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Biomedical subjects

B Lindholm

Publications and source records attributed to B Lindholm.

At least 19 recordsLinked to original sources
PubMed2006

Distributed model of peritoneal fluid absorption.

The process of water reabsorption from the peritoneal cavity into the surrounding tissue substantially decreases the net ultrafiltration in patients on peritoneal dialysis. The goal of this study was to propose a mathematical model based on data from clinical studies and animal experiments to describe the changes in absorption rate, interstitial hydrostatic pressure, and tissue hydration caused by increased intraperitoneal pressure after the initiation of peritoneal dialysis. The model describes water transport through a deformable, porous tissue after infusion of isotonic solution into the peritoneal cavity. Blood capillary and lymphatic vessels are assumed to be uniformly distributed within the tissue. Starling's law is applied for a description of fluid transport through the capillary wall, and the transport within the interstitium is modeled by Darcy's law. Transport parameters such as interstitial fluid volume ratio, tissue hydraulic conductance, and lymphatic absorption in the tissue are dependent on local interstitial pressure. Numerical simulations show the strong dependence of fluid absorption and tissue hydration on the values of intraperitoneal pressure. Our results predict that in the steady state only approximately 20-40% of the fluid that flows into the tissue from the peritoneal cavity is absorbed by the lymphatics situated in the tissue, whereas the larger (60-80%) part of the fluid is absorbed by the blood capillaries.

Absorption↗
PubMed2006

Are insulin-like growth factor and its binding proteins 1 and 3 clinically useful as markers of malnutrition, sarcopenia and inflammation in end-stage renal disease?

INTRODUCTION: Malnutrition is common in end-stage renal disease (ESRD) and affects both morbidity and mortality. The growth hormone-dependent insulin-like growth factor (IGF)-I may be a good marker of malnutrition because of its short half-life. In the present study, we investigate the influence of decreasing residual renal function as well as of chronic inflammation on the IGF system to assess its usefulness in this patient group. PATIENTS AND METHODS: Cross-sectional analysis of 220 ESRD patients (140 males) with a mean age of 52+/-1 years. Biochemical analyses of insulin, IGF-I, IGFBP-1, IGFBP-3, IL-6, high sensitivity (hs)-CRP and other routine markers. Malnutrition status was recorded using subjective global assessment (SGA), body mass index, estimated protein intake from nitrogen appearance (nPNA), handgrip strength (HGS) and insulin resistance (HOMA-IR). Dual energy X-ray absorptiometry was used to assess body composition. RESULTS: Both IGF-I and IGFBP-1 showed significant and opposite correlations with most markers of nutritional status, including SGA (rho=-0.29 and 0.27; P<0.001), nPNA (rho=0.18 and -0.22; P<0.05), S-creatinine (rho=0.19 and -0.19; P<0.01) and HGS (rho=0.21 and -0.25; P<0.01). IFG-I was strongly correlated with IGFBP-3 (rho=0.62; P<0.001) and inversely correlated with IGFBP-1 (rho=0.44; P<0.001). Both IGF-I and IGFBP-3, but not IGFBP-1, were significantly correlated with age (rho=-0.25 for IGF-I and -0.35 for IGFBP-3; P<0.001) and hsCRP (rho=-0.21 and -0.32; P<0.01). In multivariate analysis, SGA and s-albumin were independent predictors of both IGF-I and IGFBP-1. CONCLUSION: Both IGF-I and IGFBP-1 appear to correlate well with markers of protein-energy malnutrition and sarcopenia. However, IGF-I is also influenced by age, whereas IGFBP-1 is influenced by glucose metabolism. IGFBP-3 does not correlate with nutritional status in ESRD, perhaps because of a strong association with inflammation.

Age Factors↗
PubMed2006

Elevated resistin levels in chronic kidney disease are associated with decreased glomerular filtration rate and inflammation, but not with insulin resistance.

