RESUMEN
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.
Asunto(s)
Aprendizaje Profundo , Síndrome Nefrótico , Humanos , Síndrome Nefrótico/tratamiento farmacológico , Creatinina , Estudios de Cohortes , Hematuria , Japón , Proteinuria/etiologíaRESUMEN
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.
Asunto(s)
Fallo Renal Crónico , Insuficiencia Renal Crónica , Humanos , Modelos de Riesgos Proporcionales , Inhibidores de la Bomba de Protones/efectos adversos , Insuficiencia Renal Crónica/complicaciones , Estudios Retrospectivos , Factores de Riesgo , ZincRESUMEN
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.
Asunto(s)
Corticoesteroides/uso terapéutico , Glomerulonefritis Membranosa/tratamiento farmacológico , Inmunosupresores/uso terapéutico , Adulto , Factores de Edad , Anciano , Creatinina/sangre , Femenino , Glomerulonefritis Membranosa/sangre , Glomerulonefritis Membranosa/complicaciones , Hemoglobinas/metabolismo , Humanos , Japón , Fallo Renal Crónico/etiología , Masculino , Persona de Mediana Edad , Mortalidad , Modelos de Riesgos Proporcionales , Estudios Prospectivos , Recurrencia , Sistema de Registros , Inducción de Remisión , Factores de Riesgo , Resultado del TratamientoRESUMEN
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.
Asunto(s)
Glomerulonefritis Membranosa/tratamiento farmacológico , Glomeruloesclerosis Focal y Segmentaria/tratamiento farmacológico , Fallo Renal Crónico/epidemiología , Nefrosis Lipoidea/tratamiento farmacológico , Síndrome Nefrótico/tratamiento farmacológico , Proteinuria/etiología , Adulto , Anciano , Enfermedades Cardiovasculares/epidemiología , Estudios de Cohortes , Creatinina/sangre , Diabetes Mellitus/tratamiento farmacológico , Diabetes Mellitus/epidemiología , Femenino , Estudios de Seguimiento , Glomerulonefritis Membranosa/complicaciones , Glomerulonefritis Membranosa/mortalidad , Glomeruloesclerosis Focal y Segmentaria/complicaciones , Hospitalización/estadística & datos numéricos , Humanos , Hipoglucemiantes/uso terapéutico , Inmunosupresores/uso terapéutico , Incidencia , Infecciones/mortalidad , Japón/epidemiología , Fallo Renal Crónico/mortalidad , Masculino , Persona de Mediana Edad , Nefrosis Lipoidea/complicaciones , Nefrosis Lipoidea/mortalidad , Síndrome Nefrótico/complicaciones , Recurrencia , Inducción de RemisiónRESUMEN
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.
Asunto(s)
Glomeruloesclerosis Focal y Segmentaria/tratamiento farmacológico , Inmunosupresores/uso terapéutico , Síndrome Nefrótico/tratamiento farmacológico , Adulto , Anciano , Biopsia , Estudios de Cohortes , Femenino , Glomerulonefritis Membranosa/tratamiento farmacológico , Humanos , Riñón/patología , Masculino , Persona de Mediana Edad , Nefrosis Lipoidea/tratamiento farmacológicoRESUMEN
AIM: We aimed to evaluate the anti-albuminuric effects of topiroxostat in Japanese hyperuricaemic patients with diabetic nephropathy. METHODS: In this 24-week, multicentre, open-label, randomized (1 : 1) trial, we assigned hyperuricaemic patients with diabetic nephropathy (estimated glomerular filtration rate ≥ 20 mL/min per 1.73m2 ) and overt proteinuria (0.3 ≤ urine protein to creatinine ratio (UPCR) <3.5 g/g Cr) to either high dose (160 mg daily) or low dose (40 mg daily) topiroxostat. The primary endpoint was the change in albuminuria indicated by urine albumin-to-creatinine ratio (UACR) from the baseline at the final time point. RESULTS: A total of 80 patients underwent randomization. The changes in UACR after 24 weeks of treatment (or at the final time point if patients failed to reach 24 weeks) relative to the baseline were -122 mg/gCr (95% CI: -5.1 to -240.1, P = 0.041) in patients treated with high dose, while treatment with low dose topiroxostat could not show significant reduction (P = 0.067). In the linear mixed model including baseline albuminuria, eGFR, age, and sex as covariates, the decreases in UACR were still significant from baseline to 12 weeks by 228.7 ± 83.2 mg/gCr (P = 0.0075) in the high dose group. The adverse-event profile during this study was not different between the groups. CONCLUSION: Topiroxostat 160 mg daily reduced albuminuria in patients with diabetic nephropathy. (Funded by Sanwa Kagaku Kenkyusho; Trial registration, UMIN000015403).
