Cardiac remodeling associated with chronic kidney disease is enhanced in a rat model of metabolic syndrome: Preparation of mesenchymal transition.

Cardiac alteration due to chronic kidney disease is described by tissue fibrosis. This remodeling involves myofibroblasts of various origins, including epithelial or endothelial to mesenchymal transitions. In addition, obesity and insulin resistance together or separately seem to exacerbate cardiovascular risk in chronic kidney disease (CKD). The main objective of this study was to assess if pre-existing metabolic disease exacerbates CKD-induced cardiac alterations. In addition, we hypothesised that endothelial to mesenchymal transition participates in this enhancement of cardiac fibrosis. Rats fed cafeteria type diet for 6 months underwent a subtotal nephrectomy at 4 months. Cardiac fibrosis was evaluated by histology and qRT-PCR. Collagens and macrophages were quantified by immunohistochemistry. Endothelial to mesenchymal transitions were assessed by qRT-PCR (CD31, VE-cadherin, α-SMA, nestin) and also by CD31 immunofluorescence staining. Rats fed with cafeteria type regimen were obese, hypertensive and insulin resistant. Cardiac fibrosis was predominant in CKD rats and was highly majored by cafeteria regimen. Collagen-1 and nestin expressions were higher in CKD rats, independently of regimen. Interestingly, in rats with CKD and cafeteria diet we found an increase of CD31 and α-SMA co-staining with suggest an implication of endothelial to mesenchymal transition during heart fibrosis. We showed that rats already obese and insulin resistant had an enhanced cardiac alteration to a subsequent renal injury. Cardiac fibrosis process could be supported by a involvement of the endothelial to mesenchymal transition phenomenon.

Vitamin D3 Supplementation Alleviates Left Ventricular Dysfunction in a Mouse Model of Diet-Induced Type 2 Diabetes: Potential Involvement of Cardiac Lipotoxicity Modulation.

PURPOSE: To evaluate the effectiveness of vitamin D3 supplementation, in secondary prevention, on cardiac remodeling and function, as well as lipid profile, in a mouse model of diet-induced type 2 diabetes. METHODS: Mice were fed a high fat and sucrose diet for 10 weeks. Afterward, diet was maintained for 15 more weeks and two groups were formed, with and without cholecalciferol supplementation. A control group was fed with normal chow. Glucose homeostasis and cardiac function were assessed at baseline and at the 10th and 24th weeks. Animals were killed at the 10th and 25th weeks for plasma and cardiac sample analysis. Cardiac lipid profile was characterized by LC-MS/MS. RESULTS: After 10 weeks of diet, mice exhibited pre-diabetes, mild left ventricle hypertrophy, and impaired longitudinal strain, but preserved myocardial circumferential as well as global diastolic and systolic cardiac function. After 15 more weeks of diet, animals presented with well-established type 2 diabetes, pathological cardiac hypertrophy, and impaired regional myocardial function. Cholecalciferol supplementation had no effect on glucose homeostasis but improved cardiac remodeling and regional myocardial function. After 25 weeks, non-supplemented mice exhibited increased myocardial levels of ceramides and diacylglycerol, both of which were normalized by vitamin D3 supplementation. CONCLUSION: This work brought to light the beneficial effects of cholecalciferol supplementation, in secondary prevention, on cardiac remodeling and function in a mouse model of diet-induced type 2 diabetes. Those cardioprotective effects may be, at least in part, attributed to the modulation of myocardial levels of lipotoxic species by vitamin D.

Prevention of vascular calcification by the endogenous chromogranin A-derived mediator that inhibits osteogenic transdifferentiation.

