Expression profiles of urine exosomal tRNA-derived small RNAs and their potential roles in calcium oxalate stone disease.

Background and objective: Exosomes have been confirmed to be implicated in the pathogenesis of calcium oxalate (CaOx) stones. tRNA-derived small RNAs (tsRNAs) are among the oldest small RNAs involved in exosome-mediated intercellular communication, yet their role in kidney stones remains unexplored. This pilot study aimed to identify differentially expressed tsRNAs (DEtsRNAs) in urine exosomes between CaOx stone patients and healthy controls and explore their potential roles in nephrolithiasis. Method: First-morning urine samples were collected from three CaOx stone patients and three healthy controls. Urinary exosomes were isolated and analyzed by high-throughput sequencing to generate the expression profiles of tsRNAs and detect DEtsRNAs. Predicted target genes of DEtsRNAs were subjected to functional enrichment analysis. The authors also combined the public dataset GSE73680 to investigate how DEtsRNAs were related to stone formation. Results: Four DEtsRNAs were significantly upregulated in CaOx stone patients compared to healthy controls. tRF-Lys-TTT-5005c was the most elevated, followed by tRF-Lys-CTT-5006c, tRF-Ala-AGC-5017b, and tRF-Gly-CCC-5004b. Bioinformatics analysis indicated that these four types of DEtsRNAs might serve distinct biological functions. Combined with data mining from the public dataset GSE73680, the authors assumed that exosomes carrying tRF-Lys-TTT-5005c and tRF-Lys-CTT-5006c could inhibit the expression of SMAD6, FBN1, and FZD1, thereby activating the BMP signaling pathway, which might induce an osteogenic-like transformation in target cells, resulting in the formation of Randall's plaques and CaOx stones. Conclusion: The authors' findings shed light on the potential roles of tsRNAs in the pathogenesis of CaOx stone disease, highlighting exosomal DEtsRNAs as promising diagnostic biomarkers and therapeutic targets in nephrolithiasis.

Pectolinarigenin alleviates calcium oxalate-induced renal inflammation and oxidative stress by binding to HIF-1α.

Calcium oxalate (CaOx) crystals are the main constituents of renal crystals in humans and induce tubular lumen damage in renal tubules, leading to renal calcium deposition and kidney stone formation. Oxidative stress and inflammation play important roles in regulating calcium oxalate-induced injury. Here, we evaluated the efficacy in inhibiting oxidation and inflammation of pectinolinarigenin, a biologically active natural metabolite, in CaOx nephrocalcinosis and further explored its targets of action. First, we developed cellular and mouse models of calcium oxalate renal nephrocalcinosis and identified the onset of oxidative stress and inflammation according to experimental data. We found that pectolinarigenin inhibited this onset while reducing renal crystal deposition. Network pharmacology was subsequently utilized to screen for hypoxia-inducible factor-1α (HIF-1α), a regulator involved in the body's release and over-oxidation of inflammatory factors. Finally, molecular docking, cellular thermal shift assay, and other experiments to detect HIF-1α expression showed that pectolinarigenin directly combined with HIF-1α and prevented downstream reactive oxygen species activation and release. Our results indicate that pectolinarigenin can target and inhibit HIF-1α-mediated inflammatory responses and oxidative stress damage and be a novel drug for CaOx nephrocalcinosis treatment.

S100A9 promotes renal calcium oxalate stone formation via activating the TLR4-p38/MAPK-LCN2 signaling pathway.

OBJECTIVES: To explore the role of S100A9 protein in renal calcium oxalate (CaOx) stone formation. METHODS: CaOx nephrocalcinosis mice were established via intraperitoneal injection of glyoxylate. They were treated with S100A9 deficiency, Paquinimod, or p38 MAPK-IN-1. Vonkossa staining was conducted to observe the deposition of CaOx crystals. Renal expression of inflammation, macrophage polarization, and injury markers was detected using immunohistochemistry and qPCR. Effects of S100A9 on renal tubular epithelial cells (HK-2) were explored by transcriptome sequencing. The mechanism of how S100A9 regulated lipocalin 2 (LCN2) was studied through Western Blot. Flow cytometry was performed to detect the influence of LCN2 on macrophages polarization. RESULTS: S100A9 deficiency inhibited the renal deposition of CaOx crystals in nephrocalcinosis mice. S100A9 upregulated the expression of LCN2 in HK-2 cells via activating the TLR4-p38/MAPK pathway. LCN2 promoted the migration and M1 polarization of macrophages. S100A9 deficiency downregulated the renal expression of LCN2, IL1-ß, Kim-1, F4/80, and CD80 in nephrocalcinosis mice. Paquinimod and p38 MAPK-IN-1 both inhibited the renal deposition of CaOx crystals and downregulated the expression of LCN2, IL1-ß, Kim-1, F4/80, iNOS, and CD68 in nephrocalcinosis mice. CONCLUSIONS: S100A9 promotes renal inflammatory injury by activating the TLR4-p38/MAPK-LCN2 pathway and then contributes to CaOx stone formation.

