Clinical outcomes of hemodialysis patients in a public-private partnership care framework in Italy: a retrospective cohort study.

BACKGROUND: Innovative care models such as public-private partnerships (PPPs) may help meet the challenge of providing cost-effective high-quality care for the steadily growing and complex chronic kidney disease population since they combine the expertise and efficiency of a specialized dialysis provider with the population care approach of a public entity. We report the five-years main clinical outcomes of a population of patients treated on hemodialysis within a PPP-care model in Italy. METHODS: This descriptive retrospective cohort study consisted of all consecutive hemodialysis patients treated in the NephroCare-operated Nephrology and Dialysis unit of the Seriate Hospital in 2012-2016, which exercises a PPP-care model. Clinical and treatment information was obtained from the European Clinical Database. Hospitalization outcomes and cumulative all-cause mortality incidences that accounted for competing risks were calculated. RESULTS: We included 401 hemodialysis patients (197 prevalent and 204 incident patients) in our study. The mean cohort age and age-adjusted Charlson Comorbidity Index were 67.0 years and 6.7, respectively. Patients were treated with online high-volume hemodiafiltration or high-flux hemodialysis. Parameters of treatment efficiency were above the recommended targets throughout the study period. Patients in the PPP experienced benefits in terms of hospitalization (average number of hospital admissions/patient-year: 0.79 and 1.13 for prevalent and incident patients, respectively; average length of hospitalization: 8.9 days for both groups) and had low cumulative all-cause mortality rates (12 months: 10.6 and 7.8%, 5 years: 42.0 and 35.9%, for prevalent and incident patients, respectively). CONCLUSIONS: Results of our descriptive study suggest that hemodialysis patients treated within a PPP-care model framework received care complying with recommended treatment targets and may benefit in terms of hospitalization and mortality outcomes.

[Anticoagulation and chronic hemodialysis]. / Anticoagulazione ed emodialisi cronica.

The application of effective hemodialysis in humans was delayed until the development of cellulose-based membranes in 1940s, and the advent of heparin as the primary means of anticoagulation. Unfractionated heparin is still the most commonly used agent for anticoagulation, but its potentially serious complications, such as hemorrhage and heparin-induced thrombocytopenia type II, led the scientific community to consider other options to counteract coagulation. ''Low heparin dialysis'', ''heparin-free dialysis'', regional heparinization, low molecular weight heparins, citrate, prostacyclin, nafamostat, low molecular weight heparanoid and direct thrombin inhibitors are among these methods and have different safety, efficacy and cost. In general, hemodialysis patients with active hemorrhage or at high risk for bleeding complications are best treated with heparin-free hemodialysis. Low molecular weight heparanoid and direct thrombin inhibitors (recombinant hirudin or argatroban) may be useful for anticoagulation of the extracorporeal circuit in the rare patients with confirmed heparin-induced thrombocytopenia type II, who cannot be dialyzed with heparin.

[Convective and mixed dialysis technique]. / Le tecniche dialitiche miste convettive-diffusive.

Hemodiafiltration is the dialytic strategy enabling the high potential of hydraulic and solute permeability of synthetic membranes to be most properly exploited, thus greatly enhancing removal of small and middle-molecular toxic compounds. Several of those solutes have a pathogenic role or are recognized as marker of the most frequent long-term complications and causes of death in HD patients, such as dialysis related amyloidosis, cardio-vascular disease, secondary hyperparatyroidism, inflammation and malnutrition. Improved survival in dialysis has been associated, in observational studies, with the use of high-flux membranes and hemodiafiltration with high volume exchange. On-line production of unlimited amount of sterile dialysate at low cost has favored its extensive diffusion in the recent years, and optimal biocompatibility of synthetic high-flux membranes and the quality of the ultrapure dialysate have contributed to the promising results of the technique. However, to optimize its clinical application and achieve safely the most efficient convective transport, knowledge is required of dialysis systems, dialyzer characteristics and performances, and of the complex interactions between patient and membrane. New hemodiafiltration techniques have been proposed in these years with the aim to improve the efficiency and safety of the technique. More generally, technical aspects and requirements, and experimental and clinical results of the convective-mixed treatments are examined here.

