AUTHOR AND EDITOR INFORMATION

Section 1 of 10  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• References

INTRODUCTION

Section 2 of 10  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• References

Background

Chronic pyelonephritis is renal injury induced by recurrent or persistent renal infection. It occurs almost exclusively in patients with major anatomic anomalies, including urinary tract obstruction, struvite calculi, renal dysplasia, or, most commonly, vesicoureteral reflux (VUR) in young children. Sometimes, this diagnosis is established based on radiologic evidence obtained during an evaluation for recurrent urinary tract infection (UTI) in young children. VUR is a congenital defect that results in incompetence of the ureterovesical valve due to a short intramural segment. The condition is present in 30-40% of young children with symptomatic UTIs and in almost all children with renal scars. VUR may also be acquired by patients with a flaccid bladder due to spinal cord injury. VUR is classified into 5 grades (I-V), according to the increasing degree of reflux.

Pathophysiology

Chronic pyelonephritis is associated with progressive renal scarring, which can lead to end-stage renal disease (ESRD), eg, reflux nephropathy. Intrarenal reflux of infected urine is suggested to induce renal injury, which heals with scar formation. In some cases, scars may form in utero in patients with renal dysplasia with perfusion defects. Infection without reflux is less likely to produce injury. Dysplasia may also be acquired from obstruction. Scars of high-pressure reflux can occur in persons of any age. In some cases, normal growth may lead to spontaneous cessation of reflux by age 6 years. Factors that may affect the pathogenesis of chronic pyelonephritis are (1) the sex of the patient and his or her sexual activity; (2) pregnancy, which may lead to progression of renal injury with loss of renal function; (3) genetic factors; (4) bacterial virulence factors; and (5) neurogenic bladder dysfunction. In cases with obstruction, the kidney may become filled with abscess cavities (see Pyonephrosis).

Frequency

United States

VUR may be present in 30-45% of children with UTIs. The prevalence rate of VUR in siblings of patients with chronic pyelonephritis is approximately 35%. VUR and chronic pyelonephritis are less common in black children than in white children.

Mortality/Morbidity

Conditions associated with mortality and morbidity related to chronic pyelonephritis include (1) progressive renal scarring, (2) proteinuria, (3) hypertension, (4) ESRD, (5) focal glomerulosclerosis, and (6) xanthogranulomatous pyelonephritis (XPN). XPN occurs in 8.2% of patients and in 25% of patients with pyonephrosis.

Race

Chronic pyelonephritis is less common in black children than in white children.

Sex

Chronic pyelonephritis is more common in females than in males.

Age

Chronic pyelonephritis occurs in children and adults.

CLINICAL

Section 3 of 10  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• References

History

• Many cases of VUR are suggested based on prenatal sonography findings.
• Patients with chronic pyelonephritis may report the following:
• • Fever
  • Lethargy
  • Nausea and vomiting
  • Flank pain or dysuria
• Some children may present with failure to thrive.

Physical

• The following may be noted:
• • Hypertension
  • Failure to thrive in young children
  • Flank tenderness

Causes

• Chronic pyelonephritis is renal injury induced by recurrent or persistent renal infection.

DIFFERENTIALS

Section 4 of 10  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• References

Other Problems to be Considered

Analgesic abuse nephropathy
Renal tuberculosis
Renal malakoplakia

WORKUP

Section 5 of 10  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• References

Lab Studies

• Urinalysis
• • Urinalysis results may reveal pyuria.
  • Obtain a urine culture, which often isolates gram-negative bacteria such as Escherichia coli or Proteus species.
  • A negative result from urine culture does not exclude a diagnosis of chronic pyelonephritis.
  • Proteinuria may be present and is a negative prognostic factor for this disease.
• Serum creatinine and blood urine nitrogen levels are elevated (azotemia).

Imaging Studies

• Findings from an intravenous urogram help establish the diagnosis of pyelonephritis because they reveal caliceal dilatation and blunting with cortical scars. Ureteral dilatation and reduced renal size also may be evident.
• Voiding cystourethrogram (VCUG) findings may document the reflux of urine to the renal pelvis and ureteral dilatation in children with gross reflux.
• Radioisotopic scanning with technetium dimercaptosuccinic acid is more sensitive than intravenous pyelography for helping detect renal scars. This is the preferred test for many pediatric nephrologists and radiologists because it is sensitive and easy to perform.
• Cystoscopy images show evidence of reflux at the ureteral orifices.
• Renal sonography images may show calculi.
• CT scan is the procedure of choice to help diagnose XPN.
• Renal ultrasonography images may show calculi, but ultrasound is not a sensitive screening procedure for reflux nephropathy.

