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Short-term survival after kidney transplantation is excellent but long-term survival remains suboptimal. The aim of the study was to explore the relationship between soluble α-Klotho (sKlotho) and intact fibroblast growth factor 23 (iFGF23) measured 8 wk and 1 y posttransplant with long-term graft- and patient survival in a cohort of kidney transplant recipients with deficient and nondeficient vitamin D (25[OH]D) levels. Methods: Vitamin D, sKlotho, and iFGF23 were measured 8 wk and 1 y posttransplant in 132 recipients transplanted between November 2012 and October 2013. Results: Of the 132 kidney transplant recipients, 49 had deficient vitamin D levels (<30 nmol/L) and 83 had nondeficient vitamin D levels (≥30 nmol/L) at 8 wk posttransplant. The mean age was 51 y and the median follow-up was 7.4 y. At 1 y posttransplant, vitamin D increased significantly. There were no significant differences in sKlotho or iFGF23 levels between the 2 vitamin D groups neither at 8 wk nor 1 y. sKlotho increased significantly and iFGF23 decreased significantly in the whole cohort. During the follow-up, there were 36 graft losses (27%) and 27 deaths (20%). Ninety-four percent of the transplant recipients with nondeficient vitamin D levels were alive with a well-functioning graft after 5 y using Kaplan-Meier survival estimates, compared with 84% of the patients with deficient vitamin D levels (P = 0.014). Klotho and FGF23 levels did not influence graft- and patient survival. Conclusions: In this nationwide cohort of kidney transplant recipients, long-term graft- and patient survival were significantly better in patients with vitamin D ≥30 nmol/L 8 wk posttransplant compared with those with vitamin D <30 nmol/L. sKlotho levels increased and iFGF23 levels decreased from 8 wk to 1 y posttransplant. Klotho and FGF23 levels were not associated with graft- and patient survival.
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BACKGROUND: Post-transplant diabetes mellitus is one of the most important cardiovascular risk factors after solid organ transplantation. Factors other than hyperglycaemia found in patients post-transplant, affect the level of haemoglobin A1c (HbA1c), and new markers of hyperglycaemia are needed. Our aim was to establish a 95% reference interval for glycated albumin in kidney transplant recipients, and to compare glycated albumin concentrations to the diagnostic criteria for diabetes mellitus post-transplant using oral glucose tolerance test and HbA1c. METHODS: A total of 341 non-diabetic kidney transplant recipients aged ≥18 years who underwent an oral glucose tolerance test at 8 weeks and 1 year after transplantation were included. Glycated albumin was determined by liquid chromatography coupled with tandem mass spectrometry. RESULTS: The 95% reference interval for glycated albumin was 8.2 (90% CI: 7.2-8.5) to 12.8% (90% CI: 12.2-13.5) which is not significantly different from our laboratory's 95% reference interval for persons without diabetes. At both 8 weeks and 1 year after transplantation, 35 patients (10.3%) fulfilled one, two or all three diagnostic criteria for diabetes mellitus. One year after transplantation, eight additional patients had glycated albumin concentration >12.8%. CONCLUSION: Our findings are in accordance with the notion that kidney transplant recipients form glycation end products like normal controls as estimated by glycated albumin and HbA1c. Further studies should address glycated albumin as a supplemental tool for the diagnosis of post-transplant diabetes mellitus in kidney transplant recipients.
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Diabetes Mellitus Tipo 2 , Diabetes Mellitus , Hiperglucemia , Trasplante de Riñón , Albúmina Sérica , Adolescente , Adulto , Humanos , Glucemia/análisis , Diabetes Mellitus/diagnóstico , Diabetes Mellitus/etiología , Diabetes Mellitus Tipo 2/diagnóstico , Hemoglobina Glucada , Productos Finales de Glicación Avanzada , Hiperglucemia/diagnóstico , Hiperglucemia/etiología , Trasplante de Riñón/efectos adversos , Albúmina Sérica/químicaRESUMEN
BACKGROUND: A man in his fifties, originally from a Middle Eastern country, presented with left-sided otalgia and neck pain which worsened over several months. He had pre-existing hypertension, diabetes mellitus type 2 and end stage renal disease requiring dialysis. CASE PRESENTATION: His presenting complaints started whilst on a long stay in his country of origin. Symptoms progressively worsened over the coming months while he underwent extensive medical examinations and investigations. This revealed opacifications in the mastoid cavities, raised inflammatory markers, and finally a CT scan revealed osteolytic lesions in his cervical spine. The lesions continued to progress, and his clinical condition deteriorated to the point that he required surgery. Culture was obtained through perioperative biopsies and showed growth of Aspergillus flavus. INTERPRETATION: The patient had initially received topical treatment for an assumed infectious external otitis. Later culture from his outer ear also showed growth of A. flavus, the same pathogen that was found in a biopsy from his cervical spine. He was diagnosed with cervical mycotic osteomyelitis, probably secondary to a chronic external otitis. Long term antimycotic therapy and three neurosurgical operations were required to treat the patient.
