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1.
Physiol Rev ; 103(1): 787-854, 2023 Jan 01.
Artigo em Inglês | MEDLINE | ID: mdl-36007181

RESUMO

An essential step in renal function entails the formation of an ultrafiltrate that is delivered to the renal tubules for subsequent processing. This process, known as glomerular filtration, is controlled by intrinsic regulatory systems and by paracrine, neuronal, and endocrine signals that converge onto glomerular cells. In addition, the characteristics of glomerular fluid flow, such as the glomerular filtration rate and the glomerular filtration fraction, play an important role in determining blood flow to the rest of the kidney. Consequently, disease processes that initially affect glomeruli are the most likely to lead to end-stage kidney failure. The cells that comprise the glomerular filter, especially podocytes and mesangial cells, express many different types of ion channels that regulate intrinsic aspects of cell function and cellular responses to the local environment, such as changes in glomerular capillary pressure. Dysregulation of glomerular ion channels, such as changes in TRPC6, can lead to devastating glomerular diseases, and a number of channels, including TRPC6, TRPC5, and various ionotropic receptors, are promising targets for drug development. This review discusses glomerular structure and glomerular disease processes. It also describes the types of plasma membrane ion channels that have been identified in glomerular cells, the physiological and pathophysiological contexts in which they operate, and the pathways by which they are regulated and dysregulated. The contributions of these channels to glomerular disease processes, such as focal segmental glomerulosclerosis (FSGS) and diabetic nephropathy, as well as the development of drugs that target these channels are also discussed.


Assuntos
Canalopatias , Glomerulosclerose Segmentar e Focal , Nefropatias , Humanos , Canal de Cátion TRPC6/metabolismo , Canalopatias/metabolismo , Canais de Cátion TRPC/metabolismo , Glomérulos Renais/metabolismo , Glomerulosclerose Segmentar e Focal/metabolismo , Nefropatias/metabolismo
2.
J Proteomics ; 270: 104735, 2023 Jan 06.
Artigo em Inglês | MEDLINE | ID: mdl-36174949

RESUMO

Canine babesiosis is a tick-borne disease caused by Babesia canis, with acute kidney injury as one of the common complications. In the study 8 healthy control dogs and 22 dogs with naturally occurring babesiosis were enrolled, with the aim to analyse differences in serum and urinary proteomes between healthy dogs and dogs with different degree of renal dysfunction in babesiosis using a label-based high-throughput quantitative proteomic approach. In serum, 58 proteins were found differentially abundant between healthy controls and groups of dogs with different degrees of renal dysfunction in babesiosis, while in urine there were 259 differentially abundant proteins. In addition, altered biological pathways were detected in the diseased dogs using bioinformatics tools and validation of several candidate biomarkers was performed. SIGNIFICANCE: The main aim of this comprehensive study was to perform analyses of serum and urinary proteomes of dogs with renal dysfunction in babesiosis compared to healthy dogs using, for the first time, a high-throughput proteomic method and functional enrichment analyses. Serum and urine samples of the same dogs were investigated in order to gain a more complete picture of pathologic changes taking place in renal dysfunction in babesiosis. We highlighted two putative biomarkers validated herein which could be of importance for early diagnosis of renal dysfunction in canine babesiosis, as they are easily accessible from urine and their concentration rises before the appearance of azotaemia: urinary neutrophil gelatinase-associated lipocalin (NGAL) and urinary liver-type fatty acid-binding protein (L-FABP).


Assuntos
Babesiose , Doenças do Cão , Nefropatias , Cães , Animais , Babesiose/complicações , Babesiose/diagnóstico , Proteômica , Proteoma , Doenças do Cão/diagnóstico , Biomarcadores , Nefropatias/diagnóstico , Nefropatias/urina , Nefropatias/veterinária
3.
Methods Mol Biol ; 2582: 391-409, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-36370365

RESUMO

CCN2 has been shown to be closely involved in the progression of renal fibrosis, indicating the potential of CCN2 inhibition as a therapeutic target. Although the examination of the renal disease phenotypes of adult CCN2 knockout mice has yielded valuable scientific insights, perinatal death has limited studies of CCN2 in vivo. Conditional knockout technology has become widely used to delete genes in the target cell populations or time points using cell-specific Cre recombinase-expressing mice. Therefore, several lines of CCN2-floxed mice have been developed to assess the functional role of CCN2 in adult mice.CCN2 levels are elevated in renal fibrosis and proliferative glomerulonephritis, making them suitable disease models for assessing the effects of CCN2 deletion on the kidney. Renal fibrosis is characterized by glomerulosclerosis and tubulointerstitial fibrosis and transforming growth factor-ß. CCN2 is increased in fibrosis and modulates a number of downstream signaling pathways involved in the fibrogenic properties of TGF-ß. Unilateral ureteral obstruction is one of the most widely used models of renal tubulointerstitial fibrosis. In addition, anti-glomerular basement membrane antibody glomerulonephritis has become the most widely used model for evaluating the effect of increased renal CCN2 expression. Herein, we describe the construction of CCN2-floxed mice and inducible systemic CCN2 conditional knockout mice and methods for the operation of unilateral ureteral obstruction and the induction of anti-glomerular basement membrane antibody glomerulonephritis.


