RESUMO
BACKGROUND: The relationship between kidney function at 3 months after acute kidney injury (AKI) and kidney function prognosis has not been characterized. METHODS: This retrospective cohort study included adults who underwent noncardiac surgery under general anesthesia. Exclusion criteria included obstetric or urological surgery, missing data and preoperative dialysis. Linear mixed-effects models were used to compare estimated glomerular filtration rate (eGFR) slopes in patients with and without AKI. Multivariable Cox proportional hazard models were used to examine the associations of AKI with incident chronic kidney disease (CKD) and decline in eGFR ≥30%. RESULTS: Among 5272 patients, 316 (6.0%) developed AKI. Among 1194 patients with follow-up creatinine values, eGFR was stable or increased in patients with and without AKI at 3 months postoperatively and declined thereafter. eGFR decline after 3 months postoperatively was faster among patients with AKI than among patients without AKI (P = .09). Among 938 patients without CKD-both at baseline and at 3 months postoperatively-226 and 161 developed incident CKD and a decline in eGFR ≥30%, respectively. Despite adjustment for eGFR at 3 months, AKI was associated with incident CKD {hazard ratio [HR] 1.73 [95% confidence interval (CI) 1.06-2.84]} and a decline in eGFR ≥30% [HR 2.41 (95% CI 1.51-3.84)]. CONCLUSIONS: AKI was associated with worse kidney outcomes, regardless of eGFR at 3 months after surgery. Creatinine-based eGFR values at 3 months after AKI might be affected by acute illness-induced loss of muscle mass. Kidney function might be more accurately evaluated much later after surgery or using cystatin C values.
Assuntos
Injúria Renal Aguda , Insuficiência Renal Crônica , Adulto , Humanos , Estudos de Coortes , Estudos Retrospectivos , Creatinina , Diálise Renal , Rim , Taxa de Filtração Glomerular , Fatores de RiscoRESUMO
BACKGROUND: A dose of 0.5-1 mg/kg/day of prednisolone (PSL) is administered for the initial treatment of minimal change disease (MCD). However, little is known about the optimal PSL dose for the initial treatment of MCD. METHODS: We conducted a retrospective multicenter cohort study of treatment-naive adult patients with MCD diagnosed by renal biopsy from 1981 to 2015 in whom PSL monotherapy was performed as the initial treatment. The exposure of interest was an initial median PSL dose of < 0.63 mg/kg/day (Group L) compared to ≥ 0.63 mg/kg/day (Group H). Cumulative remission and relapse after remission were compared between these groups using Cox regression adjusted for baseline characteristics. RESULTS: Ninety-one patients met the inclusion criteria. During a median follow-up of 2.98 years, 87 (95.6%) patients achieved complete remission, and 47.1% relapsed after remission. There was no significant difference in the remission rate between the groups at 4 weeks of follow-up (66.7 vs. 82.6%). The median time to remission in Group L was comparable to that in Group H (17.0 vs. 14.0 days). A multivariable Cox hazard model revealed that the initial PSL dose was not a significant predictor of remission. The cumulative steroid doses at 6 months, 1 year, and 2 years after treatment initiation were significantly lower in Group L than in Group H. CONCLUSION: The initial PSL dose was not associated with time to remission, remission rate, time to relapse, or relapse rate. Therefore, a low initial steroid dose may be sufficient to achieve remission.
Assuntos
Nefrose Lipoide , Prednisolona , Adulto , Estudos de Coortes , Humanos , Imunossupressores/uso terapêutico , Nefrose Lipoide/diagnóstico , Nefrose Lipoide/tratamento farmacológico , Prednisolona/efeitos adversos , Recidiva , Indução de Remissão , Estudos Retrospectivos , Resultado do TratamentoRESUMO
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.
