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1.
Mol Med Rep ; 23(4)2021 04.
Artigo em Inglês | MEDLINE | ID: mdl-33655322

RESUMO

Diabetes and the associated complications are becoming a serious global threat and an increasing burden to human health and the healthcare systems. Diabetic nephropathy (DN) is the primary cause of end­stage kidney disease. Abnormal angiogenesis is well established to be implicated in the morphology and pathophysiology of DN. Factors that promote or inhibit angiogenesis serve an important role in DN. In the present review, the current issues associated with the vascular disease in DN are highlighted, and the challenges in the development of treatments are discussed.


Assuntos
Inibidores da Angiogênese/uso terapêutico , Nefropatias Diabéticas/tratamento farmacológico , Falência Renal Crônica/tratamento farmacológico , Rim/efeitos dos fármacos , Nefropatias Diabéticas/patologia , Humanos , Rim/patologia , Falência Renal Crônica/patologia
2.
Diabetes Res Clin Pract ; 174: 108754, 2021 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-33741351

RESUMO

AIM: Little is known about whether overhydration (OH), measured using bioimpedance assay (BIA), is associated with CKD progression in patients with type 2 diabetes mellitus (T2DM). We hypothesised that OH was a predictor, and pigment epithelium-derived factor (PEDF) was a modifiable risk factor of CKD progression. METHODS: We conducted a prospective cohort study of 1,065 patients with clinically euvolemic T2DM who attended the diabetes centre in a tertiary hospital or primary care clinic. CKD progression was defined as a combination of the worsening of the KDIGO defined CKD category by eGFR and a ≥25% decline in eGFR compared to baseline. RESULTS: Patients with T2DM in the highest tertile of OH and relative OH (OH/ extracellular water > 7%) were positively associated with CKD progression (hazard ratio [HR] 1.45 [95% confidence interval (CI) 1.14-1.85; p = 0.003 and HR 1.29 [95%CI 1.05-1.59; p = 0.017]). There were positive associations between PEDF and CKD progression (ß = 1.10; p = 0.001) and between OH and CKD progression (ß = 0.21; p = 0.036). OH remained positively associated with CKD progression mediated by PEDF. CONCLUSIONS: OH is an independent risk factor for CKD progression in patients with T2DM. Our study supports the novel definition of PEDF as a positive mediator between OH and CKD progression.


Assuntos
Diabetes Mellitus Tipo 2/fisiopatologia , Nefropatias Diabéticas/complicações , Proteínas do Olho/sangue , Falência Renal Crônica/patologia , Fatores de Crescimento Neural/sangue , Serpinas/sangue , Desequilíbrio Hidroeletrolítico/complicações , Progressão da Doença , Feminino , Taxa de Filtração Glomerular , Humanos , Falência Renal Crônica/sangue , Falência Renal Crônica/etiologia , Masculino , Pessoa de Meia-Idade , Prognóstico , Estudos Prospectivos , Fatores de Risco , Taxa de Sobrevida
3.
Am J Surg Pathol ; 45(4): 516-522, 2021 04 01.
Artigo em Inglês | MEDLINE | ID: mdl-33560656

RESUMO

We identified an unusual pattern of renal tubular proliferation associated with chronic renal disease, found in 23 patients, diffusely (n=12), or focally (n=11). Incidence was 5% of end-stage renal disease kidneys from one institution (8/177) and 7/23 patients with acquired cystic kidney disease-associated renal cell carcinoma from another. Most (19 patients) had 1 or more neoplasms including papillary (n=9), acquired cystic kidney disease (n=8), clear cell (n=4), or clear cell papillary (n=3) renal cell carcinoma. All (20 men, 3 women) had end-stage renal disease. The predominant pattern (n=18) was the indentation of chronic inflammation into renal tubules forming small polypoid structures; however, 5 had predominantly hyperplastic epithelium with less conspicuous inflammation. In 14 patients both patterns were appreciable, whereas the remainder had only the inflammatory pattern. Immunohistochemistry was positive for cytokeratin 7, high-molecular-weight cytokeratin, PAX8, and GATA3. Staining for alpha-methylacyl-CoA racemase was negative or weak, dramatically less intense than papillary neoplasms or proximal tubules. CD3 and CD20 showed a mixture of B and T lymphocytes in the inflammatory areas. Fluorescence in situ hybridization showed no trisomy 7 or 17 or loss of Y (n=9). We describe a previously uncharacterized form of renal tubular proliferation that differs from papillary adenoma (with weak or negative alpha-methylacyl-CoA racemase, lack of trisomy 7 or 17, and sometimes diffuse distribution). On the basis of consistent staining for high-molecular-weight cytokeratin and GATA3, we propose the name distal tubular hyperplasia for this process. Future studies will be helpful to assess preneoplastic potential and etiology.


