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COVID-19 is an ongoing global pandemic. There is an urgent need for identification and understanding of clinical and laboratory parameters related to progression towards a severe and fatal form of this illness, often preceded by a so-called cytokine-storm syndrome (CSS). Therefore, we explored the hemocytometric characteristics of COVID-19 patients in relation to the deteriorating clinical condition CSS, using the Sysmex XN-10 hematology analyzer. From March 1st till May 16th, 2020, all patients admitted to our hospital with respiratory complaints and suspected for COVID-19 were included (n=1,140 of whom n=533 COVID-19 positive). The hemocytometric parameters of immunocompetent cells in peripheral blood (neutrophils [NE], lymphocytes [LY] and monocytes [MO]) obtained upon admission to the emergency department (ED) of COVID-19 positive patients were compared with those of the COVID-19 negative ones. Moreover, patients with CSS (n=169) were compared with COVID-19 positive patients without CSS, as well as with COVID-19 negative ones. In addition to a significant reduction in leukocytes, thrombocytes and absolute neutrophils, it appeared that lymphocytes-forward scatter (LY-FSC), and reactive lymphocytes (RE-LYMPHO)/leukocytes were higher in COVID-19-positive than negative patients. At the moment of presentation, COVID-19 positive patients with CSS had different neutrophils-side fluorescence (NE-SFL), neutrophils-forward scatter (NE-FSC), LY-FSC, RE-LYMPHO/lymphocytes, antibody-synthesizing (AS)-LYMPHOs, high fluorescence lymphocytes (HFLC), MO-SSC, MO-SFL, and Reactive (RE)-MONOs. Finally, absolute eosinophils, basophils, lymphocytes, monocytes and MO-FSC were lower in patients with CSS. Hemocytometric parameters indicative of changes in immunocompetent peripheral blood cells and measured at admission to the ED were associated with COVID-19 with and without CSS. [ABSTRACT FROM AUTHOR]

Background End-stage renal disease (ESRD) is strongly associated with cardiovascular disease (CVD) risk. Advanced glycation endproducts (AGEs) and dicarbonyls, major precursors of AGEs, may contribute to the pathophysiology of CVD in ESRD. However, detailed data on the courses of AGEs and dicarbonyls during the transition of ESRD patients to renal replacement therapy are lacking. Methods We quantified an extensive panel of free and protein-bound serum AGEs [ N ∈-(carboxymethyl)lysine (CML), N ∈-(carboxyethyl)lysine (CEL), N δ-(5-hydro-5-methyl-4-imidazolon-2-yl)ornithine (MG-H1)], serum dicarbonyls [glyoxal (GO), methylglyoxal (MGO), 3-deoxyglucosone (3-DG)] and tissue AGE accumulation [estimated by skin autofluorescence (SAF)] in a combined cross-sectional and longitudinal observational study of patients with ESRD transitioning to dialysis or kidney transplantation (KTx), prevalent dialysis patients and healthy controls. Cross-sectional comparisons were performed with linear regression analyses, and courses following renal replacement therapy were analysed with linear mixed models. Results Free and protein-bound AGEs, dicarbonyls and SAF were higher in chronic kidney disease (CKD) Stage 5 non-dialysis (CKD 5-ND; n = 52) and CKD Stage 5 dialysis (CKD 5-D; n = 35) than in controls (n  = 42). In addition, free AGEs, protein-bound CML, GO and SAF were even higher in CKD 5-D than in CKD5-ND. Similarly, following dialysis initiation (n  = 43) free and protein-bound AGEs, and GO increased, whereas SAF remained similar. In contrast, following KTx (n  = 21), free and protein-bound AGEs and dicarbonyls, but not SAF, markedly declined. Conclusions AGEs and dicarbonyls accumulate in uraemia, which is even exaggerated by dialysis initiation. In contrast, KTx markedly reduces AGEs and dicarbonyls. Given their associations with CVD risk in high-risk populations, lowering AGE and dicarbonyl levels may be valuable. [ABSTRACT FROM AUTHOR]

