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1.
Medicine (Baltimore) ; 98(39): e17303, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31574857

RESUMO

Treatment with nitisinone (NTBC) has brought about a drastic improvement in the treatment and prognosis of hereditary tyrosinemia type I (HT1). We conducted a retrospective observational multicentric study in Spanish HT1 patients treated with NTBC to assess clinical and biochemical long-term evolution.We evaluated 52 patients, 7 adults and 45 children, treated with NTBC considering: age at diagnosis, diagnosis by clinical symptoms, or by newborn screening (NBS); phenotype (acute/subacute/chronic), mutational analysis; symptoms at diagnosis and clinical course; biochemical markers; doses of NTBC; treatment adherence; anthropometric evolution; and neurocognitive outcome.The average follow-up period was 6.1 ±â€Š4.9 and 10.6 ±â€Š5.4 years in patients with early and late diagnosis respectively. All patients received NTBC from diagnosis with an average dose of 0.82 mg/kg/d. All NBS-patients (n = 8) were asymptomatic at diagnosis except 1 case with acute liver failure, and all remain free of liver and renal disease in follow-up. Liver and renal affectation was markedly more frequent at diagnosis in patients with late diagnosis (P < .001 and .03, respectively), with ulterior positive hepatic and renal course in 86.4% and 93.2% of no-NBS patients, although 1 patient with good metabolic control developed hepatocarcinoma.Despite a satisfactory global nutritional evolution, 46.1% of patients showed overweight/obesity. Interestingly lower body mass index was observed in patients with good dietary adherence (20.40 ±â€Š4.43 vs 24.30 ±â€Š6.10; P = .08) and those with good pharmacological adherence (21.19 ±â€Š4.68 vs 28.58 ±â€Š213.79).intellectual quotient was ≥85 in all NBS- and 68.75% of late diagnosis cases evaluated, 15% of which need pedagogical support, and 6.8% (3/44) showed school failure.Among the 12 variants identified in fumarylacetoacetate hydrolase gene, 1 of them novel (H63D), the most prevalent in Spanish population is c.554-1 G>T.After NTBC treatment a reduction in tyrosine and alpha-fetoprotein levels was observed in all the study groups, significant for alpha-fetoprotein in no NBS-group (P = .03), especially in subacute/chronic forms (P = .018).This series confirms that NTBC treatment had clearly improved the prognosis and quality of life of HT1 patients, but it also shows frequent cognitive dysfunctions and learning difficulties in medium-term follow-up, and, in a novel way, a high percentage of overweight/obesity.


Assuntos
Cicloexanonas/uso terapêutico , Diagnóstico Tardio , Nitrobenzoatos/uso terapêutico , Obesidade , Qualidade de Vida , Tirosinemias , Adulto , Criança , Disfunção Cognitiva/diagnóstico , Disfunção Cognitiva/etiologia , Diagnóstico Tardio/efeitos adversos , Diagnóstico Tardio/prevenção & controle , Inibidores Enzimáticos/uso terapêutico , Feminino , Seguimentos , Humanos , Recém-Nascido , Nefropatias/diagnóstico , Nefropatias/etiologia , Masculino , Determinação de Necessidades de Cuidados de Saúde , Triagem Neonatal/métodos , Obesidade/diagnóstico , Obesidade/etiologia , Prognóstico , Estudos Retrospectivos , Espanha , Tempo para o Tratamento , Tirosinemias/complicações , Tirosinemias/diagnóstico , Tirosinemias/tratamento farmacológico , Tirosinemias/psicologia
2.
Medicine (Baltimore) ; 98(42): e17588, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31626129

RESUMO

In 2014/2015, tyrosine kinase inhibitors (TKIs) were introduced as a secondary treatment for refractory differentiated thyroid cancer (DTC) in Japan. While renal dysfunction is an adverse event of TKI, data on this adverse event in TKI-treated DTC remains insufficient. Here, we investigated renal function in patients undergoing TKI treatment for DTC and evaluated the efficacy of dose reduction/withdrawal for cases of renal dysfunction.A total of 73 cases of radioactive iodine-refractory DTC treated with sorafenib (n = 22) or lenvatinib (n = 51) were included. Patient data evaluated were TKI treatment period, estimated glomerular filtration rate (eGFR) before and after TKI therapy, incidence and degree (maximum value at time of TKI treatment) of proteinuria, and albumin levels before and after TKI therapy were compared.The mean ΔeGFR was -6.75% with lenvatinib and +5.90% with sorafenib. It was not significant (P = .15). The mean Δalbumin was -8.90% and -5.85% with lenvatinib and sorafenib, respectively; there was no significant difference between the lenvatinib and sorafenib groups (P = .77). According to our program of TKI dose reduction and withdrawal, all patients except 2 with diabetes were successfully continuing treatment.Overall, the present results demonstrated that renal function is negatively affected by long-term TKI treatment for RAI-refractory DTC. However, heightened proteinuria, decreased eGFR and albumin levels, and significant but apparently reversible renal dysfunction were more frequent with lenvatinib than sorafenib.


