The prognostic impact of fluctuating levels of C-reactive protein in Brazilian haemodialysis patients: a prospective study.

BACKGROUND: A single elevated C-reactive protein (CRP) value predicts mortality in haemodialysis (HD) patients, but the relative importance of repeated vs occasional positive systemic inflammatory response findings is not known. METHODS: To assess the influence on survival of occasional inflammation, CRP, serum albumin (S-Alb) and fibrinogen were analysed bimonthly in 180 HD patients (54% male, 49+/-14 years). Clinically significant inflammation was defined as CRP >5.1 mg/l, based on the receiver operating characteristics curve for CRP as predictor of death. Based on four consecutive measurements of CRP, patients were assigned into three groups: group 1 (n = 74; 41%), no inflammation (CRP < or = 5.1 mg/l in all measurements); group 2 (n = 65; 36%), occasional inflammation (1-3 measurements of CRP > 5.1 mg/l); and group 3 (n = 41; 23%), persistent inflammation (all measurements of CRP >5.1 mg/l). The nutritional status was evaluated by subjective global assessment (SGA) and body mass index (BMI), and the survival (21 months of follow-up) by Kaplan-Meier curve and Cox model. RESULTS: The median and range of CRP values (mg/l) for group 1, 2 and 3 were: 3.2 (3.2-5.1), 3.6 (3.2-54.9) and 13.8 (5.2-82), respectively (P<0.001), whereas the prevalence of malnutrition, assessed by SGA and BMI, did not differ significantly between the groups. The survival rate by Kaplan-Meier analysis was significantly different among the groups (chi2 = 12.34; P = 0.0004). Patients in group 3 showed the highest mortality (34%; P = 0.001), compared with group 1 (8%) and group 2 (14%; P = 0.01), respectively, whereas there was no significant difference in mortality between groups 1 and 2. Age, CRP, S-Alb level and SGA were independent predictors of mortality. CONCLUSION: The patients with a persistent elevation of CRP had a higher mortality rate than the patients with occasional CRP elevation. Thus, persistent, rather than occasional, inflammation is an important predictor of death in HD patients.     

Homocysteine, C-reactive protein, lipid peroxidation and mortality in haemodialysis patients.

BACKGROUND: Cardiovascular disease (CVD) is common in haemodialysis patients with chronic renal insufficiency and is the leading cause of death. The accelerated state of atherosclerosis found in these patients is due to a combination of different mechanisms. Recent studies confirm that inflammation plays an important role in the development of atherosclerosis. However, the role of hyperhomocysteinaemia and the immune response to oxidation of low-density lipoproteins (LDL) remains unclear and studies show contradictory results. The objective of this study was to determine whether there is a relationship between inflammation, hyperhomocysteinaemia and oxidative stress and whether these CVD risk factors are predictors of mortality in haemodialysis patients. METHODS: A prospective follow-up study was carried out in 94 stable, chronic haemodialysis patients for 24 months (July 1999-July 2001). All the patients were given folic acid and vitamin B complex supplements. Homocysteine was determined by fluorescence polarization immunoassay. C-reactive protein (CRP) levels were determined by chemiluminescent enzyme-labelled immunometric assay. Plasma copper oxidized anti-LDL (oxLDL) antibodies were measured by ELISA using native LDL and oxLDL as antigens. RESULTS: Thirty-two patients died during the study and 59.3% of the deaths could be attributed to CVD (eight to acute myocardial infarction and 11 to non-coronary vascular disease). The patients had slight hyperhomocysteinaemia (25.8 +/- 7.82 micromol/l), evidence of inflammation (CRP 5.16 mg/l (0.35-88.7)) and oxidative stress (oxLDL antibodies = 162 +/- 77 optical density at 495 nm x 1000). Age (P < 0.01), CRP (P = 0.03) and the oxLDL antibody titre (P < 0.01) were predictive of mortality. The patients who died from heart disease showed higher oxLDL antibody titres (P = 0.03). No correlation was found between homocysteine, CRP and the oxLDL antibody titre, or between serum homocysteine levels and the different causes of mortality. CONCLUSIONS: These results suggest that lipid peroxidation and inflammation, but not hyperhomocysteinaemia, are the main risk factors for mortality in haemodialysis patients receiving vitamin supplements. As the study was carried out in a relatively limited number of patients, our findings need to be confirmed in a larger patient population.     

Interleukin-6 is a stronger predictor of total and cardiovascular mortality than C-reactive protein in haemodialysis patients.

