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Diabetes Mellitus Tipo 2 , Nefrolitiasis , Inhibidores del Cotransportador de Sodio-Glucosa 2 , Humanos , Inhibidores del Cotransportador de Sodio-Glucosa 2/efectos adversos , Inhibidores del Cotransportador de Sodio-Glucosa 2/uso terapéutico , Diabetes Mellitus Tipo 2/tratamiento farmacológico , Nefrolitiasis/inducido químicamente , Masculino , Femenino , Persona de Mediana Edad , Factores de Riesgo , AncianoAsunto(s)
Diabetes Mellitus Tipo 2 , Nefrolitiasis , Inhibidores del Cotransportador de Sodio-Glucosa 2 , Humanos , Inhibidores del Cotransportador de Sodio-Glucosa 2/efectos adversos , Inhibidores del Cotransportador de Sodio-Glucosa 2/uso terapéutico , Diabetes Mellitus Tipo 2/tratamiento farmacológico , Nefrolitiasis/inducido químicamente , Hipoglucemiantes/efectos adversos , Hipoglucemiantes/uso terapéuticoRESUMEN
BACKGROUND: Calcium oxalate monohydrate (COM) forms the most common type of kidney stones observed in clinics, elevated levels of urinary oxalate being the principal risk factor for such an etiology. The objective of the present study was to evaluate the anti-nephrolithiatic effect of herbo-mineral formulation, Lithom. METHODS: The in vitro biochemical synthesis of COM crystals in the presence of Lithom was performed and observations were made by microscopy and Scanning Electron Microscope (SEM) based analysis for the detection of crystal size and morphology. The phytochemical composition of Lithom was evaluated by Ultra-High-Performance Liquid Chromatography (UHPLC). The in vivo model of Ethylene glycol-induced hyperoxaluria in Sprague-Dawley rats was used for the evaluation of Lithom. The animals were randomly allocated to 5 different groups namely Normal control, Disease control (ethylene glycol (EG), 0.75%, 28 days), Allopurinol (50 mg/kg, q.d.), Lithom (43 mg/kg, b.i.d.), and Lithom (129 mg/kg, b.i.d.). Analysis of crystalluria, oxalate, and citrate levels, oxidative stress parameters (malondialdehyde (MDA), catalase, myeloperoxidase (MPO)), and histopathology by hematoxylin and eosin (H&E) and Von Kossa staining was performed for evaluation of Lithom. RESULTS: The presence of Lithom during COM crystals synthesis significantly reduced the average crystal area, feret's diameter, and area-perimeter ratio, in a dose-dependent manner. SEM analysis revealed that COM crystals synthesized in the presence of 100 and 300 µg/mL of Lithom exhibited a veritable morphological transition from irregular polygons with sharp edges to smoothened smaller cuboid polygons. UHPLC analysis of Lithom revealed the presence of Trigonelline, Bergenin, Xanthosine, Adenosine, Bohoervinone B, Vanillic acid, and Ellagic acid as key phytoconstituents. In EG-induced SD rats, the Lithom-treated group showed a decrease in elevated urinary oxalate levels, oxidative stress, and renal inflammation. Von Kossa staining of kidney tissue also exhibited a marked reduction in crystal depositions in Lithom-treated groups. CONCLUSION: Taken together, Lithom could be a potential clinical-therapeutic alternative for management of nephrolithiasis.
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Oxalato de Calcio , Modelos Animales de Enfermedad , Hiperoxaluria , Nefrolitiasis , Estrés Oxidativo , Ratas Sprague-Dawley , Animales , Oxalato de Calcio/metabolismo , Oxalato de Calcio/química , Hiperoxaluria/inducido químicamente , Hiperoxaluria/metabolismo , Estrés Oxidativo/efectos de los fármacos , Ratas , Nefrolitiasis/inducido químicamente , Nefrolitiasis/metabolismo , Nefrolitiasis/patología , Masculino , Cristalización , Glicol de Etileno/toxicidad , Extractos Vegetales/química , Extractos Vegetales/farmacología , Extractos Vegetales/uso terapéuticoRESUMEN
Urinary stones are a growing disease that results from pathological biomineralization. Cassia fistula Lin. is traditionally used to treat urinary stones. However, no scientific evidence is available to prove its antilithiatic effect. This study evaluates the antilithiatic potential of aqueous and ethanolic extract of Cassia fistula Lin. fruit (Cff) against calcium oxalate kidney stones. Forty-two male Wistar rats were divided into seven groups (n = 6/group): Group I (control), Group II (rats treated with ethylene glycol and ammonium chloride developed nephrolithiasis after 28 days), Group III (lithiatic rats receiving distilled water for 30 days), Group IV and V (lithiatic rats receiving aqueous extract of Cff at doses of 1 and 100 mg/kg body weight for 30 days, respectively) and Group VI and VII (lithiatic rats receiving ethanolic extract of Cff at doses of 1 and 100 mg/kg body weight for 30 days, respectively). Some parameters of urine and serum, and also renal oxidative stress and histopathology were used to determine the antilithiatic effect of aqueous and ethanolic extract of Cff. Therefore, the types of extracts of Cff improved abnormal levels of urine, serum, and renal oxidative stress and histopathology parameters. This antilithiatic effect of aqueous and ethanolic extracts of Cff, can be attributed to the anti-crystallization and antioxidant properties of the extracts and the ability to improve urine and serum biochemistry. RESEARCH HIGHLIGHTS: Ethylene glycol and ammonium chloride-induced urolithiasis, aggregation of calcium oxalate deposits, increase of some urinary and serum parameters, relative kidney weight, kidney size and MDA activity, decrease of some urinary parameters, relative body weight and SOD activity. Aqueous and ethanolic extracts of Cassia fistula Lin. lead to the treatment of urolithic rats by decreasing levels of urinary oxalate, phosphate, urea, serum urea, uric acid, creatinine, calcium, phosphate, MDA, kidney weight and kidney size, increasing levels of urinary calcium, creatinine, magnesium, citrate, body weight and SOD activity in the kidney, eliminating CaOx deposition (esp. ethanolic extract).