In the present study, we explore the role of decreased renal function and a genetic polymorphism on the recently discovered protein resistin, apparently able to inhibit hepatic insulin action in mice. We also investigate possible links with inflammation and the insulin resistance present in patients with chronic kidney disease (CKD). This is a post hoc, cross-sectional study comparing 239 prevalent CKD patients with varying degrees of renal function impairment with an age- and gender-matched randomly selected control group of 25 individuals. Glomerular filtration rate (GFR) was estimated by the mean of urea and creatinine clearance (24-h urine samples) (n=204) or by iohexol clearance (n=60). Plasma analysis of blood lipids, insulin, glucose, inflammatory markers (high-sensitivity C-reactive protein, interleukin-6, tumor necrosis factor-alpha, vascular cellular adhesion molecule, intercellular adhesion molecule) and resistin (kit from LINCO Research, St Charles, MS) was performed using commercially available assays or routine methods. Insulin resistance was estimated by quantitative insulin-sensitivity check index (QUICKI) and homeostasis model assessment for insulin resistance (HOMA-IR) and body composition by dual-energy X-ray absorptiometry. Genotyping of a C/G promoter single nucleotide polymorphism (n=168) at position -180 of the resistin gene was performed by PyroSequencing. Serum levels of resistin were markedly elevated in the CKD patients with both advanced (39.9+/-1.3 ng/ml) and mild to moderate (23.2+/-1.0 ng/ml) renal function impairment, as compared to controls (8.5+/-0.7 ng/ml; P<0.001). In a multiple linear regression model in patients (adjusted r(2)=0.60), only GFR (beta=3.4; P<0.0001), lean body mass (beta=2.2; P<0.001) and the inflammatory markers were independently associated with circulating resistin levels. There was a weak but significant impact of -180 C/G genotype on plasma levels of resistin (median 43.0+/-2.4 ng/ml in CC, 37.5+/-2.0 ng/ml in CG, and 41.1+/-4.9 ng/ml in GG; P<0.05). Univariate analysis of non-diabetic patients and controls showed that serum resistin was associated with markers of glucose metabolism. However, in a multiple regression model, resistin, as well as all the measured markers of inflammation, was only associated with insulin resistance if GFR was not taken into account. Circulating resistin levels are strongly associated with both GFR and inflammatory biomarkers in CKD. As the significant relationship between plasma resistin levels and insulin resistance was lost following the correction for GFR, resistin is not a likely mediator of insulin resistance in patients with CKD. Renal function is an important factor to take into account in clinical studies relating insulin sensitivity to inflammatory biomarkers in CKD as well as in patients with diabetes mellitus, who often have an impaired renal function.

Adult↗
PubMed2006

Place of genotyping and phenotyping in understanding and potentially modifying outcomes in peritoneal dialysis patients.

With the landmark publication of the human genome sequence and its subsequent division into haplotype blocks, the characterization of genetic variations is becoming a feasible approach to study both the pathophysiology and risk factors of complex traits. A number of strategies are available today for identifying candidate genes or polymorphisms associated with pertinent phenotypes. For Mendelian diseases with high penetrance owing to mutations in a single gene, such as polycystic kidney disease, linkage studies have been very successful in mapping the disease loci owing to the availability of families with multiple affected members. In contrast to monogenic conditions, complex diseases such as end-stage renal disease (ESRD) and complex traits such as individual variations in membrane transport and complications during the course of peritoneal dialysis (PD) therapy have a number of competing determinants and inhibitors, both genetic and environmental. Current results reflect this complexity, with few studies showing a large effect of any single risk factor on survival or outcome on PD. However, these studies have so far been small (less than 500 patients) and have not utilized bioinformatics or novel technologies (e.g., multiplex genotyping equipment). In the following review, we outline current approaches for using genetic data in clinical studies as well as highlight some of the most promising results in ESRD patients, particularly those on PD.

Genetic Linkage↗
PubMed2006

Comparison of kinetic characteristics of amino acid-based and dipeptide-based peritoneal dialysis solutions.

