Congenital Hydronephrosis

Pathogenesis
Antenatal hydronephrosis is the most common condition detected by prenatal ultrasonography,
being observed in 1:100 to 1:500 studies. However, approximately 20% of abnormalities
observed in utero are not present postnatally. Although there is consensus that follow-up renal
and bladder ultrasonography should be performed on these neonates, experts debate timing.
Early scans within 48 hours (when the child may be dehydrated and have a lower GFR) may
underestimate hydronephrosis.
Robert W Shcrier, Diseases of the kidney & Urinary tract eight edition volume III 2007 by
LIPPINCOT WILLIAMS & WILKINS Philadelphia US
A VARIETY of pathological lesions may obstruct the region of the pelvi-ureteral
junction and lead to hydronephrosis, but observers agree that the most common operative
findings are various kinks and angulations, with or without lower polar vessels. Whilst it is
accepted that these pelvi-ureteral angulations may, of themselves, produce a valvular type
of obstruction, most authorities are of the opinion that they are secondary developments, the
result of pelvic dis- FIG. 1 Diagram of technique of pressure-flow study. tension, and that the
basic pathology in the majority of cases is some form of functional blockage or interference with
the transmission of peristalsis from the pelvis to the ureter. It is clearly impor- tant, from the
viewpoint of surgical technique, to know whether or not such a functional obstruc- tion is
invariably present and for this reason we have investigated the nature of the obstructive
uropathy in a series of cases of pelvic hydronephrosis in children. This was done by a close
study of the pathological anatomy and also, since the degreee of any urinary obstruction is
depen- dent upon the volume of urinary flow, by assessing the effects of an artificial diuresis .
The ability of the pelvis and the pelvi-ureteral junction to cope with a high rate of inflow of
fluid was determined firstly, by recording the intra-pelvic pressure and secondly, by
measuring the volume of fluid passing simultaneously through the upper ureter. These
investigations were carried out at operation on 36 hydronephrotic kidneys in children varying
in age from 5 days to 13 years.
THE PATHOGENESIS OF HYDRONEPHRQSIS IN CHILDREN1 By J. H. JOHNSTON,
F.R.C.S. Urological Department, Alder Hey Childrens Hospital, Liverpool British Journal of
Urology Volume 41, Issue 6, pages 724734, December 1969
The congenital progressive hydronephrosis Mutants Have Apparent Congenital Functional
Obstruction of the Urinary Tract.
The congenital progressive hydronephrosis mutants appeared grossly normal at birth and made
up 27.9% of the pups born in heterozygous intercrosses, very close to the 25% expected for an
autosomal recessive mutation following Mendelian inheritance. However, the congenital
progressive hydronephrosis mutants grew slowly and showed a significant size and weight
difference from postnatal day (P) 8 onward .About 90% of the congenital progressive

hydronephrosis mutants died between 2 and 4 weeks of age. By 2 weeks, most mutants also had
visibly enlarged abdomens and appeared lethargic. Around 10% of the congenital progressive
hydronephrosis homozygotes survived past weaning, with the oldest congenital progressive
hydronephrosis homozygote living for 10 months. The adult congenital progressive
hydronephrosis homozygotes are either infertile or have modestly reduced fertility.
Although younger mutants (<P14) had unilateral or bilateral hydronephrosis of various degrees,
older mutants (>P14) almost always had severe bilateral hydronephrosis .This observation is
consistent with the findings in the Horton et al. study but argues against the hypothesis that this
is a model of polycystic kidney disease . However, the finding of hydroureter and apparent
obstruction at the ureterovesical junction (UVJ) in 25% of the mutants suggests that these
mutants are unlikely to have complete physical blockage at the ureteropelvic junction (UPJ) level
as proposed . Furthermore, we have not found any correlation between the volume of the bladder
and the genotypes of the mice dissected, suggesting that the defect in the mutants is likely in a
location proximal to the bladder along the urinary tract. Interestingly, 66.3% of the mutants had
more severe defects in the right kidney at the time of examination, whereas only 22.8% had more
severe defects in the left and 10.9% had both kidneys equally affected.
Blood urea nitrogen (BUN) levels in the mutants were significantly elevated, suggesting renal
failure as a result of obstructive nephropathy. The mutant kidneys had pathological changes,
characteristic of obstructive nephropathy, ranging from parenchymal atrophy, erosion of the renal
pelvis, expansion of the pelvicocaliceal space, and dilatation of the collecting ducts. Molding
polymers injected into the pelvicocaliceal space were able to travel along the urinary path to the
bladder in both the controls and mutants, although the mutant urinary path is distorted by the
hydronephrosis, especially in the pelvicocaliceal space. This result argues against the existence
of physical blockage from the kidney to the bladder and suggests that hydronephrosis is likely
caused by a functional obstruction, namely urine retention in the urinary tract as a result of a
functionally, but not structurally, impaired downward urine transport. Morphological
examination of newborn mutants and their control littermates did not reveal any significant
changes in the smooth muscle cells that are important for contractability of the pyeloureteral
complexor in the innervating nerves that modulate pyeloureteric peristalsis.

Congenital progressive hydronephrosis (cph) is caused by an S256L mutation in aquaporin-2

that affects its phosphorylation and apical membrane accumulation
Bradley W. McDill *, Song-Zhe Li *, Paul A. Kovach *, Li Ding , and Feng Chen * ,
Communicated by Mario R. Capecchi, University of Utah, Salt Lake City, UT, March 14, 2006
(received for review December 20, 2005)