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Cassia , Glicol de Etileno , Frutas , Nefrolitiasis , Estrés Oxidativo , Extractos Vegetales , Ratas Wistar , Animales , Masculino , Extractos Vegetales/farmacología , Extractos Vegetales/química , Frutas/química , Ratas , Nefrolitiasis/inducido químicamente , Nefrolitiasis/tratamiento farmacológico , Cassia/química , Estrés Oxidativo/efectos de los fármacos , Riñón/efectos de los fármacos , Riñón/patología , Oxalato de Calcio , Modelos Animales de EnfermedadRESUMEN
ETHNOPHARMACOLOGICAL RELEVANCE: Calcium oxalate (CaOx) kidney stones are widely acknowledged as the most prevalent type of urinary stones, with high incidence and recurrence rates. Incarvillea diffusa Royle (ID) is a traditionally used medicinal herb in the Miao Minzu of Guizhou province, China, for treating urolithiasis. However, the active components and the underlying mechanism of its pharmacodynamic effects remain unclear. AIM OF THE STUDY: This study aimed to investigate the potential inhibitory effect of the active component of ID on the formation of CaOx nephrolithiasis and elucidate the underlying mechanism. MATERIALS AND METHODS: In vivo, a CaOx kidney stone model was induced in Sprague-Dawley (SD) rats using an ethylene glycol and ammonium chloride protocol for four weeks. Forty-eight male SD rats were randomly assigned to 6 groups (n = 8): blank group, model group, apocynin group, and low, medium, and high dose of ID's active component (IDW) groups. After three weeks of administration, rat urine, serum, and kidney tissues were collected. Renal tissue damage and crystallization, Ox, BUN, Ca2+, CRE, GSH, MDA, SOD contents, and levels of IL-1ß, IL-18, MCP-1, caspase-1, IL-6, and TNF-α in urine, serum, and kidney tissue were assessed using HE staining and relevant assay kits, respectively. Protein expression of Nrf2, HO-1, p38, p65, and Toll-4 in kidney tissues was quantified via Western blot. The antioxidant capacities of major compounds were evaluated through DPPH, O2·-, and ·OH radical scavenging assays, along with their effects on intracellular ROS production in CaOx-induced HK-2 cells. RESULTS: We found that IDW could significantly reduce the levels of CRE, GSH, MDA, Ox, and BUN, and enhancing SOD activity. Moreover, it could inhibit the secretion of TNF-α, IL-1ß, IL-18, MCP-1, caspase-1, and decreased protein expression of Nrf2, HO-1, p38, p65, and Toll-4 in renal tissue. Three major compounds isolated from IDW exhibited promising antioxidant activities and inhibited intracellular ROS production in CaOx-induced HK-2 cells. CONCLUSIONS: IDW facilitated the excretion of supersaturated Ca2+ and decreased the production of Ox, BUN in SD rat urine, and mitigated renal tissue damage by regulating Nrf2/HO-1 signaling pathway. Importantly, the three major compounds identified as active components of IDW contributed to the inhibition of CaOx nephrolithiasis formation. Overall, IDW holds significant potential for treating CaOx nephrolithiasis.
