The epidemiology of fungal infections in transplant patients.

Transplant patients, including solid-organ transplant (SOT) and hematopoietic stem cell transplant (HSCT) recipients, are exposed to various types of complications, particularly rejection. To prevent these outcomes, transplant recipients commonly receive long-term immunosuppressive regimens that in turn make them more susceptible to a wide array of infectious diseases, notably those caused by opportunistic pathogens. Among these, invasive fungal infections (IFIs) remain a major cause of mortality and morbidity in both SOT and HSCT recipients. Despite the continuing improvement in early diagnostics and treatments of IFIs, the management of these infections in transplant patients is still complicated. Here, we provide an overview concerning the most recent trends in the epidemiology of IFIs in SOT and HSCT recipients by describing the prominent yeasts and molds species involved, the timing of post-transplant IFIs and the risk factors associated with their occurrence in these particularly weak populations. We also give special emphasis into basic research advances in the field that recently suggested a role of the global and long-term prophylactic regimen in orchestrating various biological disturbances in the organism and conditioning the emergence of the most adapted fungal strains to the particular physiological profiles of transplant patients.

Sex-related differences in pre-dialysis trajectories and dialysis initiation: A French nationwide retrospective study.

BACKGROUND: In the last two decades, sex and gender differences have been documented in chronic kidney disease (CKD) management, including access to renal replacement therapy and its outcomes. The objectives of this study were to 1) compare the pre-dialysis healthcare utilization in men and women, and 2) examine the sex-specific factors associated with emergency dialysis start. METHODS: Adult patients with CKD who started dialysis in France in 2015 were extracted from the Renal Epidemiology and Information Network registry. Patients were matched to the French National Health Data System database to extract healthcare utilization data for the 2 years before dialysis start. Frequencies and monthly rates of consultations and hospitalizations were compared between men and women. Logistic regression analyses were performed separately in the two groups. RESULTS: Among the 8856 patients included, 3161 (35.7%) were women. Median age (71 years) and estimated glomerular filtration rate (8.1 and 7.7 ml/min for men and women) were similar between groups at dialysis start. Monthly consultations rates with a general practitioner and nephrology-related care were similar between women and men. Some sex-specific differences were found: higher frequencies of consultations with a psychiatrist in women and more frequent hospitalizations for circulatory system diseases in men. Emergency dialysis start rate was 30% in both groups. Emergency dialysis start was associated with acute nephropathy, compared with slowly progressive nephropathy, in women but not in men (OR = 1.48, p<0.01 vs 1.15, p = 0.18). CONCLUSIONS: This study found similar quantitative pre-dialysis healthcare utilization in men and women. To better understand sex/gender differences in CKD care trajectories, future research should focus on patients with CKD who are unknown to nephrology services, on patients receiving conservative care and on the sex/gender-specific mechanisms underlying care decision-making.

Study of therapeutic patient education practices in French renal transplantation centres.

OBJECTIVES: Therapeutic patient education (TPE) plays a critical role in the management of kidney transplant recipients. However, discrepancies exist in the guidance provided regarding the usage of immunosuppressants across different kidney transplant centres in France. METHODS: To assess the current landscape of TPE practices in this patient population, an online questionnaire consisting of 51 questions was distributed to 32 French renal transplantation centres. RESULTS: The participation rate in our survey was 96.9%, (31 of the 32 centres contacted). The respondents had diverse professions: they were nurses (15/31), physicians (9/31) and pharmacists (7/31). Virtually all institutions have implemented TPE initiatives, with an implementation rate of 93.5% (29/31). The topic of anti-rejection medication was consistently addressed, with only one centre not providing support at the conclusion of these sessions. However, the content of the sessions varied significantly from one centre to another, particularly regarding the proper management of anti-rejection medications. Only 19.4% (6/31) of the centres provided the correct recommendation regarding fasting when taking tacrolimus. Dietary guidance was a topic covered in 89.7% (26/29) of the centres, but significant divergences were also observed. TPE teams primarily consisted of nurses, with pharmacists present in only 51.6% (16/31) of the centres. We also observed limited involvement of patient partners, with just 9.7% (3/31) of the centres including them in their programme. CONCLUSION: These findings highlight considerable variability in the approach towards TPE among kidney transplant centres. Addressing counselling variability and increasing pharmacist and patient partner involvement is an essential step to improving the quality and effectiveness of TPE. By establishing a standardised and comprehensive approach to patient education, healthcare providers can ensure that kidney transplant recipients receive information that will ultimately help them improve their health and well-being.