BACKGROUND: Despite the well known association between interleukin-6 (IL-6) and cardiovascular mortality, no study has so far verified whether IL-6 adds prognostic information to that provided by C-reactive protein (CRP). METHODS: A cohort of 218 haemodialysis patients from four different dialytic centres was followed-up retrospectively. Plasma IL-6 and CRP concentrations were determined. Full information on co-morbidities was available in 162 patients. RESULTS: With respect to the lowest quartile (< 3.6 pg/ml for IL-6, and < 2.2 mg/l for CRP), the crude relative risk (RR) of death from all causes of the upper quartile (> 13.9 pg/ml for IL-6, and > 12.8 mg/l for CRP) was 5.20 (95% confidence interval 2.06-13.011) for IL-6 and 3.16 (1.41-7.12) for CRP. When both variables were included, the estimates were 4.10 (1.30-12.96) for IL-6 and 1.29 (0.47-3.57) for CRP. As to continuous variables, the relationship between both variables and mortality tended to level off for the highest values, but became fairly linear after log transformation of the variables. For one unit SD of the log (variable), the RR was 2.09 (1.52-2.88) for IL-6 and 1.66 (1.23-2.24) for CRP. When they were included in the same model, the estimates were 1.90 (1.18-2.82) for IL-6 and 1.16 (0.81-1.66) for CRP. CONCLUSIONS: IL-6 has a stronger predictive value than CRP for cardiovascular mortality and provides independent prognostic information, while conveying most of that provided by CRP.     

Omega-3 fatty acid supplementation and total homocysteine levels in end-stage renal disease patients

Aim: Elevated total homocysteine (tHcy) levels are commonplace among end‐stage renal disease (ESRD) patients increasing risk for poor cardiovascular outcomes. Specifically, when plasma levels become significantly elevated, tHcy levels appear to contribute to vascular damage and premature atherosclerosis. The purpose of this study was to examine the effect of an over‐the‐counter omega‐3 (n‐3) fatty acid supplementation on tHcy levels in ESRD patients undergoing chronic haemodialysis. Methods: The present study was conducted using a double‐blind, permuted‐randomized and placebo‐controlled experimental protocol. ESRD patients were followed prospectively while supplementing n‐3 or corn oil (n‐6) prospectively for 6 months. Patients: Sixty‐nine patients were recruited that had previously demonstrated compliance with dialysis and medication. Following a 12 h fast, participants donated 12 mL of blood for analysis of tHcy at baseline and at 6 months. Results: The results of this study using regression models revealed no differences in age and gender regarding homocysteine levels at the post‐test with P‐values of 0.6818, 0.6709 and 0.3331 for each regression model. The study findings also revealed that daily administration of 6 g of n‐3 fatty acids containing 160 mg of eicosapentaenic acid (0.96 g/day) and 100 mg of docosahexaenoic acid (0.6 g/day) had no effect on tHcy levels when compared with control. Conclusion: Potential reasons for this non‐significant result may be found in a dose–response relationship, advancement of disease progression in our sample population, or potentially the lack of a significant relationship between fish oil and tHcy. Future studies should address whether a dose–response relationship between n‐3 fatty acid supplementation and tHcy levels exists, and how stage of disease progression affects intervention success or failure.     

Pentraxin 3 is elevated in haemodialysis patients and is associated with cardiovascular disease.

BACKGROUND: Pentraxins are mediators of inflammation as well as markers of the acute-phase reaction. While elevation of C-reactive protein (CRP) in patients with renal failure and its association with cardiovascular disease is well described, there are no data on pentraxin 3 (PTX3) in this population. METHODS: Plasma was obtained from 44 chronic haemodialysis (HD) patients, 35 peritoneal dialysis (PD) patients, 39 patients with chronic renal failure (CRF) not on dialysis therapy and 14 age-matched normal subjects. PTX3 production in whole blood was also investigated in samples taken before and during HD. RESULTS: PTX3 plasma levels were significantly higher in HD patients (5.8 +/- 0.6 ng/ml) compared with the other three groups. There were no significant differences between PD patients (1.5 +/- 0.4 ng/ml), CRF patients (1.5 +/- 0.4 ng/ml) and normal subjects (0.76 +/- 0.2 ng/ml). In dialysis patients, PTX3 levels correlated significantly with time on renal replacement therapy (RRT) and with weekly erythropoietin dose. PTX3 levels were significantly higher in patients with coronary artery disease and peripheral artery disease compared with those without. During a single HD session, PTX3 production was higher in whole blood samples taken after 3 h HD compared with samples taken before HD. CONCLUSIONS: PTX3 levels are markedly elevated in HD patients. The increase in PTX3 production in whole blood after HD indicates that the HD procedure itself contributes to elevated PTX3 levels in HD patients. The association between PTX3 and cardiovascular morbidity suggests a possible connection of PTX3 with atherosclerosis and cardiovascular disease in HD patients.     

