What's the Relationship Between Hypertriglyceridemia and Stone Disease?

Selected by Pietro Cazzola
  1. Stone diseaseStone disease has increasingly been associated with systemic conditions such as hypertension,1 diabetes,and coronary artery disease,3 leading some to postulate a cause-and-effect relationship. A common thread in some of these conditions is obesity/weight gain and metabolic syndrome. Indeed, a number of investigators have demonstrated a relationship between stone disease and metabolic syndrome, with the number of features of metabolic syndrome correlating positively with the prevalence of self-reported or radiographically detected kidney stones.4,5 In some cases, the associations are derived from population-based studies, without knowledge of stone composition or urinary stone risk factors. However, some investigators have attempted to correlate components of the metabolic syndrome with specific derangements in urinary analytes in the hope of identifying the specific urinary risk associated with these conditions.6

In a recent retrospective study, Kang and colleagues sought to determine the effect of the various forms of dyslipidemia on specific urinary stone risk factors as well as on stone recurrence in a group of recurrent stone formers.7 When adjusted for other confounding factors, they found no correlation between lipid profile and 24-hour urinary analytes, but they did find that the status of particular dyslipidemic states (hypertriglyceridemia, low HDL cholesterolemia, and high LDL cholesterolemia) impacted some urinary stone risk factors. Furthermore, hypertriglyceridemia was found to be an independent risk factor for stone recurrence. These findings help us to understand the impact of individual dyslipidemic states on particular urinary stone risk factors. However, the authors were unable to adequately control for important confounding factors such as severity of stone disease, age, BMI, hypertension, and diabetes. As such, the independent effects of these conditions are not entirely clear.
In the case of uric acid stones, the pathophysiology relating to the association with metabolic syndrome has begun to be elucidated. Insulin resistance leads to impaired ammoniagenesis in the renal proximal tubule and increased production of endogenous acid, resulting in reduced buffering capacity and acidic urine, the primary risk factor for uric acid stone formation.8 The pathophysiologic mechanisms responsible for the association of dyslipidemia, hypertension, or cardiovascular disease with calcium stone disease are less clear. It remains to be determined which, if any, of these associations are truly causal or if stone disease is simply another manifestation of the same metabolic abnormalities that arise from obesity.