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BACKGROUND: Prognosis of nephrotic syndrome has been evaluated based on pathological diagnosis, whereas its clinical course is monitored using objective items and the treatment strategy is largely the same. We examined whether the entire natural history of nephrotic syndrome could be evaluated using objective common clinical items. METHODS: Machine learning clustering was performed on 205 cases from the Japan Nephrotic Syndrome Cohort Study, whose clinical parameters, serum creatinine, serum albumin, dipstick hematuria, and proteinuria were traceable after kidney biopsy at 5 measured points up to 2 years. The clinical patterns of time-series data were learned using long short-term memory (LSTM)-encoder-decoder architecture, an unsupervised machine learning classifier. Clinical clusters were defined as Gaussian mixture distributions in a two-dimensional scatter plot based on the highest log-likelihood. RESULTS: Time-series data of nephrotic syndrome were classified into four clusters. Patients in the fourth cluster showed the increase in serum creatinine in the later part of the follow-up period. Patients in both the third and fourth clusters were initially high in both hematuria and proteinuria, whereas a lack of decline in the urinary protein level preceded the worsening of kidney function in fourth cluster. The original diseases of fourth cluster included all the disease studied in this cohort. CONCLUSIONS: Four kinds of clinical courses were identified in nephrotic syndrome. This classified clinical course may help objectively grasp the actual condition or treatment resistance of individual patients with nephrotic syndrome.
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Aprendizado Profundo , Síndrome Nefrótica , Humanos , Síndrome Nefrótica/tratamento farmacológico , Creatinina , Estudos de Coortes , Hematúria , Japão , Proteinúria/etiologiaRESUMO
OBJECTIVE: Zinc (Zn) plays an important role in immune function. Several studies have identified an association between a Zn deficiency and infection. Infectious diseases are major complications of chronic kidney disease (CKD). We investigated whether serum Zn concentrations are associated with risk of infection in patients with advanced CKD. DESIGN AND METHODS: We retrospectively analyzed data from 299 patients with CKD whose serum Zn values were measured to evaluate anemia between January 2013 and December 2016. Among them, 9 who were supplemented with Zn and 67 who had started urgent dialysis at the time of measurement were excluded. We analyzed infection events, length of infection-related hospitalization and infection-related and all-cause mortality in the remaining 223 patients during a median follow-up of 36 months. We assigned the patients to groups with low or high Zn values (≤50 and >50 µg/dL, respectively) based on a median value of 50 µg/dL. Data were analyzed using Kaplan-Meier curves and Cox hazards models. RESULTS: During a median follow-up of 36 months, 40 patients were hospitalized with infections. The rate of infection-related and long-term hospitalization (>10 days) due to infection was higher for patients with low, than high, Zn values (23.3% vs. 12.6%; P = .042 and 26.2% vs. 12.4%; P = .007, respectively). After adjustment in Cox hazards models, low serum Zn values remained an independent risk factor for infection-related hospitalization (Hazard ratio [HR], 1.93; 95% confidence interval [CI], 1.01-3.71; P = .048), especially for patients on proton pump inhibitor (PPI) medications (HR, 2.66, 95%; CI, 1.22-5.81; P = .014). CONCLUSION: Patients with advanced CKD accompanied by low serum Zn concentration, and particularly those medicated with PPI, are at high risk of infection-related hospitalization, which results in long-term hospitalization.