Insulin action on glucose and protein metabolism during L-carnitine supplementation in maintenance haemodialysis patients.

BACKGROUND: Impaired protein anabolism and insulin resistance are characteristic features of maintenance haemodialysis patients. We have used a randomised, matched-paired, double-blind, placebo-controlled experimental design to determine the capability of intravenous L-carnitine supplementation to modify insulin resistance and protein catabolism in non-diabetic patients with end-stage renal disease (ESRD) undergoing chronic haemodialysis treatment. METHODS: L-carnitine (20 mg x kg(-1)) (n = 9) or placebo (n = 10) were given intravenously at the end of seven consecutive dialysis sessions. Whole-body protein and glucose metabolism were assessed on interdialytic days by the L[1-(13)C]leucine and the [2,2-(2)H(2)]glucose kinetic models in the postabsorptive state and during euglicemic hyperinsulinemic clamp studies at baseline and at the end of the treatment period. RESULTS: L-carnitine supplementation was associated with lower (P < 0.05) rates of leucine oxidation (-11 +/- 12%) and appearance from proteolysis (-6 +/- 2%) during the clamp studies than after placebo supplementation. The rates of glucose appearance in the postabsorptive state did not change significantly in the patients receiving L-carnitine treatment. Insulin-mediated glucose disappearance was improved by L-carnitine only in those patients (n = 5) (+18 +/- 3%, P < 0.05 vs placebo group, n = 5) with greater baseline insulin resistance, selected according to the median value of insulin sensitivity before treatment. CONCLUSIONS: L-carnitine supplementation was associated with protein-sparing effects in maintenance haemodialysis patients during hyperinsulinemia.     

C-reactive protein levels and ageing male symptoms in hypogonadal men treated with testosterone supplementation

C-reactive protein (CRP) is a marker of systemic low-grade inflammation, and may be associated with subjective symptoms of androgen deficiency. We studied the effects of normalisation of plasma testosterone levels in an open, nonrandomised study. Hypogonadal men (T levels: 5.9–12.1 nmol l⁻¹, aged 34–69 years) were treated for 15 months with parenteral testosterone undecanoate (1000 mg per 12 weeks). In 100 men, plasma CRP and Aging Male Symptom (AMS) self-report data were available at baseline, of 91 men at 6 months, of 59 men at 12 months and of 60 men at 15 months. Testosterone administration resulted in a profound decline in CRP levels and AMS scores (both P < 0.001). There was a positive association between CRP levels and AMS scores over time (r = 0.22; P < 0.001), while adjusting for smoking, alcohol use, age, and body mass index. Low-grade inflammation may be involved in the pathogenesis of subjective symptoms of androgen deficiency in ageing men.     

Ultrapure dialysate and inflammatory response in haemodialysis evaluated by darbepoetin requirements--a randomized study.

BACKGROUND: Dialysate quality has been suggested to influence inflammation status in patients subject to haemodialysis (HD). The aim of this study was to compare ultrapure dialysate (UPD) vs conventional dialysate (CD) with respect to darbepoetin requirements and other inflammation markers. METHODS: A controlled prospective randomized study was carried out on 78 patients from two HD units who were treated with low-flux polyamide dialysers. Patients were assigned to two groups by using different sized blocks per unit and dialysis session. One group received CD treatment while the other was treated with UPD over 12 months. From the groups, 37 patients started treatment with CD and 41 with UPD while 31 patients ended with CD and 30 with UPD. The main variables analysed were haemoglobin (Hb) and darbepoetin dose; other variables studied were C-reactive protein (CRP), albumin, interleukin-6 (IL-6) and interleukin-1 receptor antagonist (IL-1Ra). RESULTS: No significant differences were observed between the two groups for the variables analysed. At the beginning of the study the following values of CD and UPD were assessed: Hb 11.3 and 11.3 (g/dl); darbepoetin dose: 0.49 and 0.44 (microg/kg/week); CRP: 13 and 24 (mg/l); albumin: 3.8 and 3.7 (g/dl); IL-6: 5.94 and 4.18; and IL-1Ra: 345 and 420 (ng/l), respectively. At the end of the study the values of CD and UPD were: Hb 12 and 11.9 (g/dl); darbepoetin dose: 0.47 and 0.48 (microg/kg/week); CRP: 14 and 14 (mg/l); albumin: 3.8 and 3.7 (g/dl); IL-6: 14.03 and 12.93 and IL-1Ra: 322 and 340 (ng/l). CONCLUSIONS: UPD does not improve the inflammatory status evaluated by darbepoetin requirements in conventional HD patients treated with low-flux polyamide dialyser. Further controlled studies are required to evaluate the clinical influence of UPD in HD with other low- and high-flux membranes.     

