Longitudinal study of infants with high grade vesicoureteral refluxhigh-grade vesicoureteral reflux
S fi Sjö t öSofia Sjöström
Department of PediatricsInstitute of Clinical Sciencesat Sahlgrenska Academy
UNIVERSITY OF GOTHENBURG
i f bli iList of PublicationsI. Sjostrom S., Sillén U., Bachelard M., Hansson S. and Stokland E.,
Spontaneous resolution of high grade infantile vesicoureteral reflux.J Urol, 2004. 172(2): p. 694-8; discussion 699.
II. Sjostrom S., Jodal U., Sixt R., Bachelard M. and Sillén U.,Longitudinal Development of Renal Damage and Renal Function i I f t With Hi h G d V i t l R flin Infants With High Grade Vesicoureteral Reflux.J Urol, 2009. 181, 2277-2283.
III Sjostrom S Bachelard M Sixt R and Sillén UIII. Sjostrom S., Bachelard M., Sixt R. and Sillén U., Change of urodynamic patterns in infants with dilating vesicoureteral reflux;three year followup.J Urol 2009 182(5):2453-4J Urol, 2009. 182(5):2453-4 .
IV. Sjostrom S., Jodal U., Stokland E., Sixt R., Wahll L., and Sillén U.,Predictive factors for resolution of high-grade infantile vesicoureteralPredictive factors for resolution of high grade infantile vesicoureteral reflux.-Results of uni and multivariate analyses.J Urol, 2010. 183(3), 1177-1184.
h iResearch questions•What is the spontaneous resolution rate in dilated infantile VUR and which factors affect the outcome? C l t ti t ith hi h h f l ti f th Can we select patients with a high chance of resolution from those with a low probability of resolution?
•What is the frequency of renal abnormality in dilated infantile VUR and how many have impaired renal function? y pCan we identify riskfactors for deterioration of renal status?
Wh t th bl dd f ti h t i ti i i f til dil t d •What are the bladder function characteristics in infantile dilated VUR and do they change during the first years of life? How many develop bladder dysfunction?develop bladder dysfunction?
S d d iStudy design
Prospective longitudinal observational study.p g yEligable; Children with primary dilated vesicoureteral reflux (grade III V) diagnosed vesicoureteral reflux (grade III-V) diagnosed during the first year of life.Monitoring of renal status, bladder function and natural course of reflux over time.
i lMaterial
Paper I, II, IV III
Patients, year of birth 1992-1997 1992-97 / 1998-99
Number of patients 115 114 ( 94 / 20 )p ( )
Sex, N (%) : boys girls
80 (70%)35 (30%)
89 (78%)25 (22%)girls 35 (30%) 25 (22%)
Presentation: prenatal 30 (26%) 30 (26%)UTIother
82 (71%)3 (3%)
84 (74%)
G d f i l iGrade of VUR at inclusion
40
s
30
35
patie
nts
15
20
25
GirlsBoysm
ber o
f p
5
10
15 Boys
Num
0
5
Grade III Grade IV Grade V
h dMethodsNumber of investigations per child
Age at first investigationMedian months
Follow-up time
Median monthsper child Median (range)
Median months (range)
Median months (range)
VCM, (VCU) & 3 (2-5) 2.7 (0.03-12) 36 (2-69)( )Free voiding studies
( ) ( ) ( )
Scintigrams 4 (1 10) 4 7 (0 2 54) 62 (4 135)Scintigrams (DMSA&MAG3)
4 (1-10) 4.7 (0.2-54) 62 (4-135)
Clearance 3 (1-11) 7.7 (0.5-72) 53 (1-145)(51Cr-EDTA-clearance)
lResultsComplete resolution of VUR in 30 (26%)Downgrading of VUR to grade I-II in 14 (12%) Probability of dilated VURA. Split by grade of VUR at inclusion
Log-Rank test:p=0.003
All patients
ng re
flux
0.7
0.8
0.9
1.0
Log-Rank test:
All patients
0.9
1.0
All ti t
B. With or without breakthrough infections
C With or without bladder dysfunction
Not cured
Grade at entry345
Pro
babi
lity
of d
ilatin
0.2
0.3
0.4
0.5
0.6Log-Rank test:
p=<.001
Breakthrough infectionity o
f dila
ting
reflu
x
0.4
0.5
0.6
0.7
0.8
Log-Rank test:p=<.001
All patients
ng re
flux
0.7
0.8
0.9
1.0
C. With or without bladder dysfunction
n=18 7 3n= 52 39 25 16 8 5 4n= 45 34 29 18 12 5 5
0.0
0.1
Years of follow-up after first VCU0 1 2 3 4 5 6 7 Not cured
n= 61 37 23 11 8 Non= 54 43 34 25 13 5 Yes
gNo
Yes
Prob
abil
0.0
0.1
0.2
0.3
0 1 2 3 4 5 6 7N t d
Bladder dysfunctionNo
Yes
Prob
abilit
y of
dila
tin
0.2
0.3
0.4
0.5
0.6
Years of follow-up after first VCUNot curedn= 44 21 11 6 Non= 42 38 30 21 12 5 Yes
0.0
0.1
Years of follow-up after first VCU0 1 2 3 4 5 6 7
lResults
Independent variables negatively associated to VUR resolution in multivariate analyses
Variable Hazard Ratio (95% CI) p-valueRenal abnormality 0 43 (0 29-0 63) <0 0001Renal abnormality 0.43 (0.29 0.63) <0.0001
Bladder dysfunction 0.36 (0.24-0.53) <0.0001
Breakthrough UTI 0.49 (0.25-0.97) 0.0397
C l iConclusion
The spontaneous resolution rate in infantile high-grade VUR:infantile high-grade VUR:-Is high (Resolution or downgrading in 38%)I hi h i b d i th i f t -Is higher in boys during the infant year
-Is negatively associated with breakthrough infections, bladder dysfunction, higher grades of VUR and y , g grenal abnormalities.