Lower access to kidney transplantation for women in France is not explained by comorbidities and social deprivation.

BACKGROUND: Access to kidney transplantation (KT) remains challenging for patients with end-stage kidney disease. This study assessed women's access to KT in France by considering comorbidities and neighborhood social deprivation. METHODS: All incident 18-85-year-old patients starting dialysis in France between January 1, 2017 and December 31, 2019 were included. Three outcomes were assessed: (i) access to the KT waiting list after dialysis start, (ii) KT access after waitlisting, and (iii) KT access after dialysis start. Cox and Fine and Gray models were used. Gender-EDI and gender-age interactions were tested and analyses were performed among strata if required. RESULTS: 29,395 patients were included (35% of women). After adjusting for social deprivation and comorbidities, women were less likely to be waitlisted at 1 (adjHR: 0.91 [0.87-0.96]) and 3 years (adjHR: 0.87 [0.84-0.91]) post-dialysis initiation. This disparity concerned mainly ≥60-year-old women (adjHR: 0.76 [0.71-0.82] at 1 year and 0.75 [0.71-0.81] at 3 years). Access to KT, after 2 years of waitlisting was similar between genders. Access to KT was similar between genders at 3 years after dialysis start, but decreased for women after 4 years (adjHR: 0.93 [0.88-0.99]) and longer follow-up (adjHR: 0.90 [0.85-0.96]). CONCLUSIONS: In France, women are less likely to be waitlisted and undergo kidney transplantation. This is driven by the ≥60-year-old group and is not explained by comorbidities or social deprivation level.

Thrombotic microangiopathies after kidney transplantation in modern era: nosology based on chronology.

BACKGROUND: Thrombotic microangiopathies (TMAs) are rare but can be severe in kidney transplant. recipients (KTR). METHODS: We analysed the epidemiology of adjudicated TMA in consecutive KTR during the. 2009-2021 period. RESULTS: TMA was found in 77/1644 (4.7%) KTR. Early TMA (n = 24/77 (31.2%); 1.5% of all KTR) occurred during the first two weeks ((median, IQR) 3 [1-8] days). Triggers included acute antibody-mediated rejection (ABMR, n = 4) and bacterial infections (n = 6). Graft survival (GS) was 100% and recurrence rate (RR) was 8%. Unexpected TMA (n = 31/77 (40.2%); 1.5/1000 patient-years) occurred anytime during follow-up (3.0 (0.5-6.2) years). Triggers included infections (EBV/CMV: n = 10; bacterial: n = 6) and chronic active ABMR (n = 5). GS was 81% and RR was 16%. Graft-failure associated TMA (n = 22/77 (28.6%); 2.2% of graft losses) occurred after 8.8 (4.9-15.5) years). Triggers included acute (n = 4) or chronic active (n = 14) ABMR, infections (viral: n = 6; bacterial: n = 5) and cancer (n = 6). 15 patients underwent transplantectomy. RR was 27%. Atypical (n = 6) and typical (n = 2) haemolytic and uremic syndrome, and isolated CNI toxicity (n = 4) were rare. Two-third of biopsies presented TMA features. CONCLUSIONS: TMA are mostly due to ABMR and infections; causes of TMA are frequently combined. Management often is heterogenous. Our nosology based on TMA timing identifies situations with distinct incidence, causes and prognosis.

Area under the curve of tacrolimus using microsampling devices: towards precision medicine in solid organ transplantation?

