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3. Erythropoietic response to oral iron in patients with nondialysis-dependent chronic kidney disease in the FIND-CKD trial

Author

Macdougall, I. C., Bock, A. H., Carrera, F., Eckardt, K. -U., Gaillard, C., Van Wyck, D., Meier, Y., Larroque, S., Perrin, A., Roger, S. D., Gilles, Auguste, Faull, R., Toussaint, N. D., Mcmahon, L., Suranyi, M., Mudge, D., Hutchison, B., Irish, A., Kerr, P., Kulkarni, H., Elder, G., Jardine, M., Lhotta, K., Mayer, G., Vanholder, R., Maes, B. D., Evenepoel, P., Debelle, F., Jadoul, M., Dratwa, M., Macel, I., Dunaj, M., Kvapil, M., Bucek, P., Rehorova, J., Hruby, A., Honova, V., Malanova, L., Lucak, M., Lecian, D., Jirovec, M., Vlasak, J., Rychlik, I., Surel, S., Kamper, A. -L., Ostergaard, O., Steffensen, G. K., Chenine, L., Choukroun, G., Zaoui, P., Wanner, C., Backs, W., Kraatz, U., Dellanna, F., Busch, K., Marsen, T., Seeger, W., Woitas, R., Obermueller, N., Haak, T., Lueders, S., Pistrosch, F., Mueller, E., Mertens, P. R., Sutermer, W., Grebe, S. -O., Hafezi-Rachti, S., Roeser, S., Tsakiris, D., Memmos, D., Vlachakos, D., Vargemezis, V., Stefanidis, I., Syrganis, C., Alivanis, P., Papadakis, I., Papagalanis, N., Andrikos, A., Goumenos, D., Siamopoulos, K., Gouva, C., Papadakis, G., Boletis, I., Tsimnadi-Spanoudaki, M., Stamatiades, D., Stamatelou, K., Moutafis, S., Locatelli, Federica, Santoro, A., Quarello, F., Remuzzi, G., Coppola, S., Mortellaro, R. F., Icardi, A., Colussi, G., Grotta, F. D., Lombardi, L., Gallieni, M., Villa, G., Grandaliano, Giuseppe, Huisman, S., Barendregt, J., Gregoor, P. J. H., Oien, C., Rutkowski, B., Malecki, R., Nowicki, M., Rutkowski, P., Marczewski, K., Mysliwiec, M., Sydor, A., Rysz, J., Rydzewski, A., Klinger, M., Wnuk, R., Kozminski, P., Nocon, A., Ciechanowski, K., Correia, P., Neves, F., Barata, J., Mircescu, G., Voiculescu, M., Gluhovschi, G., Mota, E., De Francisco, A. L. M., Torre, A., Herreros, A., Luno, J., Gruss, E., Martins, J., Valles, M., Pascual, J., Barany, P., Ambuehl, P. M., Erturk, S., Arici, M., Paydas, S., Soypacaci, Z., Camsari, T., Ustundag, S., Thomas, M. E., D'Souza, R. J., Taylor, J. E., Pritchard, N. R., Jeffery, R., Riley, S. G., Bhatnagar, D., Bhandari, S., Reaich, D., Stevens, P. E., El Kossi, M., Roe, S., Camilleri, B., Ahmed, A., Khwaja, A., Thompson, B., Banerjee, D., Nicholas, J., Hutchison, A., Borrows, R., and Groningen Kidney Center (GKC)

Subjects
0301 basic medicine, Male, 030232 urology & nephrology, Administration, Oral, Gastroenterology, oral, 0302 clinical medicine, DIALYSIS, nondialysis, Settore MED/14 - NEFROLOGIA, Erythropoiesis, SUCROSE, Aged, 80 and over, education.field_of_study, biology, Anemia, General Medicine, Iron deficiency, RANDOMIZED CONTROLLED-TRIAL, Middle Aged, Nephrology, Female, INTRAVENOUS FERRIC CARBOXYMALTOSE, Research Article, Adult, medicine.medical_specialty, Iron, Population, supplement, 03 medical and health sciences, Multicenter trial, Internal medicine, medicine, DEFICIENCY ANEMIA, Humans, Renal Insufficiency, Chronic, education, Aged, Transferrin saturation, business.industry, ferritin, hemoglobin, medicine.disease, Ferritin, 030104 developmental biology, biology.protein, Hemoglobin, business, Kidney disease
Abstract

Aims: To evaluate erythropoietic response rates to oral iron over time in iron-deficient anemic patients with nondialysis-dependent chronic kidney disease (ND-CKD). Materials and methods: FIND-CKD was a 1-year, randomized, multicenter trial of iron therapy in patients with ND-CKD, anemia, and iron deficiency, without erythropoiesis-stimulating agent (ESA) therapy. Patients with active infection or C-reactive protein > 20 mg/L were excluded. In this post-hoc analysis, response was defined as >= 1 g/dL increase in hemoglobin (Hb) from baseline, before initiation of alternative anemia therapy (i.e., ESA, transfusion, or intravenous iron). Results: 308 patients received oral iron (200 mg elemental iron/day). Mean (SD) Hb at baseline was 10.4 (0.7) g/dL. At week 4, Hb data were available from 292 patients without alternative anemia therapy: 63/292 (21.6%) showed a response. Among the 229 nonresponders at week 4, 48.8% showed a cumulative response on >= 1 occasion by week 52 (11.1%, 19.9%, 25.9%, and 28.7% had a response at weeks 8, 12, 24, and 52, respectively), and 27.9% had received alternative iron therapy by week 52. Baseline levels of Hb, ferritin, and transferrin saturation were lower in responders than in nonresponders. Neither concomitant medication nor adherence (as assessed by medication count) was substantially different between early responders and nonresponders. Conclusion: Four weeks after starting oral iron therapy, only 21.6% of anemic patients with ND-CKD and iron deficiency showed an Hb increase of at least 1 g/dL. Among early nonresponders

Published
2017

4. Correction of anemia with erythropoietin in chronic kidney disease (stage 3 or 4): effects on cardiac performance

Author

Pappas, K. D., Gouva, C. D., Katopodis, K. P., Nikolopoulos, P. M., Korantzopoulos, P. G., Michalis, L. K., Goudevenos, J. A., and Siamopoulos, K. C.

Subjects
Adult, Aged, 80 and over, Male, Heart Rate/drug effects, Hematinics/*pharmacology/therapeutic use, Middle Aged, Anemia/*drug therapy/etiology, Blood Pressure/drug effects, Echocardiography, Doppler, Recombinant Proteins, Kidney Failure, Chronic/complications/*drug therapy, Erythropoietin/*pharmacology/therapeutic use, Humans, Female, Ventricular Function, Left/drug effects, Prospective Studies, Aged, Follow-Up Studies
Abstract