Assuntos
Glomerulonefrite , Nefropatias , Obstrução Ureteral , Camundongos , Animais , Obstrução Ureteral/metabolismo , Fator de Crescimento do Tecido Conjuntivo/metabolismo , Rim/metabolismo , Fibrose , Nefropatias/metabolismo , Camundongos Knockout , Fator de Crescimento Transformador beta/genética , Fator de Crescimento Transformador beta/metabolismo , Glomerulonefrite/genética , Glomerulonefrite/metabolismo
4.
Curr Opin Nephrol Hypertens ; 32(1): 41-48, 2023 Jan 01.
Artigo em Inglês | MEDLINE | ID: mdl-36250456

RESUMO

PURPOSE OF REVIEW: Paediatric kidney disease results in considerable burden on children and their families. Paediatric palliative care is a holistic, family-centred care approach intended to enable flourishing and address the many impediments to life participation which advanced kidney disease can impose. To date, palliative care resources have been underutilized in paediatric nephrology. This review will highlight recent literature targeting the engagement and life participation of children with advanced kidney disease through implementation of novel palliative care approaches and propose directions for future research. RECENT FINDINGS: Children with advanced kidney disease and their families highly value incorporation of their perspectives, particularly on life participation, within care plan development; but what it means to participate in life can be variable, and clinicians need improved tools to ascertain and incorporate these perspectives. Novel palliative care interventions developed for application in comparable disease states offer potential opportunities for paediatric nephrologists to support this goal. SUMMARY: Children with advanced kidney disease and their families will benefit from incorporation of their perspectives and values, facilitated by palliative interventions.


Assuntos
Nefropatias , Nefrologia , Medicina Paliativa , Criança , Humanos , Cuidados Paliativos/métodos , Nefropatias/diagnóstico , Nefropatias/terapia
5.
J Ethnopharmacol ; 302(Pt A): 115882, 2023 Feb 10.
Artigo em Inglês | MEDLINE | ID: mdl-36341817

RESUMO

ETHNOPHARMACOLOGICAL RELEVANCE: Heidihuang Wan (HDHW) is a classic Chinese herbal formula, which was first recorded in the "Suwen Bingji Qiyi Baoming Collection" written by Liu Wansu during the Jin Dynasty (1115-1234 AD). It is commonly used clinically for the treatment of kidney diseases and its curative effect is stable. Previous animal experiments have confirmed that HDHW can effectively improve renal fibrosis. However, the underlying pharmacological mechanism remains unclear. AIMS OF THIS STUDY: Renal tubular epithelial cell (RTEC) apoptosis is one of the main pathological features of renal fibrosis. This study aimed to observe the effect and underlying mechanism of HDHW on the apoptosis of RTECs to further explore the pathological mechanism of HDHW against renal fibrosis. MATERIALS AND METHODS: We examined the HDHW composition in rat serum. In vitro, we first screened out the optimal intervention concentration of HDHW on RTECs using the MTT assay. Hypoxia/reoxygenation was then used to induce apoptosis of RTECs (H/R-RTECs), which were divided into H/R-RTEC, astragaloside IV (positive control), HDHW, and RTECs groups. After 48 h of drug intervention, apoptosis of RTECs was detected using flow cytometry and protein expression was detected by western blotting. The 5/6 nephrectomy rat model was constructed and divided into the normal control, 5/6 nephrectomy, HDHW, and astragaloside IV groups. After 8 weeks of treatment, TUNEL staining was used to detect cell apoptosis, and western blotting was used to detect protein expression. RESULTS: HDHW downregulated the expression of pro-apoptotic proteins Bax and Caspase3, up-regulated the expression of anti-apoptotic protein Bcl-2, activated the PI3K/Akt/mTOR signaling pathway, and reversed the early apoptosis of RTECs, thereby resisting the apoptosis of RTECs. CONCLUSION: HDHW inhibits apoptosis of RTECs by modulating the PI3K/Akt/mTOR signaling pathway. This study provides experimental evidence for the anti-fibrotic effect of HDHW on the kidneys and partially elucidates its pharmacological mechanism of action.


Assuntos
Nefropatias , Proteínas Proto-Oncogênicas c-akt , Ratos , Animais , Proteínas Proto-Oncogênicas c-akt/metabolismo , Fosfatidilinositol 3-Quinases/metabolismo , Transdução de Sinais , Serina-Treonina Quinases TOR/metabolismo , Apoptose , Células Epiteliais , Proteínas Reguladoras de Apoptose/metabolismo , Nefropatias/patologia , Fibrose
6.
J Ethnopharmacol ; 302(Pt A): 115898, 2023 Feb 10.
Artigo em Inglês | MEDLINE | ID: mdl-36372193

