Differences in the Profile of Circulating Immune Cell Subsets in Males with Type 2 Cardiorenal Syndrome versus CKD Patients without Established Cardiovascular Disease.

Maladaptive activation of the immune system plays a key role in the pathogenesis of chronic kidney disease (CKD). Our aim was to investigate differences in circulating immune cells between type 2 cardiorenal syndrome (CRS-2) patients and CKD patients without cardiovascular disease (CVD). CRS-2 patients were prospectively followed up, with the primary endpoint being all-cause and cardiovascular mortality. METHOD: A total of 39 stable males with CRS-2 and 24 male CKD patients matched for eGFR (CKD-EPI) were enrolled. A selected panel of immune cell subsets was measured by flow cytometry. RESULTS: Compared to CKD patients, CRS-2 patients displayed higher levels of proinflammatory CD14++CD16+ monocytes (p = 0.04) and T regulatory cells (Tregs) (p = 0.03), lower lymphocytes (p = 0.04), and lower natural killer cells (p = 0.001). Decreased lymphocytes, T-lymphocytes, CD4+ T-cells, CD8+ T-cells, Tregs, and increased CD14++CD16+ monocytes were associated with mortality at a median follow-up of 30 months (p < 0.05 for all). In a multivariate model including all six immune cell subsets, only CD4+ T-lymphocytes remained independent predictors of mortality (OR 0.66; 95% CI 0.50-0.87; p = 0.004). CONCLUSION: Patients with CRS-2 exhibit alterations in immune cell profile compared to CKD patients of similar kidney function but without CVD. In the CRS-2 cohort, CD4+ T-lymphocytes independently predicted fatal cardiovascular events.

Vitamin K Supplementation for Prevention of Vascular Calcification in Chronic Kidney Disease Patients: Are We There Yet?

Chronic Kidney Disease (CKD) patients are at high risk of presenting with arterial calcification or stiffness, which confers increased cardiovascular mortality and morbidity. In recent years, it has become evident that VC is an active process regulated by various molecules that may act as inhibitors of vessel mineralization. Matrix Gla Protein (MGP), one the most powerful naturally occurring inhibitors of arterial calcification, requires vitamin K as a co-factor in order to undergo post-translational γ-carboxylation and phosphrorylation and become biologically active. The inactive form of MGP (dephosphorylated, uncarboxylated dp-ucMGP) reflects vitamin K deficiency and has been repeatedly associated with surrogate markers of VC, stiffness, and cardiovascular outcomes in CKD populations. As CKD is a state of progressive vitamin K depletion and VC, research has focused on clinical trials aiming to investigate the possible beneficial effects of vitamin K in CKD and dialysis patients. In this study, we aim to review the current evidence regarding vitamin K supplementation in uremic patients.

The Association of Circulating CD14++CD16+ Monocytes, Natural Killer Cells and Regulatory T Cells Subpopulations With Phenotypes of Cardiovascular Disease in a Cohort of Peritoneal Dialysis Patients.

The altered expression of immune cells including monocyte subsets, natural killer (NK) cells and CD4+CD25+ regulatory T cells (Tregs) in end-stage kidney disease, affect the modulation of inflammation and immunity with significant clinical implications. The aim of this study was to investigate the profile of specific immune cells subpopulations and their correlations with phenotypes of established cardiovascular disease (CVD), including coronary artery disease (CAD) and heart failure (HF) in peritoneal dialysis (PD) patients. Materials and Methods: 29 stable PD patients and 13 healthy volunteers were enrolled. Demographic, laboratory, bioimpedance measurements, lung ultrasound and echocardiography data were collected. The peripheral blood immune cell subsets analysis was performed using flow cytometry. Results: PD patients compared to normal controls had lower total lymphocytes (22.3 ± 6.28 vs. 31.3 ± 5.54%, p = <0.001) and B-lymphocytes (6.39 ± 3.75 vs. 9.72 ± 3.63%, p = 0.01) as well as higher CD14++CD16+ monocytes numbers (9.28 ± 6.36 vs. 4.75 ± 2.75%, p = 0.0002). PD patients with prevalent CAD had NK cells levels elevated above median values (85.7 vs. 40.9%, p = 0.04) and lower B cells counts (3.85 ± 2.46 vs. 7.2 ± 3.77%, p = 0.03). Patients with increased NK cells (>15.4%) had 3.8 times higher risk of CAD comparing with patients with lower NK cell levels (95% CI, 1.86 - 77.87; p = 0.034). B cells were inversely associated with the presence of CAD (increase of B-lymphocyte by 1% was associated with 30% less risk for presence of CAD (95% CI, -0.71 - 0.01; p = 0.05). Overhydrated patients had lower lymphocytes counts (18.3 ± 4.29% vs. 24.7 ± 6.18%, p = 0.006) and increased NK cells [20.5% (14.3, 23.6) vs. 13.21% (6.23, 19.2), p = 0.04)]. In multiple logistic regression analysis the CRP (OR 1.43; 95% CI, 1.00 - 2.05; p = 0.04)] and lymphocytes counts (OR 0.79; 95% CI, 0.63-0.99; p = 0.04)] were associated with the presence of lung comets. Patients with higher NK cells (>15.4%, n = 15) were more likely to be rapid transporters (D/P creatinine 0.76 ± 0.1 vs. 0.69 ± 0.08, p = 0.04). Patients displaying higher Tregs (>1.79%) were older (70.8 ± 10.7 years vs. 57.7 ± 14.7years, p = 0.011) and had higher nPCR (0.83 ± 0.14 vs. 0.91 ± 0.17, p = 0.09). Conclusion: Future research is required to evaluate the role of immune cells subsets as potential tools to identify patients at the highest risk for complications and guide interventions.

