RESUMO
In 2010, a 71-year-old man was referred to our hospital because of mild proteinuria and hematuria. At that time, he had been asymptomatic. Three months later he noticed macroscopic hematuria, followed by general malaise, and then anorexia. He was admitted for acute kidney injury (serum creatinine 2.7 mg/dL), marked proteinuria (4.35 g/gCr), and elevated C-reactive protein (7.21 mg/dL). Some vesicles were noted on the soft palate, and a throat culture yielded a growth of group A beta-hemolytic streptococci. Antistreptolysin O and antistreptokinase titers were elevated, but serum complement levels were within normal limits. Antineutrophil cytoplasmic antibodies (ANCA) directed against elastase and bactericidal permeability increasing protein (BPI)were positive. The renal function and inflammation did not improve despite oral antibiotic therapy. Pathological examination of a renal biopsy specimen revealed diffuse crescent formation, numerous subepithelial dome-shaped deposits (humps), and prominent endocapillary proliferation. Furthermore, a focal and segmental spike appearance was seen, with deposits smaller than humps. There was a striking clinical improvement after steroid pulse therapy followed by oral prednisolone. The features of this case strongly suggest crescentic PSAGN accompanied by pre-existing membranous nephropathy.
Assuntos
Antibacterianos/uso terapêutico , Glomerulonefrite Membranosa/tratamento farmacológico , Glomerulonefrite/tratamento farmacológico , Doença Aguda , Idoso , Autoanticorpos/sangue , Glomerulonefrite/complicações , Glomerulonefrite/diagnóstico , Glomerulonefrite/imunologia , Glomerulonefrite Membranosa/complicações , Glomerulonefrite Membranosa/diagnóstico , Humanos , Masculino , Proteinúria/urinaRESUMO
A 33-year-old man was diagnosed with Crohn's disease in 2001, and treated with mesalazine and ranitidine. Administration of infliximab was started in 2007 and led to a decrease in the activity of the Crohn's disease. He was referred to our department in the summer of 2011 following rapid progression of renal insufficiency, with serum creatinine levels increasing from 1.5 mg/dL to 4.3 mg/dL within 2 months. On admission, laboratory findings showed signs of inflammation, anemia, proteinuria, and hematuria. Renal biopsy results indicated the diagnosis of granulomatous interstitial nephritis. Neither clinical manifestations nor laboratory findings were suggestive of infectious disease, sarcoidosis, Wegener's granulomatosis or tubulointerstitial nephritis and uveitis. Mesalazine and ranitidine were discontinued in view of reports of drug-induced granulomatous interstitial nephritis. Levels of C-reactive protein immediately decreased, but renal function remained unimproved. Treatment with steroid pulse therapy was then initiated, followed by oral prednisolone at 40 mg/day, and his serum creatinine recovered to 2.3 mg/dL. Mesalazine and/or ranitidine appear to have been responsible for the granulomatous interstitial nephritis. In cases of Crohn's disease showing rapid deterioration of renal function, drug-induced renal disease should be considered, even if the drugs have been taken without apparent problems for a long duration.
Assuntos
Doença de Crohn/tratamento farmacológico , Doença Granulomatosa Crônica/induzido quimicamente , Nefrite Intersticial/induzido quimicamente , Adulto , Creatinina/sangue , Doença de Crohn/patologia , Doença Granulomatosa Crônica/tratamento farmacológico , Humanos , Masculino , Prednisolona/uso terapêutico , Insuficiência Renal/tratamento farmacológicoRESUMO
OBJECTIVE: Few findings are available regarding adult-onset minimal change nephrotic syndrome (MCNS) with respect to the disease course and complications, such as acute kidney injury (AKI). We therefore performed a retrospective review to characterize the clinical presentations, steroid responsiveness and complications of adult-onset MCNS patients in our hospital. PATIENTS AND METHODS: We retrospectively reviewed 40 cases of idiopathic adult-onset MCNS who had been investigated and treated at a single center. Patients between 18 and 50 years of age (Younger group) at the time of biopsy were compared with those older than 50 years (Older group) with regard to demographic data, clinical features and treatment outcome. RESULTS: Baseline characteristics of the 40 patients were: median age, 42 years (interquartile range: 28-63 years); male, 70%; mean (+/- standard deviation) systolic and diastolic blood pressures, 125 +/- 17 mmHg and 78 +/- 12 mmHg, respectively; estimated glomerular filtration rate (eGFR), 74 mL/min/1.73 m2 (range: 64-94 mL/min/1.73 m2); serum albumin, 1.8 +/- 0.3 g/dL; and urinary protein, 7.8 g/day (range: 3.9-10.4 g/day). All except for one patient received steroid pulse therapy. Time to complete response (CR) was 12 days (range: 8-21 days). Time to CR was significantly longer in the Older group (p = 0.011). The Late-responder group (time to CR > 2 weeks)was significantly older (p < 0.01), with a low eGFR (p < 0.001) and a higher prevalence of interstitial fibrosis in renal biopsy before the initiation of corticosteroid therapy (p < 0.05), compared with the Early-responder group. AKI was observed in 14 patients. Patients with an episode of AKI were significantly older (p = 0.005), with a lower eGFR (p < 0.002) and a higher prevalence of cellular casts (p < 0.05). At the follow-up, 19 patients (51%) had experienced relapses. The relapse rate was significantly lower in the Older group than in the Younger group (p < 0.05). CONCLUSION: The present study revealed that older patients had a longer period to CR and a higher risk of AKI at follow-up.
