RESUMO
Oxalate-induced damage to renal tubular epithelial cells (RTECs) is an essential factor in the incident kidney stone, but the specific mechanism is unclear. Recent research has pinpointed interacting areas within the endoplasmic reticulum and mitochondria, called mitochondria-associated membranes (MAMs). These studies have linked endoplasmic reticulum stress (ERS) and oxidative imbalance to kidney disease development. The sigma-1 receptor (S1R), a specific protein found in MAMs, is involved in various physiological processes, but its role in oxalate-induced kidney stone formation remains unclear. In this study, we established cellular and rat models of oxalate-induced kidney stone formation to elucidate the S1R's effects against ERS and apoptosis and its mechanism in oxalate-induced RTEC injury. We found that oxalate downregulated S1R expression in RTECs and escalated oxidative stress and ERS, culminating in increased apoptosis. The S1R agonist dimemorfan up-regulated S1R expression and mitigated ERS and oxidative stress, thereby reducing apoptosis. This protective effect was mediated through S1R inhibition of the CHOP pathway. Animal experiments demonstrated that S1R's activation attenuated oxalate-induced kidney injury and alleviated kidney stone formation. This is the first study to establish the connection between S1R and kidney stones, suggesting S1R's protective role in inhibiting ERS-mediated apoptosis to ameliorate kidney stone formation.
Assuntos
Apoptose , Estresse do Retículo Endoplasmático , Retículo Endoplasmático , Células Epiteliais , Túbulos Renais , Mitocôndrias , Nefrolitíase , Receptores sigma , Receptor Sigma-1 , Receptores sigma/metabolismo , Animais , Estresse do Retículo Endoplasmático/efeitos dos fármacos , Apoptose/efeitos dos fármacos , Ratos , Células Epiteliais/metabolismo , Células Epiteliais/efeitos dos fármacos , Túbulos Renais/metabolismo , Túbulos Renais/patologia , Nefrolitíase/metabolismo , Mitocôndrias/metabolismo , Mitocôndrias/efeitos dos fármacos , Retículo Endoplasmático/metabolismo , Retículo Endoplasmático/efeitos dos fármacos , Masculino , Estresse Oxidativo/efeitos dos fármacos , Ratos Sprague-DawleyRESUMO
This study aimed to examine the association between calcific rotator cuff tendinopathy (RCT) and nephrolithiasis and/or cholelithiasis. A case-control study was conducted on patients diagnosed with RCT between June 2016 and June 2022. RCT was confirmed by ultrasound, and patients were divided into 2 groups: calcific RCT (case) and non-calcific RCT (control). Data were collected retrospectively from electronic medical records and completed by phone calls, looking for a history of nephrolithiasis and/or cholelithiasis; based on clinical features or incidental findings on abdominal and pelvic imaging. A total of 210 patients with RCT were included. Among the 95 cases of calcific RCT, 43 had a history of lithiasis (45.3%) against 23 (20%) from the non-calcific RCT group (Pâ <â .001); 21 patients suffered from nephrolithiasis (22.1%) and 26 had cholelithiasis (27.4%) versus 10 (8.7%) (Pâ =â .006) and 16 (13.9%) (Pâ =â .015) in the non-calcific RCT group, respectively. Logistic regression showed that the independent predictors of calcific RCT included a history of nephrolithiasis (OR, 4.38; 95% CI: 1.61-11.92, Pâ =â .004) and a history of cholelithiasis (OR, 3.83; 95% CI: 1.64-8.94, Pâ =â .002). In patients with calcific RCT, the occurrence of lithiasis was significantly associated in the bivariate analysis with higher age, body mass index, fasting blood sugar, and HbA1c (all with Pâ <â .05), but only with the presence of another site of calcific tendinopathy than the shoulder (OR, 3.11; 95% CI: 1.12-8.65, Pâ =â .03) in the multivariate analysis. Nephrolithiasis and/or cholelithiasis are associated with calcific RCT, and their presence predicts calcific RCT at least 3 times. Further research is required to determine the common risk factors and preventive measures against lithogenesis in patients with calcific RCT, nephrolithiasis, and cholelithiasis.