Assuntos
Aprendizado Profundo , Síndrome Nefrótica , Humanos , Síndrome Nefrótica/tratamento farmacológico , Creatinina , Estudos de Coortes , Hematúria , Japão , Proteinúria/etiologiaRESUMO
BACKGROUND: Little is known about the association between pre-operative proteinuria and post-operative acute kidney injury (AKI) in noncardiac surgery. METHODS: This is a retrospective cohort study. Adults who underwent noncardiac surgery under general anesthesia from 2007 to 2011 at Nara Medical University Hospital were included. Those with obstetric or urological surgery, missing data for analyses or pre-operative dialysis were excluded. Exposure of interest was pre-operative proteinuria, defined as (+) or more by dipstick test. The outcome variable was post-operative AKI, defined by Kidney Disease: Improving Global Outcomes criteria, within 1 week after surgery. Multivariable logistic regression analyses were performed. RESULTS: Among 5168 subjects, 309 (6.0%) developed AKI. Pre-operative proteinuria was independently associated with post-operative AKI, with an odds ratio (OR) [95% confidence interval (CI)] of 1.80 (1.30-2.51). A sensitivity analysis restricted to elective surgery yielded a similar result. As proteinuria increased, the association with AKI became stronger [OR (95% CI) 1.14 (0.75-1.73), 1.24 (0.79-1.95), 2.75 (1.74-4.35) and 3.95 (1.62-9.62) for urinary protein (+/-), (+), (2+) and (3+), respectively]. Subgroup analyses showed proteinuria was especially associated with post-operative AKI among subjects with renin-angiotensin system inhibitors, other anti-hypertensives, hypoalbuminemia or impaired renal function (P for interaction = 0.05, 0.003, 0.09 or 0.02, respectively). CONCLUSIONS: In noncardiac surgery, pre-operative proteinuria was independently associated with post-operative AKI. Subjects with proteinuria should be managed with caution to avoid AKI peri-operatively.
Assuntos
Injúria Renal Aguda/etiologia , Complicações Pós-Operatórias/etiologia , Cuidados Pré-Operatórios , Proteinúria/fisiopatologia , Procedimentos Cirúrgicos Operatórios/efeitos adversos , Injúria Renal Aguda/patologia , Idoso , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Complicações Pós-Operatórias/patologia , Estudos Retrospectivos , Fatores de Risco , UrináliseRESUMO
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.
Assuntos
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.
Assuntos
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.
Assuntos
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
Placental growth factor (PlGF) contributes to atherogenesis through vascular inflammation and plaque destabilization. High levels of PlGF may be associated with mortality and cardiovascular disease, but the relationship between PlGF level and adverse outcomes in patients with CKD is unclear. We conducted a prospective cohort study of 1351 consecutive participants with CKD enrolled in the Novel Assessment of Risk management for Atherosclerotic diseases in CKD (NARA-CKD) study between April 1, 2004, and December 31, 2011. During a median follow-up of 3 years, 199 participants died and 383 had cardiovascular events, defined as atherosclerotic disease or heart failure requiring hospitalization. In adjusted analyses, mortality and cardiovascular risk increased in each successive quartile of serum PlGF level; hazard ratios (HRs) (95% confidence intervals [95% CIs]) for mortality and cardiovascular risk, respectively, were 1.59 (0.83 to 3.16) and 1.55 (0.92 to 2.66) for the second quartile, 2.97 (1.67 to 5.59) and 3.39 (2.20 to 5.41) for the third quartile, and 3.87 (2.24 to 7.08) and 8.42 (5.54 to 13.3) for the fourth quartile. The composite end point of mortality and cardiovascular events occurred during the study period in 76.4% of patients in both the highest PlGF quartile (≥19.6 pg/ml) and the lowest eGFR tertile (<30 ml/min per 1.73 m(2)). The association between PlGF and mortality or cardiovascular events was not attenuated when participants were stratified by age, sex, traditional risk factors, and eGFR. These data suggest elevated PlGF is an independent risk factor for all-cause mortality and cardiovascular events in patients with CKD.