UNLABELLED: A mixture of dipeptides (DP) has been proposed as alternatives (to glucose and amino acids, (AA)) osmotic agent in peritoneal dialysis (PD) solutions. DP based solutions may have metabolic and nutritional advantages compared to AA based solutions, as some sources of AA (such as tyrosine) are poorly soluble in water. In a previous study, we compared the kinetic characteristics of DP and AA based solutions; however, the amount of AA differed substantially. The aim of the present study was to compare solutions with almost equal amounts of AA. METHODS: The following solutions were used: (1) amino acid (AA) solution containing leucine, valine, lysine, isoleucine, threonine, phenylalanine and histidine (tyrosine was omitted because of its poor solubility), (2) dipeptide (DP) solution containing leucyl-valine, lysyl-isoleucine, threonyl-phenylalanine and histidyl-tyrosine. Sixteen Sprague-Dawley rats were divided in two groups and were subjected to intraperitoneal injection of either 25 mL of AA (n=8) or DP solution. Dialysate and blood samples were taken frequently postinfusion for measurement of AA and DP concentrations as well as AA from DP. RESULTS: Kinetic models were developed for estimation of diffusive mass transport coefficient between peritoneal cavity and blood (K BD), DP hydrolysis rate coefficient (K H) and AA clearance in the body (K C). Calculations showed that K H is about ten times lower than K BD. Thus, hydrolysis rate in peritoneal cavity is much lower than the diffusive transport rate of DP. K BD for AA appeared to be similar to K BD for dipeptides. K C was much higher than K BD for AA. This finding explains the rapid clearance of amino acids from blood. Nevertheless, the AA-based solution resulted in much higher peak concentrations of AA in blood after 120 min of the dwell than AA concentrations achieved following the use of the DP-based solution. CONCLUSIONS: Peritoneal transport characteristics of AA and DP were similar; however their kinetics in blood differs substantially. The DP solution resulted in a less pronounced increase in AA concentrations in blood, suggesting that DP solution could provide AA in a more physiological way.

Amino Acids↗
PubMed2006

Plasma pentosidine and total homocysteine levels in relation to change in common carotid intima-media area in the first year of dialysis therapy.

BACKGROUND: Homocysteine and advanced glycation end-products (AGEs), which accumulate in chronic kidney disease (CKD), are recently proposed cardiovascular risk factors. In this study, we evaluated the association between changes in calculated intima media (cIM) area of the common carotid artery during the first year of dialysis therapy and plasma total homocysteine (tHcy) level as well as circulating AGEs such as plasma pentosidine level. METHODS: We studied 63 CKD patients (38 males) aged 52 +/- 12 years at a time-point close to start of dialysis treatment and after 12 months of dialysis treatment (41 on peritoneal and 22 on hemodialysis). The tHcy and plasma pentosidine levels were measured by HPLC. Change in cIM area was evaluated by non-invasive B mode ultrasonography. Malnutrition was assessed by subjective global assessment (SGA). RESULTS: At basal, 70% of the patients had carotid plaques, 32% had symptomatic CVD, 38% had malnutrition, 30% had inflammation (CRP > or = 1 mg/dl) and 23% had diabetes mellitus, respectively. At baseline, the mean plasma pentosidine levels were similar in the patients with and without carotid plaques (36 +/- 21 vs 36 +/- 19 pmol/mg albumin, respectively), whereas the median plasma tHcy was significantly lower in the patients with carotid plaques than in the patients without carotid plaques (32 +/- 21 vs 52 +/- 42 pmol/l, p < 0.01, respectively). The prevalence of hyperhomocysteinemia (tHcy level > 13.7 micromol/l) was 95%. In univariate analysis, the change in cIM area during the first year of dialysis was significantly correlated with basal plasma pentosidine level (p = 0.31, p = 0.01), but not with basal tHcy (p = -0.11). However, neither pentosidine nor tHcy levels were correlated with cIM area at basal or at 12 months. In a stepwise multiple regression model, age and plasma pentosidine content, but not the tHcy level, associated with changes in the cIM area. CONCLUSION: Progression of atherosclerosis, as indicated by changes in carotid intima-media area during the course of dialysis treatment, was associated with pentosidine, but not with tHcy, levels at baseline in these CKD patients. This suggests that the accumulation of AGEs in CKD patients may have a role in the pathogenesis of CVD in these patients. Since almost all CKD patients have hyperhomocysteinemia, this finding, however, does not exclude a role ofhomocysteine as a risk factor for CVD in CKD patients.

Adult↗
PubMed2005

Effect of hepatitis C serology on C-reactive protein in a cohort of Brazilian hemodialysis patients.

