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P Stenvinkel

Publications and source records attributed to P Stenvinkel.

At least 19 recordsLinked to original sources
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

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

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

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↗
PubMed2003

Renal function in hypoxaemic chronic obstructive pulmonary disease: effects of long-term oxygen treatment.

UNLABELLED: Impaired renal function is an important cause for the oedema formation, which often occurs in severe chronic obstructive pulmonary disease (COPD). In the present study, the importance of nocturnal hypoxaemia (measured by a nocturnal pulse oximetry) for the renal function was determined in 19 COPD patients, with normal levels of serum creatinine. The effects on kidney function of alleviating the nocturnal hypoxaemia [using 6 months of long-term oxygen treatment (LTOT)], was assessed in 12 patients. Renal function was assessed by determining the clearances of intravenously administered inulin (C(In)) and para-amino-hippurate (C(PAH)) and orally supplemented lithium (C(Li)) and of circulating sodium (C(Na)). The 19 patients had a mean PaO2 of 7.63 +/- 1.08 kPa, a PaCO2 of 5.98 +/- 0.85 kPa, a mean nocturnal oxygen saturation (MnSaO2) of 87.7 +/- 2.8% and an FEV1 in %P of 25.6 +/- 14.6%. C(In) and C(PAH) were 35 and 45% lower than normal, respectively, whereas C(In)/C(PAH)=filtration fraction (FF) was 31% higher than normal. Six months of LTOT in 12 of the patients was not followed by any significant change in renal function in the entire study group. However, low pretreatment MnSaO2 correlated with reductions in post-treatment (FF) (r=0.73, P<0.05). Post-treatment PaCO2 did not change significantly in patients treated with oral diuretics, but increased (P<0.05) in patients without diuretics. C(Na) decreased after LTOT in six patients with an increase in PaCO2>6%, but C(Na) increased in four patients with unchanged or decreased PaCO2 following LTOT. CONCLUSIONS: Renal function (including filtration fraction) is impaired in hypoxaemic COPD. Filtration fraction is decreased following 6 months of LTOT solely in patients with severe pretreatment hypoxaemia and sodium clearance seems to be increased if improved oxygenation is not accompanied by increased PaCO2.

Body Mass Index↗
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↗
PubMed2001

Association between inflammation and changes in residual renal function and peritoneal transport rate during the first year of dialysis.

BACKGROUND: Peritoneal transport rate, a major determinant of peritoneal dialysis (PD) patient survival, increases in most patients starting on PD, while in other patients peritoneal transport rate may decline. Although several factors may contribute to changes in peritoneal transport rate, inflammation is known to be associated with a high peritoneal transport rate, and residual renal function (RRF), which often declines after start of PD, may also be related to inflammation. Therefore, we hypothesized that changes in peritoneal transport rate during patients' first year on PD and declining RRF may be linked with inflammation. METHODS: A total of 76 PD patients (40 males, mean age 56.8+/-14.1 years), who underwent two peritoneal equilibration tests at a mean of 0.4 months and 1 year after beginning PD, were included in the study. Based on the change in dialysate to plasma creatinine concentration ratio at 4-h dwell (D/P Cr) during first year on PD, the patients were divided into decreased or unchanged (group DUC; n=22) and increased (group I; n=54) groups. RESULTS: Initially, group I had a lower proportion of high transporters and more often high serum C-reactive protein (sCRP, > or =10 mg/l) and lower RRF compared with the DUC group. In group I, serum albumin and RRF decreased significantly and dialysate protein loss and glucose absorption increased significantly during the first year on PD. When patients were divided into two groups based on median change in RRF (1.9 ml/min), patients with a decrease in RRF >1.9 ml/min during first year on PD had a higher proportion of high sCRP, higher D/P Cr, and higher changes in D/P Cr compared to patients with a decrease in RRF < or =1.9 ml/min. Patients with elevated sCRP at one year included a higher proportion of patients who had high sCRP at the start of PD, higher increase in D/P Cr, lower serum albumin, lower RRF, and more decrease in RRF during first year on PD compared with patients having normal sCRP. RRF was inversely correlated with changes in D/P Cr during the first year on PD (r=-0.28, P=0.02). Multiple regression analysis revealed that the only factors affecting changes in D/P Cr were high sCRP and a low RRF. CONCLUSIONS: Our preliminary short-term study suggests that changes in peritoneal transport rate during patients' first year on PD may be linked with inflammation and declining residual renal function. Inflammation and residual renal function were identified as the only independent factors determining peritoneal transport rate during the first year on PD. It is possible that inflammation may cause both an increase in peritoneal transport rate and a decline in residual renal function, or that the decline in residual renal function and the increase in peritoneal transport rate may induce or aggravate inflammation. Further studies are needed to confirm these findings.