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Osteomielitis , Otitis Externa , Vértebras Cervicales , Conducto Auditivo Externo , Humanos , Masculino , Osteomielitis/diagnóstico , Osteomielitis/terapia , Otitis Externa/complicaciones , DolorRESUMEN
INTRODUCTION: Glycated albumin (GA), a biomarker reflecting short-term glycaemia, may be useful to assess glycaemic control in pregnancy. We examined the association between GA and continuous glucose monitoring (CGM) metrics across gestation. METHODS: In this prospective cohort study including 40 women with pre-gestational diabetes, blood samples for analysis of GA and glycated haemoglobin A1c (HbA1c) were collected at pregnancy week 12, 20, 24, 28, 32 and 36. In the CGM-group (n = 19), CGM data were collected from first trimester until pregnancy week 36. Receiver operating characteristic (ROC) curves were used to assess the accuracy of GA and HbA1c to detect poor glycaemic control, using CGM metrics as the reference standard. This study was conducted at Stavanger University Hospital, Norway, in 2016-2018. RESULTS: Glycaemic control improved across gestation with more time spent in target range, coinciding with decreased glycaemic variability and lower mean GA level. There was statistically significant correlation between GA and most CGM metrics. The area under the ROC curves (AUC) for detecting time in range <70% and time above range >25% for the pregnancy glucose target 63-140 mg/dl (3.5-7.8 mmol/L) were 0.78 and 0.82 for GA, whereas AUCs of 0.60 and 0.72 were found for HbA1c, respectively. CONCLUSIONS: Higher GA levels were associated with less time spent in target range, more time spent in the above range area and increased glycaemic variability. GA was more accurate than HbA1c to detect time above range >25% and time in range <70%.
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Glucemia , Diabetes Gestacional , Embarazo , Femenino , Humanos , Hemoglobina Glucada , Automonitorización de la Glucosa Sanguínea , Diabetes Gestacional/diagnóstico , Estudios Prospectivos , Benchmarking , Glucosa , Albúmina Sérica GlicadaRESUMEN
Glycated albumin (GA) may be a useful biomarker of glycemia in pregnancy. The aim of this study was to establish the reference interval (RI) for GA, analyzed by liquid chromatography-tandem mass spectrometry (LC-MS/MS), in healthy, nulliparous pregnant women. In addition, we assessed the accuracy of GA and glycated hemoglobin A1c (HbA1c) in the diagnosis of gestational diabetes mellitus (GDM). Finally, we explored the prevalence of GDM in healthy nulliparas, comparing three diagnostic guidelines (WHO-1999, WHO-2013 and the Norwegian guideline). The study was carried out at Stavanger University Hospital, Norway, and included a study population of 147 pregnant nulliparous women. An oral glucose tolerance test (OGTT) was performed and used as the gold standard for GDM diagnosis. Blood samples for analysis of GA and HbA1c were collected at pregnancy week 24-28. A nonparametric approach was chosen for RI calculation, and receiver operating characteristic (ROC) curves were used to evaluate the diagnostic performance of GA and HbA1c. The established RI for GA in 121 pregnant women was 7.1-11.6%. The area under the ROC curves (AUCs) were 0.531 (GA) and 0.627 (HbA1c). According to the WHO-1999, WHO-2013 and the Norwegian guideline, respectively, 24 (16%), 36 (24%) and 21 (14%) women were diagnosed with GDM. Only nine women (6%) fulfilled the GDM-criteria of all guidelines. In conclusion, we established the first LC-MS/MS-based RI for GA in pregnant women. At pregnancy weeks 24-28, neither GA nor HbA1c discriminated between those with and without GDM. Different women were diagnosed with GDM using the three guidelines.
