Stable hemoglobin in hemodialysis patients: forest for the trees--a 12-week pilot observational study.

BACKGROUND: Hemoglobin (Hb) variability is a common occurrence in hemodialysis patients treated with erythropoiesis-stimulating agents. High amplitude fluctuations have been associated with greater risk of morbidity and mortality. METHODS: This prospective, single centre pilot observational study was conducted over a 3-month period in daily practice patterns, to assess per-dialysis events and inter-dialysis complications that could interfere with erythropoiesis in patients undergoing hemodialysis. RESULTS: Mean Hb levels remained stable in the 78 evaluable patients, as did darbepoetin alfa (DA) doses, including in patients suffering from diabetes or cardiac affections. In total, an average of 7.7 events / patient / month occurred, but no significant relationship with Hb excursions was shown. CONCLUSION: The observation of 7.7 events per patient per month suggests a careful monitoring of Hb and DA dosing every other week, in order to maintain Hb level within the target.

Do two intravenous iron sucrose preparations have the same efficacy?

BACKGROUND: Intravenous (i.v.) iron sucrose similar (ISS) preparations are available but clinical comparisons with the originator iron sucrose (IS) are lacking. METHODS: The impact of switching from IS to ISS on anaemia and iron parameters was assessed in a sequential observational study comparing two periods of 27 weeks each in 75 stable haemodialysis (HD) patients receiving i.v. iron weekly and an i.v. erythropoiesis-stimulating agent (ESA) once every 2 weeks. Patients received IS in the first period (P1) and ISS in the second period (P2). RESULTS: Mean haemoglobin value was 11.78 ± 0.99 g/dL during P1 and 11.48 ± 0.98 g/dL during P2 (P = 0.01). Mean serum ferritin was similar for both treatment periods (P1, 534 ± 328 µg/L; P2, 495 ± 280 µg/L, P = 0.25) but mean TSAT during P1 (49.3 ± 10.9%) was significantly higher than during P2 (24.5 ± 9.4%, P <0.0001). The mean dose of i.v. iron per patient per week was 45.58 ± 32.55 mg in P1 and 61.36 ± 30.98 mg in P2 (+34.6%), while the mean ESA dose was 0.58 ± 0.52 and 0.66 ± 0.64 µg/kg/week, respectively (+13.8%). Total mean anaemia drug costs increased in P2 by 11.9% compared to P1. CONCLUSIONS: The switch from the originator IS to an ISS preparation led to destabilization of a well-controlled population of HD patients and incurred an increase in total anaemia drug costs. Prospective comparative clinical studies are required to prove that ISS are as efficacious and safe as the originator i.v. IS.

Extended dosing of darbepoetin alfa in peritoneal dialysis patients.

BACKGROUND: Anemia is common among peritoneal dialysis (PD) patients, and most patients require erythropoiesis-stimulating agents (ESA) to maintain their hemoglobin concentrations within current guideline recommendations. Darbepoetin alfa is an ESA with a 3-fold longer half-life and greater in vivo biological activity than recombinant human erythropoietin, allowing less frequent dosing that may simplify anemia management in these patients, providing benefits to patients, care givers and health care providers. Clinical studies have confirmed the efficacy and safety of darbepoetin alfa administered at extended dosing intervals. However, there are limited data on the management of anemia with ESAs in PD patients in routine clinical practice. The aim of this multicenter observational study in European and Australian dialysis patients was to evaluate darbepoetin alfa administered once every 2 weeks (Q2W) in routine clinical practice for 12 months. METHODS: PD patients ≥18 years old and converting to treatment with darbepoetin alfa Q2W were eligible for enrollment regardless of previous or current ESA use. Patients enrolled in the study were treated according to local usual clinical practice. Data were collected up to 6 months prior to and 12 months after conversion to darbepoetin alfa Q2W. The primary endpoint was hemoglobin concentration 12 months after conversion to darbepoetin alfa Q2W. RESULTS: Of the 741 eligible PD patients (mean age, 61 years; male, 57%), 640 (86%) completed the study. Mean hemoglobin concentration (g/dL) was 11.69 (95% CI, 11.53-11.86) 6 months before the conversion, 12.25 (95% CI, 12.13-12.38) at conversion, and 11.88 (95% CI, 11.74-12.02) 12 months after conversion to darbepoetin alfa Q2W. The weekly equivalent ESA dose (µg/wk) was a geometric mean of 25.24 (95% CI, 23.46-27.15) 6 months before conversion, 20.90 (95% CI, 19.13-22.83) immediately before conversion, 18.89 (95% CI, 18.13-19.68) at conversion and 19.04 (95% CI, 17.69-20.49) 12 months after conversion. Twelve months after conversion, 70% of patients were receiving darbepoetin alfa Q2W and 73% had hemoglobin concentrations >11.0 g/dL. CONCLUSION: In this large observational study, PD patients were able to maintain mean hemoglobin concentrations >11.0 g/dL after conversion to extended dosing of darbepoetin alfa Q2W, with no mean dose increase.

