48 results on '"Vlachojannis JG"'
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2. Desensitization during renal transplantation.
- Author
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Fourtounas C, Mouzaki A, Vlachojannis JG, Jordan SC, Vo AA, and Reinsmoen NL
- Published
- 2008
3. Parameters influencing blood erythropoietin levels of renal transplant recipients during the early post-transplantation period.
- Author
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Kalantzi M, Kalliakmani P, Papachristou E, Papasotiriou M, Savvidaki E, Zavvos V, Karavias D, Goumenos DS, and Vlachojannis JG
- Subjects
- Adult, Delayed Graft Function prevention & control, Female, Follow-Up Studies, Humans, Kidney Transplantation, Male, Middle Aged, Postoperative Period, Retrospective Studies, Time Factors, Young Adult, Delayed Graft Function blood, Erythropoietin blood, Immunosuppressive Agents therapeutic use, Transplant Recipients
- Abstract
Aim: Renal transplantation is accompanied by restoration of renal function and endogenous erythropoietin production. The purpose of this study was to investigate the time-related changes of endogenous erythropoietin secretion in the early renal post-transplant period and the influence of various parameters to this process., Methods: Fifty-eight patients were enrolled in the study and followed up for 3 months after successful renal transplantation. Erythropoietin levels were measured at regular intervals and correlated with renal function, cold ischemia time and immunosuppressive regimen used., Results: Two peaks of serum erythropoietin levels were observed: an early peak that occurred within two days after transplantation and a late one, between weeks 2 and 4, which resulted in increased blood hemoglobin levels. Factors that were found to correlate with erythropoietin levels were delayed graft function, cyclosporine use and prolonged cold ischemia time. Serum creatinine did not correlate to erythropoietin levels although the reduction of serum creatinine preceded the rise of erythropoietin levels. Normal hemoglobin values were restored about three months after successful renal transplantation., Conclusion: Serum erythropoietin levels increase during the early post-transplantation period resulting in correction of anemia three months after a successful renal transplantation. Restoration of allograft function is a prerequisite for erythropoietin secretion, while cold ischemia time and immunosuppressive regimen affect graft function.
- Published
- 2014
- Full Text
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4. Sodium removal and peritoneal dialysis modalities: no differences with optimal prescription of icodextrin.
- Author
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Fourtounas C, Dousdampanis P, Hardalias A, and Vlachojannis JG
- Subjects
- Adult, Aged, Cross-Sectional Studies, Female, Humans, Icodextrin, Male, Middle Aged, Time Factors, Treatment Outcome, Water-Electrolyte Imbalance etiology, Water-Electrolyte Imbalance physiopathology, Water-Electrolyte Imbalance prevention & control, Dialysis Solutions therapeutic use, Glucans therapeutic use, Glucose therapeutic use, Peritoneal Dialysis methods, Peritoneal Dialysis, Continuous Ambulatory, Sodium blood, Sodium urine, Water-Electrolyte Balance
- Abstract
Continuous ambulatory peritoneal dialysis (CAPD) has been considered as a more efficient modality for sodium removal than automated peritoneal dialysis (APD), due to the longer dwell times and the sodium sieving phenomenon. However, because studies regarding sodium removal in peritoneal dialysis (PD) report rather controversial results and carry various methodological flaws, it remains uncertain whether they offer enough significant information regarding PD prescription and therapy. The aim of the present observational cross-sectional study was to evaluate the impact of the optimal prescription of CAPD and APD, regarding solute clearances and daily ultrafiltrate, on daily sodium removal. Forty-six (46) patients aged 52.3 ± 14 years were studied. Twenty-six (26) patients were subjected to CAPD, and 20 patients were subjected to APD. Ten (10) patients per group were prescribed icodextrin for the long dwell to achieve optimal adequacy and ultrafiltration (UF) targets. CAPD patients removed a higher, albeit not statistically significant, daily amount of sodium (131.7 ± 98.2 mmol) compared with APD patients (79.4 ± 129.2 mmol). Their Kt/V urea was lower (1.48 ± 0.3 vs. 2.17 ± 0.33, P < 0.05), and there were no differences on daily UF (1119 ± 533 vs. 1005 ± 517 mL). In both groups, icodextrin use for the long dwell resulted in equal sodium removal with that of patients not prescribed icodextrin. Our results, derived from an unselected PD population, indicate that although classic CAPD may be more efficient for sodium removal than APD, the use of icodextrin as an adjuvant for higher daily UF not only increases solute clearance but also removes more sodium for both modalities. In addition, calculations of sodium removal in PD do not seem to benefit the everyday clinical practice, provided that PD patients can achieve the adequacy targets and present optimal daily UF without signs of volume overload., (© 2013, Copyright the Authors. Artificial Organs © 2013, International Center for Artificial Organs and Transplantation and Wiley Periodicals, Inc.)
- Published
- 2013
- Full Text
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5. Albumin upregulates eNOS mRNA through ETRA/B in human proximal tubular epithelial cells.
- Author
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Kotsantis P, Papadimitropoulos A, Drakopoulos A, Vlachojannis JG, and Katsoris P
- Subjects
- Cells, Cultured, Humans, Albumins physiology, Epithelial Cells physiology, Kidney Tubules, Proximal cytology, Nitric Oxide Synthase Type III genetics, RNA, Messenger physiology, Receptor, Endothelin A physiology, Receptor, Endothelin B physiology, Up-Regulation
- Abstract
Background: Proximal tubular cells respond to proteinuria by expressing several cytokines and inflammatory molecules that induce interstitial fibrosis. Increased attention has been drawn toward the systems of endothelin (ET) and nitric oxide (NO). This work contributes to the elucidation of the interplay between these two systems in proximal tubular epithelial cells (PTECs) after exposure in proteinuric conditions., Methods: HK-2 cells, a human PTEC line, were incubated with albumin, simulating proteinuric conditions. Cells were then lysed and either total RNA was isolated or whole cell extracts were prepared. PreproET-1, ET receptors (ETRA and ETRB) and NO synthases (eNOS, iNOS) mRNA accumulation was estimated by RT-PCR, and proteins by Western blot analysis. NO production was assessed using Griess reaction. Furthermore, we treated HK-2 cells with NO donor sodium nitroprusside, NO inhibitor L-NAME, ETRA inhibitor BQ123, ETRB inhibitor BQ788 and purified ET-1, and investigated the potential interplay between albumin-induced stimulation of NO or ET-1 systems., Results: We found that albumin upregulates preproET-1, ETRA, ETRB, eNOS and iNOS mRNA as well as protein and stimulates NO production. Additionally, we recorded an ETRA/B dependent regulation of albumin-induced eNOS expression., Conclusions: For the first time an in vitro albumin-induced ET-1 and NO interplay was revealed.
- Published
- 2013
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6. Salvage of a totally occluded peritoneal dialysis catheter by laparoscopic milking.
- Author
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Fourtounas C, Maroulis I, Karnabatidis D, Hardalias A, and Vlachojannis JG
- Subjects
- Adult, Equipment Failure, Humans, Kidney Failure, Chronic therapy, Male, Catheters, Indwelling, Laparoscopy methods, Peritoneal Dialysis methods, Salvage Therapy methods
- Abstract
Mechanical problems of the Peritoneal Dialysis (PD) catheter remain a significant cause of temporary or even permanent transfer to hemodialysis. Until recently, the most popular approach was to remove the problematic PD catheter than to try to salvage it. We report a case of severe (two-way) PD catheter obstruction that appeared after spontaneous hemoperitoneum and did not resolve with multiple conservative measures. However, it was successfully salvaged by laparoscopic surgery and milking of a big intraluminal clot., (© 2012 Wiley Periodicals, Inc.)
- Published
- 2013
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7. Ezetimibe is effective in the treatment of persistent hyperlipidemia of renal allograft recipients.
- Author
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Savvidaki E, Koukoulaki M, Benou A, Roumeliotou M, Fourtounas C, Kalliakmani P, Papachristou E, Vlachojannis JG, and Goumenos D
- Subjects
- Adult, Anticholesteremic Agents adverse effects, Azetidines adverse effects, Biomarkers blood, Cholesterol blood, Cholesterol, HDL blood, Cholesterol, LDL blood, Drug Resistance, Drug Therapy, Combination, Ezetimibe, Female, Greece, Humans, Hydroxymethylglutaryl-CoA Reductase Inhibitors adverse effects, Hyperlipidemias blood, Hyperlipidemias etiology, Immunosuppressive Agents blood, Immunosuppressive Agents therapeutic use, Male, Middle Aged, Retrospective Studies, Time Factors, Transplantation, Homologous, Treatment Outcome, Anticholesteremic Agents therapeutic use, Azetidines therapeutic use, Hydroxymethylglutaryl-CoA Reductase Inhibitors therapeutic use, Hyperlipidemias drug therapy, Kidney Transplantation adverse effects
- Abstract
Introduction: Ezetimibe is a hypolipidemic agent acting via inhibition of cholesterol absorption from the small intestine. The effectiveness and safety of long-term administration of ezetimibe was evaluated in renal allograft recipients with persistent hyperlipidemia., Patients and Methods: 67 renal allograft recipients with post-transplantation hyperlipidemia resistant to statins were included in the study; 11 were treated with ezetimibe (10 mg/day) alone and 56 with ezetimibe and statin. The effectiveness of ezetimibe was assessed by determination of total cholesterol (TC), LDL cholesterol (LDL-C), HDL cholesterol (HDL-C) and triglycerides (TR). Its safety was determined by liver enzymes (ALT, AST), LDH, CPK, serum creatinine and blood levels of immunosuppressive drugs (cyclosporine, tacrolimus, everolimus, sirolimus) over the follow-up period of 18±6 months., Results: A significant reduction of TC and LDL-C blood levels by 25% and 34% respectively, was observed during the first month of treatment with ezetimibe (p<0.001). This reduction was maintained for the whole period of ezetimibe administration. Renal function remained stable over the follow-up period, while no changes of the blood levels of immunosuppressive drugs were observed. Liver enzymes, LDH and CPK remained normal in all patients except for one diabetic patient who developed rhabdomyolysis. Apart from gastrointestinal symptoms in 2 patients, no other side effects were observed., Conclusion: Combination of ezetimibe with statins represents an effective and safe regimen for treatment of persistent hyperlipidemia in renal allograft recipients.
- Published
- 2011
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8. Benefit and cost from the long-term use of cyclosporine-A in idiopathic membranous nephropathy.
- Author
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Kalliakmani P, Koutroulia E, Sotsiou F, Vlachojannis JG, and Goumenos DS
- Subjects
- Adult, Aged, Cost-Benefit Analysis, Cyclosporine therapeutic use, Female, Glomerulonephritis, Membranous pathology, Humans, Immunosuppressive Agents therapeutic use, Male, Middle Aged, Nephrotic Syndrome pathology, Prednisolone therapeutic use, Recurrence, Remission Induction, Treatment Outcome, Cyclosporine economics, Glomerulonephritis, Membranous drug therapy, Immunosuppressive Agents economics, Nephrotic Syndrome drug therapy
- Abstract
Aim: Idiopathic membranous nephropathy (IMN), the most common cause of nephrotic syndrome in adults, is usually treated by cyclosporin A (CsA). Estimation of the effectiveness of long-term use of CsA in the remission and relapse rate of nephrotic syndrome along with histological changes in repeat renal biopsies was the aim of the study., Methods: Thirty-two nephrotic patients with well-preserved renal function treated by prednisolone and CsA were studied. A repeat biopsy was performed in 18 patients with remission of nephrotic syndrome, after 24 months of treatment, to estimate the activity of the disease and features of CsA toxicity., Results: Complete remission of nephrotic syndrome was observed in 18 (56%) and partial remission in 10 patients (31%) after 12 months of treatment (total 87%). Relapses were observed in 39% and 60% of patients with complete and partial remission, respectively, and multiple relapses in 25% of patients, who showed gradual unresponsiveness to CsA and decline of renal function. Progression of stage of the disease and more severe glomerulosclerosis and tubulointerstitial injury were recognized in 55% and 61% of patients respectively. Features of CsA nephrotoxicity were not observed. The severity of histological changes was related to the time elapsed from the first biopsy (r = 0.452, P < 0.05)., Conclusion: Low doses of CsA with prednisolone induce remission of nephrotic syndrome in most idiopathic membranous nephropathy patients. Although typical features of CsA nephrotoxicity are not observed, significant deterioration of histological lesions occurs with time, even in patients with remission. Long-term use of CsA should be examined with caution., (© 2010 The Authors. Nephrology © 2010 Asian Pacific Society of Nephrology.)
