Incidence of reflux in patients with UTI?
- [@ 40,25,20,8]
Uncircumcised male infants show a 12-fold greater risk for UTI than circumcised males, as well as a greater propensity for harboring periurethral uropathogenic flora.
Male: female prevalence of VUR can be as high as 3:1 at 0 to 6 months of age but shifts to approximately 1:1 by 21 to 24 months of age.
Anatomy of ureter?
- The ureter consists of three distinct layers. The innermost is the mucosa, the middle muscular layer is the muscularis, and the outer layer is the adventitia.
- The muscular wall of the ureter consists of two longitudinal layers separated by a middle circular layer that may not be distinct from each other, especially in the abdominal segment of the ureter.
- In the distal ureter, the inner spirals are steep and the outer spirals are horizontal, thus appearing as inner longitudinal and outer circular layers in cross section.
- These smooth muscle layers are contiguous with the smooth muscle covering the minor renal calyces, where the pacemaker is located to initiate the rhythmic peristalsis to deliver urine.
- The outermost layer, the adventitia, consists of a dense network of collagen and elastic fibers, including many blood vessels and unmyelinated nerve fibers among them. This layer is continuous proximally with the capsule at the renal pelvis while it is thickened distally by a specialized muscle fibers and fibrous tissue to form the Waldeyer sheath.
Describe the embryology and surgical anatomy of vesicoureteric junction and trigone. (TU 2073-10)
Functional anatomy of antireflux mechanism?
Ureter represents a dynamic conduit, which adequately propels the urine presented to it in a bolus fashion, antegrade, by neuromuscular propagation of peristaltic activity. In so doing, reflux is actively opposed. Moreover, if reflux were to occur, depending on its degree and timing, antegrade flow might be expected to keep refluxing urine from reaching the renal pelvis.
- Anatomic design of the UVJ -
- - The three muscles of ureter separate in extravesical hiatus
- - Outer layer - merge with outer detrusor muscle to form Waldeyer sheath, that forms the deep trigone
- - Inner muscle of the ureter merges with detrusor muscle to contribute to superficial trigone. Some of the inner ureteral fibers pass medially to contribute to the intraureteric ridge (Mercier bar)
- - Intramural ureter remains passively compressed by bladder during filling, preventing urine from entering the ureter. Adequate tunnel length to ureter diameter = 5:1
- Opening of the UVJ is achieved by active contraction of the longitudinal muscles within the tunnel. This draws the extravesical and intravesical points of the intramural ureter closer together, shortening and widening the tunnel, and allows passage of the urine bolus into the bladder.
- Indeed, when viewed cystoscopically, a lateral displacement of the ureteric orifice accompanies the classic jet of urine into the bladder. Although such lateral displacement is functionally normal and necessary to permit urine to pass.
- Permanent lateral displacement by virtue of a constitutively short tunnel characterizes the cystoscopic position of the refluxing ureteric orifice.
Causes of VUR?
- fundamental deficiency in the function of the UVJ antireflux mechanism while the remaining factors (bladder and ureter) remain normal or relatively noncontributory.
- Secondary reflux - normal function of the UVJ. Bladder dysfunction of a congenital, acquired, or behavioral nature is often the root cause of secondary reflux. Causes are
- - In male, PUV is most common
- - In the female, ureterocele that prolapse is most common
- - neurofunctional causes - occult spinal dysraphism, tethered cord
- - urodynamic extremes in absence of overt neurologic pathologic process also may exist - overactivity, inadequate sphincter relaxation
- - Bladder and bowel dysfunction - in older children, persistence of the expected early attempts to suppress bladder contractions during the toilet training months by volitional contraction of the external sphincter. If the toiled trained child has dribbling, urgency or incontinence, consider voiding disorders. Constipation should be recognized and eliminated as much as possible.
Special attention to the potential for occult spinal dysraphism, including sacral dimple, hairy patch, gluteal cleft abnormality, diminished rectal tone, or significant and often refractory constipation or encopresis, should prompt consideration for investigation of coexistent spinal cord abnormalities. In those patients who are known to have spinal dysraphism and VUR, a more conservative approach to managing the lower urinary tract is generally advised. This often includes early initiation of CIC, consideration for anticholinergic administration, and close follow-up with serial imaging.
Clinical features of UTI in children?
