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1.
Säo Paulo med. j ; 140(3): 366-371, May-June 2022. tab
Article in English | LILACS | ID: biblio-1377381

ABSTRACT

ABSTRACT BACKGROUND: The number of nephrologists has risen slowly, compared with the prevalence of chronic kidney disease (CKD) in Brazil. Data on patients referred to nephrology outpatient clinics remains scarce. OBJECTIVE: To determine the demographic and kidney function characteristics of patients at their first appointment with a nephrologist. DESIGN AND SETTING: Retrospective study conducted at three nephrology outpatient clinics (public and private services), in São Paulo, Brazil. METHODS: From December 2019 to February 2020, we collected patient data regarding demographics, kidney function parameters and comorbidities. We then analyzed data on 394 patients who met a nephrologist for their first appointment. RESULTS: The main comorbidities were hypertension (63.7%), diabetes (33.5%) and nephrolithiasis (22.3%). Regarding CKD stages, 24.1%, 9.1%, 13.7%, 15.2%, 15.2% and 2.3% of the patients were in stages 1, 2, 3a, 3b, 4 and 5, respectively. Proteinuria was absent or mild, moderate and high in 17.3%, 15.2% and 11.7%, respectively; and 16.2% had not undergone previous investigation of serum creatinine or proteinuria (55.8%). For 17.5%, referral to a nephrologist occurred late. Patients in public services were older than those in private services (59 years versus 51 years, respectively; P = 0.001), more frequently hypertensive (69.7% versus 57.5%; P = 0.01) and reached a nephrologist later (22.4% versus 12.4%; P = 0.009). CONCLUSION: Referrals to a nephrologist were not being made using any guidelines for CKD risk and many cases could have been managed within primary care. Late referral to a nephrologist happened in one-fifth of the cases and more frequently in the public service.


Subject(s)
Humans , Renal Insufficiency, Chronic/therapy , Renal Insufficiency, Chronic/epidemiology , Hypertension/epidemiology , Nephrology , Proteinuria/epidemiology , Referral and Consultation , Brazil/epidemiology , Demography , Retrospective Studies , Nephrologists , Kidney
3.
Int. braz. j. urol ; 48(2): 284-293, March-Apr. 2022. tab, graf
Article in English | LILACS | ID: biblio-1364965

ABSTRACT

ABSTRACT A major challenge in the management of ureteropelvic junction obstruction (UPJO) is the selection of patients who would benefit from surgical treatment. Tissue inhibitor metalloproteinase-2 (TIMP-2) and insulin-like growth factor-binding protein 7 (IGFBP7) indicate renal cell stress and are associated with cell cycle arrest. The [TIMP-2] [IGFBP7] ratio (Nephrocheck®) has been recently applied in patients in intensive care units patients to predict the development of acute kidney injury. In this study, we evaluated the performance of these biomarkers performance to distinguishing obstructive hydronephrosis (HN) from non-obstructive HN. Materials and Methods: Consecutive patients with UPJO were enrolled in this study. Urinary [TIMP-2] [IGFBP7] and clinical characteristics (hydronephrosis grade, differential renal function, and drainage half-time) were measured in the following groups: 26 children with obstructive HN at initial diagnosis (group 1A) and after six months of dismembered pyeloplasty (group 1B); 22 children with non-obstructive HN (group 2), and 26 children without any urinary tract condition, as the control group (group 3). Results: Comparing the initial samples, [TIMP-2] [IGFBP7] had higher levels in the HN groups and lower levels in the control group; however, no difference was observed between the HN groups (obstructive vs. non-obstructive). After six months of follow-up, patients who underwent dismembered pyeloplasty showed stability in the urinary concentration of [TIMP-2] [IGFBP7]. All patients with [TIMP-2] [IGFBP7] higher than 1.0 (ng/mL)2/1000 had diffuse cortical atrophy on ultrasonography. Conclusions: We showed that urinary levels of urinary [TIMP-2] [IGFBP7] are higher in children with HN than controls. Nephrocheck® is not reliable in predicting the need for surgical intervention for pediatric patients with UPJO.


Subject(s)
Humans , Child , Tissue Inhibitor of Metalloproteinase-2/blood , Acute Kidney Injury/diagnosis , Acute Kidney Injury/etiology , Biomarkers/urine , Insulin-Like Growth Factor Binding Proteins/urine , Tissue Inhibitor of Metalloproteinase-2/urine , Matrix Metalloproteinase 2 , Kidney/physiology
4.
Lima; Perú. Ministerio de Salud. Centro Nacional de Epidemiología, Prevención y Control de Enfermedades; 1 ed; Mar. 2022. 308-39 p. ilus.(Boletín Epidemiológico, 31, SE 10).
Monography in Spanish | LILACS, LIPECS, MINSAPERU | ID: biblio-1373028

ABSTRACT

El riñón es un órgano clave para mantener el balance "homeostasis" del medio interno (agua, electrolitos, equilibrio ácido básico y el equilibrio osmótico), depura la sangre de productos de desechos metabólicos endógenos y exógenos, regula el volumen circulante efectivo y la presión arterial, y sintetiza la eritropoyetina y la vitamina D. Todas estas funciones se ejecutan en el nefrón que constituye la unidad funcional renal


