High urinary excretion of uric acid combined with high excretion of calcium links kidney stone disease to familial hypertension

Background. Past studies identified an association between kidney stone disease (KSD) and hypertension. We recently reported a high occurrence of hypertension in families of patients with hyperuricosuric KSD. As hypercalciura frequently coexists with hyperuricosuria and high urinary excretion of calcium is found in patients with hypertension, we hypothesized that hyperuricosuria that is accompanied by hypercalciuria better describes the familial association between KSD and hypertension. Methods. Four hundred and eighty-six KSD patients, aged 18-50 years, attending a lithotripsy unit collected a 24-h urine sample for metabolic analysis and provided information on family history of hypertension. The Familial occurrence of hypertension was compared among four groups of patients: those who had combined elevation of both urinary calcium and uric acid excretions ('combined' abnormality, n = 56), those who had hyperuricosuria without concomitant hypercalciuria ('pure' hyperuricosuria, n = 67), those who had hypercalciuria without concomitant hyperuricosuira ('pure' hypercalciuria, n = 52), and a control KSD patient group ('other' abnormality, n = 311). The prevalence of treated hypertension in patients from the four groups was 16%, 12%, 2%, 10%, respectively. Results. Thirty-four per cent of the patients with the 'combined' abnormality had a positive family history of hypertension, defined as two or more First-degree relatives with treated hypertension, that was significantly higher than in patients with either 'pure' hyperuricosuira (15%, P<0.02), 'pure' hypercalciuria (8%, P<0.001), or patients with 'other' abnormality (10%, P<0.001). The adjusted OR for positive family history of hypertension in the 'combined' abnormality group compared to the control KSD patient group was 5.6 (2.39-13.30). The prevalence of hypertension in siblings of patients with the 'combined' abnormality (13%) was significantly higher than in siblings of patients with either 'pure' hyperuricosuria (3%, P<0.001), 'pure' hypercalciuria (1%, P<0.001), or siblings of control patients with 'other' abnormality (4%, P<0.001). The adjusted OR for hypertension in siblings of a patient with 'combined' abnormality compared to a control KSD patient was 3.4 (1.97-5.91). Patients in the 'combined' abnormality group were also characterized by significantly elevated urinary sodium, phosphorus, citrate and potassium excretions. Conclusions. Our data suggest that there is a strong, independent association between familial occurrence of hypertension and the phenotype characterized by combined elevation of both urinary uric acid and calcium excretions. The association is not present in those with 'pure' hyperuricosuria or 'pure' hypercalciuria. Ascertainment of patients based on this phenotype may identify more homogeneous populations for genetic analysis of hypertension.