Recent epidemiological studies revealed an association of
obesity,
diabetes mellitus,
hypertension and
metabolic syndrome (MetS) with
kidney stone disease. We examined how these disorders cause
kidney stones. A clinical study on 467 patients with
nephrolithiasis at our institution revealed that clustering of MetS traits increased the risk of
uric acid stone formation by decreasing urinary pH. A subsequent study analyzing detailed data from 30,448 patients enrolled in the 6th Nationwide Survey on
Urolithiasis in Japan showed that clustering of MetS traits were associated with an increased severity of the
kidney stone disease and elevated urinary excretion of
calcium,
uric acid and
oxalate. Finally, the OLETF rats, an animal model of MetS, showed lower urinary pH, decreased
citrate excretion, and increased
uric acid and
calcium excretion. In addition, the administration of
pioglitazone, an agent that improves
insulin resistance, significantly increased the urinary pH. These results indicate that MetS causes changes in urinary constituents, leading to an increased risk of both
uric acid and
calcium oxalate stone formation. We suggest that
kidney stone disease should be considered as a component of MetS and that the improvement in
insulin resistance by means of diet and lifestyle changes and medical
therapy might help to prevent this disorder.