Subject(s)
Epidemiologic Studies , Epidemiologic Measurements , Epidemiological Monitoring , Arterial Pressure , Homeostasis , Kidney
5.
Semina cienc. biol. saude ; 43(1): 119-128, jan./jun. 2022. ilus, tab
Article in English | LILACS | ID: biblio-1354464

ABSTRACT

Introduction: some plants such as turmeric, cinnamon, and okra are known to have therapeutic functions such as antioxidant and anti-inflammatory activity. Furthermore, an immunomodulatory role has been observed in the production of antibodies, in particular immunoglobulin A (IgA), which mediates a variety of protective functions for the organism. Objective: the aim of the present study was to investigate the effect of dietary plants on the production of IgA in healthy Wistar rats. Methods: thus, 48 male Wistar rats of 90 days of age were allocated to four groups. The animals were treated for 14 days with dried turmeric, cinnamon, or okra (50, 50, 12.5 mg/day, respectively) in phosphate buffered saline, or with only phosphate buffered saline by gavage. The animals received water and feed ad libitum. Body mass and relative weight ofperitoneal fat, adrenal gland, kidney, spleen, liver and thymus, biochemical parameters, and IgA levels were analyzed. Results: no significant changes were observed in the body mass, relative weight of organs and tissues, and biochemical parameters. An increase in serum IgA levels was observed in animals treated with turmeric or cinnamon. Conclusion: we conclude that the treatment with turmeric and cinnamon increased IgA production. Therefore, our study supports the idea that dietary supplementation with these plants may improve humoral immunity.


Introdução: algumas plantas como a cúrcuma, a canela e o quiabo são conhecidas por apresentar funções terapêuticas, como atividade antioxidante e anti-inflamatória. Além disso, tem sido observado um papel imunomodulador sobre a produção de anticorpos, em especial a imunoglobulina A (IgA), a qual medeia uma variedade de funções protetoras para o organismo. Objetivo: o objetivo do presente estudo foi investigar o efeito de plantas dietéticas na produção de IgA em ratos Wistar saudáveis. Métodos: destarte, 48 ratos machos Wistar com 90 dias de idade foram alocados em quatro grupos. Os animais foram tratados por 14 dias com cúrcuma seca, canela ou quiabo (50, 50, 12,5 mg/dia, respectivamente) em solução salina tamponada com fosfato ou apenas solução salina tamponada com fosfato, por gavagem. Os animais receberam água e ração ad libitum. Foram analisados a massa corporal e o peso relativo da gordura peritoneal, glândula adrenal, rim, baço, fígado e timo, parâmetros bioquímicos e níveis de IgA. Resultados: não foram observadas alterações significativas na massa corporal, no peso relativo dos órgãos e tecidos e nos parâmetros bioquímicos. Foi observado aumento dos níveis séricos de IgA nos animais tratados com cúrcuma ou canela. Conclusão: podemos concluir que o tratamento com cúrcuma e canela aumentou a produção de IgA. Portanto, nosso estudo suporta a ideia de que a suplementação alimentar com essas plantas pode melhorar a imunidade humoral.


Subject(s)
Rats , Spleen , Thymus Gland , Rats, Wistar , Abelmoschus , Curcuma , Kidney , Liver , Antibodies , Antibody Formation , Plants , Cinnamomum zeylanicum
6.
Rev. Col. Bras. Cir ; 49: e2022EDIT01, 2022.
Article in English | LILACS | ID: biblio-1365381

ABSTRACT

ABSTRACT Are presented results of experimental pig kidney xenotransplantation in Brazil, which aims to reduce the waiting list mortality due to shortage of organs. Recent clinical results obtained abroad are commented.


RESUMO Apresentam-se resultados de xenotransplante suíno de rim experimental no Brasil que visa reduzir as listas de espera nas quais falecem muitos inscritos à espera do transplante. Comentam-se os recentes resultados clínicos obtidos no exterior.


Subject(s)
Animals , Kidney Transplantation , Swine , Transplantation, Heterologous/methods , Brazil , Waiting Lists , Kidney
7.
Einstein (Säo Paulo) ; 20: eRC6484, 2022. graf
Article in English | LILACS | ID: biblio-1364800

ABSTRACT

ABSTRACT We describe the case of a female patient with calcification in renal topography, initially diagnosed as lithiasis in the left kidney, and later attributed to calcification of intrarenal vascular aneurysm. Next, we discuss the relevance of considering such an entity in the differential diagnoses of intrarenal calcifications before choosing any form of specific interventional treatment.