Assuntos
Doenças Cardiovasculares/sangue , Proteínas da Gravidez/sangue , Insuficiência Renal Crônica/sangue , Idoso , Aterosclerose/sangue , Aterosclerose/complicações , Doenças Cardiovasculares/complicações , Estudos de Coortes , Feminino , Taxa de Filtração Glomerular , Insuficiência Cardíaca/sangue , Insuficiência Cardíaca/complicações , Hospitalização , Humanos , Estudos Longitudinais , Masculino , Pessoa de Meia-Idade , Análise Multivariada , Peptídeo Natriurético Encefálico/sangue , Fator de Crescimento Placentário , Prognóstico , Modelos de Riscos Proporcionais , Estudos Prospectivos , Insuficiência Renal Crônica/complicações , Fatores de Risco , Fator A de Crescimento do Endotélio Vascular/sangueRESUMO
BACKGROUND: Placental growth factor (PlGF), a member of the vascular endothelial growth factor (VEGF) family, has recently emerged as a predictor of survival and cardiovascular risk. Along with others, we have shown an independent association between PlGF and cardiovascular events in CKD patients, but not much is known about patients receiving dialysis. METHODS: We studied 205 dialysis patients undergoing cardiac catheterization at the Nara Medical University between April 1, 2004, and December 31, 2012. Serum levels of PlGF and VEGF were measured with ELISA in all the patients. RESULTS: During a median follow-up of 20 months, 121 participants died from any cause or experienced a cardiovascular event. In the fully adjusted analysis, having an above-median PlGF or VEGF level was associated with a hazards ratio for adverse outcomes of 2.55 (1.72-3.83) and 1.39 (0.95-2.04), respectively. Using a multimarker strategy in a model with age, serum albumin, history of coronary artery disease, brain natriuretic peptide and PlGF, patients with 2, 3 and 4 positive markers had a 3.82-, 5.77- and 6.59-fold higher risk of mortality or a cardiovascular event, respectively, compared to those with no positive markers. The model with PlGF had a significantly higher c-statistic, integrated discrimination improvement index and category-free net reclassification improvement index than the model without PlGF. CONCLUSION: PlGF is independently associated with mortality and cardiovascular events, but the association between VEGF and adverse events was attenuated with covariate adjustment. The addition of PlGF to models with established clinical predictors provides additional useful prognostic information in patients receiving dialysis.
Assuntos
Doenças Cardiovasculares/epidemiologia , Falência Renal Crônica/terapia , Peptídeo Natriurético Encefálico/sangue , Proteínas da Gravidez/sangue , Diálise Renal , Fator A de Crescimento do Endotélio Vascular/sangue , Idoso , Dissecção Aórtica/epidemiologia , Dissecção Aórtica/mortalidade , Aneurisma Aórtico/epidemiologia , Aneurisma Aórtico/mortalidade , Doenças da Aorta/epidemiologia , Doenças da Aorta/mortalidade , Ruptura Aórtica/epidemiologia , Ruptura Aórtica/mortalidade , Doenças Cardiovasculares/mortalidade , Doença da Artéria Coronariana/epidemiologia , Doença da Artéria Coronariana/mortalidade , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Mortalidade , Doença Arterial Periférica/epidemiologia , Doença Arterial Periférica/mortalidade , Fator de Crescimento Placentário , Prognóstico , Modelos de Riscos Proporcionais , Acidente Vascular Cerebral/epidemiologia , Acidente Vascular Cerebral/mortalidadeRESUMO
OBJECTIVES: To evaluate the subclinical articular involvement in patients with primary Sjögren's syndrome (pSS) using musculoskeletal ultrasound (MSUS), and to correlate the findings with laboratory results and clinical manifestations. METHODS: Forty-eight consecutive patients with pSS were enrolled. The bilateral metacarpophalangeal, proximal interphalangeal, and interphalangeal joints were examined using MSUS, and the synovial hypertrophy and power Doppler signal were recorded for each joint using semi-quantitative scores (0 = normal, 1 = mild change compared with undamaged joint, 2 = moderate change, and 3 = severe change). RESULTS: Mild or moderate synovial hypertrophy was found in 151 (15.7%) and 2 (0.2%) out of 960 hand joints, respectively, and power Doppler signals were present in 19 (2.0%) of the 960 joints. While anti-centromere antibody (ACA) was found in 10 patients (20.8%), none of the patients with MSUS-confirmed synovitis was positive for ACA. No other autoantibodies, laboratory tests, or clinical manifestations correlated with MSUS-confirmed synovitis. CONCLUSION: MSUS is useful for detecting subclinical synovitis in pSS patients. MSUS showed that ACA-positive pSS patients had a low prevalence of synovitis.
