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Individualized pre-pregnancy counseling and antenatal care for women with chronic kidney disease (CKD) require disease-specific data. Here, we investigated pregnancy outcomes and long-term kidney function in women with COL4A3-5 related disease (Alport Syndrome, (AS)) in a large multicenter cohort. The ALPART-network (mAternaL and fetal PregnAncy outcomes of women with AlpoRT syndrome), an international collaboration of 17 centers, retrospectively investigated COL4A3-5 related disease pregnancies after the 20th week. Outcomes were stratified per inheritance pattern (X-Linked AS (XLAS)), Autosomal Dominant AS (ADAS), or Autosomal Recessive AS (ARAS)). The influence of pregnancy on estimated glomerular filtration rate (eGFR)-slope was assessed in 192 pregnancies encompassing 116 women (121 with XLAS, 47 with ADAS, and 12 with ARAS). Median eGFR pre-pregnancy was over 90ml/min/1.73m2. Neonatal outcomes were favorable: 100% live births, median gestational age 39.0 weeks and mean birth weight 3135 grams. Gestational hypertension occurred during 23% of pregnancies (reference: 'general' CKD G1-G2 pregnancies incidence is 4-20%) and preeclampsia in 20%. The mean eGFR declined after pregnancy but remained within normal range (over 90ml/min/1.73m2). Pregnancy did not significantly affect eGFR-slope (pre-pregnancy ß=-1.030, post-pregnancy ß=-1.349). ARAS-pregnancies demonstrated less favorable outcomes (early preterm birth incidence 3/11 (27%)). ARAS was a significant independent predictor for lower birth weight and shorter duration of pregnancy, next to the classic predictors (pre-pregnancy kidney function, proteinuria, and chronic hypertension) though missing proteinuria values and the small ARAS-sample hindered analysis. This is the largest study to date on AS and pregnancy with reassuring results for mild AS, though inheritance patterns could be considered in counseling next to classic risk factors. Thus, our findings support personalized reproductive care and highlight the importance of investigating kidney disease-specific pregnancy outcomes.
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Nefritis Hereditaria , Complicaciones del Embarazo , Nacimiento Prematuro , Insuficiencia Renal Crónica , Femenino , Humanos , Embarazo , Recién Nacido , Lactante , Resultado del Embarazo/epidemiología , Nefritis Hereditaria/genética , Peso al Nacer , Estudios Retrospectivos , Nacimiento Prematuro/etiología , Complicaciones del Embarazo/epidemiología , Complicaciones del Embarazo/genética , Insuficiencia Renal Crónica/diagnóstico , Insuficiencia Renal Crónica/epidemiología , Insuficiencia Renal Crónica/genética , Proteinuria , ConsejoRESUMEN
Atypical hemolytic uremic syndrome (aHUS) is a subtype of thrombotic microangiopathy (TMA) characterized by a dysregulation of the alternative complement pathway. Here, we report a previously healthy 38-year-old woman in whom aHUS developed after a COVID-19 vaccine booster. One day after receipt of a booster dose of mRNA-1273 vaccine, she felt ill. Because of persistent headache, nausea, and general malaise, she went to her general practitioner, who referred her to the hospital after detecting hypertension and acute kidney injury. A diagnosis of TMA was made. Her treatment consisted of blood pressure control, hemodialysis, plasma exchange, and respiratory support. Kidney biopsy confirmed the diagnosis of acute TMA. The patient was referred for treatment with eculizumab, and kidney function improved after initiation of this therapy. Genetic analysis revealed a pathogenic C3 variant. SARS-CoV-2 infection as a trigger for complement activation and development of aHUS has been described previously. In addition, there is one reported case of aHUS occurring after receipt of the adenovirus-based COVID-19 vaccine ChAdOx1 nCoV-19, but, to our knowledge, this is the first case of aHUS occurring after a booster dose of an mRNA COVID-19 vaccine in a patient with an underlying pathogenic variant in complement C3. Given the time frame, we hypothesize that the vaccine probably was the trigger for development of aHUS in this patient.
