Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 66
Filtrar
1.
Curr Oncol ; 31(5): 2636-2643, 2024 05 06.
Artigo em Inglês | MEDLINE | ID: mdl-38785479

RESUMO

BACKGROUND: The aim of this study is to examine the outcomes of an accelerated fractionated irradiation for N0 glottic carcinoma. METHODS: In this retrospective analysis, 29 patients with N0 glottic carcinoma treated by radiation therapy were enrolled. Thirteen patients had T1a disease, six had T1b disease, and ten had T2 disease. A fractional dose of 2.1 Gy was administered to seven patients. The total doses were 65.1 and 67.2 Gy in four and three patients, respectively. A fractional dose of 2.25 Gy was administered to 22 patients. The total doses were 63 and 67.5 Gy in 21 patients and 1 patient with T2 disease, respectively. Additionally, 13 patients underwent the use of TS-1 (80-100 mg per day). RESULTS: The median follow-up period was 33 months, and the 3-year local control rate was 95.6%. No patient had a lymph node or distant recurrence. As acute adverse events, grades 2 and 3 dermatitis were observed in 18 patients and 1 patient, and grades 2 and 3 mucositis were observed in 15 patients and 1 patient. As a late adverse event, one patient required tracheotomy because of laryngeal edema occurring. CONCLUSIONS: Accelerated fractionated irradiation may be an option in the radiation therapy of N0 glottic carcinoma because of its ability to shorten the treatment time.


Assuntos
Fracionamento da Dose de Radiação , Glote , Neoplasias Laríngeas , Humanos , Masculino , Feminino , Neoplasias Laríngeas/radioterapia , Pessoa de Meia-Idade , Idoso , Glote/patologia , Estudos Retrospectivos , Adulto , Idoso de 80 Anos ou mais , Resultado do Tratamento
2.
Surg Case Rep ; 9(1): 88, 2023 May 22.
Artigo em Inglês | MEDLINE | ID: mdl-37212955

RESUMO

BACKGROUND: The pectoralis major musculocutaneous flap (PMMF) is a pedicled flap often used as a reconstruction option in head and neck surgery, especially in cases with poor wound healing. However, applying PMMF after esophageal surgery is uncommon. We report here, the case of a successfully repaired refractory anastomotic fistula (RF) after total esophagectomy, by PMMF. CASE PRESENTATION: A 73-year-old man had a history of hypopharyngolaryngectomy, cervical esophagectomy, and reconstruction using a free jejunal graft for hypopharyngeal carcinosarcoma at the age of 54. He also received conservative treatment for pharyngo-jejunal anastomotic leakage (AL), then postoperative radiation therapy. This time, he was diagnosed with carcinosarcoma in the upper thoracic esophagus; cT3rN0M0, cStageII, according to the Japanese Classification of Esophageal Cancer 12th Edition. As a salvage surgery, thoracoscopic total resection of the esophageal remnant and reconstruction using gastric tube via posterior mediastinal route was performed. The distal side of the jejunal graft was cut and re-anastomosed with the top of the gastric tube. An AL was observed on the 6th postoperative day (POD), and after 2 months of conservative treatment was then diagnosed as RF. The 3/4 circumference of the anterior wall of the gastric tube was ruptured for 6 cm in length, and surgical repair using PMMF was performed on POD71. The edge of the defect was exposed and the PMMF (10 × 5 cm) fed by thoracoacromial vessels was prepared. Then, the skin of the flap and the wedge of the leakage were hand sutured via double layers with the skin of the flap facing the intestinal lumen. Although a minor AL was observed on POD19, it healed with conservative treatment. No complications, such as stenosis, reflux, re-leakage, were observed over 3 years of postoperative follow-up. CONCLUSIONS: The PMMF is a useful option for repairing intractable AL after esophagectomy, especially in cases with large defect, as well as difficulties for microvascular anastomosis due to previous operation, radiation, or wound inflammation.