Assuntos
Calcinose , Colelitíase , Nefrolitíase , Tendinopatia , Humanos , Feminino , Masculino , Pessoa de Meia-Idade , Colelitíase/complicações , Colelitíase/epidemiologia , Tendinopatia/epidemiologia , Tendinopatia/diagnóstico por imagem , Tendinopatia/etiologia , Tendinopatia/complicações , Estudos de Casos e Controles , Nefrolitíase/epidemiologia , Nefrolitíase/etiologia , Nefrolitíase/complicações , Estudos Retrospectivos , Calcinose/diagnóstico por imagem , Calcinose/complicações , Calcinose/epidemiologia , Manguito Rotador/diagnóstico por imagem , Manguito Rotador/patologia , Adulto , Idoso , Fatores de Risco , UltrassonografiaRESUMO
OBJECTIVE: The clinical characteristics, genetic mutation spectrum, treatment strategies and prognoses of 15 children with Dent disease were retrospectively analyzed to improve pediatricians' awareness of and attention to this disease. METHODS: We analyzed the clinical and laboratory data of 15 Chinese children with Dent disease who were diagnosed and treated at our hospital between January 2017 and May 2023 and evaluated the expression of the CLCN5 and OCRL1 genes. RESULTS: All 15 patients were male and complained of proteinuria, and the incidence of low-molecular-weight proteinuria (LMWP) was 100.0% in both Dent disease 1 (DD1) and Dent disease 2 (DD2) patients. The incidence of hypercalciuria was 58.3% (7/12) and 66.7% (2/3) in DD1 and DD2 patients, respectively. Nephrocalcinosis and nephrolithiasis were found in 16.7% (2/12) and 8.3% (1/12) of DD1 patients, respectively. Renal biopsy revealed focal segmental glomerulosclerosis (FSGS) in 1 patient, minimal change lesion in 5 patients, and small focal acute tubular injury in 1 patient. A total of 11 mutations in the CLCN5 gene were detected, including 3 missense mutations (25.0%, c.1756C > T, c.1166T > G, and c.1618G > A), 5 frameshift mutations (41.7%, c.407delT, c.1702_c.1703insC, c.137delC, c.665_666delGGinsC, and c.2200delG), and 3 nonsense mutations (25.0%, c.776G > A, c.1609C > T, and c.1152G > A). There was no significant difference in age or clinical phenotype among patients with different mutation types (p > 0.05). All three mutations in the OCRL1 gene were missense mutations (c.1477C > T, c.952C > T, and c.198A > G). CONCLUSION: Pediatric Dent disease is often misdiagnosed. Protein electrophoresis and genetic testing can help to provide an early and correct diagnosis.
Assuntos
Canais de Cloreto , Doença de Dent , Monoéster Fosfórico Hidrolases , Humanos , Masculino , Criança , Canais de Cloreto/genética , Estudos Retrospectivos , Pré-Escolar , China/epidemiologia , Doença de Dent/genética , Doença de Dent/diagnóstico , Monoéster Fosfórico Hidrolases/genética , Mutação , Proteinúria/genética , Adolescente , Hipercalciúria/genética , Nefrocalcinose/genética , Nefrolitíase/genética , Lactente , Testes Genéticos , Doenças Genéticas Ligadas ao Cromossomo X/genética , Doenças Genéticas Ligadas ao Cromossomo X/diagnóstico , Mutação de Sentido Incorreto , Feminino , Glomerulosclerose Segmentar e Focal/genética , Rim/patologia , População do Leste AsiáticoRESUMO
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.
