Effect of weight loss on urinary oxalate excretion in obese calcium oxalate kidney stone formers - SUMMARY
The prevalence of kidney stone disease has dramatically increased in the United States (US) over the last 4
decades, now afflicting 8.8% of the population. Obesity which now affects over 40% of the US population is a
recognized risk factor for the development of kidney stones. Calcium oxalate is the most common stone
composition in the obese cohort. Urinary oxalate excretion significantly impacts the development of such stones
and we and others have demonstrated that it is higher in obese kidney stone formers. Various factors can
influence the amount of oxalate excreted in urine including the amount of oxalate consumed, its bio-availability,
amount of dietary calcium, gastrointestinal and renal oxalate handling, and endogenous oxalate synthesis. We
have found that obesity appears to increase endogenous oxalate synthesis. Others have reported that it disrupts
the intestinal barrier which could result in augmented paracellular gut uptake. Obesity also appears to alter renal
proximal tubular function. Thus, any one of these factors alone or in combination with the others could drive
increased urinary oxalate excretion. The central hypothesis of this grant is that weight loss can reduce urinary
oxalate excretion. While previous dietary approaches for kidney stone prevention have focused on
macronutrients and micronutrients, caloric restriction has not been employed. We propose using an established
and effective dietary weight reduction program, Optifast VLCD®, in obese, adult calcium oxalate stone formers
and have crafted specific aims that focus on whether this will promote a reduction of the contribution of
endogenous oxalate synthesis to the urinary oxalate pool, a decrease in gastrointestinal oxalate absorption and
gut permeability, and/or alterations in renal oxalate handling. The proposed studies will be conducted in
collaboration with experts in stone disease, metabolism, nutrition, endocrinology and weight loss at 2 large state
institutions who provide care for this afflicted cohort. If the anticipated results of this feasibility study are achieved,
this will serve as a strong platform to undertake a large clinical trial which could eventuate in an attenuation of
stone disease as well as improvement or reversal of the many other co-morbidities associated with obesity.
