RESUMEN

BACKGROUND: Gitelman syndrome (GS) is a rare autosomal recessive inherited salt-losing tubulopathy, typically devoid of hypercalcemia. Herein, we described one patient of GS presenting with hypercalcemia concomitant with primary hyperparathyroidism (PHPT). METHODS: On September 28, 2020, a middle-aged female patient was admitted to our hospital with a 12-year history of hypokalemia and hypomagnesemia. Laboratory examinations unveiled hypokalemia with renal potassium wasting, hypomagnesemia, metabolic alkalosis, hypocalciuria, and gene sequencing revealed a homozygous mutation in SLC12A3 (c.179C > T [p.T60M]). Subsequently, the diagnosis of GS was confirmed. In addition, the patient exhibited hypercalcemia and elevated levels of parathyroid hormone. Parathyroid ultrasound revealed left parathyroid hyperplasia, consistent with PHPT. Following aggressive treatment with potassium chloride and magnesium oxide, her serum potassium rose to 3.23 mmol/L, serum magnesium was 0.29 mmol/L, and her joint pain was relieved. RESULTS: Based on the patient's medical history, laboratory findings, and gene sequencing results, the definitive diagnosis was GS concomitant with PHPT. CONCLUSION: PHPT should be taken into consideration when patients diagnosed with GS exhibit hypercalcemia. While the serum potassium level readily exceeded the target threshold, correcting hypomagnesemia proved challenging, primarily because PHPT augments urinary magnesium excretion.

Asunto(s)

Síndrome de Gitelman , Hipercalcemia , Hiperparatiroidismo Primario , Humanos , Síndrome de Gitelman/complicaciones , Síndrome de Gitelman/diagnóstico , Síndrome de Gitelman/genética , Femenino , Hiperparatiroidismo Primario/complicaciones , Hiperparatiroidismo Primario/diagnóstico , Hipercalcemia/diagnóstico , Hipercalcemia/etiología , Hipercalcemia/genética , Persona de Mediana Edad , Miembro 3 de la Familia de Transportadores de Soluto 12/genética , Hipopotasemia/etiología , Hipopotasemia/diagnóstico , Mutación

RESUMEN

BACKGROUND: Renal hypouricemia (RHUC), a rare inherited disorder characterized by impaired uric acid reabsorption and subsequent profound hypouricemia, occurs mainly due to variants in SLC22A12 or SLC2A9. Only anecdotal cases and one small-scale RHUC screening study have been reported in the Chinese population. METHODS: A total of 19 patients with RHUC from 17 unrelated families were recruited from our center. The medical history, clinical manifestations, biochemical exam, and clinical outcomes were collected. Next-generation sequencing-based targeted gene sequencing or whole exon sequencing was performed. RESULTS: A total of 22 variants in SLC22A12 or SLC2A9 were found in 19 patients. The variant c.944G>A (p.W315X) in SLC2A9 was identified in three patients. Three variants c.165C>A (p.D55E), c.1549_1555delGAGACCC (p.E517Rfs*17), and c.1483T>C (p.W495R) in SLC22A12 and three variants c.1215+1G>A (splicing variant), c.643A>C (p.T215P), and c.227C>A (p.S76X) in SLC2A9 were novel. A proportion of 10 out of 19 patients presented with exercise-induced acute kidney injury (EIAKI). The renal outcome was favorable. Five patients had nephrolithiasis, in whom three had hypercalciuria. CONCLUSION: The current study reported six novel variants in SLC22A12 and SLC2A9 genes of Chinese patients with RHUC. The variant c.944G>A (p.W315X) in SLC2A9 may be common in Chinese patients. EIAKI is the main clinical phenotype associated with RHUC in our cohort, with a favorable outcome. Hypercalciuria presented in some RHUC patients is a new finding.

