Cardiovascular and renal diseases in type 2 diabetes patients: 5-year cumulative incidence of the first occurred manifestation and hospitalization cost: a cohort within the French SNDS nationwide claims database.

BACKGROUND: Myocardial infarction (MI), stroke, peripheral arterial disease (PAD), heart failure (HF) and chronic kidney disease (CKD) are common cardiovascular renal diseases (CVRD) manifestations for type 2 diabetes. The objective was to estimate the incidence of the first occurring CVRD manifestation and cumulative hospitalization costs of each CVRD manifestation for type 2 diabetes without CVRD history. METHODS: A cohort study of all type 2 diabetes free of CVRD as of January 1st 2014, was identified and followed-up for 5 years within the French SNDS nationwide claims database. The cumulative incidence of the first occurring CVRD manifestation was estimated using the cumulative incidence function, with death as a competing risk. Cumulative hospitalization costs of each CVRD manifestations were estimated from the perspective of all payers. RESULTS: From 2,079,089 type 2 diabetes without cancer or transplantation, 76.5% were free of CVRD at baseline with a mean age of 65 years, 52% of women and 7% with microvascular complications history. The cumulative incidence of a first CVRD manifestation was 15.3% after 5 years of follow-up with a constant linear increase over time for all CVRD manifestations: The most frequent was CKD representing 40.6% of first occurred CVRD manifestation, followed by HF (23.0%), then PAD (13.5%), stroke (13.2%) and MI (9.7%). HF and CKD together reached about one patient out of ten after 5 years and represented 63.6% of first CVRD manifestations. The 5-year global cost of all CVRD hospitalizations was 3.9 billion euros (B€), i.e. 2,450€ per patient of the whole cohort, with an exponential increase over time for each specific CVRD manifestation. The costliest was CKD (2.0 B€), followed by HF (1.2 B€), then PAD (0.7 B€), stroke (0.6 B€) and MI (0.3 B€). CONCLUSIONS/INTERPRETATION: While MI, stroke and PAD remain classic major risks of complications for CVRD-free type 2 diabetes, HF and CKD nowadays represent individually a higher risk and cost than each of these classic manifestations, and jointly represents a risk and a cost twice as high as these three classic manifestations all together. This should encourage the development of specific HF and CKD preventive strategies.

Digital pressure with laser Doppler flowmetry is better than photoplethysmography to characterize peripheral arterial disease of the upper limbs in end-stage renal disease patients.

OBJECTIVE: There is no consensual definition of significant peripheral arterial disease of the upper limbs. Patients with end-stage renal disease are usually explored with Doppler ultrasound, which seems insufficient to characterize and quantify the arterial disease in this anatomic site. Candidates for haemodialysis access tend to be increasingly older and have polyvascular disease, and a better assessment of the vascular status of their upper limbs with finger systolic blood pressure is necessary. Photoplethysmography is simple and currently used in practice, but laser Doppler flowmetry may be more sensitive for low values. Our objective is to investigate additional information in the digit assessment over the ultrasound assessment of the upper limbs of patients awaiting haemodialysis and compare digital pressure values taken by photoplethysmography and laser Doppler. METHODS: All included patients with end-stage renal disease scheduled for haemodialysis access received a prospective evaluation of their upper limbs with a clinical examination of the hands, an arterial upper limb Doppler ultrasound, and finger systolic blood pressure using photoplethysmography and laser Doppler flowmetry. Significant upper limb arterial disease was defined by a finger systolic blood pressure below 60 mm Hg or a finger brachial pressure index below 0.7. RESULTS: Twenty-four patients were included in the study. In all, 41.7% of patients (n = 10) had parietal calcifications to the antebrachial arteries on Doppler ultrasound, 8.3% of patients (n = 2) had bilateral finger systolic blood pressure values below 60 mm Hg with laser Doppler flowmetry (but not confirmed with photoplethysmography), and 16.6% of patients (n = 4) had a finger brachial pressure index below 0.7 on both laser Doppler flowmetry and photoplethysmography. While there was an agreement between these two methods, higher values were recorded with photoplethysmography. The Pearson coefficient was 0.493 for the median of basal digital pressures in absolute values and 0.489 for finger brachial pressure index (p < 0.001). CONCLUSION: Our study confirms the need to evaluate significant upper limb arterial disease in patients with end-stage renal disease not only with Doppler ultrasound but also with an evaluation of the finger systolic blood pressure. The correlation of the finger systolic blood pressure values using laser Doppler flowmetry and photoplethysmography was poor, which was probably due to an overestimation of the pressures with photoplethysmography. Despite the absence of a gold standard, we suggest that Laser Doppler flowmetry should be used rather than photoplethysmography to better characterize significant peripheral arterial disease of the upper limbs in patients with end-stage renal disease, particularly before creation of a new haemodialysis access. Protocol Record on clinical trial 38RC19.285.

