RESUMO
BACKGROUND: Rituximab is widely used in patients with steroid-dependent nephrotic syndrome. However, information on the effect of long-term rituximab treatment is limited. This study examined the efficacy of rituximab during and after treatment in adult patients with steroid-dependent nephrotic syndrome. METHODS: This retrospective cohort study included 30 patients with steroid-dependent nephrotic syndrome. Patients received regular single-dose rituximab (500 mg) intravenously every 6 months. Discontinuation of rituximab was considered after four to six doses if there was no recurrence of nephrotic syndrome. Glucocorticoid discontinuation with remission, first relapse after rituximab initiation, and relapse after regular rituximab treatment discontinuation were evaluated. RESULTS: The median age was 38 (range 18-67) years. Of 30 patients, 13 and 17 were men and women, respectively. Prior to rituximab treatment, the median number of nephrotic syndrome relapses in the patients was 5 (range 2- > 20). The 1 year discontinuation rate of glucocorticoids with remission was 83%. All patients discontinued glucocorticoid treatment at least once until 3 years and 7 months. The 1 and 2 year relapse rates after initiation of rituximab treatment were 0% and 3%, respectively. 25 patients discontinued regular rituximab treatment after a median number of six (4-12) doses. Six patients relapsed after discontinuing rituximab, and the 1 and 2 year relapse rates after the last regular rituximab treatment were 9% and 25%, respectively. CONCLUSION: All patients with steroid-dependent nephrotic syndrome who received rituximab could discontinue glucocorticoid treatment with remission, and three-fourths of the patients remained in remission for > 2 years after discontinuing rituximab treatment.
RESUMO
BACKGROUND: International practice guidelines advocate for the use of anti-phospholipase A2 receptor (PLA2R) antibody testing to diagnose primary membranous nephropathy (pMN). This study aimed to clarify the current status of anti-PLA2R antibody testing in the diagnosis of pMN in Japan and to scrutinize the factors associated with the implementation of this antibody test. METHODS: Utilizing a web-based questionnaire for nephrologists, responses were collected from 306 facilities and 427 nephrologists between November 2021 and December 2021. Preference for anti-PLA2R antibody testing was also investigated. Factors related to the experience of quantifying anti-PLA2R antibodies were estimated by generalized estimating equations using a robust analysis of variance with clusters of facilities of affiliation. RESULTS: Of the 427 respondents, 140 (32.8%) had previous measurement experience at their current workplace and 165 (38.6%) had previous measurement experience overall. In pMN-suspected cases without contraindications to renal biopsy, 147 (34.4%) of the respondents opted to request anti-PLA2R antibody testing. The respondents' experience with anti-PLA2R antibody quantification at their current place of work was generally higher in university hospitals and increased with the annual number of kidney biopsies and the number of years since graduation. CONCLUSION: The results of this study suggest that a significant proportion of nephrologists in Japan have no experience in performing anti-PLA2R antibody assays, and that the assays may be hampered by the limited capabilities of the current workplace and the financial burden on facilities and patients.