Assuntos
Taxa de Filtração Glomerular/fisiologia , Radioisótopos do Iodo/uso terapêutico , Nefropatias/etiologia , Compostos de Fenilureia/uso terapêutico , Proteínas Tirosina Quinases/antagonistas & inibidores , Quinolinas/uso terapêutico , Sorafenibe/uso terapêutico , Neoplasias da Glândula Tireoide/terapia , Idoso , Substituição de Medicamentos , Feminino , Seguimentos , Humanos , Nefropatias/fisiopatologia , Masculino , Pessoa de Meia-Idade , Inibidores de Proteínas Quinases/uso terapêutico , Tolerância a Radiação , Estudos Retrospectivos , Neoplasias da Glândula Tireoide/complicações , Neoplasias da Glândula Tireoide/diagnóstico , Tomografia Computadorizada por Raios X , Resultado do Tratamento
3.
Zhonghua Nei Ke Za Zhi ; 58(10): 758-762, 2019 Oct 01.
Artigo em Chinês | MEDLINE | ID: mdl-31594174

RESUMO

Objective: To investigate the clinical characteristics of polyarteritis nodosa (PAN) patients with renal involvement. Methods: PAN patients admitted to the department of rheumatology, department of pediatrics, department of nephrology, general internal medicine department and department of vascular surgery at Peking Union Medical College Hospital from June 2012 to August 2018 were enrolled in this study and were divided into two groups according to renal involvement or not. The clinical characteristics were analyzed. Results: A total of 94 PAN patients were finally enrolled and 57 (60.64%) presented kidney manifestation. The mean age of onset was (37.76±17.40) years old and the interval from onset to diagnosis was 10 (0 to 240) months. Forty patients were misdiagnosed once or more times. In patients with renal involvement, 9 cases suffered from renal ischemia or infarction, 31 with microscopic haematuria, 26 with proteinuria, renal artery or its branch involved in 17 cases, renal vein thrombosis in 1 case, 4 cases with pyeloureterectasis, one case with renal fascia thickening, 33 cases with impaired renal function (serum creatinine>84 µmol/L) including creatinine>140 µmol/L in 10 patients. Renal artery branch stenosis was the most common presentation [9 cases (52.94%)] of renal vascular involvement, other abnormalities including nodular dilatation [4 cases (23.53%)], occlusion [3 cases (17.65%)]. There were significant differences (P<0.05) in the PAN patients with and without renal involvement in the following: age of onset [(33.72±16.13) years vs. (43.97±17.66) years, t(2)=2.901, P=0.005], weight loss(≥4kg since PAN onset) [25(43.86%) vs. 7(18.92%), χ(2)=6.216, P=0.013], elevation of diastolic blood pressure [22(38.60%) vs. 7(18.92%), χ(2)=4.072, P=0.044], acromegaly gangrene [18(31.58%) vs. 21(56.76%), χ(2)=5.859, P=0.015], and gastrointestinal artery involvement [20(35.09%) vs. 6(1.22%), χ(2)=3.993, P=0.046]. Laboratory parameters and the application of glucocorticoid and cyclophosphamide therapies were similar in two groups (all P>0.05). Conclusion: Young PAN patients are more likely to be associated with renal involvement, especially gastrointestinal arteries.


Assuntos
Arterite/diagnóstico , Nefropatias/etiologia , Rim/fisiopatologia , Poliarterite Nodosa/diagnóstico , Adulto , Idoso , Ciclofosfamida/uso terapêutico , Gastroenteropatias , Glomerulonefrite/diagnóstico , Glucocorticoides/uso terapêutico , Humanos , Infarto , Nefropatias/fisiopatologia , Pessoa de Meia-Idade , Poliarterite Nodosa/complicações , Poliarterite Nodosa/tratamento farmacológico , Adulto Jovem
4.
Pan Afr Med J ; 33: 162, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31565124

RESUMO

Introduction: Autodialysis is the dialysis performed by the patient himself at a local center instead of a hemodialysis center. In Morocco, the practice of hemodialysis dates back to 1970; however, an autodialysis center does not yet exist. The objective was to assess the potential medical fitness and adherence of the patients to an autodialysis program. Methods: Descriptive and analytical multicenter study conducted in March 2015 involving patients from of eight hemodialysis centers in Casablanca (Morocco). The study was conducted in two steps: 1) a transversal assessment of the medical potential to achieve autodialysis that included 556 patients; 2) a survey of the autodialysis membership that included 383 out of 556 patients who were deemed eligible for autodialysis. Results: The average age was 54.63 ± 15.16 years; the average of hemodialysis duration was 85.9 ± 78.1 months. Diabetic nephropathy (22.7%) was the predominant cause of kidney disease. The assessment of medical potential to achieve autodialysis highlighted that almost all of the patients were in good condition (93%), independent (81%), and those without major comorbidities were less than 76 years old. Regarding the potential patients' adherence to autodialysis, among the 383 patients previously deemed suited for autodialysis, 293 (76.5%) responded favorably to the proposal of self-dialysis. Conclusion: The practice of hemodialysis should be implemented in a short time in Morocco because our patients' profile is perfectly suitable to this therapeutic method especially when they are young, in good general condition, autonomous, without major comorbidities, and willing to learn.