Subject(s)
Humans , Female , Urolithiasis , Aneurysm , Kidney
8.
Article in English | WPRIM | ID: wpr-929268

ABSTRACT

The dry root and rhizome of Panax ginseng C. A. Mey has garnered much interest owing to its medicinal properties against diabetes and cardiovascular diseases. In this study, an ultra-high performance liquid chromatography coupled with quadrupole time-of-flight mass spectrometry (UHPLC-Q-TOF-MS)-based metabolomics approach was used to illustrate the therapeutic mechanisms of ginseng extract on the serum and urinary metabolic profiles in streptozotocin-induced type 1 diabetes mellitus (T1DM) rats. Pharmacological and renal parameters in response to the administration of ginseng were also evaluated. In total, 16 serum endogenous metabolites and 14 urine endogenous metabolites, including pyruvic acid, indoleacetic acid, and phenylacetylglycine, were identified as potential biomarkers for diabetes. Pathway enrichment and network analysis revealed that the biomarkers modulated by ginseng were primarily involved in phenylalanine and pyruvate metabolism, as well as in arginine biosynthesis. Moreover, the levels of several renal injury-related biomarkers in T1DM rats were significantly restored following treatment with ginseng. The administration of the extract helped maintain tissue structure integrity and ameliorated renal injury. The findings suggest that the regulatory effect of ginseng extract on T1DM involves metabolic management of diabetic rats, which subsequently attenuates T1DM-induced early renal dysfunction.


Subject(s)
Animals , Biomarkers , Chromatography, High Pressure Liquid/methods , Diabetes Mellitus, Experimental/metabolism , Diabetes Mellitus, Type 1/drug therapy , Kidney , Metabolomics/methods , Panax/chemistry , Plant Extracts/pharmacology , Rats
9.
Article in English | WPRIM | ID: wpr-929249

ABSTRACT

Nephrotic syndrome (NS) is a kidney disease characterized by hypertriglyceridemia, massive proteinuria, hypo-albuminemia and peripheral edema. Sinkihwan-gamibang (SKHGMB) was recorded in a traditional Chinese medical book named "Bangyakhappyeon ()" and its three prescriptions Sinkihwan, Geumgwe-sinkihwan, and Jesaeng-sinkihwan belong to Gamibang. This study confirmed the effect of SKHGMB on renal dysfunction in an NS model induced by puromycin aminonucleoside (PAN). The experimental NS model was induced in male Sprague Dawley (SD) rats through injection of PAN (50 mg·kg-1)via the femoral vein. SKHGMB not only reduced the size of the kidneys increased due to PAN-induced NS, but also decreased proteinuria and ascites. In addition, SKHGMB significantly ameliorated creatinine clearance, creatinine, and blood urea nitrogen. SKHGMB relieved glomeruli dilation and tubules fibrosis in the glomeruli of the NS model. SKHGMB inhibited the protein and mRNA levels of the NLRP3 inflammasome including NLRP3, ASC, and pro-caspase-1 in NS rats. SKHGMB reduced the protein and mRNA levels of fibrosis regulators in NS rats. The results indicated that SKHGMB exerts protective effects against renal dysfunction by inhibiting of renal inflammation and fibrosis in NS rats.


Subject(s)
Animals , Kidney , Male , Nephrotic Syndrome/drug therapy , Proteinuria/metabolism , Puromycin Aminonucleoside/toxicity , Rats , Rats, Sprague-Dawley
10.
Article in English | WPRIM | ID: wpr-929020

