Clinical Decisions
Treatment of a 6-Year-Old Girl with Vesicoureteral Reflux
N Engl J Med 2011; 365:266-270July 21, 2011
Comments
and
Poll
open through August 3, 2011
- Article
A 6-year-old girl was recently referred to your clinic for further evaluation and management of vesicoureteral reflux, which had first been discovered after she presented at 1 year of age with a temperature of 39.5°C and irritability. Culture of a urine specimen at that time showed more than 106 colony-forming units of pansensitive Escherichia coli per milliliter, and she was treated with intravenous ampicillin for several days, followed by oral ampicillin, for a total of 14 days of therapy. After the patient no longer had a fever and a urine culture was sterile, voiding cystourethrography was performed while the patient was still receiving ampicillin. The voiding cystourethrogram showed bilateral grade III vesicoureteral reflux, and renal ultrasonography revealed normal findings. Radionuclide renal scintiscanning was not performed.
Prophylactic trimethoprim–sulfamethoxazole was administered at bedtime each night, and during the ensuing year, the patient had no urinary tract infections, as judged by sterile surveillance cultures of urine specimens and sterile cultures when she had any febrile episodes. A follow-up radionuclide voiding cystourethrogram when the patient was 2.5 years of age still showed bilateral grade III vesicoureteral reflux.
Subsequently, the family moved a number of times. The patient had several episodes of high fever, but no urine cultures were documented. At 4 years of age, she was seen again at the center where she had been followed, and she still had bilateral grade III vesicoureteral reflux. Continued antibiotic prophylaxis was recommended, but because of the family's moves, the degree of adherence was unclear. However, the child remained well, and her parents decided to stop the prophylactic antibiotics.
The child was toilet trained at 2 years of age, and she had no history of constipation or bowel irregularities. She had occasional nocturnal enuresis until the age of 4. She has not had enuresis since that time. Studies at the center where she had been followed documented measurements of serum creatinine of 0.3 mg per deciliter (27 μmol per liter) and blood urea nitrogen of 11 mg per deciliter (3.9 mmol per liter). Family history includes no chronic kidney disease, although the child's mother had a urinary tract infection when pregnant with this child, and the child's maternal grandmother, who is 51 years old, has had hypertension.
The patient, now 6 years of age, and her family have recently moved to your city, and her new primary care pediatrician refers her to you for consultation. She has been well recently, without reports of any medical problems. On examination of the child, you find that the height and weight are at the 50th percentile for age and the blood pressure is 88/50 mm Hg. Results of a general physical examination, including examination of the external genitalia, are normal. You obtain a urine specimen; culture of the specimen shows fewer than 1000 colony-forming units. A urinalysis reveals a specific gravity of 1.018 and a pH of 6.0; urine dipstick testing is negative for leukocytes, nitrites, protein, blood, glucose, ketones, and urobilinogen. The sediment shows no bacteria, 0 to 1 white cells, no red cells, and no casts per high-power field. You also obtain a radionuclide voiding cystourethrogram, which reveals that the patient still has bilateral grade III reflux. A renal ultrasound study shows that the kidney size is normal. A radionuclide renal scan is also normal. The parents ask whether you think the patient needs antibiotic prophylaxis and whether you would recommend any procedure to stop the vesicoureteral reflux.
- Option 1 (43)
- Option 1Watchful Waiting without Antibiotics
The healthy 6-year-old girl described in the vignette had a single episode of febrile urinary tract infection 5 years earlier, caused by the most common uropathogen. Except for the persistence of vesicoureteral reflux, she has no evidence of anatomical or functional perturbations. The question is, Is any intervention better than no intervention? There are several reasons why observation should be considered as the preferred option.
In most instances, vesicoureteral reflux is an inherited abnormality that resolves over time.1 The rate of resolution depends on several variables, including the age of the patient at presentation and the grade of reflux. The younger the child and the lower the grade of reflux, the faster the resolution will be. Whether the reflux is unilateral or bilateral can also affect the rate of resolution.
It is reassuring that the renal ultrasound examinations at presentation and follow-up were normal. Most girls with low-grade or medium-grade vesicoureteral reflux who have a normal renal ultrasound examination at presentation will continue to have normal ultrasound studies. Likewise, in the vast majority of children with reflux nephropathy in whom chronic kidney disease and end-stage renal failure develop, the kidneys were most likely damaged in utero. With the routine use of maternal–fetal ultrasonography, obstructive and vesicoureteric reflux nephropathy can be detected prenatally. The knowledge that kidney damage may occur in utero has added to our understanding of the pathophysiology of reflux nephrology. Furthermore, we have learned that urinary tract infections might never develop in some children who have kidney damage in utero. Acquired reflux nephropathy has become nearly nonexistent as a cause of end-stage kidney disease in children, which further supports the concept of in utero kidney damage.2
Although older studies involving small numbers of children showed an advantage to the administration of prophylactic antibiotics, more recent studies do not confirm this advantage. Relatively recent meta-analyses showed no or only marginal advantage against recurrent urinary tract infection3,4; a prospective study from Sweden showed that treatment with antibiotics provides better protection against new scarring than no such treatment, but the population studied included children who were younger than 2 years of age and who had severe vesicoureteral reflux and, in most cases, preexisting parenchymal damage.5
Abnormal elimination patterns may play a crucial role in delaying the resolution of reflux and increasing the risk of urinary tract infection.4 The risk of infection in this child is low, since none of these clinical scenarios apply to her.
