Calcium Oxalate Crystal Deposition Research Articles

NEAT1 Regulates Calcium Oxalate Crystal-Induced Renal Tubular Oxidative Injury via miR-130/IRF1.

Aims: Calcium oxalate (CaOx) crystal deposition induces damage to the renal tubular epithelium, increases epithelial adhesion, and contributes to CaOx nephrocalcinosis. The long noncoding RNA (lncRNA) nuclear paraspeckle assembly transcript 1 (NEAT1) is thought to be involved in this process. In this study, we aimed to investigate the mechanism by which NEAT1 regulates renal tubular epithelium in response to inflammatory and oxidative injury triggered by CaOx crystals. Results: As CaOx crystals were deposited in mouse kidney tissue, the expression of NEAT1 was significantly elevated and positively correlated with interferon regulatory factor 1 (IRF1), Toll-like receptor 4 (TLR4), and NF-κB. NEAT1 targets and inhibits miR-130a-3p as a competitor to endogenous RNA. miR-130 binds to and exerts inhibitory effects on the 3'-untranslated region of IRF1. After transfected with silence-NEAT1, IRF1, TLR4, and NF-κB were also variously inhibited, and oxidative damage in renal calcinosis was subsequently attenuated. When we simultaneously inhibited NEAT1 and miR-130, renal tubular injury was exacerbated. Innovation and Conclusion: We found that the lncRNA NEAT1 can enhance IRF1 signaling through targeted repression of miR-130a-3p and activate TLR4/NF-κB pathways to promote oxidative damage during CaOx crystal deposition. This provides an explanation for the tubular epithelial damage caused by CaOx crystals and offers new ideas and drug targets for the prevention and treatment of CaOx nephrocalcinosis. Antioxid. Redox Signal. 38, 731-746.

Cucumis callosus (Rottl.) Cogn. fruit extract ameliorates calcium oxalate urolithiasis in ethylene glycol induced hyperoxaluric Rat model

Cucumis callosus dry fruits are traditionally used as folk remedy to treat conditions like urethral irritations, urine stoppage or dribbling and other urinary ailments of man in north-west India. But no study is reported to validate this ethnic practice of using Cucumis fruit in urolithiasis. To evaluate anti-urolithiatic potential of Cucumis, hyperoxaluria was induced in rats by supplying 0.75% ethylene glycol (EG) + 1% ammonium chloride (AC) in drinking water for 14 days. Anti-urolithiatic activity of Cucumis callosus hydro-ethanolic extract (CCHEE) was assessed by measuring blood and urine biochemical parameters, oxidative stress indices, histopathology and osteopontin (OPN) expression. Administration of EG-AC to rats caused hyperoxaluria, crystalluria, azotaemia, oxidant/antioxidant imbalance (increase in lipid peroxidation (LPO), and decrease in glutathione (GSH) and catalase (CAT)), up-regulation of OPN and calcium oxalate (CaOx) crystal deposition in kidney. Treatment of afflicted rats with Cucumis fruits extract restored renal function to a great extent (CCHEE group), testified by improvement of stated parameters. Findings demonstrate curative efficacy of Cucumis fruit extract in EG induced urolithiasis of rats. The restoration of renal function was possibly by regulating renal stone formation via reducing urinary oxalate excretion, correcting oxidant/antioxidant imbalances, and reduced expression of OPN. Hence, results of this study validate the ethnic practice of using Cucumis fruit and conclude that fruit extracts have beneficial effects on CaOx urolithiasis and renal function.

Meta-data analysis of kidney stone disease highlights ATP1A1 involvement in renal crystal formation

