Trends, Social Context, and Transplant Implications of Obesity Among Incident Dialysis Patients in the United States.

BACKGROUND: Kidney transplant programs have variable thresholds to accept obese candidates. This study aimed to examine trends and the social context of obesity among United States dialysis patients and implications for kidney transplant access. METHODS: We performed a retrospective cohort study of 1 084 816 adults who initiated dialysis between January 2007 and December 2016 using the United States Renal Data System data. We estimated national body mass index (BMI) trends and 1-y cumulative incidence of waitlisting and death without waitlisting by BMI category (<18.5 kg/m 2 , ≥18.5 and <25 kg/m 2 [normal weight], ≥25 and <30 kg/m 2 [overweight], ≥30 and <35 kg/m 2 [class 1 obesity], ≥35 and <40 kg/m 2 [class 2 obesity], and ≥40 kg/m 2 [class 3 obesity]). We then used Fine-Gray subdistribution hazard regression models to examine associations between BMI category and 1-y waitlisting with death as a competing risk and tested for effect modification by End Stage Renal Disease (ESRD) network, patient characteristics, and neighborhood social deprivation index. RESULTS: The median age was 65 (interquartile range 54-75) y, 43% were female, and 27% were non-Hispanic Black. From 2007 to 2016, the adjusted prevalence of class 1 obesity or higher increased from 31.9% to 38.2%. Class 2 and 3 obesity but not class 1 obesity were associated with lower waitlisting rates relative to normal BMI, especially for younger individuals, women, those of Asian race, or those living in less disadvantaged neighborhoods ( pinteraction < 0.001 for all). CONCLUSIONS: Obesity prevalence is rising among US incident dialysis patients. Relative to normal BMI, waitlisting rates with class 2 and 3 obesity were lower and varied substantially by region, patient characteristics, and socioeconomic context.

Small cyclic sodium channel inhibitors.

Voltage-gated sodium (NaV) channels play crucial roles in a range of (patho)physiological processes. Much interest has arisen within the pharmaceutical industry to pursue these channels as analgesic targets following overwhelming evidence that NaV channel subtypes NaV1.7-NaV1.9 are involved in nociception. More recently, NaV1.1, NaV1.3 and NaV1.6 have also been identified to be involved in pain pathways. Venom-derived disulfide-rich peptide toxins, isolated from spiders and cone snails, have been used extensively as probes to investigate these channels and have attracted much interest as drug leads. However, few peptide-based leads have made it as drugs due to unfavourable physiochemical attributes including poor in vivo pharmacokinetics and limited oral bioavailability. The present work aims to bridge the gap in the development pipeline between drug leads and drug candidates by downsizing these larger venom-derived NaV inhibitors into smaller, more "drug-like" molecules. Here, we use molecular engineering of small cyclic peptides to aid in the determination of what drives subtype selectivity and molecular interactions of these downsized inhibitors across NaV subtypes. We designed a series of small, stable and novel NaV probes displaying NaV subtype selectivity and potency in vitro coupled with potent in vivo analgesic activity, involving yet to be elucidated analgesic pathways in addition to NaV subtype modulation.

Technetium complexes with arylselenolato and aryltellurolato ligands.

Reactions of (NBu4)[TcOCl4] or [TcCl3(PPh3)2(CH3CN)] with in situ-prepared lithium arylselenolates and -tellurolates give (NBu4)[TcVO(ArE)4] (E = Se, Te; Ar = phenyl) and [TcIII(ArE)3(PPh3)(CH3CN)] (E = Se, Te; Ar = phenyl, 2,6-Me2phenyl, mesityl) complexes, respectively. The products contain square-pyramidal (TcV compounds) and trigonal bipyramidal (TcIII complexes) coordinated technetium atoms. Density functional theory calculations indicate that the Tc-chalcogen bonds in the TcIII compounds have a greater bond order than those in the TcV compounds.

[Health related quality of life among patients on chronic hemodialysis]. / Evaluación de la calidad de vida en pacientes en hemodiálisis crónica mediante el cuestionario "Kidney Disease Quality of Life (KDQOL-36)".

