Identification of the pivotal role of SPP1 in kidney stone disease based on multiple bioinformatics analysis

Background Kidney stone disease (KSD) is a multifactorial disease involving both environmental and genetic factors, whose pathogenesis remains unclear. This study aims to explore the hub genes related to stone formation that could serve as potential therapeutic targets. Methods Based on the GSE73680 dataset with 62 samples, differentially expressed genes (DEGs) between Randall’s plaque (RP) tissues and normal tissues were screened and weighted gene co-expression network analysis (WGCNA) was applied to identify key modules associated with KSD. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis were performed to explore the biological functions. The protein–protein interaction (PPI) network was constructed to identify hub genes. Meanwhile, CIBERSORT and ssGSEA analysis were used to estimate the infiltration level of the immune cells. The correlations between hub genes and immune infiltration levels were also investigated. Finally, the top hub gene was selected for further GSEA analysis. Results A total of 116 DEGs, including 73 up-regulated and 43 down-regulated genes, were screened in the dataset. The red module was identified as the key module correlated with KSD. 53 genes were obtained for functional enrichment analysis by taking the intersection of DEGs and genes in the red module. GO analysis showed that these genes were mainly involved in extracellular matrix organization (ECM) and extracellular structure organization, and others. KEGG analysis revealed that the pathways of aldosterone-regulated sodium reabsorption, cell adhesion molecules, arachidonic acid (AA) metabolism, and ECM-receptor interaction were enriched. Through PPI network construction, 30 hub genes were identified. CIBERSORT analysis revealed a significantly increased proportion of M0 macrophages, while ssGSEA revealed no significant differences. Among these hub genes, SPP1, LCN2, MMP7, MUC1, SCNN1A, CLU, SLP1, LAMC2, and CYSLTR2 were positively correlated with macrophages infiltration. GSEA analysis found that positive regulation of JNK activity was enriched in RP tissues with high SPP1 expression, while negative regulation of IL-1β production was enriched in the low-SPP1 subgroup. Conclusions There are 30 hub genes associated with KSD, among which SPP1 is the top hub gene with the most extensive links with other hub genes. SPP1 might play a pivotal role in the pathogenesis of KSD, which is expected to become a potential therapeutic target, while its interaction with macrophages in KSD needs further investigation.

Role of Dietary Supplements in Prevention of Renal Stones: An Update

Kidney stone disease is an oldest known and widespread medical condition characterised by its high prevalence in all over the world. Literature suggests that around 9–12% of population in industrialised countries have kidney stone disease in their lives with the 30–50% of reoccurrence rate. Because of high prevalence, recurrent and unpredictable nature of stone formation and its predominance mainly in adults contributes to the substantial impact on society, individual and health care system. In light of these trends, it’s imperative to use optimum preventive strategies to reduce the burden of kidney stone disease on individual and society. The aetiology of kidney stone disease is a multifactorial and it’s related to diet, environmental factors, genetics, metabolic syndromes and various life style factors. Its noteworthy that dietary and life style modification are the major contributors in the prevention of kidney stone reoccurrence. Dietary interventions aim to reduce the urinary abnormalities known to promote lithogenesis. Therefore, modification in the dietary factors is appealing way to patients and physicians in the treatment and prevention of stone recurrence as it is relatively inexpensive and safe. So, the present chapter is focusing on the role of dietary supplements in prevention of renal stones.

KIDNEY STONE DISEASE AND OSTEOPOROSIS - TOPIC ISSUES OF COMORBIDITY

the prevalence of kidney stone disease (KSD) and osteoporosis (OP) increases every year. In the prevention of osteoporosis, it is important to consume a sufficient amount of calcium-rich foods in the daily diet, as well as the use of calcium. One of the important reasons for the insufficient use of calcium-containing products and medicines is the anxiety not only of patients, but, very importantly, of doctors as much as possible. This has serious justification, as nephrolithiasis occurs in approximately 5% of the population, and the risk of developing kidney stones during life is 8-10%. It is believed that secondary hyperparathyroidism, which is caused by hypocalcemia due to insufficient consumption of calcium-containing products and impaired renal function, leads to increased bone resorption, formation of kidney stone disease. It is important to consider that against the background of hypertensive, atherosclerotic kidney disease, tubulo-interstitial lesions of the kidneys with decreasing glomerular filtration rate decreases the synthesis of 1α-hydroxylase - an enzyme by which 25-hydroxycholecalciferol (25 (OH) active D3, calcium) form of vitamin D3–1.25 dihydroxycholecalciferol (1.25 (OH) 2D3, calcitriol - D-hormone) and secondary hyperparathyroidism develops. In this case, the purpose of correction along with the treatment of urolithiasis (spa treatment, given the attendance of the presence of KSD, to carry out the distance lithotripsy), intake of active metabolites of vitamin D (should be started with low doses, independent of the initial PTH concentration, and then titrated based on the PTH response) conducting X-ray densitometry.

