Incidence, prevalence, and treatment of anemia of non-dialysis-dependent chronic kidney disease: A retrospective database study in France.

BACKGROUND: Minimal data are available regarding the prevalence and incidence of anemia among patients with non-dialysis-dependent chronic kidney disease (NDD-CKD) in France. METHODS: This was a retrospective non-interventional study of patients with a record of NDD-CKD in the Echantillon Généraliste des Bénéficiaires (EGB) database between January 01, 2012, and December 31, 2017. The primary objective was to estimate the annual incidence and prevalence of anemia of NDD-CKD. Secondary objectives included description of the demographics and clinical characteristics of patients with NDD-CKD-related anemia. An exploratory objective was to use machine learning to identify patients from the general population that might have NDD-CKD but without a recorded ICD-10 diagnosis of CKD. RESULTS: During 2012-2017, 9865 adult patients in the EGB database had confirmed NDD-CKD; of these, 49.1% (4848/9865) had anemia. From 2015 to 2017, estimates of incidence (108.7-114.7 per 1000 population) and prevalence (435.7-449.5 per 1000 population) of NDD-CKD-related anemia were stable. Less than half of patients with anemia of NDD-CKD were treated with oral iron, and approximately 15% were treated with erythropoiesis-stimulating agents. Based on adult French population projections in 2020 and an estimated prevalence rate in 2017 of 42.2 per 1000 population for confirmed plus possible NDD-CKD (as a proportion of the general French population), the estimated number of patients with possible NDD-CKD in France was 2,256,274, approximately five-fold greater than the number identified by diagnostic codes and hospitalizations. CONCLUSIONS: Anemia of NDD-CKD was shown to be a constant long-term burden in France, and its apparent prevalence may still be significantly underestimated. Given the potential treatment gap, additional initiatives to better identify and treat NDD-CKD anemia may improve patient management and treatment outcomes.

Management of anaemia in French dialysis patients: results from a large epidemiological retrospective study.

Background: Limited real-world data are available in Europe, especially France, regarding the therapeutic management of anaemia in patients with dialysis-dependent chronic kidney disease (DD CKD). Methods: This retrospective, longitudinal, observational study was based on medical records from the MEDIAL database of not-for-profit dialysis units in France. From January to December 2016, we included eligible patients (≥18 years), with a diagnosis of CKD and receiving maintenance dialysis. Patients with anaemia were followed up for 2 years after inclusion. Patient demographic data, anaemia status, CKD-related anaemia treatments, and treatment outcomes including laboratory test results were evaluated. Results: Of 1632 DD CKD patients identified from the MEDIAL database, 1286 had anaemia; 98.2% of patients with anaemia were receiving haemodialysis at index date (ID). Of patients with anaemia, 29.9% had haemoglobin (Hb) levels of 10-11 g/dL and 36.2% had levels of 11-12 g/dL at ID. Furthermore, 21.3% had functional iron deficiency and 11.7% had absolute iron deficiency. The most commonly prescribed treatments at ID for patients with DD CKD-related anaemia were intravenous (IV) iron with erythropoietin-stimulating agents (ESAs) (65.1%). Among patients initiating ESA treatment at ID or during follow-up, 347 (95.3%) reached the Hb target of 10-13 g/dL and maintained response within the target Hb range for a median duration of 113 days. Conclusions: Despite combined use of ESAs and IV iron, duration within the Hb target range was short, suggesting that anaemia management can be further improved.

A Prospective, Observational Study of Conversion From Immediate- to Prolonged-Release Tacrolimus in Renal Transplant Recipients in France: The OPALE Study.

