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The management of patients with kidney transplant failure (KTF) remains a complex process involving multiple stakeholders. A working group of the Transplantation Commission of the French-speaking Society of Nephrology, Dialysis and Transplantation (SFNDT) conducted a survey on the management of immunosuppressants (IS) after KTF among nephrologists at transplant centres and general nephrologists in France, Switzerland and Belgium between March and June 2023. We analysed 232 replies from 58 nephrologists at transplant centres and 174 general nephrologists, aged 43.6 (+10.6) years. In the first three months following KTF, nephrologists reported discontinuing antimetabolite, calcineurin inhibitor (CNI) and corticosteroid treatment in 83%, 39.9% and 25.8% of cases respectively. Conversely, some nephrologists reported that they were continuing to use CNI (14%) and corticosteroids (19.1%) on a long-term basis. The patient’s comorbidities associated with the discontinuation of IS treatment are cancer and opportunistic infections as KT’s complications and presence of diabetes mellitus at KTF, whereas humoral rejection encourages the IS to be maintained. Transplantectomy is proposed by nephrologists most often for graft intolerance syndrome (86.5%), more rarely to discontinue IS (17.6%) or in the absence of plans of new transplantation (9.3%). In multivariate analyses, the presence of a protocol in the centre facilitated the management of IS by the general nephrologists. The management of IS after AFG by French-speaking nephrologists is heterogeneous. Specific prospective studies are needed to establish new best practice recommendations, based on more robust evidence, which could encourage better adherence by nephrologists.

Background: Recent evidence suggests an overestimation of the benefits associated with arteriovenous (AV) fistula versus graft in certain populations. We assessed hazards of all-cause and cause-specific hospitalization and death associated with AV access type in patients who started hemodialysis with a catheter in France, overall and by subgroups of age, sex and comorbidities., Methods: We performed a target trial emulation including patients who initiated hemodialysis with a catheter from 2010 through 2018 and were followed by the REIN Registry. We identified first-created fistula or graft through the French national health-administrative database. We used joint frailty models to deal with recurrent hospitalizations and potential informative censoring by death, and inverse probability weighting to account for confounding., Results: From the 18 800 patients included (mean age 68 ± 15 years, 35% women), 5% underwent AV graft creation first. The weighted hazard ratio (wHR) of all-cause hospitalization associated with graft was 1.08 [95% confidence interval (CI) 1.02 to 1.15], that of vascular access-related hospitalization was 1.43 (95% CI 1.32 to 1.55), and those of cardiovascular- and infection-related hospitalizations were 1.14 (95% CI 1.03 to 1.26) and 1.11 (95% CI 0.97 to 1.28), respectively. Results were consistent for most subgroups, except that the highest hazard of all-cause, cardiovascular- and infection-related hospitalizations with graft was blunted in patients with comorbidities (i.e. diabetes, wHR 1.01, 95% CI 0.93 to 1.10; 1.10, 95% CI 0.96 to 1.26; and 0.94, 95% CI 0.78 to 1.12, respectively)., Conclusions: In patients starting hemodialysis with a catheter, AV graft creation is associated with increased hazard of vascular access-related hospitalizations compared with fistula. This may not be the case for death or other causes of hospitalization., (© The Author(s) 2023. Published by Oxford University Press on behalf of the ERA.)

Introduction: Pre-emptive access to the kidney transplant (KT) waiting list remains limited in France, with only 3.9% of patients on pre-emptive KT and 5.6% of patients registered at the time of initiation of dialysis. A similar trend was observed in Aquitaine. The aim of this study was to assess the impact of a regional program in terms of access to the waiting list for patients initiating a kidney replacement therapy (KRT)., Methods: We included all patients assessed for registration on the list between 2017 and 2020, 2017 being the reference year and 2018 the beginning of the program. Using the CRISTAL and REIN registries, we assessed changes in the number of patients on the list at the time of initiation of dialysis or transplantation., Results: The number of new assessed candidates increased gradually each year from 255 in 2017 to 352 in 2020 (+38%). The number of patients on the list sharply increased in 2018 from 229 in 2017 to 319 in 2018 (+39.3%) and then remained stable. At the initiation of KRT, the proportion of patients registered on the waiting list increased gradually from 7.1% in 2017 to 18.2% in 2020. The proportion of pre-emptive KT remained stable between 2017 and 2021 (around 7%) with a decrease in 2020 (4.6%). Approximately 60% of patients had a contraindication to transplantation throughout the study., Conclusion: This study showed that a regional program aimed at providing better information to healthcare professionals and patients and encouraging rapid assessment of transplant candidates could increase the rate of pre-emptive registration on the KT waiting list for eligible patients over 4 years.