Excessive use of prophylactic antibiotics may increase the prevalence of resistance. Many strains of E. coli in the community are already resistant to ampicillin and trimethoprim–sulfamethoxazole. Therefore, it might be an advantage in terms of both public health and the individual patient to minimize the use of antimicrobial agents.
This patient has remained free of infection since she stopped taking prophylactic antibiotics. She is healthy and has normal kidney anatomy and function and excellent bladder control and bowel habits. She has an anatomical abnormality that seems to have no clinical consequences; her prognosis is excellent. She may benefit from careful observation, with a high index of suspicion for urinary tract infection, but she may not require any additional evaluation or intervention while she remains free of infection.
Disclosure forms provided by the author are available with the full text of this article at NEJM.org.
Source Information
From the Department of Pediatrics, University of Missouri at Kansas City School of Medicine, Kansas City.
43 Reader's Comments
GIAN MENDIOLA, MD | Resident | Disclosure: NoneHospital de Andahuaylas - Apurimac , LIMA 12 PeruAugust 03, 2011Just Wait!
My opinion is just to wait and monitor any future febrile episode. The exists no strong data to support antibiotic prophylaxis at this time. Surgery has risks that should be taken only when they are exceeded by benefits.
ANDRES MAURICIO OLARTE MARIN | Student | Disclosure: NoneFOSCAL-UNAB, Bucaramanga, Colombia., BUCARAMANGA ColombiaAugust 02, 2011Microbial Resistance
Other treatment options should be considered instead of continuous prophylactic antibiotics. This is a serious issue, we need to considere that continuing with antimicrobial prophylaxis may increase the resistance.
Other options for this girl are: good hygiene, watch for sigs and symptoms of UTIs and visits for physician examination and DMSA scans.
Remember - no clinical evidence of worsening of the ureteral reflux and negative urine test do not support the idea of continous antibiotics. It is just not fair to the patient and public health.DR BASSAM BERNIEH, MD | Physician | Disclosure: NoneTawam Hospital, AL AIN United Arab EmiratesAugust 02, 2011Watchful Waiting without Antibiotics
I tend to adopt option 1, and if the child at any moment develops a UTI, I think it would be prudent to go for a repair after treating the infection.
NAHLA ARAB, MD | Physician | Disclosure: NoneDr Erfan and Bagedo Hospitals, Saudi ArabiaAugust 02, 2011Close Follow-up Without Treatment
The girl's history includes one documented febrile UTI episode and stationary state of reflux over 5 years. So the clinical implications of the anatomical abnormality are in favor of watchful follow-up for any progression or a second UTI episode, given the risks of long term antibiotic use and developing resistance also the risk of surgical intervention and post-operative recurrence of reflux.
WILLIAM PRIMACK, MD | Physician | Disclosure: Noneunc, CHAPEL HILL NCAugust 01, 2011What happens later?
In this situation where she has been free of infection for 2 years and does not have dysfunctional voiding or constipation I agree with watchful waiting.
My question is what to do, if anything, when she becomes sexually active and/or pregnant with an increased risk of lower UTIs? Is she at increased risk for pyelo.? Should she go on prophylaxis then??JOHN VARGHESE, MD | Physician | Disclosure: NoneKing Khalid Hospital, Najran, KOCHI IndiaAugust 01, 2011Watchful waiting
The case presented here is quite interesting. I am surprised that no one has commented on the growth of the child which is in the 50th percentile. This suggests that the child had a stormy childhood due to multiple UTI's. The presence of nocturnal enuresis until the age of 4 suggest that she has a significant post void residual. The child has probably adapted to her condition and is doing well considering the fact that there has been no recent episodes of pyelonephritis. But there is no denying the fact that she has an abnormal urinary tract with high-grade reflux. Also the DMSA scan being normal does not rule out small scars. But controlled trials have shown that there is no significant difference in outcome whether treated surgically or medically after the age of 4.
I would suggest to keep following her closely. If she does have further episodes of symptomatic UTIs, she may benefit from endoscopic injections of cellulose to the ureteric orifice. The family also needs to be counseled that we cannot promise that she will not progress to reflux nephropathy in the future.ROSS NICHOLSON, MD | Physician | Disclosure: NoneCounties_Manakau DHB Auckland New Zealand, AUKLAND New ZealandJuly 30, 2011Masterly Inactivity
After six years she has no evidence of scar, renal impairment, hypertension, or proteinuria. Her future prognosis is excellent despite her VUR. The reflux is irrelevant to decision making. I would reassure the child and her family and discharge her back to the care of her general practitioner (Primary care).