Background: Depression is common in individuals with chronic kidney disease (CKD). However, data on the association of albuminuria, which together with reduced estimated glomerular filtration rate (eGFR) defines CKD, with depression are scarce and conflicting. In addition, it is not clear when in the course from normal kidney function to CKD the association with depression appears., Methods: We examined the cross-sectional associations of albuminuria and eGFR with depressive symptoms and depressive episodes in 2872 and 3083 40- to 75-year-old individuals, respectively, who completed the baseline survey of an ongoing population-based cohort study conducted in the southern part of The Netherlands between November 2010 and September 2013. Urinary albumin excretion (UAE) was the average UAE in two 24-h urine collections and eGFR was calculated with the Chronic Kidney Disease Epidemiology Collaboration equation based on creatinine and cystatin C. Depressive symptoms were assessed with the 9-item Patient Health Questionnaire (PHQ-9) and the presence of a minor or major depressive episode was assessed with the MINI-International Neuropsychiatric Interview., Results: In total, 5.4% had a minor or major depressive episode. UAE was <15 mg/24 h in 81.2%, 15-<30 mg/24 h in 10.3% and ≥30 mg/24 h in 8.6%. In a multivariable logistic regression analysis adjusted for potential confounders, and with UAE <15 mg/24 h as reference category, the odds ratio for a minor or major depressive episode was 2.13 [95% confidence interval (CI) 1.36-3.36] for UAE 15-<30 mg/24 h and 1.81 (95% CI 1.10-2.98) for UAE ≥30 mg/24 h. The average eGFR was 88.2 ± 14.7 mL/min/1.73 m2. eGFR was not associated with the presence of a minor or major depressive episode. Results were similar when we assessed associations with depressive symptoms or clinically relevant depressive symptoms (PHQ-9 score ≥10)., Conclusions: Albuminuria was associated with depressive symptoms and depressive episodes, even at levels of UAE that do not fulfil the CKD criteria. Future longitudinal studies should examine the direction of this association and whether albuminuria could serve as a biomarker to identify individuals at risk of depression., (© The Author 2016. Published by Oxford University Press on behalf of ERA-EDTA. All rights reserved.)

Microvascular dysfunction (MVD) is considered a crucial pathway in the development and progression of cardiometabolic and renal disease and is associated with increased cardiovascular mortality. MVD often coexists with or even precedes macrovascular disease, possibly due to shared mechanisms of vascular damage, such as inflammatory processes and oxidative stress. One of the first events in MVD is endothelial dysfunction. With the use of different physiologic or pharmacologic stimuli, endothelium-dependent (micro)vascular reactivity can be studied. This reactivity depends on the balance between various mediators, including nitric oxide, endothelin, and prostanoids, among others. The measurement of microvascular (endothelial) function is important to understand the pathophysiologic mechanisms that contribute to MVD and the role of MVD in the development and progression of cardiometabolic/renal disease. Here, we review a selection of direct, noninvasive techniques for measuring human microcirculation, with a focus on methods, interpretation, and limitations from the perspective of chronic cardiometabolic and renal disease., (Copyright © 2017 by the American Society of Nephrology.)

Background: Reduced estimated glomerular filtration rate (eGFR) and albuminuria have been associated with worse cognitive performance. However, few studies have examined whether these associations are confined to older individuals or may be extended to the middle-aged population., Study Design: Cross-sectional analyses of a prospective population-based cohort study., Setting & Participants: 2,987 individuals aged 40 to 75 years from the general population (The Maastricht Study)., Predictor: eGFR and urinary albumin excretion (UAE)., Outcomes: Memory function, information processing speed, and executive function., Measurements: Analyses were adjusted for demographic variables (age, sex, and educational level), lifestyle factors (smoking behavior and alcohol consumption), depression, and cardiovascular disease risk factors (glucose metabolism status, waist circumference, total to high-density lipoprotein cholesterol ratio, triglyceride level, use of lipid-modifying medication, systolic blood pressure, use of antihypertensive medication, and prevalent cardiovascular disease)., Results: UAE was <15mg/24 h in 2,439 (81.7%) participants, 15 to <30 mg/24 h in 309 (10.3%), and ≥30mg/24 h in 239 (8.0%). In the entire study population, UAE≥30mg/24 h was associated with lower information processing speed as compared to UAE<15mg/24 h (β [SD difference] = -0.148; 95% CI, -0.263 to -0.033) after full adjustment, whereas continuous albuminuria was not. However, significant interaction terms (P for interaction < 0.05) suggested that albuminuria was most strongly and extensively associated with cognitive performance in older individuals. Mean (±SD) eGFR, estimated by the CKD-EPI (Chronic Kidney Disease Epidemiology Collaboration) creatinine-cystatin C equation (eGFR cr-cys ), was 88.4±14.6 mL/min/1.73m 2 . eGFR cr-cys was not associated with any of the domains of cognitive performance after full adjustment. However, significant interaction terms (P for interaction < 0.05) suggested that eGFR cr-cys was associated with cognitive performance in older individuals., Limitations: Cross-sectional design, which limited causal inferences., Conclusions: In the entire study population, albuminuria was independently associated with lower information processing speed, whereas eGFR cr-cys was not associated with cognitive performance. However, both were more strongly and extensively associated with cognitive performance in older individuals., (Copyright © 2016 National Kidney Foundation, Inc. Published by Elsevier Inc. All rights reserved.)