Nephrolithiasis is a complicated disease affected by various environmental and genetic factors. Crystal-cell adhesion is a critical initiation process during kidney stone formation. However, genes regulated by environmental and genetic factors in this process remain unclear. In the present study, we integrated the gene expression profile data and the whole-exome sequencing data of patients with calcium stones, and found that ATP1A1 might be a key susceptibility gene involved in calcium stone formation. The study showed that the T-allele of rs11540947 in the 5′-untranslated region of ATP1A1 was associated with a higher risk of nephrolithiasis and lower activity of a promoter of ATP1A1. Calcium oxalate crystal deposition decreased ATP1A1 expression in vitro and in vivo and was accompanied by the activation of the ATP1A1/Src/ROS/p38/JNK/NF-κB signaling pathway. However, the overexpression of ATP1A1 or treatment with pNaKtide, a specific inhibitor of the ATP1A1/Src complex, inhibited the ATP1A1/Src signal system and alleviated oxidative stress, inflammatory responses, apoptosis, crystal-cell adhesion, and stone formation. Moreover, the DNA methyltransferase inhibitor 5-aza-2′-deoxycytidine reversed ATP1A1 down-regulation induced by crystal deposition. In conclusion, this is the first study to show that ATP1A1, a gene modulated by environmental factors and genetic variations, plays an important role in renal crystal formation, suggesting that ATP1A1 may be a potential therapeutic target for treating calcium stones.

Oxalate Nephropathy.

Oxalate Nephropathy.

Hyperoside Ameliorates Renal Tubular Oxidative Damage and Calcium Oxalate Deposition in Rats through AMPK/Nrf2 Signaling Axis.

Nephrolithiasis is a common disease that seriously affects the health and life quality of patients. Despite the reported effect of hyperoside (Hyp) against nephrolithiasis, the specific mechanism has not been clarified. Therefore, this study is aimed at investigating the effect and potential mechanism of Hyp on renal injury and calcium oxalate (CaOx) crystal deposition. Rat and cell models of renal calculi were constructed by ethylene glycol (EG) and CaOx induction, respectively. The renal histopathological damage, CaOx crystal deposition, and renal function damage of rats were assessed by HE staining, Pizzolato staining, and biochemical detection of blood and urine parameters. MTT and crystal-cell adhesion assays were utilized to determine the activity of HK-2 cells and crystal adhesion ability, biochemical detection and enzyme-linked immunosorbent assay (ELISA) to measure the levels of oxidative stress-related substances and inflammatory factors, and western blot to test the expression levels of proteins related to the AMPK/Nrf2 signaling pathway. Briefly speaking, Hyp could improve the renal histopathological injury and impaired renal function, reduce the deposition of CaOx crystals in the renal tissue of rats with renal calculi, and decrease the adhesion of crystals to CaOx-treated HK-2 cells. Besides, Hyp also significantly inhibited oxidative stress response. Furthermore, Hyp was associated with the downregulation of malondialdehyde, lactate dehydrogenase, and reactive oxygen species and upregulation of superoxide dismutase activity. Additionally, Hyp treatment also suppressed inflammatory response and had a correlation with declined levels of interleukin (IL)-1β, IL-6, IL-8, and tumor necrosis factor. Further exploration of mechanism manifested that Hyp might play a protective role through promoting AMPK phosphorylation and nuclear translation of Nrf2 to activate the AMPK/Nrf2 signaling pathway. Hyp can improve renal pathological and functional damage, decrease CaOx crystal deposition, and inhibit oxidative stress and inflammatory response. Such effects may be achieved by activating the AMPK/Nrf2 signaling pathway.

Cerium oxide-based nanozyme suppresses kidney calcium oxalate crystal depositions via reversing hyperoxaluria-induced oxidative stress damage

Oxidative stress damage to renal epithelial cells is the main pathological factor of calcium oxalate calculi formation. The development of medicine that could alleviate oxidative damage has become the key to the prevention and treatment of urolithiasis. Herein, porous nanorods CeO2 nanoparticles (CNPs) were selected from CeO2 with different morphologies as an antioxidant reagent to suppress kidney calcium oxalate crystal depositions with excellent oxidation resistance due to its larger specific surface area. The reversible transformation from Ce3+ to Ce4+ could catalyze the decomposition of excess free radicals and act as a biological antioxidant enzyme basing on its strong ability to scavenge free radicals. The protection capability of CNPS against oxalate-induced damage and the effect of CNPS on calcium oxalate crystallization were studied. CNPS could effectively reduce reactive oxygen species production, restore mitochondrial membrane potential polarity, recover cell cycle progression, reduce cell death, and inhibit the formation of calcium oxalate crystals on the cell surface in vitro. The results of high-throughput sequencing of mRNA showed that CNPs could protect renal epithelial cells from oxidative stress damage caused by high oxalate by suppressing the expression gene of cell surface adhesion proteins. In addition, CNPS can significantly reduce the pathological damage of renal tubules and inhibit the deposition of calcium oxalate crystals in rat kidneys while having no significant side effect on other organs and physiological indicators in vivo. Our results provide a new strategy for CNPS as a potential for clinical prevention of crystalline kidney injury and crystal deposition.

