Is oxidative stress, a link between nephrolithiasis and obesity, hypertension, diabetes, chronic kidney disease, metabolic syndrome?

Abstract

Epidemiological studies have provided the evidence for association between nephrolithiasis and a number of cardiovascular diseases including hypertension, diabetes, chronic kidney disease, metabolic syndrome. Many of the co-morbidities may not only lead to stone disease but also be triggered by it. Nephrolithiasis is a risk factor for development of hypertension and have higher prevalence of diabetes mellitus and some hypertensive and diabetic patients are at greater risk for stone formation. An analysis of the association between stone disease and other simultaneously appearing disorders, as well as factors involved in their pathogenesis, may provide an insight into stone formation and improved therapies for stone recurrence and prevention. It is our hypothesis that association between stone formation and development of co-morbidities is a result of certain common pathological features. Review of the recent literature indicates that production of reactive oxygen species (ROS) and development of oxidative stress (OS) may be such a common pathway. OS is a common feature of all cardiovascular diseases (CVD) including hypertension, diabetes mellitus, atherosclerosis and myocardial infarct. There is increasing evidence that ROS are also produced during idiopathic calcium oxalate (CaOx) nephrolithiasis. Both tissue culture and animal model studies demonstrate that ROS are produced during interaction between CaOx/calcium phosphate (CaP) crystals and renal epithelial cells. Clinical studies have also provided evidence for the development of oxidative stress in the kidneys of stone forming patients. Renal disorders which lead to OS appear to be a continuum. Stress produced by one disorder may trigger the other under the right circumstances.

Hormetic and regulatory effects of lipid peroxidation mediators in pancreatic beta cells

“…Hyperglycemia and obesity are considered prime risk factors in the disease due to over-production of free radical species that exacerbate metabolic abnormalities and related complications (Gorlach et al, 2015;Grattagliano et al, 2008;Houstis et al, 2006;Khan, 2012;Roberts and Sindhu, 2009;Shah et al, 2007;Skalicky et al, 2008;Unger et al, 2010). Defects in the mitochondrial respiratory chain, increased activity of oxidative enzymes (e.g., NOX), protein glycation and non-enzymatic oxidation and peroxidation of carbohydrates and lipids contribute to increased generation of oxygen free radicals in T2DM (Giacco and Brownlee, 2010;Manea et al, 2015b;Rochette et al, 2014).…”

Renal tubular NEDD4-2 deficiency causes NCC-mediated salt-dependent hypertension

“…Based on these results, NEDD4-2 appears to primarily target NCC and might thus be an attractive target to treat hypertension, avoiding the most severe side effect of thiazides, namely hypokalemia. Moreover, there is an interesting clinical association of hypercalciuria with hypertension and an increased risk of nephrolithiasis in hypertension (47)(48)(49)(50). Defects in NEDD4-2 could therefore underlie these associations, and its study could lead to important mechanistic insights.…”

Hippuric acid in 24 h urine collections as a biomarker of fruits and vegetables intake in kidney stone formers

“…On one hand, some studies have showed that SFs are prone to suffer cardiovascular diseases and diabetes (Ando et al, 2013;Khan, 2012;Rule et al, 2010). On the other hand, several studies have reported the role of (poly)phenolic substances from plantbased foodstuffs in the prevention and management of certain cancers, cardiovascular diseases, and diabetes (Del Rio et al, 2013).…”