Hepatitis C (HCV) is not an uncommon feature in hemodialysis (HD) patients and may be a cause of systemic inflammation. Plasma cytokine interleukin-6 (IL-6) is mainly produced by circulating and peripheral cells and induces the hepatic synthesis of C-reactive protein (CRP), which is the main acute phase reactant. The aim of this study was to investigate the influence of HCV on two markers of systemic inflammation, serum CRP and IL-6, in HD patients. The study included 118 HD patients (47% males, age 47 +/- 13 years, 9% diabetics) who had been treated by standard HD for at least 6 months. The patients were divided into two groups depending on the presence (HCV+) or absence (HCV-) of serum antibodies against HCV. Serum albumin (S-Alb), plasma high sensitivity CRP (hsCRP), IL-6, and alanine aminotransferase (ALT) were measured and the values were compared with those for 22 healthy controls. Median hsCRP and IL-6 values and hsCRP/IL-6 ratio were: 3.5 vs 2.1 mg/l, P < 0.05; 4.3 vs 0.9 pg/ml, P < 0.0001, and 0.8 vs 2.7, P < 0.0001, for patients and controls, respectively. Age, gender, S-Alb, IL-6 and hsCRP did not differ between the HCV+ and HCV- patients. However, HCV+ patients had higher ALT (29 +/- 21 vs 21 +/- 25 IU/l) and had been on HD for a longer time (6.1 +/- 3.0 vs 4.0 +/- 2.0 years, P < 0.0001). Moreover, HCV+ patients had a significantly lower median hsCRP/IL-6 ratio (0.7 vs 0.9, P < 0.05) compared to the HCV- group. The lower hsCRP/IL-6 ratio in HCV+ patients than in HCV- patients suggests that hsCRP may be a less useful marker of inflammation in HCV+ patients and that a different cut-off value for hsCRP for this population of patients on HD may be required to define inflammation.

Adolescent↗
PubMed2005

Peroxisome proliferator-activated receptor gamma polymorphisms affect systemic inflammation and survival in end-stage renal disease patients starting renal replacement therapy.

BACKGROUND: Inflammation may contribute to the markedly increased cardiovascular morbidity and mortality in end-stage renal disease (ESRD). However, the prevalence of inflammation varies in different ESRD populations. Peroxisome proliferator-activated receptor-gamma (PPAR-gamma) is an important nuclear signaling protein that may regulate inflammatory response, and recent studies have revealed genetic polymorphisms that have significant effect on PPAR-gamma signaling. The aim of this study was to clarify whether the PPAR-gamma 161C/T and PPAR-gamma2 Pro12Ala single-nucleotide polymorphisms (SNPs) influence the inter-individual variance of inflammation and mortality in ESRD patients. METHODS: The present prospective study included 229 incident Caucasian ESRD patients (62% males) just prior to starting renal replacement therapy and 207 healthy controls (62% males). Blood samples were taken for measuring systemic inflammatory (CRP, TNF-alpha, IL-6) and nutritional (S-albumin) parameters. The presence of diabetes mellitus, malnutrition (subjective global assessment (SGA)) and cardiovascular disease (CVD) were also assessed. Genotyping of the two PPAR-gamma SNPs was performed using Pyrosequencing. During follow-up (1621+/-63 days), both all-cause and CVD-mortality were investigated. RESULTS: ESRD patients had a higher prevalence of both the PPAR-gamma 161 CC and PPAR-gamma2 Pro12Pro genotypes than the general population (p<0.01). Whereas the Pro12Pro genotype was associated with higher median serum levels of both hs-CRP (p<0.05) and TNF-alpha (p<0.01) the 161CC genotype was associated with a significantly higher (6.6 mg/L versus 3.3 mg/L; p<0.01) median hs-CRP level. Following adjustment for age, gender, SGA and CVD a significantly higher mortality rate was observed in patients with the Pro12Pro genotype. CONCLUSION: This study demonstrates significant differences in PPAR-gamma genotype distribution between ESRD patients and healthy controls. Furthermore, as the PPAR-gamma2 Pro12Pro genotype was associated with both higher levels of biomarkers of inflammation as well as shorter survival, genetic polymorphisms seem to play a role in determining systemic inflammatory status and outcome in this patient group.