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Diabetes Gestacional , Glucemia/análisis , Cromatografía Liquida , Diabetes Gestacional/diagnóstico , Femenino , Hemoglobina Glucada/análisis , Productos Finales de Glicación Avanzada , Humanos , Paridad , Embarazo , Albúmina Sérica , Espectrometría de Masas en Tándem , Albúmina Sérica GlicadaRESUMEN
BACKGROUND: Neuropsychiatric manifestations (NP) are common in systemic lupus erythematosus (SLE). However, the pathophysiological mechanisms are not completely understood. Neurofilament light protein (NfL) is part of the neuronal cytoskeleton. Increased NfL concentrations, reflecting neurodegeneration, is observed in cerebrospinal fluid (CSF) in several neurodegenerative and neuroinflammatory conditions. We aimed to explore if plasma NfL could serve as a biomarker for central nervous system (CNS) involvement in SLE. METHODS: Sixty-seven patients with SLE underwent neurological examination; 52 underwent lumbar puncture, while 62 underwent cerebral magnetic resonance imaging (MRI). We measured selected auto-antibodies and other laboratory variables postulated to have roles in NP pathophysiology in the blood and/or CSF. We used SPM12 software for MRI voxel-based morphometry. RESULTS: Age-adjusted linear regression analyses revealed increased plasma NfL concentrations with increasing creatinine (ß = 0.01, p < 0.001) and Q-albumin (ß = 0.07, p = 0.008). We observed higher plasma NfL concentrations in patients with a history of seizures (ß = 0.57, p = 0.014), impaired motor function (ß = 0.36, p = 0.008), increasing disease activity (ß = 0.04, p = 0.008), and organ damage (ß = 0.10, p = 0.002). Voxel-based morphometry suggested an association between increasing plasma NfL concentrations and the loss of cerebral white matter in the corpus callosum and hippocampal gray matter. CONCLUSION: Increased plasma NfL concentrations were associated with some abnormal neurological, cognitive, and neuroimaging findings. However, plasma NfL was also influenced by other factors, such as damage accrual, creatinine, and Q-albumin, thereby obscuring the interpretation of how plasma NfL reflects CNS involvement. Taken together, NfL in CSF seems a better marker of neuronal injury than plasma NfL in patients with SLE.
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Sistema Nervioso Central , Lupus Eritematoso Sistémico , Proteínas de Neurofilamentos , Sustancia Blanca , Albúminas , Biomarcadores/sangre , Sistema Nervioso Central/fisiopatología , Creatinina , Humanos , Lupus Eritematoso Sistémico/complicaciones , Lupus Eritematoso Sistémico/diagnóstico , Proteínas de Neurofilamentos/sangre , Proteínas de Neurofilamentos/líquido cefalorraquídeoRESUMEN
BACKGROUND: Fibroblast growth factor 23 (FGF23) is a regulator of mineral metabolism, that has been linked to myocardial remodeling including development of left ventricular (LV) hypertrophy and myocardial fibrosis. The aim of this study was to investigate the relationship between intact FGF23 (iFGF23), myocardial infarct size and LV remodeling following a first acute ST-elevation myocardial infarction (STEMI). METHODS AND RESULTS: Forty-two consecutive patients with first-time STEMI, single vessel disease, successfully treated with primary percutaneous coronary intervention were included. Cardiac magnetic resonance (CMR) imaging was performed at day 2, 1 week, 2 months and 1 year post MI, and blood samples were drawn at admittance and at the same time points as the CMRs. The cohort was divided according to the presence or not of heart failure post MI. In the total cohort, iFGF23 (mean ± SD) was significantly lower at day 0 (33.7 ± 20.6 pg/ml) and day 2 (31.5 ± 23.4 pg/ml) compared with a reference interval based on 8 healthy adults (43.9 pg/ml ± 19.0 pg/ml). iFGF23 increased to normal levels (55.8 ± 23.4 pg/ml) seven days post MI. In the subset of patients with signs of acute heart failure, FGF23 was higher at all measured timepoints, reaching significantly higher FGF23 levels at 2 months and 1 year following revascularization. CONCLUSION: There was a reduction in iFGF23 levels during the acute phase of MI, with a normalization at seven days following revascularization. During one-year follow-up, there was a gradual increase in iFGF23 levels in patients with heart failure.