Children younger than 2 years - vague symptoms, including fever, irritability, poor feeding, vomiting, diarrhea, and ill appearance with increased likelihood of UTI in the setting of at least two of the following risk factors:
- (1) age less than 12 months,
- (2) white race,
- (3) absence of other fever source,
- (4) fever greater than 39°C, and
- (5) fever of 2 or more days
However, older children and adolescents may localize symptoms to the urinary tract, reporting dysuria, suprapubic pain, voiding dysfunction, incontinence, or flank and/or abdominal pain. T
UTI and reflux?
Reflux is not a general cause of UTI, but is perceived to be a clinical accelerant of upper tract bacteriuria by mechanically delivering infected urine to the renal pelvis.
Infection-related cystitis is expected to incite bladder irritability and dysuria, upsetting the voiding pattern and lowering the threshold for reflux in a given UVJ.
Grading of VUR?
- Grade I Reflux does not reach the renal pelvis; varying degrees of ureteral dilatation
- Grade II Reflux reaches the renal pelvis; no dilatation of the collecting system; normal fornices
- Grade III Mild or moderate dilatation of the ureter, with or without kinking; moderate dilatation of the collecting system; normal or minimally deformed fornices
- Grade IV Moderate dilatation of the ureter with or without kinking; moderate dilatation of the collecting system; blunt fornices, but impressions of the papillae still visible
- Grade V Gross dilatation and kinking of the ureter, marked dilatation of the collecting system; papillary impressions no longer visible; intraparenchymal reflux
Reflux at time of cystogram phase is low pressure reflux
Shortcomings of five-point grading system?
The expected concordance between ureteral and calyceal dilation does not always occur. Either the ureter or the calyces may demonstrate dilation out of proportion to the calyces or ureter, respectively
Radionuclide cystography (RNC) grading of VUR?
Because RNC does not provide discrete images of the ureteral and calyceal architecture required to assign reflux grade, classifying reflux by RNC is difficult.
- Grades 2 and 3 - low grade
- Grades 4 and 5 - high grade
Grade I reflux into the distal ureter is often poorly detected because of the overlying exposure generated by contrast within the bladder.
The impact of the reduction in grading detail from 5 grades (1 to 5) to 2 (low and high) on understanding reflux pathophysiology and on the design of clinical studies has yet to be determined.
- The RNC has historically enjoyed a reputation for requiring approximately 1% the radiation exposure generated by the VCUG. Presently, the reduced radiation requirements of modern digital techniques have significantly narrowed the difference between fluoroscopy and RNC.
- Little anatomic detail is afforded by the RNC
- Ideal as both a screening modality and for monitoring the natural history or surgical follow-up of reflux.
AAP Clinical Practice Guideline on Febrile UTI in Febrile Infants and Young Children (2-24 months)?
Diagnosis - Both
an abnormal urinalysis result and a positive urine culture (at least 50,000CFU/ml, not 1 lakh) result are needed to confirm inflammation. Urine specimen obtained through urethral catherization or suprapubic aspiration.
Imaging - ultrasonography (bladder and kidney) with a first febrile UTI as the initial diagnostic test, VCUG is not recommended routinely after the first febrile urinary tract infection, recommended only after second
or subsequent febrile UTI
Treatment - Oral treatment is as effective as a parenteral treatment.
Follow-up - Emphasis is on urine testing with subsequent febrile illnesses, rather than on regularly repeated urine cultures after treatment
Note - Previous AAP guidelines recommended RBUS and VCUG for any child between 2-24 months of age, who presented with their first febrile UTI. In 2011, AAP recommended VCUG in first febrile UTI only if hydronephrosis, sonographic indications of possible renal scarring or dysmorphism, or other findings that suggest high-grade VUR or obstructive uropathy are present.
- - colonization alone in the presence of reflux still may pose a threat to the upper tracts.
- - AAP guidelines do not recommend routine DMSA
EAU Guideline for febrile UTI?
In all infants and girls more than one year, exclude vesicoureteral reflux (VUR) after the first episode of febrile UTI, using voiding cystourethography (VCUG) or a dimercaptosuccinic acid (DMSA) scan first (in case of a positive DMSA-scan, follow-up with VCUG). Strong
more than one year of age, exclude VUR after the second febrile UTI. Strong
Top down approach (TDA) and Bottom Up approach?
