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1.
Braz. j. biol ; 84: e254646, 2024. tab, ilus
Artigo em Inglês | LILACS, VETINDEX | ID: biblio-1360224

RESUMO

Chronic stress (CS) can contribute to dysfunction in several organs including liver and kidney. This study was performed to investigate the changes in serum biochemistry, histological structure, as well as in localization of tyrosine phosphorylated proteins (TyrPho) and Heat shock protein 70 (Hsp-70) in liver and kidney tissues of CS rats induced by two stressors (restrained and force swimming) for 60 consecutive days. Samples of blood, liver, and kidney were collected from adult male Sprague-Dawley rats in each group. Our results showed that serum biochemical parameters including corticosterone, blood sugar, urea nitrogen, creatinine, cholesterol, triglyceride, HDL-C, LDL-C, ALT, AST, alkaline phosphatase in CS group were significantly different from that in normal group in both liver and kidney tissues. Although histological structure was not changed. TyrPho expression was significantly increased in liver lysate but significantly decreased in kidney. Hsp-70 expression in liver increased whereas in kidney decreased. In conclusion, CS can induce changes in liver and kidney functions.


O estresse crônico (SC) pode contribuir para a disfunção em vários órgãos, incluindo fígado e rim. Este estudo foi realizado para investigar as alterações na bioquímica sérica, estrutura histológica, bem como na localização de proteínas tirosina fosforiladas (TyrPho) e proteína de choque térmico 70 (Hsp-70) em tecidos hepáticos e renais de ratos CS induzidas por dois estressores (restrito e natação forçada) por 60 dias consecutivos. Amostras de sangue, fígado e rim foram coletadas de ratos Sprague-Dawley machos adultos em cada grupo. Nossos resultados mostraram que os parâmetros bioquímicos séricos, incluindo corticosterona, glicemia, nitrogênio ureico, creatinina, colesterol, triglicerídeos, HDL-C, LDL-C, ALT, AST, fosfatase alcalina no grupo CS foram significativamente diferentes do grupo normal em ambos os fígados e tecidos renais. Embora a estrutura histológica não tenha sido alterada, a expressão de TyrPho aumentou significativamente no lisado hepático, mas diminuiu significativamente no rim. A expressão de Hsp-70 no fígado aumentou, enquanto que no rim diminuiu. Em conclusão, a CS pode induzir alterações nas funções hepáticas e renais.


Assuntos
Ratos , Estresse Fisiológico , Ratos Sprague-Dawley , Rim/anatomia & histologia , Fígado/anatomia & histologia
2.
Clin Interv Aging ; 18: 61-69, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-36660542

RESUMO

Purpose: To investigate the relationship between benign prostatic hyperplasia (BPH)/lower urinary tract symptoms (LUTS) and renal function in elderly men aged 80 years and older. Patients and Methods: We selected 389 elderly men aged 80-97 years with BPH/LUTS hospitalized at The Second Division of General Geriatrics, The First Affiliated Hospital of Zhengzhou University, between July 2018 and July 2020. In the cross-sectional study, patients were divided into the treatment (233 patients) and non-treatment (156 patients) groups based on whether they received treatment for BPH/LUTS. In the prospective self-case-control study, we included 129 of the non-treatment group patients who received oral BPH/LUTS medication and completed the 6-month outpatient follow-up. We compared prostate indicators and renal function in the cross-sectional study and baseline and after-treatment data in the prospective self-case-control study. Multiple linear regression analysis was performed for risk factors affecting renal function before and after BPH/LUTS treatment. Results: In the cross-sectional study, renal function was significantly better in the treatment group than in the non-treatment group. In the subgroup analysis of the prospective self-case-control study, renal function significantly improved after treatment among patients with hypertension and those with chronic kidney disease (CKD) 3a, but not in the entire cohort. Multivariable linear regression analysis showed that hypertension (ß=2.06, 95% CI 0.40 to 3.71) and CKD 3a (ß=17.16, 95% CI 15.53 to 18.79) were independent risk factors for creatinine differences before and after treatment, whereas hypertension (ß=-2.27, 95% CI -3.65 to -0.89), CKD 3a (ß=-11.93, 95% CI -13.29 to -10.58), and baseline prostate volume (ß=-0.11, 95% CI -0.20 to -0.02) were independent risk factors for estimated glomerular filtration rate differences before and after treatment. Conclusion: Treatment for moderate and severe BPH/LUTS can improve renal function in elderly patients with hypertension or CKD 3a.