3.
Biochem Biophys Res Commun ; 556: 142-148, 2021 06 04.
Artigo em Inglês | MEDLINE | ID: mdl-33845306

RESUMO

The relationship between cellular senescence and fibrosis in the kidney is being elucidated and we have identified it as therapeutic target in recent studies. Chronic kidney disease has also become a lifestyle disease, often developing on the background of hypertension and dyslipidemia. In this study, we clarify the effect of interaction between these two conditions on kidney fibrosis and senescence. Wild type mice (WT), apolipoprotein E-/- mice (ApoEKO), and endothelial nitric oxide synthase (eNOS)-/- ApoE-/- mice (DKO) were obtained by breeding. Unilateral ureteral obstruction (UUO) was performed on 8-10 week old male mice and the degree of renal tubular injury, fibrosis and kidney senescence were evaluated. DKO manifested elevated blood pressure, higher total cholesterol and lower HDL than WT. DKO showed sustained kidney injury molecule-1 protein expression. Kidney fibrosis was significantly higher in ApoEKO and DKO. mRNA expression of genes related to kidney fibrosis was the highest in DKO. The mRNA expression of Zinc-α2-Glycoprotein and heme oxygenase-1 were significantly decreased in DKO. Furthermore, mRNA expression of p53, p21 and p16 were increased both in ApoEKO and DKO, with DKO being the highest. Senescence associated ß-gal positive tubule area was significantly increased in DKO. Increased DNA damage and target of rapamycin-autophagy spatial coupling compartments (TASCCs) formation was found in DKO. Mice with endothelial dysfunction and dyslipidemia developed kidney fibrosis and accelerated senescence even in young mice after injury. These data highlight the fact managing lifestyle-related diseases from a young age is important for CKD prevention.


Assuntos
Apolipoproteínas E/deficiência , Senescência Celular/genética , Fibrose/genética , Deleção de Genes , Rim/patologia , Óxido Nítrico Sintase Tipo III/deficiência , Insuficiência Renal Crônica/genética , Animais , Apolipoproteínas E/genética , Autofagia , Pressão Sanguínea , Inibidor de Quinase Dependente de Ciclina p21 , Dano ao DNA/genética , Genes p16 , Genes p53 , Humanos , Rim/lesões , Lipídeos , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Knockout , Óxido Nítrico Sintase Tipo III/genética , Serina-Treonina Quinases TOR/metabolismo
4.
Intern Med ; 60(19): 3129-3136, 2021 Oct 01.
Artigo em Inglês | MEDLINE | ID: mdl-33840699

RESUMO

Tubulointerstitial nephritis (TIN) with IgM-positive plasma cells (IgMPC-TIN) is an autoimmune kidney disease characterized by IgM/CD138-double-positive plasma cell infiltration in the tubulointerstitium. A 50-year-old man developed IgMPC-TIN and presented with crystalline inclusions in the rough endoplasmic reticulum. Intracellular crystal formation is a rare finding in paraprotein-related kidney diseases, but this case showed no pathogenic monoclonal immunoglobulin. Prednisolone (PSL, 30 mg) improved the TIN, but PSL tapering resulted in the recurrence of TIN. Combination therapy with 15 mg PSL and 150 mg mizoribine ultimately stabilized TIN. This case offers original evidence concerning the pathophysiology and treatment strategy of IgMPC-TIN.


Assuntos
Nefrite Intersticial , Plasmócitos , Retículo Endoplasmático Rugoso , Glucocorticoides , Humanos , Imunoglobulina M , Masculino , Pessoa de Meia-Idade
5.
J Med Invest ; 67(3.4): 315-320, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-33148908

RESUMO

Autosomal dominant polycystic kidney disease (ADPKD) develops into end-stage kidney disease by 65 years of age in an estimated 45%-70% of patients. Recent trials revealed that tolvaptan inhibits disease progression both in early-stage or late-stage ADPKD ; however, stratified analysis showed a difference of favorable factors correlated with tolvaptan efficacy between early-stage and late-stage ADPKD. Thus, we examined the efficacy of tolvaptan in ADPKD with a wide range of estimated glomerular filtration rates (eGFR). We enrolled 24 patients with eGFR 35.3 (28.0-65.5) ml / min / 1.73m2 and evaluated treatment effect as ΔΔeGFR (ml / min / 1.73m2 / year) or ΔΔtotal kidney volume (TKV) (% / year) that was calculated as post-treatment annual change - pre-treatment annual change. Pre ΔeGFR was significantly low in eGFR responders, defined as ΔΔeGFR > 0 ml / min / 1.73m2 / year. In eGFR responders, pre ΔeGFR, post ΔeGFR, eGFR, TKV, and proteinuria were significantly correlated with ΔΔeGFR. In TKV responders defined as ΔΔTKV > 5 % / year, we identified hypertension history, proteinuria, TKV, and post ΔTKV as significantly correlated factors with ΔΔTKV. In conclusion, pre ΔeGFR may be a predictive factor of therapeutic efficacy on kidney function. Tolvaptan may have greater efficacy in early-stage ADPKD with rapid GFR decline or with well-controlled blood pressure. J. Med. Invest. 67 : 315-320, August, 2020.


