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OBJECTIVES: To determine the ferritin inter-assay differences between three "Conformité Européenne" (CE) marked tests, the impact on reference intervals (RI), and the proportion of individuals with iron deficiency (ID), we used plasma and serum from healthy blood donors (HBD) recruited in three different Switzerland regions. DESIGN AND METHODS: Heparinized plasma and serum from HBD were obtained from three different transfusion centers in Switzerland (Fribourg, Geneva, and Neuchatel). One hundred forty samples were recruited per center and per matrix, with a gender ratio of 50%, for a total of 420 HBD samples available per matrix. On both matrices, ferritin concentrations were quantified by three different laboratories using electrochemiluminescence (ECL), latex immunoturbidimetric assay (LIA), and luminescent oxygen channeling immunoassay (LOCI) assays, respectively. The degree of agreement between matrices and between the three sites/methods was assessed by Passing-Bablok and we evaluated the proportion of individuals deemed to have ID per method. RESULTS: Overall, no difference between serum and heparinized plasma ferritin values was observed according to Passing-Bablok analyses (proportional bias range: 1.0-3.0%; maximum constant bias: 1.84 µg/L). Significant median ferritin differences (p < 0.001 according to Kruskal-Wallis test) were observed between the three methods (i.e., 83.6 µg/L, 103.5 µg/L, and 62.1 µg/L for ECL, LIA, and LOCI in heparinized plasma, respectively), with proportional bias varying significantly between ±16% and ±32% on serum and from ±14% to ±35% on plasma with no sign of gender-related differences. Affecting the lower end of RI, the proportion of ID per method substantially varied between 4.76% (20/420) for ECL, 2.86% (12/420) for LIA, and 9.05% (38/420) for LOCI. CONCLUSIONS: Serum and heparinized plasma are exchangeable for ferritin assessment. However, the order of magnitude of ferritin differences across methods and HBD recruitment sites could lead to diagnostic errors if uniform RI were considered. Challenging the recently proposed use of uniform ferritin thresholds, our results highlight the importance of method- and region-specific RI for ferritin due to insufficient inter-assay harmonization. Failing to do so significantly impacts ID diagnosis.
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Diabetic kidney disease (DKD) is the leading cause of end-stage renal disease. Glomerular hyperfiltration and albuminuria subject the proximal tubule (PT) to a subsequent elevation of workload, growth, and hypoxia. Hypoxia plays an ambiguous role in the development and progression of DKD and shall be clarified in our study. PT-von-Hippel-Lindau (Vhl)-deleted mouse model in combination with streptozotocin (STZ)-induced type I diabetes mellitus (DM) was phenotyped. In contrary to PT-Vhl-deleted STZ-induced type 1 DM mice, proteinuria and glomerular hyperfiltration occurred in diabetic control mice the latter due to higher nitric oxide synthase 1 and sodium and glucose transporter expression. PT Vhl deletion and DKD share common alterations in gene expression profiles, including glomerular and tubular morphology, and tubular transport and metabolism. Compared to diabetic control mice, the most significantly altered in PT Vhl-deleted STZ-induced type 1 DM mice were Ldc-1, regulating cellular oxygen consumption rate, and Zbtb16, inhibiting autophagy. Alignment of altered genes in heat maps uncovered that Vhl deletion prior to STZ-induced DM preconditioned the kidney against DKD. HIF-1α stabilization leading to histone modification and chromatin remodeling resets most genes altered upon DKD towards the control level. These data demonstrate that PT HIF-1α stabilization is a hallmark of early DKD and that targeting hypoxia prior to the onset of type 1 DM normalizes renal cell homeostasis and prevents DKD development.
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Diabetes Mellitus Experimental , Diabetes Mellitus Tipo 1 , Nefropatías Diabéticas , Animales , Ratones , Nefropatías Diabéticas/genética , Riñón , Túbulos Renales Proximales , Glomérulos Renales , Diabetes Mellitus Tipo 1/complicaciones , Diabetes Mellitus Tipo 1/genética , Diabetes Mellitus Experimental/complicaciones , Diabetes Mellitus Experimental/genéticaRESUMEN
Oral anticoagulants (antivitamin K, direct oral anticoagulants) are routinely prescribed for the prevention or treatment of thromboembolic events, and many patients are now on long-term anticoagulant therapy. However, this complicates the management of urgent surgical conditions or major bleeding. Various strategies have been developed to reverse the anticoagulant effect and this narrative review provides an overview of the wide range of therapies currently available.