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Falência Renal Crônica , Insuficiência Renal Crônica , Humanos , Modelos de Riscos Proporcionais , Inibidores da Bomba de Prótons/efeitos adversos , Insuficiência Renal Crônica/complicações , Estudos Retrospectivos , Fatores de Risco , ZincoRESUMO
BACKGROUND: The aim of the present study was to clarify the prevalence of immunosuppressive drug use and outcomes in elderly and non-elderly patients with primary membranous nephropathy (MN) in nationwide real-world practice in Japan. PATIENTS AND METHODS: Between 2009 and 2010, 374 patients with primary nephrotic syndrome were enrolled in the cohort study (The Japan Nephrotic Syndrome Cohort Study, JNSCS), including 126 adult patients with MN. Their clinical characteristics were compared with those of nephrotic patients with primary MN registered in a large nationwide registry (The Japan Renal Biopsy Registry, J-RBR). Outcomes and predictors in the elderly (≥ 65 years) and non-elderly groups were identified. RESULTS: Similar clinical characteristics were observed in JNSCS patients and J-RBR patients (n = 1808). At the early stage of 1 month, 84.1% of patients were treated with immunosuppressive therapies. No significant differences were observed in therapies between age groups. However, elderly patients achieved complete remission (CR) more frequently than non-elderly patients, particularly those treated with therapies that included corticosteroids. No significant differences were noted in serum creatinine (sCr) elevations at 50 or 100%, end-stage kidney disease, or all-cause mortality between age groups. Corticosteroids were identified as an independent predictor of CR (HR 2.749, 95%CI 1.593-4.745, p = 0.000) in the multivariate Cox's model. sCr levels, hemoglobin levels, immunosuppressants, clinical remission, and relapse after CR were independent predictors of sCr × 1.5 or × 2.0. CONCLUSION: Early immunosuppressive therapy including corticosteroids for primary MN showed better remission rates in elderly patients in a nationwide cohort study.
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Corticosteroides/uso terapêutico , Glomerulonefrite Membranosa/tratamento farmacológico , Imunossupressores/uso terapêutico , Adulto , Fatores Etários , Idoso , Creatinina/sangue , Feminino , Glomerulonefrite Membranosa/sangue , Glomerulonefrite Membranosa/complicações , Hemoglobinas/metabolismo , Humanos , Japão , Falência Renal Crônica/etiologia , Masculino , Pessoa de Meia-Idade , Mortalidade , Modelos de Riscos Proporcionais , Estudos Prospectivos , Recidiva , Sistema de Registros , Indução de Remissão , Fatores de Risco , Resultado do TratamentoRESUMO
BACKGROUND: Despite recent advances in immunosuppressive therapy for patients with primary nephrotic syndrome, its effectiveness and safety have not been fully studied in recent nationwide real-world clinical data in Japan. METHODS: A 5-year cohort study, the Japan Nephrotic Syndrome Cohort Study, enrolled 374 patients with primary nephrotic syndrome in 55 hospitals in Japan, including 155, 148, 38, and 33 patients with minimal change disease (MCD), membranous nephropathy (MN), focal segmental glomerulosclerosis (FSGS), and other glomerulonephritides, respectively. The incidence rates of remission and relapse of proteinuria, 50% and 100% increases in serum creatinine, end-stage kidney disease (ESKD), all-cause mortality, and other major adverse outcomes were compared among glomerulonephritides using the Log-rank test. Incidence of hospitalization for infection, the most common cause of mortality, was compared using a multivariable-adjusted Cox proportional hazard model. RESULTS: Immunosuppressive therapy was administered in 339 (90.6%) patients. The cumulative probabilities of complete remission within 3 years of the baseline visit was ≥ 0.75 in patients with MCD, MN, and FSGS (0.95, 0.77, and 0.79, respectively). Diabetes was the most common adverse events associated with immunosuppressive therapy (incidence rate, 71.0 per 1000 person-years). All-cause mortality (15.6 per 1000 person-years), mainly infection-related mortality (47.8%), was more common than ESKD (8.9 per 1000 person-years), especially in patients with MCD and MN. MCD was significantly associated with hospitalization for infection than MN. CONCLUSIONS: Patients with MCD and MN had a higher mortality, especially infection-related mortality, than ESKD. Nephrologists should pay more attention to infections in patients with primary nephrotic syndrome.