Homocysteine and C-reactive protein levels in Haemodialysis patients

Background: Mild to moderatehyperhomocysteinemia is very common amongpatients undergoing haemodialysis. There issufficient evidence that hyperhomocysteinemiais an independent risk factor forcardiovascular and or atheromatous disease inend stage renal failure patients. Vitaminsupplementation such as vitamin B6, B12 orfolate has been proposed to correct thismetabolic disturbance and it is to be proved ifthis intervention benefit these patients, butthere is no agreement whether oral folatesupplementation is capable to normalizehomocysteine levels in end stage renal failurepatients.Methods: In 53 patients, undergoinghaemodialysis, homocysteine levels (Hcy),folate, vitamin B12, ferritin and C-reactiveprotein (CRP) were estimated before and afterdialysis, without folate supplementation.Thirty voluntary blood donors were used ascontrols to compare homocysteine levels. Afterfour weeks of oral folate supplementation(10 mg/24 hours) the levels of homocysteine,serum folate and intra-erythrocyte folate wereestimated again. Eighteen months later thesurvival rate of our patients was recorded andanalyzed in relation to Hcy and CRP levels.Results: The results showed thathaemodialysis patients exhibited, almost,fourfold higher homocysteine levels thancontrols (27.39 ± 11.54 vs 7.38 ± 3.5, t = –8.2, p = 0.000000). Folate levels, vitamin B12 and CRP increase significantly afterhaemodialysis where as homocysteine levelsdecrease (Hcy1 vs. Hcy2: z = 2.08, p = 0.03).Fourteen (14) patients suffered from coronaryheart disease (CHD) and they exhibited thehigher levels of homocysteine (Hcy1 vs. CHD: z =–3.4, p = 0.0006). All estimations performedrevealed a negative correlation betweenhomocysteine levels and plasma orintra-erythrocyte folate. No other variableexhibited any significant influence uponhomocysteine levels. After folatesupplementation homocysteine levels in thewhole number of patients were unchanged(Hcy(before) vs. Hcy(after): 27.39 ± 11.54vs. 26.95 ± 8.22, z = 0.3, p = 0.7, NS). Whenpatients with homocysteine levels higher than24 µmol/L were selected, a significantdecrease was observed (34.77 ± 9.32 vs.30.0 ± 8.05, z = 2.09, p = 0.02). Forty-twopatients were treated with erythropoietin fortheir anemia and we found a positivecorrelation between C-reactive protein levelsand rhu-Epo dose (CRP vs. Epo: r = 0.45,p = 0.002). Homocysteine levels did not exhibitany significant influence upon short-termsurvival (U = –0.37, p = 0.3, NS) where as CRPlevels exhibit a significant influence uponshort-term survival (U = 2.15, p = 0.005).Conclusions: Homocysteine levels inhaemodialysis patients are fourfold higher thanhealthy controls. Folate, vitamin B12 and CRPincrease significantly after dialysis. Patientswith coronary heart disease exhibit the highestlevels of homocysteine. The homocysteine levelsare inversely related with the folate levels.The exogenous folate supplementation increasethe serum folate levels but decreaseshomocysteine only in patients with higher thanmild hyperhomocysteinemia. Hcy doesn't exertany significant effect upon the short-termsurvival of the haemodialysis patients but CRPlevel is a god predictor of the short-termsurvival of these patients.     

Expression of C-reactive protein in myointimal hyperplasia in a porcine arteriovenous graft model.