Asunto(s)
Nefropatías Diabéticas/tratamiento farmacológico , Hiperuricemia/tratamiento farmacológico , Riñón/efectos de los fármacos , Nitrilos/farmacología , Piridinas/farmacología , Anciano , Anciano de 80 o más Años , Albuminuria/tratamiento farmacológico , Presión Sanguínea , Creatinina/orina , Nefropatías Diabéticas/fisiopatología , Proteínas de Unión a Ácidos Grasos/orina , Femenino , Tasa de Filtración Glomerular , Hemoglobina Glucada/análisis , Humanos , Hiperuricemia/fisiopatología , Masculino , Persona de Mediana Edad , Nitrilos/uso terapéutico , Estudios Prospectivos , Piridinas/uso terapéuticoRESUMEN
BACKGROUND: The number of elderly dialysis patients in Japan is dramatically increasing. Receiving therapy with better satisfaction through home care is one of the important factors in their daily lives. Thus, the quality of life of elderly patients on hemodialysis (HD) or peritoneal dialysis (PD) was evaluated. METHODS: Clinical information of patients aged ≥80 years who started dialysis at our hospital between January 2013 and December 2015 was retrospectively collected. The mortality rate, length of hospitalization, and place of death were identified to evaluate patient quality of life. RESULTS: In total, 56 patients (14 PD and 42 HD) were enrolled. The mean age of study subjects was 85.2 ± 4.0 years. The proportion of PD patients who lived with their family or have professional caregivers who could assist them in their daily life was higher than that of HD patients (100 vs. 76.2%, respectively; p = 0.044). Mortality rate was higher in PD patients than in HD patients (p = 0.003), but long-term hospitalization of >180 days was observed only in HD patients (PD vs. HD: 0.0 vs. 16.7%; p = 0.102). In patients with Barthel index scores <100, the long-term hospitalization difference was significant (PD vs. HD: 0.0 vs. 30.4%; p = 0.040). Of note, 6 of 7 deceased PD patients and 1 of 10 deceased HD patients died at home (p = 0.002). CONCLUSION: PD is a desirable home care therapy for elderly patients, but the burden on caregivers should be considered.
Asunto(s)
Hemodiálisis en el Domicilio , Enfermedades Renales/terapia , Diálisis Peritoneal , Calidad de Vida , Actividades Cotidianas , Factores de Edad , Anciano de 80 o más Años , Envejecimiento/psicología , Cuidadores/psicología , Costo de Enfermedad , Femenino , Hemodiálisis en el Domicilio/efectos adversos , Humanos , Japón , Estimación de Kaplan-Meier , Enfermedades Renales/mortalidad , Enfermedades Renales/fisiopatología , Enfermedades Renales/psicología , Tiempo de Internación , Masculino , Admisión del Paciente , Satisfacción del Paciente , Diálisis Peritoneal/efectos adversos , Estudios Retrospectivos , Factores de Riesgo , Factores de Tiempo , Resultado del TratamientoRESUMEN
BACKGROUND: Early withdrawal within 3 years after starting peritoneal dialysis (PD) and PD-related peritonitis have been major obstacles preventing increases in the population of PD patients. To address these problems, we implemented education programs for medical staff. This study analyzed the recent status and outcomes of PD therapy, focusing on findings such as the incidence and prognosis of peritonitis as of 5 years after our last study. METHODS: We investigated background, laboratory data and status of PD therapy, reasons for withdrawal from PD and incidental statements on peritonitis from 2010 to 2012 (R2), and compared findings with those from our last study of 2005-2007 (R1). RESULTS: Early PD therapy withdrawal in R2 clearly improved to 44.7 %, compared with 50.9 % in R1. Peritonitis incidence improved slightly from once per 42.8 months/patient in R1 to once per 47.3 months/patient in R2. Notably, PD-related peritonitis as a cause of mortality improved markedly in R2, but outcomes of PD-related peritonitis did not change significantly between R1 and R2. In contrast, social problems increased as a reason for withdrawal from PD therapy. CONCLUSION: Our efforts at education might have been useful for improving early withdrawal from PD and deaths attributable to PD-related peritonitis. However, since improvements to incidence of PD-related peritonitis were limited by education, further improvement in PD-related peritonitis incidence requires development of new sterilized connecting systems during PD-bag exchanges to decrease PD-related peritonitis opportunities. Construction of medical support systems to address social problems is required to maintain long-term PD therapy.