Assuntos
Adenoma/patologia , Carcinoma de Células Renais/patologia , Proliferação de Células , Doenças Renais Císticas/patologia , Falência Renal Crônica/patologia , Neoplasias Renais/patologia , Túbulos Renais/patologia , Lesões Pré-Cancerosas/patologia , Adenoma/química , Adenoma/genética , Adulto , Idoso , Biomarcadores Tumorais/análise , Biomarcadores Tumorais/genética , Carcinoma de Células Renais/química , Carcinoma de Células Renais/genética , Diagnóstico Diferencial , Feminino , Humanos , Hiperplasia , Imuno-Histoquímica , Hibridização in Situ Fluorescente , Doenças Renais Císticas/genética , Doenças Renais Císticas/metabolismo , Falência Renal Crônica/genética , Falência Renal Crônica/metabolismo , Neoplasias Renais/química , Neoplasias Renais/genética , Túbulos Renais/química , Masculino , Pessoa de Meia-Idade , Lesões Pré-Cancerosas/genética , Lesões Pré-Cancerosas/metabolismo , Valor Preditivo dos Testes , Estados Unidos , Adulto Jovem
4.
PLoS One ; 16(1): e0244081, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33471808

RESUMO

RATIONAL AND OBJECTIVE: Prognosis provides critical knowledge for shared decision making between patients and clinicians. While several prognostic indices for mortality in dialysis patients have been developed, their performance among elderly patients initiating dialysis is unknown, despite great need for reliable prognostication in that context. To assess the performance of 6 previously validated prognostic indices to predict 3 and/or 6 months mortality in a cohort of elderly incident dialysis patients. STUDY DESIGN: Validation study of prognostic indices using retrospective cohort data. Indices were compared using the concordance ("c")-statistic, i.e. area under the receiver operating characteristic curve (ROC). Calibration, sensitivity, specificity, positive and negative predictive values were also calculated. SETTING & PARTICIPANTS: Incident elderly (age ≥75 years; n = 349) dialysis patients at a tertiary referral center. ESTABLISHED PREDICTORS: Variables for six validated prognostic indices for short term (3 and 6 month) mortality prediction (Foley, NCI, REIN, updated REIN, Thamer, and Wick) were extracted from the electronic medical record. The indices were individually applied as per each index specifications to predict 3- and/or 6-month mortality. RESULTS: In our cohort of 349 patients, mean age was 81.5±4.4 years, 66% were male, and median survival was 351 days. The c-statistic for the risk prediction indices ranged from 0.57 to 0.73. Wick ROC 0.73 (0.68, 0.78) and Foley 0.67 (0.61, 0.73) indices performed best. The Foley index was weakly calibrated with poor overall model fit (p <0.01) and overestimated mortality risk, while the Wick index was relatively well-calibrated but underestimated mortality risk. LIMITATIONS: Small sample size, use of secondary data, need for imputation, homogeneous population. CONCLUSION: Most predictive indices for mortality performed moderately in our incident dialysis population. The Wick and Foley indices were the best performing, but had issues with under and over calibration. More accurate indices for predicting survival in older patients with kidney failure are needed.


Assuntos
Falência Renal Crônica/mortalidade , Idoso , Idoso de 80 Anos ou mais , Área Sob a Curva , Comorbidade , Feminino , Humanos , Falência Renal Crônica/patologia , Masculino , Valor Preditivo dos Testes , Prognóstico , Curva ROC , Diálise Renal , Estudos Retrospectivos , Medição de Risco , Taxa de Sobrevida , Centros de Atenção Terciária
5.
Nephrol Dial Transplant ; 36(2): 355-365, 2021 01 25.
Artigo em Inglês | MEDLINE | ID: mdl-33439995

RESUMO

BACKGROUND: Outcomes after renal transplantation have traditionally been poor in systemic amyloid A (AA) amyloidosis and systemic light chain (AL) amyloidosis, with high mortality and frequent recurrent disease. We sought to compare outcomes with matched transplant recipients with autosomal dominant polycystic kidney disease (ADPKD) and diabetic nephropathy (DN), and identify factors predictive of outcomes. METHODS: We performed a retrospective cohort study of 51 systemic AL and 48 systemic AA amyloidosis patients undergoing renal transplantation. Matched groups were generated by propensity score matching. Patient and death-censored allograft survival were compared via Kaplan-Meier survival analyses, and assessment of clinicopathological features predicting outcomes via Cox proportional hazard analyses. RESULTS: One-, 5- and 10-year death-censored unadjusted graft survival was, respectively, 94, 91 and 78% for AA amyloidosis, and 98, 93 and 93% for AL amyloidosis; median patient survival was 13.1 and 7.9 years, respectively. Patient survival in AL and AA amyloidosis was comparable to DN, but poorer than ADPKD [hazard ratio (HR) = 3.12 and 3.09, respectively; P < 0.001]. Death-censored allograft survival was comparable between all groups. In AL amyloidosis, mortality was predicted by interventricular septum at end diastole (IVSd) thickness >12 mm (HR = 26.58; P = 0.03), while survival was predicted by haematologic response (very good partial or complete response; HR = 0.07; P = 0.018). In AA amyloidosis, recurrent amyloid was associated with elevated serum amyloid A concentration but not with outcomes. CONCLUSIONS: Renal transplantation outcomes for selected patients with AA and AL amyloidosis are comparable to those with DN. In AL amyloidosis, IVSd thickness and achievement of deep haematologic response pre-transplant profoundly impact patient survival.