Potential life-years gained over a 5-year period by correcting DOPPS-identified modifiable practices in haemodialysis: results from the European MONITOR-CKD5 study.

BACKGROUND: DOPPS reported that thousands of life-years could be gained in the US and Europe over 5 years by correcting six modifiable haemodialysis practices. We estimated potential life-years gained across 10 European countries using MONITOR-CKD5 study data. METHODS: The DOPPS-based target ranges were used, except for haemoglobin due to label changes, as well as DOPPS-derived relative mortality risks. Percentages of MONITOR-CKD5 patients outside targets were calculated. Consistent with the DOPPS-based analyses, we extrapolated life-years gained for the MONITOR-CKD5 population over 5 years if all patients were within targets. RESULTS: Bringing the 10 MONITOR-CKD5 countries' dialysis populations into compliance on the six practices results in a 5-year gain of 97,428 patient-years. In descending order, survival impact was the highest for albumin levels, followed by phosphate levels, vascular access, haemoglobin, dialysis adequacy, and interdialytic weight gain. CONCLUSIONS: Optimal management of the six modifiable haemodialysis practices may achieve 6.2% increase in 5-year survival. TRIAL REGISTRATION: NCT01121237 . Clinicaltrials.gov registration May 12, 2010 (retrospectively registered).

Long-term treatment with biosimilar epoetin-α (HX575) in hemodialysis patients with renal anemia: real-world effectiveness and safety in the MONITOR-CKD5 study
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AIMS: To assess real-world effectiveness and safety of intravenous (IV) HX575, a biosimilar epoetin-α, in hemodialysis (HD) patients. MATERIALS AND METHODS: This prospective, observational, pharmacoepidemiological study of adult HD patients treated with IV HX575 for renal anemia for up to 24 months was conducted in 114 centers in 10 European countries. Of 2,086 enrolled subjects (safety sample), 2,023 had ≥ 1 follow-up visit (effectiveness sample). RESULTS: Most (59.3%) patients were male, median age was 68 years. At enrollment, most (82.5%) had been treated with an erythropoiesis-stimulating agent, and 73.0% had adequate iron stores. At baseline, mean (± standard deviation) baseline hemoglobin (Hb) was 11.09 (± 1.14) g/dL and HX575 dose 106.5 (± 78.7) international units (IU)/kg/week; at month 24, Hb was 11.25 (± 1.19) g/dL and HX575 dose 113.0 (± 102.5) IU/kg/week. Variations in mean HX575 dose and Hb over the study were not statistically significant. As to safety, 140 patients (6.7%) experienced ≥ 1 adverse event; of these, 19 events (16 patients; 0.8%) were related to HX575 treatment, 148 (108 patients; 5.2%) were reported as serious, including 12 events in 11 patients (0.5%) stated to be related. No cases of anti-epoetin antibodies or pure red cell aplasia were reported. CONCLUSIONS: MONITOR-CKD5 confirmed the real-world effectiveness and safety profile of IV biosimilar HX575. HD patients treated for up to 24 months showed stable dosing patterns and Hb outcomes. The safety profile of HX575 is likewise comparable to reference epoetin-α.
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Anti-TGF-ß1 Antibody Therapy in Patients with Diabetic Nephropathy.