Background: The trajectories of haemoglobin in patients with chronic kidney disease (CKD) have been poorly described. In such patients, we aimed to identify typical haemoglobin trajectory profiles and estimate their risks of major adverse cardiovascular events (MACE)., Methods: We used 5-year longitudinal data from the CKD-REIN cohort patients with moderate to severe CKD enrolled from 40 nationally representative nephrology clinics in France. A joint latent class model was used to estimate, in different classes of haemoglobin trajectory, the competing risks of (i) MACE + defined as the first event among cardiovascular death, non-fatal myocardial infarction, stroke or hospitalization for acute heart failure, (ii) initiation of kidney replacement therapy (KRT) and (iii) non-cardiovascular death., Results: During the follow-up, we gathered 33 874 haemoglobin measurements from 3011 subjects (median, 10 per patient). We identified five distinct haemoglobin trajectory profiles. The predominant profile (n = 1885, 62.6%) showed an overall stable trajectory and low risks of events. The four other profiles had nonlinear declining trajectories: early strong decline (n = 257, 8.5%), late strong decline (n = 75, 2.5%), early moderate decline (n = 356, 11.8%) and late moderate decline (n = 438, 14.6%). The four profiles had different risks of MACE, while the risks of KRT and non-cardiovascular death consistently increased from the haemoglobin decline., Conclusion: In this study, we observed that two-thirds of patients had a stable haemoglobin trajectory and low risks of adverse events. The other third had a nonlinear trajectory declining at different rates, with increased risks of events. Better attention should be paid to dynamic changes of haemoglobin in CKD., (© The Author(s) 2023. Published by Oxford University Press on behalf of the ERA.)

Background: Acute kidney injury (AKI) in intensive care unit (ICU) patients with severe COVID-19 is common (> 50%). A specific inflammatory process has been suggested in the pathogenesis of AKI, which could be improved by dexamethasone (DXM). In a small monocenter study (n = 100 patients), we reported a potential protective effect of DXM on the risk of AKI. This study aimed to investigate the preventive impact of DXM on AKI in a multicenter study of patients with severe COVID-19., Methods: We conducted a multicenter study in three French ICUs from March 2020 to August 2021. All patients admitted to ICU for severe COVID-19 were included. Individuals with preexistent AKI or DXM administration before admission to ICU were excluded. While never used during the first wave, DXM was used subsequently at ICU entry, providing two treatment groups. Multivariate Cause-specific Cox models taking into account changes in ICU practices over time, were utilized to determine the association between DXM and occurrence of AKI., Results: Seven hundred and ninety-eight patients were included. Mean age was 62.6 ± 12.1 years, 402/798 (50%) patients had hypertension, and 46/798 (6%) had previous chronic kidney disease. Median SOFA was 4 [3-6] and 420/798 (53%) required invasive mechanical ventilation. ICU mortality was 208/798 (26%). AKI was present in 598/798 (75%) patients: 266/598 (38%), 163/598 (27%), and 210/598 (35%) had, respectively, AKI KDIGO 1, 2, 3, and 61/598 (10%) patients required renal replacement therapy. Patients receiving DXM had a significantly decreased hazard of AKI occurrence compared to patients without DXM (HR 0.67; 95CI 0.55-0.81). These results were consistent in analyses that (1) excluded patients with DXM administration to AKI onset delay of less than 12 h, (2) incorporating the different 'waves' of the COVID-19 pandemic., Conclusions: DXM was associated with a decrease in the risk of AKI in severe COVID-19 patients admitted to ICU. This supports the hypothesis that the inflammatory injury of AKI may be preventable., (© 2024. The Author(s).)

