Morphologic Correlates of Renal Growth Arrest in Neonatal Partial Ureteral Obstruction

Abstract

ABSTRACT. To investigate the morphologic correlates of decreased renal blood flow and growth arrest resulting from chronic partial ureteral obstruction in the neonate, guinea pigs were subjected to unilateral ureteral constriction within the first 2 days of life and were studied at 3 and 8 wk of age. Severity of histologic changes in the obstructed and intact contralateral kidney was assessed by light microscopy. Morphometric glomerular measurements were made using a computerized tracing device. Since contralateral nephrectomy or administration of angiotensin converting enzyme inhibitor (enalapril) result in increased blood flow to the obstructed kidney, morphologic changes were also examined in separate groups of animals subjected to these maneuvers, and were compared to appropriate controls. Ipsilateral chronic partial ureteral obstruction resulted in decreased glomerular volume ( p < 0.0001) and increased glomerular crowding associated with tubular dilatation and progressive glomerular sclerosis, tubular atrophy, and interstitial fibrosis. The intact contralateral kidney underwent hypertrophy with increase in glomerular volume ( p < 0.0001) and decreased glomerular density.Contralateral nephrectomy prevented the decrease in glomerular volume in the obstructed kidney and resulted in decreased glomerular density and reduced tubular atrophy at 3 wk of age. Enalapril prevented the decrease in glomerular volume at 3 wk of age, but glomerular and tubular changes progressed and were unaffected by enalapril at 8 wk. Left kidney glomerular volume was directly related to renal blood flow ( r = 0.71, p < 0.05). We conclude that renal growth arrest due to chronic partial ureteral obstruction in the neonatal guinea pig is related at least in part to renal ischemia which contributes to progressive parenchymal damage. Ischemia is mediated initially by angiotensin I1 and by endogenous renal growth factor(s) controlled by functional renal mass. (Pediatr Res 21: 338-346, 1987) Abbreviations CPUO, chronic partial ureteral obstruction RBF, renal blood flow PAS, periodic acid-Schiff Obstructive nephropathy remains an important cause of renal insufficiency in infancy and childhood (I).

Suspected Pyelo-Ureteral Junction Obstruction in the Fetus: When to Do What? II. Experimental Viewpoints

“…In the newborn guinea pig, Taki et al [20] found a reduction in dry KW of 20% after 5 weeks, but none in wet KW; histology was not studied. Chevalier et al [21,28] found that both wet and dry KW were reduced by 30-40% after 8 weeks. They observed a moderate degree of tubular dilatation and atrophy, of interstitial fibrosis and of sclerosis in 30% of the glomeruli.…”

“…was decreased by about 95%, but glomerular number was not affected. Chevalier et al [21,28] found that GFR was decreased by about 95%, renal blood flow (RBF) by 85% and glomerular number by 35%. The large differences found between our results and those of the groups are probably due to the different degrees of obstruction, as shown by the above-mentioned ureteral resistance figures [20,[23][24][25] Tubular Functions.…”

Partial Ureteric Obstruction in the Pubescent Rat

“…Differences between parameters were evaluated by using analysis of variance according to the model X ijkl = u + Gi + Tj + SI + Bk(ij) + GT ij + GS il + GTS ijl + SB kl(ij). u is a constant, Gi the treatment factor (experimental or control/spontaneously hy dronephrotic animals), Tj the time factor (7,8,9,15 or 21 weeks of age), SI the side (left or right kidney), Bk(ij) the individual biological variation within each group. GT ij, GS il, GTS ijl and SB kl(ij) are the different interaction terms.…”

“…A reduction in the number of glomeruli has been seen after the creation of a com plete obstruction in rabbit fetuses (which appears almost immediately), but not after obstruction in newborn rab bits [6] or adult dogs [7], Partial obstruction, which should be less harmful, led to a reduction in the number when it was created in newborn rats [2] and guinea pigs [8] or (again rather quickly) in weanling rats [4], The morphology of glomeruli is obviously resistant; shrink age and sclerosis have not been seen until after months of obstruction [9], In infant kidneys, no reduction in number was recorded [10]. However, microstructural changes have been observed, such as lesions suggestive of type II cystic kidneys (early ampullary inhibition) in fetuses [11] and focal glomerulosclerosis in infants and older children [12,13] together with inflammatory changes [14].…”

Renal Tissue Endothelin in Long-Term Complete Ureteric Obstruction in the Young Rat

“…In the post ischemic kidney, on the other hand, ET was found to be dominating [7], In previous studies of ureteric obstruction, Josephson and co-authors [8][9][10][11] and other researchers [12,13] found a moderate reduction in glomerular number, not confined to any specific renal zone [9]. Glomeruli have been found to degenerate, but this does not develop until after weeks or months and is surprisingly heterogeneous [14][15][16][17], One reason for these changes might be a reduc tion in blood flow. However, this does not cease totally [18], and some filtration may continue for a long period, the filtrate being drained via pyelo-renal, pyelo-venous and pyelo-lymphatic exits [19,20] Clinical ureteric obstruction is usually a congenital dis order.…”