Real-world safety and effectiveness of sucroferric oxyhydroxide for treatment of hyperphosphataemia in dialysis patients: a prospective observational study.

BACKGROUND: The iron-based phosphate binder (PB), sucroferric oxyhydroxide (SFOH), is indicated to control serum phosphorus levels in patients with chronic kidney disease on dialysis. METHODS: This non-interventional, prospective, multicentre, cohort study conducted in seven European countries evaluated the safety and effectiveness of SFOH in dialysis patients with hyperphosphataemia in routine practice. Safety outcomes included adverse drug reactions (ADRs) and changes in iron-related parameters. SFOH effectiveness was evaluated by changes-from-baseline (BL) in serum phosphorus and percentage of patients achieving in-target phosphorus levels. RESULTS: The safety analysis set included 1365 patients (mean observation: 420.3 ± 239.3 days). Overall, 682 (50.0%) patients discontinued the study. Mean SFOH dose during the observation period was 1172.7 ± 539.9 mg (2.3 pills/day). Overall, 617 (45.2%) patients received concomitant PB(s) during SFOH treatment. ADRs and serious ADRs were observed for 531 (38.9%) and 26 (1.9%) patients. Most frequent ADRs were diarrhoea (194 patients, 14.2%) and discoloured faeces (128 patients, 9.4%). Diarrhoea generally occurred early during SFOH treatment and was mostly mild and transient. Small increases from BL in serum ferritin were observed (ranging from +12 to +75 µg/L). SFOH treatment was associated with serum phosphorus reductions (6.3 ± 1.6 mg/dL at BL versus 5.3 ± 1.8 mg/dL at Month 30; ΔBL: -1.0 mg/dL, P < 0.01). Percentage of patients achieving serum phosphorus ≤4.5 mg/dL increased from 12.0% at BL to 34.8% at Month 30, while the percentage achieving serum phosphorus ≤5.5 mg/dL increased from 29.9% to 63.0%. CONCLUSIONS: SFOH has a favourable safety and tolerability profile in a real-world setting, consistent with results of the Phase 3 study. Moreover, SFOH improved serum phosphorus control with a low daily pill burden.

Are oxyphil cells responsible for the ineffectiveness of cinacalcet hydrochloride in haemodialysis patients?

Parathyroid glands consist primarily of chief cells. In some cases, the proportion of parathyroid oxyphil cells increases in patients with chronic kidney disease. We describe a case of secondary hyperparathyroidism (SHPT) in a patient treated with haemodialysis who initially received large doses of vitamin D and calcium (Ca) supplements, as well as high doses of cinacalcet hydrochloride (C-HCl), but without any effect on parathyroid hormone levels. Following a successful parathyroidectomy, histopathological examination revealed that two of the parathyroid glands consisted of 40% of oxyphil cells. Oxyphil cells have significantly more Ca-sensing receptors (CaSRs) than chief cells, suggesting that CaSRs are involved in the transdifferentiation of chief cells to oxyphil cells. C-HCl treatment leads to a significant increase in parathyroid oxyphil cell content. This case suggests that C-HCl may induce specific phenotypic alterations in hyperplastic parathyroid glands in patients with severe SHPT.