Background: In France, kidney diseases of undetermined origin account for 5%-20% of all causes of end-stage kidney disease. We investigated the impact of social disadvantage on the lack of aetiological diagnosis of nephropathies., Methods: Data from patients who started dialysis in France between 1 January 2017 and 30 June 2018 were extracted from the French Renal Epidemiology and Information Network registry. The social deprivation of each individual was estimated by the European Deprivation Index (EDI) defined by the patient's address. Logistic regression was used to perform mediation analysis to study the potential association between social deprivation and unknown nephropathy., Results: Of the 7218 patients included, 1263 (17.5%) had unknown kidney disease. A total of 394 (31.4%) patients in the unknown kidney disease belonged to the most deprived quintile of the EDI [fifth quintile (Q5)], vs 1636 (27.5%) patients in the known kidney disease group. In the multivariate analysis, unknown kidney disease was associated with Q5 (odds ratio 1.40, 95% confidence interval 1.12-1.74, P = .003). Mediation analysis did not identify any variables (e.g. obesity, initiation of dialysis in emergency, number of visits to the general practitioner and nephrologist before initiation of dialysis, date of first nephrology consultation) that mediated the association between social deprivation and nephropathy of unknown origin., Conclusions: Our results show that, compared with nondeprived subjects, individuals experiencing social deprivation have a higher risk of unknown nephropathy at dialysis initiation. However, mediation analysis did not identify any variables that explained the association between social deprivation and nephropathy of unknown origin., (© The Author(s) 2023. Published by Oxford University Press on behalf of the ERA.)

On the occasion of the 20th anniversary of the REIN (French Renal Epidemiology and Information Network), a summary work on the contributions of the national French ESKD register was carried out. On the issue of access to renal transplantation for ESKD patients, the following key messages were retained. The registry of the REIN includes data about kidney transplant and dialysis. It thus allows evaluating the access to kidney transplant in France based on the needs of the population with stage 5 CKD treated by renal replacement therapy. The data produced by the registry is complementary to the data in the report of the Agence de la biomédecine (Agency of Biomedicine) based on the activity of the transplant centres and the population of registered patients waiting for a transplant. The proportion of preemptive transplant (transplant without prior recourse to dialysis) as well as that of preemptive registration (before starting dialysis) have increased since 2012 but remain low. The proportion of preemptive transplant as the first replacement therapy remains low and stable over time at around 3 to 4%. The access to the waiting list and the transplant varies depending on the age and co-morbidities of the patients (diabetes, obesity) as well as on the region. The rates of registration on the kidney transplant waiting list at the time of initiation of dialysis and at 1 year from the start have been increasing since 2012, irrespective of the patients’ characteristics, though it remains low in elderly, diabetic and severely obese patients. This is partly the result related to the publication of the HAS (French National Authority for Health) recommendations in 2015 and the publications on the disparities in access to transplants established thanks to the REIN registry. The causes of non-registration at the time of initiation of dialysis have changed over time with some patients not registering for contraindication steadily decreasing since 2012. Thanks to several studies conducted using data from the registry, the variations in access to the list could be explained, partly, by the health condition of the dialysis population as well as by the socio-economic context and differences in practices according to dialysis networks. The median waiting time for a kidney transplant has been gradually increasing since 2012, with a delta of about 8 months between 2012 and 2020. However, the waiting time between the initiation of dialysis and the transplant has increased less significantly. The probability of receiving a first kidney transplant depends on the age, diabetic status and obesity of the patient, and has remained stable over time.

Launched in 2013 supported by the Program “Cohorts – Investments for the Future”, the CKD-REIN (Chronic Kidney Disease – Renal Epidemiology and Information Network) study is a prospective cohort that included and followed for 5 years more than 3000 patients with moderate or advanced chronic kidney disease (CKD), from 40 nationally representative nephrology clinics. A large amount of data was collected on CKD and its treatments, patient social characteristics and reported outcomes, and nephrology practices and services. A total of 170,000 blood and urine samples were collected and stored in a central biobank. Coordinated with the CKD outcomes and practice pattern study (CKDopps) and collaborating with the international Network of CKD cohorts (iNETCKD), CKD-REIN contributes to the understanding of CKD and the positioning of France with respect to CKD epidemiology and care in the world. This review highlights major findings from the cohort, and their potential implications for clinical practices and the health system, grouped into the following themes: (1) the complexity of patients with CKD; (2) adherence to clinical guidelines; (3) treatment practices and drug risk; (4) acute on chronic kidney disease; (5) CKD metabolic complications; (6) prediction of kidney failure; (7) sex differences in CKD; (8) patient perspective on CKD; (9) transition to kidney failure and replacement therapy; (10) conservative care.