Adult↗
PubMed2005

End-stage renal disease--not an equal opportunity disease: the role of genetic polymorphisms.

Despite several decades of development in renal replacement therapy, end-stage renal disease (ESRD) patients continue to have markedly increased morbidity and mortality especially caused by cardiovascular disease (CVD). This shows that current strategies, e.g. the focus on dialysis adequacy, to improve the clinical outcome in ESRD patients have to be complemented by novel approaches. Although traditional risk factors are common in dialysis patients they cannot alone explain the unacceptably high prevalence of CVD in this patient group. Much recent interest has therefore focused on the role of various nontraditional cardiovascular risk factors, such as inflammation, vascular calcification and oxidative stress. Recent studies show that genetic factors, such as DNA single nucleotide polymorphisms, may significantly influence the immune response, the levels of inflammatory markers, as well as the prevalence of atherosclerosis in this patient group. To elucidate the respective roles of DNA polymorphisms in genes that encode inflammatory markers (such as IL-10, IL-6 and TNF-alpha) and other factors that may affect the development of atherosclerosis (such as apolipoprotein E, transforming growth factor and fetuin-A), sufficiently powered studies are needed in which genotype, the protein product and the specific phenotype all are analysed in relation to outcome. The recent developments in the field of genetics have opened up entirely new possibilities to understand the impact of genotype on disease development and progress and thus offer new options and strategies for treatment. It seems conceivable that in the near future, prognostic or predictive multigene DNA assays will provide the nephrological community with a more precise approach for the identification of "high-risk" ESRD patients and the development of accurate individual treatment strategies. For this purpose, integrative studies on genotype-phenotype associations and impact on clinical outcome are needed.

Arteriosclerosis↗
PubMed2005

Fluid and solute transport in CAPD patients before and after permanent loss of ultrafiltration capacity.

BACKGROUND: Two major types of permanent loss of ultrafiltration capacity (UFC) were previously distinguished among patients treated with CAPD: 1) type HDR with high diffusive peritoneal transport rate of small solutes and low osmotic conductance,but with normal fluid absorption rate, and 2) type HAR with high fluid absorption rate, but with normal diffusive peritoneal transport rate of small solutes and normal osmotic conductance. However, the detailed pattern of changes in peritoneal transport parameters in patients developing loss of ultrafiltration capacity is not known. OBJECTIVE: Analysis of solute and fluid transport parameters in the same patient before and after UFC loss. PATIENTS: Seven CAPD patients who had undergone repeated dwell studies,which were carried out before and/or after the onset of UFC loss. METHODS: Dialysis fluids (2 L) with glucose or a mixture of amino acids as osmotic agent at three basic tonicities were applied during 6 hour dwell studies. Fluid and solute transport parameters were previously shown not to be affected by these dialysis solutions (except by hypertonic amino acid-based solution). Intraperitoneal dialysate volume and fluid absorption rate were assessed using radiolabeled human serum albumin (RISA). Osmotic conductance (a(OS))was estimated by a mathematical model as ultrafiltration rate induced by unit osmolality gradient. Diffusive mass transport coefficients, K(BD), for glucose,urea,and creatinine were estimated using the modified Babb-Randerson-Farrell model. RESULTS: Five patients had increased K(BD) for small solutes after the onset of UFC loss,and three of them had decreased a(OS),whereas two patients had normal a(OS). In one of them, a(OS) decreased with time after the onset of UFC loss with concomitant normalization of glucose absorption. In all studies of these five patients the fluid absorption rate was within the normal range. Two other patients had increased fluid absorption rate (about 5 ml/min),and one of them also had increased K(BD) for small solutes,in two consecutive dwell studies in each patient with the second study being carried out at 1 and 7 months respectively after the first one. In all four studies in these two patients, the a(OS) was within the normal range. The sodium dip during dialysis with 3.86% glucose-based solution was lost, not only among most patients with UFC loss related to reduced osmotic conductance, but also in patients with increased K(BD). CONCLUSIONS: The occurrence of two major types of UFC loss was confirmed. However, a case of a mixed type of UFC loss with high fluid absorption rate and high K(BD) for small solutes, but normal osmotic conductance, and with normalization of initially high K(BD) for small solutes, linked with decreasing initially normal osmotic conductance,was also found. As a reduced sodium dip with hypertonic glucose solution is not only seen in patients with reduced osmotic conductance, it cannot reliably be used as a single measure of decreased aquaporin function. Permanent ultrafiltration capacity loss may be a dynamic phenomenon with a variety of alterations in peritoneal transport characteristics.