Clinical hemodialysis experience with percutaneous arteriovenous fistulas created using the Ellipsys® vascular access system.

INTRODUCTION: The aim of this study is to report our clinical hemodialysis experience using a percutaneous arteriovenous fistula (pAVF) created with the Ellipsys® vascular access system. This pAVF device creates a permanent AVF anastomosis between the proximal radial artery (PRA) and the deep communicating vein (DCV) in the proximal forearm. METHODS: The medical records of all patients with a pAVF were retrospectively reviewed. The clinical data analyzed included reliability of pAVF use, quality of dialysis, rate and success of puncture, and pAVF related complications, along with incidence of subsequent interventions. FINDINGS: Between May 2017 and November 2018, 34 patients had a pAVF created with technical success in 33 patients (97%). Twenty-eight out of 34 (82%) patients had successful two-needle cannulation within 10 days to 6 weeks after pAVF creation. The mean Kt/v was 1.6 (1.2-2) and the average recirculation was 10%. Fifteen patients (44%) needed no further access intervention. Twelve patients (35%) required an additional procedure to assist maturation of the pAVF in order to facilitate puncture. The average blood flow measured at the brachial artery, before the first cannulation, was 850 ml/min. From causes unrelated to the procedure, four patients died during the follow-up study. Two patients required revision to a surgical AVF. None of the pAVFs developed aneurysmal degeneration steal syndrome, or high access flow related issues. DISCUSSION: The Ellipsys® pAVF offers a safe and functional vascular access for hemodialysis. Advantages included prompt access maturation, avoidance of high flow AVFs, and a simple nonsurgical procedure with high patient satisfaction. Functional outcomes are equivalent and likely better than surgical fistulas. There appears to be less aneurysmal degeneration and need for future re-intervention. Objective dialysis parameters indicate excellent quality of hemodialysis for the patient.

Factors associated with parathyroid hormone control in haemodialysis patients with secondary hyperparathyroidism treated with cinacalcet in real-world clinical practice: Mimosa study.

BACKGROUND: Secondary hyperparathyroidism (SHPT) is frequent in haemodialysis (HD) patients. Oral cinacalcet-hydrochloride (HCl) decreases parathyroid hormone (PTH); however, real-life PTH data, according to Kidney Disease: Improving Global Outcomes (KDIGO) guidelines, are still lacking. Our goal is to assess the percentage of cinacalcet-HCl-treated HD patients with controlled SHPT (PTH <9× upper limit of the normal range) after 12 months (M12) of treatment. METHODS: This is a retrospective observational study in HD patients with SHPT treated by cinacalcet-HCl between 2005 and 2015 and dialysed in seven French HD centres using the same database (Hemodial™). RESULTS: The study included 1268 patients with a mean (standard deviation) follow-up of 21 ± 12 months. Their mean dialysis vintage was 4.3 ± 5.6 years. PTH values were available and exploitable at M12 in 50% of them (645 patients). Among these patients, 58.9% had controlled (mean PTH of 304 ± 158 pg/mL) and 41.1% uncontrolled SHPT (mean PTH of 1084 ± 543) at M12. At the baseline, patients with controlled SHPT were older (66 ± 15 versus 61 ± 17 years), and had lower PTH (831 ± 346 versus 1057 ± 480 pg/mL) and calcaemia (2.18 ± 0.2 versus 2.22 ± 0.19 mmol/L) than uncontrolled patients. In multivariate analysis, these three factors still remained significantly associated with controlled SHPT. CONCLUSION: In this real-life study, 41.1% of HD patients with SHPT treated with cinacalcet-HCl remained with a PTH above the KDIGO recommended target after 12 months of treatment. Apart from the possibility of non-compliance, the severity of SHPT appears to be a major factor determining the response to cinacalcet-HCl treatment, reinforcing the importance of treating SHPT at earlier stages.