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Síndrome Hemolítico Urémico Atípico , COVID-19 , Femenino , Humanos , Adulto , Síndrome Hemolítico Urémico Atípico/genética , Síndrome Hemolítico Urémico Atípico/diagnóstico , Vacunas contra la COVID-19/efectos adversos , Vacuna nCoV-2019 mRNA-1273 , ChAdOx1 nCoV-19 , COVID-19/prevención & control , SARS-CoV-2RESUMEN
BACKGROUND: Renal pathology in tuberous sclerosis complex (TSC) is characterized by the growth of angiomyolipoma and renal cysts, and in rare cases renal cell carcinoma. Other consequences of renal involvement in TSC, including hypertension, proteinuria, and hyperfiltration, are not well studied. We aimed to analyze the early manifestations of the renal TSC phenotype in a young TSC cohort and to explore common, modifiable risk factors. METHODS: In this retrospective cohort study, TSC patients attending the TSC clinics of two tertiary hospitals were included. Data on demographics, history, genotype, kidney function, hematuria, proteinuria, blood pressure, and renal imaging were collected. RESULTS: Eighty patients were included, with a median age of 0.8 years (0.0-63.0) at first presentation, and a median follow-up time of 10.2 (0.4-41.0) years. Mutation analysis was available in 64 patients (80%). Renal lesions (cysts or angiomyolipoma) were observed in 55/73 (75%). Thirty-two percent (19/60) were hypertensive, 8/51 (16%) had proteinuria, and 18/71 (25%) had hyperfiltration (median eGFR 154 ml/min/m2). Six (7.5%) patients had developed end stage renal disease at the last follow-up. No association was found between hyperfiltration, hypertension, or proteinuria and CKD ≥ 3. Cox regression showed a significant positive association between the presence of a renal intervention and CKD ≥ 3 (Hazard-Ratio 3.91, P < 0.05). CONCLUSIONS: Besides renal cysts and angiomyolipoma, the modifiable progression factors hypertension, proteinuria, and hyperfiltration occur frequently and early in TSC patients. This represents a preventive treatment target.
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Fallo Renal Crónico/epidemiología , Esclerosis Tuberosa/complicaciones , Adolescente , Adulto , Anciano , Angiomiolipoma/epidemiología , Angiomiolipoma/etiología , Angiomiolipoma/patología , Niño , Preescolar , Progresión de la Enfermedad , Femenino , Estudios de Seguimiento , Tasa de Filtración Glomerular , Humanos , Hipertensión/epidemiología , Hipertensión/etiología , Hipertensión/patología , Lactante , Recién Nacido , Riñón/patología , Enfermedades Renales Quísticas/epidemiología , Enfermedades Renales Quísticas/etiología , Enfermedades Renales Quísticas/patología , Fallo Renal Crónico/etiología , Fallo Renal Crónico/patología , Neoplasias Renales/epidemiología , Neoplasias Renales/etiología , Neoplasias Renales/patología , Masculino , Persona de Mediana Edad , Prevalencia , Proteinuria/epidemiología , Proteinuria/etiología , Proteinuria/patología , Estudios Retrospectivos , Factores de Riesgo , Adulto JovenRESUMEN
BACKGROUND: Cystinosis is a rare, inherited autosomal recessive disease caused by the accumulation of free cystine in lysosomes. It is treated by the administration of cysteamine, which should be monitored by trough white blood cell (WBC) cystine measurements to ensure effective treatment. CASE-DIAGNOSIS/TREATMENT: The index case had an older brother who had previously been diagnosed with cystinosis, allowing early diagnosis of the index case at the age of 5 months. Cysteamine therapy was started at the age of 3 years; however, monitoring of WBC cystine levels did not occur on a regular basis during most of his life. Growth retardation improved after correction of electrolyte disturbances, the initiation of cysteamine therapy and treatment with recombinant human growth hormone. Renal replacement therapy was started at the age of 11 years, and renal transplantation was performed at the age of 12 years. Extra-renal cystine accumulation caused multiple endocrinopathies (including adrenal insufficiency, hypothyroidism and primary hypogonadism), neurological symptoms, pancytopenia owing to splenomegaly and portal hypertension due to nodular regenerative hyperplasia, aggravated by splenic vein thrombosis and partial portal vein thrombosis. The patient died of diffuse intra-abdominal bleeding caused by severe portal hypertension. CONCLUSION: Cysteamine treatment should be started as early as possible, and dosage should be monitored and adapted based on trough WBC cystine levels. RELEVANT INTERNATIONAL GUIDELINE: Emma F et al. (2014) Nephropathic cystinosis: an international consensus document. Nephrol Dial Transplant 29:iv87-iv94.