Assuntos
Nefrose Lipoide/tratamento farmacológico , Nefrose Lipoide/fisiopatologia , Injúria Renal Aguda/diagnóstico , Injúria Renal Aguda/tratamento farmacológico , Injúria Renal Aguda/fisiopatologia , Adulto , Fatores Etários , Feminino , Taxa de Filtração Glomerular/efeitos dos fármacos , Taxa de Filtração Glomerular/fisiologia , Taxa de Filtração Glomerular/efeitos da radiação , Humanos , Masculino , Pessoa de Meia-Idade , Nefrose Lipoide/diagnóstico , Recidiva , Estudos Retrospectivos , Esteroides/uso terapêutico , Resultado do TratamentoRESUMO
Immune check point inhibitors (ICIs) are now increasingly used for cancer therapy. At the same time, by activating the immune system, ICIs induce unique side effects, termed immune-related adverse events (irAEs). Renal irAEs, although uncommon, result in acute tubulointerstitial nephritis. Recently, because of an increase in ICI administration, renal irAEs, including glomerulonephritis, are being increasingly reported. A 69-year-old man presented with nephrotic syndrome after use of the ICI nivolumab. He underwent renal biopsy and was diagnosed with membranous nephropathy (MN) without acute tubulointerstitial nephritis. Immunofluorescence staining was negative for IgG4 and phospholipase A2 receptor (PLA2R), suggesting a malignancy-associated pattern. Oral glucocorticoid therapy was started as the standard treatment for irAEs, which resulted in complete remission of the nephrotic syndrome in 20 months. We suggest his MN was induced or accelerated by immune activation due to nivolumab. It means that ICIs possibly induce not only acute tubulointerstitial nephritis but also nephrotic syndrome due to MN as renal irAEs which is treatable with glucocorticoid.
Assuntos
Adenocarcinoma de Pulmão , Glomerulonefrite Membranosa , Neoplasias Pulmonares , Síndrome Nefrótica , Adenocarcinoma de Pulmão/tratamento farmacológico , Idoso , Feminino , Glomerulonefrite Membranosa/diagnóstico , Glomerulonefrite Membranosa/tratamento farmacológico , Glucocorticoides/uso terapêutico , Humanos , Neoplasias Pulmonares/tratamento farmacológico , Masculino , Nefrite Intersticial , Síndrome Nefrótica/induzido quimicamente , Síndrome Nefrótica/diagnóstico , Síndrome Nefrótica/tratamento farmacológico , Nivolumabe/efeitos adversosRESUMO
In December 2008, a 69-year-old Japanese woman was admitted to the Department of Otorhinolaryngology because of hearing impairment due to bilateral exudative otitis media, and was discharged without complete recovery despite conventional treatment. Two weeks later, she was readmitted for worsened deafness, numbness, gait disturbance, and general fatigue. She was referred to our department for general investigation. On admission, laboratory examination revealed severe inflammatory signs and active nephritic urinary sediments. Cranial computed tomography (CT) revealed progressive exudative otitis media and sinusitis. Initially, Wegener's granulomatosis was suspected. Nasal cavity biopsy, however, showed no granuloma formation or vasculitis. Serology revealed high titer of myeloperoxidase-antineutrophil cytoplasmic antibody (MPO-ANCA), suggestive of microscopic polyangitis (MPA). However, contrast CT identified stenosis of a celiac artery, and renal biopsy showed tubulointerstitial changes with minor glomerular abnormalities. Therefore, polyarteritis nodosa (PAN) was suspected and treatment with intravenous methylprednisolone was initiated. However, a lacunar infarct developed followed by cerebral hemorrhage, and the patient died 19 days after readmission. Autopsy revealed fibrinoid necrosis, neutrophilic infiltration, and giant cell reaction in small to medium-sized arteries in multiple organs. These findings led to diagnosis of systemic vasculitis anatomically compatible with PAN. This was a rare case of a patient with MPO-ANCA-positive PAN who may have developed bilateral exudative otitis media and hearing loss as the initial manifestation of PAN.