Assuntos
Oxalato de Cálcio , Modelos Animais de Doenças , Hiperoxalúria , Nefrolitíase , Estresse Oxidativo , Ratos Sprague-Dawley , Animais , Oxalato de Cálcio/metabolismo , Oxalato de Cálcio/química , Hiperoxalúria/induzido quimicamente , Hiperoxalúria/metabolismo , Estresse Oxidativo/efeitos dos fármacos , Ratos , Nefrolitíase/induzido quimicamente , Nefrolitíase/metabolismo , Nefrolitíase/patologia , Masculino , Cristalização , Etilenoglicol/toxicidade , Extratos Vegetais/química , Extratos Vegetais/farmacologia , Extratos Vegetais/uso terapêuticoRESUMO
Sarcoidosis is a systemic inflammatory disorder characterized by granuloma formation in various organs. It has been associated with nephrolithiasis. The vitamin K epoxide reductase complex subunit 1 (VKORC1) gene, which plays a crucial role in vitamin K metabolism, has been implicated in the activation of proteins associated with calcification, including in the forming of nephrolithiasis. This study aimed to investigate the VKORC1 C1173T polymorphism (rs9934438) in a Dutch sarcoidosis cohort, comparing individuals with and without a history of nephrolithiasis. Retrospectively, 424 patients with sarcoidosis were divided into three groups: those with a history of nephrolithiasis (Group I: n = 23), those with hypercalcemia without nephrolithiasis (Group II: n = 38), and those without nephrolithiasis or hypercalcemia (Group III: n = 363). Of the 424 sarcoidosis patients studied, 5.4% had a history of nephrolithiasis (Group I), only two of whom possessed no VKORC1 polymorphisms (OR = 7.73; 95% CI 1.79-33.4; p = 0.001). The presence of a VKORC1 C1173T variant allele was found to be a substantial risk factor for the development of nephrolithiasis in sarcoidosis patients. This study provides novel insights into the genetic basis of nephrolithiasis in sarcoidosis patients, identifying VKORC1 C1173T as a potential contributor. Further research is warranted to elucidate the precise mechanisms and explore potential therapeutic interventions based on these genetic findings.
Assuntos
Nefrolitíase , Polimorfismo de Nucleotídeo Único , Sarcoidose , Vitamina K Epóxido Redutases , Humanos , Feminino , Vitamina K Epóxido Redutases/genética , Masculino , Sarcoidose/genética , Sarcoidose/complicações , Pessoa de Meia-Idade , Nefrolitíase/genética , Fatores de Risco , Adulto , Predisposição Genética para Doença , Estudos Retrospectivos , Idoso , AlelosRESUMO
Purpose: Population-based and registry studies have shown that chronic hypoparathyroidism is accompanied by long-term complications. We aimed to evaluate the risk of incident comorbidity among patients with chronic postsurgical hypoparathyroidism in real-life clinical practice in Spain. Methods: We performed a multicenter, retrospective cohort study including patients with chronic postsurgical hypoparathyroidism lasting ≥3 years with at least a follow-up visit between January 1, 2022 and September 15, 2023 (group H). The prevalence and incidence of chronic complications including chronic kidney disease, nephrolithiasis/nephrocalcinosis, hypertension, dyslipidemia, diabetes, cardiovascular disease, central nervous system disease, mental health disorders, eye disorders, bone mineral density alterations, fracture and cancer were evaluated. Patient data were compared with a group of patients who did not develop hypoparathyroidism, matched by gender, age, and follow-up time after thyroidectomy (group NH). Results: We included 337 patients in group H (median [IQR] age, 45 [36-56] years; median time of follow-up, 8.9 [6.0-13.0] years; women, 84.3%) and 669 in group NH (median age, 47 [37-55] years; median time of follow-up, 8.0 [5.3-12.0] years; women, 84.9%). No significant differences were found in the prevalence of comorbidities at the time of thyroidectomy between both groups. In multivariable adjusted analysis, patients with chronic hypoparathyroidism had significantly higher risk of incident chronic kidney disease (OR, 3.45; 95% CI, 1.72-6.91; P<0.001), nephrolithiasis (OR, 3.34; 95% CI, 1.55-7.22; P=0.002), and cardiovascular disease (OR, 2.03; 95% CI, 1.14-3.60; P=0.016), compared with patients without hypoparathyroidism. On the contrary, the risk of fracture was decreased in patients with hypoparathyroidism (OR, 0.09; 95% CI, 0.01-0.70; P=0.021). Conclusion: This study demonstrates that, in the clinical practice of Spanish endocrinologists, a significant increase in the risk of chronic kidney disease, nephrolithiasis and cardiovascular disease, as well as a reduction in the risk of fractures is detected. These results are of interest for the development of new clinical guidelines and monitoring protocols for patients with hypoparathyroidism.