TGF-ß has been implicated as a major pathogenic factor in diabetic nephropathy. This randomized, double-blind, phase 2 study assessed whether modulating TGF-ß1 activity with a TGF-ß1-specific, humanized, neutralizing monoclonal antibody (TGF-ß1 mAb) is safe and more effective than placebo in slowing renal function loss in patients with diabetic nephropathy on chronic stable renin-angiotensin system inhibitor treatment. We randomized 416 patients aged ≥25 years with type 1 or type 2 diabetes, a serum creatinine (SCr) level of 1.3-3.3 mg/dl for women and 1.5-3.5 mg/dl for men (or eGFR of 20-60 ml/min per 1.73 m2), and a 24-hour urine protein-to-creatinine ratio ≥800 mg/g to TGF-ß1 mAb (2-, 10-, or 50-mg monthly subcutaneous dosing for 12 months) or placebo. We assessed a change in SCr from baseline to 12 months as the primary efficacy variable. Although the Data Monitoring Committee did not identify safety issues, we terminated the trial 4 months early for futility on the basis of their recommendation. The placebo group had a mean±SD change in SCr from baseline to end of treatment of 0.33±0.67 mg/dl. Least squares mean percentage change in SCr from baseline to end of treatment did not differ between placebo (14%; 95% confidence interval [95% CI], 9.7% to 18.2%) and TGF-ß1 mAb treatments (20% [95% CI, 15.3% to 24.3%], 19% [95% CI, 14.2% to 23.0%], and 19% [95% CI, 14.0% to 23.3%] for 2-, 10-, and 50-mg doses, respectively). Thus, TGF-ß1 mAb added to renin-angiotensin system inhibitors did not slow progression of diabetic nephropathy.

ANGPTL2 is associated with an increased risk of cardiovascular events and death in diabetic patients.

AIMS/HYPOTHESIS: A high serum angiopoietin-like 2 (ANGPTL2) concentration is an independent risk factor for developing diabetes and is associated with insulin resistance and atherosclerosis. In this work, we have examined the impact of serum ANGPTL2 on improving cardiovascular (CV) risk stratification in patients with type 2 diabetes. METHODS: A prospective, monocentric cohort of consecutive type 2 diabetes patients (the SURDIAGENE cohort; total of 1353 type 2 diabetes patients; 58% men, mean ± SD age 64 ± 11 years) was followed for a median of 6.0 years for death as primary endpoint and major adverse CV events (MACE; i.e. CV death, myocardial infarction or stroke) as a secondary endpoint. Patients with end-stage renal disease, defined as a requirement for dialysis or a history of kidney transplantation, were excluded. Patients were grouped into quartiles according to ANGPTL2 concentrations at inclusion: <11.2 (Q1), 11.2-14.7 (Q2), 14.8-19.5 (Q3) or >19.5 (Q4) ng/ml. RESULTS: During follow up, 367 patients (representing 4.5% of the total person-years) died and 290 patients (representing 3.7% of the total person-years) presented with MACE. Both the survival and MACE-free survival rates were significantly different between ANGPTL2 quartiles (logrank 82.12, p < 0.0001 for death; and logrank 65.14, p < 0.0001 for MACE). Patients with ANGPTL2 concentrations higher than 19.5 ng/ml (Q4) had a significantly higher risk of death and MACE than those with ANGPTL2 levels of 19.5 ng/ml or less (Q1-3) (HR for death 2.44 [95% CI 1.98, 3.00], p < 0.0001; HR for MACE 2.43 [95% CI 1.92, 3.06], p < 0.0001) after adjustment for sex, age and established CV risk factors. Using ANGPTL2 concentrations, prediction of the risk of mortality, as assessed by integrated discrimination improvement (IDI), was significantly improved (IDI 0.006 ± 0.002, p = 0.0002). CONCLUSIONS/INTERPRETATION: In patients with type 2 diabetes, serum ANGPTL2 concentrations were independently associated with death and MACE. Therefore, ANGPTL2 is a promising candidate biomarker for improving risk stratification in type 2 diabetes patients, and may prove to be a valuable therapeutic target.

Differential impact of glucose levels and advanced glycation end-products on tubular cell viability and pro-inflammatory/profibrotic functions.

