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.

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 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.

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.

[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.

[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.

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).

[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.

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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[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.

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.

Association of Circulating Biomarkers (Adrenomedullin, TNFR1, and NT-proBNP) With Renal Function Decline in Patients With Type 2 Diabetes: A French Prospective Cohort.

OBJECTIVE: We explored the prognostic value of three circulating candidate biomarkers-midregional-proadrenomedullin (MR-proADM), soluble tumor necrosis factor receptor 1 (sTNFR1), and N-terminal prohormone brain natriuretic peptide (NT-proBNP)-for change in renal function in patients with type 2 diabetes. RESEARCH DESIGN AND METHODS: Outcomes were defined as renal function loss (RFL), ≥40% decline of estimated glomerular filtration rate (eGFR) from baseline, and rapid renal function decline (RRFD), absolute annual eGFR slope <-5 mL/min/year. We used a proportional hazard model for RFL and a logistic model for RRFD. Adjustments were performed for established risk factors (age, sex, diabetes duration, HbA1c, blood pressure, baseline eGFR, and urinary albumin-to-creatinine ratio [uACR]). C-statistics were used to assess the incremental predictive value of the biomarkers to these risk factors. RESULTS: Among 1,135 participants (mean eGFR 76 mL/min, median uACR 2.6 mg/mmol, and median GFR slope -1.6 mL/min/year), RFL occurred in 397, RRFD developed in 233, and 292 died during follow-up. Each biomarker predicted RFL and RRFD. When combined, MR-proADM, sTNFR1, and NT-proBNP predicted RFL independently from the established risk factors (adjusted hazard ratio 1.59 [95% CI 1.34-1.89], P < 0.0001; 1.33 [1.14-1.55], P = 0.0003; and 1.22 [1.07-1.40], P = 0.004, respectively) and RRFD (adjusted odds ratio 1.56 [95% CI 1.7-2.09], P = 0.003; 1.72 [1.33-2.22], P < 0.0001; and 1.28 [1.03-1.59], P = 0.02, respectively). The combination of the three biomarkers yielded the highest discrimination (difference in C-statistic = 0.054, P < 0.0001; 0.067, P < 0.0001 for RFL; and 0.027, P < 0.0001 for RRFD). CONCLUSIONS: In addition to established risk factors, MR-proADM, sTNFR1, and NT-proBNP improve risk prediction of loss of renal function in patients with type 2 diabetes.

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.

Continuous renal replacement therapy versus intermittent hemodialysis in intensive care patients: impact on mortality and renal recovery.

PURPOSE: The best renal replacement therapy (RRT) modality remains controversial. We compared mortality and short- and long-term renal recovery between patients treated with continuous RRT and intermittent hemodialysis. METHODS: Patients of the prospective observational multicenter cohort database OUTCOMEREA™ were included if they underwent at least one RRT session between 2004 and 2014. Differences in patients' baseline and daily characteristics between treatment groups were taken into account by using a marginal structural Cox model, allowing one to substantially reduce the bias resulting from confounding factors in observational longitudinal data analysis. The composite primary endpoint was 30-day mortality and dialysis dependency. RESULTS: Among 1360 included patients with RRT, 544 (40.0 %) and 816 (60.0 %) were initially treated by continuous RRT and intermittent hemodialysis, respectively. At day 30, 39.6 % patients were dead. Among survivors, 23.8 % still required RRT. There was no difference between groups for the primary endpoint in global population (HR 1.00, 95 % CI 0.77-1.29; p = 0.97). In patients with higher weight gain at RRT initiation, mortality and dialysis dependency were significantly lower with continuous RRT (HR 0.54, 95 % CI 0.29-0.99; p = 0.05). Conversely, this technique appeared to be deleterious in patients without shock (HR 2.24, 95 % CI 1.24-4.04; p = 0.01). Six-month mortality and persistent renal dysfunction were not influenced by the RRT modality in patients with dialysis dependence at ICU discharge. CONCLUSION: Continuous RRT did not appear to improve 30-day and 6-month patient outcomes. It seems beneficial for patients with fluid overload, but might be deleterious in the absence of hemodynamic failure.

Dynamic Changes in Renal Function Are Associated With Major Cardiovascular Events in Patients With Type 2 Diabetes.

