Abstract
Estrogen may help to preserve renal function in chronic kidney disease. This study examined whether estrogen administration or deprivation affected the split renal function in rats subjected to chronic unilateral ureteral obstruction (UUO). Fifteen adult female Sprague-Dawley rats were randomly divided into three groups. Low- and high-estrogen groups were modeled by female castration or estrogen intraperitoneal injection, respectively, and the rats in the normal-estrogen group were untreated. Intermittent split renal function [glomerular filtration rate (GFR)] examination was performed on rats on days 2, 6 and 16 after UUO surgery via single-photon emission computed tomography (SPECT/CT). Routine hematoxylin and eosin (H&E) staining, immunohistochemistry, pathology examination and electron microscopy were performed to compare the histological differences. Low-, normal- and high-estrogen groups were successfully established (P<0.001). In the acute stage, the GFR of the contralateral healthy kidney showed a greater compensatory rise in the normal- and high-estrogen groups than in the low-estrogen group (P<0.05). In the chronic stage, the GFR of the obstructed kidney continued to decrease with the GFR of the high-estrogen group being significantly better preserved than that of the low-estrogen group (P<0.05). The GFR of the contralateral kidney compensated to the greatest extent in the high-estrogen group (P=0.01), and the total GFR was significantly superior (P<0.05). Routine H&E examination showed significant histological changes following surgery. The low-estrogen group had significant renal interstitial fibrosis compared with the normal- and high-estrogen groups (P<0.05), as observed by immunohistochemical (IHC) examination of transforming growth factor-β (TGF-β) and α-smooth muscle actin (α-SMA). Electron-microscopic (EM) examination also differentiated between groups. In conclusion, estrogen administration and deprivation significantly affected renal function. Estrogen may preserve the split renal function (GFR) in rats with chronic UUO.
Highlights
The annual incidence of upper urinary tract calculi has steadily increased in Asia and this trend is likely to continue in the near future [1,2]
The calculi may lead to hydronephrosis, a type of renal atrophy that may result in renal insufficiency or a unilateral non-functioning kidney (NFK) [3]
Urinary tract stones may occasionally be solved without any treatment, but may lead to heavy hydronephrosis and NFK
Summary
The annual incidence of upper urinary tract calculi has steadily increased in Asia and this trend is likely to continue in the near future [1,2]. The calculi may lead to hydronephrosis, a type of renal atrophy that may result in renal insufficiency or a unilateral non-functioning kidney (NFK) [3]. Estrogen has been implicated in the pathophysiology of chronic kidney disease and has been shown to provide a protective effect against chronic renal damage [5,6,7]. The protective effects likely act through the renin-angiotensin system [8,9,10], nitric oxide pathway [11,12], extracellular matrix metabolic pathway, inflammatory response pathway [13,14,15,16,17], lipid metabolic pathway and numerous other pathways [18,19,20]
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