We investigated the shape of the relationship between longitudinal uric acid (UA) and the hazard of kidney failure and death in chronic kidney disease (CKD) patients, and attempted to identify thresholds associated with increased hazards. We included CKD stage 3-5 patients from the CKD-REIN cohort with one serum UA measurement at cohort entry. We used cause-specific multivariate Cox models including a spline function of current values of UA (cUA), estimated from a separate linear mixed model. We followed 2781 patients (66% men, median age, 69 years) for a median of 3.2 years with a median of five longitudinal UA measures per patient. The hazard of kidney failure increased with increasing cUA, with a plateau between 6 and 10 mg/dl and a sharp increase above 11 mg/dl. The hazard of death had a U-shape relationship with cUA, with a hazard twice higher for 3 or 11 mg/dl, compared to 5 mg/dl. In CKD patients, our results indicate that UA above 10 mg/dl is a strong risk marker for kidney failure and death and that low UA levels below 5 mg/dl are associated with death before kidney failure., (© 2023. The Author(s).)

Background: Patients suffering from acute kidney injury(AKI) in the intensive care unit (ICU) can have various renal trajectories and outcomes. Aims were to assess the various clinical trajectories after AKI in the ICU and to determine risk factors for developing chronic kidney disease (CKD)., Methods: We conducted a prospective 5-year follow-up study in a medical ICU at Bordeaux University Hospital (France). The patients who received invasive mechanical ventilation, catecholamine infusion or both and developed an AKI from September 2013 to May 2015 were included. In the Cox analysis, the violation of the proportional hazard assumption for AKD was handled using appropriate interaction terms with time, resulting in a time-dependent hazard ratio (HR)., Results: A total of 232 patients were enrolled, with an age of 62 ± 16 years and a median follow-up of 52 days (interquartile range 6-1553). On day 7, 109/232 (47%) patients progressed to acute kidney disease (AKD) and 66/232 (28%) recovered. A linear trajectory (AKI, AKD to CKD) was followed by 44/63 (70%) of the CKD patients. The cumulative incidence of CKD was 30% [95% confidence interval (CI) 24-36] at the 5-year follow-up. In a multivariable Cox model, in the 6 months following AKI, the HR for CKD was higher in AKD patients [HR 29.2 (95% CI 8.5-100.7); P < 0.0001). After 6 months, the HR for CKD was 2.2 (95% CI 0.6-7.9; P = 0.21; n = 172 patients)., Conclusion: There were several clinical trajectories of kidney disease after ICU-acquired AKI. CKD risk was higher in AKD patients only in the first 6 months. Lack of renal recovery rather than AKD per se was associated with the risk of CKD., (© The Author(s) 2022. Published by Oxford University Press on behalf of the ERA.)

To assess quality of care, groups of care units that cared for the same patients at various stages of end-stage renal disease, might be more appropriate than the centre level. These groups constitute "communities" that need to be delineated to evaluate their practices and outcomes. In this article, we describe the use of an agglomerative (Fast Greedy) and a divisive (Edge Betweenness) method to describe dialysis activities in France. The validation was based on the opinion of the field actors at the regional level of the REIN registry. At the end of 2018, ESRD care in France took place in 1,166 dialysis units. During 2016-2018, 32 965 transfers occurred between dialysis units. With the Edge Betweenness method, the 1,114 French dialysis units in metropolitan France were classified into 156 networks and with the Fast Greedy algorithm, 167 networks. Among the 32 965 transfers, 23 168 (70%) were defined in the same cluster by the Edge Betweenness algorithm and 26 016 (79%) in the same cluster by the Fast Greedy method. According to the Fast Greedy method, during the study period, 95% of patients received treatment in only one network. According to the opinion of the actors in the field, the Fast Greedy algorithm seemed to be the best method in the context of dialysis activity modelling. The Edge Betweenness classification was not retained because it seemed too sensitive to the volume of links between dialysis units., Competing Interests: The authors have declared that no competing interests exist

Background: Although kidney transplantation (KT) is considered the best treatment for end-stage renal disease (ESRD), there are concerns about its benefit in the obese population because of the increased incidence of post-transplant adverse events. We compared patients who underwent KT versus patients awaiting KT on dialysis., Methods: We estimated the life expectancy [restricted mean survival time (RMST)] for a 10-year follow-up by matching on time-dependent propensity scores. The primary outcome was time to death., Results: In patients with a body mass index (BMI) ≥30 kg/m2 (n = 2155 patients per arm), the RMST was 8.23 years [95% confidence interval (CI) 8.05-8.40] in the KT group versus 8.00 years (95% CI 7.82-8.18) in the awaiting KT group, a difference of 2.71 months (95% CI -0.19-5.63). In patients with a BMI ≥35 kg/m2 (n = 212 patients per arm), we reported no significant difference [8.56 years (95% CI 7.96-9.08) versus 8.66 (95% CI 8.10-9.17)]. Hence we deduced that KT in patients with a BMI between 30 and 35 kg/m2 was beneficial in terms of life expectancy., Conclusion: Regarding the organ shortage, KT may be questionable for those with a BMI ≥35 kg/m2. These results do not mean that a BMI ≥35 kg/m2 should be a barrier to KT, but it should be accounted for in allocation systems to better assign grafts and maximize the overall life expectancy of ESRD patients., (© The Author(s) 2022. Published by Oxford University Press on behalf of the ERA.)

