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Aims: Hypertriglyceridaemia (hTG) is associated with atherosclerotic cardiovascular disease, pancreatitis, and non-alcoholic fatty liver disease (NAFLD) in large population-based studies. The understanding of the impact of hereditary hTG and cardiometabolic disease status on the development of hTG and its associated cardiometabolic outcomes is more limited. We aimed to establish a multigenerational cohort to enable studies of the relationship between hTG, cardiometabolic disease and hereditary factors. Methods and results: The population-based observational Stockholm hyperTRIglyceridaemia REGister (STRIREG) study includes 1 460 184 index individuals who have measured plasma triglycerides in the clinical routine in Region Stockholm, Sweden, between 1 January 2000 and 31 December 2021. The laboratory measurements also included basic haematology, blood lipid panel, liver function tests, and HbA1c. Using the Swedish Multi-Generation register, 2 147 635 parents and siblings to the indexes were identified to form the complete study cohort. Laboratory data from participants were combined with data from several national registers that provided information on the cause of death, medical diagnoses, dispensed medicines, and socioeconomic factors including country of birth, education level, and marital status. Conclusion: The multi-generational longitudinal STRIREG cohort provides a unique opportunity to investigate different aspects of hTG as well as heredity for other metabolic diseases. Important outcome measures include mortality, cardiovascular mortality, major cardiovascular events, development of incident diabetes, and NAFLD. The STRIREG study will provide a deeper understanding of the impact of hereditary factors and associated cardiometabolic complications.
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BACKGROUND: A new cystatin C based European Kidney Function Consortium (EKFCCysC) equation was recently developed for adults, using the same mathematical form as the previously published full age spectrum creatinine based EKFC-equation (EKFCCrea). In the present study the cystatin C based EKFC-equation is extended to children, by defining the appropriate cystatin C rescaling factor QCysC. METHODS: Rescaling factor QCysC for cystatin C was defined as: a) 0.83 mg/L, exactly as it was defined for young adults in the adult equation, and b) a more complex QCysC-age relationship based on 4th degree cystatin C-age polynomials after evaluation of data from Uppsala, Stockholm and Canada and aggregated data from Germany. The EKFCCysC equation was then validated in an independent dataset in European children (n = 2,293) with measured GFR, creatinine, cystatin C, age, height and sex available. RESULTS: The EKFCCysC with the simple QCysC-value of 0.83 had a bias of -7.6 [95%CI -8.4;-6.5] mL/min/1.73 m2 and a P30-value of 85.8% [95%CI 84.4;87.3] equal to the EKFCCysC with the more complex 4th degree QCysC-value. The arithmetic mean of the EKFCCrea and EKFCCysC with the simple QCysC of 0.83 had a bias of -4.0 [95%CI -4.5;-3.1] mL/min/1.73 m2 and P30 of 90.4% [95%CI 89.2;91.6] similar to using the more complex 4th degree QCysC-polynomial. CONCLUSION: Using exactly the same QCysC of 0.83 mg/L, the adult EKFCCysC can easily be extended to children, with some bias but acceptable P30-values. The arithmetic mean of EKFCCrea and EKFCCysC results in bias closer to zero and P30 slightly over 90%.
Subject(s)
Algorithms , Cystatin C , Kidney , Child , Humans , Young Adult , Creatinine , Cystatin C/analysis , Europe , Glomerular Filtration Rate , Renal Insufficiency, Chronic , Kidney/chemistry , Kidney/physiologyABSTRACT
BACKGROUND: The accuracy of estimation of kidney function with the use of routine metabolic tests, such as measurement of the serum creatinine level, has been controversial. The European Kidney Function Consortium (EKFC) developed a creatinine-based equation (EKFC eGFRcr) to estimate the glomerular filtration rate (GFR) with a rescaled serum creatinine level (i.e., the serum creatinine level is divided by the median serum creatinine level among healthy persons to control for variation related to differences in age, sex, or race). Whether a cystatin C-based EKFC equation would increase the accuracy of estimated GFR is unknown. METHODS: We used data from patients in Sweden to estimate the rescaling factor for the cystatin C level in adults. We then replaced rescaled serum creatinine in the EKFC eGFRcr equation with rescaled cystatin C, and we validated the resulting EKFC eGFRcys equation in cohorts of White patients and Black patients in Europe, the United States, and Africa, according to measured GFR, levels of serum creatinine and cystatin C, age, and sex. RESULTS: On the basis of data from 227,643 patients in Sweden, the rescaling factor for cystatin C was estimated at 0.83 for men and women younger than 50 years of age and 0.83 + 0.005 × (age - 50) for those 50 years of age or older. The EKFC eGFRcys equation was unbiased, had accuracy that was similar to that of the EKFC eGFRcr equation in both White patients and Black patients (11,231 patients from Europe, 1093 from the United States, and 508 from Africa), and was more accurate than the Chronic Kidney Disease Epidemiology Collaboration eGFRcys equation recommended by Kidney Disease: Improving Global Outcomes. The arithmetic mean of EKFC eGFRcr and EKFC eGFRcys further improved the accuracy of estimated GFR over estimates from either biomarker equation alone. CONCLUSIONS: The EKFC eGFRcys equation had the same mathematical form as the EKFC eGFRcr equation, but it had a scaling factor for cystatin C that did not differ according to race or sex. In cohorts from Europe, the United States, and Africa, this equation improved the accuracy of GFR assessment over that of commonly used equations. (Funded by the Swedish Research Council.).