PURPOSE: Therapeutic drug monitoring of tacrolimus using trough concentration (Cmin) is mandatory to ensure drug efficacy and safety in solid organ transplantation. However, Cmin is just a proxy for the area under the curve of drug concentrations (AUC) which is the best pharmacokinetic parameter for exposure evaluation. Some studies suggest that patients may present discrepancies between these two parameters. AUC is now easily available through mini-invasive microsampling approach. The aim of this study is to evaluate the relationship between AUC and Cmin in patients benefiting from a complete pharmacokinetic profile using a microsampling approach. METHODS: Fifty-one transplant recipients benefited from a complete pharmacokinetic profile using a microsampling approach, and their 24-h AUC were calculated using the trapezoidal method. The correlation with Cmin was then explored. In parallel, we estimated AUC using the sole Cmin and regression equations according to the post-transplantation days and the galenic form. RESULTS: Weak correlations were found between 24-h AUC observed and the corresponding Cmin (R2 = 0.60) and between AUC observed and expected using the sole Cmin (R2 = 0.62). Therapeutic drug monitoring of tacrolimus using Cmin leads to over- or under-estimate drug exposure in 40.3% of patients. CONCLUSION: Tacrolimus Cmin appears to be an imperfect reflection of drug exposure. Evaluating AUC using a microsampling approach offers a mini-invasive strategy to monitor tacrolimus treatment in transplant recipients.

Care trajectory differences in women and men with end-stage renal disease after dialysis initiation.

Few studies investigated sex-related differences in care consumption after dialysis initiation. Therefore, the aim of this study was to compare the care trajectory in the first year after dialysis start between men and women by taking into account the context of dialysis initiation. All patients who started dialysis in France in 2015 were included. Clinical data of patients and context of dialysis initiation were extracted from the Renal Epidemiology and Information Network (REIN) registry. Data on care consumption in the first year after dialysis start came from the French national health data system (SNDS): hospital stays <24h, hospital stays to prepare or maintain vascular access, hospital stays >24h for kidney problems and hospital stays >24h for other problems, and consultations with a general practitioner. Variables were compared between men and women with the χ2 test and Student's or Welch t-test and logistic regression models were used to identify the factors associated with care consumption after dialysis start. The analysis concerned 8,856 patients (36% of women). Men were less likely to have a hospital stays >24h for kidney problems than women (OR = 0.8, 95% CI = [0.7-0.9]) and less general practitioner consultations (OR = 0.8, 95% CI = [0.8-0.9]), in the year after dialysis initiation, after adjustment on patient's characteristics. Moreover, hospital stays for vascular access preparation or maintenance were longer in women than men (median duration: 2 days [0-2] vs. 1 day [0-2], p < 0.001). In conclusion, despite greater comorbidities in men, this study found few differences in post-dialysis care trajectory between men and women.

Predictors of acute ischemic cerebral lesions in immune-mediated thrombotic thrombocytopenic purpura and hemolytic uremic syndrome.

BACKGROUND: The immune form of thrombotic thrombocytopenic purpura (iTTP) and the hemolytic and uremic syndrome (HUS) are two major forms of thrombotic microangiopathy (TMA). Their treatment has been recently greatly improved. In this new era, both the prevalence and predictors of cerebral lesions occurring during the acute phase of these severe conditions remain poorly known. AIM: The prevalence and predictors of cerebral lesions appearing during the acute phase of iTTP and Shiga toxin-producing Escherichia coli-HUS or atypical HUS were evaluated in a prospective multicenter study. METHODS: Univariate analysis was performed to report the main differences between patients with iTTP and those with HUS or between patients with acute cerebral lesions and the others. Multivariable logistic regression analysis was used to identify the potential predictors of these lesions. RESULTS: Among 73 TMA cases (mean age 46.9 ± 16 years (range 21-87 years) with iTTP (n = 57) or HUS (n = 16), one-third presented with acute ischemic cerebral lesions on magnetic resonance imagery (MRI); two individuals also had hemorrhagic lesions. One in ten patients had acute ischemic lesions without any neurological symptom. The neurological manifestations did not differ between iTTP and HUS. In multivariable analysis, three factors predicted the occurrence of acute ischemic lesions on cerebral MRI: (1) the presence of old infarcts on cerebral MRI, (2) the level of blood pulse pressure, (3) the diagnosis of iTTP. CONCLUSION: At the acute phase of iTTP or HUS, both symptomatic and covert ischemic lesions are detected in one third of cases on MRI. Diagnosis of iTTP and the presence of old infarcts on MRI are associated with the occurrence of such acute lesions as well as increased blood pulse pressure, that may represent a potential target to further improve the therapeutic management of these conditions.