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Anticoagulantes , Tromboembolia , Humanos , Anticoagulantes/uso terapéutico , Hemorragia/inducido químicamente , Hemorragia/prevención & control , Hemorragia/tratamiento farmacológico , Tromboembolia/prevención & control , Administración OralRESUMEN
BACKGROUND: Cardiology guidelines recommend measuring high-sensitivity cardiac troponin (hs-cTn) for the diagnostic work-up of acute coronary syndromes (ACS). Many hospitals measure hs-cTnT, but preliminary data have shown that hs-cTnT is higher than normal in many hemodialysis patients without evidence of ACS. The purpose of this study was therefore to determine the hs-cTnT levels every month for 1 year in asymptomatic hemodialysis patients, in order to assess their changes over time relative to creatine kinase. METHODS: Fourty-four hemodialysis patients (mean age 67 ± 14 years) were included. The predialysis levels of fifth-generation hs-cTnT, CK, and CK-MB were measured every month for 1 year using a Cobas® 6000 analyzer (Roche Diagnostics, Switzerland). RESULTS: Almost 100% of hs-cTnT measurements were higher than normal (N < 14 ng/L); the mean ± SD annual level was 84 ± 59 ng/L, ranging from a minimum of 24 ± 2 to 241 ± 28 ng/L in individual patients. The mean levels of CK and CK-MB were normal. Thirteen myocardial infarctions were analyzed, which were all associated with an initial elevation in hs-cTnT >45% from the individual baseline value. By comparison, CK and CK-MB only increased in 38% and 31% of these myocardial infarctions, respectively. DISCUSSION: hs-cTnT is persistently higher than normal in chronic hemodialysis patients. Standard algorithms for diagnosing ACS can obviously not be used and alternative diagnostic strategies need to be developed. According to our data, and given the huge variation in baseline hs-cTnT levels among patients, the use of higher cut-offs as proposed in the literature cannot be recommended. Instead, we consider that hs-cTnT should be checked at regular intervals (e.g., every 3-6 months) in order to establish individual baseline levels for hs-cTnT. This approach, in most instances, not only makes it possible to more rapidly rule-in but also to rapidly rule-out, cases of ACS in hemodialysis patients who develop cardiac symptoms.
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Creatina Quinasa , Troponina T , Anciano , Anciano de 80 o más Años , Biomarcadores , Humanos , Persona de Mediana Edad , Estudios Prospectivos , Diálisis RenalRESUMEN
BACKGROUND AND AIMS: This experimental study assesses the influence of different gases and insufflation pressures on the portal, central-venous and peripheral-arterial pH during experimental laparoscopy. METHODS: Firstly, 36 male WAG/Rij rats were randomized into six groups (n = 6) spontaneously breathing during anaesthesia: laparoscopy using carbon dioxide or helium at 6 and 12 mmHg, gasless laparoscopy and laparotomy. 45 and 90 min after setup, blood was sampled from the portal vein, vena cava and the common femoral artery with immediate blood gas analysis. Secondly, 12 animals were mechanically ventilated at physiological arterial pH during 90 min of laparotomy (n = 6) or carbon dioxide laparoscopy at 12 mmHg (n = 6) with respective blood gas analyses. RESULTS: Over time, in spontaneously breathing rats, carbon dioxide laparoscopy caused significant insufflation pressure-dependent portal acidosis (pH at 6 mmHg, 6.99 [6.95-7.04] at 45 min and 6.95 [6.94-6.96] at 90 min, pH at 12 mmHg, 6.89 [6.82-6.90] at 45 min and 6.84 [6.81-6.87] at 90 min; p < 0.05) compared to laparotomy (portal pH 7.29 [7.23-7.30] at 45 min and 7.29 [7.20-7.30] at 90 min; p > 0.05). Central-venous and peripheral-arterial acidosis was significant but less severely reduced during carbon dioxide laparoscopy. Laparotomy, helium laparoscopy and gasless laparoscopy showed no comparable acidosis in all vessels. Portal and central-venous acidosis during carbon dioxide laparoscopy at 12 mmHg was not reversible by mechanical hyperventilation maintaining a physiological arterial pH (pH portal 6.85 [6.84-6.90] (p = 0.004), central-venous 6.93 [6.90-6.99] (p = 0.004), peripheral-arterial 7.29 [7.29-7.31] (p = 0.220) at 90 min; Wilcoxon-Mann-Whitney test). CONCLUSION: Carbon dioxide laparoscopy led to insufflation pressure-dependent severe portal and less severe central-venous acidosis not reversible by mechanical hyperventilation.