BACKGROUND: It is not clear whether the correction of anemia with erythropoietin (rhuEpo) in patients with chronic kidney disease (CKD) has any benefit on cardiac function and geometry. Most studies are based on indices of systolic function and left ventricular mass (LVM) and the results are conflicting. PATIENTS AND METHODS: We sought to investigate the effect of rhuEpo on LV systolic and diastolic performance using conventional and novel echocardiographic indices. Thirty one patients with CKD (stage 3 or 4) were included. Fifteen patients (group I) treated with rhuEpo targeting at Hb >or=13.0 g/dL, while the remaining (group II) were not treated. Clinical and laboratory parameters were recorded at baseline and 1 year later. Ejection fraction (EF) and LVM were carefully determined. Diastolic function was assessed by mitral inflow indices (E and A wave velocities, Edt deceleration time and E/A) and novel indices of mitral annulus motion using Tissue Doppler Imaging (Em, Am, and E/Em). An index of global cardiac function (Tei) was also calculated. RESULTS: At baseline, the 2 groups had comparable clinical and laboratory characteristics. After 1 year, a significant improvement in Hb levels (13.6 +/- 1.2 vs 10.3 +/- 1.2 g/dL, p < 0.05) as well as in systolic and diastolic function indexes was observed in group I compared to group II patients: EF (70.5 +/- 7.6 vs 63.4 +/- 9.3%, p < 0.05), LVM (116.5 +/- 34.9 vs 155.6 +/- 51.6 g/m(2), p < 0.05), Edt (233.9 +/- 98.6 vs 166.9 +/- 45.1 ms, p < 0.05), Tei index (0.35 +/- 0.12 vs 0.51 +/- 0.17, p < 0.01) and E/Em (9.7 +/- 2.4 vs 14.8 +/- 5.2, p < 0.05), respectively. Blood pressure and heart rate did not show significant changes. CONCLUSIONS: Correction of anemia with rhuEpo in patients with CKD seems to improve cardiac performance and geometry. Cardiovasc Drugs Ther

Published
2008

5. Long-term treatment with EPO increases serum levels of high-density lipoprotein in patients with CKD

Author

Siamopoulos, K. C., Gouva, C., Katopodis, K. P., Tzallas, C., Nikolopoulos, P., Papavasiliou, E. C., and Tselepis, A. D.

Subjects
activating factor-acetylhydrolase, ester transfer protein, renal-failure, paf-acetylhydrolase activity, lipids, lipid profile, risk-factor, hemodialysis-patients, recombinant-human-erythropoietin, chronic kidney disease (ckd), erythropoietin (epo), chronic kidney-disease, coronary-heart-disease, renal anemia
Abstract

Background. Among lipid abnormalities observed in patients with chronic kidney disease (CKD) is a significant decrease in serum high-density lipoprotein cholesterol (HDL-C) levels. In a previously published randomized control trial, we showed that early erythropoietin (EPO) administration in a predialysis population slowed the progression of CKD. In the present nested substudy, we examine whether EPO has an influence on serum HDL-C levels in comparison to other lipid parameters in this population. Methods: Eighty-eight patients with CKD stages 3 and 4 were enrolled in the study. Forty-five patients (group 1) were treated with EPO (50 U/kg/wk), targeting to increase hemoglobin levels to 13 g/dL or greater ( >= 130 g/L). The other patients (group 2) remained without treatment until hemoglobin levels decreased to less than 9 g/dL (

Published
2006

6. PAF-acetylhydrolase activity in plasma of patients with chronic kidney disease. Effect of long-term therapy with erythropoietin

Author

Papavasiliou, E. C., Gouva, C., Siamopoulos, K. C., and Tselepis, A. D.

Subjects
paf-acetylhydrolase, renal-failure, blood cell-cultures, lipoproteins, lipoprotein-associated phospholipase-a2, inflammation, hemodialysis-patients, recombinant-human-erythropoietin, a(2), atherosclerosis, monocytes, platelet-activating-factor, coronary-heart-disease, epoetin, paraoxonase-1, chronic kidney disease
Abstract

Background. Platelet activating factor acetylhydrolase (PAF-AH) is a Ca2+-independent phospholipase A(2) that is secreted mainly from monocytes/macrophages. In human plasma, PAF-AH is associated primarily with low-density lipoprotein (LDL), while a small proportion of enzyme is associated with high-density lipoprotein (HDL). The ratio of HDL-PAF-AH to total plasma enzyme activity may represent a potential marker of atherogenicity. We evaluated possible alterations of lipoprotein-associated enzyme activity in Chronic Kidney Disease (CKD) patients, stages 3-4, and further investigated whether long-term therapy with recombinant human erythropoietin (epoetin) has any influence on the plasma PAF-AH activity in vivo or on the enzyme activity secreted from peripheral blood monocytes (PBMs), in vitro. Methods. Forty-eight patients, 28 men and 20 women, with CKD (stages 3-4) participated in the study. Patients were randomized into groups I and II. Patients of group I (n = 28) were administered subcutaneously epoetin, 50 units/kg once per week. The Hb target was 13 g/dl. In group II (n = 20), epoetin was initiated only when the Hb levels decreased during follow-up to less than 9 g/dl. All patients were seen on an outpatient basis at 2, 4 and 6 months. Twenty-two normolipidemic age- and sex-matched healthy volunteers also participated in the study and were used as controls. Results. The PAF-AH activity in plasma of both patient groups at baseline was higher compared to controls, whereas no difference in the HDL-PAF-AH activity was observed among the studied groups. Thus, the ratio of HDL-PAF-AH to the plasma enzyme activity was significantly lower in both patient groups compared to controls. Epoetin administration in the patients of group I was associated with a significant increase in the plasma PAF-AH and in HDL-PAF-AH activities 2 months after treatment, which remained stable for up to 6 months of therapy, a phenomenon not observed in untreated patients of group II. Thus, the ratio of HDL-PAF-AH to the plasma enzyme activity was significantly increased in patients of group I compared to the baseline values, a phenomenon not observed in patients of group II. In vitro treatment with epoetin of PBMs from patients of group I (undergoing therapy with epoetin) resulted in a dose-dependent increase in total and secreted enzyme activity, a phenomenon not observed in patients of group II who did not receive therapy with epoetin. This suggests that the in vivo increase in lipoprotein-associated PAF-AH observed in patients treated with epoetin may be attributed to the drug-induced enhanced secretion of PAF-AH from PBMs of these patients. Conclusions. CKD patients of stages 3-4 are characterized by an increase in plasma PAF-AH activity and a low ratio of HDL-PAF-AH to total plasma enzyme activity. Long-term therapy with epoetin may improve this atherogenic ratio thus this drug may play an important antiatherogenic role in CKD. Nephrology Dialysis Transplantation

Published
2006

7. Sevelamer hydrochloride versus aluminum hydroxide: effect on serum phosphorus and lipids in CAPD patients

Author

Katopodis, K. P., Andrikos, E., Gouva, C. D., Bairaktari, E. T., Nikolopoulos, P. M., Takouli, L. K., Tzallas, C. S., Elisaf, M. S., Pappas, M. V., and Siamopoulos, K. C.