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Oxalato de Calcio , Nefrolitiasis , Ratas , Masculino , Animales , Oxalato de Calcio/orina , Especies Reactivas de Oxígeno/metabolismo , Interleucina-18/efectos adversos , Interleucina-18/metabolismo , Factor 2 Relacionado con NF-E2/metabolismo , Antioxidantes/efectos adversos , Ratas Sprague-Dawley , Factor de Necrosis Tumoral alfa/metabolismo , Nefrolitiasis/inducido químicamente , Nefrolitiasis/tratamiento farmacológico , Riñón/metabolismo , Superóxido Dismutasa/metabolismo , Caspasas/metabolismoRESUMEN
Importance: Type 2 diabetes (T2D) is associated with an increased risk of kidney stones. Sodium-glucose cotransporter 2 inhibitors (SGLT2is) might lower the risk of nephrolithiasis by altering urine composition. However, no studies have investigated the association between SGLT2i use and nephrolithiasis risk in patients receiving routine care in the US. Objective: To investigate the association between SGLT2i use and nephrolithiasis risk in clinical practice. Design, Setting, and Participants: This new-user, active comparator cohort study used data from commercially insured adults (aged ≥18 years) with T2D who initiated treatment with SGLT2is, glucagon-like peptide 1 receptor agonists (GLP-1RAs), or dipeptidyl peptidase 4 inhibitors (DPP4is) between April 1, 2013, and December 31, 2020. The data were analyzed from July 2021 through June 2023. Exposure: New initiation of an SGLT2i, GLP-1RA, or DPP4i. Main Outcomes and Measures: The primary outcome was nephrolithiasis diagnosed by International Classification of Diseases codes in the inpatient or outpatient setting. New SGLT2i users were 1:1 propensity score matched to new users of a GLP-1RA or DPP4i in pairwise comparisons. Incidence rates, rate differences (RDs), and estimated hazard ratios (HRs) with 95% CIs were calculated. Results: After 1:1 propensity score matching, a total of 716â¯406 adults with T2D (358â¯203 pairs) initiating an SGLT2i or a GLP-1RA (mean [SD] age, 61.4 [9.7] years for both groups; 51.4% vs 51.2% female; 48.6% vs 48.5% male) and 662â¯056 adults (331â¯028 pairs) initiating an SGLT2i or a DPP4i (mean [SD] age, 61.8 [9.3] vs 61.7 [10.1] years; 47.4% vs 47.3% female; 52.6% vs 52.7% male) were included. Over a median follow-up of 192 (IQR, 88-409) days, the risk of nephrolithiasis was lower in patients initiating an SGLT2i than among those initiating a GLP-1RA (14.9 vs 21.3 events per 1000 person-years; HR, 0.69 [95% CI, 0.67-0.72]; RD, -6.4 [95% CI, -7.1 to -5.7]) or a DPP4i (14.6 vs 19.9 events per 1000 person-years; HR, 0.74 [95% CI, 0.71-0.77]; RD, -5.3 [95% CI, -6.0 to -4.6]). The association between SGLT2i use and nephrolithiasis risk was similar by sex, race and ethnicity, history of chronic kidney disease, and obesity. The magnitude of the risk reduction with SGLT2i use was larger among adults aged younger than 70 years vs aged 70 years or older (HR, 0.85 [95% CI, 0.79-0.91]; RD, -3.46 [95% CI, -4.87 to -2.05] per 1000 person-years; P for interaction <.001). Conclusions and Relevance: These findings suggest that in adults with T2D, SGLT2i use may lower the risk of nephrolithiasis compared with GLP-1RAs or DPP4is and could help to inform decision-making when prescribing glucose-lowering agents for patients who may be at risk for developing nephrolithiasis.
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Diabetes Mellitus Tipo 2 , Inhibidores de la Dipeptidil-Peptidasa IV , Nefrolitiasis , Adulto , Humanos , Femenino , Masculino , Adolescente , Persona de Mediana Edad , Diabetes Mellitus Tipo 2/complicaciones , Diabetes Mellitus Tipo 2/tratamiento farmacológico , Estudios de Cohortes , Nefrolitiasis/inducido químicamente , Nefrolitiasis/epidemiología , Pacientes Internos , Inhibidores de la Dipeptidil-Peptidasa IV/efectos adversos , Glucosa , Sodio , Hipoglucemiantes , Receptor del Péptido 1 Similar al Glucagón , Estudios RetrospectivosRESUMEN
This study investigates the mechanism by which butyric acid can protect against calcium oxalate (CaOx) nephrolithiasis. To do so, a rat model was used with 0.75% ethylene glycol administration to induce CaOx crystal formation. Histological and von Kossa staining revealed calcium deposits and renal injury, while dihydroethidium fluorescence staining was used to detect reactive oxygen species (ROS) levels. Flow cytometry and TUNEL assays were used to assess apoptosis, respectively. Treatment with sodium butyrate (NaB) was found to partially reverse the oxidative stress, inflammation, and apoptosis associated with CaOx crystallization in the kidney. In addition, in HK-2 cells, NaB reversed the decreased cell viability, increased ROS levels and apoptosis damage caused by oxalate exposure. Network pharmacology was employed to predict the target genes of butyric acid, CYP2C9. Subsequently, NaB was found to significantly reduce CYP2C9 levels in vivo and in vitro, and inhibition of CYP2C9 by Sulfaphenazole (a specific CYP2C9 inhibitor), was able to reduce ROS levels, inflammation injury, and apoptosis in oxalate-induced HK-2 cells. Collectively, these findings suggest that butyric acid may inhibit oxidative stress and reduce inflammation injury in CaOx nephrolithiasis by suppressing CYP2C9.