Assuntos
Glomerulonefrite Membranosa , Guias de Prática Clínica como Assunto , Padrões de Prática Médica , Receptores da Fosfolipase A2 , Humanos , Glomerulonefrite Membranosa/diagnóstico , Glomerulonefrite Membranosa/imunologia , Glomerulonefrite Membranosa/sangue , Receptores da Fosfolipase A2/imunologia , Japão , Padrões de Prática Médica/estatística & dados numéricos , Autoanticorpos/sangue , Inquéritos e Questionários , Síndrome Nefrótica/diagnóstico , Síndrome Nefrótica/imunologia , Masculino , População do Leste AsiáticoRESUMO
Fanconi syndrome is a disorder of the proximal renal tubule. Recently, advanced genetic analysis technology has revealed that several genes cause familial Fanconi syndrome. We identified a family with autosomal dominant Fanconi syndrome and chronic kidney disease with a novel glycine amidinotransferase (GATM) variant. Case 1 was a 57-year-old Japanese woman. Her father and two siblings had Fanconi syndrome or chronic kidney disease. She presented to our hospital at the age of 34 years with recurrent glucosuria. Her height and weight were 151 cm and 46.6 kg, respectively. Laboratory tests showed glucosuria, hypophosphatemia, hypouricemia, and normal renal function. Her serum creatinine level gradually increased over the following next two decades, and she developed end-stage renal disease. Case 2, the daughter of Case 1, was a 26-year-old woman. Her height and weight were 151 cm and 37.5 kg, respectively. Glucosuria was detected at the age of 13 years, which led to a referral to our hospital. Urinalysis showed low-molecular-weight proteinuria. She was diagnosed with Fanconi syndrome. At the age of 26 years, she had glucosuria, low-molecular-weight proteinuria, hypouricemia, and normal renal function. Genetic testing of both cases revealed a novel missense variant in GATM. The heterozygous missense variants in GATM have been reported to cause familial Fanconi syndrome, which manifests early in life and progresses to renal glomerular failure by mid-adulthood. The novel GATM variant detected in our cases was suspected to be associated with the development of Fanconi syndrome. GATM variants should be tested in patients with idiopathic Fanconi syndrome.
Assuntos
Síndrome de Fanconi , Insuficiência Renal Crônica , Humanos , Feminino , Adulto , Adolescente , Pessoa de Meia-Idade , Síndrome de Fanconi/genética , Amidinotransferases/genética , Mutação de Sentido IncorretoRESUMO
BACKGROUND: With the publication of the "Evidence-Based Clinical Practice Guideline for Nephrotic Syndrome 2020," we examined nephrologists' adherence to the recommendations of four of its clinical questions (CQs). METHODS: This was a cross-sectional web-based survey conducted between November and December 2021. The target population comprised nephrologists certified by the Japanese Society of Nephrology who were recruited using convenience sampling. The participants answered six items regarding the four CQs about adult patients with nephrotic syndrome and their characteristics. RESULTS: In total, 434 respondents worked in at least 306 facilities, of whom 386 (88.9%) provided outpatient care for primary nephrotic syndrome. Of these patients, 179 (41.2%) answered that they would not measure anti- phospholipase A2 receptor antibody levels in cases of suspected primary membranous nephropathy (MN) in which kidney biopsy was not possible (CQ1). Regarding immunosuppressants as maintenance therapy after relapse of minimal change nephrotic syndrome (CQ2), cyclosporine was the most common choice (290 [72.5%] and 300 [75.0%] of 400 respondents after the first and second relapses, respectively). The most common treatment for steroid-resistant cases of primary focal segmental glomerulosclerosis (CQ3) was cyclosporine (323 of 387, 83.5%). For the initial treatment of primary MN with nephrotic-range proteinuria (CQ4), corticosteroid monotherapy was the most common choice (240 of 403, 59.6%), followed by corticosteroid and cyclosporine (114, 28.3%). CONCLUSION: Gaps in recommendations and practices regarding serodiagnosis and treatment of MN (i.e., CQ1 and 4) are observed, suggesting the need to address the barriers to their insurance reimbursement and the lack of evidence behind them.