Assuntos
Amiloidose/complicações , Falência Renal Crônica/mortalidade , Transplante de Rim/efeitos adversos , Idoso , Amiloidose/cirurgia , Feminino , Humanos , Falência Renal Crônica/etiologia , Falência Renal Crônica/patologia , Masculino , Pessoa de Meia-Idade , Prognóstico , Estudos Retrospectivos , Taxa de Sobrevida , Fatores de Tempo , Transplante Homólogo
6.
Anticancer Res ; 40(11): 6525-6530, 2020 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-33109593

RESUMO

BACKGROUND/AIM: End-stage kidney disease is characterized by chronic inflammation and frequent development of cancer. The level of circulating vitamin D is generally low in patients with end-stage renal disease (ESRD). Experimental studies have implicated the role of dysfunctional vitamin D metabolism in tumorigenesis. PATIENTS AND METHODS: We analyzed the expression of vitamin D receptor (VDR), cytochrome P450 family 27 subfamily B member 1 (CYP27B1) and cytochrome P450 family 24 subfamily A member 1 (CYP24A1), the key genes involved in vitamin D signaling, in kidneys from patients with ESRD, tissue microarrays containing ESRD-associated renal cell tumors, as well as in their precursor lesions by immunohistochemistry. RESULTS: Kidneys from patients with ESRD showed strong structural rearrangement with only few tubules and epithelial cell groups embedded in fibrotic-inflammatory stroma. Only an estimated 1-3% of the epithelial cells showed positive staining with antibodies to VDR, CYP27B1 and CYP24A1, which contrasted with the 100%, 40-50% and 40-50% of positively stained cells, respectively, found in normal kidneys. Down-regulation of the vitamin D signaling proteins was found in patients with renal cancer, with the exception of tumors and their precursors occurring exclusively in ESRD. CONCLUSION: The significantly reduced activity of CYP27B1 in kidney from patients with ESRD explains the low level of circulating vitamin D. We suggest that the lack of anti-tumorigenic effect of vitamin D is a crucial factor in the frequent development of unique types of renal cell cancer in in patients with ESRD.


Assuntos
25-Hidroxivitamina D3 1-alfa-Hidroxilase/genética , Carcinoma de Células Renais/genética , Falência Renal Crônica/genética , Receptores de Calcitriol/genética , Vitamina D3 24-Hidroxilase/genética , Carcinoma de Células Renais/sangue , Carcinoma de Células Renais/complicações , Carcinoma de Células Renais/patologia , Feminino , Regulação Neoplásica da Expressão Gênica/genética , Humanos , Rim/metabolismo , Rim/patologia , Falência Renal Crônica/sangue , Falência Renal Crônica/complicações , Falência Renal Crônica/patologia , Túbulos Renais/metabolismo , Túbulos Renais/patologia , Masculino , Redes e Vias Metabólicas/genética , Vitamina D/sangue
7.
Biomolecules ; 10(8)2020 08 09.
Artigo em Inglês | MEDLINE | ID: mdl-32784866

RESUMO

Glycosylation may strongly affect protein structure and functions. A high risk of cardiovascular complications seen in patients with end-stage renal disease (ESRD) is, at least partly associated with delayed clot formation, increased clot strength, and delayed cloth lysis. Taking into consideration that fibrinogen mediates these processes, we isolated fibrinogen from the plasma from patients with ESRD on peritoneal dialysis (ESRD-PD), and examined glycosylation of native fibrinogen and its subunits by lectin-based microarray and lectin blotting. Compared to healthy controls, fibrinogen from patients had increased levels of A2BG2 and decreased levels of FA2 glycan. The distribution of glycans on individual chains was also affected, with the γ chain, responsible for physiological functions of fibrinogen (such as coagulation and platelet aggregation), being most prone to these alterations. Increased levels of multi-antennary N-glycans in ESRD-PD patients were also associated with the type of dialysis solutions, whereas an increase in the fucosylation levels was strongly related to the peritoneal membrane damage. Consequently, investigation of fibrinogen glycans can offer better insight into fibrinogen-related complications observed in ESRD-PD patients and, additionally, contribute to prognosis, choice of personalised therapy, determination of peritoneal membrane damage, and the length of utilization of peritoneum for dialysis.


Assuntos
Fibrinogênio/química , Fibrinogênio/metabolismo , Fucose/metabolismo , Falência Renal Crônica/sangue , Diálise Peritoneal , Idoso , Idoso de 80 Anos ou mais , Biomarcadores/sangue , Feminino , Glicosilação , Humanos , Falência Renal Crônica/metabolismo , Falência Renal Crônica/patologia , Lectinas/sangue , Lectinas/química , Masculino , Pessoa de Meia-Idade , Polissacarídeos/sangue , Polissacarídeos/química , Polissacarídeos/metabolismo , Prognóstico , Análise Serial de Proteínas
8.
Transplantation ; 104(8): 1703-1711, 2020 08.
Artigo em Inglês | MEDLINE | ID: mdl-32732850

