An Association Between Inflammatory State and Left Ventricular Hypertrophy in Hemodialysis Patients

This study was performed to investigate the potential relationship between left ventricular hypertrophy (LVH) and proinflammatory cytokines in hemodialysis (HD) patients and the effect of HD on cytokine production. Serum interleukin 1 beta (IL-1 β), interleukin 6 (IL-6) and tumor necrosis factor alpha (TNF-α) measurements and echocardiographic studies were performed in 35 stable HD patients. A variety of probable risk factors for LVH including age, HD duration, blood pressure (BP), body mass index, lipid profile, hemoglobin, albumin, parathormone and homocysteine levels were also investigated. Additionally, the effect of HD procedure on cytokine levels was evaluated. Predialysis serum levels of IL-1β, IL-6, TNF-α, and homocysteine in HD patients were compared with 12 healthy subjects. Left ventricular hypertrophy was demonstrated in 20 (57%) of HD patients by echocardiography. Left ventricular mass index (LVMI) was correlated positively with systolic BP (r = 0.556, p = 0.001), diastolic BP (r = 0.474, p = 0.004), and serum levels of TNF-α (r = 0.446, p = 0.009).Multiple regression analysis showed that systolic BP and TNF-α levels were significant independent predictors of LVH. No relationship was observed between LVH and other parameters. The mean predialysis serum level of IL-6 was significantly higher in HD patients compared to healthy controls (15.7 ± 8.7 vs. 7.3 ± 0.7 pg/mL, p = 0.001). Predialysis serum levels of TNF-α in HD patients were higher when compared to healthy subjects, but the difference was not statistically significant (8.3 ± 3 vs. 7 ± 1.45 pg/mL, respectively, p > 0.05). However, serum levels of IL-6 and TNF-α significantly elevated after HD, when compared to predialysis levels (from 15.7 ± 8.7 to 17.8 ± 9.5 pg/mL, p = 0.001 and from 8.3 ± 3.0 to 9.9 ± 3.5 pg/mL p = 0.004, respectively). As a conclusion, in addition to BP, proinflammatory cytokines, TNF-α in particular, seem to be associated with LVH in ESRD patients.     

Impact of rHuEPO therapy initiation on soluble adhesion molecule levels in haemodialysis patients

Background: Increased levels of soluble adhesion molecules have been reported in haemodialysis (HD) patients. Recent studies have shown that recombinant human erythropoietin (rHuEPO) elicits proliferation and migration of endothelial cells and modifies endothelial function. The present study was design to explore the effects of rHuEPO on serum levels of soluble adhesion molecules in HD patients. Methods: Soluble serum levels of E‐selectin (sE‐selectin), intracellular adhesion molecule‐1 (sICAM‐1) and vascular cell adhesion molecule‐1 (sVCAM‐1) were measured by ELISA in 29 rHuEPO naïve HD patients (20 males, 9 females) and 10 control subjects at baseline and second month. The HD patients with a haemoglobin level lower than 10.0 mg/dL (n = 19) were administered rHuEPO therapy and other HD patients (n = 10) were followed as a placebo group. Results: Serum levels of soluble adhesion molecules were significantly higher in HD patients compared with the control group. A significant rise from the baseline in sE‐selectin levels (77 ± 70 vs 100 ± 86 ng/mL, P < 0.05) was observed 2 months after rHuEPO initiation, while sICAM‐1 and sVCAM‐1 levels decreased (271 ± 261 vs 197 ± 89 and 1043 ± 243 vs 990 ± 236 ng/mL, respectively, P < 0.05). Conclusions: The present data indicate that rHuEPO could have an important action on serum levels of soluble adhesion molecules in HD patients. rHuEPO might modify the expression of adhesion molecules from endothelial cells either. However, the exact mechanism responsible for the serum elevation of these molecules in HD patients is yet to be fully elucidated.     

Liver and serum expression of matrix metalloproteinases in asymptomatic pediatric liver transplant recipients

We related hepatic gene and serum expression of matrix metalloproteinases (MMP) and their tissue inhibitors (TIMP) to liver histology in pediatric LT recipients. Liver biopsies and serum samples were obtained from 52 patients 10.6 years post‐LT and age‐matched controls for analyses of MMPs and TIMPs. Patients with fibrosis had significantly higher hepatic gene expression of MMP‐2, MMP‐9, MMP‐14, TIMP‐1, and TIMP‐2 than patients without. Expression of these genes correlated with graft Metavir fibrosis stage (r = 0.494–0.684, P ≤ 0.006 for all). Gene expression of MMP‐1, MMP‐3, MMP‐8, TIMP‐3, and TIMP‐4 was undetectable in both patients and controls. Portal inflammation and cytokeratin 7 correlated positively with gene expression of TIMP‐1. Gene expression of MMP‐2, MMP‐9, and TIMP‐2 correlated negatively with the time of low‐dose cortisone usage (r = ?0.448 to ?0.422, P < 0.05 for all). Serum concentrations of MMP‐8 and TIMP‐1 were significantly increased and MMP‐9 decreased among patients compared with controls, but no correlations to graft histology or gene expression were observed. Hepatic gene expression of certain MMPs and TIMPs is increased in stable pediatric LT recipients displaying graft fibrosis, but this did not reflect to their serum concentrations. Increased hepatic gene expression of TIMP‐1 correlated with graft fibrosis stage, inflammation, and chronic cholestasis.     