BACKGROUND: The migration and proliferation of myofibroblasts are prominent features of myointimal hyperplasia associated with haemodialysis polytetrafluoroethylene (PTFE) grafts. Since C-reactive protein (CRP) possesses functional activities on vascular smooth muscle cells (SMCs), we examined the expression of this protein in PTFE grafts early in the course of myointimal hyperplasia development in a porcine model. METHOD: Bilateral carotid-jugular PTFE loop grafts were placed in pigs. After euthanasia at 2-4 weeks, the graft-venous and graft-arterial anastomoses and the adjacent blood vessels were excised en bloc and subjected to immunohistochemical analyses and in situ hybridization for CRP. The ability of CRP to stimulate proliferation was examined in cultured porcine venous SMCs using the bromodeoxyuridine assay after incubation for 48 h. RESULTS: Severe myointimal hyperplasia was found at 3 weeks after graft placement at both graft-venous and graft-arterial anastomoses. Compared to normal tissues, staining for CRP was far more intense in cells in the hyperplastic lesions at both anastomoses, which also stained positive for smooth muscle alpha-actin. In situ hybridization showed that these cells also expressed mRNA for CRP. At 1 microg/ml, CRP increased the proliferation of cultured porcine venous SMCs by 45.9+/-5.8%. CONCLUSION: CRP was produced in venous and arterial SMCs and its expression was enhanced in the hyperplastic lesions associated with arteriovenous PTFE grafts in a porcine model. Together with the ability of CRP to promote SMC proliferation, these data suggest that CRP might play a pathogenic role in the development of myointimal hyperplasia in PTFE grafts.     

Serum levels of beta-trace protein and its association to diuresis in haemodialysis patients.

BACKGROUND: Beta-trace protein (BTP) has been proposed as an alternative endogenous marker of the glomerular filtration rate. However, possible determinants of BTP in ESRD patients undergoing regular renal replacement therapy have not been evaluated. METHODS: Serum levels of BTP, beta-2-microglobulin, creatinine and urea were analysed before and after dialysis treatment in 73 patients [haemodialysis (HD) n=52; haemodiafiltration (HDF) n=21]. Patients were categorized into four groups with residual diuresis (RD)<0.5 l/day (group 1; n=24), 0.5-1 l/day (group 2; n=18), 1.1-1.5 l/day (group 3; n=12) and >1.5 l/day (group 4; n=19). Subsequently RD was compared to pre-treatment levels of BTP. RESULTS: HD treatment did not affect BTP serum levels [pre-treatment 8.1+/-4.1 mg/l (mean+SD) vs post-treatment 7.7+/-4.1 mg/l; -0.6 +/- 16.1%; ns]. However, in 6 out of 21 patients undergoing HDF BTP levels were reduced by more than 20%. Overall, the resulting decrease in serum concentration was minuscule (9.6+/-6.2 vs 8.3+/-4.9 mg/l; -14+/-21.9%; P=0.03). BTP serum levels were tightly associated to RD of the four groups. Comparison of BTP levels showed significant differences between patients of groups 1 vs 3 and 4 as well as 2 vs 4. CONCLUSIONS: BTP serum levels may serve as a surrogate marker for residual renal function since HD and HDF do not exert clinical relevant alterations on them. Furthermore, BTP serum concentrations appear strongly associated to RD.     

Relationship of serum C-reactive protein and blood glucose levels with injury severity and patient morbidity in a pediatric trauma population

Purpose

Serum markers of inflammation and of glucose production are known to reflect the immediate metabolic response to injury. We hypothesized that monitoring of the early C-reactive protein (CRP) and blood glucose (BG) concentrations would correlate with clinical morbidity and outcome measures in pediatric trauma patients.

Methods

A five-year retrospective chart review of pediatric trauma patients admitted to our Level I pediatric trauma center was conducted to establish the relationships between early (first 3 hospital days) serum CRP and BG concentrations, Injury Severity Score (ISS), and hospital length of stay (HLOS). Statistical significance (P < 0.05) was determined using Student’s t-test.

Results

Forty-two trauma patients (8.0 ± 5.2 years) were evaluated. The early inflammatory response (CRP ≥ 10 vs <10 mg/dl) was significantly correlated to the glycemic response (BG;121 ± 24 vs 97.3 ± 14.2 mg/dl, P < 0.05). Severely injured patients (ISS ≥ 25 vs <25) were significantly more hyperglycemic (BG;156 ± 56.9 vs 125 ± 31.6 mg/dL, P = 0.003). Both increased inflammatory response (CRP;8.1 ± 6.4 vs 2.5 ± 3.5 mg/dL) and increased glycemic response (BG;111 ± 15.9 vs 97.4 ± 11.7 mg/dL) were independently and significantly associated with prolonged hospitalization (HLOS > 7 vs ≤7 days, P < 0.05).

Conclusion

This study establishes a significant relationship between the early inflammatory and glycemic injury response and the association of that response with pediatric trauma patient morbidity and outcome measures.     