RESUMO

BACKGROUND: There are limited data on the outcome of transplant recipients with familial Mediterranean fever (FMF)-associated AA amyloidosis. The aim of the present study is to evaluate demographic, clinical, laboratory, and prognostic characteristics and outcome measures of these patients. METHODS: Eighty-one renal transplant recipients with FMF-associated AA amyloidosis (group 1) and propensity score-matched transplant recipients (group 2, n = 81) with nonamyloidosis etiologies were evaluated in this retrospective, multicenter study. Recurrence of AA amyloidosis was diagnosed in 21 patients (group 1a), and their features were compared with 21 propensity score-matched recipients with FMF amyloidosis with no laboratory signs of recurrence (group 1b). RESULTS: The risk of overall allograft loss was higher in group 1 compared with group 2 (25 [30.9%] versus 12 [14.8%]; P = 0.015 [hazard ratio, 2.083; 95% confidence interval, 1.126-3.856]). Patients in group 1 were characterized by an increased risk of mortality compared with group 2 (11 [13.6%] versus 0%; P = 0.001 [hazard ratio, 1.136; 95% confidence interval, 1.058-1.207]). Kaplan-Meier analysis revealed that 5- and 10-year patient survival rates in group 1 (92.5% and 70.4%) were significantly lower than in group 2 (100% and 100%; P = 0.026 and P = 0.023, respectively). Although not reaching significance, overall, 5- and 10-year graft survival rates (57.1%, 94.7%, and 53.8%, respectively) in group 1a were worse than in group 1b (76.2%, 95%, and 77.8%, respectively; P = 0.19, P = 0.95, and P = 0.27, respectively). CONCLUSIONS: AA amyloidosis is associated with higher risk of mortality after kidney transplantation. Inflammatory indicators should be monitored closely, and persistent high levels of acute-phase reactants should raise concerns about amyloid recurrence in allograft.


Assuntos
Amiloidose/cirurgia , Febre Familiar do Mediterrâneo/complicações , Rejeição de Enxerto/mortalidade , Falência Renal Crônica/cirurgia , Transplante de Rim/efeitos adversos , Adulto , Aloenxertos/imunologia , Aloenxertos/patologia , Amiloidose/imunologia , Amiloidose/mortalidade , Amiloidose/patologia , Biópsia , Febre Familiar do Mediterrâneo/imunologia , Febre Familiar do Mediterrâneo/mortalidade , Febre Familiar do Mediterrâneo/cirurgia , Feminino , Seguimentos , Rejeição de Enxerto/imunologia , Rejeição de Enxerto/patologia , Sobrevivência de Enxerto/imunologia , Humanos , Estimativa de Kaplan-Meier , Rim/imunologia , Rim/patologia , Falência Renal Crônica/imunologia , Falência Renal Crônica/mortalidade , Falência Renal Crônica/patologia , Masculino , Pessoa de Meia-Idade , Recidiva , Estudos Retrospectivos , Proteína Amiloide A Sérica/imunologia , Proteína Amiloide A Sérica/metabolismo , Taxa de Sobrevida , Resultado do Tratamento , Adulto Jovem
9.
PLoS One ; 15(8): e0238029, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32857782

RESUMO

BACKGROUND: This study analyzed the survival and protective predictors of in-hospital cardiopulmonary cerebral resuscitation (CPCR) to potentially help physicians create effective treatment plans for End-stage kidney disease (ESKD) patients. METHODS: We extracted the data of 7,116 ESKD patients who received their first in-hospital CPCR after initial dialysis between 2004 and 2012 from the National Health Insurance Research Database. The primary outcome was the survival rate during the first in-hospital CPCR. The secondary outcome was the median post-discharge survival. RESULTS: From 2004 through 2012, the incidence of in-hospital CPCR decreases from 3.97 to 3.67 events per 1,000 admission days (P for linear trend <0.001). The survival rate for the first in-hospital CPCR did not change significantly across the 9 years (P for trend = 0.244), whereas the median survival of post-discharge survival increased significantly from 3.0 months in 2004 to 6.8 months in 2011 (P for linear trend <0.001). In addition, multivariable analysis identified older age as a risk factor and prior intracardiac defibrillator (ICD) or cardiac resynchronization therapy defibrillator (CRT-D) implantation as a protective factor for in-hospital death during the first in-hospital CPCR. CONCLUSION: The incidence of in-hospital CPCR and the duration post-discharge among ESKD patients improved despite there being no significant difference in the survival rate of ESKD patients after CPCP. Either ICD or CRT-D implantation may be advisable for ESKD patients with a high risk of sudden cardiac death.