Assuntos
Injúria Renal Aguda/etiologia , Otite Média Supurativa/complicações , Poliarterite Nodosa/complicações , Vasculite/complicações , Idoso , Anticorpos Anticitoplasma de Neutrófilos/sangue , Evolução Fatal , Feminino , Perda Auditiva Bilateral/etiologia , Humanos , Mononeuropatias/complicações , Peroxidase/imunologia , Acidente Vascular Cerebral Lacunar/etiologiaRESUMO
In 2003, a 64-year-old woman was diagnosed with mixed connective tissue disease and treated with oral prednisolone (30 mg/day). The prednisolone dose was gradually decreased, and a dose of 5 mg/day had been maintained since 2004. In 2009, she gradually developed vision loss, malaise, anorexia, and throat pain due to hydrodipsia. She was noted to have iritis and vitreous opacity by an ophthalmologist, and was referred for further evaluation. Fine rales were audible throughout the entire lung field, and chest CT showed diffuse small nodules that were more prominent on the upper and middle lobes, and swelling of the mediastinal and hilar lymph nodes. Transbronchial lung biopsy showed many epithelioid granulomas with multinuclear giant cells, compatible with sarcoidosis. Polyuria was identified as a cause of hydrodipsia and a diagnosis of partial central diabetes insipidus was made. High-dose prednisolone (40 mg/day) together with intranasal administration of desmopressin resulted in improvement of all of her clinical symptoms. MCTD followed by sarcoidosis is rare. Furthermore, this is the first reported case of MCTD complicated by sarcoidosis and central diabetes insipidus.
Assuntos
Diabetes Insípido Neurogênico/etiologia , Doença Mista do Tecido Conjuntivo/complicações , Sarcoidose Pulmonar/complicações , Desamino Arginina Vasopressina/administração & dosagem , Diabetes Insípido Neurogênico/diagnóstico , Diabetes Insípido Neurogênico/tratamento farmacológico , Feminino , Humanos , Pessoa de Meia-Idade , Doença Mista do Tecido Conjuntivo/tratamento farmacológico , Prednisolona/administração & dosagem , Sarcoidose Pulmonar/diagnóstico , Sarcoidose Pulmonar/tratamento farmacológico , Resultado do TratamentoRESUMO
A 76-year-old man developed fever and appetite loss, and then was referred to our hospital because of rapidly progressive renal insufficiency; his serum creatinine increased from 1.2 to 5.9 mg/dl within 1 month. On admission, his blood pressure was 166/92 mmHg, and laboratory findings showed signs of inflammation, anemia, proteinuria, and hematuria. Chest computed tomography (CT) suggested interstitial pneumonia, while a renal biopsy revealed that small arteries and arterioles were affected, and there was pauci-immune glomerulonephritis with cellular and fibrocellular crescents. In addition, an increased myeloperoxidase antineutrophil cytoplasmic antibody titer confirmed microscopic polyangiitis. Treatment with oral prednisolone was initiated and seemed to successfully resolve the vasculitis activity. On the 11th day of admission, a calcium channel blocker, azelnidipine, was added to treat hypertension. Two days later, the patient developed abdominal distension, and abdominal CT showed massive ascites. The ascitic fluid was a milky white transudate with a normal leukocyte count. Neither clinical manifestations nor laboratory findings suggestive of liver cirrhosis, malignancy, infectious peritonitis, or bowel perforation were observed. On the 18th day of admission, azelnidipine was discontinued in view of reports of calcium channel blocker-induced chyloperitoneum in patients undergoing peritoneal dialysis. Immediately, the abdominal distension disappeared, and the ascites appeared to decrease. Azelnidipine appears to have been responsible for the chyloperitoneum. Since a few cases of secondary vasculitis developing chyloperitoneum have been previously reported, vasculitis may have played a role in the development of chyloperitoneum.