RESUMO

ETHNOPHARMACOLOGICAL RELEVANCE: Fructus Ligustri Lucidi (FLL), the fruit of Ligustrum lucidum Ait., is a traditional Chinese medicine that has been used for tonifying the kidney and liver for decades. AIM OF THE STUDY: This study aimed to explore and identify polysaccharides from FLL and elucidate its protective effect against renal fibrosis. MATERIALS AND METHODS: Polysaccharides were extracted and isolated from FLL. The purified fraction was identified by serial phytochemical work, such as gel-permeation chromatography, ion chromatography, gas chromatography-mass spectrometry, and nuclear magnetic resonance. Mice with unilateral ureteral obstruction (UUO) were applied as a renal fibrosis model. The male UUO mice were pretreated with heteropolysaccharide (Poly) 1 week prior to surgery and continuously treated for 7 days after the operation. Renal fibrosis was assessed by Periodic Acid-Schiff (PAS) staining and Masson's trichrome staining in paraffin-embedded slides. The murine mesangial cells SV40-MES13 upon angiotensin II (Ang II) treatment were developed as an in vitro fibrotic model. The cells were treated by Poly in the presence of Ang II. Molecular expression was detected by RT-PCR, immunoblotting, and immunofluorescence staining. RESULTS: We identified a heteropolysaccharide composed of arabinose and galactose (molar ratio, 0.73:0.27) with a predicted chemical structure characterized by a backbone composed of 1,5-α-Araf, 1,3,5-α-Araf, 1,6-α-Galp, and 1,3,6-ß-Galp and side chains comprised of T-α-Araf, T-α-Arap, and 1,3-α-Araf. Pretreatment of UUO mice with Poly effectively alleviated glomerulosclerosis and tubulointerstitial fibrosis. Moreover, Poly pretreatment down-regulated the expression of extracellular matrix (ECM) protein fibronectin (FN), profibrotic factor VEGF, proinflammatory cytokines MCP-1 and Rantes in the obstructed kidney. Similarly, the incubation of SV40-MES13 cells with Poly significantly inhibited Ang II-induced elevation in accumulation and expression level of FN and attenuated Ang II-evoked up-regulation in protein expression of MCP-1 and Rantes. CONCLUSIONS: Our study isolated and identified a naturally occurring heteropolysaccharide in FLL and revealed its potential in protecting the kidneys from fibrosis.


Assuntos
Nefropatias , Ligustrum , Obstrução Ureteral , Masculino , Camundongos , Animais , Ligustrum/química , Quimiocina CCL5/metabolismo , Fibrose , Nefropatias/tratamento farmacológico , Rim , Obstrução Ureteral/metabolismo , Polissacarídeos/farmacologia , Polissacarídeos/uso terapêutico , Angiotensina II/metabolismo
7.
Cytokine ; 161: 156048, 2023 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-36279697

RESUMO

BACKGROUND: Endothelin-1 (ET-1), a potent endogenous vasoconstrictor, stimulates production of reactive oxygen species. Endothelial monocyte-activating polypeptide-II (EMAP-II) is a multifunctional polypeptide. AIM: To assess ET-1 gene polymorphism (G8002A) in pediatric patients with ß-thalassemia major (ß-TM) as a potential genetic marker for vascular dysfunction and its possible relation to EMAP II, oxidative stress and vascular complications. METHODS: ß-TM patients (n = 95) without symptomatic cardiac or renal disease were compared with 95 healthy controls. Markers of hemolysis, serum ferritin, urinary albumin-to-creatinine ratio, serum EMAP II, malondialdehyde (MDA) and antioxidant enzymes; superoxide dismutase (SOD), glutathione peroxidase (GPx), reduced glutathione (GSH), glutathione reductase and catalase were measured. ET-1 gene polymorphism (G8002A) was determined using polymerase chain reaction­restriction fragment length polymorphism. RESULTS: ß-TM patients had significantly higher EMAP II than healthy controls. EMAP II was significantly higher among patients with cardiac disease, pulmonary hypertension (PH) risk, nephropathy, poor compliance to therapy and ferritin ≥ 2500 µg/L. There were significant correlations between EMAP II and transfusion index, LDH, ferritin and oxidative stress markers. The AA genotype of ET-1 gene polymorphism (G8002A) was significantly higher among ß-TM patients than controls. The number of patients with cardiac disease, PH risk or nephropathy was significantly higher among AA genotype compared with GG and GA genotypes. Lactate dehydrogenase (LDH), serum ferritin, EMAP II, MDA, SOD and GPx were significantly higher in AA genotype. CONCLUSION: ET-1 gene polymorphism (G8002A) could be a possible genetic marker for prediction of increased susceptibility to cardiopulmonary and renal complications among pediatric patients with ß-TM.


Assuntos
Endotelina-1 , Proteínas de Ligação a RNA , Talassemia beta , Criança , Humanos , Talassemia beta/genética , Talassemia beta/complicações , Talassemia beta/terapia , Endotelina-1/genética , Ferritinas , Marcadores Genéticos , Cardiopatias/complicações , Polimorfismo Genético , Superóxido Dismutase , Nefropatias , Proteínas de Ligação a RNA/genética
8.
J Ethnopharmacol ; 301: 115755, 2023 Jan 30.
Artigo em Inglês | MEDLINE | ID: mdl-36181985