Asunto(s)

Lesión Renal Aguda , Transportadores de Anión Orgánico , Defectos Congénitos del Transporte Tubular Renal , Cálculos Urinarios , Humanos , Hipercalciuria , Proteínas Facilitadoras del Transporte de la Glucosa/genética , Transportadores de Anión Orgánico/genética , Proteínas de Transporte de Catión Orgánico/genética , Genotipo , Fenotipo , China

RESUMEN

Gitelman syndrome (GS) is caused by SLC12A3 biallelic variants. A previous study showed that large rearrangements (LRGs) of SLC12A3 accounted for the low sensitivity of genetic testing. However, a systematic screening for LRGs in Chinese GS patients is lacking. Massively parallel sequencing (MPS) and multiplex ligation-dependent probe amplification (MLPA) were performed to sequence the genomic DNA of patients with clinically diagnosed GS. Of 165 index cases, MPS identified 151 cases with two or more affected alleles and 14 cases with one variant allele. LRGs were detected by MLPA in 20 out of 27 cases, including 15 cases with suspected LRGs by MPS. Among these 20 cases with LRGs, the results of MPS and MLPA were identical in only 8 cases. Additional LRGs in 6 cases were detected by MLPA alone. In 6 cases, E4_E6del was identified by MPS, while E4_E5del and Intron6del were identified by MLPA. Among the 102 distinct variants, 30 are novel. LRGs were found in 20 cases (12.1%). LRGs were found in 12.1% of our Chinese GS patients cohort. We show that MPS and MLPA are two complementary techniques with the ability to improve the diagnostic yield of GS.

Asunto(s)

Pueblos del Este de Asia , Síndrome de Gitelman , Humanos , Pueblos del Este de Asia/genética , Pruebas Genéticas , Síndrome de Gitelman/genética , Mutación , Miembro 3 de la Familia de Transportadores de Soluto 12/genética

RESUMEN

Background: Dysregulation of cell death and defective clearance of dying cells are closely related to the pathogenesis of lupus nephritis (LN). However, the contribution of a recently discovered form of programmed cell death (PCD) called ferroptosis to LN has not been explored in detail. The purpose of this study was to investigate the role of ferroptosis and its associated metabolic pathways in the pathogenesis of LN. Methods: The composite gene expression scores were calculated by averaging the z-scored transformed log2 expressed genes within each form of PCD and pathway. Immunohistochemistry and immunofluorescence assays were used to verify the bioinformatics results. Results: We determined that ferroptosis is prominently and specifically elevated in the glomerular compartment of LN patients compared to other forms of PCD and kidney disease. This finding was then verified by immunohistochemical staining of 4-HNE (a key indicator for ferroptosis) expression in our own cohort (P < 0.0001). Intercorrelation networks were observed between 4-HNE and blood urea nitrogen, SLE disease activity index, serum creatinine, and complement 4, and negatively correlated with glomerular filtration rate in our own LN cohort (P < 0.05). Furthermore, enhanced iron metabolism and reduced fatty acid synthesis may be the most important factors for ferroptosis within the glomerulus. Through analysis of a single cell sequencing dataset and verification of immunohistochemical and immunofluorescence staining, aberrantly activated lipid peroxidation in CD163+ macrophages and CD10+ PC+ (pyruvate carboxylase) epithelial cells indicated that they may be undergoing ferroptosis in the glomerular compartment. Conclusions: Two dysregulated genes, CD163 and PC, were identified and verified that were significantly associated with lipid peroxidation. Targeting ferroptosis in CD163+ macrophages and CD10+ PC+ epithelial cells may provide novel therapeutic approaches in LN.

Asunto(s)

Ferroptosis , Nefritis Lúpica , Humanos , Nefritis Lúpica/metabolismo , Macrófagos/metabolismo , Células Epiteliales/metabolismo

RESUMEN

BACKGROUND: Gitelman syndrome (GS) is a rare autosomal recessive inherited salt-losing tubulopathy (SLT). Here, we report, for the first time, a case of GS overlapping nephrotic syndrome (NS) related to PLA2R-associated membranous nephropathy (MN). CASE PRESENTATION: We described a male patient had a 4-year history of recurrent fatigue. Serum biochemistry revealed hypokalemia with renal potassium wasting, hypomagnesemia, metabolic alkalosis, hyperreninemia, hypocalciuria, as well as nephrotic-range proteinuria, hypoalbuminemia, and elevated serum anti-phospholipase A2 receptor (PLA2R) antibody. Gene sequencing identified compound heterozygous mutations in SLC12A3 [c.536T > A(p.V179D) and c.1456G > A(p.D486N)]. The unusual association of SLTs and nephrotic-range glomerular proteinuria prompted us to perform a renal biopsy. Renal biopsy showed idiopathic MN. Due to the potential to activate the sodium-chloride co-transporter (NCC) and cause hyperkalemia, tacrolimus was selected to treat NS. Following treatment with potassium chloride, magnesium oxide, low-dose glucocorticoid combined with tacrolimus, the fatigue significantly improved, and concurrently hypokalemia, hypomagnesemia were corrected and NS was remitted. CONCLUSIONS: Renal biopsy should be warranted for GS patients with moderate to nephrotic-range proteinuria. Tacrolimus was preferred to the management of GS patients with NS.