Diet-Derived Antioxidants and Risk of Kidney Stone Disease: Results From the NHANES 2007–2018 and Mendelian Randomization Study

We aimed to explore the associations between diet-derived antioxidants and kidney stone disease (KSD) risk in this study. We performed weighted multivariable-adjusted logistic regression to assess the associations between the six main diet-derived antioxidants and the risk of KSD by using data from the National Health and Nutrition Examination Survey (NHANES) 2007–2018. Then, we used the Mendelian randomization (MR) approach to verify the causal relationships between circulating antioxidants levels and KSD risk. Genetic tools were extracted from published genome-wide association studies (GWAS). Summary data for KSD was from the FinnGen study and UK biobank. Inverse variance weighted (IVW) was the primary analysis. The 26,438 participants, including 2,543 stone formers, were included for analyses. There were no significant associations between retinol, vitamin B6, vitamin C, vitamin E, and lycopene intake with the risk of KSD across all the quartile categories. Similarly, pooled odds ratio (OR) for KSD risk in genetically predicted per unit change were 1.25 (95% CI: 0.39, 4.02; p = 0.712), 1.14 (95% CI: 0.84, 1.53; p = 0.400), 0.75 (95% CI: 0.52, 1.10; p = 0.141), 1.66 (95% CI: 0.80, 3.46; p = 0.178), 1.27 (95% CI: 0.29, 5.62; p = 0.756), and 0.92 (95% CI: 0.76, 1.12; p = 0.417) for retinol, β-carotene, vitamin B6, vitamin C, α-tocopherol, and lycopene, respectively. The above estimates were replicated in the secondary analyses using UK biobank data. Our study did not support a causal association between circulating antioxidants levels and KSD risk. However, these findings should be verified in larger sample-size MR due to the pleiotropy and other limitations.

Mathematical postprocessing analysis of contrast-enhanced computed tomography data of the kidneys in evaluation of split renal function in patients with kidney stone disease

Introduction. An original research work was performed to assess split kidney function by glomerular filtration rate (GFR) with mathematical analysis of the kidneys computed tomography (CT) data in patients with kidney stone disease (KSD). Objective was to evaluate the GFR and the parenchyma structure of each kidney and identify the possible patterns of contrast medium intrarenal transport with mathematical analysis of the kidneys CT data in patients with KSD.Materials and methods. Data of 27 patients of both genders with KSD were retrospectively analyzed. To evaluate GFR separately for each kidney we analyzed the data of contrast-enhanced CT (GFR reference values are 0.55 % of contrast medium per second). Inclusion criteria are as follows: 1) newly diagnosed SKD; 2) stone size ≤1,5-2,0 cm, no obstruction of the urine flow registered; 3) no kidney or upper urinary tract surgical history; 4) age - ≤45 years; 5) no severe chronic diseases. All of these allowed to minimize influence of any other disorders on split renal function except for SKD and conduct per se research.Results. The mathematic analysis of the contrast-enhanced CT data revealed GFR changes in 26 (96.3 %) out of 27 patients. Hyperfiltration was found in 12 (44.4 %) patients: right kidney GFR - 0.6-0.77 %, mean value - 0.65 %; left kidney GFR - 0.59-0.79 %, mean value - 0.67 %. Hypofiltration was found in 13 (48.1 %) patients: right kidney GFR - 0.2-0.54 %, mean value - 0.37 %; left kidney GFR - 0.2-0.53 %, mean value - 0.4 %. The GFR values significantly differed between the groups both for the right (p = 0.000014) and left (p = 0.000045) kidneys. We found no significant age-related difference between the groups (p = 0.895). As well as that no significant differences in Resistance Index both in magistral (right kidney: p = 0.221; left kidney: p = 0.850) and segmental (right kidney: p = 0.306; left kidney: p = 0.957) arteries between the groups with hyperfiltration and hypofiltration were observed. One patient demonstrated no changes in GFR, and the other one had hyperfiltration (0,62 %) in one kidney and hypofiltration (0,48 %) in another.Conclusion. Most of the patients (92.6 %) with SKD demonstrate GFR changes (either hyperfiltration or hypofiltration) that may indicate the disturbed intrarenal blood and urine flow through the kidney.