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Acidosis , Insuflación , Laparoscopía , Acidosis/etiología , Animales , Dióxido de Carbono , Helio , Humanos , Hiperventilación , Insuflación/efectos adversos , Laparotomía/efectos adversos , Masculino , Neumoperitoneo Artificial/efectos adversos , Ratas , RoedoresRESUMEN
Background Since December 2019, an emerging outbreak of novel coronavirus disease 2019 (COVID-19) is caused by the severe acute respiratory syndrome-coronavirus-2 (SARS-CoV-2). The aim of the present report is to describe a population with elevated levels of high-sensitive cardiac troponin T (hs-cTnT) and report on their management during the pandemic of COVID-19. Methods In this retrospective cohort, we collected data from all patients with hs-cTnT levels of >50 ng/mL admitted to Fribourg Hospital between February 15, 2020, and April 15, 2020. The primary diagnosis for troponin elevation was recorded. Echocardiographic, electrocardiographic, and coronary angiographic data were analyzed for signs of myocardial ischemia, infarction, or other cardiomyopathies. In-hospital follow-up was performed for deaths from all causes and for cardiac deaths. Propensity score matching was used in a subgroup analysis to match COVID-19 and non-COVID-19 patients ( n = 21 per group). Results Overall, 215 patients with high hs-cTnT levels were enrolled. The median age was 75 [65-83] years and 30% were women. 21 patients (10%) were diagnosed with COVID-19. Of these, acute myocardial injury related to COVID-19 was the most commonly described cardiovascular manifestation during the pandemic peak. Median troponin values were not different between COVID-19 patients and non-COVID-19 patients (94 vs. 137, p = 0.14). The number of cardiological examinations was globally low (echocardiography 51% and coronary angiography 52%) in the context of the pandemic. Patients in the COVID-19 group underwent significantly less echocardiographic examinations (19 vs. 55%, p ≤ 0.01) and coronary angiographies (5 vs. 58%, p ≤ 0.01) than non-COVID-19 patients. Overall mortality in patient with COVID-19 and elevated troponins was very high, as 38% of patients died during hospitalization including 14% for cardiac death. This trend was confirmed in the propensity score-matched analysis. Conclusion Interpretation of troponins during the COVID-19 pandemic was complicated due to the low number of cardiovascular investigations in this context. Follow-up of patients with COVID-19 and cardiovascular events is important to assess their prognosis and to improve their care.
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BACKGROUND: Hemolytic blood samples are the number one cause for specimen rejection at emergency departments. Triggered by unsuitable blood sampling material or incorrect handling and a related strong vacuum force, hemolytic samples often must be retaken. The objective of this study was to assess whether correct manual aspiration using S-Monovette® could reduce the number of hemolytic samples. METHODS: Between January and April 2019, a head-to-head study was conducted. Whereas in the first eight weeks, all specimens were collected using Vacutainer®, in the second eight weeks, blood was taken using S-Monovette® in aspiration mode. Specimens were categorized into five classes (0-30, 31-50, 51-75, 76-100, and 101+ mg/dl of cell-free hemoglobin) and for the statistical analyses, all samples exceeding 30 mg/dl were classified as hemolytic. RESULTS: Data were collected on 4794 blood specimens (Vacutainer®: 2634 samples, S-Monovette®: 2160 samples). While the percentage of non-hemolytic samples (HI of 0-30 mg/dl) was substantially higher for specimens drawn by S-Monovette® (95.7 %) than Vacutainer® (83.0 %), the opposite was true for all HI categories above 30 mg/dl. Importantly, the reduction of hemolytic samples took place immediately following the imposition of S-Monovette® and remained stable at a low level until the end of the study. CONCLUSIONS: Based on our results, we conclude that switching to S-Monovette® in manual aspiration mode in the blood sampling process could be highly beneficial, not only from a financial point of view, but also with regards to reducing unnecessary tasks and stress for nursing staff and improving patient outcome overall.