Assuntos
Hipertensão , Sintomas do Trato Urinário Inferior , Hiperplasia Prostática , Insuficiência Renal Crônica , Masculino , Idoso , Humanos , Hiperplasia Prostática/complicações , Hiperplasia Prostática/tratamento farmacológico , Estudos de Casos e Controles , Estudos Prospectivos , Estudos Transversais , Sintomas do Trato Urinário Inferior/tratamento farmacológico , Sintomas do Trato Urinário Inferior/etiologia , Hipertensão/complicações , Insuficiência Renal Crônica/complicações , Rim/fisiologia
3.
Pediatr Surg Int ; 39(1): 85, 2023 Jan 20.
Artigo em Inglês | MEDLINE | ID: mdl-36662290

RESUMO

INTRODUCTION: A non-functional kidney (NFK) has been defined as one having paper-thin parenchyma, and split renal function (SRF) of < 10% on a nuclear scan. There are differences of opinion about nephrectomy or pyeloplasty in these patients. The present study was conducted to assess our management strategy of renal salvage for NFK. MATERIALS AND METHODS: It was a retrospective cohort study from January 2015 to July 2022, patients having SRF < 10% were included. These patients underwent ultrasound-guided percutaneous nephrostomy (PCN). A repeat nuclear scan was performed after 3 months. If SRF increased to > 10%, pyeloplasty was performed. RESULTS: Fifteen patients were managed. The mean age was 24.67 ± 23.61 months. Male to female ratio was 4:1. The initial mean SRF was 6.67 ± 2.85, which improved to 16.80 ± 4.69 after 3 months of placing the PCN (p < 0.001). The corresponding changes in the mean effective renal plasma flow (ERPF) were 60.13 ± 24.08 to 106.53 ± 24.61 (p < 0.001). There was no complaint after the placement of PCN. All patients underwent dismembered pyeloplasty. CONCLUSION: In NFK due to PUJO, expectant treatment in form of PCN followed by pyeloplasty appears to be the primary treatment modality, and nephrectomy may not be needed in any of them.


Assuntos
Hidronefrose , Obstrução Ureteral , Criança , Humanos , Masculino , Feminino , Lactente , Pré-Escolar , Pelve Renal/diagnóstico por imagem , Pelve Renal/cirurgia , Estudos Retrospectivos , Obstrução Ureteral/diagnóstico por imagem , Obstrução Ureteral/cirurgia , Rim/diagnóstico por imagem , Rim/cirurgia , Hidronefrose/cirurgia , Resultado do Tratamento , Procedimentos Cirúrgicos Urológicos
4.
PLoS One ; 18(1): e0279944, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-36662718

RESUMO

Extracellular histones are cytotoxic molecules involved in experimental acute kidney injury. In patients receiving a renal transplant from donors after circulatory death, who suffer from additional warm ischemia, worse graft outcome is associated with higher machine perfusate extracellular histone H3 concentrations. We now investigated temperature-dependent extracellular histone release in an ex vivo porcine renal perfusion model, and subsequently studied histone release in the absence and presence of non-anticoagulant heparin. Seven pairs of ischemically damaged porcine kidneys were machine perfused at 4°C (cold ischemia) or 28°C (warm ischemia). Perfusate histone H3 concentration was higher after warm as compared to cold ischemia (median (IQR) = 0.48 (0.20-0.83) µg/mL vs. 0.02 (0.00-0.06) µg/mL; p = .045, respectively). Employing immune-electron microscopy (EM), histone containing cytoplasmic protrusions of tubular and endothelial cells were found after warm ischemic injury. Furthermore, abundant histone localization was detected in debris surrounding severely damaged glomerular cells, in a "buck shot" pattern. In vitro, histones were cytotoxic to endothelial and kidney epithelial cells in a temperature-dependent manner. In a separate ex vivo experiment, addition of heparin did not change the total histone H3 levels observed in the perfusate but revealed a continuous increase in the level of a lower molecular weight histone H3 variant. Our findings show that ischemically damaged kidneys release more extracellular histones in warm ischemia, which by EM was due to histone release by renal cells. Blocking of histone-mediated damage during transplantation may be beneficial in prevention of renal injury.


Assuntos
Lesão por Frio , Histonas , Suínos , Animais , Células Endoteliais , Preservação de Órgãos , Perfusão , Rim , Isquemia , Isquemia Quente
5.
Nutrients ; 15(1)2023 Jan 03.
Artigo em Inglês | MEDLINE | ID: mdl-36615896

