Immune Monitoring-Guided Versus Fixed Duration of Antiviral Prophylaxis Against Cytomegalovirus in Solid-Organ Transplant Recipients: A Multicenter, Randomized Clinical Trial.

BACKGROUND: The use of assays detecting cytomegalovirus (CMV)-specific T cell-mediated immunity may individualize the duration of antiviral prophylaxis after transplantation. METHODS: In this randomized trial, kidney and liver transplant recipients from 6 centers in Switzerland were enrolled if they were CMV-seronegative with seropositive donors or CMV-seropositive receiving antithymocyte globulins. Patients were randomized to a duration of antiviral prophylaxis based on immune monitoring (intervention) or a fixed duration (control). Patients in the control group were planned to receive 180 days (CMV-seronegative) or 90 days (CMV-seropositive) of valganciclovir. Patients were assessed monthly with a CMV ELISpot assay (T-Track CMV); prophylaxis in the intervention group was stopped if the assay was positive. The co-primary outcomes were the proportion of patients with clinically significant CMV infection and reduction in days of prophylaxis. Between-group differences were adjusted for CMV serostatus. RESULTS: Overall, 193 patients were randomized (92 in the immune-monitoring group and 101 in the control group), of whom 185 had evaluation of the primary outcome (87 and 98 patients). CMV infection occurred in 26 of 87 (adjusted percentage, 30.9%) in the immune-monitoring group and in 32 of 98 (adjusted percentage, 31.1%) in the control group (adjusted risk difference, -0.1; 95% confidence interval [CI], -13.0% to 12.7%; P = .064). The duration of prophylaxis was shorter in the immune-monitoring group (adjusted difference, -26.0 days; 95%, CI, -41.1 to -10.8 days; P < .001). CONCLUSIONS: Immune monitoring resulted in a significant reduction of antiviral prophylaxis, but we were unable to establish noninferiority of this approach on the co-primary outcome of CMV infection. CLINICAL TRIALS REGISTRATION: NCT02538172.

Sodium bicarbonate for kidney transplant recipients with metabolic acidosis in Switzerland: a multicentre, randomised, single-blind, placebo-controlled, phase 3 trial.