G2/M cell-cycle arrest and apoptosis by n-3 fatty acids in a pancreatic cancer model

BACKGROUND: n-3 fatty acids (n-3FA) have anti-inflammatory and anti-proliferative effects including modulation of pro-inflammatory cascade mediators and cytokine elaboration (i.e., TNF-alpha, IL-10 and PGE(2)) in many cell lines. However, mechanisms of anti-proliferative effects have not been clearly defined. MATERIALS AND METHODS: MIA PaCa-2 pancreatic cancer cells were treated either with n-3FA (treatment), media (control), or n-6FA (control) for all experiments. Cellular proliferation was evaluated with WST-1 reagent. Cells were stained with propidium iodide and analyzed by flow cytometry for cell-cycle arrest, which was further analyzed by cdc2 expression. Membrane and media lipid concentrations were analyzed by high-performance liquid chromatography. Apoptosis was evaluated by AnnexinV-FITC flow cytometry and reconfirmed by poly (ADP-ribose) polymerase (PARP) cleavage and B(cl)-2 expression. RESULTS: Propidium iodide flow cytometry of MIA PaCa-2 dosed with n-3FA showed a decrease in cells in G1 phase (11-17%) and an increase cells in G2 phase (7-13%) from controls. cdc2 expression was also decreased at 24 h compared to controls. Annexin-V staining of n-3FA-treated cells demonstrated time-dependent increased apoptosis and PARP cleavage was present only in the n-3FA treatment group. Phospho-B(cl)-2 was also decreased in the n-3FA-treated cells compared to controls. CONCLUSIONS: Co-incubation of MIA PaCa-2 cells with n-3FA results in both dose- and time-dependent cell-cycle arrest. Cells also progress to cell death via apoptosis. These data support the potential applicability for n-3FA as an antiproliferative and pro-apoptotic strategy.     

Predictive value of white blood cell count and C-reactive protein in children with appendicitis

Background/Purpose

Few studies have addressed the predictive value of white blood cells (WBCs) and C-reactive protein (CRP) at different cutoff values in appendicitis. Our purpose was to determine the cutoff values for WBC and CRP at different periods during clinical evolution of appendicitis and to establish their use for the diagnosis of appendicitis and differentiation of simple from perforated appendicitis.

Methods

We studied 198 patients operated on for appendicitis, which were further divided into 4 subgroups according to the time from the onset of symptoms to diagnosis. Receiver operating characteristic curves were constructed for CRP and WBC; the best cutoff points were used to calculate the sensitivity and specificity to discriminate patients with and without appendicitis and patients with simple and perforated appendicitis.

Results

White blood cell and CRP individually and together had a high sensitivity to differentiate patients with and without appendicitis. The specificity of WBC and CRP taken individually and together to differentiate patients with simple and perforated appendicitis was high, but the sensitivity was low.

Conclusions

White blood cell and CRP could be used to support the clinical diagnosis of appendicitis, and, depending on the time from the onset of symptoms to diagnosis, to differentiate patients with and without appendicitis and discriminate simple from perforated appendicitis.     

Elevated levels of C-reactive protein independently predict accelerated deterioration of graft function in renal transplant recipients.

BACKGROUND: Chronic transplant dysfunction is characterized by a gradual decline in renal function with slowly rising serum creatinine. The underlying mechanism is thought to include inflammation and atherosclerosis. C-reactive protein (CRP) is a well-established marker of both inflammation and atherosclerosis. In this prospective study, we investigated whether CRP could be of use as a clinical marker for early identification of renal transplant recipients at increased risk of deterioration of graft function. METHODS: In this prospective study, all participating patients (n = 606) visited the out-patient clinic at least once a year, and serum creatinine was assessed at every visit. Subjects with a follow-up of <1 year (n = 31) were excluded from analysis. RESULTS: A total of 575 patients participated at a median (interquartile range) time of 5.9 (2.6-11.3) years post-transplantation. Median time of follow-up was 3.0 (2.4-3.4) years. Changes in serum creatinine during follow-up were -0.45 (-4.83-4.76) micromol/l/year in 172 subjects with CRP <1.0 mg/l, 1.04 (-3.36-6.12) micromol/l/year in 184 subjects with CRP 1.0-3.0 mg/l and 2.34 (-3.33-9.07) micromol/l/year in 219 subjects with CRP >3.0 mg/l (P < 0.05 for comparison of the three groups). Proteinuria (P = 0.003), CMV IgG titre (P = 0.01), donor age (P = 0.01), CRP concentration (P = 0.02), recipient age (P = 0.02) and recipient gender (P = 0.047) were independently associated with change in serum creatinine during follow-up in a multivariate analysis. CONCLUSIONS: Elevated levels of CRP independently predict accelerated deterioration of graft function in renal transplant recipients >1 year post-transplantation. Further prospective studies are required to investigate whether early intervention can prevent deterioration of graft function in subjects with elevated levels of CRP.     