Pre-dialysis care trajectory and post-dialysis survival and transplantation access in patients with end-stage kidney disease.

BACKGROUND: The pre-dialysis care trajectory impact on post-dialysis outcomes is poorly known. This study assessed survival, access to kidney transplant waiting list and to transplantation after dialysis initiation by taking into account the patients' pre-dialysis care consumption (inpatient and outpatient) and the conditions of dialysis start: initiation context (emergency or planned) and vascular access type (catheter or fistula). METHODS: Adults who started dialysis in France in 2015 were included. Clinical data came from the French REIN registry and data on the care trajectory from the French National Health Data system (SNDS). The Cox model was used to assess survival and access to kidney transplantation. RESULTS: We included 8856 patients with a mean age of 68 years. Survival was shorter in patients with emergency or planned dialysis initiation with a catheter compared to patients with planned dialysis with a fistula. The risk of death was lower in patients who were seen by a nephrologist more than once in the 6 months before dialysis than in those who were seen only once. The rate of kidney transplant at 1 year post-dialysis was lower for patients with emergency or planned dialysis initiation with a catheter (respectively, HR = 0.5 [0.4; 0.8] and HR = 0.7 [0.5; 0.9]) compared to patients with planned dialysis start with a fistula. Patients who were seen by a nephrologist more than three times between 0 and 6 months before dialysis start were more likely to access the waiting list 1 and 3 years after dialysis start (respectively, HR = 1.3 [1.1; 1.5] and HR = 1.2 [1.1; 1.4]). CONCLUSIONS: Nephrological follow-up in the year before dialysis initiation is associated with better survival and higher probability of access to kidney transplantation. These results emphasize the importance of early patient referral to nephrologists by general practitioners.

Prognostic value of complement serum C3 level and glomerular C3 deposits in anti-glomerular basement membrane disease.

Background and objectives: Activation of the complement system is involved in the pathogenesis of anti-glomerular basement membrane (anti-GBM) disease. Glomerular deposits of complement 3 (C3) are often detected on kidney biopsies. The primary objective of this study was to analyze the prognostic value of the serum C3 level and the presence of C3 glomerular deposits in patients with anti-GBM disease. Methods: We conducted a retrospective cohort study of 150 single-positive patients with anti-GBM disease diagnosed between 1997 and 2017. Patients were categorized according to the serum C3 level (forming a low C3 (C3<1.23 g/L) and a high C3 (C3≥1.23 g/L) groups) and positivity for C3 glomerular staining (forming the C3+ and C3- groups). The main outcomes were kidney survival and patient survival. Results: Of the 150 patients included, 89 (65%) were men. The median [interquartile range (IQR)] age was 45 [26-64]. At diagnosis, kidney involvement was characterized by a median [IQR] peak serum creatinine (SCr) level of 578 [298-977] µmol/L, and 106 (71%) patients required dialysis. Patients in the low C3 group (72 patients) had more severe kidney disease at presentation, as characterized by higher prevalences of oligoanuria, peak SCr ≥500 µmol/L (69%, vs. 53% in the high C3 group; p=0.03), nephrotic syndrome (42%, vs. 24%, respectively; p=0.02) and fibrous forms on the kidney biopsy (21%, vs. 8%, respectively; p=0.04). Similarly, we observed a negative association between the presence of C3 glomerular deposits (in 52 (41%) patients) and the prevalence of cellular forms (83%, vs. 58% in the C3- group; p=0.003) and acute tubulo-interstitial lesions (60%, vs. 36% in the C3- group; p=0.007). When considering patients not on dialysis at diagnosis, the kidney survival rate at 12 months was poorer in the C3+ group (50% [25-76], vs. 91% [78-100] in the C3- group; p=0.01), with a hazard ratio [95% confidence interval] of 5.71 [1.13-28.85] (p=0.04, after adjusting for SCr). Conclusion: In patients with anti-GBM disease, a low serum C3 level and the presence of C3 glomerular deposits were associated with more severe disease and histological kidney involvement at diagnosis. In patients not on dialysis at diagnosis, the presence of C3 deposits was associated with worse kidney survival.