- Top Down Approach-
- - DMSA scan after first febrile UTI
- - VCUG only when abnormal DMSA scan
- Children with a negative DMSA scan undergo no further evaluation unless they develop recurrent UTI, in which case a VCUG should be obtained.
- Replaces screening sonography with a DMSA renal scan to identify acute pyelonephritis and/or renal scarring. Proponents of this algorithm recommend VCUG only in response to abnormal DMSA scans as an indicator of high-risk patients.
- - based on the notion that only clinically relevant reflux with potential to cause renal injury is worthy of uncovering, with the critical assumption that VUR in the absence of scintigraphic renal abnormality is unlikely to cause future renal damage.
- Bottom-up approach
- - relies on VCUG after sonography to identify all cases of VUR that may result in overtreatment of low-grade VUR.
Top Down approach - looking for VUR in those who have scar Bottom up approach - looking for VUR in each case
- We do VCUG only after 3 weeks of infection
National Institutes for Clinical Excellence (NICE) Guidelines?
- Routinely obtain an ultrasound in children less than 6 months old
- Do not recommend obtaining an ultrasound in children between 6 months and 3 years of age after the first febrile UTI unless it is recurrent or atypical. Atypical UTI as defined by being seriously ill, by poor urine flow, by abdominal or bladder mass, by raised creatinine and septicemia, by failure to respond to treatment within 48 hours, or by infection with a non–E. coli organism.
- Cystography reserved for infants younger than 6 months and in older infants when dilation is observed by ultrasonography.
- They do not recommend early DMSA renal scans to confirm or exclude renal involvement and rely solely on ultrasonography in sicker patients to determine the need for further investigation.
- DMSA 4-6 months after recurrent or atypical UTI
- Criticism - poor correlation between the appearance of kidney on USG and presence of renal parenchymal changes or presence and grade of VUR
The NICE committee did not provide any clinical outcomes to validate these guidelines, and until confirmation of the safety of this approach is established prospectively, it cannot be recommended for general clinical use.
[@ NICE UMND - Nice Upper Motor neuron Disease - In NICE - USG first, followed by MCUG, No DMSA till 6 months of age]
Assessment in VUR?
- Lower tract assessment
- - MCUG, RNC, Ultrasonic cystogram
- - Uroflowmetry
- - Cystoscopy and Positioning of the instillation of contrast at ureteric orifice and cystogram
- Assessment of upper urinary tract
- - Renal sonography
- - Renal Scintigraphy
How to do PIC test?
Cystoscopy and Positioning of the instillation of contrast at ureteric orifice and cystogram - detects reflux under GA in patients with history of febrile UTI.
In a select group of patients who present with recurrent febrile UTIs and no evidence of VUR on VCUG, there is some evidence to suggest that the positional instillation of contrast (PIC) with fluoroscopy may have some benefit.
With the bladder empty, the cystoscope beak is positioned close to and facing the ureteric orifice. Contrast is instilled at the ureteric orifice using the irrigation port of the cystoscope from a height of 1 meter above the bladder. Fluoroscopic spot imaging is done simultaneously with the instillation. PIC-VUR is confirmed if retrograde flow of contrast into the ureter/kidney pelvis is observed. The bladder is emptied before the procedure is repeated on the contralateral side.
Furthermore, PIC cystography does not allow for age-adjusted instillation pressures; some pressures may be too high in younger patients and maybe creating iatrogenic reflux rather than unmasking relevant, physiologically borderline reflux.
Routine cystoscopy is contraindicated in reflux management.
Renal sonogram in reflux?
USG the initial mainstay of renal imaging in VUR management.
Pyelonephritis propagated by reflux causes renal scarring, impedes attainment of full renal growth potential, and increases risk for renovascular hypertension. Therefore imaging of the upper tracts is directed at assessing renal structure and function, with attention to the aforementioned parameters.
In reflux diagnosed in the neonatal period, baseline renal dimensions are obtained and appropriate renal growth can be monitored over time.
Loss of corticomedullary differentiation, or an increase in the overall echogenicity of the kidney, is associated with some degree of renal functional impairment.
Resistive Index - increased in reflux nephropathy, pyelonephritis
Post-void residual urine should be measured in toilet-trained children to exclude voiding abnormalities as a cause of UTI.