Asunto(s)

Síndrome de Gitelman , Glomerulonefritis Membranosa , Hipopotasemia , Fatiga , Síndrome de Gitelman/complicaciones , Síndrome de Gitelman/diagnóstico , Síndrome de Gitelman/genética , Glomerulonefritis Membranosa/complicaciones , Glomerulonefritis Membranosa/diagnóstico , Glomerulonefritis Membranosa/genética , Humanos , Hipopotasemia/complicaciones , Magnesio , Masculino , Potasio , Proteinuria/complicaciones , Miembro 3 de la Familia de Transportadores de Soluto 12/genética , Tacrolimus/uso terapéutico

RESUMEN

Gitelman syndrome (GS) and Bartter syndrome (BS) type III are both rare, recessively inherited salt-losing tubulopathies caused by SLC12A3 and CLCNKB mutations, respectively. We described a 48-year-old male patient with fatigue, carpopedal spasm, arthralgia, hypokalemic alkalosis, mild renal dysfunction, hypomagnesemia, hypocalciuria, hyperuricemia, normotension, hyperreninemia and chondrocalcinosis in knees and Achilles tendons. His parents are first cousin. Genetic analysis revealed simultaneous homozygous mutations in SLC12A3 gene with c.248G>A, p.Arg83Gln and CLCNKB gene with c.1171T>C, p.Trp391Arg. The second younger brother of the proband harbored the same simultaneous mutations in SLC12A3 and CLCNKB and exhibited similar clinical features except normomagnesemia and bilateral kidney stones. The first younger brother of the proband harbored the same homozygous mutations in CLCNKB and exhibited clinical features of hypokalemia, normomagnesemia, hypercalciuria and hyperuricemia. Potassium chloride, spironolactone and potassium magnesium aspartate were prescribed to the proband to correct electrolytic disturbances. Benzbromarone and febuxostat were prescribed to correct hyperuricemia. The dose of potassium magnesium aspartate was subsequently increased to alleviate arthralgia resulting from calcium pyrophosphate deposition disease (CPPD). To the best of our knowledge, we are the first to report an exceptionally rare case in an inbred Chinese pedigree with simultaneous homozygous mutations in SLC12A3 and CLCNKB. GS and BS type III have significant intrafamilial phenotype heterogeneity. When arthralgia is developed in patients with GS and BS, gout and CPPD should both be considered.

Asunto(s)

Síndrome de Bartter/genética , Canales de Cloruro/genética , Síndrome de Gitelman/genética , Adulto , Anciano , Sustitución de Aminoácidos , Síndrome de Bartter/diagnóstico por imagen , China , Consanguinidad , Femenino , Síndrome de Gitelman/diagnóstico por imagen , Homocigoto , Humanos , Masculino , Persona de Mediana Edad , Linaje , Miembro 3 de la Familia de Transportadores de Soluto 12/genética

RESUMEN

RATIONALE: Hereditary hemochromatosis (HH) is a hereditary disorder of iron metabolism. It is classified into 4 main types depending on the underlying genetic mutation: human hemochromatosis protein (HFE) (type 1), hemojuvelin (HJV) (type 2A), HAMP (type 2B), transferrin receptor-2 (TFER2) (type 3), and ferroportin (type 4). Type 4 HH is divided into 2 subtypes according to different mutations: type 4A (classical ferroportin disease) and type 4B (non-classical ferroportin disease). Type 4B HH is a rare autosomal dominant disease that results from mutations in the Solute Carrier Family 40 member 1 (SLC40A1) gene, which encodes the iron transport protein ferroportin. PATIENT CONCERNS: Here we report 2 elderly Chinese Han men, who were brothers, presented with liver cirrhosis, diabetes mellitus, skin hyperpigmentation, hyperferritinaemia as well as high transferrin saturation. DIAGNOSIS: Subsequent genetic analyses identified a heterozygous mutation (p. Cys326Tyr) in the SLC40A1 gene in both patients. INTERVENTIONS: We treated the patient with iron chelator and followed up for 3 years. OUTCOMES: Iron chelator helped to reduce the serum ferritin and improve the condition of target organs, including skin, pancreas, liver as well as pituitary. LESSONS: Type 4B HH is rare but usually tends to cause multiple organ dysfunction and even death. For those patients who have difficulty tolerating phlebotomy, iron chelator might be a good alternative.