- Published
- 2010
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9. Interaction of endothelin-1 and nitric oxide pathways in human tubular epithelial cells under the influence of cyclosporine-A.
- Author
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Papachristou E, Papadimitropoulos A, Kotsantis P, Goumenos DS, Katsoris PG, and Vlachojannis JG
- Subjects
- Biosynthetic Pathways, Cells, Cultured, Cyclosporine adverse effects, Humans, Immunosuppressive Agents adverse effects, Kidney Diseases chemically induced, Kidney Tubules cytology, Cyclosporine pharmacology, Endothelin-1 physiology, Epithelial Cells drug effects, Epithelial Cells enzymology, Immunosuppressive Agents pharmacology, Kidney Tubules drug effects, Kidney Tubules enzymology, Nitric Oxide physiology, Nitric Oxide Synthase biosynthesis, Nitric Oxide Synthase drug effects
- Abstract
Background: The exact mechanism of cyclosporine (CsA) nephrotoxicity has not been clarified. In this study, we investigated the effect of pharmacological doses of CsA on the production of nitric oxide synthases (NOSs) and endothelin (ET) receptors (ETR-A, ETR-B), in human tubular cells [human kidney (HK)-2], to identify any implication of these pathways in CsA nephrotoxicity., Methods: Human tubular epithelial cells (HK-2) were cultured in the presence of CsA at various concentrations (0-1000 ng/mL). Reverse transcriptase-polymerase chain reaction (RT-PCR) was used to determine mRNA synthesis of NOSs (eNOS, iNOS) and ET receptors (ETR-A, ETR-B) and western blot analysis for the subsequent proteins., Results: A dose-dependent induction of synthesis of NO synthases eNOS and iNOS and ET receptors ETR-A and ETR-B was observed, even at therapeutic doses of CsA. An interaction between NO and ET-1 systems under the influence of CsA was also observed. Blockage of NO production was followed by down-regulation of ETR-B whereas blockade of ET pathway with ET receptor antagonists was followed by down-regulation of eNOS expression., Conclusion: CsA induces NOSs as well as ET receptor mRNA and protein synthesis in tubular epithelial cells. The up-regulation of NO and ET-1 pathways is probably implicated in the nephrotoxic action of CsA, whereas an interplay between ETR-B and eNOS seems to be involved.
- Published
- 2010
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10. The prognostic value of frozen section preimplantation graft biopsy in the outcome of renal transplantation.
- Author
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Goumenos DS, Kalliakmani P, Tsamandas AC, Maroulis I, Savidaki E, Fokaefs E, Papachristou E, Karavias D, and Vlachojannis JG
- Subjects
- Adult, Age Factors, Biopsy, Needle, Female, Humans, Immunosuppression Therapy methods, Kidney Diseases surgery, Male, Middle Aged, Prognosis, Risk Factors, Frozen Sections, Kidney Diseases pathology, Kidney Transplantation, Preoperative Care
- Abstract
Introduction: Preimplantation biopsy provides a window on the state of the renal allograft. In this study, the prognostic value of frozen section preimplantation graft biopsy was estimated and compared to regularly processed formalin-fixed biopsy., Materials and Methods: Seventy-four renal allograft recipients were studied. The degree of glomerulosclerosis, acute tubular necrosis, interstitial fibrosis, arteriosclerosis, and arteriolosclerosis was rapidly estimated in frozen sections and correlated to the renal function in the immediate posttransplantation period and 3 months thereafter. The histological changes were also examined in paraffin-embedded sections., Results: The histological changes observed in rapidly processed frozen sections were comparable to those observed on regularly processed sections and their differences did not reach statistical significance. Glomerulosclerosis and arteriolosclerosis were underestimated, whereas acute tubular necrosis and interstitial fibrosis were overestimated, in the frozen sections compared to permanent ones, but those differences were not statistically significant. Immediate graft function was observed in 45 patients (61%). Delayed graft function was more frequently observed among recipients with donor age above 60 years (57% vs. 32%). Serum creatinine 3 months after transplantation was above 2 mg/dL in 33 recipients (44.5%) and was positively correlated to the degree of tubular necrosis (p = 0.04) and donor age (p = 0.03). Donor age was correlated to the degree of arteriolosclerosis (p < 0.01)., Conclusions: Frozen section preimplantation biopsy gives reliable information for the situation of the graft that is related to the outcome of renal transplantation.
- Published
- 2010
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11. Different immunosuppressive combinations on T-cell regulation in renal transplant recipients.
- Author
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Fourtounas C, Dousdampanis P, Sakellaraki P, Rodi M, Georgakopoulos T, Vlachojannis JG, and Mouzaki A
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- Adult, Aged, Antibodies, Monoclonal administration & dosage, Basiliximab, Cyclosporine administration & dosage, Drug Therapy, Combination, Everolimus, Female, Graft Rejection immunology, Humans, Immunophenotyping, Male, Middle Aged, Mycophenolic Acid administration & dosage, Mycophenolic Acid analogs & derivatives, Recombinant Fusion Proteins administration & dosage, Sirolimus administration & dosage, Sirolimus analogs & derivatives, Steroids administration & dosage, T-Lymphocytes, Regulatory immunology, Tacrolimus administration & dosage, Young Adult, Graft Rejection drug therapy, Immunosuppressive Agents administration & dosage, Kidney Transplantation immunology, T-Lymphocytes, Regulatory drug effects
- Abstract
Background/aims: Recent studies indicate that regulatory T-cells (Tregs) promote transplant tolerance. We studied Treg levels in 39 stable renal transplant recipients to determine the sizes of the Treg populations and the effects of treatment regimens thereof., Methods: All patients (19 with good graft function and 20 with chronic allograft nephropathy) received induction therapy (basiliximab) and were on triple immunosuppressive regimens with calcineurin inhibitors (cyclosporine or tacrolimus), mycophenolate mofetil (MMF) or everolimus and steroids. Twenty healthy subjects served as controls. Whole blood samples were stained with anti-CD4, CD25, CD127, and FoxP3 antibodies and analyzed by flow cytometry to determine CD4+CD25(high)FoxP3+/- and CD4+ CD25(high)CD127(-/low) Treg levels., Results: All patients had significantly reduced CD4+CD25(high)FoxP3+/- but no CD4+ CD25(high)CD127(-/low) Treg levels compared to controls. Renal allograft function did not correlate with Treg levels. Statistically significant correlations between CD4+CD25(high)Foxp3+ Tregs and tacrolimus levels and CD4+CD25(high)Foxp3- Tregs and HLA-DR mismatching were detected. Patients receiving MMF had significantly higher CD4+CD25(high)Foxp3+ Tregs compared to patients on everolimus who were also receiving lower doses of calcineurin inhibitors., Conclusion: Overall, immunosuppression lowers CD4+CD25(high)FoxP3+/- Treg levels significantly in the periphery in renal transplant recipients. In addition, different immunosuppressive regimens have different impacts on CD4+CD25(high)FoxP3+ Tregs, a fact that may influence long-term allograft survival., (Copyright 2010 S. Karger AG, Basel.)
- Published
- 2010
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12. Early histological changes in the kidney of people with morbid obesity.
- Author
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Goumenos DS, Kawar B, El Nahas M, Conti S, Wagner B, Spyropoulos C, Vlachojannis JG, Benigni A, and Kalfarentzos F
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- Adult, Female, Humans, Male, Time Factors, Kidney pathology, Obesity, Morbid pathology
- Abstract
Background: Morbid obesity represents a major health problem with increasing incidence worldwide. The clinical manifestation of renal involvement in obesity is proteinuria, and the histological feature is glomerulomegaly with or without focal and segmental glomerulosclerosis (FSGS). In this study, we have investigated the very early histological changes in kidneys of people with morbid obesity and no proteinuria. Patients and methods. Eighteen patients with body mass index (BMI) >50 kg/m(2) who underwent a variant of biliopancreatic diversion with Roux-en-Y reconstruction (BPD-RYGBP) and consented to undergo a renal biopsy during the surgical procedure were included in the study. The estimation of early histological changes was performed on light (n = 18) and electron microscopy (n = 13)., Results: The mean glomerular cross-sectional area was 30 943 +/- 10,984 microm(2) that is higher than that observed in non-obese individuals. In 21% of the examined glomeruli, the glomerular planar surface area (GPSA) was >40,000 microm(2). Thickening of the glomerular basement membrane (GBM) and scattered paramesangial deposits were identified in 9 of 13 patients (70%) whose renal tissue was examined by electron microscopy. A reduction in the slit pore frequency was observed in obese patients due to extensive foot process effacement. Significant positive correlations between mean GPSA and body weight (r = 0.462, P = 0.05), and between GBM thickness and HbA1c, serum total cholesterol and triglyceride levels (r = 0.60, P = 0.05; r = 0.789, P = 0.004; r = 0.70, P = 0.016, respectively), were observed., Conclusions: Glomerulomegaly as well as histological lesions resembling those of early diabetic nephropathy are observed in kidney biopsies of patients with morbid obesity even before the appearance of microalbuminuria. The potential regression of these changes after weight loss needs to be clarified.
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- 2009
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13. Intermittent peritoneal dialysis (IPD): an old but still effective modality for severely disabled ESRD patients.
- Author
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Fourtounas C, Hardalias A, Dousdampanis P, Savidaki E, and Vlachojannis JG
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- Aged, Aged, 80 and over, Female, Humans, Male, Middle Aged, Retrospective Studies, Severity of Illness Index, Kidney Failure, Chronic therapy, Peritoneal Dialysis methods
- Abstract
Background: Hospital-based intermittent peritoneal dialysis (IPD) is an old PD modality applied for as long as 40 h per week using high volumes of PD fluid, but it has almost been abandoned due to its low solute clearances. However, IPD might be the only option for elderly dialysis patients with significant comorbidities, unable to undergo haemodialysis (HD) or PD at home without any assistance, for various reasons., Methods: We describe our experience with 25 patients aged 71.2 +/- 7.5 years with a previous history of HD for 55.4 +/- 54 months, dialysed with IPD for more than 3 months. IPD was performed three times weekly for 8-10 h., Results: Mean values for haematocrit, serum urea, creatinine, sodium, potassium and calcium were comparable with other ESRD populations, whereas there were significantly lower values for albumin (3.2 +/- 0.3 mg/dL) and significantly higher values for phosphorus (7.1 +/- 1.7 mg/dL) despite the use of phosphate binders. The patients survived for a mean of 16.8 +/- 11.5 (3-43) months despite very low solute clearances, as expressed by Kt/V urea (1 +/- 0.26) and weekly creatinine clearance (27.2 +/- 7.6 L/week). However, by using 22.9 +/- 4.5 L of various combinations of isotonic and hypertonic PD fluids, the mean ultrafiltrate was 1854 +/- 326 mL per session. There were only two cases of peritonitis, unrelated to IPD per se., Conclusions: Considering the underlying comorbidities, IPD remains a valuable and effective option with acceptable survival rates, for a special population of ESRD patients not able for various reasons to undergo HD, neither PD at home.
- Published
- 2009
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14. Peritoneoscopic reinsertion of a peritoneal dialysis catheter after fungal peritonitis: the advantage of visual information.