High glucose (HG) or synthetic advanced glycation end-products (AGE) conditions are generally used to mimic diabetes in cellular models. Both models have shown an increase of apoptosis, oxidative stress and pro-inflammatory cytokine production in tubular cells. However, the impact of the two conditions combined has rarely been studied. In addition, the impact of glucose level variation due to cellular consumption is not clearly characterized in such experiments. Therefore, the aim of this study was to compare the effect of HG and AGE separately and of both on tubular cell phenotype changes in the HK2 cell line. Moreover, glucose consumption was monitored every hour to maintain the glucose level by supplementation throughout the experiments. We thus observed a significant decrease of apoptosis and H2O2 production in the HK2 cell. HG or AGE treatment induced an increase of total and mitochondrial apoptosis as well as TGF-ß release compared to control conditions; however, AGE or HG led to apoptosis preferentially involving the mitochondria pathway. No cumulative effect of HG and AGE treatment was observed on apoptosis. However, a pretreatment with RAGE antibodies partially abolished the apoptotic effect of HG and completely abolished the apoptotic effect of AGE. In conclusion, tubular cells are sensitive to the lack of glucose as well as to the HG and AGE treatments, the AGE effect being more deleterious than the HG effect. Absence of a potential synergistic effect of HG and AGE could indicate that they act through a common pathway, possibly via the activation of the RAGE receptors.

Conversion to mammalian target of rapamycin inhibitors increases risk of de novo donor-specific antibodies.

In kidney transplantation, conversion to mammalian target of rapamycin (mTOR) inhibitors may avoid calcineurin inhibitor (CNI) nephrotoxicity, but its impact on post-transplant allo-immunization remains largely unexplored. This retrospective cohort study analyzed the emergence of donor-specific antibodies (DSA) in kidney transplant recipients relative to their immunosuppressive therapy. Among 270 recipients without pretransplant immunization who were screened regularly for de novo DSA, 56 were converted to mTOR inhibitors after CNI withdrawal. DSA emergence was increased in patients who were converted to mTOR inhibitors (HR 2.4; 95% CI 1.06-5.41, P = 0.036). DSA were mainly directed against donor HLA-DQB1 antigens. The presence of one or two DQ mismatches was a major risk factor for DQ DSA (HR 5.32; 95% CI 1.58-17.89 and HR 10.43; 95% CI 2.29-47.56, respectively; P < 0.01). Rejection episodes were more likely in patients converted to mTOR inhibitors, but this difference did not reach significance (16% vs. 7.9%, P = 0.185). Concerning graft function, no significant change was observed one year after conversion (P = 0.31). In conclusion, conversion to mTOR inhibitors may increase the risk of developing class II DSA, especially in the presence of DQ mismatches: this strategy may favor chronic antibody-mediated rejection and thus reduce graft survival.

Phase 1b/2a Study Assessing the Safety and Efficacy of Felzartamab in Anti-Phospholipase A2 Receptor Autoantibody-Positive Primary Membranous Nephropathy.

Introduction: Primary membranous nephropathy (PMN) is most often caused by autoantibodies to phospholipase A2 receptor (PLA2R). M-PLACE (NCT04145440) is an open-label, phase 1b/2a study that assessed the safety and efficacy of the fully human anti-CD38 monoclonal antibody felzartamab in high-risk anti-PLA2R+ PMN. Methods: Patients with newly diagnosed or relapsed PMN (cohort 1 [C1]; n = 18) or PMN refractory to immunosuppressive therapy (IST) (cohort 2 [C2]; n = 13) received 9 infusions of felzartamab 16 mg/kg in the 24-week treatment period, followed by a 28-week follow-up. The primary end point was the incidence and severity of treatment-emergent adverse events (TEAEs). Results: A total of 31 patients were enrolled and received felzartamab. Twenty-seven patients (87.1%) had TEAEs, including infusion-related reactions (IRRs) (29.0%), hypogammaglobulinemia (25.8%), peripheral edema (19.4%), and nausea (16.1%). Five patients (16.1%) had serious TEAEs that all resolved. Immunologic response (anti-PLA2R titer reduction ≥50%) was achieved by 20 of 26 efficacy-evaluable patients (76.9%) (C1, 13/15 [86.7%]; C2, 7/11 [63.6%]). Anti-PLA2R titer reductions were rapid (week 1 response, 44.0%; response 7 months after last felzartamab dose [end of study, EOS], 53.8%). Partial proteinuria remission (urine protein-to-creatinine ratio [UPCR] reduction ≥50%, UPCR <3.0 g/g, and stable estimated glomerular filtration rate [eGFR]) was achieved by 9 of 26 patients (34.6%) (C1, 7/15 [46.7%]; C2, 2/11 [18.2%]) before or at EOS (median follow-up, 366 days). Serum albumin increased from baseline to EOS in 20 of 26 patients (76.9%) (C1, 12/15 [80.0%]; C2, 8/11 [72.7%]). Conclusion: In this population with high-risk anti-PLA2R+ PMN, felzartamab was tolerated and resulted in rapid partial and complete immunologic responses and partial improvements in proteinuria and serum albumin in some patients.