The Number of Calcium Oxalate Deposits Significantly Correlate with Elevated Serum Creatinine Levels in Calcium Oxalate Nephropathy

Abstract Introduction/Objective Calcium oxalate nephropathy is defined as acute and/or chronic decrease in renal function due to deposition of calcium oxalate crystals in renal tubules leading to acute tubular injury, acute or chronic interstitial nephritis, and elevated serum creatinine levels. However, the correlation between serum creatinine (SCr) levels and the number of calcium oxalate deposits has not been well described in the literature. Methods/Case Report Eight controls with mild to moderate acute tubular injury and 10 cases with calcium oxalate nephropathy (calcium group) were selected for the study. The patient’s SCr values were obtained from electronic medical records and the number of polarizable calcium oxalate crystal deposits in the lumen of proximal tubules seen on Hematoxylin & Eosin stained slides at 40x high power field were recorded for each biopsy. Umpired student T-test was used to compare the two groups. Linear regression analysis was used to correlate SCr and the number of calcium oxalate deposits. Results (if a Case Study enter NA) Mean ages were not significantly different between two groups (49 ± 8 years in controls and 64 ± 6 years in calcium group). SCr was significantly higher in the calcium group (5.97 ± 0.68 mg/dl*) than in the control group (2.59 ± 0.37 mg/dl). No calcium oxalate deposits were seen in any of the controls, but the number of calcium oxalate deposits ranged from 3 to 7 in the calcium group (Table 1). In our study, we found a significant linear correlation between SCr and the number of crystals/high power field, when all cases were taken together (r value = 0.783, p value = 0.0002*). Conclusion Our data suggest that there is a direct association between the number of calcium oxalate crystals in proximal tubules with the severity of renal dysfunction. Although the etiologies for calcium oxalate nephropathy can be multifactorial, counting the deposit number on renal biopsies is simple method to predict SCr levels.

Chronic liver disease and hepatic calcium-oxalate deposition in patients with primary hyperoxaluria type I

Patients with primary hyperoxaluria type I (PH I) are prone to develop early kidney failure. Systemic deposition of calcium-oxalate (CaOx) crystals starts, when renal function declines and plasma oxalate increases. All tissue, but especially bone, heart and eyes are affected. However, liver involvement, as CaOx deposition or chronic hepatitis/fibrosis has never been reported. We examined liver specimen from 19 PH I patients (aged 1.5 to 52 years at sample collection), obtained by diagnostic biopsy (1), at autopsy (1), or transplantation (17). With polarization microscopy, birefringent CaOx crystals located in small arteries, but not within hepatocytes were found in 3/19 patients. Cirrhosis was seen in one, fibrosis in 10/19 patients, with porto-portal and nodular fibrosis (n = 1), with limitation to the portal field in 8 and/or to central areas in 5 patients. Unspecific hepatitis features were observed in 7 patients. Fiber proliferations were detectable in 10 cases and in one sample transformed Ito-cells (myofibroblasts) were found. Iron deposition, but also megakaryocytes as sign of extramedullary erythropoiesis were found in 9, or 3 patients, respectively. Overall, liver involvement in patients with PH I was more pronounced, as previously described. However, CaOx deposition was negligible in liver, although the oxalate concentration there must be highest.

Acute oxalate nephropathy: A potential cause of acute kidney injury in diabetes mellitus-A case series from a single center.