Influence of protein catabolic rate on nutritional status, morbidity and mortality in elderly uraemic patients on chronic haemodialysis: a prospective 3-year follow-up study

It has been recently reported that elderly chronic haemodialysis(CHD) patients have a reduced protein catabolic rate (PCRn)in spite of an adequate K_t/V. However until now the long-termconsequences of this fact on the nutritional status, morbidity,and mortality were not known. This prospective study evaluates,over a period of 3 years, the effect of the reduced PCRn onsome nutritional parameters, morbidity and mortality in CHDpatients older than 65 years with adequate and stable K_t/V.Over the period 1990–1993 we evaluated 42 CHD patientsover 65 years (mean±SD 72±5 years). PCRn, totalserum proteins, serum albumin concentration, body weight, bodymass index (BMI) and serum transferrin were determined at thestart of the study and followed yearly until the end of observation.The incidence of hospitalization/patient-year, the mortalityrate and the causes of death were also recorded. All the patientswere managed to maintain a K_t/V>0.9 throughout the study.Twenty-two patients (Group A), mean age 70±4 years, completedthe entire period of observation. Their K_t/V was 1.10±0.12,PCRn was 0.95±0.12 g/kg/day, and serum albumin concentrationwas 40.2±1.5 g/l, and these did not change significantly.The other parameters also remained stable over time. Twentypatients (Group B) died. Their mean age was 74±6 years.This group's K_t/V was 1.11±0.15, PCRn was 0.94±0.18g/kg/day, and serum albumin concentration was 39±3.1g/l, and there were no significant variations between the startand the end of observation for all the parameters studied. Therewere no differences between the two groups of patients at thestart of observation for all the parameters with the exceptionof age, which was significantly higher in patients in GroupB (P=0.017). The data derived by the Cox proportional hazardsregression model showed that PCRn and serum albumin concentrationwere not significant predictors of death, as well as K_t/V, totalserum proteins, BMI, total number of risk factors and numberof hospital admissions/patient-year, but confirmed the predominantrole of age (P<0.009) in predicting and conditioning thesurvival of patients. In conclusion this prospective study showsthat elderly CHD patients with adequate and stable K_t/V havePCRn values lower than those commonly suggested as necessaryto prevent chronic malnutrition. However, this reduced proteinintake did not exert any specific negative influence on thenutritional status, morbidity and mortality after a follow-upof 3 years. It is possible that, in this group of patients,a declining PCRn with age does not indicate impending malnutritionand does not influence morbidity and mortality. Therefore ageremains the strongest factor influencing mortality.     

ω-3鱼油脂肪乳剂对肠梗阻患者肠通透性及细菌移位的影响

【摘要】 目的 ω-3鱼油脂肪乳剂对其肠粘膜通透性及细菌移位的影响。 方法 90例肠梗阻患者随机分为治疗组和对照组。对照组按照常规治疗方法,如禁食、胃肠减压、全胃肠外营养、应用抗生素以及纠正水电解质和酸碱平衡紊乱。治疗组在对照组的基础上加用ω-3鱼油脂肪乳剂。检测比较两组病例入院时、治疗后第3日、第7日的常规指标、免疫学指标,采集两组患者外周血进行血浆谷氨酞胺(Gln)浓度和全血细菌DNA检测,同时进行尿中乳果糖/甘露醇(L/M)比值测定。 结果ω-3鱼油脂肪乳剂治疗组血糖升高幅度明显降低(P<0.05),血清白蛋白(ALB)、血清前白蛋白(PA)、血清转铁蛋白(TF)恢复性升高(P<0.05);早期IgA水平较对照明显增高(P<0.05)。另外对照组尿乳果糖/甘露醇(L/M)比值、外周血中细菌DNA阳性率高于治疗组(P<0.01),而血浆谷氨酰胺浓度低于治疗组(P<0.01)。 结论 ω-3鱼油脂肪乳剂使用具有维护肠梗阻患者肠粘膜屏障功能、减少细菌移位、减少并发症起着重要的作用。     

Dietary fish oil does not influence acute rejection rate and graft survival after renal transplantation: a randomized placebo-controlled study.

