Abstract
Aims
Both hypo- and hyperkalaemia can have immediate deleterious physiological effects, and less is known about long-term risks. The objective was to determine the risks of all-cause ...mortality, cardiovascular mortality, and end-stage renal disease associated with potassium levels across the range of kidney function and evaluate for consistency across cohorts in a global consortium.
Methods and results
We performed an individual-level data meta-analysis of 27 international cohorts 10 general population, 7 high cardiovascular risk, and 10 chronic kidney disease (CKD) in the CKD Prognosis Consortium. We used Cox regression followed by random-effects meta-analysis to assess the relationship between baseline potassium and adverse outcomes, adjusted for demographic and clinical characteristics, overall and across strata of estimated glomerular filtration rate (eGFR) and albuminuria. We included 1 217 986 participants followed up for a mean of 6.9 years. The average age was 55 ± 16 years, average eGFR was 83 ± 23 mL/min/1.73 m2, and 17% had moderate- to-severe increased albuminuria levels. The mean baseline potassium was 4.2 ± 0.4 mmol/L. The risk of serum potassium of >5.5 mmol/L was related to lower eGFR and higher albuminuria. The risk relationship between potassium levels and adverse outcomes was U-shaped, with the lowest risk at serum potassium of 4–4.5 mmol/L. Compared with a reference of 4.2 mmol/L, the adjusted hazard ratio for all-cause mortality was 1.22 95% confidence interval (CI) 1.15–1.29 at 5.5 mmol/L and 1.49 (95% CI 1.26–1.76) at 3.0 mmol/L. Risks were similar by eGFR, albuminuria, renin–angiotensin–aldosterone system inhibitor use, and across cohorts.
Conclusions
Outpatient potassium levels both above and below the normal range are consistently associated with adverse outcomes, with similar risk relationships across eGFR and albuminuria.
Progressive CKD is generally detected at a late stage by a sustained decline in eGFR and/or the presence of significant albuminuria. With the aim of early and improved risk stratification of patients ...with CKD, we studied urinary peptides in a large cross-sectional multicenter cohort of 1990 individuals, including 522 with follow-up data, using proteome analysis. We validated that a previously established multipeptide urinary biomarker classifier performed significantly better in detecting and predicting progression of CKD than the current clinical standard, urinary albumin. The classifier was also more sensitive for identifying patients with rapidly progressing CKD. Compared with the combination of baseline eGFR and albuminuria (area under the curve AUC=0.758), the addition of the multipeptide biomarker classifier significantly improved CKD risk prediction (AUC=0.831) as assessed by the net reclassification index (0.303±-0.065; P<0.001) and integrated discrimination improvement (0.058±0.014; P<0.001). Correlation of individual urinary peptides with CKD stage and progression showed that the peptides that associated with CKD, irrespective of CKD stage or CKD progression, were either fragments of the major circulating proteins, suggesting failure of the glomerular filtration barrier sieving properties, or different collagen fragments, suggesting accumulation of intrarenal extracellular matrix. Furthermore, protein fragments associated with progression of CKD originated mostly from proteins related to inflammation and tissue repair. Results of this study suggest that urinary proteome analysis might significantly improve the current state of the art of CKD detection and outcome prediction and that identification of the urinary peptides allows insight into various ongoing pathophysiologic processes in CKD.
Using genome-wide association, we identify common variants at 2p12-p13, 6q26, 17q23 and 19q13 associated with serum creatinine, a marker of kidney function (P = 10−10 to 10−15). Of these, rs10206899 ...(near NAT8, 2p12-p13) and rs4805834 (near SLC7A9, 19q13) were also associated with chronic kidney disease (P = 5.0 × 10−5 and P = 3.6 × 10−4, respectively). Our findings provide insight into metabolic, solute and drug-transport pathways underlying susceptibility to chronic kidney disease.
Celotno besedilo
Dostopno za:
DOBA, IJS, IZUM, KILJ, NUK, PILJ, PNG, SAZU, UILJ, UKNU, UL, UM, UPUK
Non-equivalence in serum creatinine (SCr) measurements across Dutch laboratories and the consequences hereof on chronic kidney disease (CKD) staging were examined.