ELISE BROWN, MD | Physician | Disclosure: NoneEGSMC, ERIE COJuly 30, 2011Watch and Wait
I'm voting with the Watch & Wait crowd. That's why we went into pediatrics, right? They get better... However, my 2nd choice would be surgical repair. I think the antibiotics would be worst -- just fostering resistance, etc.
Leonardo Canessa | Physician | Disclosure: NoneDayton Children's,July 30, 2011Observation
I agree that if healthy, with a normal voiding pattern, and NO UTI for 2 years, at age 6 she could be observed with no antibiotics at bed time.
She should have a f/u study by age 8 to 10 to decide if an intervention then would be adequate. Repair before her menses if possible.
I would probably do an US in between to be sure both kidneys continue growing as is expected.
Of course BP checks are important, and UA + C/S with symptoms or high fevers.
It still is possible she will have favorable resolution of VUR if good and healthy habits for evacuation are insisted upon by the family.
Close observation for constipation is mandatory as constipation could reverse any progress and increase the risk for UTI.MANISH JETHANI | Resident | Disclosure: Nonegovt. medical college, akola, DESAIGANJWADSA IndiaJuly 29, 2011wait n watch uptil puberty
Just wait n watch as she is asymtomatic now. Give antibiotics when you suspect UTI. Observe up to 12yrs of age, (i.e until puberty). Then, if not spontaneously resolved, do surgery as it will be difficult to do at a later age.
NOEMIA GOLDRAICH, MD | Physician | Disclosure: NoneHospital de Clinicas Porto Alegre - Brazil, PORTO ALEGRE BrazilJuly 28, 2011Can she become better?
This young child has normal kidneys, normal bladder, and has been free of UTI. The question is: After 6 years, is reflux causing any problem to her? She had only one UTI five years ago. No recurrence of UTI. She is toilet trained and is not constipated. She needs urine cultures just if she becomes symptomatic (asymptomatic bacteriuria should not be treated). An ultrasound should be repeated in 18 months. DMSA scan only if she presents with a febrile UTI. Emotional pressure on the child and parents should also be considered when deciding how to approach the patient.
mohsen akhavansepahi | Physician | Disclosure: NoneMedical School, Iran, Islamic Republic ofJuly 28, 2011Don´t Use Antibiotics
I think this girl has to be observed. She does not need antibiotics since she is asymptomatic.
You have to wait and treat her when she has a UTI or new scar in DMSA Scan.ROBERT BAKER, MD | Physician | Disclosure: NoneMHS, INDIANAPOLIS INJuly 28, 2011Episode based treatment
It would be appropriate to treat when symptomatic and otherwise monitor. Antibiotic prophylaxis offers all the potential adverse effects of treatment for minimal benefit. Surgery in a patient who has shown no progression of renal damage in 6 years is overly aggressive.
RONNIE KLEIN, MD | Physician | Disclosure: NoneLinksfield Clinic Johannesburg, JOHANNESBURG South AfricaJuly 28, 2011Watchful Waiting
Without infections or renal damage, operative treatment is not neccessary.She should submit frequent mid stream urines for evaluation of infection. Many urine samples are contaminated by vaginal flora. Hence many patients are treated for UTIs unneccessarily.She should thus be instructed on how to properly collect her urine.
Haluk Burçak Sayman | Physician | Disclosure: NoneCerrahpasa Medical Faculty of Istanbul University, TurkeyJuly 28, 2011WAIT&C
No reason for antibiotic prophlaxis. Just keep periodic follow-up examinations, laboratory tests and DMSA scans when appropriate.
Rezan Topaloglu, MD | Physician - Nephrology | Disclosure: NoneHacettepe University Faculty of Medicine Department of Pediatric Nephrology Ankara TURKEY, Ankara TurkeyJuly 27, 2011Watchful Waiting Please
I have read the case discussion with great interest. We all come across such cases. In such cases one should always have a detailed history in regards to voiding dysfunction. Even have an uroflowmetry if the history is not assuring enough. The present case does not seem to have a voiding dysfunction by history, and no clue for the abnormal appearance of bladder or any other associated urinary tract abnormality but only bilateral III reflux in voiding cystouretrogram.
The key point here is she does not have any recurrent urinary tract infection and has a normal DMSA scan. This means she has bilateral III reflux with no clinical significance. The best approach for her is watchful waiting. During follow up if recurrent urinary tract infection is suspected or documented at that time endoscopic injection can be considered.THOMAS MCGRAW, MD | Physician | Disclosure: NoneStrate,July 26, 2011Personal Experience
My granddaughter had this condition. She is now 17 years old. With careful evaluation and follow-up by parents and a urologist who pursued watchful waiting and evaluation, she achieved a good result. Thank you.