Asunto(s)
Diálisis Peritoneal/estadística & datos numéricos , Sistema de Registros , Adulto , Anciano , Calcio/metabolismo , Femenino , Humanos , Masculino , Persona de Mediana Edad , Educación del Paciente como Asunto , Diálisis Peritoneal/efectos adversos , Peritonitis/etiología , Pronóstico , Vitamina D/uso terapéuticoAsunto(s)
Azotemia/sangre , Cistatina C/sangre , Histerectomía/efectos adversos , Ovariectomía/efectos adversos , Dolor Abdominal/sangre , Dolor Abdominal/etiología , Enfermedad Aguda , Adulto , Azotemia/etiología , Femenino , Humanos , Leiomioma/cirugía , Oliguria/sangre , Oliguria/etiología , Quistes Ováricos/cirugía , Neoplasias Uterinas/cirugíaRESUMEN
BACKGROUND: Immunoglobulin A nephropathy often requires kidney replacement therapy because of its refractoriness and because corticosteroids pose infection risks. However, mesenchymal stem cells offer clinical benefits because of their regenerative and immunomodulatory properties. This prospective clinical trial assessed the safety and tolerability of adipose-derived mesenchymal stem cell therapy and evaluated its therapeutic efficacy. METHODS: This phase 1 study included adult patients with refractory immunoglobulin A nephropathy that was difficult to treat with traditional therapies. Adipose-derived mesenchymal stem cell therapy comprising one intravenous dose of 1 × 108 cells was administered to three to six patients in cohort 1. The same intravenous dose was administered twice with a 2-week interval to six patients in cohort 2. Heparin was administered simultaneously. This study continued for 52 weeks, and the primary endpoints were safety and tolerability during the 6-week period after treatment administration. Secondary endpoints included adverse events and efficacy measures such as clinical remission, partial remission, urine protein remission, hematuria remission, time to remission, changes in the urine protein and hematuria levels, and changes in the estimated glomerular filtration rate. RESULTS: The three patients in cohort 1 and six patients in cohort 2 who received adipose-derived mesenchymal stem cell therapy achieved the primary endpoints. No severe adverse clinical events were observed. Therefore, the safety and tolerability of adipose-derived mesenchymal stem cells were confirmed. Improvements such as significantly decreased kidney damage markers and urinary protein levels were observed immediately after adipose-derived mesenchymal stem cell administration. CONCLUSIONS: The safety and tolerability of adipose-derived mesenchymal stem cells are acceptable for patients with immunoglobulin A nephropathy. TRIAL REGISTRATION: This trial was registered with the Japan Registry of Clinical Trials (jRCT2043200002; registration date: April 14, 2020) and ClinicalTrials.gov (NCT04342325; registration date: April 13, 2020).
RESUMEN
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.