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Cisteamina/administración & dosificación , Cistinosis/tratamiento farmacológico , Cistinosis/fisiopatología , Adolescente , Adulto , Niño , Preescolar , Cistinosis/complicaciones , Manejo de la Enfermedad , Resultado Fatal , Humanos , Lactante , Recién Nacido , Trasplante de Riñón , Masculino , Nefrología , Pediatría , Linaje , Insuficiencia Renal/etiología , Insuficiencia Renal/cirugía , Adulto JovenRESUMEN
Functional catheter problems are a major challenge for peritoneal dialysis (PD) programs. Here we performed a retrospective single-center study of 110 consecutive patients receiving a first PD catheter (swan neck double-cuff Missouri curled catheters, open surgical technique). Using postimplantation X-ray, the following categories were defined: swan neck angle (posterioanterio view (PA): under 45°, 45-90°, over 90°), inclination (angle between intramural part of catheter and horizontal line; lateral view: greater than/equal to 30°, under 30°), and the position of silicone bead relative to spine (PA view: L1-2, L3-4, lower) and catheter tip (PA view: hypogastric, umbilical, subcostal). Covariates included demographics, body size, previous abdominal surgery, and abdominal wall hernias. During a mean follow-up of 36 months, the time to first functional catheter problem was significantly associated with both the swan neck angle and inclination. The need for surgical intervention was significantly associated with inclination only. Technique failure was not associated with any parameter. In multivariate analysis, inclination was the sole variable significantly associated with functional catheter problems (hazard ratio 3.65 [1.98-6.72]) and the need for surgical intervention (hazard ratio 2.86 [1.19-6.88]). Thus, our study defines a set of X-ray variables that predict functional PD catheter problems and can be used for troubleshooting in individual cases as well as for education and internal audit purposes.
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Obstrucción del Catéter/etiología , Catéteres de Permanencia , Migración de Cuerpo Extraño/etiología , Diálisis Peritoneal/efectos adversos , Diálisis Peritoneal/instrumentación , Radiografía Abdominal , Adulto , Anciano , Bélgica , Diseño de Equipo , Femenino , Migración de Cuerpo Extraño/cirugía , Humanos , Estimación de Kaplan-Meier , Masculino , Auditoría Médica , Persona de Mediana Edad , Análisis Multivariante , Valor Predictivo de las Pruebas , Modelos de Riesgos Proporcionales , Estudios Retrospectivos , Factores de Riesgo , Factores de Tiempo , Resultado del TratamientoRESUMEN
BACKGROUND: Although renal transplantation (Tx) improves the outcome of patients with renal disease, cardiovascular (CV) risk remains high. Recently, it was demonstrated that asymmetric dimethylarginine (ADMA) levels predict CV events and graft survival in renal transplant recipients (RTRs). Little is known about the impact of renal Tx on the plasma levels of ADMA and symmetric dimethylarginine (SDMA). The present study aimed to define the time course of ADMA and SDMA after Tx. METHODS: We prospectively followed 167 incident RTRs with visits at the time of Tx and 3 and 12 months thereafter. At all visits, demographics and relevant biochemistry were recorded and blood was sampled for analysis of ADMA and SDMA (high-performance liquid chromatography). Eighty-four patients had an additional sampling in the immediate postoperative period. In a case-controlled substudy (n = 31), we compared ADMA and SDMA levels between RTRs and chronic kidney disease (CKD) patients, matched for glomerular filtration rate, gender, age, CV history and diabetes. RESULTS: Overall, plasma ADMA and SDMA levels decreased after Tx. The decline of SDMA was more pronounced and paralleled the recovery of renal function. Interestingly, the decline of ADMA was preceded by an increase in the immediate postoperative period. In the case-controlled substudy, SDMA levels were similar, whereas ADMA levels were significantly higher in RTRs compared with the CKD counterparts (P = 0.003). CONCLUSION: ADMA levels follow a biphasic pattern after successful renal Tx with a transient rise in the immediate postoperative period followed by a decline. Levels remain elevated compared with CKD patients, matched for age, gender, diabetes, CV history and renal function.