Subject(s)
Black People , Cystatin C , Glomerular Filtration Rate , Renal Insufficiency, Chronic , White People , Adult , Female , Humans , Infant , Male , Middle Aged , Africa/epidemiology , Biomarkers/blood , Black People/statistics & numerical data , Creatinine/blood , Cystatin C/blood , Europe/epidemiology , Glomerular Filtration Rate/physiology , Race Factors , Renal Insufficiency, Chronic/blood , Renal Insufficiency, Chronic/epidemiology , Renal Insufficiency, Chronic/ethnology , Sex Factors , Sweden/epidemiology , United States/epidemiology , White People/statistics & numerical data , Reproducibility of ResultsABSTRACT
BACKGROUND: A new Chronic Kidney Disease Epidemiology Collaboration equation without the race variable has been recently proposed (CKD-EPIAS). This equation has neither been validated outside USA nor compared with the new European Kidney Function Consortium (EKFC) and Lund-Malmö Revised (LMREV) equations, developed in European cohorts. METHODS: Standardized creatinine and measured glomerular filtration rate (GFR) from the European EKFC cohorts (n = 13 856 including 6031 individuals in the external validation cohort), from France (n = 4429, including 964 Black Europeans), from Brazil (n = 100) and from Africa (n = 508) were used to test the performances of the equations. A matched analysis between White Europeans and Black Africans or Black Europeans was performed. RESULTS: In White Europeans (n = 9496), both the EKFC and LMREV equations outperformed CKD-EPIAS (bias of -0.6 and -3.2, respectively versus 5.0 mL/min/1.73 m², and accuracy within 30% of 86.9 and 87.4, respectively, versus 80.9%). In Black Europeans and Black Africans, the best performance was observed with the EKFC equation using a specific Q-value (= concentration of serum creatinine in healthy males and females). These results were confirmed in matched analyses, which showed that serum creatinine concentrations were different in White Europeans, Black Europeans and Black Africans for the same measured GFR, age, sex and body mass index. Creatinine differences were more relevant in males. CONCLUSION: In a European and African cohort, the performances of CKD-EPIAS remain suboptimal. The EKFC equation, using usual or dedicated population-specific Q-values, presents the best performance in the whole age range in the European and African populations included in this study.