[The reality on peritoneal dialysis in France: 40years after]. / La réalité de la dialyse péritonéale en France : 40 ans après.

The share of peritoneal dialysis (PD) in the spectrum of chronic dialysis has decreased in France over the last ten years. Despite various facilities offered by the health authorities, PD remains confidential in many private units and some public hospitals. The enthusiasm present at the beginning of this technology, forty years ago, is declining, despite a real improvement in new developments, a real increase in patient survival, today at least similar to that on hemodialysis. Then, the aim of this review is first to give a summary of the principles and practice of patient and staff education and to describe the role of the medical contribution in decision-making. The second aim is to review patient and technique survival data of PD patients henceforth prolonged, and the new insights into dialysis adequacy. The presence of residual renal function is a main determinant of patient comfort together with prevention of over-hydratation. Improvement of the peritoneal catheter is underlined. The prevention and management of infections is reviewed, and also the regular assessment of peritoneal function. Free water transport is a predictor of encapsulating peritoneal sclerosis, which should be assessed regularly. The physiopathology and the pathogenesis of this devastating complication allow now the prevention, and a better treatment.

[The use of generics in transplantation: Towards rational and safe solutions!] / L'utilisation de génériques en transplantation : vers des solutions rationnelles et sures !

Generic immunosuppressive drugs are available in Europe Canada and the United States. Between countries, there are large differences in penetration of generic drugs in general, and for immunosuppressive drugs in particular. The registration for generic immunosuppressive drugs are slightly different, but the criteria for registration of narrow therapeutic index drugs and bioequivalence studies, performed only in healthy volunteers, will remain in the medical landscape. About 50 studies compare the clinical efficacy and bioequivalence of the generic immunosuppressive drugs in patients with solid organ transplants. To allow for safe substitution, a number of criteria need to be fulfilled. Consensus statements were made by most transplant organizations. Authorities and payers should refrain from forcing pharmacists to dispense generic drugs in patients on maintenance immunosuppressive treatment. Generic substitution could be safe if realized by the treating physician, for a well-informed patient. Substitution must be followed by control visits to check if the patient is taking the medication correctly and if the drug exposure, through a close monitoring, remains stable. Substitution from one generic to another generic should be avoided, in all cases.

[How to reach and maintain the K/DOQI recommendations for bone and mineral metabolism in patients undergoing haemodialysis: an efficient strategy]. / Comment atteindre et maintenir les recommandations K/DOQI sur le métabolisme phosphocalcique chez les patients dialysés: une stratégie efficace.

INTRODUCTION: Recent publications have indicated that alterations in bone and mineral metabolism are known to participate to a high mortality rate in patients undergoing haemodialysis. A new therapeutic strategy is progressively undertaken in the dialysis unit over a 36 months period covering years 2002 to 2004. METHODS: This new strategy includes the prescription of non-calcium, non-aluminium phosphate binder, sevelamer hydrochloride, an increase in vitamin D analogues prescription and a moderation in calcium carbonate administration. Sixty patients participated to the entire study and are evaluated three times a year on the four K/DOQI parameters. Other indicators such as haemoglobin, bicarbonate, total cholesterol and HDL cholesterol levels were studied. RESULTS: At the beginning of the study, 7% of the patients achieved the four K/DOQI parameters. This proportion seemed identical to those observed in the major studies. But progressively with the new therapeutic strategy 13%, then 21%, and at the end of the study 35% reached the four criteria. Therapeutic calcium intakes decreased from 100 g per patient/month to 28 g per patient-month. Prescription of vitamin D analogues increased from 3.3 microg per patient-month to 18.3 microg per patient/month. At the end of the study 60% of the patients received sevelamer hydrochloride at the mean dosage of 4800 mg per day. Haemoglobin remains stable. Bicarbonate level decreased due to a minor prescription in calcium carbonate. Under statins the ratio total cholesterol/HDL cholesterol decreased to 3.3. CONCLUSION: A modification in the therapeutic strategy offer to patients undergoing haemodialysis, the possibility to achieve the K/DOQI recommendations with the hope to obtain a beneficial effect on patient outcomes.

