Potential Mediating Role of Iron Biomarkers in the Association of Sex With Glucose, Insulin, and Type 2 Diabetes.

Context: Sex-specific prevalence and incidence of type 2 diabetes (T2D) have been reported, but the underlying mechanisms are uncertain. Objective: In this study, we aimed to investigate whether iron biomarkers mediate the association between biological sex and glucose metabolism and the incidence of T2D. Methods: We used data from the general population enrolled in the prospective Prevention of REnal and Vascular ENd-stage Disease study in Groningen, The Netherlands. We measured ferritin, transferrin saturation (TSAT), hepcidin, soluble transferrin receptor (sTfR), fasting plasma glucose (FPG), fasting plasma insulin (FPI) levels, and incidence of T2D. We used multivariable regression and mediation analyses to investigate our hypothesis. All iron biomarkers, FPG, and FPI were log-transformed. Results: The mean (SD) age of the 5312 (51.3% female) individuals was 52.2 (11.6) years. Compared with males, females had lower FPG (ß = -.01; 95% CI -0.02, -0.01) and FPI (ß = -.03; 95% CI -0.05, -0.02) levels. Ferritin, hepcidin, and sTfR showed potential mediating effects on the association between sex and FPG, 21%, 5%, and 7.1%, respectively. Furthermore, these variables mediated 48.6%, 5.7%, and 3.1% of the association between sex and FPI, respectively. Alternatively, TSAT had a suppressive mediating role in the association of sex with FPG and FPI. The incidence of T2D was lower in females than in males (hazard ratio 0.58; 95% CI 0.44, 0.77), with 19.2% of this difference being mediated by ferritin. Conclusion: Iron biomarkers may partially mediate the association between sex and glucose homeostasis. Future studies addressing the causality of our findings are needed.

Preoperative cognitive performance and its association with postoperative complications in vascular surgery patients: A prospective study.

BACKGROUND: Cognitive impairment affects nearly half of vascular surgery patients, but its association with postoperative outcomes remains poorly understood. This study explores the link between preoperative cognitive performance and postoperative complications, including postoperative delirium, in vascular surgery patients. METHODS: A prospective cohort study was conducted on vascular surgery patients aged ≥65. Preoperative cognitive performance was assessed using the Montreal Cognitive Assessment, and postoperative complications were evaluated using the Comprehensive Complication Index. The association was analyzed through multivariable logistic regression. RESULTS: Among 110 patients (18.2 â€‹% female, mean age 73.8 â€‹± â€‹5.7 years), cognitive impairment was evident in 48.2 â€‹%. Of the participants, 29 (26.3 â€‹%) experienced postoperative complications, among which 11 (10 â€‹%) experienced postoperative delirium. The adjusted odds ratio for the association between cognitive performance and postoperative complications was 1.19 (95 â€‹% CI 1.02-1.38; p â€‹= â€‹0.02). CONCLUSION: Worse preoperative cognitive performance correlated with increased odds of postoperative complications and postoperative delirium in vascular surgery patients.

Circulating Trimethylamine-N-Oxide Is Elevated in Liver Transplant Recipients.

Liver transplant recipients (LTRs) have lower long-term survival rates compared with the general population. This underscores the necessity for developing biomarkers to assess post-transplantation mortality. Here we compared plasma trimethylamine-N-oxide (TMAO) levels with those in the general population, investigated its determinants, and interrogated its association with all-cause mortality in stable LTRs. Plasma TMAO was measured in 367 stable LTRs from the TransplantLines cohort (NCT03272841) and in 4837 participants from the population-based PREVEND cohort. TMAO levels were 35% higher in LTRs compared with PREVEND participants (4.3 vs. 3.2 µmol/L, p < 0.001). Specifically, TMAO was elevated in LTRs with metabolic dysfunction-associated steatotic liver disease, alcohol-associated liver disease, and polycystic liver disease as underlying etiology (p < 0.001 for each). Among LTRs, TMAO levels were independently associated with eGFR (std. ß = -0.43, p < 0.001) and iron supplementation (std. ß = 0.13, p = 0.008), and were associated with mortality (29 deaths during 8.6 years follow-up; log-rank test p = 0.017; hazard ratio of highest vs. lowest tertile 4.14, p = 0.007). In conclusion, plasma TMAO is likely elevated in stable LTRs, with impaired eGFR and iron supplementation as potential contributory factors. Our preliminary findings raise the possibility that plasma TMAO could contribute to increased mortality risk in such patients, but this need to be validated through a series of rigorous and methodical studies.

