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-2009
CR
/2012
CR/CYS/CR+CYS
, FAS
CR/CYS/CR+CYS
, LMR
CR
, Schwartz-Lyon
CR
, Berg
CYS
, CAPA
CYS
, CKD-EPI
CYS
, Andersen
CR+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% (P
10
) and ± 30% (P
30
) of mGFR.
Results
Three of the cystatin C equations, Berg
CYS
, CAPA
CYS
and CKD-EPI
CYS
, exhibited low bias and generally satisfactory accuracy across all levels of mGFR; CKD-EPI
CYS
had more stable performance across gender than the two other equations. Among creatinine equations, Schwartz-Lyon
CR
had the best performance but was inaccurate at mGFR < 30 mL/min/1.73 m
2
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.
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.
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Background In randomized trials (SHARP Study of Heart and Renal Protection, IMPROVE -IT Improved Reduction of Outcomes: Vytorin Efficacy International Trial), combination of statin and ezetimibe ...resulted in additional reduction of cardiovascular events. The reduction was greater in patients with type 2 diabetes mellitus (T2 DM ), where elevated remnant cholesterol and high cardiovascular disease risk is characteristic. To evaluate possible causes behind these results, 40 patients eligible for cholecystectomy, randomized to simvastatin, ezetimibe, combined treatment (simvastatin+ezetimibe), or placebo treatment during 4 weeks before surgery, were studied. Methods and Results Fasting blood samples were taken before treatment start and at the end (just before surgery). Bile samples and liver biopsies were collected during surgery. Hepatic gene expression levels were assessed with qPCR . Lipoprotein, apolipoprotein levels, and content of cholesterol, cholesteryl ester, and triglycerides were measured after lipoprotein fractionation. Lipoprotein subclasses were analyzed by nuclear magnetic resonance. Apolipoprotein affinity for human arterial proteoglycans ( PG ) was measured. Biomarkers of cholesterol biosynthesis and intestinal absorption and bile lipid composition were analyzed using mass spectrometry. Combined treatment caused a statistically significant decrease in plasma remnant particles and apolipoprotein B (ApoB)/lipoprotein content of cholesterol, cholesteryl esters, and triglycerides. All treatments reduced ApoB-lipoprotein PG binding. Simvastatin and combined treatment modified the composition of lipoproteins. Changes in biomarkers of cholesterol synthesis and absorption and bile acid synthesis were as expected. No adverse events were found. Conclusions Combined treatment caused atheroprotective changes on ApoB-lipoproteins, remnant particles, bile components, and in ApoB-lipoprotein affinity for arterial PG . These effects might explain the decrease of cardiovascular events seen in the SHARP and IMPROVE - IT trials. Clinical Trial Registration URL : www.clinicaltrialsregister.eu . Unique identifier: 2006-004839-30).
Autologous stem-cell transplantation (ASCT) is a common treatment for lymphoma but it has some mortality.
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.
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.
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.
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.
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.
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.
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.).
To investigate the association of the cardiovascular risk factor lipoprotein (Lp)(a) and vascular complications in patients with type 1 diabetes.
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 HbA
, and Lp(a) was studied.
The patients (
= 1,860) had a median age of 48 years, diabetes duration of 25 years, and HbA
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,
= 0.048); coronary heart disease, 1.70 (95% CI 0.97-3.00,
= 0.063); albuminuria, 1.68 (95% CI 1.12-2.50,
= 0.01); and calcified aortic valve disease, 2.03 (95% CI 1.03-4.03;
= 0.042). Patients with good metabolic control, HbA
<6.9% (<52 mmol/mol), had significantly lower Lp(a) levels than patients with poorer metabolic control, HbA
>6.9% (>52 mmol/mol).
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.
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).
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.
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.
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.
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•Men and women with calcified aortic valve stenosis have elevated lipoprotein(a).•Lipoprotein(a) associates with development of calcified aortic valve stenosis.•Lipoprotein(a) is a cardiovascular risk factor that should be measured in the clinical routine.
ABSTRACT
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.
Graphical Abstract
Graphical Abstract
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