Recurrent calcium oxalate calculi: the culprit in disguise.

Congenital sucrase isomaltase deficiency (CSID) is a rare autosomal recessive monogenic disorder of small intestinal malabsorption and manifests typically in early childhood with chronic osmotic diarrhoea. Though there have been case reports in adults presenting with hypercalcemia and renal calculi in CSID, this is quite rare in children. We hereby report a 6-year-old boy who presented with recurrent episodes of calcium oxalate calculi without any gastrointestinal symptoms and was confirmed as having sucrase isomaltase deficiency by genetic analysis.

Tensile Properties of Cattail Fibres at Various Phenological Development Stages.

Cattails (Typha latifolia L.) are naturally occurring aquatic macrophytes with significant industrial potential because of their abundance, high-quality fibers, and high fiber yields. This study is the first attempt to investigate how phenological development and plant maturity impact the quality of cattail fibers as they relate to composite applications. It was observed that fibers from all five growth stages exhibited a Weibull shape parameter greater than 1.0, with a goodness-of-fit exceeding 0.8. These calculations were performed using both the Least Square Regression (LSR) and Maximum Likelihood Estimation (MLE) methods. Among the estimators, the MLE method provided the most conservative estimation of Weibull parameters. Based on the Weibull parameters obtained with all estimators, cattail fibers from all five growth stages appear suitable for composite applications. The consistency of shape parameters across all five growth stages can be attributed to the morphological and molecular developments of cattail fiber during the vegetative period. These developments were confirmed through the presence of calcium oxalate (CaOx) plates, elemental composition, and specific infrared peaks at 2360 cm-1 contributing to the strength, cellulose peaks at 1635 cm-1, 2920 cm-1, and 3430 cm-1. In conclusion, it was found that the mechanical properties of cattail fiber remain similar when harvested multiple times in a single growing season.

Expression Profiles of Claudin Gene Family Members in Patients With Recurrent Calcium Oxalate Kidney Stones.

INTRODUCTION: In this study, we aimed to evaluate and compare the expression profiles of CLDN gene family members responsible for the mechanism of stone formation in patients with recurrent calcium oxalate stones and in a control group without a history of renal stones. METHODS: Nineteen patients with recurrent calcium oxalate renal calculi who underwent percutaneous nephrolithotomy and 21 control patients without renal calculi who underwent surgery for other reasons were included in the study. The urinary calcium, oxalate, and citrate levels of the patients included in the study, as well as those in the control group, were within normal ranges. They did not have proteinuria in their urine. The biochemical parameters were also within normal limits. Biopsy samples taken from the intact renal cortex parenchymal tissue were consistent. Total RNA was isolated from biopsy samples and expression profiles of target genes (Claudin 1-4, 7, 8, 10, 14, 16, 18, 19) were determined by real-time polymerase chain reaction (PCR). RESULTS: It was determined that CLDN1 gene expression in patients with recurrent calcium oxalate kidney stones was approximately four times higher than in the control group; this difference was statistically significant (p<0.050). CLDN1 expression was also strongly positively correlated with CLDN4 (r=0.642), CLDN7 (r=0.753) and CLDN14 (r=0.651) Conclusions: We thought that CLDN1 overexpression might play a role in the pathogenesis of recurrent calcium oxalate stone formation. CLDN1 together with CLDN2, CLDN4, CLDN7, and CLDN14 are also probably responsible for this pathogenesis.

Two distinct phenotypes of calcium oxalate stone formers could imply different long-term risks for renal function.