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Oxalato de Calcio , Nefrolitiasis , Ratas , Animales , Oxalato de Calcio/química , Oxalato de Calcio/metabolismo , Ácido Butírico/metabolismo , Citocromo P-450 CYP2C9/metabolismo , Especies Reactivas de Oxígeno/metabolismo , Nefrolitiasis/inducido químicamente , Nefrolitiasis/tratamiento farmacológico , Nefrolitiasis/prevención & control , Riñón/metabolismo , Estrés OxidativoRESUMEN
Nephrolithiasis is highly prevalent and brings health and economic burdens to patients. The augmentation of nephrolithiasis may be associated with exposure to phthalate metabolites. However, few studies investigated the effect of various phthalates exposure on nephrolithiasis. We analyzed data from 7139 participants aged 20 years or above from the National Health and Nutrition Examination Survey (NHANES) 2007-2018. Serum calcium level-stratified univariate and multivariate linear regression analyses were performed to explore the relationship between urinary phthalate metabolites and nephrolithiasis. As a result, the prevalence of nephrolithiasis was approximately 9.96%. After adjusting for confounding factors, associations were found between serum calcium concentration with monoethyl phthalate (P = 0.012) and mono-isobutyl phthalate (P = 0.003) compared with tertile 1 (T1). In adjusted analysis, nephrolithiasis was positively associated with middle and high tertiles of mono benzyl phthalate (P < 0.05) compare with low tertile group. Furthermore, high-level exposure to mono-isobutyl phthalate had a similar positive association with nephrolithiasis (P = 0.028). Our findings provide evidence that exposure to certain phthalate metabolites (i.e. MiBP and MBzP) may be associated with a high risk of nephrolithiasis depending on serum calcium level.
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Contaminantes Ambientales , Nefrolitiasis , Ácidos Ftálicos , Adulto , Humanos , Exposición a Riesgos Ambientales/análisis , Encuestas Nutricionales , Contaminantes Ambientales/análisis , Estudios Transversales , Calcio/análisis , Ácidos Ftálicos/metabolismo , Nefrolitiasis/inducido químicamente , Nefrolitiasis/epidemiologíaRESUMEN
Drug-induced nephrolithiasis can arise from insoluble components within medications or crystallization of metabolites due to changes in metabolism and urinary pH. The connection between drugs utilized for iron chelation therapy (ICT) and nephrolithiasis is not well understood. In this report, we describe two pediatric patients diagnosed with nephrolithiasis while undergoing treatment with the chelating agents deferasirox, deferiprone, and deferoxamine for iron overload secondary to repeat blood transfusion.
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Sobrecarga de Hierro , Nefrolitiasis , Talasemia beta , Humanos , Niño , Terapia por Quelación/efectos adversos , Quelantes del Hierro/efectos adversos , Deferasirox/efectos adversos , Deferiprona/uso terapéutico , Deferoxamina/efectos adversos , Benzoatos/efectos adversos , Triazoles , Sobrecarga de Hierro/tratamiento farmacológico , Sobrecarga de Hierro/etiología , Nefrolitiasis/inducido químicamente , Nefrolitiasis/complicaciones , Nefrolitiasis/tratamiento farmacológico , Hierro/uso terapéutico , Talasemia beta/terapiaRESUMEN
The effect of carnosine on MMP-2 activity and oxidative stress in the kidneys in experimental urate nephrolithiasis was studied. Urate nephrolithiasis was modeled in Wistar rats by intragastric administration of a mixture of oxonic and uric acids. Carnosine was administered intragastrically through a tube in a dose of 15 mg/kg. In rats treated with carnosine, the concentration of MMP-2 in the urine decreased by 3.7 times, and the excretion of MMP-2 with urine decreased by 4.3 times. In the homogenate of the kidneys from rats treated with carnosine, the concentration of TBA-reactive substances decreased by 5 times and the concentration of MMP-2 decreased by 12.7%. After treatment with carnosine, the number of histologically confirmed cases of urate nephrolithiasis decreased by 2 times, while the mean size of urate deposits decreased by 2.7 times. Thus, carnosine inhibits MMP-2 and reduces the intensity of oxidative stress in the kidneys, which prevents the development of urate nephrolithiasis.