ABSTRACT

OBJECTIVES@#Farnesoid X receptor (FXR) is a member of the nuclear receptor superfamily of ligand activated transcription factors and belongs to bile acid receptor. Studies have shown that the expression of FXR in renal tissue can reduce renal injury via regulation of glucose and lipid metabolism, inhibition of inflammatory response, reduction of oxidative stress and renal fibrosis. However, it is unclear whether FXR is involved in autophagy in renal diseases. This study aims to investigate the role of FXR in cisplatin-induced acute renal injury and whether its mechanism is related to autophagy regulation.@*METHODS@#Twelve male WT or FXR-KO mice at 12 weeks were randomly divided into a WT group, a WT+cisplatin group, a FXR-KO group, and a FXR-KO+cisplatin group, with 6 mice in each group. The WT+cisplatin group and the FXR-KO+cisplatin group were intraperitoneally injected with cisplatin (20 mg/kg), and the WT group and the FXR-KO group were intraperitoneally injected with equal volume of cisplatin solvent. Seventy-two hours later, the mice were killed and blood and renal tissue samples were collected. The levels of SCr and BUN were detected by immunoturbidimetry. After the staining, the pathological changes of renal tissue were observed under optical microscope. The protein levels of LC3 and p62 were detected by Western blotting and immunohistochemistry. The clearance of damaged mitochondria and the accumulation of lysosomal substrate were observed under electron microscope. The apoptosis of renal tubular epithelial cells was detected by TUNEL.@*RESULTS@#Compared with the WT group or the FXR-KO group, both SCr and BUN levels in the WT+cisplatin group or the FXR-KO+cisplatin group were significantly increased (P<0.01 or P<0.001), and SCr and BUN levels in the FXR-KO+cisplatin group were significantly higher than those in the WT+cisplatin group (both P<0.05). Under the light microscope, there were no obvious pathological changes in the renal tissue of mice in the WT group and the FXR-KO group. Both the WT+cisplatin group and the FXR-KO+cisplatin group had vacuolar or granular degeneration of renal tubular epithelial cells, flat cells, lumen expansion, brush edge falling off, and even exposed basement membrane and tubular formation. The scores of renal tubular injury in the WT+cisplatin group and the FXR-KO+cisplatin group were significantly higher than those in the WT group and the FXR-KO group, respectively (both P<0.001), and the score in the FXR-KO+cisplatin group was significantly higher than that in the WT+cisplatin group (P<0.05). Under the transmission electron microscope, the mitochondria of mouse tubular epithelial cell in the WT+cisplatin group and the FXR-KO+cisplatin group was swollen, round, vacuolated, cristae broken or disappeared; the lysosome was uneven and high-density clumps, and the change was more obvious in the FXR-KO+cisplatin group. Western blotting showed that the ratio of LC3-II to LC3-I was decreased and the expression of p62 was increased in the WT+cisplatin group compared with the WT group and the FXR-KO+cisplatin group compared with FXR-KO group (P<0.05 or P<0.01); compared with the FXR-KO group, the ratio of LC3-II to LC3-I was decreased and the expression of p62 was increased significantly in the FXR-KO+cisplatin group (both P<0.05). Immunohistochemistry results showed that the expression of total LC3 and p62 in renal cortex of the WT+cisplatin group and the FXR-KO+cisplatin group was increased significantly, especially in the FXR-KO+cisplatin group. TUNEL results showed that the mice in the WT group and the FXR-KO group had negative staining or only a few apoptotic tubular epithelial cells, and the number of apoptotic cells in the WT+cisplatin group and the FXR-KO+cisplatin group were increased. The apoptosis rates of renal tubular epithelial cells in the WT+cisplatin group and the FXR-KO+cisplatin group were significantly higher than those in the WT group and the FXR-KO group, respectively (both P<0.001), and the apoptosis rate in the FXR-KO+cisplatin group was significantly higher than that in the WT+cisplatin group (P<0.05).@*CONCLUSIONS@#Knockout of FXR gene aggravates cisplatin induced acute renal injury, and its mechanism may be related to inhibiting autophagy and promoting apoptosis.


Subject(s)
Acute Kidney Injury/pathology , Animals , Apoptosis/physiology , Cisplatin/adverse effects , Female , Humans , Kidney/pathology , Male , Mice , Mice, Inbred C57BL , Mice, Knockout
11.
Article in English | WPRIM | ID: wpr-929000

ABSTRACT

OBJECTIVES@#Acute kidney injury (AKI) can be caused by ischemia/reperfusion (I/R), nephrotoxin, and sepsis, with poor prognosis and high mortality. Leptin is a protein molecule that regulates the body's energy metabolism and reproductive activities via binding to its specific receptor. Leptin can inhibit cardiomyocyte apoptosis caused by I/R, but its effect on I/R kidney injury and the underlying mechanisms are still unclear. This study aims to investigate the effect and mechanisms of leptin on renal function, renal histopathology, apoptosis, and autophagy during acute I/R kidney injury.@*METHODS@#Healthy adult male mice were randomly divided into 4 groups: a sham+wild-type mice (ob/+) group, a sham+leptin gene-deficient mice (ob/ob) group, an I/R+ob/+ group, and an I/R+ob/ob group (n=8 per group). For sham operation, a longitudinal incision was made on the back of the mice to expose and separate the bilateral kidneys and renal arteries, and no subsequent treatment was performed. I/R treatment was ischemia for 30 min and reperfusion for 48 h. The levels of BUN and SCr were detected to evaluate renal function; HE staining was used to observe the pathological changes of renal tissue; TUNEL staining was used to observe cell apoptosis, and apoptosis-positive cells were counted; Western blotting was used to detect levels of apoptosis-related proteins (caspase 3, caspase 9), autophagy-related proteins [mammalian target of rapamycin (mTOR), phosphorylated mTOR (p-mTOR), LC3 I, LC3 II], mTOR-dependent signaling pathway proteins [phosphate and tension homology (PTEN), adenosine monophosphate-activated protein kinase (AMPK), protein kinase B (AKT), extracellular regulated protein kinase (ERK), phosphorylated PTEN (p-PTEN), phosphorylated AMPK (p-AMPK), phosphorylated AKT (p-AKT), phosphorylated ERK (p-ERK)].@*RESULTS@#There was no significant difference in the levels of BUN and SCr between the sham+ob/+ group and the sham+ob/ob group (both P>0.05). The levels of BUN and SCr in the I/R+ob/+ group were significantly higher than those in the sham+ob/+ group (both P<0.05). Compared with the mice in the sham+ob/ob group or the I/R+ob/+ group, the levels of BUN and SCr in the I/R+ob/ob group were significantly increased (all P<0.05). There was no obvious damage to the renal tubules in the sham+ob/+ group and the sham+ob/ob group. Compared with sham+ob/+ group and sham+ob/ob group, both the I/R+ob/+ group and the I/R+ob/ob group had cell damage such as brush border shedding, vacuolar degeneration, and cast formation. Compared with the I/R+ob/+ group, the renal tubules of the mice in the I/R+ob/ob group were more severely damaged. The pathological score of renal tubular injury showed that the renal tubular injury was the most serious in the I/R+ob/ob group (P<0.05). Compared with the sham+ob/+ group, the protein levels of caspase 3, caspase 9, PTEN, and LC3 II were significantly up-regulated, the ratio of LC3 II to LC3 I was significantly increased, and the protein levels of p-mTOR, p-PTEN, p-AMPK, p-AKT, and p-ERK were significantly down-regulated in the I/R+ob/+ group (all P<0.05). Compared with the sham+ob/ob group, the protein levels of caspase 3, caspase 9, PTEN, and LC3 II were significantly up-regulated, and the ratio of LC3 II to LC3 I was significantly increased, while the protein levels of p-mTOR, p-PTEN, p-AMPK, p-AKT, and p-ERK were significantly down-regulated in the I/R+ob/ob group (all P<0.05). Compared with the I/R+ob/+ group, the levels of p-mTOR, p-PTEN, p-AMPK, p-AKT were more significantly down-regulated, while the levels of caspase 3, caspase 9, PTEN, and LC3 II were more significantly up-regulated, and the ratio of LC3 II to LC3 I was more significantly increase in the I/R+ob/ob group (all P<0.05).@*CONCLUSIONS@#Renal function and tubular damage, and elevated levels of apoptosis and autophagy are observed in mice kidneys after acute I/R. Leptin might relieve I/R induced AKI by inhibiting apoptosis and autophagy that through a complex network of interactions between mTOR-dependent signaling pathways.


