The presence of diabetes mellitus further impairs structural and functional capillary density in patients with chronic kidney disease.

OBJECTIVE: Endothelial dysfunction has been associated with increased cardiovascular events and overall mortality. Microvascular damage is prevalent both in diabetes mellitus (DM) and chronic kidney disease (CKD). Our aim was to compare microcirculatory function parameters in diabetic and non-diabetic CKD patients via nailfold video-capillaroscopy. METHODS: We included 48 diabetic and 48 non-diabetic adult CKD patients. All participants underwent nailfold video-capillaroscopy, during which capillary density was measured at normal conditions (baseline), after a 4-minute arterial occlusion (postocclusive reactive hyperemia), and at the end of a 2-minute venous occlusion (congestion phase). RESULTS: Diabetic patients presented significantly lower capillary density during reactive hyperemia (36.3 ± 3.8 vs 38.3 ± 4.3 capillaries/mm2 , P = .022) and at venous congestion (37.8 ± 4.0 vs 39.8 ± 4.2 capillaries/mm2 , P = .015). When stratified according to CKD stages, only in stage 3b capillary density was significantly lower in diabetic compared to non-diabetic subjects at baseline, during postocclusive hyperemia (36.8 ± 2.7 vs 40.0 ± 4.3 capillaries/mm2 , P = .037) and venous congestion (38.3 ± 2.8 vs 41.5 ± 3.5 capillaries/mm2 , P = .022). CONCLUSIONS: Capillary density during postocclusive hyperemia and after venous congestion is lower in diabetic compared to non-diabetic CKD patients, a finding indicative that diabetes is an additional factor contributing to microcirculatory structural and functional impairment in CKD. These differences are more prominent in CKD stage 3b.

Assessment of Endothelial and Microvascular Function in CKD: Older and Newer Techniques, Associated Risk Factors, and Relations with Outcomes.

BACKGROUND: Endothelium is the inner cellular lining of the vessels that modulates multiple biological processes including vasomotor tone, permeability, inflammatory responses, hemostasis, and angiogenesis. Endothelial dysfunction, the basis of atherosclerosis, is characterized by an imbalance between endothelium-derived relaxing factors and endothelium-derived contracting factors. SUMMARY: Starting from the semi-invasive venous occlusion plethysmography, several functional techniques have been developed to evaluate microvascular function and subsequently used in patients with CKD. Flow-mediated dilatation of the forearm is considered to be the "gold standard," while in the last years, novel, noninvasive methods such as laser speckle contrast imaging and near-infrared spectroscopy are scarcely used. Moreover, several circulating biomarkers of endothelial function have been used in studies in CKD patients. This review summarizes available functional methods and biochemical markers for the assessment of endothelial and microvascular function in CKD and discusses existing evidence on their associations with comorbid conditions and outcomes in this population. Key Messages: Accumulated evidence suggests that endothelial dysfunction occurs early in CKD and is associated with target organ damage, progression of renal injury, cardiovascular events, and mortality. Novel methods evaluating microvascular function can offer a detailed, real-time assessment of underlying phenomena and should be increasingly used to shed more light on the role of endothelial dysfunction on cardiovascular and renal disease progression in CKD.

Ambulatory Blood Pressure Trajectories and Blood Pressure Variability in Diabetic and Non-Diabetic Chronic Kidney Disease.