Assuntos
Ácido Azetidinocarboxílico/análogos & derivados , Bloqueadores dos Canais de Cálcio , Ascite Quilosa/induzido quimicamente , Di-Hidropiridinas , Glomerulonefrite , Poliangiite Microscópica , Idoso , Ácido Azetidinocarboxílico/efeitos adversos , Ácido Azetidinocarboxílico/uso terapêutico , Bloqueadores dos Canais de Cálcio/efeitos adversos , Bloqueadores dos Canais de Cálcio/uso terapêutico , Ascite Quilosa/diagnóstico , Di-Hidropiridinas/efeitos adversos , Di-Hidropiridinas/uso terapêutico , Glomerulonefrite/tratamento farmacológico , Glomerulonefrite/patologia , Humanos , Rim/irrigação sanguínea , Rim/patologia , Masculino , Poliangiite Microscópica/tratamento farmacológico , Poliangiite Microscópica/patologiaRESUMO
A 67-year-old, hepatitis C virus (HCV)-positive woman was admitted to our hospital because of proteinuria and leg edema. Laboratory examination showed decreased serum albumin and complement activity and positive cryoglobulin. The HCV RNA genotype was 1b with high viral load. Kidney biopsy showed membranoproliferative glomerulonephritis (MPGN) with capillary deposition of C3, IgM, and IgG, indicating HCV-associated glomerulonephritis. In addition to interferon (IFN) therapy, double-filtration plasmapheresis (DFPP) was performed to reduce HCV RNA blood levels in the early stage of IFN therapy. This treatment greatly reduced the viral load and induced clinical remission of MPGN, suggesting that DFPP plus IFN combination therapy may represent a potentially effective modality for refractory-type HCV-associated glomerulonephritis.
Assuntos
Antivirais/uso terapêutico , Crioglobulinemia/terapia , Glomerulonefrite Membranoproliferativa/terapia , Hepatite C/terapia , Interferon-alfa/uso terapêutico , Plasmaferese , Polietilenoglicóis/uso terapêutico , Ribavirina/uso terapêutico , Idoso , Biópsia , Terapia Combinada , Crioglobulinemia/tratamento farmacológico , Crioglobulinemia/virologia , Quimioterapia Combinada , Edema/terapia , Edema/virologia , Feminino , Genótipo , Glomerulonefrite Membranoproliferativa/tratamento farmacológico , Glomerulonefrite Membranoproliferativa/virologia , Hepacivirus/genética , Hepatite C/complicações , Hepatite C/diagnóstico , Hepatite C/tratamento farmacológico , Humanos , Interferon alfa-2 , Rim/patologia , Rim/virologia , Proteinúria/terapia , Proteinúria/virologia , RNA Viral/sangue , Proteínas Recombinantes , Fatores de Tempo , Resultado do Tratamento , Carga ViralRESUMO
Henoch-Schönlein purpura (HSP) is a systemic disorder characterized by small vessel vasculitis with the deposition of IgA immune complexes. Renal involvement is the major cause of morbidity and mortality in patients with HSP. We report here a 37-year-old female patient with HSP nephritis (HSPN) associated with steroid-resistant nephrotic syndrome and renal dysfunction despite conventional therapy. The patient was successfully treated with intravenous cyclophosphamide following treatment with intravenous pulse methylprednisolone and oral prednisolone. The combination therapy resulted in a significant decrease in proteinuria, together with improvement of renal function. The patient finally reached a stage of clinical remission.
Assuntos
Ciclofosfamida/administração & dosagem , Vasculite por IgA/complicações , Vasculite por IgA/tratamento farmacológico , Síndrome Nefrótica/tratamento farmacológico , Síndrome Nefrótica/etiologia , Adulto , Complexo Antígeno-Anticorpo/metabolismo , Resistência a Medicamentos , Feminino , Mesângio Glomerular/metabolismo , Humanos , Imunoglobulina A/metabolismo , Infusões Intravenosas , Metilprednisolona/administração & dosagem , Prednisolona/administração & dosagem , Proteinúria/tratamento farmacológico , Proteinúria/etiologia , Pulsoterapia , Índice de Gravidade de Doença , Resultado do TratamentoRESUMO
Although hypokalemia is a common clinical problem, symptoms generally do not become manifest unless the serum potassium (K) falls rapidly. We encountered five cases with symptomatic severe hypokalemia (K<2.0 mEq/L) hospitalized for the past 15 months at our hospital. We examined the clinical characteristics and treatment of these patients. All five patients were women, and their mean age was 77.8 (73-82)years. They suffered from hypertension. Mean K level at admission was 1.66 (1.4-1.9) mEq/L and HCO3(-) was 48.3 (33.6-56.1) mmol/L. Plasma aldosterone level was low and plasma rennin activity was suppressed. All patients developed progressive muscle weakness with elevated creatinine phosphokinase. Three of the patients had received Chinese medicine which contained licorice, one received glycyrrhizin and the other one had received both. We diagnosed these cases as pseudoaldosteronism induced by glycyrrhizin. With discontinuation of the drugs and intravenous as well as oral K supplementation, serum K were normalized and clinical symptoms improved within 12 days. For one patient who developed cardiac dysfunction, concentrated K solution (230 mEq/L) was infused into the central vein. These findings show that glycyrrhizin ingestion should be kept in mind as a cause of an extreme degree of an hypokalemia, especially in elderly patients.