Asunto(s)

Proteínas de Transporte de Catión/deficiencia , Hemocromatosis/genética , Hemocromatosis/terapia , Quelantes del Hierro/uso terapéutico , Mutación/genética , Anciano , Pueblo Asiatico/genética , Proteínas de Transporte de Catión/genética , Humanos , Masculino , Persona de Mediana Edad

RESUMEN

BACKGROUND: Gitelman syndrome (GS) is an autosomal recessive inherited salt-losing tubulopathy (SLT). Here, we describe, for the first time, a case of GS without Gitelman-like features and with concomitant kidney stones, cysts and diabetic nephropathy (DN). CASE PRESENTATION: We described a male patient had a 19-year history of recurrent fatigue. From childhood, he had polydipsia and polyuria, paroxysmal tetany and palpitation. Serum biochemistry revealed chronic hypokalemia, metabolic alkalosis, normomagnesemia, mildly elevated Cr. Concomitant 24 h urine collection showed inappropriate renal potassium wasting, borderline hypercalciuria, moderate proteinuria consisting of major glomerular. Ultrasound of urinary tract showed bilateral and multiple kidney stones and cysts. Whole exome sequencing (WES) identified compound heterozygous mutations of SLC12A3. The unusual association of SLTs and glomerular proteinuria prompted us to perform a renal biopsy. Renal pathology showed renal involvement consistent with GS and early stage of diabetic nephropathy (DN). After treatment with KCl, magnesium oxide, perindopril and acarbose, the patient had been cured. The fatigue didn't relapse. CONCLUSION: GS had high variability of phenotype, GS may have no Gitelman-like features, kidney stones are not the exclusion criteria of GS. Renal biopsy should be warranted for GS patients with moderate to massive glomerular proteinuria.

Asunto(s)

Síndrome de Gitelman/complicaciones , Cálculos Renales/etiología , Proteinuria/etiología , Adulto , Síndrome de Gitelman/diagnóstico , Humanos , Masculino , Índice de Severidad de la Enfermedad

RESUMEN

Podocytic infolding glomerulopathy (PIG) is a newly proposed disease entity, and only 29 cases have been reported worldwide so far, characterized by microspheres or microtubular structures or both associated with podocytic infolding into the glomerular basement membrane (GBM) on electron microscopy. We present two new cases of PIG with connective tissue disease (CTD), one with primary Sjögren's syndrome and the other with systemic lupus erythematosus (SLE), and make a systemic review of the literature. In the entire 31 patients of PIG, 24 (77.42%) were women and seven (22.58%) were men, with an average age of 41.2 ± 15.2 (ranging from 14 to 79) years old. Almost two-thirds of patients (67.74%) were diagnosed with CTD, in which 76.19% were SLE. All patients presented with proteinuria and six (19.35%) patients were accompanied with hematuria. Serum creatinine was elevated in six (19.35%) patients. Pathological findings of all patients were consistent with PIG characteristics, and four patients with repeated renal biopsies further provided profound insights.

Asunto(s)

Membrana Basal Glomerular/patología , Enfermedades Renales/patología , Lupus Eritematoso Sistémico/patología , Podocitos/patología , Síndrome de Sjögren/patología , Adulto , Creatinina/sangre , Femenino , Hematuria/etiología , Humanos , Proteinuria/etiología , Adulto Joven