Brain natriuretic peptide and P wave duration in dialysis patients

Objectives P wave duration and dispersion, defined as the difference between the maximum and minimum P duration, are regarded as very important non-invasive ECG markers for assessing atrial arrhythmia risk. Plasma brain natriuretic peptide (BNP) level is an independent predictor of recurrence of atrial fibrillation. We compared the effects of hemodialysis (HD) and continuous ambulatory peritoneal dialysis (CAPD) on P wave duration, P dispersion, and BNP in end-stage renal disease (ESRD) patients and examined the relationship between BNP levels, P wave duration, and P dispersion. Design and methods Age-matched 22 HD patients (mean age 52.3 ± 14.0 years) and 19 CAPD patients (mean age 46.7 ± 10.9 years) were studied. Results BNP levels were greater in HD patients before the HD session (459.0 ± 465.1 pg mL⁻¹) than in CAPD patients (139.0 ± 170.1 pg mL⁻¹). The maximum and minimum P duration, and P dispersion, were similar for both groups (P > 0.05). Whereas BNP levels were negatively related to minimum P duration (r = −0.518, P = 0.019), BNP levels were positively correlated with systolic blood pressure and diastolic blood pressure (r = 0.672, P = 0.001 and r = 0.497, P = 0.022, respectively) in HD patients. Conclusions Whereas BNP levels are higher in HD patients when they are at peak-volume status, just before HD, P wave duration and P dispersion were similar for both groups. A negative relationship was detected between BNP levels and minimum P duration in HD patients. Expansion of extra-cellular volume causing myocardial stretching may be the principal cause of increased BNP in HD patients. A functional relationship between BNP and the P wave was not found. Additional studies are needed to evaluate the effect of BNP on the P wave.     

Cut‐off values for serum matrix metalloproteinase‐9: Is there a threshold to predict renal involvement for Henoch–Schonlein purpura in children?

Aim: To clarify whether the level of matrix metalloproteinase‐9 (MMP‐9), tissue inhibitor matrix metalloproteinase‐1 (TIMP‐1) or the ratio of MMP‐9/TIMP‐1 was associated with the renal involvement in Henoch–Schonlein purpura (HSP); and to explore whether there existed early diagnostic measure for HSP nephritis (HSPN). Methods: Sixty‐six patients with HSPN, 68 patients with HSP and 60 healthy children (control group) were enrolled into our study. Serum and urine samples before treatment were collected for detection. Results: Compared with the HSP group and control group, serum MMP‐9, TIMP‐1 and ratio of MMP‐9/TIMP‐1 in the HSPN group were significantly higher (P < 0.05 and P < 0.01, respectively). Urine MMP‐9, TIMP‐1 and ratio of MMP‐9/TIMP‐1 in the HSPN group were obviously higher than those of the control group (P < 0.05) and the HSP group (P < 0.05). Receiver–operator curve (ROC) analysis was performed to obtain the area under the curve (AUC) and the AUC and its 95% confidence interval (CI) of serum MMP‐9 were 0.97 and 0.95–0.99, respectively. The optimal cut‐off point (sensitivity; specificity) of serum MMP‐9 for diagnosing HSPN was 179.79 mg/L (0.96; 0.88). Conclusion: Levels of MMP‐9, TIMP‐1 and ratio of MMP‐9/TIMP‐1 in serum and urine were remarkably high in the patients with HSPN, but the serum MMP‐9 was more sensitive. Serum MMP‐9 may be associated with the occurrence and development of renal involvement in HSPN and become an important indicator for early diagnosis of HSPN.     