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BACKGROUND: To test the hypothesis that neurofilament light (NfL) in CSF is a biomarker of CNS involvement in patients with systemic lupus erythematosus (SLE) and primary Sjögren's syndrome (pSS), we measured NfL in CSF from 52 patients with lupus and 54 with pSS and explored associations with clinical, structural, immunological and biochemical abnormalities. METHODS: In CSF, we measured NfL, anti-P antibodies, protein S100B and TWEAK by ELISA and anti-NR2 antibodies by electrochemiluminescence. Anti-phospholipid antibodies and routine immunological tests were performed in blood. IgG and albumin were measured in CSF and serum for assessment of the blood-brain barrier function (Q-albumin) and intrathecal IgG production (IgG index). Cerebral MRI and neuropsychological testing were performed. RESULTS: A multivariable regression model showed that increasing CSF anti-NR2 antibody levels were associated with increasing NfL levels in patients with SLE (B 1.27, 95% CI 0.88-1.65, p < 0.001). Age contributed significantly in the model (B 0.04, 95% CI 0.03-0.05, p < 0.001). Similar findings were observed in the pSS group. Adjusted for age and sex, no associations were found between NfL levels and any MRI data. In SLE patients, higher NfL concentrations were associated with impairments in psychomotor speed and motor function, and in pSS with motor dysfunction. These associations remained in multivariable regression models. CONCLUSIONS: Increased concentration of NfL in CSF is a marker of cerebral involvement in patients with SLE and pSS, is strongly associated with the presence of anti-NR2 antibodies, and correlates with cognitive impairment in several domains.
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Lupus Eritematoso Sistémico , Síndrome de Sjögren , Biomarcadores , Encéfalo/diagnóstico por imagen , Humanos , Filamentos Intermedios , Lupus Eritematoso Sistémico/complicaciones , Lupus Eritematoso Sistémico/diagnóstico por imagen , Proteínas de Neurofilamentos , Síndrome de Sjögren/complicaciones , Síndrome de Sjögren/diagnóstico por imagenRESUMEN
BACKGROUND: Patients with chronic kidney disease make day-to-day decisions about how to self-manage their disease. Chronic kidney disease (CKD) includes a risk for progression towards end-stage renal disease and the development of comorbidities, such as cardiovascular disease, which represents the leading cause of death among these patients. To reduce these risks, CKD patients are recommended to follow a healthy lifestyle with physical activity, food and fluid restrictions, and adherence to complex medication regimes throughout all phases of the disease. To manage the complexity of this health situation, health literacy (HL) is considered essential. The current prevailing understanding is that HL is a multidimensional concept and comprises a range of cognitive, affective, social, and personal skills that determine the motivation and ability to gain access to, understand, and use health information. Recently, we investigated multiple aspects of HL in CKD patients in a quantitative cross-sectional study utilizing the Health Literacy Questionnaire (HLQ) and observed that finding good health information and appraising health information were the most challenging aspects of HL. This study aimed to explore CKD patients' lived experiences of different dimensions of HL presented in the HLQ. METHODS: This qualitative study utilized in-depth semistructured interviews. Twelve patients with different levels of HL were included. The interviews were analyzed using thematic analysis as described by Braun and Clarke. RESULTS: We identified three main themes that were significant for CKD patients' HL: 1. Variation in people's attitudes and behavior as health information seekers, 2. The problem of fragmented healthcare in the context of multimorbidity makes the healthcare system challenging to navigate, and 3. The value of a good relationship with healthcare providers. CONCLUSION: CKD patients take different approaches to health information. Limiting or avoiding health information may be a strategy used by some individuals to cope with the disease and does not necessarily mean that health information is inaccessible or difficult to understand. Comorbidity and a fragmented healthcare system can make the healthcare system challenging to navigate. A good and trusting relationship with healthcare providers seems to promote several aspects of HL and should be promoted to optimize CKD patients' HL.