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Arginina/análogos & derivados , Biomarcadores/sangre , Trasplante de Riñón , Insuficiencia Renal Crónica/sangre , Adulto , Anciano , Arginina/sangre , Estudios de Casos y Controles , Cromatografía Líquida de Alta Presión , Femenino , Tasa de Filtración Glomerular , Humanos , Masculino , Persona de Mediana Edad , Complicaciones Posoperatorias , Estudios Prospectivos , Insuficiencia Renal Crónica/cirugía , Factores de Riesgo , Adulto JovenRESUMEN
BACKGROUND AND OBJECTIVE: Treatment of sickle cell disease (SCD) has traditionally focused on symptomatic and preventative care. Recent advances in novel therapeutic developments, likely to be orphan-designated, are anticipated to carry a substantial price tag. This study assesses the potential budget impact of adopting disease-modifying treatments, crizanlizumab and voxelotor, and pioneering CRISPR gene-edited therapy, CTX001, in the Belgian healthcare system. METHODS: The perspective of the Belgian healthcare payer (RIZIV-INAMI including patient copayments), a 5-year horizon with a 2-10% uptake of disease-modifying interventions, and a 2% uptake of CTX001 were considered. Data, encompassing target population, current (chronic and acute management, curative hematopoietic stem cell transplantation) and new (crizanlizumab, voxelotor, and CTX001) interventions, clinical effectiveness, adverse events, healthcare resource utilization, and associated costs, were gathered through a comprehensive literature review (first phase) and two Delphi panels involving hematologists (second phase). The cost difference between a "world with and without crizanlizumab, voxelotor, and CTX001" was calculated to obtain the budget impact. Three scenario analyses were conducted: a 5-13% and 4% uptake analysis, a 10-18% and 8% uptake analysis, respectively for disease-modifying treatments (crizanlizumab and voxelotor) and CTX001, and a 0% crizanlizumab uptake and managed entry agreements analysis . A ± 20% univariate sensitivity analysis was performed to test the robustness of the analysis. RESULTS: The total five-year cumulative budget impact was estimated at 30,024,968, with 91% attributed to drug acquisition costs. The largest budget impact share was for CTX001 (25,575,150), while crizanlizumab (2,301,095) and voxelotor (2,148,723) was relatively small. In scenarios one and three, a two-fold increase of the cumulative budget impact to 60,731,772 and a four-fold increase to 120,846,256 from the base case was observed. In scenario three, this budget impact decreased by 63% to 11,212,766. Patient population size, number of treated patients, and drug costs influenced the analysis the most, while discontinuation, acute crisis, and adverse event rates had comparatively minimal impact. CONCLUSIONS: Belgian decision-makers may consider alternative financing models, such as outcome-based risk-sharing agreements or annuities, to ensure sustainable coverage of these treatments. This study adheres to recommended practices for assessing budget impact of orphan drugs, distinguishing it from earlier studies with potentially weaker methodologies.