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The NPHS2 gene, encoding the slit diaphragm protein podocin, accounts for genetic and sporadic forms of nephrotic syndrome (NS). Patients with NS often present symptoms of volume retention, such as oedema formation or hypertension. The primary dysregulation in sodium handling involves an inappropriate activation of the epithelial sodium channel, ENaC. Plasma proteases in a proteinuria-dependent fashion have been made responsible; however, referring to the timeline of symptoms occurring and underlying mechanisms, contradictory results have been published. Characterizing the mouse model of podocyte inactivation of NPHS2 (Nphs2∆pod ) with respect to volume handling and proteinuria revealed that sodium retention, hypertension and gross proteinuria appeared sequentially in a chronological order. Detailed analysis of Nphs2∆pod during early sodium retention, revealed increased expression of full-length ENaC subunits and αENaC cleavage product with concomitant increase in ENaC activity as tested by amiloride application, and augmented collecting duct Na+ /K+ -ATPase expression. Urinary proteolytic activity was increased and several proteases were identified by mass spectrometry including cathepsin B, which was found to process αENaC. Renal expression levels of precursor and active cathepsin B were increased and could be localized to glomeruli and intercalated cells. Inhibition of cathepsin B prevented hypertension. With the appearance of gross proteinuria, plasmin occurs in the urine and additional cleavage of γENaC is encountered. In conclusion, characterizing the volume handling of Nphs2∆pod revealed early sodium retention occurring independent to aberrantly filtered plasma proteases. As an underlying mechanism cathepsin B induced αENaC processing leading to augmented channel activity and hypertension was identified.
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Catepsina B/metabolismo , Canales Epiteliales de Sodio/metabolismo , Hipertensión/etiología , Hipertensión/metabolismo , Síndrome Nefrótico/complicaciones , Síndrome Nefrótico/metabolismo , Amilorida/farmacología , Animales , Catepsina B/antagonistas & inhibidores , Catepsina B/genética , Bloqueadores del Canal de Sodio Epitelial/farmacología , Glomeruloesclerosis Focal y Segmentaria/enzimología , Glomeruloesclerosis Focal y Segmentaria/genética , Glomeruloesclerosis Focal y Segmentaria/metabolismo , Glomeruloesclerosis Focal y Segmentaria/orina , Hipertensión/genética , Péptidos y Proteínas de Señalización Intracelular/genética , Péptidos y Proteínas de Señalización Intracelular/metabolismo , Túbulos Renales/citología , Túbulos Renales/metabolismo , Lisosomas/enzimología , Lisosomas/metabolismo , Proteínas de la Membrana/genética , Proteínas de la Membrana/metabolismo , Ratones , Ratones Transgénicos , Síndrome Nefrótico/genética , Proteinuria/metabolismo , Proteolisis , Sodio/metabolismoRESUMEN
BACKGROUND: Subclinical inflammation was shown to play a role in the context of cardiovascular disorder processes. American College of Cardiology/American Heart Association guidelines on cardiovascular risk assessment in specific clinical contexts recommend the use of C-reactive protein (CRP) measurement with high sensitive (hs)-CRP assays that meet the precision requirements for values <2 mg/L. Until now, only hs-CRP assays reached the required limit of quantification. However, new regular CRP assays allow measuring CRP down to 0.6 mg/L. METHODS: A multisite comparative study between hs-CRP and a new conventional CRP assay (Tina-quant) was performed to evaluate the possibility of using regular CRP assays for cardiovascular risk assessment. RESULTS: A satisfactory concordance was observed between regular CRP assays and the hs-CRP assay. Both assays met the analytical precision requirements at the different cutpoints tested (1.00, 2.00, and 3.00 mg/L). CONCLUSION: These results suggest that this new regular CRP assay can be used for cardiovascular risk assessment, which is expected to provide substantial operational and financial advantages when compared with hs-CRP assays.