RESUMO

ETHNOPHARMACOLOGICAL RELEVANCE: The prevalence of kidney disease has increased rapidly in recent years and has emerged as one of the leading causes of mortality worldwide. Natural products have been suggested as valuable nephroprotective agents due to their multi-target and synergistic effects on modulating important proteins involved in kidney injury. There is a large number of plant species that have been used traditionally for kidney-related conditions in Mesoamerican medicine by different cultural groups that could provide a valuable source of nephroprotective therapeutic candidates and could lead to potential drug discovery. AIM OF REVIEW: This review aims to provide an overview of the currently known efficacy of plant species used traditionally in Mesoamerica by Mayan groups to treat kidney-related conditions and to analyze the phytochemical, pharmacological, molecular, toxicological, and clinical evidence to contribute to public health efforts and for directing future research. METHODS: Primary sources of plant use reports for traditional kidney-related disorders in Mesoamerica were searched systematically from library catalogs, theses, and scientific databases (PubMed, Google Scholar; and Science Direct), and were filtered according to usage frequency in Mayan groups and plant endemism. The database of traditional plants was further analyzed based on associations with published reports of the phytochemical, pharmacological, molecular, toxicological, and clinical evidence. RESULTS: The most reported kidney-related conditions used traditionally in Mayan medicine involve reducing renal damage (a cultural interpretation that considers an inflammatory or infectious condition), cleaning or purifying the blood and kidney, reducing kidney pain, and eliminating kidney stones. A total of 208 plants used for kidney-related problems by 10 Mayan groups were found, representing 143 native species, where only 42 have reported pharmacological activity against kidney damage, mainly approached by in vitro and in vivo models of chemical- or drug-induced nephrotoxicity, diabetes nephropathy, and renal injury produced by hypertension. Nephroprotective effects are mainly mediated by reducing oxidative stress, inflammatory response, fibrosis mechanisms, and apoptosis in the kidney. The most common nephroprotective compounds associated with traditional Mayan medicine were flavonoids, terpenoids, and phenolic acids. The most widely studied traditional plants in terms of pharmacological evidence, bioactive compounds, and mechanisms of action, are Annona muricata L., Carica papaya L., Ipomoea batatas (L.) Lam., Lantana camara L., Sechium edule (Jacq.) Sw., Tagetes erecta L., and Zea mays L. Most of the plant species with reported pharmacological activity against kidney damage were considered safe in toxicological studies. CONCLUSION: Available pharmacological reports suggest that several herbs used in traditional Mayan medicine for renal-associated diseases may have nephroprotective effects and consistent pharmacological evidence, nephroprotective compounds, and mechanisms of action in different models of kidney injury. However, more research is required to fully understand the potential of traditional Mayan medicine in drug discovery given the limited ethnobotanical studies and data available for most species with regards to identification on bioactive components, pharmacological mechanisms, and the scarce number of clinical studies.


Assuntos
Nefropatias , Medicina Tradicional , Humanos , Compostos Fitoquímicos/farmacologia , Compostos Fitoquímicos/uso terapêutico , Nefropatias/tratamento farmacológico , Rim , Substâncias Protetoras , Extratos Vegetais/farmacologia , Extratos Vegetais/uso terapêutico , Etnofarmacologia , Fitoterapia
9.
Curr Opin Nephrol Hypertens ; 32(1): 58-66, 2023 Jan 01.
Artigo em Inglês | MEDLINE | ID: mdl-36444663

RESUMO

PURPOSE OF REVIEW: Glomerular filtration rate (GFR) assessment and its estimation (eGFR) is a long-lasting challenge in medicine and public health. Current eGFR formulae are indexed for standardized body surface area (BSA) of 1.73 m2, ignoring persons and populations wherein the ratio of BSA or metabolic rate to nephron number might be different, due to increased BSA, increased metabolic rate or reduced nephron number. These equations are based on creatinine, cystatin C or a combination of the two, which adds another confounder to eGFR assessment. Unusually high GFR values, also known as renal hyperfiltration, have not been well defined under these equations. RECENT FINDINGS: Special conditions such as solitary kidney in kidney donors, high dietary protein intake, obesity and diabetes are often associated with renal hyperfiltration and amenable to errors in GFR estimation. In all hyperfiltration types, there is an increased intraglomerular pressure that can be physiologic, but its persistence over time is detrimental to glomerulus leading to progressive glomerular damage and renal fibrosis. Hyperfiltration might be underdiagnosed due to BSA standardization embedded in the formula. Hence, timely intervention is delayed. Reducing intraglomerular pressure in diabetes can be achieved by SGLT2 inhibitors or low protein diet to reverse the glomerulopathy process. SUMMARY: Accurate identification of glomerular hyperfiltration as a pre-CKD condition needs accurate estimation of GFR in the above normal range should establish a threshold for timely intervention.