Endoscopic and biopsy findings have identified two distinct phenotypes among individuals with calcium oxalate (CaOx) kidney stones. The first type has normal renal papillae but shows interstitial mineral deposition, known as Randall's plaque. The other phenotype presents with collecting duct plugging and a higher incidence of loss of papilla tissue mass. With Randall's plaque, renal papilla injury involves the loss of small patches of calcified tissue (Randall's plaque detaching with the stone), which likely results in damage to only a few nephrons. In contrast, collecting duct mineral plugs are very large, causing obstruction to tubular flow. Since each terminal collecting duct drains thousands of nephrons, ductal plugs could lead to the degeneration of many nephrons and a significant loss of renal glomeruli. New visualization techniques for immune cells in papillary biopsies have revealed that the Randall's plaque phenotype is marked by the accumulation of macrophages around the plaque regions. In contrast, preliminary data on the plugging phenotype shows collecting duct damage with mineral plugs and increased T-lymphocytes throughout the papilla. These regions also show tubulitis, i.e., T-cell infiltration into nearby collecting duct epithelium. This suggests that while some CaOx stone formers may have some papillary inflammation but with minimal damage to nephrons, others suffer from obstruction to flow for many nephrons that may also include destructive inflammation in the renal tissue. We propose that CaOx stone formers with the plugging phenotype will have a higher long-term risk for loss of renal function.

Research on key pathogenesis and potential intervention targets of idiopathic renal calculi composed of calcium oxalate (CaOx) based on bioinformatics.

Background: Calcium oxalate (CaOx) kidney stones are the most common type of stones in the urinary system, and their formation involves a complex mechanism with multiple contributing factors. In recent years, with the development of bioinformatics, there has been a deeper understanding of the pathogenesis of this type of disease. This study aimed to analyze the gene expression profiles of idiopathic kidney stones composed of CaOx using bioinformatics methods. By investigating the pathogenesis at the molecular level and identifying potential therapeutic targets, the study also integrated clinical data to validate the clinical relevance of the target genes. Methods: Gene expression profiles from the GSE73680 dataset were analyzed via the Gene Expression Omnibus (GEO) database to identify differentially expressed genes (DEGs) between Randall's plaques (RPs) from kidney papillae associated with CaOx stones and normal kidney papillae tissues. The Search Tool for the Retrieval of Interacting Genes/Proteins (STRING) database was employed to construct transcription factor (TF)-DEG-microRNA (miRNA) networks, and key genes were screened using the Molecular Complex Detection (MCODE) plugin. A gene set enrichment analysis (GSEA) was performed to investigate the possible underlying mechanisms of the key genes. The clinical data of idiopathic CaOx kidney stone patients who received treatment at the General Hospital of Northern Theater Command from January 2020 to December 2022 were retrospectively analyzed. Enzyme-linked immunosorbent assay (ELISA) kits were used to measure the transcriptional activity of the key genes in calcified kidney papillae tissues. Univariate and multivariate logistic regression analyses were employed to analyze the transcriptional activity of the key genes and their association with idiopathic kidney stones composed of CaOx. Results: In the GSE73680 dataset, 276 upregulated and 538 downregulated DEGs were identified. Protein-protein interaction network construction revealed one significant module and three candidate genes [interleukin 11 (IL-11), interleukin 16 (IL-16), and interleukin 32 (IL-32)]. The TF-DEG-miRNA network indicated that IL-11 might be regulated by 25 TFs and interact with six miRNAs. The GSEA suggested that IL-11 could influence the development of idiopathic CaOx stones through chemokine expression and via the signaling pathways of the nucleotide-binding oligomerization domain-like receptors [NOD-like receptors (NLRs)] and toll-like receptors (TLRs). The clinical data analysis revealed that the IL-11 serum levels were significantly elevated in the patients with idiopathic kidney stones composed of CaOx compared to the control subjects (P<0.001). Additionally, IL-11 was identified as an independent risk factor for the development of idiopathic CaOx kidney stones (P<0.001). Conclusions: The bioinformatically identified key genes and signaling pathways provide a deeper understanding of the potential mechanisms underlying idiopathic CaOx kidney stones. Preliminary clinical trials suggest that elevated serum IL-11 levels in idiopathic CaOx kidney stone patients could serve as a possible diagnostic biomarker and treatment target.

Quercus dentata Thunb. leaves extract inhibits CaOx crystallization and ameliorates ethylene glycol-induced CaOx kidney stones via the OPN/CD44 and NLRP3 pathways.