LUCIANO WOLFFENBUTTEL, MD | Physician | Disclosure: NoneHosp Clinicas Porto Alegre, PORTO ALEGRE BrazilJuly 26, 2011Primun Non Nocere
Assuming she had had only one episode of UTI, this asymptomatic girl should not undergo an operation. According to the literature, antibiotic prophylaxis has a small effect in clinically relevant end-points in asymptomatic stage III reflux. Based on this, the potential harm of prophylaxis is not justifiable.
Daniel Nale | Physician | Disclosure: NonePrivate practice, Dallas, Tx,July 26, 2011Further Risk Stratification: A Fourth Option
Another option may be in order. The question is whether this child is at risk for long term renal damage. Studies show that only a minority of children will develop reflux nephropathy. Thus surgical repair would not be necessary in a child who is at little or no risk. Rencent data show that obtaining DMSA scans on children at least 3 months after a febrile UTI may be the best way to identify the high risk children. Children with negative DMSA scans regardless of reflux status are likey very low risk. Children with scarring on DMSA and reflux are at high risk for further scarring and deserve closer followup and consideration for surgical intervention. This child should receive a DMSA scan to help define her risk.
S BHATTACHARJEE, MD | Physician | Disclosure: NoneSCR Central Hospital,Secunderabad, HYDERABAD IndiaJuly 26, 2011Wait and Watch
It is better to wait and watch for grade III vesicoureteric reflux in a child and follow up with urine examination and USG of the abdomen. Proper bladder training will correct the reflux as well as the UTI.
ZAKIUDDIN OONWALA, MD | Physician | Disclosure: NoneHamdard College of Medicine and Dentistry., PakistanJuly 25, 2011Watchful Waiting
The reflux does not seem to be causing any harm. The child is symptom-free, growing up normally and imaging shows normal kidneys and urine examinantion is within normal limits. I would recommend follow-up at least every six months or earlier if the child develops a urinary tract infection.
DIANA MASSO | Physician | Disclosure: NonePosadas Hospital BsAs , ArgentinaJuly 24, 2011Watchful Waiting Without Antibiotics
Watchful waiting without antibiotics is the appropriate management option. Of note, the renal ultrasound study shows that the kidney size is normal and a radionuclide renal scan is also normal. She has normal renal function and the only symptomatic UTI was five years ago.
RIYAD SAID, MD | Physician | Disclosure: NoneJordan Hospital Amman Jordan, JordanJuly 24, 2011Just Follow-up; No Treatment for Now
Please leave this girl alone. She has no need for treatment now. Follow-up with urine cultures once febrile and most of the time grade III reflux will disappear.
DALE FULLER, MD | Physician | Disclosure: NoneRetired, DALLAS TXJuly 24, 2011A blast from the past......
About 50 years ago, after one year of training, Uncle Sam drafted me to be a urologist in the Air Force. I recall a few pediatric patients with reflux, and how hard it was to get a little kid to cooperate in obtaining a voiding CUG, but somehow I got it done. In most instances there was a ballooning of the urethra and a very tight urethral meatus. Dilation of the stenotic area under anesthesia seemed to relieve the problem. But as in the story where the patient moved around a lot, in this case, so did the doc, and I went back to the civilian world when I had served my time. I wonder what the long-term outcome for those little kids really was?
PS: I am a disciple of the “not-fixing-it” tenet stated by the earlier respondent. - Option 2 (5)
- Option 2Continuous Antimicrobial Prophylaxis
Children with vesicoureteral reflux of grade III or more that was diagnosed after a febrile urinary tract infection, like the girl in the vignette, have a risk of renal scarring that is 4 to 6 times as great as the risk among children with grade I or II reflux and 8 to 10 times as great as the risk among children without reflux.6 Some recently published trials showed no reduction in the incidence of recurrent infections in children receiving antimicrobial prophylaxis; this finding has led some clinicians to question the role of antimicrobial prophylaxis or even the need to evaluate children for reflux.6 However, these trials were small and underpowered to detect even large differences in rates of recurrent infection.