National data from the Dutch annual ...external quality organization of 2009 were used. 144 participating laboratories examined 11 pairs of commutable, value-assigned SCr specimens in the range 52-262 μmol/L, using Jaffe or enzymatic techniques. Regression equations were created for each participating laboratory (by regressing values as measured by participating laboratories on the target values of the samples sent by the external quality organization); area under the curves were examined and used to rank laboratories. The 10th and 90th percentile regression equation were selected for each technique separately. To evaluate the impact of the variability in SCr measurements and its eventual clinical consequences in a real patient population, we used a cohort of 82424 patients aged 19-106 years. The SCr measurements of these 82424 patients were introduced in the 10th and 90th percentile regression equations. The newly calculated SCr values were used to calculate an estimated glomerular filtration rate (eGFR) using the 4-variable Isotope Dilution Mass Spectrometry traceable Modification of Diet in Renal Disease formula. Differences in CKD staging were examined, comparing the stratification outcomes for Jaffe and enzymatic SCr techniques.
Jaffe techniques overestimated SCr: 21%, 12%, 10% for SCr target values 52, 73 and 94 μmol/L, respectively. For enzymatic assay these values were 0%, -1%, -2%, respectively. eGFR using the MDRD formula and SCr measured by Jaffe techniques, staged patients in a lower CKD category. Downgrading to a lower CKD stage occurred in 1-42%, 2-37% and 12-78.9% of patients for the 10th and 90th percentile laboratories respectively in CKD categories 45-60, 60-90 and >90 ml/min/1.73 m2. Using enzymatic techniques, downgrading occurred only in 2-4% of patients.
Enzymatic techniques lead to less variability in SCr measurements than Jaffe techniques, and therefore result in more accurate staging of CKD. Therefore the specific enzymatic techniques are preferably used in clinical practice in order to generate more reliable GFR estimates.
As many elderly patients are not able to stand for several minutes, sitting orthostatic blood pressure (BP) measurements are sometimes used as an alternative. We aimed to investigate the difference ...in BP response and orthostatic hypotension (OH) prevalence between the standard postural change to the sitting and the standing position in a cross-sectional observational study. BP was measured with a continuous BP measurement device during two postural changes, from supine to the sitting and from supine to the standing position. Linear mixed models were used to investigate the differences in changes (Δ) of systolic BP (SBP) and diastolic BP (DBP) between the two postural changes. The prevalence and the positive and negative proportions of agreement of OH were calculated of the two postural changes. One hundred and four patients with a mean age of 69 years were included. ΔSBP was significantly larger in the standing position compared with the sitting between 0 and 44 s. ΔDBP was significantly larger in the sitting position compared with the standing 75-224 s after postural change. The prevalence of OH was 66.3% (95% confidence interval (CI) 57.2, 75.4) in the standing position and 67.3% (95% CI 58.3, 76.3) in the sitting position. The positive proportion of agreement was 74.8% and the negative proportion of agreement was 49.3%. A clear difference was seen in BP response between the two postural changes. Although no significant difference in prevalence of OH was observed, the positive and negative proportion of agreement of the prevalence of OH were poor to moderate, which indicates a different outcome between both postural changes.
Self-monitoring of blood glucose (SMBG), including self-regulation, is an important tool to achieve good glycemic control. However, many patients measure their glucose concentrations less often than ...is recommended. This study investigates patients' perspectives of SMBG and all relevant aspects influencing SMBG in patients with type 1 and insulin-treated type 2 diabetes.
In depth interviews were conducted with 13 patients with type 1 diabetes from an outpatient clinic and 15 patients with type 2 diabetes from general practices. All interviews were transcribed verbatim and analyzed using the Grounded Theory approach.