Background: Kidney transplantation (KT) is the optimal treatment for children with end-stage kidney disease. The aim of this study was to evaluate the impact of preemptive kidney transplantation (PKT) and of pretransplant dialysis duration on graft survival among French pediatric kidney transplant recipients., Methods: We analyzed all first pediatric kidney-only transplantations performed in France between 1993 and 2012. A Cox multivariable model was used to investigate the association of PKT and pretransplant dialysis time with the hazard of graft failure defined as death, return to dialysis, or retransplant, whichever occurred first., Results: Patients (n = 1911) were included, of which 380 (19.8%) received a PKT. Median time of follow-up was 7.0 y. PKT was associated with a 55% reduction of the hazard of graft failure at any time after KT compared with patients transplanted after dialysis (hazard ratio, 0.45; 95% confidence interval, 0.33-0.62), after adjustment for recipient sex and age, primary kidney disease, donor age and type (living or deceased donor), number of HLA mismatches, cold ischemia time, and year of transplantation. A reduction of the hazard of graft failure was found in PKT whatever the compared duration of dialysis, even when <6 mo and whatever the dialysis modality. Results were similar in multiple sensitivity analyses., Conclusions: In France, PKT among pediatric patients is associated with a better graft survival when compared with KT after dialysis, even when <6 mo. Based on these findings, we suggest that PKT should be considered as the treatment of choice for children with end-stage kidney disease., Competing Interests: The authors declare no conflicts of interest., (Copyright © 2021 Wolters Kluwer Health, Inc. All rights reserved.)

Background: Early diagnosis of thrombotic thrombocytopenic purpura (TTP) versus hemolytic and uremic syndrome (HUS) is critical for the prompt initiation of specific therapies., Objective: To evaluate the diagnostic performance of the proteinuria/creatininuria ratio (PU/CU) for TTP versus HUS., Patients/methods: In a retrospective study, in association with the "French Score" (FS) (platelets < 30 G/L and serum creatinine level < 200 µmol/L), we assessed PU/CU for the diagnosis of TTP in patients above the age of 15 with thrombotic microangiopathy (TMA). Patients with a history of kidney disease or with on-going cancer, allograft or pregnancy were excluded from the analysis., Results: Between February 2011 and April 2019, we identified 124 TMA. Fifty-six TMA patients for whom PU/CU were available, including 35 TTP and 21 HUS cases, were considered. Using receiver-operating characteristic curves (ROC), those with a threshold of 1.5 g/g for the PU/CU had a 77% sensitivity (95% CI (63, 94)) and a 90% specificity (95% CI (71, 100)) for TTP diagnosis compared with those having an 80% sensitivity (95% CI (66, 92)) and a 90% specificity (95% CI (76, 100) with a FS of 2. In comparison, a composite score, defined as a FS of 2 or a PU/CU ≤ 1.5 g/g, improved sensitivity to 99.6% (95% CI (93, 100)) for TTP diagnosis and enabled us to reclassify seven false-negative TTP patients., Conclusions: The addition of urinary PU/CU upon admission of patients with TMA is a fast and readily available test that can aid in the differential diagnosis of TTP versus HUS alongside traditional scoring.

Background: Kidney failure with replacement therapy and hemodialysis are associated with a decrease in quality of life (QOL). Self-reported QOL symptoms are not always prioritized by the medical team, potentially leading to conflicting priorities with patients. Electronic patient-reported outcome measures (ePROMs) allow physicians to better identify these symptoms. The objective was to describe the prevalence of symptoms self-reported by hemodialysis (HD) patients., Methods: A multicenter cross-sectional study was conducted in three HD centers. Patients were included if they were 18 years old or over treated with HD for at least 3 months in a center. Data were collected by the patient via a self-administered ePROMs questionnaire. Data included patient characteristics, post-dialysis fatigue and intensity, recovery time after a session, perceived stress, impaired sleep the day before the dialysis session, current state of health and the change from the past year. A multivariate analysis was conducted to identify relations between symptoms., Results: In total, we included 173 patients with a mean age of 66.2 years, a mean ± SD hemodialysis duration of 48.9 ± 58.02 months. The prevalence of fatigue was 72%. 66% had a high level of stress (level B or C). Recovery time was more than 6 h after a HD session for 25% of patients and 78% declared they had a better or unchanged health status than the previous year. Sleep disturbance was associated with cardiovascular comorbidities (OR 5.08 [95% CI, 1.56 to 16.59], p = 0.007)., Conclusions: Fatigue and stress were the main symptoms reported by HD patients. The patient's care teams should better consider these symptoms., (© 2021. The Author(s).)

