Previous studies have suggested that kidney stone formers are associated with a higher risk of cardiovascular events. To our knowledge, there have been no previous examinations of the relationship between carotid intima-media thickness (IMT) and urinary stone risk factors. This study was aimed toward an investigation of the association between dyslipidemia, IMT, and 24-hour urinalysis in patients with calcium oxalate (CaOx) or calcium phosphate (CaP) stones. We prospectively enrolled 114 patients with kidney stones and 33 controls between January 2016 and August 2016. All patients were divided into four groups, according to the stone compositions—CaOx ≥ 50% group, CaP group, struvite group, and uric acid stones group. Carotid IMT and the carotid score (CS) were evaluated using extracranial carotid artery doppler ultrasonography. The results of a multivariate analysis indicated that a higher serum total cholesterol (TC) and low-density lipoprotein (LDL) were all associated with lower urinary citrate and higher CS in both the CaOx ≥ 50% and CaP groups. Higher serum TC and LDL were also associated with increased serum 8-OHdG levels in both groups. The levels of carotid IMT and CS in the CaOx ≥ 50% and CaP groups were all significantly higher than in the controls. These findings suggest a strong link between dyslipidemia, carotid atherosclerosis, and calcium kidney stone disease.

Calcium (Ca²⁺) is an important mediator of multicellular homeostasis and is involved in several diseases. The interplay among the kidney, bone, intestine, and parathyroid gland in Ca²⁺ homeostasis is strictly modulated by numerous hormones and signaling pathways. The calcium-sensing receptor (CaSR) is a G protein–coupled receptor, that is expressed in calcitropic tissues such as the parathyroid gland and the kidney, plays a pivotal role in Ca²⁺ regulation. CaSR is important for renal Ca²⁺, as a mutation in this receptor leads to hypercalciuria and calcium nephrolithiasis. In addition, CaSR is also widely expressed in the vascular system, including vascular endothelial cells (VECs) and vascular smooth muscle cells (VSMCs) and participates in the process of vascular calcification. Aberrant Ca²⁺ sensing by the kidney and VSMCs, owing to altered CaSR expression or function, is associated with the formation of nephrolithiasis and vascular calcification. Based on emerging epidemiological evidence, patients with nephrolithiasis have a higher risk of vascular calcification, but the exact mechanism linking the two conditions is unclear. However, a dysregulation in Ca²⁺ homeostasis and dysfunction in CaSR might be the connection between the two. This review summarizes renal calcium handling and calcium signaling in the vascular system, with a special focus on the link between nephrolithiasis and vascular calcification.

Calcium oxalate (CaOx) is the major constituent of kidney stones. Growing evidence shows a close connection between hyperlipidemia, cardiovascular disease (CVD), and the formation of kidney stones. Owing to their antioxidant properties, statins control hyperlipidemia and may ameliorate CaOx stone formation. The present study was designed to investigate the suppressive effects of statins on CaOx urolithiasis and their potential mechanism. We used rats fed a high-fat diet (HFD) to achieve hyperlipidemia (HL) and hydroxyproline (HP) water to establish a hyperoxaluric CaOx nephrolithiasis model; the animals were administered statins (A) for 28 days. The rats were divided into eight groups treated or not with A, i.e., Control, HP, HL, HL + HP. HL aggravated urinary calcium crystallization compared to the control. Due to increased expression of renal osteopontin (OPN), a key anti-lithic protein, and reduced free radical production, the calcium crystals in the urinary bladder increased as renal calcium deposition decreased. The levels of the ion activity product of CaOx (AP(CaOx)) decreased after statins administration, and AP(Calcium phosphate) (CaP) increased, which suggested the dominant calcium crystal composition changed from CaOx to CaP after statin administration. In conclusion, atorvastatin decreases renal CaOx stone deposits by restoring OPN expression in hyperoxaluric rats fed a HFD.

Uric acid urolithiasis constitutes approximately 7–10% of all urinary stones. Previous studies have revealed that patients with gout do not equally have uric acid stones. Instead, the risk of gout in patients with uric acid stones remains controversial. This study aimed to investigate whether there is different associated risk of gout for diabetes mellitus (DM) and non-diabetes patients with uric acid urolithiasis. Therefore, we examined all baseline chemistries to determine any risk factors or protective factors related to developing gout in patients with uric acid stones. Ninety-nine patients from a single medical center, who had a uric acid component in their stone specimen were enrolled and their medical records were reviewed retrospectively between January 2010 and December 2016. All patients were divided into gout and non-gout groups. Gout was confirmed in 24 patients in this study (24.2%). The proportion of DM was significantly higher in the non-gout group (34.7%) than in the gout group (4.3%, p < 0.05). Renal function was decreased and serum triglyceride was higher in patients with gout. Uric acid urolithiasis patients with DM had a lower risk for gout (adjusted odds ratio: 0.08; 95% confidence interval (CI) = 0.01–0.61, p = 0.015). In 89 patients with predominant uric acid stones (>50% uric acid composition), the risk for gout was still lower in patients with diabetes than non-diabetes (adjusted odds ratio: 0.08; 95% confidence interval (CI) = 0.01–0.61, p = 0.015). These findings suggest that decreased risk of gout is found in uric acid urolithiasis patients with diabetes. Our results imply that patients with uric acid stones should have complete diabetes evaluation before the administration of uric acid controlling medication.