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UNLABELLED: Coronary artery ligations to induce myocardial infarction (MI) in mice and rats are widely used in preclinical investigation. However, myocardial ischemic damage and subsequent infarct size are highly variable. The lack of standardization of the model impairs the probability of effective translation to the clinic. Cardiac Troponin I (cTnI) is a major clinically relevant biomarker. AIM: In the present study, we investigated the prognostic value of cTnI for early estimation of the infarct size. METHODS AND RESULTS: Infarcts of different sizes were induced in mice and rats by ligation, at a random site, of the coronary artery. Kinetics of the plasma levels of cTnI were measured. Heart function was evaluated by echocardiography, the percentage of infarcted left ventricle and infarct expansion index were assessed from histological section. We observed that plasma cTnI level peaked at 24 h in the infarcted rats and between 24 and 48 h in mice. Sham operated animals had a level of cTnI below 15 ng/mL. Infarct expansion index (EI) assessed 4 weeks after ligation showed a large variation coefficient of 63 and 71% in rats and mice respectively. We showed a significative correlation between cTnI level and the EI demonstrating its predictive value for myocardial injury in small animal models. CONCLUSION: we demonstrated the importance of cTnI plasma level as a major early marker to assist in the optimal and efficient management of MI in laboratory animals model. The presented results stress the need for comparable biomarkers in the animal model and clinical trials for improved translation.
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To evaluate the incidence of gestational diabetes mellitus (GDM), gestational glucose intolerance (GGI), and birth major complications, a population of 1042 pregnant women was screened after the end of the second trimester with a two-step screening method. Patients with a positive 50-g screening test (plasma glucose ≥ 7.8 mmol/l at 1 h) underwent a 3-h standard 100-g oral glucose tolerance test. Clinical records of patients and newborns were analysed and compared to normotolerant patients group. GDM was found in 4.8% and GGI in 2.6% of all screened women of this study population. The patient group with GDM significantly differed from control, with a higher proportion of Asiatic women (32.0% versus 2.9%, p = 0.001) and high prevalence of previous GDM (26.0% versus 0.0%, p < 0.001). Major neonatal complications occurred more frequently in the dysmetabolic groups compared to normotolerant group. Macrosomia was not noted in our population. Asiatic origin and previous GDM were strongly associated with an increased incidence of GDM in multivariate analysis. This study represents the first epidemiological evaluation of GDM/GGI in Switzerland, with a two-step screening method. Incidence of GDM and GGI as well as birth complications resulted significant in our country.
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Diabetes Gestacional/epidemiología , Enfermedades del Recién Nacido/epidemiología , Complicaciones del Trabajo de Parto/epidemiología , Diabetes Gestacional/diagnóstico , Estudios de Factibilidad , Femenino , Prueba de Tolerancia a la Glucosa , Humanos , Incidencia , Recién Nacido , Embarazo , Resultado del Embarazo/epidemiología , Diagnóstico Prenatal/métodos , Suiza/epidemiologíaRESUMEN
Insertion of central venous port (CVP) catheter in the cancer population is associated with increased incidence of venous thromboembolic events (VTE). However, trials have shown limited benefit of antithrombotic treatment to prevent catheter-related venous thrombosis. This prospective observational cohort study was designed to assess the incidence of VTE closely related to CVP implantation in patients with cancer and undergoing chemotherapy, and to identify a high risk subgroup of patients. Between February 2006 and December 2011, 1097 consecutive cancer patients with first CVP implantation were included. Catheter-related VTE were defined as deep venous thrombosis in the arm, with or without pulmonary embolism (PE), or isolated PE. The incidence of CVP-associated VTE was 5.9% (IC95 4.4-7.3%) at 3 months, and 11.3% (IC95 9.4-13.2%) at 12 months. The incidence of any VTE was 7.6% (IC95 6.0-9.3%) at 3 months, and 15.3% (IC95 13.1-17.6%) at 12 months. High Khorana risk score and lung cancer were significant predictors of 3 month VTE. In conclusion, this large cohort study of patients with first CVP catheter implantation confirms the high incidence of VTE associated with the CVP implantation and allow identifying high risk patients who may benefit from thromboprophylaxis.
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The aim of the present study was to evaluate the dose of postdialysis cholecalciferol needed to maintain the 25-hydroxyvitamin D [25(OH)D] levels in the optimal range of 75-150 nmol/L. Twenty-six patients who had low baseline 25(OH)D levels (mean 27.5 ± 14.9 nmol/L) were studied. The 25(OH)D levels were measured every 2 months for one year. During the first two months, all the patients received 2000 IU of cholecalciferol after each hemodialysis (=6000 IU/wk). Thereafter, the dose was individualized and adapted every 2 months by administering 1 to 6 cholecalciferol tablets (2000 IU each) per week (total weekly dose = 2000-12000 IU/wk). During cholecalciferol supplementation, the 25(OH)D concentrations rapidly increased from baseline to 140.1 ± 28.3 nmol/L at month 6 and 95.6 ± 20.9 nmol/L at month 12. At month twelve, 86% of the patients had 25(OH)D levels within the target range with a mean dose of 5917 ± 4106 IU/wk of cholecalciferol; however, the amount needed to maintain these levels varied widely from 0 (n = 2) to 12000 IU/wk (n = 5). In conclusion, postdialysis cholecalciferol prescription is quite effective in correcting vitamin D deficiency/insufficiency, but the amount of cholecalciferol needed to maintain the 25(OH)D levels within the optimal range over the long-term varies widely among patients and must be individualized.