BackgroundAcute oxalate nephropathy (AON) is an uncommon condition that causes acute kidney injury (AKI), characterized by the massive deposition of calcium oxalate crystals in the renal parenchyma. In previous studies, urinary oxalate excretion has been found to be increased in patients with diabetes mellitus (DM). Here, we report a case series of diabetic patients with AKI with biopsy-proven AON, aiming to alert physicians to the potential of AON as a trigger of AKI in diabetic patients in clinical practice.Materials and methodsCases with pathological diagnosis of AON who presented with AKI clinically and had DM between January 2016 and December 2020 were retrospectively enrolled. Their clinical and pathological manifestations, treatment, and prognosis were collected.ResultsSix male patients with biopsy-proven AON out of a total of 5,883 native kidney biopsies were identified, aged 58.3 ± 9.1 years at the time of kidney biopsy. Only one patient who had received Roux-en-Y gastric bypass surgery took oxalate-rich food before the onset of the disease. None of them had clinical features of enteric malabsorption. Three patients were currently on renin-angiotensin system inhibitor treatment for hypertension, and 5 of them received non-steroidal anti-inflammatory drugs. Three patients presented with oliguria and 4 patients needed dialysis at the beginning with none requiring dialysis at discharge. Four patients received a course of corticosteroid treatment empirically. Among them, two patients had estimated glomerular filtration rate (eGFR) recovered to over 60 ml/min/1.73 m2, while the other two patients remained with kidney dysfunction at the last follow-up. In two patients without corticosteroid treatment, one patient fully recovered with eGFR over 90 ml/min/1.73 m2 and the other patient remained with kidney dysfunction at the last follow-up.ConclusionAON might be a rare but potentially trigger of AKI in patients with DM. A kidney biopsy could help physicians to make the correct diagnosis. The proper treatment to alleviate oxalate-induced injury needs to be further studied.

Small-molecule inhibitor of intestinal anion exchanger SLC26A3 for treatment of hyperoxaluria and nephrolithiasis.

Nephrolithiasis is a common and recurrent disease affecting 9% of the US population. Hyperoxaluria is major risk factor for calcium oxalate kidney stones, which constitute two-thirds of all kidney stones. SLC26A3 (DRA, downregulated in adenoma) is an anion exchanger of chloride, bicarbonate, and oxalate thought to facilitate intestinal oxalate absorption, as evidenced by approximately 70% reduced urine oxalate excretion in knockout mice. We previously identified a small-molecule SLC26A3 inhibitor (DRAinh-A270) that selectively inhibited SLC26A3-mediated chloride/bicarbonate exchange (IC50 ~ 35 nM) and, as found here, oxalate/chloride exchange (IC50 ~ 60 nM). In colonic closed loops in mice, luminal DRAinh-A270 inhibited oxalate absorption by 70%. Following oral sodium oxalate loading in mice, DRAinh-A270 largely prevented the 2.5-fold increase in urine oxalate/creatinine ratio. In a mouse model of oxalate nephropathy produced by a high-oxalate low-calcium diet, vehicle-treated mice developed marked hyperoxaluria with elevated serum creatinine, renal calcium oxalate crystal deposition, and renal injury, which were largely prevented by DRAinh-A270 (10 mg/kg twice daily). DRAinh-A270 administered over 7 days to healthy mice did not show significant toxicity. Our findings support a major role of SLC26A3 in intestinal oxalate absorption and suggest the therapeutic utility of SLC26A3 inhibition for treatment of hyperoxaluria and prevention of calcium oxalate nephrolithiasis.

Primary Hyperoxaluria Type 1: A great masquerader

Primary hyperoxaluria (PH) Types I, II, and III is an autosomal recessive inherited disorder of defect in glyoxylate metabolism due to specific hepatic enzyme deficiencies causing renal damage due to deposition of oxalate crystals that induce renal epithelial cell injury, and inflammation resulting in reduced renal oxalate elimination leading to extra renal deposition of calcium oxalate crystals. PH is under diagnosed because of phenotypic heterogeneity masquerading as infantile nephrocalcinosis (NC) with or without renal failure or renal calculus disease in adults. We present three children with genetically proven PH1 seen over last 2 years along with a brief review of the literature. In this series all cases were female. Two girls had infantile onset of symptoms and one presented in childhood. Renal failure in all with varying sonography features including small size kidneys, multiple renal calculi, bulky kidneys with loss of corticomedullary differentiation were seen. Extrarenal affection was seen in one child. Renal replacement therapy was provided in all. Awareness of PH and early diagnosis by measurement of plasma and urinary oxalate and molecular characterization helps in prompt aggressive therapy, preventing extrarenal manifestations and plan long term management.