RESUMO

Chronic kidney disease (CKD) is a stealthy disease, and its development is linked to mechanisms including inflammation and oxidative stress. Catalpol (CAT), an iridoid glucoside from the root of Rehmannia glutinosa, is reported to manifest anti-inflammatory, antioxidant, antiapoptotic and antifibrotic properties. Hence, we studied the possible nephroprotective effects of CAT and its mechanisms in an adenine-induced (0.2% w/w in feed for 4 weeks) murine model of CKD by administering 5 mg/kg CAT to BALB/c mice for the duration of 4 weeks except during weekends. Upon sacrifice, the kidney, plasma and urine were collected and various physiological, biochemical and histological endpoints were assessed. CAT significantly ameliorated the adenine-induced altered body and kidney weight, water intake, urine volume, and concentrations of urea and creatinine in plasma, as well as the creatinine clearance and the albumin and creatinine ratio. Moreover, CAT significantly ameliorated the effect of adenine-induced kidney injury by reducing the kidney injury molecule-1, neutrophil gelatinase-associated lipocalin, cystatin C and adiponectin. Similarly, the augmented concentrations of markers of inflammation and oxidative stress in the adenine-treated group were markedly reduced with CAT pretreatment. Furthermore, CAT prevented adenine-induced deoxyribonucleic acid damage and apoptotic activity in the kidneys. Histologically, CAT significantly reduced the formation of tubular necrosis and dilation, as well as interstitial fibrosis in the kidney. In addition to that, CAT significantly decreased the adenine-induced increase in the phosphorylated NF-κB and reversed the reduced expression of sirtuin-1 in the kidney. In conclusion, CAT exhibits salutary effects against adenine-induced CKD in mice by mitigating inflammation, oxidative stress and fibrosis via mechanisms involving sirtuin-1 activation and NF-κB inhibition. Confirmatory studies are warranted in order to consider CAT as a potent nephroprotective agent against CKD.


Assuntos
Insuficiência Renal Crônica , Sirtuínas , Camundongos , Animais , Glucosídeos Iridoides/farmacologia , Glucosídeos Iridoides/uso terapêutico , NF-kappa B/metabolismo , Creatinina , Insuficiência Renal Crônica/induzido quimicamente , Insuficiência Renal Crônica/tratamento farmacológico , Estresse Oxidativo , Rim/metabolismo , Inflamação/metabolismo , Adenina/farmacologia , Fibrose , Sirtuínas/metabolismo
6.
Sci Rep ; 13(1): 85, 2023 Jan 03.
Artigo em Inglês | MEDLINE | ID: mdl-36596813

RESUMO

Biallelic pathogenic variants in the SLC34A3 gene, encoding for the NPT2c cotransporter, cause Hereditary Hypophosphatemic Rickets with Hypercalciuria (HHRH). However, the associated phenotype is highly variable. In addition, mice deleted for Slc34a3 exhibit a different phenotype compared to humans, without urinary phosphate leakage. The mechanisms by which SLC34A3 variants disrupt phosphate/calcium metabolism are un-completely understood. In this study we explored these mechanisms in vitro using SLC34A3 variants identified in patients with urinary phosphate leakage. We analyzed the consequences of these variants on NPT2c function and the link with the phenotype of the patients. We studied 20 patients with recurrent nephrolithiasis and low serum phosphate concentration harboring variants in the SLC34A3 gene. Half of the patients carried homozygous or composite heterozygous variants. Three patients had in addition variants in SLC34A1 and SLC9A3R1 genes. All these patients benefited from a precise analysis of their phenotype. We generated 13 of these mutants by site-directed mutagenesis. Then we carried out transient transfections of these mutants in HEK cells and measured their phosphate uptake capacity under different conditions. Among the 20 patients included, 3 had not only mutations in NPT2c but also in NPT2a or NHERF1 genes. Phosphate uptake was decreased in 8 NPT2c mutants studied and normal for 5. Four variants were initially categorized as variants of uncertain significance. Expression of the corresponding mutants showed that one did not modify phosphate transport, two reduced it moderately and one abolished it. Co-transfection of the NPT2c mutants with the wild-type plasmid of NPT2c or NPT2a did not reveal dominant negative effect of the mutants on NPT2c-mediated phosphate transport. A detailed analysis of patient phenotypes did not find a link between the severity of the disorder and the level of phosphate transport impairment. NPT2c mutations classified as ACMG3 identified in patients with renal phosphate leak should be characterized by in vitro study to check if they alter NPT2c-mediated phosphate transport since phosphate uptake capacity may not be affected. In addition, research for mutations in NHERF1 and NPT2a genes should always be associated to NPT2c sequencing.


Assuntos
Raquitismo Hipofosfatêmico Familiar , Humanos , Camundongos , Animais , Raquitismo Hipofosfatêmico Familiar/genética , Raquitismo Hipofosfatêmico Familiar/patologia , Rim/metabolismo , Mutação , Fenótipo , Fosfatos/metabolismo
7.
Langenbecks Arch Surg ; 408(1): 8, 2023 Jan 05.
Artigo em Inglês | MEDLINE | ID: mdl-36602631