Subject(s)
Renal Insufficiency, Chronic , Female , Humans , Male , Africa , Brazil , Creatinine , Europe , Glomerular Filtration Rate , Renal Insufficiency, Chronic/epidemiology , White People , Black PeopleABSTRACT
Background: Differences in the performance of estimated glomerular filtration rate (eGFR) equations have been attributed to the mathematical form of the equations and to differences between patient demographics and measurement methods. We evaluated differences in serum creatinine (SCr) and eGFR in cohorts matched for age, sex, body mass index (BMI) and measured GFR (mGFR). Methods: White North Americans from Minnesota (n = 1093) and the Chronic Renal Insufficiency Cohort (CRIC) (n = 1548) and White subjects from the European Kidney Function Consortium (EKFC) cohort (n = 7727) were matched for demographic patient characteristics (sex, age ± 3 years, BMI ± 2.5 kg/m2) and renal function (mGFR ± 3 ml/min/1.73 m2). SCr was measured with isotope dilution mass spectrometry (IDMS)-traceable assays in the Minnesota and EKFC cohorts and with non-standardized SCr assays recalculated to IDMS in the CRIC. The Minnesota cohort and CRIC shared a common method to measure GFR (renal clearance of iothalamate), while the EKFC cohort used a variety of exogenous markers and methods, all with recognized sufficient accuracy. We compared the SCr levels and eGFR predictions [for Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) and EKFC equations] of patients fulfilling these matching criteria. Results: For 305 matched individuals, mean SCr (mg/dL) was not different between the Minnesota and EKFC cohorts (females 0.83 ± 0.20 versus 0.86 ± 0.23, males 1.06 ± 0.23 versus 1.12 ± 0.37; P > .05) but significantly different from the CRIC [females 1.13 ± 0.23 (P < .0001), males 1.42 ± 0.31 (P < .0001)]. The CKD-EPI equations performed better than the EKFC equation in the CRIC, while the opposite was true in the Minnesota and EKFC cohorts. Conclusion: Significant differences in SCr concentrations between the Minnesota and EKFC cohorts versus CRIC were observed in subjects with the same level of mGFR and equal demographic characteristics and can be explained by the difference in SCr calibration.
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Familial hypercholesterolemia (FH) is an autosomal dominant hereditary dyslipidemia that leads to high plasma cholesterol levels and a severely increased risk for premature cardiovascular disease. Early primary prevention with lipid lowering drugs can markedly reduce this risk. FH is underdiagnosed in Sweden. With a prevalence of 1:311, approximately 33 000 individuals in Sweden are expected to have FH but only a small percentage have been diagnosed up until now. We developed a digiphysical cascade screening model to diagnose FH in relatives of an index case with a confirmed pathogenic mutation in a FH disease gene. It has the potential to provide high-throughput and effective screening and the work model is now part of the clinical routine care at Karolinska University Hospital.
Subject(s)
Hyperlipoproteinemia Type II , Genetic Testing , Humans , Hyperlipoproteinemia Type II/diagnosis , Hyperlipoproteinemia Type II/genetics , Mass Screening , Mutation , SwedenSubject(s)
Renal Insufficiency, Chronic , Child , Young Adult , Humans , Glomerular Filtration Rate , Kidney Function Tests , Cohort Studies , CreatinineABSTRACT
BACKGROUND AND AIMS: Lipoprotein(a) [Lp(a)] is a causal cardiovascular risk factor recommended to be measured at least once in a lifetime. We aimed to establish the association between routinely measured Lp(a) levels and the development of incident calcified aortic valve stenosis (CAVS). METHODS: This retrospective registry based observational study includes all individuals who had their Lp(a) measured in clinical routine between 2003 and 2017 at Karolinska University Laboratory, Stockholm. Data on pre-existing medical conditions, pharmacological treatment and outcomes were retrieved from national patient registries. RESULTS: The study comprised 23,298 individuals of which 489 received a CAVS diagnosis during the study period. The CAVS group (71 ± 11 years, 62% males) had a larger cardiovascular burden than the group without CAVS (55 ± 17 years and 48% males). Individuals with CAVS had higher Lp(a) 90th percentile (117 mg/dL or 249 nmol/L) than those without (89 mg/dL or 179 nmol/L) (p < 0.001), a difference seen in both sexes. The incident rates of CAVS per 10,000 person-years was 22.3 for individuals at >90th Lp(a) percentile compared to 12.8 for the 0th - 50th percentiles (p < 0.001). Sex and age adjusted hazard ratios for development of incident CAVS was 1.53 (95% CI 1.08-2.15; p = 0.016) and for surgical or endovascular intervention for CAVS 1.42 (95% CI 0.73-2.79; p = 0.304) for individuals at Lp(a) > 90th percentile compared to the 0th - 50th percentile. CONCLUSIONS: Lp(a) measured in the clinical routine is higher in individuals with CAVS. An Lp(a) level above >90th percentile is associated with the development of incident CAVS during a 14-year observational period.