BACKGROUND: Health-related quality of life (HRQOL) among patients on chronic hemodialysis (CHD), is associated with mortality, complications and compliance to treatment. AIM: To assess HRQOL in a group of patients on CHD. PATIENTS AND METHODS: A cross-sectional multicenter study was carried out, involving 224 patients from five CHD units (3 private and 2 public) in Bio Bio Region, using the Kidney Disease Quality of Life -36 items (KDQOL-36) questionnaire and Karnofsky scale. Scores range from 0 to 100, with higher values representing a better HRQOL. RESULTS: Physical and Mental scales and subscales of symptoms, effect and the burden of kidney disease subscales rendered scores below 50 (the referential value), in 80%, 61%, 8%, 43% and 80% of evaluations, respectively. The lower scores were observed in patients with diabetes, coronary artery disease, hypoalbuminemia, serum creatinine below 9.4 mg/dL, age >or=55 years and in those with a low economic and educational level (p <0.05). CONCLUSIONS: HRQOL in patients on hemodialysis had values below the referential score in subjects with diabetes and coronary artery disease, poor nutritional status and a low educational and socioeconomic level. The incorporation of support professionals, such as social workers, psychologists, dieticians, covering psychosocial factors, could improve the patients quality of life.

Evaluación de la calidad de vida en pacientes en hemodiálisis crónica mediante el cuestionario "Kidney Disease Quality of Life (KDQOL-36)" / Health related quality of life among patients on chronic hemodialysis

patients on chronic hemodialysis Background: Health-related quality of life (HRQOL) among patients on chronic hemodialysis (CHD), is associated with mortality, complications and compliance to treatment. Aim: To assess HRQOL in a group of patients on CHD. Patients andmethods: A cross-sectional multicenter study was carried out, involving 224 patients from five CHD units (3 private and 2 public) in Bio Bio Region, using the Kidney Disease Quality of Life – 36 items (KDQOL-36) questionnaire and Karnofsky scale. Scores range from 0 to 100, with higher values representing a better HRQOL. Results: Physical and Mental scales and subscales of symptoms, effect and the burden of kidney disease subscales rendered scores below 50 (the referential value), in 80%, 61%, 8%, 43% and 80% of evaluations, respectively. The lower scores were observed in patients with diabetes, coronary artery disease, hypoalbuminemia...

Oxidized low density lipoproteins induce apoptosis in human lymphocytes: involvement of mitogen-activated protein kinases.

Oxidized low density lipoproteins (oxLDL), macrophages and T-lymphocytes are present in atherosclerotic lesions. We and others have shown that oxLDL is cytotoxic for macrophages, endothelial, smooth muscle and activated T-lymphocytes and induce apoptosis. Here we demonstrate that (i) oxidized LDL (oxLDL), oxidized VLDL (oxVLDL) and hydrogen peroxide (H2O2) induce apoptosis in human T-lymphocytes and (ii) mitogen-activated protein kinases are involved in this process. Apoptosis was monitored by immunofluorescence microscopy and flow cytometry for annexin V binding, Apo 2.7 expression, the TUNEL reaction and caspase 3 activity. In the presence of oxLDL (100 microg/ml), oxVLDL (50 microg/ml) and H2O2 (5 mM), the fraction of apoptotic cells increased within 6 hours to more than 70%. Preincubation of lymphocytes with the MAPKK inhibitor PD-98059 and the p38MAPK inhibitor SB-203580 almost completely abolished these effects. Furthermore, oxLDL and H2O2 but not native LDL strongly enhanced phosphorylation of JNK, p38MAPK and p42/44MAPK. The results suggest that in the resting lymphocyte apoptosis triggered by oxidized lipoproteins and oxidative stress depends on the activation of p44/42MAPK and p38MAPK cascades.

[Autoantibodies against advanced glycation products in patients with type 1 diabetes mellitus]. / Autoanticuerpos dirigidos contra productos de glicación avanzada en pacientes con diabetes mellitus tipo 1.

BACKGROUND: Advanced glycation end products are associated with chronic complications of diabetes mellitus. This glycation process renders many proteins immunogenic. AIM: To detect the presence of antibodies against albumin, collagen and low density lipoprotein glycation products in boys and teenagers with diabetes mellitus. PATIENTS AND METHODS: Thirty one patients with diabetes mellitus type I, aged 11 +/- 3.8 years and with a mean duration of disease of 3.7 +/- 2.7 years and 31 healthy controls aged 12.4 +/- 5.3 years were studied. Antibodies against glycation end products were detected by ELISA and results were expressed as a ratio of the optical density of the glycated protein/optical density of the native protein. RESULTS: Diabetic patients and healthy controls did not have antibodies against albumin glycation end products. Diabetics had higher levels of antibodies than controls for collagen glycation end products (2.6 +/- 0.4 and 1.8 +/- 0.2 respectively, p < 0.01) and low density lipoprotein glycation end products (3.07 +/- 0.92 and 2.2 +/- 0.72 respectively, p < 0.05). CONCLUSIONS: The biological role of these antibodies is not clear. They could be a depuration mechanism for glycation end products or contribute to chronic complications of diabetes mellitus.

