalities, including vesicoureteric reflux (VUR).
- Calculi and urinary tract catheterisation.
- Stents or drainage procedures.
- Primary biliary cirrhosis.
- Immunocompromised patients.
- Neuropathic bladder.
- Prostate enlargement.
Onset is usually rapid with symptoms appearing over a day or two. There is unilateral or bilateral loin pain, suprapubic pain 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. 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 young, can be much less specific and culture of urine should be a routine investigation in pyrexial and unwell infants.
- Urinalysis: the urine is often cloudy with an offensive smell. It may be positive on dipstick urinalysis for blood, protein, leukocyte esterase and nitrite. A midstream specimen of urine (MSU) should always 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. (Clean catch, catheter or suprapubic aspiration are methods used which reduce the risk of contamination. Occasionally a collection bag or pad may be used when a sample is not obtainable by superior means.) Microscopy of urine shows pyuria.
- Inflammatory markers: CRP, ESR, and plasma viscosity may be raised.
- Recent studies identified procalcitonin as a biological marker in diagnosing acute pyelonephritis in children, potentially more useful than white cell count or CRP.National Institute for Health and Care Excellence (NICE) guidance advises CRP alone is not useful in differentiating lower UTI from pyelonephritis in children. A Cochrane review in 2015 came to the conclusion that although procalcitonin seemed the most helpful, there was not enough evidence to recommend routine use of any of these blood tests in clinical practice at this time.
- FBC: this shows elevated white cell count with neutrophilia.
- Blood cultures: these are positive in approximately 15-30% of cases.
- Imaging is useful if the clinical picture or biochemical markers are ambivalent, as structural problems are not uncommon. Ultrasonography is usually the first-line investigation. Whether advised for all varies between guidelines. Imaging is normally recommended in men and children; it is mandatory in patients with recurrent pyelonephritis and may help to identify obstruction or stones.
- Contrast-enhanced helical/spiral CT (CECT) scan is the best investigation in adults where diagnosis is in doubt, improvement does not occur after 72 hours of treatment, or deterioration occurs. Non-contrast helical/spiral CT scans will pick up moderate-to-severe disease but may be normal in milder cases. In pregnant women, ultrasound or MRI is preferred.
- In children, where imaging is required, ultrasound is the first-line investigation as dictated by NICE guidance. See the separate Urinary Tract Infection in Children article for details.
- Dimercaptosuccinic acid (DMSA) scan is mainly used for detailed renal cortical views in recurrent cases, to detect scarring.
- MRI is also useful in detecting scarring but may require sedation in children. In adults, it is increasingly used where renal infection, masses and urinary obstruction are suspected but its use is limited by cost and availability.
- Renal biopsy is occasionally employed to exclude papillary necrosis.
- 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, due to the risk of complications.Other indications for admission include:
- Severe vomiting.
- Comorbidity such as diabetes.
- Signs of sepsis (eg, tachypnoea, tachycardia, hypotension).
- Dehydration or inability to take fluids/medication.
- Severe pain or debility.
- Failure of response to treatment in primary care within 24 hours.
- Urinary tract obstruction.
- Oliguria or anuria.
- Suspected complications (see 'Complications', below).
- Uncertain diagnosis.
- Social issues.
- Non-concordance with treatment.
- Inadequate access to follow-up.
- Relapse of symptoms as soon as antibiotics have been stopped.
- Antibiotics:start empirical antibiotic treatment whilst awaiting culture and sensitivity. For adults, current UK protocols recommend that the first-line antibiotic should be either ciprofloxacin or co-amoxiclav for seven days (500 mg bd or 500/125 mg tds respectively). Trimethoprim may be used if culture confirms sensitivity (200 mg bd for 14 days). For children co-amoxiclav is recommended as first-line treatment, with cefixime second-line. There is a theoretical concern that children who are not treated with early intravenous antibiotics could develop renal scarring. However, studies increasingly suggest that most cases in children over the age of one month can be managed with oral therapy.
- Surgery: this may rarely be required to drain renal or perinephric abscesses, or to relieve obstructions causing the infection (eg, stones).
Potential complications include:
- Perinephric abscess (more common if there is urinary tract abnormality).
- Renal abscess, including emphysematous pyelonephritis (rare, life-threatening form with tissue necrosis and accumulation of gas in the renal parenchyma, perinephric space and collecting systems - particularly occurs in obese, elderly women who have diabetes and develop urinary tract obstruction).
- Acute papillary necrosis, which 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.
- Impaired renal function or renal damage potentially leading to acute kidney injury or chronic kidney disease (CKD).
Risk factors for complications include:
- Severe illness.
- Age over 65.
- Renal tract structural abnormality, or foreign bodies within the renal tract (including calculi and stents).
- Diabetes mellitus.
- Renal transplant (especially the first three months).
- AIDS and other immunocompromised states.
Premature labour can occur in pregnant women. In other cases, there is usually uncomplicated recovery, providing there are no significant comorbidities.
Consider prophylactic treatment in women with at least three symptomatic infections a year. Trimethoprim is widely used. In children, the current approach is to reserve antibiotic prophylaxis for those who are at highest risk of complications (eg, demonstrable VUR, recurrent infections or renal scarring on imaging).[4, 12]
Chronic pyelonephritis is a characteristic scarring on the kidney which occurs after recurrent or persistent infections.
There are few data available. VUR, which is a common risk factor, is found in up to one third of children investigated for UTI.VUR has been estimated to be present in around 1% of children.Children who have recurrent episodes of infection or VUR are most likely to develop renal scarring.
- Any structural renal tract anomalies, obstruction or calculi.
- Intrarenal reflux in neonates.
