Minu Bajpai, Pradeep K Chaturvedi, Chandra S Bal, Meher C Sharma, Mani Kalaivani Journal of Indian Association of Pediatric Surgeons

Year : 2013 | Volume : 18 | Issue : 2 | Page : 74-78

CRF:in a significant no. of children with PUVs. 16.8% of population of children with ESRD. RAS activation as a mediator of renal injury & interstitial fibrosis reported . Prospective study Role of RAS blockade by ACE-I after PUV ablation evaluated & correlated it with tests of renal function, micro albuminuria, and PRA

To study renin angiotensin system (RAS) activity after PUV ablation & role of early induction of ACE-I on the outcome of renal function

Study group: 34 children underwent valve ablation b/w 3 -7.5 m. Serum creatinine and PRA :measured before, between 1 month and 3 months after valve ablation & at 1 yearly intervals. GFR : at 60, 90, 150, and 180 min after 99mTech DTPA injection. Renal scars evaluated by DMSA scan.

pts with GFR < 50 mL/min/1.73 m 2 severely scarred kidneys & refluxing units

Group 1: no e/o VUR & scar formation (n = 13) Group 2: e/o VUR , no e/o scar formation (n = 6)

Group 3: e/o renal scarring , no e/o VUR ( n = 3)

Group 4: e/o both VUR &scar formation ( n = 12)

State of RAS activation : by measuring PRA. ACE inhibitor (Enalapril) : dose - 0.14 mg/kg/day The urinary micro albumin levels :documented before and after RAS blockade Pre-valve ablation data : serum creatinine &PRA. Post-valve ablation phase, (early and late) : S.Creatinine, PRA, VUR, DMSA scan, GFR, urinary micro albuminuria, & blood pressure.

Post ACE-I therapy data collected after mean duration 18.2 4.0; range 12-28 months Statistical analysis : using statistical package for the social sciences (SPSS 11.5 Inc. Chicago, Illinois, USA) Renal function parameters: compared using paired sample t-test. P values < 0.05 : statistically significant.

N= 34 Mean age : 3.5 1.9 (range 3-7.5 months) Duration of follow-up before initiating therapy with ACE-I was 40.5 4.1 (range 32-47 months). Mean follow-up after initiating therapy with ACE-I was 18.2 4.0 (range 12-28 months).

GROUPS

% FALL IN PRA

% FALL IN SERUM CREATININ E 23.1

Group 1

66.9

Fall w.r.t pre valve ablation value Sustained fall in PRA & S. Creatinine in all groups

Group 2

67

33.3

Group 3

71.4

25

Group 4

70.7

40

GROUP S

%FALL IN GFR

%RISE IN PRA

%RISE IN SERUM CREATINI NE 30

Group 1

18.5

Group 2

24.2

13.3

75

Marginal rise in PRA due to gradual reactivation of RAS accompanied by deterioration in renal function parameters

Group 3

13

10

33.3

Group 4

70.7

23.5

8.3

GROUP % RISE S IN GFR

% RISE IN PRA

% FALL IN SERUM CREAT ININE 23.1

% FALL IN MICRO ALBUMI NURIA 55

Group 1 5.9

19.2

Group 2 5.8 Group 3 4.2

21.6 48.4

28.6 5.5

55.6 64.6

ACE-I -> fall in angiotensin II -> ve feedback-> marginal rise in PRA accompanied by improvement in renal function parameters.

Group 4 5.7

17.7

23.8

55.3

Decline in renal function after valve ablation accompanied by reactivation of RAS reflected in a gradual rise in PRA. Therapy with ACE-I stabilizes & improves renal function retarding the pace of renal damage.

Progression to CRF even after successful PUV ablation multi-factorial PRA primary player in RAS pathway & Angiotensin II the final mediator of tubulointerstitial damage. VUR & renal scars :poor prognosis in PUV. VUR: high rate of spontaneous resolution following decompression,may take years

ACE-inhibitors reduced micro albuminuria even in the absence of VUR (55.0%) viz-a-viz with VUR (55.6%). In both the group also improvement in GFR & serum creatinine INFERENCE: In absence of VUR: ACE-I retard the pace of ongoing renal damage In presence of VUR: stabilize renal function waiting for spontaneous resolution

Post-valve ablation:gradual re-activation of RAS apparent in the form of rising PRA & accompanied by deterioration in renal function parameters. After ACE-I therapy:rise in PRA accompanied by improvement in renal function parameters.

Large no of pts with PUVs: renal dysplasia, detected on DMSA scan as photopenic areas similar to the new renal scars. Prior to this study, information on PRA not available in patients without renal scars. In the present study, high PRA associated with decline in renal function & elevated levels of micro albuminuria even without renal scars ( post-ablation, before ACE-I therapy).

Early periglomerular fibrosis may repesent 'nascent scars' , forerunner of scars visible later on as photopenic areas on DMSA scan ACE-I reduced micro albuminuria even in absence of scars viz-a-viz when scars were present by 54.0% and 64.2%, respectively Also improved GFR and serum creatinine

Need for initiating ACE-I therapy early, retarding the pace of renal damage and preventing future scarring, substantial no. of which progress to renal failure Study highlights urgent need for a randomized controlled trial for establishing PRA as an early prognostic marker

angiotensin II, as well as metabolites of the PGTX system, may be important determinants of postobstructive renal hemodynamics in rats

ACE-I (enalapril) ameliorates tubulointerstitial fibrosis following complete unilateral ureteral obstruction in rats. Increased level of angiotensin II has a major role in the development of tubulointerstitial fibrosis following ureteral obstruction.

Considerable injury is also inflicted to the contralateral normal kidney while ipsilateral kidney remains obstructed. Use of RAS blocking drugs found to significantly improve renal recovery on contralateral kidney. Postulated that contralateral renal parenchymal injury was mediated through activation of RAS.