The adrenal glands participate in cardiovascular (CV) physiology and the pathophysiology of CV diseases through their effects on sodium and water metabolism, vascular tone and cardiac function. In the present study, we identified a new adrenal compound controlling mesenchymal cell differentiation that regulates osteoblastic differentiation in the context of vascular calcification. This peptide was named the "calcification blocking factor" (CBF) due to its protective effect against vascular calcification and is released from chromogranin A via enzymatic cleavage by calpain 1 and kallikrein. CBF reduced the calcium content of cells and thoracic aortic rings under calcifying culture conditions, as well as in aortas from animals treated with vitamin D and nicotine (VDN animals). Furthermore, CBF prevented vascular smooth muscle cell (VSMC) transdifferentiation into osteoblast-like cells within the vascular wall via the sodium-dependent phosphate transporter PIT-1 and by inhibition of NF-κB activation and the subsequent BMP2/p-SMAD pathway. Pulse pressure, a marker of arterial stiffness, was significantly decreased in VDN animals treated with CBF. In line with our preclinical data, CBF concentration is significantly reduced in diseases characterized by increased calcification, as shown in patients with chronic kidney disease. In preparation for clinical translation, the active site of the native 19-AS long native CBF was identified as EGQEEEED. In conclusion, we have identified the new peptide CBF, which is secreted from the adrenal glands and might prevent vascular calcification by inhibition of osteogenic transdifferentiation. The anti-calcific effects of CBF and short active site may therefore promote the development of new tools for the prevention and/or treatment of vascular calcification.

High dietary intake of palm oils compromises glucose tolerance whereas high dietary intake of olive oil compromises liver lipid metabolism and integrity.

PURPOSE: Palm (PO) and olive oils (OO) are the two most consumed and/or used oils in the world for food elaboration. These oils should not be confused with the solid palm stearin which is widely used in pastry making. Large number of studies was reported dealing with adverse/beneficial cardiovascular effects of PO and OO, whereas few studies were conducted to compare their potential effects on hepatic steatosis and liver lipid metabolism. The aim of this study was to compare the metabolic effects of high intake of POs (both crude and refined) and virgin OO on surrogate parameters of glucose tolerance, hepatic lipid metabolism and liver integrity. METHODS: Thirty-two young male Wistar rats were divided into four equal groups and fed either control diet (11% energy from fat) or three high-fat diets rich in crude or refined POs or in OO (56% energy from fat), during 12 weeks. Systemic blood and liver biochemical parameters linked to glucose and lipid metabolism as well as hepatic steatosis and liver fatty acid composition were explored. The inflammation and oxidative stress status as well as the expression of several genes/proteins were also analyzed. RESULTS: The major effects of POs intake concerned glucose metabolism and liver fatty acid composition, whereas the major effects of OO intake concerned hepatic TG accumulation, inflammation, and cytolysis. CONCLUSIONS: In conclusion, high dietary intake of PO compromises glucose tolerance whereas high dietary intake of OO compromises hepatic lipid composition and liver integrity. However, adverse hepatic effects of OO observed in this study may not be transposed to human since, (a) the rodent model could lead to different effects than those observed in humans and (b) the average normal OO amounts ingested in the population are lower than those corresponding to a high-fat diet. So, further studies are needed to determine a maximum non-invasive dietary intake of OO.

New insights in molecular mechanisms involved in chronic kidney disease using high-resolution plasma proteome analysis.

BACKGROUND: The reduced glomerular filtration rate in the advanced stages of chronic kidney disease (CKD) leads to plasma accumulation of uraemic retention solutes including proteins. It has been hypothesized that these changes may, at least in part, be responsible for CKD-associated morbidity and mortality. However, most studies focused on the role of individual proteins, while a holistic, large-scale, integrative approach may generate significant additional insight. METHODS: In a discovery study, we analysed the plasma proteome of patients with stage 2-3 CKD (n = 14) and stage 5 CKD with haemodialysis (HD) (n = 15), using high-resolution LC-MS/MS analysis. Selected results were validated in a cohort of 40 patients with different CKD stages with or without HD, using ELISA. RESULTS: Of a total of 2054 detected proteins, 127 displayed lower, while 206 displayed higher abundance in the plasma of patients on HD. Molecular pathway analysis confirmed the modification of known processes involved in CKD complications, including decreased haemostasis and increased inflammation, complement activation and vascular damage. In addition, we identified the plasma increase during CKD progression of lysozyme C and leucine-rich alpha-2 glycoprotein, two proteins related to vascular damage and heart failure. High level of leucine-rich alpha-2 glycoprotein was associated with higher mortality in stage 5 CKD patients on HD. CONCLUSIONS: This study provides for the first time a comprehensive assessment of CKD plasma proteome, contributing to new knowledge and potential markers of CKD. These results will serve as a basis for future studies investigating the relevance of these molecules in CKD associated morbidity and mortality.