Subject(s)
Aortic Valve Stenosis , Lipoprotein(a) , Adult , Aged , Aged, 80 and over , Aortic Valve/pathology , Aortic Valve Stenosis/diagnosis , Aortic Valve Stenosis/epidemiology , Aortic Valve Stenosis/etiology , Calcinosis , Constriction, Pathologic , Female , Humans , Male , Middle Aged , Retrospective Studies , Risk FactorsABSTRACT
AIMS: To investigate plasma lipoprotein(a) [Lp(a)] levels measured in routine clinical care and their association with mortality and cardiovascular disease. METHODS AND RESULTS: This retrospective registry-based observational cohort study includes all individuals with plasma Lp(a) results measured at the Karolinska University Laboratory 2003-17. Outcome data were captured in national outcome registries. Levels of Lp(a) expressed in mass or molar units were examined separately. In adjusted Cox regression models, association between deciles of plasma Lp(a) concentrations, mortality, and cardiovascular outcomes were assessed. A total of 23 398 individuals [52% females, mean (standard deviation) age 55.5 (17.2) years, median Lp(a) levels 17 mg/dL or 19.5 nmol/L] were included. Individuals with an Lp(a) level >90th decile (>90 mg/dL or >180 nmol/L) had hazard ratios (95% confidence interval) of 1.25 (1.05-1.50) for major adverse cardiovascular events (P = 0.013), 1.37 (1.14-1.64) for atherosclerotic cardiovascular disease (P = 0.001), and 1.62 (1.28-2.05) for coronary artery disease (P ≤ 0.001), compared to individuals with Lp(a) ≤50th decile. No association between Lp(a) and mortality, peripheral artery disease, or ischaemic stroke was observed. CONCLUSION: High Lp(a) levels are associated with adverse cardiovascular disease outcomes also in individuals with Lp(a) measured in routine clinical care. This supports the 2019 ESC/EAS recommendation to measure Lp(a) at least once during lifetime to assess cardiovascular risk and implies the need for intensive preventive therapy in patients with elevated Lp(a).
Subject(s)
Atherosclerosis , Cardiovascular Diseases , Lipoprotein(a)/blood , Adult , Aged , Atherosclerosis/diagnosis , Atherosclerosis/epidemiology , Biomarkers , Brain Ischemia/epidemiology , Cardiovascular Diseases/diagnosis , Cardiovascular Diseases/epidemiology , Female , Follow-Up Studies , Humans , Male , Middle Aged , Retrospective Studies , Risk Factors , Stroke/epidemiologyABSTRACT
AIM: The Cockcroft-Gault (CG) creatinine-based equation is still used to estimate glomerular filtration rate (eGFR) for drug dosage adjustment. Incorrect eGFR may lead to hazardous over- or underdosing. METHODS: In a cross-sectional analysis, CG was validated against measured GFR (mGFR) in 14 804 participants and compared with the Modification-of-Diet-in-Renal-Diseases (MDRD), Chronic-Kidney-Disease-Epidemiology (CKD-EPI), Lund-Malmö-Revised (LMR) and European-Kidney-Function-Consortium (EKFC) equations. Validation focused on bias, imprecision and accuracy (percentage of estimates within ±30% of mGFR, P30), overall and stratified for mGFR, age and body mass index at mGFR <60 mL/min, as well as classification in mGFR stages. RESULTS: The CG equation performed worse than the other equations, overall and in mGFR, age and BMI subgroups in terms of bias (systematic overestimation), imprecision and accuracy except for patients ≥65 years where bias and P30 were similar to MDRD and CKD-EPI, but worse than LMR and EKFC. In subjects with mGFR <60 mL/min and at BMI 18.5-25 kg/m2 , all equations performed similarly, and for BMI < 18.5 kg/m2 CG and LMR had the best results though all equations had poor P30-accuracy. At BMI ≥ 25 kg/m2 the bias of the CG increased with increasing BMI (+17.2 mL/min at BMI ≥ 40 kg/m2 ). The four more recent equations also classified mGFR stages better than CG. CONCLUSIONS: The CG equation showed poor ability to estimate GFR overall and in analyses stratified for mGFR, age and BMI. CG was inferior to correctly classify the patients in the mGFR staging compared to more recent creatinine-based equations.