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UNLABELLED: Mycophenolate mofetil (MMF) decreases the risk of acute rejection and is associated with improved graft survival in renal transplant recipients. However, MMF-related side effects often necessitate dose reduction, which may expose patients to a higher risk of acute rejection and graft loss. This study's aim was to examine the reasons for MMF dose reduction during the first post-transplant year and its impact on acute rejection, overall and death-censored graft loss. METHODS: Single-center retrospective analysis of 749 renal transplant recipients treated with MMF in their initial maintenance immunosuppressive protocol. RESULTS: In 365 patients (48.7%) a total of 530 MMF dose reductions were done. Reasons for reduction were hematologic toxicity (46.5%), infection (16.1%), gastrointestinal side effects (12.3%), malignancy (2.1%), study protocol (14.6%), and unknown (13.5%). MMF dose reduction as such was not an independent predictor of acute rejection or graft survival, although reductions in ≥ 50% of initial dose were significantly associated with acute rejection. CONCLUSIONS: In this retrospective cohort, by far the most important reason for MMF dose reduction during the first post-transplantation year was hematologic. MMF dose reductions in ≥ 50% increased the risk of acute rejection but did not compromise graft survival.
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Supervivencia de Injerto , Inmunosupresores/administración & dosificación , Trasplante de Riñón , Ácido Micofenólico/análogos & derivados , Adulto , Anciano , Anemia/inducido químicamente , Femenino , Rechazo de Injerto , Humanos , Inmunosupresores/efectos adversos , Trasplante de Riñón/mortalidad , Leucopenia/inducido químicamente , Masculino , Persona de Mediana Edad , Ácido Micofenólico/administración & dosificación , Ácido Micofenólico/efectos adversos , Pancitopenia/inducido químicamente , Estudios Retrospectivos , Trombocitopenia/inducido químicamenteRESUMEN
Renal transplant recipients have an increased risk of cardiovascular (CV) disease. Arterial stiffness (AS) and aortic calcifications (ACs) are well-known CV risk factors in patients with chronic kidney disease. We aimed to determine the prognostic value of AS and AC in incident renal transplant recipients (RTRs). We conducted a prospective study in 253 single RTR. AC were scored by means of lumbar X-ray. Carotid-femoral pulse wave velocity (PWV) was assessed in a subgroup of 115 patients. AC were present in 61% of patients. After a mean follow-up of 36 months, 32 CV events occurred in the overall group and 13 events in the PWV subgroup. When we accounted for age, gender, and CV history, AC score (HR, hazard ratio 1.09 per 1 unit increase; 95% CI 1.02-1.17) and PWV (HR 1.45 per 1 m/s; 95% CI 1.16-1.8) remained an independent predictor of CV events in Cox-regression analyses. Using receiver operating characteristics, the area under the curve for predicting CV events amounted to 0.80 and 0.72 for sum AC and PWV, respectively. Both AS and AC are strong predictors of future CV events in an incident RTR population. These vascular assessments are readily available and easy to perform, making them ideal tools for further risk stratification. (ClinicalTrials.gov number: NCT00547040).
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Aorta/patología , Calcinosis/diagnóstico , Enfermedades Cardiovasculares/diagnóstico , Trasplante de Riñón/métodos , Rigidez Vascular , Adulto , Área Bajo la Curva , Enfermedades Cardiovasculares/complicaciones , Arterias Carótidas/patología , Femenino , Estudios de Seguimiento , Hemodinámica , Humanos , Masculino , Persona de Mediana Edad , Valor Predictivo de las Pruebas , Modelos de Riesgos Proporcionales , Estudios Prospectivos , Curva ROC , Insuficiencia Renal/complicaciones , Insuficiencia Renal/terapia , Factores de Riesgo , Resultado del TratamientoRESUMEN