BACKGROUND: Metabolic acidosis is common in kidney transplant recipients and is associated with declining graft function. Sodium bicarbonate treatment effectively corrects metabolic acidosis, but no prospective studies have examined its effect on graft function. Therefore, we aimed to test whether sodium bicarbonate treatment would preserve graft function and slow the progression of estimated glomerular filtration rate (GFR) decline in kidney transplant recipients. METHODS: The Preserve-Transplant Study was a multicentre, randomised, single-blind, placebo-controlled, phase 3 trial at three University Hospitals in Switzerland (Zurich, Bern, and Geneva), which recruited adult (aged ≥18 years) male and female long-term kidney transplant recipients if they had undergone transplantation more than 1 year ago. Key inclusion criteria were an estimated GFR between 15 mL/min per 1·73 m2 and 89 mL/min per 1·73 m2, stable allograft function in the last 6 months before study inclusion (<15% change in serum creatinine), and a serum bicarbonate of 22 mmol/L or less. We randomly assigned patients (1:1) to either oral sodium bicarbonate 1·5-4·5 g per day or matching placebo using web-based data management software. Randomisation was stratified by study centre and gender using a permuted block design to guarantee balanced allocation. We did multi-block randomisation with variable block sizes of two and four. Treatment duration was 2 years. Acid-resistant soft gelatine capsules of 500 mg sodium bicarbonate or matching 500 mg placebo capsules were given at an initial dose of 500 mg (if bodyweight was <70 kg) or 1000 mg (if bodyweight was ≥70 kg) three times daily. The primary endpoint was the estimated GFR slope over the 24-month treatment phase. The primary efficacy analyses were applied to a modified intention-to-treat population that comprised all randomly assigned participants who had a baseline visit. The safety population comprised all participants who received at least one dose of study drug. The trial is registered with ClinicalTrials.gov, NCT03102996. FINDINGS: Between June 12, 2017, and July 10, 2019, 1114 kidney transplant recipients with metabolic acidosis were assessed for trial eligibility. 872 patients were excluded and 242 were randomly assigned to the study groups (122 [50%] to the placebo group and 120 [50%] to the sodium bicarbonate group). After secondary exclusion of two patients, 240 patients were included in the intention-to-treat analysis. The calculated yearly estimated GFR slopes over the 2-year treatment period were a median -0·722 mL/min per 1·73 m2 (IQR -4·081 to 1·440) and mean -1·862 mL/min per 1·73 m2 (SD 6·344) per year in the placebo group versus median -1·413 mL/min per 1·73 m2 (IQR -4·503 to 1·139) and mean -1·830 mL/min per 1·73 m2 (SD 6·233) per year in the sodium bicarbonate group (Wilcoxon rank sum test p=0·51; Welch t-test p=0·97). The mean difference was 0·032 mL/min per 1·73 m2 per year (95% CI -1·644 to 1·707). There were no significant differences in estimated GFR slopes in a subgroup analysis and a sensitivity analysis confirmed the primary analysis. Although the estimated GFR slope did not show a significant difference between the treatment groups, treatment with sodium bicarbonate effectively corrected metabolic acidosis by increasing serum bicarbonate from 21·3 mmol/L (SD 2·6) to 23·0 mmol/L (2·7) and blood pH from 7·37 (SD 0·06) to 7·39 (0·04) over the 2-year treatment period. Adverse events and serious adverse events were similar in both groups. Three study participants died. In the placebo group, one (1%) patient died from acute respiratory distress syndrome due to SARS-CoV-2 and one (1%) from cardiac arrest after severe dehydration following diarrhoea with hypotension, acute kidney injury, and metabolic acidosis. In the sodium bicarbonate group, one (1%) patient had sudden cardiac death. INTERPRETATION: In adult kidney transplant recipients, correction of metabolic acidosis by treatment with sodium bicarbonate over 2 years did not affect the decline in estimated GFR. Thus, treatment with sodium bicarbonate should not be generally recommended to preserve estimated GFR (a surrogate marker for graft function) in kidney transplant recipients with chronic kidney disease who have metabolic acidosis. FUNDING: Swiss National Science Foundation.

Anonymity in Kidney Paired Donation: A Systematic Review of Reasons.

The objective of this study was to investigate reasons for or against anonymity that are pertinent to kidney paired donations (KPD). We conducted a systematic review of reasons using PubMed and Google Scholar until May 2022 and through snowballing. Inclusion criteria were publications that: 1) discussed organ donation anonymity; 2) was peer-reviewed; 3) presented at least one reason on anonymity. Exclusion criteria: 1) not published in a scientific journal; 2) grey literature and dissertations. Four researchers independently reviewed and selected papers based on the criteria, extracted text passages and coded them into narrow and broad reason types, selected reasons that were valid for kidney paired donations. 50 articles were included, 62 narrow reasons (n = 24 for; n = 38 against) and 13 broad reasons were coded. Broad reasons were: protection against harm, general benefits, gratitude, curiosity, unrealistic to implement, fundamental rights, respect people's wishes, professional neutrality, timing is important, information disclosure, altruism, reciprocity and donation pool. We did not find reasons that justify legal prohibition of donor-recipient interactions for KPD, if they consented to meet. Professional counselling, follow-up and careful evaluations to prevent potential harm.

Deceased donor kidney transplanted in childhood functioning well after 52 years.