Assuntos
Reanimação Cardiopulmonar/estatística & dados numéricos , Falência Renal Crônica/patologia , Fatores Etários , Idoso , Comorbidade , Bases de Dados Factuais , Morte Súbita Cardíaca/epidemiologia , Morte Súbita Cardíaca/prevenção & controle , Desfibriladores Implantáveis , Feminino , Hospitais , Humanos , Falência Renal Crônica/complicações , Falência Renal Crônica/mortalidade , Masculino , Pessoa de Meia-Idade , Razão de Chances , Diálise Renal , Estudos Retrospectivos , Fatores de Risco , Taxa de Sobrevida
10.
PLoS One ; 15(7): e0235640, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32730268

RESUMO

BACKGROUND: Fluid overload is common in patients with diabetes and chronic kidney disease (DM and CKD; DMCKD) and can lead to structural and functional cardiac abnormalities including left ventricular hypertrophy (LVH) and left ventricular diastolic dysfunction (LVDD). Fluid overload represents a crucial step in the pathophysiological pathways to chronic heart failure in patients with end-stage renal disease. We evaluated the impact of fluid overload on cardiac alterations in patients with diabetes and non-dialysis-dependent CKD stage 5 (DMCKD5-ND) without intrinsic heart disease. METHODS: Bioimpedance spectroscopy, echocardiography, and N-terminal prohormone of B-type natriuretic peptide (NT-proBNP) measurement were performed in 135 consecutive patients on the same day. Patients were divided into groups by tertiles of overhydration/extracellular water (OH/ECW) per bioimpedance spectroscopy. RESULTS: Fluid balance markers including OH/ECW and NT-proBNP were significantly higher in the LVDD+LVH group. OH/ECW and its exacerbation were positively associated with the ratio between early mitral inflow and annular early diastolic velocities (E/e' ratio) and left ventricular mass index (LVMI). The prevalence of LVH progressively increased across increasing tertiles of OH/ECW. In multiple regression analyses, OH/ECW as a continuous and categorical variable was independently associated with the E/e' ratio and LVMI after adjustment for multiple confounding factors. CONCLUSIONS: Fluid overload was independently associated with LVDD and LVH in patients with DMCKD5-ND. Our study suggests that structural and functional cardiac abnormalities and volume status should be evaluated simultaneously in patients with early-stage DMCKD rather than only DMCKD5-ND, in addition to intensive blood pressure and glycemic control, regardless of evident cardiovascular disease.


Assuntos
Diabetes Mellitus Tipo 2/patologia , Hidratação , Falência Renal Crônica/patologia , Idoso , Espectroscopia Dielétrica , Ecocardiografia , Feminino , Taxa de Filtração Glomerular , Humanos , Hipertrofia Ventricular Esquerda/epidemiologia , Hipertrofia Ventricular Esquerda/patologia , Falência Renal Crônica/terapia , Modelos Lineares , Masculino , Pessoa de Meia-Idade , Peptídeo Natriurético Encefálico/sangue , Fragmentos de Peptídeos/sangue , Prevalência , Diálise Renal , Índice de Gravidade de Doença , Disfunção Ventricular Esquerda/patologia
11.
PLoS One ; 15(7): e0235900, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32649701

RESUMO

With the global problem of aging, it has become more difficult to improve the prognosis of older dialysis patients. Extended-hours hemodialysis offers longer treatment time compared to conventional hemodialysis regimen and provides favorable metabolic status, hemodynamic stability, and increased dietary intake. Despite prior studies reporting that in-center extended-hours hemodialysis can reduce the mortality rate, the treatment impact on elderly patients remains unclear. Therefore, we examined the association between extended-hours hemodialysis compared to conventional hemodialysis and all-cause mortality. Survival analyses using Cox proportional hazard model with multivariable adjustments and propensity-score based method were performed to compare mortality risk between 198 consecutive patients who started in-center extended-hours hemodialysis (Extended-HD) and 1407 consecutive patients who initiated conventional hemodialysis. The median age was 67.1 years in the Extended-HD group and 70.7 years in the conventional hemodialysis group. Extended-HD was associated with lower all-cause mortality in overall patients and the subgroup >70 years (adjusted hazard ratios of 0.60 [95% CI, 0.39-0.91] and 0.35 [95% CI, 0.18-0.69], respectively). There was a significant interaction between age >70 years and Extended-HD. In conclusion, extended-hours hemodialysis was associated with a lower mortality rate, especially in elderly patients.


Assuntos
Falência Renal Crônica/patologia , Diálise Renal/métodos , Fatores Etários , Idoso , Feminino , Humanos , Estimativa de Kaplan-Meier , Falência Renal Crônica/mortalidade , Falência Renal Crônica/terapia , Masculino , Pessoa de Meia-Idade , Pontuação de Propensão , Modelos de Riscos Proporcionais , Estudos Retrospectivos , Fatores de Risco
12.
PLoS One ; 15(7): e0235607, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32614909

RESUMO

Global climate change has led to a significant increase in temperature over the last century and has been associated with significant increases in the severity and frequency of heat injury (HI). The consequences of HI included dehydration and rhabdomyolysis, leading to acute kidney injury, which is now recognized as a clear risk factor for chronic kidney disease (CKD). We aimed to investigate the effects of HI on the risk of CKD. This nationwide longitudinal population-based retrospective cohort study utilized the Taiwan National Health Insurance Research Database (NHIRD) data. We enrolled patients with HI who were followed in NHIRD system between 2000 and 2013.We excluded patients diagnosed with CKD or genital-urinary system-related disease before the date of the new HI diagnosis. The control cohort consisted of individuals without HI history. The patients and control cohort were selected by 1:4 matching according to the following baseline variables: sex, age, index year, and comorbidities. The outcome measure was CKD diagnosis. In total, 815 patients diagnosed with HI were identified. During the 13 year observation period, we identified 72 CKD events (8.83%) in the heat stroke group and 143 (4.38%) CKD events in the control group. Patients with heat stroke had an increased risk of CKD than the control patients (adjusted HR = 4.346, P < 0.001) during the follow-up period. The risk of end-stage renal disease was also significantly increased in the heat stroke group than in the control group (adjusted hazards ratio: 9.078, p < 0.001). HI-related CKD may represent one of the first epidemics due to global warming. When compared to those without HI, patients with HI have an increased CKD risk.