Assuntos
Anti-Inflamatórios/efeitos adversos , Medicamentos de Ervas Chinesas/efeitos adversos , Ácido Glicirrízico/efeitos adversos , Hipopotassemia/induzido quimicamente , Rabdomiólise/induzido quimicamente , Idoso , Idoso de 80 Anos ou mais , Aldosterona/sangue , Aldosterona/deficiência , Alcalose , Medicamentos de Ervas Chinesas/química , Feminino , Humanos , Hipertensão , Hipopotassemia/tratamento farmacológico , Fitoterapia/efeitos adversos , Potássio/administração & dosagem , Renina/sangue , Renina/deficiência , Índice de Gravidade de Doença , TerapêuticaRESUMO
A 74-year-old man presented with nephrotic syndrome and kidney insufficiency. Laboratory tests revealed monoclonal gammopathy of immunoglobulin A-lambda. Renal biopsy revealed diffuse mesangial proliferation and double-contoured basement membranes. Immunofluorescent analyses showed granular deposition of immunoglobulin A and C3 at the capillary walls and mesangial regions. Immunohistochemistry suggested monoclonal deposition of immunoglobulin A1-lambda. Electron microscopic analyses showed finely granular electron-dense deposits at mesangial and subendothelial areas. These findings suggested immunoglobulin A-type proliferative glomerulonephritis with monoclonal immunoglobulin deposits. Based on the results of bone marrow aspiration, multiple myeloma was diagnosed. Because the renal manifestation was considered to be affected by monoclonal gammopathy, chemotherapy was initiated rather than immunomodulatory therapy. Although bortezomib and dexamethasone proved ineffective, second chemotherapy with elotuzumab, lenalidomide, and dexamethasone was successful, and kidney function recovered. Effective treatments for proliferative glomerulonephritis with monoclonal immunoglobulin deposits have not been established. This represents the first description of a patient successfully treated for proliferative glomerulonephritis with monoclonal immunoglobulin deposits by chemotherapy using elotuzumab.
Assuntos
Glomerulonefrite Membranoproliferativa/diagnóstico , Imunoglobulina A/imunologia , Cadeias lambda de Imunoglobulina/imunologia , Mieloma Múltiplo/complicações , Mieloma Múltiplo/tratamento farmacológico , Idoso , Anticorpos Monoclonais Humanizados/administração & dosagem , Anticorpos Monoclonais Humanizados/uso terapêutico , Antineoplásicos Hormonais/administração & dosagem , Antineoplásicos Hormonais/uso terapêutico , Protocolos de Quimioterapia Combinada Antineoplásica/administração & dosagem , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Biópsia por Agulha/métodos , Medula Óssea/patologia , Dexametasona/administração & dosagem , Dexametasona/uso terapêutico , Glomerulonefrite Membranoproliferativa/etiologia , Glomerulonefrite Membranoproliferativa/imunologia , Glomerulonefrite Membranoproliferativa/patologia , Humanos , Imunoglobulina A/efeitos dos fármacos , Imunoglobulina A/metabolismo , Imuno-Histoquímica/métodos , Fatores Imunológicos/administração & dosagem , Fatores Imunológicos/uso terapêutico , Lenalidomida/administração & dosagem , Lenalidomida/uso terapêutico , Masculino , Microscopia Eletrônica/métodos , Mieloma Múltiplo/diagnóstico , Mieloma Múltiplo/patologia , Síndrome Nefrótica/diagnóstico , Síndrome Nefrótica/etiologia , Paraproteinemias/etiologia , Paraproteinemias/imunologia , Insuficiência Renal/diagnóstico , Insuficiência Renal/etiologia , Resultado do TratamentoRESUMO
A 66-year-old male with scleroderma developed rapidly progressive glomerulonephritis (RPGN). Renal pathology revealed crescentic glomerulonephritis with interstitial inflammation and fibrosis. Immunofluorescent micrography showed linear deposition of IgG along the glomerular capillary wall. Both anti-glomerular basement membrane antibody (anti-GBM Ab), and myeloperoxidase-antineutrophil cytoplasmic antibody (MPO-ANCA) were detected by an enzyme-linked immunosorbent assay (ELISA). These findings were compatible with ANCA-related vasculitis and anti-GBM Ab nephritis. Laboratory findings showed rapid elevation of the serum creatinine level (5.9 mg/dL), and a high titer of MPO-ANCA (530 EU) and anti-GBM Ab (21 EU). He was started on methylprednisolone pulse therapy and temporary hemodialysis. Since the immunosuppressive therapy lowered both antibody titers steadily and improved renal function, hemodialysis was discontinued 4 weeks after the therapy. It has been reported that some scleroderma patients developed rapid progressive glomerulonephritis due to ANCA-associated vasculitis in addition to the typical scleroderma renal crisis. There have been few reports of a scleroderma patient associated with RPGN, in whom both MPO-ANCA and anti GBM antibodies were detected.