Assuntos
Rim Policístico Autossômico Dominante/tratamento farmacológico , Tolvaptan/uso terapêutico , Adulto , Feminino , Taxa de Filtração Glomerular , Humanos , Rim/patologia , Masculino , Pessoa de Meia-Idade , Rim Policístico Autossômico Dominante/patologia , Rim Policístico Autossômico Dominante/fisiopatologia
6.
BMC Nephrol ; 21(1): 369, 2020 08 26.
Artigo em Inglês | MEDLINE | ID: mdl-32847543

RESUMO

BACKGROUND: When we encounter patients who present with both a neck mass and nephrotic syndrome, both malignancy and Kimura's disease need to be evaluated as the therapeutic strategies differ vastly between them. CASE PRESENTATION: We present the case of a 27-year-old male patient with neck mass and nephrotic syndrome. The presence of both eosinophilia and elevated immunoglobulin E levels were concerning for Kimura's disease, which is an allergic syndrome defined by eosinophilic granulomas of neck soft tissue along with peripheral eosinophilia. The eventual final diagnosis, however, was sclerosing mucoepidermoid carcinoma of parotid gland with both eosinophilia and membranous nephropathy. Following the surgical resection of the mass, the nephrotic syndrome completely resolved. CONCLUSION: Detailed histopathological assessments of both the parotid gland and renal tissue were key aspects of the diagnosis and management to exclude Kimura's disease.


Assuntos
Carcinoma Mucoepidermoide/diagnóstico , Eosinofilia/sangue , Glomerulonefrite Membranosa/diagnóstico , Imunoglobulina E/sangue , Doença de Kimura/diagnóstico , Neoplasias Parotídeas/diagnóstico , Adulto , Carcinoma Mucoepidermoide/complicações , Carcinoma Mucoepidermoide/patologia , Carcinoma Mucoepidermoide/cirurgia , Diagnóstico Diferencial , Eosinofilia/complicações , Glomerulonefrite Membranosa/etiologia , Glomerulonefrite Membranosa/patologia , Humanos , Masculino , Neoplasias Parotídeas/complicações , Neoplasias Parotídeas/patologia , Neoplasias Parotídeas/cirurgia
8.
Sci Rep ; 9(1): 14869, 2019 10 16.
Artigo em Inglês | MEDLINE | ID: mdl-31619724

RESUMO

Circulating ApolipoproteinL1 (ApoL1) is a component of pre-ß-high-density lipoprotein (HDL), however little is known about the relationship of ApoL1 with cardiometabolic factors. Considering previous studies reporting the correlation of ApoL1 to triglyceride, we have hypothesized that ApoL1 associates with insulin-related metabolism. The current study examined their associations in 126 non-diabetic subjects and 36 patients with type 2 diabetes (T2DM). Non-diabetic subjects demonstrated triglyceride (standardized coefficients [s.c.] = 0.204, p < 0.05), body mass index (s.c. =0.232, p < 0.05) and HDL cholesterol (s.c. = -0.203, p < 0.05) as independent determinant of ApoL1 levels, and the significant elevation of ApoL1 in metabolic syndrome. Lipoprotein fractionation analysis revealed the predominant distribution of ApoL1 in large HDL fraction, and the significant increase of ApoL1 in large LDL fraction in high ApoL1 samples with insulin resistance. In T2DM, ApoL1 was higher in T2DM with metabolic syndrome, however ApoL1 was lower with ß cell dysfunction. Insulin significantly promotes ApoL1 synthesis and secretion in HepG2 cells. In conclusion, circulating ApoL1 may be associated with abnormal HDL metabolism in insulin resistant status. This may suggest a regulation of insulin signal on the ApoL1 level, leading to offer a novel insight to the ApoL1 biology.


Assuntos
Apolipoproteína L1/sangue , Diabetes Mellitus Tipo 2/sangue , Células Secretoras de Insulina/metabolismo , Insulina/sangue , Síndrome Metabólica/sangue , Adulto , Apolipoproteína L1/genética , Índice de Massa Corporal , Estudos de Casos e Controles , HDL-Colesterol/sangue , LDL-Colesterol/sangue , Diabetes Mellitus Tipo 2/genética , Diabetes Mellitus Tipo 2/patologia , Feminino , Expressão Gênica , Células Hep G2 , Humanos , Insulina/genética , Insulina/farmacologia , Resistência à Insulina/genética , Células Secretoras de Insulina/patologia , Metabolismo dos Lipídeos/genética , Masculino , Síndrome Metabólica/genética , Síndrome Metabólica/patologia , Triglicerídeos/sangue
9.
PLoS One ; 14(5): e0216788, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31150422