Adult↗
PubMed2001

Effect of 6 weeks of vitamin E administration on renal haemodynamic alterations following a single dose of neoral in healthy volunteers.

BACKGROUND: A single oral dose of cyclosporin-A (CsA) transiently reduces renal plasma flow (RPF) and glomerular filtration rate (GFR) in transplant patients and, in some patients, chronic administration of CsA leads to renal impairment and fibrosis. Based on experimental studies, several mediators including free radicals have been proposed to account for CsA-nephrotoxicity. We have previously reported that administration of the antioxidant vitamin E in a rat model of chronic CsA-nephrotoxicity reduces renal fibrosis and maintains renal function. METHODS: In the present study, the effect on renal haemodynamics of a single dose of the new oral formulation of CsA (neoral) was assessed before and after 6 weeks of vitamin E (800 IU/day, 2-fold increase in serum vitamin E). GFR (inulin clearance) and RPF (para-amino hippuric acid clearance) were measured before and after a single dose of 5 mg/kg of neoral in 12 healthy subjects under standardised conditions. RESULTS: Although the mean area under the curve of the CsA levels was 21% lower after the vitamin E period, the peak CsA level at 120 min after neoral was similar both before and after vitamin E administration. At 120 min after neoral, a transient reduction in RPF and GFR was noted both before and after vitamin E administration. The nadir of the reductions in RPF (-81 +/-27 ml/min) and GFR (-14 +/- 6 ml/min) at 120 min compared with baseline tended to be lower before than after the treatment with vitamin E (-51 +/- 33 ml/min of RPF and -12 +/- 8, ml/min of GFR, respectively). Plasma and urine levels of F2-isoprostanes (free radical-catalysed vasoconstrictive prostanoids (F2-iso) at 120 min after the administration of neoral were not different from the pre-neoral levels. CONCLUSION: The findings demonstrate that a single oral dose of neoral causes transient, yet significant, reductions in RPF and GFR, and suggest that F2-iso might not be involved in the CsA-induced acute renal vasoconstriction. The tendency for a lower reduction in RPF and GFR following CsA during the vitamin E period in healthy humans warrants additional studies in transplant patients.

Adult↗
PubMed2001

The role of inflammation in the anaemia of end-stage renal disease.

Chronic inflammation is a common feature of end-stage renal disease (ESRD) that is gaining increasing attention as a major cause of morbidity and mortality. It is well established that ESRD per se carries a heightened risk of inflammatory disorders and other co-morbid conditions, but it should also be pointed out that dialysis treatment per se can bring additional risk factors for inflammation, such as impure dialysate or bio-incompatible membranes. Inflammation has recently been associated with atherosclerosis and malnutrition in ESRD, and this link has led to the development of the malnutrition, inflammation, atherosclerosis (MIA) hypothesis. This describes a syndrome whereby raised levels of pro-inflammatory cytokines (such as IL-1, IL-6 and TNF-alpha) are a common link between malnutrition, inflammation and atherosclerosis. Also, anaemia appears to be an important element linking elevated cytokine levels with poor patient outcomes. Several mechanisms for cytokine-induced anaemia have been proposed, including intestinal bleeding, impaired iron metabolism and suppression of bone marrow erythropoiesis and erythropoietin production. These effects suggest that pro-inflammatory cytokines may also be an important cause of lack of response to recombinant human erythropoietin (rh-Epo) therapy. In the light of this putative role of pro-inflammatory cytokines, anti-cytokine agents may prove useful to optimize efficacy of rh-Epo in anaemic chronic renal failure patients. Other potential therapeutic strategies include minimizing exposure to causes of inflammation from various co-morbid conditions, such as persistent infections and chronic heart failure.

Anemia↗