CHRONIC PYELONEPHRITIS

Definition

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), 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.

Clinical Finding

History Taking

Many cases of VUR are suggested based on prenatal sonography findings. Patients with chronic pyelonephritis may report the following:

o Fevero Lethargyo Nausea and vomitingo Flank pain or dysuria

Some children may present with failure to thrive.

Physical Examination

The following may be noted:o Hypertensiono Failure to thrive in young childreno Flank tenderness

Causes

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

Workup diagnosis

Laboratory Studies

Urinalysiso Urinalysis results may reveal pyuria.o Obtain a urine culture, which often isolates gram-negative bacteria, such as

Escherichia coli or Proteus species.o A negative result from urine culture does not exclude a diagnosis of chronic

pyelonephritis.o 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.

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.

Medical Care

Stages I and II VURo This is reflux of urine to the ureter or renal pelvis without ureteral dilatation.o Medical therapy with antibiotics, such as amoxicillin,

trimethoprim/sulfamethoxazole (Bactrim), trimethoprim alone, or nitrofurantoin, is usually sufficient.

o Continue antibiotic therapy until reflux resolves.o The rule in these cases is spontaneous resolution; surgery is not indicated.

Stages III and IV VUR (severe reflux)o Data from the Birmingham Reflux Study (international reflux study in children)

show that medical and surgical therapies for reflux are equally effective.

o Surgery for severe reflux involves reimplantation of the ureters.o 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:o Failure to comply with medical regimeno Breakthrough infections occurring in patients who are complianto 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.

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)

o The characteristic renal scars of VUR are often present at the time of initial diagnosis of chronic pyelonephritis.

o New renal scars may develop in 3-5% of patients after the initial evaluation.o The progression of renal scars is inversely related to the promptness with which

specific antibiotic therapy is instituted.o The presence of new scars often suggests the occurrence of breakthrough

infections. Hypertension

o Hypertension contributes to the accelerated loss of renal function in persons with this disease.

o Reflux nephropathy is the most common cause of hypertension in children, occurring in 10-20% of children with VUR and renal scars.

o 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.