Assuntos
Glomerulonefrite Membranosa , Glomerulosclerose Segmentar e Focal , Fidelidade a Diretrizes , Nefrose Lipoide , Síndrome Nefrótica , Adulto , Humanos , Corticosteroides/uso terapêutico , Estudos Transversais , Ciclosporina , População do Leste Asiático , Glomerulonefrite Membranosa/diagnóstico , Glomerulonefrite Membranosa/tratamento farmacológico , Glomerulosclerose Segmentar e Focal/tratamento farmacológico , Internet , Nefrologistas , Nefrose Lipoide/diagnóstico , Nefrose Lipoide/tratamento farmacológico , Síndrome Nefrótica/diagnóstico , Síndrome Nefrótica/tratamento farmacológico , Padrões de Prática Médica , Inquéritos e QuestionáriosRESUMO
A 35-year-old man with persistent urine abnormalities and renal dysfunction was referred to our hospital. May-Hegglin anomaly was suspected, and a renal biopsy showed focal segmental glomerulosclerosis (FSGS) with IgA deposition. Electron microscopy revealed foot process effacements and intense bleb-like morphological changes in podocytes. Nonmuscle myosin heavy chain IIA (NMMHCIIA) staining of granulocytes revealed a localized, type II pattern, and genomic DNA sequencing of MYH9 exon 40 revealed MYH9 5773delG mutation (c.5773delG [p.(Asp1925Thrfs*23)]). Podocytes were significantly stained by an antibody specific for NMMHC-IIA abnormalities associated with this mutation. Colocalization observation of vimentin and NMMHC-IIA demonstrated a diminished form of NMMHC-IIA in podocytes. Taking these observations into account, it was determined that the present case was likely associated with MYH9 disorder. Treatment was started with olmesartan, followed by methylprednisolone pulse therapy 3 times bi-monthly. Finally, the patient began hemodialysis 18 months later. This is the first known report of renal phenotype expression associated with this MYH9 mutation. FSGS can occur in association with MYH9 mutations at the 3' regions, such as exon 40. Abnormal expression or metabolism of NMMHC-IIA in podocytes might be related to the formation of FSGS lesions due to this MYH9 mutation.
Assuntos
Glomerulosclerose Segmentar e Focal , Trombocitopenia , Humanos , Glomerulosclerose Segmentar e Focal/patologia , Rim/patologia , Glomérulos Renais/patologia , Proteínas Motores Moleculares/genética , Proteínas Motores Moleculares/metabolismo , Mutação , Cadeias Pesadas de Miosina/genética , Cadeias Pesadas de Miosina/metabolismo , Trombocitopenia/genética , Trombocitopenia/patologia , Masculino , AdultoRESUMO
OBJECTIVES: The aim of this article is to evaluate the effectiveness and safety of rituximab (RTX) for microscopic polyangiitis and granulomatosis with polyangiitis in Japan. METHODS: In this prospective observational study, all patients with microscopic polyangiitis and granulomatosis with polyangiitis administered RTX were enrolled at each institution. During the observation period of 2 years, data up to 6 months were analysed. Cox proportional hazards analysis was used to assess the factors associated with an outcome. RESULTS: Of the 75 patients who received RTX for remission induction therapy, 53 achieved remission by the sixth month and 50 were in remission at the sixth month. During therapy, 38 serious adverse events were observed in 24 patients, 21 serious infections in 16 patients, and 9 patients died. No factors were associated with remission; however, there was a significant difference between patients with and without remission in serious adverse events (22.6% vs. 54.5%), serious infections (11.3% vs. 45.4%), and death (1.9% vs. 36.4%). The hazard ratio (95% confidence interval) for serious infection was 3.49 (1.29-9.74) for patients aged ≥ 75 years and 3.53 (1.31-9.53) for pulmonary complications. Four patients maintained remission for 6 months. CONCLUSIONS: The effectiveness and safety of RTX for microscopic polyangiitis and granulomatosis with polyangiitis for up to 6 months was demonstrated.