The Effects of Angiotensin Converting Enzyme Inhibitors on Potassium Homeostasis in Dialysis Patients With and Without Residual Renal Function

Hyperkalemia is exacerbated by angiotensin converting enzyme inhibitors (ACE‐I). Distal potassium (K⁺) secretion is negligible in anuric patients. ACE‐I therapy may reduce renal, peritoneal, and colonic K⁺ losses. We examined the effect of ACE‐I therapy on serum, urinary, and dialysate K⁺ in a cross‐section of peritoneal and hemodialysis patients. Serum, 24‐h urine K⁺, and peritoneal dialysate excretion K⁺ levels were measured and the results were compared in the various dialysis and treatment groups. Eighty‐one hemodialysis (HD) and 32 peritoneal dialysis (PD) patients were included. Serum K⁺ in HD patients with no residual renal function (RRF) was higher in those receiving ACE‐I therapy (P = 0.02). Serum K⁺ levels in HD patients receiving ACE‐I treatments with RRF was similar to that in oligoanuric HD patients not receiving an ACE‐I. Urinary K⁺ excretion was significantly reduced in those on ACE‐I therapy versus those not on an ACE‐I (P < 0.05). Mean serum K⁺ was lower in PD versus HD patients (P < 0.05). PD patients with no RRF on ACE‐I therapy had higher serum K⁺ concentrations (P = 0.002) and dialysate K⁺ excretion was lower (P = 0.05), in comparison with PD patients not on an ACE‐I. PD patients with RRF on ACE‐I therapy had higher serum K⁺ concentrations compared with those not on ACE‐I therapy (P = 0.03). Both urinary and dialysate K⁺ excretion were reduced (P = 0.001 and P = 0.002, respectively). ACE‐I therapy increases serum K⁺ concentration in dialysis patients. PD patients have relatively lower serum K⁺ levels compared with HD patients. In PD patients, ACE‐I therapy reduces dialysate K⁺. These changes may result from reduced peritoneal movement of K⁺.     

Urinary matrix metalloproteinase‐7 level is associated with the presence of metastasis in bladder cancer

Study Type – Therapy (case series)
Level of Evidence 4 What’s known on the subject? and What does the study add? Recent data suggest that MMP‐7 is critically involved in metastasis formation. In accordance, we formerly found significantly elevated MMP‐7 tissue expression and serum concentration in samples of patients with metastatic bladder cancer and observed an independent correlation between MMP‐7 levels and patients’ prognosis. In the present study we demonstrated that high preoperative urinary MMP‐7 concentrations are associated with metastatic bladder cancer.

OBJECTIVE

? To assess the presence of matrix metalloproteinase (MMP)‐7 in urine samples of patients with bladder cancer and to investigate the correlation between MMP‐7 urine concentration and clinicopathological variables.

PATIENTS AND METHODS

? The presence of MMP‐7 in the urine of patients with bladder cancer was tested in 32 representative cases using immunoprecipitation followed by western blot analysis. ? Urinary MMP‐7 concentration levels were analyzed in 132 patients with bladder cancer and 96 controls using an enzyme‐linked immunosorbent assay.

RESULTS

? MMP‐7 levels did not differ significantly between patients with localized bladder cancer and controls (P= 0.174). On the other hand, we detected a fourfold, significantly elevated MMP‐7 concentration in urine samples of patients with bladder cancer with regional or distant metastasis (P= 0.003). ? Using a threshold value of 6.88 ng/ml, determined by receiver‐operating characteristic curve analysis, a specificity of 82% and a sensitivity of 78% were observed. ? Western blot analysis revealed that the 55‐kDa tissue inhibitor of metalloproteinase 1 complexed MMP‐7 is the dominant form of urinary matrilysin.

CONCLUSIONS

? MMP‐7 is present in detectable amounts in the urine of patients with bladder cancer. Its concentrations are significantly elevated in patients with metastatic disease. ? Determination of urinary matrilysin level could help to detect bladder cancer metastasis, and may therefore provide a more reliable prognosis and influence therapy decisions.     

Van Buchem disease: Clinical,biochemical, and densitometric features of patients and disease carriers