Assuntos
Autoanticorpos , Articulação da Mão/diagnóstico por imagem , Síndrome de Sjogren/diagnóstico por imagem , Sinovite/diagnóstico por imagem , Adulto , Idoso , Centrômero/imunologia , Feminino , Articulação da Mão/imunologia , Humanos , Masculino , Pessoa de Meia-Idade , Síndrome de Sjogren/complicações , Síndrome de Sjogren/imunologia , Sinovite/complicações , Sinovite/imunologia , UltrassonografiaAssuntos
Terapia de Reposição de Enzimas , Doença de Fabry/tratamento farmacológico , Glicoesfingolipídeos/metabolismo , Miócitos Cardíacos/efeitos dos fármacos , alfa-Galactosidase/administração & dosagem , Idoso , Doença de Fabry/enzimologia , Doença de Fabry/patologia , Feminino , Humanos , Hidrólise , Masculino , Pessoa de Meia-Idade , Miócitos Cardíacos/enzimologia , Miócitos Cardíacos/ultraestrutura , Resultado do Tratamento , alfa-Galactosidase/metabolismoRESUMO
BACKGROUND: It is important to establish glycemic markers which reflect accurate glycemic status in advanced chronic kidney disease (CKD) patients; however, adequate glycemic markers have not been established. We evaluated the accuracy of glycemic markers in non-dialysis CKD patients. PATIENTS AND METHODS: 139 non-dialysis CKD patients with diabetes were enrolled. The patients were divided into three groups as follows: group 1 (G1), patients with an estimated glomerular filtration rate (eGFR) >= 60 mL/min/1.73 m2; group 2 (G2), 30 ≤ eGFR < 60; and group 3 (G3), eGFR < 30. The patients were also classified by serum albumin: patients with serum albumin >= 3.5 g/dL as group S1 (S1) and serum albumin < 3.5 as group S2 (S2). RESULTS: Glycated hemoglobin (A1C) was positively correlated with random PG in G1 and G2; however, no significant correlation was observed in G3. Whereas glycated albumin (GA) was correlated with random PG in S1, there was no significant correlation in S2. To clarify the significance of A1C and GA, the relationships among A1C, GA, and various clinical parameters were examined. GA was correlated with serum albumin and the urinary albumin-creatinine ratio, whereas A1C was significantly correlated with hemoglobin, the dose of recombinant human erythropoietin, and eGFR. CONCLUSION: A1C was affected by eGFR, and GA was influenced by hypoalbuminemia; therefore, it is necessary to choose adequate glycemic markers according to the CKD stage and serum albumin level. GA is a superior glycemic marker in patients with eGFR < 30 mL/min/1.73 m2 and serum albumin >= 3.5 g/dL.
Assuntos
Diabetes Mellitus Tipo 2/sangue , Nefropatias Diabéticas/sangue , Insuficiência Renal Crônica/sangue , Idoso , Albuminúria/diagnóstico , Biomarcadores/sangue , Biomarcadores/urina , Glicemia/análise , Creatinina/urina , Feminino , Taxa de Filtração Glomerular , Hemoglobinas Glicadas/análise , Produtos Finais de Glicação Avançada , Humanos , Masculino , Albumina Sérica/análise , Albumina Sérica GlicadaRESUMO
Fibroblast-specific protein 1 (FSP1)-expressing cells accumulate in damaged kidneys, but whether urinary FSP1 could serve as a biomarker of active renal injury is unknown. We measured urinary FSP1 in 147 patients with various types of glomerular disease using ELISA. Patients with crescentic GN, with or without antinuclear cytoplasmic antibody-associated GN, exhibited elevated levels of urinary FSP1. This assay had a sensitivity of 91.7% and a specificity of 90.2% for crescentic GN in this sample of patients. Moreover, we found that urinary FSP1 became undetectable after successful treatment, suggesting the possible use of FSP1 levels to monitor disease activity over time. Urinary FSP1 levels correlated positively with the number of FSP1-positive glomerular cells, predominantly podocytes and cellular crescents, the likely source of urinary FSP1. Even in patients without crescent formation, patients with high levels of urinary FSP1 had large numbers of FSP1-positive podocytes. Taken together, these data suggest the potential use of urinary FSP1 to screen for active and ongoing glomerular damage, such as the formation of cellular crescents.