Cafeteria Diet-Induced Obesity Worsens Experimental CKD.

Obesity is a significant risk factor for chronic kidney disease (CKD). This study aimed to evaluate the impact of obesity on the development of kidney fibrosis in a model of cafeteria diet rats undergoing 5/6th nephrectomy (SNx). Collagen 1, 3, and 4 expression, adipocyte size, macrophage number, and the expression of 30 adipokines were determined. Collagen 1 expression in kidney tissue was increased in Standard-SNx and Cafeteria-SNx (7.1 ± 0.6% and 8.9 ± 0.9 tissue area, respectively). Renal expression of collagen 3 and 4 was significantly increased (p < 0.05) in Cafeteria-SNx (8.6 ± 1.5 and 10.9 ± 1.9% tissue area, respectively) compared to Cafeteria (5.2 ± 0.5 and 6.3 ± 0.6% tissue area, respectively). Adipocyte size in eWAT was significantly increased by the cafeteria diet. In Cafeteria-SNx, we observed a significant increase in macrophage number in the kidney (p = 0.01) and a consistent tendency in eWAT. The adipokine level was higher in the Cafeteria groups. Interleukin 11, dipeptidyl peptidase 4, and serpin 1 were increased in Cafeteria-SNx. In the kidney, collagen 3 and 4 expressions and the number of macrophages were increased in Cafeteria-SNx, suggesting an exacerbation by preexisting obesity of CKD-induced renal inflammation and fibrosis. IL11, DPP4, and serpin 1 can act directly on fibrosis and participate in the observed worsening CKD.

Implications of Senescent Cell Burden and NRF2 Pathway in Uremic Calcification: A Translational Study.

Increased senescent cell burden and dysregulation of the nuclear factor erythroid 2-related factor 2 (NRF2) pathway have been associated with numerous age-related pathologies; however, their role in promoting vascular calcification (VC) in chronic kidney disease (CKD) has yet to be determined. We investigated whether senescence and NRF2 pathways may serve as drivers of uremia-induced VC using three complementary approaches: a novel model of induced VC in 5/6-nephrectomized rats supplemented with high phosphate and vitamin D; epigastric arteries from CKD patients with established medial calcification; and vascular smooth muscle cells (VSMCs) incubated with uremic serum. Expression of p16Ink4a and p21Cip1, as well as γ-H2A-positive cells, confirmed increased senescent cell burden at the site of calcium deposits in aortic sections in rats, and was similarly observed in calcified epigastric arteries from CKD patients through increased p16Ink4a expression. However, uremic serum-induced VSMC calcification was not accompanied by senescence. Expression of NRF2 and downstream genes, Nqo1 and Sod1, was associated with calcification in uremic rats, while no difference was observed between calcified and non-calcified EAs. Conversely, in vitro uremic serum-driven VC was associated with depleted NRF2 expression. Together, our data strengthen the importance of senescence and NRF2 pathways as potential therapeutic options to combat VC in CKD.

Renal insufficiency and chronic kidney disease - Promotor or consequence of pathological post-translational modifications.

More than 840 million people, representing almost 10% of world population, were estimated to have chronic kidney disease (CKD) in 2017. In CKD, many systemic changes relative to oxidative stress, inflammation, energy balance or neuroendocrine signalling are observed and can be linked to dysfunctional proteins, including protein post-translational modifications (PTMs). Recent technical advances enabled the detection of PTMs and allowed understanding their participation in CKD pathophysiology and kidney damage. In this review article, the interconnections between CKD and PTMs, both as causes and consequences, are described. PTMs, particularly non-enzymatic PTMs, are frequently observed in CKD, as they are the direct consequence of systemic changes following the decline in kidney function. Other PTMs, mainly enzymatic ones, are critical for proper kidney physiology. Still, both types of PTMs have been shown to induce damage not only in kidney but also in other organs (brain, cardiovascular system). Therapeutic approaches focusing on metabolic changes responsible for PTMs alteration have shown interesting results. Targeting specific PTMs responsible for kidney damage is also being considered, which could lead to the development of innovative treatments.