Creatine homeostasis and the kidney: comparison between kidney transplant recipients and healthy controls.

Creatine is a natural nitrogenous organic acid that is integral to energy metabolism and crucial for proper cell functioning. The kidneys are involved in the first step of creatine production. With kidney transplantation being the gold-standard treatment for end-stage kidney disease, kidney transplant recipients (KTR) may be at risk of impaired creatine synthesis. We aimed to compare creatine homeostasis between KTR and controls. Plasma and urine concentrations of arginine, glycine, guanidinoacetate, creatine and creatinine were measured in 553 KTR and 168 healthy controls. Creatine intake was assessed using food frequency questionnaires. Iothalamate-measured GFR data were available in subsets of 157 KTR and 167 controls. KTR and controls had comparable body weight, height and creatine intake (all P > 0.05). However, the total creatine pool was 14% lower in KTR as compared to controls (651 ± 178 vs. 753 ± 239 mmol, P < 0.001). The endogenous creatine synthesis rate was 22% lower in KTR as compared to controls (7.8 ± 3.0 vs. 10.0 ± 4.1 mmol per day, P < 0.001). Despite lower GFR, the plasma guanidinoacetate and creatine concentrations were 21% and 41% lower in KTR as compared to controls (both P < 0.001). Urinary excretion of guanidinoacetate and creatine were 66% and 59% lower in KTR as compared to controls (both P < 0.001). In KTR, but not in controls, a higher measured GFR was associated with a higher endogenous creatine synthesis rate (std. beta: 0.21, 95% CI: 0.08; 0.33; P = 0.002), as well as a higher total creatine pool (std. beta: 0.22, 95% CI: 0.11; 0.33; P < 0.001). These associations were fully mediated (93% and 95%; P < 0.001) by urinary guanidinoacetate excretion which is consistent with production of the creatine precursor guanidinoacetate as rate-limiting factor. Our findings highlight that KTR have a disturbed creatine homeostasis as compared to controls. Given the direct relationship of measured GFR with endogenous creatine synthesis rate and the total creatine pool, creatine supplementation might be beneficial in KTR with low kidney function.Trial registration ID: NCT02811835.Trial registration URL: https://clinicaltrials.gov/ct2/show/NCT02811835 .

Creatinine, cystatin C, muscle mass, and mortality: Findings from a primary and replication population-based cohort.

BACKGROUND: Serum creatinine is used as initial test to derive eGFR and confirmatory testing with serum cystatin C is recommended when creatinine-based eGFR is considered less accurate due to deviant muscle mass. Low muscle mass is associated with increased risk of premature mortality. However, the associations of serum creatinine and cystatin C with muscle mass and mortality remain unclear and require further investigation to better inform clinical decision-making. METHODS: We included 8437 community-dwelling adults enrolled in the Dutch PREVEND study and 5033 in the US NHANES replication cohort. Associations of serum creatinine and/or cystatin C with muscle mass surrogates and mortality were quantified with linear and Cox proportional hazards regression, respectively. Missing observations in covariates were multiply imputed using Substantive Model Compatible Fully Conditional Specification. RESULTS: Mean (SD) age of PREVEND and NHANES participants (50% and 48% male) were 49.8 (12.6) and 48.7 (18.7) years, respectively. Median (Q1-Q3) serum creatinine and cystatin C were 71 (61-80) and 80 (62-88) µmol/L and 0.87 (0.78-0.98) and 0.91 (0.80-1.10) mg/L, respectively. Higher serum creatinine was associated with greater muscle mass, while serum cystatin C was not associated with muscle mass. Adjusting both markers for each other strengthened the positive relationship between serum creatinine and muscle mass and revealed an inverse association between serum cystatin C and muscle mass. In the PREVEND cohort, 1636 (19%) deaths were registered over a median follow-up of 12.9 (5.8-16.3) years with a 10-year mortality rate (95% CI) of 7.6% (7.1-8.2%). In the NHANES, 1273 (25%) deaths were registered over a median follow-up of 17.9 (17.3-18.5) years with a 10-year mortality rate of 13.8% (12.8-14.7%). Both markers were associated with increased mortality. Notably, when adjusted for each other, higher serum creatinine was associated with decreased mortality, while the association between serum cystatin C and increased mortality strengthened. The shapes of the associations in the PREVEND study and NHANES were almost identical. CONCLUSIONS: The strong association between serum creatinine and muscle mass challenges its reliability as GFR marker, necessitating a more cautious approach in its clinical use. The minimal association between serum cystatin C and muscle mass supports its increased use as a more reliable alternative in routine clinical practice.