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QUESTIONS UNDER STUDY: Diagnosis of acute kidney injury (AKI) relies on measurement of serum creatinine (SCr). SCr is a late marker of impaired renal function. Urinary Neutrophil Gelatinase-Associated Lipocalin (uNGAL) has given encouraging results for an early and sensitive detection of AKI. This cohort study was conducted (1) to assess the value of uNGAL as early marker of contrast-induced AKI (CI-AKI) in unselected patients undergoing percutaneous coronary procedure (PCP) and (2) to investigate whether uNGAL levels correlate with the volume of contrast medium (CM) used during the procedure. METHODS: We enrolled 244 consecutive adult patients undergoing PCP done with the low-osmolar CM Iomeprolum (median volume of CM 122 [88-168] ml per procedure). uNGAL was measured at its peak with a standardised clinical laboratory platform (ARCHITECT uNGAL assay, Abbott). RESULTS: Overall, the post-PCP uNGAL levels were extremely low in our cohort with a median value of 7.7 [4.0-14.5] ng/ml (N ≤132 ng/ml). Twenty-five (10%) patients developed CI-AKI according to the classical diagnostic criteria (≥25% or ≥44.2 µmol/l increase in SCr) and 8 (3.3%) patients according to the AKIN criteria. Regardless of the definition considered, uNGAL levels did not significantly differ in patients with or without CI-AKI. Similarly, we found no significant correlation between the volume of CM used and the post-PCP uNGAL levels (r = -0.11). CONCLUSIONS: In a large cohort of unselected adult patients, uNGAL measured four to six hours after PCP was ineffective to predict the risk of CI-AKI and did not correlate with the volume of CM used during the procedure.
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Lesión Renal Aguda/orina , Proteínas de Fase Aguda/orina , Medios de Contraste/efectos adversos , Yopamidol/análogos & derivados , Lipocalinas/orina , Proteínas Proto-Oncogénicas/orina , Lesión Renal Aguda/sangre , Lesión Renal Aguda/inducido químicamente , Anciano , Biomarcadores/orina , Estudios de Cohortes , Angiografía Coronaria/efectos adversos , Creatinina/sangre , Relación Dosis-Respuesta a Droga , Diagnóstico Precoz , Femenino , Humanos , Yopamidol/efectos adversos , Lipocalina 2 , Masculino , Persona de Mediana EdadRESUMEN
BACKGROUND: The prevalence and significance of higher than normal cardiac troponin I (cTnI) levels in asymptomatic chronic hemodialysis (HD) patients remains a source of discussion. The aim of the present study was to evaluate the prevalence of higher than normal cTnI levels in asymptomatic HD patients, as determined by the last generation of immunoassay, and to perform further cardiological investigations in those patients with persistently elevated cTnI levels. METHODS: All chronic HD patients in our center who had exhibited no symptoms of coronary artery disease (CAD) during the previous four weeks were screened. cTnI levels were determined before dialysis in all patients using the last generation AccuTnI assay (UniCel DxI 800, Beckman Coulter). The cTnI levels of those patients with elevated cTnI at the screening evaluation were then measured monthly for six months. We were thus able to identify a group of patients with persistently elevated cTnI levels (> 3 consecutive months) who subsequently underwent cardiac echography and dipyridamole-exercise (D-E) thallium testing. If stress myocardial ischemia was detected, a coronary angiography was then performed. RESULTS: Fifty patients (32 males) were included: mean age 62.8 +/- 13.6 years, 20 (40%) with a history of CAD, and 21 (42%) diabetic. At the initial screening, the mean cTnI concentration was 0.05 +/- 0.06 microg/L and the cTnI levels were higher than normal (> 0.09 microg/L) in six patients (12%). In the follow-up, the cTnI normalized immediately in two patients but remained persistently elevated (range, 0.10-0.48 microg/L) in four (8%). These four patients (all males, one diabetic) had a mean age of 70.2 +/- 6.6 years, and all had heart failure with a history of severe CAD with previous myocardial infarction (n = 4), coronary stenting (n = 3), and/or bypass (n = 2). D-E thallium imaging showed reversible myocardial ischemia in all. The stress ischemia involved one to four cardiac segments and was slight to moderate in three patients and severe in the diabetic patient. A coronary angiogram was performed in all patients, and showed lesions of variable severity: severe three-vessel CAD with severe systolic dysfunction in two patients (including the diabetic), and non-critical/peripheral coronary stenosis in the other two. CONCLUSIONS: Among the asymptomatic HD patients in our center, we identified four (8%) with persistently elevated cTnI levels, as determined using the last generation AccuTnI assay. All of them had a history of severe CAD with heart failure and exhibited reversible myocardial ischemia upon D-E thallium imaging; coronary angiography revealed coronary lesions of variable severity. Overall, our data indicate that persistent low-grade cTnI elevation occurs in HD patients having longstanding severe cardiac disease, but, from our data, it is difficult to reach a conclusion as to the best clinical approach for this group of patients.