ETHNOPHARMACOLOGICAL RELEVANCE: The leaves of Quercus dentata Thunb. (QD), a member of the Fagaceae family and genus Quercus, with distributions in China, Japan, Korea, and other regions. As recorded in the Ben Cao Gang Mu (Compendium of Materia Medica) and other classical Chinese medical texts, QD has been traditionally employed in Traditional Chinese Medicine (TCM) for their hemostatic and diuretic effects and has been used to treat urinary stones (Lin Zheng). It is also the main ingredient of the Mishitong capsule (MST), a Chinese patent drug, used for kidney stones and ureteral stones. Nonetheless, the specific active ingredients and the mechanisms of QD in treating kidney stones remain to be elucidated, which is crucial for advancing the scientific understanding and clinical application of this traditional medicine. AIM OF STUDY: This study aimed to identify the active constituents of QD water extract (QDWE), explore its inhibitory effects on kidney stones through in vitro and in vivo studies, and elucidate the underlying mechanisms of the OPN/CD44 axis and the NLRP3 signaling pathway to provide a full understanding of its potential as a novel treatment approach against kidney stones. MATERIALS AND METHODS: The micromolecular components in the supernatant of QDWE (QDS) were analyzed by UPLC-Q-Exactive-Orbitrap-MS and the monosaccharide composition of the macromolecular polysaccharide components in the crude polysaccharide (QDP) was determined by pre-column derivatization in HPLC. The effects of QDWE, QDS and QDP on the shape, size, and structure of calcium oxalate (CaOx) crystals in vitro were explored by XRD, FTIR and SEM. The effects of QDWE, QDS and QDP on CaOx kidney stones in SD rats induced by ethylene glycol and VD3 were compared in vivo. Furthermore, the underlying mechanisms of OPN/CD44 and NLRP3 pathways were investigated by Western blot analysis. RESULTS: There were 32 compounds identified in QDS. The monosaccharide composition ratio of QDP was Man: L-Rha: D-GlcA: D-GalA: D-Glc: D-Gal: L-Ara = 1.01: 22.52: 8.27: 38.61: 3.43: 17.80: 6.38, indicating a mixture of pectin-type acidic heteropolysaccharides. QDP had a more significant inhibitory effect on CaOx crystals in vitro than QDWE, which can inhibit the formation of CaOx monohydrate crystals (COM) and convert them into thermodynamically unstable CaOx dihydrate (COD) crystals. The high dose of QDWE exhibited significant in vivo efficacy (P < 0.05), including anti-calculus, diuretic effects, and kidney protection, marked by decreased calcification and stone formation, alongside improved kidney vitality. Furthermore, the protective effects of QDWE were demonstrated to be associated with the OPN/CD44 and NLRP3 pathways. CONCLUSION: The studies identified and analyzed the active constituents of QDWE. Among these, QDP significantly inhibited CaOx crystal generation in vitro and could be a potential component for the treatment of urinary stones in QDWE. Moreover, the results indicated that QDWE had a remarkable therapeutic effect on CaOx stones by modulating the OPN/CD44 axis to affect stone formation and the NLRP3 signaling pathway to mediate inflammation, providing an experimental basis for the mechanism of anti-urinary stone and deep development of QD.

Morin hydrate mitigates calcium oxalate urolithiasis by inhibiting oxalate synthesis and modulating crystal formation.

Calcium oxalate (CaOx) urolithiasis is a prevalent urinary disorder with significant clinical impact. This study investigates the therapeutic potential of Morin Hydrate (MH), a natural bioflavonoid, in preventing CaOx stone formation. Molecular docking studies revealed that MH binds strongly to glycolate oxidase (GO), suggesting its inhibitory effect on oxalate synthesis. In vitro assays demonstrated that MH effectively inhibits CaOx crystal nucleation, aggregation, and growth, altering crystal morphology to less stable forms. Diuretic activity studies in Wistar rats showed that MH substantially increased urine volume and ion excretion, indicating its moderate diuretic effect. In vivo experiments further supported these findings, with MH treatment improving urinary and serum markers, reducing oxidative stress, and protecting renal tissue, as evidenced by histopathological analysis. Notably, MH administration significantly decreased GO and lactate dehydrogenase activities in urolithiatic rats, indicating a reduction in oxalate production. These results suggest that MH is a promising candidate for the prevention and treatment of CaOx urolithiasis, with the potential for clinical application in reducing the risk and recurrence of kidney stones.