Serum Calcification Propensity Is Increased in Myocardial Infarction and Hints at a Pathophysiological Role Independent of Classical Cardiovascular Risk Factors.

BACKGROUND: Vascular calcification is associated with increased mortality in patients with cardiovascular disease. Secondary calciprotein particles are believed to play a causal role in the pathophysiology of vascular calcification. The maturation time (T50) of calciprotein particles provides a measure of serum calcification propensity. We compared T50 between patients with ST-segment-elevated myocardial infarction and control subjects and studied the association of T50 with cardiovascular risk factors and outcome. METHODS: T50 was measured by nephelometry in 347 patients from the GIPS-III trial and in 254 matched general population controls from PREVEND (Prevention of Renal and Vascular End-Stage Disease). We also assessed the association between T50 and left ventricular ejection fraction, as well as infarct size, the incidence of ischemia-driven reintervention during 5 years of follow-up, and serum nitrite as a marker of endothelial dysfunction. RESULTS: Patients with ST-segment-elevated myocardial infarction had a significantly lower T50 (ie, higher serum calcification propensity) compared with controls (T50: 289±63 versus 338±56 minutes; P<0.001). In patients with ST-segment-elevated myocardial infarction, lower T50 was associated with female sex, lower systolic blood pressure, lower total cholesterol, lower LDL (low-density lipoprotein) cholesterol, lower triglycerides, and higher HDL (high-density lipoprotein) cholesterol but not with circulating nitrite or nitrate. Ischemia-driven reintervention was associated with higher LDL (P=0.03) and had a significant interaction term for T50 and sex (P=0.005), indicating a correlation between ischemia-driven reintervention and T50 above the median in men and below the median in women, between 150 days and 5 years of follow-up. CONCLUSIONS: Serum calcification propensity is increased in patients with ST-segment-elevated myocardial infarction compared with the general population, and its contribution is more pronounced in women than in men. Its lack of/inverse association with nitrite and blood pressure confirms T50 to be orthogonal to traditional cardiovascular disease risk factors. Lower T50 was associated with a more favorable serum lipid profile, suggesting the involvement of divergent pathways of calcification stress and lipid stress in the pathophysiology of myocardial infarction.

Self-reported smoking, urine cotinine, and risk of type 2 diabetes: Findings from the PREVEND prospective cohort study.

BACKGROUND: Smoking is a major risk factor for type 2 diabetes (T2D), but the evidence has mostly relied on self-reports. We aimed to compare the associations of smoking exposure as assessed by self-reports and urine cotinine with T2D. METHODS: Using the PREVEND prospective study, smoking status was assessed at baseline by self-reports and urine cotinine in 4708 participants (mean age, 53 years) without a history of diabetes. Participants were classified as never, former, light current and heavy current smokers according to self-reports and analogous cut-offs for urine cotinine. Hazard ratios (HRs) with 95% CIs were estimated for T2D. RESULTS: During a median follow-up of 7.3 years, 259 participants developed T2D. Compared with self-reported never smokers, the multivariable adjusted HRs (95% CI) of T2D for former, light current, and heavy current smokers were 1.02 (0.75-1.4), 1.41 (0.89-2.22), and 1.30 (0.88-1.93), respectively. The corresponding adjusted HRs (95% CI) were 0.84 (0.43-1.67), 1.61 (1.12-2.31), and 1.58 (1.08-2.32), respectively, as assessed by urine cotinine. Urine cotinine-assessed but not self-reported smoking status improved T2D risk prediction beyond established risk factors. CONCLUSION: Urine cotinine assessed smoking status may be a stronger risk indicator and predictor of T2D compared to self-reported smoking status.

