| Associations between kidney stone disease (KSD), hypertension, obesity, excessive weight gain and type 2 diabetes suggest the possibility that susceptible individuals share a common genetic background and are influenced by similar environmental factors. To test this hypothesis, this thesis examined (1) the aggregation of these conditions in families of KSD patients with hypercalciuria, and (2) the combined effect of dietary potassium (K+), measured by its urinary excretion, and hypercalciuria on the familial risk of these conditions. Consecutive KSD patients, aged 18-50 years, were recruited from a population-based Kidney Stone Center and collected a 24-hour urine sample. The first-degree relatives of eligible subjects (n=333) and their spouse were interviewed by telephone to collect demographic and health information. Familial aggregation was assessed using Generalized Estimating Equations. Multivariate-adjusted odds ratios (OR) revealed significant associations between hypercalciuria in patients and hypertension and KSD in first-degree relatives and specifically in siblings (OR and 95% confidence interval for hypertension = 2.9, 1.4-6.2 and for KSD = 1.9, 1.03-3.5). No significant associations were found in parents or spouses, or in patients with hyperuricosuria. Similarly, no aggregation with other conditions was observed. When examining the effects of urinary K+, relatives of low K+ excretors had a higher frequency of obesity and excessive weight gain, but not hypertension, KSD or diabetes, than those of normal excretors. In hypercalciuric patients, however, low K+ excretion predicted hypertension (OR = 3.3, 1.5-7.4) and KSD (OR = 2.9, 1.1-7.3) in first-degree relatives, and diabetes in siblings (OR = 4.1, 1.1-15.6). No conditions aggregated in spouses. In a validation study, increased 24-hour urinary K+ was associated with a progressive increase in diet quality score, the intake of foods recommended by current dietary guidelines and a lower BMI, diastolic blood pressure and heart rate. While an environmental effect cannot be fully excluded, the findings suggest that the disturbance in calcium metabolism in hypertension and KSD has a genetic basis. Furthermore, the combination of a low K+ diet, an environmental factor, and hypercalciuria, a suspected inherited trait, identified a subset of patients with an apparent common pathway for the development of KSD, hypertension and possibly diabetes. |
