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Animal study identifies DKD improvement post-bypass
Researchers from the Conway Institute of Biomolecular and Biomedical Research, University College Dublin, Dublin, Ireland, have reported that roux-en-Y gastric bypass (RYGB) can improve histopathological changes associated with diabetic kidney disease (DKD) in rats.
"Although it is known that RYGB can result in sustained weight loss and improvements in glycaemic control in patients with diabetes, it is not known whether the procedure improves or prevents diabetic end organ complications," said study presenter, Jessie Elliott. "As a result, the study team wanted to determine the precise effect of RYGB on DKD in rats.
Eighteen week old Zucker diabetic fatty (ZDF) fa/fa rats (n = 21) were randomly assigned to RYGB (n = 15) or sham surgery (n = 6). Five Zucker fa/+ rats acted as non-operated healthy controls. The team measured the body weight and blood glucose twice and four times weekly, respectively. In addition, urinary protein was measured at 12 weeks and kidneys harvested 13 weeks post-operatively.
Periodic Acid Schiff stained sections were subjectively assessed for glomerulosclerosis, and both glomerular size and prevalence were measured. Immunohistochemistry for collagen subtypes (I, III, IV) and macrophage marker ED-1 (CD68) was performed. Immunostained sections were quantitatively analysed using Imagescope and findings were correlated with qPCR and western blot analysis.
The results revealed that RYGB and sham surgery were associated with 27% and 17% perioperative mortality rates, respectively. The procedure was associated with significant weight loss (mean final weight 380g vs. 480g, p=0.02) and improved glycaemic control (glucose AUC, p<0.001), but no significant difference in proteinuria was detected (mean urinary protein 2.58 versus 3.12g/dL, p=0.65).
Bypass also resulted in significantly less glomerulosclerosis (17% vs. 30%, p= 0.01), more glomeruli per unit area (p=0.02), reduced glomerular hypertrophy (p=0.001) and a trend towards reduced macrophage infiltration (p= 0.057), compared with the sham-operated group.
However there was no difference in total cortical collagen I, III or IV between sham-operated and either control or RYGB groups.
“The model did not develop significant cortical fibrosis at 31 weeks,” concluded Elliott. “Therefore, further investigation is required to determine the timing of progression to renal fibrosis in the ZDF rat, to characterise the functional improvements associated with pathological disease regression and to determine mechanisms that may contribute to improvement in DKD after RYGB.”
Co-authors of the study were Karl J Neff, Debra Higgins, Catherine Godson and Carel W le Roux (Conway Institute of Biomolecular and Biomedical Research, University College Dublin, Dublin, Ireland), Caroline Corteville, Thomas Lutz and Marco Bueter (Dept of Visceral and Transplant Surgery Research, Zurich Centre for Integrative Human Physiology, Zurich, Switzerland).