Van Buchem disease (VBD) is a rare bone sclerosing dysplasia caused by the lack of a regulatory element of the SOST gene, which encodes for sclerostin, an osteocyte‐derived negative regulator of bone formation. We studied the demographic, clinical, biochemical, and densitometric features of 15 patients with VBD (12 adults and 3 children) and 28 related carriers of the gene mutation. The most common clinical findings in patients were facial palsy (100%) and various degrees of hearing impairment (93%); raised intracranial pressure had been documented in 20%. The clinical course of the disease appeared to stabilize in adulthood, with the majority of patients reporting no progression of symptoms or development of complications with time. Carriers of the disease had none of the clinical features or complications of the disease. Sclerostin could be detected in the serum in all but 1 VBD patients (mean 8.0 pg/mL; 95% confidence interval [CI], 4.9–11.0 pg/mL), and were lower than those of carriers (mean 28.7 pg/mL; 95% CI, 24.5–32.9 pg/mL; p < 0.001) and healthy controls (mean 40.0 pg/mL; 95% CI, 34.5–41.0 pg/mL; p < 0.). Serum procollagen type 1 amino‐terminal propeptide (P1NP) levels were also significantly higher in adult patients (mean 96.0; 95% CI, 54.6–137.4 ng/mL versus mean 47.8; 95% CI, 39.4–56.2 ng/mL, p = 0.003 in carriers and mean 37.8; 95% CI, 34.5–41.0 ng/mL, p = 0.028 in healthy controls) and declined with age. Bone mineral density (BMD) was markedly increased in all patients (mean Z‐score 8.7 ± 2.1 and 9.5 ± 1.9 at the femoral neck and spine, respectively); BMD of carriers was significantly lower than that of patients but varied widely (mean Z‐scores 0.9 ± 1.0 and 1.3 ± 1.5 at the femoral neck and spine, respectively). Serum sclerostin levels were inversely correlated with serum P1NP levels (r = –0.39, p = 0.018) and BMD values (femoral neck r = –0.69, p < 0.001; lumbar spine r = –0.78, p < 0.001). Our results show that there is a gene‐dose effect of the VBD deletion on circulating sclerostin and provide further in vivo evidence of the role of sclerostin in bone formation in humans. The small amounts of sclerostin produced by patients with VBD may explain their milder phenotype compared to that of patients with sclerosteosis, in whom serum sclerostin is undetectable. © 2013 American Society for Bone and Mineral Research.     

Testosterone and Hemoglobin in Hemodialysis Male and Female Patients

It has been speculated that testosterone stimulates erythropoiesis. We hypothesized that hemoglobin levels in hemodialysis (HD) patients are associated with serum testosterone concentrations. Testosterone, hemoglobin, and other biochemical parameters were measured in a representative sample of 98 chronic HD patients (50 male, 48 female; age 30–90 years, mean 65 ± 13.9 years). We investigated relations among serum testosterone concentration, hemoglobin, ferritin, albumin, body mass index, lean body mass, total cholesterol, low‐density lipoprotein and high‐density lipoprotein cholesterol, triglycerides, high‐sensitivity C‐reactive protein (hsCRP), calcium (Ca), P, intact parathyroid hormone, N‐terminal pro‐brain natriuretic peptide, Karnofsky performance status, and blood pressure (BP) before and after HD. A statistically significant positive correlation between testosterone and hemoglobin was found in all patients (r = 0.25, P < 0.01), men (r = 0.34, P < 0.02), but not in women (r = 0.27, P = 0.07). Multiple regression analysis for all patients has shown statistically significant association between hemoglobin and testosterone (P < 0.001), hsCRP (P < 0.005), lean body mass (P < 0.05), post‐HD systolic (P < 0.04), and diastolic BP (P < 0.005). Multiple regression analysis in men has shown an association between hemoglobin and testosterone (P < 0.04) and post‐HD diastolic BP (P < 0.04) and in women association between hemoglobin and testosterone (P < 0.04), Ca (P < 0.03), and post‐HD diastolic BP (P < 0.03). We found an association between serum testosterone concentration and hemoglobin in male and female HD patients.     

Relationships between Brain Natriuretic Peptide,Troponin I and QT Dispersion in Asymptomatic Dialysis Patients

Objectives. The relationships between increased wall stress, myocyte death, and ventricular repolarization instability in patients with heart failure were reported. Design and Methods. The relationships between brain natriuretic peptide (BNP), a predictor of increased wall stress of hearth; troponin I (cTnI), a predictor of myocyte death; and QT dispersion (QT_d), a reflection of ventricular repolarization instability were evaluated in age- and sex-matched asymptomatic 29 hemodialysis (HD) patients and 26 peritoneal dialysis (PD) patients, and the finding were compared. Results. Serum BNP and cTnI levels in HD patients (722.9 ± 907.9 pg/mL, 0.05 ± 0.07 μg/L, respectively), just before HD, were significantly higher than those of PD patients (255.4 ± 463.7 pg/mL, 0.02 ± 0.02 μg/L, respectively; p < 0.05). There was no significant difference between groups with regard to corrected QT_d and maximum and minimum QT intervals (p > 0.05). Serum cTnI levels were significantly and positively correlated with serum BNP levels in both dialysis groups (r = 0.447, p = 0.048). No relationship was found between plasma BNP and ECG parameters studied in both groups (p > 0.05). Conclusion. Increased serum cTnI levels were associated with elevated BNP levels in both dialysis groups. The increases in BNP and troponin I are more likely to reflect hypervolemia. Although CAPD patients were receiving dialysis daily and HD patients were more hypervolemic, CAPD patients have similar QT_dc and accordingly a similar tendency toward arrhythmias. This suggests that factors other than electromechanical interaction may be important in determining the QT interval length in patients on dialysis.     