Assuntos
Anticorpos Anticitoplasma de Neutrófilos/análise , Autoanticorpos/análise , Membrana Basal Glomerular/imunologia , Glomerulonefrite/complicações , Peroxidase/imunologia , Escleroderma Sistêmico/complicações , Idoso , Biomarcadores/análise , Progressão da Doença , Glomerulonefrite/diagnóstico , Glomerulonefrite/patologia , Glomerulonefrite/terapia , Humanos , Imunoglobulina G/análise , Masculino , Metilprednisolona/administração & dosagem , Prednisolona/administração & dosagem , Pulsoterapia , Diálise Renal , Escleroderma Sistêmico/diagnósticoAssuntos
Doença Antimembrana Basal Glomerular/terapia , Autoanticorpos/sangue , Glomerulonefrite Membranosa/terapia , Cirrose Hepática Biliar/terapia , Idoso , Doença Antimembrana Basal Glomerular/diagnóstico , Doença Antimembrana Basal Glomerular/etiologia , Glomerulonefrite Membranosa/diagnóstico , Glomerulonefrite Membranosa/etiologia , Glomerulonefrite Membranosa/imunologia , Humanos , Rim/ultraestrutura , Cirrose Hepática Biliar/complicações , Cirrose Hepática Biliar/diagnóstico , Resultado do TratamentoRESUMO
A 53-year-old male was admitted to our hospital for a high fever. He suffered a change in personality, memory loss and disorientation as well. The findings of cerebrospinal fluid showed monocytosis, but the titers of glucose, C1 and ADA were all normal. Although there was no bacterium in the CSF, the patient's electroencephalography finding was abnormal. We diagnosed his condition as viral meningoencephalitis and started treatment with antiviral agents. Blood chemistry showed serum sodium of 130 mEq/l and plasma osmolarity was reduced to 272 mOsm/kg, while urine osmolarity was high at 353 mOsm/kg. Two potential causes of hyponatremia in this patient were the syndrome of inappropriate secretion of antidiuretic hormone (SIADH) or cerebral salt wasting syndrome (CSWS). Physical findings revealed a contracted extracellular fluid volume, strongly suggesting the presence of CSWS. The massive urine sodium loss overcoming sodium intake supported this diagnosis. After treatment with vigorous sodium and volume replacement for over 4 weeks, hyponatremia as well as meningoencephalitis were improved without any complication. To the best of our knowledge, this is the first report on CSWS in a patient with viral meningoencephalitis.
Assuntos
Hiponatremia/etiologia , Síndrome de Secreção Inadequada de HAD/diagnóstico , Meningoencefalite/complicações , Viroses/complicações , Diagnóstico Diferencial , Humanos , Síndrome de Secreção Inadequada de HAD/etiologia , Masculino , Pessoa de Meia-IdadeRESUMO
We investigated the prevalence of renal artery disease and outcome in a cohort of atherosclerotic patients with renal dysfunction. We studied 44 consecutive patients who were older than 50 years of age, who had renal dysfunction and in whom one or more of the following atherosclerotic diseases was confirmed: cerebral infarction, coronary artery disease or peripheral vascular disease. Renal artery stenosis was assessed by gadolinium-enhanced magnetic-resonance angiography. Patients who were treated medically were prospectively followed up in our outpatient clinic and the impact of renal artery stenosis on survival was evaluated. Renal artery stenosis was found in 22 (50%) of the 44 patients. Difference in kidney length and carotid artery stenosis were identified as independent predictors of renal artery stenosis. Among the patients who were treated medically (n=42), rates of mortality were 4.4, 12.7 and 18.1 per 100 patient-years in those without renal artery stenosis, those with unilateral renal artery stenosis and those with bilateral renal artery stenosis, respectively. The mortality and renal survival curves were significantly different among these three groups. These findings indicate that renal artery stenosis is common in patients with renal dysfunction and concomitant cardiovascular disease, especially in those with carotid artery stenosis, and that a substantial difference in the length of kidneys may be a predictor of renovascular disease. Patients with renal dysfunction resulting from renal artery stenosis are at risk of death from cardiovascular disease and end-stage renal failure.