Assuntos
Proteínas na Dieta , Nefropatias , Humanos , Glomérulos Renais , Taxa de Filtração Glomerular , Rim
10.
J Hypertens ; 41(1): 194-197, 2023 Jan 01.
Artigo em Inglês | MEDLINE | ID: mdl-36129111

RESUMO

Renal artery aneurysmal (RAA) disease is a rare, but potentially life-threatening cause of renovascular disease presenting with hypertension. Conventional management involves aneurysmal excision followed by renal auto-transplantation. We present the management of a 13-year-old girl with complex multiple saccular aneurysmal disease of the left renal artery with hilar extension and symptomatic hypertension. We used 3D printing to print a patient-specific model that was not implanted in the patient but was used for surgical planning and discussion with the patient and their family. Endovascular options were precluded due to anatomical complexities. Following multi-disciplinary review and patient-specific 3D printing, she underwent successful in-situ RAA repair with intraoperative cooling, without the need for auto-transplantation. 3D printing enabled appreciation of aneurysmal spatial configuration and dimensions that also helped plan the interposition graft length needed following aneurysmal excision. The models provided informed multidisciplinary communications and proved valuable during the consent process with the family for this high-risk procedure. To our knowledge, this is the first reported case utilizing 3D printing to facilitate in-situ complex repair of RAA with intra-hilar extension for paediatric renovascular disease.


Assuntos
Aneurisma , Hipertensão Renovascular , Hipertensão , Nefropatias , Feminino , Humanos , Criança , Adolescente , Artéria Renal/cirurgia , Aneurisma/diagnóstico por imagem , Aneurisma/cirurgia , Aneurisma/complicações , Hipertensão Renovascular/etiologia , Nefropatias/complicações , Impressão Tridimensional
11.
J Steroid Biochem Mol Biol ; 225: 106179, 2023 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-36150640

RESUMO

Various endocrinometabolic diseases, inclusively polycystic ovarian syndrome (PCOS) has been linked with increased risk of renal dysfunction with attendant cardiovascular disease (CVD) in women of reproductive age. Short chain fatty acids (SCFAs) especially acetate have been suggested as an immunometabolic modulator. However, the impact of SCFAs, particularly acetate on renal disorder in PCOS individuals is unknown. The present study therefore hypothesized that acetate would circumvent renal dysfunction in a rat model of PCOS, probably by suppressing NF-κB-dependent mechanism. Eight-week-old female Wistar rats were randomly distributed into four groups (n = 6), which received vehicle, sodium acetate (200 mg/kg), letrozole (1 mg/kg) and letrozole plus sodium acetate, respectively. The administrations were done by oral gavage once daily for a duration of 21 days. Animals with PCOS showed insulin resistance, lipid dysmetabolism, hyperandrogenism, hyperleptinemia and hypoadiponectinemia. Besides, the result also revealed increased renal malondialdehyde, lactate production, inflammatory mediators (NF-κB and TNF-α), urea and creatinine concentration. Immunohistochemical evaluation of renal tissue also demonstrated severe expression of apoptosis and inflammation with BAX/NLRP3 antibodies. However, supplementation with acetate significantly attenuated these anomalies. Collectively, the present results suggest that acetate abolishes renal dysfunction in experimentally induced PCOS animals by attenuating androgen excess, apoptosis, oxidative stress and NF-κB/NLRP3 immunoreactivity.


Assuntos
Resistência à Insulina , Nefropatias , Síndrome do Ovário Policístico , Animais , Feminino , Ratos , Modelos Animais de Doenças , Letrozol/uso terapêutico , NF-kappa B , Proteína 3 que Contém Domínio de Pirina da Família NLR , Síndrome do Ovário Policístico/metabolismo , Ratos Wistar , Acetato de Sódio
12.
Vet Clin North Am Small Anim Pract ; 53(1): 53-71, 2023 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-36270837

RESUMO

A variety of urinary markers of the renal disease show promise for the identification of glomerular and tubular damage and monitoring treatment. Most of the markers are currently not widely available, and all could benefit from further study. This review summarizes recent studies on urinary biomarkers of renal disease in dogs and cats.


Assuntos
Doenças do Gato , Doenças do Cão , Nefropatias , Cães , Gatos , Animais , Lipocalina-2 , Doenças do Gato/diagnóstico , Doenças do Cão/diagnóstico , Nefropatias/diagnóstico , Nefropatias/veterinária , Biomarcadores
13.
Clin Exp Nephrol ; 26(1): 22-28, 2022 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-34342776

RESUMO

BACKGROUND: Cytomegalovirus (CMV) is a herpes virus that causes latent infections, and its reactivation due to immunosuppression can cause fatal complications. CMV reactivation is a complication frequently occurring in patients with kidney disease who require immunosuppressive therapy, and, therefore, this study retrospectively examined its risk factors. METHODS: Patients who received immunosuppressive therapy and underwent the CMV antigenemia test (CMV antigenemia: C7-HRP) for the treatment of primary nephritis (minimal change disease, membranous nephropathy, membranoproliferative glomerulonephritis, focal glomerulosclerosis, and IgA nephropathy) and anti-neutrophil cytoplasmic autoantibody (ANCA)-associated nephritis diagnosed at Saiseikai Kurihashi Hospital from January 2014 to December 2019 were recruited as study participants. Risk factors of CMV reactivation were examined using univariable and multivariable analyses. RESULTS: Among the 64 patients (36 men and 28 women; median age, 72 years) included, 34 had primary nephritis (20 minimal disease changes, 10 membranous nephropathy, 1 membranoproliferative glomerulonephritis, 1 focal glomerulosclerosis, and 2 IgA nephropathy) and 30 had ANCA-associated nephritis. Regarding glucocorticoid (GC), 43 patients received oral GC therapy, whereas 21 received GC pulse therapy. CMV reactivation participants showed significant differences in age, ANCA-associated nephritis, hemoglobin level, lymphocyte count, maximum GC dosage, and hemodialysis in univariable analysis. Multivariate analysis showed significantly lower lymphocyte counts in CMV-reactivated patients, but no significant difference in other factors. CONCLUSION: In patients with kidney disease, who require immunosuppressive therapy, CMV reactivation risk is high in patients with low lymphocyte count, and monitoring CMV during the treatment course could lead to early diagnosis and treatment of CMV disease.


