eMedicine Specialties > Nephrology > Tubulointerstitial Diseases of the Kidney

Pyelonephritis, Chronic

Anupama Gowda, MBBS, MD, Consulting Staff, Atlanta Nephrology Associates, PC
Chike Magnus Nzerue, MD, Associate Dean for Clinical Affairs, Meharry Medical College

Updated: Sep 15, 2008

Introduction

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.

See related CME at Renal Tract Malformations: Perspectives for Nephrologists.

Pathophysiology

Chronic pyelonephritis is associated with progressive renal scarring, which can lead to end-stage renal disease (ESRD), for example, 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 as follows: (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 African American children than in white children.

Mortality/Morbidity

Conditions associated with mortality and morbidity related to chronic pyelonephritis include the following: (1) progressive renal scarring, (2) proteinuria, (3) hypertension, (4) end-stage renal disease, (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 3 times more common in white children than in African American children.

Sex

Chronic pyelonephritis is 2 times more common in females than in males.

Age

Chronic pyelonephritis occurs more often in infants and young children (younger than 2 y) than in older children and adults.

Clinical

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.

Differential Diagnoses

Other Problems to Be Considered

Analgesic abuse nephropathy
Renal tuberculosis
Renal malakoplakia

Workup

Laboratory 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

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 the following: (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

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.

Antibiotics

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

Amoxicillin (Amoxil)

Interferes with synthesis of cell wall mucopeptides during active multiplication, resulting in bactericidal activity against susceptible bacteria.

Dosing

Adult

500 mg PO q8h

Pediatric

125 mg PO q8h

Interactions

Reduces efficacy of oral contraceptives

Contraindications

Documented hypersensitivity

Precautions

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; may enhance chance of candidiasis

Cephalexin (Keflex)

First-generation cephalosporin arrests bacterial growth by inhibiting bacterial cell wall synthesis. Bactericidal activity against rapidly growing organisms.

Dosing

Adult

500 mg PO qid

Pediatric

25-50 mg/kg/d PO divided qid; not to exceed 4 g/d

Interactions

Coadministration with aminoglycosides increase nephrotoxic potential

Contraindications

Documented hypersensitivity

Precautions

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

Trimethoprim and sulfamethoxazole (Bactrim DS, Septra DS)

Inhibits bacterial growth by inhibiting synthesis of dihydrofolic acid. Antibacterial activity includes common urinary tract pathogens, except Pseudomonas aeruginosa.

Dosing

Adult

1 DS tab (TMP 160 mg/SMZ 800 mg) PO bid

Pediatric

8-12 mg/kg/d (TMP component) PO divided bid

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

Contraindications

Documented hypersensitivity; megaloblastic anemia due to folate deficiency

Precautions

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

Nitrofurantoin (Furadantin, Macrodantin)

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.

Dosing

Adult

50-100 mg PO hs

Pediatric

Not established

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

Contraindications

Documented hypersensitivity; renal insufficiency

Precautions

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

Inpatient & Outpatient Medications

• 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 end-stage renal disease
• 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

Medicolegal 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

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Keywords

chronic pyelonephritis, reflux nephropathy, kidney disease, renal injury, renal disease, kidney infection, renal infection, urinary tract obstruction, struvite calculi, renal dysplasia, vesicoureteral reflux, VUR, UTI, urinary tract infection, renal scar, renal scarring, flaccid bladder, end-stage renal disease, ESRD, end-stage kidney disease, intrarenal reflux, intra-renal reflux, progressive renal scarring, proteinuria, hypertension, focal glomerulosclerosis, FGS, xanthogranulomatous pyelonephritis, XPN, failure to thrive, Proteus, Escherichia coli, E coli, azotemia

Contributor Information and Disclosures

Author

Anupama Gowda, MBBS, MD, Consulting Staff, Atlanta Nephrology Associates, PC
Disclosure: Nothing to disclose.

Coauthor(s)

Chike Magnus Nzerue, MD, Associate Dean for Clinical Affairs, Meharry Medical College
Chike Magnus Nzerue, MD is a member of the following medical societies: American Association for the Advancement of Science, American College of Physicians, American College of Physicians-American Society of Internal Medicine, American Society of Nephrology, and National Kidney Foundation
Disclosure: Nothing to disclose.

Medical Editor

Richard A Santucci, MD, FACS, Chief of Urology, Detroit Receiving Hospital; Specialist-in-Chief of Urology, Detroit Medical Center; Chief of Urologic Trauma Surgery, Sinai Grace Hospital; Director, The Center for Urologic Reconstruction; Clinical Professor of Urology, Michigan State College of Medicine
Richard A Santucci, MD, FACS is a member of the following medical societies: American College of Surgeons, American Urological Association, and Société Internationale d'Urologie (International Society of Urology)
Disclosure: Nothing to disclose.

Pharmacy Editor

Francisco Talavera, PharmD, PhD, Senior Pharmacy Editor, eMedicine
Disclosure: Nothing to disclose.

CME Editor

Rebecca J Schmidt, DO, FACP, FASN, Professor of Medicine, Section Chief, Department of Medicine, Section of Nephrology, West Virginia University School of Medicine
Rebecca J Schmidt, DO, FACP, FASN is a member of the following medical societies: American College of Osteopathic Internists, American College of Physicians, American Medical Association, American Society of Nephrology, International Society of Nephrology, National Kidney Foundation, Renal Physicians Association, and West Virginia State Medical Association
Disclosure: Abbott Grant/research funds Speaking and teaching; Genzyme Honoraria Consulting; Roche Honoraria Consulting

Chief Editor

Vecihi Batuman, MD, FACP, FASN, Professor of Medicine, Section of Nephrology-Hypertension, Tulane University School of Medicine; Chief, Medicine Service, Southeast Louisiana Veterans Health Care System
Vecihi Batuman, MD, FACP, FASN is a member of the following medical societies: American College of Physicians, American Society of Hypertension, American Society of Nephrology, and International Society of Nephrology
Disclosure: Nothing to disclose.

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