Association of Serum Pentosidine With Arterial Stiffness in Hemodialysis Patients

Pentosidine is an advanced glycation end product (AGE). The present study was undertaken to investigate the association of serum pentosidine with carotid distensibility as a measure of arterial stiffness in hemodialysis patients. One hundred and three patients on maintenance hemodialysis were recruited. The distensibility coefficient of the common carotid artery was evaluated by an ultrasonic phase‐locked echo‐tracking system. Serum pentosidine was measured by competitive enzyme‐linked immunosorbent assay. Serum albumin, lipid profile, calcium, phosphorus, intact parathyroid hormone (iPTH), high‐sensitivity C‐reactive protein (hs‐CRP), and oxidized low‐density lipoprotein (ox‐LDL) levels were also measured. Correlation was determined by linear and multiple stepwise regression analysis. Serum pentosidine level studied in hemodialysis patients was 0.54 ± 0.13 µg/mL. No significant difference in serum pentosidine level was noted between patients with and without diabetes (0.59 ± 0.10 µg/mL vs. 0.53 ± 0.13 µg/mL, P = 0.062) as well as between patients with and without prior cardiovascular disease (CVD) history (0.56 ± 0.14 µg/mL vs. 0.53 ± 0.12 µg/mL, P = 0.206). In multivariate regression analysis, only age (β = 0.363, P < 0.001) and ox‐LDL (β = 0.262, P = 0.004) were identified as independent determinants for serum pentosidine. Serum pentosidine was significantly correlated with carotid distensibility (r = ?0.387, P < 0.001), as well as age, ox‐LDL, and hs‐CRP. After adjustment for age, blood pressure, history of diabetes, prior CVD history, lipid profile, calcium, phosphorus, iPTH, hs‐CRP, and ox‐LDL, serum pentosidine was still negatively correlated with distensibility (β = ?0.175, P = 0.044). Serum pentosidine was independently associated with carotid distensibility in hemodialysis patients. This finding suggested that the accumulation of AGE might be an important pathway in the development of arterial stiffness in end‐stage renal disease.     

Decreased serum carnitine is independently correlated with increased tissue accumulation levels of advanced glycation end products in haemodialysis patients

Aim: There is accumulating evidence that advanced glycation end products (AGE) play a role in cardiovascular disease (CVD) in patients with haemodialysis (HD). Carnitine deficiency is frequently observed in HD patients, which may also contribute to CVD. In this study, we examined whether carnitine deficiency was independently associated with increased tissue accumulation levels of AGE in HD patients. Methods: One hundred and twenty‐nine HD patients underwent determinations of blood chemistries including serum level of carnitine. Tissue AGE levels were evaluated by measuring skin autofluorescence with an AGE‐reader. Results: Serum carnitine levels were significantly lower, while skin AGE levels were significantly higher in HD patients compared with healthy controls (P < 0.001). In univariate analysis, β₂‐microglobulin (β₂‐MG) and carnitine (inversely) were correlated with skin AGE levels. Multiple stepwise regression analysis revealed that carnitine levels were one of the independent determinants of skin AGE levels (P = 0.024). When β₂‐MG‐adjusted skin AGE levels were stratified by serum carnitine levels, a statistical significance and dose‐response relationship were observed (P = 0.043). Furthermore, skin AGE levels were one of the independent determinants of serum carnitine levels as well (P = 0.012). Conclusion: The present study demonstrated that decreased carnitine levels were independently associated with increased skin AGE levels in HD patients. Since carnitine is reported to inhibit the formation of AGE in vitro, our study suggests that supplementation of carnitine may be a therapeutic target for preventing the accumulation of tissue AGE and subsequently reducing the risk of CVD in HD patients.     

Plasma levels of fibroblast growth factor-23 and mineral metabolism in diabetic and non-diabetic patients on chronic hemodialysis

Objective  Fibroblast growth factor (FGF) 23 is a circulating factor that regulates phosphate (P) metabolism. Since higher P levels are associated with vascular calcification, we examined the role of serum FGF-23 levels in P metabolism and vascular calcification in hemodialysis (HD) patients with and without diabetes mellitus (DM). Materials and methods  Chronic HD patients with DM (n = 39) and without DM (n = 50) were enrolled. Serum samples were obtained before the start of dialysis sessions, and the FGF-23 levels were determined by enzyme-linked immunosorbent assay. Abdominal computed tomography (CT) scan was performed, and the aortic calcification index (ACI) was determined by one examiner, blinded to the patient characteristics. Measurements of bone mineral density (BMD) were performed at the time of ACI estimation. Results  Log plasma FGF-23 levels were higher in non-DM (3.74 ± 0.71 pg/ml) than in DM (3.35 ± 0.74 pg/ml) patients. The log FGF-23 correlated positively with serum creatinine (r = 0.424, P < 0.0001), albumin (r = 0.225, P = 0.0337), Ca (r = 0.392, P = 0.0001), P (r = 0.735, P < 0.0001), and Ca × P product (r = 0.780, P < 0.0001). There were negative correlations between log FGF-23 and age (r = −0.208, P = 0.0497), glucose (r = −0.231, P = 0.0294), and CRP (r = −0.222, P = 0.0359). Multiple regression analyses were performed to explore the correlations between plasma FGF-23 and other factors associated with vascular calcification in all HD patients. Independent variables were selected based on the results of univariate analyses. The significant factors associated with FGF-23 in HD patients were age, serum levels of creatinine, albumin, glucose, Ca, P, and Ca × P product. Plasma FGF levels did not correlate significantly with either ACI or BMD in these patients. Conclusion  Our findings indicate that the plasma FGF-23 level is associated with calcium-phosphate metabolism disorders, but not with aortic calcification, in both non-DM and DM patients on chronic HD. In addition, plasma FGF-23 is associated with serum levels of creatinine and albumin. Therefore, the plasma FGF-23 level may provide a reliable marker for Ca and P imbalance and nutritional status in HD patients.     