BACKGROUND: Diabetic kidney disease is the leading cause of end-stage renal disease worldwide. Whether diabetes mellitus (DM) is an additional factor leading to elevated blood pressure (BP) levels and BP variability (BPV) in patients with chronic kidney disease (CKD) is unknown. This study aimed to compare ambulatory BP levels, BP trends and BPV in diabetic and non-diabetic patients with CKD. METHODS: This study included 48 diabetic and 48 non-diabetic adult patients (>18 years) with CKD (estimated glomerular filtration rate [eGFR] <90 and ≥15 mL/min/1.73 m2), matched in a 1:1 ratio for age, sex and eGFR within each CKD stage (2, 3a, 3b and 4). All patients underwent 24-h ambulatory BP measurement with the Mobil-O-graph device. To evaluate the effect of DM and time on the trajectories of 24-h BP levels, we performed two-way mixed ANOVA analysis for repeated measurements using hourly means. BPV was calculated with validated formulas. RESULTS: In total, patients with DM had significantly higher 24-h systolic BP (SBP; 132.13 ± 10.71 vs. 124.16 ± 11.45; p = 0.001) and pulse pressure (PP; 57.1 ± 9.6 vs. 49.5 ± 10.9; p < 0.001), but similar 24-h diastolic BP (DBP; 75.00 ± 8.43 vs. 74.62 ± 6.86 mm Hg; p = 0.809) compared to patients without DM. A similar trend was evident across all CKD stages. The effect of DM on BP trajectories during the recording period was significant for SBP (F = 18.766, p < 0.001, partial η2 = 0.261) and marginally significant for DBP (F = 3.782, p = 0.057, partial η2 = 0.067). Twenty-four hour SBP SD, weighted SD (wSD) and average real variability (ARV; 10.94 ± 2.75 vs. 9.46 ± 2.10; p = 0.004), as well as 24 h DBP SD, wSD, coefficient of variation (CV) and ARV (8.23 ± 2.10 vs. 7.10 ± 1.33; p = 0.002) were significantly higher in diabetic compared to non-diabetic CKD patients. CONCLUSIONS: Ambulatory SBP and PP levels are higher and SBP-profile is different in patients with diabetic compared to those with non-diabetic CKD. Systolic and diastolic BPV are also higher in diabetics. These findings may signify a higher cardiovascular risk for patients with both DM and CKD compared to patients with CKD alone, through higher BP levels and BPV.

Antioxidation improves in puberty in normal weight and obese boys, in positive association with exercise-stimulated growth hormone secretion.

BACKGROUND: Oxidative stress is associated with obesity while the evidence for the role of GH in pro- and antioxidation is inconclusive. This study investigates the relationships between growth hormone (GH), pro- and antioxidation in relation to obesity and puberty before and after an acute bout of exercise. METHODS: In this case-control study, 76 healthy normal-weight and obese, prepubertal and pubertal boys underwent a blood sampling before and immediately after an aerobic exercise bout until exhaustion at 70% maximal oxygen consumption. Markers of prooxidation (thiobarbituric acid reactive substances (TBARS) and protein carbonyls (PCs)) and antioxidation (glutathione (GSH), oxidized glutathione disulfide (GSSG), GSH/GSSG ratio, glutathione peroxidase (GPX), catalase, and total antioxidant capacity (TAC)) and hormones (GH, insulin-like growth factor (IGF)-1, IGF-BP-3, luteinizing hormone, follicle-stimulating hormone, and testosterone) were measured. RESULTS: Baseline and postexercise TBARS and PCs were greater, while baseline GSH, GSH/GSSG ratio, GPX, and TAC were lower in obese than that in normal-weight participants. In all participants, waist was the best negative and positive predictor for postexercise GPX and TBARS, respectively. Baseline TAC was greater in pubertal than that in pre-pubertal participants. In all participants, baseline GH was the best negative predictor for postexercise PCs. Significant positive linear correlation exists between the exercise-associated GH, and GSSG increases in pubertal normal-weight boys. CONCLUSIONS: Higher prooxidation and lower antioxidation were observed in obese boys, while antioxidation improves with puberty and postexercise, paralleling GH accentuated secretion.

Microcirculatory function deteriorates with advancing stages of chronic kidney disease independently of arterial stiffness and atherosclerosis.

Cardiovascular disease is the main cause of mortality in chronic kidney disease (CKD). Endothelial dysfunction and capillary rarefaction are established cardiovascular risk factors. Nailfold video capillaroscopy provides a thorough assessment of capillary density and functional reserve. This study aimed to examine possible differences in structural and functional capillary density in CKD stages 2-4 with nailfold video capillaroscopy. Ninety-six CKD patients, divided into four equally sized groups according to CKD stage (2, 3a, 3b, 4), underwent nailfold video capillaroscopy, during which capillary density was measured at baseline, after 4-min arterial occlusion and after 2-min venous occlusion. Arterial stiffness and wave parameters were measured with applanation tonometry and common carotid intima-media thickness (ccIMT) with ultrasound. Baseline capillary density showed a progressive reduction with advancing CKD stages (stage 2: 32.6 ± 2.8, stage 3a: 31.2 ± 3.8, stage 3b: 32.5 ± 3.3, stage 4: 28.5 ± 3.1, p = 0.011). Similar reductions were observed during postocclusive hyperemia (39.4 ± 3.0, 37.6 ± 4.2, 38.4 ± 3.8, and 33.8 ± 3.3, respectively; p = 0.021) and after venous congestion (41.1 ± 3.1, 39.0 ± 4.4, 39.9 ± 3.5, and 35.2 ± 3.4; p = 0.032). Office PWV and ccIMT showed nonsignificant increasing trends with advancing CKD. In multivariate analysis, eGFR showed a positive association (per ml/min increase; ß: 0.053, 95% CI: 0.004-0.101), whereas diabetes (ß: -1.706, 95% CI: -3.176 to -0.236) and parathyroid hormone (PTH) (per pg/ml increase; ß: -0.022, 95% CI: -0.036 to -0.008) had negative associations with postocclusive capillary density. Both structural and functional capillary density progressively decrease with advancing CKD stages. Apart from reduced eGFR, diabetes and increased PTH levels are independently associated with this reduction. This capillary rarefaction may largely contribute to the increased cardiovascular risk of CKD patients.