Subject(s)
AMP-Activated Protein Kinases/metabolism , Acute Kidney Injury/pathology , Animals , Apoptosis , Apoptosis Regulatory Proteins/pharmacology , Autophagy , Caspase 3/metabolism , Caspase 9/metabolism , Female , Humans , Ischemia , Kidney/pathology , Leptin/pharmacology , Male , Mammals/metabolism , Mice , Proto-Oncogene Proteins c-akt/metabolism , Reperfusion/adverse effects , Reperfusion Injury/metabolism , TOR Serine-Threonine Kinases/metabolism
12.
Article in English | WPRIM | ID: wpr-928822

ABSTRACT

BACKGROUND@#A Japanese woman in her early twenties had committed suicide, jumped from a 25-meter high bridge into a lake. She had been suffering from severe dysmenorrhea and general fatigue monthly.@*RESULTS@#A forensic autopsy revealed indications of a bicorporeal uterus, obstructed hemi-vagina, and ipsilateral renal agenesis, which lead to a diagnosis of obstructed hemi-vagina and ipsilateral renal anomaly (OHVIRA) syndrome. On the right side of the uterus, an enclosed cavity composed of black clots was observed. Histological findings suggested that her endometrium was in the early proliferative phase, implying that she was in the menstrual phase just before her death. She may have been suffering from severe lower abdominal pain from the increased pressure of the closed uterus cavity.@*CONCLUSIONS@#This case indicates that dysmenorrhea from undiagnosed OHVIRA syndrome can possibly lead to a suicide attempt. In Japan, because suicide was the leading cause of death for people aged 15 to 39 in 2019, preventive measures for suicide should be promoted. The present case also suggests that intervention for dysmenorrhea may prevent this in adolescent woman.


Subject(s)
Adult , Causality , Dysmenorrhea/etiology , Female , Humans , Kidney , Syndrome , Vagina , Young Adult
13.
Article in Chinese | WPRIM | ID: wpr-928394

ABSTRACT

OBJECTIVE@#To analyze the clinical phenotype and genetic basis for a male neonate featuring hypoparathyroidism, sensorineural hearing loss, and renal dysplasia (HDR) syndrome.@*METHODS@#The child was subjected to genome-wide copy number variation (CNVs) analysis and whole exome sequencing (WES). Clinical data of the patient was analyzed. A literature review was also carried out.@*RESULTS@#The patient, a male neonate, had presented with peculiar facial appearance, simian crease and sacrococcygeal mass. Blood test revealed hypocalcemia, hypoparathyroidism. Hearing test suggested bilateral sensorineural deafness. Doppler ultrasound showed absence of right kidney. Copy number variation sequencing revealed a 12.71 Mb deletion at 10p15.3-p13 (chr10: 105 001_12 815 001) region. WES confirmed haploinsufficiency of the GATA3 gene. With supplement of calcium and vitamin D, the condition of the child has improved.@*CONCLUSION@#The deletion of 10p15.3p13 probably underlay the HDR syndrome in this patient.