Assuntos
Nefropatias/terapia , Diálise Renal/métodos , Autocuidado/métodos , Adulto , Idoso , Nefropatias Diabéticas/epidemiologia , Nefropatias Diabéticas/terapia , Feminino , Humanos , Nefropatias/etiologia , Masculino , Pessoa de Meia-Idade , Marrocos , Cooperação do Paciente/estatística & dados numéricos
5.
Pol Merkur Lekarski ; 47(278): 52-59, 2019 Aug 30.
Artigo em Polonês | MEDLINE | ID: mdl-31473752

RESUMO

Tuberous sclerosis complex (TSC) is a genetic disease that leads to formation of tumors i.e. in brain kidneys, heart, lungs, and skin. AIM: The aim of the study was to summarize center's experience in the first year of program of nephrologic follow-up in patients with TSC. MATERIALS AND METHODS: During 12 months 30 children with TSC (14 boys and 16 girls aged from 3 months to 17 years 11 months, mean 7.57±5.02 years) were hospitalized. Following parameters were evaluated: genetic and biochemical tests, blood pressure in ambulatory blood pressure monitoring (ABPM), kidney lesions in ultrasonography (30 patients) and in magnetic resonance (14 patients). RESULTS: Genetic tests were performed in 6 children - in 5 TSC2 mutation was found, in one boy with TSC and numerous renal cysts only PKD1 mutation was revealed. Mean GFR was 130.81±23.23 mL/ min/1.73 m2. Four children (13.3%) had arterial hypertension. Renal lesions were found in 28 (93.3%) children: 18 patients had angiomyolipomas (AML) (mean diameter 15.4±12.5, max 38 mm), 23 patients had renal cysts (mean diameter 7.6±7.0, max 30 mm); 13 patients had AMLs and cysts. A dysplastic lesion (39x26x15 mm) in right kidney was found in one girl. Children with AML were older than remaining patients (10.08±4.55 vs. 4.25±3.50 [years], p<0.001). Children with cysts were characterized by higher systolic (p=0.017), diastolic (p=0.027) and mean (p=0.014) arterial pressure, and mean arterial pressure Z-score (p=0.025) in ABPM. Maximal kidney cyst diameter correlated positively with systolic, diastolic, mean arterial pressure, mean arterial pressure Z-score, and diastolic blood pressure load in ABPM (r = 0.61-0.75, p = 0.033-0.005). Two children with numerous AML with diameter >30 mm were treated with sirolimus. CONCLUSIONS: Because of common focal lesions in kidneys children with TSC should be kept under regular nephrologic follow-up. Presence of large renal cysts may predispose children with TSC to arterial hypertension.


Assuntos
Angiomiolipoma , Nefropatias , Esclerose Tuberosa , Adolescente , Angiomiolipoma/etiologia , Monitorização Ambulatorial da Pressão Arterial , Criança , Pré-Escolar , Feminino , Seguimentos , Humanos , Lactente , Recém-Nascido , Nefropatias/etiologia , Masculino , Esclerose Tuberosa/complicações
6.
Adv Exp Med Biol ; 1155: 369-380, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31468415

RESUMO

The present study was carried out in diabetic rats to examine the effects of ethanol (EtOH) and taurine (TAU), singly and in combination, in reducing the changes of laboratory test values indicating renal dysfunction. For this purpose, male Sprague-Dawley rats, 250-280 g in weight and in groups of 6, were made diabetic with a single, 60 mg/kg intraperitoneal dose of streptozotocin in 10 mM citrate buffer pH 4.5. On day 15 and for the remaining 14 days of the study, the diabetic rats (a) started to drink 5% EtOH in place of water, (b) received a single daily 2.4 mM/kg oral dose of TAU or (c) were allowed to drink 5% EtOH after receiving a dose of TAU. Starting from day 28 and ending on day 29, a 24 h urine sample was collected, its volume was measured, and then used to measure glucose (GLC), total protein (TP) and electrolytes (Na+, K+, Ca++, Mg++). Blood samples collected immediately thereafter via cardiac puncture were processed for the plasma fractions which were analyzed for their creatinine (CRT) and urea nitrogen (UN) contents. In comparison to normal (control) rats, diabetic ones showed a higher output of urine (+5.6-fold), a massive increase in plasma GLC (+473%), passed more GLC (+73.8-fold) and TP (+8.2-fold) in the urine, showed higher plasma CRT (+241%) and UN (+74%) levels, a lower plasma UN/CRT ratio (-47%) and a greater output of electrolytes in the urine (by at least twofold). By themselves both EtOH and TAU were found to markedly lower the effects of diabetes, with EtOH generally appearing more effective than TAU. However, the concurrent availability of EtOH and TAU was found to be more protective than either treatment alone.


Assuntos
Diabetes Mellitus Experimental/tratamento farmacológico , Etanol/farmacologia , Nefropatias/tratamento farmacológico , Taurina/farmacologia , Animais , Glicemia , Diabetes Mellitus Experimental/complicações , Nefropatias/etiologia , Masculino , Ratos , Ratos Sprague-Dawley , Urinálise
7.
Transplant Proc ; 51(6): 1706-1716, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31399161

RESUMO

BACKGROUND: Living kidney donors (LKDs) are at high risk of renal dysfunction after undergoing a donor nephrectomy (DN), resulting in poor prognosis associated with the development of cardiovascular or cerebrovascular disease. Decreasing this risk can improve the survival rate of LKDs. We investigated the effects of preoperative conditions in LKDs on renal dysfunction after DN using abdominal adipose tissue, inflammation, nutritional status, and muscle mass as markers for this assessment. METHODS: Our retrospective study included 79 LKDs. Body composition markers were assessed using preoperative unenhanced computed tomographic images. Inflammation- and nutritional status-based markers were assessed using preoperative laboratory blood tests. The association between each marker was investigated, and prognostic markers for renal dysfunction after DN were identified. RESULTS: The LKDs in this cohort comprised 30 men and 49 women. The median age at the time of DN and the preoperative estimated glomerular filtration rate were 58 years and 81.9 mL/min/1.73 m2, respectively. Abdominal subcutaneous adipose tissue and muscle mass significantly differed between the sexes. Each adipose tissue-, inflammation-, nutritional status-, and muscle mass-based marker showed an association with each other. Abdominal visceral adipose tissue and nutritional status could be independent prognostic markers for renal dysfunction after DN. CONCLUSIONS: Our findings suggest that the preoperative condition of LKDs (assessed using specific markers such as abdominal visceral adipose tissue mass per volume and nutritional status) could affect renal dysfunction after DN. Optimal preoperative management can lead to better outcomes in LKDs. Further research is needed to establish appropriate exercise programs and nutritional interventions.