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Alfabetización en Salud , Insuficiencia Renal Crónica , Automanejo , Adulto , Anciano , Anciano de 80 o más Años , Femenino , Humanos , Masculino , Persona de Mediana Edad , Investigación CualitativaRESUMEN
BACKGROUND: Health literacy (HL) is a multidimensional concept with significance for self-management and health outcomes in patients with chronic kidney disease (CKD); however, research with a multidimensional perspective on HL is scarce. OBJECTIVES: This study aimed to explore the relationship between multidimensional HL, quality of life (QoL) and adherence to long-term therapy in CKD patients. DESIGN: A descriptive single-centre cross-sectional study. PARTICIPANTS: Patients with CKD in stages 3-5 were recruited from the nephrology unit in a Norwegian hospital. MEASUREMENTS: The Health Literacy Questionnaire (HLQ) was used to assess HL, QoL was measured by the Short Form-12 (SF-12) and a Visual Analogue Scale (VAS-QoL). Adherence to long-term therapy was measured by the Medical Adherence Rating Scale 5 (MARS-5), participants' prescription withdrawals from pharmacies, and a VAS (VAS-adherence). Hierarchical cluster analysis was performed to group patients with similar HLQ scores, and multiple linear regression analysis was performed to identify the HL dimensions that were associated with QoL and adherence to long-term therapy. RESULTS: A total of 187 patients were included, 65% were male, and the mean (SD) age was 67 (13) years. The high-level HL group (N = 52) had significantly better QoL than patients in the mid-level (N = 106) and low-level (N = 27) HL groups. The HL dimensions "actively managing health," "actively engage with healthcare providers," "ability to find good health information" and "ability to understand health information" were predictive of QoL and adherence to long-term therapy. CONCLUSION: HL seems to be important for both QoL and adherence to long-term therapy.
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Alfabetización en Salud/normas , Enfermedades Renales/complicaciones , Calidad de Vida/psicología , Cumplimiento y Adherencia al Tratamiento/psicología , Femenino , Alfabetización en Salud/estadística & datos numéricos , Humanos , Enfermedades Renales/psicología , Masculino , Persona de Mediana Edad , Encuestas y CuestionariosRESUMEN
AIM: The aim of this study was to investigate health literacy in patients with chronic kidney disease in a multidimensional perspective. DESIGN: A descriptive, cross-sectional study. METHODS: Patients with chronic kidney disease at stages 3-5 were included in the study between February-August 2017 (N = 187). Health literacy was measured by the Health Literacy Questionnaire (HLQ). Multiple linear regression analysis was performed to identify associations between health literacy and demographic and clinical variables. Hierarchical cluster analysis was performed to identify characteristics of groups with high and low health literacy. RESULTS: Finding and critical appraise health information were the most challenging dimensions of health literacy. Female gender, lower level of education, greater number of prescribed medications and depressive symptoms were associated with lower health literacy. The group identified with lowest health literacy was further characterized by living alone and presence of comorbidity.
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BACKGROUND: Purple urine bag syndrome (PUBS) can occur in cases of bacteriuria with species expressing enzymes capable of converting tryptophan metabolites to red and blue pigments which are excreted in urine, leaving a characteristic purple colour. Risk factors include urinary catheterisation, constipation and chronic kidney disease. Treatment includes catheter replacement, and antibiotics in case of urinary tract infection. CASE PRESENTATION: A man in his 70s with myelodysplastic syndrome, stage 5 chronic kidney disease and chronic indwelling urinary catheterisation due to benign prostatic hyperplasia was admitted for transfusion for symptomatic anaemia. On the second day of hospitalisation, his urine turned purple. There was no sign of transfusion reaction, haemoglobinuria, myoglobinuria or bilirubinuria. Urine cultures were positive for Proteus vulgaris and Enterococcus faecalis, two species associated with PUBS. INTERPRETATION: The constellation was consistent with PUBS. His bacteriuria was considered colonisation not requiring antibiotic treatment. The catheter was replaced and the urine colour returned to normal.