Assessing health literacy in transplant patients to better tailor the content of their therapeutic education: an observational study.

OBJECTIVES: Evaluate health literacy in transplant patients to better tailor the content of their continuing therapeutic education. METHODS: A 20-item questionnaire divided into five themes (sport/recreation, dietary measures, hygiene measures, recognition of the signs of graft rejection and medication management) was sent to transplant patient associations. Participants' responses (a score out of 20 points), were analysed according to demographic characteristics, transplanted organ (kidney, liver or heart), type of donor (living or deceased), participation in a therapeutic patient education (TPE) programme, management of end-stage renal disease (with or without dialysis) and the date of transplant. RESULTS: 327 individuals completed the questionnaires (mean age 63.3±12.7 years, mean time post-transplant 13.1±12.1 years). From 2 years after transplantation, the patients' score decreases significantly compared with the score obtained at hospital discharge. Patients who received TPE had significantly higher scores than patients who did not receive it, but only in the first 2 years post-transplant. The scores were different depending on the organs transplanted. Patients' knowledge varied according to the theme; the percentage of errors being higher for questions related to hygienic and dietary rules. CONCLUSION: These findings highlight the importance of the role of the clinical pharmacist in maintaining the transplant recipient's health literacy level over time to increase graft life. We show the topics on which pharmacists must acquire solid knowledge to best meet the needs of transplant patients.

Fate of discarded kidney transplants: experience of the transplant university hospital center of Rennes / Devenir des greffons rénaux refusés : expérience du centre de transplantation du CHU de Rennes

Introduction: In a context of tension on the number of available kidney transplants compared to the number needed, the practices of refusal of transplants in the Rennes transplantation center were evaluated. Materials and methods: The donors completely refused by our team (no kidney accepted for any Rennes recipient) between January 1st 2012 and December 31st 2015 were identified from the national CRISTAL registry. The outcome of these refused transplants (possible transplantation in another center), the data of the recipients (from Rennes and other centers) and the data of the donors (refused and then finally accepted) were extracted. The outcome of recipients (from Rennes and other centers) was compared: graft survival (censored on death) and patient survival (not censored on cessation of function). The Kidney Donor Profile Index (KDPI) score was calculated and its usefulness studied. Results: Among the 203 rejected donors, 172 (85 %) were accepted for transplantation in another center; 89% of these grafts were functional at one year. In univariate analysis, Rennes recipients transplanted after a refusal had a better graft survival (censored on death) than recipients transplanted in another center with the refused graft (p < 0.001). The main limitation of this analysis is the non-comparability of the groups. The KDPI score was significantly associated with graft survival (censored on death). Of the 151 Rennes patients who had a refusal, 3% were still on the waiting list at the end of the observation period, the others spent a median additional time on dialysis of 220 days (Q1-Q3 81-483). Conclusion: Rennes recipients transplanted after a first refusal seem to have a better graft survival (censored on death) than recipients from other centers transplanted with refused grafts. This is to be weighed against the additional time on dialysis and even the risk of non-transplantation.