Subject(s)
DNA Copy Number Variations , Hearing Loss, Sensorineural/genetics , Humans , Hypoparathyroidism/genetics , Infant, Newborn , Kidney/abnormalities , Male , Syndrome , Urogenital Abnormalities/genetics
14.
Article in Chinese | WPRIM | ID: wpr-928157

ABSTRACT

This study aims to explore the effect of icariin(ICA) on mitochondrial dynamics in a rat model of chronic renal failure(CRF) and to investigate the molecular mechanism of ICA against renal interstitial fibrosis(RIF). CRF was induced in male Sprague-Dawley(SD) rats with 5/6(ablation and infarction, A/I) surgery(right kidney ablation and 2/3 infarction of the left kidney). Four weeks after surgery, the model rats were randomized into the following groups: 5/6(A/I) group, 5/6(A/I)+low-dose ICA group, and 5/6(A/I)+high-dose ICA group. Another 12 rats that received sham operation were randomly classified into 2 groups: sham group and sham+ICAH group. Eight weeks after treatment, the expression of collagen-Ⅰ(Col-Ⅰ), collagen-Ⅲ(Col-Ⅲ), mitochondrial dynamics-related proteins(p-Drp1 S616, p-Drp1 S637, Mfn1, Mfn2), and mitochondrial function-related proteins(TFAM, ATP6) in the remnant kidney tissues was detected by Western blot. The expression of α-smooth muscle actin(α-SMA) was examined by immunohistochemical(IHC) staining. The NRK-52 E cells, a rat proximal renal tubular epithelial cell line, were cultured in vitro and treated with ICA of different concentration. Cell viability was detected by CCK-8 assay. In NRK-52 E cells stimulated with 20 ng·mL~(-1) TGF-β1 for 24 h, the effect of ICA on fibronectin(Fn), connective tissue growth factor(CTGF), p-Drp1 S616, p-Drp1 S637, Mfn1, Mfn2, TFAM, and ATP6 was detected by Western blot, and the ATP content and the mitochondrial morphology were determined. The 20 ng·mL~(-1) TGF-β1-stimulated NRK-52 E cells were treated with or without 5 μmol·L~(-1) ICA+10 μmol·L~(-1) mitochondrial fusion promoter M1(MFP-M1) for 24 h and the expression of fibrosis markers Fn and CTGF was detected by Western blot. Western blot result showed that the levels of Col-Ⅰ, Col-Ⅲ, and p-Drp1 S616 were increased and the levels of p-Drp1 S637, Mfn1, Mfn2, TFAM, and ATP6 were decreased in 5/6(A/I) group compared with those in the sham group. The levels of Col-Ⅰ, Col-Ⅲ, and p-Drp1 S616 were significantly lower and the levels of p-Drp1 S637, Mfn1, Mfn2, TFAM, and ATP6 were significantly higher in ICA groups than that in 5/6(A/I) group. IHC staining demonstrated that for the expression of α-SMA in the renal interstitium was higher in the 5/6(A/I) group than in the sham group and that the expression in the ICA groups was significantly lower than that in the 5/6(A/I) group. Furthermore, the improvement in the fibrosis, mitochondrial dynamics, and mitochondrial function were particularly prominent in rats receiving the high dose of ICA. The in vitro experiment revealed that ICA dose-dependently inhibited the increase of Fn, CTGF, and p-Drp1 S616, increased p-Drp1 S637, Mfn1, Mfn2, TFAM, and ATP6, elevated ATP content, and improved mitochondrial morphology of NRK-52 E cells stimulated by TGF-β1. ICA combined with MFP-M1 further down-regulated the expression of Fn and CTGF in NRK-52 E cells stimulated by TGF-β1 compared with ICA alone. In conclusion, ICA attenuated RIF of CRF by improving mitochondrial dynamics.


Subject(s)
Adenosine Triphosphate/pharmacology , Animals , Female , Fibrosis , Flavonoids , Humans , Infarction/pathology , Kidney , Kidney Failure, Chronic , Male , Mitochondrial Dynamics , Rats , Rats, Sprague-Dawley , Renal Insufficiency, Chronic , Transforming Growth Factor beta1/metabolism
15.
Article in Chinese | WPRIM | ID: wpr-928091

ABSTRACT

This study aimed to investigate the effects of geniposide(GP) on the expression of prokineticin(PK2) and prokineticin receptor 1(PKR1) in db/db mice with diabetic nephropathy(DN), so as to explore how the PK2 signaling pathway participated in the pathological changes of DN and whether GP exerted the therapeutic effect through this signaling pathway. Male mice were randomly divided into four groups, namely db/m, db/db, db/db+GP, and db/m+GP groups, with five in each group. The mice in the db/db+GP and db/m+GP groups were gavaged with 150 mg·kg~(-1) GP for eight successive weeks. Afterwards, all the mice were sacrificed and the renal tissues were embedded. The morphological changes in glomerulus and renal tubules were observed by Masson and PAS staining. The expression levels of PK2, PKR1, and Wilm's Tumor Protein 1(WT_1) in podocytes were detected by immunohistochemistry, and the protein expression levels of PK2 and PKR1 in mouse kidney by Western blot. The morphological results showed serious glomerular and tubular fibrosis(Masson), high glomerular and tubular injury score(PAS), increased glomerular mesangial matrix, thickened basement membrane, exfoliated brush border of renal tubules, decreased WT_1 in glomerular podocytes, and massive loss of podocytes in the db/db group. After administration with GP, the glomerular and tubular fibrosis was alleviated, accompanied by improved glomerular basement membrane and renal tubule brush edge, and up-regulated WT_1. As revealed by further protein detection, in the db/db group, the expression levels of PK2 and PKR1 and p-Akt/Akt ratio declined, whereas the ratio of Bax/Bcl-2 rose. Ho-wever, PKR2 and p-ERK/ERK ratio did not change significantly. After administration with GP, the PK2 and PKR1 expression was elevated, and p-Akt/Akt ratio was increased. There was no obvious change in PKR2, Bax/Bcl-2 ratio, or p-ERK/ERK ratio. All these have demonstrated that GP improves the renal damage in DN mice, and PK2/PKR1 signaling pathway may be involved in such protection, which has provided reference for clinical treatment of DN with GP.