RESUMO

Diabetic nephropathy (DN) is among the most serious complications of diabetes mellitus, and often leads to end-stage renal disease ultimately requiring dialysis or renal transplantation. The loss of podocytes has been reported to have a role in the onset and progression of DN. Here, we addressed the activation mechanism of Smad3 signaling in podocytes. Expression of RII and activation of Smad3 were induced by AGE exposure (P<0.05). Reduction of the activation of RII-Smad3 signaling ameliorated podocyte injuries in Smad3-knockout diabetic mice. The bone morphogenetic protein 4 (BMP4) significantly regulated activation of RII-Smad3 signalings (P<0.05). Moreover, the epithelium-specific transcription factor, Elf3was induced by AGE stimulation and, subsequently, upregulated RII expression in cultured podocytes. Induction of Elf3 and activation of RII-Smad3 signaling, leading to a decrease in WT1 expression, were observed in podocytes in diabetic human kidneys. Moreover, AGE treatment induced the secretion of Elf3-containing exosomes from cultured podocytes, which was dependent on the activation of the TGF-ß-Smad3 signaling pathway. In addition, exosomal Elf3 protein in urine could be measured only in urinary exosomes from patients with DN. The appearance of urinary exosomal Elf3 protein in patients with DN suggested the existence of irreversible injuries in podocytes. The rate of decline in the estimated Glomerular Filtration Rate (eGFR) after measurement of urinary exosomal Elf3 protein levels in patients with DN (R2 = 0.7259) might be useful as an early non-invasive marker for podocyte injuries in DN.


Assuntos
Proteínas de Ligação a DNA/urina , Nefropatias Diabéticas/urina , Exossomos/metabolismo , Podócitos/metabolismo , Transdução de Sinais , Proteína Smad3/urina , Fatores de Transcrição/urina , Animais , Biomarcadores/urina , Nefropatias Diabéticas/patologia , Exossomos/patologia , Taxa de Filtração Glomerular , Masculino , Camundongos , Podócitos/patologia
10.
J Med Invest ; 66(1.2): 172-177, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31064933

RESUMO

BACKGROUND: IVC diameter on expiration (IVCdexp) is measured by echocardiography routinely. It is used to estimate volume status and designated as a definitive marker for determining dry weight (DW) in patients undergoing hemodialysis (HD). METHODS: A cross-sectional study. Outpatients (n = 107), and inpatients (n = 35) undergoing HD were enrolled. IVCdexp was measured on non-dialysis days in outpatients and dialysis days before and after the dialysis session in inpatients. In outpatients, the relationship of IVCdexp with echocardiography findings and clinical characteristics was analyzed. IVCdexp was compared with the other DW markers as a predictive factor for intradialytic hypotension. In inpatients, IVCdexp was analyzed by dividing inpatients with or without fluid in extravascular space. RESULTS: IVCdexp ranged from 5.4 to 16.9 mm in outpatients who had optimal DW. IVCdexp could reflect on volume status, but not predictive for intradialytic hypotension and not suggestive of fluid in extravascular space. CONCLUSIONS: IVCdexp was a rough marker to estimate volume status and only useful in suggesting apparent hypervolemia or hypovolemia. We should know that the IVCdexp value is affected by a lotof factors and not a definitive marker for estimating practical DW. J. Med. Invest. 66 : 172-177, February, 2019.


Assuntos
Veia Cava Inferior/anatomia & histologia , Idoso , Idoso de 80 Anos ou mais , Biomarcadores , Estudos Transversais , Ecocardiografia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Diálise Renal , Veia Cava Inferior/diagnóstico por imagem
11.
CEN Case Rep ; 8(2): 134-138, 2019 05.
Artigo em Inglês | MEDLINE | ID: mdl-30721455

RESUMO

Thromboembolism is a major complication of nephrotic syndrome, with the renal vein being the most frequent site. However, the incidence of portal vein thrombosis (PVT) in patients with nephrotic syndrome is rare. We report a case of a relapsed steroid-dependent minimal change disease with incidental PVT. A 38-year-old man presented with anasarca. Elevated liver enzymes were discovered during routine blood testing within days after commencing treatment. Although drug-induced liver injuries are frequently observed with mild aminotransferase abnormality during therapy with steroid or immune-suppressive agents, imaging revealed a massive thrombus of the portal vein, which was treated by anticoagulant therapy with edoxaban. Treatment with anticoagulant therapy could normalize liver function. Two months after the initiation of treatment with edoxaban, the follow-up CT scan and ultrasound showed the disappearance of PVT. Our case suggests that much attention should be paid to PVT as a cause of liver enzyme elevation when treating patients with nephrotic syndrome.


