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.

The impact of heat on kidney stone presentations in South Carolina under two climate change scenarios

The risk of kidney stone presentations increases after hot days, likely due to greater insensible water losses resulting in more concentrated urine and altered urinary flow. It is thus expected that higher temperatures from climate change will increase the global prevalence of kidney stones if no adaptation measures are put in place. This study aims to quantify the impact of heat on kidney stone presentations through 2089, using South Carolina as a model state. We used a time series analysis of historical kidney stone presentations (1997–2014) and distributed lag non-linear models to estimate the temperature dependence of kidney stone presentations, and then quantified the projected impact of climate change on future heat-related kidney stone presentations using daily projections of wet-bulb temperatures to 2089, assuming no adaptation or demographic changes. Two climate change models were considered—one assuming aggressive reduction in greenhouse gas emissions (RCP 4.5) and one representing uninibited greenhouse gas emissions (RCP 8.5). The estimated total statewide kidney stone presentations attributable to heat are projected to increase by 2.2% in RCP 4.5 and 3.9% in RCP 8.5 by 2085–89 (vs. 2010–2014), with an associated total excess cost of ~ $57 million and ~ $99 million, respectively.

Genetic Risk Factors for Idiopathic Urolithiasis: The Causative Role of Genes in Stones Formation

Background: The genetic factor of urolithiasis plays an important role in the etiology. Elucidation of responsible genes can lead to better targeted gene therapy and prevention in the future. This article aims to explain various genetic factors that play a role in kidney stone formation Method: A review article on urolithiasis based on a genetic approach is reported to underlie stone formation. A total of 41 abstracts and research articles published by internationally reputed journals were selected based on the keywords genetic factors and urolithiasis. Summary: A deeper understanding of the genetic factors that play a role in the mechanisms of stone formation and advances in molecular and pharmacogenomics have revolutionized diagnosis and treatment, and paved the way for the identification of new therapeutic targets and treatment approaches based on genetic engineering.

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.

Prevalence of Kidney Stones Among Patients Presenting to Orotta Medical Surgical National Referral Hospital

Background Nephrolithiasis is a condition of having stones in the kidneys, which progressively lead to loss of renal function if untreated properly.1 The prevalence and incidence of kidney stones is increasing across the world.2 Methods A retrospectively collected data of kidney stone disease was reviewed on patients who visited the outpatient department of Orotta Medical Surgical National Referral Hospital from January 2012 to December 2012. Results Out of 30,335 patients 173 were confirmed to have stones making them 0.5%. Generally results show male predominance with male to female ratio of 2.46:1. Results also show prevalence decreases as age increases with the highest among the age group 15-25 making a prevalence rate of 27.7% with observed significance of 0.002. Out of those patients who visited the outpatient department patients from Zoba Maekel were the highest in number (59.9%) followed by Debub (19.1%) while the southern Red Sea Zone had the lowest prevalence (2.3%). Majority of the stones were found on the kidney comprising about 80.3%, followed by ureter 16.8% of patients and 2.9% stones were located on the bladder. When data was reviewed for associated co morbidity only one patient had associated Diabetes mellitus and Hypertension, three had ectopic kidney(1.7%), one had renal cyst (0.6%) and 12 (6.9%) patients were complicated with hydronephrosis. (P=0.548) Conclusions The prevalence of kidney stone in Orotta Medical Surgical National Referral hospital from January to December 2012 is 0.5%, with higher predominance in men than in women with a ratio of 2.46:1.

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.