RESUMO

PURPOSE: Autosomal dominant polycystic kidney disease (ADPKD) is a common hereditary disorder and accounts for 5-10% of all cases of kidney failure. 50% of ADPKD patients reach kidney failure by the age of 58 years requiring dialysis or transplantation. Nephrectomy is performed in up to 20% of patients due to compressive symptoms, renal-related complications or in preparation for kidney transplantation. However, due to the large kidney size in ADPKD, nephrectomy can come with a considerable burden. Here we evaluate our institution's experience of laparoscopic nephrectomy (LN) as an alternative to open nephrectomy (ON) for ADPKD patients. MATERIALS AND METHODS: We report the results of the first 12 consecutive LN for ADPKD from August 2020 to August 2021 in our institution. These results were compared with the 12 most recent performed ON for ADPKD at the same institution (09/2017 to 07/2020). Intra- and postoperative parameters were collected and analyzed. Health related quality of life (HRQoL) was assessed using the SF36 questionnaire. RESULTS: Age, sex, and median preoperative kidney volumes were not significantly different between the two analyzed groups. Intraoperative estimated blood loss was significantly less in the laparoscopic group (33 ml (0-200 ml)) in comparison to the open group (186 ml (0-800 ml)) and postoperative need for blood transfusion was significantly reduced in the laparoscopic group (p = 0.0462). Operative time was significantly longer if LN was performed (158 min (85-227 min)) compared to the open procedure (107 min (56-174 min)) (p = 0.0079). In both groups one postoperative complication Clavien Dindo ≥ 3 occurred with the need of revision surgery. SF36 HRQol questionnaire revealed excellent postoperative quality of life after LN. CONCLUSION: LN in ADPKD patients is a safe and effective operative procedure independent of kidney size with excellent postoperative outcomes and benefits of minimally invasive surgery. Compared with the open procedure patients profit from significantly less need for transfusion with comparable postoperative complication rates. However significant longer operation times need to be taken in account.


Assuntos
Laparoscopia , Rim Policístico Autossômico Dominante , Insuficiência Renal , Humanos , Pessoa de Meia-Idade , Rim Policístico Autossômico Dominante/cirurgia , Qualidade de Vida , Estudos Retrospectivos , Nefrectomia/métodos , Laparoscopia/métodos , Complicações Pós-Operatórias/etiologia , Insuficiência Renal/complicações , Insuficiência Renal/cirurgia , Perda Sanguínea Cirúrgica , Rim
8.
Mikrochim Acta ; 190(1): 45, 2023 01 05.
Artigo em Inglês | MEDLINE | ID: mdl-36602584

RESUMO

A nanosensor comprising of gold nanostars (Au-Nstars)-graphitic carbon nitride (g-C3N4) nanocomposite layered on a glassy carbon electrode (GCE) to detect serotonin (ST) in various body fluids has been fabricated. The nanocomposite and the sensing platform have been thoroughly characterized with UV-visible spectroscopy (UV-vis), transmission electron microscopy (TEM), selected area electron diffraction (SAED), energy dispersive X-ray photoelectron spectroscopy (EDX), and electrochemical techniques such as cyclic voltammetry (CV), linear sweep voltammetry (LSV), and electrochemical impedance spectroscopy (EIS). The designed ST detection probe has achieved a linear dynamic range (LDR) in the range 5 × 10-7 and 1 × 10-3 M with a limit of detection (LOD) of 15.1 nM (RSD < 3.3%). The ST detection capability of the fabricated sensor ranges between the normal and several abnormal pathophysiological situations. The sensor effectively detects ST in real matrices such as urine and blood serum, thus, showing its direct diagnostic applicability. Additionally, the sensor has been tested in the microenvironment of human embryonic kidney (HEK) cells to assess the possibility of ST secretion in cell lines. Interferences because of co-existing molecules have been evaluated, and the shelf-life of the fabricated sensor has been obtained as 8 weeks.


Assuntos
Nanocompostos , Serotonina , Humanos , Ouro/química , Nanocompostos/química , Espectroscopia Dielétrica , Rim
9.
J Feline Med Surg ; 25(1): 1098612X221145477, 2023 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-36649073

RESUMO

OBJECTIVES: Ultrasonography is used in the evaluation of urinary disorders, and the resistivity index (RI) and pulsatility index (PI) have been successfully used to detect early hemodynamic changes in the course of kidney diseases in humans and dogs. The aim of this study was to investigate RI and PI in cats with feline lower urinary tract disease (FLUTD). METHODS: Twenty-nine client-owned cats were selected and divided into a control group (CG; n = 10), a group of animals with obstructive FLUTD (OG; n = 11) and non-obstructive FLUTD (nOG; n = 8). Clinical, laboratory and ultrasound evaluations were performed in all cats. RESULTS: RI and PI values for cats in the CG were below the upper limit of normal suggested in other studies, while cats with FLUTD showed significantly higher values in the assessment of RI (P = 0.027 and P = 0.034, respectively) and PI (P = 0.044 and P = 0.048, respectively) of the right and left kidneys. CONCLUSIONS AND RELEVANCE: Alteration in renal blood flow was observed in cats with lower urinary tract disorders, even in the nOG group. To the best of our knowledge, this is the first report of renal blood flow changes related to non-obstructive FLUTD.