Procedures

• Cystoscopy findings show evidence of previous reflux at the ureteral orifices, even if VCUG images show no reflux because of the spontaneous cessation of reflux due to puberty.

Histologic Findings

Renal biopsy specimens show focal glomerulosclerosis in advanced reflux nephropathy, while XPN must be distinguished from renal malakoplakia based on the presence of inclusions called Michaelis-Gutmann bodies.

TREATMENT

Section 6 of 10  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• References

Medical Care

• Stages I and II VUR
• • This is reflux of urine to the ureter or renal pelvis without ureteral dilatation.
  • Medical therapy with antibiotics such as amoxicillin, trimethoprim/sulfamethoxazole (Bactrim), trimethoprim alone, or nitrofurantoin is usually sufficient.
  • Continue antibiotic therapy until puberty or until reflux resolves.
  • The rule in these cases is spontaneous resolution; surgery is not indicated.
• Stages III and IV VUR (severe reflux)
• • Data from the Birmingham Reflux Study (international reflux study in children) show that medical and surgical therapies for reflux are equally effective.
  • Surgery for severe reflux involves reimplantation of the ureters.
  • The indications for surgery include (1) medical noncompliance with formation of new scars and (2) reflux persisting after puberty in women (should be surgically treated to prevent possible complications, eg, pyelonephritis, abortions in pregnancy).

Surgical Care

• The following are indications for surgical therapy:
• • Failure to comply with medical regimen
  • Breakthrough infections occurring in patients who are compliant
  • Women of childbearing age who prefer surgical therapy
• Surgery entails the reimplantation of the ureters with the creation of an adequate submucosal tunnel and detrusor support.

Diet

• Progressive renal injury can be reduced by restricting dietary protein intake.

MEDICATION

Section 7 of 10  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• References

The penicillins (amoxicillin) and first-generation cephalosporins are the drugs of choice because of good activity against gram-negative rods and good oral bioavailability. In infants, the choice of antibiotics is either amoxicillin or a first-generation cephalosporin. In patients aged 3-6 months, therapy can be changed to sulfamethoxazole or nitrofurantoin. Older children and adults may be treated with trimethoprim-sulfamethoxazole (Bactrim). Once one antibiotic is chosen, frequent changes in the antibiotic regimen are discouraged to help prevent the development of resistance.

Drug Category: Antibiotics

Therapy must be comprehensive and cover all likely pathogens in the context of this clinical setting.

Drug Name	Cephalexin (Keflex)
Description	First-generation cephalosporin arrests bacterial growth by inhibiting bacterial cell wall synthesis. Bactericidal activity against rapidly growing organisms.
Adult Dose	500 mg PO qid
Pediatric Dose	25-50 mg/kg/d PO divided qid; not to exceed 4 g/d
Contraindications	Documented hypersensitivity
Interactions	Coadministration with aminoglycosides increase nephrotoxic potential
Pregnancy	B - Fetal risk not confirmed in studies in humans but has been shown in some studies in animals
Precautions	Adjust dose in renal impairment