BACKGROUND: The identification of complement defects as major drivers of primary atypical hemolytic uremic syndrome (HUS) has transformed the landscape of thrombotic microangiopathies (TMAs), leading to the development of targeted therapies and better patient outcomes. By contrast, little is known about the presentation, genetics, and outcomes of TMA associated with specific diseases or conditions, also referred to as secondary TMA. METHODS: In this study, we assessed the relative incidence, clinical and genetic spectra, and long-term outcomes of secondary TMA versus other TMAs in consecutive patients hospitalized with a first episode of TMA from 2009 to 2019 at two European reference centers. RESULTS: During the study period, 336 patients were hospitalized with a first episode of TMA. Etiologies included atypical HUS in 49 patients (15%), thrombotic thrombocytopenic purpura (TTP) in 29 (9%), shigatoxin-associated HUS in 70 (21%), and secondary TMA in 188 (56%). The main causes of secondary TMA were hematopoietic stem-cell transplantation ( n =56, 30%), solid-organ transplantation ( n =44, 23%), and malignant hypertension ( n =25, 13%). Rare variants in complement genes were identified in 32 of 49 patients (65%) with atypical HUS and eight of 64 patients (13%) with secondary TMA; pathogenic or likely pathogenic variants were found in 24 of 49 (49%) and two of 64 (3%) of them, respectively ( P < 0.001). After a median follow-up of 1157 days, death or kidney failure occurred in 14 (29%), eight (28%), five (7%), and 121 (64%) patients with atypical HUS, TTP, shigatoxin-associated HUS, and secondary TMA, respectively. Unadjusted and adjusted Cox regressions showed that patients with secondary TMA had the highest risk of death or kidney failure (unadjusted hazard ratio [HR], 3.35; 95% confidence interval [CI], 1.85 to 6.07; P < 0.001; adjusted HR, 4.11; 95% CI, 2.00 to 8.46; P < 0.001; considering atypical HUS as reference). CONCLUSIONS: Secondary TMAs represent the main cause of TMA and are independently associated with a high risk of death and progression to kidney failure.
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BACKGROUND/AIMS: Sudden death is the major cause of cardiac mortality in dialysis patients, accounting for approximately 60% of cardiovascular deaths. A prolonged QT interval and arterial calcification have been associated with increased cardiovascular morbidity and mortality in different patient populations including patients with chronic kidney disease (CKD). In the present study, we aimed to elucidate the association of vascular calcification with corrected QT interval duration in patients with end-stage renal disease. METHODS: We performed a single-center cross-sectional study in patients referred for renal transplantation. Patients taking QT-prolonging agents or with conduction abnormalities were excluded. Aortic calcifications were scored by means of lumbar X-rays. RESULTS: In the final analysis, 193 patients (118 men, 52 years old) were included. A prolonged QT interval was observed in 26% of the patients. Multivariate analysis showed an independent and direct association between corrected QT duration and the extent of aortic calcifications (p = 0.0004) independent of age, gender, cardiovascular history, electrolytes and parameters of mineral metabolism. CONCLUSIONS: A prolonged QT interval is prevalent in patients with CKD stage 5D. Aortic calcification is associated with a prolonged QT duration, independent of traditional determinants.
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Electrocardiografía/métodos , Trasplante de Riñón/efectos adversos , Calcificación Vascular/patología , Anciano , Aorta/patología , Estudios Transversales , Electrólitos , Femenino , Humanos , Fallo Renal Crónico/complicaciones , Fallo Renal Crónico/terapia , Masculino , Persona de Mediana Edad , Análisis Multivariante , Radioinmunoensayo/métodos , Factores Sexuales , Resultado del Tratamiento , Calcificación Vascular/complicacionesRESUMEN
Background In participants with concomitant chronic coronary disease and advanced chronic kidney disease (CKD), the effect of treatment strategies on the timing of dialysis initiation is not well characterized. Methods and Results In ISCHEMIA-CKD (International Study of Comparative Health Effectiveness With Medical and Invasive Approaches-Chronic Kidney Disease), 777 participants with advanced CKD and moderate or severe ischemia were randomized to either an initial invasive or conservative management strategy. Herein, we compare the proportion of randomized participants with non-dialysis-requiring CKD at baseline (n=362) who initiated dialysis and compare the time to dialysis