Vascular calcification in different arterial beds in ex vivo ring culture and in vivo rat model.

Vascular calcification is a risk factor for cardiovascular and kidney diseases. Medial calcification may differently affect the arterial tree depending on vessel location and smooth muscle injury. The aim was to map the anatomical distribution of vascular calcifications on different arteries and artery locations, in cultured artery rings (ex vivo) and in a rat model of elastocalcinosis (in vivo). Vascular calcification was assessed histologically (von Kossa staining of the media) and by calcium content measurement. Arteries of different sizes were harvested from untreated rats for ring culture and from the vitamin D3-nicotine (VDN) rat model for direct observation. When cultured in pro-calcifying conditions, thoracic aorta exhibited similar calcification from the arch to the diaphragm. Calcification increased in abdominal aorta along with the reduction in cross sectional area. Carotid and renal arteries exhibited similar ex vivo calcification. In VDN rats, calcification was greater in carotid artery than in aorta, and was accompanied by fibrosis and apoptosis. Ex vivo, calcification was increased by the induction of lesions on arteries. Along the vascular tree, calcification of the arterial wall increases with the narrowing of vessels in ex vivo ring culture and in vivo. The observed differences represent local susceptibility of the vessels to the calcifying processes.

Gut-Kidney Axis Investigations in Animal Models of Chronic Kidney Disease.

Chronic kidney disease (CKD) is an incurable disease in which renal function gradually declines, resulting in no noticeable symptoms during the early stages and a life-threatening disorder in the latest stage. The changes that accompany renal failure are likely to influence the gut microbiota, or the ecosystem of micro-organisms resident in the intestine. Altered gut microbiota can display metabolic changes and become harmful to the host. To study the gut-kidney axis in vivo, animal models should ideally reproduce the disorders affecting both the host and the gut microbiota. Murine models of CKD, but not dog, manifest slowed gut transit, similarly to patient. Animal models of CKD also reproduce altered intestinal barrier function, as well as the resulting leaky gut syndrome and bacterial translocation. CKD animal models replicate metabolic but not compositional changes in the gut microbiota. Researchers investigating the gut-kidney axis should pay attention to the selection of the animal model (disease induction method, species) and the setting of the experimental design (control group, sterilization method, individually ventilated cages) that have been shown to influence gut microbiota.

The use of SDS-PAGE scanning of spent dialysate to assess uraemic toxin removal by dialysis.

BACKGROUND: Uraemic toxins in the 8 to 60 kDa molecular weight range have been attracting increasing attention in dialysis therapy. However, there are no available standardized methods to evaluate their removal. Using new filtering membranes, we evaluated SDS-PAGE of spent dialysate to assess cut-off ranges and removal capacities into dialysate, while also measuring classical markers of dialyser function. METHODS: Eighteen dialysis patients were washed out for 2 weeks with FX 100 (Helixone(®)), followed by randomization to Xevonta Hi 23 (Amembris(®)) or FX dialysers for 2 weeks, then crossed over for an additional 2 weeks, and finally placed on Xenium 210 (Purema(®)) for 2 weeks. SDS-PAGE scanning of the removed proteins contained in the spent dialysate was performed during all dialysis sessions. Total mass of urea, creatinine, total proteins, beta 2 microglobulin (ß2m), retinol-binding protein (RBP) and albumin were measured. The reduction rates of serum urea, creatinine, ß2m, leptin, RBP, alpha 1-antitrypsin, albumin and total proteins were also determined. RESULTS: SDS-PAGE scanning identified four major protein peaks (10-18, 20-22.5, 23-30 and 60-80 kDa molecular weight) and showed clear differences in the amounts of removed proteins between the dialysers, particularly in the 20-22.5, 23-30 and 60-80 kDa ranges. Total mass of removed ß2m, RBP and albumin were in agreement with SDS-PAGE, while serum assays showed differing results. CONCLUSIONS: SDS-PAGE scanning provided a good characterization of protein patterns in the spent dialysate; it extended and agreed with protein determinations and allowed a better assessment of dialyser performance in removing 10 to 80 kDa molecular weight substances. It also identified differences between the three mainly filtrating polysulfone dialysers that were not detected with blood measurements.