Metabolomics analysis reveals a protective effect of hydroxycitric acid on calcium oxalate-induced kidney injury.

Objectives: Prior research has indicated that hydroxycitric acid (HCA) can impede the formation of calcium oxalate (CaOx) crystals, yet the specific mechanisms underlying its therapeutic effects remain unclear. In this study, we delved into the protective effects of HCA against glyoxylate-induced renal stones in rats and sought to elucidate the underlying metabolic pathways. Materials and Methods: Forty rats were randomly assigned to five groups: control group, model group, L-HCA-treated group, M-HCA-treated group, and H-HCA-treated group. Von Kossa staining was conducted on renal sections, and blood urea nitrogen and serum creatinine were determined by biochemical analysis. Meanwhile, body weight and urine volume were also measured. We subjected urine samples from the rats to analysis using ultra-performance liquid chromatography-quadrupole time-of-flight mass spectrometry. Next, we employed a metabolomic approach to scrutinize the metabolic profiles of each group. Results: HCA significantly reduced blood urea nitrogen and serum creatinine, and increased body weight and urine volume. It also reduced CaOx crystal deposition. A total of 24 metabolites, exhibiting a significant reversal pattern following HCA administration, were identified as urine biomarkers indicative of HCA's preventive effects against CaOx crystal-induced renal injury. These metabolites are primarily associated with glycine, serine, and threonine metabolism; phenylalanine metabolism; tricarboxylic acid cycle; taurine and hypotaurine metabolism; and tryptophan metabolism. Conclusion: It was demonstrated that HCA has a protective effect against CaOx crystal-induced kidney injury in rats by modulating various metabolic pathways. Additionally, results suggest that HCA holds promise as a potential clinical therapeutic drug for both the prevention and treatment of renal stones.

The Elephant in the Room: Clinical Progression and Management of Elephant Ear Plant Toxicity in an Adult.

Elephant ear plants are popular ornamental plants renowned for their large foliage. These plants have been implicated in various inadvertent and deliberate ingestions. The leaves and roots of these plants contain raphides, which are needle-shaped calcium oxalate crystals. Ingestion of these crystals results in a localized inflammatory response, typically manifesting as irritation, edema, hypersalivation, and dysphagia. Herein, we describe a case of an older gentleman who presented to our institution following intentional ingestion of the leaves and roots of an elephant ear plant. This report describes the clinical manifestations secondary to the toxicities related to the ingestion of this plant and displays the successful conservative management approach employed following multiple diagnostic studies.

Chronic Kidney Disease and Kidney Stone in a Wild Chimpanzee (Pan troglodytes verus) in Côte d'Ivoire.

An older wild female chimpanzee (Pan troglodytes) was found dead with a large calcium oxalate stone in the renal pelvis. Histopathological changes included glomerulosclerosis, interstitial nephritis and fibrosis, focal mineralization, and medial hypertrophy. Urinary albumin-creatinine-ratio showed increased values from 15 months before death. Causes of the kidney disease remain unconfirmed.

Comparison of cat stone matrix and cat urine proteomes to human calcium oxalate stone matrix and urine proteomes.

Cat calcium oxalate monohydrate kidney stone matrix proteome showed great similarity to human calcium oxalate monohydrate stone matrix proteome, but inference of mechanistic similarity was limited by the absence of cat urine proteomic data. In this study, urine proteome distributions were measured by the same methods in 7 healthy cats for comparison to both the published human urine and cat calcium oxalate stone matrix proteomes to assess for similar enrichment patterns in both species. Furthermore, proteomic distributions were determined in cat struvite stone matrix to test for similarity to calcium oxalate monohydrate stone matrix and urine proteomes. Cat urine proteins demonstrated a similar distribution of abundance as a function of isoelectric points or net charge to human urine samples, and consequently the similarly altered patterns of protein distributions seen in calcium oxalate monohydrate stone matrix seen from both cat and human stones likely derives from the same preferential adsorption mechanism. Furthermore, the fact that protein abundance patterns seen in cat struvite stone matrix samples differ from both urine and calcium oxalate monohydrate stone matrix proteomes in systematic ways suggests that a combination of protein-protein and protein crystal interactions underly the formation of the crystal aggregates that comprise stones.

