Obesity and
metabolic syndrome are well-known risk factors for
chronic kidney disease (CKD); however, less is known about the mechanism(s) by which
metabolic syndrome might accelerate
kidney disease. We hypothesized that
metabolic syndrome should accelerate the development of
kidney disease and that it might be associated with alterations in energy metabolism. We studied the pound mouse (which develops early
metabolic syndrome due to a
leptin receptor deletion) and wild-type littermates and compared the level of renal injury and muscle wasting after equivalent injury with oral
adenine. Renal function, histology, and biochemical analyses were performed. The presence of
metabolic syndrome was associated with earlier development of renal disease (12 mo) and earlier mortality in pound mice compared with controls. After administration of
adenine,
kidney disease was worse in pound mice, and this was associated with greater tubular injury with a decrease in kidney mitochondria, lower tissue
ATP levels, and worse oxidative stress. Pound mice with similar levels of renal function as
adenine-treated wild-type mice also showed worse
sarcopenia, with lower tissue
ATP and intracellular
phosphate levels. In summary, our data demonstrate that
obesity and
metabolic syndrome accelerate the progression of CKD and worsen CKD-dependent
sarcopenia. Both conditions are associated with renal alterations in energy metabolism and lower tissue
ATP levels secondary to
mitochondrial dysfunction and reduced mitochondrial number.