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Bacteriuria/microbiología , Infecciones Relacionadas con Catéteres/microbiología , Catéteres Urinarios/microbiología , Infecciones Urinarias/microbiología , Anciano , Bacteriuria/terapia , Infecciones Relacionadas con Catéteres/terapia , Enterococcus faecalis/aislamiento & purificación , Humanos , Masculino , Proteus vulgaris/aislamiento & purificación , Infecciones Urinarias/terapia , Orina/microbiologíaRESUMEN
BACKGROUND: Short-term survival after kidney transplantation is excellent, but long-term survival remains low and is equivalent to non-end-stage renal disease patients with many invasive malignancies. The aim of the study was to explore vitamin D status in the early phase after transplantation as a prognostic marker for long-term graft and patient survival. METHODS: All first-time kidney transplant recipients between October 2007 and October 2012 in Norway were included. Vitamin D was measured 10 weeks post-transplant. Information on graft failure and death was obtained from the Norwegian Renal Registry. RESULTS: Seven hundred and sixty-two first-time kidney transplant recipients were included, with a median age of 57 years and a median follow-up of 82 months. In the follow-up period, there were 172 graft failures (23%) and 118 deaths (15%). Eighty-six percent of the transplant recipients with sufficient vitamin D levels were alive with a well-functioning graft after 5 years using Kaplan-Meier survival estimates, compared with 79% and 76% of the patients with vitamin D deficiency and insufficiency, respectively (P = 0.006). CONCLUSION: In a nation-wide cohort of 762 first-time kidney transplant recipients, long-term graft and patient survival were better in recipients with vitamin D sufficiency 10 weeks post-transplant compared with those with vitamin D deficiency and insufficiency.
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Rechazo de Injerto/mortalidad , Fallo Renal Crónico/mortalidad , Trasplante de Riñón/mortalidad , Complicaciones Posoperatorias/mortalidad , Deficiencia de Vitamina D/sangre , Vitamina D/sangre , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Femenino , Estudios de Seguimiento , Tasa de Filtración Glomerular , Rechazo de Injerto/sangre , Rechazo de Injerto/epidemiología , Supervivencia de Injerto , Humanos , Incidencia , Fallo Renal Crónico/sangre , Fallo Renal Crónico/cirugía , Pruebas de Función Renal , Masculino , Persona de Mediana Edad , Noruega/epidemiología , Complicaciones Posoperatorias/sangre , Complicaciones Posoperatorias/epidemiología , Pronóstico , Estudios Prospectivos , Factores de Riesgo , Tasa de Supervivencia , Receptores de Trasplantes , Deficiencia de Vitamina D/complicaciones , Deficiencia de Vitamina D/epidemiología , Adulto JovenRESUMEN
AIMS: Iron deficiency is common in patients with chronic kidney disease (CKD). Appropriate iron substitution is critical and intravenous iron is an established therapy for these patients. The objective of this study was to assess treatment routine, -effectiveness, and safety of iron isomaltoside (Monofer®, Pharma-cosmos A/S, Holbaek, Denmark) in CKD patients in clinical practice. MATERIALS AND METHODS: This was a prospective observational study conducted in predialysis CKD patients treated with iron isomaltoside according to the product label and to routine clinical care. RESULTS: The study included 108 patients with predialysis CKD: 22 were in stage 2 - 3, 41 in stage 4, and 45 in stage 5. The mean (standard deviation) age was 67 (15) years, and 55% of patients were male. The majority of patients (65%) received one iron isomaltoside treatment. In patients with a baseline Hb < 10 g/dL, the mean dose of iron isomaltoside in the study was lower than the estimated total iron requirement (567 mg versus 921 mg). A treatment response of Hb ≥ 1 g/dL was achieved in 16/28 (57%) of patients, and the mean post-treatment Hb level was 10.5 g/dL. The probability of retreatment did not correlate with dose, but no dose administered was > 1,000 mg. There were no serious adverse drug reactions. One non-serious adverse drug reaction - injection site discoloration - was reported, and the patient had an uneventful recovery. CONCLUSION: Iron isomaltoside shows a good effectiveness and safety profile in predialysis CKD patients. However, some patients did not receive adequate iron doses to allow for optimal correction of their iron deficiency anemia.