Asunto(s)
Inhibidores de la Bomba de Protones , Insuficiencia Renal Crónica , Humanos , Inhibidores de la Bomba de Protones/efectos adversos , Factores de Riesgo , Incidencia , Insuficiencia Renal Crónica/complicaciones , Insuficiencia Renal Crónica/terapia , Diálisis Renal/efectos adversosRESUMEN
BACKGROUND: Pozzi et al. reported the effectiveness of steroid pulse therapy (Pozzi's regimen) in IgA nephropathy (IgAN). The present study was performed to clarify the predictive factors for IgAN patients treated with Pozzi's regimen. METHODS: One hundred nine IgAN patients treated by Pozzi's regimen were observed for up to 112.6 (median 39.7) months, and remission of proteinuria (PR) and disappearance of urinary abnormalities [complete remission (CR)] after Pozzi's regimen were analyzed. Predictive factors for the glomerular filtration rate (GFR) slopes for up to 5 years were analyzed among 81 patients who were observed for at least 2 years. The outcome of a 50 % increase in sCr was compared between the CR and non-CR groups within 2 years. RESULTS: Cumulative PR and CR rates increased rapidly until 2 years (54.5 and 46.8 % at 2 years), and then slowly but steadily up to 6 years (72.8 and 66.4 % at 6 years). Baseline characteristics of the CR and non-CR groups within 2 years were similar except for proteinuria. GFR slope was steeper in the non-CR group than in the CR group (-2.44 ± 5.12 vs. -0.32 ± 3.34 ml/min/1.73 m(2)/year). On multivariate analysis, sex and CR within 2 years were associated with GFR slope. Kaplan-Meier analysis demonstrated a better survival rate in CR group patients without a 50 % increase in sCr (p = 0.024). CONCLUSIONS: Among IgAN patients treated with Pozzi's regimen, CR within 2 years predicts a good prognosis.
Asunto(s)
Glomerulonefritis por IGA/tratamiento farmacológico , Glucocorticoides/administración & dosificación , Glucocorticoides/uso terapéutico , Metilprednisolona/administración & dosificación , Metilprednisolona/uso terapéutico , Adulto , Creatinina/sangre , Femenino , Estudios de Seguimiento , Tasa de Filtración Glomerular/fisiología , Glomerulonefritis por IGA/sangre , Glomerulonefritis por IGA/fisiopatología , Humanos , Estimación de Kaplan-Meier , Estudios Longitudinales , Masculino , Quimioterapia por Pulso , Inducción de Remisión , Estudios Retrospectivos , Factores Sexuales , Tasa de Supervivencia , Resultado del TratamientoRESUMEN
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.
Asunto(s)
Encefalopatías , Hemoperfusión , Síndromes de Neurotoxicidad , Antibacterianos/efectos adversos , Encefalopatías/inducido químicamente , Ceftriaxona/efectos adversos , Humanos , Síndromes de Neurotoxicidad/etiología , Diálisis Renal/efectos adversosRESUMEN
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.
RESUMEN
Previous studies reported conflicting results regarding an association between serum albumin concentration and the cumulative incidence of remission of proteinuria in adult patients with minimal change disease (MCD). The present study aimed to clarify the clinical impact of serum albumin concentration and the cumulative incidence of remission and relapse of proteinuria in 108 adult patients with MCD at 40 hospitals in Japan, who were enrolled in a 5-year prospective cohort study of primary nephrotic syndrome, the Japan Nephrotic Syndrome Cohort Study (JNSCS). The association between serum albumin concentration before initiation of immunosuppressive treatment (IST) and the cumulative incidence of remission and relapse were assessed using multivariable-adjusted Cox proportional hazards models. Remission defined as urinary protein < 0.3 g/day (or g/gCr) was observed in 104 (96.3%) patients. Of 97 patients with remission within 6 month of IST, 42 (43.3%) developed relapse defined as ≥ 1.0 g/day (or g/gCr) or dipstick urinary protein of ≥ 2+. Serum albumin concentration was significantly associated with remission (multivariable-adjusted hazard ratio [95% confidence interval] per 1.0 g/dL, 0.57 [0.37, 0.87]), along with eGFR (per 30 mL/min/1.73 m2: 1.43 [1.08, 1.90]), whereas they were not associated with relapse. A multivariable-adjusted model showed that patients with high eGFR level (≥ 60 mL/min/1.73 m2) and low albumin concentration (≤ 1.5 g/dL) achieved significantly early remission, whereas those with low eGFR (< 60 mL/min/1.73 m2) and high albumin concentration (> 1.5 g/dL) showed significantly slow remission. In conclusion, lower serum albumin concentration and higher eGFR were associated with earlier remission in MCD, but not with relapse.