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.

Case report: detection of a hepatitis B surface antigen variant emerging in an elderly patient after an ischemic cerebral vascular accident.

HBV reactivations are observed frequently in patients with past hepatitis B infection receiving cytotoxic and/or immunosuppressive chemotherapy for hemato-oncological malignancies or autoimmune diseases. Recent ischemic stroke was shown to induce immunodepression by misunderstood mechanisms. To our knowledge, the association between HBV reactivation and ischemic stroke has not been reported before. This study reports the case of an anti-HBs- and anti-HBc-positive patient who presented HBV reactivation in a context of recent ischemic stroke, with no other intercurrent iatrogenic phenomenon or usual immunosuppressive pathology.

Are triplicate urine samples necessary to assess albuminuria?

BACKGROUND/AIMS: Urinary albumin excretion is subject to intra-individual variability. Thus, for research purposes, it is recommended to test three urine samples collected over a short period of time. The objective of our analysis was to check the usefulness of triplicate samples to determine the albuminuric status of diabetic patients. METHODS: We present the results of the non-planned retrospective analysis of 246 triplicate morning urine samples obtained from 95 type 2 diabetics included in three multinational, randomized, double-blind studies. Albuminuria was determined by immunoturbidimetry on fresh samples in the same central laboratory. Microalbuminuria was defined by a urine albumin to creatinine ratio (UACR) between 2.5 and 25 mg/mmol in males and between 3.5 and 35 mg/mmol in females. Concordance was obtained when the second and/or third sample (UACR2 and UACR3) confirmed the albuminuric status obtained from the first sample (UACR1). RESULTS: Considering the first samples, 9% were within the normal range, 35% showed microalbuminuria and 56% showed macroalbuminuria. The overall concordance rate was 95%. The log of UACR was highly correlated between samples. Bland-Altman plots expressed in percent variations between two samples confirmed that the mean variation was low (around 8%) but revealed the scattering of values, 95% being between -60 and +77% of variation between samples. CONCLUSIONS: There is no benefit in repeating morning UACR determination in diabetic patients to accurately categorize a subject as having normo-, micro- or macroalbuminuria. However, in order to accurately quantify albuminuria, repeated determinations are required.

A Specific High-Protein Weight Loss Program Does Not Impair Renal Function in Patients Who Are Overweight/Obese.

Although high-protein diets appear to be the most efficient way to lose weight, concerns may arise about their innocuity on renal function. The objective of this study is to assess the impact of a weight loss program on renal function. A multicentric cohort-based study was performed using the RNPC© French national weight loss program. Patients with at least two creatinine measurements at the beginning of the program and at the end of the weight loss phase between 1 January 2016 and 1 July 2021 were included. Renal function was assessed by Modification of Diet in Renal Disease (MDRD) equation-based estimated glomerular filtration rate (eGFR). From 4394 patients with two creatinine measurements included, 1579 (35.9%) had normal eGFR (MDRD 90-120 mL/min/1.73 m2), 210 (4.8%) had hyperfiltration (MDRD > 120 mL/min/1.73 m2), 2383 (54.2%) had chronic kidney disease (CKD) grade 2 (MDRD 60-90 mL/min/1.73 m2), and 221 (5.0%) had CKD grade 3 (MDRD 30-60 mL/min/1.73 m2). Multivariable analyses showed no eGFR change for patients in initial CKD grade 2, normal eGFR and hyperfiltration, and a significant increase in CKD grade 3. The RNPC© program avoids renal function impairment during the two first phases, regardless of the initial eGFR.

Long-term health-related quality of life outcomes of adults with pediatric onset of frequently relapsing or steroid-dependent nephrotic syndrome.