Assuntos
Golpe de Calor/patologia , Insuficiência Renal Crônica/diagnóstico , Adulto , Bases de Dados Factuais , Feminino , Golpe de Calor/complicações , Temperatura Alta , Humanos , Falência Renal Crônica/complicações , Falência Renal Crônica/patologia , Estudos Longitudinais , Masculino , Pessoa de Meia-Idade , Modelos de Riscos Proporcionais , Insuficiência Renal Crônica/complicações , Insuficiência Renal Crônica/patologia , Estudos Retrospectivos , Fatores de Risco , Índice de Gravidade de Doença , Adulto Jovem
13.
PLoS One ; 15(5): e0232885, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32379841

RESUMO

There is no effectual pathological factor to predict the long-term renal prognosis of IgA nephropathy. Glomerular hypertrophy plays a crucial role in kidney disease outcomes in both experimental models and humans. This study aimed to 1) confirm the long-term prognostic significance of a maximal glomerular diameter (Max GD) ≥ 242.3 µm, 2) test a renal prognosis prediction model adding Max GD ≥ 242.3 µm to the Oxford classification (MEST-C), and 3) examine the time series changes in the long-term renal prognosis of patients with IgA nephropathy. The study included 43 patients diagnosed with IgA nephropathy from 1993 to 1998 at Kameda General Hospital. Renal prognosis with the endpoint of a 50% reduction in estimated glomerular filtration rate (eGFR) or the development of end-stage renal disease requiring dialysis was examined using logistic regression analysis, Cox regression analysis, and the Kaplan-Meier method. Pathological evaluation was performed using MEST-C and Max GD, and the validity of the prediction model was evaluated. Patients with Max GD ≥ 242.3 µm had significantly poor renal prognosis with multivariate Cox analysis (P = 0.0293). The results of the Kaplan-Meier analysis showed that kidney survival rates in the high-Max GD group were significantly lower than those in the low-Max GD group (log rank, P = 0.0043), which was confirmed in propensity score-matched models (log rank, P = 0.0426). Adding Max GD ≥ 242.3 µm to MEST-C improved diagnostic power of the renal prognosis prediction model by renal pathology tissue examination (R2: 3.3 to 14.5%, AICc: 71.8 to 68.0, C statistic: 0.657 to 0.772). We confirm that glomerular hypertrophy is useful as a long-term renal prognostic factor.


Assuntos
Glomerulonefrite por IGA/diagnóstico , Glomerulonefrite por IGA/patologia , Glomérulos Renais/patologia , Adulto , Progressão da Doença , Feminino , Seguimentos , Taxa de Filtração Glomerular , Glomerulonefrite por IGA/fisiopatologia , Humanos , Falência Renal Crônica/diagnóstico , Falência Renal Crônica/patologia , Falência Renal Crônica/fisiopatologia , Masculino , Prognóstico , Índice de Gravidade de Doença , Fatores de Tempo
14.
Orv Hetil ; 161(24): 993-1001, 2020 06.
Artigo em Húngaro | MEDLINE | ID: mdl-32469845

RESUMO

The basic structural units of the renal filtration are the glomeruli, which, in addition to their passive hemodynamic function, also participate in complex immune-mediated mechanisms. The immune system as a double-edged sword maintains the physiological homeostasis of the glomeruli, but also plays a crucial role in the induction of glomerular damage. The immune-mediated chronic glomerular injures are the most common cause of end-stage renal diseases. The unregulated and overactive immune response can damage both the structural and the cellular components of the glomeruli, including the glomerular basal membrane, mesangial and capillary endothelial cells, podocytes, and parietal epithelium. The manuscript summarizes the role of the glomerular components and the natural and adaptive immune response in the pathomechanism of glomerular diseases. Orv Hetil. 2020; 161(24): 993-1001.


Assuntos
Falência Renal Crônica/patologia , Glomérulos Renais/lesões , Células Endoteliais , Humanos
15.
Sci Rep ; 10(1): 6586, 2020 04 20.
Artigo em Inglês | MEDLINE | ID: mdl-32313061

RESUMO

Matrix Gla protein (MGP) is a potent inhibitor of vascular calcification (VC) and requires carboxylation by vitamin K to exert calcification inhibition. Chronic kidney disease (CKD) patients undergo early vascular aging often involving extensive VC. The present cross-sectional study investigated the association between circulating dp-ucMGP levels, MGP expression in vascular tissue and MGP polymorphisms. In 141 CKD stage 5 patients, CAC score was significantly increased in the highest tertile of dp-ucMGP (p = 0.002), and a high medial VC score was associated with elevated dp-ucMGP levels. MGP vascular expression was associated with increased circulating dp-ucMGP and CAC scores. MGP SNP analysis revealed that patients homozygous for the C allele of the rs1800801 variant had a higher CAC score (median 15 [range 0-1312]) compared to patients carrying a T allele (median 0 [range 0-966] AU). These results indicate that plasma levels of dp-ucMGP are an independent predictor of increased VC in CKD5 patients and correlate with both higher CAC scores and degree of medial calcification. Additionally, high vascular expression of MGP was associated with higher CAC scores and plasma dp-ucMGP levels. Taken together, our results support that MGP is involved in the pathogenesis of VC.