Subject(s)
Animals , Diabetes Mellitus , Diabetic Nephropathies/genetics , Iridoids , Kidney , Male , Mice , Signal Transduction
16.
Article in Chinese | WPRIM | ID: wpr-927963

ABSTRACT

The present study explored the biological connotation of traditional Chinese medicine(TCM) syndromes of rheumatoid arthritis(RA) from the "disease-syndrome-symptom" association network. RA patients with four TCM syndromes(dampness-heat obstruction, phlegm-stasis obstruction, Qi-blood deficiency, and liver and kidney deficiency), three for each type, were assigned as the RA TCM syndrome group, and three healthy volunteers as the normal control group. The differential gene sets of four syndromes were screened out through transcriptome expression profiling and bioinformatics mining. The relevant gene sets of syndrome-related clinical symptoms were collected from TCMIP v2.0(http://www.tcmip.cn/). The "disease-syndrome-symptom" association networks of four RA syndromes were established by using the intersection genes of syndrome-related differential genes and symptom-related genes, and the key network target genes of each syndrome were screened out and the corresponding biological functions were mined through topological feature calculation and enrichment analysis. The genes associated with clinical symptoms such as vasculitis, joint pain, and fever in the damp-heat obstruction syndrome ranked the top, and the key network target genes of this syndrome were most significantly enriched in the pathways related to material and energy metabolism and thermal reaction biological processes. The clinical symptom-related genes of the phlegm-stasis obstruction syndrome were most significantly enriched in the pathways related to "immunity-inflammation", nervous system regulation, and sensory response. The clinical symptoms such as hypoglycemia, hypotension, weight loss, palpitation, and arrhythmia in Qi-blood deficiency syndrome were predominant, and its key network target genes were most significantly enriched in the pathways related to the nervous system and "immunity-inflammation" response. The abnormal symptoms in the liver and kidney in the liver and kidney deficiency syndrome were commonly seen, and its key network target genes were most significantly enriched in the "immunity-inflammation" regulatory pathways, and liver and kidney development and metabolic response. In conclusion, the differences and connections of the biological basis between different TCM syndromes of RA are in line with the theoretical interpretation of TCM on the etiology and pathogenesis of RA. This study summarized the objective essence of syndromes to a certain extent from the "disease-syndrome-symptom" association network and is expected to provide a theoretical basis for the discovery of serum biomarkers of RA syndromes.


Subject(s)
Arthritis, Rheumatoid/genetics , Hot Temperature , Humans , Kidney , Medicine, Chinese Traditional , Syndrome
17.
Article in Chinese | WPRIM | ID: wpr-927954

ABSTRACT

This study investigated the protective effects of Moutan Cortex polysaccharides components(MCPC) on the renal tissues of diabetic nephropathy(DN) rats and explored their regulation effect on inflammatory response and oxidative stress. The DN rat model was induced by high-glucose and high-fat diet combined with streptozotocin(STZ), and then the rats were randomly divided into control group, model group, positive group and MCPC high(120 mg·kg~(-1)·d~(-1)), low(60 mg·kg~(-1)·d~(-1)) dose groups. After 12 weeks treatment, blood was taken from the orbit of the rats, and then they were sacrificed before the kidney tissues were collected. The serum and tissues were detected for related biochemical indicators and pathological changes of the kidney. Immunohistochemical methods were used to determine the expression of FN and ColⅣ in the kidney tissue of DN rats. Compared with the model group, blood glucose, serum creatinine, blood urea nitrogen and 24 h urine protein in the MCPC high-dose group were significantly reduced(P<0.01). The results of HE, PAS, Masson staining showed that glomerular basement membrane thickening, Bowman's capsule narrowing and inflammatory cell infiltration in DN rats were improved in the MCPC high-dose group; the activity of T-SOD and GSH-Px in serum significantly increased(P<0.001), and the expression level of FN significantly decreased(P<0.001). The high-dose MCPC treatment could effectively inhibit the abnormal expression of Col Ⅳ(P<0.001) and significantly reduce the levels of AGEs and RAGE in serum(P<0.001), the content of VCAM-1 and IL-1β in serum(P<0.001), and the levels of IL-1β mRNA in kidney tissue(P<0.001), but failed to effectively reduce VCAM-1 mRNA levels in kidney tissues. The high-dose MCPC could significantly improve pathological injury of renal tissue and related renal indicators in DN rats, and achieve renal protection in DN rats mainly by regulating oxidative stress and inflammatory factors.