BACKGROUND: Kidney transplantation in children in 1970 was considered by many to be unethical, as long-term survival was minimal. It was therefore risky at the time to offer transplantation to a child. CASE DIAGNOSIS/TREATMENT: A 6-year-old boy with kidney failure due to haemolytic uraemic syndrome received 4 months of intermittent peritoneal dialysis followed by 6 months of haemodialysis until at 6 years and 10 months, he underwent bilateral nephrectomy and received a kidney transplant from a deceased 18-year-old donor. Despite moderate long-term immunosuppression of prednisone (20 mg/48 h) and azathioprine (62.5 mg/day), at the last visit in September 2022, he was well, normotrophic, with a serum creatinine of 157 µmol/l (eGFR 41 ml/min/1.73 m2) and no haematuria, proteinuria or hypertension. Except for benign skin lesions due to azathioprine, and undergoing an aortic valve replacement and an aortic aneurysm repair in adulthood, the now 58-year-old man has had no major complications. CONCLUSIONS: We speculate that stable and unmodified immunosuppressive therapy, started before the era of calcineurin inhibitors, the lack of significant rejection episodes, the absence of donor-specific antibodies, and the young donor age have contributed to maintaining exceptional long-term kidney transplant survival. Luck, a robust health system and an adherent patient are also important. To the best of our knowledge, this is the longest functioning kidney transplant from a deceased donor performed in a child worldwide. Despite its risky nature at the time, this transplant paved the way for others.

Impact of different urinary tract infection phenotypes within the first year post-transplant on renal allograft outcomes.

In this study, we investigated the clinical impact of different urinary tract infection (UTI) phenotypes occurring within the first year after renal transplantation. The population included 2368 transplantations having 2363 UTI events. Patients were categorized into four groups based on their compiled UTI events observed within the first year after transplantation: (i) no colonization or UTI (n = 1404; 59%), (ii) colonization only (n = 353; 15%), (iii) occasional UTI with 1-2 episodes (n = 456; 19%), and (iv) recurrent UTI with ≥3 episodes (n = 155; 7%). One-year mortality and graft loss rate were not different among the four groups, but patients with recurrent UTI had a 7-10 ml/min lower eGFR at year one (44 ml/min vs. 54, 53, and 51 ml/min; p < .001). UTI phenotypes had no impact on long-term patient survival (p = .33). However, patients with recurrent UTI demonstrated a 10% lower long-term death-censored allograft survival (p < .001). Furthermore, recurrent UTI was a strong and independent risk factor for reduced death-censored allograft survival in a multivariable analysis (HR 4.41, 95% CI 2.53-7.68, p < .001). We conclude that colonization and occasional UTI have no impact on pertinent outcomes, but recurrent UTI are associated with lower one-year eGFR and lower long-term death-censored allograft survival. Better strategies to prevent and treat recurrent UTI are needed.

Recurrence of IgA nephropathy after kidney transplantation: experience from the Swiss transplant cohort study.

BACKGROUND: Recurrence of IgA nephropathy (IgAN) after kidney transplantation occurs in about 30% of patients. The relevance of recurrence for the long-term graft survival is expected to increase, since graft survival continues to improve. METHODS: In a nested study within the Swiss Transplant Cohort Study the incidence of IgAN recurrence, predictive factors, graft function and graft and patient survival were evaluated. Serum concentration of total IgA, total IgG, Gd-IgA1 and IgA-IgG immune complex were measured using ELISA-based immunologic assays. RESULTS: Between May 2008 and December 2016, 28 women and 133 men received their kidney allograft for end-stage kidney disease due to IgAN in Switzerland. Over a median follow-up time of 7 years after transplantation, 43 out of 161 patients (26.7%) developed an IgAN recurrence, of which six (13.9%) had an allograft failure afterwards and further four patients (9.3%) died. During the same follow-up period, 6 out of 118 patients (5%) each experienced allograft failure or died without prior IgAN recurrence. After 11 years the risk for IgAN recurrence was 27.7% (95%-CI: 20.6-35.3%). Renal function was similar in patients with and without recurrence up to 7 years after transplantation, but worsened thereafter in patients with recurrence (eGFR median (interquartile range) at 8 years: 49 ml/min/1.73m2 (29-68) vs. 60 ml/min/1.73m2 (38-78)). Serum concentration of total IgA, total IgG, Gd-IgA1 and IgA-IgG immune complex within the first year posttransplant showed no significant effect on the recurrence of IgAN. Younger recipients and women had a higher risk of recurrence, but the latter only in the short term. CONCLUSIONS: Our study showed a recurrence risk of 28% at 11 years after transplantation, which is consistent with previous literature. However, the predictive value of known biomarkers, such as serum Gd-IgA1 and IgA-IgG IC, for IgAN recurrence could not be confirmed.

