1. The spectrum of renal scarring
Parvex, Willi, Kossovsky, Girardin, pediatric nephrology, Geneva University, Switzerland

2. Background
UTI is common condition in childhood with a prevalence of 3%, the prevalence of pyelonephritis (PNA) is not clearly reported
Infant and children presenting unexplained fever of ≥ 38° and positive urine culture will be diagnosed with PNA

3. Background The goal of medical management of PNA
Initiate early treatment to decrease renal inflammation and subsequently scars
Identify risk factor to avoid new infections episodes and prevent scars development
Exclude urologic anomalies (renal echography)
Detect vesico-ureteral reflux (cystography)

4. Pathogenesis of scars
It is important to differentiate acquired segmental scarring associated with VUR and PNA
From congenital “scars” corresponding to an anomaly in the metanephric development in boys and associated with high grade VUR
Histological analyses of these later lesions showed renal dysplasia which may mimic scarring without an acute episode of PNA

5. Renal scintigraphy
Since 1980, renal scintigraphy with TechnetiumTc labeled with dimercapto-succinyl-acid DMSA
replaced IVP and improved in the detection of renal scars
has been validated to be the most sensitive method for imaging in the diagnosis of acute PNA and for renal scars

6. Normal kidney
Acute PNA
Renal scars

7. What is known form the literature
Did early antibiotic treatment avoid scar formation?
How important is the grade of VUR?
Is the risk to do scars related to age?
Are scars leading to hypertension (HTA) in adulthood?

8. Early treatment (T)?
Recent data suggest that if early T decrease renal inflammation in the acute phase
However in this patients (n=186) early T seems not to decrease the risk of later scars (T<24H or T>24H)
Doganis, D. et al. Pediatrics 2007;120:e922-e928

9. Role of VUR?
VUR is considered to be the principal risk factor to favor PNA and therefore renal scars
The incidence of VUR in children presenting PNA varies among studies from 30 to 50%
Even if scars can develop without VUR or low grade VUR however the risk increased with high grade VUR

10. VUR and severity of scars
Gonzalez et al. The Journal of Urology , Volume 173 , Issue 2 , Pages

11. Age and risk factor
Benador et al Vol 379, January 1997, Pages 17-19

12. Vol 379, January 1997, Pages 17-19

13. HTA
One of the main concern are further development of hypertension in children presenting scars
Hypertension affects among series 5-27% of children; however the literature have not showed strong evidence until known

14. Risk for the future: HTA
A 15 years follow-up of BP studied 78 Pts with reflux nephropathy
All were normal BP at time of inclusion
18/78 pts became HTA(>95th) during the following 15 years; 6 from them had a family history for HTA

15. Systolic and diastolic BP at 5,10,15 years follow-ups
Chulananda et al. Vol 347, March 9,1996

16. Risks for the future: HTA
The following recorded 24HBP in 61 pts classified in different groups according to the severity of DMSA lesions
Type 1: normal reniforme shape but polar area with photon deficiency
Type 2: focal defect in a nondeformed kidney
Type 3: Smaller kidney compared to controlateral
Type 4a:Loss of renal contour with normal size kidney
Type 4b:similar from above with small kidney

18. Is this increase of BP at night a sign of further evolution of HTA in adulthood needs to be confirmed by long term studies
J Pediatr. Patzer et al 2003 Feb;142(2):

19. What is the long
term significance of scars?

20. Background
The presence of lesions on DMSA 6 month after PNA are considered to be definitive kidney scars
According to the literature the rate of acute lesions and later scars varies among studies

22. Questions?
Did these lesions still have the potential to evolve after 6 month
Did this lesions interfere with normal renal growth

23. Aim of the study
To analyze long term progression of renal lesions in children with presence of scars on the first DMSA
To assess long term renal growth
To identify variables which could impact on renal growth in this children

24. Material
This prospective study was conducted over two years and included
Children from 0-18 years with a diagnosis of PNA and who presented renal scars 6 month after the first episode of PNA
Exclusion criteria
Children with complex uro-genital malformations, dysplastic kidneys, megaurether, hydronephrosis

25. Methods
Each patient with scars was contacted to have a repeated DMSA 3 years later
At the same time we repeated a renal echography to measure kidney size

26. To analyze progression of DMSA defects, RU was divided in 3 areas
Scar progression was analyzed separately for each area by 3 observers in a blinded fashion and classified as follow
No change
Partial resolution
Total disappearance
Upper pole
Mid zone
Lower pole