Subjects
Adult, Male, Cross-Over Studies, Kidney Diseases/classification/therapy, Aluminum Hydroxide/adverse effects/*therapeutic use, Phosphates/*blood, Humans, Lipids/*blood, Female, Polyamines/adverse effects/*therapeutic use, Middle Aged, Peritoneal Dialysis, Continuous Ambulatory/*methods, Aged
Abstract

BACKGROUND: Dietary phosphorus restriction, oral administration of phosphorus binders, and dialysis are the main strategies to control hyperphosphatemia in patients with stage 5 chronic kidney disease. Aluminum hydroxide (AH) and calcium carbonate, the most commonly used phosphorus binders, have serious disadvantages, such as aluminum toxicity and hypercalcemia. Sevelamer hydrochloride (SH) is a relatively new nonabsorbed calcium- and aluminum-free phosphorus binder. The present study was designed to evaluate the efficacy of SH in the control of hyperphosphatemia and its effect, compared to AH, on serum lipid parameters in patients on continuous ambulatory peritoneal dialysis (CAPD). METHODS: 30 stable patients on CAPD were included in an open-label, randomized crossover study. After a 2-week phosphorus binder washout period, 15 patients (group I) were administered SH for 8 weeks and in the remaining patients (group II), AH was introduced (phase A). After a new 2-week washout period, patients crossed over to the alternate agent for another 8 weeks (phase B). RESULTS: There were similar reductions in serum phosphorus levels over the course of the study with both agents: by 1.18 +/- 0.07 mg/dL (0.38 +/- 0.03 mmol/L) with SH and by 1.25 +/- 0.15 mg/dL (0.40 +/- 0.05 mmol/L) with AH in phase A (p = NS), and by 1.35 +/- 0.25 mg/dL (0.43 +/- 0.08 mmol/L) with AH and by 1.23 +/- 0.80 mg/dL (0.39 +/- 0.25 mmol/L) with SH in phase B (p = NS). Moreover, SH administration was associated with a 10.5% +/- 9.4% and a 20.1% +/- 6.8% fall in total cholesterol (p < 0.05) and low-density Lipoprotein cholesterol (p < 0.001) in phase A, and 11.9% +/- 7.2% (p < 0.05) and 21.5% +/- 2.4% (p < 0.001), respectively, in phase B. In both phases of the study, AH administration was not followed by a significant change in serum lipid parameters. CONCLUSION: Sevelamer hydrochloride is a well-tolerated alternative to calcium- or aluminum-containing phosphorus binder in the control of serum phosphorus in CAPD patients. Furthermore, SH improves the lipid profile in these patients. Perit Dial Int

Published
2006

8. Erythrocyte PAF-acetylhydrolase activity in various stages of chronic kidney disease: Effect of long-term therapy with erythropoietin

Author

Papavasiliou, E. C., Gouva, C., Siamopoulos, K. C., and Tselepis, A. D.

Subjects
paf-acetylhydrolase, anemia, glutathione-peroxidase, inflammation, hemodialysis-patients, oxidative stress, erythrocyte, erythropoietin, platelet-activating-factor, uremic patients, cell membrane, chronic kidney disease, plasma, chronic-renal-failure
Abstract

Background. Erythrocytes represent an important component of the antioxidant capacity of blood, comprising, in particular, intracellular enzymes, including platelet-activating factor acetylhydrolase (PAF-AH) and glutathione peroxidase (Gpx). We evaluated the erythrocyte PAF-AH and Gpx activities in various stages of chronic kidney disease (CKD), and further investigated whether erythropoietin (EPO) administration in these patients has any influence on the enzyme activities. Methods. Thirty-six patients (19 men and 17 women) with CKD (stages 1 to 5) participated in the study. Thirteen of them presented with CKD stage 1 to 2 (group I), whereas 23 patients presented with CKD stage 3 to 5 and randomized into two groups (i.e., groups II and III). Patients of group II (N= 11) were administered EPO subcutaneously, 50 units per kg once per week. In group III (N= 12), EPO was initiated only when the hemoglobin (Hb) levels decreased during follow-up to less than 9 g/dL. All patients were seen on an outpatient basis at 2 and 4 months. Fifteen normolipidemic age- and sex-matched healthy volunteers also participated in the study and were used as controls. The PAF-AH and Gpx activities were determined in isolated washed erythrocytes. Results. The erythrocyte-associated PAF-AH and Gpx activities were higher in all CKD patient groups at baseline compared to controls, the groups II and III exhibiting significantly higher enzyme activities compared with group I. In all studied populations, both enzyme activities were negatively correlated with the creatinine clearance values. Importantly, the PAF-AH and Gpx activities were progressively decreased during the follow-up in patients not treated with EPO (group III), a phenomenon not observed in patients receiving EPO (group II), or in patients of group I. This reduction in enzyme activities was positively correlated with the decrease in the creatinine clearance values in patients of group III. Conclusion. Significant alterations in the erythrocyte-associated PAF-AH and Gpx activities related to the disease stage are observed in CKD patients. Administration of EPO prevented the reduction in enzyme activities observed during the progression of the renal insufficiency, thus preserving the erythrocyte defense mechanisms against oxidative stress. Kidney Int

Published
2005

10. Treating anemia early in renal failure patients slows the decline of renal function: a randomized controlled trial

Author

Gouva, C., Nikolopoulos, P., Ioannidis, J. P., and Siamopoulos, K. C.

Subjects
Male, Hemoglobins, Treatment Outcome, Erythropoietin/*administration & dosage/adverse effects, Kidney Failure, Chronic/*complications/*physiopathology, Disease Progression, Humans, Female, Middle Aged, Anemia/*drug therapy/etiology, Aged, Follow-Up Studies
Abstract

BACKGROUND: Erythropoietin is known to improve outcomes in patients with anemia from chronic renal disease. However, there is uncertainty about the optimal timing of initiation of erythropoietin treatment in predialysis patients with non-severe anemia. METHODS: We conducted a randomized controlled trial of early versus deferred initiation of erythropoietin in nondiabetic predialysis patients with serum creatinine 2 to 6 mg/dL and hemoglobin 9 to 11.6 g/dL. The early treatment arm was immediately started on 50 U/kg/wk of erythropoietin alpha with appropriate titration aiming for hemoglobin of > or =13 g/dL. The deferred treatment arm would start erythropoietin only when hemoglobin decreased to