Phase angle and donor type are determinants of coronary artery calcification in stable kidney transplant recipients at twelve months after transplantation.

BACKGROUND AND AIM: Coronary artery calcification (CAC) partially explains the excess cardiovascular morbidity and mortality after kidney transplantation. This study aimed to investigate determinants of CAC in stable kidney transplant recipients at 12 months post-transplantation. METHODS AND RESULTS: CAC-score was quantified by the Agatston method using non-contrast enhanced computed tomography, and age- and sex-standardized CAC-percentiles were calculated. Univariable and multivariable multinomial logistic regression was performed to study potential determinants of CAC. The independent determinants were included in multivariable multinomial logistic regression adjusting for potential confounders. 203 KTRs (age 54.0 ± 14.7 years, 61.1% male) were included. Participants were categorized into four groups according to CAC percentiles (p = 0 [CAC-score = 0], n = 68; p ≥ 1%-p ≤ 50% [CAC score = 29.0 (4.0-166.0)], n = 31; p > 50 ≤ 75% [CAC score = 101.0 (23.8-348.3)], n = 26; and p>75% [CAC score = 581.0 (148.0-1652)], n = 83). Upon multivariable multinomial logistic regression, patients with a narrower phase angle and patients who had received a graft from a deceased donor had a higher risk of being in the >75th CAC-percentile. CONCLUSIONS: This study identifies not only metabolic and transplant-related factors, but also phase angle, a composite marker of cell integrity, as an independent determinant of CAC at 12 months after kidney transplantation. This study offers new perspectives for future research into the value of bioelectrical impedance analysis in relation to vascular calcification in kidney transplant recipients.

Association of High-Density Lipoprotein Parameters and Risk of Heart Failure: A Multicohort Analysis.

BACKGROUND: High-density lipoprotein (HDL) is commonly characterized by its cholesterol concentration (HDL-C) and inverse association with atherosclerotic cardiovascular disease. OBJECTIVES: The authors sought to evaluate the association of HDL particle concentration (HDL-P), HDL particle size (HDL-size), HDL-C, and cholesterol content per particle (HDL-C/HDL-P) with risk of overall heart failure (HF) and subtypes. METHODS: Participants from the Atherosclerosis Risk In Communities Study, Dallas Heart Study, Multi-Ethnic Study of Atherosclerosis, and Prevention of Renal and Vascular End-stage Disease studies without HF history were included. Associations of HDL-P, HDL-size, HDL-C, and HDL-C/HDL-P with risk of overall HF, HF with reduced and preserved ejection fraction were assessed using adjusted Cox models. RESULTS: Among 16,925 participants (53.5% women; 21.8% Black), there were 612 incident HF events (3.6%) (HF with reduced ejection fraction, 309 [50.5%]; HF preserved ejection fraction, 303 [49.5%]) over median follow-up of 11.4 years. In adjusted models, higher HDL-P was significantly associated with lower HF risk (HR of highest vs lowest tertile of HDL-P: 0.76 [95% CI: 0.62-0.93]). Larger HDL-size was significantly associated with higher overall HF risk (HR of largest vs smallest tertile of HDL-size: 1.27 [95% CI: 1.03-1.58]). HF risk associated with HDL-P and HDL-size was similar for HF subtypes. In adjusted analyses, there was no significant association between HDL-C and HF risk. Higher HDL-C/HDL-P was significantly associated with higher overall HF risk (HR of highest vs lowest tertile of HDL-C/HDL-P: 1.29 [95% CI: 1.04-1.60]). CONCLUSIONS: Higher HDL-P was associated with a lower risk of HF. In contrast, larger HDL-size was associated with higher risk of HF and there was no significant association observed between HDL-C and HF risk after accounting for cardiovascular risk factors.