Assuntos
Doenças Cardiovasculares , Fraturas Ósseas , Hipoparatireoidismo , Nefrolitíase , Insuficiência Renal Crônica , Feminino , Humanos , Pessoa de Meia-Idade , Doenças Cardiovasculares/etiologia , Comorbidade , Fraturas Ósseas/etiologia , Hipoparatireoidismo/etiologia , Hipoparatireoidismo/complicações , Nefrolitíase/complicações , Insuficiência Renal Crônica/etiologia , Insuficiência Renal Crônica/complicações , Estudos Retrospectivos , Tireoidectomia/efeitos adversos , Masculino , AdultoRESUMO
BACKGROUND: We aimed to investigate the prevalence, characteristics, and management of nephrolithiasis in primary hyperparathyroidism (PHPT) patients. METHODS: Medical records of patients who underwent parathyroidectomy at a tertiary care hospital in British Columbia from January 2016 to April 2023 were retrospectively reviewed. Demographic data, laboratory results, imaging reports, and urologic consultations were examined. Descriptive statistics and relevant statistical tests, including logistic regressions, were utilized for data analysis. RESULT: Of the 413 PHPT patients included in the study population, 41.9% harbored renal stones, and nearly half (48.6%) required urological interventions. Male sex, elevated preoperative serum ionized calcium (iCa) and 24-h urinary calcium (24 âh urine Ca) levels were independent risk factors for stone formation. Additionally, male sex, younger age, and lower preoperative serum 25-hydroxyvitamin D (25(OH)D) level were associated with higher odds of requiring urological intervention for stones. CONCLUSIONS: This study identified significant prevalence of asymptomatic renal calcifications in PHPT patients, with a substantial proportion necessitating urological intervention. These findings emphasize the importance of incorporating screening and treatment of renal stones into the management of PHPT patients.
Assuntos
Hiperparatireoidismo Primário , Nefrolitíase , Humanos , Masculino , Cálcio , Hiperparatireoidismo Primário/complicações , Hiperparatireoidismo Primário/cirurgia , Estudos Retrospectivos , Nefrolitíase/complicações , Nefrolitíase/diagnóstico , Nefrolitíase/epidemiologia , Colúmbia Britânica , Paratireoidectomia/efeitos adversos , Hormônio ParatireóideoRESUMO
OBJECTIVE: To prospectively capture patient-reported outcomes to assess the recovery profile of ureteroscopy (URS). MATERIALS AND METHODS: Adults undergoing URS for renal/ureteral stones were eligible for inclusion (11/2020-8/2022). Patients prospectively completed PROMIS - Pain Intensity, - Pain Interference, and - Ability to participate in social roles and activities in-person preoperatively (POD 0) and via email on POD 1, 7, 14, and 30. Scores are reported as T-scores (normalized to U.S. population, mean=50) with a change of 5 (0.5 SD) considered clinically significant. RESULTS: One hundred and seventy-eight participants enrolled at POD 0 (POD 1 =87, POD 7 =83, POD 14 =70, POD30 =67). There was a worsening of quality of life from day 0 to day 1 and day 0 to 7. All dimensions then improved with an increase in scores from day 0 to day 14 and day 0 to day 30. On multivariable analysis, the presence of a preoperative ureteral stent (OR 0.14) and use of semirigid URS (OR 0.33) were associated with a reduced odds for severe pain interference at day 1. The use of semirigid URS (OR 0.20) was associated with a reduced odds for severe worsening in the ability to participate in social roles at day 1. CONCLUSION: Ability to participate in social roles declines immediately postoperatively, while pain intensity and interference sharply increase. There is a gradual improvement until POD 30. Findings suggest preoperative stents may influence postoperative recovery. Results offer meaningful insight to assist in counseling and setting expectation for patients postoperatively.