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Anemia Ferropénica/tratamiento farmacológico , Disacáridos/uso terapéutico , Compuestos Férricos/uso terapéutico , Hematínicos/uso terapéutico , Insuficiencia Renal Crónica/complicaciones , Adulto , Anciano , Anciano de 80 o más Años , Anemia Ferropénica/sangre , Anemia Ferropénica/complicaciones , Disacáridos/efectos adversos , Femenino , Compuestos Férricos/efectos adversos , Hematínicos/efectos adversos , Hemoglobinas/metabolismo , Humanos , Hierro , Masculino , Persona de Mediana Edad , Estudios Prospectivos , Países Escandinavos y Nórdicos , Resultado del TratamientoRESUMEN
BACKGROUND: This study investigated medication adherence in kidney transplant patients (KTPs) converted from immediate-release tacrolimus (IR-T) to prolonged-release tacrolimus (PR-T)-based immunosuppression in routine practice. METHODS: Noninterventional, observational, multicenter study in Norway. Included adult KTPs with stable graft function, converted from IR-T (baseline) to PR-T (1 mg:1 mg) in routine practice. Data were collected at baseline, and months 1, 3, 6, and 12 postconversion. Primary endpoint: adherence using the Basel Assessment of Adherence to Immunosuppressive Medication Scale. Secondary assessments: tacrolimus dose and trough levels (target, 3-7 ng/mL), clinical laboratory parameters (eg, estimated glomerular filtration rate [Modified Diet in Renal Disease]), and adverse events. RESULTS: Ninety-one KTPs (mean ± SD age 47.7 ± 14.3 years) were analyzed. Mean ± SD change in PR-T dose from baseline (4.4 ± 2.4 mg/d) to month 12 was -0.1 ± 0.9 mg/d; mean tacrolimus trough levels remained within target. Overall medication adherence increased from 45.6% at baseline to 58.1% at month 1, but was similar to baseline thereafter; taking and timing adherence followed a similar pattern. Odds ratio (OR) for adherence at month 1 (but not at other time points) was greater versus baseline for overall (OR, 1.71; P = 0.0205), taking (OR, 3.38; P = 0.0004), and timing (OR, 1.77, P = 0.0252) dimensions. Mean ± SD Basel Assessment of Adherence to Immunosuppressive Medication Scale visual analogue scale score at baseline was 96.4 ± 5.5%, and increased postconversion. Estimated glomerular filtration rate remained stable (month 12, 61.6 ± 17.7 mL/min per 1.73 m2), as did other laboratory parameters. Two (2.2%) patients had adverse events considered probably/possibly treatment-related. CONCLUSIONS: There was disparity between high, patient-perceived and low, actual adherence. Converting stable KTPs from IR-T to PR-T in routine practice did not impact long-term adherence to immunosuppression; renal function remained stable.
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Sjögren's syndrome (SS) is a common, autoimmune exocrinopathy distinguished by keratoconjunctivitis sicca and xerostomia. Patients frequently develop serious complications including lymphoma, pulmonary dysfunction, neuropathy, vasculitis, and debilitating fatigue. Dysregulation of type I interferon (IFN) pathway is a prominent feature of SS and is correlated with increased autoantibody titers and disease severity. To identify genetic determinants of IFN pathway dysregulation in SS, we performed cis-expression quantitative trait locus (eQTL) analyses focusing on differentially expressed type I IFN-inducible transcripts identified through a transcriptome profiling study. Multiple cis-eQTLs were associated with transcript levels of 2'-5'-oligoadenylate synthetase 1 (OAS1) peaking at rs10774671 (PeQTL = 6.05 × 10-14). Association of rs10774671 with SS susceptibility was identified and confirmed through meta-analysis of two independent cohorts (Pmeta = 2.59 × 10-9; odds ratio = 0.75; 95% confidence interval = 0.66-0.86). The risk allele of rs10774671 shifts splicing of OAS1 from production of the p46 isoform to multiple alternative transcripts, including p42, p48, and p44. We found that the isoforms were differentially expressed within each genotype in controls and patients with and without autoantibodies. Furthermore, our results showed that the three alternatively spliced isoforms lacked translational response to type I IFN stimulation. The p48 and p44 isoforms also had impaired protein expression governed by the 3' end of the transcripts. The SS risk allele of rs10774671 has been shown by others to be associated with reduced OAS1 enzymatic activity and ability to clear viral infections, as well as reduced responsiveness to IFN treatment. Our results establish OAS1 as a risk locus for SS and support a potential role for defective viral clearance due to altered IFN response as a genetic pathophysiological basis of this complex autoimmune disease.