If DMSA is normal, <1% chance of having high grade VUR
- The NICE guidelines recommend DMSA 4 to 6 months after acute recurrent UTI.
- AAP guidelines do not recommend routine DMSA.
- A baseline DMSA scan at the time of diagnosis can be used for comparison with successive scans later during follow-up.
Severely dysplastic kidney with high grade reflux, asymptomatic child, how to manage?
- More common in male child
- Antibiotic prophylaxis - does not work in such type of kidney, but if there is contralateral reflux, Ab may benefit
- Surgery - not required for VUR, actually high grade reflux in one side is masking the low grade reflux in the other side.
- If recurrent infection, proteinuria, HTN - nephrectomy, but you can get the reflux in the other side and follow this child for reflux
Difference in congenital defects and acquired scars?
The term scar is defined as fibrous tissue replacing normal tissues destroyed by injury or disease.
This scar tissue often appears as a smaller and photopenic area by scintigraphy or, when larger, as hyperechoic and shrunken areas on sonographic images. They are preventable complication of pyelonephritis, the latter being directly influenced by VUR in the presence of a bladder infection.
Abnormal origin of the ureteric bud will interact suboptimally with the metanephric blastema. The latter process is currently believed to be the likely cause of renal dysmorphism associated with reflux.
The challenge in imaging is to differentiate congenital reflux–associated renal dysmorphism from scarring acquired after infection.
Pathophysiology of acquired scarring?
Renal scarring is a sequela of infectious pyelonephritis.
Reflux provides a mechanical hydrodynamic mechanism that facilitates the ascension of microorganisms from the bladder to the kidneys. Thus reflux may be considered an accelerant for renal tissue infection after bacterial colonization of the bladder.
The kidney’s predilection for postpyelonephritic scarring is inversely proportional to age. The greatest risk for postinfectious renal scarring occurs within the first year of life. Similarly, patients younger than 4 years are more prone to developing scarring after a single UTI than older children, though scarring may still occur beyond 5 years of age. Scarring may still occur beyond 5 years of age. Thus some practitioners are withdrawing prophylaxis as the child approaches the age of 5.
What is big bang theory?
- Theory for the origin of scars after infant pyelonephritis.
- Most of the scarring to which the kidney is ultimately susceptible occurs after the initial bout of pyelonephritis and that further scarring in the absence of repeated pyelonephritic episodes is unlikely to occur. Consequently, the assumption is that little change in the initial scarring pattern is to be expected in follow-up scintigraphic imaging.
- Uncertainties introduced by such factors as
- (1) the weakly substantiated assumption that a relatively greater scarring propensity exists in younger kidneys,
- (2) the reports of new follow-up scarring in the landmark reflux studies (see later discussion),
- (3) the failure to differentiate between post-pyelonephritic imaging defects resulting from infection versus intrinsic developmental dysmorphism associated with reflux,
- (4) the changing appearance of such imaging defects with renal growth over time, and
- (5) the limited ability to compare disparate imaging modalities in the reflux literature (urograms vs. nuclear scans) together must challenge the notion that the greatest postinfection parenchymal loss occurs after the first infection
Papillary anatomy and reflux?
Papillae with a concave architecture (compound papillae) present their ducts at right angles, whereas more convex papillae possess ducts that end obliquely, producing a valvular effect that guards against backflow of urine into the medullary collecting ducts.
- The more polar calyces are composed preferentially of compound papillae compared with the middle calyces. The former are more commonly the site of intrarenal reflux (reflux into the ducts) and are the prime regions of susceptibility to scarring.
- Intrarenal reflux can occur with as little as 2 mm Hg pressure in the neonate . By 1 year of age, the pressure required is one order of magnitude greater and helps explain the relative infrequency of intrarenal reflux in older children.
VUR and HTN?
Cause of reflux-associated hypertension - deranged renal microvascular mechanisms associated with parenchymal defects. Successful correction of reflux alone is unlikely to ameliorate blood pressure. Indeed, removal of renal segments verified by selective renal vein sampling of arteriolar or segmental vessel renin levels has provided durable normalization of blood pressure in carefully selected patients with up to 67% of patients becoming normotensive after nephrectomy. On occasion, complete removal of a small unilateral congenitally dysplastic or globally scarred and shrunken kidney also may correct renovascular hypertension because such kidneys are clearly not amenable to partial nephrectomy for any discrete segment.