Assuntos
Doença Hepática Induzida por Substâncias e Drogas/tratamento farmacológico , Síndrome Nefrótica/complicações , Veia Porta/patologia , Trombose Venosa/tratamento farmacológico , Administração Oral , Adulto , Anticoagulantes/uso terapêutico , Doença Hepática Induzida por Substâncias e Drogas/complicações , Doença Hepática Induzida por Substâncias e Drogas/diagnóstico por imagem , Inibidores do Fator Xa/uso terapêutico , Humanos , Masculino , Piridinas/uso terapêutico , Tiazóis/uso terapêutico , Resultado do Tratamento , Trombose Venosa/diagnóstico por imagem
12.
Am J Physiol Endocrinol Metab ; 316(3): E418-E431, 2019 03 01.
Artigo em Inglês | MEDLINE | ID: mdl-30601699

RESUMO

Diabetic nephropathy (DN) causes mesangial matrix expansion, which results in glomerulosclerosis and renal failure. Collagen IV (COL4) is a major component of the mesangial matrix that is positively regulated by bone morphogenetic protein 4 (BMP4)/suppressor of mothers against decapentaplegic (Smad1) signaling. Because previous studies showed that retinoids treatment had a beneficial effect on kidney disease, we investigated the therapeutic potential of retinoids in DN, focusing especially on the regulatory mechanism of BMP4. Diabetes was induced with streptozotocin in 12-wk-old male Crl:CD1(ICR) mice, and, 1 mo later, we initiated intraperitoneal injection of all-trans retinoic acid (ATRA) three times weekly. Glomerular matrix expansion, which was associated with increased BMP4, phosphorylated Smad1, and COL4 expression, worsened in diabetic mice at 24 wk of age. ATRA administration alleviated DN and downregulated BMP4, phosopho-Smad1, and COL4. In cultured mouse mesangial cells, treatment with ATRA or a retinoic acid receptor-α (RARα) agonist significantly decreased BMP4 and COL4 expression. Genomic analysis suggested two putative retinoic acid response elements (RAREs) for the mouse Bmp4 gene. Chromatin immunoprecipitation analysis and reporter assays indicated a putative RARE of the Bmp4 gene, located 11,488-11,501 bp upstream of exon 1A and bound to RARα and retinoid X receptor (RXR), which suppressed BMP4 expression after ATRA addition. ATRA suppressed BMP4 via binding of a RARα/RXR heterodimer to a unique RARE, alleviating glomerular matrix expansion in diabetic mice. These findings provide a novel regulatory mechanism for treatment of DN.


Assuntos
Proteína Morfogenética Óssea 4/efeitos dos fármacos , Colágeno Tipo IV/efeitos dos fármacos , Nefropatias Diabéticas/metabolismo , Células Mesangiais/efeitos dos fármacos , Tretinoína/farmacologia , Animais , Proteína Morfogenética Óssea 4/genética , Proteína Morfogenética Óssea 4/metabolismo , Células Cultivadas , Colágeno Tipo IV/genética , Colágeno Tipo IV/metabolismo , Células Mesangiais/metabolismo , Camundongos , Elementos de Resposta , Receptor alfa de Ácido Retinoico/agonistas , Receptores X de Retinoides/metabolismo , Proteína Smad1/efeitos dos fármacos , Proteína Smad1/genética , Proteína Smad1/metabolismo
13.
Intern Med ; 58(5): 679-684, 2019 Mar 01.
Artigo em Inglês | MEDLINE | ID: mdl-30449791

RESUMO

A 61-year-old man was diagnosed with sarcoidosis involving the lungs, eyes, parotid gland and extrathoracic lymph nodes complicated by chronic kidney injury and hypercalcemia. Kidney biopsy showed non-specific interstitial nephritis and nephrosclerosis. However, immunohistochemical staining of cell surface markers revealed a multinucleated giant macrophage surrounded by T-cells, suggesting granulomatous interstitial nephritis. Corticosteroid improved the kidney function, and reduced the serum levels of calcium and angiotensin-converting enzyme. Sarcoid nephropathy may be caused by the combination of several sarcoidosis-associated pathophysiological conditions and a comprehensive kidney examination should be performed to assess the type of injury when determining a treatment strategy.