To detect a 10% reduction in the rate of recurrent infection among children receiving antimicrobial prophylaxis (assuming a baseline reinfection rate of 20% with placebo), 600 children would have to be enrolled. Therefore, the lack of observed reduction in recurrences may have resulted from insufficient statistical power, rather than lack of efficacy of antimicrobial prophylaxis. Furthermore, since these studies were conducted outside the United States, a large number of uncircumcised boys were included, thereby limiting the generalizability of the findings to a U.S. population in which most newborn boys are circumcised. Finally, lack of blinding may have led to an underestimation of recurrent infection in the prophylaxis group, whereas the use of nonstringent criteria for urinary tract infections, as well as surveillance cultures of urine specimens — which potentially identify children with asymptomatic bacteriuria rather than infection — may have diluted the actual benefit of antimicrobial prophylaxis, biasing results toward the null.6
Reports of two larger and more carefully designed investigations have been published. In a study involving 576 children in whom urinary tract infections were diagnosed with the use of stringent criteria, Craig et al. reported that in children with vesicoureteral reflux, antimicrobial prophylaxis was moderately more effective than placebo in reducing reinfections (reinfection rate, 11% vs. 17%).7 Although not all children underwent voiding cystourethrography, the reduction in risk was greatest among children with grade III, IV, or V reflux (−6.8%), as compared with that among children with grade I or II reflux (−5.4%) or those with no reflux (−1.8%). Brandström et al. reported on 203 children 1 to 2 years of age with grade III or IV reflux who were randomly assigned to antimicrobial prophylaxis, endoscopic surgery, or surveillance. Antimicrobial prophylaxis was the most effective — only in girls — in decreasing the likelihood of febrile urinary tract infections (19%, 23%, and 57% had infections, respectively) and renal scarring (6%, 12%, and 18% had scarring, respectively).8
The patient in the vignette had several episodes of high fever during which urine specimens were not cultured; accordingly, it is unknown whether she had additional infections. The most benign course of action, which avoids both additional radiation exposure and surgery, would be to observe her during 1 to 2 years of antimicrobial prophylaxis with aggressive evaluation of all febrile episodes.9 During this period, if she does have reinfections, surgical repair of vesicoureteral reflux would be warranted; conversely, if she does not have reinfections, antimicrobial prophylaxis could be discontinued, provided meticulous follow-up were ensured. It would also be judicious to avoid repeating voiding cystourethrography, to minimize exposure to radiation, unless the patient has a breakthrough infection.
More conclusive evidence on the benefits of antimicrobial prophylaxis is expected from the Randomized Intervention for Children with Vesicoureteral Reflux study, sponsored by the National Institute of Diabetes and Digestive and Kidney Diseases, which has completed enrollment of 607 children 2 months to 6 years of age. The children have grade I through grade IV reflux that was diagnosed after urinary tract infections that were defined according to stringent criteria.10 Continuing the use of established practices derived from careful clinical observations, such as antimicrobial prophylaxis in children with dilating reflux, seems prudent until this more conclusive and generalizable evidence becomes available.
Disclosure forms provided by the author are available with the full text of this article at NEJM.org.
Source Information
From the Department of Pediatrics, University of Pittsburgh School of Medicine, Pittsburgh.
5 Reader's Comments
SAI LAKSHMIKANTH | Student | Disclosure: NoneSRMC, CHENNAI IndiaAugust 02, 2011Option 2
It's prudent to continue the antibiotic prophylaxis as there is every chance of the patient getting repeated infections leading to permanent kidney damage.
DR GOUTHAM SERALATHAN | Student | Disclosure: NoneMMHRC, KARUR IndiaAugust 02, 2011Prophylaxis is a Must
As this child has a cfu of 1000, she should be put on antibiotic prophylaxis as a freely refluxing infected urine tends to cause renal scarring and there are studies which show that toilet trained VUR children tend to get repeated UTIs!
SHYAM BANSAL, MD | Physician | Disclosure: NoneMedanta- Medicity, Gurgaon, NOIDA IndiaAugust 02, 2011Continuous Antimicrobial Prophylaxis
I agree with the second option of continuing antibiotic prophylaxis as she has history of intercurrent UTI's. As she has not taken prophylaxis regularly, the surgical correction should be done as the last option.
norman canter | Physician | Disclosure: Nonenone,August 02, 2011All Antibacterial Regimens are not the Same
It seems logical to monitor the bacterial content of the bladder on a regular basis. The medications that are safest with fewer side effects might tried first: hippuric acid might be adequate, nitrofurantoin is safe and might be a second choice in sequence, sulfamethoxazole and then with trimethoprim if needed. If medications fail in maintaining adequate bacterial control more invasive measures may be considered if recurrent UTIs are noted. I do not think that the question is antibacterials versus none but rather a proper selection and progression of antibacterials according to their risk of side effects.
JOSE IGLESIAS, MD | Physician | Disclosure: NonePrivate practice, El SalvadorJuly 20, 2011Medical Follow-Up is Warranted
This girl should be followed with urine cultures and antibiotic prophylaxis until around nine years of age. If her reflux persists at that age it should be corrected surgically before she enters puberty. Surgical correction would be warranted earlier if she has febrile breakthrough infections or develops renal scars. Most renal scars appear in the first five years of age. VCUG and DMSA scans should also be done yearly to assess for renal reflux and scarring.