Assuntos
Proteínas de Ligação ao Cálcio/urina , Glomerulonefrite/diagnóstico , Biomarcadores , Proteínas de Ligação ao Cálcio/sangue , Creatinina/sangue , Ensaio de Imunoadsorção Enzimática , Glomerulonefrite/urina , Humanos , Proteína A4 de Ligação a Cálcio da Família S100 , Sensibilidade e EspecificidadeRESUMO
Upadacitinib is a relatively new drug used to treat autoimmune diseases. However, patients treated with upadacitinib may develop infections. We report a case of cytomegalovirus (CMV) retinitis that developed during upadacitinib administration. A 79-year-old woman presented with progressively decreasing vision in both eyes. Her decimal best-corrected visual acuity (BCVA) was 0.2 in the right and 0.01 in the left eye. The patient was taking upadacitinib for one year. Fundus examination revealed vitreous opacities and extensive white retinal lesions with hemorrhage in both eyes. CMV was detected in the anterior aqueous humor, vitreous humor, and blood samples. We diagnosed her with panuveitis and CMV retinitis, performed a vitrectomy in both eyes, and administered intravenous ganciclovir and steroids. After treatment, her BCVA improved to 0.6 in the right and 0.1 in the left eye. Ophthalmologists and physicians should be aware of CMV infections in patients being treated with upadacitinib.
RESUMO
Association of preoperative regular use of anti-adrenergic agents with postoperative acute kidney injury (AKI) and with trajectory of kidney function after AKI is still unknown. In a retrospective cohort study, adults undergoing non-cardiac surgery under general anesthesia were included. Obstetric or urological surgery, missing data, or preoperative dialysis was excluded. The exposure of interest was preoperative regular use of anti-adrenergic agents. The outcomes were AKI within 1 week postoperatively and trajectories of kidney function within 2 weeks postoperatively among patients with AKI. Multivariable logistic regression models were used to examine the association of anti-adrenergic agents with AKI. Linear mixed-effects models were used to compare the trajectories of postoperative kidney function after AKI between patients with and without anti-adrenergic agents. Among 5168 patients, 245 had used anti-adrenergic agents. A total of 309 (6.0%) developed AKI, and the use of anti-adrenergic agents was independently associated with postoperative AKI even after adjustment for preoperative and intraoperative potential confounders [odds ratio (95% confidence interval): 1.76 (1.14-2.71)]. The association was similar across preexisting hypertension or cardiovascular disease. Analyses restricted to patients with AKI suggested that the timing and stage of AKI were similar among those with and without anti-adrenergic agents; however, the recovery of kidney function was delayed among those with anti-adrenergic agents (P for interaction = 0.004). The use of anti-adrenergic agents was associated with postoperative AKI and delayed recovery of kidney function after AKI. Temporary withdrawal of anti-adrenergic agents during perioperative periods may contribute to prevent AKI and shorten the duration of AKI.
Assuntos
Injúria Renal Aguda , Adulto , Humanos , Estudos de Coortes , Estudos Retrospectivos , Fatores de Risco , Injúria Renal Aguda/etiologia , RimRESUMO
Patient data from the National Database of Health Insurance Claims and Specific Health Checkups of Japan (NDB) are used to assess the effect of biguanide administration on rates of lactic acidosis (LA) in hospitalized diabetes mellitus (DM) patients. In this retrospective cohort study (from April 2013 to March 2016), we compare DM inpatients prescribed biguanides to DM inpatients who were not prescribed biguanides to quantify the association between biguanides and incidence of LA. In total, 8,111,848 DM patient records are retrieved from the NDB. Of the 528,768 inpatients prescribed biguanides, 782 develop LA. Of the 1,967,982 inpatients not prescribed biguanides, 1310 develop LA. The rate ratio of inpatients who develop LA and are administered biguanides to those who developed LA without receiving biguanides is 1.44 (95% CI, 1.32-1.58). Incidence rates and rate ratios for both sexes are elevated in the group prescribed biguanides for patients aged 70 years and older, markedly in those 80 years and older: 40.12 and 6.31 (95% CI, 4.75-8.39), respectively, for men and 34.96 and 5.40 (95% CI, 3.91-7.46), respectively, for women. Biguanides should be used conservatively in patients older than 70 years, particularly for those with comorbidities, and with caution in patients 80 years and older.