Assuntos
Nefrite Intersticial/etiologia , Sarcoidose/complicações , Biomarcadores/sangue , Biópsia , Cálcio/sangue , Glucocorticoides/uso terapêutico , Humanos , Hipercalcemia/etiologia , Rim/patologia , Masculino , Pessoa de Meia-Idade , Nefrite Intersticial/sangue , Nefrite Intersticial/tratamento farmacológico , Nefrite Intersticial/patologia , Nefroesclerose/sangue , Nefroesclerose/etiologia , Nefroesclerose/patologia , Peptidil Dipeptidase A/sangue , Cintilografia , Sarcoidose/sangue , Sarcoidose/tratamento farmacológico , Sarcoidose/patologia
14.
Biochem Biophys Res Commun ; 508(2): 654-659, 2019 01 08.
Artigo em Inglês | MEDLINE | ID: mdl-30522864

RESUMO

The glomerulus is a network of capillaries known as a tuft, located at the beginning of a nephron in the kidney. Here we describe a novel method for the induction of a macroscopically visible three-dimensional glomerulus-like sphere (GLS). This procedure did not require any additional cytokines and completed the formation of spheres within 24 h. After the formation was complete, GLS maintained a steady state for at least five days without proliferation and without a decrease in viability. Therefore, this procedure assists various assays for a prolong period of time. Overall, our protocol allows for a very simple mixing of cells from different sources to obtain fine-grained and highly dispersed GLSs. The kidney filtration barrier is a unique structure characterized by a complex three-dimensional framework of podocytes and endothelial cells. GLS exhibited the induction of many podocyte-specific gene profiles similar to those in adult human kidneys, suggesting that the sphere formation process is important for the maturation of podocytes. Focal segmental glomerulosclerosis (FSGS) is one of the major causes of steroid-resistant nephrotic syndrome, and some circulating permeability factors in the patient's serum FSGS have been implicated in the pathogenesis of the disease. Serum from patients with FSGS induced the collapse of GLS, which imitates the appearance of glomerulosclerosis in patients. In conclusion, the investigation and use of GLS may provide a novel method to elucidate the molecular mechanisms underlying complicated and unexplained events in glomeruli in a similar condition in adult kidneys.


Assuntos
Glomerulosclerose Segmentar e Focal/metabolismo , Glomérulos Renais/metabolismo , Células Cultivadas , Glomerulosclerose Segmentar e Focal/sangue , Humanos
15.
J Med Invest ; 65(3.4): 208-215, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-30282862

RESUMO

Diabetic nephropathy (DN) is the major cause of end-stage renal failure and is associated with increased morbidity and mortality as compared to other causes of renal disease. Albuminuria is often the first clinical indicator of the presence of DN. However, albuminuria or proteinuria is a common symptom in patients with various renal disorders. Therefore, specific biomarkers for the diagnosis of DN are required. A primary hallmark of DN is the progressive damage and death of glomerular podocytes, resulting in the leaking of proteins into the urine. Urinary exosomes released by podocytes are microvesicles containing information of the originated cells. Podocyte-derived signal transduction factors (PDSTFs) are good candidates to assess podocyte injuries. The profile of PDSTFs in urinary exosomes from patients with DN is different from that from patients with minimal change nehrotic syndrome. In addition, PDSTFs molecules in exosomes were derived from primary murine podocytes under high glucose conditions. Among PDSTFs in urinary exosomes, Wilms tumor 1 (WT1) levels reflected damage of diabetic glomeruli in the patients. Urinary exosomal WT1 can predict the decline in eGFR for the following several years. In conclusion, urinary exosomal WT1 is a useful biomarker to improve risk stratification in patients with DN. J. Med. Invest. 65:208-215, August, 2018.


Assuntos
Nefropatias Diabéticas/diagnóstico , Genes do Tumor de Wilms , RNA Mensageiro/genética , RNA Mensageiro/urina , Adolescente , Adulto , Biomarcadores/urina , Estudos de Casos e Controles , Células Cultivadas , Nefropatias Diabéticas/genética , Nefropatias Diabéticas/urina , Exossomos/genética , Marcadores Genéticos , Humanos , Pessoa de Meia-Idade , Nefrose Lipoide/diagnóstico , Nefrose Lipoide/genética , Nefrose Lipoide/urina , Podócitos/metabolismo , Prognóstico , Proteínas WT1/genética , Proteínas WT1/metabolismo , Adulto Jovem
16.
Intern Med ; 57(24): 3597-3602, 2018 Dec 15.
Artigo em Inglês | MEDLINE | ID: mdl-30101939

RESUMO

Light Chain Proximal Tubulopathy (LCPT) is a rare form of paraprotein-related kidney disease in which monoclonal free light chains damage the proximal renal tubular epithelial cells. We herein report the case of a 78-year-old woman who presented with anemia and kidney dysfunction. Serum and urine protein electrophoresis analyses revealed a monoclonal IgD and λ free light chains. Proximal tubular injury and the accumulation of λ light chains were found by kidney biopsy. Electron microscopy revealed no organized structure suggestive of crystals. LCPT was caused by IgD lambda myeloma and bortezomib and dexamethasone therapy led to very good partial response (VGPR) without a worsening of the kidney function.