Drug Name	Trimethoprim and sulfamethoxazole (Bactrim DS, Septra DS)
Description	Inhibits bacterial growth by inhibiting synthesis of dihydrofolic acid. Antibacterial activity includes common urinary tract pathogens, except Pseudomonas aeruginosa.
Adult Dose	1 DS tab (TMP 160 mg/SMZ 800 mg) PO bid
Pediatric Dose	8-12 mg/kg/d (TMP component) PO divided bid
Contraindications	Documented hypersensitivity; megaloblastic anemia due to folate deficiency
Interactions	May increase PT when used with warfarin (perform coagulation tests and adjust dose accordingly); coadministration with dapsone may increase blood levels of both drugs; coadministration of diuretics increases incidence of thrombocytopenia purpura in elderly persons; phenytoin levels may increase with coadministration; may potentiate effects of methotrexate in bone marrow depression; hypoglycemic response to sulfonylureas may increase with coadministration; may increase levels of zidovudine
Pregnancy	C - Fetal risk revealed in studies in animals but not established or not studied in humans; may use if benefits outweigh risk to fetus
Precautions	Discontinue at first appearance of skin rash or sign of adverse reaction; obtain CBC counts frequently; discontinue therapy if significant hematologic changes occur; goiter, diuresis, and hypoglycemia may occur with sulfonamides; prolonged IV infusions or high doses may cause bone marrow depression (if signs occur, administer 5-15 mg/d of leucovorin) Caution in folate deficiency (eg, chronic alcoholism, elderly, anticonvulsant therapy, malabsorption syndrome); hemolysis may occur in G-6-PD deficiency; patients with AIDS may not tolerate or respond to TMP/SMZ; caution in renal or hepatic impairment (perform urinalyses and renal function tests during therapy); administer fluids to prevent crystalluria and stone formation

Drug Name	Nitrofurantoin (Furadantin, Macrodantin)
Description	Synthetic nitrofuran that interferes with bacterial carbohydrate metabolism by inhibiting acetylcoenzyme A. Bacteriostatic at low concentrations (5-10 mcg/mL) and bactericidal at higher concentrations.
Adult Dose	50-100 mg PO hs
Pediatric Dose	Not established
Contraindications	Documented hypersensitivity; renal insufficiency
Interactions	Anticholinergics may delay gastric emptying and increase absorption, increasing nitrofurantoin bioavailability; antacids made of magnesium salts may decrease effects, decreasing absorption; high doses of concurrent probenecid decrease renal clearance and increase toxicity
Pregnancy	B - Fetal risk not confirmed in studies in humans but has been shown in some studies in animals
Precautions	May cause severe and irreversible peripheral neuropathy that can be fatal; renal impairment, diabetes, electrolyte imbalance, anemia, and vitamin B deficiency increase risk for adverse effects; prolonged use may result in fungal or bacterial overgrowth of resistant or nonsusceptible organisms

FOLLOW-UP

Section 8 of 10  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• References

In/Out Patient Meds

• In young children, the choice of antibiotics is either amoxicillin or a first-generation cephalosporin.
• In children aged 3-6 months, therapy can be changed to sulfamethoxazole or nitrofurantoin.
• Once an antibiotic is chosen, frequent changes in the antibiotic regimen are discouraged to help prevent the development of resistance.

Deterrence/Prevention

• Diet: Progressive renal injury can be reduced by dietary protein restriction.
• Hypertension therapy: Aggressive blood pressure control is beneficial to slow the progression of renal failure. ACE inhibitors are particularly beneficial in this setting.
• Pregnancy: Careful follow-up and monitoring of renal function is beneficial. Vigorously treat a UTI or bacteriuria in a patient who is pregnant to prevent renal failure, preeclampsia, and abortions.
• Screening: Renal sonography is recommended for siblings of patients with VUR. If an abnormality is found, then perform a VCUG.

Complications

• Proteinuria
• Focal glomerulosclerosis
• Progressive renal scarring leading to ESRD
• XPN (may occur in approximately 8.2% of cases)
• Pyonephrosis (may occur in cases of obstruction)
• Progressive renal scarring (reflux nephropathy)
• • The characteristic renal scars of VUR are often present at the time of initial diagnosis of chronic pyelonephritis.
  • New renal scars may develop in 3-5% of patients after the initial evaluation.
  • The progression of renal scars is inversely related to the promptness with which specific antibiotic therapy is instituted.
  • The presence of new scars often suggests the occurrence of breakthrough infections.
• Hypertension
• • Hypertension contributes to the accelerated loss of renal function in persons with this disease.
  • Reflux nephropathy is the most common cause of hypertension in children, occurring in 10-20% of children with VUR and renal scars.
  • The resolution of reflux does not appear to correct hypertension.

Prognosis

• Although most children with chronic pyelonephritis due to VUR may experience spontaneous resolution of reflux, approximately 2% can still progress to renal failure and 5-6% can have long-term complications, including hypertension.
• The Birmingham Reflux Study clearly shows that medical and surgical management are equally effective in preventing subsequent renal damage.
• Almost all children should receive a trial of medical management.