Assuntos
Nefropatias/diagnóstico , Doadores Vivos , Nefrectomia/efeitos adversos , Complicações Pós-Operatórias/etiologia , Adulto , Biomarcadores/análise , Feminino , Humanos , Inflamação , Gordura Intra-Abdominal , Nefropatias/etiologia , Transplante de Rim/métodos , Masculino , Pessoa de Meia-Idade , Estado Nutricional , Complicações Pós-Operatórias/diagnóstico , Prognóstico , Estudos Retrospectivos
8.
Mymensingh Med J ; 28(3): 527-535, 2019 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-31391422

RESUMO

Renal involvement may be the presenting feature in a vast majority of patients with multiple myeloma and is one of the key for clinical manifestations of symptomatic multiple myeloma. The purpose of the study was to find out the pattern of renal involvement at the time of presentation of multiple myeloma and to explore its association with clinical, laboratory and pathologic features of these cases. This cross sectional study was conducted in the Department of Nephrology at Bangabandhu Sheikh Mujib Medical University (BSMMU), Dhaka, Bangladesh from February 2016 to September 2017. Forty seven (47) patients of newly diagnosed multiple myeloma having renal involvement were included in the study. Multiple myeloma was diagnosed as per criteria proposed by the International Myeloma Working Group, 2003. Renal involvement was considered to be present when any one of proteinuria, microscopic haematuria, renal impairment or urinary tract infection (UTI) was found in the patient. Renal biopsy was done in suitable patients under ultrasound guidance after taking informed written consent. The pattern of renal involvement was detected and status of renal function was assessed and its clinical, laboratory and pathologic associations were analyzed. Data were managed by using computer based software, the Statistical Package for Social Sciences (SPSS) version 23 (IBM Corp.). Median age at presentation was 59 years with the range of 37-76 years. Female (53.2%) was slightly predominant than male (46.8%) and male to female ratio was 1:1.14. Renal impairment, microscopic haematuria, proteinuria, nephrotic range proteinuria, urinary Bence Jones protein and UTI were found in 70%, 19%, 79%, 25%, 19% and 17% of patients respectively. Median serum creatinine and proteinuria were 256µmol/l and 1.24gm/day. Hypercalcaemia and Bence Jones proteinuria were detected in 36% and 27% of patients respectively with renal impairment which were statistically significant. The precipitating factors for renal impairment were NSAIDs use (67%), hyperuricaemia (49%), hypercalcaemia (36%), dehydration (27%), UTI (18%) and no identifiable factor (3%). Dialysis was required in 15% new myeloma patient. Renal biopsy and histopathological examination revealed myeloma cast nephropathy (30%), amyloidosis (30%), glomerulosclerosis (chronic kidney disease) (20%), monoclonal immunoglobulin deposition disease (MIDD) (10%) and interstitial nephritis with fibrosis (10%). Renal involvement was a common and severe complication of multiple myeloma. Renal impairment was strongly associated with hypercalcaemia, NSAIDs use, hyperuricaemia, Bence Jones proteinuria etc.


Assuntos
Nefropatias , Mieloma Múltiplo , Adulto , Idoso , Bangladesh , Proteína de Bence Jones , Estudos Transversais , Feminino , Humanos , Nefropatias/etiologia , Masculino , Pessoa de Meia-Idade , Mieloma Múltiplo/complicações , Mieloma Múltiplo/diagnóstico
9.
Methodist Debakey Cardiovasc J ; 15(2): 158-159, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31384382

RESUMO

This column is supplied by Benjamin J. Lee, MD, MAS, an assistant professor of clinical medicine at both the Houston Methodist Institute for Academic Medicine and Weill Cornell Medical College. After earning his medical degree at Harvard Medical School, Dr. Lee completed a residency in internal medicine at the University of California, San Francisco (UCSF). He subsequently completed a nephrology fellowship at UCSF while simultaneously obtaining a Master of Advanced Study in clinical research from the UCSF Department of Epidemiology and Biostatistics. Dr. Lee is a Fellow of the American Society of Nephrology, a Certified Hypertension Specialist through the American Hypertension Specialist Certification Program, and a member of the American Society of Transplantation. He maintains his clinical practice with the Houston Kidney Consultants.