Adult↗
PubMed2005

The role of peritoneal dialysis in renal replacement therapy: an update on medical aspects.

In this brief review, we discuss various medical factors that are of importance for the role of peritoneal dialysis (PD) in renal replacement therapy (RRT), whereas the complex role of non medical factors will only be mentioned briefly. The aim of any RRT, including hemodialysis, PD and renal transplantation, is to normalize the volume and composition of the body fluids, to remove uremic toxins, and to improve clinical outcome. In the following, we will focus on adequacy, preservation of residual renal function, fluid balance, infections, nutrition, cardiovascular disease and systemic inflammation in PD as these factors are strong predictors of clinical outcome in end stage renal disease patients.

Humans↗
PubMed2004

Inhibition of the effect of high glucose on the expression of Smad in human peritoneal mesothelial cells.

OBJECTIVE: As high glucose (HG) concentration in peritoneal dialysis (PD) solution is thought to contribute to peritoneal fibrosis, and angiotensin II receptor blockers (ARBs) may have a key role in preventing fibrosis as they may inhibit the TGF-beta1-Smad pathway, the aims of this in vitro study were to investigate 1) if HG affects the expression of Smad in human peritoneal mesothelial cells (HPMCs) and 2) if ARB (losartan) can inhibit this effect METHODS: HPMCs, obtained from non-renal patients undergoing elective abdominal surgery, were stimulated by HG solutions with different concentrations (1.5%, 2.5%, 4.25%) of dextrose and mannitol, and by solutions containing combination with dextrose and losartan. The supernatant was assayed for TGF- beta1 by ELISA and cells were collected for the analysis of Smad family by RT-PCR and Western Blot. RESULTS: 1) HG up-regulated the expression of Smad2 on both gene and protein levels, especially in 2.5% and 4.25% dextrose groups (P<0.05), and also stimulated the expression of Smad4 in 4.25% dextrose group. However, the expression of Smad3 was not affected. 2) High osmolality as such (using mannitol) did not affect the TGF-beta1-Smad signaling pathway. 3) Losartan inhibited the expression of Smad2 on the gene level but not on the protein level. 4) HG up-regulated the level of TGF-beta1 with increasing dextrose concentration, while losartan partially inhibited this effect of HG on releasing of TGF-beta1. CONCLUSION: A high glucose solution up-regulated the expression of Smad2 and Smad4, suggesting that the TGF-beta1-Smad pathway could be involved in the fibrosis of the peritoneum during PD. As losartan inhibited the expression of Smad2 on the gene level and reduced the concentration of TGF-beta1 in our study, the results of this in vitro study suggest that the use of angiotensin II receptor blockers might represent a possible way to prevent and treat peritoneal fibrosis in PD patients. However, further studies in vivo are needed to confirm this hypothesis.

Angiotensin II Type 1 Receptor Blockers↗
PubMed2004

Possible pathologic involvement of receptor for advanced glycation end products (RAGE) for development of encapsulating peritoneal sclerosis in Japanese CAPD patients.