BACKGROUND: Long-term psychosocial outcomes and health-related quality of life (HRQOL) in adults with pediatric onset of frequently relapsing or steroid-dependent idiopathic nephrotic syndrome (FRNS or SDNS) remain to be determined. METHODS: In this prospective cohort study, 59 adults with pediatric onset of FRNS/SDNS and persistent active glomerular disease in adulthood completed the GEDEPAC-2 questionnaire exploring 11 well-being domains. Data were compared to the French general population (FGP) with standardized incidence ratio ([SIR]; adjusted for period, age, gender). Regression models were performed to identify predictive factors of psychosocial well-being. RESULTS: In 82% of cases, the questionnaire was completed while the participants (n = 59; 47 men; median age = 32 years; median number of relapses = 13) were in complete remission (under specific therapy in 76% of cases). Participants had higher educational degree than in the FGP (SIR = 6.3; p < 0.01) and more frequently a managerial occupation (SIR = 3.1; p < 0.01). Social integration was acceptable with regard to marital status and experience of sexual intercourse, but experiences of discrimination were far more frequent (SIR = 12.5; p < 0.01). The SF-12 mental component summary (MCS) score was altered (Z-score = - 0.6; p < 0.01) and mean multidimensional fatigue inventory (MFI-20) global fatigue score appeared high (12). Transfer from pediatric to adult healthcare was followed by a period of discontinued care for 33% of participants. Multivariate analysis revealed a close relationship between MFI-20, physical health, and MCS. CONCLUSIONS: This study shows that pediatric onset FRNS and SDNS may have a long-term negative impact on mental HRQOL and highlights the impact of fatigue, which is often not adequately considered in routine care.

[Use of iron in nephrology: Results of a French practical survey]. / Utilisation du fer en néphrologie : enquête sur les pratiques des néphrologues français.

The French-speaking Society of Nephrology, Dialysis and Transplantation conducted, in 2018, a survey among French nephrologists into their iron prescribing habits for patients with chronic kidney disease stages 3 to 5 before dialysis. The results show that 73% of nephrologists use intravenous iron before dialysis stage. When a patient has gastrointestinal symptoms under oral iron therapy, only 48% of nephrologists use intravenous route. The starting thresholds for iron are for 78% of nephrologists a transferrin saturation <20% and for 80% a serum ferritin <100 µg/L. Only 14% start iron when a transferrin saturation <25% or higher and 29% start iron when serum ferritin <200 µg/L or higher. High dosages of iron (500 and 1000 mg) are used by 58% of nephrologists. Finally, about 30% of nephrologists refer to various barriers to intravenous iron prescription, such as cost, unavailability of intravenous iron in their facility or lack of day hospital unit. The correction of iron deficiency without anemia remains controversial. It is performed by only 43% of nephrologists. These results show an improvement of the practices compared to a 2006 survey. However, they indicate a sub-prescription of iron compared to the European recommendations which recommend a starting threshold of iron of transferrin saturation <25% and ferritinemia <200 µg/L in anemic patients not treated with erythropoietin-stimulating agents.

[Assessment of iron deficiency anemia management in the general hospital of Grenoble: A 12-month follow-up of an intravenous ferric carboxymaltose treatment program in a cohort of patients with non-dialysis-dependent chronic kidney disease]. / Évaluation de la prise en charge de l'anémie ferriprive au CHU de Grenoble-Alpes : suivi d'un programme de traitement par carboxymaltose ferrique intraveineux pendant 12 mois dans une cohorte de patients atteints de maladie rénale chronique non dépendants d'une dialyse.