Comparison of ambulatory central hemodynamics and arterial stiffness in patients with diabetic and non-diabetic CKD.

Increased arterial stiffness is independently associated with renal function decline in patients with diabetes mellitus (DM). Whether DM has additional deleterious effects on central hemodynamics and arterial stiffness in chronic kidney disease (CKD) patients is yet unknown. This study aimed to compare ambulatory central BP, arterial stiffness parameters, and trajectories between patients with diabetic and non-diabetic CKD. This study examined 48 diabetic and 48 non-diabetic adult patients (>18 years) with CKD (eGFR: <90 and ≥15 ml/min/1.73 m2 ), matched in a 1:1 ratio for age, sex, and eGFR within CKD stages (2, 3a, 3b and 4). All patients underwent 24-h ABPM with the Mobil-O-Graph device. Parameters of central hemodynamics [central systolic (cSBP) and diastolic blood pressure (cDBP), pulse pressure (PP)], wave reflection [augmentation index (AIx), and pressure (AP)] and pulse wave velocity (PWV) were estimated from the 24-h recordings. Diabetic CKD patients had higher 24-h cSBP (118.57 ± 10.05 vs. 111.59 ± 9.46, P = .001) and 24-h cPP (41.48 ± 6.80 vs. 35.25 ± 6.98, P < .001) but similar 24-h cDBP (77.09 ± 8.14 vs. 76.34 ± 6.75 mmHg, P = .625) levels compared to patients with non-diabetic CKD. During day- and nighttime periods, cSBP and cPP levels were higher in diabetics compared to non-diabetics. 24-h PWV (10.10 ± 1.62 vs. 9.61 ± 1.80 m/s, P = .165) was numerically higher in patients with DM, but no between-group differences were noted in augmentation pressure and index. In multivariate analysis, DM, female gender, and peripheral SBP were independently associated with higher cPP levels. Patients with diabetic CKD have higher ambulatory cSBP and increased arterial stiffness, as indicated by higher ambulatory cPP. These finding suggest that DM is a factor independently contributing to the adverse macrocirculatory profile of CKD patients.

Ambulatory blood pressure profile and blood pressure variability in peritoneal dialysis compared with hemodialysis and chronic kidney disease patients.

Hypertension in end-stage renal disease patients is highly prevalent and poorly controlled. Data on the ambulatory blood pressure (BP) profile and BP variability (BPV) in peritoneal dialysis (PD) patients are absent. This study examined the BP profile and BPV of patients undergoing PD in comparison with hemodialysis (HD) and predialysis chronic kidney disease CKD patients. Thirty-eight PD patients were matched for age, sex, and dialysis vintage with 76 HD patients and for age and sex with 38 patients with CKD stage 2-4. Patients under PD or HD underwent 48-h and CKD patients 24-h ambulatory BP monitoring. BP levels and BPV indices were compared for the 48-h, first and second 24 h, daytime and nighttime periods. Two-way mixed ANOVA for repeated measurements was used to evaluate the effects of dialysis modality and time on ambulatory BP in PD and HD. During all periods studied, SBP and DBP were numerically higher but not significantly different in PD than in HD patients. Systolic BP was significantly higher in PD or HD than in predialysis CKD (PD: 138.38 ± 20.97 mmHg; HD: 133.75 ± 15.5 mmHg; CKD: 125.52 ± 13.4 mmHg, p = 0.003), a difference evident also during daytime and nighttime periods. Repeated-measurements ANOVA showed no effect of dialysis modality on ambulatory BP during any period studied. All BPV indices studied were similar between PD and HD patients, in whom they were higher than in CKD individuals (first 24-h systolic-ARV: PD: 11.86 ± 3.19 mmHg; HD: 11.23 ± 3.45 mmHg; CKD: 9.81 ± 2.49 mmHg, p = 0.016). Average BP levels and BPV indices are similar between PD and HD patients, in whom they are higher than in their CKD counterparts. The dialysis modality has no effect on the ambulatory BP profile. These results suggest that PD is no better than HD with regard to overall BP control or BP fluctuations over time.

