Association between metabolic syndrome components and the risk of developing nephrolithiasis: A systematic review and bayesian meta-analysis

Abstract

Background: There is increasing evidence that nephrolithiasis is a systemic disease, as opposed to an isolated urinary metabolic problem, after considerable links were found between nephrolithiasis and systemic diseases such as hypertension, obesity, dyslipidemia, and insulin resistance. The interplay between these four factors defines metabolic syndrome (MetS). In this review we aim to clarify the associations of MetS and its components to kidney stone incident. Methods: Online databases of EMBASE, MEDLINE, and Google Scholar were searched from January 1998 up to October 2020 to identify observational studies examining the association between metabolic syndrome components and kidney stone incident. Bayesian random-effects meta-analysis and meta-regression were performed to observe the association. Linear dose-response analysis was conducted to shape the direction of the association. Data analysis was performed using STATA, and R statistics. Results: A total of 25 potentially relevant studies (n = 934,588 participants) were eventually identified. The pooled results suggested that metabolic syndrome was associated with an increased risk of nephrolithiasis with an odds ratio (OR) of 1.769 (95% CI: 1.386 – 2.309). The summary OR of hypertension and dyslipidemia for developing nephrolithiasis were 1.613 (95% CI: 1.213 – 2.169) and 1.586 (95% CI: 1.007 – 2.502) respectively. The presence of diabetes mellitus and obesity had an OR of 1.552 (95% CI: 1.027 – 2.344) and 1.531 (95% CI: 1.099 – 2.109) respectively. Our results revealed that the increasing number of MetS traits will increase the risk of developing nephrolithiasis, the higher the fasting plasma glucose, and body mass index, the higher the risk of kidney stones incident. Conclusions: Our results suggest that hypertension, diabetes, obesity and dyslipidemia are associated with increased risk of developing nephrolithiasis. Linear significant association between MetS components and nephrolithiasis were revealed in our study which reinforced the notion that should be considered a systemic disorder.

Systematic assessment of monogenic etiology in adult‐onset kidney stone formers undergoing urological intervention–evidence for genetic pretest probability

“…Nevertheless, KSD in a patient with MS is likely to be multifactorial, hence based on environmental factors and complex genetics rather than a monogenic disorder: a notion is principally corroborated by our data. Despite a huge body of evidence on the association of MS traits with KSD (Chang et al, 2021; Kohjimoto et al, 2013; Rahman, Nusaly, Syahrir, Nusaly, & Mansyur, 2021), defining aggregate genetic determinants in this KSD subgroup remains a major challenge for future studies.…”

Nephrolithiasis: A Red Flag for Cardiovascular Risk

“…The long-known association between DM2 and nephrolithiasis has been recently confirmed in a Bayesian meta-analysis [ 44 ]. Diabetes may both precede or follow the onset of nephrolithiasis [ 4 , 45 ].…”

“…A meta-analysis showed that dyslipidaemic subjects had a 1.6-fold higher risk of developing nephrolithiasis than non-dyslipidaemic subjects [ 44 ]. The hypothesis was that renal lipotoxicity was the pathogenic trigger of nephrolithiasis; i.e., lipid accumulation in proximal tubular cells induces the impairment of ammoniagenesis and acidic urine, thereby promoting uric acid lithiasis [ 50 , 71 ].…”

“…Several studies and a meta-analysis established the association between nephrolithiasis and MS [ 3 , 5 , 6 , 7 , 44 ]. In stone formers, the risk of developing MS is almost double that of non-stone formers and even higher in patients with uric acid stones [ 73 ].…”

A pilot dynamic analysis of formative factors of nephrolithiasis related to metabolic syndrome: evidence in a rat model

“…One recent systematic review that included 25 potentially relevant studies ( n = 934,588 participants) suggested that all components of MS were linked to an increased incidence of nephrolithiasis. The possible mechanisms associated with MS are often related to lipotoxicity and insulin resistance, which induce systemic inflammation and oxidative stress [ 9 ]. However, this link has been explored for only a short time, and there are clinical limitations.…”