Assuntos
Cianose/etiologia , Cardiopatias Congênitas/complicações , Nefropatias/etiologia , Rim/fisiopatologia , Cianose/diagnóstico , Cianose/fisiopatologia , Cardiopatias Congênitas/diagnóstico , Cardiopatias Congênitas/tratamento farmacológico , Cardiopatias Congênitas/fisiopatologia , Humanos , Rim/efeitos dos fármacos , Rim/patologia , Nefropatias/diagnóstico , Nefropatias/tratamento farmacológico , Nefropatias/fisiopatologia , Prognóstico , Fatores de Risco
10.
Br J Radiol ; 92(1103): 20190448, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31335170

RESUMO

Immunoglobulin G4-related disease (IgG4-RD) is an autoimmune disorder characterized by the infiltration of one or more organs with IgG4-positive plasma cells resulting in inflammatory lesions and fibrosis. Although the pancreas is the most commonly affected organ, involvement of extrapancreatic organs is an increasingly recognized manifestation of the disease. Patients may be asymptomatic and serum IgG4 concentrations may be elevated or normal. Treatment consists of glucocorticosteroid treatment, with excellent response. A definitive diagnosis requires histopathology with imaging playing a key role in avoiding treatment delays. This pictorial review will focus on the most current knowledge regarding IgG4-RD including its common and less common manifestations and the roles of multidetector CT, MRI and ultrasound in the diagnosis and management of suspected IgG4-RD. Knowledge of the varied imaging findings of this multi systemic disease is essential for radiologists to avoid misdiagnosis and assist with timely and effective treatment.


Assuntos
Doença Relacionada a Imunoglobulina G4/complicações , Adulto , Doenças Cardiovasculares/diagnóstico , Doenças Cardiovasculares/etiologia , Dacriocistite/diagnóstico , Dacriocistite/etiologia , Feminino , Doenças da Vesícula Biliar/diagnóstico , Doenças da Vesícula Biliar/etiologia , Humanos , Doença Relacionada a Imunoglobulina G4/diagnóstico , Nefropatias/diagnóstico , Nefropatias/etiologia , Pneumopatias/diagnóstico , Pneumopatias/etiologia , Imagem por Ressonância Magnética , Masculino , Mastite/diagnóstico , Mastite/etiologia , Pessoa de Meia-Idade , Tomografia Computadorizada Multidetectores , Pseudotumor Orbitário/diagnóstico , Pseudotumor Orbitário/etiologia , Pancreatopatias/diagnóstico , Pancreatopatias/etiologia , Fibrose Retroperitoneal/diagnóstico , Fibrose Retroperitoneal/etiologia , Sialadenite/diagnóstico , Sialadenite/etiologia , Ultrassonografia
11.
Clin Nephrol ; 92(2): 81-88, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31232268

RESUMO

BACKGROUND: This study was performed to determine whether the urinary albumin excretion rate (%UAE) could distinguish myeloma cast nephropathy (MCN) without glomerular amyloid deposition from MCN with glomerular amyloid deposition. MATERIALS AND METHODS: We retrospectively reviewed clinicopathological data on 16 patients with MCN diagnosed by renal biopsy at Toranomon Hospital from 2004 to 2014. RESULTS: A total of 10 patients had pure MCN without glomerular amyloid deposition (group 1), and 6 patients had MCN with glomerular amyloid deposition (group 2). In all 10 patients from group 1, the underlying disease was multiple myeloma (MM), while 4 patients had MM, and 2 patients had lymphoplasmacytic lymphoma/Waldenström macroglobulinemia (LPL/WM) in group 2. Total protein did not show a significant difference between the two groups, but serum albumin was significantly higher in group 1 than group 2 (p = 0.0101). Serum-adjusted calcium did not show a significant difference between the groups, while serum creatinine (Cre) was significantly higher in group 1 than group 2 (p = 0.0343). Although urinary protein excretion did not differ significantly between the groups, the %UAE was significantly lower in group 1 than group 2 (p = 0.00198). In group 2, 3 of the 4 patients with MM died within 15 months of diagnosis, but the 2 patients with LPL/WM are alive after 32 months. In group 1, only 1 patient died (of unknown causes) within 15 months after diagnosis. CONCLUSION: In patients with MCN, %UAE may be a useful marker for the detection of coexistence of glomerular lesions, such as amyloidosis, which are associated with a poor outcome.


Assuntos
Albuminúria/diagnóstico , Nefropatias/diagnóstico , Nefropatias/metabolismo , Mieloma Múltiplo/complicações , Idoso , Albuminúria/etiologia , Biomarcadores/metabolismo , Creatinina/sangue , Feminino , Humanos , Nefropatias/etiologia , Masculino , Pessoa de Meia-Idade , Mieloma Múltiplo/diagnóstico , Mieloma Múltiplo/metabolismo , Estudos Retrospectivos , Albumina Sérica/metabolismo
12.
Chemosphere ; 234: 579-588, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31229719

RESUMO

Mercury (Hg), a significant toxic metal for nephrotoxicity, can be found in food (vegetable and seafood) and drinking water by contamination. Oxidative stress is involved in inorganic Hg-induced nephrotoxicity, but the Sirtuin1 (Sirt1)/Nrf2/OH-1 pathway and sodium (Na)/calcium (Ca) ions actions in mercuric chloride (HgCl2)-induced nephrotoxicity remains unclear to date. In this study, Kunming mice were treated HgCl2 (5 mg/kg) for 24 h to evaluate potential mechanism. Here, along with Sirt1 activation, pale kidney, hisologic conditions, typical apoptotic changes and TUNEL positive nuclei were observed under acute HgCl2 exposure. Specifically, although HgCl2 increased the expression of Nrf2, Keap1, OH-1 and NQO1, the mRNA levels of GSS, GCLC and GCLM showed no significant alterations in mice kidney. Moreover, mice exposed to HgCl2 decreased the concentrations of Mg, K, P, Mn, Fe, Zn, and elevated Na, Ca, Cu and Se in kidney. It was also observed that HgCl2 suppressed the ATPases (Na+-K+-ATPase, Ca2+-ATPase, Mg2+-ATPase and Ca2+-Mg2+-ATPase) activities and decreased the mRNA levels of Atp1a1, Atp1a2 in the kidney. Further study showed that HgCl2 elevated Na+ concentrations by markedly increased the mRNA levels of Na+ transporter. The present study revealed that HgCl2 induced Sirt1/Nrf2/OH-1 pathway activation while did not inhibit apoptosis in kidney of mice. Additionally, HgCl2 regulates Na+ concentrations, which might create secondary disorders in absorption and excretion of other ions. Altogether we assume that Sirt1/Nrf2/Na+/Ca2+ pathway might be a potential therapeutic target for treating acute HgCl2 induced nephrotoxicity.