OBJECTIVE: The pattern of renal function decline prior to cardiovascular (CV) events in type 2 diabetes is not well known. Our aim was to describe the association between renal function trajectories and the occurrence of a CV event. RESEARCH DESIGN AND METHODS: We considered patients with type 2 diabetes from the SURDIAGENE (Survie, Diabete de type 2 et Genetique) study (discovery cohort) and the DIABHYCAR (Non-Insulin-Dependent Diabetes, Hypertension, Microalbuminuria or Proteinuria, Cardiovascular Events, and Ramipril) study (replication cohort). Global patterns of estimated glomerular filtration rate (eGFR) (Chronic Kidney Disease Epidemiology Collaboration [CKD-EPI]) and serum creatinine (SCr) prior to a major CV event (MACE) or last update were determined using a linear mixed-effects model and annual individual slopes computed by simple linear regression. RESULTS: In the 1,040 participants of the discovery cohort, establishment of global patterns including 22,227 SCr over 6.3 years of follow-up showed an annual eGFR decline and an annual SCr increase that were significantly greater in patients with MACE compared with patients without (-3.0 and -1.7 mL/min/1.73 m(2)/year and +10.7 and +4.0 µmol/L/year, respectively; P < 0.0001 for both). Median annual individual slopes were also significantly steeper in patients with MACE, and adjusted risk of MACE was 4.11 times higher (3.09-5.45) in patients with rapid decline in eGFR (change less than -5 mL/min/1.73 m(2)/year). Consideration of renal function trajectories provided significant additive information helping to explain the occurrence of MACE for both SCr and eGFR (PIDI < 0.0001 and P = 0.0005, respectively). These results were confirmed in the replication cohort. CONCLUSIONS: Renal function decline was associated with a higher risk of MACE. The pattern of renal function decline, beyond baseline kidney function, is an independent factor of CV risk.

One-year Results of the Effects of Rituximab on Acute Antibody-Mediated Rejection in Renal Transplantation: RITUX ERAH, a Multicenter Double-blind Randomized Placebo-controlled Trial.

BACKGROUND: Treatment of acute antibody-mediated rejection (AMR) is based on a combination of plasma exchange (PE), IVIg, corticosteroids (CS), and rituximab, but the place of rituximab is not clearly specified in the absence of randomized trials. METHODS: In this phase III, multicenter, double-blind, placebo-controlled trial, we randomly assigned patients with biopsy-proven AMR to receive rituximab (375 mg/m) or placebo at day 5. All patients received PE, IVIg, and CS. The primary endpoint was a composite of graft loss or no improvement in renal function at day 12. RESULTS: Among the 38 patients included, at 1 year, no deaths occurred, but 1 graft loss occurred in each group. The primary endpoint frequency was 52.6% (10/19) and 57.9% (11/19) in the rituximab and placebo groups, respectively (P = 0.744). Renal function improved in both groups, as soon as day 12 with no difference in serum creatinine level and proteinuria at 1, 3, 6, and 12 months. Supplementary administration of rituximab and total number of IVIg and PE treatments did not differ between the 2 groups. Both groups showed improved histological features of AMR and Banff scores at 1 and 6 months, with no significant difference between groups but with a trend in favor of the rituximab group. Both groups showed decreased mean fluorescence intensity of donor-specific antibodies as soon as day 12, with no significant difference between them but with a trend in favor of the rituximab group at 12 months. CONCLUSIONS: After 1 year of follow-up, we observed no additional effect of rituximab in patients receiving PE, IVIg, and CS for AMR. Nevertheless, our study was underpowered and important differences between groups may have been missed. Complementary trials with long-term follow-up are needed.

RAGE and CYBA polymorphisms are associated with microalbuminuria and end-stage renal disease onset in a cohort of type 1 diabetes mellitus patients over a 20-year follow-up.

AIMS: We investigated the association of polymorphisms of three genes implicated in oxidative stress: CYBA C242T, RAGE -374T/A and -429T/C, and ALOX12 Arg261Gln, with the delay of microalbuminuria onset in patients with type 1 diabetes mellitus (DT1). METHODS: A total of 162 T1D patients presenting with diabetes for 32.9 ± 9 years were included in the study; 53 had persistent microalbuminuria (>30 mg/l) and 109 did not. Onset of diabetes, microalbuminuria and end-stage renal disease (ESRD) were recorded as bio-clinical data. We determined polymorphism association of microalbuminuria with a Cox regression model. RESULTS: All polymorphisms respected the Hardy-Weinberg equilibrium. The Cox regression model validated four significant variables associated with microalbuminuria: RAGE 374AA (HR 4.19 [1.84-9.58] (p = 0.001)), CYBA TT+TC (HR 2.1 [1.16-3.80], p = 0.015), male sex (HR 1.92 [1.07-3.43], p = 0.028) and diabetes diagnosis at the pediatric stage (HR 1.85 [1.03-3.32], p = 0.039). The same association was found with ESRD (p = 0.028 and p = 0.033 for CYBA TC+TT and RAGE 374AA, respectively). CYBA C242T and RAGE 374T/A were not significantly associated with diabetic retinopathy. CONCLUSIONS: CYBA C242T and RAGE -374T/A correlate with microalbuminuria onset in the French DT1 cohort. The same correlation with ESRD onset supports the argument for the involvement of a genetic predisposition involving kidney-specific oxidative stress for diabetic nephropathy.