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Carnosina , Nefrolitiasis , Animales , Ratas , Carnosina/farmacología , Riñón , Metaloproteinasa 2 de la Matriz , Nefrolitiasis/inducido químicamente , Nefrolitiasis/tratamiento farmacológico , Nefrolitiasis/orina , Estrés Oxidativo , Ratas Wistar , Ácido ÚricoRESUMEN
We induced experimental nephrolithiasis in female rats using ethylene glycol (EG) and ammonium chloride (AC). We investigated the effects of carvacrol, an essential oil with antioxidant and anti-inflammatory properties, on nephrolithiasis using histopathology, immunohistochemistry and biochemistry. We used 40 female rats divided into four equal groups: control group, administered olive oil; carvacrol group, administered carvacrol in olive oil; nephrolithiasis group, administered EG and AC to induce experimental nephrolithiasis; treatment group with induced nephrolithiasis and administered carvacrol in olive oil. We observed no significant difference in crystal accumulation in the treatment group compared to the nephrolithiasis group. We found a significant reduction in hydropic degeneration of tubules and degree of inflammatory cell infiltration of intertubule areas. We also found a significant reduction in immunohistochemical staining of macrophage- and monocyte-specific antigens. Carvacrol treatment reversed the induced nephrolithiasis, increased malondialdehyde and urea, and decreased levels of glutathione peroxidase and catalase. Although carvacrol did not decrease crystal accumulation, it reduced pathological and biochemical damage, and improved kidney function by lowering the serum urea level.
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Nefrolitiasis , Femenino , Ratas , Animales , Aceite de Oliva/farmacología , Ratas Wistar , Nefrolitiasis/inducido químicamente , Nefrolitiasis/tratamiento farmacológico , Nefrolitiasis/patología , Antioxidantes/farmacología , Antioxidantes/metabolismo , Glicol de Etileno/efectos adversos , Urea/efectos adversos , Estrés Oxidativo , TimolRESUMEN
BACKGROUND: High prevalence and reoccurrence rate of nephrolithiasis bring about serious socioeconomic and healthcare burden, necessitating the need of effective therapeutic agents. Previous study revealed that gallic acid (GAL) alters the nucleation pathway of calcium oxalate (CaOx). On the other hand, it appears protective role against oxidative injury. Whether GAL could protect against crystal-induced lesion in vivo, and its underlying mechanism is yet unsolved. PURPOSE: This study aims to investigate the protective effects of GAL on the crystal-induced renal injury and its underlying mechanism in the mouse model of stone formation induced by glyoxylic acid. STUDY DESIGN AND METHODS: The mouse model of stone formation was established via successive intraperitoneal injection of glyoxylate. Proximal tubular epithelial cell line HK-2 treated with calcium oxalate monohydrate (COM) was used as in vitro model. The protective role of GAL on nephrolithiasis was tested by determination of tubular injury, crystal deposition and adhesion, levels of inflammatory cytokines, macrophage infiltration and the redox status of kidney. In vitro, effect of GAL on the ROS level and oxidative tubular injury induced by COM were detected, as well as major antioxidant pathway Nrf2/HO-1. RESULTS: Administration of GAL alleviates the renal deposition and adhesion of CaOx stone. Meanwhile, GAL ameliorates the inflammation and renal tubular injury. Level of intracellular ROS, osteopontin and CD44 are reduced, either in the mouse model of stone formation or in the COM-treated HK-2 cells after treatment of GAL. Mechanistically, GAL activates Nrf2/HO-1 pathway in HK-2 cells. Silencing Nrf2 abrogates the protective effect of GAL on the oxidative injury and adhesion of COM in HK-2 cells. CONCLUSION: Taken together, our study demonstrates the protective effect of GAL on the deposition of kidney stone and consequent tubular injury. Induction of the antioxidant pathway Nrf2/HO-1 was found to decrease the level of ROS and oxidative injury, thus implying that GAL could be a potential therapeutic agent for the treatment of nephrolithiasis.
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Oxalato de Calcio , Nefrolitiasis , Animales , Ratones , Antioxidantes/metabolismo , Oxalato de Calcio/metabolismo , Modelos Animales de Enfermedad , Ácido Gálico/farmacología , Glioxilatos , Riñón , Nefrolitiasis/inducido químicamente , Nefrolitiasis/tratamiento farmacológico , Factor 2 Relacionado con NF-E2/metabolismo , Osteopontina/metabolismo , Estrés Oxidativo , Especies Reactivas de Oxígeno/metabolismo , Regulación hacia ArribaRESUMEN
INTRODUCTION AND OBJECTIVE: To examine the dynamic changes in the formative factors of nephrolithiasis and the final micromorphological changes in an obesity-initiated metabolic syndrome (MS) rat model. METHODS: Forty five-week-old male Sprague-Dawley (SD) rats were randomly divided into four groups: the regular diet group (RD), high-fat diet group (HFD), regular diet with drug (ethylene glycol and ammonium chloride) group (RDD), and high-fat diet with drug group (HFDD). A dynamic assessment of MS components (body weight (BW), body length (BL), Lee's index (LI), blood glucose (BG), total cholesterol (TC), and triglycerides (TGs)) and stone-forming factors (urinary pH, urinary calcium, and urinary oxalate acid) was carried out. In addition, the levels of oxidative stress (OS) markers (CAT, SOD, TAC, GSH-PX, and MDA) were measured, and histological analysis was carried out at the end of 16 weeks. RESULTS: MS-related parameters, such as BW, LI, BG, TC, and TG, were significantly higher in HFD-fed rats than in RD-fed rats (p < 0.001). In the HFDD group, significantly lower urinary pH, hyperoxaluria, and hypocalciuria were noted in the dynamic assessment of stone-forming factors (p < 0.001). CAT, TAC, and MDA were notably changed in the HFD-fed groups, particularly the HFDD rats. Histological analysis showed that the renal tubules of HFDD rats had the highest scores for both inflammation and renal crystallization deposition (p < 0.05). CONCLUSIONS: Our results suggest that male SD rats with MS are prone to developing nephrolithiasis. Validation in an in vivo model may lead to an understanding of the underlying pathophysiological mechanisms of action of MS-related nephrolithiasis in humans.Key messagesMale SD rats with metabolic syndrome are more prone to developing calcium oxalate nephrolithiasis after treatment with ethylene glycol and ammonium chloride compared to control lean rats.MS-related nephrolithiasis in rats induced by ethylene glycol and ammonium chloride is mainly related to increased hyperoxaluria and inflammation and decreased antioxidant levels.High-fat diet-fed SD rats treated with ethylene glycol and ammonium chloride are a stable and valid in vivo model for understanding the potential mechanism of action of MS-related nephrolithiasis.