Background: Muscle strength decreases as kidney failure progresses. Low muscle strength affects more than 50% of hemodialysis patients and leads to daily life activities impairment. In the general population, numerous studies have linked low 25OH-vitamin D (25OHD) concentrations to the loss of the muscle strength and low physical performances. Data on native vitamin D and muscle function are scarce in the chronic kidney disease (CKD) population, but low 25OHD levels have been associated with poor muscle strength. We present in this article the protocol of an ongoing study named VITADIAL testing if cholecalciferol supplementation in hemodialysis patients with low 25OHD improves their muscle strength., Methods/design: VITADIAL is a prospective open randomized French multicenter study. All patients will have 25OHD levels ≤50nmol/L at randomization. One group will receive 100,000 UI cholecalciferol once a month during 6 months; the other group will receive no treatment during 6 months. In order to randomize patients with 25OHD ≤50nmol/L, supplemented patients will undergo a 3 months wash-out period renewable 3 times (maximum of 12 months wash-out) until 25OHD reaches a level ≤50nmol/L. The main objective of this study is to analyze if a 6-month period of oral cholecalciferol (i.e., native vitamin D) supplementation improves muscle strength of hemodialysis patients with low 25OHD vitamin D levels. Muscle strength will be assessed at 0, 3, and 6 months, by handgrip strength measured with a quantitative dynamometer. Secondary objectives are (1) to analyze 25OHD plasma levels after vitamin D wash-out and/or supplementation, as well as factors associated with 25OHD lowering speed during wash-out, and (2) to analyze if this supplementation improves patient's autonomy, reduces frailty risk, and improves quality of life. Fifty-four patients are needed in each group to meet our main objective., Discussion: In the general population, around 30 randomized studies analyzed the effects of vitamin D supplementation on muscle strength. These studies had very different designs, sizes, and studied population. Globally, these studies and the meta-analysis of studies favor a beneficial effect of vitamin D supplementation on muscle strength, but this effect is mainly found in the subgroup of aged patients and those with the lowest 25OHD concentrations at inclusion. We reported a positive independent association between 25OHD and handgrip strength in a population of 130 hemodialysis patients in a dose-dependent manner. In our cohort, a plateau effect was observed above 75 nmol/L. Only two randomized studies analyzed the effect of native vitamin D supplementation on muscle strength in hemodialysis patients, but unfortunately, these two studies were underpowered. VITADIAL is a trial specifically designed to assess whether cholecalciferol might benefit to hemodialysis patient's muscle strength., Trial Registration: ClinicalTrials.gov NCT04262934 . Registered on 10 February 2020 - Retrospectively registered.

Background: Non-adherence with immunosuppressant medication (MNA) fosters development of de novo donor-specific antibodies ( dn DSA), rejection, and graft failure (GF) in kidney transplant recipients (KTRs). However, there is no simple tool to assess MNA, prospectively. The goal was to monitor MNA and analyze its predictive value for dn DSA generation, acute rejection and GF., Methods: We enrolled 301 KTRs in a multicentric French study. MNA was assessed prospectively at 3, 6, 12, and 24 months (M) post-KT, using the Morisky scale. We investigated the association between MNA and occurrence of dn DSA at year 2 post transplantation, using logistic regression models and the association between MNA and rejection or graft failure, using Cox multivariable models., Results: The initial percentage of MNA patients was 17.7%, increasing to 34.6% at 24 months. Nineteen patients (8.4%) developed dn DSA 2 to 3 years after KT. After adjustment for recipient age, HLA sensitization, HLA mismatches, and maintenance treatment, MNA was associated neither with dn DSA occurrence, nor acute rejection. Only cyclosporine use and calcineurin inhibitor (CNI) withdrawal were strongly associated with dn DSA and rejection. With a median follow-up of 8.9 years, GF occurred in 87 patients (29.0%). After adjustment for recipient and donor age, CNI trough level, dn DSA, and rejection, MNA was not associated with GF. The only parameters associated with GF were dn DSA occurrence, and acute rejection., Conclusions: Prospective serial monitoring of MNA using the Morisky scale does not predict dn DSA occurrence, rejection or GF in KTRs. In contrast, cyclosporine and CNI withdrawal induce dnDSA and rejection, which lead to GF.