- Option 3 (32)
- Option 3Repair of the Vesicoureteral Reflux
The compelling reason for corrective repair in this child is the high likelihood of recurrent pyelonephritis as long as she has vesicoureteral reflux. Regardless of vesicoureteral reflux status, patients who have recurrent urinary tract infections are susceptible to infection because they have alterations in the urothelium of the bladder that enhance bacterial attachment and alter local immune response. Clinical studies in women and children show that the likelihood of future urinary tract infection correlates directly with previous urinary tract infection. Increased odds of recurrent urinary tract infections in young women are associated with an age of less than 15 years at the first urinary tract infection, as well as whether their mothers had urinary tract infection.11
Whether refluxing kidneys are embryologically dysmorphic and then acquire renal scars and hypotrophy from urinary tract infections is debatable, but recurrent pyelonephritis can cause new scars, and the risk of scarring is associated with the number of urinary tract infections sustained.12 In the patient in the vignette, the results of renal ultrasonography and scanning were normal. However, these imaging techniques cannot show subtle scars or hypotrophy,13 making the assessment of renal damage difficult. Markers of renal dysfunction — elevated creatinine levels, hypertension, and proteinuria — may not be evident until adulthood or pregnancy.
Antimicrobial prophylaxis has been ineffective in the prevention of recurrent urinary tract infections in this girl. Medical claims data suggest that nonadherence to prophylaxis is common, and the reasons include expense, bother, patient distaste, and caregiver concern about increasing bacterial resistance. Whether resistance results from excessive antimicrobial usage, inappropriate dosing, or increased global and environmental usage, optimal drugs that can be used for pediatric urinary prophylaxis and that have low bacterial resistance and low serum and high urinary concentrating properties are few.
Surgical intervention turns the morbidity and costs associated with this chronic disease into a cure. Children with vesicoureteral reflux have annual or more frequent visits to their doctors, undergo imaging studies, take daily medication, and see their medical doctor when symptoms dictate. This child had a hospitalization and at least two renal ultrasound examinations, one fluoroscopic voiding cystourethrogram, three radionuclide voiding cystourethrograms, one radionuclide renal scan, and multiple urine cultures; she also has undergone multiple urinalyses, four or more urethral catheterizations, and several blood tests. Thus, she has had substantial exposure to ionizing radiation, has undergone long periods of daily medication, and has had to make multiple medical visits. These medical encounters have direct and indirect costs, such as discomfort to the child, time and dollars spent on the child, and time and dollars spent by caregivers and society.14 Extended treatment of vesicoureteral reflux makes it into a chronic disease that could adversely affect this girl's quality of life and that of her caregivers, just as asthma can. Repair decreases the frequency of febrile urinary tract infections (i.e., pyelonephritis) and eliminates the need for frequent routine follow-up visits.
The discomfort previously associated with ureteroneocystostomy or laparoscopic or robotic-assisted repair has been reduced in recent years by the supplemental use of regional and local anesthesia, avoidance of ureteral and urethral catheters, good postoperative pain management, and post-procedure hospitalizations of 1 or 2 days. Endoscopic injections of bulking agents for repair further reduce incisional pain, although the durable surgical cure rate (measured by an absence of vesicoureteral reflux on postoperative voiding cystourethrography 1 to 2 years later) for ureteroneocystostomy is 98% and for endoscopic injection (with up to three separate injection procedures) is 45 to 60%; other complications are uncommon.
Curative intervention in this 6-year-old girl should be seriously considered in order to decrease her risk of another episode of pyelonephritis, to avoid the chronic administration of medication that has not been effective, to arrest a chronic disease, and to limit her current and future disease-related discomfort. Recent guidelines from the American Urological Association panel on vesicoureteral reflux in children recommend surgical intervention as a treatment option for children with breakthrough febrile and afebrile recurrent urinary tract infections.15
Disclosure forms provided by the author are available with the full text of this article at NEJM.org.
Source Information
From the Department of Urology, Stanford University Medical Center, Stanford, CA.
32 Reader's Comments
Fumio Tsukuda | Physician | Disclosure: NoneTanushimaru central hospital, JapanAugust 02, 2011Surgical Repair
We couldn`t expect spontaneous improvement. Surgical repair is recommended.
Vijendra Jhameria | Other | Disclosure: NoneS.M.S. Medical College, Jaipur, Rajasthan, IndiaAugust 02, 2011Why Not Deflux Injection?
As the girl is presenting with grade III reflux she is definitely prone to infections. She is now already six years of age and renal invovement may now follow, which may be missed as the family is on the move. I would make a suggestion to the parents about the Deflux injecton treatment so that the reflux is controlled so that the child is less prone to infections and antibiotic therapy may not be then required in the future. Of course a close follow-up is mandatory
JOSEPH REYNOLDS | Physician | Disclosure: NoneMGH Bastrop, La,August 02, 2011Surgical Repair
It sounds like this condition should have been surgically repaired earlier. I am familiar with repair in children under 4, but at 6 years old I'm not. Rather than allow the child to continue to have a condition that will expose her to ascending pyelonephritis in the future, it would seem to be appropriate to have re-implantation done. If we knew how many kidney infections it took to wipe out the kidneys we could wait, but if the kidneys got wiped out because of not fixing a fixable condition we would be sorry later.
