MO788ERYPTOSIS AND PARATHORMONE IN PATIENTS WITH END STAGE RENAL DISEASE TREATED BY HEMODIALYSIS

Background and Aims Eryptosis (Red cell apoptosis) has been recognized as one of the mechanisms that mediate anaemia in patients with chronic kidney disease whether pre or on dialysis. Phosphorus (Ph) and parathormone (PTH) can be considered as uremic toxins which are associated with renal anaemia, and both were suggested to be associated with shortened red blood cell (RBC) life span. We aimed to assess the relation between each of PTH and phosphorus levels and eryptosis in a cohort of patients with end stage renal disease (ESRD) treated by haemodialysis. Method We studied a cohort of 85 patients with ESRD on conventional hemodialysis for at least 3 months. Blood was drawn prior to the mid-week dialysis session. Patients are dialysed on Fresenius 4008s machines. The percent of Annexin V-binding RBCs was assessed by flow cytometry in fresh blood samples and was used to indicate the percent of Eryptotic RBCs. Data were represented as median (interquartile range). Results The study included 85 patients on prevalent hemodialysis for a median of 8 (3-12) years, 52.9% females. Hypertension was the most common cause of ESRD (49.4%). The median hemoglobin was 10.9 (9.3 - 13) gm/dl and most patients received erythropoietin therapy (83/85) at a median dose of 8000 (4000 – 8000 units/weak). The median percent of Annexin V- binding RBCs was 2.3 (1.4 – 4.7%). On multilinear regression analysis, only PTH was independently associated with the percent of Annexin V- binding RBCs (standardized β= 0.630; 95.0% CI: 0.001 – 0.003; p<0.001). Patients were then stratified according to the PTH level into: low PTH (< 150 ng/dl; 25/85, 29.4%), target PTH (150 – 600 ng/dl; 33/85, 38.8%) and high PTH (> 600 ng/dl; 27/85, 31.8%) groups. The 3 groups differed significantly in the percent of Annexin V- binding RBCs (1.2 (0.7-1.7); 2.5 (1.8-3.6) and 4.8 (3.2-5.6) % respectively; p<0.001) (Figure). The percent of Annexin V- binding RBCs was similar in patients with high (>5.5) and target (<5.5 mg/dl) Ph levels (p=0.318). It was higher in patients with above-target CaXPh product (>55) than those with target CaXPh product (<55 mg2/dl2) (5 (2-5.4) % vs 2.3 (4.1 – 1.2) %), yet this was not statistically significant (p=0.068). Conclusion Patients with ESRD treated by hemodialysis express high rates of eryptosis. Parathormone excess in those patients may result in further eryptosis enhancement, and this represents a potential pathogenic mechanism linking hyperparathyroidism with the anemia of CKD. Larger interventional studies are thus warranted to further explore the association between parathormone and eryptosis.

FC 133HEMODIAFILTRATION IS ASSOCIATED WITH REDUCED INFLAMMATION AND INCREASED BONE TURNOVER COMPARED TO CONVENTIONAL HEMODIALYSIS IN CHILDREN - THE HDF, HEART AND HEIGHT (3H) STUDY

Background and Aims Children on dialysis have a high burden of bone related comorbidities and fractures. We report a post-hoc analysis of the HDF-Hearts-Height study to determine the prevalence and risk factors for mineral bone disease in children on hemodiafiltration (HDF) and conventional hemodialysis (HD). Method 144 children were included in baseline cross-sectional analysis, of which 103 (61 HD, 42 HDF) completed 12-month follow-up. Biomarkers of bone formation and resorption, inflammatory markers, fibroblast growth factor-23 (FGF23) and klotho were measured. Results Inflammatory markers interleukin-6 [IL-6], tumor necrosis factor-alfa [TNF-α], and high-sensitivity CRP [hsCRP] were lower in the HDF compared to HD cohorts at baseline and 12 months (p<0.001). Concentrations of bone formation (bone-specific alkaline phosphatase, BAP) and resorption (tartrate-resistant acid phosphatase 5b [TRAP5b]) markers were comparable between cohorts at baseline, but after 12-months the BAP/TRAP5b ratio increased in HDF (p=0.004) and was unchanged in HD (p=0.44). On adjusted analysis the BAP/TRAP5b ratio was 2.66-fold lower (95%CI -3.91, -1.41; p<0.0001) in HD compared to HDF. FGF23 was comparable between groups at baseline (p=0.52) but increased in HD (p<0.0001) and remained static in HDF (p=0.34) at 12-months. Klotho levels were similar between groups and unchanged during follow-up. The FGF23/klotho ratio was 3.86-fold higher (95% CI 2.15, 6.93; p<0.0001) in HD compared to HDF. Conclusion We conclude that children on HDF have increased bone turnover, an attenuated inflammatory profile and lower FGF23/klotho ratios compared to those on HD. Long-term studies are required to determine the effect, if any, of an improved bone biomarker profile on fracture risk and growth.