Assuntos
Citomegalovirus , Nefropatias , Idoso , Feminino , Humanos , Nefropatias/diagnóstico , Masculino , Estudos Retrospectivos , Fatores de Risco , Ativação Viral
14.
BMJ Open ; 12(12): e064970, 2022 Dec 01.
Artigo em Inglês | MEDLINE | ID: mdl-36456002

RESUMO

OBJECTIVES: This study aimed to assess whether an excess mortality related to kidney and other urinary tract diseases exists among Italian people with AIDS (PWA), as compared with the general population without AIDS (non-PWA). DESIGN: Population-based, retrospective cohort study. SETTING AND PARTICIPANTS: We conducted a nationwide study including 9481 Italian PWA, aged 15-74 years, reported to the National AIDS Registry between 2006 and 2018. METHODS: Vital status and causes of death were retrieved by record linkage with the National Register of Causes of Death up to 2018. Excess mortality for PWA versus non-PWA was estimated through sex-standardised and age-standardised mortality ratios (SMRs) with corresponding 95% CIs. RESULTS: Among 2613 deceased PWA, 262 (10.0%) reported at least one urinary tract disease at death, including 254 (9.7%) non-cancer diseases-mostly renal failures (225 cases, 8.6%)-and 9 cancers (0.3%). The overall SMR for non-cancer urinary tract diseases was 15.3 (95% CI 13.4 to 17.3) with statistically significant SMRs for acute (SMR=22.3, 95% CI 18.0 to 27.4), chronic (SMR=8.4, 95% CI 6.0 to 11.3), and unspecified renal failure (SMR=13.8, 95% CI 11.2 to 16.8). No statistically significant excess mortality was detected for urinary tract cancers (SMR=1.7, 95% CI 0.8 to 3.3). The SMRs were particularly elevated among PWA aged <50 years, injecting drug users, or those with the first HIV-positive test >6 months before AIDS diagnosis. CONCLUSIONS: The excess mortality related to non-cancer kidney and other urinary tract diseases reported among PWA highlights the importance of implementing the recommendation for screening, diagnosis and management of such conditions among this population.


Assuntos
Síndrome de Imunodeficiência Adquirida , Nefropatias , Insuficiência Renal , Humanos , Estudos de Coortes , Estudos Retrospectivos , Rim , Itália/epidemiologia
15.
Enfoque Revista Científica de Enfermería ; 31(27): 24-38, jul.-dic.2022. ilus
Artigo em Espanhol | LILACS, BDENF - Enfermagem | ID: biblio-1380493

RESUMO

Los ensayos y escritos relacionados con el cuidado del paciente renal a través de los años se han enfocado a la calidad de vida, estilos de afrontamiento, satisfacción o percepciones que experimentan los pacientes durante su enfermedad. El presente articulo pretende reconocer que el cuidado de enfermería para con el paciente renal es un aspecto fundamental que proporciona al profesional la comprensión de la realidad del paciente y contribuye de manera positiva a comprender la realidad de enfermería como disciplina; enmarcadas en algunas posiciones que permiten garantizar su significado. Estas posiciones son la ética, la ontología y la epistemología. La ética se logra cuando el profesional de enfermería consigue proteger y respetar la dignidad humana del paciente renal que reciben atención de salud, la ontología se ocupa de reflexionar acerca de las concepciones de la realidad y sus relaciones centrando su finalidad en la búsqueda de la salud, del bienestar, la independencia y la trascendencia del paciente renal y la epistemología consiste en mostrar, de manera holística, la evolución del conocimiento de la enfermería para brindar un cuidado de excelencia al paciente renal.


Abstract Over the years, essays and writings related to kidney patient care have focused on quality of life, coping styles, satisfaction, or perceptions experienced by patients during their illness. This article aims to recognize that nursing care for kidney patients is a fundamental aspect that provides the professional with an understanding of the patient's reality and contributes positively to understanding the reality of nursing as a discipline framed in some positions that guarantee their meaning. These positions are ethics, ontology, and epistemology. Ethics is achieved when the nursing professional manages to protect and respect the human dignity of kidney patients who receive health care. Ontology deals with reflecting on the conceptions of reality and their relationships, focusing its purpose on the search for health, well-being, independence, and transcendence of kidney patients. And epistemology consists of showing, in a holistic way, the evolution of nursing knowledge to provide excellent care to kidney patients.