C-reactive protein but not hepcidin,NGAL and transferrin determines the ESA resistance in hemodialysis patients

Background: Erythropoiesis-stimulating agents (ESA) are commonly used for the treatment of anemia in hemodialysis (HD) patients, however, 5–10% of these patients have resistance to ESA treatment. Hepcidin and neutrophil-gelatinase associated lipocalin (NGAL) are induced by inflammation and these proteins may take role in ESA resistance. Herein, we aimed to investigate the effects of serum hepcidin, NGAL, transferrin and C-reactive protein (CRP) levels on ESA resistance in HD patients. Methods: A total of 63 chronic HD patients (6.0?±?17?years, M/F:44/19) and 20 healthy controls (6.0?±?4?years, M/F:14/6) were enrolled. ESA resistance index (ERI) was calculated as weekly ESA dose (IU)/body weight (kg)/hemoglobin level (g/dL). Patients on ESA treatment were divided into two groups depending on the median ERI value as low and high ERI groups. Results: Serum ferritin, hepcidin and NGAL levels were significantly higher in HD patients compared with controls. Serum transferrin levels were lower in high ESA index group compared with patients without ESA treatment and healthy controls. ERI was significantly correlated with serum CRP levels (r?=?0.55, p?r?=?0.55, p?r?=?0.27, p?=?0.03). Dose of ESA was significantly associated with serum CRP (r?=?0.34, p?=?0.02), total protein (r?=??0.34, p?=?0.01), transferrin (r?=??0.28, p?=?0.04) and ferritin (r?=?0.31, p?=?0.02). In linear regression analysis to predict ERI, age, gender, serum CRP, hepcidin, NGAL, albumin, ferritin and BMI were included (Model R?=?0.62, R²?=?0.38, p?=?0.02). Serum CRP was the only significant factor predicting ERI. Conclusion: CRP was the only predictor of ESA resistance index in HD patients. Hepcidin, NGAL and transferrin were not found to be markers of ESA resistance.     

Very low doses of direct intravenous iron in each session as maintenance therapy in hemodialysis patients

Background: Intravenous (IV) iron supplementation is widely used in hemodialysis (HD) patients to treat their periodic losses. However, the ideal dose and frequency is unknown. The goal of the study is to see if a 20?mg dose of iron IV at the end of each session of HD as iron maintenance is better than the iron prior therapy. We analyze the erythropoiesis activity (EA) and functional iron (FI) after four weeks of treatment.

Methods: In 36 patients, we measure reticulocyte count and content of hemoglobin reticulocyte (CHr) as EA and FI markers, respectively, before and after the treatment. Before the study, 23 patients received another different therapy with IV iron as maintenance therapy.

Results: Reticulocyte count: 49.7?±?23.8?×?10³ before and 47.2?±?17.2?×?10³ after the treatment (p=?0.51). The CHr: 34.8?±?3.7?pg and 34.4?±?3.5?pg, respectively, (p=?0.35), showing an excellent correlation with the other FI markers (serum iron r?=?0.6; p?=?0.001; saturation transferrin r?=?0.49; p?=?0.004); that is not shown with the serum ferritin (r?=?0.23; p?=?0.192) or the hepcidin levels (r?=?0.22; p?=?0.251). There was not a correlation between the C-Reactive Protein, reticulocyte count, and CHr. The 13 patients who did not receive the iron prior to the study showed high FI levels, but not an increased of the serum ferritin or the serum hepcidin levels.

Conclusions: The administration of a small quantity of iron at the end of every HD session keeps the EA and the FI levels and allows reducing the iron overload administered and/or decreasing the iron stores markers in some patients.     