Objectives: Physical inactivity in end-stage renal disease (ESRD) patients is associated with increased mortality, and might be related to abnormalities in body composition (BC) and physical performance. It is uncertain to what extent starting dialysis influences the effects of ESRD on physical activity (PA). This study aimed to compare PA and physical performance between stage 5 chronic kidney disease (CKD-5) non-dialysis and dialysis patients, and healthy controls, to assess alterations in PA during the transition from CKD-5 non-dialysis to dialysis, and to relate PA to BC., Methods: For the cross-sectional analyses 44 CKD-5 non-dialysis patients, 29 dialysis patients, and 20 healthy controls were included. PA was measured by the SenseWear™ pro3. Also, the walking speed and handgrip strength (HGS) were measured. BC was measured by the Body Composition Monitor©. Longitudinally, these parameters were assessed in 42 CKD-5 non-dialysis patients (who were also part of the cross-sectional analysis), before the start of dialysis and 6 months thereafter., Results: PA was significantly lower in CKD-5 non-dialysis patients as compared to that in healthy controls but not as compared to that in dialysis patients. HGS was significantly lower in dialysis patients as compared to that in healthy controls. Walking speed was significantly lower in CKD-5 non-dialysis patients as compared to that in healthy controls but not as compared to that in dialysis patients. Six months after starting dialysis, activity related energy expenditure (AEE) and walking speed significantly increased., Conclusions: PA is already lower in CKD-5 non-dialysis patients as compared to that in healthy controls and does not differ from that of dialysis patients. However, the transition phase from CKD-5 non-dialysis to dialysis is associated only with a modest improvement in AEE., (© 2017 The Author(s) Published by S. Karger AG, Basel.)

Albuminuria may be a biomarker of generalized (i.e., microvascular and macrovascular) endothelial dysfunction. According to this concept, endothelial dysfunction of the renal microcirculation causes albuminuria by increasing glomerular capillary wall permeability and intraglomerular pressure, the latter eventually leading to glomerular capillary dropout (rarefaction) and further increases in intraglomerular pressure. However, direct evidence for an association between capillary rarefaction and albuminuria is lacking. Therefore, we examined the cross-sectional association between the recruitment of capillaries after arterial occlusion (capillary density during postocclusive peak reactive hyperemia) and during venous occlusion (venous congestion), as assessed with skin capillaroscopy, and albuminuria in 741 participants of the Maastricht Study, including 211 participants with type 2 diabetes. Overall, 57 participants had albuminuria, which was defined as a urinary albumin excretion ≥30 mg/24 h. After adjustment for potential confounders, participants in the lowest tertile of skin capillary recruitment during postocclusive peak reactive hyperemia had an odds ratio for albuminuria of 2.27 (95% confidence interval, 1.07 to 4.80) compared with those in the highest tertile. Similarly, a comparison between the lowest and the highest tertiles of capillary recruitment during venous congestion yielded an odds ratio of 2.89 (95% confidence interval, 1.27 to 6.61) for participants in the lowest tertile. In conclusion, lower capillary density of the skin microcirculation independently associated with albuminuria, providing direct support for a role of capillary rarefaction in the pathogenesis of albuminuria., (Copyright © 2016 by the American Society of Nephrology.)