Assuntos
Imunoglobulina D/análise , Cadeias Leves de Imunoglobulina/análise , Nefropatias/complicações , Nefropatias/imunologia , Túbulos Renais Proximais/imunologia , Mieloma Múltiplo/complicações , Mieloma Múltiplo/imunologia , Idoso , Anemia/etiologia , Antineoplásicos/uso terapêutico , Biópsia , Bortezomib/uso terapêutico , Dexametasona/uso terapêutico , Feminino , Humanos , Nefropatias/patologia , Nefropatias/fisiopatologia , Túbulos Renais Proximais/patologia , Túbulos Renais Proximais/fisiopatologia , Mieloma Múltiplo/fisiopatologia
17.
Sci Rep ; 8(1): 13011, 2018 08 29.
Artigo em Inglês | MEDLINE | ID: mdl-30158674

RESUMO

Podocyte injury has been proposed to play an important role in diabetic nephropathy; however, its pathological mechanism remains unclear. We have shown that bone morphogenetic protein 4 (BMP4) signaling leads to the glomerular changes characteristic of this disorder. To analyze the molecular mechanism of podocyte injury, the effect of BMP4 was investigated using streptozotocin (STZ)-induced, Bmp4 heterozygous knockout (Bmp4+/-) and podocyte-specific Bmp4 knockout mice. Mice with STZ-induced diabetes exhibited glomerular matrix hyperplasia and decreased numbers of podocyte nucleus-specific WT1-positive cells. The number of podocytes and proteinuria were improved in both diabetic Bmp4 knockout mouse models compared to the effects observed in the control mice. The effect of BMP4 overexpression on Bmp4-induced or podocyte-specific transgenic mice was examined. Tamoxifen-induced Bmp4-overexpressing mice exhibited mesangial matrix expansion and decreased numbers of WT1-positive cells. Podocyte-specific Bmp4-overexpressing mice displayed increased kidney BMP4 expression and mesangial matrix expansion but decreased nephrin expression and numbers of WT1-positive cells. Both lines of Bmp4-overexpressing mice exhibited increased albuminuria. In cultured podocytes, BMP4 increased phospho-p38 levels. BMP4 decreased nephrin expression but increased cleaved caspase-3 levels. p38 suppression inhibited caspase-3 activation. Apoptosis was confirmed in STZ-diabetic glomeruli and Bmp4-overexpressing mice. Bmp4 +/- mice with diabetes displayed reduced apoptosis. Based on these data, the BMP4 signaling pathway plays important roles in the development of both podocyte injury and mesangial matrix expansion in diabetic nephropathy.


Assuntos
Proteína Morfogenética Óssea 4/metabolismo , Diabetes Mellitus Experimental/complicações , Nefropatias Diabéticas/patologia , Nefropatias Diabéticas/fisiopatologia , Podócitos/patologia , Transdução de Sinais , Albuminúria , Animais , Proteína Morfogenética Óssea 4/deficiência , Células Mesangiais/patologia , Camundongos , Camundongos Knockout , Proteínas Repressoras/análise , Proteínas WT1
18.
Sci Rep ; 8(1): 10548, 2018 Jul 12.
Artigo em Inglês | MEDLINE | ID: mdl-30002389

RESUMO

Diabetic nephropathy (DN) is the major cause of end-stage renal failure and is associated with increased morbidity and mortality compared with other causes of renal diseases. We previously found that Smad1 plays a critical role in the development of DN both in vitro and in vivo. However, functional interaction between Smad1 and Smad3 signaling in DN is unclear. Here, we addressed the molecular interplay between Smad1 and Smad3 signaling under a diabetic condition by using Smad3-knockout diabetic mice. Extracellular matrix (ECM) protein overexpression and Smad1 activation were observed in the glomeruli of db/db mice but were suppressed in the glomeruli of Smad3+/-; db/db mice. Smad3 activation enhanced the phosphorylation of Smad1 C-terminal domain but decreased the phosphorylation of linker domain, thus regulating Smad1 activation in advanced glycation end product-treated mesangial cells (MCs). However, forced phosphorylation of the Smad1 linker domain did not affect Smad3 activation in MCs. Phosphorylation of the Smad1 linker domain increased in Smad3+/-; db/db mice and probucol-treated db/db mice, which was consistent with the attenuation of ECM overproduction. These results indicate that Smad3 expression and activation or probucol treatment alters Smad1 phosphorylation, thus suggesting new molecular mechanisms underlying DN development and progression.


