Longitudinal study of infants with high-grade ......high-grade vesicoureteral refluxgrade...
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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
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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.
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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?
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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.
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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%)
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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
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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)
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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
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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
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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.
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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.
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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)
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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.
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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%)
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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.
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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.
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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.
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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