Subject(s)
Renal Insufficiency, Chronic , Body Mass Index , Creatinine , Cross-Sectional Studies , Glomerular Filtration Rate , HumansABSTRACT
Age-adjustment of creatinine, i.e. recalculation of childhood levels of creatinine to corresponding levels at 18 years of age and applied in the adult revised Lund-Malmö GFR equation led to markedly improved accuracy in Swedish children (n=1 718) at measured GFR <75 mL/min/1.73 m2 (n=318) and preserved high accuracy at ≥75 mL/min/1.73 m2 (n=1 400). The adjusted LMR equation performed as well as dedicated paediatric equations based on height. The proposed adjustment strategy has four strengths: (i) the original coefficients of the adult GFR equation can be used, (ii) the same equation can be used across the entire lifespan without artificial changes in estimated GFR when switching from paediatric to adult care, (iii) the lack of height factor makes it easier to automatically report estimated GFR by the laboratories and (iv) age-adjusted creatinine values imply that well-established creatinine reference intervals for adults can also be used for children.
Subject(s)
Laboratories , Transition to Adult Care , Adult , Child , Creatinine , Glomerular Filtration Rate , Humans , SwedenABSTRACT
BACKGROUND: Nephrotic syndrome causes severe hypercholesterolaemia due to increased production and altered clearance of lipoproteins from the liver. It is challenging for patients with nephrotic syndrome and coronary heart disease to meet LDL-cholesterol (LDL-C) goals for secondary prevention with conventional lipid-lowering therapy. CASE SUMMARY: We present a man with nephrotic syndrome caused by focal segmental glomerular sclerosis (FSGS) and hypercholesterolaemia. He presented at the emergency room (ER) with an ST-elevation myocardial infarction at the age of 26. On follow-up, the patient had persistent hypercholesterolaemia [LDL-C 3.9 mmol/L and lipoprotein(a) 308 nmol/L] despite a combination of lipid-lowering therapy with atorvastatin 80 mg/day and ezetimibe 10 mg/day. Addition of the proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitory antibody evolocumab 140 mg bi-monthly did not improve cholesterol levels. However, after addition of the sodium-glucose cotransporter 2 (SGLT2) inhibitor empagliflozin 10 mg/day on top of other anti-proteinuric treatments, the patient's proteinuria was reduced and a dramatic drop in LDL-C level by 3.2-0.6 mmol/L (-81%) was observed when evolocumab was re-introduced. DISCUSSION: We show that target LDL-C levels were obtained in this patient with therapy-resistant FSGS and hypercholesterolaemia following multi-pharmacological treatment with SGLT2 and PCSK9 inhibitors on top of conventional lipid-lowering therapy. The SGLT2-inhibitor reduced proteinuria and, speculatively, also reduced urinary loss of PCSK9-antibody. Therefore, in patients with nephrotic syndrome and cardiovascular disease novel therapeutic options to manage proteinuria could be considered to improve the efficacy of the lipid-lowering therapy, especially when the protein-based PCSK9 inhibitors are used.
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BACKGROUND: The Chronic Kidney Disease in Children Study (CKiD) equation for children and the Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) equation for adults are recommended serum creatinine (SCr)-based calculations for estimating glomerular filtration rate (GFR). However, these equations, as well as their combination, have limitations, notably the problem of implausible changes in GFR during the transition from adolescence to adulthood and overestimation of GFR in young adults. The full age spectrum (FAS) equation addresses these issues but overestimates GFR when SCr levels are low. OBJECTIVE: To develop and validate a modified FAS SCr-based equation combining design features of the FAS and CKD-EPI equations. DESIGN: Cross-sectional analysis with separate pooled data sets for development and validation. SETTING: Research and clinical studies (n = 13) with measured GFR available. PATIENTS: 11 251 participants in 7 studies (development and internal validation data sets) and 8378 participants in 6 studies (external validation data set). MEASUREMENTS: Clearance of an exogenous marker (reference method), SCr level, age, sex, and height were used to develop a new equation to estimate GFR. RESULTS: The new European Kidney Function Consortium (EKFC) equation is a FAS equation with low bias (-1.2 mL/min/1.73 m2 [95% CI, -2.7 to 0.0 mL/min/1.73 m2] in children and -0.9 mL/min/1.73 m2 [CI, -1.2 to -0.5 mL/min/1.73 m2] in adults) across the FAS (2 to 90 years) and SCr range (40 to 490 µmol/L [0.45 to 5.54 mg/dL]) and with fewer estimation errors exceeding 30% (6.5% [CI, 3.8% to 9.1%] in children and 3.1% [CI, 2.5% to 3.6%] in adults) compared with the CKiD and CKD-EPI equations. LIMITATION: No Black patients were included. CONCLUSION: The new EKFC equation shows improved accuracy and precision compared with commonly used equations for estimating GFR from SCr levels. PRIMARY FUNDING SOURCE: Swedish Research Council (Vetenskapsrådet).