Placental Growth Factor in Patients with Decreased Renal Function

Background: Patients with decreased renal function are characterized by high cardiovascular morbidity and mortality due to complications of premature atherosclerosis. Placental growth factor (PlGF) is a proatherogenic cytokine and new biomarker of cardiovascular events. The aim of this study was to determine PlGF levels and describe their relationship to renal function and risk factors of atherogenesis in patients with decreased renal function. Methods: The study group consisted of 114 subjects: 45 patients with various degrees of decreased renal function (CHRI), 31 long-term hemodialysis (HD) patients, and 38 age-matched healthy control subjects. PlGF was assessed immunochemically (enzyme-linked immunosorbent assay) and routine biochemical parameters were measured using standard laboratory methods. Results: PlGF levels were significantly increased in CHRI and HD patients compared to controls (10.5 ± 3.3 pg/mL in CHRI patients and 11.5 ± 3.4 pg/mL HD patients vs. 8.1 ± 1.8 pg/mL in controls, both p < 0.0001). In CHRI patients, PlGF was detectable in the urine, and its urine concentration correlated with its serum levels. In HD patients, PlGF correlated with low-density lipoproteins (r?=?0.36, p < 0.05), but was not related to C-reactive protein levels. Higher levels of PlGF were found in CHRI patients with cardiovascular disease, compared with those free of such complication. Conclusions: PlGF levels are increased in patients with decreased kidney function. PlGF is detectable in the urine, and serum and urine levels of PlGF are significantly interrelated. It is higher in CHRI patients with cardiovascular disease. Further studies are required to demonstrate the usefulness and significance of PlGF in patients with chronic kidney disease.     

Damage-associated molecular patterns derived from mitochondria may contribute to the hemodialysis-associated inflammation

Purpose

Inflammation is common in hemodialysis (HD) patients. Mitochondrial damage-associated molecular patterns (DAMPs) are released during cell necrosis or apoptosis and induce inflammation. Cell apoptosis is increased in HD patients. The mitochondrial protein cytochrome c, as a marker of released mitochondrial DAMPs, and interleukin-6 (IL-6), as a marker of inflammation, were evaluated in HD patients.

Methods

Thirty-four HD patients and 20 controls were enrolled in the study. Serum cytochrome c and IL-6 were measured by means of enzyme-linked immunosorbent assay.

Results

Compared to controls, cytochrome c was markedly increased in HD patients (1392.88 ± 905.24 pg/mL vs. 212.95 ± 91.71 pg/mL). IL-6 was also significantly increased in HD patients (50.32 ± 35.89 pg/mL vs. 14.27 ± 6.83 pg/mL). In HD patients serum IL-6 was positively related to serum cytochrome c (r = 0.458).

Conclusion

Both circulating cytochrome c and IL-6 are markedly increased in HD patients. Cytochrome c is positively related to IL-6.     

Blood pressure assessment in haemodialysis patients: Comparison between pre-dialysis blood pressure and ambulatory blood pressure measurement

Aim: Hypertension is common in haemodialysis (HD) patients. Determining the most appropriate method of blood pressure (BP) measurement, representative of target organ damage, is still an issue. BP variations between pre‐ and post‐HD treatment, or between on‐dialysis day and off‐dialysis day, are common. The aim of this study was to examine the possible differences between pre‐HD office BP (OBP) levels, inter‐HD (iHD) or HD day 24 h ambulatory BP measurement (ABPM) with 48 h ABPM, where the latter was considered the gold standard. Methods: 163 HD patients were studied. BP was monitored consecutively for 48 h with a Takeda TM2421 device, then sub‐analysed into two periods of 24 h: HD and iHD day. An average of 12 sessions pre‐HD OBP measurements was determined. Results: OBP significantly overestimates systolic (SBP) and diastolic BP (DBP) when compared with 48 h ABPM. SBP and DBP are significantly higher on iHD day than on HD day: 141.2 ± 20.8 versus 137.9 ± 20.9, and 77.1 ± 11.1 versus 76.1 ± 10.9 (P < 0.01). No differences of SBP night/day ratio were reported between 48 h ABPM and iHD 24 h ABPM or HD 24 h ABPM. The highest correlations were reported between 48 h SBP/DBP with iHD or HD 24 h ABPM (r² = 0.95, P < 0.001), while the lowest between 48 h SBP/DBP and OBP (r² = 0.40, P < 0.01, r² = 0.12, P < 0.01). The narrowest limits of agreement using the Bland and Altman test were reported between 48 h SBP or DBP and 24 h iHD or HD day ABPM. Considering 48 h ABPM, 80.5% of patients had BP higher than the norm, compared with 61.7% of patients in the case of OBP (χ² = 13.28, P < 0.001). The sensibility for detecting hypertension for iHD day 24 h ABPM was 98.4%, with specificity of 90%. The sensibility of 24 h HD day ABPM was 90.3%, with specificity 96.6%. In the case of OBP, sensibility and specificity were considerably lower, that is, 72.6% and 83.3% respectively. Conclusion: Significant differences are shown between OBP and 48 h ABPM in the recognition of a hypertensive state. OBP measurement has a lower sensibility and specificity than 24 h ABPM, which remains a valid alternative approach to 48 h ABPM in HD patients. Errors of OBP estimation should be taken into account, with possible negative impact on treatment strategies and epidemiology studies.     