Long-term risks after kidney donation: how do we inform potential donors? A survey from DESCARTES and EKITA transplantation working groups.

BACKGROUND: Publications from the last decade have increased knowledge regarding long-term risks after kidney donation. We wanted to perform a survey to assess how transplant professionals in Europe inform potential kidney donors regarding long-term risks. The objectives of the survey were to determine how they inform donors and to what extent, and to evaluate the degree of variation. METHODS: All transplant professionals involved in the evaluation process were considered eligible, regardless of the type of profession. The survey was dispatched as a link to a web-based survey. The subjects included questions on demographics, the information policy of the respondent and the use of risk calculators, including the difference of relative and absolute risks and how the respondents themselves understood these risks. RESULTS: The main finding was a large variation in how often different long-term risks were discussed with the potential donors, i.e. from always to never. Eighty percent of respondents stated that they always discuss the risk of end-stage renal disease, while 56% of respondents stated that they always discuss the risk of preeclampsia. Twenty percent of respondents answered correctly regarding the relationship between absolute and relative risks for rare outcomes. CONCLUSIONS: The use of written information and checklists should be encouraged. This may improve standardization regarding the information provided to potential living kidney donors in Europe. There is a need for information and education among European transplant professionals regarding long-term risks after kidney donation and how to interpret and present these risks.

Outcome of kidney transplantation from very senior donors in Switzerland - a national cohort study.

Kidney transplantation from older and marginal donors is effective to confront organ shortage. However, limitations after transplantation of kidneys from very marginal kidney donors remain unclear. We compared patient and graft outcome, achieved allograft function and quality of life of renal transplantations from Very Senior Donors (VSD, defined as donors aged 70 years and older) with Senior Donors (SD, aged 60-70 years) and Regular Donors (RD, aged younger than 60 years) in Switzerland. We evaluated the outcome of 1554 adult recipients of deceased donor kidney transplantations from 05/2008 to 12/2019; median follow-up was 4.7 years. Failure-free survival (freedom from graft loss or death), glomerular filtration rate (eGFR), and quality of life at 12 months were analyzed for RD (reference group, n = 940), SD (n = 404), and VSD (n = 210). Failure-free survival decreased with increasing donor age, mainly attributable to premature graft loss. Still, overall 5-year failure-free survival reached 83.1%, 81.0%, and 64.0% in the RD, SD, and VSD subgroups, respectively. eGFR 12 months post-transplantation was significantly higher in RD compared with SD and VSD. The acceptance rate of donor candidates for kidney TPL was 78% for the entire cohort (87% for RD, 79% for SD, and 56% for VSD). Deceased donor kidney transplantation from donors aged 70 years or older is associated with an inferior, yet acceptable failure-free outcome, with sustained quality of life.

Pre-transplant donor-specific HLA antibodies and risk for poor first-year renal transplant outcomes: results from the Swiss Transplant Cohort Study.

The aim of this study was to analyze first year renal outcomes in a nationwide prospective multicenter cohort comprising 2215 renal transplants, with a special emphasis on the presence of pre-transplant donor-specific HLA antibodies (DSA). All transplants had a complete virtual crossmatch and DSA were detected in 19% (411/2215). The investigated composite endpoint was a poor first-year outcome defined as (i) allograft failure or (ii) death or (iii) poor allograft function (eGFR ≤25 ml/min/1.73 m2 ) at one year. Two hundred and twenty-one (221/2215; 10%) transplants showed a poor first-year outcome. Rejection (24/70; 34%) was the most common reason for graft failure. First-year patient's death was rare (48/2215; 2%). There were no statistically significant differences between DSA-positive and DSA-negative transplants regarding composite and each individual endpoint, as well as reasons for graft failure and death. DSA-positive transplants experienced more frequently rejection episodes, mainly antibody-mediated rejection (both P < 0.0001). The combination of DSA and any first year rejection was associated with the overall poorest death-censored allograft survival (P < 0.0001). In conclusion, presence of pre-transplant DSA per se does not affect first year outcomes. However, DSA-positive transplants experiencing first year rejection are a high-risk population for poor allograft survival and may benefit from intense clinical surveillance.