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Glomerulonefrite Membranosa/tratamento farmacológico , Glomerulosclerose Segmentar e Focal/tratamento farmacológico , Falência Renal Crônica/epidemiologia , Nefrose Lipoide/tratamento farmacológico , Síndrome Nefrótica/tratamento farmacológico , Proteinúria/etiologia , Adulto , Idoso , Doenças Cardiovasculares/epidemiologia , Estudos de Coortes , Creatinina/sangue , Diabetes Mellitus/tratamento farmacológico , Diabetes Mellitus/epidemiologia , Feminino , Seguimentos , Glomerulonefrite Membranosa/complicações , Glomerulonefrite Membranosa/mortalidade , Glomerulosclerose Segmentar e Focal/complicações , Hospitalização/estatística & dados numéricos , Humanos , Hipoglicemiantes/uso terapêutico , Imunossupressores/uso terapêutico , Incidência , Infecções/mortalidade , Japão/epidemiologia , Falência Renal Crônica/mortalidade , Masculino , Pessoa de Meia-Idade , Nefrose Lipoide/complicações , Nefrose Lipoide/mortalidade , Síndrome Nefrótica/complicações , Recidiva , Indução de RemissãoRESUMO
BACKGROUND: The lack of high-quality clinical evidences hindered broad consensus on optimal therapies for primary nephrotic syndromes. The aim of the present study was to compare prevalence of immunosuppressive drug use in patients with primary nephrotic syndrome across 6 regions in Japan. METHODS: Between 2009 and 2010, 380 patients with primary nephrotic syndrome in 56 hospitals were enrolled in a prospective cohort study [Japan Nephrotic Syndrome Cohort Study (JNSCS)], including 141, 151, and 38 adult patients with minimal change disease (MCD), membranous nephropathy (MN), and focal segmental glomerulosclerosis (FSGS), respectively. Their clinical characteristics were compared with those of patients registered in a large nationwide registry of kidney biopsies [Japan Renal Biopsy Registry (J-RBR)]. The regional prevalence of use of each immunosuppressive drug was assessed among adult MCD, MN, and FSGS patients who underwent immunosuppressive therapy in the JNSCS (n = 139, 127, and 34, respectively). Predictors of its use were identified using multivariable-adjusted logistic regression models. RESULTS: The clinical characteristics of JNSCS patients were comparable to those of J-RBR patients, suggesting that the JNSCS included the representatives in the J-RBR. The secondary major immunosuppressive drugs were intravenous methylprednisolone [n = 33 (24.6%), 24 (19.7%), and 9 (28.1%) in MCD, MN, and FSGS, respectively] and cyclosporine [n = 25 (18.7%), 62 (50.8%), and 16 (50.0%), respectively]. The region was identified as a significant predictor of use of intravenous methylprednisolone in MCD and MN patients. CONCLUSION: Use of intravenous methylprednisolone for MCD and MN differed geographically in Japan. Its efficacy should be further evaluated in a well-designed trial.
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Glomerulosclerose Segmentar e Focal/tratamento farmacológico , Imunossupressores/uso terapêutico , Síndrome Nefrótica/tratamento farmacológico , Adulto , Idoso , Biópsia , Estudos de Coortes , Feminino , Glomerulonefrite Membranosa/tratamento farmacológico , Humanos , Rim/patologia , Masculino , Pessoa de Meia-Idade , Nefrose Lipoide/tratamento farmacológicoRESUMO
BACKGROUND: Infection is one of the most common causes of death in patients with chronic kidney disease (CKD). Proton pump inhibitors (PPIs) are not only widely used in patients with CKD but also represent a known risk factor for infection in the general population. Here, we investigated associations between PPIs and infection events in patients with incident hemodialysis. METHODS: We analyzed data from 485 consecutive patients with CKD who started hemodialysis at our hospital between January 2013 and December 2019. We analyzed associations between infection events and long-term (≥6 months) PPI use before and after propensity score-matched analysis. RESULTS: Of the 485 patients, PPIs were administered to 177 patients (36.5%). During 24 months of follow-up, infection events occurred in 53 patients (29.9%) with PPIs and 40 patients (13.0%) without PPIs (p < 0.001). Patients with PPIs had a significantly higher cumulative incidence rate of infection events than those without PPIs (hazard ratio [HR] 2.13, 95% confidence interval [CI]: 1.36-3.32; p < 0.001). Even after propensity score-matched analysis (132 patients matched in each), the rate of infection events was higher for patients with PPIs (28.8% vs. 12.1%, HR 2.88, 95% CI: 1.61-5.16; p < 0.001). Similar results were obtained for severe infection events in both unmatched (14.1% vs. 4.5%, HR 2.97, 95% CI: 1.47-6.00; p = 0.002) and propensity score-matched analyses (14.4% vs. 3.8%, HR 4.54, 95% CI: 1.85-11.13; p < 0.001). CONCLUSIONS: In patients with incident hemodialysis, long-term PPI use increases the risk of infection. Clinicians should be wary of unnecessarily prolonging PPI therapy.