Assuntos
Nefropatias/induzido quimicamente , Cloreto de Mercúrio/toxicidade , Fator 2 Relacionado a NF-E2/metabolismo , Sirtuína 1/metabolismo , Sódio/metabolismo , Adenosina Trifosfatases/metabolismo , Animais , Cálcio/metabolismo , Proteína 1 Associada a ECH Semelhante a Kelch , Rim/metabolismo , Nefropatias/etiologia , Camundongos , Estresse Oxidativo/efeitos dos fármacos
13.
Urologiia ; (2): 103-107, 2019 Jun.
Artigo em Russo | MEDLINE | ID: mdl-31162910

RESUMO

The results of recent studies on the mechanisms of kidney damage are presented in the review of literature. The role of the immune system in the occurrence, development and outcome of damage to the epithelium of the renal tubules, as well as molecular, genetic and metabolic changes which determine the extent and consequences of renal trauma are described in details. The mechanisms of restoration of the renal parenchyma and the development of fibrosis following the cessation of injury are given.


Assuntos
Nefropatias/fisiopatologia , Túbulos Renais/fisiopatologia , Rim/fisiopatologia , Urotélio/fisiopatologia , Fibrose/fisiopatologia , Humanos , Rim/lesões , Nefropatias/etiologia , Túbulos Renais/lesões , Urotélio/lesões
14.
Chem Biol Interact ; 310: 108719, 2019 Sep 01.
Artigo em Inglês | MEDLINE | ID: mdl-31238026

RESUMO

Both obesity and arsenic exposure are global public health problems that are associated with increased risk of renal disease. The effect of whole-life exposure to environmentally relevant levels of arsenic within dietary high fat diet on renal pathogenesis were examined. In this study, C57BL/6 J mice were parentally exposed to 100 ppb arsenic before conception. After weaning, both male and female offspring were maintained on 100 ppb arsenic and fed either a normal (LFD) or high fat diet (HFD). At 10 and 24 weeks of age, the offspring were sacrificed and kidneys collected. Exposure to arsenic led to an increase body-weight in LFD diet-fed female but not male mice. This response was not observed in HFD-fed female mice; however male mice showed significant increases in body weight in both As- and non-treated animals. Histological analysis shows that arsenic exposure significantly increases HFD-induced glomerular area expansion, mesangial matrix accumulation and fibrosis compared to LFD control animals. HFD alone increases renal inflammation and fibrosis; reflected by increases in IL-1ß, ICAM-1 and fibronectin levels. Arsenic exposure significantly increases HFD-induced inflammatory and oxidative stress responses. In general, male mice have more severe responses than female mice to HFD or arsenic treatment. These results demonstrate that arsenic exposure causes sex-dependent alterations in HFD-induced kidney damage.


Assuntos
Arsênico/efeitos adversos , Dieta Hiperlipídica/efeitos adversos , Nefropatias/etiologia , Rim/efeitos dos fármacos , Animais , Arsênico/toxicidade , Peso Corporal/efeitos dos fármacos , Inflamação/etiologia , Rim/lesões , Nefropatias/induzido quimicamente , Nefropatias/patologia , Camundongos , Camundongos Endogâmicos C57BL , Estresse Oxidativo/efeitos dos fármacos , Fatores Sexuais
15.
Expert Rev Clin Pharmacol ; 12(6): 513-521, 2019 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-31035801

RESUMO

Introduction: Advanced cancers that did not respond to chemotherapy were once a death sentence, but now there are newer therapies utilizing the patient's own immune system to fight cancer that are proving effective in chemotherapy-refractory malignancies. However, this success against cancer cells may be accompanied by immune-related adverse events that can affect the kidneys. Areas covered: Using Medline and Scopus, we compiled all publications through February 2019 that pertained to immune checkpoint inhibitors (ICPIs) and chimeric antigen receptor T-cells (CAR T-cells).  The focus of this review is the discussion of these new cancer therapies, with attention to the reported kidney-related adverse effects.. Expert opinion: Autoimmunity is repressed by molecular pathways that inhibit T-cell activation against selected antigens. These self-protective mechanisms have been appropriated by tumor cells as a means of evading immune detection and destruction. New immunotherapies such as immune checkpoint inhibitors and chimeric antigen receptor T-cell therapy incite an aggressive immune response directed against tumor cells. This unrestrained activation of the immune system may result in kidney injury via multiple mechanisms.