Transmembrane pressure modulation in high-volume mixed hemodiafiltration to optimize efficiency and minimize protein loss.

The aim of the present study was transmembrane pressure (TMP) modulation in high-volume mixed hemodiafiltration (HDF) to optimize efficiency and minimize protein loss. The optimal flow/pressure conditions in on-line mixed HDF assisted with a feedback control of TMP were defined in this prospective randomized study in order to obtain maximal efficiency in solute removal while minimizing potential side effects. Two different TMP profiles in mixed HDF were compared in 12 unselected patients who underwent two study periods of 2 weeks each in cross-over randomized sequence: (A) constant TMP at around 300 mmHg and (B) profiled TMP, in which TMP was slowly increased from a low initial value to the maximal value. In both procedures, the mean volume exchange was 10.6+/-1.4 l/h. Mean filtration fraction was 53%. Instantaneous beta2-microglobulin (beta2-m) clearance was higher at the start of the session with profiled TMP (207+/-35 vs 194+/-28 ml/min, P<0.005), whereas no differences were found at the end (135+/-19 vs 132+/-19 ml/min). Profiled TMP resulted in a higher mean beta2-m clearance of the session (97.0+/-15.4 vs 87.8+/-18.3 ml/min, P<0.01), in lower albumin loss in the first 30 min (0.62+/-0.14 vs 0.98+/-0.18 g, P<0.0001), and, in the whole session (3.98+/-1.19 vs 5.24+/-0.77 g, P<0.001), in higher dialyzer ultrafiltration coefficients and lower resistance indexes. This study showed that the TMP feedback modulation in mixed HDF was highly effective in maintaining very high ultrafiltration rates and filtration fractions, and minimized potential side effects as a result of the improved preservation of membrane permeability and more favorable dialyzer pressure regimen.

Effects of the infusion mode on bicarbonate balance in on-line hemodiafiltration.

BACKGROUND: Electrolyte and acid-base balance may be differently affected by the infusion mode in on-line hemodiafiltration (HDF). We studied the effects of the different infusion modes on bicarbonate transport across the dialyzer membrane, and thus on the final bicarbonate balance of the HDF sessions. METHODS: Instantaneous HCO3- transfer across the dialyzer membrane, blood bicarbonate profile and the total balance of the sessions were studied in six dialysis patients under the same operating conditions over 36 HDF sessions, in order to compare the effects of predilution HDF (pre-HDF), postdilution HDF (post-HDF), and mixed HDF on the final bicarbonate balance. RESULTS: The final HCO3- balance was more positive in post-HDF vs pre-HDF (142 +/- 36 vs 99 +/- 41 mmol/session, p<0.05), with a final blood HCO3- concentration of 26.6 +/- 1.0 vs 25.4 +/- 1.1 mmol/L, (p<0.05). Mixed HDF yielded intermediate results (balance: 119 +/- 42 mmol/session, final HCO3- 26.2 (1.2 mmol/L). These differences were seen to result from the increased HCO3- concentration of blood entering the filter in predilution, due to the infused HCO3-, enhancing convective loss and reducing the driving force for diffusive HCO3- gain. CONCLUSIONS: Bicarbonate concentration in dialysate-reinfusate is critical in order to obtain an adequate end of session HCO3- balance in on-line HDF. The predilution method produced the lowest cumulative net HCO3- gain between the three studied infusion modes. Our data suggest that, under the same operating conditions and excluding the effect of ultrafiltration, dialysate HCO3- should be increased by about 2 mmol/L in pre-HDF, and 1 mmol/L in mixed HDF, to yield the same final balance as in post-HDF.

Rate dependence of acute PTH release and association between basal plasma calcium and set point of calcium-PTH curve in dialysis patients.