- Author
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Fourtounas C, Dousdampanis P, Hardalias A, and Vlachojannis JG
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- Device Removal, Humans, Male, Middle Aged, Peritonitis etiology, Peritonitis microbiology, Candidiasis therapy, Catheterization methods, Catheters, Indwelling, Laparoscopy, Peritoneal Dialysis adverse effects, Peritoneal Dialysis instrumentation, Peritonitis therapy
- Published
- 2009
15. Corticosteroids vs. corticosteroids plus cycloporin A in adult minimal changes disease.
- Author
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Goumenos DS, Kalliakmani P, Savvidaki E, and Vlachojannis JG
- Abstract
Background: Adult minimal changes disease (MCD) is usually treated by high corticosteroids dose in order to achieve remission of nephrotic syndrome. In this study, the administration of high steroid dose (prednisolone 1 mg/kg BW/day) is compared with the combination of lower prednisolone dose (0.3 mg/kg BW/day) and cyclosporine A (CsA) (2-3 mg/kg BW/day) in a small number of patients., Findings: Eighteen patients were allocated to either prednisolone monotherapy or prednisolone and CsA combination, according to the risk of developing steroid side-effects. Complete remission of the nephrotic syndrome was observed in all patients treated by steroids or combination of steroids and CsA. Complete remission occurred in 67%, 89% and 100% of patients after 4, 8 and 12 weeks of treatment. Relapses occurred in 50% of patients from both groups, treated with the combination of low prednisolone dose and CsA and followed by sustained remission. Corticosteroidal side effects were observed only in high prednisolone dose (accumulated dose: 92.7 +/- 22 mg/kg/BW vs. 58.5 +/- 21 mg/kg/BW, p = 0.004)., Conclusion: Treatment of adult MCD with low prednisolone dose and CsA seems to be equally effective with high prednisolone dose to induce remission of nephrotic syndrome. It is also effective as maintenance therapy for prevention of relapses and less frequently followed by corticosteroidal side effects.
- Published
- 2009
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16. Gingival hyperplasia and calcium channel blockers.
- Author
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Fourtounas C and Vlachojannis JG
- Subjects
- Anti-Bacterial Agents administration & dosage, Azithromycin administration & dosage, Humans, Treatment Outcome, Calcium Channel Blockers adverse effects, Gingival Hyperplasia chemically induced, Gingival Hyperplasia prevention & control, Hypertension drug therapy
- Published
- 2009
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17. Cyclosporine induces endothelin-1 mRNA synthesis and nitric oxide production in human proximal tubular epithelial cell cultures.
- Author
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Papachristou E, Papadimitropoulos A, Kotsantis P, Goumenos DS, Katsoris PG, and Vlachojannis JG
- Subjects
- Cell Proliferation drug effects, Cells, Cultured, Culture Media, Conditioned, Dose-Response Relationship, Drug, Epithelial Cells cytology, Humans, Probability, RNA, Messenger biosynthesis, Reverse Transcriptase Polymerase Chain Reaction, Cyclosporine pharmacology, Endothelin-1 biosynthesis, Kidney Tubules, Proximal cytology, Nitric Oxide biosynthesis
- Abstract
Background: Cyclosporine (CsA) is implicated in the development of chronic allograft nephropathy, which is related to reduced long-term allograft survival. The activation of tubular epithelial cells is involved in the renal scarring process via stimulation of factors such as endothelin-1 (ET-1) and nitric oxide (NO). The effect of CsA on the activation of tubular epithelial cells towards increased production of ET-1 and NO was investigated in this study., Methods: Human tubular epithelial cells (HK-2) were cultured in the presence of CsA at different concentrations (125, 250, 500, and 1,000 ng/mL). ET-1 m-RNA and NO production were measured using RT-PCR and Griess method, respectively. The cytotoxic effect of CsA was examined by the MTT method and cell count., Results: A statistically significant and dose-dependent cytotoxic effect of cyclosporine on HK-2 cells was observed. A dose-dependent up-regulation of ET-1 mRNA production and NO accumulation was observed under the influence of CsA., Conclusion: Increased synthesis of endothelin-1 mRNA and nitric oxide as well as a significant cytotoxic effect on tubular epithelial cells under the influence of CsA might be related to the development of CsA nephrotoxicity.
- Published
- 2009
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18. Serum 25-hydroxyvitamin D status and cardiovascular outcomes in chronic peritoneal dialysis patients.
- Author
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Fourtounas C and Vlachojannis JG
- Subjects
- Cardiovascular Diseases blood, Cardiovascular Diseases epidemiology, Cardiovascular Diseases etiology, Cardiovascular Physiological Phenomena, Humans, Kidney Failure, Chronic therapy, Treatment Outcome, Vitamin D blood, Vitamin D Deficiency blood, Vitamin D Deficiency complications, Vitamin D Deficiency epidemiology, Cardiovascular Diseases mortality, Kidney Failure, Chronic blood, Peritoneal Dialysis adverse effects, Vitamin D analogs & derivatives
- Published
- 2009
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19. Microchimerism in peripheral blood and urine in renal transplant recipients: preliminary results.
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Fourtounas C, Spyridonidis A, Dousdampanis P, Savidaki E, Kalliakmani P, Papachristou E, Goumenos D, and Vlachojannis JG
- Subjects
- Adult, Creatinine blood, Female, Glomerular Filtration Rate, Humans, Kidney Diseases classification, Kidney Diseases surgery, Kidney Transplantation immunology, Living Donors, Male, Microsatellite Repeats genetics, Microsatellite Repeats immunology, Middle Aged, Polymerase Chain Reaction, Renal Replacement Therapy statistics & numerical data, Reoperation statistics & numerical data, Tissue Donors, Chimerism, Kidney Transplantation physiology, Transplantation Chimera
- Abstract
The role of microchimerism in peripheral blood and urine of renal transplant recipients remains a matter of debate, depending on the sensitivity of the methods used for detection. We studied 17 female renal transplant recipients who had received renal allografts from male donors. Polymerase chain reaction (PCR) was applied to blood and urine for the microsatellite markers D1S80, DYZ1, TH01, and kalphai SE33. Detection of DYZ1 that is present only on the Y chromosome was considered proof for microchimerism. No microchimerism was detected in peripheral blood, whereas it could be detected in the urine of 8/17 (48%) patients. There were no differences between patients with and without microchimerism regarding patient age, dialysis vintage, immunosuppression, time post-transplantation, and allograft function as measured using serum creatinine, creatinine clearance, and proteinuria. Two patients in each group showed chronic allograft dysfunction. These findings raise questions regarding the role of microchimerism in renal transplantation.
- Published
- 2008
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20. Growth factors and apoptosis-related protein expression in human crescentic nephritis.
- Author
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Goumenos DS, Kalliakmani P, Tsakas S, Papachristou E, and Vlachojannis JG
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- Adolescent, Adult, Aged, Female, Fibrosis metabolism, Fibrosis pathology, Humans, Male, Middle Aged, Nephritis pathology, Nephritis therapy, Treatment Outcome, Young Adult, Apoptosis Regulatory Proteins metabolism, Intercellular Signaling Peptides and Proteins metabolism, Nephritis metabolism
- Abstract
Background: Crescentic nephritis is a renal disease that rapidly progresses toward renal failure unless aggressive immunosuppressive treatment is administered. Gene-directed apoptosis is involved in the resolution of renal injury or its progression toward scarring. In the present study, the expressions of growth factors, myofibroblasts [alpha-SMA(+) cells], and apoptosis-related proteins, were estimated to identify their contribution to the organization of crescents and to the clinical course of the disease., Material/methods: The extent of immunostaining for EGF, IGF-1, TGF-beta1, alpha-SMA(+) cells, as well as bax and bcl-2 proteins was estimated in cellular, fibrocellular, and fibrotic crescents of 17 kidney biopsy specimens from patients with crescentic nephritis, and correlated with the clinical course of the disease., Results: Growth factors, apoptosis-related proteins, and myofibroblasts were identified within crescents, glomeruli, and tubulointerstitial area. EGF and bax protein were mainly identified in cellular crescents (>50%) whereas TGF-beta1, myofibroblasts, and bcl-2 protein were observed in fibrocellular crescents (>50%). The expression of all parameters was significantly reduced in fibrotic crescents. The presence of glomeruli with a ruptured Bowman capsule and an increased serum creatinine level at diagnosis were associated with an unfavorable clinical course with no response to immunosuppressive therapy (P<0.05 and P<0.02, respectively)., Conclusions: Growth factors and the apoptotic process are involved in the organization of cellular to fibrotic crescents resulting in irreversible damage and an unfavorable clinical outcome. Identifying different patterns among growth factors and apoptosis-related proteins during the organization of crescents suggests an interplay between growth factors and the apoptotic process in the development of crescentic nephritis.
- Published
- 2008
21. Effect of clopidogrel on arteriovenous fistulas for dialysis.
- Author
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Fourtounas C and Vlachojannis JG
- Subjects
- Arteriovenous Shunt, Surgical methods, Clopidogrel, Humans, Thrombosis etiology, Ticlopidine therapeutic use, Arteriovenous Shunt, Surgical adverse effects, Graft Occlusion, Vascular prevention & control, Platelet Aggregation Inhibitors therapeutic use, Renal Dialysis methods, Thrombosis prevention & control, Ticlopidine analogs & derivatives
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- 2008
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22. PD underutilization in Europe: a call to action.
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Fourtounas C and Vlachojannis JG
- Subjects
- Europe, Humans, Kidney Failure, Chronic therapy, Nephrology education, Renal Dialysis statistics & numerical data, Peritoneal Dialysis statistics & numerical data
- Published
- 2008
- Full Text
- View/download PDF
23. Eosinophilic peritonitis following air entrapment during peritoneoscopic insertion of peritoneal dialysis catheters.
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Fourtounas C, Dousdampanis P, Hardalias A, Liatsikos E, and Vlachojannis JG
- Subjects
- Adult, Eosinophilia diagnosis, Eosinophilia therapy, Humans, Male, Middle Aged, Peritonitis diagnosis, Peritonitis therapy, Pneumoperitoneum diagnosis, Pneumoperitoneum therapy, Catheterization adverse effects, Eosinophilia etiology, Kidney Failure, Chronic therapy, Peritoneal Dialysis instrumentation, Peritonitis etiology, Pneumoperitoneum etiology
- Abstract
Eosinophilic peritonitis following peritoneal dialysis catheter insertion is an infrequent but important complication. While allergic reaction to catheter material has been noted to be a culprit, air infusion into the abdominal cavity has also been highlighted to be a cause of this complication. In this article, we report two patients with end-stage renal disease where air entrapment in the peritoneal cavity during a peritoneal dialysis catheter insertion resulted in eosinophilic peritonitis. The complication resolved with the reabsorption of entrapped intraperitoneal air and treatment with ketotifen. Peritonitis observed in the postoperative period during the peritoneoscopic insertion of a peritoneal dialysis catheter could be the result of air entrapment. Such patients might not require antibiotic therapy or catheter removal. Reabsorption of entrapped air and treatment with ketotifen might be all that is required.
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- 2008
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24. Sodium removal in peritoneal dialysis: the role of icodextrin and peritoneal dialysis modalities.
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Fourtounas C, Hardalias A, Dousdampanis P, Papachristopoulos B, Savidaki E, and Vlachojannis JG
- Subjects
- Female, Humans, Icodextrin, Male, Middle Aged, Peritoneal Dialysis, Continuous Ambulatory, Glucans pharmacology, Glucose pharmacology, Hemodialysis Solutions pharmacology, Peritoneal Dialysis, Peritoneum metabolism, Sodium metabolism
- Abstract
One of the main goals of dialysis is the control of extracellular volume, because inadequate sodium and fluid removal result in fluid overload and increased mortality. In the present study, we evaluated the roles of continuous ambulatory peritoneal dialysis (CAPD), continuous cycling peritoneal dialysis (CCPD), and the use of icodextrin on sodium removal in 29 patients (n = 18 on CAPD, n = 11 on CCPD). Daily removal of sodium by each modality and dialysis adequacy by Kt/V and creatinine clearance were evaluated. A significantly higher amount of sodium was removed in CAPD patients than in CCPD patients, although peritoneal dialysis clearances were lower in CAPD, and no difference in daily ultrafiltration was observed between the modalities. In the CAPD group, patients using icodextrin for the long dwell showed significantly increased 24-hour sodium removal (218 +/- 65 mmol/L) as compared with patients not using icodextrin (96.3 +/- 58 mmol/L, p < 0.001); they also showed increased daily ultrafiltration (1685 +/- 302 mL vs. 717 +/- 440 mL, p < 0.001). In the CCPD group, 8 patients were using icodextrin for the long dwell, and they showed significantly increased sodium removal only for the day exchange (43 +/- 49 mmol/L) as compared with patients not using icodextrin (-60 +/- 6, p < 0.001). Hypertension was less common in the CAPD patients than in the CCPD patients. These results indicate that CAPD is a more efficient modality than CCPD for sodium removal. Icodextrin is an effective tool not only for increasing adequacy, but also for removing more sodium in both modalities.