Assuntos
Arteriosclerose/complicações , Arteriosclerose/fisiopatologia , Rim/fisiopatologia , Obstrução da Artéria Renal/complicações , Obstrução da Artéria Renal/epidemiologia , Idoso , Idoso de 80 Anos ou mais , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Mortalidade , Prevalência , Estudos Prospectivos , Obstrução da Artéria Renal/fisiopatologia , Obstrução da Artéria Renal/cirurgia , Análise de SobrevidaRESUMO
A 63-year-old man was diagnosed with periodontitis and underwent tooth extraction. Several days later, he suffered a high fever, ischuria, a change in personality, and disorientation. A urologist examined him and found severe hyponatremia (117 mEq/L), and he was then transferred to our hospital. On admission, physical findings revealed dysfunction of the bladder and bowel, altered mental status, and hypovolemia. Blood chemistry showed serum sodium of 120 mEq/L, a serum urate of 1.4 mg/dL, urinary Na of 61 mEq/L, and fractional urate excretion of 16 %. Examination of the cerebrospinal fluid (CSF) showed monocytosis. Magnetic resonance imaging (MRI) of the brain and spinal cord showed multiple lesions characterized by hyperintensity on T2-weighted sequences, suggesting demyelinating disease. His sodium concentration normalized 3 days after volume replacement therapy, and his altered mental status along with the dysfunction of the bladder and bowel were promptly improved after the initiation of high-dose glucocorticoids. Additionally, the abnormal lesions on MRI markedly decreased. This clinical course led to the likely diagnosis of acute disseminated encephalomyelitis (ADEM). Hyponatremia in neurologically injured patients is usually attributed to the syndrome of inappropriate antidiuretic hormone (SIADH) or cerebral salt-wasting syndrome (CSWS). In the present patient, the uric acid level remained low and uric acid excretion remained elevated despite correction of the hyponatremia, which suggested CSWS. The differentiation of CSWS from SIADH is difficult but critically important due to the fact that the disorders are managed differently. Coexistence of ADEM and CSWS has rarely been reported.
RESUMO
Myofibroblasts are a major source of proinflammatory cytokines and extracellular matrix in progressive tissue fibrosis leading to chronic organ failure. Myofibroblasts are characterized by de novo expression of smooth muscle alpha-actin (SMalphaA), which correlates with the extent of disease progression, although their exact role is unknown. In vitro cultured myofibroblasts from kidney of SMalphaA knock-out mice demonstrate significantly more prominent cell motility, proliferation, and type-I procollagen expression than those of wild-type myofibroblasts. These pro-fibrotic properties are suppressed by adenovirus-mediated SMalphaA re-expression, accompanied by down-regulation of focal adhesion proteins. In interstitial fibrosis model, tissue fibrosis area, proliferating interstitial cell number, and type-I procollagen expression are enhanced under SMalphaA deficiency. In mesangioproliferative glomerulonephritis model, cell proliferation in the mesangial area is also enhanced in SMalphaA knock-out mice. Adenoviral SMalphaA introduction into renal interstitium obviously ameliorates tissue fibrosis in interstitial fibrosis model. These results indicate that SMalphaA suppresses the pro-fibrotic properties of myofibroblasts, highlighting the significance of smooth muscle-related proteins in moderating chronic organ fibrosis under pathological conditions.