Published
2004

13. Extracorporeal dialysis: techniques and adequacy

Author

Donadio, C., primary, Kanaki, A., additional, Martin-Gomez, A., additional, Garcia, S., additional, Palacios-Gomez, M., additional, Donadio, C., additional, Calia, D., additional, Colombini, E., additional, DI Francesco, F., additional, Ghimenti, S., additional, Onor, M., additional, Tognotti, D., additional, Fuoco, R., additional, Marka-Castro, E., additional, Torres Zamora, M. I., additional, Giron-Mino, J., additional, Jaime-Solis, M. A., additional, Arteaga, L. M., additional, Romero, H., additional, Akonur, A., additional, Leypoldt, K., additional, Asola, M., additional, Culleton, B., additional, Eloot, S., additional, Glorieux, G., additional, Nathalie, N., additional, Vanholder, R., additional, Perez de Jose, A., additional, Verdalles Guzman, U., additional, Abad Esttebanez, S., additional, Vega Martinez, A., additional, Barraca, D., additional, Yuste, C., additional, Bucalo, L., additional, Rincon, A., additional, Lopez-Gomez, J. M., additional, Bataille, P., additional, Celine, P., additional, Raymond, A., additional, Francois, G., additional, Herve, L., additional, Michel, D., additional, Jean Louis, R., additional, Zhu, F., additional, Kotanko, P., additional, Thijssen, S., additional, Levin, N. W., additional, Papamichail, N., additional, Bougiakli, M., additional, Gouva, C., additional, Antoniou, S., additional, Gianitsi, S., additional, Vlachopanou, A., additional, Chachalos, S., additional, Naka, K., additional, Kaarsavvidou, D., additional, Katopodis, K., additional, Michalis, L., additional, Sasaki, K., additional, Yasuda, K., additional, Yamato, M., additional, Surace, A., additional, Rovatti, P., additional, Steckiph, D., additional, Bandini, R., additional, Severi, S., additional, Dellacasa Bellingegni, A., additional, Santoro, A., additional, Arias, M., additional, Sentis, A., additional, Perez, N., additional, Fontsere, N., additional, Vera, M., additional, Rodriguez, N., additional, Arcal, C., additional, Ortega, N., additional, Uriza, F., additional, Cases, A., additional, Maduell, F., additional, Abbas, S. R., additional, Georgianos, P., additional, Sarafidis, P., additional, Nikolaidis, P., additional, Lasaridis, A., additional, Ahmed, A., additional, Kaoutar, H., additional, Mohammed, B., additional, Zouhir, O., additional, Balter, P., additional, Ginsberg, N., additional, Taylor, P., additional, Sullivan, T., additional, Usvyat, L. A., additional, Zabetakis, P., additional, Moissl, U., additional, Ferrario, M., additional, Garzotto, F., additional, Wabel, P., additional, Cruz, D., additional, Tetta, C., additional, Signorini, M. G., additional, Cerutti, S., additional, Brendolan, A., additional, Ronco, C., additional, Heaf, J., additional, Axelsen, M., additional, Pedersen, R. S., additional, Amine, H., additional, Oualim, Z., additional, Ammirati, A. L., additional, Guimaraes de Souza, N. K., additional, Nemoto Matsui, T., additional, Luiz Vieira, M., additional, Alves de Oliveira, W. A., additional, Fischer, C. H., additional, Dias Carneiro, F., additional, Iizuka, I. J., additional, Aparecida de Souza, M., additional, Mallet, A. C., additional, Cruz Andreoli, M. C., additional, Cardoso Dos Santos, B. F., additional, Rosales, L., additional, Dou, Y., additional, Carter, M., additional, Testa, A., additional, Sottini, L., additional, Giacon, B., additional, Prati, E., additional, Loschiavo, C., additional, Brognoli, M., additional, Marseglia, C., additional, Tommasi, A., additional, Sereni, L., additional, Palladino, G., additional, Bove, S., additional, Bosticardo, G., additional, Schillaci, E., additional, Detoma, P., additional, Bergia, R., additional, Park, J. W., additional, Moon, S. J., additional, Choi, H. Y., additional, Ha, S. K., additional, Park, H.-C., additional, Liao, Y., additional, Zhang, L., additional, Fu, P., additional, Igarashi, H., additional, Suzuki, N., additional, Esashi, S., additional, Masakane, I., additional, Panichi, V., additional, De Ferrari, G., additional, Saffiotti, S., additional, Sidoti, A., additional, Biagioli, M., additional, Bianchi, S., additional, Imperiali, P., additional, Gabrielli, C., additional, Conti, P., additional, Patrone, P., additional, Rombola, G., additional, Falqui, V., additional, Mura, C., additional, Icardi, A., additional, Rosati, A., additional, Santori, F., additional, Mannarino, A., additional, Bertucci, A., additional, Jeong, J., additional, Kim, O. K., additional, Kim, N. H., additional, Bots, M., additional, Den Hoedt, C., additional, Grooteman, M. P., additional, Van der Weerd, N. C., additional, Mazairac, A. H. A., additional, Levesque, R., additional, Ter Wee, P. M., additional, Nube, M. J., additional, Blankestijn, P., additional, Van den Dorpel, M. A., additional, Park, Y., additional, Jeon, J., additional, Tessitore, N., additional, Bedogna, V., additional, Girelli, D., additional, Corazza, L., additional, Jacky, P., additional, Guillaume, Q., additional, Julien, B., additional, Marcinkowski, W., additional, Drozdz, M., additional, Milkowski, A., additional, Rydzynska, T., additional, Prystacki, T., additional, August, R., additional, Benedyk-Lorens, E., additional, Bladek, K., additional, Cina, J., additional, Janiszewska, G., additional, Kaczmarek, A., additional, Lewinska, T., additional, Mendel, M., additional, Paszkot, M., additional, Trafidlo, E., additional, Trzciniecka-Kloczkowska, M., additional, Vasilevsky, A., additional, Konoplev, G., additional, Lopatenko, O., additional, Komashnya, A., additional, Visnevsky, K., additional, Gerasimchuk, R., additional, Neivelt, I., additional, Frorip, A., additional, Vostry, M., additional, Racek, J., additional, Rajdl, D., additional, Eiselt, J., additional, Malanova, L., additional, Pechter, U., additional, Selart, A., additional, Ots-Rosenberg, M., additional, Krieter, D. H., additional, Seidel, S., additional, Merget, K., additional, Lemke, H.-D., additional, Wanner, C., additional, Canaud, B., additional, Rodriguez, A., additional, Morgenroth, A., additional, Von Appen, K., additional, Dragoun, G.-P., additional, Fluck, R., additional, Fouque, D., additional, Lockridge, R., additional, Motomiya, Y., additional, Uji, Y., additional, Hiramatsu, T., additional, Ando, Y., additional, Furuta, M., additional, Kuragano, T., additional, Kida, A., additional, Yahiro, M., additional, Otaki, Y., additional, Hasuike, Y., additional, Nonoguchi, H., additional, Nakanishi, T., additional, Sain, M., additional, Kovacic, V., additional, Ljutic, D., additional, Radic, J., additional, Jelicic, I., additional, Yalin, S. F., additional, Trabulus, S., additional, Yalin, A. S., additional, Altiparmak, M. R., additional, Serdengecti, K., additional, Ohtsuka, A., additional, Fukami, K., additional, Ishikawa, K., additional, Ando, R., additional, Kaida, Y., additional, Adachi, T., additional, Sugi, K., additional, Okuda, S., additional, Nesterova, O. B., additional, Suglobova, E. D., additional, Golubev, R. V., additional, Vasiliev, A. N., additional, Lazeba, V. A., additional, Smirnov, A. V., additional, Arita, K., additional, Kihara, E., additional, Maeda, K., additional, Oda, H., additional, Doi, S., additional, Masaki, T., additional, Hidaka, S., additional, Ishioka, K., additional, Oka, M., additional, Moriya, H., additional, Ohtake, T., additional, Nomura, S., additional, Kobayashi, S., additional, Wagner, S., additional, Gmerek, A., additional, Wagner, J., additional, Wizemann, V., additional, Eftimovska - Otovic, N., additional, Spaseska-Gjurovska, K., additional, Bogdanovska, S., additional, Babalj - Banskolieva, E., additional, Milovanceva, M., additional, Grozdanovski, R., additional, Pisani, A., additional, Riccio, E., additional, Mancini, A., additional, Ambuhl, P., additional, Astrid, S., additional, Ivana, P., additional, Martin, H., additional, Thomas, K., additional, Hans-Rudolf, R., additional, Daniel, A., additional, Denes, K., additional, Marco, M., additional, Wuthrich, R. P., additional, Andreas, S., additional, Andrulli, S., additional, Altieri, P., additional, Sau, G., additional, Bolasco, P., additional, Pedrini, L. A., additional, Basile, C., additional, David, S., additional, Feriani, M., additional, Nebiolo, P. E., additional, Ferrara, R., additional, Casu, D., additional, Logias, F., additional, Tarchini, R., additional, Cadinu, F., additional, Passaghe, M., additional, Fundoni, G., additional, Villa, G., additional, DI Iorio, B. R., additional, Zoccali, C., additional, Locatelli, F., additional, Hamamoto, M., additional, Lee, D.-Y., additional, Kim, B., additional, Moon, K. H., additional, LI, Z., additional, Ahrenholz, P., additional, Winkler, R. E., additional, Waitz, G., additional, Wolf, H., additional, Grundstrom, G., additional, Alquist, M., additional, Holmquist, M., additional, Christensson, A., additional, Bjork, P., additional, Abdgawad, M., additional, Ekholm, L., additional, Segelmark, M., additional, Corsi, C., additional, De Bie, J., additional, Mambelli, E., additional, Mortara, D., additional, Arroyo, D., additional, Panizo, N., additional, Quiroga, B., additional, Reque, J., additional, Melero, R., additional, Rodriguez-Ferrero, M., additional, Rodriguez-Benitez, P., additional, Anaya, F., additional, Luno, J., additional, Ragon, A., additional, James, A., additional, Brunet, P., additional, Ribeiro, S., additional, Faria, M. S., additional, Rocha, S., additional, Rodrigues, S., additional, Catarino, C., additional, Reis, F., additional, Nascimento, H., additional, Fernandes, J., additional, Miranda, V., additional, Quintanilha, A., additional, Belo, L., additional, Costa, E., additional, Santos-Silva, A., additional, Arund, J., additional, Tanner, R., additional, Fridolin, I., additional, Luman, M., additional, Clajus, C., additional, Kielstein, J. T., additional, Haller, H., additional, Libutti, P., additional, Lisi, P., additional, Vernaglione, L., additional, Casucci, F., additional, Losurdo, N., additional, Teutonico, A., additional, Lomonte, C., additional, Krisp, C., additional, Wolters, D. A., additional, Matsuyama, M., additional, Tomo, T., additional, Ishida, K., additional, Matsuyama, K., additional, Nakata, T., additional, Kadota, J., additional, Caiazzo, M., additional, Monari, E., additional, Cuoghi, A., additional, Bellei, E., additional, Bergamini, S., additional, Tomasi, A., additional, Baranger, T., additional, Seniuta, P., additional, Berge, F., additional, Drouillat, V., additional, Frangie, C., additional, Rosier, E., additional, Labonia, W., additional, Lescano, A., additional, Rubio, D., additional, Von der Lippe, N., additional, Jorgensen, J. A., additional, Osthus, T. B., additional, Waldum, B., additional, Os, I., additional, Bossola, M., additional, DI Stasio, E., additional, Antocicco, M., additional, Tazza, L., additional, Griveas, I., additional, Karameris, A., additional, Pasadakis, P., additional, Savica, V., additional, Santoro, D., additional, Saitta, S., additional, Tigano, V., additional, Bellinghieri, G., additional, Gangemi, S., additional, Daniela, R., additional, Checherita, I. A., additional, Ciocalteu, A., additional, Vacaroiu, I. A., additional, Niculae, A., additional, Stefaniak, E., additional, Pietrzak, I., additional, Krupa, D., additional, Garred, L., additional, Mancini, E., additional, Corrazza, L., additional, Atti, M., additional, Afsar, B., additional, Stamopoulos, D., additional, Mpakirtzi, N., additional, Gogola, B., additional, Zeibekis, M., additional, Stivarou, D., additional, Panagiotou, M., additional, Grapsa, E., additional, Vega Vega, O., additional, Barraca Nunez, D., additional, Fernandez-Lucas, M., additional, Gomis, A., additional, Teruel, J. L., additional, Elias, S., additional, Quereda, C., additional, Hignell, L., additional, Humphrey, S., additional, Pacy, N., additional, and Afentakis, N., additional