Two distinct phenotypes of calcium oxalate stone formers could imply different long-term risks for renal function.

Endoscopic and biopsy findings have identified two distinct phenotypes among individuals with calcium oxalate (CaOx) kidney stones. One phenotype exhibits normal renal papillae but shows interstitial mineral deposition, known as Randall's plaque. The other phenotype presents with collecting duct plugging and a higher incidence of loss of papilla tissue mass. With Randall's plaque, renal papilla injury involves the loss of small patches of calcified tissue (Randall's plaque detaching with the stone), which likely results in damage to only a few nephrons. In contrast, collecting duct mineral plugs are very large, causing obstruction to tubular flow. Since each terminal collecting duct drains thousands of nephrons, ductal plugs could lead to the degeneration of many nephrons and a significant loss of renal glomeruli. New visualization techniques for immune cells in papillary biopsies have revealed that the Randall's plaque phenotype is marked by the accumulation of macrophages around the plaque regions. In contrast, preliminary data on the plugging phenotype shows collecting duct damage with mineral plugs, increased T-lymphocytes throughout the papilla, and tubulitis, characterized by T-cell infiltration into nearby collecting duct epithelium. This suggests that while some CaOx stone formers may have some papillary inflammation but with minimal damage to nephrons, others suffer from obstruction to flow for many nephrons that may also include destructive inflammation in the renal tissue. We propose that the long-term risks for loss of renal function will be greater for CaOx stone formers with the plugging phenotype.

[Epidemiology of urolithiasis in south of Tunisia]. / Épidémiologie des calculs urinaires dans le Sud de la Tunisie.

Determine the epidemiological characteristics of urolithiasis in the South region of Tunisia and the impact of age and sex on stone composition. We conducted a retrospective study including patient records whose urinary lithiasis was analyzed within the biochemistry department of CHU Habib Bourguiba of Sfax (2011-2020). Stone analysis was performed using a stereomicroscope and infrared spectroscopy. A total of 1127 stones were analyzed. The sex ratio was 2,6. Renal Colic pain was the most common symptom (48,3%). The most frequent localization of the stones (84.6%) was the upper urinary tract. Whewellite was the most common component (64.1%). The study of stone component according to age showed a decrease in the frequency of weddellite (p = 0,024) and an increase in the frequency of uric acid stones with age (p < 0,001). Whewellite was more frequent in men (p = 0.022) and, notably in our series, uric acid was significantly more frequent in women (p < 0.001). The epidemiological profile of urolithiasis in south of Tunisia is similar to that observed in industrialized countries.

Oral supplementation with probiotics, potassium citrate, and magnesium in reducing crystalluria in stone formers: A phase II study.

INTRODUCTION: Crystalluria is an important indicator of renal stone recurrence. Mechanisms underlying urinary stone formation are still not fully understood and raising interests has been giving to intestinal commensal bacteria for their contribute in maintaining urinary solutes equilibrium. The aim of our phase II study was to examine the administration of potassium citrate, magnesium and probiotics in order to reduce crystalluria. MATERIALS AND METHODS: Since May 2021, we enrolled 23 patients candidates for ureterorenolithotripsy for calcium oxalate kidney stones with crystalluria and a normal metabolic profile. The analysis was validated by the Institution's Ethical Committee (no. approval STS CE Lazio 1/N-823). At discharge, patients were provided with daily food supplementation for 20 days of 1 billion Lactobacillus paracasei LPC09, 1 billion Lactobacillus plantarum LP01, 1 billion Bifidobacterium breve BR03, potassium (520 mg), citrate (1400 mg), and magnesium (80 mg). Crystalluria was re-assessed at 1, 3, 6, and 12-months follow-up by polarized light microscopy. RESULTS: After one month from the oral supplementation, no patient reported crystalluria; at 3 months, among the 20 participants available for re-evaluation, still no patient reported crystalluria. Instead, crystalluria was reported in three patients (15%) at 6 months, and in five patients (25%) at 12 months follow-up. CONCLUSIONS: The oral supplementation with Lactobacillus spp. and Bifidobacterium spp. was found able to reduce the prevalence of crystalluria in a cohort of patients with diagnosis of calcium oxalate kidney stones with crystalluria candidate to ureterorenolithotripsy.