A wide variety of SMBG was encountered. Perceptions, goals of SMBG and personal and contextual factors were identified, influencing the respondents' perspective of SMBG, and leading to this variety. Respondents experienced a discrepancy between their own and the professionals' perceptions and goals. Respondents' perception of SMBG ranged along a continuum from 'friend' to 'foe'. With respect to the goals, the respondents experienced tension between achieving good glycemic control and quality of life, and deliberately made their own choices. The performance of SMBG was tailored to their perceptions and personal goals. Personal and contextual factors such as hypo- or hyper (un)awareness, knowledge, and contact with professionals acted as either facilitating factors or as barriers to SMBG, depending on the respondents' perspective. A SMBG model was developed providing a representation of the factors and their interrelations.Respondents with type 1 diabetes seemed more resigned to their situation and SMBG was more integrated into their lives.
From the patients' perspective, professionals positively present SMBG as a 'friend' in order to achieve strict glycemic control. Whereas patients can also perceive SMBG as a 'foe'. They primarily seek a personal balance between achieving glycemic control and quality of life, leading them to deliberately make other choices regarding SMBG performance than was recommended. Gaining insight and discussing all factors affecting SMBG will help professionals and patients come to mutually agreed goals and to tailor the performance of SMBG to the individual patient. This should result in a more optimal use of SMBG, an improved quality of life, and improved clinical parameters.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Gliclazide has been associated with a low risk of hypoglycemic episodes and beneficial long-term cardiovascular safety in observational cohorts. The aim of this study was to assess in a systematic ...review and meta-analysis of randomized controlled trials the safety and efficacy of gliclazide compared to other oral glucose-lowering agents (PROSPERO2013:CRD42013004156).
Medline, EMBASE, Clinicaltrials.gov, Trialregister.nl, Clinicaltrialsregister.eu and the Cochrane database.
Included were randomized studies of at least 12 weeks duration with the following outcomes: HbA1c change, incidence of severe hypoglycemia, weight change, cardiovascular events and/or mortality when comparing gliclazide with other oral blood glucose lowering drugs. Bias was assessed with the Cochrane risk of bias tool. The inverse variance random effects model was used.
Nineteen trials were included; 3,083 patients treated with gliclazide and 3,155 patients treated with other oral blood glucose lowering drugs. There was a considerable amount of heterogeneity between and bias in studies. Compared to other glucose lowering agents except metformin, gliclazide was slightly more effective (-0.13% (95%CI: -0.25, -0.02, I(2) 55%)). One out of 2,387 gliclazide users experienced a severe hypoglycemic event, whilst also using insulin. There were 25 confirmed non-severe hypoglycemic events (2.2%) in 1,152 gliclazide users and 22 events (1.8%) in 1,163 patients in the comparator group (risk ratio 1.09 (95% CI: 0.20, 5.78, I² 77%)). Few studies reported differences in weight and none were designed to evaluate cardiovascular outcomes.
The methodological quality of randomized trials comparing gliclazide to other oral glucose lowering agents was poor and effect estimates on weight were limited by publication bias. The number of severe hypoglycemic episodes was extremely low, and gliclazide appears at least equally effective compared to other glucose lowering agents. None of the trials were designed for evaluating cardiovascular outcomes, which warrants attention in future randomized trials.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Objective To investigate the prevalence of overt thyroid disease in children in The Netherlands with and without type 1 diabetes mellitus (T1DM). Study design Nationwide, retrospective cohort study ...in The Netherlands. Using the national registry of both healthcare reimbursement and pharmaceutical care, data of all Dutch children (aged 0-14 years) with a diagnosis of T1DM, or a diagnosis of hypothyroidism or hyperthyroidism in the period 2009-2011. Results The prevalence of thyroid disease was 0.15% in children without T1DM, and 3.43% in children with T1DM (rate ratio 23.59; 95% CI 19.92-27.93; P < .001). Both hyperthyroidism and hypothyroidism were 24 times more likely in children with T1DM than in those without. Thyroid disease was more common in girls than in boys, both in children with T1DM (rate ratio of girls vs boys 3.07; 95% CI 2.10-4.49) and in children without T1DM (rate ratio 1.59; 95% CI 1.49-1.69). This sex difference was more pronounced for hypothyroidism than for hyperthyroidism. Conclusions Children with T1DM in The Netherlands are 24 times more likely to develop thyroid disease than their peers without diabetes. Girls with T1DM were more prone to thyroid disease, particularly hypothyroidism.