Patient Education

• For excellent patient education resources, visit eMedicine's Kidneys and Urinary System Center. Also, see eMedicine's patient education article Urinary Tract Infections.

MISCELLANEOUS

Section 9 of 10  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• References

Medical/Legal Pitfalls

• Failure to continue outpatient follow-up, which is considered mandatory, because the potential for long-term renal injury can be ameliorated with appropriate therapy

Special Concerns

• XPN may be confused with renal cancer.
• Analgesic abuse nephropathy may resemble chronic pyelonephritis.
• Renal tuberculosis and renal malakoplakia also may resemble chronic pyelonephritis. However, in malakoplakia, the characteristic Michaelis-Gutmann bodies may be seen.

REFERENCES

Section 10 of 10

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• References

• Alan C, Ataus S, Tunc B. Xanthogranulomatous pyelonephritis with psoas abscess: 2 cases and review of the literature. Int Urol Nephrol. 2004;36(4):489-93. [Medline].
• Birmingham Reflux Study Group. Prospective trial of operative versus non-operative treatment of severe vesicoureteric reflux in children: five years'' observation. Br Med J (Clin Res Ed). Jul 25 1987;295(6592):237-41. [Medline].
• Dillon MJ, Goonasekera CD. Reflux nephropathy. J Am Soc Nephrol. Dec 1998;9(12):2377-83. [Medline].
• Dracon M, Lemaitre L. [Urinary tract infection in adult. Leukocyturia]. Rev Prat. May 15 2003;53(10):1137-42. [Medline].
• Eke N, Echem RC. Chronic pyonephrosis associated with renal neovascularisation. Afr J Med Med Sci. Sep 2004;33(3):267-9. [Medline].
• Gillenwater JL, Grayhack JT, Howards SS, eds. Adult and Pediatric Urology. 3rd ed. St. Louis, Mo: Mosby-Year Book; 1996:. 320-5.
• Gonzalez Resina R, Barrero Candau R, Arguelles Salido E, et al. [Xanthogranulomatous pyelonephritis in childhood. A case report]. Actas Urol Esp. Jun 2005;29(6):596-8. [Medline].
• Hiraoka M, Hori C, Tsukahara H, et al. Vesicoureteral reflux in male and female neonates as detected by voiding ultrasonography. Kidney Int. Apr 1999;55(4):1486-90. [Medline].
• Kohler J, Tencer J, Thysell H, Forsberg L. Vesicoureteral reflux diagnosed in adulthood. Incidence of urinary tract infections, hypertension, proteinuria, back pain and renal calculi. Nephrol Dial Transplant. Dec 1997;12(12):2580-7. [Medline].
• Muter E, Nath KA. Chronic tubulointerstitial nephritis. In: Jacobson HR, Striker GE, Klahr S, eds. The Principle and Practice of Nephrology. 2nd ed. St. Louis, Mo: Mosby-Year Book; 1995:. 218-9.
• Noe HN. The long-term results of prospective sibling reflux screening. J Urol. Nov 1992;148(5 Pt 2):1739-42. [Medline].
• Oosterhof GO, Delaere KP. Xanthogranulomatous pyelonephritis. A review with 2 case reports. Urol Int. 1986;41(3):180-6. [Medline].
• Saavedra Jo S, Pow-Sang Godoy M, Benavente Corrales V, et al. [Xanthogranulomatous pyelonephritis: clinical, radiological and pathologic characteristics]. Arch Esp Urol. Jul-Aug 2004;57(6):595-600. [Medline].
• Takayasu H, Ishimaru Y, Kisaki Y. Diffuse xanthogranulomatous pyelonephritis in a patient with myotonic dystrophy and cerebral palsy. Int J Urol. May 2005;12(5):497-9. [Medline].
• Zermann DH, Loffler U, Reichelt O. Bladder dysfunction and end stage renal disease. Int Urol Nephrol. 2003;35(1):93-7. [Medline].
• Zugor V, Amann K, Schrott KM, Schott GE. [Xanthogranulomatous pyelonephritis: presentation of an unusual case]. Aktuelle Urol. Jun 2005;36(3):245-8. [Medline].

Article Last Updated: Nov 22, 2006