Assuntos
Doenças do Gato , Doenças Urológicas , Animais , Gatos , Doenças do Gato/diagnóstico , Rim/irrigação sanguínea , Ultrassonografia/veterinária , Ultrassonografia Doppler/veterinária , Doenças Urológicas/veterinária
10.
PLoS One ; 18(1): e0280270, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-36649229

RESUMO

The podocyte is a specialized cell type critically involved in maintaining the selective filtration barrier of the kidney. Podocytes are primary or secondary targets for a multitude of kidney diseases. Despite intense investigation, the transcriptome and proteome of human podocytes remain incompletely characterized. Here, we analyzed publicly available RNA-Seq data from human kidneys (n = 85) to computationally identify potential novel podocyte markers. For confirmation, we used an online histology resource followed by in-house staining of human kidneys and biochemical fractionation of glomeruli. Initial characterization of the novel podocyte transcripts was performed using viral overexpression and mRNA silencing. Several previously unrecognized gene products were identified that correlated to established podocyte markers on the RNA level and that were histologically localized to podocytes. ARMH4 (a.k.a. UT2 or C14orf37) and WIPF3 (a.k.a CR16) were among the hits. We show that these transcripts increase in response to overexpression of the podocyte transcription factor LMX1B. Overexpression of ARMH4 from low endogenous levels in primary kidney epithelial cells reduced the release of the inflammatory mediators IL-1B and IL-8 (CXCL8). The opposite effect was seen in mature human podocytes when ARMH4 was silenced. Overexpression of WIPF3 stabilized N-WASP, known to be required for maintenance of podocyte foot processes, and increased cell motility as shown using a scratch assay. Moreover, data from normal and diseased human kidneys showed that ARMH4 was downregulated in glomerular pathologies, while WIPF3 remained constantly expressed. ARMH4 and WIPF3 are new potential markers of human podocytes, where they may modulate inflammatory insults by controlling cytokine release and contribute to cytoskeletal dynamics, respectively.


Assuntos
Nefropatias , Proteínas dos Microfilamentos , Podócitos , Humanos , Imunomodulação , Rim/patologia , Nefropatias/patologia , Glomérulos Renais/patologia , Podócitos/metabolismo , Fatores de Transcrição/metabolismo , Proteínas dos Microfilamentos/metabolismo
11.
Sci Rep ; 13(1): 49, 2023 Jan 02.
Artigo em Inglês | MEDLINE | ID: mdl-36593273

RESUMO

Simultaneous deceased donor pancreas and living donor kidney transplant (SPLK) has certain advantages over conventional simultaneous pancreas-kidney transplant (SPK) and may be beneficial for overcoming the paucity of organs needed for diabetic patients requiring transplant. We compared the clinical outcomes of patients who underwent either SPK (n = 149) or SPLK (n = 46) in terms of pre- and post-transplantation variables, development of de novo DSA, occurrence of biopsy-proven acute rejection (BPAR), and graft survival rates. There were no significant differences in the baseline characteristics between the SPK and SPLK groups except for the shorter cold ischemic time of kidney grafts, shorter duration of diabetes, older age of pancreas graft-donors, and younger age of kidney graft-donors in the SPLK group. Our results showed that the death-censored pancreas graft survival rate was lower in the SPLK group. In addition, the incidence of BPAR of the pancreas graft was higher in the SPLK group. There was no significant difference in the presence of de novo DSA and the rates of kidney graft failure, kidney BPAR, and mortality. Our results show that SPLK can be considered an alternative option for SPK although higher incidences of BPAR and graft failure of pancreas after SPLK need to be overcome.


Assuntos
Diabetes Mellitus Tipo 1 , Diabetes Mellitus , Transplante de Rim , Transplante de Pâncreas , Humanos , Transplante de Rim/efeitos adversos , Doadores Vivos , Pâncreas/cirurgia , Transplante de Pâncreas/efeitos adversos , Diabetes Mellitus/etiologia , Sobrevivência de Enxerto , Rim , Diabetes Mellitus Tipo 1/etiologia
12.
Am J Transplant ; 23(1): 11-25, 2023 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-36695612

RESUMO

Ischemia/reperfusion injury (IRI) is prone to occur after kidney transplantation, leading to delayed graft function (DGF). MicroRNAs play a crucial role in the pathogenesis of ischemia/reperfusion-induced acute kidney injury, and miR-20a-5p was found to be the most significantly upregulated gene in a DGF patient cohort. However, the roles of microRNAs in transplanted kidneys remain largely unknown. In this study, we found that miR-20a-5p was upregulated in the kidneys of acute kidney injury mice and in patients with DGF. We identified early growth response-1 as a critical upstream target and verified the binding of early growth response-1 to a predicted sequence in the promoter region of the miR-20a-5p gene. Functionally, the miR-20a-5p mimic attenuated IRI and postischemic renal fibrosis, whereas the miR-20a-5p inhibitor delivery aggravated IRI and fibrosis. Importantly, delivery of the miR-20a-5p mimic or inhibitor in the donor kidneys attenuated or aggravated renal loss and structural damage in cold storage transplantation injury. Furthermore, our study identified miR-20a-5p as a negative regulator of acyl-CoA synthetase long-chain family member 4 (ACSL4) by targeting the 3' untranslated region of ACSL4 mRNA, thereby inhibiting ACSL4-dependent ferroptosis. Our results suggest a potential therapeutic application of miR-20a-5p in kidney transplantation through the inhibition of ACSL4-dependent ferroptosis.