Assuntos
Nefropatias Diabéticas/patologia , Produtos Finais de Glicação Avançada/metabolismo , Proteína Smad1/metabolismo , Proteína Smad3/metabolismo , Animais , Antioxidantes/farmacologia , Antioxidantes/uso terapêutico , Células Cultivadas , Nefropatias Diabéticas/sangue , Nefropatias Diabéticas/tratamento farmacológico , Nefropatias Diabéticas/genética , Modelos Animais de Doenças , Progressão da Doença , Proteínas da Matriz Extracelular/metabolismo , Feminino , Mesângio Glomerular/citologia , Mesângio Glomerular/patologia , Produtos Finais de Glicação Avançada/sangue , Humanos , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Knockout , Fosforilação/efeitos dos fármacos , Cultura Primária de Células , Probucol/farmacologia , Probucol/uso terapêutico , Domínios Proteicos , Proteína Smad3/genética
19.
Oxf Med Case Reports ; 2018(4): omy009, 2018 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-29713488

RESUMO

Alectinib is a second generation anaplastic lymphoma kinase (ALK) tyrosine kinase inhibitor and is generally effective and tolerated in patients who have demonstrated disease progression or adverse effects while on the first generation inhibitor, crizotinib. ALK inhibitors can cause a reversible chronic increase of serum creatinine concentration; however, they rarely induce progressive renal insufficiency. We herein report a case of a 68-year-old woman diagnosed with ALK-positive advanced non-small cell lung cancer and who received ALK inhibitors. Due to dysgeusia and transaminitis, her medication was switched from crizotinib to alectinib. Rapid progressive glomerulonephritis developed 1 year after the initiation of alectinib treatment. A renal biopsy revealed unique kidney lesions in both tubules and glomeruli. Glucocorticoid therapy partially reversed kidney impairment. However, re-administration of alectinib caused kidney dysfunction, which was improved by the cessation of alectinib. Our case suggests that much attention should be paid to kidney function when using ALK inhibitors.

20.
PLoS One ; 13(4): e0195523, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-29624611

RESUMO

Urinary type IV collagen (U-Col4) and albumin excretion is evaluated to monitor the development of diabetic kidney disease. However, U-Col4 excretion in the general population without diabetes has not yet been fully elucidated. In this study, 1067 participants without diabetes and with urinary albumin-creatinine ratio <300 mg/gCr (normo- or microalbuminuria) who underwent an annual health examination in 2004 were enrolled and observed for 5 years. They were divided according to the amount of U-Col4 or urinary albumin excreted. The decline in estimated glomerular filtration rate (eGFR) was calculated. In participants with eGFR ≥80 mL/min, abnormal U-Col4 excretion was indicated as a significant independent risk factor for 10% eGFR change per year, which is one of the prognostic factors for the development of end-stage kidney disease. Moreover, in contrast to urinary albumin excretion, U-Col4 excretion was not related to age or kidney function, suggesting that some individuals with abnormal U-Col4 excretion can have an independent hidden risk for the development of kidney dysfunction. In conclusion, it is important to measure U-Col4 excretion in the general population without diabetes to determine changes in renal features in every individual and help detect future complications such as diabetic kidney disease. If U-Col4 excretion is abnormal, kidney manifestation should be carefully followed up, even if the kidney function and urinalysis findings are normal.


Assuntos
Colágeno Tipo IV/urina , Taxa de Filtração Glomerular/fisiologia , Insuficiência Renal/urina , Adulto , Idoso , Idoso de 80 Anos ou mais , Albuminúria/etiologia , Albuminúria/urina , Povo Asiático , Nefropatias Diabéticas/etiologia , Nefropatias Diabéticas/urina , Progressão da Doença , Feminino , Humanos , Japão , Estimativa de Kaplan-Meier , Masculino , Pessoa de Meia-Idade , Prognóstico , Insuficiência Renal/etiologia , Fatores de Risco , Adulto Jovem
SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA
...