A Prospective Study of the Association Between Plasma Calprotectin Levels and New-Onset CKD in the General Population.

Introduction: Systemic inflammation has been associated with chronic kidney disease (CKD). In this study, we aimed to investigate a potential association between the plasma biomarker of inflammation calprotectin and new-onset CKD in a population-based cohort study. Methods: Individuals without CKD at baseline (n = 4662) who participated in the Prevention of REnal and Vascular ENd-stage Disease (PREVEND) prospective population-based cohort study in the Netherlands were included. Baseline plasma calprotectin levels were assessed in samples that had been stored at -80 °C. Occurrence of new-onset CKD was defined as a composite outcome of an estimated glomerular filtration rate (eGFR) <60 ml/min per 1.73 m2, urinary albumin excretion (UAE) >30 mg/24h, or both. Results: Baseline median (interquartile range) plasma calprotectin levels were 0.49 (0.35-0.68) mg/l and baseline median eGFR was 95.9 (interquartile range: 85.0-105.7) ml/min per 1.73 m2. After median follow-up of 8.3 (7.8-8.9) years, 467 participants developed new-onset CKD. Baseline plasma calprotectin levels were significantly associated with an increased risk of new-onset CKD (hazard ratio [HR] per doubling 1.28 [95% confidence interval, CI: 1.14-1.44], P < 0.001), independent of potentially confounding factors (HR 1.14 [95% CI: 1.01-1.29], P = 0.034), except for baseline high-sensitive C-reactive protein (hs-CRP) (HR 1.05 [0.91-1.21], P = 0.494). In secondary analyses, the association between plasma calprotectin and occurrence of UAE >30 mg/24h remained significant (HR 1.17 [1.02-1.34], P = 0.027), but not significantly so for the incidence of eGFR <60 ml/min per 1.73 m2 as individual outcome (HR 1.15 [0.92-1.43], P = 0.218). Conclusion: Higher plasma calprotectin levels are associated with an increased risk of developing CKD in the general population. This association is mitigated after adjustment for hs-CRP, and more pronounced with new-onset CKD defined by UAE.

The gut microbiome in end-stage lung disease and lung transplantation.

Gut dysbiosis has been associated with impaired outcomes in liver and kidney transplant recipients, but the gut microbiome of lung transplant recipients has not been extensively explored. We assessed the gut microbiome in 64 fecal samples from end-stage lung disease patients before transplantation and 219 samples from lung transplant recipients after transplantation using metagenomic sequencing. To identify dysbiotic microbial signatures, we analyzed 243 fecal samples from age-, sex-, and BMI-matched healthy controls. By unsupervised clustering, we identified five groups of lung transplant recipients using different combinations of immunosuppressants and antibiotics and analyzed them in relation to the gut microbiome. Finally, we investigated the gut microbiome of lung transplant recipients in different chronic lung allograft dysfunction (CLAD) stages and longitudinal gut microbiome changes after transplantation. We found 108 species (58.1%) in end-stage lung disease patients and 139 species (74.7%) in lung transplant recipients that were differentially abundant compared with healthy controls, with several species exhibiting sharp longitudinal increases from before to after transplantation. Different combinations of immunosuppressants and antibiotics were associated with specific gut microbial signatures. We found that the gut microbiome of lung transplant recipients in CLAD stage 0 was more similar to healthy controls compared to those in CLAD stage 1. Finally, the gut microbial diversity of lung transplant recipients remained lower than the average gut microbial diversity of healthy controls up to more than 20 years post-transplantation. Gut dysbiosis, already present before lung transplantation was exacerbated following lung transplantation.IMPORTANCEThis study provides extensive insights into the gut microbiome of end-stage lung disease patients and lung transplant recipients, which warrants further investigation before the gut microbiome can be used for microbiome-targeted interventions that could improve the outcome of lung transplantation.