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Inibidores da Bomba de Prótons , Insuficiência Renal Crônica , Humanos , Inibidores da Bomba de Prótons/efeitos adversos , Fatores de Risco , Incidência , Insuficiência Renal Crônica/complicações , Insuficiência Renal Crônica/terapia , Diálise Renal/efeitos adversosRESUMO
Ceftriaxone is a third-generation cephalosporin commonly used to treat infection. However, encephalopathy is an emerging adverse effect of ceftriaxone infusion. These patients present with various symptoms, including those of neurotoxicity, that typically resolve 1 week after discontinuation of ceftriaxone. We experienced two cases of ceftriaxone-induced encephalopathy that were successfully treated by rapid removal of ceftriaxone by hemoperfusion.
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Encefalopatias , Hemoperfusão , Síndromes Neurotóxicas , Antibacterianos/efeitos adversos , Encefalopatias/induzido quimicamente , Ceftriaxona/efeitos adversos , Humanos , Síndromes Neurotóxicas/etiologia , Diálise Renal/efeitos adversosRESUMO
Introduction: Immunoglobulin A (IgA) nephropathy is a disease that presents with urinary symptoms such as glomerular hematuria and urinary protein positivity, with predominant deposition of IgA in the mesangial region of the glomerulus. Corticosteroids are mainly used for treatment; however, infection is a serious adverse event, and evidence regarding therapeutic efficacy is insufficient, thus new treatments are strongly desired. Mesenchymal stem cells (MSCs) contribute to the amelioration of inflammation and recovery of organ function in inflammatory environments by converting the character of leukocytes from inflammatory to anti-inflammatory and inducing the proliferation and differentiation of organ component cells, respectively. These properties of MSCs have led to their clinical application in various inflammatory diseases, but this study is the first clinical trial of MSCs for refractory glomerulonephritis in the world. This study is registered and assigned the number, jRCT2043200002 and NCT04342325. Methods: This will be a phase 1, open-label, multiple-center, dose-escalation study of adult patients with refractory IgA nephropathy resistant to or difficult to treat with existing therapies. ADR-001 will be administered intravenously to from three to six patients at a dose of 1 × 108 cells once in the first cohort and to six patients twice at 2-week intervals in the second cohort, and observation will continue until 52 weeks. The primary endpoint will be the evaluation of adverse events up to 6 weeks after the start of ADR-001 administration. Secondary endpoints will be the respective percentages of patients with adverse events, clinical remission, partial remission, remission of urine protein, remission of hematuria, time to remission, changes in urine protein, hematuria, and estimated glomerular filtration rate. Results: Following the administration of ADR-001 to patients with IgA nephropathy, the respective percentages of patients with adverse events, asymptomatic pulmonary emboli, clinical remission, partial remission, urine protein remission, hematuria remission, their time to remission, changes in urine protein, hematuria, and glomerular filtration rate will be determined. Conclusion: This study will evaluate the safety and tolerability of ADR-001 and confirm its therapeutic efficacy in adult patients with refractory IgA nephropathy.