BACKGROUND: Dietary fish oil, rich in omega-3 polyunsaturated fatty acids, decreases TNF-alpha, IL-1beta and IL-2 levels, which may benefit renal transplant recipients. To explore this possibility, we studied the effect of fish oil on the incidence of acute rejection, in situ expression of interleukins (TNF-alpha, IL-1beta and IL-2) and renal function after renal transplantation. METHODS: In a double-blind clinical trial, 86 subjects with no immunological risk randomly received either 6 g/day of fish oil (fish oil group; n=46) or soy oil (control group; n=40) during the first 3 months after transplantation. The mRNA expression of interleukins (TNF-alpha, IL-1beta and IL-2) was determined by RT-PCR using fine-needle aspiration during follow-up (at baseline and the 1st, 2nd and 3rd month after renal transplantation), as well as during acute rejection episodes and after anti-rejection therapy. The glomerular filtration rate was determined at baseline, and at 1 and 3 months post-graft by [(51)Cr]EDTA clearances. RESULTS: The incidence of acute rejection during the first post-transplant year was similar in both groups (44 vs. 47%), as was 1-year graft survival (86 vs. 89%). There were no differences between groups in overall renal expression of interleukins in patients who did not suffer rejections during the study. At rejection episodes, the fish oil group showed a trend toward a lower renal expression of TNF-alpha (3.7+/-6.8 vs. 15+/-18.6 TNF-alpha/actin, ratio of arbitrary optical units; P=0.05). In addition, a trend toward a lower IL-1beta expression after therapy was observed in the fish oil group (49.3+/-54 vs. 84.4+/-59 IL-1beta/actin, ratio of arbitrary optical units; P=0.05). However, the severity of acute rejections (Banff criteria) as well as renal function after anti-rejection treatment were similar in both groups. Finally, a greater reduction in triglyceride levels was observed in the fish oil group compared with the control group (-6.6+/-52.7 vs. 12.7+/-40.2%; P<0.05). CONCLUSIONS: Treatment with fish oil during the first 3 months post-transplantation does not influence acute rejection rate and has no beneficial effect on renal function or graft survival.     

降钙素原、C反应蛋白及白细胞计数鉴别小儿感染性肺炎的意义

目的探究降钙素原、C反应蛋白及白细胞计数在小儿感染性肺炎的临床鉴别诊断中的意义。方法选取我院2013年10月-2014年4月住院小儿肺炎90例患儿为观察组,选取同期住院的非肺炎小儿54例为对照组,对两组患儿进行降钙素原、C反应蛋白及白细胞计数的检验,并进行比较分析。结果观察组中CRP的（＋）检出率为47.78%,WBC的（＋）检出率为38.87%,PCT的（＋）检出率为91.11%;两组患儿在CRP、WBC、PCT三项检测指标的比较上x2分别为36.5287、16.8201、109.3631,差异有统计学意义（P〈0.05）。结论降钙素原、C反应蛋白及白细胞计数的监测有助于临床上对小儿感染性肺炎的鉴别诊断,对其动态的检测可促进细菌性肺炎的确诊,具有高度的临床使用价值。     

Ibuprofen use is associated with reduced C-reactive protein and interleukin-6 levels in chronic spinal cord injury

Objective: To assess the association between ibuprofen use and the systemic inflammatory biomarkers C-reactive protein (CRP) and interleukin-6 (IL-6) in chronic Spinal Cord Injury (SCI).Study design: Prospective cohort study.Setting: Community dwelling individuals with SCI.Participants: 338 (278 male, 60 female) community dwelling individuals with chronic SCI (≥1-year post-injury).Interventions: None.Main outcome measures: CRP and IL-6 levels were quantified by ultra-sensitive ELISA assay. General linear models were used to assess associations between various clinical and demographic factors and CRP and IL-6 levels.Results: There were 50 active ibuprofen users and 288 non-users. After adjusting for clinical and demographic factors, ibuprofen users had significantly lower CRP levels (2.3 mg/L versus 3.5 mg/L, P = 0.04) and IL-6 levels (3.2 pg/ml versus 4.0 pg/ml, P = 0.04) compared to nonusers.Conclusions: Our study suggests that self-reported ibuprofen use may be negatively associated with CRP and IL-6 levels in chronic SCI after adjusting for known confounding factors, and suggests ibuprofen use may be an important, potential variable to consider in future studies focused on systemic inflammation in SCI. Future prospective studies require assessing frequency, duration, and dosage-dependent effects of ibuprofen on systemic markers of inflammation in chronic SCI. These findings may support future clinical trials to determine safety and efficacy of ibuprofen treatment for various outcomes in chronic SCI.