Subject(s)
Creatinine/blood , Glomerular Filtration Rate , Adolescent , Adult , Age Factors , Aged , Child , Child, Preschool , Cross-Sectional Studies , Female , Humans , Male , Middle Aged , Reproducibility of Results , Sex Factors , Young AdultABSTRACT
BACKGROUND: The Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) creatinine equation is routinely used to assess renal function but exhibits varying accuracy depending on patient characteristics and clinical presentation. The overall aim of the present study was to assess if and to what extent glomerular filtration rate (GFR) estimation based on creatinine can be improved. METHODS: In a cross-sectional analysis covering the years 2003-17, CKD-EPI was validated against measured GFR (mGFR; using various tracer methods) in patients with high likelihood of chronic kidney disease (CKD; five CKD cohorts, n = 8365) and in patients with low likelihood of CKD (six community cohorts, n = 6759). Comparisons were made with the Lund-Malmö revised equation (LMR) and the Full Age Spectrum equation. RESULTS: 7In patients aged 18-39 years old, CKD-EPI overestimated GFR with 5.0-16 mL/min/1.73 m2 in median in both cohort types at mGFR levels <120 mL/min/1.73 m2. LMR had greater accuracy than CKD-EPI in the CKD cohorts (P30, the percentage of estimated GFR within 30% of mGFR, 83.5% versus 76.6%). CKD-EPI was generally the most accurate equation in the community cohorts, but all three equations reached P30 above the Kidney Disease Outcomes Quality Initiative benchmark of 90%. CONCLUSIONS: None of the evaluated equations made optimal use of available data. Prospects for improved GFR estimation procedures based on creatinine exist, particularly in young adults and in settings where patients with suspected or manifest CKD are investigated.
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BACKGROUND: Homozygous familial hypercholesterolaemia (FH) is an autosomal-dominant inherited disease presenting with highly elevated low-density lipoprotein cholesterol (LDL-C) levels. Untreated, the patient can develop atherosclerosis and cardiovascular disease already in adolescence. Treatment with statins and ezetimibe is usually not sufficient and LDL apheresis is often required. Lomitapide, an inhibitor of the microsomal triglyceride transfer protein, reduces LDL-C and triglyceride levels and can be used alone or in combination with other therapies in homozygous FH. However, experience with this agent is still limited. CASE SUMMARY: We present a young female who was diagnosed with homozygous FH at 6 years of age. She shows a complete lack of normal LDL receptor activity and no cholesterol-lowering effect from statins. The patient was treated with LDL apheresis from 7 years of age. When LDL apheresis treatment extended to twice a week, she began to experience adverse effects, including catheter-related complications, infections, and hospital admissions. When lomitapide treatment was initiated, the frequency of apheresis reduced, the LDL-C levels improved and she has not had any further hospital admissions since. Initially, she suffered from gastrointestinal disturbances. However, after 3 years of treatment with lomitapide 20 mg/day, the patient has not experienced any adverse effects. DISCUSSION: In this female with homozygous FH adding lomitapide treatment to LDL apheresis has contributed to improved LDL-C levels, a reduction in LDL apheresis sessions and enhanced quality of life. No adverse effects have been reported. These findings suggest that lomitapide can be a drug of choice in patients with homozygous FH.
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INTRODUCTION: Haemostatic balance shifted towards hypercoagulability in normal pregnancy is even more pronounced in pre-eclampsia (P-EC). The aim of this study was to analyse haemostatic disturbances and fibrin clot properties in women with pre-eclampsia and to investigate their association with maternal and foetal outcomes. METHODS: Forty-six pregnant women diagnosed with pre-eclampsia were included in the study, with blood sampling done on the morning following admission to hospital, as well as after delivery (mean duration 4.8 days). Two global haemostatic assays-endogenous thrombin potential (ETP) and assay of overall haemostatic potential (OHP)-were employed, including fibrin clot turbidity measurements and scanning electron microscopy (SEM) of representative samples. RESULTS: Three thrombin generation parameters (ETP, t_lag and peak height) and OHP were significantly increased in pre-eclampsia compared with controls, whereas overall fibrinolytic potential (OFP-determined as a parameter of the OHP assay) had significantly lower values. Clot lysis time was significantly prolonged in patients with pre-eclampsia. In the pre-eclamptic group after delivery, we observed a significant elevation in the peak height and a reduction in the time to peak and OFP compared with values before delivery. Pre-eclamptic patients with renal complications had significantly higher values for ETP, peak height and D-dimer. Turbidity measurements and SEM revealed dense fibrin structure in patients with pre-eclampsia. CONCLUSION: Patients with pre-eclampsia have enhanced coagulation and impaired fibrinolysis before, and even after, delivery. In particular, the presence of multi-organ dysfunction, such as renal dysfunction, may be associated with increased thrombin generation in pre-eclampsia.