Assuntos
Medidas de Resultados Relatados pelo Paciente , Qualidade de Vida , Ureteroscopia , Humanos , Masculino , Feminino , Pessoa de Meia-Idade , Estudos Prospectivos , Dor Pós-Operatória/etiologia , Dor Pós-Operatória/psicologia , Dor Pós-Operatória/diagnóstico , Medição da Dor , Adulto , Participação Social , Idoso , Cálculos Renais/cirurgia , Cálculos Ureterais/cirurgia , Nefrolitíase/cirurgia , Recuperação de Função FisiológicaRESUMO
PURPOSE: Calcium-sensing receptor (CASR) influences the expression pattern of multiple genes in renal tubular epithelial cells. The objective of this inquiry was to explore the molecular mechanisms of CASR in renal tubular epithelial cells and nephrolithiasis. METHODS: HK-2 cells were transfected with lentiviruses carrying either CASR (named CASR) or an empty vector negative control (named NC), as well as shRNA intended to target CASR (named shCASR) or its corresponding negative control (named shNC). CCK-8 assay was used to detect the effect of CASR on the proliferation of HK-2 cells. RNA-Sequencing was applied to explore potential pathways regulated by CASR in HK-2 cells. RESULTS: PCR and western blot results showed that CASR expression was significantly increased in CASR cells and was decreased in shCASR cells when compared to their corresponding negative control, respectively. CCK-8 assay revealed that CASR inhibited the proliferation of HK-2 cells. RNA-Sequencing results suggested that the shCASR HK-2 cells exhibited a significant up-regulation of 345 genes and a down-regulation of 366 genes. These differentially expressed genes (DEGs) were related to cell apoptosis and cell development. In CASR HK-2 cells, 1103 DEGs primarily functioned in mitochondrial energy metabolism, and amino acid metabolism. With the Venn diagram, 4 DEGs (Clorf116, ENPP3, IL20RB, and CLDN2) were selected as the hub genes regulated by CASR. Enrichment analysis revealed that these hub genes were involved in cell-cell junction, and epithelial cell development. CONCLUSIONS: In summary, our investigation has the potential to offer novel perspectives on CASR regulating cell-cell junction in HK-2 cells.
Assuntos
Células Epiteliais , Túbulos Renais , Receptores de Detecção de Cálcio , Receptores de Detecção de Cálcio/genética , Receptores de Detecção de Cálcio/metabolismo , Humanos , Células Epiteliais/metabolismo , Túbulos Renais/citologia , Túbulos Renais/metabolismo , Junções Intercelulares/metabolismo , Células Cultivadas , Proliferação de Células , Nefrolitíase/genética , Nefrolitíase/metabolismo , Regulação da Expressão Gênica , Linhagem CelularRESUMO
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).
Assuntos
Cassia , Etilenoglicol , Frutas , Nefrolitíase , Estresse Oxidativo , Extratos Vegetais , Ratos Wistar , Animais , Masculino , Extratos Vegetais/farmacologia , Extratos Vegetais/química , Frutas/química , Ratos , Nefrolitíase/induzido quimicamente , Nefrolitíase/tratamento farmacológico , Cassia/química , Estresse Oxidativo/efeitos dos fármacos , Rim/efeitos dos fármacos , Rim/patologia , Oxalato de Cálcio , Modelos Animais de DoençasRESUMO
The compound "ADE" is an injectable oil for veterinary use which contains large amounts of vitamins A, D and E. The parenteral application in humans leads to a granuloma reaction which triggers hypercalcemia. A 42-year-old man was admitted with lower limb pain, nephrolithiasis and nephrocalcinosis. Laboratory tests revealed creatinine 4.59 mg/dl, calcium 13.3 mg/dl and parathormone 13.8 pg/ml. He underwent an ureterolithotripsy, stent placement, intravenous crystalloid fluids, and corticosteroid. He improved symptoms, kidney function and normalized serum calcium. The "ADE"-induced hypercalcemia diagnosis can be challenging. The early diagnosis may avoid negative outcomes.
O composto "ADE'' é um óleo veterinário injetável que contém grandes quantidades de vitaminas A, D e E. A aplicação parenteral causa reação granulomatosa e hipercalcemia. Um homem de 42 anos foi admitido com dor no membro inferior, nódulos musculares endurecidos, nefrolitíase e nefrocalcinose. O laboratório revelou creatinina 4,59 mg/dl, cálcio 13,3 mg/dl e paratormônio 13,8 pg/ml. Foi tratado com ureterolitotripsia, cateter duplo-J, cristaloide intravenoso e corticoterapia. Ele apresentou melhora dos sintomas, função renal e normalizou cálcio. O diagnóstico da hipercalcemia pelo "ADE'' pode ser desafiador. O diagnóstico precoce pode evitar desfechos negativos.