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Hiperoxaluria , Cálculos Renales , Síndrome Metabólico , Nefrolitiasis , Cloruro de Amonio/efectos adversos , Animales , Glicol de Etileno/efectos adversos , Humanos , Hiperoxaluria/complicaciones , Inflamación , Cálculos Renales/etiología , Masculino , Síndrome Metabólico/complicaciones , Nefrolitiasis/inducido químicamente , Ratas , Ratas Sprague-DawleyRESUMEN
In hypoparathyroidism (HypoPT), calcium supplementation is virtually always required, although the disease is likely to be associated with an increased risk of nephrolithiasis. The use of calcium citrate (Ca-Cit) theoretically could have a positive impact on the nephrolithiasis risk because citrate salts are used to reduce this risk. Our objective was to evaluate the potential therapeutic advantage of Ca-Cit in comparison with calcium carbonate (CaCO3 ) in HypoPT, on nephrolithiasis risk factors, as well as to their ability to maintain desirable serum calcium levels. We also evaluated these preparations on quality of life (QOL). This randomized, double-blind, crossover trial recruited 24 adults with postsurgical chronic hypoparathyroidism at Campus Bio-Medico University of Rome. Participants were randomized 1:1 to Ca-Cit or CaCO3 for 1 month and then crossed over to the other treatment for another month. The primary outcomes were changes in albumin-adjusted serum calcium and in ion activity product of calcium oxalate levels (AP[CaOx] index). Secondary efficacy outcomes included changes in SF-36 survey score, fatigue score, constipation, and adverse events. No difference in terms of AP(CaOx) index was observed between the two groups. However, Ca-Cit was associated with a significant reduction in the oxalate/creatinine ratio compared with CaCO3 (-2.46 mmol/mol [SD 11.93] versus 7.42 mmol/mol [SD 17.63], p = 0.029). Serum calcium and phosphorus concentration was not different between the two calcium preparations. Ca-Cit was associated with less constipation (p = 0.047). No difference was found in QOL scores. Although Ca-Cit did not modify the AP(CaOx) index when compared with CaCO3, it was associated with a reduction in urinary oxalate excretion that could have a potential beneficial effect on nephrolithiasis risk. These results are likely to have clinical implications in HypoPT, particularly those who do not tolerate CaCO3 and those affected by nephrolithiasis. A longer-term experience is needed to confirm these findings. © 2022 The Authors. Journal of Bone and Mineral Research published by Wiley Periodicals LLC on behalf of American Society for Bone and Mineral Research (ASBMR).
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Hipoparatiroidismo , Nefrolitiasis , Adulto , Calcio , Carbonato de Calcio/uso terapéutico , Citrato de Calcio/uso terapéutico , Oxalato de Calcio/orina , Calcio de la Dieta , Estreñimiento/inducido químicamente , Estudios Cruzados , Humanos , Hipoparatiroidismo/inducido químicamente , Hipoparatiroidismo/tratamiento farmacológico , Nefrolitiasis/inducido químicamente , Oxalatos/orina , Calidad de VidaRESUMEN
BACKGROUND/OBJECTIVES: Routine use of vitamin D supplements has increased substantially in the United States. However, the safety and tolerability of long-term use of high-dose vitamin D are not known. We assessed the safety and tolerability of high-dose, daily vitamin D3 in the vitamin D and type 2 diabetes (D2d) study. SUBJECTS/METHODS: In total, 2423 overweight/obese persons with prediabetes were randomized in a double-blind manner to either 4000 IU of vitamin D3 (the tolerable upper intake level for adults by the National Academy of Medicine) taken daily or matching placebo. All participants were included in this analysis. Incident adverse events (AE) were ascertained 4 times a year at in-person visits (twice a year) and interim remote encounters (twice a year) and were defined as untoward or unfavorable medical occurrences. Serious adverse events (SAE) included death, life-threatening events, and hospitalizations. RESULTS: A total of 8304 AEs occurred during 3 years of follow-up and were less frequent in the vitamin D group compared to placebo (Incidence Rate Ratio [IRR] = 0.94; 95% Confidence Interval (CI) 0.90, 0.98). The overall frequency of protocol-specified AEs of interest, which included nephrolithiasis, hypercalcemia, hypercalciuria, or low estimated glomerular filtration rate, was low and did not differ by group. There were no significant between-group differences in total SAEs (IRR = 0.96 (0.81, 1.14)). CONCLUSION: Vitamin D3 supplementation at 4000 IU per day was safe and well tolerated among overweight/obese participants at high risk for diabetes who were appropriately monitored for safety. In this population, this dose of vitamin D3 did not increase risk of AEs or SAEs, including those previously associated with vitamin D such as hypercalcemia, hypercalciuria, or nephrolithiasis. CLINICAL TRIAL REGISTRATION: ClinicalTrials.gov NCT01942694, prospectively registered September 16, 2013.