[Use of intravenous iron supplementation in chronic kidney disease: Interests, limits, and recommendations for a better practice]. / Utilisation des dérivés injectables du fer au cours de la maladie rénale chronique : intérêts, limites et conseils pour un bon usage.

Iron deficiency is an important clinical concern in chronic kidney disease (CKD), giving rise to iron-deficiency anaemia, and various impaired cellular functions. Oral supplementation, in particular with ferrous salts, is associated with a high rate of gastro-intestinal side effects and is poorly absorbed, a problem that is avoided with intravenous (IV) irons. Recently, with the approval of the European Medicines Agency's Committee for Medicinal Products for Human Use, the French Agence nationale de sécurité du médicament et des produits de santé (ANSM) took adequate measures to minimize the risk of allergic reactions, by correction on the summary of intravenous iron products characteristics. All IV iron products should be prescribed, administered and injected, inside public or private hospitals exclusively, and a clinical follow-up after the infusion for at least 30 minutes is mandatory. The most stable intravenous iron complexes (low molecular weight iron dextran, ferric carboxymaltose, and iron isomaltoside 1000 [under agreement]) can be given in higher single doses and more rapidly than less recent preparations such as iron sucrose (originator or similars). Test doses are advisable for conventional low molecular weight iron dextrans, but are no more mandatory. Iron supplementation is recommended for all CKD patients with iron-deficiency anaemia and those who receive erythropoiesis-stimulating agents, whether or not they require dialysis. Intravenous iron is the preferred route of administration in haemodialysis patients, with randomized trials showing a significantly greater increase in haemoglobin levels for intravenous versus oral iron and a low rate of treatment-related adverse events during these trials. According ANSM, physicians should apply the product's label recommendations especially the posology. In the non-dialysis CKD population, the erythropoietic response is also significantly higher using intravenous versus oral iron, and tolerability is at least as good. Moreover in some non-dialysis patients, intravenous iron supplementation might avoid or at least delay the need for erythropoiesis-stimulating agents. Following the new ANSM's recommendations, we now have the ability to achieve iron stores replenishment correctly and conveniently in dialysis dependent and non-dialysis dependent CKD patients without compromising safety using the various pharmaceutical forms of iron products especially intravenous compounds.

Cost of managing anemia in end-stage renal disease: the experience of five French dialysis centers.

OBJECTIVE: The aim of this retrospective study was to evaluate the direct cost of anemia treatment in hemodialysis patients and to evidence factors predictive of 1-year cost. METHODS: Retrospective study which included hemodialyzed patients during year 2009 in five centers. Patients were evaluable if they had at least one hemoglobin (Hb) assay per month and were monitored for at least 4 months. Patients were classified in different "annual Hb category" according to their monthly mean Hb [Hb categories: Ideal (10 ≤ Hb ≤ 12 g/dL); High (Hb > 12 g/dL) and Low (Hb < 10 g/dL) if >75% of time in respective category, otherwise classified in the Fluctuating category]. RESULTS: We analyzed 636 patients (male, 59.4%) with a mean age of 67 years who underwent 144 hemodialysis sessions (median number per patient) in 2009. The cost of anemia treatment was largely driven by erythropoiesis-stimulating agents (ESA) (68% of total cost for Low Hb category and approximately 90% for the other Hb categories). Adjusted predictive factors for 1-year direct cost of anemia treatment (p < 0.0001) were dialysis center (2,518-5,617), death (6,091 vs. 4,911), age (4,911 for ≤55 years and 5,378 for 65-75 years), female gender (4,911 vs. 4,398 for male), Low Hb category (13,005 vs. 5,034 for Ideal, 4,911 for Fluctuating and 2,418 for High), serum ferritin level (5,102 for 200-500 µg/mL and 4,646 for ≥500 µg/mL) and duration of dialysis (4,911 if ≤2 years and 2,952 if 4-6 years). LIMITATIONS: Retrospective study, and low number of patients in the Low Hb category. CONCLUSIONS: The main factors that were predictive of 1-year cost of anemia treatment in hemodialysis patients were centers, patients in the Low Hb category, and dialysis duration of less than 2 years.

