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Annotations Prognosis for Vesicoureteric Reflux Arch Dis Child 1999;81:287–294 287 Arch Dis Child: first published as 10.1136/adc.81.4.287 on 1 October 1999. Downloaded from The Journal of the Royal College of Paediatrics and Child Health Annotations Prognosis for vesicoureteric reflux The prevalence of vesicoureteric reflux (VUR) has been to disentangle in this group of patients. The development estimated to be 2% of the child population.1 In children with of proteinuria is indicative of progressive glomerulosclero- VUR demonstrated on micturating cystourethrography sis and is a bad prognostic feature particularly when the there is a tendency for the grade of VUR to improve or for patient also has hypertension. VUR to disappear with time and with increasing age.23VUR has been identified as a risk factor for the development of Historical perspective urinary tract infections (UTI) and is present in a third of A review of literature in the preantibiotic era suggests that young children presenting with this problem. In addition, it chronic pyelonephritis was a very serious condition in chil- is a risk factor for renal scarring, otherwise called reflux dren and adults. Weiss and Parker described a series of nephropathy.45 VUR is also associated with renal dysplasia postmortem cases16: antecedent clinical features included and other developmental abnormalities of the urinary tract.6 recurrent fevers, presumably due to persistent untreated There is now abundant evidence for inheritance by an auto- infection, anaemia, hypertension, growth failure, and preg- somal dominant mechanism.7 nancy complications. There is evidence for a falling preva- lence of this condition, which is probably due to a true reduction of reflux nephropathy because of modern medi- Pathogenesis of reflux nephropathy cal care, particularly the treatment of acute pyelonephritis Studies have suggested that reflux nephropathy develops with antibiotics; alternatively the decline may represent following UTI in very early childhood or infancy.8 New changing fashions in disease classification. The historical http://adc.bmj.com/ scars have been observed relatively infrequently; however, aspects are discussed in detail by MacGregor17 who there are suYcient case reports of new scar formation both considered that VUR was crucial to the development of on intravenous urography and using 99mTc DMSA scans to reflux nephropathy. accept that at least a proportion of renal scars are acquired following UTI.910The probability that most scars develop Long term outcome of VUR in this way cannot be proved because relatively few children In her elegant long term study Smellie describes the natu- have serial imaging studies; in particular, few children have ral history of VUR in 226 children, 85 of whom had renal had imaging investigations before the first UTI. The link scarring modified by close medical supervision, including on September 26, 2021 by guest. Protected copyright. between UTI, VUR, and renal scarring has been confirmed 411 long term, low dose prophylaxis, advice on double micturi- by several independent groups. Smellie et al have also tion, treatment of intercurrent UTI, and management of demonstrated a link between delay in diagnosis and treat- 18 912 hypertension. In addition 33 patients had surgical proce- ment of UTI and the development of new renal scars. dures (nephroureterectomy or reimplantation of the ureter, or both). Twenty (9%) had hypertension and six (4%) had Symptoms and signs of VUR and reflux chronic renal failure, two of whom reached end stage. New nephropathy scars visible on intravenous urography developed in only a VUR and reflux nephropathy are silent conditions that do small proportion of the cohort and this was attributed to not usually give rise to symptoms or signs except when the benefits of careful medical supervision. The incidence complications such as UTI develop. They can only be of new scars is lower than in other studies,19–21 but the diag- detected by invasive tests that are not routinely carried out nosis of new scars is imprecise and subjective so that com- in healthy children and are not usually indicated during the parisons between studies are diYcult. New scars have only acute phase of treatment. Thus knowledge of pathogenesis rarely been seen to develop after the age of 4 to 5 years.22 If and natural history has been gleaned from observational scars are acquired following UTI the prompt treatment of studies and additional imaging investigations carried out symptomatic episodes particularly in early childhood may on the advice of paediatricians in the belief that they are be equally or even more important than long term important for management.13 The evolution of reflux preventative measures. The natural history of asympto- nephropathy is a slow process. Most renal scarring matic bacteriuria is not significantly diVerent in terms of develops very early in childhood, but progressive deteriora- incidence of new scars, although many girls have prolonged tion of damaged kidneys may continue slowly throughout periods of exposure to infection.19 23 The long gestation life. The relative contributions of congenital renal dyspla- period for scar formation visible on intravenous urography sia, acquired reflux nephropathy, and the final common makes it diYcult to link new scars to specific episodes of pathway of progressive glomerulosclerosis14 15 are diYcult infection. 