RESUMEN

RATIONALE: Renal Fanconi syndrome (FS) is a rare complication of monoclonal gammopathy. It is characterized by the impairment of renal proximal tubular function leading to normoglycemic glycosuria, aminoaciduria, hypophosphatemia, hypouricemia and proximal renal tubular acidosis. Renal impairment in monoclonal gammopathy, without fulfilling the criteria of multiple myeloma, is categorized as monoclonal gammopathy of renal significance (MGRS). PATIENT CONCERNS: A 54-year-old male presented with progressively aggravated bone pain and limitation of activity was admitted to our department. A proximal renal tubular damage was suggested by hypophosphatemia, compensated metabolic acidosis, renal glycosuria, aminoaciduria, and hypouricemia. M-protein of IgA kappa was detected by immunofixation electrophoresis. Mildly increased plasma cells were found in bone marrow cytomorphologic examination. Renal biopsy revealed diffuse linear monoclonal IgA-kappa light chain deposits along tubular basement membranes (TBMs), while lambda was negative. Electron microscopy showed granular electron-dense deposits along the outer aspect of TBMs. DIAGNOSES: The patient was diagnosed as FS induced osteomalacia secondary to monoclonal gammopathy of renal significance (MGRS) (IgA-κ type) and LCDD. INTERVENTIONS: He was treated with bortezomib, supplementation by phosphate, alkali agents, and active vitamin D. He responded well to the treatment symptomatically. OUTCOMES: We reported a rare case of adult acquired FS with hypophosphatemic osteomalacia secondary to LCDD associated with MGRS and the patient was successfully treated with bortezomib. LESSONS: Although few cases of LCDD with isolated symptoms of tubulointerstitial nephropathy, rather than glomerular symptoms have been reported. It still needs to be recognized as a differential diagnosis in monoclonal gammopathy.

Asunto(s)

Síndrome de Fanconi/etiología , Cadenas kappa de Inmunoglobulina/análisis , Enfermedades Renales/complicaciones , Paraproteinemias/complicaciones , Diagnóstico Diferencial , Síndrome de Fanconi/diagnóstico , Síndrome de Fanconi/tratamiento farmacológico , Síndrome de Fanconi/patología , Humanos , Enfermedades Renales/diagnóstico , Enfermedades Renales/tratamiento farmacológico , Enfermedades Renales/patología , Masculino , Persona de Mediana Edad , Paraproteinemias/diagnóstico , Paraproteinemias/tratamiento farmacológico , Paraproteinemias/patología

RESUMEN

Hyperlipidemia is a key clinical feature in patients with nephrotic syndrome (NS) that is associated with the incidence of cardiovascular events. Recent studies have suggested that the disorders of triglycerides, gluconeogenesis and liver glucose metabolism are associated with the abnormal transcription of clock genes. However, changes to the circadian rhythm of blood lipids in NS require further exploration, and the effects of NS on the hepatic clock system remain to be elucidated. In the present study, the impaired diurnal rhythm of the hepatic core clock genes (BMAL1, CLOCK, CRY1, CRY2, PER1 and PER2) significantly induced circadian rhythm abnormalities in liver­specific clock­controlled genes (LXR, CYP7A1, SREBP­1, ABCA1, DEC1 and DEC2; all P<0.05), which were significantly associated with the abnormal diurnal rhythms of triglyceride, total cholesterol, aspartate aminotransferase and alanine aminotransferase (all P<0.05) in rats with Adriamycin­induced nephropathy. Furthermore, a protein­protein interaction network was identified. Gene Ontology and Kyoto Encyclopedia of Genes and Genomes pathway analyses based on the human database was conducted to obtain signaling pathway and correlation prediction analyses of overall human clock and clock­controlled gene correlations. Strong correlations of the aforementioned clock genes were detected (avg. local clustering coefficient, 0.849) which suggested significant enrichment in circadian rhythm signaling. The present results indicated that damage to hepatic clock systems may impact blood lipid circadian rhythm disorders in NS, and offer a starting point for understanding the crosstalk between peripheral organs and peripheral clock systems.

Asunto(s)

Ritmo Circadiano/fisiología , Metabolismo de los Lípidos/fisiología , Hígado/metabolismo , Animales , Glucemia/metabolismo , Colesterol/sangre , Ritmo Circadiano/genética , Regulación de la Expresión Génica/genética , Regulación de la Expresión Génica/fisiología , Metabolismo de los Lípidos/genética , Masculino , Microscopía Electrónica de Transmisión , Unión Proteica , Ratas , Ratas Sprague-Dawley , Triglicéridos/sangre

RESUMEN

The right internal jugular vein (IJV) is an important access site for hemodialysis catheterization. Venous cannulation failure is usually caused by central venous stenosis and is rarely related to vessel malformation. We herein present a case of failure to place a tunneled hemodialysis catheter into the right IJV. The patient had an arteriovenous fistula in the right arm with inadequate flow and a history of multiple central venous catheterizations. The guidewire was repeatedly misplaced into the right subclavian vein (SV) regardless of the technique used. Computed tomography venography revealed that the inferior segment of the right IJV drained into the ipsilateral SV. To the best of our knowledge, this is the first report of catheterization failure due to abnormal drainage of the right IJV into the ipsilateral SV.