27. b b a a 1B 1A
1A DMSA 6 month after PNA 1B DMSA 3 years later: we observe 2 types of lesions: a) the lesion situated in the mid-zone of left kidney did not change b) The lesion located in the right upper pole improved. 2A a a 2A b 2B b
2A DMSA 6 month 2B DMSA 3 years later: we observe a) disappearance of mid-zone lesion of left kidney b) no change in lower lesion of right kidney
Parvex et al The Journal of Urology on Press

28. Kidney growth
(cm)
Kidney size was measured Time 0 corresponding to the PNA (T0) and 3 years later Time 3 (T3) at the same time of the repeated DMSA

29. *AJR Am J Roentgenol 1984;142(3):467-9.
Renal size was measured at T0 and T 3 and values compared to standard deviation score (SDS ) renal sizes* relative to age
The following equation were used*to calculate
Z-score
*<1 year length (cm)= x age(mths)(t90 = 6.86, p<0.001;SD=0.69;r2=0.3437
*≥ 1 year length (cm)= x age(years)(t326 = 28, <0.001;SD=0.79;r2=0.7077
Renal growth between T0 and T3 was calculated with the ∆z-score
= or + ∆z-score correspond to adequate renal growth
- ∆z-score correspond in loss of renal growth
*AJR Am J Roentgenol 1984;142(3):467-9.

30. Results 50 (30G:20B) children; M age of 4.1
Boys were younger 15/20 ≤2years(75%) against 9/30 (30%) girls
VUR was present in 36% of patients and 25% of renal units (RU)

31. Incidence and evolution of VUR

32. Number of scars & Grade of VUR
P=0.01
Number of scars
NO VUR VUR GI-II VUR GIII-IV
Parvex et al The Journal of Urology in Press

33. Progression of renal scars
% scar improvement
27%
63% 9%
no change partial improvement total disappearance
Altogether 72% of lesions improved over 3 years

34. Impact of scars on kidney growth
Analyze
Coefficient
∆z-score
Significance (p)
95% conf. interval
1 defect*
Reference -
2 defects
-0.32
0.41
-1.09 to 0.45
3 defects
-0.81
-2.75 to 1.14
4 defects
-1.59
0.000
-2.10 to -1.09
5 defects
-1.73
0.006
-2.94 to -0.51
Table1: Univariate linear regression analysis of the association between the numbers of defects and renal growth (coefficient=∆ z-score)
Parvex et al The Journal of Urology in Press

35. Analyze
coefficient
Significance (p)
95% conf. interval
Sex (M vs. F)
0.49
0.14
-0.16 to 1.14
Age (years)
≤ 1* (n=13)
> 1 to ≤ 4 (n=20)
> 5 (n=17) -
0.28
0.72
0.42
0.12
-0.41 to 0.96
-0.18 to 1.62
Total n° of defects
(Per additional defect)
-0.70
<0.001
-1.05 to -0.35
Lesions progression (Improvement vs. no change)
0.70
0.15
-0.26 to 1.66
Grade of VUR at time of PNA
No reflux * Grade I or II Grade III or IV
0.34
-0.21 to 1.72
-0.36 to 1.02
Improvement of VUR >3 years (Yes vs. No)
0.25
0.23
-0.17 to 0.67
Persistence of VUR >3 years (Yes vs. No)
-1.67 to 0.30
Surgery (Yes vs. No)
0.41
-0.36 to 0.86
Table 2: Multivariable analysis of factors associated with renal growth (coefficient = ∆z-score)
Parvex et al The Journal of Urology in Press

36. In summary
The topographic analyses of renal defects over 3 years showed 72% of improvement
The number of scars were statistically significantly higher in RU with high grade VUR versus low grade or no VUR.
Parvex et al The Journal of Urology in Press

37. Loss of kidney growth over 3 years was observed
with an increased number of scars and this was highly significantly >3 scars
persistence of VUR>3 years
The kidney growth did not seem affected by
Sexe, age
Grade of VUR
Improvement of DMSA defects
Parvex et al The Journal of Urology in Press

38. Conclusion
Renal defects seen at 6 month post PNA can still evolve with time and this raise the question of the definition of scars
From this study preventing additional renal defects seems to be the best way to optimize kidney growth during childhood
Parvex et al The Journal of Urology on Press

39. Open questions and further perspectives
Improve knowledge of the congenital “scar” associating renal dysplasia and HGVUR
To define if the best way to prevent renal lesions in high grade VUR is prophylaxis? surgery?
Long term studies to assess the risk HTA in scarred kidneys, with decreased renal growth

40. Thanks' for your attention