Encapsulating peritoneal sclerosis (EPS) is a serious complication of PD. The cause(s) of EPS are unknown but may include peritonitis and long duration of PD treatment. However, EPS may also develop in some patients without a history of peritonitis or with rather short duration of PD therapy. It has been suggested that an increasing peritoneal solute transport rate (PSTR) as a function of time on PD treatment is a risk factor for EPS development after transfer to hemodialysis, and that high PSTR is associated with an increased peritoneal microvessels surface area. Other putative mechanisms might include advanced glycated end products (AGE) and their receptors, RAGE. The purpose of this study was to investigate genetic variations in PD patients developing EPS in comparison to PD patients without EPS. SNPs in genes related to angiogenesis as well as RAGE were analyzed. Twenty patients (M/F: 12/8, mean age at start of PD 42.2 years, mean duration of PD 8.4 years) who were diagnosed as EPS during the period 1982 - 2002 at Jikei University Hospital and a matched control group (n = 20) of nonEPS PD patients were studied. The following 5 SNPs were analyzed: VEGF 936 C/T, ecNOS -786 T/C, 298 Glu/Asp, and RAGE -374 T/A, and -429 T/C. The SNPs were analyzed by the pyrosequencing method. The C allele (T/C and C/C) in the RAGE -429T/C genotype was not found in any of the EPS patients (EPS, T/T: 20/20 (100%), nonEPS, T/T: 15/20 (75%), T/C: 4/20 (20%), C/C: 1/2 0(5%), nonC allele vs C allele, p = 0.013), although every allele was found in other SNPs. We conclude that these preliminary data show that whereas genotypes directly related to angiogenesis did not differ between EPS and nonEPS patients, it is noteworthy that no patients in the EPS group had a C allele in the RAGE -429T/C genotype. This might indicate a possible genetic contribution to the development of EPS that is related to RAGE.

Adult↗
PubMed2004

Systemic inflammation in dialysis patients with end-stage renal disease: causes and consequences.

Despite rapid improvements in dialysis technology during the last 20 years, the mortality rate in end-stage renal disease (ESRD) patients treated with dialysis is still unacceptably high and comparable to that of many cancer patients with metastases. The main cause of the increased mortality in ESRD patients is cardiovascular disease (CVD), which is twice as common and advances at twice the rate already in patients with earlier stages of chronic kidney disease as compared to the general population. Although traditional risk factors are common in dialysis patients, they can only in part explain the very high prevalence of CVD in this patient group. Recent evidence demonstrates that chronic inflammation, a non-traditional risk factor which is a commonly observed in dialysis patients, may cause malnutrition and progressive atherosclerotic CVD by several pathogenetic mechanisms. Available data suggest that pro-inflammatory cytokines play a central role in the genesis of both malnutrition and CVD in ESRD. While the long-term effects of chronic inflammation may be most important in the pathogenesis of CVD, the acute-phase reaction may also be a direct cause of acute vascular injury by several pathogenetic mechanisms. The cause(s) of inflammation in dialysis are multifactorial and include both dialysis-related and unrelated factors. Thus, it could be speculated that suppression of the vicious cycle of malnutrition, inflammation, and atherosclerosis (MIA syndrome) would improve survival in dialysis patients. As there are currently no established guidelines for the treatment of chronic inflammation in ESRD patients, studies on the long-term effects of various anti-inflammatory treatment strategies on the nutritional and cardiovascular status as well as outcome in this patient group are warranted.

Humans↗
PubMed2003

Elevated cardiac troponin T in predialysis patients is associated with inflammation and predicts mortality.