Age at Time of Kidney Transplantation as a Predictor for Mortality, Graft Loss and Self-Rated Health Status: Results From the Swiss Transplant Cohort Study.

Introduction: The effect of age on health outcomes in kidney transplantation remains inconclusive. This study aimed to analyze the relationship between age at time of kidney transplantation with mortality, graft loss and self-rated health status in adult kidney transplant recipients. Methods: This study used data from the Swiss Transplant Cohort Study and included prospective data of kidney transplant recipients between 2008 and 2017. Time-to-event analysis was performed using Cox' regression analysis, and -in the case of graft loss- competing risk analysis. A random-intercept regression model was applied to analyse self-rated health status. Results: We included 2,366 kidney transplant recipients. Age at transplantation linearly predicted mortality. It was also predictive for graft loss, though nonlinearly, showing that recipients aged between 35 and 55 years presented with the lowest risk of experiencing graft loss. No relationship of age with self-rated health status was detected. Conclusion: Higher mortality in older recipients complies with data from the general population. The non-linear relationship between age and graft loss and the higher scored self-rated health status at all follow-up time-points compared to the pre-transplant status -regardless of age- highlight that age alone might not be an accurate measure for risk prediction and clinical decision making in kidney transplantation.

Dialysis after graft loss: a Swiss experience.

BACKGROUND: Patients returning to dialysis after graft loss have high early morbidity and mortality. METHODS: We used data from the Swiss Transplant Cohort Study to describe the current practice and outcomes in Switzerland. All patients who received a renal allograft between May 2008 and December 2014 were included. The patients with graft loss were divided into two groups depending on whether the graft loss occurred within 1 year after transplantation (early graft loss group) or later (late graft loss group). Patients with primary non-function who never gained graft function were excluded. RESULTS: Seventy-seven out of 1502 patients lost their graft during follow-up, 40 within 1 year after transplantation. Eleven patients died within 30 days after allograft loss. Patient survival was 86, 81 and 74% at 30, 90 and 365 days after graft loss, respectively. About 92% started haemodialysis, 62% with definitive vascular access, which was associated with decreased mortality (hazard ratio = 0.28). At the time of graft loss, most patients were on triple immunosuppressive therapy with significant reduction after nephrectomy. One year after graft loss, 77.5% (31 of 40) of patients in the early and 43.2% (16 out of 37) in the late-loss group had undergone nephrectomy. Three years after graft loss, 36% of the patients with early and 12% with late graft loss received another allograft. CONCLUSION: In summary, our data illustrate high mortality, and a high number of allograft nephrectomies and re-transplantations. Patients commencing haemodialysis with a catheter had significantly higher mortality than patients with definitive access. The role of immunosuppression reduction and allograft nephrectomy as interdependent factors for mortality and re-transplantation needs further evaluation.

Validation of the corticomedullary difference in magnetic resonance imaging-derived apparent diffusion coefficient for kidney fibrosis detection: a cross-sectional study.