Assuntos
Proteínas de Ligação ao Cálcio/sangue , Proteínas da Matriz Extracelular/sangue , Falência Renal Crônica/sangue , Insuficiência Renal Crônica/sangue , Calcificação Vascular/sangue , Adulto , Biomarcadores/sangue , Proteínas de Ligação ao Cálcio/genética , Espessura Intima-Media Carotídea , Proteínas da Matriz Extracelular/genética , Feminino , Regulação da Expressão Gênica/genética , Humanos , Falência Renal Crônica/genética , Falência Renal Crônica/patologia , Masculino , Pessoa de Meia-Idade , Polimorfismo de Nucleotídeo Único/genética , Insuficiência Renal Crônica/genética , Insuficiência Renal Crônica/patologia , Fatores de Risco , Calcificação Vascular/genética , Calcificação Vascular/patologia
16.
Transplant Proc ; 52(5): 1272-1278, 2020 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-32245622

RESUMO

BACKGROUND: Recurrent glomerulopathy (GP) after kidney transplantation is a complication of kidney transplantation that could negatively affect kidney function and graft survival. This study aimed to evaluate the outcome, graft survival, and GP recurrence and its predictive factors in kidney-transplanted patients. METHODS: Patients were divided into 2 groups: G1 (with GP; n = 95) and G2 (with other causes of end-stage renal disease; n = 373). Graft survival analyses were performed using the Kaplan-Meier for living donor (LD) and deceased donor (DD). Cox proportional hazards regression were used to investigate the predictors for graft loss and for GP recurrence. RESULTS: Disease recurrence was observed in 9 patients who received a kidney from an LD, of which 4 lost their grafts. In patients who received a kidney from a DD, recurrence was also observed in 9 patients, of which 3 lost their grafts. No statistically significant differences in graft survival between G1 and G2 in relation to LD and DD were noted (P = .299 and .434, respectively). However, differences in graft survival were found when GP subtypes and GP recurrence were analyzed. The predictors of graft loss were delayed graft function (hazard ratio [HR] = 2.226, P = .002), rejection episodes (HR = 1.904, P = .017), and recurrence or transplant GP (HR = 3.243, P = .006). The predictors of disease recurrence or transplant GP were age (HR = 0.945, P = .028) and cold ischemia time (HR = 1.117, P = .003). CONCLUSION: Kidney transplantation could be a reasonable treatment for GP with end-stage renal disease. Despite the disease recurrence, which is a significant cause of graft loss in transplant recipients, graft survival remains satisfactory.


Assuntos
Isquemia Fria/efeitos adversos , Função Retardada do Enxerto/epidemiologia , Sobrevivência de Enxerto , Falência Renal Crônica/cirurgia , Transplante de Rim/efeitos adversos , Adulto , Função Retardada do Enxerto/patologia , Feminino , Humanos , Estimativa de Kaplan-Meier , Rim/patologia , Falência Renal Crônica/patologia , Transplante de Rim/métodos , Masculino , Pessoa de Meia-Idade , Período Pós-Operatório , Modelos de Riscos Proporcionais , Recidiva , Fatores de Risco , Transplantes/patologia , Resultado do Tratamento
17.
PLoS One ; 15(4): e0230493, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32255786

RESUMO

Phosphate toxicity is a major threat to cardiovascular health in chronic kidney disease. It is associated with oxidative stress, inflammation and the accumulation of calcium phosphate commonly known as calcification in soft tissues leading to functional disorders of blood vessels. An improved calcification propensity test for the assessment of phosphate toxicity was developed, which measures the velocity of calcium phosphate mineralization from colloidal precursors in vitro. This so called T50 test measures the transformation from a primary into a secondary form of nanosized colloidal plasma protein-calcium phosphate particles known as calciprotein particles. The T50 test in its previous form required a temperature controlled nephelometer and several hours of continuous measurement, which precluded rapid bed side testing. We miniaturized the test using microfluidic polymer chips produced by ultrasonic hot embossing. A cartridge holder contained a laser diode for illumination, light dependent resistor for detection and a Peltier element for thermo control. Increasing the assay temperature from 37°C to 75°C reduced the T50 test time 36-fold from 381 ± 10 min at 37°C to 10.5 ± 0.3 min at 75°C. Incorporating sputtered micro mirrors into the chip design increased the effective light path length, and improved signal-to-noise ratio 9-fold. The speed and reproducibility of the T50 chip-based assay run at 75°C suggest that it may be suitable for rapid measurements, preferably in-line in a dialyser or in a portable microfluidic analytic device with the chip inserted as a disposable cartridge.