Associated anomalies with VUR?
- Ureteral duplication
- Bladder diverticula
- Renal anomalies - renal agenesis, MCDK
- Megacystis-megaureter association
Radiological signs that may suggest the presence of concomitant UVJ obstruction in the context of VUR?
- (1) dilated proximal ureter/not necessarily kidney,
- (2) transition area to distal, aperistaltic juxtavesical segment,
- (3) decrease in contrast caused by mixing with trapped, nonopaque urine, and
- (4) delay in drainage on postvoid film above aperistaltic distal ureteral segment
Radiologic signs might suggest the existence of UPJO in the setting of reflux?
- 1. If the pelvis shows little or no filling while the ureter is dilated by contrast, this may indicate a point of kinking secondary to reflux or from a primary UPJO.
- 2. Contrast that enters the pelvis may be poorly visualized because of dilution in a large pelvic volume and exhibits markedly
- lower radiodensity compared with the ureter or bladder.
- 3. A large pelvis that fails to drain promptly and retains contrast postvoid is also suggestive of UPJO
What is megacystis-megaureter syndrome?
- Massive bilateral VUR can cause a gradual remodeling of the entire upper urinary tract. The gross inefficiency of the bladder that expels urine to both the exterior and the upper tracts results in gradual bladder dilation as the refluxed urine returns to the bladder.
- This perpetuates marked ureteral dilation, leading to the radiographic appearance of massive hydroureter and a thin-walled enlarged bladder. The phenomenon is referred to as the megacystis-megaureter association or syndrome.
- Megacystis-megaureter is a nonobstructive condition akin to cardiac dilation by regurgitation from incompetent valves.
Vesicostomy can temporize by eliminating the residual urine volume and establishing safe drainage of the upper tracts until ureteral reimplantation can be performed.
Describe the recent advances in managementof reflux nephropathy. (TU 71-10)
History of management of VUR?
- 1972 - Politano surgery
- 1980 - Concept of antibiotic prophylaxis
- Between 1973-1985 - Extensive surgery was done for VUR, later came the concept of antibiotic prophylaxis in VUR.
- 1982 -beginning of widespread use of antenatal USG, concept of congenital scarring
Describe the principles of management of VUR/ (TU 69,5)
Principles of reflux management?
Principle of management is the preservation of renal function and prevention of UTI and renal scarring is paramount.
In the face of the paradigm shift after the 2011 AAP recommendation to limit the initial investigation to RBUS and ultimate reduction in cystography and associated diagnosis of VUR, clinical practices have evolved to refocus management into a risk-based fashion. This upholds the notion that VUR cannot be distilled into a dichotomous process. Patients present with a wider spectrum of severity, which extends beyond the classic grading system, including a multitude of dynamic factors, which can alter a child’s overall risk for infection or progression over time. For example the perceived impact of associated BBD on resolution of VUR and recurrent UTIs is significant.
- The essential tenets of reflux management are as follows:
- 1. Spontaneous resolution of reflux is very common and facilitated by correction of BBD.
- 2. Higher grades of reflux are less likely to resolve spontaneously, especially when diagnosed in older children after UTI.
- 3. Sterile reflux is unlikely to cause significant renal damage.
- 4. Prevention of UTI is more important than VUR resolution.
- 5. The use of prophylactic antibiotics is safe and beneficial, particularly in high-risk patients.
- 6. There is a role for medical management for most forms of reflu
- The classic approach has been to offer daily low-dose prophylactic antibiotic suppression of infections as the first line of treatment while awaiting spontaneous reflux resolution, regardless of grade.
- In patients diagnosed after one or more episodes of pyelonephritis, the presence of scarring on renal scans may temper a decision for extended prophylaxis and observation, particularly if scarring is extensive, the reflux is high grade, renal function is already globally depressed, or congenital dysplasia of one or both kidneys is present. In such cases, tolerance for another infection despite prophylaxis may be low, or simple uneasiness with the notion of ongoing reflux may invite strong consideration for reflux correction.