BACKGROUND: Kidney cortical interstitial fibrosis (IF) is highly predictive of renal prognosis and is currently assessed by the evaluation of a biopsy. Diffusion magnetic resonance imaging (MRI) is a promising tool to evaluate kidney fibrosis via the apparent diffusion coefficient (ADC), but suffers from inter-individual variability. We recently applied a novel MRI protocol to allow calculation of the corticomedullary ADC difference (ΔADC). We here present the validation of ΔADC for fibrosis assessment in a cohort of 164 patients undergoing biopsy and compare it with estimated glomerular filtration rate (eGFR) and other plasmatic parameters for the detection of fibrosis. METHODS: This monocentric cross-sectional study included 164 patients undergoing renal biopsy at the Nephrology Department of the University Hospital of Geneva between October 2014 and May 2018. Patients underwent diffusion-weighted imaging, and T1 and T2 mappings, within 1 week after biopsy. MRI results were compared with gold standard histology for fibrosis assessment. RESULTS: Absolute cortical ADC or cortical T1 values correlated poorly to IF assessed by the biopsy, whereas ΔADC was highly correlated to IF (r=-0.52, P < 0.001) and eGFR (r = 0.37, P < 0.01), in both native and allograft patients. ΔT1 displayed a lower, but significant, correlation to IF and eGFR, whereas T2 did not correlate to IF nor to eGFR. ΔADC, ΔT1 and eGFR were independently associated with kidney fibrosis, and their combination allowed detection of extensive fibrosis with good specificity. CONCLUSION: ΔADC is better correlated to IF than absolute cortical or medullary ADC values. ΔADC, ΔT1 and eGFR are independently associated to IF and allow the identification of patients with extensive IF.

[Diabetes after kidney transplantation†: current knowledge]. / Diabète après transplantation rénale†: mise au point.

The onset of diabetes after kidney transplantation is a frequently encountered entity by both the nephrologist, the diabetologist and the primary care physician. This article discusses various aspects related to diabetes after kidney transplantation such as epidemiology, risk factors, pathogenesis, diagnosis, associated complications and therapeutic management.

La survenue d'un diabète après transplantation rénale est une entité fréquemment rencontrée tant par le néphrologue, le diabétologue que par le médecin de premier recours. Cet article fait le point sur différents aspects liés au diabète après transplantation rénale tels que l'épidémiologie, les facteurs de risque, la pathogenèse, le diagnostic, les complications associées et la prise en charge thérapeutique.

[Nephrology†: what's new in 2019†?] / Néphrologie.

Impact of gliflozines and rituximab in the treatments of diabetic and membranous nephropathies respectively has been confirmed. Roxadustat may be the new promising treatment of renal anemia. Long-acting erythropoietins may be associated with a higher death rate than short-acting ones in hemodialysis patients. Kidneys of HCV-seropositive donors can be proposed to any wait-listed patient for renal transplantation. Immunosupression minimizing the use of calcineurin inhibitors may be achieved with an everolimus-based protocol.

L'intérêt des gliflozines dans le traitement de la néphropathie diabétique et du rituximab dans celui de la néphropathie membraneuse est confirmé. Le roxadustat pourrait devenir un nouveau traitement prometteur de l'anémie rénale. En hémodialyse, les érythropoïétines à longue durée d'action seraient associées à une plus forte mortalité que celles à courte durée d'action. En transplantation rénale, les reins de donneurs VHC-séropositifs (virus de l'hépatite C-séropositifs) peuvent être proposés à tous les receveurs potentiels. L'emploi de l'évérolimus permettrait une immunosupression avec épargne des inhibiteurs de la calcineurine.

Usefulness of a systematic approach at listing for vaccine prevention in solid organ transplant candidates.

Solid organ transplant (SOT) candidates may not be immune against potentially vaccine-preventable diseases because of insufficient immunizations and/or limited vaccine responses. We evaluated the impact on vaccine immunity at transplant of a systematic vaccinology workup at listing that included (1) pneumococcal with and without influenza immunization, (2) serology-based vaccine recommendations against measles, varicella, hepatitis B virus, hepatitis A virus, and tetanus, and (3) the documentation of vaccines and serology tests in a national electronic immunization registry (www.myvaccines.ch). Among 219 SOT candidates assessed between January 2014 and November 2015, 54 patients were transplanted during the study. Between listing and transplant, catch-up immunizations increased the patients' immunity from 70% to 87% (hepatitis A virus, P = .008), from 22% to 41% (hepatitis B virus, P = .008), from 77% to 91% (tetanus, P = .03), and from 78% to 98% (Streptococcus pneumoniae, P = .002). Their immunity at transplant was significantly higher against S. pneumoniae (P = .006) and slightly higher against hepatitis A virus (P = .07), but not against hepatitis B virus, than that of 65 SOT recipients transplanted in 2013. This demonstrates the value of a systematic multimodal serology-based approach of immunizations of SOT candidates at listing and the need for optimized strategies to increase their hepatitis B virus vaccine responses.