Asunto(s)

Cateterismo Venoso Central/efectos adversos , Venas Yugulares/anomalías , Fallo Renal Crónico/terapia , Diálisis Renal/instrumentación , Derivación Arteriovenosa Quirúrgica/efectos adversos , Cateterismo Venoso Central/métodos , Humanos , Venas Yugulares/diagnóstico por imagen , Masculino , Persona de Mediana Edad , Diálisis Renal/métodos , Vena Subclavia/diagnóstico por imagen , Insuficiencia del Tratamiento

Asunto(s)

Vena Ácigos/diagnóstico por imagen , Cateterismo , Venas Yugulares/diagnóstico por imagen , Diálisis Renal , Cateterismo/efectos adversos , Cateterismo/instrumentación , Cateterismo/métodos , Angiografía por Tomografía Computarizada , Femenino , Fluoroscopía , Humanos , Persona de Mediana Edad , Diálisis Renal/efectos adversos , Diálisis Renal/instrumentación , Diálisis Renal/métodos

RESUMEN

Chronic kidney disease (CKD) is a worldwide health problem with growing prevalence in developing countries. Renal tubular epithelial-mesenchymal transition (EMT) is a critical step and key factor in the development of this condition. Renal tubulointerstitial fibrosis is a basic pathological change at the later stages of the disease. Therefore, blocking the development of EMT could be a critical factor in curing CKD. We have established a cell-based high-content screening (HCS) method to identify inhibitors of EMT in human proximal tubular epithelial (HK-2) cells by automatic acquisition and processing of dual-fluorescent labeled images. With the aid of chromatographic separation and mass spectrometry, we achieved the rapid and reliable screening of active compounds from the Chinese herbal medicine Tong-Mai-Yang-Xin-Wan (TMYX) for treating EMT. Five fractions were found to exert anti-EMT activity and were further identified by liquid chromatography coupled with tandem mass spectrometry. Glycyrrhizic acid, glyasperin A, and licorisoflavan A were found to inhibit EMT. The proposed approach was successfully applied to screen active compounds from TMYX on TGF-ß1-stimulated HK-2 cells and may offer a new means for identifying lead compounds for treating EMT from registered Chinese herbal medicines.

Asunto(s)

Descubrimiento de Drogas , Medicamentos Herbarios Chinos/farmacología , Transición Epitelial-Mesenquimal/efectos de los fármacos , Ensayos Analíticos de Alto Rendimiento , Biomarcadores , Línea Celular , Cromatografía/métodos , Medicamentos Herbarios Chinos/química , Células Epiteliales/efectos de los fármacos , Células Epiteliales/metabolismo , Expresión Génica , Humanos , Espectrometría de Masas/métodos , Microscopía Fluorescente/métodos , Reproducibilidad de los Resultados

RESUMEN

Chronic kidney disease is increasingly considered to be a worldwide public health problem and usually leads to renal fibrosis. In the present study, curcumin, a polyphenol pigment extracted from turmeric, was demonstrated to exert protective effects on renal fibrosis via the suppression of transforming growth factor­ß (TGF­ß) downstream signaling, such as plasminogen activator inhibitor­1 (PAI­1), α­smooth muscle actin (α­SMA) and collagen I (Col I) downregulation. The present findings demonstrate that curcumin exerted a protective effect on cyclosporine A­induced renal fibrosis via a klotho (KL)­dependent mechanism, which inhibits the TGF­ß signaling pathway. Further research indicated that curcumin induced KL expression in HK­2 tubular epithelial cells by inhibiting CpG hypermethylation in the KL promoter, which mediates the loss of expression in cells. Methylation­specific polymerase chain reaction (PCR) combined with bisulfite sequencing identified numerous key CpG sites, such as 249, 240 and 236, whose methylation statuses are important for KL expression. A PCR reporter assay was utilized to further confirm these findings. In addition, the effects of curcumin on the regulation of DNA methyltransferase 1 (Dnmt1) expression were evaluated, and the data suggest that curcumin inhibits Dnmt1 expression and restricts CpG hypermethylation. Thus, the current study reveals that curcumin attenuated renal fibrosis by suppressing CpG methylation in the KL promoter, thus inducing KL expression, which inhibited TGF­ß signaling, which may provide a novel therapeutic approach for the treatment of renal fibrosis.