Assuntos
Imunoterapia/efeitos adversos , Nefropatias/etiologia , Neoplasias/terapia , Autoimunidade/imunologia , Humanos , Imunoterapia/métodos , Imunoterapia Adotiva/efeitos adversos , Imunoterapia Adotiva/métodos , Nefropatias/imunologia , Neoplasias/imunologia
16.
Life Sci ; 229: 104-115, 2019 Jul 15.
Artigo em Inglês | MEDLINE | ID: mdl-31100324

RESUMO

AIM: Blockage of the urinary tract is often connected with renal function impediment, including reductions in glomerular filtration rate (GFR) and the power to control sodium as well as water elimination through urination. Melatonin, known to be the primary product of the pineal gland, prevents renal damage caused by ischemic reperfusion. However, the effects of melatonin on urinary obstruction, as well as release of obstruction induced kidney injury are still largely unknown. The aim of present study was to investigate the effect of melatonin on mediating protection against renal injury triggered from either bilateral ureteral obstruction (BUO) or BUO release (BUO-R). MAIN METHODS: Adult male Sprague-Dawley rats (n = 60) were clustered into six treatment groups: sham treated-1; BUO-non-treated (24 h BUO only); BUO + melatonin; sham treated-2; BUO-48hR (24 h of BUO and then release for 2 days); and BUO-48hR + melatonin. Kidney tissues, blood and urine samples were obtained for further assessment. KEY FINDINGS: It was found that melatonin treatment remarkably promoted the recovery of the handling capacity of urinary excretion of water as well as sodium in BUO and BUO-48hR models. Melatonin treatment partially inhibited inflammatory cytokine expression and the downregulation of aquaporin (AQPs, AQP-1, -2 and -3) expression in these two models. Moreover, the cytoarchitecture of BUO rats exposed to melatonin was well preserved. SIGNIFICANCE: Melatonin treatment potently prevents BUO or BUO-R induced renal injury, which may be partially attributed to restoring the expression of AQPs and inhibition of inflammatory response, as well as preserving renal ultrastructural integrity.


Assuntos
Antioxidantes/farmacologia , Nefropatias/prevenção & controle , Melatonina/farmacologia , Substâncias Protetoras/farmacologia , Obstrução Ureteral/complicações , Animais , Aquaporinas/genética , Aquaporinas/metabolismo , Taxa de Filtração Glomerular , Nefropatias/etiologia , Nefropatias/patologia , Masculino , Ratos , Ratos Sprague-Dawley , Obstrução Ureteral/fisiopatologia
17.
Transplant Proc ; 51(5): 1525-1530, 2019 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-31056248

RESUMO

PURPOSE: Renal dysfunction more frequently occurs after intestinal transplantation (ITx) than after heart, lung, or liver transplantation. We provide a clinical analysis of renal function after adult ITx. METHODS: We retrospectively analyzed 8 adult ITx patients who survived for at least 6 months between 2004 and 2018. Glomerular filtration rate (GFR) measurements were performed at baseline, at 3 and 6 months post-transplantation, and yearly. The median follow-up duration was 53.5 months. RESULTS: All cases were isolated ITx; 3 received living-donor ITx, and 5 received deceased-donor ITx. The mean baseline GFR was 97 mL/min/1.73 m2. The GFR had decreased by more than 50% of baseline at 1 year post-transplant. Renal dysfunction was observed in 4 patients. Two patients developed acute kidney injury due to acute rejection and sepsis. One of these patients fully recovered renal function, but the second patient died. Another 2 patients developed chronic kidney disease and required hemodialysis (HD) within 6 and 3 years, respectively. The first living-donor ITx patient lost renal function progressively over 6 years after ITx. She received a renal graft from the same living donor as for the ITx after 3 years of HD. The other patient (deceased-donor ITx) received a kidney from his daughter at 5 months after HD. CONCLUSIONS: To obtain an accurate assessment of renal function, frequent direct measurements of GFR should be performed to facilitate early diagnosis of renal impairment and to determine subsequent strategies to improve renal function after ITx.


Assuntos
Intestinos/transplante , Nefropatias/etiologia , Adulto , Idoso , Feminino , Taxa de Filtração Glomerular , Humanos , Rim/fisiopatologia , Nefropatias/epidemiologia , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Adulto Jovem
18.
Int J Mol Sci ; 20(10)2019 May 18.
Artigo em Inglês | MEDLINE | ID: mdl-31109047

RESUMO

Mesenchymal stem cells constitute a pool of cells present throughout the lifetime in numerous niches, characteristic of unlimited replication potential and the ability to differentiate into mature cells of mesodermal tissues in vitro. The therapeutic potential of these cells is, however, primarily associated with their capabilities of inhibiting inflammation and initiating tissue regeneration. Owing to these properties, mesenchymal stem cells (derived from the bone marrow, subcutaneous adipose tissue, and increasingly urine) are the subject of research in the settings of kidney diseases in which inflammation plays the key role. The most advanced studies, with the first clinical trials, apply to ischemic acute kidney injury, renal transplantation, lupus and diabetic nephropathies, in which beneficial clinical effects of cells themselves, as well as their culture medium, were observed. The study findings imply that mesenchymal stem cells act predominantly through secreted factors, including, above all, microRNAs contained within extracellular vesicles. Research over the coming years will focus on this secretome as a possible therapeutic agent void of the potential carcinogenicity of the cells.