Published
2012
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14. Bone disease in CKD 1-5

Author

Yilmaz, M. I., primary, Sonmez, A., additional, Saglam, M., additional, Yaman, H., additional, Kilic, S., additional, Eyileten, T., additional, Caglar, K., additional, Oguz, Y., additional, Vuaral, A., additional, Yenicesu, M., additional, Mallamaci, F., additional, Zoccali, C., additional, Mazzaferro, S., additional, Pasquali, M., additional, Rotondi, S., additional, Tartaglione, L., additional, Pirro, G., additional, Muci, M. L., additional, Conte, C., additional, Mandanici, G., additional, Frasheri, A., additional, Pugliese, F., additional, Fehmi, H., additional, Long, Y., additional, Kono, K., additional, Fujii, H., additional, Nakai, K., additional, Goto, S., additional, Shite, J., additional, Hirata, K.-i., additional, Fukagawa, M., additional, Nishi, S., additional, Wu-Wong, J. R., additional, Nakane, M., additional, Chen, Y.-w., additional, Nikolopoulos, P., additional, Vlachopanou, A., additional, Giannaki, C., additional, Siapera, V., additional, Papachristopoulos, V., additional, Gouva, C., additional, Sakhuja, V., additional, Dheerendra, P., additional, Jha, V., additional, Rathi, M., additional, Kohli, H. S., additional, Hadjiyannakos, D., additional, Trompouki, S., additional, Filiopoulos, V., additional, Sonikian, M., additional, Karatzas, I., additional, Panagiotopoulos, K., additional, Vlassopoulos, D., additional, Taskapan, H., additional, Baysal, O., additional, Karahan, D., additional, Ulutas, O., additional, Mircescu, G., additional, Capusa, C., additional, Stancu, S., additional, Badulescu, M., additional, Barsan, L., additional, Dorobantu, N., additional, Maria, D., additional, Mota, E., additional, Yildiz, I., additional, Sagliker, Y., additional, Demirhan, O., additional, Acharya, V., additional, Zhang, L., additional, Golea, O., additional, Sabry, A., additional, Ookalkar, D., additional, Radulescu, D., additional, Garneata, L., additional, Ben Maiz, H., additional, Hsu Chen, C., additional, Prado Rome, J., additional, Benzegoutta, M., additional, Paylar, N., additional, Eyuboglu, K., additional, Karatepe, E., additional, Esenturk, M., additional, Yavascan, O., additional, Adam, S. M., additional, Emir, I., additional, Grzegorzevska, A., additional, Tunc, E., additional, Ocal, F., additional, Usta, E., additional, Shilo, V., additional, Mazdeh, M. M., additional, Francesco, R. C., additional, Levin-Iaina, N., additional, Malyszko, J., additional, Kozminski, P., additional, Koc-Zorawska, E., additional, Mysliwiec, M., additional, Lipan, M., additional, Reichel, H., additional, Ringel, J., additional, Guggenberger, C., additional, Dellanna, F., additional, Teixeira, C., additional, Almeida, E., additional, Raimundo, M., additional, Neves, F., additional, Santana, A., additional, Fortes, A., additional, Abreu, F., additional, Pinto Abreu, C., additional, El Bouazzaoui, Z., additional, Cortesao Costa, A., additional, Nogueira, E., additional, Gomes da Costa, A., additional, ElShafey, E., additional, Alsahow, A., additional, Saran, K., additional, Attia, M., additional, Di Lullo, L., additional, Gorini, A., additional, Cecilia, A., additional, Comegna, C., additional, Galderisi, C., additional, Iannacci, G. R., additional, Vitale, M., additional, Polito, P., additional, Kyritsis, I., additional, Roumelioti, M.-E., additional, Agroyannis, I., additional, Vrachnis, S., additional, Kapelleris, V., additional, Fituri, O., additional, Ismail, G., additional, Donia, A., additional, Sezer, S., additional, Karakan, S., additional, Atesagaoglu, B., additional, Tutal, E., additional, Ozdemir Acar, N., additional, Ozturk, S., additional, Uzun, S., additional, Kaya, A. H., additional, Gursu, M., additional, Kaya, B., additional, Sarbay Kemik, A., additional, Aydin, Z., additional, Karadag, S., additional, Feyizoglu, H., additional, Kazancioglu, R., additional, and Vlad, I., additional

Published
2011
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15. Cardiovascular complications in CKD 5D (1)