Autoanticuerpos dirigidos contra productos de glicación avanzada en pacientes con diabetes mellitus tipo 1 / Antibodies against advanced glycation end products in patients with type 1 diabetes mellitus

Background: Advanced glycation end products are associated with chronic complications of diabetes mellitus. This glycation process renders many proteins immunogenic. Aim: To detect the presence of antibodies against albumin, collagen and low density lipoprotein glycation products in boys and teenagers with diabetes mellitus. Patients and methods : Thirty one patients with diabetes mellitus type I, aged 11ñ3.8 years and with a mean duration of disease of 3.7ñ2.7 years and 31 healthy controls aged 12.4ñ5.3 years were studied. Antibodies against glycation end products were detected by ELISA and results were expressed as a ratio of the optical density of the glycated protein/optical density of the native protein. Results : Diabetic patients and healthy controls did not have antibodies against albumin glycation end products. Diabetics had higher levels of antibodies than controls for collagen glycation end products (2.6ñ0.4 and 1.8ñ0.2 respectively, p< 0.01) and low density lipoprotein glycation end products (3.07ñ0.92 and 2.2ñ0.72 respectively, p< 0.05). Conclusions: The biological role of these antibodies is not clear. They could be a depuration mechanism for glycation end products or contribute to chronic complications of diabetes mellitus

Efecto inmunosupresor in vitro de las lipoproteínas de baja densidad / In vitro inhibition of lymphocyte proliferation by low density lipoproteins

Background: immune cells participate in the formation of atheromatous plate, however little is known about the effects of native or oxidatively modified lipoproteins on these cells. Aim: To study the effects of lipoproteins on in vitro mononuclear cell proliferation. Material and methods: peripheral blood mononuclear cells were obtained from 10 patients with type 2 diabetes mellitus (aged 52 ñ 9 years old with a disease duration of 8.2 ñ 5.7 years and a mean glycosilated hemoglobin of 9.3 ñ 2.2 percent) and 10 non diabetic healthy controls (aged 50.3 ñ 7.1 years old). These were stimulated with phytohemagglutinin (PHA) alone or in the presence of native LDLS, malondialdehyde modified LDLs or glycated LDLs. Proliferation was measured as 3H-thymidine incorporation and expressed as Stimulation Index (SI). Results: SI of patients and healthy subjects, after PHA stimulation were similar: (57.5 ñ 29.8 and 61.1 ñ 23.5) respectively LDLs did not induce proliferation in neither group. Native LDLs produced a 98 percent inhibition of PHA induced proliferation. Malondialdehyde modified and glycated LDLs caused a 50 percent inhibition. The suppressive effect was maintained when lipoproteins were incorporated to culture media 60 min prior or after PHA stimulation. Conclusions: Lipoproteins inhibit in vitro PHA induced peripheral blood mononuclear cell proliferation both in diabetic and in non diabetic subjects

[In vitro immunosuppressive effect of low density lipoproteins]. / Efecto inmunosupresor in vitro de las lipoproteínas de baja densidad.

BACKGROUND: Immune cells participate in the formation of atheromatous plate, however little is known about the effects of native or oxidatively modified lipoproteins on these cells. AIM: To study the effects of lipoproteins on in vitro mononuclear cell proliferation. MATERIAL AND METHODS: Peripheral blood mononuclear cells were obtained from 10 patients with type 2 diabetes mellitus (aged 52 +/- 9 years old with a disease duration of 8.2 +/- 5.7 years and a mean glycosilated hemoglobin of 9.3 +/- 2.2%) and 10 non diabetic healthy controls (aged 50.3 +/- 7.1 years old). These were stimulated with phytohemagglutinin (PHA) alone or in the presence of native LDLS, malondialdehyde modified LDLs or glycated LDLs. Proliferation was measured as 3H-thymidine incorporation and expressed as Stimulation Index (SI). RESULTS: SI of patients and healthy subjects, after PHA stimulation were similar: (57.5 +/- 29.8 and 61.1 +/- 23.5) respectively LDLs did not induce proliferation in neither group. Native LDLs produced a 98% inhibition of PHA induced proliferation. Malondialdehyde modified and glycated LDLs caused a 50% inhibition. The suppressive effect was maintained when lipoproteins were incorporated to culture media 60 min prior or after PHA stimulation. CONCLUSIONS: Lipoproteins inhibit in vitro PHA induced peripheral blood mononuclear cell proliferation both in diabetic and in non diabetic subjects.