Subject(s)
Fibrin Fibrinogen Degradation Products/metabolism , Fibrinolysis , Kidney Diseases/blood , Pre-Eclampsia/blood , Thrombin/metabolism , Adult , Female , Humans , PregnancyABSTRACT
OBJECTIVE: To investigate the association of the cardiovascular risk factor lipoprotein (Lp)(a) and vascular complications in patients with type 1 diabetes. RESEARCH DESIGN AND METHODS: Patients with type 1 diabetes receiving regular care were recruited in this observational cross-sectional study and divided into four groups according to their Lp(a) levels in nmol/L (very low <10, low 10-30, intermediate 30-120, high >120). Prevalence of vascular complications was compared between the groups. In addition, the association between metabolic control, measured as HbA1c, and Lp(a) was studied. RESULTS: The patients (n = 1,860) had a median age of 48 years, diabetes duration of 25 years, and HbA1c of 7.8% (61 mmol/mol). The median Lp(a) was 19 (interquartile range 10-71) nmol/L. No significant differences between men and women were observed, but Lp(a) levels increased with increasing age. Patients in the high Lp(a) group had higher prevalence of complications than patients in the very low Lp(a) group. The age- and smoking-status-adjusted relative risk ratio of having any macrovascular disease was 1.51 (95% CI 1.01-2.28, P = 0.048); coronary heart disease, 1.70 (95% CI 0.97-3.00, P = 0.063); albuminuria, 1.68 (95% CI 1.12-2.50, P = 0.01); and calcified aortic valve disease, 2.03 (95% CI 1.03-4.03; P = 0.042). Patients with good metabolic control, HbA1c <6.9% (<52 mmol/mol), had significantly lower Lp(a) levels than patients with poorer metabolic control, HbA1c >6.9% (>52 mmol/mol). CONCLUSIONS: Lp(a) is a significant risk factor for macrovascular disease, albuminuria, and calcified aortic valve disease in patients with type 1 diabetes. Poor metabolic control in patients with type 1 diabetes is associated with increased Lp(a) levels.
Subject(s)
Blood Glucose/metabolism , Cardiovascular Diseases/epidemiology , Diabetes Mellitus, Type 1/epidemiology , Diabetes Mellitus, Type 1/metabolism , Lipoprotein(a)/blood , Adult , Aged , Cardiovascular Diseases/blood , Cardiovascular Diseases/etiology , Coronary Disease/blood , Coronary Disease/epidemiology , Coronary Disease/etiology , Cross-Sectional Studies , Diabetes Mellitus, Type 1/blood , Diabetes Mellitus, Type 1/complications , Diabetic Angiopathies/blood , Diabetic Angiopathies/epidemiology , Female , Glycated Hemoglobin/metabolism , Humans , Male , Middle Aged , Prevalence , Risk FactorsABSTRACT
The current Kidney Disease Improving Global Outcomes (KDIGO) guidelines recommend the use of the bedside creatinine-based Chronic Kidney Disease in Children (CKiD) equation to estimate glomerular filtration rate (GFR) in children and the Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) equation in adults. However, this approach causes implausible changes in estimated GFR (eGFR) at the transition from pediatric to adult care. We investigated the performance of the KDIGO strategy and various creatinine-based eGFR equations in a cross-sectional dataset of 5,764 subjects (age 10-30 years), using directly measured GFR (mGFR) as reference. We also evaluated longitudinal GFR slopes in 136 subjects who transitioned to adult care. Implausible changes in eGFR resulted from the large overestimation (bias=+21 mL/min/1.73m2) and poor precision of the CKD-EPI equation in the 18-20 year age group, compared to CKiD in the 16-18 year age group (bias=-2.7 mL/min/1.73m2), resulting in a mean change of 23 mL/min/1.73m2 at the transition to adult care. Averaging the CKiD and CKD-EPI estimates in young adults only partially mitigated this issue. The Full Age Spectrum equation (with and without height), the Lund-Malmö Revised equation, and an age-dependent weighted average of CKiD and CKD-EPI resulted in much smaller changes in eGFR at the transition (change of 0.6, -2.1, -0.9 and -1.8 mL/min/1.73m2, respectively). The longitudinal analysis revealed a significant difference in average GFR slope between mGFR and the KDIGO strategy (-2.2 vs. +2.9 mL/min/1.73 m2/year), which was not observed with the other approaches. These results suggest that the KDIGO recommendation for GFR estimation at the pediatric-adult care transition should be revisited.