Assuntos
Injúria Renal Aguda , Ferroptose , MicroRNAs , Traumatismo por Reperfusão , Animais , Camundongos , MicroRNAs/genética , Rim/metabolismo , Traumatismo por Reperfusão/genética , Traumatismo por Reperfusão/prevenção & controle , Injúria Renal Aguda/genética , Isquemia , Coenzima A Ligases/genética
13.
Am J Transplant ; 23(1): 45-54, 2023 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-36695620

RESUMO

The demand for donors' kidneys continues to increase amid a shortage of available donors. Managing policies to thoughtfully allocate this scarce resource is a complex process. Although human leukocyte antigen (HLA) matching has been shown to prolong graft survival, its relative contribution to allocation schemes is empirically compromised owing to competing priorities. We explored using a new metric, Matched Donor Potential (MDP), to facilitate improved HLA matching while promoting equity. We interrogated all active kidney waitlist patients (N = 164 427), their corresponding unacceptable antigen files, and all effective donors in the Scientific Registry of Transplant Recipients (January 1, 2016-December 31, 2017). Cause-specific hazard functions were evaluated to assess the potential impact of the MDP metric on deceased donor transplant access rates for all candidates. Access was affected by ethnicity, blood group type, and calculated Panel Reactive Antibody (cPRA). Importantly, we show that access to transplantation is influenced by the patient's own HLA makeup regardless of their ethnicity and by the HLA makeup of effective donors. The MDP metric demonstrates a high association with access to transplantation. Adjusting Cox models to include this new metric resulted in improved access to kidney transplantation for waitlist candidates of minority heritage while significantly promoting HLA matching. Thus, the MDP metric accounts for balanced, equitable organ allocation algorithms.


Assuntos
Transplante de Rim , Obtenção de Tecidos e Órgãos , Humanos , Transplante de Rim/métodos , Doadores de Tecidos , Rim , Antígenos HLA , Sobrevivência de Enxerto , Teste de Histocompatibilidade/métodos
15.
Sci Rep ; 13(1): 861, 2023 Jan 17.
Artigo em Inglês | MEDLINE | ID: mdl-36650247

RESUMO

Iron plays an important role in hemodynamics and the immunity, independent of anemia. Since dynamic changes occur in iron storage after kidney transplantation (KT), we investigated the association between iron status and kidney outcomes in KT patients. We analyzed data from the KoreaN cohort study for Outcome in patients With KT (KNOW-KT). The iron status was classified into three groups based on ferritin or transferrin saturation (TSAT) levels one year after KT, with reference ranges of 20‒35% and 100‒300 ng/mL for TSAT and ferritin, respectively. The primary outcome was the composite outcome, which consisted of death, graft failure, and an estimated glomerular filtration rate decline ≥ 50%. In total, 895 patients were included in the final analysis. During a median follow-up of 5.8 years, the primary outcome occurred in 94 patients (19.8/1000 person-years). TSAT levels decreased one year after KT and thereafter gradually increased, whereas ferritin levels were maintained at decreased levels. The adjusted hazard ratios (95% confidence intervals) for the composite outcome were 1.67 (1.00-2.77) and 1.20 (0.60-2.40) in the TSAT > 35% and ferritin > 300 ng/mL groups, respectively. High iron status with high TSAT levels increases the risk of graft failure or kidney functional deterioration after KT.


Assuntos
Ferro , Transplante de Rim , Humanos , Estudos de Coortes , Transplante de Rim/efeitos adversos , Transferrina/análise , Ferritinas , Rim/química
16.
Sci Rep ; 13(1): 881, 2023 Jan 17.
Artigo em Inglês | MEDLINE | ID: mdl-36650223

RESUMO

We recently reported exacerbated endotoxic signs of neuroinflammation and autonomic defects in offspring of preeclamptic (PE) dams. Here, we investigated whether PE programming similarly modifies hemodynamic and renal vasoconstrictor responsiveness to endotoxemia in PE offspring and whether this interaction is modulated by gestational angiotensin 1-7 (Ang1-7). Preeclampsia was induced by gestational treatment with L-NAME. Adult offspring was challenged with lipopolysaccharides (LPS, 5 mg/kg) and systolic blood pressure (SBP) and renal vasoconstrictions were assessed 4 h later. Male, but not female, offspring of PE rats exhibited SBP elevations that were blunted by LPS. Renal vasoconstrictions induced by angiotensin II (Ang II), but not phenylephrine, were intensified in perfused kidneys of either sex. LPS blunted the heightened Ang II responses in male, but not female, kidneys. While renal expressions of AT1-receptors and angiotensin converting enzyme (ACE) were increased in PE offspring of both sexes, ACE2 was upregulated in female offspring only. These molecular effects were diminished by LPS in male offspring. Gestational Ang1-7 caused sex-unrelated attenuation of phenylephrine vasoconstrictions and preferentially downregulated Ang II responses and AT1-receptor and nuclear factor-kB (NFkB) expressions in females. Together, endotoxemia and Ang1-7 offset in sexually-related manners imbalances in renal vasoconstriction and AT1/ACE/ACE2 signaling in PE offspring.