Author

Kuo, K.-L., primary, Hung, S.-C., additional, Tarng, D.-C., additional, Selim, G., additional, Stojceva-Taneva, O., additional, Tozija, L., additional, Gelev, S., additional, Stojcev, N., additional, Dzekova, P., additional, Trajcevska, L., additional, Severova, G., additional, Pavleska, S., additional, Sikole, A., additional, Combe, C., additional, Thumma, J., additional, Gillespie, B., additional, De Sequera, P., additional, Yamamoto, H., additional, Robinson, B., additional, Matsushita, Y., additional, Tasaki, H., additional, Tohara, Y., additional, Yamauchi, E., additional, Matsuoka, K., additional, Arizono, K., additional, Bellasi, A., additional, Ferramosca, E., additional, Ratti, C., additional, Block, G., additional, Raggi, P., additional, Drozdz, M., additional, Krasniak, A., additional, Chmiel, G., additional, Podolec, P., additional, Pasowicz, M., additional, Tracz, W., additional, Kowalczyk-Michalek, M., additional, Sulowicz, W., additional, Kalantzi, K., additional, Korantzopoulos, P., additional, Bechlioulis, A., additional, Vlachopanou, A., additional, Foulidis, V., additional, Pagiati, E., additional, Nikolopoulos, P., additional, Gouva, C., additional, Arroyave, I., additional, Rodelo, J., additional, Cardona, M., additional, Garcia, A., additional, Henao, J., additional, Mejia, G., additional, Rico, J., additional, Arbelaez, M., additional, Fujimori, A., additional, Okada, S., additional, Yamamoto, K., additional, Okamoto, S., additional, Kamiura, N., additional, Sakai, M., additional, Tanikake, M., additional, Kutlay, S., additional, Sengul, S., additional, Keven, K., additional, Nergizoglu, G., additional, Erturk, S., additional, Ates, K., additional, Duman, N., additional, Karatan, O., additional, Erbay, B., additional, Sameiro-Faria, M., additional, Costa, E., additional, Rocha-Pereira, P., additional, Borges, A., additional, Nascimento, H., additional, Mendonca, D., additional, Amado, L., additional, Reis, F., additional, Miranda, V., additional, Quintanilha, A., additional, Belo, L., additional, Santos-Silva, A., additional, Oh, J. S., additional, Kim, S. M., additional, Sin, Y. H., additional, Kim, J. K., additional, Ishihara, M., additional, Otsubo, S., additional, Kimata, N., additional, Akiba, T., additional, Nitta, K., additional, Kim, K. M., additional, Baek, C. H., additional, Kim, S. B., additional, Testa, A., additional, Sanguedolce, M. C., additional, Spoto, B., additional, Mallamaci, F., additional, Malatino, L., additional, Tripepi, G., additional, Zoccali, C., additional, Lee, J. E., additional, Moon, S. J., additional, Kim, J.-K., additional, An, H. R., additional, Ha, S. K., additional, Pakr, H. C., additional, Bahlmann, F. H., additional, Becker, E., additional, Sperber, V., additional, Triem, S., additional, Noll, C., additional, Zewinger, S., additional, Fliser, D., additional, Laufs, U., additional, Thijssen, S., additional, Usvyat, L. A., additional, Raimann, J. G., additional, Balter, P., additional, Kotanko, P., additional, Levin, N. W., additional, Hornum, M., additional, Bay, J. T., additional, Clausen, P., additional, Melchior Hansen, J., additional, Mathiesen, E. R., additional, Feldt-Rasmussen, B., additional, Garred, P., additional, Sural, S., additional, Panja, C. S., additional, Bhattacharya, S. K., additional, Cernaro, V., additional, Lacquaniti, A., additional, Lorenzano, G., additional, Romeo, A., additional, Donato, V., additional, Buemi, M., additional, Usvyat, L., additional, Rogus, J., additional, Lacson, E., additional, Robinson, B. M., additional, Karaboyas, A., additional, Sen, A., additional, Hecking, M., additional, Mendelssohn, D., additional, Jadoul, M., additional, Kawanishi, H., additional, Saran, R., additional, Kolarz, M., additional, Undas, A., additional, Wyroslak, J., additional, Malyszko, J., additional, Klejna, K., additional, Naumnik, B., additional, Koc-Zurawska, E., additional, Mysliwiec, M., additional, Piecha, G., additional, Kuczera, P., additional, Adamczak, M., additional, Fedorova, O. V., additional, Bagrov, A. Y., additional, Wiecek, A., additional, Gungor, O., additional, Kircelli, F., additional, Asci, G., additional, Carrero, J. J., additional, Tatar, E., additional, Demirci, M., additional, Toz, H., additional, Ozkahya, M., additional, Ok, E., additional, Bansal, V., additional, Shareain, K., additional, Hoppensteadt, D., additional, Litinas, E., additional, Fareed, J., additional, Kim, M.-J., additional, Lee, S. W., additional, Song, J. H., additional, Kweon, J., additional, Kim, W. H., additional, Sasaki, K., additional, Yasuda, K., additional, Hatanaka, M., additional, Hayashi, T., additional, Katsipi, I., additional, Tatsiopoulos, A., additional, Papanikolaou, P., additional, Doulgerakis, C., additional, Kollia, K., additional, Kardouli, E., additional, Asmanis, E., additional, Gennadiou, M., additional, Kyriazis, J., additional, Panizo, S., additional, Barrio-Vazquez, S., additional, Carrillo-Lopez, N., additional, Fernandez-Vazquez, A., additional, Braga, S., additional, Rodriguez-Rebollar, A., additional, Naves-Diaz, M., additional, Cannata-Andia, J. B., additional, Nikodimopoulou, M., additional, Liakos, S., additional, and Kapoulas, S., additional

Published
2011
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18. Impaired coronary microcirculation is associated with left ventricular diastolic dysfunction in end-stage chronic kidney disease patients.

Author

Papamichail N, Bechlioulis A, Lakkas L, Bougiakli M, Giannitsi S, Gouva C, Katopodis K, Michalis LK, and Naka KK

Subjects
Coronary Circulation, Hemodialysis Units, Hospital, Humans, Microcirculation, Middle Aged, Pulse Wave Analysis, Renal Dialysis, Renal Insufficiency, Chronic complications, Ventricular Dysfunction, Left complications, Ventricular Dysfunction, Left diagnostic imaging
Abstract

Introduction: Coronary vascular dysfunction, as assessed by coronary flow reserve (CFR) in the left anterior descending coronary artery, is found in various conditions including end-stage chronic kidney disease (CKD). Currently, we investigated the associations of CFR with echocardiographic indices of systolic and diastolic cardiac function and identified independent predictors of CFR in hemodialysis patients., Methods: End-stage CKD patients treated with hemodialysis (n = 29) without known cardiovascular disease were recruited from a Hemodialysis Unit in Northwestern Greece. A thorough echocardiographic evaluation including CFR measurement following dipyridamole infusion was performed in all participants. Arterial stiffness was assessed by measurement of carotid-femoral pulse wave velocity and aortic augmentation index., Results: The mean age of the patients was 63 years, and mean duration of hemodialysis was 2.9 years. CFR was 1.60 ± 0.37 while dipyridamole caused a significant increase in E' sep , S lat , E' lat , and Stroke volume (P < .05 for all). Independent predictors of CFR were posterior wall thickness (B -0.408, P = .013) and dipyridamole-induced changes in Tei index (B -0.425, P = .007). A severely decreased CFR < 1.5 was observed in 52% of the patients. E/E' ratio (B 10.84, P = .014) was the single independent predictor of severely decreased CFR., Conclusions: In end-stage CKD patients on hemodialysis without known cardiovascular disease, impaired coronary vascular function was prevalent and related to increased left ventricular wall thickness, increased filling pressures, and dipyridamole-induced deteriorated myocardial function independently of the presence of wall-motion abnormalities. Further studies are required to clarify the prognostic role of dipyridamole-induced cardiac changes in hemodialysis patients., (© 2020 Wiley Periodicals, Inc.)