Subject(s)
Glomerular Filtration Rate , Kidney/physiopathology , Models, Biological , Renal Insufficiency, Chronic/physiopathology , Adolescent , Adult , Age Factors , Child , Creatinine/blood , Creatinine/urine , Cross-Sectional Studies , Datasets as Topic , Female , Humans , Longitudinal Studies , Male , Nephrology/methods , Nephrology/standards , Practice Guidelines as Topic , Renal Insufficiency, Chronic/blood , Renal Insufficiency, Chronic/urine , Transition to Adult Care , Young AdultABSTRACT
BACKGROUND: Autologous stem-cell transplantation (ASCT) is a common treatment for lymphoma but it has some mortality. METHODS: All 433 lymphoma patients who underwent ASCT for lymphoma at Karolinska Huddinge 1994-2016 were investigated, including CD34+ cell amounts, medications, infectious and other complications, intensive care, longitudinal laboratory values, and secondary myeloid neoplasia. RESULTS: The 100-day non-relapse and overall mortalities were 5.6% and 7.2%. Stem-cell harvests < 5 million CD34+ cells/kg correlated with inferior 100-day and long-term survival. Prior to conditioning (93% BEAM), elevated (both 3-9 and ≥ 10 mg/L) C-reactive protein (CRP) and creatinine, and low albumin (but not higher age) predicted inferior higher 100-day survival. Intravenous antibiotics were given to 97% (22% positive blood cultures) and parenteral nutrition to 89%. After 1 year, 86% had normalized hemoglobin. The 5-year risk for secondary myeloid neoplasia was 4.1%, associated with smaller harvests. CONCLUSIONS: Before starting conditioning, patients should have preferably harvested ≥ 5 million CD34+ cells/kg and normal CRP, albumin, and creatinine. It appears safe to transplant patients ≥ 66 years.
ABSTRACT
BACKGROUND: Most validations of paediatric glomerular filtration rate (GFR) estimating equations using standardized creatinine (CR) and cystatin C (CYS) assays have comprised relatively small cohorts, which makes accuracy across subgroups of GFR, age, body mass index (BMI) and gender uncertain. To overcome this, a large cohort of children referred for GFR determination has been established from several European medical centres. METHODS: Three thousand four hundred eight measurements of GFR (mGFR) using plasma clearance of exogenous substances were performed in 2218 children aged 2-17 years. Validated equations included Schwartz-2009CR/2012CR/CYS/CR+CYS, FASCR/CYS/CR+CYS, LMRCR, Schwartz-LyonCR, BergCYS, CAPACYS, CKD-EPICYS, AndersenCR+CYS and arithmetic means of the best single-marker equations in explorative analysis. Five metrics were used to compare the performance of the GFR equations: bias, precision and three accuracy measures including the percentage of GFR estimates (eGFR) within ± 10% (P10) and ± 30% (P30) of mGFR. RESULTS: Three of the cystatin C equations, BergCYS, CAPACYS and CKD-EPICYS, exhibited low bias and generally satisfactory accuracy across all levels of mGFR; CKD-EPICYS had more stable performance across gender than the two other equations. Among creatinine equations, Schwartz-LyonCR had the best performance but was inaccurate at mGFR < 30 mL/min/1.73 m2 and in underweight patients. Arithmetic means of the best creatinine and cystatin C equations above improved bias compared to the existing composite creatinine+cystatin C equations. CONCLUSIONS: The present study strongly suggests that cystatin C should be the primary biomarker of choice when estimating GFR in children with decreased GFR. Arithmetic means of well-performing single-marker equations improve accuracy further at most mGFR levels and have practical advantages compared to composite equations.