Weight loss interventions and progression of diabetic kidney disease.

Progressive renal impairment (diabetic kidney disease (DKD)) occurs in upwards of 40 % of patients with obesity and type 2 diabetes mellitus (T2DM) and is a cause of significant morbidity and mortality. Means of attenuating the progression of DKD focus on amelioration of risk factors. Visceral obesity is implicated as a causative agent in impaired metabolic and cardiovascular control in T2DM, and various approaches primarily targeting weight have been examined for their impact on markers of renal injury and dysfunction in DKD. The current report summarises the evidence base for the impact of surgical, lifestyle and pharmacological approaches to weight loss on renal end points in DKD. The potential for a threshold of weight loss more readily achievable by surgical intervention to be a prerequisite for renal improvement is highlighted. Comparing efficacious non-surgical weight loss strategies with surgical strategies in appropriately powered and controlled prospective studies is a priority for the field.

Stage II colonic adenocarcinoma: a detailed study of pT4N0 with emphasis on peritoneal involvement and the role of tumour budding.

AIMS: Evaluation of peritoneal involvement in colonic cancer (CC) can be difficult. We studied pT4N0 cancers and their association with pathological prognostic markers, including tumour budding. METHOD AND RESULTS: Tumours were classified as (i) at the peritoneal surface or free in the peritoneal cavity (pT4a subgroup n = 44); (ii) directly invading adjacent organ (pT4b subgroup n = 8); or (iii) showing inflammatory involvement of the peritoneum (pT4I subgroup n = 25). A published pT3N0 cohort was used to compare Stage II subgroups. Standard pathological markers including tumour budding were assessed. Elastin staining was performed in the pT4I subgroup. Seventy-seven Stage II CCs met inclusion criteria. There was no significant difference in survival across subgroups. pT4b tumours were larger than pT4a tumours (P < 0.001). Over-represented features in pT4a versus pT4b tumours were tumour budding (P = 0.02) and infiltrative margin (P = 0.02). Tumour budding did not predict survival. Using multivariate analysis, neural invasion was the only parameter predictive of survival (hazard ratio = 2.8; 95% CI 1.2-6.4; P = 0.02). CONCLUSION: Stage II pT4I CCs have a similar outcome to T4a/b tumours. Elastin staining is useful in defining this group. Tumour budding may facilitate peritoneal invasion in pT4a tumours, but does not predict outcome in pT4N0 disease. Only neural invasion independently predicted poor outcome.

Improvements in diabetic albuminuria and podocyte differentiation following Roux-en-Y gastric bypass surgery.

BACKGROUND: Multiple studies demonstrate an albuminuria-lowering impact of Roux-en-Y gastric bypass surgery, but neither evaluation of its penetrance across different baseline levels of albuminuria nor its association with alterations in podocyte phenotype has previously been reported. METHODS: We profiled changes in body weight, glycaemic control and urinary albumin excretion following Roux-en-Y gastric bypass surgery in 105 patients with type 2 diabetes, albuminuria of varying degrees of severity and classified as being at moderate or high risk of chronic kidney disease progression according to the Kidney Disease: Improving Global Outcomes 2012 criteria. In parallel pre-clinical studies, the impact of Roux-en-Y gastric bypass surgery on markers of podocyte injury was assessed in the Zucker diabetic fatty rat model of diabetic kidney disease. RESULTS: At 12- to 18-month post-operative follow-up in patients at moderate or high risk of chronic kidney disease, significant reductions in albuminuria were observed across all tertiles of baseline albumin-creatinine ratio, with remission of albuminuria occurring in 78% of patients. Relative to sham-operated control animals, weight loss and improvements in glycaemia following Roux-en-Y gastric bypass surgery in Zucker diabetic fatty rats were paralleled by normalisation of glomerular tuft-size, reductions in podocyte expression of desmin, and preservation of podocyte foot process morphology. CONCLUSION: Improvements in podocyte differentiation likely underpin the reductions in albuminuria observed following Roux-en-Y gastric bypass surgery.