PhD ceremony Ms. A. Klooster: Thiamine, fasting and the kidney

PhD ceremony: Ms. A. Klooster, 16.15 uur, Academiegebouw, Broerstraat 5, Groningen

Dissertation: Thiamine, fasting and the kidney

Promotor(s): prof. H. van Goor

Faculty: Medical Sciences

In this thesis we researched the role of thiamine in ischaemia-reperfusion injury of the kidney. Thiamine is crucial for optimal amounts of reduced glutathione (anti-oxidant) and for regeneration of ATP (energy source) in cells. We describe the hypothesis that thiamine deficiency is an important determinant of the occurrence of acute tubule necrosis and delayed graft function in kidney transplantation.    

We could not show that thiamine deficiency aggravated ischaemia-reperfusion injury. Moreover, when thiamine deficiency was complicated by a decreased food intake and weight loss this prevented ischaemia-reperfusion injury. Thereby we surmised that the weight loss and reduced food may explain the unexpected protective effect.

We also investigated the hypothesis whether benfotiamine could decrease albuminuria in diabetic nephropathy. We did not find an effect of benfotiamine treatment on albuminuria and other markers of kidney damage. Also, we were unable to find an effect of peri-operative fasting on ischaemia-reperfusion injury in rats.

In renal transplant recipients we describe the protective effects of non-esterified fatty acids and malondialdehyde on graft failure. When people are fasted these markers will rise.

Therefore, we also studied whether caloric restriction in combination with ketogenic diet protects against nephropathy in a proteinuric rat model. We showed that caloric restriction lowers proteinuria and decreases renal damage. This was irrespective of ketogenesis since a ketogenic diet did not shown any changes. This suggests that other mechanisms rather than ketogenesis underlie the beneficial effects of caloric restriction.