Introduction: Dans un contexte de tension sur le nombre de greffons rénaux disponibles comparé au nombre nécessaire, les pratiques de refus des greffons du centre de transplantation rennais ont été évaluées. Matériels et méthodes: À partir du registre national CRISTAL, les donneurs complètement refusés par notre équipe (aucun rein accepté pour aucun receveur rennais) entre le 1er janvier 2012 et le 31 décembre 2015 ont été identifiés. Le devenir de ces greffons refusés (éventuelle greffe dans un autre centre), les données des receveurs (rennais et des autres centres) et les données des donneurs (refusés puis finalement acceptés) ont été extraits. Le devenir des receveurs (rennais et des autres centres) a été comparé : survie du greffon (censurée sur le décès) et du patient (non censurée sur l'arrêt de fonction). Le score KDPI (Kidney Donor Profile Index) a été calculé et son intérêt étudié. Résultats: Parmi les 203 donneurs refusés, 172 (85 %) ont permis une transplantation dans un autre centre, dont 89 % de greffons fonctionnels à un an. En analyse univariée, les receveurs rennais greffés après un refus avaient une meilleure survie greffon (censurée sur le décès) que les receveurs greffés dans un autre centre avec le greffon refusé (p < 0,001). La principale limite de cette analyse est la non-comparabilité des groupes. Le score KDPI était significativement associé à la survie greffon (censurée sur le décès). Parmi les 151 patients rennais qui ont eu un refus, 3 % étaient toujours sur liste d'attente à l'issue de la période d'observation, les autres passaient un temps médian supplémentaire en dialyse de 220 jours (Q1-Q3 81-483). Conclusion: Les receveurs rennais greffés après un premier refus semblent avoir une meilleure survie du greffon (censurée sur le décès) que les receveurs des autres centres greffés avec les greffons refusés. C'est à mettre en balance avec le temps supplémentaire en dialyse, voire le risque de non-greffe.

Pneumococcal vaccination coverage at the initiation of chronic dialysis, and its association with mortality during the first year.

OBJECTIVES: Pneumococcal immunization is recommended in dialysis patients. We aimed to estimate pneumococcal vaccination coverage among patients who initiate dialysis in France, and its association with mortality. METHODS: Data were extracted from two prospective national databases, merged using a deterministic linkage method: renal epidemiology and information network (REIN) registry, which includes all patients on dialysis and kidney transplants recipients in France, and the national health insurance information system (SNIIRAM) which collects individual data on health expenditure reimbursement, including vaccines. We enrolled all patients who initiated chronic dialysis in 2015. Data on health status at dialysis initiation, dialysis modalities, and pneumococcal vaccine prescribed from 2 years before to 1 year after dialysis start were collected. Univariate and multivariate Cox proportional hazard models were used to assess one-year all-cause mortality. RESULTS: Among the 8,294 incident patients included, 1,849 (22.3 %) received at least one pneumococcal vaccine before (n = 542, 6.5 %), or after (n = 1,307, 15.8 %) dialysis start, as follows: 13-valent pneumococcal conjugated vaccine (PCV13) followed by 23-valent pneumococcal polysaccharide vaccine (PPSV23), n = 938 (50.7 %); only PPSV23, n = 650 (35.1 %); or only PCV13, n = 261 (14.1 %). Vaccinated patients were younger (mean, 66.5 ± 14.8 years vs. 69.0 ± 14.9 years, P ≤ 0.001), more likely to suffer from glomerulonephritis (17.0 % vs. 11.0 %, P ≤ 0.001), and less likely to start dialysis in emergency (27.2 % vs. 31.1 %, P = 0.001). On multivariate analysis, patients who received PCV13 and PPSV23, or only PCV13 were less likely to die (respectively, HR = 0.37; 95 %CI 0.28-0.51, and HR = 0.35; 95 %CI 0.19-0.65). CONCLUSIONS: Pneumococcal immunization with PCV13 followed by PPSV23, or with PCV13 alone, but not with PPSV23 alone, is independently associated with decreased one year-mortality in patients who start dialysis.

Pregnancy in women on chronic dialysis in the last decade (2010-2020): a systematic review.

