Renal Replacement Therapy in Slovenia: Excerpts From 2013 Data.

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.

Influence of renin-angiotensin-aldosterone system-blocking drugs on peritoneal membrane in peritoneal dialysis patients.

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-ß (TGF-ß) 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-ß 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.

Renal replacement therapy in Slovenia: excerpts from 2011 data.

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 ± 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.

Increased bone resorption in HD patients: is it caused by elevated RANKL synthesis?

BACKGROUND: The receptor activator of nuclear factor kappaB ligand (RANKL), produced by osteoblasts/stromal cells, is a member of the RANK/RANKL/OPG system, which regulates bone resorption by osteoclasts. Since RANKL and osteoprotegerin (OPG) production in bone is influenced by parathyroid hormone (PTH), we measured serum RANKL and OPG concentrations in haemodialysis (HD) patients, who commonly hypersecrete PTH. We aimed to determine if clinically demonstrated PTH-enhanced bone resorption is a consequence of increased RANKL synthesis. METHODS: RANKL, OPG, osteocalcin, intact PTH, bone-specific alkaline phosphatase, tartrate-resistant acid phosphatase 5b and beta-CrossLaps (CTx) were measured in blood samples from 80 HD patients and 50 age-matched controls. HD patients were stratified to tertiles according to their serum PTH levels: 29.3-103.0, 109.7-263.0 and 262.0-1700.0 pg/ml in the first, second and third tertiles, respectively. RESULTS: Mean serum RANKL levels were 1.6 times higher in HD patients than in age-matched controls (1.36+/-0.39 vs 0.83+/-0.70 pmol/l; P<0.001). All the measured bone markers significantly differed between patients and controls (P<0.001). Spearman's tests of correlation showed a statistically significant association of RANKL with PTH, osteocalcin and CTx (r=0.322, P=0.004; r=0.231, P=0.039; and r=0.230, P=0.040, respectively). Mean serum RANKL levels were significantly different between PTH tertiles (P = 0.003), but serum OPG levels were not (P=0.144). The highest RANKL levels were measured in the upper PTH tertile (1.54+/-0.39 pmol/l) and were significantly higher than in the middle or lower tertiles (1.27+/-0.42 and 1.23+/-0.26 pmol/l, respectively; P=0.003). Both of the measured bone-resorption markers, tartarate-resistant acid phosphatase 5b and CTx, as well as both bone formation markers, osteocalcin and bone-specific alkaline phosphatase were also significantly higher in the upper tertile, indicating that whole-bone remodelling is activated at high PTH and RANKL levels. CONCLUSIONS: 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.

Increased levels of osteoprotegerin in hemodialysis patients.

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.