- 1. Antibiotic prophylaxis appears to provide little benefit for those with grade II or lower VUR, particularly in the absence of BBD. Conversely, antibiotic prophylaxis does appear to be beneficial for those with grade III or higher VUR, at least among girls.
- 2. Approximately 15% of children with VUR will have a recurrent febrile UTI within 2 years, and about 15% of these children will develop a renal scar.
- 3. Bowel and/or bladder dysfunction is a major risk factor for recurrent UTIs on or off antibiotics, which will occur in about 45% of children with BBD, as opposed to 15% of those without BBD.
- 4. A higher grade of VUR is associated with an increased risk for both pyelonephritis and new renal damage.
- 5. The effect of age on the risk for renal damage is not well defined, although many believe that younger children are more susceptible to renal damage from pyelonephritis.
Basis of conservative management in VUR?
- • VUR resolves spontaneously, mostly in young patients with low-grade reflux. Resolution is nearly 80% in VUR grades I and II and 30-50% in VUR grades III-V within four to five years of follow-up. Spontaneous resolution is low for bilateral high-grade reflux].
- • Vesicoureteric reflux does not damage the kidney when patients are free of infection and have normal LUT function.
- • There is no evidence that small scars can cause hypertension, renal insufficiency or problems during pregnancy. Indeed, these are possible only in cases of severe bilateral renal damage.
- • The conservative approach includes watchful waiting, intermittent or continuous antibiotic prophylaxis, and bladder rehabilitation in those with LUTD.
- • Circumcision reduces the rate of UTI development in the first 6 months of life by almost 10 folds.
Resolution of VUR by grade?
- Most cases of low-grade reflux (grade I and II) will resolve
- Grade 3 reflux will resolve in approximately 50% of cases
- Very few cases of higher-grade reflux (grades 4 and 5, and bilateral grade 3) will resolve spontaneously
Resolution of VUR by increasing age?
- Note the difference in resolution between Grade IV - unilateral and bilateral reflux
The prevalence of reflux is higher in siblings. It cannot be assumed that all cortical abnormalities in refluxing siblings are acquired. Mass screening of siblings is unnecessary, and clinicians should be selective based on sibling risk profile.
- In males, after 5 year of age, prophylaxis can be stopped
- Girls have traditionally undergone open surgical correction, even for asymptomatic reflux that fails to resolve by the age of 5, on the premise that it will reduce maternal and fetal morbidity during a future pregnancy. (C11-3154)
Components of watchful waiting medical management
Maintaining urine sterility (through both prophylactic antibiotics and strict attention to bladder and bowel management) is the cornerstone of watchful waiting medical management. Teaching and periodic review of perineal hygiene techniques, timely bladder-emptying habits, healthy dietary and bowel measures to prevent constipation, and carefully evaluating family compliance and access to prompt care should influence treatment plans. Patients identified as high risk benefit from initiation of CAP.
1. Antibiotic prophylaxis
2. Bladder training (urotherapy)
3. Treatment of BBD - The AUA guidelines 2010 suggest that BBD is by far one of the most critical and modifiable variables that affect VUR resolution, overall management, and attendant UTIs. Ensure that a detailed investigation for the presence of lower urinary tract dysfunction (LUTD) is done in all and especially in children after toilet-training
. If LUTD is found, the initial treatment should always be for LUTD. Strong (EAU 2020)
4. Status of circumcision should be checked in boys and treatment of the phimosis considered in those with pyelonephritis. (EAU 2020)
- 5. Periodic assessment of reflux and child well-being
- - Serial assessment of blood pressure, renal function, and somatic growth
- - Serial urinalysis or urine culture
- - Serial voiding cystourethrogram or radionuclide cystogram
- - Serial upper urinary tract studies
Risk factors and risk groups for vesicoureteral reflux. (Modified from Hidas G, 2013)
Tool to help stratify patients at each encounter and assess the likelihood of BUTIs.
A clinician can use this risk characterization to better understand the specific child’s risk for infection in the context of VUR and guide each patient’s care, identifying which factors need to be modified to reduce each child’s risk profile, not only to prevent infection, but also to decrease the intensity of treatment and follow-up when possible.