Assuntos
Nefropatias/terapia , Transplante de Células-Tronco Mesenquimais , Células-Tronco Mesenquimais/citologia , Células-Tronco Mesenquimais/metabolismo , Animais , Células da Medula Óssea/citologia , Células da Medula Óssea/metabolismo , Diferenciação Celular , Nefropatias Diabéticas/etiologia , Nefropatias Diabéticas/metabolismo , Nefropatias Diabéticas/terapia , Exossomos/metabolismo , Vesículas Extracelulares/metabolismo , Glomerulonefrite/etiologia , Glomerulonefrite/metabolismo , Glomerulonefrite/terapia , Humanos , Imunomodulação , Nefropatias/etiologia , Nefropatias/metabolismo , MicroRNAs/genética , Interferência de RNA , Regeneração , Pesquisa
19.
Radiat Res ; 192(1): 63-74, 2019 07.
Artigo em Inglês | MEDLINE | ID: mdl-31095446

RESUMO

Radiotherapy with sparsely ionizing photons is a cornerstone of successful cancer treatment. Age at time of exposure to radiation is known to influence biological outcomes for many end points. The effect of dose and age at exposure upon the occurrence of radiogenic cardiovascular disease is poorly understood. The goal of this work was to determine the response of maleWAG/RijCmcr rats at 6 months of age to gamma rays, and at 6 months or 6 weeks of age to X rays, using clinically relevant biomarkers of cardiovascular disease and kidney injury. Overall, there were significant radiation-induced effects on the levels of bicarbonate (P=0.0016), creatinine (P=0.0002), calcium (P = 0.0009), triglycerides (P = 0.0269) and blood urea nitrogen, albumin, protein, AST, alkaline phosphatase, total cholesterol and HDL (all P < 0.0001). Of those variables with a significant radiation-dose effect, there were significant modifications by age at time of exposure for bicarbonate (P = 0.0033), creatinine (P = 0.0015), AST (P = 0.0040), total cholesterol (P = 0.0006) and blood urea nitrogen, calcium, albumin, protein, alkaline phosphatase and HDL (all P < 0.0001). Cardiac perivascular collagen content was significantly increased in rats that were 8.0 Gy X-ray irradiated at 6 weeks of age (P < 0.047) but not at 6 months of age. While systemic blood pressure was elevated in both cohorts after 8.0 Gy X-ray irradiation (compared to agematched sham-irradiated controls), the magnitude of the increase above baseline was greater in the younger rats (P < 0.05). These findings indicate that dose and age at time of irradiation determine the timeline and severity of cardiac and renal injury.


Assuntos
Cardiopatias/etiologia , Nefropatias/etiologia , Lesões Experimentais por Radiação/etiologia , Fatores Etários , Animais , Relação Dose-Resposta à Radiação , Raios gama/efeitos adversos , Cardiopatias/sangue , Nefropatias/sangue , Masculino , Lesões Experimentais por Radiação/sangue , Ratos , Ratos Wistar , Fatores de Risco
20.
BMJ ; 365: l1516, 2019 04 29.
Artigo em Inglês | MEDLINE | ID: mdl-31036557

RESUMO

OBJECTIVE: To investigate associations between pre-eclampsia and later risk of kidney disease. DESIGN: Nationwide register based cohort study. SETTING: Denmark. POPULATION: All women with at least one pregnancy lasting at least 20 weeks between 1978 and 2015. MAIN OUTCOME MEASURE: Hazard ratios comparing rates of kidney disease between women with and without a history of pre-eclampsia, stratified by gestational age at delivery and estimated using Cox regression. RESULTS: The cohort consisted of 1 072 330 women followed for 19 994 470 person years (average 18.6 years/woman). Compared with women with no previous pre-eclampsia, those with a history of pre-eclampsia were more likely to develop chronic renal conditions: hazard ratio 3.93 (95% confidence interval 2.90 to 5.33, for early preterm pre-eclampsia (delivery <34 weeks); 2.81 (2.13 to 3.71) for late preterm pre-eclampsia (delivery 34-36 weeks); 2.27 (2.02 to 2.55) for term pre-eclampsia (delivery ≥37 weeks). In particular, strong associations were observed for chronic kidney disease, hypertensive kidney disease, and glomerular/proteinuric disease. Adjustment for cardiovascular disease and hypertension only partially attenuated the observed associations. Stratifying the analyses on time since pregnancy showed that associations between pre-eclampsia and chronic kidney disease and glomerular/proteinuric disease were much stronger within five years of the latest pregnancy (hazard ratio 6.11 (3.84 to 9.72) and 4.77 (3.88 to 5.86), respectively) than five years or longer after the latest pregnancy (2.06 (1.69 to 2.50) and 1.50 (1.19 to 1.88). By contrast, associations between pre-eclampsia and acute renal conditions were modest. CONCLUSION: s Pre-eclampsia, particularly early preterm pre-eclampsia, was strongly associated with several chronic renal disorders later in life. More research is needed to determine which women are most likely to develop kidney disease after pre-eclampsia, what mechanisms underlie the association, and what clinical follow-up and interventions (and in what timeframe post-pregnancy) would be most appropriate and effective.


Assuntos
Hipertensão Renal/epidemiologia , Nefropatias/diagnóstico , Nefropatias/etiologia , Pré-Eclâmpsia/diagnóstico , Adulto , Doenças Cardiovasculares/complicações , Doenças Cardiovasculares/epidemiologia , Dinamarca/epidemiologia , Feminino , Idade Gestacional , Humanos , Hipertensão/complicações , Hipertensão/epidemiologia , Hipertensão Renal/complicações , Nefropatias/epidemiologia , Monitorização Fisiológica/normas , Período Pós-Parto , Pré-Eclâmpsia/epidemiologia , Gravidez , Fatores de Risco , Adulto Jovem
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