- Published
- 2008
25. Corticosteroids and ciclosporin A in idiopathic membranous nephropathy: higher remission rates of nephrotic syndrome and less adverse reactions than after traditional treatment with cytotoxic drugs.
- Author
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Goumenos DS, Katopodis KP, Passadakis P, Vardaki E, Liakopoulos V, Dafnis E, Stefanidis I, Vargemezis V, Vlachojannis JG, and Siamopoulos KC
- Subjects
- Adrenal Cortex Hormones adverse effects, Adult, Aged, Cyclosporine administration & dosage, Cyclosporine adverse effects, Cytotoxins adverse effects, Cytotoxins therapeutic use, Drug Therapy, Combination, Female, Humans, Immunosuppressive Agents administration & dosage, Immunosuppressive Agents adverse effects, Kidney Function Tests, Male, Middle Aged, Recurrence, Remission Induction, Retrospective Studies, Treatment Outcome, Adrenal Cortex Hormones therapeutic use, Cyclosporine therapeutic use, Glomerulonephritis, Membranous drug therapy, Immunosuppressive Agents therapeutic use, Nephrotic Syndrome drug therapy
- Abstract
Background/aim: Idiopathic membranous nephropathy, the most common cause of nephrotic syndrome in adults, has been traditionally treated with corticosteroids and cytotoxic drugs. Ciclosporin A (CsA) is used in resistant cases, but also as a first-line treatment, due to the serious side effects of cytotoxic drugs. In this study, the remission rates of nephrotic syndrome and the incidence of side effects of corticosteroids and low CsA doses are compared with those after treatment with cytotoxic drugs., Methods: Seventy-seven nephrotic patients with well-preserved renal function who were treated with methylprednisolone and CsA (n = 46) or cytotoxic drugs (n = 31) were studied. The effects of treatments were estimated on the basis of remission rates of nephrotic syndrome and preservation of the renal function., Results: Remission (complete or partial) of nephrotic syndrome was observed in 85% of the patients treated with CsA and in 55% of the patients treated with cytotoxic drugs (p < 0.01). Deterioration of the renal function, more common in patients with multiple relapses and interstitial fibrosis, was observed in 26 and 23% of the patients, respectively (p = NS). Serious side effects and discontinuation of treatment were more frequent in patients treated with cytotoxic drugs (10 vs. 4%)., Conclusion: The combination of corticosteroids with CsA represents a better regimen for patients having idiopathic membranous nephropathy, since it is associated with higher remission rates of nephrotic syndrome and less severe side effects than corticosteroids and cytotoxic drugs., (2007 S. Karger AG, Basel)
- Published
- 2007
- Full Text
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26. Severe vitamin D deficiency in chronic renal failure patients on peritoneal dialysis.
- Author
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Taskapan H, Ersoy FF, Passadakis PS, Tam P, Memmos DE, Katopodis KP, Ozener C, Akcicek F, Camsari T, Ates K, Ataman R, Vlachojannis JG, Dombros NA, Utas C, Akpolat T, Bozfakioglu S, Wu G, Karayaylali I, Arinsoy T, Stathakis CP, Yavuz M, Tsakiris DJ, Dimitriades AD, Yilmaz ME, Gültekin M, and Oreopoulos DG
- Subjects
- Adult, Aged, Cross-Sectional Studies, Diabetic Nephropathies therapy, Female, Humans, Kidney Failure, Chronic etiology, Male, Middle Aged, Vitamin D blood, Vitamin D Deficiency epidemiology, Kidney Failure, Chronic complications, Peritoneal Dialysis adverse effects, Vitamin D Deficiency complications, Vitamin D Deficiency etiology
- Abstract
Unlabelled: The aim of this study was to evaluate the prevalence of vitamin D deficiency in chronic renal failure (CRF) patients on peritoneal dialysis (PD) and to correlate the findings with various demographic and renal osteodystrophy markers., Method: This cross-sectional, multicenter study was carried out in 273 PD patients with a mean age of 61.7 +/- 10.9 years and mean duration of PD 3.3 +/- 2.2 years. It included 123 female and 150 male patients from 20 centers in Greece and Turkey, countries that are on the same latitude, namely, 36-42 degrees north. We measured 25(OH)D3 and 1.25(OH)2D3 levels and some other clinical and laboratory indices of bone mineral metabolism., Results: Of these 273 patients 92% (251 patients) had vitamin D deficiency i.e. serum 25(OH)D3 levels less than 15 ng/ml, 119 (43.6%) had severe vitamin D deficiency i.e., serum 25(OH)D3 levels, less than 5 ng/ml, 132 (48.4%) had moderate vitamin D deficiency i.e., serum 25(OH)D3 levels, 5-15 ng/ml, 12 (4.4%) vitamin D insufficiency i.e., serum 25(OH)D3 levels 15 - 30 ng/ml and only 10 (3.6%) had adequate vitamin D stores. We found no correlation between 25(OH)D3 levels and PTH, serum albumin, bone alkaline phosphatase, P, and Ca x P. In multiple regression analyses, the independent predictors of 25(OH)D3 were age, presence of diabetes (DM-CRF), levels of serum calcium and serum 1.25(OH)2D3., Conclusion: We found a high prevalence (92%) of vitamin D deficiency in these 273 PD patients, nearly one half of whom had severe vitamin D deficiency. Vitamin D deficiency is more common in DM-CRF patients than in non-DM-CRF patients. Our findings suggest that these patients should be considered for vitamin D supplementation.
- Published
- 2006
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27. Calciphylaxis: a complication of end-stage renal disease improved by parathyroidectomy.
- Author
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Maroulis JC, Fourtounas C, Vlachojannis JG, Siasos N, Karavias D, Chartoumpekis D, and Habeos I
- Subjects
- Adult, Bone and Bones diagnostic imaging, Calciphylaxis diagnosis, Calcium blood, Humans, Male, Phosphates blood, Radiography, Whole Body Imaging, Calciphylaxis etiology, Calciphylaxis surgery, Kidney Failure, Chronic complications, Parathyroidectomy
- Abstract
A 43-year old Caucasian male with end-stage renal disease presented with painful skin lesions and high calcium phosphate product that did not respond to medical treatment. Skin biopsy confirmed the diagnosis of calciphylaxis. Urgent parathyroidectomy was performed and resulted in decrease in the calcium phosphate product and improvement of his symptoms and signs.
- Published
- 2006
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28. Cyclosporin-A in the treatment of nephrotic syndrome: the importance of monitoring C0 (trough) and C2 (two hours after its administration) blood levels.
- Author
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Goumenos DS, Kalliakmani P, Tsakas S, Savidaki I, and Vlachojannis JG
- Subjects
- Female, Humans, Inactivation, Metabolic, Male, Middle Aged, Monitoring, Physiologic, Nephrotic Syndrome blood, Recurrence, Remission Induction, Cyclosporine administration & dosage, Cyclosporine blood, Cyclosporine therapeutic use, Immunosuppressive Agents administration & dosage, Immunosuppressive Agents blood, Immunosuppressive Agents therapeutic use, Nephrotic Syndrome drug therapy
- Abstract
Cyclosporin-A (CsA) is often used in the treatment of nephrotic syndrome. The effectiveness of CsA and the value of C2 blood levels in the treatment of nephrotic syndrome, due to various glomerular diseases, were studied. Forty-two nephrotic patients (M/F 21/21), with well-preserved renal function (creatinine clearance 87+/-20 ml/min) were included in the study. The original diagnoses were minimal change disease (MCD), focal segmental glomerulosclerosis (FSGS), membranous nephropathy (MN), IgA nephropathy (IgAN), and lupus nephritis (LN). All patients were treated with prednisolone and CsA for 24 months. Cyclosporin-A C0 and C2 blood levels were determined at regular intervals. Remission of the nephrotic syndrome was observed in all patients with MCD, IgAN and LN, in 75% with FSGS and in 83% with MN. Relapses were observed in some patients with MCD (25%) and MN (36%). The C0 levels were 93+/-15 ng/ml and the corresponding C2 levels were 498+/-110 ng/ml. However, significantly lower (340+/-83 ng/ml) or higher (680+/-127 ng/ml) to the average C2 levels were found in 6 patients (14%). No relation of C0 and C2 levels with the remission and relapse rate of the nephrotic syndrome and with renal function impairment was observed. Small doses of CsA with prednisolone are effective in the treatment of nephrotic syndrome. Although an individual variation of C2 was observed for the same target C0 levels, no relation of C2 levels was found with the remission or relapse rate of the nephrotic syndrome.
- Published
- 2006
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29. Bone mineral density and its correlation with clinical and laboratory factors in chronic peritoneal dialysis patients.
- Author
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Ersoy FF, Passadakis SP, Tam P, Memmos ED, Katopodis PK, Ozener C, Akçiçek F, Camsari T, Ateş K, Ataman R, Vlachojannis JG, Dombros AN, Utaş C, Akpolat T, Bozfakioğlu S, Wu G, Karayaylali I, Arinsoy T, Stathakis PC, Yavuz M, Tsakiris JD, Dimitriades CA, Yilmaz ME, Gültekin M, Karayalçin B, Yardimsever M, and Oreopoulos DG
- Subjects
- Absorptiometry, Photon, Adult, Aged, Body Mass Index, Body Weight, Cross-Sectional Studies, Female, Femur Neck, Humans, Kidney Diseases physiopathology, Kidney Diseases therapy, Lumbar Vertebrae, Male, Middle Aged, Osteoporosis ethnology, Parathyroid Hormone, Racial Groups, Reference Values, Risk Factors, Sex Factors, Bone Density, Osteoporosis physiopathology, Peritoneal Dialysis
- Abstract
The aim of this study was to assess the clinical and laboratory correlations of bone mineral density (BMD) measurements among a large population of patients on chronic peritoneal dialysis (PD). This cross-sectional, multicenter study was carried out in 292 PD patients with a mean age of 56 +/- 16 years and mean duration of PD 3.1 +/- 2.1 years. Altogether, 129 female and 163 male patients from 24 centers in Canada, Greece, and Turkey were included in the study. BMD findings, obtained by dual-energy X-ray absorptiometry (DEXA) and some other major clinical and laboratory indices of bone mineral deposition as well as uremic osteodystrophy were investigated. In the 292 patients included in the study, the mean lumbar spine T-score was -1.04 +/- 1.68, the lumbar spine Z-score was -0.31 +/- 1.68, the femoral neck T-score was -1.38 +/- 1.39, and the femoral neck Z score was -0.66 +/- 1.23. According to the WHO criteria based on lumbar spine T-scores, 19.2% of 292 patients were osteoporotic, 36.3% had osteopenia, and 44.4% had lumbar spine T-scores within the normal range. In the femoral neck area, the prevalence of osteoporosis was slightly higher (26%). The prevalence of osteoporosis was 23.3% in female patients and 16.6% in male patients with no statistically significant difference between the sexes. Agreements of lumbar spine and femoral neck T-scores for the diagnosis of osteoporosis were 66.7% and 27.3% and 83.3% for osteopenia and normal BMD values, respectively. Among the clinical and laboratory parameters we investigated in this study, the body mass index (BMI) (P < 0.001), daily urine output, and urea clearance time x dialysis time/volume (Kt/V) (P < 0.05) were statistically significantly positive and Ca x PO(4) had a negative correlation (P < 0.05) with the lumbar spine T scores. Femoral neck T scores were also positively correlated with BMI, daily urine output, and KT/V; and they were negatively correlated with age. Intact parathyroid hormone levels did not correlate with any of the BMD parameters. Femoral neck Z scores were correlated with BMI (P < 0.001), and ionized calcium (P < 0.05) positively and negatively with age, total alkaline phosphatase (P < 0.05), and Ca x P (P < 0.01). The overall prevalence of fractures since the initiation of PD was 10%. Our results indicated that, considering their DEXA-based BMD values, 55% of chronic PD patients have subnormal bone mass-19% within the osteoporotic range and 36% within the osteopenic range. Our findings also indicate that low body weight is the most important risk factor for osteoporosis in chronic PD patients. An insufficient dialysis dose (expressed as KT/V) and older age may also be important risk factors for osteoporosis of PD patients.