[Nephrology : what's new in 2018 ?] / Néphrologie.

Major advances in the treatment of ANCA associated-renal vasculitides, IGA nephropathy and renal autosomal dominant polycystic disease were published within the past year. There is neither clear benefit of early initiation of renal replacement therapy in the intensive care unit nor with the use of chloride-poor solutions to prevent kidney failure. Maintenance parenteral iron supplementation in hemodialysis patients is neither associated with infectious nor cardiovascular risks. Cognitive decline may be more associated with hemodialysis than peritoneal dialysis. In transplantation, the persistence of complement-binding donor-specific antibodies after treatment is predictor of graft loss. Tocilizumab is a promising treatment for chronic antibody-mediated rejection.

Des progrès importants ont été effectués cette année dans le traitement des vascularites rénales à ANCA (anticorps anti-cytoplasme des polynucléaires neutrophiles), de la néphropathie à IgA et de la polykystose rénale. Il n'y a pas d'avantage clair à l'initiation précoce de la dialyse en cas d'insuffisance rénale sévère et à l'utilisation des solutions pauvres en chlore dans le remplissage volémique. En hémodialyse chronique, une supplémentation en fer parentéral jusqu'à 400 mg par mois n'est pas associée à un risque infectieux ou cardiovasculaire augmenté. L'hémodialyse pourrait être associée à un déclin cognitif plus important que la dialyse péritonéale. En transplantation, la persistance d'anticorps dirigés contre le greffon et liant le complément après traitement du rejet, est prédicteur de perte du greffon. Le tocilizumab serait un traitement prometteur du rejet chronique médié par les anticorps.

Clinical and histological evolution after de novo donor-specific anti-human leukocyte antigen antibodies: a single centre retrospective study.

BACKGROUND: Donor-specific anti-human leukocyte antigen (HLA) antibodies (DSA) can be preformed or de novo (dn). Strategies to manage preformed DSA are well described, but data on the management and outcomes of dnDSA are lacking. METHODS: We performed a retrospective analysis of data from a single centre of the management and outcomes of 22 patients in whom a dnDSA was identified with contemporary and follow up biopsies. RESULTS: Evolution from baseline to follow up revealed a statistically significant loss of kidney function (estimated glomerular filtration rate: 45.9 ± 16.7 versus 37.4 ± 13.8 ml/min/1.73 m2; p = 0.005) and increase in the proportion of patients with transplant glomerulopathy (percentage with cg lesion ≥1: 27.2% vs. 45.4%; p = 0.04). Nine patients were not treated at the time of dnDSA identification, and 13 patients received various drug combinations (e.g., corticosteroids, plasmapheresis, thymoglobulins and/or rituximab). No significant pathological changes were observed for the various treatment combinations. CONCLUSION: Our retrospective analysis of a small sample suggests that dnDSA should be considered a risk factor for the loss of kidney function independent of the baseline biopsy, and multidisciplinary evaluations of the transplant patient are a necessary requirement. Further confirmation in a multicentre prospective trial is required.

Preservation of kidney function in kidney transplant recipients by alkali therapy (Preserve-Transplant Study): rationale and study protocol.

