Recently identified soluble circulating osteoprotegerin (OPG), a member of tumor necrosis factor receptor family, is the osteoclastogenesis inhibitory factor (OCIF). It acts as a "decoy" receptor for receptor activator of NF-kappaB ligand (RANKL) and antagonises RANKL/RANK activity. This way OPG exerts the protective effect on bone, which is also important in hyperparathyroidism. The studies measuring OPG levels in secondary hyperparathyroidism have shown contradictory results and inconsistent conclusions. The aim of our work was to evaluate OPG levels in hemodialysis patients and their correlation with the intensity of bone turnover, bone formation and bone resorption. Serum OPG levels, bone alkaline phosphatase activity (bALP) and beta-CrossLaps (CTx) were measured in a control group (n = 20, age 30+/-6.7 years) and in two groups of dialysis patients: the first group with serum intact parathyroid hormone (iPTH) concentration below 200 pg/ml (n = 28, age 62.6+/-14.8 years) and the second group with iPTH concentration above 200 pg/ml (n = 16, age 63.7+/-14.8 years). Compared to controls, serum OPG levels were 6.4-fold higher in dialysis patients. OPG levels in patients with high PTH were approximately 1.2-fold higher than in the low-PTH group. OPG correlated weakly with bALP (r = 0.277, p = 0.153), as well as with CTx (r = 0.018, p = 0.929) in the low-PTH group, and there was an insignificant negative correlation in the high-PTH group (r = -0.145, p = 0.593 and r = -0.219, p = 0.416, respectively). In conclusion, 6.4-fold increase in OPG might protect bone against intensive bone loss in hemodialysis patients, but this increase is probably not mediated by the increased bone formation; rather, it seems to be the consequence of the imbalance of bone kinetics in renal disease. The precise role of OPG in the pathogenesis of renal osteodystrophy remains unknown and establishing it requires further studies.

Serum RANKL levels were significantly higher in HD patients than in healthy age-matched controls. Moreover, RANKL levels were significantly higher in the upper PTH tertile, indicating enhanced RANKL synthesis in a PTH-dependent fashion. Thus, our clinical findings clearly support published in vitro studies that demonstrated a stimulating effect of PTH on RANKL synthesis. Therefore, the hypothesis that PTH increases bone resorption in HD patients through RANKL appears valid.

Therapy with renin-angiotensin-aldosterone system (RAAS)-blocking drugs prevents the development of fibrosis and angiogenesis in animal models and humans. In our study we have evaluated the systemic effect of RAAS blockade and the effect on peritoneal growth factors, cytokine production and membrane transport characteristics in patients on peritoneal dialysis. Thirty-seven peritoneal dialysis (PD) patients were enrolled in our cross-sectional study. Aldosterone and angiotensin II concentrations were measured in serum to determine the RAAS activity. The inflammatory and profibrotic activity was evaluated by measuring the concentration of C-reactive protein (CRP), serum albumin, and peritoneal concentration of interleukin-6 (IL-6), vascular endothelial growth factor (VEGF), plasminogen activator inhibitor-1 (PAI-1), transforming growth factor-β (TGF-β) and cancer antigen-125 (CA-125). The transport characteristics of the peritoneal membrane were analyzed with a peritoneal equilibration test (PET). Results were compared between the group with RAAS-blocking drugs (RAAS group) and the group without them (non-RAAS group). Mean serum aldosterone concentration was significantly lower in patients treated with ARB-blocking drugs (P = 0.001) and serum angiotensin II concentration was lower in patients treated with ACE inhibitors (P = 0.009). RAAS blockade resulted in lower peritoneal PAI-1 levels (748.1 to 1222.7 ng/L; P = 0.07) without any influence on CRP, peritoneal concentrations of IL-6, VEGF, TGF-β and CA-125, or alteration in peritoneal membrane characteristics tested by PET. RAAS-blocking drugs could be effective in preventing peritoneal fibrosis due to possible reduction of peritoneal PAI-1 concentrations that have already been etiologically linked with fibrin deposition in the pathogenesis of encapsulating peritoneal sclerosis.