Longitudinal Assessment of Electrolyte Disorders in a Cohort of Chronic Stable Kidney Transplant Recipients.

BACKGROUND: Kidney transplantation is complicated by various electrolyte disturbances with variable reported prevalence and incidence and of multifactorial pathogenesis. The aim of our study was the retrospective longitudinal assessment of the serum electrolytes in a cohort of stable kidney transplant recipients (KTRs) and the possible associated parameters, including graft function and medications. METHODS: We included 93 stable KTRs under follow-up in our hospital's kidney transplant unit. Serum magnesium, calcium, phosphorus, potassium, sodium, and urine sodium levels were recorded retrospectively during 3 consecutive years. In addition, comorbidities, biochemical parameters, medications, and graft function (estimated glomerular filtration rate (eGFR) using the Chronic Kidney Disease Epidemiology Collaboration equation and 24-hour urinary protein [uTpr]) were recorded. RESULTS: Mean age at baseline was 51 ± 11 years; 64 KTRs were men (68.8%), 17 (18.3%) had diabetes, 79 (85%) had hypertension, and 11 (11.8%) had cardiovascular disease. Mean eGFR and uTpr (mg/24 h) at study initiation were 47.1 ± 13.5 mL/min/1.73 m2 and 369.4 ± 404.2 mg/24 h, respectively. Hypomagnesemia was the most common disturbance observed in 21.7% of KTRs. Patients with hypomagnesemia displayed higher parathyroid hormone levels and more frequently had diabetes. Hypophosphatemia was recorded in 9.7% of KTRs during the first year. Hyperkalemia, hypokalemia, and hypercalcemia were rare (<5%). Mean serum and urine sodium concentration remained stable during the study, whereas urinary sodium levels showed a positive correlation with uTpr (P < .05). CONCLUSIONS: In our cohort of KTRs, there were no significant electrolyte disorders, either in terms of frequency or severity, with hypomagnesemia being the most prevalent disturbance. The identification of potential associated risk factors and clinical data correlations are pivotal for the development of individualized and evidence-based therapeutic approach and decisions.

Serum vitamin D in obese and overweight subjects according to estimated glomerular filtration rate.

OBJECTIVE: Obesity and renal disease are both associated with low serum 25(OH)D. The aims of the present study were to (a) assess vitamin D status and compare serum vitamin D levels in overweight/obese versus normal-weight individuals according to eGFR and (b) assess the role of 25(OH)D in the development of secondary hyperparathyroidism (SHPT). DESIGN: Serum 25(OH)D, 1,25(OH)2D, parathyroid hormone (PTH), calcium, and phosphate were measured in 104 subjects with BMI > 25 kg/m2. Participants were categorized according to eGFR (ml/min/1.73m2): G1 ≥ 60 (n = 53), G2 30-59 (n = 35), and G3 15-29 (n = 16). Fifty normal-weight individuals with comparable eGFR served as controls: G1-nw (n = 23), G2-nw (n = 18), and G3-nw (n = 9). RESULTS: 25(OH)D levels were lower in G1 compared to those in G1-nw (21.7 ± 6.5 vs 26.5 ± 7.0 ng/ml, p = 0.005), G2 versus G2-nw (19.0 ± 6.0 vs 25.0 ± 5.2 ng/ml, p = 0.001), and G3 vs G3-nw (15.8 ± 4.7 vs 20.3 ± 4.5 ng/ml, p = 0.030). 1,25(OH)2D and PTH levels were similar in obese/overweight versus normal-weight individuals in each of the eGFR categories. Factors independently associated with low 25(OH)D levels were BMI > 25 kg/m2, lower eGFR, and female gender. Mean 25(OH)D levels were < 30 ng/ml in both overweight and controls, in all eGFR groups. SHPT was universally observed when eGFR was < 30 ml/min/1.73m2. CONCLUSIONS: Lower serum 25(OH)D but similar 1,25(OH)2D and PTH levels were observed in overweight/obese compared to normal-weight individuals. Even though vitamin D insufficiency was common across all eGFR categories, secondary hyperparathyroidism was more prevalent as eGFR declined.

Estimation of Residual Peritoneal Volume Using Technetium-99m Sulfur Colloid Scintigraphy.

Residual peritoneal volume (RPV) may contribute in the development of ultrafiltration failure in patients with normal transcapillary ultrafiltration. The aim of this study was to estimate the RPV using intraperitoneal technetium-99m Sulfur Colloid (Tc). Twenty patients on peritoneal dialysis were studied. RPV was estimated by: 1) intraperitoneal instillation of Tc (RPV-Tc) and 2) classic Twardowski calculations using endogenous solutes, such as urea (RPV-u), creatinine (RPV-cr), and albumin (RPV-alb). Each method's reproducibility was assessed in a subgroup of patients in two consecutive measurements 48 h apart. Both methods displayed reproducibility (r = 0.93, p = 0.001 for RPVTc and r = 0.90, p = 0.001 for RPV-alb) between days 1 and 2, respectively. We found a statistically significant difference between RPV-Tc and RPV-cr measurements (347.3 ± 116.7 vs. 450.0 ± 67.8 ml; p =0.001) and RPV-u (515.5 ± 49.4 ml; p < 0.001), but not with RPV-alb (400.1 ± 88.2 ml; p = 0.308). A good correlation was observed only between RPV-Tc and RPV-alb (p < 0.001). The Tc method can estimate the RPV as efficiently as the high molecular weight endogenous solute measurement method. It can also provide an imaging estimate of the intraperitoneal distribution of RPV.