Assuntos
Humanos , Masculino , Adulto , Injúria Renal Aguda , Hipercalcemia , Nefrolitíase , NefrocalcinoseRESUMO
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.
Assuntos
Oxalato de Cálcio , Nefrolitíase , Ratos , Masculino , Animais , Oxalato de Cálcio/urina , Espécies Reativas de Oxigênio/metabolismo , Interleucina-18/efeitos adversos , Interleucina-18/metabolismo , Fator 2 Relacionado a NF-E2/metabolismo , Antioxidantes/efeitos adversos , Ratos Sprague-Dawley , Fator de Necrose Tumoral alfa/metabolismo , Nefrolitíase/induzido quimicamente , Nefrolitíase/tratamento farmacológico , Rim/metabolismo , Superóxido Dismutase/metabolismo , Caspases/metabolismoRESUMO
Pediatric nephrolithiasis is increasing in incidence and presents differently compared to adults. We report a case of nephrolithiasis in a pediatric patient, presenting with complaints of emesis, anuria, hematuria, and abdominal distension, leading to a diagnosis of bilateral obstructing cystine stones requiring bilateral percutaneous nephrolithotomy. Pediatric patients with anuria should be evaluated for bilateral nephrolithiasis as an etiology. Calculous anuria requires prompt recognition of the pathologic process and relief of the obstruction with close follow-up and supportive care until definitive stone management. Bilateral percutaneous nephrolithotomy can provide definitive surgical intervention without significant morbidity.
Assuntos
Anuria , Cistinúria , Cálculos Renais , Nefrolitíase , Nefrolitotomia Percutânea , Nefrostomia Percutânea , Adulto , Humanos , Criança , Lactente , Cistinúria/complicações , Nefrolitotomia Percutânea/efeitos adversos , Anuria/etiologia , Nefrolitíase/cirurgia , Nefrostomia Percutânea/efeitos adversos , Cálculos Renais/cirurgia , Resultado do TratamentoRESUMO
INTRODUCTION: Both Holmium:yttrium-aluminium-garnet (Ho:YAG) laser and Thulium Fiber Laser (TFL) can effectively treat all urinary stone types. This in vitro study evaluated the ablation volume per pulse (AVP) and required energy needed to ablate 1mm3 (RE, J/mm3) of various stone types at different laser settings with TFL. METHODS: 272-µm core-diameter laser fibers (Boston Scientific©) were connected to a 50 Watts TFL generator (IPG®). An experimental setup immerged human stones of calcium oxalate monohydrate (COM), uric acid (UA), and cystine (CYS) with a single pulse lasing emission (0.5/0.8/1 J), in contact mode. Stones were dried out before three-dimensional scanning to measure AVP and deduce from the pulse energy (PE) and AVP the RE. A direct comparison with known Ho:YAG's AVP and RE was then carried out. RESULTS: AVP for COM stones was significantly greater than those for CYS stones and similar to UA stones (p = 0.02 and p = 0.06, respectively). If AVP increased with PE against COM and UA stones, AVP decreased against CYS stones. 1 J PE resulted in a threefold lower RE compared with other PE for COM stones. On the contrary, RE for CYS increased with PE, whereas PE did not had influence on RE for UA. TFL was associated with greater AVP for COM, but lower for UA and CYS stones compared to Ho:YAG laser. CONCLUSION: This in vitro study firstly describes the ablation volume per pulse and required energy to treat a cubic millimeter of three frequent human stone types, and suggest TFL could not be suited for cystine. Therefore, stone composition could be considered when choosing the laser source for lithotripsy.