Abstract:This report provides a summary of the 2011 Slovenian renal replacement therapy (RRT) data. Data were obtained from 24 renal centers: 23 dialysis and one transplant center, referred as of 31 December 2011, with 100% response rate to individual patient questionnaires. Slovenia has a population of approximately 2 million (2 052 496 in 2011). The total number of patients treated by RRT was 2011,that is, 980 per million of population (pmp); 0.4% decrease compared to 2010. 1347 (67.0%) were treated by hemodialysis, 60 (3.0%) by peritoneal dialysis, and 604 (30.0%) had a functioning kidney graft. A total of 236 incident patients, 115 pmp (at day one), started RRT, their median age was 68 years, 64.8% were men, 36.4% were diabetics. Regarding hemodialysis patients, 59.3% were treated with on-line hemodiafiltration, 86% with ultrapure dialysis fluid. Median weekly duration of hemodialysis was 12.5 h, median dry body weight 70 kg, mean blood flow 275 Ϯ 46 mL/min, 7.1% were dialyzed in a single-needle mode. Vascular accesses were native arteriovenous fistula in 79%, polytetrafluoroethylene graft in 6%, and catheter in 15%. The crude death rate was 15.9% in dialysis patients, 1.9% in transplant recipients, and 12.0% in all RRT patients (both dialysis and transplant, incident patients at day 1 included). Slovenia has been a member of Eurotransplant since 2000. Forty-six kidney transplantations were performed in 2011, all from deceased donors. A slight decrease in prevalent number of RRT patients was observed in 2011, for the first time in 40 years. The number and proportion of patients with functioning kidney grafts is increasing, reaching 30% in 2011.

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This report provides a summary of the 2013 Slovenian renal replacement therapy (RRT) data, obtained from 24 renal centers: 23 dialysis and one transplant center, referring from 31 December 2013, with 100% response rate to individual patient questionnaires. Slovenia had a population of 2 061 085 on 1 January 2014. The total number of patients treated by RRT was 2077, i.e. 1008.3 per million of population (pmp); 1349 (65%) were treated by hemodialysis, 52 (2.5%) by peritoneal dialysis, and 676 (32.5%) had a functioning kidney graft. A total of 260 incident patients, 126.2 pmp (at day one), started RRT, their median age was 69 years, 59.8% were men,. 58.5% of hemodialysis patients were treated with on-line hemodiafiltration. Vascular access was arteriovenous fistula in 79%, polytetrafluoroethylene graft in 8%, and catheter in 13% of patients, mean blood flow 276 ± 41 mL/min, 5.5% dialyzed in a single-needle mode. The crude death rate was 11.4% in all RRT patients (incident patients day 1 included, 15.9% in hemodialysis, 12.3% in peritoneal dialysis, 2.1% in transplant recipients). 60 kidney transplantations were performed in 2013, from deceased donors.

Objectives The aim of our study was to: (i) assess the number of patients who need epoetin treatment and the adequacy of iron treatment, (ii) assess the influence of presence of diabetes mellitus, polycystic kidney disease and the influence of therapy with aluminum phosphate binders and angiotensin system antagonists on the epoetin requirements, (iii) assess the role of other factors possibly influencing epoetin resistance -secondary hyperparathyroidism, inflammation, dialysis dose and residual renal function. š č č č Design and Methods Fifty-one stable peritoneal dialysis (PD) patients (mean age ± SD was 52 ± 13 years, 20 women) without recent bleeding, surgery, bone marrow disease, malignancy, or hypothyroidism were recruited in four Slovenian centers. The dose of epoetin was adjusted to maintain a target hemoglobin of above 110 g/L. At the time of inclusion (median 36 months of PD, range 3-124 months) the PET test results and relevant clinical and laboratory parameters were recorded. Index of epoetin resistance (IRE) was expressed as weekly epoetin dose/body weight/hemoglobin concentration. ResultsTwenty four percent of patients did not need epoetin treatment, the rest were treated with Epoetin-beta at a dose of 70 ± 56 U/kg/week s.c.; hemoglobin concentration was 124 ± 15 g/ L; 14% had hemoglobin below 110 g/L. Iron adequacy parameters (ferritin > 100 m g/L and TSAT > 20%) were fulfilled by 63% of patients, and their IRE was lower (0.43 ± 0.5 U/kg/week/g/L vs. 0.6 ± 0.72 U/kg/week/g/L), but not significantly ( P = 0.502). Patients with polycystic kidneys had lower IRE (0.13 ± 0.3 vs. 0.52 ± 0.55 U/kg/week/g/L, P = 0.011) and majority of them (71%) did not need epoetin treatment ( P = 0.006). No difference was found for diabetic patients. Treatment with angiotensin system antagonists, but not with aluminum phosphate binders, is associated with increased IRE (0.56 ± 0.59 vs. 0.3 ± 0.4 U/kg/week/g/L, P = 0.038). A statistically significant correlation was found for IRE and CRP (r = 0.48, P = 0.001) and iPTH (r = 0.46, P = 0.001). No correlation between IRE and residual renal function was found (r = -0.2, P = 0.173). Stepwise linear regression analysis for multiple variables (residual renal glomerular filtration rate, total weekly creatinine clearance, CRP, iPTH, iron adequacy, angiotensin system antagonist treatment, presence of polycystic kidneys) showed CRP and treatment with angiotensin system antagonists to be the most significant variables influencing IRE. Conclusion Our results show that systemic inflammation and angiotensin system antagonist treatment are the most important parameters affecting epoetin requirements in stable peritoneal dialysis patients. IntroductionThe problems of divalent ions, trace elements and bones are present in chronic dialysis patients despite optimal diet and therapy. Many patients have signs and symptoms of uremic osteopathy. Aim of the study To evaluate divalent ion metabolism and bone diseases in patients of our center for peritoneal dialysis.Methods In cross-section study, w...