Background: Pregnant women with end-stage renal disease on chronic dialysis are at a high risk of maternal and foetal complications. Over the years, the prognosis of their pregnancies has improved with advances in dialysis treatments and maternal and neonatal care. We conducted this systematic review to examine the recent data on maternal and foetal outcomes in pregnant women with end-stage renal failure on chronic dialysis over the last decade. Methods: We made a systematic review of studies on pregnant women on chronic dialysis published between 1 January 2010 and 31 December 2020. We searched the following electronic databases: Medline via PubMed, Embase and the Cochrane Library, with search strategies for each database. We checked the titles and abstracts identified by the search equation, and two independent reviewers assessed the articles retrieved. For each study, the two reviewers separately recorded the data from each selected article on a standardized data extraction form. For each article, we recorded relevant general information on the study, patient demographic characteristics, dialysis schedule, pregnancy complications and outcomes, maternal complications, and foetal and neonatal outcomes. Results: The literature search yielded 1668 potentially relevant abstracts. After reviewing the titles, abstracts and full text, we identified 14 studies according to the inclusion criteria. All studies were observational, nine of them were retrospective and eight were from a single-centre experience. The total number of women included in these studies was 2364 (range 8-2008) and the total number of pregnancies was 2754 (range 8-2352). The patients' ages ranged from 15 to 45 years. Obesity was observed in 808 (34.2%) women and ranged from 1 to 778. Haemodialysis was the predominant modality with 2551 (92.6%) pregnancies, and 203 (7.4%) on peritoneal dialysis. Overall, 68 out of 402 (16.9%) spontaneous miscarriages, 21 out of 402 (5.2%) therapeutic abortions and 26 (8.3%) stillbirths among 313 (stillbirths and live births) were recorded. The mean or median gestational age at delivery ranged from 25.2 to 36 weeks. The main maternal complications were preeclampsia 11.9%, hypertension 7.7% and anaemia 3.9%. Live births represented 287 (71.4%) out of 402 pregnancies, birth weight ranged from 590 to 3500 g and preterm birth was the main, most common complication in all studies, ranging from 50% to 100%. Intrauterine growth restriction was present in 5.9% and small-for-gestational-age was reported in 18.9% of neonates. There were 22 (7.6%) neonatal deaths among 287 live births and 48 (15.3%) perinatal deaths among 313 total births (stillbirths and live births). Conclusions: Presumably, considering the increase in the number of publications and the total number of pregnancies reported therein, the frequency of pregnancy in patients with end-stage chronic kidney disease treated by chronic dialysis has increased. However, the practice of treating pregnant women on dialysis differs significantly among countries. These findings highlight the need to standardize the definition of outcomes and healthcare for pregnant women on dialysis.

A pharmacist-led intervention to improve kidney transplant recipient outcomes and identify patients at risk of highly variable trough tacrolimus levels: a cohort study.

OBJECTIVES: Given the positive impact of appropriate medication management on graft outcome and therefore of patient survival and graft function, the pharmacist's role in the kidney transplantation team has evolved over recent decades. The primary objective of this study was to determine whether pharmacist-led intervention after kidney transplantation is associated with a lower graft rejection rate and intra-patient variation in tacrolimus trough concentrations (Cmin). The study's secondary objective was to develop a questionnaire to identify patients at risk for highly variable Cmin. METHODS: We retrospectively analysed kidney transplant recipients at Rennes University Hospital (France) between January 2013 and December 2020. Patients who received pharmacist-led education (intervention group, n=139) were compared with patients who did not (control group, n=131), according to graft survival at 1 year post-transplant, coefficient of variation (%CV) for the tacrolimus Cmin, age, sex, length of hospital stay post-transplantation, body mass index, and Charlson Comorbidity Index. In the intervention group, a questionnaire assessing patient knowledge was introduced to compare scores with the %CV. RESULTS: In the intervention group, 1 year post-transplant graft survival was higher (95.7% vs 88.5%, p=0.0289) and patients had fewer variabilities in Cmin. The %CV was correlated with questionnaire scores (r=-0.9758, p<0.0001). CONCLUSIONS: Pharmacist-led interventions may have contributed to improved graft survival and patient management of immunosuppressants. Because %CV correlates with the patient questionnaire score, its introduction could be useful in identifying kidney transplant patients who would benefit most from a pharmacist-led patient education.