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Diabetes Mellitus Tipo 2 , Hipercalcemia , Nefrolitiasis , Estado Prediabético , Adulto , Colecalciferol , Diabetes Mellitus Tipo 2/tratamiento farmacológico , Suplementos Dietéticos/efectos adversos , Método Doble Ciego , Humanos , Hipercalcemia/inducido químicamente , Hipercalcemia/tratamiento farmacológico , Hipercalcemia/epidemiología , Hipercalciuria/inducido químicamente , Hipercalciuria/tratamiento farmacológico , Nefrolitiasis/inducido químicamente , Nefrolitiasis/tratamiento farmacológico , Obesidad/tratamiento farmacológico , Sobrepeso/complicaciones , Sobrepeso/tratamiento farmacológico , Estado Prediabético/tratamiento farmacológico , Vitamina D , VitaminasRESUMEN
Hydroxycitrate (HCA) is a derivative of citric acid, and previous studies of HCA have revealed its ability to inhibit the formation of calcium oxalate crystals in vitro. To date, there has been little evidence proving that HCA has the same effectiveness in vivo. The present study was designed to investigate the ameliorating effect of HCA on calcium oxalate deposition and renal impairment in a male rat model. Male Sprague-Dawley rats were randomly divided into four groups: a control group, a model group (glyoxalic acid), a CA group (glyoxalic acid + CA), and an HCA group (glyoxalic acid + HCA). Kidney stone formation was induced by injection of glyoxalic acid (60 mg/kg). The results showed that serum and urinary parameters were significantly improved by HCA treatment. In addition, differences in the formation of calcium oxalate crystals between groups were observed, and HCA was superior to CA in inhibiting crystal accumulation. The ultrastructure of renal tubules and glomeruli occurred in the model group, and the above lesions were significantly reduced in the HCA group. Both OPN and SOD expression levels were promoted by HCA, while CA only promoted OPN. In this article, we provided data on whether HCA affected kidney stones and the expression levels of OPN and SOD in a male rat model.
Asunto(s)
Cálculos Renales , Nefrolitiasis , Animales , Oxalato de Calcio , Citratos , Cristalización , Riñón , Masculino , Nefrolitiasis/inducido químicamente , Nefrolitiasis/prevención & control , Ratas , Ratas Sprague-DawleyRESUMEN
Exposure to heavy metals in the environment exerts serious effects on kidney health. However, the effects of joint exposure on the kidneys have been rarely studied, particularly in non-occupational exposure high-risk populations. This study provided a reference threshold range of heavy metals in urine and explored the effect of joint exposure on nephrolithiasis in men. The data were obtained from the China Multi-Ethnic Cohort database, and 1502 men were included in the study. A two-piece-wise regression model was used to assess the dose-response relationship between heavy metal exposure and nephrolithiasis. The least absolute shrinkage and selection operator regression model was used to calculate the score of joint exposure to heavy metals. The threshold effect analysis revealed a linear relationship between the concentration of arsenic (As) in the urine and the prevalence of nephrolithiasis, whereas a nonlinear relationship was observed with cadmium (Cd), chromium (Cr), mercury (Hg), and lead (Pb). In addition, As, Cd, Cr, Hg, and Pb may significantly affect the joint exposure effect. Moreover, the final risk of nephrolithiasis increased by 123% (P for trend < 0.001). This study found a threshold relationship between heavy metals (Cd, Cr, Hg, Pb) in male urine and the occurrence of nephrolithiasis. Joint exposure to heavy metals in urine caused a high-risk effect on nephrolithiasis. The study provided a reference threshold value of related studies and indicated that environmental pollution caused by heavy metals should be reduced.