Objectives The aim of our study was to: (i) assess the number of patients who need epoetin treatment and the adequacy of iron treatment, (ii) assess the influence of presence of diabetes mellitus, polycystic kidney disease and the influence of therapy with aluminum phosphate binders and angiotensin system antagonists on the epoetin requirements, (iii) assess the role of other factors possibly influencing epoetin resistance -secondary hyperparathyroidism, inflammation, dialysis dose and residual renal function. š č č č Design and Methods Fifty-one stable peritoneal dialysis (PD) patients (mean age ± SD was 52 ± 13 years, 20 women) without recent bleeding, surgery, bone marrow disease, malignancy, or hypothyroidism were recruited in four Slovenian centers. The dose of epoetin was adjusted to maintain a target hemoglobin of above 110 g/L. At the time of inclusion (median 36 months of PD, range 3-124 months) the PET test results and relevant clinical and laboratory parameters were recorded. Index of epoetin resistance (IRE) was expressed as weekly epoetin dose/body weight/hemoglobin concentration. ResultsTwenty four percent of patients did not need epoetin treatment, the rest were treated with Epoetin-beta at a dose of 70 ± 56 U/kg/week s.c.; hemoglobin concentration was 124 ± 15 g/ L; 14% had hemoglobin below 110 g/L. Iron adequacy parameters (ferritin > 100 m g/L and TSAT > 20%) were fulfilled by 63% of patients, and their IRE was lower (0.43 ± 0.5 U/kg/week/g/L vs. 0.6 ± 0.72 U/kg/week/g/L), but not significantly ( P = 0.502). Patients with polycystic kidneys had lower IRE (0.13 ± 0.3 vs. 0.52 ± 0.55 U/kg/week/g/L, P = 0.011) and majority of them (71%) did not need epoetin treatment ( P = 0.006). No difference was found for diabetic patients. Treatment with angiotensin system antagonists, but not with aluminum phosphate binders, is associated with increased IRE (0.56 ± 0.59 vs. 0.3 ± 0.4 U/kg/week/g/L, P = 0.038). A statistically significant correlation was found for IRE and CRP (r = 0.48, P = 0.001) and iPTH (r = 0.46, P = 0.001). No correlation between IRE and residual renal function was found (r = -0.2, P = 0.173). Stepwise linear regression analysis for multiple variables (residual renal glomerular filtration rate, total weekly creatinine clearance, CRP, iPTH, iron adequacy, angiotensin system antagonist treatment, presence of polycystic kidneys) showed CRP and treatment with angiotensin system antagonists to be the most significant variables influencing IRE. Conclusion Our results show that systemic inflammation and angiotensin system antagonist treatment are the most important parameters affecting epoetin requirements in stable peritoneal dialysis patients. IntroductionThe problems of divalent ions, trace elements and bones are present in chronic dialysis patients despite optimal diet and therapy. Many patients have signs and symptoms of uremic osteopathy. Aim of the study To evaluate divalent ion metabolism and bone diseases in patients of our center for peritoneal dialysis.Methods In cross-section study, w...