BACKGROUND Potential benefits of once-daily, prolonged-release tacrolimus over the immediate-release formulation include improved adherence to immunosuppressives post transplantation. An observational study was performed to characterize real-world practice surrounding conversion from immediate- to prolonged-release tacrolimus in kidney transplant recipients. MATERIAL AND METHODS We performed a prospective, observational study of renal transplant recipients converted from immediate- to prolonged-release tacrolimus capsules. Conversion took place at the baseline visit, within the first 6 months of transplantation (early conversion group) or between 6 and 12 months of transplantation (late conversion group). Data collection was performed at routine follow-up at 6 and 12 months. Endpoints included conversion ratio from immediate- to prolonged-release tacrolimus, reasons for conversion, additional visits due to conversion, safety, and tolerability. RESULTS The analysis population comprised 591 patients. Baseline characteristics were similar between the 2 groups. The mean conversion ratio of the daily dose of tacrolimus was 0.98±0.17 in the early group and 0.99±0.09 in the late group. Time from conversion (mean ±SD) to first measurement of trough tacrolimus blood concentration was 12.1±11.6 and 27.6±26.7 days in the early and late groups, respectively. The highest number of additional visits required was 6 in the early conversion group, in 3 patients (0.7%), and 3 in the late conversion group, in 2 patients (1.6%). Conversion from immediate- to prolonged-release tacrolimus was associated with a very low rate of graft rejection. CONCLUSIONS Favorable clinical outcomes and safety profiles were observed with conversion from immediate- to prolonged-release tacrolimus over 1 year following renal transplantation, with no marked differences between the early and late conversion groups.

A Multicenter, Prospective, Observational Study of Conversion from Twice-Daily Immediate-Release to Once-Daily Prolonged-Release Tacrolimus in Liver Transplant Recipients in France: The COBALT Study.

BACKGROUND In adult liver transplant patients, the use of prolonged-release tacrolimus may have treatment adherence benefits over the immediate-release formulation. The aim of this study was to characterise real-world practice data on conversion of liver transplant recipients from immediate- to prolonged-release tacrolimus in France. MATERIAL AND METHODS A prospective, observational study (NCT02143479) was conducted in 18 transplant centers in France between June 2014 and March 2016. Liver transplant recipients (n=398) included patients who changed from immediate-release to prolonged-release tacrolimus within the first three months (early conversion group) (n=205) or between three and 12 months after transplantation (late conversion group) (n=184). Clinical data were collected at an initial baseline outpatient visit and six-month and 12-month follow-up visits. Endpoints included the dose conversion ratio from immediate-release to prolonged-release tacrolimus, number of and reasons for additional visits due to conversion, safety, and tolerability. RESULTS Baseline clinical and demographic characteristics were similar between the two cohorts. The mean ±SD ratio of conversion of tacrolimus dose was 1.04±0.28; 1.01±0.28 (early) and 1.08±0.28 (late) (p=0.0247). The mean ±SD time from conversion to the first tacrolimus trough blood concentration was 30.8±42.8 days; 24.8±45.4 days (early) and 37.5±38.7 days (late). Only one patient required an additional visit due to conversion. Reasons for conversion included the physician's preference (56.3%), center practice (38.6%), and the dosing frequency (36.0%). Conversion was associated with a low rate of graft rejection, and no new safety issues were reported. CONCLUSIONS Conversion of liver transplant recipients from immediate-release to prolonged-release tacrolimus within three to 12 months of transplantation was easy to manage and associated with favorable clinical outcomes and safety profiles.

Tacrolimus Granules for Oral Suspension as Post-Transplant Immunosuppression in Routine Medical Practice in France: The OPTIMOD Study.