C l iConclusion
Multivariate analysesMultivariate analyses
Renal damage Bladder dysfunctionRenal damage, Bladder dysfunctionand Breakthrough UTIhave shown to be three strong independent factors for prediction of resolution of VUR pin multivariate analyses.
lResults
0.9
1.0
0.9
1.0
0.9
1.0
atus
Probability of unchanged or deteriorated renal statusf u
ncha
nged
rena
l sta
tus
0 4
0.5
0.6
0.7
0.8
Breakth0 4
0.5
0.6
0.7
0.8
Uni or bilater0 4
0.5
0.6
0.7
0.8
Rena
Breakthrough UTI No/Yes
unch
ange
d ren
al st
Uni or bilateral renal abnormality
Renal function (GFR)Normal/Subnormal
Prob
abilit
y of
0.0
0.1
0.2
0.3
0.4
0 1 2 3 4 5 6 7 8
Unchanged status
Log-Rank test:p=0.041
n= 56 55 49 44 33 26 21 15 1n= 52 51 44 41 31 22 15 6 5
0.0
0.1
0.2
0.3
0.4
Unchanged status
Log-Rank test:p=0.038
n= 27 26 23 18 16 11 8 5n= 71 70 63 61 46 36 28 16
0.0
0.1
0.2
0.3
0.4
0 1 2 3 4 5 6 7 8
Unchanged status
Log-Rank test:p=0.001
n= 32 31 25 22 19 13 10 5n= 75 74 67 63 45 35 26 17 1
Prob
abilit
y of u
Breakthrough UTI, bilateral renal damage and subnormal GFR were predictors for deterioration in renal status
Years of follow-up0 1 2 3 4 5 6 7 8
Years of follow-up0 1 2 3 4 5 6 7 8
Years of follow-up0 1 2 3 4 5 6 7 8
Years of follow-up Years of follow-up Years of follow-up
were predictors for deterioration in renal status.Deterioration was more frequent in prenatally diagnosed patients (p=0.047) (p 0.047)
C l iConclusionThe frequency of renal abnormalityin infantile dilated VUR is high (85%).g ( )Subnormal renal function is seen in 30%.
Renal status-Remains unchanged in the majority (82%) during the first years of life.-Breakthrough UTI, bilateral renal damage and subnormal renal function are predictors for deterioration in renal status.
ResultsResultsTYPE OF BLADDER DYSFUNCTION
•HIGH CAPACITY &
Bladder dysfunction was found in 48 (42%) of study patients
•HIGH CAPACITY & INCOMPLETE EMPTYING34 of 48 (71%)34 of 48 (71%)•OVERACTIVE CONTRACTIONS14 of 48 (29%)14 of 48 (29%)
C l iConclusion
In infants with ditated VUR:Bladder dysfunction is common-Bladder dysfunction is common.
-The urodynamic pattern changes during the first f lifyears of life.
-High pressure and low capacity turns into high capacity with incomplete emptying.-Bladder dysfunction can only be diagnosed from adde dys u ct o ca o y be d ag osed othe second year of life and is seen in almost half of the patientsof the patients.
G l C l iGeneral Conclusion
This observational study has resulted in: d t il d d i ti f th h t i ti d -a detailed description of the characteristics and
course of dilated VUR in infants. d i ti f h i d i d i th -a description of changes in urodynamics during the
first years of life. d i ti f l t t t i l i d -a description of renal status at inclusion and over
time.i k f t ff ti th t h b -risk factors affecting the outcome have been
identified.
Cli i l li iClinical Implications
Our study has provided tools for distinguishing infants with a high chance of spontaneous infants with a high chance of spontaneous resolution from those with a high risk of remaining dilated refluxdilated reflux.
The study results can be used to formulate hypotheses for future management of infants with dilated VUR.
Thank You!
The doctoral thesis Longitudinal study of infants Longitudinal study of infants with high-grade vesicoureteral refluxis avaliable on internet
http:hdl handle net/2077/20459http:hdl.handle.net/2077/20459