Assuntos
Vasculite Associada a Anticorpo Anticitoplasma de Neutrófilos , Granulomatose com Poliangiite , Poliangiite Microscópica , Humanos , Rituximab/efeitos adversos , Anticorpos Anticitoplasma de Neutrófilos , Estudos de Coortes , População do Leste Asiático , Resultado do Tratamento , Indução de RemissãoRESUMO
OBJECTIVES: This study investigated the current practice of prophylactic treatment against Pneumocystis jirovecii pneumonia (PCP) and its effectiveness in patients with anti-neutrophil cytoplasmic antibody-associated vasculitis (AAV). METHODS: This study included 319 patients registered from 53 institutions in Japan and newly diagnosed with AAV. During the 2-year observation period, we examined the frequency of usage, effectiveness and safety of prophylactic drugs against PCP. RESULTS: Most patients received prophylactic drugs against PCP with the initiation of immunosuppressive agents, and >50% of them remained on chemoprophylaxis against PCP at 2 years after. The initial daily dose of oral prednisolone and the proportion of cyclophosphamide administration were higher in patients who received chemoprophylaxis against PCP than in those who did not. PCP occurred in nine patients (3%) and resulted in the death of four. The incidence rate of PCP in patients who received chemoprophylaxis was 1.13/100 patient-years (95% confidence interval, 0.38-2.68) and that in those who did not was 2.74 (1.04-6.02). The incidence rate ratio was 0.41 (0.11-1.53). CONCLUSIONS: The markedly low incidence of PCP may be attributed to the continuous chemoprophylaxis against PCP received by >50% of Japanese patients with AAV, although the effectiveness of chemoprophylaxis against PCP was not statistically confirmed.
Assuntos
Vasculite Associada a Anticorpo Anticitoplasma de Neutrófilos , Pneumocystis carinii , Pneumonia por Pneumocystis , Humanos , Pneumonia por Pneumocystis/etiologia , População do Leste Asiático , Vasculite Associada a Anticorpo Anticitoplasma de Neutrófilos/tratamento farmacológico , Imunossupressores/uso terapêutico , Quimioprevenção/efeitos adversosRESUMO
The reclassification of membranoproliferative glomerulonephritis (MPGN) into immune-complex MPGN (IC-MPGN) and C3 glomerulopathy (C3G) based on immunofluorescence findings in kidney biopsies has provided insights into these two distinct diseases. C3G is further classified into dense deposit disease and C3 glomerulonephritis (C3GN) based on electron micrographic findings. Although these diseases have poor outcomes, limited Japanese literature confined to small, single-center cohorts exist on these diseases. We retrospectively analyzed 81 patients with MPGN type I and III from 15 hospitals in the Japan Renal Biopsy Registry to compare demographic, clinical characteristics and treatment outcomes of patients with IC-MPGN to those with C3GN. Of the 81 patients reviewed by immunofluorescence findings in kidney biopsies, 67 patients had IC-MPGN and 14 patients had C3GN. Age at diagnosis and systolic and diastolic pressure were higher and proteinuria and impaired renal function were significantly more prevalent in patients with IC-MPGN than those with C3GN. About 80% of the patients in both groups were treated with immunosuppressive therapy. At last follow-up (median 4.8 years), complete remission rate of proteinuria was significantly higher in patients with C3GN (64.3%) than in those with IC-MPGN (29.9%; P = 0.015). The renal survival rate was lower in patients with IC-MPGN when compared to C3GN (73.1% vs. 100%; log-rank, P = 0.031). Systolic blood pressure and renal function at baseline were independent predictors of progression to end-stage kidney disease. The overall prognosis of patients with C3GN is more favorable than for patients with IC-MPGN.
Assuntos
Demografia/métodos , Glomerulonefrite/diagnóstico , Glomerulonefrite/fisiopatologia , Adolescente , Adulto , Fatores Etários , Idoso , Complexo Antígeno-Anticorpo , Biópsia , Pressão Sanguínea , Feminino , Imunofluorescência , Seguimentos , Humanos , Japão , Rim , Masculino , Pessoa de Meia-Idade , Sistema de Registros , Indução de Remissão , Estudos Retrospectivos , Resultado do TratamentoRESUMO
Our patient was a 69-year-old woman admitted to our hospital for heavy proteinuria and hematuria. A renal biopsy showed findings similar to those of membranoproliferative glomerulonephritis associated with nodular lesions, and immunofluorescence showed marked deposits of IgG, C1q, and C3 on the peripheral capillary walls. IgG3 alone was observed on IgG subclass staining with no κ or λ light chains, and Congo red staining was negative. These findings suggested IgG3-heavy-chain deposition disease (HCDD). However, we did not find a deletion of the first heavy-chain constant domain, which is commonly observed in HCDD. Electron microscopy showed randomly arranged subendothelial microtubular structures with diameters of 70-90 nm. Altogether, the diagnosis of HCDD could not be made, although monoclonal IgG3 deposits in glomeruli were observed. This is the first case report of monoclonal IgG3-heavy-chain glomerulonephritis with subendothelial-based, randomly arranged microtubular structures with diameters of 70-90 nm.