- Published
- 2006
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30. Immunosuppressive treatment of idiopathic focal segmental glomerulosclerosis: a five-year follow-up study.
- Author
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Goumenos DS, Tsagalis G, El Nahas AM, Shortland JR, Davlouros P, Vlachojannis JG, and Brown CB
- Subjects
- Adult, Drug Combinations, Female, Follow-Up Studies, Humans, Longitudinal Studies, Male, Treatment Outcome, Azathioprine administration & dosage, Cyclosporine administration & dosage, Glomerulosclerosis, Focal Segmental drug therapy, Immunosuppressive Agents administration & dosage, Prednisolone administration & dosage
- Abstract
Background/aims: Focal segmental glomerulosclerosis (FSGS) is a common type of glomerular disease that can lead to chronic renal failure. Various therapeutic regimens have been used in nephrotic FSGS patients. The effect of treatment with prednisolone alone or its combination with azathioprine and cyclosporin and parameters related to a poor outcome are studied., Methods: Fifty-one patients with idiopathic FSGS and a follow-up period of 5 years were included. Twenty-five were treated with prednisolone alone (1 mg/kg BW/day) or combination of prednisolone (0.5 mg/kg BW/day) with azathioprine (2 mg/kg BW/day) or cyclosporine (3 mg/kg BW/day) in gradually reduced doses whereas 26 patients received no immunosuppressive drugs. Lower prednisolone dose regimens were used as initial treatment in obese, borderline diabetics or patients with bone disease. The clinical course was estimated using the end-points of 50% or doubling of baseline serum creatinine and/or end-stage renal failure. The contribution of clinical and histological parameters in the clinical outcome was estimated by univariate and multivariate analyses., Results: Increase of baseline serum creatinine by 50% during the follow-up period was observed in 2 treated and 9 untreated patients (8% vs. 35%, p = 0.03) whereas doubling of serum creatinine in 2 and 5 patients respectively (8% vs. 19%, p = NS). End-stage renal failure developed in 4 of 51 patients (8%), 2 treated and 2 untreated (p = NS). Parameters related to a poor outcome were baseline serum creatinine and severity of glomerulosclerosis (multivariate analysis OR = 1.08, p = 0.01). Most of patients (68%) who reached end-points had persistent nephrotic syndrome during the follow-up. Remission of nephrotic syndrome was observed more frequently among treated (75 vs. 30.7%, p = 0.05). Prednisolone alone was followed by remission of nephrotic syndrome in 62.5% whereas combination of lower prednisolone dose with azathioprine and cyclosporin in 80 and 85.7% of patients. No serious side-effects were observed., Conclusion: This and previous studies suggest that steroid and/or immunosuppressive therapy have a role in amelioration of the clinical course and remission of nephrotic syndrome in patients with FSGS A combination of low predisolone dose with cyclosporine could be used as initial treatment in patients with higher risk for side-effects from the usual prednisolone dose., (Copyright 2006 S. Karger AG, Basel.)
- Published
- 2006
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31. Treatment of peritoneal dialysis related fungal peritonitis with caspofungin plus amphotericin B combination therapy.
- Author
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Fourtounas C, Marangos M, Kalliakmani P, Savidaki E, Goumenos DS, and Vlachojannis JG
- Subjects
- Aged, Antifungal Agents therapeutic use, Candida albicans drug effects, Candidiasis diagnosis, Candidiasis etiology, Caspofungin, Drug Therapy, Combination, Echinocandins, Follow-Up Studies, Humans, Kidney Failure, Chronic diagnosis, Kidney Failure, Chronic therapy, Lipopeptides, Male, Peritoneal Dialysis, Continuous Ambulatory methods, Peritonitis diagnosis, Risk Assessment, Severity of Illness Index, Treatment Outcome, Amphotericin B therapeutic use, Candida albicans isolation & purification, Candidiasis drug therapy, Peptides, Cyclic therapeutic use, Peritoneal Dialysis, Continuous Ambulatory adverse effects, Peritonitis drug therapy
- Published
- 2006
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32. Endothelin receptors in the kidney of patients with proteinuric and non-proteinuric nephropathies.
- Author
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Drakopoulos A, Goumenos DS, Vlachojannis JG, and Tsakas S
- Subjects
- Adult, Endothelin-1 urine, Female, Fluorescent Antibody Technique, Indirect, Glomerulonephritis, IGA metabolism, Glomerulonephritis, IGA pathology, Glomerulonephritis, Membranous metabolism, Glomerulonephritis, Membranous pathology, Humans, Kidney pathology, Kidney Diseases pathology, Male, Middle Aged, Nephrosis, Lipoid metabolism, Nephrosis, Lipoid pathology, Nephrotic Syndrome metabolism, Nephrotic Syndrome pathology, Proteinuria pathology, Kidney metabolism, Kidney Diseases metabolism, Proteinuria metabolism, Receptor, Endothelin A metabolism, Receptor, Endothelin B metabolism
- Abstract
Background: Endothelin-1 (ET-1), which acts via the specific receptors ET-A and ET-B, has been implicated in the development of renal scarring. The activation of the endothelin system was observed in experimental models of glomerular diseases and was attributed to the toxic action of proteinuria on the tubular epithelial cells. The aim of this study was to investigate whether the endothelin system in the kidney is altered in glomerular diseases and possibly related to proteinuria., Methods: Thirty-seven patients with different types of glomerulonephritis and 14 controls were included. Patients presented either nephrotic syndrome (n=25) or mild proteinuria (<1g/24h, n=12). The expression of ET-A and ET-B receptors in the renal tissue was examined immunohistochemically. At the time of biopsy, urinary ET-1 was determined., Results: Both receptors were mainly localized within tubular epithelial cells, and their expression was significantly higher in patients with glomerulonephritis compared to controls. The expression of ET-B was higher in nephrotic compared to non-nephrotic patients, while no difference was observed in the expression of ET-A receptors. A significant positive correlation of the degree of proteinuria with the excreted ET-1 (r= 0.487, p<0.05) and the extent of immunostaining for ET-B receptors (r=0.420, p<0.05) was observed. The expression of ET-B receptors and the excretion of ET-1 decreased significantly in patients with remission of nephrotic syndrome after therapy., Conclusion: This study provides evidence that the endothelin system is activated in human glomerular disease, confirming data from experimental studies. Proteinuria seems to be related to the activation of endothelin system, though further investigation is necessary to clarify this issue.
- Published
- 2006
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33. Peritonitis during the first year after commencement of peritoneal dialysis has an impact on technique survival and patient morbidity.
- Author
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Fourtounas C, Savidaki E, Dousdabanis P, Hardalias A, Kalliakmani P, Papachristou E, Drakopoulos A, Goumenos DS, and Vlachojannis JG
- Subjects
- Adolescent, Adult, Aged, Humans, Middle Aged, Peritoneal Dialysis methods, Peritonitis microbiology, Survival Analysis, Time Factors, Peritoneal Dialysis adverse effects, Peritonitis etiology
- Abstract
The timing of the first episode of peritonitis in peritoneal dialysis (PD) might have some special characteristics and may depend on many factors such as a patient's attitudes, age, comorbidity, or training capacity. It may also have a significant impact on further peritonitis episodes and technique failure. We retrospectively analyzed data for 168 PD patients who were undergoing continuous ambulatory PD by a twin-bag system, automated PD, or in-center intermittent PD over 12 years. There were 121 cases of peritonitis recorded in 60 patients, with an overall peritonitis rate of 1 episode per 45.75 patient-months. The mean time to the first episode of peritonitis after commencement of PD was 26.4 +/- 22 months (range: 1-110 months). In 20 patients, a first peritonitis episode presented rather early--during the first 12 months on PD (group A)--and in 27 patients, a first episode presented rather late-after at least 24 months on PD (group B). Group A had lower technique survival (30.4 +/- 26.5 months), were more prone to further episodes of peritonitis during follow-up, and had a total peritonitis rate of 1 episode per 14.85 patient-months. In group B, technique survival was longer (69.3 +/- 33.8 months), and the total peritonitis rate was 1 episode per 45.68 patient-months. We observed no differences between the two groups in comorbidity, age, or PD modality. These results indicate that patients with early-onset peritonitis are prone to making mistakes during connection, resulting usually in infection with gram-positive pathogens. These patients may present repeated peritonitis episodes and experience decreased technique survival.
- Published
- 2006
34. Acid-base profile and predictors of metabolic acidosis in patients undergoing peritoneal dialysis with lactate- and bicarbonate-buffered peritoneal dialysis solutions.
- Author
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Fourtounas C, Savidaki E, Roumelioti M, Dousdampanis P, Hardalias A, Kalliakmani P, Papachristou E, Drakopoulos A, Goumenos DS, and Vlachojannis JG
- Subjects
- Acidosis blood, Adult, Bicarbonates blood, Biocompatible Materials, Buffers, Female, Humans, Male, Middle Aged, Peritoneal Dialysis, Continuous Ambulatory, Acid-Base Equilibrium, Acidosis chemically induced, Bicarbonates adverse effects, Hemodialysis Solutions adverse effects, Lactates adverse effects, Peritoneal Dialysis
- Abstract
Metabolic acidosis correction is one of the goals of renal replacement therapy. Correction of acidosis in peritoneal dialysis (PD) may be affected by PD modalities such as automated PD (APD) or by new solutions containing a combination of bicarbonate and lactate as a buffer [bicarbonate continuous ambulatory PD (CAPD)]. The aim of the present study was to examine the acid-base status of our PD population and to compare the effects of APD, lactate CAPD, and bicarbonate CAPD on serum bicarbonate levels. We studied 35 stable patients undergoing APD (n = 15), lactate-buffered (35 mEq/L) CAPD (n = 14), and bicarbonate/lactate-buffered CAPD (n = 6) for 48.5 +/- 38.1 months. Most of our patients had serum bicarbonate levels in the normal range. In 3 patients (8%), HCO3 was below 22 mEq/L, and in 8 patients (22%; APD = 2, lactate CAPD = 2, bicarbonate CAPD = 4), HCO3 was above 28 mEq/L. We found no statistically significant correlations between HCO3 serum levels and PD prescription, peritoneal membrane characteristics, or intake of calcium carbonate and sevelamer hydrochloride. Patients on bicarbonate CAPD had higher HCO3 serum levels, but this difference disappeared when corrections for duration of dialysis, residual urine volume, and PD adequacy indices were applied. In the studied PD population, adequate correction of metabolic acidosis was achieved, as reflected in serum bicarbonate levels. We observed no difference in serum bicarbonate levels between APD and lactate CAPD patients. The new bicarbonate-buffered PD solutions are more biocompatible and can result in higher serum bicarbonate levels. However, a significant number of PD patients on bicarbonate-buffered solutions may become alkalotic. The clinical significance of these results needs further examination in prospective studies.
- Published
- 2006
35. Urinary Transforming Growth Factor-beta 1 as a marker of response to immunosuppressive treatment, in patients with crescentic nephritis.