I wonder how many females that have frequent kidney infections had undiagnosJOSEPH FERRARA, MD | Physician | Disclosure: NoneAmerican Medical Center, Brooklyn, NY, ROCKVILLE CENTRE NYAugust 02, 2011An Argument for Surgical Repair
According to Current Clinical Medicine, Cleveland Clinic, Second Edition: "The gravid uterus causes physiologic alterations that increase the risk of pyelonephritis. Pyelonephritis has been associated with infant prematurity, low birth weight, perinatal mortality, and high blood pressure."
Assuming that this patient may want to raise a family someday, it may be best to provide reasons for immediate surgical repair. A pyelonephritis occurring in a future pregnancy would bring up the concern of retrocecal appendicitis, require imaging, etc.rashid ali | Physician | Disclosure: Noneshifa, PakistanAugust 02, 2011Intervene
I think, keeping in mind the frequent moves of the patient, lack of proper follow up, and the need to schedule every three-month DMSA, urine culture, and ultrasound, surgery is the best option. This degree of follow up would be a difficult task for even the best of motivated patients and parents. So the timely action would be to intervene and solve this matter once for all, if surgery can offer the best success rate.
chacko jacob | Physician | Disclosure: NoneIbin Sina Medical centre, United Arab EmiratesAugust 02, 2011watchful waiting till when?
Grade III VUR detected at the age of I year at the time of 1st febrile UTI, did not show any resolution for the last 5 years in this female child.
She was in and out of UTI prophylaxis in the past, but her renal function is normal and she has no renal scars.
So after 5 years of detection of B/L grade III VUR, the management decisions have to be based on
• the natural course and prognosis
• follow up prospects
• potential harm of the reflux on renal health
In this situation I recommend trial of endoscopic debulking injection and follow up if possible or surgical repair, ideally before puberty.PROF ARUNAVA CHOUDHURY, MD | Physician | Disclosure: NoneCalcutta Hospital-RKMSP, CALCUTTA 700 029 IndiaAugust 02, 2011Surgery is indicated
Over 6 years her grade 3 VUR has persisted despite occasional antibiotic prophylaxis. Further antibiotic prophylaxis is unlikely to prove more effective. Moreover her family seems to be unreliable & having to move from town to town; that will make follow up difficult. If one could ensure regular follow up, one could put her on surveillance. However under the circumstance described she will require active intervention - in the form of injecting bulking agent. Failing that, surgery may be required.
DILEEP TIWARI, DO | Resident | Disclosure: Nonesir ganga ram hospital, HARI NAGAR NEW DELHI IndiaAugust 02, 2011Surgery is the better option
The only cure of this condition is surgery (bilateral implantation of ureters). Why should we wait for permanent disability or morbidity?
SOUMYA SAHA, DO | Physician | Disclosure: NoneAMRI, KOLKATA IndiaAugust 02, 2011Pursue a Definitive Cure
Due to the vesico-ureteric reflux of the child, she has much more propensity to suffer from UTI's, specially, when she starts menstruating,and in later life. Neither continuing with antibiotic prophylaxis for an indefinite period, nor not doing anything, believing she will comply with the advice of doctors to come for regular follow-up, is sensible. Therefore, we need to cure the etiological factor, responsible for the probable episodes of UTI. With modern techniques in surgery, long-term complications are very less. So, in my opinion, surgery should be the treatment of choice.
GEORGES MOUAWAD, MD | Physician | Disclosure: Noneabou jaodeh hospital, BEIRUT LebanonAugust 02, 2011Surgery is a Better Solution
The mean age at reflux resolution is 6 years. The incidence of reflux nephropathy increases with the grade of reflux and with bilaterality. With the success rate of surgical repair greater than 98% and incidence of clinical pyelonephritis 2.5 times higher in children treated medically, I think surgery is a better solution.
MOHAMMAD BUDRUDDIN | Physician | Disclosure: NoneHospital, OmanAugust 02, 2011Urgent Need for Corrective Surgery
This girl needs to be subjected to corrective surgery at the earliest to prevent the further possible morbid condition of pyelonephritis with is longterm sequelae.
RICARDO GOMES, MD | Physician | Disclosure: NonePrivate practice, BARRA DO PIRAI RJ BrazilAugust 02, 2011Definitive Cure
All three management strategies could be tried in this case but because of the constant moving of the family I would recommend surgery.
HENRY MUELLER, MD | Physician | Disclosure: Nonenone retired, GREENVILLE PAAugust 02, 2011Weakly favor surgery
I feel that if surgery is available by an appropriate subspecialist, and if a high rate of cure is probable, it should be offered as the primary modality for treatment.
