Nephrolithiasis: A Red Flag for Cardiovascular Risk

Abstract

Epidemiological evidence shows that nephrolithiasis is associated with cardiovascular (CV) morbidities. The association between nephrolithiasis and CV disease is not surprising because both diseases share conditions that facilitate their development. Metabolic conditions, encompassed in the definition of metabolic syndrome (MS), and habits that promote nephrolithiasis by altering urine composition also promote clinical manifestations of CV disease. By inducing oxidative stress, these conditions cause endothelial dysfunction and increased arterial stiffness, which are both well-known predictors of CV disease. Furthermore, the subtle systemic metabolic acidosis observed in stone formers with CV disease may have a pathogenic role by increasing bone turnover and leading to reduced mineral content and osteoporosis/osteopenia. Heart valves and/or coronary artery and aortic calcifications are frequently associated with reduced mineral density. This is known as the ‘calcification paradox’ in osteoporosis and has also been observed in subjects with calcium nephrolithiasis. Evidence supports the hypothesis that osteoporosis/osteopenia is an independent risk factor for the development of CV calcifications. In the long term, episodes of renal stones may occur from the onset of metabolic derangements/MS to arterial stiffness/atherosclerosis and CV morbidities. These episodes should be considered a warning sign of an ongoing and silent atherosclerotic process. The evaluation of cardiometabolic risk factors and MS components should be routine in the assessment of renal stone formers. This would allow for treatment and prevention of the development of CV complications, which are much more severe for the patient and for public health.

Vitamin D and Calcium Supplementation and Urolithiasis: A Controversial and Multifaceted Relationship

“…Since SF patients are also more prone to develop CV disease, it has also been claimed that vitamin D administration, thanks to its alleged CVD protective effects, could play a preventing role against this type of complication [ 86 ].…”

The Optimal Length of Pharmacological Prophylaxis in Calcium Kidney Stone Formers

“… 29 The second study, which involved a large cohort, significantly associated the presence of renal stones with coronary artery calcifications. 30 Because patients with urolithiasis have frequently several cardiometabolic risk factors which are often the consequence of diet and lifestyle, 31 including hypertension, 32 if they exist, patients with stone might require treatment with either dietary and lifestyle interventions or, in severer cases, drugs. Prolonged kidney stone prophylaxis with thiazides could, therefore, be proposed in combination with strict adherence to a Mediterranean or dietary approaches to stop hypertension diet, both of which have known effects on CV risk and incidence of urolithiasis.…”

Unravelling the Complex Relationship between Diet and Nephrolithiasis: The Role of Nutrigenomics and Nutrigenetics

“…The paradigm to explain the relationship between nutrients and nephrolithiasis is mechanistic; nutritional modifications have a direct and immediate impact on urine composition: higher sodium intake leads to higher natriuresis and to higher urinary excretion of calcium, higher oxalate intake (after balancing in the gut with the calcium intake) leads to increased oxaluria, and higher animal protein/sulphated amino acid intake leads to a bodily acidogenic tide compensated by more acidic urine. The beneficial effect on the development of kidney stones of dietary patterns, such as the Dietary Approach to Stop Hypertension (DASH) diet [ 12 ] or the Mediterranean diet [ 13 , 14 ], is explained in the mechanistic way of the previous paradigm [ 15 ]. In fact, both diets are characterised by a high intake of fruits and vegetables (a diet rich in alkali) and a reduced intake of animal protein (a diet poor in acids) and sodium.…”

“…In fact, both diets are characterised by a high intake of fruits and vegetables (a diet rich in alkali) and a reduced intake of animal protein (a diet poor in acids) and sodium. However, there are nutrition-dependent conditions that are associated with the risk of developing nephrolithiasis, such as insulin resistance, diabetes, obesity, and metabolic syndrome, and whose association cannot be entirely mechanistically explained [ 13 ].…”

“…A large body of evidence now supports the idea that nephrolithiasis is one of the manifestations of systemic conditions, which include bone and cardiovascular (CV) diseases [ 14 , 16 , 17 ]. While mechanistic explanations might be possible for the association between metabolic bone disease and kidney stones, the mechanisms of the association with CV morbidities are not straightforward [ 13 ].…”