Assuntos
Endotoxemia , Pré-Eclâmpsia , Animais , Feminino , Masculino , Ratos , Angiotensina II/metabolismo , Enzima de Conversão de Angiotensina 2/metabolismo , Endotoxemia/induzido quimicamente , Endotoxemia/metabolismo , Endotoxinas/metabolismo , Rim/metabolismo , Lipopolissacarídeos/farmacologia , Pré-Eclâmpsia/metabolismo , Sistema Renina-Angiotensina , Vasoconstrição
17.
BMJ Case Rep ; 16(1)2023 Jan 17.
Artigo em Inglês | MEDLINE | ID: mdl-36653047

RESUMO

A man in his 70s visited the hospital for chronic kidney disease with hypertension. He had anuria for several days before visiting the hospital. His creatinine level rose to 8.97 mg/dL (from 3 mg/dL) and his systemic blood pressure increased to 183 mm Hg. Other uraemic symptoms were also observed, and he was therefore admitted to the hospital and started continuous haemodiafiltration. MRI and angiography showed a highly stenotic lesion with calcification at the origin of the renal artery; a CT scan showed atrophy of the left kidney. Renal Doppler ultrasonography was performed and renal resistive indexes were: 0.92 for the left kidney and 0.68 for the right kidney. The viability of the right kidney was thought to be maintained, and percutaneous transluminal renal angioplasty (PTRA) for the right renal artery stenosis was performed; his creatinine level improved (3 mg/dL) and his systolic blood pressure decreased (120 mm Hg). We implanted a stent on the right stenotic lesion and the right renal artery blood flow improved. We experienced an effective PTRA for the right renal artery for bilateral renal artery stenosis. Although the indications of PTRA for renal artery stenosis are limited, the evaluation of renal function using ultrasonography could be a useful index for determining the culprit lesion.


Assuntos
Angioplastia com Balão , Falência Renal Crônica , Obstrução da Artéria Renal , Insuficiência Renal Crônica , Masculino , Humanos , Obstrução da Artéria Renal/complicações , Obstrução da Artéria Renal/diagnóstico por imagem , Obstrução da Artéria Renal/terapia , Creatinina , Rim/diagnóstico por imagem , Rim/fisiologia , Angioplastia , Insuficiência Renal Crônica/complicações , Insuficiência Renal Crônica/terapia
18.
Sichuan Da Xue Xue Bao Yi Xue Ban ; 54(1): 165-170, 2023 Jan.
Artigo em Chinês | MEDLINE | ID: mdl-36647661

RESUMO

Objective: To explore the clinical characteristics and the prognosis of diabetic foot ulcers (DFU) inpatients of different renal function statuses. Methods: A retrospective analysis of 962 inpatients with DFU was conducted. The patients were divided into three groups according to their renal function statuses, and the clinical characteristics of the three groups were compared to identify differences. In addition, the patients were followed up in outpatient clinics or by telephone and their prognostic status and risk factors for death were analyzed. Results: Analysis of the clinical characteristics showed that, compared with diabetic patients with normal renal function or mild renal function impairment, diabetic patients with moderate and severe renal function impairment had a longer course of disease ( P<0.001). Patients with foot ulcers of Wagner grade 4 predominates the moderate and severe renal function impairment groups ( P<0.05). Patients in the moderate and severe renal function impairment groups had a relatively higher proportion of comorbidities, including hypertension, coronary heart disease, and peripheral arterial disease ( P<0.05). These patients had relatively lower levels of glycosylated hemoglobin and hemoglobin (all P<0.05) and relatively higher levels of neutrophil ratio and procalcitonin (all P<0.05). Of the two groups, patients in the moderate renal function impairment group were older ( P<0.001) and had lower ankle-brachial index ( P<0.001). The severe renal function impairment group had a higher proportion of patients with foot ulcers of Wagner grades 3 and 5 (all P<0.05). For the purpose of conducting prognostic analysis, 748 patients were followed up in outpatient clinics or by telephone for a median length of 41 months. Among them, 239 died. The all-cause mortality was 31.9%, and the mortality in the three groups was 25.8%, 46.2% ( P<0.001), and 59.4% ( P<0.001), respectively. The survival rate of patients in the moderate and severe renal function impairment groups was significantly lower than those in the normal renal function and mild renal function impairment groups ( P<0.001). Univariate Cox regression analysis showed that age, concomitant coronary heart disease and peripheral arterial disease, degree of renal function impairment, and foot ulcers of Wagner grade 4 and 5 were associated with all-cause deaths. Furthermore, multivariate Cox regression analysis showed that moderate and severe renal function impairment was an independent risk factor for all-cause deaths in DFU patients ( P<0.001). Conclusions: As renal function impairment worsens, patients with DFU present clinical characteristics of greater complexity, higher risks of cardiovascular events, and higher mortality. It is essential to prevent kidney damage and foot ulcers, to pay attention to the cardiovascular risks of DFU patients with moderate and severe renal function impairment, and to reduce mortality.