The Evolving Role of Genetic Testing in Monogenic Kidney Stone Disease: Spotlight on Primary Hyperoxaluria.

PURPOSE: Multiple factors are thought to give rise to common, recurrent kidney stone disease, but for monogenic stone disorders a firm diagnosis is possible through genetic testing. The autosomal recessive primary hyperoxalurias (PH) are rare forms of monogenic kidney stone disease. All 3 types of PH are caused by inborn errors of glyoxylate metabolism in the liver, leading to hepatic oxalate overproduction and excessive renal urinary oxalate excretion. These conditions are characterized by kidney stones, nephrocalcinosis, progressive chronic kidney disease, and kidney failure. Systemic oxalosis, the extra-renal deposition of oxalate resulting in severe morbidity and mortality, occurs in chronic kidney disease when oxalate clearance by the kidneys declines. Novel small interfering RNA-based therapeutics targeting the liver to reduce urinary oxalate excretion have been approved, introducing precision medicine to treat primary hyperoxaluria type 1. The goal of this narrative review is to address the benefits and practicalities of genetic testing for suspected monogenic kidney stone disease and the critical roles of a multidisciplinary team. MATERIALS AND METHODS: We collated our procedures, education, training, and workflows to help other clinicians integrate genetic assessment into their diagnostic routines. RESULTS: In our experience, increased access to genetic testing facilitates early detection of PH and other monogenic causes of kidney stone disease so that individualized care can be instituted promptly. CONCLUSIONS: Alongside biochemical assessments, more widespread genetic testing may ensure more timely diagnoses so that patients with suspected monogenic kidney stone disease gain access to an expanded range of services and enrollment in clinical trials and registries.

Hair-straightening cosmetics containing glyoxylic acid induce crystalline nephropathy.

We recently reported the case of a patient who experienced three consecutive episodes of acute kidney injury, all of them following a "Brazilian" hair-straightening treatment. The cream used for the straightening procedure contained glyoxylic acid. To examine possible underlying mechanisms causing kidney injury, four groups of mice were exposed to topical application of (i) the straightening product, (ii) a cream containing 10% glyoxylic acid, (iii) a cream containing 10% glycolic acid or (iv) a control cream. Application of glycolic acid slightly increased urine oxalate excretion, while glyoxylic acid and the straightening product dramatically increased urine oxalate excretion and caused calcium oxalate nephropathy after transcutaneous absorption. Thus, glyoxylic acid was presumptively absorbed through the skin, metabolized to oxalate and promoted crystallization of calcium oxalate in urine. Hence, cosmetic products containing glyoxylic acid may induce acute kidney injury and should be discontinued. Further studies are needed to investigate the metabolism of glycolic acid and glyoxylic acid following topical application.

FGF21 relieves calcium oxalate-induced cell injury, apoptosis, oxidative damage and ferroptosis of renal tubular epithelial cells through activating Nrf2 signaling pathway.

Nephrolithiasis is a common urological disease accompanied by high morbidity worldwide. Evidences indicate that high-level CaOx crystals in the body can lead to renal tubular epithelial cell (RTEC) injury and RTEC injury is a critical precipitating factor for the formation of kidney stones. FGF21 has recently been revealed as the considerable marker in various kidney dysfunction and exerts the nephroprotective effects in various kidney diseases. This current study was formulated to fully elucidate the biological role of FGF21 in nephrolithiasis and probe into the intrinsic mechanisms underlying the protective effects of FGF21 against RTEC injury. In this work, HK-2 cells were incubated with 100 mg/ml COM for 24 h to establish in vitro RTEC injury model. COM-treated HK-2 cells were transfected with Oe-FGF21 to perform gain-of-function experiments. For rescue experiments, HK-2 cells were pretreated with 10 µM Nrf2 inhibitor ML385 for 24 h to thoroughly discuss the role of Nrf2 signaling in FGF21-mediating nephroprotective effects. It was verified that overexpression of FGF21 relieved COM-induced proliferation inhibition, cell injury, apoptosis, oxidative damage and ferroptosis of RTECs. ML385 treatment partially abolished the protective effects of FGF21 against COM injury in RTECs. In conclusion, up-regulation of FGF21 can relieve COM-induced proliferation inhibition, cell injury, apoptosis, oxidative damage and ferroptosis of RTECs through activating Nrf2 signaling pathway.