Vitamin C deficiency after kidney transplantation: a cohort and cross-sectional study of the TransplantLines biobank.

PURPOSE: Vitamin C deficiency is associated with excess mortality in kidney transplant recipients (KTR). We aim to evaluate plasma vitamin C status at different post-transplantation moments and assess the main characteristics associated with vitamin C deficiency in KTR. METHODS: Plasma vitamin C was assessed in 598 KTR at 3-, 6-, 12-, 24-, and 60-months post-transplantation, 374 late KTR with a functioning graft ≥ 1 year, and 395 potential donors. Vitamin C deficiency was defined as plasma vitamin C ≤ 28 µmol/L. Diet was assessed by a 177-item food frequency questionnaire. Data on vitamin C-containing supplements use were extracted from patient records and verified with the patients. RESULTS: Vitamin C deficiency ranged from 46% (6-months post-transplantation) to 30% (≥ 1 year post-transplantation). At all time points, KTR had lower plasma vitamin C than potential donors (30-41 µmol/L vs 58 µmol/L). In cross-sectional analyses of the 953 KTR at their first visit ≥ 12 months after transplantation (55 ± 14 years, 62% male, eGFR 55 ± 19 mL/min/1.73 m2), the characteristics with the strongest association with vitamin C deficiency were diabetes and smoking (OR 2.67 [95% CI 1.84-3.87] and OR 1.84 [95% CI 1.16-2.91], respectively). Dietary vitamin C intake and vitamin C supplementation were associated with lower odds (OR per 100 mg/day 0.38, 95% CI 0.24-0.61 and OR 0.21, 95% CI 0.09-0.44, respectively). CONCLUSION: Vitamin C deficiency is frequent among KTR regardless of the time after transplantation, especially among those with diabetes and active smokers. The prevalence of vitamin C deficiency was lower among KTR with higher vitamin C intake, both dietary and supplemented. Further research is warranted to assess whether correcting this modifiable risk factor could improve survival in KTR.

Validity and diagnostic overlap of functional somatic syndrome diagnoses.

OBJECTIVE: We present the first study that investigates the validity and the diagnostic overlap of the three main functional somatic syndrome (FSS) diagnoses, i.e. chronic fatigue syndrome (CFS), fibromyalgia (FM), and irritable bowel syndrome (IBS), irrespective of help-seeking behaviour or diagnostic habits, and irrespective of differences in diagnostic thresholds for chronicity or symptom interference. METHODS: This cross-sectional analysis was performed in 89,781 participants of the general-population cohort Lifelines. Diagnostic criteria for CFS (Centers for Disease Control and Prevention), FM (American College of Rheumatology) and IBS (Rome IV) were assessed by questionnaire. Additional items were added to enable studying the effects of differences in thresholds for minimum symptom chronicity (varying from three for FM to six months for CFS and IBS), and symptom interference (required for CFS but not for FM and IBS). RESULTS: The diagnostic criteria were met by 3.1% for CFS, 6.6% for FM, and 5.5% for IBS participants. The number of participants that met criteria for all three diagnoses was 45 times higher than what would have been expected based on chance. After alignment of the chronicity and symptom interference criteria to circumvent differences in diagnostic thresholds, the overlap between diagnoses increased to 152 times. Furthermore, there was a similar pattern of symptom occurrence, particularly for those fulfilling diagnostic criteria for CFS and FM. CONCLUSION: The diagnostic overlap of different FSS was much higher than would be expected by chance, and substantially increased when FSS were more chronic and serious in nature.

Time-updated Fibroblast Growth Factor 23 Is Predictive for Posttransplant Diabetes Mellitus in Kidney Transplant Recipients.