Calcium and Vitamin D Supplementation and Their Association with Kidney Stone Disease: A Narrative Review

Kidney stone disease is a multifactorial condition influenced by both genetic predisposition and environmental factors such as lifestyle and dietary habits. Although different monogenic polymorphisms have been proposed as playing a causal role for calcium nephrolithiasis, the prevalence of these mutations in the general population and their complete pathogenetic pathway is yet to be determined. General dietary advice for kidney stone formers includes elevated fluid intake, dietary restriction of sodium and animal proteins, avoidance of a low calcium diet, maintenance of a normal body mass index, and elevated intake of vegetables and fibers. Thus, balanced calcium consumption protects against the risk for kidney stones by reducing intestinal oxalate availability and its urinary excretion. However, calcium supplementation given between meals might increase urinary calcium excretion without the beneficial effect on oxalate. In kidney stone formers, circulating active vitamin D has been found to be increased, whereas higher plasma 25-hydroxycholecalciferol seems to be present only in hypercalciuric patients. The association between nutritional vitamin D supplements and the risk for stone formation is currently not completely understood. However, taken together, available evidence might suggest that vitamin D administration worsens the risk for stone formation in patients predisposed to hypercalciuria. In this review, we analyzed and discussed available literature on the effect of calcium and vitamin D supplementation on the risk for kidney stone formation.

The Relationship between Modern Fad Diets and Kidney Stone Disease: A Systematic Review of Literature

Objectives: Kidney stone disease (KSD) has a strong association with diet metabolic syndrome. This review aims at exploring the lithogenic risk posed by the current most popular diets. Our approach was to search for the effect of each diet type on the major urinary risk factors, to try to draw conclusions regarding the association of a specific diet type and KSD. Methods: This systematic review searched for the available literature exploring the association between the existing popular fad diets and KSD. Articles in English, French and Spanish were included, without restriction of the search period with the final search done in August 2021. Results: Total number of studies and studies for each diet type was as follows: 22 articles for the low carbohydrate diet, 20 articles for high protein diets, 26 articles for vegetarian and vegan diets. There exists a substantial variability in different low carbohydrate and high protein diets, and considerable overlap between modern popular fad diets. High carbohydrate intake might increase urine uric acid, calcium and oxalate levels. High protein diets increase urine calcium and uric acid and lower urine pH and citrate. Consumption of fruits and vegetables increases the urinary volume and urinary citrate. In vegan diets, sufficient daily calcium intake is important to avoid possible secondary hyperoxaluria. Conclusions: Few studies evaluated the direct relationship between modern fad diets and KSD. In general, the reduction of carbohydrate in the diet, and counterbalancing protein rich diets with sufficient intake of fruits and vegetables, seem to play a protective role against KSD formation. Maintaining sufficient calcium intake in vegan and vegetarian diets is important. Additional research is needed to directly evaluate the link between KSD and each diet type.

Metabolic Syndrome Increases the Risk of Kidney Stone Disease: A Cross-Sectional and Longitudinal Cohort Study

We aimed to examine the association between metabolic syndrome and the risk of kidney stone development in a large-scale community-based cohort. A total of 121,579 participants enrolled in the Taiwan Biobank were analyzed. They were divided into two groups on the basis of presence of metabolic syndrome. The presence of kidney stone disease was defined by self-reported history of kidney stones. The mean age of participants was 50 years old, and self-reported kidney stones were observed in 3446 (10%) and 4292 (5%) participants with metabolic syndrome and without metabolic syndrome, respectively. Higher prevalence of kidney stone disease was found in participants with metabolic syndrome compared to those without metabolic syndrome (odds ratio (OR), 1.32; 95% confidence interval (95% CI), 1.25 to 1.39). In addition, the risk of incident kidney stone development was analyzed in a longitudinal cohort of 25,263 participants without kidney stones at baseline during a mean follow-up of 47 months. Multivariable Cox regression analysis revealed that the risk for incident kidney stone disease was higher in participants with metabolic syndrome than those without metabolic syndrome (hazard ratio, 1.24; 95% CI, 1.04 to 1.49). Our study suggests that metabolic syndrome does increase the risk of kidney stones.