As an example: An uncircumcised male child evaluated and found to have BBD and intermediate grade VUR puts him at intermediate risk for BUTI. The clinician may opt to continue or start CAP until the BBD and potential phimosis is confidently treated, at which point the child’s risk might be considered to have been downgraded and the risk for BUTI is sufficiently lowered (from 28% to 8.6%) such that CAP can be safely discontinued. Conversely, if a child presents with high-grade VUR, BBD, and is a female, the clinician may consider a trial of CAP, but given that the risk for BUTI is high, discussion with the family regarding a more aggressive approach with up-front correction of VUR may not be entirely unreasonable.
- Infection - None - Recurrent
- African descent - VUR rare, Caucasian (european white) - more
- [@ BASIS for PG - BBD, Age, Sex, Infection, Scaring, Presentation, Grade]
- The only time when UTI are more prevalent in boys than in girls is less than 1 year of age
How is the antibiotic given in VUR?
Daily or Intermittent (i.e., treatment of UTIs when they are diagnosed)
Antibiotic prophylaxis appears to provide little benefit to grade II or lower VUR, particularly in the absence of BBD, maximum benefit with grade III or higher VUR, at least among girls.
Principle - every case of reflux should be offered time to resolve spontaneously, despite grade. The principal rationale for antibiotic use in the management of reflux is the prevention of UTI, principally febrile pyelonephritis, which may lead to permanent postinfection renal scarring.
Antibiotic is given once per day, and preferably at night. Nighttime dosing allows for antibiotic concentration in the bladder urine over the longest period of expected physiologic retention when infection is most likely to develop.
The typical dose is one fourth of normal dose. Low dose to prevent resistance, side effects and gut bacteria protection. ( C12-443) One-third of the treatment dose - EAU
Common choices for prophylactic antibiotics - TMP-SMX, TMP, nitrofurantoin, and first-generation cephalosporins. For children younger than 2 months of age, the most commonly used medications are trimethoprim and amoxicillin. Children younger than 2 months of age possess relative hepatic immaturity and are unable to clear sulfamethoxazole efficiently; the drug displaces fetal bilirubin and leads to jaundice.
In the absence of infection, sterile urinary reflux is insufficient to cause renal damage.
Normal dose and prophylactic dose of commonly used antibiotics?
Normal dose /prophylactic dose
- - Amoxicillin - <30mg/kg/day / 5
- - Nitrofurantoin - 6 mg/kg/day BD / 2
- - Cotrim - trimethoprim/sulfamethoxazole (>2 months) - 8mg/kg/day BD/ 2
- - trimethoprim - -/2 [@2,2,2,5]
- - Cefixime - 8mg/kg/day OD / .....
- - Ceftriaxone - 75mg/kg/day OD / ....
- - Amikacin - 7.5mg/kg/day divided q8h / ...
- - Piperacillin - 300mg/kg/day q8h/ ......
Causes of breakthrough UTI?
- (1) If the organism is sensitive to the prescribed prophylactic antibiotic, the child or parent has likely not been compliant or the dose is too low
- (2) If the organism is resistant to the prescribed antibiotic, either the residual bladder volume is too high too often or the dose is too high
When to stop antibiotic prophylaxis?
Once the radiographic resolution of reflux has been documented, antibiotic prophylaxis is terminated, usually a few days after the cystogram.
However, because reflux resolution will likely herald a tapering or discharge from regular urologic follow-up, this also is the precise time for reinforcing a lifelong adoption of good toileting and bladder behaviors.
EAU 2020 - Use CAP in most patients. Use CAP until after children have been toilet-trained and ensuring that there is no LUTD. Continuous antibiotic prophylaxis is mandatory in patients with LUTD and reflux. Active surveillance of UTI is needed after CAP is discontinued.
Various studies in VUR
RIVUR study - Placebo Vs Antibiotics
International reflux study in children - Antibiotics Vs Surgery vs watchful waiting
Swedish Reflux Study - Antibiotics Vs Surgery Vs Surveillance
- Birmingham Reflux Study 1987
- - antibiotic vs surgery
- - incidence of new scars was the same using either treatment modality
- PRIVENT study 2009
- - CAP or placebo
- - There was a decrease in the number of UTIs when placed on a low-dose, long-term regime with an absolute risk reduction of 6% from 19% to 13%
International reflux study in children 1992
- - children younger than 9 years of age with high-grade reflux to watchful waiting with prophylaxis or corrective open surgery
- - Although surgery was complicated by temporary postoperative obstruction in some patients, it was more effective than prophylaxis in reducing, but not eliminating, the occurrence of pyelonephritis.