- Author
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Goumenos DS, Kalliakmani P, Tsakas S, Sotsiou F, and Vlachojannis JG
- Subjects
- Adult, Aged, Biomarkers urine, Epithelial Cells metabolism, Female, Glomerulonephritis metabolism, Glomerulonephritis pathology, Humans, Immunohistochemistry, Kidney metabolism, Kidney Glomerulus pathology, Kidney Tubules metabolism, Male, Middle Aged, Necrosis, Transforming Growth Factor beta metabolism, Transforming Growth Factor beta1, Treatment Outcome, Glomerulonephritis therapy, Glomerulonephritis urine, Immunosuppression Therapy, Transforming Growth Factor beta urine
- Abstract
Background: Crescentic nephritis is characterized by formation of cellular crescents that soon become fibrotic and result in irreversible damage, unless an effective immunosuppressive therapy is rapidly commenced. TGF-beta1 is involved in the development of crescents through various pathways. The aim of this study was to identify whether the determination of urinary TGF-beta1 levels in patients with crescentic nephritis could be used as a marker of response to treatment., Methods: Fifteen patients with crescentic nephritis were included in the study. The renal expression of TGF-beta1 was estimated in biopsy sections by immunohistochemistry and urinary TGF-beta1 levels were determined by quantitative sandwich enzyme immunoassay (EIA). TGF-beta1 levels were determined at the time of renal biopsy, before the initiation of immunosuppressive treatment (corticosteroids, cyclophosphamide and plasma exchange). Twelve patients with other types of proliferative glomerulonephritis and ten healthy subjects were used as controls., Results: Improvement of renal function with immunosuppressive therapy was observed in 6 and stabilization in 4 patients (serum creatinine from 3.2 +/- 1.5 to 1.4 +/- 0.1 mg/dl and from 4.4 +/- 1.2 to 4.1 +/- 0.6 mg/dl, respectively). In 5 patients, with severe impairment of renal function who started on dialysis, no improvement was noted. The main histological feature differentiating these 5 patients from others with improved or stabilized renal function was the percentage patients with poor response to treatment were the percentage of glomeruli with crescents and the presence of ruptured Bowman's capsule and glomerular necrosis. Urinary TGF-beta1 levels were significantly higher in patients who showed no improvement of renal function with immunosuppressive therapy (930 +/- 126 ng/24 h vs. 376 +/- 84 ng/24 h, p < 0.01). TGF-beta1 was identified in crescents and tubular epithelial cells, whereas a significant correlation of TGF-beta1 immunostaining with the presence of fibrocellular cresents was observed (r = 0.531, p < 0,05)., Conclusion: Increased TGF-beta1 renal expression and urinary excretion that is related to the response to immunosuppressive therapy was observed in patients with crescentic nephritis. Evaluation of urinary TGF-beta1 levels may be proved a useful marker of clinical outcome in patients with crescentic nephritis.
- Published
- 2005
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36. Expression of apoptosis-related proteins bcl-2 and bax along with transforming growth factor (TGF-beta1) in the kidney of patients with glomerulonephritides.
- Author
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Goumenos DS, Tsamandas AC, Kalliakmani P, Tsakas S, Sotsiou F, Bonikos DS, and Vlachojannis JG
- Subjects
- Apoptosis physiology, Case-Control Studies, Female, Glomerulonephritis pathology, Humans, Kidney pathology, Male, Transforming Growth Factor beta1, bcl-2-Associated X Protein, Glomerulonephritis metabolism, Kidney metabolism, Proto-Oncogene Proteins c-bcl-2 metabolism, Transforming Growth Factor beta metabolism
- Abstract
Background: Apoptosis, a gene-directed form of cell death, has been involved in the resolution of renal injury but also in the development of scarring. Bcl-2 and bax are proteins related to apoptotic process that either provides a survival advantage to rapidly proliferating cells (bcl-2) or promote cell death by apoptosis (bax). Various cytokines and growth factors are involved in this process. This study investigates the expression of bcl-2 and bax and the presence of apoptotic bodies in relation to the TGF-beta1 expression at the time of diagnosis in the renal biopsies of patients with glomerulonephritis (GN)., Methods: Fifty patients with various types of GN and ten controls were included in the study. Bcl-2, bax and Transforming Growth Factor (TGF-beta1) positive cells were detected in kidney biopsies by immunohistochemistry, while apoptotic cells were detected by in situ end labeling of fragmented DNA (ISEL). Morphometric analysis was used for quantitation of immunostaining., Results: The intensity of bcl-2, bax and TGF-beta1 immunostaining in the renal tissue of patients with GN was significantly more to the observed in the control biopsies. Bcl-2 and bax were expressed within the epithelial cells of proximal, distal and collecting tubules and in the renal interstitium. Bax and bcl-2 proteins were also identified within the glomeruli in a few patients but their distribution was not related to the type of GN. TGF-beta1 was expressed in the cytoplasm of tubular epithelial cells and to a lesser extent in the renal interstitium and glomeruli. A positive correlation of TGF-beta1 with the extent of bax immunostaining (r=0.498, p<0.05) and an inverse correlation with that of bcl-2 (r= -0.490, p<0.05) were identified. Apoptotic bodies were identified only in the renal tissue of patients with GN and were mainly localized among tubular epithelial and interstitial cells., Conclusion: The intensity of bcl-2 and bax proteins expression and the presence of apoptotic bodies in the renal tissue of patients with GN suggest that apoptotic process is ongoing during the evolution of renal disease. The correlation of TGF-beta1 expression with that of apoptosis-related proteins might represent an implication of this growth factor with apoptotic process in the human diseased kidney.
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- 2004
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37. The remission of nephrotic syndrome with cyclosporin treatment does not attenuate the progression of idiopathic membranous nephropathy.
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Goumenos DS, Kalliakmani P, Tsakas S, Sotsiou F, and Vlachojannis JG
- Subjects
- Biopsy, Cyclosporine adverse effects, Disease Progression, Female, Follow-Up Studies, Glomerulonephritis, Membranous complications, Glomerulonephritis, Membranous pathology, Humans, Immunosuppressive Agents adverse effects, Kidney pathology, Male, Middle Aged, Nephrotic Syndrome etiology, Nephrotic Syndrome pathology, Recurrence, Remission Induction, Cyclosporine administration & dosage, Glomerulonephritis, Membranous drug therapy, Glucocorticoids administration & dosage, Immunosuppressive Agents administration & dosage, Nephrotic Syndrome drug therapy, Prednisolone administration & dosage
- Abstract
Background: Idiopathic membranous nephropathy (IMN), a common cause of nephrotic syndrome in adults, is usually treated by combination of corticosteroids with cytotoxic drugs. In cases resistant to this regimen, the use of cyclosporin A (CsA) is followed by frequent remissions of the nephrotic syndrome., Aim: The purpose of this study was to estimate the effectiveness of prednisolone and small doses of CsA as first-line treatment of nephrotic patients with IMN, in relation to the progression of the disease, based on functional and histological changes., Patients and Methods: Sixteen patients, with nephrotic syndrome due to IMN and well-preserved renal function, were treated with prednisolone (starting dose: 0.5 mg/kg bw/day) and CsA (starting dose: 3 mg/kg bw/day) for 24 months. A repeat renal biopsy was performed after 18 months of treatment in 10 patients with remission of nephrotic syndrome, to estimate the activity of the disease and to identify any features of CsA toxicity., Results: Remission of the nephrotic syndrome was observed in 14 out of 16 patients after 5 +/- 2 months of treatment. Complete remission was observed in 8 and partial remission in 6 patients (urinary protein was reduced from 6.9 +/- 3.4-0.2 +/- 0.06 g/24 h and 1.2 +/- 1.0 g/24 h, respectively, p < 0.01). The renal function was well preserved in 13 out of 16 patients over a 24-month period of treatment. Deterioration of renal function was observed in 3 patients (creatinine clearance reduced from 86 +/- 21-37 +/- 17 ml/min, p < 0.05) who had either persistent nephrotic syndrome or frequent relapses. Relapses of the nephrotic syndrome were observed in 5 of 14 patients. Repeat renal biopsies showed that glomerular sclerosis, tubulointerstitial injury, vascular hyalinosis and stage of the disease were deteriorated in most patients. Isometric vacuolization of tubular epithelial cells was observed in 2 of 10 patients., Conclusion: IMN nephrotic patients treated with prednisolone and low doses of cyclosporin A showed a high remission rate of nephrotic syndrome. However, progression of chronic histological lesions was found in repeat renal biopsies. This suggests that cyclosporin can frequently induce remission of nephrotic syndrome in IMN patients, but even low doses of the drug are not free of potential renal toxicity.
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- 2004
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38. Histologic change of peritoneal membrane in relation to adequacy of dialysis in continuous ambulatory peritoneal dialysis patients.
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Savidaki I, Karavias D, Sotsiou F, Alexandri S, Kalliakmani P, Presvelos D, Papachristou E, Goumenos DS, and Vlachojannis JG
- Subjects
- Adult, Aged, Aged, 80 and over, Female, Humans, Male, Middle Aged, Peritoneal Dialysis adverse effects, Peritoneal Dialysis standards, Young Adult, Peritoneal Dialysis, Continuous Ambulatory adverse effects, Peritoneal Dialysis, Continuous Ambulatory standards, Peritoneum pathology
- Abstract
Background: Long-term exposure of peritoneal membrane to bioincompatible dialysis solutions leads to structural changes and loss of ultrafiltration capability., Objective: We studied the possible relationship between histologic change and the transport characteristics of peritoneal membrane and adequacy of dialysis in continuous ambulatory peritoneal dialysis (CAPD) patients., Patients and Methods: The study included 18 CAPD patients (11 men, 7 women) who underwent a peritoneal biopsy either at initiation of treatment (group A, n = 9) or after a mean of 4 years on CAPD (group B, n = 9). The morphologic changes in the mesothelial cells and the vascular compartment and the thickness of the submesothelial collagenous zone were estimated and compared with observations from 6 patients with normal renal function who underwent biopsy of the parietal peritoneum during abdominal surgery. The relationship of the observed changes in CAPD patients to results from a peritoneal equilibration test (PET) and to adequacy of dialysis [total weekly creatinine clearance (CCr) and Kt/V urea] were also investigated., Results: The main histologic changes in both groups of patients were loss of mesothelial cells and decrease in the normal mesothelial surface, thickening of the submesothelial collagenous zone, and presence of vascular hyalinosis. The thickness of the submesothelial collagenous zone in both groups of patients was significantly greater than that found in controls (410 mum and 580 mum vs 50 mum, p < 0.05). Although no significant difference was found between morphologic change in the peritoneal membrane of uremic patients starting on CAPD and those who had been on peritoneal dialysis (PD) for a mean period of 4 years, a trend was observed toward more severe lesions in the latter patients. The PET, CCr, and Kt/V urea were not significantly different in the two groups of patients. Those parameters also showed no significant changes when examined at initiation of CAPD and after a mean of 4 years of PD in the same patients (group B). No significant correlations were observed between the histologic changes and the PET, CCr, or Kt/V in both groups of patients., Conclusions: Significant structural changes are observed in the peritoneal membrane of uremic patients, and those changes become worse with CAPD treatment. Structural changes are not followed by functional changes during the first 4 years on CAPD.
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- 2003
39. Urinary transforming growth factor-beta1 excretion in renal allograft recipients during the early post-transplantation period.
- Author
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Goumenos DS, Tsakas S, Karavias D, Savidaki I, Karatzas T, and Vlachojannis JG
- Subjects
- Adult, Biomarkers urine, Biopsy, Creatinine metabolism, Cyclosporine metabolism, Cyclosporine therapeutic use, Female, Follow-Up Studies, Humans, Immunohistochemistry, Immunosuppressive Agents metabolism, Immunosuppressive Agents therapeutic use, Kidney drug effects, Kidney pathology, Kidney Diseases metabolism, Kidney Diseases pathology, Kidney Diseases therapy, Male, Middle Aged, Postoperative Period, Renal Dialysis, Statistics as Topic, Time Factors, Transforming Growth Factor beta1, Treatment Outcome, Kidney metabolism, Kidney Transplantation, Transforming Growth Factor beta urine
- Abstract
Background: Transforming growth factor-beta1 (TGF-beta1), the major fibrogenic growth factor, is implicated in the pathogenesis of renal scarring in experimental and clinical nephropathies as well as in chronic allograft nephropathy. In this study we examined the pattern of changes of TGF-beta1 excretion in the urine and the sites of TGF-beta1 expression in the kidney of transplanted patients during the early post-transplantation period., Methods: Eighteen renal allograft recipients were included in the study. In all patients urinary TGF-beta1 levels were determined by ELISA in sequential measurements during the first two postoperative months and compared to that of 14 healthy subjects. The renal expression of TGF-beta1 protein was studied in 4 patients that underwent a biopsy of the transplanted kidney at the same period. All patients were treated with prednisolone, cyclosporin, and mycophenolate mofetil., Results: Urinary TGF-beta1 levels were increased during the first postoperative days. Although they were gradually reduced during the first two post-operative months, they remained significantly higher compared to those of normal subjects (580 +/- 148 ng/24 h vs. 310 +/- 140 ng/ 24 h p < 0.01). The decline of urinary TGF-beta1 excretion followed that of serum creatinine. TGF-beta1 protein expression was identified within the cytoplasm of tubular epithelial cells of transplanted patients., Conclusions: Elevated urinary TGF-beta1 levels are observed during the early post-transplantation period in renal allograft recipients and are maintained high even after restoration of renal function to normal.