After kidney transplantation, withdrawal of calcineurin inhibitors (CNI) and conversion to sirolimus (SRL) may reduce the occurrence of new non-melanoma skin cancer (NMSC). Conversely, a reduced CNI exposure with everolimus (EVR) is an alternative strategy that has not been thoroughly evaluated. We retrospectively compared the occurrence of newly diagnosed NMSCs in two cohorts of kidney transplant recipients (KTR) with at least one NMSC: 35 patients were converted to EVR with reduced CNI exposure (CNI/EVR group), whereas 46 patients were converted to SRL in association with mycophenolic acid (MPA) (SRL/MPA group). Two years after conversion, survival free of new NMSC was similar between the two cohorts (p = .37), with 19 KTR (54.3%) in the CNI/EVR group and 22 (47.8%) in the SRL/MPA group being diagnosed of at least one new NMSC. Half of the KTR from both groups showed adverse events, leading to mTORi discontinuation for 37.1% of KTR in the CNI/EVR group and 21.7% in the SRL/MPA group (p = .09). The incidence of rejections was similar between the two groups. In a retrospective cohort of KTR with at least one post-transplant NMSC, the outcome of the patients converted to a CNI/EVR regimen was not different from those converted to a SRL/MPA regimen., (© 2021 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Background: Tuberous sclerosis complex (TSC) is a rare autosomal dominant genetic disorder. Due to the various manifestations of TSC and their potential complications, a multidisciplinary care approach is recommended by consensus guidelines., Objectives: Our study aimed to give a complete description of our TSC adult cohort and to evaluate the multidisciplinary and interdisciplinary management model., Methods: Data on each adult patient diagnosed with TSC, including disease manifestations, interventions and outcomes, were collected at baseline and updated annually. A multidisciplinary TSC approach with all the recommended explorations was carried out annually., Results: 90 patients were enrolled in Centre Hospitalier Universitaire de Bordeaux, between January 2000 and September 2018. Median age of patients at inclusion was 37 years (range, 27-47) and 20 years old at diagnosis of TSC. Regarding the occurrence of TSC manifestations, 97% of the patients had cutaneous lesions, 89% had neurological manifestations, 83% had renal manifestations and 100% had dental lesions with pits. More than half the patients had sclerotic bone lesions (68%), TSC-associated neuropsychiatric disorders (64%) and lymphangioleiomyomatosis (59%). A TSC multidisciplinary approach was developed including a global follow-up and an evaluation of TSC targeting organs, according to the recommendations. A satisfaction survey revealed global and entire satisfaction of patients with TSC., Conclusion: We obtained an accurate description of a cohort of adult patients with TSC. Our multidisciplinary approach model allowed us to provide optimal management of patients with TSC with a high level of patient satisfaction., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2021. No commercial re-use. See rights and permissions. Published by BMJ.)

Background: Early kidney transplantation (KT) is the best option for patients with end-stage kidney disease, but little is known about dialysis access strategy in this context. We studied practice patterns of dialysis access and how they relate with outcomes in adults wait-listed early for KT according to the intended donor source., Methods: This study from the REIN registry (2002-2014) included 9331 incident dialysis patients (age 18-69) wait-listed for KT before or by 6 months after starting dialysis: 8342 candidates for deceased-donor KT and 989 for living-donor KT. Subdistribution hazard ratios (SHR) of KT and death associated with hemodialysis by catheter or peritoneal dialysis compared with arteriovenous (AV) access were estimated with Fine and Gray models., Results: Living-donor candidates used pretransplant peritoneal dialysis at rates similar to deceased-donor KT candidates, but had significantly more frequent catheter than AV access for hemodialysis (adjusted OR 1.25; 95%CI 1.09-1.43). Over a median follow-up of 43 (IQR: 23-67) months, 6063 patients received transplants and 305 died before KT. Median duration of pretransplant dialysis was 15 (7-27) months for deceased-donor recipients and 9 (5-15) for living-donor recipients. Catheter use in deceased-donor candidates was associated with a lower SHR for KT (0.88, 95%CI 0.82-0.94) and a higher SHR for death (1.53, 95%CI 1.14-2.04). Only five deaths occurred in living-donor candidates, three of them with catheter use., Conclusions: Pretransplant dialysis duration may be quite long even when planned with a living donor. Advantages from protecting these patients from AV fistula creation must be carefully evaluated against catheter-related risks.