Assuntos
Anticorpos Monoclonais/ultraestrutura , Glomerulonefrite/patologia , Imunoglobulina G/ultraestrutura , Idoso , Anticorpos Monoclonais/isolamento & purificação , Feminino , Humanos , Imunoglobulina G/isolamento & purificaçãoRESUMO
BACKGROUND: Few good-quality clinical trials on adults with nephrotic syndrome exist. Thus, there are discrepancies between real-world practice and clinical practice guidelines. We conducted a questionnaire-based survey to investigate potential discrepancies and the factors associated with variations in clinical practice. METHODS: A questionnaire was administered electronically to all board-certified nephrologists in Japan. To examine clinical practice variations in relation to physician characteristics, we estimated the ratio of the mean duration of steroid therapy using a generalized linear model, and the odds ratio of higher level ordinal variables using an ordered logistic regression model. RESULTS: Responses of the 116 participants showed some variation for the majority of questions. Most participants (94.8%) indicated that screening for malignant tumors was "Conducted for almost all patients". The duration of steroid therapy was found to be longer among physicians seeing ≥ 30 patients with nephrotic syndrome per month, both for minimal-change disease (ratio of mean 1.69; 95% CI 1.07-2.66) and membranous nephropathy (ratio of mean 1.71; 95% CI 1.09-2.69). CONCLUSIONS: We identified practice patterns for nephrotic syndrome and discrepancies between clinical practice guidelines and actual practice. Defining the standard therapy for nephrotic syndrome may be necessary to generate high-quality evidence and develop clinical guidelines.
Assuntos
Fidelidade a Diretrizes/estatística & dados numéricos , Neoplasias Renais/diagnóstico , Nefrologia/estatística & dados numéricos , Síndrome Nefrótica/tratamento farmacológico , Padrões de Prática Médica/estatística & dados numéricos , Corticosteroides/uso terapêutico , Detecção Precoce de Câncer , Glomerulonefrite Membranosa/tratamento farmacológico , Humanos , Imunossupressores/uso terapêutico , Japão , Nefrologia/normas , Nefrose Lipoide/tratamento farmacológico , Guias de Prática Clínica como Assunto , Inquéritos e QuestionáriosRESUMO
AIM: Advanced glycation end products and their precursors cause vascular damage through oxidative stress. We investigated the hypothesis that methylglyoxal (MG), 3-deoxyglucosone (3-DG) and pentosidine influence outcomes of chronic kidney disease (CKD) patients. METHODS: We conducted a 3 years prospective observational study involving 150 outpatients at CKD stages 3-5. At enrolment, MG, 3-DG and pentosidine plasma concentrations were measured; patients were divided into tertiles according to the concentration of each substance. The primary endpoint was death, a cardiovascular event or end-stage renal disease. Survival analysis was performed using the Cox regression model. RESULTS: The patients' mean age was 62 ± 12 years, 97 were men, and 20 had diabetic nephropathy. The mean estimated glomerular filtration rate was 25.0 ± 12.1 mL/min per 1.73 m2 , which negatively correlated with MG but not with 3-DG and pentosidine. Forty-eight patients reached the primary endpoint. Compared with the lowest MG tertile, the hazard ratio for the primary endpoint was 7.57 (95% confidence interval (CI): 1.71-33.54) in the middle tertile and 27.00 (CI: 6.46-112.82) in the highest tertile. When adjusted for characteristics at baseline, the corresponding hazard ratio decreased to 2.09 (CI: 0.37-11.96) and 6.13 (CI: 0.97-38.82), but MG tertile remained an independent risk factor for the primary endpoint. However, 3-DG and pentosidine were not related to the primary outcome. CONCLUSION: Methylglyoxal has a close clinical association with CKD. Higher MG concentrations may contribute renal function deterioration in CKD. In CKD patients, MG concentration might be useful when determining the prognosis.