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BACKGROUND: Minimal change disease (MCD) is characterized by a nephrotic syndrome usually steroid-sensitive and a high incidence of relapse of proteinuria. Previous cohort studies have reported conflicting results regarding the association between the time to remission and incidence of relapse. METHODS: This multicenter prospective cohort study included 102 adult patients with steroid-sensitive MCD or focal segmental glomerulosclerosis from a 5-year cohort study of primary nephrotic syndrome, the Japan Nephrotic Syndrome Cohort Study, who achieved remission of proteinuria within 2 months of immunosuppressive therapy (IST). The association between the time to remission of proteinuria after immunosuppressive therapy and incidence of relapse was assessed using Cox proportional hazards models adjusted for clinically relevant factors. RESULTS: Remission was observed at 3-7, 8-14, 15-21, 22-28, and 30-56 days after initiation of immunosuppressive therapy in 17 (16.7%), 37 (36.3%), 21 (20.6%), 13 (12.7%), and 14 (13.7%) patients, respectively. During a median observation period of 2.3 years after the end of the 2nd month after initiation of immunosuppressive therapy, 46 (45.1%) patients relapsed. The time to remission was associated with the incidence of relapse in an inverse U-shaped pattern (multivariable-adjusted hazard ratios [95% confidence intervals] of the time to remission of 3-7, 8-14, 15-21, 22-28, 30-56 days: 1.00 [reference], 1.76 [0.56, 5.51], 6.06 [1.85, 19.80], 5.46 [1.44, 20.64], and 2.19 [0.52, 9.30], respectively). CONCLUSION: The time to remission was identified as a significant predictor of relapse in steroid-sensitive patients.
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Glomerulosclerose Segmentar e Focal , Nefrose Lipoide , Síndrome Nefrótica , Adulto , Estudos de Coortes , Feminino , Glomerulosclerose Segmentar e Focal/diagnóstico , Glomerulosclerose Segmentar e Focal/tratamento farmacológico , Glomerulosclerose Segmentar e Focal/epidemiologia , Humanos , Imunossupressores/uso terapêutico , Incidência , Japão/epidemiologia , Masculino , Nefrose Lipoide/diagnóstico , Nefrose Lipoide/tratamento farmacológico , Nefrose Lipoide/epidemiologia , Síndrome Nefrótica/diagnóstico , Síndrome Nefrótica/tratamento farmacológico , Síndrome Nefrótica/epidemiologia , Estudos Prospectivos , Proteinúria/diagnóstico , Proteinúria/tratamento farmacológico , Proteinúria/epidemiologia , Recidiva , Esteroides/uso terapêuticoRESUMO
Thrombocytopenia, anasarca, fever, renal insufficiency, and organomegaly constitute TAFRO syndrome, a variant of Castleman disease. We describe a patient with TAFRO syndrome who underwent renal biopsy. A 79-year-old woman was referred to us with fever and leg edema. She also had thrombocytopenia, pleural effusion, ascites, and acute kidney injury, and was admitted to our hospital. Her response to initial therapy with corticosteroid and cyclosporine was poor. Therefore, she received 4 doses of rituximab per week, which resulted in clinical improvement, including recovery of thrombocytopenia. A kidney biopsy thereafter showed diffuse, global glomerular endothelial injury indicating thrombotic microangiopathy (TMA). These findings suggested that TMA is associated with the thrombocytopenia and renal insufficiency of TAFRO syndrome.
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BACKGROUND: Reportedly, thiamine deficiency, resulting from malnutrition and long-term diuretic therapy, is observed in patients with chronic kidney disease (CKD). The risk of thiamine deficiency might be enhanced, especially in end-stage CKD patients. Here, we assessed thiamine status in incident dialysis patients. METHODS: This study was a single-center cross-sectional study which included 288 consecutive patients initiated into dialysis between April 2013 and March 2017 at our hospital. Thiamine status was evaluated by high-performance liquid chromatography of whole blood samples. We evaluated the association between blood thiamine concentration and other clinical parameters. RESULTS: Of the 288 patients, 21 patients receiving thiamine supplementation at the time of dialysis initiation and 26 patients without blood thiamine measurements were excluded. In 30 patients (12.4%), blood thiamine concentration was lower than the lower limit of normal (21.3 ng/mL; dotted line). Blood thiamine concentration correlated with age, body mass index, and Barthel index (BI) score (p = 0.008, 0.012 and 0.009, respectively). Stepwise multivariate regression analysis indicated that BI scores were independent risk factors for thiamine deficiency (ß coefficients = 0.169, p = 0.013). CONCLUSIONS: The proportion of end-stage CKD patients with low blood thiamine concentration is high. Low physical function (low BI score) is an independent risk factor of thiamine deficiency. Clinicians should be aware of thiamine deficiency in end-stage CKD patients, especially those with low physical function.