COLLAGEN STUDIES IN NEWBORN RAT KIDNEYS WITH INCOMPLETE URETERAL OBSTRUCTION

Collagen studies in newborn rats with incomplete ureteric obstruction were performed to describe and quantify changes in collagen deposition resulting from urinary tract obstruction at an early developmental ag e. Incomplete ureteric obstruction was created in three-day-old rats b y placing the left ureter in a tunnel formed by the psoas muscle, and sham-operated controls underwent a laparotomy. The rats were sacrifice d at 10, 17, 24 or 31 days. Collagen types I, III, IV, and V were loca lized by indirect immunofluorescence microscopy, the total collagen co ntent of the kidney was quantitated using hydroxyproline analysis, and collagen types I and III were quantitated using cyanogen bromide (CNB r) peptide analysis. Increased immunofluorescent staining for all of t he collagens was found in the diffusely widened medullary interstitium of the obstructed kidney, and more focally in the cortical interstiti um. Collagen types I, III and V, but not collagen type IV, were also f ound in bands in the interstitium at the junction of the cortex with t he medulla. Increased staining for collagen type IV was found in thick ened and tortuous tubular basement membranes (TBM) of the obstructed k idneys. The total collagen content of the obstructed kidney was signif icantly increased compared to the amounts in both the contralateral ki dneys and in the kidneys from sham-operated controls at 24 and 31 days of age (P < 0.01 in each case, Wilcoxon matched pairs rank sum test a nd Mann Whitney U-test, respectively). The amount of collagen in the k idneys correlated with the degree of hydronephrosis (Spearman correlat ion test, r = 0.78, P < 0.02). CNBr peptide analysis demonstrated that over 50% of the collagen in the normal neonatal rat kidney was collag en type I and approximately 25% was collagen type III. In the obstruct ed kidneys most of the collagen was also collagen type I and collagen type III, although the proportion of total collagen comprised by these collagen types was decreased compared with the controls. The amount o f collagen type III in the contralateral kidneys was reduced compared to that in the controls. Thus, the neonatal renal response to obstruct ion resulted in increased amounts of a range of collagens in the inter stitium and TBM, and the extent of this response was partially related to the degree of hydronephrosis.