Long-term lithium therapy and risk of chronic kidney disease, hyperparathyroidism and hypercalcemia: a cohort study.

BACKGROUND: Lithium is well recognized as the first-line maintenance treatment for bipolar disorder (BD). However, besides therapeutic benefits attributed to lithium therapy, the associated side effects including endocrinological and renal disorders constitute important parameters in prescribing patterns and patient adherence. The objectives of this study is to (i) determine whether long-term lithium therapy is associated with a decrease in renal function, hyperparathyroidism and hypercalcemia and (ii) identify risk factors for lithium-induced chronic kidney disease (CKD). METHODS: We conducted a single-centered cohort study of adult patients (≥ 18 years) treated with lithium, who were enrolled at Rennes University Hospital in France between January 1, 2018 and June 1, 2020. Required data were collected from the patient's medical records: demographics characteristics (age, sex, body mass index), biologic parameters (GFR, lithium blood level, PTH and calcium), medical comorbidities (hypertension and diabetes), lithium treatment duration and dosage, and length of hospitalization. RESULTS: A total of 248 patients were included (mean age: 60.2 ± 16.5 years). Duration of lithium treatment correlated with (i) deterioration of renal function estimated at - 2.9 mL/min/year (p < 0.0001) and (ii) the development of hyperparathyroidism (p < 0.01) and hypercalcemia (p < 0.01). We also noted that patients with lithium blood level > 0.8 mEq/mL had significantly lower GFR than patients with lithium blood level < 0.8 mEq/mL (61.8 mL/min versus 77.6 mL/min, respectively, p = 0.0134). Neither diabetes mellitus nor hypertension was associated with more rapid deterioration of renal function. CONCLUSION: This study suggests that the duration of lithium treatment contribute to the deterioration of renal function, raising the question of reducing dosages in patients with a GFR < 60 mL/min. Overdoses has been identified as a risk factor for CKD, emphasizing the importance of regular re-evaluation of the lithium dose regimen. Also, long-term lithium therapy was associated with hyperparathyroidism and hypercalcemia. Particular vigilance is required on these points in order to limit the occurrence of endocrinological and renal lithium adverse effects.

Unexpected overdose of oral cyclosporine in a kidney transplant patient: a case report.

Cyclosporine is a widely used immunosuppressive agent to prevent rejection of solid organ transplant. Here, we describe the case of a 71-year-old man who received the prescribed dose of cyclosporine 10 times 6 days after a kidney transplantation because of a concentration miscalculation involving two galenic forms. The patient presented gastrointestinal and neurological disorders. Therapeutic drug monitoring revealed high cyclosporine blood concentrations (693 ng/mL, therapeutic range 100-300 ng/mL). Symptomatic management of digestive disorders was performed, and haemodialysis was started the day after the cyclosporine overdose in the face of acute renal failure. The patient's disorders were quickly resolved. The dosing regimen was adapted in order to administer the most appropriate galenic form and to avoid another administration error. Long-term follow-up showed no failure of renal transplantation. The purpose of this case report is to warn physicians and clinical pharmacists about the vigilance required on cyclosporine prescription, especially when two galenic forms are administered to obtain the prescribed dose.

Women's Access to Kidney Transplantation in France: A Mixed Methods Research Protocol.

Kidney transplantation is the best renal replacement therapy (medically and economically) for eligible patients with end-stage kidney disease. Studies in some French regions and in other countries suggest a lower access to the kidney transplant waiting listing and also to kidney transplantation, once waitlisted, for women. Using a mixed methods approach, this study aims to precisely understand these potential sex disparities and their causes. The quantitative study will explore the geographic disparities, compare the determinants of access to the waiting list and to kidney transplantation, and compare the reasons and duration of inactive status on the waiting list in women and men at different scales (national, regional, departmental, and census-block). The qualitative study will allow describing and comparing women's and men's views about their disease and transplantation, as well as nephrologists' practices relative to the French national guidelines on waiting list registration. This type of study is important in the current societal context in which the reduction of sex/gender-based inequalities is a major social expectation.