Asunto(s)

Antifúngicos/efectos adversos , Curcumina/uso terapéutico , Ciclosporina/efectos adversos , Glucuronidasa/genética , Riñón/efectos de los fármacos , Sustancias Protectoras/uso terapéutico , Insuficiencia Renal Crónica/inducido químicamente , Insuficiencia Renal Crónica/tratamiento farmacológico , Animales , Línea Celular , Metilación de ADN/efectos de los fármacos , Femenino , Fibrosis , Humanos , Riñón/patología , Proteínas Klotho , Ratones Endogámicos C57BL , Regiones Promotoras Genéticas/efectos de los fármacos , Insuficiencia Renal Crónica/genética , Insuficiencia Renal Crónica/patología

RESUMEN

INTRODUCTION: Gitelman syndrome(GS) is a rare inherited tubular disorder which is characterized by hypokalemia, metabolic alkalosis, hypomagnesemia, and hypocalciuria. Here, we report a case of schizophrenia-like psychosis concomitant with GS and related literatures are reviewed. CASE DESCRIPTION: An 18-year-old male patient with 1-week history of auditory hallucinations, sense of insecurity, delusions of reference and feelings of being followed and controlled by others unknown, insomnia was admitted to Psychiatry department in December, 2013. Hypokalemia and hypomagnesemia were noted. He was diagnosed as schizophrenia-like psychosis. Treatment with paliperidone at the dose of 6 mg/day and magnesium and potassium supplementations was commenced. However, electrolyte disturbances failed to improve following psychosis remission. Therefore, other underlying diseases resulting in electrolyte disturbances were suspected. Along with hypokalemia and hypomagnesemia, additional investigation showing metabolic alkalosis, hypocalciuria, renal loss of potassium, were consistent with GS. Gene analysis revealed this patient carried out c. 2687 G > A homozygous mutation of exon 23 in the SLC12A3 gene which led to p.Arg896Gln. Eventually, GS was identified. Thus, additional spironolactone (40 mg/day) combined with increased doses of oral potassium chloride sustained-release tablets (3.0 g/day) and potassium magnesium aspartate (0.3 g/day) were administered. During next half a year, fatigue resolved, paliperidone gradually tapered and eventually discontinued while psychosis maintained complete remission. His serum potassium was near normal (3.2-3.5 mmol/L), hypomagnesemia significantly improved (0.57-0.67 mmol/L). DISCUSSION AND EVALUATION: Electrolyte abnormalities secondary to GS might cause or contribute to development of neuropsychiatric symptoms. In turn, hypokalemia was common among acute psychiatric inpatients. As a consequence, when concomitant with psychosis, GS was readily concealed. CONCLUSION: Electrolyte disturbances are common in acute psychiatric patients. However, when electrolyte disturbances are not improved following psychosis remission, other underlying diseases such as GS should be considered.

RESUMEN

OBJECTIVE: To investigate the relationship of the circadian rhythm of the urine volume and urine electrolytes excretion rate and the daily expression pattern of the clock genes and clock-controlled genes with the water electrolyte transportation circadian pattern in rat kidneys. METHODS: Male adult SD rats were exposed to in a light:dark (12:12) cycles. We collected two period urine from zeitgeber time (ZT)00:00-ZT12:00 (light time,rest period) and ZT12:00-24:00 (dark time,activity period) and then compared the urinary excretion rates of volume, sodium, potassium, and chloride at light time with those at dark time. Rats were sacrificed every 4 hours throughout a 24-hour day-night cycle. Circadian clock gene CLOCK, BMAL1,Per1,Per2,Cry1,Cry2 and kidney specific clock-controlled gene NHE3,αENaC、NCC,Ptges,V1aR,V2R expression were profiled by real-time quantitative polymerase chain reaction. Data were analysed by a partial Fourier analysis and a stepwise regression technique. RESULTS: Urine volume and urine potassium excretion rate displayed high level at dark time and low at light time in SD rats (P<0.05),and urine sodium and chloride excretion rate also showed the trend(P>0.05).Clock gene CLOCK,BMAL1,Per1,Per2,Cry1,Cry2(P<0.05)and kidney specific clock-controlled gene NHE3, αENaC, NCC, Ptges, V1aR, V2R (P<0.05)mRNA expression showed circadian pattern,and the peak times of the genes were in the dark time. CONCLUSION: Urine volume and urine electrolyte excretion rate which displayed circadian pattern were temporally coupled with the rhythm of expression of clock and clock-controlled genes associated with water electrolyte transportation in rats kidney.