Subject(s)
Animals , Diabetes Mellitus, Experimental/genetics , Diabetic Nephropathies/genetics , Drugs, Chinese Herbal , Kidney , Paeonia , Polysaccharides/pharmacology , Rats
18.
Acta Physiologica Sinica ; (6): 320-332, 2022.
Article in Chinese | WPRIM | ID: wpr-927608

ABSTRACT

Renal ischemia-reperfusion injury (IRI) is histologically characterized by tubular cell death. Diverse pathways of regulated cell death (RCD) have been reported to contribute to renal IRI in recent studies. In this review, we discuss the signaling pathways, regulators and crosstalk of RCD, including necroptosis, ferroptosis and pyroptosis, and their role in renal IRI in order to pave the way for new therapeutic opportunities.


Subject(s)
Apoptosis , Ferroptosis , Humans , Kidney/metabolism , Necroptosis , Regulated Cell Death , Reperfusion Injury/drug therapy
19.
Acta Physiologica Sinica ; (6): 125-133, 2022.
Article in English | WPRIM | ID: wpr-927588

ABSTRACT

Captopril can have nephrotoxic effects, which are largely attributed to accumulated renin and "escaped" angiotensin II (Ang II). Here we test whether angiotensin converting enzyme-1 (ACE1) inhibition damages kidneys via alteration of renal afferent arteriolar responses to Ang II and inflammatory signaling. C57Bl/6 mice were given vehicle or captopril (60 mg/kg per day) for four weeks. Hypertension was obtained by minipump supplying Ang II (400 ng/kg per min) during the second 2 weeks. We assessed kidney histology by periodic acid-Schiff (PAS) and Masson staining, glomerular filtration rate (GFR) by FITC-labeled inulin clearance, and responses to Ang II assessed in afferent arterioles in vitro. Moreover, arteriolar H2O2 and catalase, plasma renin were assayed by commercial kits, and mRNAs of renin receptor, transforming growth factor-β (TGF-β) and cyclooxygenase-2 (COX-2) in the renal cortex, mRNAs of angiotensin receptor-1 (AT1R) and AT2R in the preglomerular arterioles were detected by RT-qPCR. The results showed that, compared to vehicle, mice given captopril showed lowered blood pressure, reduced GFR, increased plasma renin, renal interstitial fibrosis and tubular epithelial vacuolar degeneration, increased expression of mRNAs of renal TGF-β and COX-2, decreased production of H2O2 and increased catalase activity in preglomerular arterioles and enhanced afferent arteriolar Ang II contractions. The latter were blunted by incubation with H2O2. The mRNAs of renal microvascular AT1R and AT2R remained unaffected by captopril. Ang II-infused mice showed increased blood pressure and reduced afferent arteriolar Ang II responses. Administration of captopril to the Ang II-infused mice normalized blood pressure, but not arteriolar Ang II responses. We conclude that inhibition of ACE1 enhances renal microvascular reactivity to Ang II and may enhance important inflammatory pathways.


Subject(s)
Angiotensin II/pharmacology , Animals , Arterioles/metabolism , Captopril/pharmacology , Hydrogen Peroxide/pharmacology , Kidney , Mice
20.
Acta Physiologica Sinica ; (6): 110-116, 2022.
Article in Chinese | WPRIM | ID: wpr-927586

ABSTRACT

Hypertension is one of the strongest risk factors for cardiovascular diseases, cerebral stroke, and kidney failure. Lifestyle and nutrition are important factors that modulate blood pressure. Hypertension can be controlled by increasing physical activity, decreasing alcohol and sodium intake, and stopping tobacco smoking. Chronic kidney disease patients often have increased blood pressure, which indicates that kidney is one of the major organs responsible for blood pressure homeostasis. The decrease of renal sodium reabsorption and increase of diuresis induced by high potassium intake is critical for the blood pressure reduction. The beneficial effect of a high potassium diet on hypertension could be explained by decreased salt reabsorption by sodium-chloride cotransporter (NCC) in the distal convoluted tubule (DCT). In DCT cells, NCC activity is controlled by with-no-lysine kinases (WNKs) and its down-stream target kinases, Ste20-related proline-alanine-rich kinase (SPAK) and oxidative stress-responsive 1 (OSR1). The kinase activity of WNKs is inhibited by intracellular chloride ([Cl-]i) and WNK4 is known to be the major WNK positively regulating NCC. Based on our previous studies, high potassium intake reduces the basolateral potassium conductance, decreases the negativity of DCT basolateral membrane (depolarization), and increases [Cl-]i. High [Cl-]i inhibits WNK4-SPAK/OSR1 pathway, and thereby decreases NCC phosphorylation. In this review, we discuss the role of DCT in the blood pressure regulation by dietary potassium intake, which is the mechanism that has been best dissected so far.


Subject(s)
Blood Pressure , Diet , Humans , Kidney/metabolism , Kidney Tubules, Distal/metabolism , Phosphorylation , Potassium/pharmacology , Protein Serine-Threonine Kinases , Solute Carrier Family 12, Member 3/metabolism
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