Peripancreatic Adipose Tissue Remodeling and Inflammation during High Fat Intake of Palm Oils or Lard in Rats.

Excessive fat consumption leads to the development of ectopic adipose tissues, affecting the organs they surround. Peripancreatic adipose tissue is implicated in glucose homeostasis regulation and can be impaired in obesity. High palm oil consumption's effects on health are still debated. We hypothesised that crude and refined palm oil high-fat feeding may have contrasting effects on peripancreatic adipocyte hypertrophy, inflammation and lipid oxidation compound production in obese rats. In Wistar rats, morphological changes, inflammation and isoprostanoid production following oxidative stress were assessed in peripancreatic adipose tissue after 12 weeks of diets enriched in crude or refined palm oil or lard (56% energy from fat in each case) versus a standard chow diet (11% energy from fat). Epididymal white and periaortic brown adipose tissues were also included in the study. A refined palm oil diet disturbed glucose homeostasis and promoted lipid deposition in periaortic locations, as well as adipocyte hypertrophy, macrophage infiltration and isoprostanoid (5-F2c-isoprostane and 7(RS)-ST-Δ8-11-dihomo-isofuran) production in peripancreatic adipose tissue. Crude palm oil induced a lower impact on adipose deposits than its refined form and lard. Our results show that the antioxidant composition of crude palm oil may have a protective effect on ectopic adipose tissues under the condition of excessive fat intake.

Effects of high-fat diets on inflammation and antioxidant status in rats : comparison between palm olein and olive oil.

Palm olein (PO) and olive oil (OO) are widely consumed in the world. PO is considered harmful to health, whereas OO is considered healthy. The aim of the study was to compare the effects of consumption of these oils on antioxidant status and inflammation in rats. This was an experimental study in male wistar rats fed a diet containing 30% of each oil. Rats had free access to food and water. After being fed for 12 weeks, animals were sacrificed and liver and aortic blood were collected. Plasma was used for the determination of interleukin-6 (IL-6) and oxidative stress parameters (Superoxide dismutase -SOD; Gluthation peroxidase - GPx; Thiobarbituric acid reactive substances - TBARS; Thiol groups and isoprostane). The inflammation and oxidative stress status as well as the expression of several genes/proteins were also analyzed in liver homogenate. No significant differences were observed between PO and OO in plasma and liver levels of the studied inflammation and oxidative stress parameters. This study showed that the consumption of PO induces an antioxidant status superimposable to that of OO.   Key words : Palm olein - Olive oil - Oxidative stress - Inflammation - High fat diet.

Use of spent dialysate analysis to estimate blood levels of uraemic solutes without blood sampling: urea.

BACKGROUND: Urea kinetic modelling-based methods are widely used to assess dialysis efficacy. However, they require blood sampling and are susceptible to a number of errors, mainly from the calculated parameters (particularly V). Spent dialysate determinations have been used and have been shown to be reliable and simple to use. In this study, we associated dialysate-based and clearance determinations along with Kt/V to estimate blood urea levels. METHODS: Urea kinetic modelling, continuous sampling of spent dialysate and ionic dialysance were determined in 18 stable dialysis patients during 126 dialysis sessions. Mean blood urea levels were estimated as follows: mean urea level = spent dialysate - urea mass/(dialysance T). Blood urea levels before and after dialysis were calculated based on the same determinations and extended formulae. RESULTS: Estimated mean urea level was significantly correlated with measured mean blood urea level (R(2) = 0.957; P < 0.0001), and Bland and Altman analysis showed significant agreement between estimated and measured levels. Estimated and measured blood urea levels were also correlated before and after dialysis (R(2) = 0.972 , P < 0.0001 and R(2) = 0.903 , P < 0.0001, respectively), with good agreement for both blood urea before and after dialysis and their respective estimates. CONCLUSIONS: Blood urea levels may be reliably estimated from the total mass of urea removed in the dialysate and the dialysance measured during dialysis. Coupling both measurements allows a precise monitoring of dialysis efficacy and a specific evaluation of the patient's urea metabolism status. Technical dysfunctions and patient variations may be easily identified using this approach without blood sampling.