Assuntos
Actinas/deficiência , Actinas/genética , Fibroblastos/metabolismo , Fibroblastos/patologia , Rim/metabolismo , Rim/patologia , Músculo Liso Vascular/metabolismo , Músculo Liso Vascular/patologia , Actinas/biossíntese , Animais , Proliferação de Células , Células Cultivadas , Modelos Animais de Doenças , Fibrose , Regulação da Expressão Gênica/genética , Masculino , Células Mesangiais/metabolismo , Células Mesangiais/patologia , Camundongos , Camundongos Knockout , Nefrite Intersticial/genética , Nefrite Intersticial/metabolismo , Nefrite Intersticial/patologia , Obstrução Ureteral/genética , Obstrução Ureteral/metabolismo , Obstrução Ureteral/patologiaRESUMO
BACKGROUND: The small GTPase Rho is involved in cell-to-substratum adhesion and cell contraction. These actions of Rho mediated by downstream Rho effectors such as Rho-associated coiled-coil forming protein kinase (ROCK) may be partly responsible for the progression of renal interstitial fibrosis. METHODS: The anti-fibrosis effects of Y-27632, a specific ROCK inhibitor, were studied both in vivo (unilateral ureteral obstruction; UUO) and in vitro. To investigate the therapeutic efficacy of Y-27632 in UUO kidneys, smooth muscle alpha actin (SMalphaA) expression, macrophage infiltration and fibrosis in the obstructed kidneys were studied. SMalphaA, transforming growth factor beta (TGF-beta), alpha1 (I) collagen, osteopontin, macrophage chemoattractant peptide-1 (MCP-1), and intercellular adhesion molecule-1 (ICAM-1) gene expression were examined by Northern blotting. To elucidate the mechanism linking the Rho-ROCK pathway with renal fibrosis, the effects of Y-27632 on in vitro cell proliferation and cell migration were studied. RESULTS: In vivo analysis showed that Y-27632 suppressed SMalphaA expression, macrophage infiltration and interstitial fibrosis, and that Y-27632 suppressed SMalphaA, TGF-beta and alpha1 (I) collagen mRNA expression. In vitro analysis showed that Y-27632 did not suppress proliferation of renal fibroblasts but suppressed migration of macrophages. CONCLUSIONS: The Rho-ROCK system may play an important role in the development of tissue fibrosis, and the Rho-ROCK signaling pathway may be a new therapeutic target for preventing interstitial fibrosis in progressive renal disease.
Assuntos
Amidas/farmacologia , Inibidores Enzimáticos/farmacologia , Rim/patologia , Nefrite Intersticial/tratamento farmacológico , Piridinas/farmacologia , Obstrução Ureteral/patologia , Actinas/genética , Administração Oral , Animais , Divisão Celular/efeitos dos fármacos , Movimento Celular/efeitos dos fármacos , Movimento Celular/imunologia , Células Cultivadas , Fibroblastos/citologia , Fibroblastos/fisiologia , Fibrose , Expressão Gênica/efeitos dos fármacos , Peptídeos e Proteínas de Sinalização Intracelular , Macrófagos/citologia , Macrófagos/efeitos dos fármacos , Camundongos , Nefrite Intersticial/patologia , Nefrite Intersticial/prevenção & controle , Proteínas Serina-Treonina Quinases/antagonistas & inibidores , Proteínas Serina-Treonina Quinases/genética , RNA Mensageiro/análise , Transdução de Sinais/efeitos dos fármacos , Obstrução Ureteral/complicações , Proteínas ras , Proteínas rho de Ligação ao GTP/genética , Quinases Associadas a rho , Proteína rhoA de Ligação ao GTP/genética , Proteína rhoB de Ligação ao GTP/genética , Proteína de Ligação a GTP rhoCRESUMO
Myofibroblasts are pivotal participants in pathologic processes in a wide variety of organs, such as lung, liver, and kidney, by producing several inflammatory cytokines and extracellular matrices. The mechanism by which transdifferentiation from original cell to myofibroblast occurs, however, is still unclear. The expression of smooth muscle alpha-actin (SMalphaA) is the most characteristic feature of myofibroblasts; therefore, it was speculated that any factors that promote SMalphaA expression might be the key to transdifferentiation to myofibroblasts and disease exacerbation. A transcription factor CCAAT/enhancer-binding protein delta (C/EBPdelta) was identified and demonstrated to bind to sequences including the CArG motif from SMalphaA intron 1 and to increase transcriptional activity of this promoter. Expression of SMalphaA and C/EBPdelta in the glomerular area was upregulated in rat anti-Thy1 glomerulonephritis and mouse Habu-venom glomerulonephritis, both of which are models of mesangioproliferative glomerulonephritis. In the latter model, C/EBPdelta knockout mice demonstrated significantly less SMalphaA expression in the glomerular area on day 8 and less renal functional deterioration on day 14, compared with wild-type mice. These data suggest an important role for C/EBPdelta in myofibroblast transdifferentiation and glomerulonephritis exacerbation.