Assuntos
Terapia a Laser , Lasers de Estado Sólido , Litotripsia a Laser , Nefrolitíase , Cálculos Urinários , Humanos , Litotripsia a Laser/métodos , Túlio , Cistina , Cálculos Urinários/cirurgia , Lasers de Estado Sólido/uso terapêutico , HólmioRESUMO
INTRODUCTION: Mizoribine (MZR) is used to prevent rejection reactions after kidney transplantation and increase the risk of hyperuricemia. There is a lack of reports of MZR-induced ureteral stones after kidney transplantation. The surgery treatment of ureteral stones in transplanted kidney is a challenging clinical issue that should only be performed by experienced urologists at professional centers. It is very important to have a thorough understanding of the patient's medical history, analyze the causes of stone formation, and choose a reasonable treatment plan based on the characteristics of the stones. The case report is aim to emphasize the recognition of the possibility of mizoribine-induced ureteral uric acid stones in transplanted kidney and to avoid unnecessary surgery. CASE PRESENTATION: A patient after kidney transplantation was diagnosed with acute renal failure caused by ureteral stones. The medical history, CT images of the renal graft, the results of laboratory test and stone composition analysis were provided. Based on medical history and laboratory test results, it was determined that the ureteral stones of renal graft was induced by MZR. To our best knowledge, this is the first report of MZR-induced stones in transplanted kidney and ureters. It was completely cured by urinary alkalinization, avoiding surgery treatment. We summarize the characteristics, treatment and methods for preventing the formation of uric acid stones of patients with MZR. CONCLUSION: By analyze our case report, it shows that acute renal failure with ureteral stones after kidney transplantation can caused by MZR. Urinary alkalinization for MZR induced uric acid stones is simple and effective.
Assuntos
Injúria Renal Aguda , Transplante de Rim , Nefrolitíase , Humanos , Transplante de Rim/efeitos adversos , Transplante de Rim/métodos , Imunossupressores/uso terapêutico , Ácido Úrico , Injúria Renal Aguda/induzido quimicamente , Injúria Renal Aguda/diagnóstico , Nefrolitíase/tratamento farmacológicoRESUMO
PURPOSE: Dry eye syndrome (DES) is one of the most common diseases of the ocular surface. Affected persons suffer from different subjective complaints, with sometimes severe impairment in the quality of life. The aetiology and pathogenesis are multifactorial, multifaceted, and not yet fully understood. The present study is intended to provide deeper insights into possible triggering factors and correlating comorbidities. MATERIALS AND METHODS: In German ophthalmological practices, 306 persons (174 women, 132 men, age: 18â-â87 years) were interviewed by questionnaire on concomitant diseases and possible further triggering factors. DES was diagnosed by an ophthalmologist in 170 cases. The statistical comparative analysis between persons with and without DES was carried out using the chi-squared test (SPSS statistical software). RESULTS: DES occurred with significantly (p < 0.05) increased frequency in women over 40 years of age, as well as in persons exposed to screen work, air conditioning, persons with chronic ocular inflammation, myomas (hysterectomy), dry skin, arterial hypertonicity in need of medication, cardiac arrhythmias, fatty liver, gastric ulcer, appendicitis, cholecystectomy, depression, hyperlipidaemia, hyperuricaemia, osteoporosis, and nephrolithiasis. CONCLUSION: Some of the known comorbidities and DES risk factors, e.g., computer work or depression, were confirmed. In contrast, the higher prevalence of hyperlipidaemia, hyperuricaemia, osteoporosis, nephrolithiasis, and fibroids among DES patients has not previously been reported. Additional studies should be performed on causal connections between DES and specific comorbidities.