288 Annotations Surgery for prevention of UTI and reflux The imaging investigations recommended in the RCP Arch Dis Child: first published as 10.1136/adc.81.4.287 on 1 October 1999. Downloaded from nephropathy guidelines are in eVect screening tests as they are carried Following the original observations by Hodson and out in a high risk population after the acute illness has been Edwards24 of the strong association between UTI, VUR, treated successfully, in the hope that better knowledge of and reflux nephropathy, surgeons developed operations to the underlying anatomy will improve future management correct VUR in the belief that this would reduce the risk of and prognosis. Unfortunately, there is no evidence that the recurrent UTI and prevent the development of reflux prognosis is altered by these tests or by the widespread use nephropathy.25 Although reimplantation of the ureter was of long term, low dose prophylaxis or successful surgery. quite successful for elimination of VUR, there was a However, the use of published guidelines has provided a significant complication rate26 and the overall risk of UTI very useful step in the evaluation of current practice, as the was altered little by successful surgery.20 21 27 Similarly, suc- guidelines are followed widely throughout the UK and it is cessful surgery did not benefit glomerular filtration rate or now possible to audit and assess the outcome of this stand- prevent new scar formation. More recently a procedure ard practice.33 Published studies suggest that many involving the suburothelial injection of Teflon or collagen children do not have the recommended management.34 has been used to correct VUR endoscopically.28 The Stark, in 1997, challenged the view that these imaging success rate of this procedure in eliminating VUR is less tests are worthwhile and suggested that they are excessively than for surgery but the procedure is simpler and involves costly and invasive without giving any benefit to most a shorter hospital stay. Long term benefits from this proce- children.35 Tertiary specialists were heavily represented in dure on infection rates and new scar formation have not the working group of the research unit of the RCP; their been evaluated. Teflon has now been abandoned because views and experiences represented the most severe end of of concerns about embolisation of particles causing granu- the clinical spectrum of UTI and reflux nephropathy. In lomas at distant sites; collagen has been found to be safe contrast, general practitioners and general paediatricians but benefits are not permanent and VUR may recur after a who see most children at the time of their first UTI were in period of months or years. the minority. Although there was no formal attempt to inform general practitioners of the guidelines some general Long term, low dose prophylaxis practices are now referring large numbers of children for An alternative approach to correction of VUR is the use of imaging investigations and a paediatric opinion following long term, low dose prophylaxis initially with cotrimoxa- simple, non-febrile UTI. This has generated a massive zole or nitrofurantoin29 and later using trimethoprim. It was workload for radiology departments and exposed large postulated that UTI usually develop as a result of ascend- numbers of children to significant radiation without much ing infection and that from time to time bacteria ascend the evidence of benefit. The proportion of children seen with urethra and establish infection in the bladder or kidneys. A evidence of renal damage is lower than in earlier studies. nightly dose of a broad spectrum antibiotic can sterilise the This may be because UTI are diagnosed quickly in infants urine on a daily basis if the bacteria are sensitive to the drug when they are referred to hospital,36 or it may reflect the chosen, reducing the chance that UTI can become fact that many more straightforward cases are being established. Breakthrough infections can occur if the referred for further investigation. Unfortunately, there is child’s gut and perineum are colonised with resistant continuing evidence of delay in diagnosis of UTI in infants organisms. Breakthrough with sensitive organisms suggests and toddlers in primary care where urine collection is per- 37 that prophylaxis has been omitted. There was evidence of ceived as diYcult, and some children have several consul- http://adc.bmj.com/ eVectiveness of this treatment in reducing the rate of rein- tations before the diagnosis of UTI is considered and fur- fection in children with normal urinary tracts,30 but there ther delays before it is confirmed.38 are no controlled studies demonstrating that long term, low dose prophylaxis is superior to prompt treatment of UTI Practice in Sweden for the prevention of renal scarring.
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