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2',5'-Oligoadenilato Sintetasa/genética , Interferón Tipo I/genética , Sitios de Carácter Cuantitativo/genética , Síndrome de Sjögren/genética , 2',5'-Oligoadenilato Sintetasa/biosíntesis , Alelos , Empalme Alternativo/genética , Femenino , Regulación de la Expresión Génica , Estudios de Asociación Genética , Predisposición Genética a la Enfermedad , Humanos , Interferón Tipo I/metabolismo , Masculino , Síndrome de Sjögren/metabolismo , Síndrome de Sjögren/patología , Virosis/genética , Virosis/virologíaRESUMEN
BACKGROUND: Neutrophil gelatinase-associated lipocalin (NGAL), a protein with bacteriostatic functions rapidly excreted from stimulated or damaged epithelial cells, is elevated in acute and chronic kidney disease. A calcineurin dependent signaling pathway for fibroblast growth factor 23 (FGF23) has been revealed, but the effect of calcineurin inhibitors (CNIs) on the levels of NGAL and markers of mineral metabolism in long-term kidney transplant patients has not been explored. METHODS: In a cross-sectional study, 39 patients who received a first kidney transplant more than 10 years ago were split into two groups based on whether (n=28) or not (n=11) they used CNIs. Only patients with well-functioning grafts defined as an estimated glomerular filtration rate ≥45 mL/min per 1.73 m2 were included. RESULTS: The median levels of NGAL, intact parathyroid hormone (iPTH), and iFGF23 were significantly higher in CNI users vs CNI nonusers, 167.0 (134.0-235.0) ng/mL vs 105.0 (91.3-117.0) ng/mL, P<.001, 13.8 (10.0-17.3) pmol/L vs 8.4 (6.4-9.9) pmol/L, P=.003, and 81.6 (56.4-116.5) pg/mL vs 61.8 (43.3-72.1) pg/mL, P=.04 respectively. CONCLUSIONS: The median levels of iFGF23 were higher in CNI users compared to CNI nonusers giving support to the notion of a CNI induced FGF23 resistance in the parathyroid. The net result of CNIs side effects needs to be further explored.
Asunto(s)
Inhibidores de la Calcineurina/farmacología , Factores de Crecimiento de Fibroblastos/sangre , Trasplante de Riñón , Riñón/efectos de los fármacos , Lipocalina 2/sangre , Glándulas Paratiroides/efectos de los fármacos , Adulto , Anciano , Biomarcadores/sangre , Estudios Transversales , Femenino , Factor-23 de Crecimiento de Fibroblastos , Humanos , Riñón/metabolismo , Modelos Lineales , Masculino , Persona de Mediana Edad , Glándulas Paratiroides/metabolismo , Hormona Paratiroidea/sangreRESUMEN
OBJECTIVE: The main aims of this study were to assess longitudinal glycemic control and the prevalence of retinopathy and nephropathy in young people (aged 14-30 yr) with type 1 diabetes in Norway. METHOD: Data on 874 patients were obtained by linking two nationwide, population-based medical quality registries: The Norwegian Diabetes Register for Adults and The Norwegian Childhood Diabetes Registry. RESULTS: Median age was 23 yr, median diabetes duration 9 yr and 51% were male. Median HbA1c increased through adolescence to peak at ages of 17 yr for females and 19 yr for males, females had higher HbA1c than males: 9.3% (78 mmol/mol) vs. 9.1% (76 mmol/mol). Subsequently, median HbA1c declined but was still >8% (>64 mmol/mol) for patients approaching 30 yr. Half of the patients aged 14-17 yr and 40% of patients aged 18-25 yr had HbA1c >9% (75 mmol/mol). Retinopathy was found in 16% and nephropathy in 13% of the population. Patients transferring from the pediatric department to adult care between the ages of 14 and 17 yr had higher median HbA1c and prevalence of late complications than those transferring at ages 18-22 yr. Less than 40% of patients with albuminuria were treated with ACE inhibitors or angiotensin II receptor blocker. CONCLUSION: Our results demonstrate that treatment of adolescents and young adults with type 1 diabetes in Norway is not optimal, especially for patients in their late teens. We suggest that pediatricians and endocrinologists should critically assess the care offered to this group and consider new approaches to help them improve glycemic control.