Background: Kidney transplantation (KT) is the treatment of choice for end-stage renal disease. Preemptive KT (PKT) should be considered when glomerular filtration rate is <15 mL/min/1.73 m2 but European reports on the results of PKT and the effect of pretransplant dialysis are scarce., Methods: We analysed all first kidney-only transplants performed in adults in France between 2002 and 2012. A Cox multivariable model was used to investigate the association of PKT and of pretransplant dialysis time with the hazard of graft failure defined as death, return to dialysis or retransplant, whichever occurred first., Results: We included 22 345 patients, with a mean ± SD age at KT of 50.5 ± 13.4 years; 61.9% were men and 3112 (14.0%) received a PKT. Median time of follow-up was 4.7 years. Graft failure occurred in 4952 patients up to 31 December 2013. After adjustment for recipients' age and sex, primary kidney disease, donor type (living or deceased donor, expanded criteria donor), HLA mismatches, cold ischaemia time, centre and year of transplantation, PKT was associated with a decreased hazard of graft failure when compared with pretransplant dialysis [hazard ratio (HR) 0.57; 95% confidence interval (CI) 0.51-0.63], whatever the duration of dialysis, even in the first 6 months. The effect of PKT on the hazard of graft failure was stronger in living kidney donors (HR 0.32; 95% CI 0.19-0.55)., Conclusions: In France, PKT was associated with a lower risk of graft failure than KT performed after the initiation of dialysis, whatever the duration of dialysis., (© The Author(s) 2018. Published by Oxford University Press on behalf of ERA-EDTA. All rights reserved.)

There are various histopathological forms of idiopathic nephrotic syndrome, including minimal change disease (MCD) and focal segmental glomerulosclerosis (FSGS). Whereas some relapse predictor factors have been identified in renal transplantation, the clinical future of idiopathic nephrotic syndrome in the native kidney remains uncertain. We designed a multicentric retrospective descriptive cohort study including all patients aged 15 years and over whose renal biopsy confirmed MCD or FSGS between January 2007 and December 2014. We studied 165 patients with idiopathic nephrotic syndrome; 97 with MCD and 68 with FSGS. In the MCD cohort, 91.7% of patients were treated with corticosteroids for a median total duration of 13 months. During 45 months of follow-up, 92.8% of patients achieved remission and 45.5% experienced relapse. In this cohort, 5% of patients experienced terminal kidney disease. With respect to FSGS patients, 51.5% were treated with corticosteroids for a median total duration of 15 months. During 66 months of follow-up, 73.5% of patients achieved remission and 20% experienced relapse. In this cohort, 26.5% of patients experienced terminal kidney disease. No statistical association was observed between clinical and biological initial presentation and relapse occurrence. This study describes the characteristics of a cohort of patients with the nephrotic idiopathic syndromes of MCD and FSGS from the time of renal biopsy and throughout follow-up.

The acid production of endogenous origin depends mainly on the metabolism of the food and varies with the nature of these. Of the order of 1mEq/kg/day for contemporary food in industrialized countries, it is reduced by more than one third among vegetarians and close to neutrality among vegans. The dietary acid load is eliminated by the normal kidneys, thus maintaining the acid-base equilibrium. In the setting of CKD, it will overflow the capacities of the nephrons, generating a retention of H+ ions, promoting subclinical acidosis. This tissue retention of H+ ions was confirmed by direct techniques in animal models and indirect techniques in humans. The systemic retention of H+ ions and the accompanying compensatory mechanisms have negative consequences on bone tissue, skeletal muscle, cardiovascular risk and renal function. In the animal, the substitution of casein (acid) by soy (alkaline) prevents metabolic acidosis and slows the progression of renal insufficiency. In man, various prospective studies have confirmed that the risk of renal insufficiency was positively correlated with the dietary acid load. Conversely, bicarbonate supplementation and/or a diet enriched with fruits and vegetables, have a favorable effect on renal insufficiency, including in subjects with normal bicarbonate. These results lead to reconsider the K/DOQI recommendations to correct acidosis when the bicarbonate level falls below 22mEq/L, since tissue retention of H+ ions and its negative consequences appear at higher or even normal levels of bicarbonates., (Copyright © 2017 Société francophone de néphrologie, dialyse et transplantation. Published by Elsevier Masson SAS. All rights reserved.)