INTRODUCTION: The FIND-CKD study has validated the use of ferric carboxymaltose (FCM) injection with a target of ferritin level between 400 and 600ng/mL to treat iron deficiency anemia in non-dialysis-dependent chronic kidney disease (ND-CKD) patients. In order to assess this strategy in clinical practice, we constituted a cohort of patients within our nephrology department. PATIENTS AND METHODS: Patients had CKD stages 3 to 5, hemoglobin level (Hb)<13g/dL (men) or<12g/dL (women), and ferritin level (F)<100ng/mL or transferrin saturation (TSAT)<20%. They were not treated by erythropoiesis-stimulating agent (ESA) for at least one month, and oral iron had been poorly tolerated or ineffective. FCM first dose was adjusted according to patient weight. A new infusion was possible, at least one month after the first, with a half-dose if TSAT<20% but F≥200ng/mL; no perfusion was performed if F≥400ng/mL. RESULTS: In all, 53 patients were included with a mean Hb of 11.4g/dL and a mean TSAT of 16%. Over one year of follow-up, only 12 patients (22.6%) needed another treatment for anemia (blood transfusion or ESA). No patient showed a significant decrease in Hb. In all, 62% of patients received only one infusion of FCM. CONCLUSION: The administration of FCM IV with ferritin levels in the recommended target has proven effective in correcting anemia of ND-CKD patients while limiting the use of another therapeutic strategy.

[Impact of comorbidities on hemoglobin stability in patients with chronic kidney insufficiency on hemodialysis, treated with CERA in current practice: The MIRIADE study]. / Impact des comorbidités sur la stabilité de l'hémoglobine chez des patients insuffisants rénaux chroniques en hémodialyse, traités par CERA en pratique courante : l'étude MIRIADE.

This national, prospective and multicenter study aimed to describe the real-life impact of comorbidities on hemoglobin stability in patients with chronic kidney disease on hemodialysis, treated with CERA in relay of an erythropoietin stimulating agent. Comorbidities were defined by the Charlson Index (adjusted on age) and hemoglobin stability as a variation of ±1g/dL after the 6-month treatment period. The 585 analyzed patients were distributed as follows according to the adjusted Charlson index: score≤3 (12% of patients), 4≤score≤5 (17%), 6≤score≤7 (31%) and score≥8 (40%). At CERA start, its median monthly dose was of 100µg for the overall population, with no changes during the treatment period and with little variation according to the comorbidity score. Patients with stable hemoglobin (56%, 67% if score≤3) were more numerous to reach the therapeutic target range between 10 and 12g/dL after 6 months (85% versus 43% if not stable hemoglobin). Patients with low C-reactive protein value (≤5mg/L ; P=0.04), no red blood cell transfusion (P=0.03), or no/low dose of intravenous iron (≤200mg ; P=0.03) were more likely to reach stable hemoglobin under CERA after 6 months. Among the 644 CERA-treated patients, 4 patients (<1%) had one serious adverse event related to treatment. A stable hemoglobin within the therapeutic target was reached in the majority of the patients after 6 months in current practice with a lower CERA dose, regardless of the comorbidities scores of patients on hemodialysis.

[Discrepancies (and confluences) in perception between patients and nephrologists of chronic kidney disease impact on vital impetus in adults not undergoing hemodialysis: Results of the French MAEVA study]. / Divergences (et convergences) de perceptions entre patients et néphrologues de l'impact de l'insuffisance rénale chronique non terminale sur l'élan vital en France : résultats de l'enquête MAEVA.

RATIONALE: The impact of chronic kidney disease (CKD) on vital impetus is poorly documented in patients not undergoing renal dialysis and discrepancies can be observed between patients and physicians in perception of QoL and impact of the disease. METHODS: A self-questionnaire was sent to 1282 French nephrologists and a mirrored self-questionnaire was given to patients (CKD stage 3, 4 or 5) by their nephrologist. Data were collected prospectively and anonymously. RESULTS: A total of 261 nephrologists and 172 patients participated in the survey. Sixty-six percent of patients reported a negative impact of the disease on their quality of life, which is also identified by nephrologists: important impact 22% vs 27%, mild or inconstant 44% vs 47%, mild or absent 34% vs 31% in patients and nephrologists, respectively. They had different perceptions about factors contributing to vital force; in particular, nephrologists underestimated their key role in psychological support. Indeed, the optimism and encouragements of nephrologists were considered to be a key factor of vital force for 60% of patients vs 20% of nephrologists (P<0,001). During consultations, nephrologists were primarily focused on biological abnormalities and adherence to treatment while mood or sexual disorders were rarely investigated. The main objective of treatment was to maintain a normal life for patients and to delay dialysis for nephrologists. CONCLUSION: Nephrologists have a relative knowledge of CKD impact on the vital impetus of patients, but there are differences of perception. It could be improved through specific trainings.