Novel Starting Points for Human Glycolate Oxidase Inhibitors, Revealed by Crystallography-Based Fragment Screening

Primary hyperoxaluria type I (PH1) is caused by AGXT gene mutations that decrease the functional activity of alanine:glyoxylate aminotransferase. A build-up of the enzyme’s substrate, glyoxylate, results in excessive deposition of calcium oxalate crystals in the renal tract, leading to debilitating renal failure. Oxidation of glycolate by glycolate oxidase (or hydroxy acid oxidase 1, HAO1) is a major cellular source of glyoxylate, and siRNA studies have shown phenotypic rescue of PH1 by the knockdown of HAO1, representing a promising inhibitor target. Here, we report the discovery and optimization of six low-molecular-weight fragments, identified by crystallography-based fragment screening, that bind to two different sites on the HAO1 structure: at the active site and an allosteric pocket above the active site. The active site fragments expand known scaffolds for substrate-mimetic inhibitors to include more chemically attractive molecules. The allosteric fragments represent the first report of non-orthosteric inhibition of any hydroxy acid oxidase and hold significant promise for improving inhibitor selectivity. The fragment hits were verified to bind and inhibit HAO1 in solution by fluorescence-based activity assay and surface plasmon resonance. Further optimization cycle by crystallography and biophysical assays have generated two hit compounds of micromolar (44 and 158 µM) potency that do not compete with the substrate and provide attractive starting points for the development of potent and selective HAO1 inhibitors.

MO096: Chronic Liver Disease and Hepatic Calcium-Oxalate Deposition in Patients with Primary Hyperoxaluria Type I

Abstract BACKGROUND AND AIMS Patients with primary hyperoxaluria type I (PH I) are prone to develop early end-stage kidney failure (ESKF). Systemic deposition of calcium-oxalate (CaOx) crystals starts when renal function declines and plasma oxalate (Pox) increases >30 µmol/L. It is anticipated that all parenchymal organs, but also bone (marrow), retina and the central nervous system can be involved. However, liver involvement, either as CaOx deposition or as chronic hepatitis/fibrosis, was never reported. METHOD We now examined liver involvement in 19 patients with PH I aged 1.5–52 years. Liver specimen was obtained by biopsy for diagnostic purposes (1), at autopsy (1) or at the time of combined or sequential liver kidney transplantation (17). RESULTS With polarization microscopy, crystals with the typical star-like appearance of CaOx were found in 3/19 patients. The crystals were located in small arteries but not within hepatocytes. Cirrhosis was seen in one patient. Fibrosis was seen in 10/19 patients, with porto-portal and nodular fibrosis (n = 1), and a limitation of fibrosis to the portal field in eight and/or to central areas in five patients. Unspecific hepatitis features were observed in seven patients. Fiber proliferations were detectable in 10 cases, and in one sample, transformed Ito-cells (myofibroblasts) were found. Iron deposition but also megakaryocytes as a sign of extramedullary erythropoiesis were found in nine and three patients, respectively. CONCLUSION Overall, liver involvement in patients with PH I was more pronounced, as previously described. However, compared with CaOx deposition in other organs/tissue, such crystal accumulations were only minimal in the liver, although the oxalate concentration must be the highest.

Protective effects of interleukin-22 on oxalate-induced crystalline renal injury via alleviating mitochondrial damage and inflammatory response.

Oxalate-induced crystalline kidney injury is one of the most common types of crystalline nephropathy. Unfortunately, there is no effective treatment to reduce the deposition of calcium oxalate crystals and alleviate kidney damage. Thus, proactive therapeutic is urgently needed to alleviate the suffering it causes to patient. Here, we investigated whether IL-22 exerted nephroprotective effects to sodium oxalate-mediated kidney damage and its potential mechanism. Crystalline kidney injury models were developed in vitro and in vivo that was often observed in clinic. We provided evidence that IL-22 could effectively decrease the accumulation of ROS and mitochondrial damage in cell and animal models and reduce the death of TECs. Moreover, IL-22 decreased the expression of the NLRP3 inflammasome and mature IL-1β in renal tissue induced by sodium oxalate. Further studies confirmed that IL-22 could play an anti-inflammatory role by reducing the levels of cytokines such as IL-1β, IL-18, and TNF-α in serum. In conclusion, our study confirmed that IL-22 has protective effects on sodium oxalate-induced crystalline kidney injury by reducing the production of ROS, protecting mitochondrial membrane potential, and inhibiting the inflammatory response. Therefore, IL-22 may play a potential preventive role in sodium oxalate-induced acute renal injury. KEY POINTS: • IL-22 could reduce sodium oxalate-mediated cytotoxicity and ameliorate renal injury. • IL-22 could alleviate oxidative stress and mitochondrial dysfunction induced by sodium oxalate. • IL-22 could inhibit inflammatory response of renal injury caused by sodium oxalate.