Assuntos
Acidose Láctica , Diabetes Mellitus , Metformina , Masculino , Humanos , Feminino , Idoso , Idoso de 80 Anos ou mais , Biguanidas/uso terapêutico , Acidose Láctica/induzido quimicamente , Acidose Láctica/epidemiologia , Estudos Retrospectivos , Metformina/efeitos adversos , Estudos de Coortes , Japão/epidemiologia , Diabetes Mellitus/tratamento farmacológico , Diabetes Mellitus/epidemiologia , Diabetes Mellitus/induzido quimicamente , Pacientes InternadosRESUMO
Hypercalciuria is one of the early manifestations of diabetic nephropathy. We explored here the role of α-Klotho, a protein expressed predominantly in distal convoluted tubules that has a role in calcium reabsorption. We studied 31 patients with early diabetic nephropathy and compared them with 31 patients with IgA nephropathy and 7 with minimal change disease. Renal α-Klotho expression was significantly lower and urinary calcium excretion (UCa/UCr) significantly higher in diabetic nephropathy than in IgA nephropathy or minimal change disease. Multiple regression analyses indicated that α-Klotho mRNA was inversely correlated with calcium excretion. We next measured these parameters in a mouse model of streptozotocin (STZ)-induced diabetic nephropathy, characterized by glomerular hyperfiltration, as seen in early diabetic nephropathy. We also confirmed a reduction of renal α-Klotho mRNA down to almost 50% and enhanced calcium excretion in mice with STZ-induced diabetic nephropathy in comparison with nondiabetic mice. Hypercalciuria was exacerbated in heterozygous α-Klotho knockout mice in comparison with wild-type mice, each with STZ-induced diabetic nephropathy. Thus, α-Klotho expression was decreased in distal convoluted tubules in diabetic nephropathy in humans and mice. Renal loss of α-Klotho may affect urinary calcium excretion in early diabetic nephropathy.
Assuntos
Cálcio/urina , Diabetes Mellitus Experimental/complicações , Nefropatias Diabéticas/etiologia , Glucuronidase/metabolismo , Hipercalciúria/etiologia , Túbulos Renais Distais/metabolismo , Receptores de Superfície Celular/metabolismo , Adulto , Animais , Canais de Cálcio/genética , Canais de Cálcio/metabolismo , Diabetes Mellitus Experimental/induzido quimicamente , Diabetes Mellitus Experimental/metabolismo , Diabetes Mellitus Experimental/urina , Nefropatias Diabéticas/genética , Nefropatias Diabéticas/metabolismo , Nefropatias Diabéticas/urina , Regulação para Baixo , Glucuronidase/genética , Células HEK293 , Heterozigoto , Humanos , Hipercalciúria/genética , Hipercalciúria/metabolismo , Hipercalciúria/urina , Proteínas Klotho , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Knockout , Pessoa de Meia-Idade , RNA Mensageiro/metabolismo , Receptores de Superfície Celular/deficiência , Receptores de Superfície Celular/genética , Canais de Cátion TRPV/genética , Canais de Cátion TRPV/metabolismo , Fatores de Tempo , Transfecção , Adulto JovemRESUMO
Recently, plasma globotriaosylsphingosine (lyso-Gb3) has attracted attention as a biomarker of Fabry disease. However, we found a subset of Fabry disease patients who did not show any increase in the plasma lyso-Gb3 concentration, although other patients exhibited apparent enhancement of it. This subset predominantly exhibited the clinical phenotype of later-onset Fabry disease, and gene analysis revealed that the patients harbored the M296I mutation common to Japanese Fabry patients. This amino acid substitution is predicted to cause a small conformational change on the surface of the α-galactosidase A molecule, resulting in residual enzyme activity. Plasma lyso-Gb3 is a good biomarker of Fabry disease but care should be taken when it is used for a definitive diagnosis.