Published
2020
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19. The impact of hemodialysis on the dispersion of ventricular repolarization.

Author

Kalantzi K, Gouva C, Letsas KP, Vlachopanou A, Foulidis V, Bechlioulis A, Katopodis KP, Goudevenos JA, and Korantzopoulos P

Subjects
Aged, Female, Humans, Kidney Failure, Chronic complications, Male, Pilot Projects, Electrocardiography, Heart Ventricles physiopathology, Kidney Failure, Chronic physiopathology, Renal Dialysis
Abstract

Background: Sudden cardiac death is prevalent in chronic hemodialysis (HD) patients while the dialysis process may have arrhythmogenic potential. We sought to examine the effect of HD on conventional electrocardiographic parameters as well as on novel indexes of repolarization, given that increased spatial dispersion of repolarization is related to ventricular arrhythmias., Methods: We recorded clinical, echocardiographic, and laboratory parameters as well as electrocardiographic indexes before and after a single HD session. Specifically, we calculated the QTc interval, the QRS duration, the T peak-to-end (Tpe) interval, and the Tpe/QT ratio., Results: The study population consisted of 66 chronic HD patients (mean age: 68.9 ± 11.8 years, 40 males). Heart rate, blood pressure, QRS duration, QTc interval, and QT dispersion did not change significantly after the HD session. However, the Tpe interval and the Tpe/QT ratio increased significantly (80 [65-90] ms vs 85 [77.5-100] ms; P = 0.04, and 0.21 [0.18-0.24] vs 0.25 [0.21-0.28]; P = 0.05, respectively). Correlation analysis and multiple regression analysis failed to show significant associations between the baseline parameters and the baseline values of Tpe and Tpe/QT or between the change of the laboratory parameters during HD and the corresponding change of the Tpe and the Tpe/QT values. No significant arrhythmias were observed during the HD sessions., Conclusions: HD induces an increase in novel markers of spatial dispersion of ventricular repolarization. Whether the assessment of these indexes of heterogeneity of repolarization at baseline or their change during HD has a prognostic value with regard to future untoward events, remains to be elucidated., (©2013, The Authors. Journal compilation ©2013 Wiley Periodicals, Inc.)

Published
2013
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20. Acute effect of heparin on lipid parameters in patients on renal replacement therapy.

Author

Katopodis KP, Koliousi E, Gouva C, Balafa O, Bairaktari E, Ikonomou M, Elisaf MS, and Siamopoulos KC

Subjects
Adult, Aged, Cholesterol blood, Female, Humans, Lipoprotein Lipase metabolism, Male, Middle Aged, Triglycerides blood, Anticoagulants pharmacology, Heparin pharmacology, Lipids blood, Peritoneal Dialysis, Renal Dialysis
Abstract

Dialyzer membrane and the type of heparin used can influence lipid parameters. However, there are limited and debatable data concerning lipid alterations during a single hemodialysis session. Moreover, the role of hemoconcentration after every hemodialysis session confuses the real effect of the heparin on lipid profile. We investigated the acute effect of heparin administration on lipids in hemodialysis patients, but on an off-hemodialysis day in order to eliminate any effect of ultrafiltration. We studied six patients on hemodialysis, six patients on peritoneal dialysis, and six healthy persons. The study was performed in two phases (1 week apart). In phase A, we used unfractionated heparin (5000 IU, intravenous), whereas in phase B, low-molecular-weight heparin (3500 anti-FXa, intravenous) was used. Total cholesterol, triglycerides, high-density lipoprotein cholesterol, low-density lipoprotein cholesterol, and Lp(a) were estimated before and 1, 2, 3, and 4 hours after heparin administration. We observed a reduction only in triglycerides (at the first, second, and third hour) in both phases in all groups. The other lipid parameters were not affected. In conclusion, acute administration of both types of heparin seems to affect only triglyceride levels in patients on renal replacement therapy.

Published
2007
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21. Long-term treatment with EPO increases serum levels of high-density lipoprotein in patients with CKD.

Author

Siamopoulos KC, Gouva C, Katopodis KP, Tzallas C, Nikolopoulos P, Papavasiliou EC, and Tselepis AD

Subjects
Adult, Aged, Aged, 80 and over, Cholesterol, HDL blood, Chronic Disease, Female, Hemoglobins analysis, Humans, Male, Middle Aged, Renal Dialysis, Cholesterol, HDL drug effects, Erythropoietin pharmacology, Erythropoietin therapeutic use, Kidney Diseases complications, Kidney Diseases drug therapy
Abstract

Background: Among lipid abnormalities observed in patients with chronic kidney disease (CKD) is a significant decrease in serum high-density lipoprotein cholesterol (HDL-C) levels. In a previously published randomized control trial, we showed that early erythropoietin (EPO) administration in a predialysis population slowed the progression of CKD. In the present nested substudy, we examine whether EPO has an influence on serum HDL-C levels in comparison to other lipid parameters in this population., Methods: Eighty-eight patients with CKD stages 3 and 4 were enrolled in the study. Forty-five patients (group 1) were treated with EPO (50 U/kg/wk), targeting to increase hemoglobin levels to 13 g/dL or greater (>or=130 g/L). The other patients (group 2) remained without treatment until hemoglobin levels decreased to less than 9 g/dL (<90 g/L). The duration of the study was 12 months., Results: At the end of the study, we observed a statistically significant decrease in serum levels of total cholesterol, low-density lipoprotein cholesterol (LDL-C), and triglycerides in both groups. However, serum HDL-C levels significantly increased in only group 1 (from 42.5 +/- 10.4 to 55.9 +/- 8.1 mg/dL [1.10 +/- 0.27 to 1.45 +/- 0.21 mmol/L]; P < 0.001), whereas they were unchanged in group 2. In addition, a significant decrease in atherogenic LDL-C/HDL-C ratio was observed in only group 1. Importantly, the increase in serum HDL-C levels correlated positively with the increase in hemoglobin values in EPO-treated patients., Conclusion: Our results show that EPO treatment of predialysis patients with CKD significantly increases serum HDL-C levels, which may represent an important antiatherogenic effect of this hormone.

Published
2006
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22. PAF-acetylhydrolase activity in plasma of patients with chronic kidney disease. Effect of long-term therapy with erythropoietin.