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Síndromes do Olho Seco , Hiperlipidemias , Hiperuricemia , Nefrolitíase , Osteoporose , Masculino , Humanos , Feminino , Adulto , Pessoa de Meia-Idade , Adolescente , Adulto Jovem , Idoso , Idoso de 80 Anos ou mais , Qualidade de Vida , Hiperuricemia/complicações , Síndromes do Olho Seco/diagnóstico , Síndromes do Olho Seco/epidemiologia , Fatores de Risco , Hiperlipidemias/complicações , Osteoporose/complicações , Nefrolitíase/complicaçõesRESUMO
OBJECTIVE: The present study compared the clinical features of patients with primary Sjögren's syndrome (pSS) with and without nephrolithiasis and/or nephrocalcinosis to determine factors related to renal dysfunction. METHODS: The clinical features of 68 patients with anti-Sjogren's syndrome antigen A (SSA)/Ro-antibody-positive pSS with and without nephrolithiasis and/or nephrocalcinosis who underwent abdominal computed tomography and/or ultrasonography were retrospectively analysed. RESULTS: Of the 68 patients with anti-SSA-antibody-positive pSS, 23 (33%) had renal nephrolithiasis and/or nephrocalcinosis, whereas 45 (67%) did not. Fourteen (20%) patients had renal dysfunction at diagnostic imaging. Among five patients who underwent renal biopsy, four patients with renal nephrolithiasis and/or nephrocalcinosis were diagnosed with tubulointerstitial nephritis, and one without nephrolithiasis and/or nephrocalcinosis was diagnosed with minimal change nephrotic syndrome. Estimated glomerular filtration rate at diagnostic imaging was significantly lower in patients with than without nephrolithiasis and/or nephrocalcinosis group (P = 0.010). In addition to nephrolithiasis and/or nephrocalcinosis (odds ratio [OR], 3.467; P = 0.045), the gap between serum sodium and chloride concentrations (OR, 10.400; P = 0.012) and increased urinary ß2-microglobulin (OR, 5.444; P = 0.033) were associated with renal dysfunction at the time of diagnostic imaging. CONCLUSION: Nephrolithiasis and/or nephrocalcinosis, normal anion gap metabolic acidosis, and tubulointerstitial damage are associated with renal dysfunction in patients with pSS.
Assuntos
Acidose Tubular Renal , Nefrocalcinose , Nefrolitíase , Síndrome de Sjogren , Humanos , Nefrocalcinose/complicações , Nefrocalcinose/diagnóstico por imagem , Síndrome de Sjogren/complicações , Síndrome de Sjogren/diagnóstico , Estudos Retrospectivos , Acidose Tubular Renal/complicações , Nefrolitíase/complicações , Nefrolitíase/diagnóstico por imagem , AnticorposRESUMO
BACKGROUND: Primary hyperoxaluria type 1 (PH1) is an autosomal recessive inborn error of metabolism that causes oxalate deposition, leading to recurrent calcium oxalate kidney stones, chronic kidney disease and systemic oxalosis, which produces a broad range of serious life-threatening complications. Patients with PH1 have delayed diagnosis due to the rarity of the disease and the overlap with early-onset kidney stone disease not due to primary hyperoxaluria. OBJECTIVE: The objective of this study was to determine the clinical features of individuals <21 years of age with PH1 that precede its diagnosis. We hypothesized that a parsimonious set of features could be identified that differentiate patients with PH1 from patients with non-primary hyperoxaluria-associated causes of early-onset kidney stone disease. STUDY DESIGN: We determined the association between clinical characteristics and PH1 diagnosis in a case-control study conducted between 2009 and 2021 in PEDSnet, a clinical research network of eight US pediatric health systems. Each patient with genetically confirmed PH1 was matched by sex and PEDSnet institution to up to 4 control patients with kidney stones without PH of any type. We obtained patient characteristics and diagnostic test results occurring before to less than 6 months after study entrance from a centralized database query and from manual chart review. Differences were examined using standardized differences and multivariable regression. RESULTS: The study sample included 37 patients with PH1 and 147 controls. Patients with PH1 were younger at diagnosis (median age of 3 vs 13.5 years); 75 % of children with PH1 were less than 8 years-old. Patients with PH1 were more likely to have combinations of nephrocalcinosis on ultrasound or CT (43 % vs 3 %), lower eGFR at diagnosis (median = 52 mL/min/1.73 m2 vs 114 mL/min/1.73 m2), and have normal mobility. Patients with PH1 had higher proportion of calcium oxalate monohydrate kidney stones than controls (median = 100 % vs 10 %). There were no differences in diagnosis of failure to thrive, stone size, or echocardiography results. CONCLUSIONS: Children with PH1 are characterized by presentation before adolescence, nephrocalcinosis, decreased eGFR at diagnosis, and calcium oxalate monohydrate stone composition. If externally validated, these characteristics could facilitate earlier diagnosis and treatment of children with PH1.