Chronic pyelonephritis is characterized by renal inflammation and scarring induced by recurrent or persistent renal infection, vesicoureteral reflux, or other causes of urinary tract obstruction. It occurs almost exclusively in patients with major anatomic anomalies, most commonly young children with vesicoureteral reflux (VUR).[1]
VUR is a congenital condition that results from incompetence of the ureterovesical valve due to a short intramural segment. VUR is present in 30-40% of young children with symptomatic urinary tract infections (UTIs) and in almost all children with renal scars.[2] It may also be acquired by patients with a flaccid bladder due to spinal cord injury. The diagnosis of VUR is frequently established on the basis of radiologic evidence obtained during an evaluation for recurrent UTI in young children.
VUR is classified into 5 grades (I-V), according to the increasing degree of reflux as follows[3] :
The diagnosis of chronic pyelonephritis is made on the basis of imaging studies such as ultrasound or CT scanning. Treatment options include prophylactic antibiotics, endoscopic injection of dextranomer hyaluronic acid, and antireflux surgery.[4] Selecting the treatment option for different grades of VUR reflux depends on the clinical presentation and renal function.
For patient education information, see Urinary Tract Infections (UTIs) in Children and Urinary Tract Infections.
Chronic pyelonephritis is associated with progressive renal scarring, which can lead to end-stage renal disease (ESRD). For example, in reflux nephropathy, intrarenal reflux of infected urine is suggested to induce renal injury, which heals with scar formation.[5] 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).
In the United States, VUR may be present in 30-40% of children with UTIs. The prevalence rate of VUR in siblings of patients with chronic pyelonephritis is approximately 35%.[6] VUR and chronic pyelonephritis are less common in African-American children than in white children, with chronic pyelonephritis occurring 3 times more often in white children.[7] Chronic pyelonephritis is also twice as common in females as it is in males.
Chronic pyelonephritis occurs more often in infants and young children (younger than 2 y) than it does in older children and adults.
The Birmingham Reflux Study clearly showed that medical and surgical management are equally effective in preventing renal damage from VUR.[8] Almost all children should receive a trial of medical management.
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.[9]
Hypertension contributes to the accelerated loss of renal function in persons with chronic pyelonephritis. 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.
Complications of chronic pyelonephritis can also include the following:
Some children with chronic pyelonephritis may report the following:
The following may be noted on physical examination:
The characteristic renal scars of vesicoureteral reflux (VUR) are often present at the time of the 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.
Urinalysis results may reveal pyuria. Obtain a urine culture, which often isolates gram-negative bacteria, such as Escherichia coli or Proteus species. A negative urine culture does not exclude a diagnosis of chronic pyelonephritis. Proteinuria may be present and is a negative prognostic factor for this chronic pyelonephritis. Serum creatinine and blood urea nitrogen (BUN) levels are elevated (azotemia).
Renal biopsy specimens show focal glomerulosclerosis in advanced reflux nephropathy, while xanthogranulomatous pyelonephritis must be distinguished from renal malakoplakia based on the presence of inclusions called Michaelis-Gutmann bodies in the latter.
On an intravenous urogram, caliceal dilatation and blunting with cortical scars helps to establish the diagnosis of pyelonephritis. 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.[19] To strike the balance between obtaining high-quality images and minimizing radiation exposure, radiology departments should observe the “as low as (is) reasonably achievable” (ALARA) Image Gently guidelines.[20]
Radioisotopic scanning with technetium dimercaptosuccinic acid (DMSA) is the gold standard for detecting renal scars and is more sensitive than intravenous pyelography.[21]
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.
Computed tomography (CT) scanning is the procedure of choice to help diagnose XPN.[14, 22] Renal ultrasonographic images may show calculi, but ultrasonography is not a sensitive screening procedure for reflux nephropathy. However, many cases of VUR are suggested by prenatal ultrasonographic findings.
In the child with vesicoureteral reflux (VUR) who is experiencing chronic pyelonephritis, the goals of management of are to 1) prevent recurring febrile urinary tract infections (UTIs); 2) prevent renal injury; and 3) minimize the morbidity of treatment and follow-up. Preventive strategies include the administration of prophylactic antibiotics, endoscopic injection of dextranomer hyaluronic acid, and antireflux surgery.[4] Selecting the treatment option for different grades of VUR depends on the clinical presentation and renal function.