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Enfermedad de la Arteria Coronaria/diagnóstico , Fallo Renal Crónico/terapia , Diálisis Renal/métodos , Troponina I/análisis , Troponina T/análisis , Distribución por Edad , Anciano , Biomarcadores/análisis , Estudios de Cohortes , Angiografía Coronaria , Enfermedad de la Arteria Coronaria/epidemiología , Enfermedad de la Arteria Coronaria/etiología , Ecocardiografía Doppler , Femenino , Estudios de Seguimiento , Humanos , Incidencia , Fallo Renal Crónico/complicaciones , Fallo Renal Crónico/diagnóstico , Pruebas de Función Renal , Cuidados a Largo Plazo , Masculino , Tamizaje Masivo , Persona de Mediana Edad , Valores de Referencia , Diálisis Renal/efectos adversos , Medición de Riesgo , Sensibilidad y Especificidad , Índice de Severidad de la Enfermedad , Distribución por SexoRESUMEN
Previous studies reported cardiac troponin I (cTnI) and T (cTnT) levels to be higher than normal in a significant proportion of asymptomatic chronic hemodialysis (HD) patients without evidence of acute myocardial injury. We have therefore evaluated in such patients the accuracy of cTnI and cTnT determinations measured with last generation assays. Fifty chronic HD patients (34 males) without symptoms of acute myocardial ischemia were studied. Their mean age (+/-SD) was 64.4+/-12.7 years, 22 patients (44%) had an history of cardiac ischemic disease and 19 (38%) were diabetics. Serum cardiac markers were measured with last generation assays before and after a single HD session and in a control group including 30 hospitalized patients without renal failure. The cTnI were determined with Dimension RxL "Improved method" assay (Dade Behring), the cTnT with Elecys "Third generation" assay (Roche Diagnostics) and the creatine kinase (CK) with Integra (Roche Diagnostics). The cTnI were also simultaneously determined with the assay previously used at our institution (Dimension RxL, Dade Behring), indicated as old-method-cTnI. With the last generation assay only 1 patient (2%) had elevated cTnI (>0.1 microg/l) in the study group compared to none in the control group (P=NS). Instead, with the old-method-cTnI assay 11 patients (22%) had elevated (>0.3 microg/l) predialysis cTnI levels (P<0.01 compared to the "Improved method" assay). The predialysis cTnT levels were higher than normal (>0.1 microg/l) in 23 patients (46%), compared to none in the control group (P<0.01). The CK levels were elevated (>170 IU/L) in 4 dialysis patients (8%) compared to one (3,3%) in the control group (P=NS). The cTnT levels slightly but non-significantly diminished during dialysis (from 0.102+/-0.070 to 0.085+/-0.067 mug/l, P=NS), while in the same time no changes were observed for cTnI and CK levels. In conclusion, the specificity of cTnI determinations in HD patients is greatly improved by the last generation assay (from 78 to 98%), and is actually similar to that observed in a population with normal renal function. Therefore cTnI, determined with the last generation assay used in the present study, can be reliably used for the diagnosis of acute coronary syndromes in HD patients. Instead, cTnT levels remain higher than normal in a significant proportion of asymptomatic HD patients (46%) and the reasons for this fact need further investigations.