Asunto(s)
Arsénico , Mercurio , Metales Pesados , Nefrolitiasis , Arsénico/análisis , China/epidemiología , Monitoreo del Ambiente , Humanos , Masculino , Mercurio/toxicidad , Metales Pesados/análisis , Metales Pesados/toxicidad , Nefrolitiasis/inducido químicamente , Nefrolitiasis/epidemiología , Prevalencia , Medición de RiesgoRESUMEN
AIM: Nephrolithiasis is a chronic metabolic condition affecting 10% of population worldwide. The present study aimed to investigate the possible protective role of candesartan (CAND) and sodium thiosulfate (STS) in ameliorating ethylene glycol (EG) induced nephrolithiasis. METHODS: One hundred male Wistar rats were divided into five groups: Normal control group, nephrolithiasis (EG) group (1% EG in drinking water), Cystone (CYS) group (EG + 750 mg/kg CYS, orally, once daily), STS group (EG + 0.4 gm/kg STS, intraperitoneally, 3 times/week) and CAND group (EG + 70 µg/mL CAND in drinking water). Treatments and EG administration commenced on the same day and continued for 28 days. CYS was used as reference drug. Urine, blood, and renal tissues were collected at the end of the experiment for assessment of kidney function tests (serum creatinine and urea), urinary (8-hydroxydeoxyguanosine (8-OHdG), calcium and oxalate), inflammatory and oxdative stress biomarkers (transforming growth factor beta (TGF-ß), osteopontin (OPN) and ratio of reduced glutathione to oxidized glutathione (GSH/GSSG)) in renal tissue. RESULTS: Serum (creatinine and urea), urinary (8-OHdG and oxalate) and renal (OPN and TGF-ß) were significantly reduced in CAND and STS groups compared to EG group. Furthermore, renal GSH/GSSG and urinary calcium were significantly increased in CAND and STS groups compared to EG group. Histopathological results support the biochemical findings; CAND and STS groups showed less retention of crystals and necrotic damage in kidney. Also, microscopic examination of urine revealed less crystal for CAND and STS groups. CONCLUSION: Candesartan and sodium thiosulfate exhibited protective effect against nephrolithiasis.
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Bencimidazoles/uso terapéutico , Compuestos de Bifenilo/uso terapéutico , Nefrolitiasis/tratamiento farmacológico , Sustancias Protectoras/uso terapéutico , Tetrazoles/uso terapéutico , Tiosulfatos/uso terapéutico , Animales , Glicol de Etileno , Riñón/efectos de los fármacos , Riñón/patología , Masculino , Nefrolitiasis/inducido químicamente , Nefrolitiasis/patología , Ratas WistarRESUMEN
Evaluation of the effects of methanolic extract of Cucumis melo in ethylene glycol-induced nephrolithiasis on Wistar rats. 0.75% solution of ethylene glycol (EG) in payable water was given to produce nephrolithiasis on Wistar rats. The action of oral intake of methanolic extract of Cucumis melo seed in nephrolithiasis is studied and is matched with the action of oral intake of Cystone (standard) on Wistar rats. EG resulted in hyperoxaluria and deposition of calcium oxalate as well as raised urinary excretion of oxalate and calcium. Supplementation with methanolic extract of Cucumis melo seed decreased the increased renal oxalate, indicating a regulatory effect on oxalate formation endogenously. The outcomes stipulate that the seed of Cucumis melo is endowed with antinephrolithiatic action.
Asunto(s)
Cucumis melo , Nefrolitiasis/tratamiento farmacológico , Fitoterapia , Extractos Vegetales/uso terapéutico , Animales , Glicol de Etileno/administración & dosificación , Metanol , Nefrolitiasis/inducido químicamente , Ratas , Ratas WistarRESUMEN
Background: Calcium oxalate stones are the most common cause of nephrolithiasis in the United States. Smaller studies of <15 patients investigating ezetimibe, a selective cholesterol absorption inhibitor, have suggested increased urine oxalate levels with use of the drug. We attempt to better define this relationship of ezetimibe on urinary oxalate using a larger patient sample analysing multiple urine collections on and off treatment. Materials and Methods: We retrospectively reviewed all consecutive patients from 01/2018 through 04/2019 evaluated for nephrolithiasis with use of ezetimibe documented in their medical record at Mayo Clinic Florida. Primary outcomes included increase in urinary oxalate with use of ezetimibe and reduction in urinary oxalate with discontinuation of medication. Results: Of 57 reviewed patients, 30 (53%) met inclusion criteria yielding 117 24-h urine measurements either on ezetimibe (72 measurements) or off ezetimibe (41 measurements). The mean urinary oxalate level off ezetimibe was 39.86 mg versus 40.45 mg with ezetimibe. After adjusting for age and sex, the estimated difference was 1.239 mg (95% CI, -4.856 to 7.335 mg; p = 0.93). A subset of six patients with urinary oxalate values both on and off ezetimibe showed a difference in 24-h urinary oxalate levels ranged from -16.40 to 14.95 mg (mean difference = 0.93 mg; median difference = 3.84 mg). Conclusion: Use of ezetimibe does not provide clear evidence of a difference in urinary oxalate levels.