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- 2003
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40. Prednisolone and azathioprine in IgA nephropathy - a ten-year follow-up study.
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Goumenos DS, Davlouros P, El Nahas AM, Ahuja M, Shortland JR, Vlachojannis JG, and Brown CB
- Subjects
- Adult, Azathioprine adverse effects, Comorbidity, Diabetes Mellitus chemically induced, Drug Therapy, Combination, Female, Follow-Up Studies, Glomerulonephritis, IGA epidemiology, Humans, Immunosuppressive Agents adverse effects, Kidney Function Tests, Male, Multivariate Analysis, Neoplasms chemically induced, Prednisolone adverse effects, Proteinuria epidemiology, Reference Values, Retrospective Studies, Survival Rate, Treatment Outcome, Azathioprine administration & dosage, Glomerulonephritis, IGA drug therapy, Immunosuppressive Agents administration & dosage, Prednisolone administration & dosage
- Abstract
Background: Immunoglobulin A nephropathy (IgAN) is one of the most common primary glomerular diseases. Although its clinical course is usually benign, some patients develop end-stage renal failure (ESRF). The role of immunosuppressive drugs in the treatment of IgAN remains controversial. The effect of treatment with prednisolone and azathioprine and the clinical and histological parameters related to a poor outcome are examined retrospectively in this analysis., Methods: Seventy-four patients with IgAN and a follow-up period of 10 years were included in this study. Forty-one were treated with prednisolone (initially 60 mg/day) and azathioprine (initially 2 mg/kg BW/day) in gradually reduced doses for 24 +/- 9 months, whereas 33 patients received no immunosuppressive drugs. The clinical course was estimated using the end-points of doubling of baseline serum creatinine and/or ESRF. The contribution of clinical and histological parameters in the clinical outcome was estimated by univariate and multivariate analyses., Results: The overall clinical courses of both groups of patients showed a rather similar pattern. Doubling of serum baseline creatinine was observed in 9 of 41 treated (22%) and in 10 of 33 untreated (30%), whereas ESRF developed in 6 treated (15%) and 6 untreated patients (18%) (p = NS). However, treated patients with heavy proteinuria (>3 g/24 h) had a significantly better outcome compared to untreated (doubling of serum creatinine in 29 vs. 78% and ESRF in 17 vs. 55%, p < 0.05). Proteinuria (p < 0.01), mean blood pressure (p < 0.02), baseline serum creatinine (p = 0.02) and severity of interstitial myofibroblast expression (p = 0.02) were identified as independent risk factors related to a poor outcome by multivariate analysis. Side effects of treatment were not uncommon and observed in 10 (24%) patients., Conclusion: Treatment with prednisolone and azathioprine is beneficial in ameliorating the clinical course of a subset of IgAN patients with heavy proteinuria or impaired renal function. Patients with advanced renal failure and severe chronic histological lesions should not be treated by this regimen as no benefit is expected and there is a risk of side effects., (Copyright 2003 S. Karger AG, Basel)
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- 2003
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41. Transforming growth factor-beta(1) in the kidney and urine of patients with glomerular disease and proteinuria.
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Goumenos DS, Tsakas S, El Nahas AM, Alexandri S, Oldroyd S, Kalliakmani P, and Vlachojannis JG
- Subjects
- Adult, Aged, Cyclosporine therapeutic use, Female, Glucocorticoids therapeutic use, Humans, Immunohistochemistry, Immunosuppressive Agents therapeutic use, In Situ Hybridization, Kidney Diseases blood, Kidney Diseases urine, Male, Middle Aged, Nephrotic Syndrome drug therapy, Nephrotic Syndrome physiopathology, Osmolar Concentration, Prednisolone therapeutic use, Proteinuria etiology, RNA, Messenger metabolism, Remission Induction, Transforming Growth Factor beta genetics, Transforming Growth Factor beta urine, Transforming Growth Factor beta1, Kidney Diseases metabolism, Kidney Glomerulus, Proteinuria metabolism, Transforming Growth Factor beta metabolism
- Abstract
Background: Transforming growth factor-beta(1) (TGF-beta(1)) is the major fibrogenic growth factor implicated in the pathogenesis of renal scarring. Proteinuria is a poor prognostic feature for various types of glomerular disease and its toxic action may be related to the activation of tubular epithelial cells towards increased production of cytokines and chemoattractant peptides. In this work we studied the site of synthesis and expression profile of TGF-beta(1) in the renal tissue of patients with heavy proteinuria and examined the relation of this expression with the urinary excretion of TGF-beta(1)., Methods: Twenty-five patients with heavy proteinuria (8.4+/-3.0 g/24 h) were included in the study. All patients underwent a diagnostic kidney biopsy and were commenced on immunosuppressive therapy with corticosteroids and cyclosporin. The sites of synthesis and expression profile of TGF-beta(1) mRNA and protein in the kidney were examined by in situ hybridization and immunohistochemistry. Urinary and plasma TGF-beta(1) levels were determined by ELISA before the initiation of treatment and 6 months later and compared with those of normal subjects and of patients with IgA nephropathy and normal urinary protein excretion., Results: The site of synthesis and expression of TGF-beta(1) in the renal tissue of patients with heavy proteinuria was mainly localized within the cytoplasm of tubular epithelial cells. Interstitial expression was also present but glomerular TGF-beta(1) expression was found only in patients with mesangial proliferation. Urinary TGF-beta(1) excretion was significantly higher in nephrotic patients compared with normal subjects and with patients with IgA nephropathy and normal urinary protein excretion (783+/-280 vs 310+/-140 and 375+/-90 ng/24 h, respectively; P<0.01). In patients with remission of proteinuria after immunosuppressive therapy, urinary TGF-beta(1) excretion was significantly reduced (from 749+/-290 to 495+/-130 ng/24 h; P<0.01), while in patients with persistent nephrotic syndrome, it remained elevated., Conclusions: The localization of TGF-beta(1) mRNA and protein within tubular epithelial cells, along with its increased urinary excretion in patients with nephrotic syndrome, suggest the activation of these cells by filtered protein towards increased TGF-beta(1) production.
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- 2002
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42. Endothelin-1 in the kidney and urine of patients with glomerular disease and proteinuria.
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Vlachojannis JG, Tsakas S, Petropoulou C, Goumenos DS, and Alexandri S
- Subjects
- Adult, Anti-Inflammatory Agents therapeutic use, Cyclosporine therapeutic use, Female, Humans, Immunosuppressive Agents therapeutic use, Kidney Diseases drug therapy, Kidney Glomerulus drug effects, Male, Middle Aged, Proteinuria drug therapy, Remission Induction, Severity of Illness Index, Endothelin-1 analysis, Endothelin-1 urine, Kidney Diseases pathology, Kidney Diseases urine, Kidney Glomerulus pathology, Prednisolone therapeutic use, Proteinuria pathology, Proteinuria urine
- Abstract
Background: Endothelin-1 (ET-1) is a strong vasoconstrictive peptide that is involved in the pathogenesis of arterial hypertension. There is increasing evidence, based on studies in experimental animals, that endothelin-1 is produced by tubular epithelial cells in response to activation by filtered protein and is involved in the development of renal scarring. The aim of this study is to examine the distribution of ET-1 in the renal tissue of patients with heavy proteinuria and to estimate the changes in its urinary excretion after immunosuppressive therapy., Patients and Methods: Twenty-four patients with severe proteinuria (7.5 +/- 6.5 g/24 h) due to different types of glomerular disease and normal renal function (creatinine clearance 91 +/- 14 ml/ min) were investigated. All patients underwent a renal biopsy and commenced on immunosuppressive therapy with corticosteroids and cyclosporin A. The localization of ET-1 in the renal tissue was examined by immunohistochemistry and compared to control renal tissue from 9 patients who underwent nephrectomies because of hypernephroma. In patients with proteinuria, endothelin-1 excretion in the urine at diagnosis was determined by radioimmunoassay and compared to that of 14 healthy subjects. A second measurement of urinary ET-1 excretion was performed after remission of proteinuria or 6 months after the initiation of treatment in patients with persistent nephrotic syndrome., Results: ET-1 in renal tissue of patients and controls was localized within the cytoplasm of endothelial cells. In nephrotic patients, it was also localized within the cytoplasm of tubular epithelial cells. Urinary ET-1 levels were higher in nephrotic patients compared to healthy subjects (746 +/- 180 ng/24 h vs 410 +/- 112 ng/ml, p < 0.001). In 17 of 24 patients who showed remission of proteinuria with immunosuppressive therapy, the urinary ET-1 levels decreased (from 803 +/- 168 ng/24 h to 511 +/- 80 ng/24 h, p < 0.001) whereas in 7 patients with persistent proteinuria, urinary ET-1 excretion remained elevated., Conclusions: The increased urinary excretion of ET-1 in patients with severe proteinuria followed by a significant decrease after remission ofproteinuria with immunosuppressive treatment, along with its expression within tubular epithelial cells, suggests a possible relationship between proteinuria and renal ET-1 production.
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- 2002
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43. Apoptosis and myofibroblast expression in human glomerular disease: a possible link with transforming growth factor-beta-1.
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Goumenos DS, Tsamandas AC, El Nahas AM, Thomas G, Tsakas S, Sotsiou F, Bonikos DS, and Vlachojannis JG
- Subjects
- Actins metabolism, Adult, Aged, Female, Fibroblasts pathology, Fibrosis, Glomerulonephritis etiology, Glomerulonephritis, Membranoproliferative metabolism, Glomerulonephritis, Membranoproliferative pathology, Glomerulosclerosis, Focal Segmental metabolism, Glomerulosclerosis, Focal Segmental pathology, Humans, Immunohistochemistry, Male, Middle Aged, Muscle, Smooth metabolism, Transforming Growth Factor beta1, Apoptosis, Glomerulonephritis metabolism, Glomerulonephritis pathology, Transforming Growth Factor beta metabolism
- Abstract
Background/aims: The pathophysiological pathways involved in the pathogenesis and evolution of renal fibrosis, have not been fully elucidated. Transforming growth factor-beta(1) (TGF-beta(1)) is involved in the development of renal scarring. Apoptosis is responsible for intrinsic cell deletion observed in end-stage kidney disease. Myofibroblasts are involved in the development of renal fibrosis. This study investigates whether there is a potential relationship between apoptosis, myofibroblast infiltration and TGF-beta(1) expression in the kidney of patients with glomerulonephritis (GN)., Methods: Forty patients with various types of GN were included in the study. Myofibroblasts and TGF-beta(1) positive cells were detected in kidney biopsies by immunohistochemistry, while apoptotic cells were detected by the in situ end labelling of fragmented DNA., Results: Myofibroblasts were identified in the glomeruli of some patients with severe mesangioproliferative GN and glomerulosclerosis but a more intensive myofibroblast expression was found in the renal interstitium. TGF-beta(1) was expressed in the cytoplasm of tubular epithelial cells, in the renal interstitium and in the glomeruli of patients with GN. Apoptotic cells were mainly detected in the tubules and interstitium and were present in areas with intense myofibroblast infiltration. Positive correlations were observed between the intensity of myofibroblast expression in the interstitium and apoptosis in the tubulointerstitial area (r = 0.521, p < 0.01) as well as TGF-beta(1) expression (r = 0.462, p < 0.05) and degree of renal impairment (r = 0.430, p < 0.05)., Conclusions: These observations suggest that myofibroblast infiltration and apoptosis along with TGF-beta(1) expression are associated with the development of interstitial fibrosis in patients with glomerular disease., (Copyright 2002 S. Karger AG, Basel)
- Published
- 2002
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44. Transforming growth factor-beta(1) and myofibroblasts: a potential pathway towards renal scarring in human glomerular disease.