OBJECTIVES: Cardiac troponin T (cTnT) is a highly sensitive and specific marker of myocardial damage. It has been shown that elevated serum concentrations of cTnT in haemodialysis (HD) patients are associated with poor prognostic outcome. The aim of the present study was to investigate the predictive value of cTnT in samples from predialysis patients and to investigate associations between cTnT and inflammatory markers, such as C-reactive protein (CRP) and interleukin-6 (IL-6). DESIGN: Cohort, follow-up study. SETTING: Huddinge University Hospital, Sweden. SUBJECTS: A total of 115 (62% males, 28% diabetic patients) end-stage renal disease (ESRD) patients (52 +/- 1 years), of which 29% had cardiovascular disease (CVD), were studied shortly before the onset of dialysis therapy. Sixty-four patients started peritoneal dialysis (PD) as renal replacement therapy, whilst 49 started HD during the follow-up. MAIN OUTCOME MEASURES: The cTnT was analysed with the third generation TnT assay on Elecsys 2010. The prognostic value was calculated for cTnT, IL-6, age, CVD, malnutrition, diabetes mellitus (DM) and gender. Survival analyses were made with Kaplan-Meier and Cox regression analyses, with all-cause mortality as the clinical end point (mean follow-up period 2.7 +/- 0.1 years). RESULTS: Significant correlations were found between cTnT and CKMB (rho = 0.52, P < 0.0001), IL-6 (rho = 0.23, P < 0.05), CRP (rho = 0.30, P < 0.05), and serum albumin (rho = -0.31, P < 0.001), respectively. Diabetic patients had higher median serum cTnT level (0.09 microg L-1; range <0.01-0.51 vs. 0.04 microg L-1; range <0.01-0.67 microg L-1; P < 0.005) compared with nondiabetic patients. Likewise, patients with CVD had a significantly higher median level (0.08 microg L-1; range <0.01-0.67 microg L-1 vs. 0.04 microg L-1; range <0.01-0.61 microg L-1; P < 0.01) of cTnT compared with patients without CVD. Patients with cTnT > or =0.10 microg L-1 had a higher cumulative mortality rate than patients with cTnT < 0.10 microg L-1 (chi2 = 7.04; P < 0.01). Whilst age, CVD, malnutrition, DM, IL-6, cTnT and male gender were associated with poor outcome in the univariate analysis, only DM (P < 0.05) and cTnT (P < 0.05) were independently associated with mortality in a multivariate analysis. CONCLUSIONS: The present study demonstrates that serum concentrations of cTnT > or =0.10 microg L-1 is a significant predictor of mortality in patients starting dialysis. Moreover, the positive correlations between cTnT and IL-6, and CRP, respectively, suggest an association between inflammation and cTnT levels. Finally, the results of the present study suggest that cTnT is an independent predictor of mortality in ESRD patients starting dialysis.

Biomarkers↗
PubMed2002

Soluble leptin receptors and serum leptin in end-stage renal disease: relationship with inflammation and body composition.

BACKGROUND: Elevated serum leptin (S-leptin) levels have been reported in patients with end-stage renal disease (ESRD). Apart from the decreased glomerular filtration rate (GFR), body composition and inflammation may affect leptin levels in ESRD. Leptin circulates both free of and bound to soluble leptin receptors (sOB-R), which are the main determinants of leptin activity and have not been described in ESRD until now. DESIGN: To analyze the association between S-leptin, sOB-R, and inflammation and body composition, we studied 149 (62% males) normal weight (BMI 24.7 +/- 0.4 kg m(-2)) ESRD patients (51 +/- 1 years old) shortly before the start of dialysis (GFR 7.0 +/- 0.2 mL min(-1)). sOB-R and plasma interleukin-6 (IL-6; n= 113) levels were evaluated using ELISA, S-leptin using RIA, and body composition was assessed by X-ray absorptiometry (n = 139). Forty-one healthy subjects age (51 +/- 1 years), BMI (23.6 +/- 0.5 kg m(-2)) and gender-matched (59% males) were used as controls. RESULTS: Median S-leptin was higher in the ESRD patients (10.0 ng mL(-1)) compared with the controls (3.9 ng mL(-1)) (P < 0.001). The median sOB-R did not differ significantly between the ESRD patients (44 U mL-1) and the controls (37 U mL-1). Thus, the sOB-R/S-leptin ratio was lower in the ESRD patients (9.5 +/- 1.2 vs. 12.3 +/- 1.8; P < 0.01) than the controls. A negative correlation was observed between S-leptin and sOB-R (Rho = -0.42; P < 0.0001) in the ESRD patients, a positive correlation was observed between lean body mass and the sOB-R/S-leptin ratio (Rho = 0.33, P = 0.0001) whereas fat mass was negatively correlated to both sOB-R (Rho = -0.26, P = 0.002), and the sOB-R/S-leptin ratio (Rho = -0.62, P < 0.0001). Positive correlations were observed between IL-6 and S-leptin (Rho = 0.19; P < 0.05) and weak but significant body fat mass (Rho = 0.20; P < 0.05), respectively. CONCLUSIONS: This study demonstrates that despite markedly elevated S-leptin levels in the ESRD patients, sOB-R did not differ from the controls. In view of the anorexigenic and pro-atherogenic effects of leptin, further elucidation of the consequences of free bioactive leptin in the development of complications such as malnutrition and cardiovascular disease in ESRD patients is required.

Body Composition↗