Child Morbidity and Disease Burden in Refugee Camps in Mainland Greece.

The crisis conflicts in Syria have forced a lot of people to relocate and live in mainland Greece, where they are hosted in refugee camps. In the present study, our aim was to assess child morbidity and overall disease burden in two camps in northern Greece during a six-month winter period. A primary health care office was founded in each camp. Refugees of all ages with health problems were examined daily by specialty doctors. Cases were classified into two categories: Infectious or non-infectious. In total, 2631 patients were examined during this period (out of the 3760 refugees hosted). Of these patients, 9.8% were infants, 12.7% were toddlers, and 13.4% were children. Most of the visits for children aged less than 12 years old were due to infectious diseases (80.8%). The most common sites of communicable diseases among children were the respiratory tract (66.8%), the skin (23.2%), and the urinary (3.2%) and gastrointestinal tracts (6.2%). Non-communicable diseases were mostly due to gastrointestinal (20.2%), respiratory (18.2%), surgical (13.1%), and allergic (10.3%) disorders. Infants, toddlers, and children suffered more frequently from respiratory infections, while in adolescents and adults, non-infectious diseases were more common. Toddlers and children were more likely to fall ill in comparison to infants. Conclusions: During the winter period, infectious diseases, especially of the respiratory tract, are the main reason for care seeking among refugees in Greek camps, with toddlers suffering more than other age groups. The overall mortality and referral percentage were low, indicating that adequate primary care is provided in this newly established refugee hosting model.

Interrelations among the adipocytokines leptin and adiponectin, oxidative stress and aseptic inflammation markers in pre- and early-pubertal normal-weight and obese boys.

PURPOSE: Presumed interrelationships among deleterious aspects of adipose tissue metabolism, inflammation, and cellular oxidative stress could be influenced by pubertal hormonal changes. They were investigated in pre- and early pubertal normal-weight and obese boys before and after an exercise bout employed as an energy demanding stimulator. METHODS: Cross-sectional study. Seventy-six healthy pre- (mean ± SD, 10.6 ± 0.2 years old, 28 normal-weight, and 11 obese) and early-(11.4 ± 0.2 years old, 25 normal-weight, and 12 obese) pubertal boys, were blood-sampled before and after a bout of exercise at 70% VO2 max. Leptin, adiponectin, markers of inflammation (high-sensitivity C-reactive protein, high sensitivity IL-6), pro- (thiobarbitouric acid reactive substances, protein carbonyls) and anti- (glutathione, oxidized glutathione, glutathione peroxidase, catalase, total antioxidant capacity) oxidation were measured. RESULTS: Baseline and post-exercise adiponectin was greater and leptin and high-sensitivity C-reactive protein were lower in normal-weight than in obese pre- and early pubertal boys, while high sensitivity IL-6 was greater in obese than in normal-weight pre-pubertal boys. In pre-pubertal obese boys: at baseline, high-sensitivity C-reactive protein correlated negatively with catalase; high sensitivity IL-6 correlated positively with protein carbonyls; Δ (difference during exercise) adiponectin correlated positively with Δcatalase. In all boys: at baseline, high sensitivity IL-6 correlated positively with leptin and was the best negative and the second best positive predictor for post-exercise glutathione/oxidized glutathione and protein carbonyls, respectively; leptin was the best negative predictor for post-exercise glutathione; waist to height ratio was the best positive predictor for post-exercise thiobarbitouric acid reactive substances; body mass index z-score and adiponectin were, respectively, the best positive predictor for post-exercise protein carbonyls and catalase. CONCLUSIONS: In all subjects, leptin and adiponectin predict negatively and positively anti-oxidation, respectively, while high sensitivity IL-6 predicts positively and negatively pro- and anti-oxidation, respectively. High-sensitivity C-reactive protein is increased and negatively associated with anti-oxidation in pre-pubertal obese boys, suggesting that childhood obesity is associated with aseptic inflammation and oxidative stress.