Asunto(s)
Nefrosis Lipoidea , Síndrome Nefrótico , Adulto , Estudios de Cohortes , Humanos , Inmunosupresores/uso terapéutico , Nefrosis Lipoidea/complicaciones , Nefrosis Lipoidea/tratamiento farmacológico , Síndrome Nefrótico/tratamiento farmacológico , Estudios Prospectivos , Proteinuria/tratamiento farmacológico , Recurrencia , Inducción de Remisión , Estudios Retrospectivos , Albúmina SéricaRESUMEN
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.
Asunto(s)
Glomeruloesclerosis Focal y Segmentaria , Nefrosis Lipoidea , Síndrome Nefrótico , Adulto , Estudios de Cohortes , Femenino , Glomeruloesclerosis Focal y Segmentaria/diagnóstico , Glomeruloesclerosis Focal y Segmentaria/tratamiento farmacológico , Glomeruloesclerosis Focal y Segmentaria/epidemiología , Humanos , Inmunosupresores/uso terapéutico , Incidencia , Japón/epidemiología , Masculino , Nefrosis Lipoidea/diagnóstico , Nefrosis Lipoidea/tratamiento farmacológico , Nefrosis Lipoidea/epidemiología , Síndrome Nefrótico/diagnóstico , Síndrome Nefrótico/tratamiento farmacológico , Síndrome Nefrótico/epidemiología , Estudios Prospectivos , Proteinuria/diagnóstico , Proteinuria/tratamiento farmacológico , Proteinuria/epidemiología , Recurrencia , Esteroides/uso terapéuticoRESUMEN
BACKGROUND: In Japan, the population of patients on peritoneal dialysis (PD) is <4% of the total number of patients with end-stage renal disease. Few systemic analyses have examined why the number of PD patients has not increased in Japan. We organized a registry to analyze PD patients and retrospectively investigated 561 PD patients (about 5% of all Japanese PD patients) from 13 hospitals in the Tokai area for 3 years from 2005. METHODS: We investigated background, physical status, laboratory data, status of PD therapy, and the occurrence of PD-related complications, and analyzed reasons for withdrawal from PD. RESULTS: Nutrition did not change significantly during our observation. Urinary volume showed continued decreases after the introduction period. In contrast, PD fluid demand and ultrafiltration volume were significantly increased. For calcium metabolism, multiple phosphate binders were required after the second year of PD therapy. Early drop-out within 3 years after starting PD therapy comprised 50.9% of total withdrawals, with PD-related peritonitis as the most common reason, mainly caused by Gram-positive organisms. Incidence of peritonitis was 42.8 months/patient. Culture-negative results were obtained for 32% of peritonitis cultures. Diabetes affects the prognosis of PD therapy, but not the incidence of peritonitis. CONCLUSION: We examined clinical status over 3 years in the Tokai area. The results suggest that the incidence of peritonitis needs to be decreased to prevent early withdrawal of PD patients. Education systems to decrease the incidence of peritonitis and techniques to decrease culture-negative results might be important for improving the prognosis of peritonitis.
Asunto(s)
Fallo Renal Crónico/terapia , Diálisis Peritoneal/efectos adversos , Peritonitis/etiología , Anciano , Calcio/sangre , Femenino , Humanos , Japón , Fallo Renal Crónico/complicaciones , Masculino , Persona de Mediana Edad , Hormona Paratiroidea/sangre , Fosfatos/sangre , Sistema de Registros , Estudios Retrospectivos , Análisis de Supervivencia , Negativa del Paciente al TratamientoRESUMEN
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.