If symptomatic breakthrough UTI occurs during preventive therapy, a change in therapy is recommended. The clinical scenario (ie, VUR grade, degree of renal scarring, and evidence of bowel/bladder dysfuntion), as well as parental preferences, will guide the choice of alternative treatment. In the absence of new renal cortical abnormalities, a change in the antibiotic used for prophylaxis may be effective. Therapy with curative intent, including open surgery, offers protection against febrile UTI, but is associated with morbidity. Endoscopic injection therapy may have decreased success in VUR resolution.[4]
Continuous antibiotic prophylaxis (CAP), such as amoxicillin, trimethoprim/sulfamethoxazole (Bactrim), trimethoprim alone, or nitrofurantoin, is often the initial treatment. CAP should continue until puberty or until reflux resolves.
Endoscopic injection have advantages over open surgery, including less postoperative pain and fewer bladder spasms and infections, and the absence of surgical scarring. Endoscopic injection can be performed in a shorter operation time, in an outpatient setting, and with minimal use of postoperative analgesics and is preferred as the first-line treatment for children with VUR.[23]
The American Urological Association (AUA) Vesicoureteral Reflux Guideline Update Committee analyzed data from 17,972 patients, and reported that the overall success rate of a single endoscopic treatment was 83.0% compared to 98% success rates for open surgery.[4] When an injection treatment fails, open ureteral reimplantation may be needed to treat persistent VUR.[23]
Surgery entails the reimplantation of the ureters, with the creation of an adequate submucosal tunnel and detrusor support. Open reimplantation surgery may be a primary treatment or may be performed as second-line therapy after endoscopic injection failure. Studies have reported no adverse effect on success rates, operation time, or complications when open reimplantation follows endospic injection treatment.[23]
Robot-assisted laparoscopic extravesical ureteral reimplantation has been proposed as a minimally invasive alternative to open ureteral reimplantation for correcting primary vesicoureteral reflux in children. However, the current literature contains conflicting data regarding the safety and efficacy of this approach. In a multi-institutional review, a success rate of 87.9% was reported in a series of 260 patients who underwent robot-assisted laparoscopic extravesical ureteral reimplantation for primary vesicoureteral reflux.[24]
Progressive renal injury can be reduced by dietary protein restriction, while aggressive blood pressure control aids in slowing progression of renal failure. Angiotensin-converting enzyme (ACE) inhibitors are particularly beneficial in treating hypertension.
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.[25]
Renal ultrasonography is recommended for siblings of patients with VUR.[26] If an abnormality is found, then perform a voiding cystourethrogram (VCUG).
The 2010 American Urological Association (AUA) guidelines for management and screening of primary vesicoureteral reflux (VUR) in children were reconfirmed in 2017. Key recommendations for initial management of children less than 12 months old include the following[4] :
For children over one year old, several factors influence clinical outcome including a greater liklihood of bowel and bladder dysfunction (BBD), lower probability of spontaneous resolution of VUR, lower risk of acute morbidity from febrile UTI and a greater ability of the child to communicate complaint of symptoms of acute infection. Thus, the AUA notes that management decisions must take into account recognition of the clinical context (i.e., age, VUR grade, presence of scarring and parental preferences). The guidelines make the following treatment recommendations[4] :
The penicillins (amoxicillin) and first-generation cephalosporins are the drugs of choice for chronic pyelonephritis 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.
Clinical Context: Amoxicillin interferes with the synthesis of cell wall mucopeptides during active multiplication, resulting in bactericidal activity against susceptible bacteria..
Clinical Context: Cephalexin is a first-generation cephalosporin that arrests bacterial growth by inhibiting bacterial cell wall synthesis. It has bactericidal activity against rapidly growing organisms.
Clinical Context: Trimethoprim/sulfamethoxazole inhibits bacterial growth by inhibiting the synthesis of dihydrofolic acid. Bacterial species it acts against include common urinary tract pathogens, except Pseudomonas aeruginosa.
Clinical Context: This is a synthetic nitrofuran that interferes with bacterial carbohydrate metabolism by inhibiting acetylcoenzyme A. Nitrofurantoin is bacteriostatic at low concentrations (5-10 mcg/mL) and bactericidal at higher concentrations.
Antibiotic therapy must be comprehensive and cover all likely pathogens in the context of this clinical setting.