BACKGROUND: In vivo, the control of calcium-mediated acute PTH release during induced hypo- or hypercalcaemia is linked not only to plasma calcium concentration per se but also to the rate and direction of calcium change. In fact, during induced hypocalcaemia, the predominant mechanism that causes PTH to be released is the reduction of plasma Ca(2+) irrespective of the absolute starting concentration of ionized calcium. This mechanism, which is rate-dependent and even activated in conditions of hypercalcaemia, may be involved in the association, reported in several papers, between the basal Ca(2+) and the set point of the calcium-PTH curve. METHODS: The calcium-PTH relationship was studied in 12 dialysis patients under conditions of induced low and high predialysis plasma Ca(2+). At each level of basal Ca(2+), dynamic tests were conducted using two methodological approaches. In method A patients underwent low (0.5 mmol/l) calcium dialysis in the stimulation test and high (2 mmol/l) calcium dialysis in the inhibition test, while the dialysate calcium (CaD) was kept constant during each test. In this way a higher but variable rate of change in plasma Ca(2+) was achieved. In method B, CaD was progressively decreased (stimulation test) and increased (inhibition test) during the tests in order to obtain a lower but more constant rate of change in plasma Ca(2+). Consequently, for each patient, four calcium-PTH curves were produced: low basal Ca(2+) with methods A and B, and high basal Ca(2+) with methods A and B. RESULTS: Basal plasma Ca(2+) was similar in A and B at low (1.16+/-0.02 vs 1.15+/-0.02 mmol/l) and high (1.25+/-0.02 vs 1.26+/-0.02 mmol/l) basal plasma Ca(2+). The set point was higher in A than in B both at low (1.12+/-0.02 vs 1.10+/-0.02 mmol/l, P=0.01) and high (1.20+/-0.02 vs 1.16+/-0.02 mmol/l, P=0.03) basal Ca(2+) as was the slope (542+/-41 vs 426+/-44%/mmol, P=0.02; 615+/-73 vs 389+/-25%/mmol, P=0.01). No significant difference was found between A and B as regards minimal PTH and plasma Ca(2+) at minimal PTH (Camin) in both calcaemic states. Maximal PTH was slightly higher in B at low (510+/-97 vs 548+/-107 pg/ml, P=NS) and high basal plasma Ca(2+) (410+/-97 vs 464+/-108 pg/ml, P=0.02). Plasma calcium at maximal PTH (Camax) was significantly higher in A (1.1+/-0.03 vs 0.99+/-0.02 mmol/l, P=0.001) at high basal plasma Ca(2+). The set point was strictly related to basal plasma Ca(2+) in both methods, but the slope of the linear regression was significantly steeper with method A. The set point was predicted to increase by 0.881 (CI 0.772-0.990) mmol/l for each mmol/l of increase in basal plasma Ca(2+) with method A and by 0.641 (CI 0.546-0.737) mmol/l for each mmol/l of increase in basal plasma Ca(2+) with method B. CONCLUSIONS: (i) Higher and variable rates of change in plasma Ca(2+) produce a higher set point value and a steeper slope of the calcium-PTH curve when compared to lower and more constant rates of calcium change. (ii) The different slope of the linear correlations between basal plasma Ca(2+) and set point in the two methods suggests that the rate-dependent mechanism of acute PTH release plays a significant role in the association between set point and basal plasma Ca(2+). (iii) The significance of the set point is questionable when the calcium-PTH curve is carried out in vivo.

Mixed predilution and postdilution online hemodiafiltration compared with the traditional infusion modes.