BACKGROUND: Graft survival after kidney transplantation has significantly improved within the last decades but there is a substantial number of patients with declining transplant function and graft loss. Over the past years several studies have shown that metabolic acidosis plays an important role in the progression of Chronic Kidney Disease (CKD) and that alkalinizing therapies significantly delayed progression of CKD. Importantly, metabolic acidosis is highly prevalent in renal transplant patients and a recent retrospective study has shown that metabolic acidosis is associated with increased risk of graft loss and patient death in kidney transplant recipients. However, no prospective trial has been initiated yet to test the role of alkali treatment on renal allograft function. METHODS: The Preserve-Transplant Study is an investigator-initiated, prospective, patient-blinded, multi-center, randomized, controlled phase-IV trial with two parallel-groups comparing sodium bicarbonate to placebo. The primary objective is to test if alkali treatment will preserve kidney graft function and diminish the progression of CKD in renal transplant patients by assesing the change in eGFR over 2 years from baseline. Additionally we want to investigate the underlying pathomechanisms of nephrotoxicity of metabolic acidosis. DISCUSSION: This study has the potential to provide evidence that alkali treatment may slow or reduce the progression towards graft failure and significantly decrease the rate of end stage renal disease (ESRD), thus prolonging long-term graft survival. The implementation of alkali therapy into the drug regimen of kidney transplant recipients would have a favorable risk-benefit ratio since alkali supplements are routinely used in CKD patients and represent a well-tolerated, safe and cost-effective treatment. TRIAL REGISTRATION: ClinicalTrials.gov NCT03102996 . Trial registration was completed on April 6, 2017.

[Nephrology]. / Néphrologie.

New antidiabetic drugs which slow effectively the course of diabetic nephropathy are now available. There is no benefit of prophylactic hydratation to prevent contrast nephropathy in patients with moderate chronic kidney disease. In elderly hemodialysis patients, hemodiafiltration seems better tolerated than conventional hemodialysis, although there is a similar dialysis-induced myocardial stress with both methods. Role of de novo donor-specific antibodies is better characterized, which may subsequently lead to new treatments of graft rejection.

La prise en charge de la néphropathie diabétique a connu une avancée majeure avec de nouvelles classes thérapeutiques aux propriétés néphro- et cardioprotectrices importantes. L'hydratation prophylactique n'apporte pas de bénéfice avéré lors d'administration de produit de contraste chez des patients avec insuffisance rénale chronique modérée. En hémodialyse chonique, l'hémodiafiltration semble mieux tolérée chez les personnes âgées que l'hémodialyse traditionnelle, bien qu'elle engendre durant la séance de dialyse le même stress myocardique. En transplantation, le rôle des anticorps dirigés contre le donneur est mieux précisé et laisse espérer à l'avenir des traitements mieux ciblés pour éviter le rejet.

ExplorinG frailty and mild cognitive impairmEnt in kidney tRansplantation to predict biomedicAl, psychosocial and health cost outcomeS (GERAS): protocol of a nationwide prospective cohort study.

AIM: To present the rationale, design and methodology of the GERAS project, which examines whether assessment of frailty and mild cognitive impairment could enhance risk prediction for biomedical, psychosocial outcomes and foster efficient resource allocation in kidney transplantation. BACKGROUND: For the burgeoning cohort of older patients considered for kidney transplantation, evidence gaps regarding frailty and mild cognitive impairment limit clinical decision-making and medical management. As known risk factors for 'hard' clinical outcomes in chronic illness, both require further study in transplantation. Integrating these and other bio-psychosocial factors into a comprehensive pre-transplant patient assessment will provide insights regarding economic implications and may improve risk prediction. DESIGN: A nation-wide multi-centre prospective cohort study nested in the Swiss Transplant Cohort Study. METHODS: Our nationally representative convenience sample includes 250 adult kidney transplant recipients. Data sources include the Swiss Transplant Cohort Study and primary data collected at time of transplantation, 6 months, 1 and 2 years post-transplant via established measures (the Montreal Cognitive Assessment, Psychosocial Questionnaire, Fried Frailty Instrument and a blood analysis), investigator-developed instruments and datasets compiled by hospitals' management control units, sickness funds, the Swiss Federal Statistical Office and the European Renal Association. Descriptive, competing risk survival and mixed effects analyses will be performed. Research Ethics Committee approval was obtained in January 2016. DISCUSSION: This pioneering project jointly examines frailty and mild cognitive impairment from bio-psychosocial and health economic perspectives. Results may significantly inform risk prediction, care tailoring and resource optimization to improve health outcomes in the ageing kidney transplant cohort.