OPTIMIZED CONVECTIVE VOLUME IN ONLINE HEMODIAFILTRATION

Hemodiafiltration (HDF) adds convective elimination of middle molecules (MM), proportional to filtered volume (Vconv) on the top of diffusion-based elimination of small molecules (SM) by conventional hemodialysis (HD). Studies, both observational and randomized controlled ones, performed so far generally indicated positive impact of higher Vconv on all-cause mortality in HDF patients, although the magnitude of Vconv at which HDF becomes apparently superior to HD differed widely among the studies. Also the issue of a suitable anthropometric parameter by which the Vconv should be normalized has not yet been solved. Data from the ESHOL study seems to indicate that patient´s body surface area (BSA) could well be used for this—mortality was decreasing with increasing Vconv/BSA with a bottom plateau starting at about 15 L/m2. We have therefore devised a formula and a graph for determination of Vconv which fulfils the requirement Vconv/BSA= 15. Assuming maximum feasible and safe filtration fraction QF/QB= 0.3, the Vconv actually defines the necessary blood flow (QB) to reach Vconv/BSA= 15 as QB=15·BSA/(0.3·t) (t – session time). It is also possible to check what QB is needed in terms of sufficient diffusion-based transport (target Kt/V) and compare both QB values to see if adequate combined elimination of both SM and MM can be achieved at the same time and under what conditions, respectively.

The effect of ultrafiltration transmembrane permeation on the flow field in a surrogate system of an artificial kidney

Renal Replacement Therapies generally associated to the Artificial Kidney (AK) are membrane-based treatments that assure the separation functions of the failing kidney in extracorporeal blood circulation. Their progress from conventional hemodialysis towards high-flux hemodialysis (HFHD) through the introduction of ultrafiltration membranes characterized by high convective permeation fluxes intensified the need of elucidating the effect of the membrane fluid removal rates on the increase of the potentially blood-traumatizing shear stresses developed adjacently to the membrane. The AK surrogate consisting of two-compartments separated by an ultrafiltration membrane is set to have water circulation in the upper chamber mimicking the blood flow rates and the membrane fluid removal rates typical of HFHD. Pressure drop mirrors the shear stresses quantification and the modification of the velocities profiles. The increase on pressure drop when comparing flows in slits with a permeable membrane and an impermeable wall is ca. 512% and 576% for $ \mathrm{CA}22/5\%{\mathrm{SiO}}_2 $ and $ \mathrm{CA}30/5\%{\mathrm{SiO}}_2 $ membranes, respectively.

Progression of coronary artery calcification in conventional hemodialysis, nocturnal hemodialysis, and kidney transplantation

Introduction Cardiovascular disease is the leading cause of death in end-stage renal disease (ESRD) and is strongly associated with vascular calcification. An important driver of vascular calcification is high phosphate levels, but these become lower when patients initiate nocturnal hemodialysis or receive a kidney transplant. However, it is unknown whether nocturnal hemodialysis or kidney transplantation mitigate vascular calcification. Therefore, we compared progression of coronary artery calcification (CAC) between patients treated with conventional hemodialysis, nocturnal hemodialysis, and kidney transplant recipients. Methods We measured CAC annually up to 3 years in 114 patients with ESRD that were transplantation candidates: 32 that continued conventional hemodialysis, 34 that initiated nocturnal hemodialysis (≥4x 8 hours/week), and 48 that received a kidney transplant. We compared CAC progression between groups as the difference in square root transformed volume scores per year (ΔCAC SQRV) using linear mixed models. Reference category was conventional hemodialysis. Results The mean age of the study population was 53 ±13 years, 75 (66%) were male, and median dialysis duration was 28 (IQR 12–56) months. Median CAC score at enrollment was 171 (IQR 10–647), which did not differ significantly between treatment groups (P = 0.83). Compared to conventional hemodialysis, CAC progression was non-significantly different in nocturnal hemodialysis -0.10 (95% CI -0.77 to 0.57) and kidney transplantation -0.33 (95% CI -0.96 to 0.29) in adjusted models. Conclusions Nocturnal hemodialysis and kidney transplantation are not associated with significantly less CAC progression compared to conventional hemodialysis during up to 3 years follow-up. Further studies are needed to confirm these findings, to determine which type of calcification is measured with CAC in end-stage renal disease, and whether that reflects cardiovascular risk.