BACKGROUND Different pharmaceutical forms of oral tacrolimus allow tailored administration. The granular formulation facilitates accurate dose adjustment of tacrolimus according to patient characteristics, such as weight, or potential concomitant drug interactions. Currently, there are no data describing the use of tacrolimus granules in transplant recipients in France. MATERIAL AND METHODS OPTIMOD was a 6-month prospective, observational multicenter study that aimed to describe patient characteristics and conditions of use of tacrolimus granules. The 25 participating centers enrolled patients at time of tacrolimus granules initiation and were to collect patient and treatment data at initiation and after 6 months of follow-up. All analyses were descriptive. RESULTS Of 61 patients included, 55.7% were children (mainly kidney graft recipients) and 44.3% were adults (mostly lung graft recipients). Overall, 24.6% of patients (all children) initiated tacrolimus granules immediately post-transplant; the remaining 75.4% converted to tacrolimus granules from ciclosporin or immediate-release tacrolimus hard capsules. The main reasons for initiating tacrolimus granules, irrespective of whether first- or second-line therapy, were to offset potential drug-drug interactions in adults by adjusting dose, and to adapt to the particular needs of children as patients. Most patients (78.7%) underwent ≥1 dose modification during follow-up. Eleven rejection episodes occurred during follow-up, of which none led to graft loss. The adverse-event profile of the tacrolimus granules was similar to that of other tacrolimus formulations and 7 treatment-related adverse events were recorded. CONCLUSIONS Results suggest that tacrolimus granules are well tolerated and effective in preventing transplant rejection when administered in routine practice in France.

Adherence with immunosuppressive treatment after transplantation: results from the French trial PREDICT.

Although immunosuppressive therapy after organ transplantation is paramount for long-term outcomes, patients do not comply with their immunosuppressive treatment as much as might be expected. In this observational study, patients having undergone a kidney or liver transplantation were enrolled. Adherence was evaluated by patients using the compliance evaluation test and by physicians using a visual analogic scale. A linear regression was performed to identify determinants of adherence. Less patients having undergone kidney transplantation (27%) described themselves as good compliers than liver transplanted patients (40%). Discrepancy was noted between the physician and patient assessments. Rates of good adherence were significantly different depending on gender, age at transplantation, retransplantation, and time elapsed since transplantation, in at least one of the groups evaluated (whole cohort, kidney liver transplantation groups). In all three groups, adherence decreased with the number of immunosuppressants prescribed. In the whole cohort, the rate of good adherence was significantly higher in patients taking lower number of immunosuppressive drugs (45% for 1 vs. 24% for 3 immunosuppressants; p = 0.02). In this study, which is the first study of this scale in France, we confirmed that adherence with immunosuppressant treatment was low and that simpler treatment regimens may favor adherence.

Assessing renal function with daclizumab induction and delayed tacrolimus introduction in liver transplant recipients.

BACKGROUND: Calcineurin inhibitor-induced renal dysfunction is a major problem in liver transplantation. Interleukin-2 receptor antagonist induction followed by delayed tacrolimus (Tac) administration may minimize the renal insult without compromising immunoprotection. METHODS: This open, randomized, multicenter trial evaluated the benefit of daclizumab induction with delayed Tac on renal function at 6 months; an observational study was continued for 18 months. Liver transplant patients with a 12-hr serum creatinine (SrC) level less than 180 micromol/L received either delayed Tac with daclizumab induction (n=98) or standard Tac (n=101) both combined with mycophenolate mofetil and steroids. The primary endpoint was the incidence of SrC level more than 130 micrommol/L at 6 months. RESULTS: The incidence was 22.4% with delayed Tac and 29.7% with standard Tac (P=ns), which remained unchanged at 12 months (21.6% and 23.9%) but increasing slightly at 24 months (29.0% and 32.9%), respectively. A post hoc analysis of renal function was done based on patients stratification by SrC at 12 hr (100 micromol/L) showing no difference in SrC values at 6 months regardless of the 12-hr values despite a trend toward better estimated glomerular filtration rate for patients with 12-hr value less than 100 micromol/L in the delayed Tac group. Biopsy-proven acute rejection was similar at 6 months (17.5% and 18.75%), 12 months (23.5% and 23.8%), and 24 months (24.5% and 25.7%), respectively. Patient and graft survival in both groups were comparable and good. Similar types and incidences of adverse events were reported in both groups at all time. CONCLUSIONS: Delay of Tac does not benefit renal function in liver transplant recipients with a good renal function at baseline.