initiation between invasive versus conservative management arms. Using multivariable Cox regression analysis, we also sought to identify the effect of invasive versus conservative chronic coronary disease management strategies on dialysis initiation. At a median follow-up of 23 months (25th-75th interquartile range, 14-32 months), dialysis was initiated in 18.9% of participants (36/190) in the invasive strategy and 16.9% of participants (29/172) in the conservative strategy (P=0.22). The median time to dialysis initiation was 6.0 months (interquartile range, 3.0-16.0 months) in the invasive group and 18.2 months (interquartile range, 12.2-25.0 months) in the conservative group (P=0.004), with no difference in procedural acute kidney injury rates between the groups (7.8% versus 5.4%; P=0.26). Baseline clinical factors associated with earlier dialysis initiation were lower baseline estimated glomerular filtration rate (hazard ratio [HR] associated with 5-unit decrease, 2.08 [95% CI, 1.72-2.56]; P<0.001), diabetes (HR, 2.30 [95% CI, 1.28-4.13]; P=0.005), hypertension (HR, 7.97 [95% CI, 1.09-58.21]; P=0.041), and Hispanic ethnicity (HR, 2.34 [95% CI, 1.22-4.47]; P=0.010). Conclusions In participants with non-dialysis-requiring CKD in ISCHEMIA-CKD, randomization to an invasive chronic coronary disease management strategy (relative to a conservative chronic coronary disease management strategy) is associated with an accelerated time to initiation of maintenance dialysis for kidney failure. Registration URL: https://www.clinicaltrials.gov; Unique identifier: NCT01985360.
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Enfermedad Coronaria , Cardiopatías , Insuficiencia Renal Crónica , Enfermedad Coronaria/complicaciones , Tasa de Filtración Glomerular , Cardiopatías/complicaciones , Humanos , Isquemia/complicaciones , Diálisis Renal/métodos , Insuficiencia Renal Crónica/complicaciones , Insuficiencia Renal Crónica/diagnóstico , Insuficiencia Renal Crónica/epidemiologíaAsunto(s)
Vesícula/etiología , Diálisis Peritoneal/efectos adversos , Síndrome Estafilocócico de la Piel Escaldada/diagnóstico , Anciano , Vesícula/microbiología , Vesícula/patología , Resultado Fatal , Humanos , Masculino , Choque Séptico/microbiología , Staphylococcus aureus/aislamiento & purificaciónRESUMEN
CONTEXT: Sclerostin, a Wnt antagonist produced by osteocytes, regulates osteoblast activity and is a well-established key player in bone turnover. Recent data indicate that the Wnt pathway may also be involved in vascular calcification. OBJECTIVE: The present study tests the hypothesis that serum sclerostin levels are associated with vascular calcification in patients with chronic kidney disease (CKD) not yet receiving dialysis. DESIGN, SETTING, PARTICIPANTS, AND MEASUREMENTS: We performed a cross-sectional analysis in 154 patients with CKD. Aortic calcification (AC) was assessed by lumbar X-ray and scored with a maximum score of 24. In addition to traditional and nontraditional cardiovascular (CV) risk factors, serum sclerostin levels were assessed (ELISA). Regression analysis was performed to identify determinants of serum sclerostin and AC. RESULTS: AC was present in 59% of patients. Older age (P < .0001), male sex (P = .006), lower estimated glomerular rate (eGFR) (P = .0008), lower bone-specific alkaline phosphatase (P = .03), and the absence of AC (P = .006) were identified as independent determinants of higher serum sclerostin levels. In univariate logistic regression, higher age, diabetes, CV history, higher body mass index, higher serum C-reactive protein and sclerostin levels and lower estimated glomerular rate were all associated with the presence of AC. In multivariate analysis, lower, not higher, sclerostin levels (P = .04, odds ratio [OR] per ng/mL of 0.24), higher age (P < .0001, OR per year of 1.17) and CV history (P = .02, OR for a positive CV history of 3.83) were identified as independent determinants of AC. CONCLUSIONS: In this cohort of patients with CKD, we found that patients with aortic calcifications (ACs) had higher sclerostin levels. However, in multivariate analysis, the association became inverse. Additional clinical and experimental studies are urgently required to clarify whether or not sclerostin protects against progression of vascular calcification.