Diabetes and obesity seem to be partly overlapping risk factors for the development of obesity-related cancer (mainly breast, prostate and colorectal cancer) in patients with type 2 diabetes (T2DM). ...In the general population, women have a lower risk for obesity-related cancer compared to men. Previous studies involving cardiovascular disease have shown that T2DM eliminates a female advantage of lower CVD risk in the general population compared to men. It is unclear whether the same could be true for obesity-related cancer. This study aimed to this investigate obesity-related cancer incidence in women and men known with T2DM as compared to the Dutch general population.
This study included 69,583 patients with T2DM selected from a prospective primary care cohort, which was linked to the Dutch National Cancer Registry to obtain cancer specific data. Obesity-related cancers included liver, kidney, colorectal, gallbladder, pancreas, ovarian, endometrial, advanced prostate cancer, post-menopausal breast cancer and oesophageal adenocarcinoma. Primary outcome was sex-stratified, age and year of cancer diagnosis adjusted standardized incidence ratios (SIRs) for three time periods: 5 years before, the year after diagnosis and the next 4 years after T2DM diagnosis. The Dutch general population was used as reference group.
Women with T2DM were at an increased risk for obesity-related cancer compared to women in the general population already 5 years before diabetes diagnosis (SIR 1.77; 95%CI: 1.63-1.91). In both men and women, there was a peak in obesity-related cancer incidence following diabetes diagnosis (SIR: 1.38; 95%CI 1.11-1.64 and SIR: 2.21; 95%CI 1.94-2.30, respectively). From the second to the fifth year after diabetes diagnosis the obesity-related cancer incidence was higher in women compared to women in the general population (SIR: 2.12; 95%CI 1.94-2.30).
Women with T2DM seem to have a substantially higher obesity-related cancer risk. As opposed to men, in women this risk was already increased years before diabetes diagnosis. These results could imply that a relative advantage of women in the general population with regard to cancer risk is lost in women with T2DM.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Guideline-adherent prescribing for treatment of multiple risk factors in type 2 diabetes (T2D) patients is expected to improve clinical outcomes. However, the relationship to Health-Related Quality ...of Life (HRQoL) is not straightforward since guideline-adherent prescribing can increase medication burden.
To test whether guideline-adherent prescribing and disease-specific medication burden are associated with HRQoL in patients with T2D.
Cross-sectional study including 1,044 T2D patients from the e-VitaDM/ZODIAC study in 2012 in the Netherlands. Data from the diabetes visit, such as laboratory and physical examinations and prescribed medication, and from two HRQoL questionnaires, the EuroQol 5 Dimensions 3 Levels (EQ5D-3L) and the World Health Organization Well-Being Index (WHO-5) were collected. Twenty indicators assessing prescribing of recommended glucose lowering drugs, statins, antihypertensives and renin-angiotensin-aldosterone system (RAAS)-inhibitors and potentially inappropriate drugs from a validated diabetes indicator set were included. Disease-specific medication burden was assessed using a modified version of the Medication Regimen Complexity Index (MRCI). Associations were tested with regression models, adjusting for age, gender, diabetes duration, comorbidity, body mass index and smoking.
The mean MRCI was 7.1, the median EQ5D-3L-score was 0.86 and the mean WHO-5 score was 72. Seven indicators included too few patients and were excluded from the analysis. The remaining thirteen indicators focusing on recommended start, intensification, current and preferred use of glucose lowering drugs, statins, antihypertensives, RAAS inhibitors, and on inappropriate prescribing of glibenclamide and dual RAAS blockade were not significantly associated with HRQoL. Finally, also the MRCI was not associated with HRQoL.
We found no evidence for associations between guideline-adherent prescribing or disease-specific medication burden and HRQoL in T2D patients. This gives no rise to refrain from prescribing intensive treatment in T2D patients as recommended, but the interpretation of these results is limited by the cross-sectional study design and the selection of patients included in some indicators.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
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