Resumo: Ensaios e escritos relacionados com os cuidados aos pacientes renais ao longo dos anos têmse focado na qualidade de vida, estilos de enfrentamento, satisfação ou percepções que os pacientes experimentam durante a sua doença. Este artigo tem como objetivo reconhecer que o cuidado de enfermagem para o doente renal é um aspecto fundamental que proporciona ao profissional uma compreensão da realidade do doente e contribui positivamente para a compreensão da realidade da enfermagem como disciplina; emoldurado em algumas posições que permitem garantir seu significado. Estas posições são ética, ontologia e epistemología. A ética é alcançada quando o profissional de enfermagem consegue proteger e respeitar a dignidade humana do paciente renal que recebe cuidados de saúde, a ontologia se preocupa em refletir sobre as concepções da realidade e as suas relações centrando o seu propósito na procura de saúde, bem-estar, independência e transcendência do paciente renal e epistemologia consiste em mostrar, holisticamente, a evolução do conhecimento de enfermagem para prestar um excelente cuidado ao paciente renal.


Assuntos
Humanos , Masculino , Feminino , Idoso , Conhecimento , Ética , Nefropatias/enfermagem , Cuidados de Enfermagem , Qualidade de Vida , Diagnóstico de Enfermagem , Conforto do Paciente
16.
Ren Fail ; 44(1): 2046-2055, 2022 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-36420664

RESUMO

The research and application of immune checkpoint inhibitors (ICIs) have enormously promoted the progression of tumor treatment. Gradual implementation of ICIs in clinical practice is largely limited as they exert uncontrolled collateral effects on the immune system, such as immune-related adverse events (irAEs); this includes rarely reported glomerular diseases. This study aimed to describe the clinical and pathological manifestation of ICIs-induced glomerular diseases and focused on the mechanism and therapeutic strategy for glomerular diseases associated with ICIs. The data of 53 patients with glomerular diseases related to ICIs were retrieved from the PubMed database. The most frequently reported ICIs-related glomerular diseases were pauci-immune glomerulonephritis (28.3%), podocytopathies (26.4%), and immune-complex glomerulonephritis (18.9%). Moreover, anti-PD1 antibodies were the most commonly used ICIs (71.4%). Most patients receiving ICIs discontinued the treatment (89.4%) and were initiated with steroids (87.2%). Rituximab was also useful in the treatment, especially for renal vasculitis. Rechallenging ICIs could be considered for cancer progression or as salvage therapy, where rechallenging ICI therapy with steroids may be beneficial. We believe the treatment should be personalized based on the degree of renal pathology, serum creatinine (Scr), and tumor progression to obtain a good prognosis.


Assuntos
Glomerulonefrite , Nefropatias , Neoplasias , Humanos , Inibidores de Checkpoint Imunológico/efeitos adversos , Neoplasias/tratamento farmacológico , Nefropatias/tratamento farmacológico , Glomerulonefrite/induzido quimicamente , Glomerulonefrite/tratamento farmacológico
17.
Hum Genomics ; 16(1): 53, 2022 11 03.
Artigo em Inglês | MEDLINE | ID: mdl-36329547

RESUMO

BACKGROUND: Proteins and metabolites are essential for many biological functions and often linked through enzymatic or transport reactions. Individual molecules have been associated with all-cause mortality. Many of these are correlated and might jointly represent pathways or endophenotypes involved in diseases. RESULTS: We present an integrated analysis of proteomics and metabolomics via a local dimensionality reduction clustering method. We identified 224 modules of correlated proteins and metabolites in the Atherosclerosis Risk in Communities (ARIC) study, a general population cohort of older adults (N = 4046, mean age 75.7, mean eGFR 65). Many of the modules displayed strong cross-sectional associations with demographic and clinical characteristics. In comprehensively adjusted analyses, including fasting plasma glucose, history of cardiovascular disease, systolic blood pressure and kidney function among others, 60 modules were associated with mortality. We transferred the network structure to the African American Study of Kidney Disease and Hypertension (AASK) (N = 694, mean age 54.5, mean mGFR 46) and identified mortality associated modules relevant in this disease specific cohort. The four mortality modules relevant in both the general population and CKD were all a combination of proteins and metabolites and were related to diabetes / insulin secretion, cardiovascular disease and kidney function. Key components of these modules included N-terminal (NT)-pro hormone BNP (NT-proBNP), Sushi, Von Willebrand Factor Type A, EGF And Pentraxin (SVEP1), and several kallikrein proteases. CONCLUSION: Through integrated biomarkers of the proteome and metabolome we identified functions of (patho-) physiologic importance related to diabetes, cardiovascular disease and kidney function.


Assuntos
Aterosclerose , Doenças Cardiovasculares , Diabetes Mellitus , Hipertensão , Nefropatias , Humanos , Idoso , Pessoa de Meia-Idade , Afro-Americanos/genética , Estudos Transversais , Proteômica , Fatores de Risco , Biomarcadores , Hipertensão/epidemiologia , Hipertensão/genética , Metabolômica , Aterosclerose/genética
18.
Food Funct ; 13(22): 11896-11914, 2022 Nov 14.
Artigo em Inglês | MEDLINE | ID: mdl-36321482

