Department of Small Animal Medicine and Clinical Biology, Faculty of Veterinary Medicine, Ghent University, Salisburylaan, Merelbeke, Belgium.
PLoS One. 2012;7(2):e31702. doi: 10.1371/journal.pone.0031702. Epub 2012 Feb 29.
Objectives of this study were to evaluate glomerular filtration rate (GFR), renal structural changes and proteinuria in aged Beagle dogs before and after hydrocortisone (HC) administration. Eleven Beagle dogs ≥10 years old were treated with either hydrocortisone (HC group, n = 6) or placebo (control group, n = 5). Urinary markers, GFR and kidney biopsies were evaluated before (T0), during (T16 wks) and after discontinuing HC administration (T24 wks). Results indicate that HC administration causes a significant increase in GFR. At all time points except T16 wks, proteinuria was higher in the control group than in the HC group, and there was no significant difference in urinary markers between groups. At T16 wks, proteinuria, urinary albumin-to-creatinine (c) ratio, immunoglobulin G/c and retinol-binding protein/c were higher compared to baseline in the HC group. At T0, rare to mild renal lesions were detected in all HC dogs and rare to moderate changes in all control dogs. Glomerulosclerosis progressed in both groups until T24 wks. Tubular atrophy was detected in three HC dogs at T16 wks and T24 wks, but also in five control dogs throughout the study. At every time point, five HC dogs and all control dogs had rare to moderate interstitial inflammation. Rare to mild interstitial fibrosis was found in up to three HC dogs at T16 wks and T24 wks, and severe fibrosis in one HC dog at T24 wks. Up to four control dogs had rare to mild fibrosis at all time points. These findings indicate that clinically healthy, aged Beagle dogs may have considerable renal lesions and proteinuria, which could have implications for experimental or toxicological studies. Additional research is needed to elucidate glucocorticoid effects on renal structure, but functional changes such as hyperfiltration and proteinuria warrant attention to kidney function of canine patients with Cushing's syndrome or receiving exogenous glucocorticoids.
本研究旨在评估氢化可的松(HC)给药前后老年比格犬的肾小球滤过率(GFR)、肾脏结构变化和蛋白尿。11 只≥10 岁的比格犬分别接受 HC(HC 组,n=6)或安慰剂(对照组,n=5)治疗。在开始 HC 给药前(T0)、给药期间(16 周)和停药后(24 周)评估尿液标志物、GFR 和肾脏活检。结果表明,HC 给药导致 GFR 显著增加。除 T16 周外,所有时间点对照组的蛋白尿均高于 HC 组,两组间尿液标志物无显著差异。在 T16 周时,与基线相比,HC 组的蛋白尿、尿白蛋白/肌酐(c)比值、免疫球蛋白 G/c 和视黄醇结合蛋白/c 均升高。在 T0 时,所有 HC 犬均检测到罕见至轻度的肾脏病变,所有对照犬均检测到罕见至中度的变化。肾小球硬化在两组中均进展至 T24 周。在 T16 周和 T24 周时,3 只 HC 犬和 5 只对照犬均检测到肾小管萎缩,但在整个研究过程中,所有对照犬均有肾小管萎缩。在每个时间点,5 只 HC 犬和所有对照犬均有罕见至中度的间质炎症。在 T16 周和 T24 周时,多达 3 只 HC 犬和 1 只 HC 犬有严重纤维化。多达 4 只对照犬在所有时间点均有罕见至轻度纤维化。这些发现表明,临床健康的老年比格犬可能有相当数量的肾脏病变和蛋白尿,这可能对实验或毒理学研究有影响。需要进一步研究阐明糖皮质激素对肾脏结构的影响,但功能变化如超滤和蛋白尿需要关注患有库欣综合征或接受外源性糖皮质激素的犬患者的肾功能。