BACKGROUND: On postdilution hemodiafiltration (post-HDF), convective removal of medium-high molecular weight solutes is, at the highest ultrafiltration rates, limited by high blood viscosity and protein concentration. Prefilter reinfusion (pre-HDF) may overcome this problem, but plasma dilution may affect the overall efficiency of the technique. In this study, an experimental system of online HDF with combined prefilter and postfilter infusion (mixed HDF) was evaluated and compared with the traditional predilution and postdilution modes. METHODS: Removal of urea (U), creatinine (Cr), phosphate (Phos), and beta(2)-microglobulin (beta(2)m), ultrafiltration coefficients of the dialyzer (K(UF)), and rheologic conditions of the blood circuit were evaluated during the three infusion modes (a total of 36 runs lasting 180 min), performed with a polysulfone hemofilter 1.8 m(2), blood flow (Q(b)) 400 mL/min, dialysate flow (Q(d)) 700 mL/min, and infusion rate 120 mL/min (pre-HDF and post-HDF), or 60 + 60 mL/min (mixed HDF). RESULTS: The mean effective U and Cr clearances and urea index of dialysis dose (eKt/V) were significantly higher on post-HDF than on pre-HDF (K(WB) (U) 210 vs. 193 mL/min, K(DQ) (Cr) 152 vs. 142 mL/min, eKt/V 1.41 vs. 1.30), while mixed HDF did not show significant differences versus post-HDF (K(WB) (U) 201 mL/min, K(DQ) (Cr) 149 mL/min). K(DQ) for Phos and beta(2)m were higher on post-HDF in only absolute values. Similar differences were found for instantaneous dialyzer clearances (K(I)) at 60, 120, and 180 minutes of the sessions, with a common trend to decrease with time. K(UF) and the apparent beta(2)m sieving coefficient showed their lowest values toward the end of post-HDF sessions. Increasing filtration fractions (FFs) were associated with increasing transmembrane pressure (TMP) and solute clearances up to FF values of 0.45. These were values achieved in only post-HDF, at which point the curve of the relationship between TMP and FF assumed its steepest exponential trend. CONCLUSIONS: Mixed HDF, by better preserving the characteristics of water and solute transport of the membrane, ensured safer operating conditions than post-HDF, while achieving similar removal of small- and large-size solutes. Optimizing the ratio of prefilter/postfilter infusion and the total infusion according to the relationships found in our study between solute clearances, FF, and TMP, convective flux and transport may avoid excessive hemoconcentration and dangerous pressure gradients.

Sodium modeling in hemodiafiltration.

A computer model was developed to simulate sodium and water kinetics during hemodiafiltration (HDF), acetate-free biofiltration (AFB) and hemodialysis (HD). Multiple regression analysis of the results of 3,240 simulated applications of the model (1,620 HDF, 1,080 AFB, 540 HD) showed that, during HDF and AFB, there is a close correlation (R2 = 0.92 and 0.91) between plasma water sodium concentration [( Na+P]) and a set of three variables: 1) the sodium gradient between plasma water and dialysate, 2) the sodium concentration of the substitution fluid and 3) ultrafiltration (UF) rate. With HD, a close correlation (R2 = 0.94) was found between changes in [Na+P] and combined changes in sodium gradient and the UF rate. On this basis, a regression equation was formulated for each procedure which allowed a reliable prediction of final [Na+P] to be made on the basis of knowledge of the imposed Na gradient, the programmed infusion (during HDF and AFB), and the UF rate. Clinical validation of the model was obtained in 12 patients: predicted final [Na+P] agreed well with the values measured by means of direct potentiometry (141.9 vs. 142.1 mEq/liter; P = NS), with a mean difference (-0.16 mEq/liter) and limits of agreement (+0.8 to -1.03 mEq/liter) fully acceptable for clinical purposes.(ABSTRACT TRUNCATED AT 250 WORDS)

Causes, kinetics and clinical implications of post-hemodialysis urea rebound.

The rapid increase in end-dialysis urea concentration (Co) immediately after the end of dialysis (HD), which greatly exceeds that expected as an effect of urea generation and defined as "net rebound," was assessed in 21 chronic HD patients. The curve of serial values of net rebound correlated (r = 0.70) with the theoretical curve predicted by the two pool urea kinetics model (UKM). A mean equilibrium concentration (Ce) was achieved in 48 minutes, with a 7.58% increase in Co. Stabilized rebound (Re) was compared after four different HD procedures, and significant correlations were found between the magnitude of Re and the indexes of HD efficiency, dialyzer clearance (r = 0.75) and Kt/V (r = 0.68). The highest values of Re (8.6% and 8.8%) were observed after the procedures with largest urea removal, irrespective of the biocompatibility conditions (new or reused dialyzers). The single pool UKM applied with the stabilized end-HD urea concentration Ce instead of Co resulted in more physiological values of urea distribution volume (56.1% vs. 50.5% of body wt) and in lower values of Kt/V (0.64 vs. 0.73, P less than 0.001) and protein catabolic rate (1.07 vs. 1.17 g/kg/day, P less than 0.001). A reequilibration process, rather than protein hypercatabolism, seems to be responsible for most rebound, the magnitude of which correlated with the efficiency of the procedure. Only by considering Ce as the true end-HD urea concentration it is possible to minimize the errors arising from the application of a single pool analysis to a two pool system.