- Author
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Goumenos DS, Tsamandas AC, Oldroyd S, Sotsiou F, Tsakas S, Petropoulou C, Bonikos D, El Nahas AM, and Vlachojannis JG
- Subjects
- Adolescent, Adult, Aged, Cicatrix pathology, Collagen analysis, Extracellular Space metabolism, Female, Fibrosis, Glomerulonephritis pathology, Humans, Immunohistochemistry, In Situ Hybridization, Kidney metabolism, Male, Middle Aged, RNA, Messenger analysis, RNA, Messenger metabolism, Severity of Illness Index, Statistics as Topic, Transforming Growth Factor beta analysis, Transforming Growth Factor beta1, Cicatrix metabolism, Collagen biosynthesis, Fibroblasts metabolism, Glomerulonephritis metabolism, Kidney pathology, Transforming Growth Factor beta biosynthesis
- Abstract
Background/aims: The cellular and humoral factors involved in the development and progression of renal scarring have not been fully investigated. Transforming growth factor-beta (TGF-beta(1)) is considered to be the main fibrogenic growth factor and it is implicated in the pathogenesis of renal fibrosis in experimental and clinical nephropathies. On the other hand, collagen III is an important component of the extracellular matrix. In this study we attempted to identify any possible links between TGF-beta(1) and collagen III synthesis and expression with the expression of myofibroblasts in the evolution of renal scarring in human glomerular diseases., Methods: We studied retrospectively 40 patients with various types of primary and secondary glomerulonephritis (GN), with either proliferative or nonproliferative pattern, with emphasis on the renal synthesis of TGF-beta(1) and collagen III (detected by in situ hybridization) and their expression (detected by immunohistochemistry) as well as myofibroblast expression. The possible links of TGF-beta(1) expression with myofibroblast distribution (alpha-smooth muscle actin, alpha-SMA(+) cells) and with conventional histopathology and renal function was also examined., Results: TGF-beta(1) protein and mRNA were detected in the renal tubular epithelial cells and interstitium and to a lesser extent within glomeruli of patients with GN. Collagen III was mainly detected in the interstitium (peritubular and periglomerular areas) and to a lesser extent in the glomeruli. Messenger RNA for collagen III followed a similar peritubular and periglomerular distribution to that of TGF-beta(1) and alpha-SMA(+) interstitial cells. The intensity of interstitial TGF-beta(1) protein expression was significantly related to the degree of interstitial fibrosis (r = 0.628, p < 0.01), tubular atrophy (r = 0.612, p < 0.01), interstitial collagen III expression (r = 0.478, p < 0.05), and serum creatinine values (r = 0.722, p < 0.001). Also there was a close positive correlation between the severity of interstitial myofibroblast expression and interstitial TGF-beta(1) (r = 0.412, p < 0.05), as well as collagen III (r = 0.409, p < 0.05). In addition, a significant correlation was found between glomerular TGF-beta(1) expression and severity of glomerulosclerosis (r = 0.620, p < 0.01)., Conclusion: The results of this study suggest that TGF-beta(1) plays an important role in the pathogenesis of fibrosis developing in human kidney, during the evolution of glomerular disease. Interstitial myofibroblasts may contribute to interstitial fibrosis through the synthesis and release of both TGF-beta1 and collagen III., (Copyright 2001 S. Karger AG, Basel)
- Published
- 2001
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45. Polymorphonuclear leukocyte rigidity is defective in patients with chronic renal failure.
- Author
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Skoutelis AT, Kaleridis VE, Goumenos DS, Athanassiou GM, Missirlis YF, Vlachojannis JG, and Bassaris HP
- Subjects
- Female, Glomerular Filtration Rate, Humans, Interleukin-1 blood, Kidney Failure, Chronic physiopathology, Kidney Failure, Chronic therapy, Male, Middle Aged, Neutrophils pathology, Renal Dialysis, Time Factors, Tumor Necrosis Factor-alpha analysis, Cytokines blood, Kidney Failure, Chronic blood, Neutrophils physiology
- Abstract
Background: The purpose of the study was to investigate the rigidity of polymorphonuclear leukocytes (PMNs) in non-dialysed chronic renal failure (CRF) and haemodialysis (HD) patients., Methods: PMN rigidity as well as tumour necrosis factor alpha (TNF-alpha) and interleukin 1beta (IL-1beta) plasma levels were assessed in 10 early-stage CRF, 10 late-stage non-HD, and 10 HD patients, before and during dialysis. In HD patients both cellulose acetate and polysulphone membranes were used. Ten healthy subjects served as controls. Rigidity was tested by counting the deformability in morphologically passive PMNs by the micropipette method. Cytokine levels were measured by enzyme-linked immunosorbent assay., Results: PMN rigidity was significantly increased in end-stage CRF patients regardless of HD but not in early-stage CRF. In HD patients PMN rigidity increased significantly 60 min after initiation of HD. There was an increase of TNF-alpha and IL-1beta levels in end-stage non-HD and HD patients and a further increase at 60 min after initiation of HD. The percentage of morphologically activated PMNs was increased only during dialysis. The nature of the HD membrane had no influence on rigidity, PMN activation, or cytokine production., Conclusions: The results indicate that PMN rigidity is defective in end-stage chronic CRF patients and is further increased 60 min after initiation of HD, regardless of the nature of the HD membrane used. PMN activation, increased TNF-alpha and IL-1beta levels, or a direct PMN impairment may cause the observed cell rigidity.
- Published
- 2000
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46. Continuous ambulatory peritoneal dialysis is responsible for an increase in plasma norepinephrine.
- Author
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Vlachojannis JG, Tsakas S, Alexandri S, Petropoulou C, and Goumenos DS
- Subjects
- Adult, Chromatography, High Pressure Liquid, Creatinine analysis, Female, Humans, Kidney Failure, Chronic therapy, Male, Middle Aged, Norepinephrine metabolism, Peritoneal Dialysis, Continuous Ambulatory methods, Probability, Reference Values, Sensitivity and Specificity, Urea analysis, Kidney Failure, Chronic blood, Norepinephrine blood, Peritoneal Dialysis, Continuous Ambulatory adverse effects
- Abstract
Objective: To investigate the reason for increasing norepinephrine (NE) levels reported in continuous ambulatory peritoneal dialysis (CAPD) patients., Methods: Norepinephrine was measured in the plasma and peritoneal dialysate of CAPD patients (n = 22) and in the plasma and the urine of healthy subjects (n = 20). It was also measured in the plasma of patients with chronic renal failure (CRF) (n = 15) and patients on hemodialysis (HD) (n = 15)., Results: It was found that NE was increased in CAPD patients compared with healthy individuals (687+/-221 pg/mL vs 199+/-25 pg/mL, p < 0.01). The daily removal of NE from the peritoneum of CAPD patients was lower compared with the amount of NE excreted in the urine of healthy subjects. Plasma NE increased after infusion of peritoneal dialysate. In 15 new patients on CAPD, it was found that NE plasma levels increased from 329+/-67 pg/mL before initiation of dialysis, to 584+/-173 pg/mL after 12 months of treatment (p < 0.01). Finally, plasma NE in CAPD patients (687+/-221 pg/mL) was significantly higher compared with the already increased levels in patients on HD or with CRF (406+/-143 pg/mL and 378+/-142 pg/mL, respectively)., Conclusions: It is concluded that CAPD in patients with end-stage renal disease is responsible for a progressive increase of plasma norepinephrine.
- Published
- 2000
47. Technetium-99m-tetrofosmin for parathyroid scintigraphy: comparison to thallium-technetium scanning.
- Author
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Apostolopoulos DJ, Houstoulaki E, Giannakenas C, Alexandrides T, Spiliotis J, Nikiforidis G, Vlachojannis JG, and Vassilakos PJ
- Subjects
- Female, Humans, Hyperparathyroidism, Secondary diagnostic imaging, Hyperplasia diagnostic imaging, Male, Middle Aged, Parathyroid Glands diagnostic imaging, Parathyroid Glands pathology, Prospective Studies, Radionuclide Imaging, Sensitivity and Specificity, Sodium Pertechnetate Tc 99m, Subtraction Technique, Thyroid Gland diagnostic imaging, Time Factors, Adenoma diagnostic imaging, Organophosphorus Compounds, Organotechnetium Compounds, Parathyroid Neoplasms diagnostic imaging, Radiopharmaceuticals, Thallium Radioisotopes
- Abstract
Unlabelled: The efficacy of 99mTc-tetrofosmin for the detection of parathyroid lesions was investigated prospectively in patients with hyperparathyroidism referred for surgical treatment., Methods: Twenty-seven patients with primary and 18 with tertiary hyperparathyroidism were studied. Twelve patients had undergone one or more previous neck explorations. Static imaging with 201Tl was performed first, immediately followed by a 30-min 99mTc-tetrofosmin dynamic study. Delayed views of up to 3 hr postinjection were also obtained. Technetium-99m-pertechnetate was used for thyroid delineation. The tetrofosmin/99mTc-pertechnetate subtraction scan (TF/TC), the single-tracer washout technique and the thallium/technetium subtraction (TL/TC) were compared. Quantification of relative uptakes of tracers in the thyroid and abnormal parathyroids was accomplished by measuring activity within regions of interest. Kinetics of tetrofosmin in the thyroid and abnormal parathyroids were studied by evaluating the plots of the parathyroid to thyroid ratios against time as well as by calculation of the half-clearance times from the slow component of the time-activity curves., Results: The overall sensitivity, specificity and accuracy of TF/TC and TL/TC were 76%, 92% and 83% and 52%, 85% and 65%, respectively. The respective sensitivities were 87% and 70% for adenomas and 72% and 46% for hyperplasia. The parathyroid-to-thyroid activity ratios of tetrofosmin were significantly higher than those of thallium (p < 0.001). The tetrofosmin single-tracer washout study was less accurate than the subtraction technique (overall sensitivity and specificity, 70% and 69%, respectively). The washout properties of tetrofosmin in abnormal parathyroids were not substantially different from those in the thyroid, with a few exceptions (p = 0.4). No correlation of half-clearance times with parathyroid size, degree of early uptake, parathyroid hormone levels or histology could be established. Comparing adenomas to hyperplasia in respect to tetrofosmin retention, a statistically significant difference was observed (p = 0.005)., Conclusion: Technetium-99m-tetrofosmin is suitable for parathyroid imaging. The kinetic properties of this agent in parathyroid and thyroid tissues do not warrant differential washout protocols. The diagnostic impact of the observed difference in tetrofosmin kinetics between parathyroid adenomas and hyperplasia requires further investigation.
- Published
- 1998
48. Renin-angiotensin system stimulates erythropoietin secretion in chronic hemodialysis patients.
- Author
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Vlahakos DV, Balodimos C, Papachristopoulos V, Vassilakos P, Hinari E, and Vlachojannis JG
- Subjects
- Erythropoietin therapeutic use, Female, Hematocrit, Humans, Male, Middle Aged, Recombinant Proteins therapeutic use, Renin blood, Erythropoietin metabolism, Renal Dialysis, Renin-Angiotensin System physiology
- Abstract
A series of observations suggests an interrelationship between the renin-angiotensin system (RAS) and erythropoietin (EPO) secretion. To further evaluate the role of RAS in erythropoiesis of chronic hemodialysis patients, we studied two groups of such patients: Group A consisted of 16 patients (14 male and 2 female, 54.7 +/- 3.3 years old), who maintained a target hematocrit value of 0.30 (0.32 +/- 0.01), without recombinant human EPO (rhEPO) supplementation. Group B consisted of 14 patients (7 male and 7 female, 50 +/- 5.3 years old), who required subcutaneous injections of rhEPO (90.8 +/- 10 IU.kg-1.week-1), to maintain the same target hematocrit value of 0.30 (30 +/- 0.01). Plasma renin activity (PRA) was found to be the major feature to distinguish patients in these two Groups and it was five times higher in Group A (10 +/- 2 ng.ml-1.h-1) compared to Group B patients (1.8 +/- 0.6 ng.ml-1.h-1) (p < 0.001). Moreover, activation of RAS in Group A patients by volume depletion (2.2 +/- 0.2 l) during hemodialysis resulted in a 118 +/- 33 percent increment of PRA (p < 0.01) which was accompanied by a 69 +/- 25 percent increment of serum EPO levels (p < 0.05). Repetition of the same protocol after inhibiting the converting enzyme with 50 mg of Captopril prior to dialysis session, resulted in a 315 +/- 64 percent increment of PRA (p < 0.001), while at the same time completely blocked the expected rise in serum EPO levels (1.25 +/- 12.5 percent increment).(ABSTRACT TRUNCATED AT 250 WORDS)
- Published
- 1995
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