Insights into the cytoprotective potential of Bergenia ligulata against oxalate-induced oxidative stress and epithelial-mesenchymal transition (EMT) via TGFβ1/p38MAPK pathway in human renal epithelial cells.

Oxalate exposure to human renal epithelial cells triggers a vicious cycle of oxidative stress leading to cellular injury and deposition of calcium oxalate crystals on the injured cells. This results in further oxidative damage causing inflammation and loss of cell-cell adhesion factors, ultimately leading to irreparable kidney damage. However, these events can be attenuated or prevented by plants rich in antioxidants used in the traditional system of medicine for treatment of kidney stones. To delineate the mechanism by which Bergenia ligulata extract exerts its cytoprotective role in oxalate-induced injury we designed this study. Our results revealed that oxalate-injured HK2 cells cotreated with ethanolic extract of Bergenia ligulata displayed increased viability, reduced oxidative stress due to lowered production of intracellular reactive oxygen species (ROS) and decreased apoptosis. We also observed lowered markers of inflammation, along with increased expression of epithelial marker E-cadherin and decreased expression of mesenchymal markers Vimentin, F-actin, Transforming growth factor beta 1 (TGF-β1) and EMT-related proteins in renal tubular epithelial cells through immunocytochemistry, real-time PCR and western blotting. Our findings collectively suggest that by reducing oxidative stress, modulating crystal structure and preventing crystal-cell adhesion, B. ligulata inhibits the EMT pathway by downregulating the various mediators and thereby exerts its cytoprotective effect.

Speckle tracking echocardiography (STE) in patients with primary hyperoxularia type 1 (PH1)

Abstract Funding Acknowledgements Type of funding sources: None. Introduction Primary Hyperoxaluria type 1 (PH1) is a rare, inherited metabolic disorder of glyoxylate metabolism characterized by oxalate overproduction, leading to end-stage kidney disease (ESKD) in more than half of all patients. As renal function deteriorates the ability of the kidneys to excrete the excess of oxalate is increasingly compromised resulting in elevated concentrations of oxalate in the blood and progressive systemic deposition of calcium-oxalate crystals in virtually all tissues, a situation referred to as systemic oxalosis. A wide spectrum of cardiac abnormalities are reported in PH1 patients, including presymptomatic myocardial disease early in the disease course. We aimed to further determine cardiac manifestations in a heterogenous cohort of PH1 patients by conventional and speckle tracking echocardiography (STE). Methods Data from 38 genetically confirmed PH1 patients were included in this two-centre study and compared to age- and sex-matched controls. Comprehensive echocardiographic analysis (including STE) was performed. PH1 patients were subdivided in three groups based on stage of chronic kidney disease (CKD) and transplantation status (CKD1-4 (n = 24), CKD5 (n = 7) and post-liver transplantation (n = 7)). Results Left-ventricle ejection fraction (LV EF) was preserved in all subjects. PH1 patients had a decreased global longitudinal strain compared to healthy controls, with a mean difference of -2.28 (p < 0.001). In patients with CKD1-4 decreased LS values were solely found in all apical segments, with a mean difference of -5.3 (p < 0.001) as compared to healthy controls. In patients whom already progressed to end-stage kidney disease (ESKD, defined as CKD5) diastolic dysfunction is noted, with preserved systolic function. Conclusion Pre-symptomatic myocardial dysfunction is present in PH1 patients with mild renal impairment and relatively normal plasma oxalate values. This indicates that cardiac screening is warranted in all PH1 patients, irrespective of renal function.

