Clinical and molecular markers of chronic interstitial nephropathy in congenital unilateral ureteropelvic junction obstruction.
OBJECTIVE
We evaluated clinical and biological variables, and their meaning as reliable markers of chronic interstitial nephropathy in a selected group of children with prenatally detected hydronephrosis who underwent pyeloplasty because of congenital unilateral ureteropelvic junction obstruction.


METHODS
We reviewed the clinical, prenatal and postnatal ultrasonographic, and scintigraphic records of children for whom intraoperative biopsy records were available. We performed histological analysis, and evaluated tubulointerstitial immunostaining for vimentin and alpha-smooth muscle actin, and the immunohistochemical and mRNA expression of the renin-angiotensin system peptides and transforming growth factor-beta1.


RESULTS
The children were divided in 2 groups according to the absence (group 1) or presence (group 2) of chronic interstitial nephropathy in the biopsy. Patients in group 2 were significantly younger at prenatal diagnosis (p = 0.031), and had decreased split renal function (p = 0.005) and worse drainage (p = 0.035) on preoperative diuretic renography. No differences were found in terms of degree of hydronephrosis, or its prenatal and postnatal variation. Group 2 biopsies exhibited greater immunostaining for alpha-smooth muscle actin and vimentin (p = 0.004 and p = 0.047, respectively), and transforming growth factor-beta1 mRNA levels (p = 0.06). Vimentin and alpha-smooth muscle actin positivity correlated with renin, angiotensin II receptors 1 and 2, and transforming growth factor-beta1 mRNA levels, and all correlated with preoperative split renal function and post-void washout.


CONCLUSIONS
In congenital unilateral ureteropelvic junction obstruction chronic interstitial nephropathy and poor postoperative recovery seem to be associated with an earlier diagnosis of hydronephrosis, functional loss greater than 10% and worse scintigraphic drainage. Moreover, there is a strong correlation between molecular fibrogenic markers and histologically and scintigraphically demonstrated renal damage.
Murer
L
L
Pediatric Nephrology, Dialysis and Transplant Unit, Department of Pediatrics, Institute of Urology, University of Padova, Padua, Italy.
Benetti
E
E
Centi
S
S
Della Vella
M
M
Artifoni
L
L
Capizzi
A
A
Zucchetta
P
P
Del Prete
D
D
Carasi
C
C
Montini
G
G
Rigamonti
W
W
Zaccello
G
G
D000199:Actins / Q000378:metabolism; D018450:Disease Progression; D005260:Female; D005315:Fetal Diseases / Q000000981:diagnostic imaging; D006801:Humans; D006869:Hydronephrosis / Q000151:congenital / Q000175:diagnosis*; D007124:Immunoenzyme Techniques; D007150:Immunohistochemistry; D007223:Infant; D007684:Kidney Tubules / Q000378:metabolism / Q000473:pathology; D008297:Male; D009395:Nephritis, Interstitial / Q000175:diagnosis* / Q000209:etiology / Q000378:metabolism / Q000473:pathology; D016133:Polymerase Chain Reaction; D011379:Prognosis; D012189:Retrospective Studies; D016216:Ultrasonography, Prenatal; D014517:Ureteral Obstruction / Q000150:complications* / Q000151:congenital / Q000601:surgery; D014746:Vimentin / Q000378:metabolism
D000199:Actins; D014746:Vimentin