Assuntos
Nefropatias Diabéticas/sangue , Falência Renal Crônica/sangue , Aldeído Pirúvico/sangue , Insuficiência Renal Crônica/sangue , Idoso , Arginina/análogos & derivados , Arginina/sangue , Biomarcadores/sangue , Doenças Cardiovasculares/sangue , Doenças Cardiovasculares/mortalidade , Desoxiglucose/análogos & derivados , Desoxiglucose/sangue , Nefropatias Diabéticas/diagnóstico , Nefropatias Diabéticas/mortalidade , Progressão da Doença , Feminino , Humanos , Japão , Falência Renal Crônica/diagnóstico , Falência Renal Crônica/mortalidade , Lisina/análogos & derivados , Lisina/sangue , Masculino , Pessoa de Meia-Idade , Valor Preditivo dos Testes , Estudos Prospectivos , Insuficiência Renal Crônica/diagnóstico , Insuficiência Renal Crônica/mortalidade , Fatores de Risco , Fatores de Tempo , Regulação para CimaRESUMO
BACKGROUND: Liddle's syndrome is a rare monogenic form of hypertension caused by truncating or missense mutations in the C termini of the epithelial sodium channel (ENaC) ß or γ subunits. Patients with this syndrome present with early onset of hypertension, hypokalemia, metabolic alkalosis, hyporeninemia and hypoaldosteronism, and a potassium-sparing diuretics (triamterene or amiloride) can drastically improves the disease condition. Although elderly patients having these characteristics were considered to have Liddle's syndrome or Liddle's-like syndrome, no previous report has indicated that Liddle's-like syndrome could be caused by nephrotic syndrome of primary glomerular disease, which is characterized by urinary excretion of > 3 g of protein/day plus edema and hypoalbuminemia, or has explained how the activity function of ENaC could be affected in the setting of high proteinuria. CASE PRESENTATION: A 65-year-old Japanese man presented with nephrotic syndrome. He had no remarkable family history, but had a medical history of hypertension and hyperlipidemia. On admission, hypertension, spironolactone-resistant hypokalemia (2.43 mEq/l), hyporeninemic hypoaldosteronism, and metabolic alkalosis, which suggested Liddle's syndrome, were observed. Treatment with triamterene together with a steroid for nephrotic syndrome resulted in rapid and remarkable effective on improvements of hypertension, hypokalemia, and edema of the lower extremities. Renal biopsy revealed membranous nephropathy (MN) as the cause of nephrotic syndrome, and advanced gastric cancer was identified on screening examination for cancers that could be associated with the development of MN. After total gastrectomy, triamterene was not required and proteinuria decreased. A mutation in the ß or γ subunits of the ENaC gene was not identified. CONCLUSION: We reported for the first time a case of Liddle's-like syndrome associated with nephrotic syndrome secondary to MN. Aberrant activation of ENaC was suggested transient during the period of high proteinuria, and the activation was reversible with a decrease in proteinuria.