- - the incidence of UTI (38%) was the same with both modalities.
- - the modalities were equally effective in reducing, but not eliminating, new scar formation.
Swedish Reflux Study 2010
- - prospective trial evaluated prophylaxis and endoscopic injection for children with dilating VUR compared with surveillance
- - 203 children, 1 to 2 years of age, with VUR grade III or IV randomized to CAP, up-front corrective surgery with endoscopic injection, or surveillance
- - Patients underwent VCUG and renal scintigraphy at entry, and at the end of the 2-year study
- - Conclusion - there is a role for up-front treatment with either endoscopic injections or CAP, predominantly in girls, with associated reductions in both recurrent UTIs and new renal scars. [@ SwED-I-sh - EnDoscopic Injection]
Randomized Intervention for the Management of Vesicoureteral Reflux (RIVUR study)?
RIVUR is a National Institutes of Health multicenter, double-blind, randomized, placebo-controlled trial designed to evaluate the effectiveness of antimicrobial prophylaxis in children found to have reflux after an initial UTI.
- 600 children with grade 1 to 4 reflux after an initial or second febrile or symptomatic UTI.
- Randomized to oral placebo versus oral TMP-SMX antibiotic prophylaxis.
- The primary outcome measure - development of recurrent febrile or symptomatic UTI
Criteria for treatment failure - multiple UTI recurrences, ± fever, ± symptoms
- - antibiotic prophylaxis reduced recurrent UTI risk by 50%
- - renal scarring findings appeared unaffected by prophylaxis (11.9% vs. 10.2% in antibiotic vs. prophylaxis groups, respectively
- - The most significant benefit with CAP was seen in those subgroups who had BBD or presented with a febrile UTI.
- - Additional review of the RIVUR data based on a risk classification system in 2018 defines a high-risk group (uncircumcised males; the presence of BBD and high-grade reflux) who would benefit from antibiotic prophylaxis significantly. Therefore selective prophylaxis for this group is recommended
Why RIVUR trial still debated?
No difference in renal scarring (11.9% vs 10.2% in placebo)
50% relative risk reduction in recurrant UTI -
Treatment failure in 9.5% in placebo vs 5% in antibiotic group - the converse means that 90% treatment success was acheived with placebo alone - then why to use antibiotics and get side effects and resistance?
Breakthough UTI, what should be done next?
- Antibiotics dose
- Prepucial hygiene - very important, if not good - plan for circumcision. Circumcision can be done as early as 3 months.
- Bladder bowel habits. Circumcision is only helpful in first year of life
- ?Termination of medical management with CAP and correcting the reflux
- Proper antibiotic selection and dosing
- Patient and parental acceptance and compliance with the chosen therapy
- Meticulous attention to proper collection and handling of urine culture specimens
Management of VUR in neuropathic dysfunction of the lower urinary bladder?
Reflux grades 1 to 3 who void spontaneously or have a complete lesion with little or no bladder outlet resistance and empty their bladder completely, management consists solely of prophylaxis with antibiotics to prevent recurrent infection.
High-grade reflux (grade 4 or 5) - CIC is begun to ensure complete emptying. Children who cannot empty their bladder spontaneously, regardless of the grade of reflux, are treated with CIC to improve emptying efficiency.
Children with poor detrusor compliance with or without hydroureteronephrosis are also started on antimuscarinic agents to lower intravesical pressure and ensure adequate upper urinary tract decompression.
Credé voiding should be avoided in children with reflux, especially those with a reactive external urethral sphincter. In this circumstance, the Credé maneuver results in a reflex response in the external sphincter that increases urethral resistance and raises the pressure needed to expel urine from the bladder. This has the effect of aggravating the degree of reflux and accentuating its waterhammer effect on the kidneys.
The indications for antireflux surgery in this group of children are not very different from those applicable to children with normal bladder function. Antireflux surgery can be very effective in children with neurogenic bladder dysfunction as long as it is combined with measures to ensure complete bladder emptying.
- Reflux secondary to bladder hostility may not need surgical correction if the bladder is adequately managed.
- Most secondary reflux ill likely resolve with adequate reconstruction of bladder, correction needs in high grade reflux.