Author

Papavasiliou EC, Gouva C, Siamopoulos KC, and Tselepis AD

Subjects
1-Alkyl-2-acetylglycerophosphocholine Esterase blood, Adult, Aged, Aged, 80 and over, Biomarkers blood, Dose-Response Relationship, Drug, Drug Administration Schedule, Female, Humans, Kidney Failure, Chronic mortality, Kidney Function Tests, Male, Middle Aged, Phospholipases A2, Probability, Prognosis, Reference Values, Risk Assessment, Severity of Illness Index, Survival Rate, Treatment Outcome, 1-Alkyl-2-acetylglycerophosphocholine Esterase drug effects, Erythropoietin therapeutic use, Kidney Failure, Chronic drug therapy, Kidney Failure, Chronic enzymology
Abstract

Background: Platelet activating factor acetylhydrolase (PAF-AH) is a Ca2+-independent phospholipase A2 that is secreted mainly from monocytes/macrophages. In human plasma, PAF-AH is associated primarily with low-density lipoprotein (LDL), while a small proportion of enzyme is associated with high-density lipoprotein (HDL). The ratio of HDL-PAF-AH to total plasma enzyme activity may represent a potential marker of atherogenicity. We evaluated possible alterations of lipoprotein-associated enzyme activity in Chronic Kidney Disease (CKD) patients, stages 3-4, and further investigated whether long-term therapy with recombinant human erythropoietin (epoetin) has any influence on the plasma PAF-AH activity in vivo or on the enzyme activity secreted from peripheral blood monocytes (PBMs), in vitro., Methods: Forty-eight patients, 28 men and 20 women, with CKD (stages 3-4) participated in the study. Patients were randomized into groups I and II. Patients of group I (n = 28) were administered subcutaneously epoetin, 50 units/kg once per week. The Hb target was 13 g/dl. In group II (n = 20), epoetin was initiated only when the Hb levels decreased during follow-up to less than 9 g/dl. All patients were seen on an outpatient basis at 2, 4 and 6 months. Twenty-two normolipidemic age- and sex-matched healthy volunteers also participated in the study and were used as controls., Results: The PAF-AH activity in plasma of both patient groups at baseline was higher compared to controls, whereas no difference in the HDL-PAF-AH activity was observed among the studied groups. Thus, the ratio of HDL-PAF-AH to the plasma enzyme activity was significantly lower in both patient groups compared to controls. Epoetin administration in the patients of group I was associated with a significant increase in the plasma PAF-AH and in HDL-PAF-AH activities 2 months after treatment, which remained stable for up to 6 months of therapy, a phenomenon not observed in untreated patients of group II. Thus, the ratio of HDL-PAF-AH to the plasma enzyme activity was significantly increased in patients of group I compared to the baseline values, a phenomenon not observed in patients of group II. In vitro treatment with epoetin of PBMs from patients of group I (undergoing therapy with epoetin) resulted in a dose-dependent increase in total and secreted enzyme activity, a phenomenon not observed in patients of group II who did not receive therapy with epoetin. This suggests that the in vivo increase in lipoprotein-associated PAF-AH observed in patients treated with epoetin may be attributed to the drug-induced enhanced secretion of PAF-AH from PBMs of these patients., Conclusions: CKD patients of stages 3-4 are characterized by an increase in plasma PAF-AH activity and a low ratio of HDL-PAF-AH to total plasma enzyme activity. Long-term therapy with epoetin may improve this atherogenic ratio thus this drug may play an important antiatherogenic role in CKD.

Published
2006
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23. Erythrocyte PAF-acetylhydrolase activity in various stages of chronic kidney disease: effect of long-term therapy with erythropoietin.

Author

Papavasiliou EC, Gouva C, Siamopoulos KC, and Tselepis AD

Subjects
Adult, Aged, Aged, 80 and over, Anemia etiology, Erythrocytes drug effects, Female, Follow-Up Studies, Glutathione Peroxidase metabolism, Hemoglobins, Humans, In Vitro Techniques, Male, Middle Aged, Oxidation-Reduction, Thiobarbituric Acid Reactive Substances metabolism, 1-Alkyl-2-acetylglycerophosphocholine Esterase metabolism, Anemia drug therapy, Erythrocytes enzymology, Erythropoietin administration & dosage, Kidney Failure, Chronic complications
Abstract

Background: Erythrocytes represent an important component of the antioxidant capacity of blood, comprising, in particular, intracellular enzymes, including platelet-activating factor acetylhydrolase (PAF-AH) and glutathione peroxidase (Gpx). We evaluated the erythrocyte PAF-AH and Gpx activities in various stages of chronic kidney disease (CKD), and further investigated whether erythropoietin (EPO) administration in these patients has any influence on the enzyme activities., Methods: Thirty-six patients (19 men and 17 women) with CKD (stages 1 to 5) participated in the study. Thirteen of them presented with CKD stage 1 to 2 (group I), whereas 23 patients presented with CKD stage 3 to 5 and randomized into two groups (i.e., groups II and III). Patients of group II (N= 11) were administered EPO subcutaneously, 50 units per kg once per week. In group III (N= 12), EPO was initiated only when the hemoglobin (Hb) levels decreased during follow-up to less than 9 g/dL. All patients were seen on an outpatient basis at 2 and 4 months. Fifteen normolipidemic age- and sex-matched healthy volunteers also participated in the study and were used as controls. The PAF-AH and Gpx activities were determined in isolated washed erythrocytes., Results: The erythrocyte-associated PAF-AH and Gpx activities were higher in all CKD patient groups at baseline compared to controls, the groups II and III exhibiting significantly higher enzyme activities compared with group I. In all studied populations, both enzyme activities were negatively correlated with the creatinine clearance values. Importantly, the PAF-AH and Gpx activities were progressively decreased during the follow-up in patients not treated with EPO (group III), a phenomenon not observed in patients receiving EPO (group II), or in patients of group I. This reduction in enzyme activities was positively correlated with the decrease in the creatinine clearance values in patients of group III., Conclusion: Significant alterations in the erythrocyte-associated PAF-AH and Gpx activities related to the disease stage are observed in CKD patients. Administration of EPO prevented the reduction in enzyme activities observed during the progression of the renal insufficiency, thus preserving the erythrocyte defense mechanisms against oxidative stress.

Published
2005
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24. Treating anemia early in renal failure patients slows the decline of renal function: a randomized controlled trial.

Author

Gouva C, Nikolopoulos P, Ioannidis JP, and Siamopoulos KC

Subjects
Aged, Anemia etiology, Disease Progression, Erythropoietin adverse effects, Female, Follow-Up Studies, Hemoglobins, Humans, Male, Middle Aged, Treatment Outcome, Anemia drug therapy, Erythropoietin administration & dosage, Kidney Failure, Chronic complications, Kidney Failure, Chronic physiopathology
Abstract

Background: Erythropoietin is known to improve outcomes in patients with anemia from chronic renal disease. However, there is uncertainty about the optimal timing of initiation of erythropoietin treatment in predialysis patients with non-severe anemia., Methods: We conducted a randomized controlled trial of early versus deferred initiation of erythropoietin in nondiabetic predialysis patients with serum creatinine 2 to 6 mg/dL and hemoglobin 9 to 11.6 g/dL. The early treatment arm was immediately started on 50 U/kg/wk of erythropoietin alpha with appropriate titration aiming for hemoglobin of > or =13 g/dL. The deferred treatment arm would start erythropoietin only when hemoglobin decreased to <9 g/dL. The primary end point was a composite of doubling of creatinine, renal replacement, or death., Results: Eighty-eight patients were randomized (early treatment N= 45, deferred treatment N= 43) and followed for a median of 22.5 months. During follow-up, 13 versus 23 patients reached the primary end point in the two arms, respectively (log-rank P= 0.0078). The relative hazard for reaching an end point was 0.42 (P= 0.012). Adjusting for baseline serum creatinine, the adjusted relative hazard was 0.37 (P= 0.004), while the risk increased 2.23-fold (P < 0.001) per 1 mg/dL higher creatinine at baseline. The benefit was similar regardless of the baseline hemoglobin and proteinuria. No patients had any severe adverse events., Conclusion: Early initiation of erythropoietin in predialysis patients with non-severe anemia significantly slows the progression of renal disease and delays the initiation of renal replacement therapy.

Published
2004
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