- Any factors predisposing to recurrent urinary infection - eg, neurogenic bladder.
Chronic pyelonephritis is often asymptomatic. There may be features of acute or recurrent infection, or of complications of significant renal damage:
- Loin pain
- Failure to thrive
- Features of CKD
- Urine microscopy, culture and sensitivity: this may be helpful in identifying the organism involved in recurrent infection but negative urine culture does not exclude diagnosis.
- Renal ultrasound may show small kidneys with a thin cortex.
- Intravenous pyelogram (IVP) may show small kidneys, ureteric and caliceal dilatation/blunting with cortical scarring.
- Micturating cystourethrogram (MCUG) may help to identify reflux.
- Ultrasound and KUB X-ray may show stones but are not sensitive for reflux nephropathy.
- Technetium-99m Tc-DMSA scan is the most sensitive for demonstration of renal scars.
- Renal biopsy may be required to rule out other causes of damage.
Aims of management are to control active or recurrent infection and to treat/correct any underlying causes.
- Blood pressure should be controlled to slow the progression of chronic kidney disease. Ideally angiotensin-converting enzyme (ACE) inhibitors should be used.
- Supervening UTI may require lengthier courses of antibiotics than are normally given.
- Severe underlying VUR diagnosed in children may require antibiotics prophylactically until puberty or until the reflux resolves (see 'Prevention', below).
- Calculi may need removal.
- Surgical re-implantation of the ureters may be needed in severe cases but, in most cases, surgical management is not superior to medical.
- In severe cases, there may eventually be a need for dialysis or renal transplantation.
As with all other forms of CKD, the patient should be monitored for the development of hyperlipidaemia, hypertension, diabetes and deteriorating renal function.
- Progressive renal scarring with reflux nephropathy and CKD.
- Secondary hypertension.
- Focal glomerulosclerosis.
- Urea-splitting organisms can lead to staghorn calculi - the usual culprit is Proteus spp.
Adults with chronic pyelonephritis generally have good prognosis with preserved renal function if treated promptly.
Many children with VUR do not develop renal scarring, although data are lacking. Higher grades of VUR correlate with higher rates of renal scars.
- 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 with severe VUR, long-term antibiotics may be of benefit but there is no evidence that they are beneficial in mild reflux.
- The evidence for the preventative benefits of cranberry juice is increasingly weak.
- A Cochrane review of antibiotic treatment of asymptomatic bacteriuria in pregnancy found it effective in reducing the risk of pyelonephritis in pregnancy but that the estimate of the effect is very uncertain due to poor-quality evidence.Antibiotics lead to a reduction in low birth weight and preterm birth but the conclusion was that this should be interpreted with caution.
Saadeh SA, Mattoo TK; Managing urinary tract infections. Pediatr Nephrol. 2011 Nov26(11):1967-76. Epub 2011 Mar 16.
Urinary Tract Infection - Children; NICE CKS, July 2015 (UK access only)
Colgan R, Williams M, Johnson JR; Diagnosis and treatment of acute pyelonephritis in women. Am Fam Physician. 2011 Sep 184(5):519-26.
Leroy S, Fernandez-Lopez A, Nikfar R, et al; Association of procalcitonin with acute pyelonephritis and renal scars in pediatric UTI. Pediatrics. 2013 May131(5):870-9. doi: 10.1542/peds.2012-2408. Epub 2013 Apr 29.
Urinary tract infection in children: diagnosis, treatment and long-term management; NICE Clinical Guideline (August 2007)
Shaikh N, Borrell JL, Evron J, et al; Procalcitonin, C-reactive protein, and erythrocyte sedimentation rate for the diagnosis of acute pyelonephritis in children. Cochrane Database Syst Rev. 2015 Jan 201:CD009185. doi: 10.1002/14651858.CD009185.pub2.
Guidelines on Urological Infections; European Association of Urology (2015)
Chen KC, Hung SW, Seow VK, et al; The role of emergency ultrasound for evaluating acute pyelonephritis in the ED. Am J Emerg Med. 2011 Sep29(7):721-4. Epub 2010 May 1.
Pyelonephritis - acute; NICE CKS, June 2013 (UK access only)
Management of suspected bacterial urinary tract infection in adults; Scottish Intercollegiate Guidelines Network - SIGN (updated July 2012)
Managing common infections: guidance for primary care; Public Health England, August 2015
Strohmeier Y, Hodson EM, Willis NS, et al; Antibiotics for acute pyelonephritis in children. Cochrane Database Syst Rev. 2014 Jul 287:CD003772. doi: 10.1002/14651858.CD003772.pub4.
Nickavar A, Sotoudeh K; Treatment and prophylaxis in pediatric urinary tract infection. Int J Prev Med. 2011 Jan2(1):4-9.
Nagler EV, Williams G, Hodson EM, et al; Interventions for primary vesicoureteric reflux. Cochrane Database Syst Rev. 2011 Jun 15(6):CD001532. doi: 10.1002/14651858.CD001532.pub4.
Guidelines on Paediatric Urology; European Association of Urology (2015)
McCullough PA, Steigerwalt S, Tolia K, et al; Cardiovascular disease in chronic kidney disease: data from the Kidney Early Evaluation Program (KEEP). Curr Diab Rep. 2011 Feb11(1):47-55.
Jepson RG, Williams G, Craig JC; Cranberries for preventing urinary tract infections. Cochrane Database Syst Rev. 2012 Oct 1710:CD001321. doi: 10.1002/14651858.CD001321.pub5.
Smaill FM, Vazquez JC; Antibiotics for asymptomatic bacteriuria in pregnancy. Cochrane Database Syst Rev. 2015 Aug 78:CD000490. doi: 10.1002/14651858.CD000490.pub3.
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