Assuntos
Glomerulonefrite Membranosa/diagnóstico , Síndrome de Liddle/diagnóstico , Síndrome Nefrótica/diagnóstico , Idoso , Glomerulonefrite Membranosa/complicações , Glomerulonefrite Membranosa/genética , Humanos , Síndrome de Liddle/etiologia , Síndrome de Liddle/genética , Masculino , Síndrome Nefrótica/etiologia , Síndrome Nefrótica/genéticaRESUMO
INTRODUCTION: Late referral to a nephrologist, the type of vascular access, nutritional status, and the estimated glomerular filtration rate (eGFR) at the start of hemodialysis (HD) have been reported as independent risk factors of survival for patients who begin HD. The aim of this study was to clarify the influence of the HD-free interval from the time of an eGFR of 10 ml/min per 1.73 m2 (IGFR10-HD) on patient outcome. METHODS: We enrolled 124 patients aged older than 20 years who had HD initiated in a general hospital. The predictive factor was the HD-free IGFR10-HD. The primary outcome was the relationship of the HD-free interval on death or the onset of a cardiovascular event. Survival analysis was performed using the Cox regression model. RESULTS: The median IGFR10-HD was 159 days (range: 2-1687 days). The median eGFR at the initiation of HD was 5.48 ml/min per 1.73 m2. Sixty-seven of 124 patients (54.0%) reached the primary outcome. Of these, 29 died and 38 experienced a cardiovascular event. In univariate analysis, older age, a history of cardiovascular disease, nephrologic care for <6 months, higher modified Charlson comorbidity index score, poor performance status, temporary catheter, edema, diabetic retinopathy, and nonuse of erythropoiesis-stimulating agent were statistically related to the primary outcome. The unadjusted hazard ratio per log-transformed IGFR10-HD was 0.393 (95% confidence interval [CI]; 0.244-0.635; P < 0.001) and the hazard ratio adjusted for confounding factors was 0.507 (95% CI: 0.267-0.956; P = 0.036). DISCUSSION: A longer HD-free IGFR10-HD was associated with a lower risk of death or a cardiovascular event. The interval could be considered an independent prognostic factor for outcomes in patients on HD.
Assuntos
Imunoglobulina D/análise , Cadeias lambda de Imunoglobulina/análise , Nefropatias/imunologia , Rim/imunologia , Mieloma Múltiplo/imunologia , Idoso , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Biópsia , Bortezomib/administração & dosagem , Cristalização , Dexametasona/administração & dosagem , Feminino , Humanos , Rim/ultraestrutura , Nefropatias/diagnóstico , Microscopia Eletrônica , Mieloma Múltiplo/complicações , Mieloma Múltiplo/diagnóstico , Mieloma Múltiplo/tratamento farmacológico , Resultado do TratamentoRESUMO
BACKGROUND: The aim of this study was to determine the efficacy of cyclophosphamide (CY) on anti-neutrophil cytoplasmic antibody (ANCA)-positive microscopic polyangiitis (MPA) with renal involvement in Japanese patients. METHODS: Eighty-two patients with newly diagnosed ANCA-positive MPA were enrolled in this retrospective study. Patients were divided into two groups based on whether they received combination therapy with a corticosteroid (CS) plus CY (CY group) or CS alone or with other therapies (non-CY group). The primary outcome was defined as the combination of death and end-stage renal disease (ESRD). RESULTS: The CY and non-CY groups included 29 and 53 patients, respectively. In the non-CY group, 31 patients were treated with CS alone, and 22 with a combination of CS and other therapeutics. The percentage of males and mean Birmingham vasculitis activity scores were higher in the CY group than those in the non-CY group, but other factors such as age, serum creatinine, serum albumin, or CRP at baseline were equivalent in the two groups. No differences were observed in remission rates using induction therapy for the two groups. However, the survival rate 5 years after induction therapy was lower in the CY group than in the non-CY group (0.50 vs. 0.73; P = 0.041), although the hazard ratio of CY for the primary outcome adjusted for all confounding factors was 1.321 [95 % confidence interval (CI), 0.662-2.637; P = 0.171]. CONCLUSIONS: CY may not have an additive effect on induction therapy with CS for Japanese patients with renal vasculitis associated with ANCA-positive MPA.