Objective: This work aimed to study whether fibroblast growth factor 23 (FGF23) is predictive for incident posttransplant diabetes mellitus (PTDM) in kidney transplant recipients (KTRs). Methods: We repeatedly analyzed plasma C-terminal FGF23 concentrations in 170 KTRs enrolled in the TransplantLines Biobank and Cohort Study. Associations of time-updated plasma FGF23 with incident PTDM were studied by Cox regression. Results: A total of 170 KTRs (46% female, aged 54.4 ± 12.4 years) with 540 FGF23 measurements were included. Plasma FGF23 concentrations at transplantation were 31.1 (0.76-2576) pmol/L. During a follow-up of 24 (12-24) months, 38 patients developed PTDM. The highest FGF23 tertile (compared to the lowest) was associated with an increased risk for PTDM (fully adjusted hazard ratio 20.9; 95% CI, 3.4-130.0; P < .001). Conclusion: In KTRs without diabetes at baseline, the highest tertile of FGF23, compared to the lowest, is predictive for development of PTDM.

Kidney Transplantation Improves Health-Related Quality of Life in Older Recipients.

Kidney transplantation is the best treatment for kidney failure in older patients. However, little is known regarding changes in health-related quality of life (HRQoL) from before to after transplantation and determinants of HRQoL in older kidney transplant recipients (KTR). We studied both, using data of older (≥65 years) patients waitlisted for kidney transplantation and older KTR 1 year after transplantation from the TransplantLines Biobank and Cohort Study. HRQoL was assessed using the SF-36 questionnaire. We included 145 older waitlisted patients (68% male, age 70 ± 4 years) and 115 older KTR at 1 year after transplantation (73% male, age 70 ± 4 years). Both mental (48.5 ± 8.4 versus 51.2 ± 7.7, p = 0.009) and physical (47.4 ± 8.5 versus 52.1 ± 7.2, p < 0.001) HRQoL were higher among included KTR, compared to the waitlisted patients. In paired analyses among 46 patients with HRQoL-data both before and after transplantation, there was a trend towards increased mental HRQoL (49.1 ± 8.4 to 51.6 ± 7.5, p = 0.054), and significantly increased physical HRQoL (48.1 ± 8.0 to 52.4 ± 6.7, p = 0.001) after transplantation. Among all assessed factors, the number of patient-reported immunosuppressive drug-related side effects was most strongly negatively associated with both mental and physical HRQoL. In conclusion, HRQoL is significantly higher among older KTR after kidney transplantation compared to older waitlisted patients.

Serum T50 predicts cardiovascular mortality in individuals with type 2 diabetes: A prospective cohort study.

BACKGROUND AND AIMS: Individuals with type 2 diabetes (T2D) have a higher risk of cardiovascular disease, compared with those without T2D. The serum T50 test captures the transformation time of calciprotein particles in serum. We aimed to assess whether serum T50 predicts cardiovascular mortality in T2D patients, independent of traditional risk factors. METHODS: We analyzed 621 individuals with T2D in this prospective cohort study. Cox regression models were performed to test the association between serum T50 and cardiovascular and all-cause mortality. Causes of death were categorized according to ICD-10 codes. Risk prediction improvement was assessed by comparing Harrell's C for models without and with T50. RESULTS: The mean age was 64.2 ± 9.8 years, and 61% were male. The average serum T50 time was 323 ± 63 min. Higher age, alcohol use, high-sensitive C-reactive protein, and plasma phosphate were associated with lower serum T50 levels. Higher plasma triglycerides, venous bicarbonate, sodium, magnesium, and alanine aminotransferase were associated with higher serum T50 levels. After a follow-up of 7.5[5.4-10.7] years, each 60 min decrease in serum T50 was associated with an increased risk of cardiovascular (fully adjusted HR 1.32, 95% CI 1.08-1.50, and p = 0.01) and all-cause mortality (HR 1.15, 95%CI 1.00-1.38, and p = 0.04). Results were consistent in sensitivity analyses after exclusion of individuals with estimated glomerular filtration rate <45 or <60 mL/min/1.73 m2 and higher plasma phosphate levels. CONCLUSIONS: Serum T50 improves prediction of cardiovascular and all-cause mortality risk in individuals with T2D. Serum T50 may be useful for risk stratification and to guide therapeutic strategies aiming to reduce cardiovascular mortality in T2D.