Asunto(s)

Ritmo Circadiano , Animales , Electrólitos , Riñón , Masculino , Ratas , Ratas Sprague-Dawley , Reacción en Cadena en Tiempo Real de la Polimerasa , Agua

RESUMEN

Renal hypouricemia (RHU) is an autosomal recessive hereditary disease characterized by impaired renal urate reabsorption and subsequent profound hypouricemia. There are two types of RHU, type 1 and type 2, caused by the loss-of-function mutation of SLC22A12 and SLC2A9 genes, respectively. RHU predisposes affected people to exercise-induced acute renal failure (EIARF), posterior reversible encephalopathy syndrome (PRES) and nephrolithiasis. A Chinese patient had experienced three episodes of EIARF and one episode of PRES. The investigations showed profound hypouricemia and significantly increased renal excretion of UA. Cranial magnetic resonance imaging showed communicating hydrocephalus. Renal biopsy displayed interlobular artery intimal thickening with reduction of lumen and acute tubulointerstitial injury. The mutational analysis revealed a homozygous splice-site mutation in the SLC2A9 gene encoding glucose transporter 9. The patient was diagnosed as RHU type 2 caused by a loss-of-function mutation of the SLC2A9 gene. Consequently, he was strictly prohibited from strenuous exercise. During the 5-year follow-up, EIARF and PRES never recurred. Strenuous exercise may induce systemic (including renal and cerebrovascular) vasoconstriction eventually resulting in EIARF and PRES in patients with RHU. To our knowledge, this is the first report of a homozygous splice-site mutation in the SLC2A9 gene, renal arteriolar chronic lesion, concurrence of RHU and communicating hydrocephalus.

Asunto(s)

Lesión Renal Aguda/genética , Ejercicio Físico , Proteínas Facilitadoras del Transporte de la Glucosa/genética , Homocigoto , Mutación , Síndrome de Leucoencefalopatía Posterior/genética , Defectos Congénitos del Transporte Tubular Renal/genética , Cálculos Urinarios/genética , Lesión Renal Aguda/diagnóstico , Lesión Renal Aguda/fisiopatología , Adolescente , Biopsia , Niño , Análisis Mutacional de ADN , Predisposición Genética a la Enfermedad , Herencia , Humanos , Imagen por Resonancia Magnética , Masculino , Linaje , Fenotipo , Síndrome de Leucoencefalopatía Posterior/diagnóstico , Síndrome de Leucoencefalopatía Posterior/fisiopatología , Valor Predictivo de las Pruebas , Sitios de Empalme de ARN , Recurrencia , Defectos Congénitos del Transporte Tubular Renal/diagnóstico , Defectos Congénitos del Transporte Tubular Renal/fisiopatología , Factores de Riesgo , Factores de Tiempo , Cálculos Urinarios/diagnóstico , Cálculos Urinarios/fisiopatología , Adulto Joven

RESUMEN

Adefovir dipivoxil (ADV) at a low-dose (10 mg daily), which was previously considered not nephrotoxic, was reported to have induced acquired Fanconi syndrome (FS). We report one 64-year-old Chinese woman and 2 Chinese men (ages 45 and 63 years) with bone pain, and/or muscle weakness on ADV therapy were diagnosed with low-dose ADV-induced FS. The serum phosphate normalized, or nearly normalized in the first and second patients after changing ADV to entecavir with, or without phosphate supplement, but did not improve significantly in the third patient after changing ADV to tenofovir, even though he was supplied with a higher dose of phosphate. Low-dose ADV-related FS is not rare in the Asian population. Regular monitoring of urine and serum phosphate is necessary during therapy with ADV. Prognosis was favorable, however, tenofovir is not a suitable replacement for ADV.

Asunto(s)

Adenina/análogos & derivados , Síndrome de Fanconi/inducido químicamente , Organofosfonatos/efectos adversos , Inhibidores de la Transcriptasa Inversa/efectos adversos , Adenina/efectos adversos , Relación Dosis-Respuesta a Droga , Femenino , Humanos , Persona de Mediana Edad