[Intravenous iron during predialysis period improves anemia management and cardiovascular parameters in incident hemodialysis patients]. / La prise en charge de l'anémie et de ses conséquences chez les patients débutant l'hémodialyse : importance du fer intraveineux en prédialyse.

Individualized use of iron therapy (IT) and erythropoiesis-stimulating agents (ESA) may effectively correct anemia and its symptoms in CKD patients (Pts). The aim of this retrospective study was to precise the anemia management (AM) in incident HD Pts, and to compare Pts treated by intravenous (i.v.) IT and ESA during predialysis to those treated by oral IT and ESA on AM and cardiovascular parameters during the first year of HD. One hundred and two Pts performed their first dialysis in the unit, mean age 58.5 (15.9) years, 70% males, 27% diabetes. Ninety Pts started with a native arteriovenous fistula. Charlson comorbidity index was 7.3 (3.5). Mortality rate was 3% at one year. Hb level was at start 10.6 (1.7) and at one year 11.7 (1.1) g/dL (P<0.0001). DA injected every 2weeks was at the beginning at 107 (56) µg and then at 61 (46) (P<0.0001). i.v. IT injected every week was at the dosage of 87 (23) mg and then at 57 (40mg) per injection (P<0.001). Out of 102 Pts, 33 received i.v. IT during predialysis. These Pts started dialysis with a better Hb level: 11.1 (1.3) versus 10.4 (1.55) g/dL (P<0.01), had a TSAT at 50.0 (19.2) versus 30.1 (15.2) % (P<0.001), received less ESA 0.58 (0.28) versus 0.82 (0.37) µg/kg per week (P<0.01). More important were the changes on the cardiovascular functions: left ventricular mass at 116 (34) versus 134 (39) g/m(2) (P<0.02), left ventricular ejection fraction at 64.7 (4.4) versus 61.4 (8.7) % (P<0.02) and mean arterial pressure at 104.7 (80) versus 109 (13.2) mmHg (P<0.02). These Pts were also less hospitalized. This study revealed the importance of i.v. IT during predialysis care not only on AM but also on cardiovascular status in HD Pts starting dialysis.

[Feasibility strategy of darbepoetin alfa administration every other week: 2005-2007 experience in a dialysis unit]. / Faisabilité de la stratégie d'administration de la darbepoetin alfa tous les 15 jours : expérience 2005-2007 d'un centre de dialyse.

Darbepoetin alfa is a recombinant erythropoiesis-stimulating agent, with a longer half-life leaving the possibility to extending dosing administration in haemodialysis patients. A protocol of injection every 2weeks was initiated in the dialysis unit. From 2005 to 2007, 176 dialysis patients were studied with a target haemoglobin level between 11 and 12.5g/dL: the median haemoglobin level was ranged from 11.32 and 11.72g/dL during the study with a median darbepoetin alfa dose injected between 60 and 64µg per injection (0.46 to 0.47µg/kg per week). The mean number of dose changes was three per year per patient. The diabetic population did not differ from the general population in terms of haemoglobin levels and doses of darbepoetin alfa. Ten percent of the patients had to resume one injection per week for medical reasons: the profile of these patients was carefully studied. Hospitalisations resulted in a decrease in haemoglobin level and an increase in the darbepoetin alfa doses. Patients who died showed during the last 3months, a particular profile. Hyporesponsiveness has been explored. Time saving with this protocol was important for all the nursing staff. Although numerous factors of variability have been studied, there still a room for improvement of anemia management in haemodialysis patient.