Assuntos
Diabetes Mellitus , Pé Diabético , Doença Arterial Periférica , Humanos , Pé Diabético/complicações , Estudos Retrospectivos , Fatores de Risco , Prognóstico , Doença Arterial Periférica/complicações , Rim/fisiologia
19.
Function (Oxf) ; 4(1): zqac065, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-36654930

RESUMO

Nephrotoxicity is a major cause of kidney disease and failure in drug development, but understanding of cellular mechanisms is limited, highlighting the need for better experimental models and methodological approaches. Most nephrotoxins damage the proximal tubule (PT), causing functional impairment of solute reabsorption and systemic metabolic complications. The antiviral drug tenofovir disoproxil fumarate (TDF) is an archetypal nephrotoxin, inducing mitochondrial abnormalities and urinary solute wasting, for reasons that were previously unclear. Here, we developed an automated, high-throughput imaging pipeline to screen the effects of TDF on solute transport and mitochondrial morphology in human-derived RPTEC/TERT1 cells, and leveraged this to generate realistic models of functional toxicity. By applying multiparametric metabolic profiling-including oxygen consumption measurements, metabolomics, and transcriptomics-we elucidated a highly robust molecular fingerprint of TDF exposure. Crucially, we identified that the active metabolite inhibits complex V (ATP synthase), and that TDF treatment causes rapid, dose-dependent loss of complex V activity and expression. Moreover, we found evidence of complex V suppression in kidney biopsies from humans with TDF toxicity. Thus, we demonstrate an effective and convenient experimental approach to screen for disease relevant functional defects in kidney cells in vitro, and reveal a new paradigm for understanding the pathogenesis of a substantial cause of nephrotoxicity.


Assuntos
Antivirais , Insuficiência Renal , Humanos , Tenofovir/efeitos adversos , Antivirais/metabolismo , Rim , Mitocôndrias , Insuficiência Renal/tratamento farmacológico , Metabolômica
20.
J Clin Ultrasound ; 51(1): 96-106, 2023 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-36639848

RESUMO

PURPOSE: Antenatal detection of limb anomalies is not uncommon, and pregnancies are usually terminated in view of the expected physical handicap. The aim of this retrospective observational study is to delineate the spectrum of fetal limb anomalies and provide evidence in support of complete postnatal evaluation in establishing recurrence risk. METHODS: We present 54 cases of limb malformations detected antenatally and discuss the spectrum of abnormalities, the utility of fetal autopsy, and genetic testing to establish recurrence risk in subsequent pregnancies. RESULTS: 16/54 cases were isolated radial ray anomalies. There were five cases of amniotic band syndrome, five limb body wall complex cases, three VACTERL (vertebral defects, anal atresia, cardiac defects, tracheo-esophageal fistula, renal anomalies, and limb abnormalities) associations, one case of sirenomelia, two cases of limb pelvis hypoplasia, and one case of OEIS (Omphalocele Exstrophy Imperforate anus and spinal defects). Four fetuses with non-isolated radial ray anomaly had trisomy 18. One case with bilateral radial ray defect had a mutation in the FANC-E gene confirming fanconi anemia. Twelve cases were unclassified. CONCLUSION: Autopsy is the most important investigation in fetuses with limb anomalies. We suggest chromosomal microarray (CMA) as a first-tier test after autopsy. However, in cases of bilaterally symmetrical limb anomalies, in case of previous similarly affected child, or history of consanguinity, whole exome sequencing (WES) can be offered as the primary investigation, followed by CMA if WES is normal.


Assuntos
Cardiopatias Congênitas , Deformidades Congênitas dos Membros , Fístula Traqueoesofágica , Feminino , Humanos , Gravidez , Feto/diagnóstico por imagem , Cardiopatias Congênitas/diagnóstico por imagem , Cardiopatias Congênitas/genética , Rim/anormalidades , Deformidades Congênitas dos Membros/diagnóstico por imagem , Deformidades Congênitas dos Membros/genética , Traqueia/anormalidades , Fístula Traqueoesofágica/diagnóstico por imagem , Fístula Traqueoesofágica/genética , Diagnóstico Pré-Natal
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