Endothelial dysfunction in hemodialysis patients with failed renal transplants

Gorgulu N, Yelken B, Caliskan Y, Elitok A, Cimen AO, Yazici H, Oflaz H, Golcuk E, Ekmekci A, Turkmen A, Yildiz A, Sever MS. Endothelial dysfunction in hemodialysis patients with failed renal transplants.
Clin Transplant 2009 DOI: 10.1111/j.1399‐0012.2009.01160.x
© 2009 John Wiley & Sons A/S. Abstract: Background: Endothelial dysfunction (ED) is a common precursor and denominator of cardiovascular events including development of atherosclerosis. In this cross‐sectional study, we aimed to investigate ED, measured by coronary flow reserve (CFR) in hemodialysis (nHD) patients who were never transplanted and patients with failed renal transplants restarting hemodialysis (fTx‐HD). Methods: Forty nHD (24 males, mean age 39 ± 9 yr) and 43 fTx‐HD patients (27 males, mean age 36 ± 9 yr) were included in the study. Clinical and biochemical parameters, including high‐sensitive C‐reactive protein (hs‐CRP) levels were determined. Also, CFR measurements were used to evaluate ED. Results: There were no significant differences regarding age, gender, smoking status, systolic and diastolic blood pressure levels, mean duration of HD treatment as well as Kt/V_(urea) values between the two groups. Time spent on dialysis in the nHD group and dialysis duration following failure of renal allograft in the fTx‐HD group were similar. Serum creatinine, hemoglobin, hematocrit, calcium and phosphorus levels were similar between the two groups as well. When compared to nHD group, serum total cholesterol (139 ± 3 vs. 154 ± 3 mg/dL, p = 0.045), serum albumin (3.8 ± 0.3 g/dL vs. 4.1 ± 0.2 g/dL, p < 0.0001) and CFR (1.60 ± 0.2 vs. 1.75 ± 0.3, p = 0.028) levels were significantly lower, while serum hs‐CRP levels (11 ± 15 mg/L vs. 3 ± 4 mg/L, p = 0.001) were significantly higher in the fTx‐HD group. Serum hs‐CRP negatively correlated (r = ?0254, p = 0.021), while serum albumin positively correlated (r = 0402, p = 0.001) with CFR values. Conclusion: ED is more prominent in fTx‐HD than the nHD patients. Inflammation, caused by failed renal allograft can be responsible for this abnormality.     

High serum phosphorus and FGF 23 levels are associated with progression of coronary calcifications

Background

Coronary calcifications (CC) portend increased mortality in adults receiving hemodialysis (HD), however the risk factors associated with CC progression are not well known in pediatric patients. Our previous cross-sectional studies demonstrated high CC prevalence (31 %) in pediatric patients, which were significantly associated with high serum phosphorus (P), fibroblast growth factor 23 (FGF) levels, dialysis vintage, and low cholesterol. The current study was undertaken to determine and elucidate CC progression in pediatric HD patients.

Methods

A 1-year prospective longitudinal study of 16 pediatric patients (ten male; mean age, 16.9 ± 3 years; range, 10.1–20.4 years) receiving chronic HD was conducted.

Results

CC were observed in five of 16 (31.3 %) patients on baseline computed tomogram (CT) scan; 14/16 patients underwent 1-year CT. All patients with initial CC who completed CT at 1 year (3/5) progressed; one patient had new CC and none of the patients had resolved CC. Mean Agatston score increased from 23.4 ± 18.06 HU (baseline) to 169 ± 298.9 HU. Patients with CC progression had higher mean serum P (8.6 ± 1.8 mg/dl vs. 6.3 ± 1.1 mg/dl, p = 0.015) and FGF 23 levels (3,994 ± 860.5 pg/ml vs. 2,327 ± 1,206.4 pg/ml, p = 0.028). Serum P and FGF 23 levels were positively correlated with final Agatston scores (R = 0.65, p = 0.01 for serum P and R = 0.54, p = 0.045 for FGF 23) and change in Agatston scores (R = 0.65, p = 0.01 for serum P and R = 0.52, p = 0.048 for FGF 23).

Conclusions

Our study shows that CC is progressive in pediatric patients receiving HD and that increased serum P and FGF 23 levels are associated with this progression.