A0915 - High concentration oxalate promotes intrarenal calcium oxalate crystals deposition via altering macrophage M1 polarization with change of the IRF-1/miR-301/CSF-1 signals

A0915 - High concentration oxalate promotes intrarenal calcium oxalate crystals deposition via altering macrophage M1 polarization with change of the IRF-1/miR-301/CSF-1 signals

Combined effect of polyacrylic acid and vitamin E in preventing calcium oxalate crystal deposition in the kidneys of experimental hyperoxaluric rats

Our study explores the combined effect of polyacrylic acid and vitamin E as prophylactic and curative agent against ethylene glycol (EG) induced calcium oxalate stone formation in Wistar rats. Male Wistar rats (54) were divided into nine groups, including control. The experimental groups were equally segregated into two for preventive study (4) and curative study (4). Urolithiasis was induced with 0.75% (v/v) EG in drinking water. Polyacrylic acid (10 mg/kg) and vitamin E (300 IU/day) were supplemented from day 1 for preventive and day 30 for curative studies. Restoration of urinary lithogenic factors (calcium, oxalate, phosphate, citrate and magnesium) and renal function (urea and creatinine in serum) by intervening agents were accomplished compared to urolithic rats (P < .001). Abnormal localization and increased expression of Tamm-Horsfall Protein, osteopontin and transferrin were observed in the kidneys of urolithic rats (P < .001) from immunohistochemistry and immunoblotting analysis. Polyacrylic acid and vitamin E supplementation have regulated the expression of the urinary macromolecules. Pro-inflammatory cytokines in kidney were significantly reduced (P < .001) by the intervening agents compared to urolithic rats. Therefore, polyacrylic acid and vitamin E in combination could be a potential formulation for better management of urolithiasis.

Primary hyperoxaluria diagnosed after kidney transplantation: a case report and literature review

BackgroundPrimary hyperoxaluria (PH) is a rare inherited autosomal recessive disease caused by disturbed glyoxylate metabolism. The disease is characterized by calcium oxalate crystal deposition in various organs, especially in the kidney. Due to the lack of current understanding of PH, nearly all patients are only initially diagnosed with PH when recurrent lithiasis and progressive end-stage renal disease occur. Many cases are not diagnosed in patients until renal allograft insufficiency occurs after renal transplantation. This case report and literature review aim to emphasize the need for careful pre-transplant PH screening of patients with bilateral nephrocalcinosis or nephrolithiasis.Case presentationRenal allograft insufficiency was diagnosed as PH after kidney transplantation. Here, we detail the complete clinical course, including computed tomography images of the original kidney and renal graft, histopathological images of a biopsy of the transplanted kidney, the results of laboratory and molecular genetic tests, and the treatment. In addition, we reviewed the literature from 2000 to 2021 and analyzed 19 reported cases of PH diagnosed after kidney transplantation, and provide a summary of the characteristics, complications, treatment, and prognosis of these cases.ConclusionsBy reviewing and analyzing these cases, we concluded that patients with a history of nephrocalcinosis or nephrolithiasis in both kidneys need preoperative screening for PH and appropriate treatment before kidney transplantation. Delayed graft function caused by PH is easily misdiagnosed as acute rejection, and needle biopsy should be performed at an early stage.

MicroRNA-204 attenuates oxidative stress damage of renal tubular epithelial cells in calcium oxalate kidney-stone formation via MUC4-mediated ERK signaling pathway.

Oxalate-induced oxidative stress causes damage to cells, accompanied with renal deposition of calcium oxalate crystals. Recent studies have highlighted the extensive functions of microRNAs (miRNAs) in various processes, including cellular responses to oxidative stress. Hence, this study was intended to analyze the role of miR-204 in the calcium oxalate kidney-stone formation and the underlying mechanism. In silico analysis was performed to determine the miRNA/mRNA interaction involved in calculus, while dual-luciferase reporter assay was conducted for validation. A calcium oxalate kidney-stone model was established by H2O2 induction in RTEC HK-2 cells, in which the expression of miR-204 was examined. Gain- and loss-of-function approaches were employed to alter the expression of miR-204/MUC4 so as to assess the detailed role of miR-204 in oxidative stress injury in renal tubular epithelial cells (RTECs) and calcium oxalate kidney-stone formation. MUC4, an up-regulated gene in H2O2-induced HK-2 cells, was a target of MUC4. miR-204 functionally targeted MUC4 and blocked the ERK pathway activation. Furthermore, up-regulated miR-204 contributed to promotion of RTEC proliferation and suppression of ROS levels, RTEC apoptosis as well as formation of calcium oxalate crystal. Taken together, miR-204 impairs MUC4-dependent activation of the ERK signaling pathway and consequently ameliorates oxidative stress damage to RTECs and prevents calcium oxalate kidney-stone formation.