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  • Effect of diabetes mellitus...
    Bakoush, Omran; Lubbad, Loay; Öberg, Carl M.; Hammad, Fayez T.

    Journal of diabetes, August 2019, Letnik: 11, Številka: 8
    Journal Article

    Background Following reversal of short periods of ureteral obstruction (UO), glomerular and tubular renal dysfunction recovers with time. Diabetes mellitus (DM) affects glomerular function; thus, the ability of diabetic kidneys to recover from UO may be impaired. This study investigated the effects of long‐term DM on the recovery of glomerular and tubular function, as well as permeability of the glomerular filtration barrier (GFB), after unilateral UO (UUO) reversal. Methods Diabetes mellitus was induced in Wistar rats by intraperitoneal streptozotocin. All diabetic and age‐matched control rats underwent reversible 24‐hour left UUO. The renal function of both kidneys was measured using clearance techniques 3 hours and 7 and 30 days after UUO reversal. Glomerular permeability was assessed by measuring the glomerular sieving coefficients for fluorescein isothiocyanate‐conjugated Ficoll (molecular radius: 20‐90 Å). Results Unilateral UO induced transient changes in the size selectivity of GFB small pores. However, the size selectivity function of large pores had not returned to baseline even 30 days after UUO reversal. Diabetes mellitus caused exaggerated early alterations in glomerular hemodynamic and tubular function, as well as size selectivity dysfunction of both small and large pores. At 30 days after UUO reversal, despite glomerular hemodynamic and tubular function and the size selectivity of small pores returning to normal in both diabetic and non‐diabetic rats, the residual size selectivity dysfunction of large pores was more severe in diabetic rats. Conclusion Unilateral UO caused long‐term dysfunction in the size selectivity of large pores of the GFB. In addition, DM significantly exaggerated this dysfunction, indicating a more ominous outcome in diabetic kidneys following UUO. 摘要 背景 在短期输尿管梗阻(ureteral obstruction,UO)得到治愈后,肾小球与肾小管功能障碍会随着时间的推移而逐渐恢复。糖尿病(DM)可以影响肾小球功能;因此,糖尿病肾脏从UO中恢复的能力可能会受损。这项研究在单侧UO(unilateral UO,UUO)得到治愈后,探究了长期DM对肾小球与肾小管功能恢复、以及肾小球滤过屏障(glomerular filtration barrier,GFB)通透性的影响。 方法 Wistar大鼠腹腔注射链脲佐菌素后诱发糖尿病。所有的糖尿病大鼠以及年龄匹配的对照组大鼠都要进行可逆性的24小时左侧UUO手术。在UUO逆转后的第3小时、7天以及30天,通过测定清除率的方法,测量双侧肾脏的肾功能。通过测定荧光素‐异硫氰酸盐‐共轭聚蔗糖(分子半径:20‐90Å)的肾小球滤过系数评估肾小球通透性。 结果 单侧UO可以导致GFB小孔的尺寸选择性出现短暂的变化。然而,即使UUO逆转30天后大孔的尺寸选择性功能仍然没有能够恢复到基线水平。糖尿病可加剧肾小球血流动力学以及肾小管功能的早期改变,除此之外还会导致大孔和小孔的尺寸选择性功能都出现障碍。UUO逆转后第30天,尽管在糖尿病大鼠与非糖尿病大鼠中肾小球血流动力学与肾小管功能以及小孔的尺寸选择性功能都恢复正常,但是在糖尿病大鼠中,大孔的尺寸选择性功能仍然有较严重的障碍。 结论 单侧UO可导致GFB大孔的尺寸选择性出现长期功能障碍。另外,DM可导致这种功能障碍显著加重,这表明UUO后糖尿病肾脏的预后更差。 Highlights Following reversal of ureteral obstruction, diabetes mellitus results in exaggerated early alterations in glomerular hemodynamic and tubular function, as well as in size selectivity dysfunction of both small and large pores of the glomerular filtration barrier. This was accompanied by a more severe residual dysfunction of large pores, indicating a more ominous outcome in diabetic kidneys following ureteral obstruction.