Guanidino compounds as cause of cardiovascular damage in chronic kidney disease: an in vitro evaluation.

Chronic kidney disease is considered a major cause of cardiovascular risk and non-traditional risk factors remain largely unknown. The in vitro toxicity of 10 guanidino compounds (GCs) was evaluated via a standardized approach on different cell systems of relevance in cardiovascular disease. The parameters evaluated were production of reactive oxygen species, expression of surface molecules, cell proliferation, cytotoxicity and calcification. Several GCs had a stimulatory effect on monocytes and granulocytes (SDMA, creatine and guanidinobutyric acid (GBA)). Some GCs (guandine (G), guanidinosuccinic acid (GSA) and SDMA) inhibited endothelial cell proliferation or reduced calcification in osteoblast-like human VSMC (ADMA, GSA and SDMA). Stimulation of osteoclastogenesis could be demonstrated for ADMA, G, guanidinoacetic acid and GBA in a RAW264.7 cell line. No compounds were cytotoxic to AoSMC or endothelial cells, nor influenced their viability. GCs, especially SDMA, likely contribute to cardiovascular complications in uremia, mainly those related to microinflammation and leukocyte activation.

Optimisation of cell and ex vivo culture conditions to study vascular calcification.

Medial vascular calcification (MVC) is a highly prevalent disease associated with a high risk of severe, potentially lethal, complications. While animal studies may not systematically be circumvented, in vitro systems have been proven useful to study disease physiopathology. In the context of MVC, the absence of a clinically relevant standardized in vitro method prevents the appropriate comparison and overall interpretation of results originating from different experiments. The aim of our study is to establish in vitro models mimicking in vivo vascular calcification and to select the best methods to unravel the mechanisms involved in MVC. Human aortic smooth muscle cells and rat aortic rings were cultured in different conditions. The influence of fetal calf serum (FCS), alkaline phosphatase, phosphate and calcium concentrations in the medium were evaluated. We identified culture conditions, including the herein reported Aorta Calcifying Medium (ACM), which allowed a reproducible and specific medial calcification of aortic explants. Studying cells and aortic explants cultured, the involvement of bone morphogenetic protein 2 (BMP2) pathway, fibrosis and apoptosis processes in in vitro MVC were demonstrated. Expression of osteoblastic markers was also observed suggesting the occurrence of transdifferentiation of smooth muscle cells to osteoblasts in our models. The use of these models will help researchers in the field of vascular calcification to achieve reproducible results and allow result comparison in a more consistent way.

Measuring intradialyser transmembrane and hydrostatic pressures: pitfalls and relevance in haemodialysis and haemodiafiltration.

BACKGROUND: Post-dilutional haemodiafiltration (HDF) with high convection volumes (HCVs) could improve survival. HCV-HDF requires a significant pressure to be applied to the dialyser membrane. The aim of this study was to assess the pressure applied to the dialysers in HCV-HDF, evaluate the influence of transmembrane pressure (TMP) calculation methods on TMP values and check how they relate to the safety limits proposed by guidelines. METHODS: Nine stable dialysis patients were treated with post-dilutional HCV-HDF with three different convection volumes [including haemodialysis (HD)]. The pressures at blood inlet (Bi), blood outlet (Bo) and dialysate outlet (Do) were continuously recorded. TMP was calculated using two pressures (TMP2: Bo, Do) or three pressures (TMP3: Bo, Do, Bi). Dialysis parameters were analysed at the start of the session and at the end of treatment or at the first occurrence of a manual intervention to decrease convection due to TMP alarms. RESULTS: During HD sessions, TMP2 and TMP3 remained stable. During HCV-HDF, TMP2 remained stable while TMP3 clearly increased. For the same condition, TMP3 could be 3-fold greater than TMP2. This shows that the TMP limit of 300 mmHg as recommended by guidelines could have different effects according to the TMP calculation method. In HCV-HDF, the pressure at the Bi increased over time and exceeded the safety limits of 600 mmHg provided by the manufacturer, even when respecting TMP safety limits. CONCLUSIONS: This study draws our attention to the dangers of using a two-pressure points TMP calculation, particularly when performing HCV-HDF.

