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-estradiol replacement improves renal function and pathology associated with diabetic nephropathy
1 Department of Medicine, Georgetown University Medical Center, Washington, DC, USA
2 Department of Medicine, Georgetown University Medical Center, Washington, DC, USA; Center for the Study of Sex Differences: in Health, Aging and Disease, Georgetown University Medical Center, Washington, DC, USA
* To whom correspondence should be addressed. E-mail: cm255{at}georgetown.edu.
The protective factor of female gender appears to be lost in diabetes; the incidence of diabetes and its complications, including diabetic nephropathy is equal in women and men. This study examined the effects of estrogen deficiency by ovariectomy (OVX) and replacement with 17
-estradiol (OVX+E2) on renal function and pathology in the non-diabetic (ND) and streptozotocin (STZ)-induced diabetic (D) rat kidneys for 12 weeks. Diabetes was associated with an increase in urine albumin excretion (UAE) (ND, 0.39±0.03; D, 5.9±0.8 mg/day; P<0.001), decrease in creatinine clearance (CrCl) (ND, 0.69±0.03; D, 0.43±0.09
mg/min/100 g bw; P<0.05), increase in the index of glomerulosclerosis (GSI, ND, 0.01±0.01;
D, 0.15±0.04 AU; P<0.01) and tubulointerstitial fibrosis (TIFI, ND, 0.04±0.04; D, 0.68±0.2 AU; P<0.01) and transforming growth factor beta (TGF-) protein expression (ND, 0.61±0.02; D,
1.25±0.07 AU; P<0.01). In the D group, the severity of these changes was augmented with OVX (UAE, 8.1±0.6 mg/day; CrCl, 0.40±0.04 mg/min/100 g bw; GSI, 0.29±0.04 AU; TIFI, 0.90±0.06 AU; TGF-, 1.26±0.10 AU), while E2 replacement attenuated these changes (UAE,
6.3±0.8 mg/day; CrCl, 0.66±0.03 mg/min/100 g bw; GSI, 0.06±0.02 AU; TIFI, 0.36±0.08 AU; TGF-, 0.57±0.08 AU). We conclude that E2 deficiency increases the severity of renal disease in a diabetic animal model and that E2 replacement is renoprotective by attenuating the decline in renal function and pathology associated with diabetes.
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