Assuntos
Fosfatos de Cálcio/sangue , Microfluídica/métodos , Polímeros/química , Calcinose/sangue , Calcinose/diagnóstico , Humanos , Falência Renal Crônica/patologia , Dispositivos Lab-On-A-Chip , Microfluídica/instrumentação , Diálise Renal , Razão Sinal-Ruído , Temperatura
18.
Curr Urol Rep ; 21(2): 14, 2020 Mar 13.
Artigo em Inglês | MEDLINE | ID: mdl-32166462

RESUMO

PURPOSE OF REVIEW: Nowadays many ESRD patients awaiting kidney transplantation have known unsuitable iliac vessels for vascular anastomosis, due to severe atheromatosis, occupied iliac fossa, or other uncommon vascular abnormalities. In these cases, orthotopic kidney transplantation (OKT) could be the solution. RECENT FINDINGS: Since the update on OKT published in 2010, no more large series have been reported. Some small series or case reports being described in the literature. The orthotopic position has shown good recipient and graft results with acceptable complication rate in selected patients. This technique permits the possibility of kidney transplantation, in patients unfit for heterotopic kidney transplantation (HKT), and consequently the avoidance of the dialysis treatment. In this paper, we review what is new in the literature, analyzing indications, technique, and results of this surgical approach.


Assuntos
Falência Renal Crônica/cirurgia , Transplante de Rim/métodos , Humanos , Falência Renal Crônica/etiologia , Falência Renal Crônica/patologia , Seleção de Pacientes
19.
Biochem Biophys Res Commun ; 525(3): 773-779, 2020 05 07.
Artigo em Inglês | MEDLINE | ID: mdl-32147096

RESUMO

In chronic kidney disease, elevated levels of circulating uremic toxins are associated with a variety of symptoms and organ dysfunction. Indoxyl sulfate (IS) and p-cresyl sulfate (pCS) are microbiota-derived metabolites and representative uremic toxins. We have previously shown that the oral adsorbent AST-120 profoundly reduced pCS compared to IS in adenine-induced renal failure in mice. However, the mechanisms of the different attenuation effects of AST-120 between IS and pCS are unclear. To clarify the difference of AST-120 on IS and pCS, we investigated the levels of fecal indole and p-cresol, the respective precursors of IS and pCS, and examined the influence on the gut microbiota. Although fecal indole was detected in all groups analyzed, fecal p-cresol was not detected in AST-120 treatment groups. In genus level, a total of 23 organisms were significantly changed by renal failure or AST-120 treatment. Especially, AST-120 reduced the abundance of Erysipelotrichaceae uncultured and Clostridium sensu stricto 1, which have a gene involved in p-cresol production. Our findings suggest that, in addition to the adsorption of the uremic toxin precursors, AST-120 affects the abundance of some gut microbiota in normal and renal failure conditions, thereby explaining the different attenuation effects on IS and pCS.


Assuntos
Carbono/administração & dosagem , Carbono/farmacologia , Cresóis/metabolismo , Fezes/química , Microbioma Gastrointestinal/efeitos dos fármacos , Indóis/metabolismo , Óxidos/administração & dosagem , Óxidos/farmacologia , Administração Oral , Adsorção , Animais , Bactérias/efeitos dos fármacos , Falência Renal Crônica/microbiologia , Falência Renal Crônica/patologia , Masculino , Camundongos Endogâmicos C57BL
20.
Int J Mol Sci ; 21(6)2020 Mar 13.
Artigo em Inglês | MEDLINE | ID: mdl-32183005

RESUMO

Despite considerable advancements in medicine, the optimal treatment for chronic kidney disease (CKD), especially diabetic kidney disease (DKD), remains a major challenge. More patients with DKD succumb to death due to cardiovascular events than due to progression to end-stage renal disease (ESRD). Moreover, patients with DKD and ESRD have remarkably poor prognosis. Current studies have appreciated the contribution of inflammation and inflammatory mediators, such as tumor necrosis factor (TNF)-related biomarkers, on the development/progression of DKD. The present review focuses on molecular roles, serum concentrations of TNF receptors (TNFRs), and their association with increased albuminuria, eGFR decline, and all-cause mortality in diabetes. Experimental studies have suggested that DKD progression occurs through the TNFα-TNFR2 inflammatory pathway. Moreover, serum TNFR levels were positively associated with albuminuria and negatively associated with estimated glomerular filtration rate (eGFR), while circulating levels of TNFRs exhibited an independent effect on all-cause mortality and eGFR decline, including ESRD, even after adjusting for existing risk factors. However, their precise function has yet to be elucidated and requires further studies.


Assuntos
Nefropatias Diabéticas/sangue , Falência Renal Crônica/sangue , Receptores do Fator de Necrose Tumoral/sangue , Biomarcadores/sangue , Nefropatias Diabéticas/complicações , Nefropatias Diabéticas/patologia , Taxa de Filtração Glomerular , Humanos , Falência Renal Crônica/etiologia , Falência Renal Crônica/patologia
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