The CKD plasma lipidome varies with disease severity and outcome.

BACKGROUND: Various alterations in lipid metabolism have been observed in patients with chronic kidney disease (CKD). OBJECTIVES: To determine the levels of lipid species in plasma from CKD and hemodialysis (HD) patients and test their association with CKD severity and patient outcome. METHODS: Seventy-seven patients with CKD stage 2 to HD were grouped into classes of CKD severity at baseline and followed-up for 3.5 years for the occurrence of transition to HD or death (combined outcome). Plasma levels of phosphatidylcholines (PCs), lysophosphatidylcholines (LPCs), sphingomyelins (SMs), and fatty acids were analyzed by flow-injection analysis coupled to tandem mass spectrometry or gas chromatography coupled with mass spectrometry. Kruskal Wallis rank tests and Cox regressions were used to analyze the association of lipids with CKD severity and the risk of combined outcome, respectively. RESULTS: The plasma level of PCs, LPCs, and SMs was decreased in HD patients compared with nondialyzed CKD patients (all P < .05), whereas esterified and/or nonesterified fatty acids level did not change. Thirty-four lipids displayed significantly lower abundance in plasma of HD patients, whereas elaidic acid (C18:1ω9t) level was increased (P < .001). The total amount of LPCs and individual LPCs were associated with better outcome (P < .05). In particular, LPC 18:2 and LPC 20:3 were statistically associated with outcome in adjusted models (P < .05). DISCUSSION: In HD patients, a reduction in plasma lipids is observed. Some of the alterations, namely reduced LPCs, were associated with the risk of adverse outcome. These changes could be related to metabolic dysfunctions.

Correction: Consequences of increasing convection onto patient care and protein removal in hemodialysis.

[This corrects the article DOI: 10.1371/journal.pone.0171179.].

Geographical Variations in Blood Pressure Level and Seasonality in Hemodialysis Patients.

Seasons and climate influence the regulation of blood pressure (BP) in the general population and in hemodialysis patients. It is unknown whether this phenomenon varies across the world. Our objective was to estimate BP seasonality in hemodialysis patients from different geographical locations. Patients from 7 European countries (Spain, Italy, France, Belgium, Germany, United Kingdom, and Sweden) participating in the DOPPS (Dialysis Outcomes and Practice Patterns Study) on years 2005 to 2011 were studied. Factors influencing pre- and postdialysis systolic BP and diastolic BP levels were analyzed by mixed models. There were 9655 patients (median age, 68; 59% male) from 263 facilities, seen every 4 months during a median duration of 1.3 years. Pre- and postdialysis systolic BP increased by a mean estimate of 5.1 mm Hg (95% confidence interval [CI], 3.7-6.4 mm Hg) and 4.4 mm Hg (95% CI, 2.9-5.9 mm Hg) for each 10° increase in latitude (1111 km to the North). In the longitudinal analysis, predialysis systolic BP was lower in summer and higher in winter (difference, 1.7 mm Hg; 95% CI, 1.3-2.2 mm Hg), with greater differences in southern locations (Pinteraction=0.04). Predialysis systolic BP was inversely associated with outdoor temperature (-0.8 mm Hg/7.2°C; 95% CI, -1.0 to -0.5 mm Hg/7.2°C), with steeper slopes in southern locations (Pinteraction=0.005). Results were similar for predialysis diastolic BP. In conclusion, there is a geographical and seasonal gradient of BP in European hemodialysis patients. There is a need to consider these effects when evaluating and treating BP in this population and potentially in others.