RESUMO

Luteolin is a natural flavonoid exhibiting multiple pharmacological activities. Renal anaemia is an important complication of chronic kidney disease (CKD). Whether luteolin can ameliorate renal interstitial fibrosis-induced renal anaemia remains unclear. We examined the therapeutic effects of luteolin in in vitro and in vivo models of renal interstitial fibrosis-induced renal anaemia. After high-throughput sequencing analysis of animal samples, we screened differentially expressed genes (DEGs) associated with luteolin-mediated improvements, performed GO and KEGG functional and pathway enrichment analyses, and validated the mechanism in vitro and in vivo. In vivo, haemoglobin and haematocrit were increased significantly, blood urea nitrogen and creatinine were decreased significantly, and the degree of renal interstitial injury and fibrosis was significantly alleviated in luteolin-treated mice compared with model mice. Erythropoietin (EPO) and hypoxia inducible factor 2A (HIF2A) levels were significantly increased and alpha smooth muscle actin (α-SMA), collagen I (COLI) and fibronectin (FN) levels were significantly decreased. Transcriptomic analysis revealed significant increases in sirtuin 1 (SIRT1) and forkhead box O3 (FOXO3) after luteolin intervention; these effects were validated in vitro and in vivo. Combined treatment with luteolin and the SIRT1 activator resveratrol or the SIRT1 inhibitor sirtinol and SIRT1-siRNA transfection revealed that blocking SIRT1 reduced FOXO3 expression and significantly decreased the benefits of luteolin, while resveratrol had the opposite effects. Molecular docking analysis indicated a stable conformation between luteolin and SIRT1. In vitro and in vivo systematic and transcriptomic studies showed that luteolin attenuates renal anaemia caused by renal fibrosis through the SIRT1/FOXO3 pathway.


Assuntos
Anemia , Nefropatias , Camundongos , Animais , Sirtuína 1/genética , Sirtuína 1/metabolismo , Luteolina/farmacologia , Resveratrol , Simulação de Acoplamento Molecular , Fibrose , Nefropatias/etiologia , Nefropatias/genética , Anemia/etiologia , Anemia/genética
19.
Molecules ; 27(22)2022 Nov 19.
Artigo em Inglês | MEDLINE | ID: mdl-36432138

RESUMO

Renal fibrosis progression is closely associated with aging, which ultimately leads to renal dysfunction. Salidroside (SAL) is considered to have broad anti-aging effects. However, the roles and mechanisms of SAL in aging-related renal fibrosis remain unclear. The study aimed to evaluate the protective effects and mechanisms of SAL in SAMP8 mice. SAMP8 mice were administered with SAL and Ferrostatin-1 (Fer-1) for 12 weeks. Renal function, renal fibrosis, and ferroptosis in renal tissue were detected. The results showed that elevated blood urea nitrogen (BUN) and serum creatinine (SCr) levels significantly decreased, serum albumin (ALB) levels increased, and mesangial hyperplasia significantly reduced in the SAL group. SAL significantly reduced transforming growth factor-ß (TGF-ß) and α-smooth muscle actin (α-sma) levels in SAMP8 mice. SAL treatment significantly decreased lipid peroxidation in the kidneys, and regulated iron transport-related proteins and ferroptosis-related proteins. These results suggested that SAL delays renal aging and inhibits aging-related glomerular fibrosis by inhibiting ferroptosis in SAMP8 mice.


Assuntos
Ferroptose , Nefropatias , Camundongos , Animais , Fibrose , Glucosídeos/farmacologia , Nefropatias/tratamento farmacológico
20.
Front Immunol ; 13: 1024068, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36420256

RESUMO

The specific B-cell depleting anti-CD20 monoclonal antibody rituximab (RTX) is effective in terms of the treatment of various immune-mediated glomerulopathies. The administration of RTX has been shown to be reliable and highly effective particularly in patients with ANCA-associated vasculitis, which is manifested predominantly with non-nephrotic proteinuria. Stable long-term B-cell depletion is usually readily attained in such patients using standard dosing regimens. However, in patients with nephrotic syndrome and non-selective proteinuria, the RTX pharmacokinetics is altered profoundly and RTX does not maintain high enough levels for a sufficiently long period, which may render RTX treatment ineffective. Since complement-derived cytotoxicity is one of the important modes of action of RTX, hypocomplementemia, frequently associated with systemic lupus erythematodes, may act to hamper the efficacy of RTX in the treatment of patients with lupus nephritis. This review provides a description of RTX pharmacokinetics and pharmacodynamics in several selected glomerulopathies, as well as the impact of proteinuria, anti-drug antibodies and other clinical variables on the clearance and volume of distribution of RTX. The impact of plasmapheresis and peritoneal dialysis on the clearance of RTX is also discussed in the paper. A review is provided of the potential association between pharmacokinetic and pharmacodynamic alterations in various kidney-affecting glomerular diseases, the sustainability of B-cell depletion and the clinical efficacy of RTX, with proposals for potential dosing implications. The role of therapeutic drug monitoring in treatment tailoring is also discussed, and various previously tested RTX dosing schedules are compared in terms of their clinical and laboratory treatment responses. Since alternative anti-CD20 molecules may prove effective in RTX unresponsive patients, their pharmacokinetics, pharmacodynamics and current role in the treatment of glomerulopathies are also mentioned.


Assuntos
Antígenos CD20 , Nefropatias , Humanos , Rituximab/uso terapêutico , Proteinúria , Anticorpos Monoclonais
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