CHINEDU NWEKE, MD | Physician | Disclosure: NoneNUMC, EAST MEADOW NYAugust 01, 2011Corrective surgery
Corrective surgery will reduce the risk of irreversible damage in the long-run.
MS JULIE HOLMES | Student | Disclosure: NoneUniversity of Hawaii, HONOLULU HIJuly 30, 2011Repair
This is a disaster waiting to happen. Fix it now -- antibiotics carry too much risk over time and they compromise all systems even if highly selective. Although nerve function and adherence are not issues yet, once they occur, they cannot be retracted. Cut to the chase and let the girl have a normal life. And despite hating anecdotal evidence, I just have to say that having had 80+ UTIs, dealing with the constant battle of the microbes, AB resistance, etc. It is not worth it!
I would also like to add that because this patient has a non-stable lifestyle, careful evaluation is NOT an option. Why do you think she'll be in the same location under your care in 6-12 months? She hasn't been stable and that will likely continue based on history. Therefore, the problem will proceed without anyone really knowing the true course and because medical files are rarely provided to patient or guardian, the probability of her being truly observed over time is unrealistic. A stitch in time saves nine -- especially when dealing with a patient who is transitory.CANIO CASALE, MD | Physician | Disclosure: NonePhysician, SAN SEVERO FG ItalyJuly 30, 2011Surgical Intervention is the appropriate Treatment.
In fact I believe she was supposed to be operated upon earlier.
SHAHED SWAID, MD | Physician | Disclosure: Noneprivate office, DAMASCUS Syrian Arab RepublicJuly 28, 2011surgical treatment
No spontanous improvement is anticipated( I guess), and it is preferable not to keep her with this reflux, so surgical repair should preferably be considered
misbah zahra | Resident | Disclosure: Noneshaikh zayed postgraguate medical institute, lahore, Pakistan., PakistanJuly 28, 2011surgical repair is the ulimate cure
I think delaying definite treatment & waiting for permanent damage, or at least all those years of followup or prophylactic antibiotics, which will not ensure definite cure, is not recommendable
T HUGHES-DAVIES, MD | Physician | Disclosure: NoneRetired, HAMPSHIRE United KingdomJuly 27, 2011Pressure not flow
The ureter and pelvis form a cul de sac and there can be little reflux flow. When the one way flap valve is incompetent, however slightly, ureteric pressure will match that of the bladder. If this is high there may be progressive damage and dilation of the upper tract with stagnation and a risk of infection, especially when supine.
Outflow obstruction might be reflected in low initial flow at high velocity. Holding back to the end of a lesson or journey should be avoided by regular micturition and comfortable lavatories rather than by restricting drink.Mindaugas Ziukas | Physician | Disclosure: Nonenone, LithuaniaJuly 26, 2011Intervention
I argue for intervention before onset of sexual activity.
ADRIAN RODRIGUES | Student | Disclosure: NoneMedical School, SOUTH EL MONTE CAJuly 22, 2011Family Migration
After the number of visits this patient has had with her medical institution, I would assume that surgery was at least mentioned once. Perhaps her family's constant moving has influenced that decision.
Krunal Patel | Student | Disclosure: NoneSt. Luke Aurora,WI,July 22, 2011Agree with option 3
Sooner or later she needs surgical management.
BIMAL K AGRAWAL, MD | Physician - Emergency Medicine | Disclosure: NoneMMIMSR, M M University,Mullana (India), MULLANAAMBALA IndiaJuly 21, 2011Repair of the VUR Recommended, But Patient Should Decide
It's ideal to repair the vesicoureteral reflux in such a situation instead of waiting for any renal damage to occur. Risk of waiting has to be explained to the patient's parents. Till that time careful followup for any febrile episode is necessary. If the patient develops a UTI , it should be managed with antibiotics and again discussing the issue with the patient and re-emphasizing the relative benefit of surgery.
CHARLES STEPHENSON, MD | Physician | Disclosure: Noneretired, VICTORIA BC CanadaJuly 21, 2011A Politano-Leadbeater Refashioning of the Ureterocystic Junction
This should be done from inside the bladder with adequate tunnel length say 1.5 cms.
Henrique Aquino | Physician | Disclosure: NoneRio de Janeiro State University, BrazilJuly 21, 2011Surgical Intervention is the Most Appropriate Treatment
I agree with option 3 (surgical correction).
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- Citing Articles (2)
Citing Articles
1
Diamond, David A., Mattoo, Tej K., . (2012) Endoscopic Treatment of Primary Vesicoureteral Reflux. New England Journal of Medicine 366:13, 1218-1226
Full Text2
Lamas, Daniela J., Ingelfinger, Julie R., Rosenbaum, Lisa S., . (2011) Treatment of a 6-Year-Old Girl with Vesicoureteral Reflux — Polling Results. New England Journal of Medicine 365:8,
Full Text
Wait and See
Option 1 is better for this child; I think the following years of her development will be the most important for the final recommendation.