Assuntos
Anticorpos Anticitoplasma de Neutrófilos/imunologia , Ciclofosfamida/uso terapêutico , Imunossupressores/uso terapêutico , Nefropatias/tratamento farmacológico , Poliangiite Microscópica/tratamento farmacológico , Corticosteroides/uso terapêutico , Idoso , Progressão da Doença , Quimioterapia Combinada , Feminino , Humanos , Japão , Estimativa de Kaplan-Meier , Nefropatias/diagnóstico , Nefropatias/imunologia , Nefropatias/mortalidade , Falência Renal Crônica/imunologia , Falência Renal Crônica/mortalidade , Falência Renal Crônica/prevenção & controle , Masculino , Poliangiite Microscópica/diagnóstico , Poliangiite Microscópica/imunologia , Poliangiite Microscópica/mortalidade , Pessoa de Meia-Idade , Modelos de Riscos Proporcionais , Indução de Remissão , Estudos Retrospectivos , Fatores de Risco , Fatores de Tempo , Resultado do TratamentoRESUMO
OBJECTIVE: The aim of this study was to elucidate the efficacy of cyclophosphamide (CY) in Japanese patients with antineutrophil cystoplasmic antibody (ANCA)-associated microscopic polyangiitis (MPA). METHODS: Sixty-four patients, newly diagnosed with ANCA-associated MPA were included in this retrospective study. The patients were divided into two groups based on whether they received combination therapy of CY and corticosteroid (CS) (CY group, n=29) or CS alone (CS group, n=35) for remission induction. The primary outcome was all-cause mortality. RESULTS: Most patients in the CY group were treated with oral CY. Between the two groups, there were no differences in the baseline characteristics except for a higher proportion of male patients in the CY group. The remission rate was not substantially different between the two groups (86.2% in the CY group vs. 91.4% in the CS group). The survival rate was slightly higher in the CY group than in the CS group (not statistically significant; 0.86 vs. 0.77 at 1 year and 0.73 vs. 0.64 at 5 years, p=0.648). In the CY group, the hazard ratio after adjusting for age, sex, Birmingham vasculitis activity score values, serum albumin levels and C-reactive protein (CRP) levels was 0.657 (95% CI, 0.254-1.699; p=0.386). CONCLUSION: We observed no increased efficacy of CY in ANCA-positive MPA in the Japanese patients, and hence, its efficacy may be limited in these patients.
Assuntos
Ciclofosfamida/uso terapêutico , Poliangiite Microscópica/tratamento farmacológico , Corticosteroides/administração & dosagem , Idoso , Idoso de 80 Anos ou mais , Anticorpos Anticitoplasma de Neutrófilos/sangue , Povo Asiático , Ciclofosfamida/administração & dosagem , Quimioterapia Combinada , Feminino , Humanos , Japão , Masculino , Metilprednisolona/administração & dosagem , Poliangiite Microscópica/imunologia , Pessoa de Meia-Idade , Prednisolona/administração & dosagem , Estudos Retrospectivos , Resultado do TratamentoRESUMO
BACKGROUND: Bevacizumab, a recombinant humanized monoclonal antibody for vascular endothelial growth factor, has been widely used in various cancers offering substantial clinical benefit. It is reportedly associated with development of high-grade proteinuria and nephrotic syndrome with the histology of thrombotic microangiopathy, but there has been no report describing the development of immunoglobulin A nephropathy in bevacizumab-treated patients. CASE PRESENTATION: A 68-year-old man with metastatic rectal cancer was treated with bevacizumab. He presented with hematuria and proteinuria 15 and 17 months, respectively, after bevacizumab initiation. Bevacizumab was stopped at 17 months. Renal biopsy at 19 months revealed immunoglobulin A nephropathy, with numerous paramesangial hemispherical deposits and thrombotic microangiopathy. Electron microscopy showed numerous paramesangial electron-dense deposits of various sizes, and subendothelial injuries. Proteinuria almost completely resolved 8 months after bevacizumab cessation, although hematuria persisted. Follow-up renal biopsy 11 months after bevacizumab cessation showed a marked decrease in mesangial immunoglobulin A deposits and paramesangial electron-dense deposits, which correlated with a gradual decrease in serum immunoglobulin A. CONCLUSION: This is the first case report that confirmed histologically the development and resolution of immunoglobulin A nephropathy during and after bevacizumab therapy. This case shows that there may be other mechanisms of glomerular injury by bevacizumab besides glomerular endothelial injury leading to thrombotic microangiopathy.