Objectives: The assessment of body composition (BC) in dialysis patients is of clinical importance given its role in the diagnosis of malnutrition and sarcopenia. Bioimpedance techniques routinely express BC as a 2-compartment (2-C) model distinguishing fat mass (FM) and fat-free mass (FFM), which may be influenced by the hydration of adipose tissue and fluid overload (OH). Recently, the BC monitor was introduced which applies a 3-compartment (3-C) model, distinguishing OH, adipose tissue mass, and lean tissue mass. The aim of this study was to compare BC between the 2-C and 3-C models and assess their relation with markers of functional performance (handgrip strength [HGS] and 4-m walking test), as well as with biochemical markers of nutrition., Methods: Forty-seven dialysis patients (30 males and 17 females) (35 hemodialysis, 12 peritoneal dialysis) with a mean age of 64.8 ± 16.5 years were studied. 3-C BC was assessed by BC monitor, whereas the obtained resistivity values were used to calculate FM and FFM according to the Xitron Hydra 4200 formulas, which are based on a 2-C model., Results: FFM (3-C) was 0.99 kg (95% confidence interval [CI], 0.27 to 1.71, P = .008) higher than FFM (2-C). FM (3-C) was 2.43 kg (95% CI, 1.70-3.15, P < .001) lower than FM (2-C). OH was 1.4 ± 1.8 L. OH correlated significantly with ΔFFM (FFM 3-C - FFM 2-C) (r = 0.361; P < .05) and ΔFM (FM 3-C - FM 2-C) (r = 0.387; P = .009). HGS correlated significantly with FFM (2-C) (r = 0.713; P < .001), FFM (3-C) (r = 0.711; P < .001), body cell mass (2-C) (r = 0.733; P < .001), and body cell mass (3-C) (r = 0.767; P < .001). Both physical activity (r = 0.456; P = .004) and HGS (r = 0.488; P = .002), but not BC, were significantly related to walking speed., Conclusions: Significant differences between 2-C and 3-C models were observed, which are partly explained by the presence of OH. OH, which was related to ΔFFM and ΔFM of the 2-C and 3-C models, is therefore an important parameter for the differences in estimation of BC parameters of the 2-C and 3-C models. Both FFM (3-C) and FFM (2-C) were significantly related to HGS. Bioimpedance, HGS, and the 4-m walking test may all be valuable tools in the multidimensional nutritional assessment of both hemodialysis and peritoneal dialysis patients., (Copyright © 2015 National Kidney Foundation, Inc. Published by Elsevier Inc. All rights reserved.)

Background: Cerebral small vessel disease is thought to result from endothelial dysfunction. The glycocalyx, lining the endothelium, is a major determinant of endothelial function. The glycocalyx is partially accessible to flowing red blood cells at its luminal side, called the perfused boundary region (PBR). Glycocalyx damage results in increased PBR, which can be measured in the sublingual microvasculature. We tested whether PBR is increased in patients with cerebral small vessel disease, i.e. lacunar stroke patients, and further distinguished patients with presence of white matter lesions as a sign of extensive cerebral small vessel disease., Methods: We used sidestream dark field imaging of the sublingual microcirculation in 31 lacunar stroke patients (6 with and 25 without white matter lesions) and 19 healthy controls. In each subject, automatic image analyzing software analyzed PBR in more than 3,000 vessel segments and the average dimension of glycocalyx PBR was determined in vessel segments with a diameter of 5-25 μm., Results: PBR did not differ between lacunar stroke patients and healthy controls (2.10 ± 0.25 vs. 2.08 ± 0.24 μm, p = 0.8). However, lacunar stroke patients with white matter lesions had an increased PBR compared with both healthy controls (2.35 ± 0.23 vs. 2.08 ± 0.24 μm, p = 0.03) and patients without white matter lesions (2.04 ± 0.22 μm, p = 0.004)., Conclusions: White matter lesions are associated with an increase in the red blood cell permeable part of the sublingual microvascular glycocalyx in lacunar stroke patients. This implicates compromised glycocalyx barrier properties, which is consistent with impaired endothelial function in lacunar stroke patients with white matter lesions., (Copyright © 2013 S. Karger AG, Basel.)