Continuous glucose monitoring with FreeStyle Libre PRO sensor in patients with type 2 diabetes and end-stage renal failure on haemoDIALysis (FSLPRO-DIAL pilot study).

AIMS: For end-stage renal disease (ESRD) patients with diabetes on haemodialysis, diabetes control is difficult to achieve. Hypoglycaemia is a major problem in these frailty subjects. Continuous glucose monitoring (CGM) devices appear therefore to be a good tool to help patients monitor their glycaemic control and to help practitioners optimize treatment. We aimed to compare the laboratory value of Hba1c with the sensor-estimated value of Hba1c (= glucose management indicator, GMI) in ESRD patients with type 2 diabetes (T2D) (with or without insulin treatment) on haemodialysis. Secondly, we aimed to identify CGM-derived monitoring parameters [time in range, time in hypo/hyperglycaemia, glycaemic variability (coefficient of variation, CV)] to identify patients at risk of frequent hypo- or hyperglycaemia. METHODS: The FSLPRO-DIAL pilot study (NCT04641650) was a prospective monocentric cohort study including 29 subjects with T2D who achieve the protocol. Inclusion criteria were: age ≥ 18 years, haemodialysis duration for at least 3 months, type 2 diabetes with no change in treatment for at least 3 months. Demographic data and blood sample were collected at the day of inclusion. Freestyle Libre pro IQ sensor (blinded CGM) was inserted for 14 days. After this period, all CGMs data were collected and analysed. RESULTS: Data were available for 27 patients. Mean age was 73 ± 10, mean BMI 27.2 kg/m2, mean duration of diabetes 16.9 years and mean dialysis duration 2.9 years. Twenty-four subjects were treated with insulin. Mean HbA1c was 6.6% (SD 1.2), and mean GMI was 6.7% (SD 0.9) (no significant difference, p = 0.3). Twelve subjects (44.4%) had a discordance between HbA1c and GMI of < 0.5%, 11 (40.8%) had a discordance between 0.5 and 1%, and only 4 (14.8%) had a discordance of > 1%. Mean time in range (70-180 mg/dl) was 71.9%, mean time below range (< 70 mg/dl) was 5.6%, and mean time above range (> 180 mg/dl) was 22.1%. Mean CV was 31.8%. For 13 out of 27 patients, we reduced antidiabetic treatment by stopping treatments or reducing insulin doses. CONCLUSION: In this pilot study, there was no global significant difference between HbA1c and GMI in this particular cohort with very well-controlled diabetes. However, the use of the sensor enabled us to identify an excessive time in hypoglycemia in this fragile population and to adapt their treatment.

Idiopathic nephrotic syndrome relapse following COVID-19 vaccination: a series of 25 cases.

Background: Several cases of idiopathic nephrotic syndrome (INS) relapse following the administration of coronavirus disease 2019 (COVID-19) vaccines have recently been reported, raising questions about the potential relationship between the immune response to COVID-19 vaccination and INS pathogenesis. Methods: We performed a retrospective multicentre survey describing the clinical and biological characteristics of patients presenting a relapse of INS after COVID-19 vaccination, with an assessment of outcome under treatment. Results: We identified 25 patients (16 men and 9 women) presenting a relapse within 1 month of a COVID-19 vaccine injection. The glomerular disease was of childhood onset in half of the patients and most patients (21/25) had received at least one immunosuppressive drug in addition to steroids for frequently relapsing or steroid-dependent nephrotic syndrome (NS). All patients were in a stable condition at the time of injection and 11 had no specific treatment. In five patients, the last relapse was reported >5 years before vaccine injection. The Pfizer-BioNTech (BNT162b2) vaccine was used in 80% of the patients. In 18 cases, INS relapse occurred after the first injection, a mean of 17.5 days after vaccination. A second injection was nevertheless administered in 14 of these patients. Five relapses occurred after administration of the second dose and two relapses after the administration of the third dose. All but one of the patients received steroids as first-line treatment, with an additional immunosuppressive agent in nine cases. During follow-up, complete remission was achieved in 21 patients, within 1 month in 17 cases. Only one patient had not achieved at least partial remission after 3 months of follow-up. Conclusions: This case series suggests that, in rare patients, COVID-19 vaccination may trigger INS relapse that is generally easy to control. These findings should encourage physicians to persuade their patients to complete the COVID-19 vaccination schedule.

Trimethoprim/sulfamethoxazole for nocardiosis in solid organ transplant recipients: Real-life data from a multicentre retrospective study.

BACKGROUND: Little is known regarding the optimal management of nocardiosis among solid organ transplant (SOT) recipients. It is often suggested to avoid trimethoprim/sulfamethoxazole (TMP-SMX) monotherapy in heavily immunocompromised patients (such as SOT recipients) and/or in case of severe or disseminated nocardiosis. Our aim was to report our experience with TMP-SMX monotherapy in SOT recipients with nocardiosis. METHODS: Using data from a previously published European study, we assessed the incidence of adverse events in SOT recipients receiving TMP-SMX monotherapy and assessed its effectiveness. RESULTS: Thirty-one SOT recipients with nocardiosis were included, mostly kidney transplant recipients (20/31, 65%). Eleven (36%) had disseminated infection, and four (13%) had brain nocardiosis. Most patients had lung and/or pleural involvement (26/31, 84%). Daily dose of trimethoprim at initiation was 10 [6.4-14.8] mg/kg. The median estimated glomerular filtration rate at time of diagnosis of nocardiosis was 44 [30-62] ml/min/1.73 m². TMP-SMX was discontinued prematurely in one third of the patients (10/31, 32%, mostly for hematological toxicity [n = 3] or increased serum creatinine [n = 3]). Focusing on the 24 (77%) patients who completed at least 30 days of TMP-SMX monotherapy, 4 had late (>30 days) drug discontinuation, 1 experienced treatment failure, and 19 completed planned TMP-SMX monotherapy. Clinical outcome was favorable in these 19 patients, despite the fact that 8 (42%) had disseminated infection and 2 (11%) brain nocardiosis. Overall, all-cause 1-year mortality was 10% (3/31). CONCLUSIONS: TMP-SMX monotherapy appears to be effective for the treatment of most nocardiosis among SOT recipients. Interventional studies are needed to compare its safety and effectiveness with those of other regimens used to treat posttransplant nocardiosis.

Uncontrolled donation after circulatory death: comparison of two kidney preservation protocols on graft outcomes.

BACKGROUND: Kidney transplantation following uncontrolled donation after circulatory death (uDCD) presents a high risk of delayed graft function due to prolonged warm ischemia time. In order to minimise the effects of ischemia/reperfusion injury during warm ischemia, normothermic recirculation recently replaced in situ perfusion prior to implantation in several institutions. The aim of this study was to compare these preservation methods on kidney graft outcomes. METHODS: The primary endpoint was the one-year measured graft filtration rate (mGFR). We collected retrospective data from 64 consecutive uDCD recipients transplanted over a seven-year period in a single centre. RESULTS: Thirty-two grafts were preserved by in situ perfusion and 32 by normothermic recirculation. The mean ± SD mGFR at 1 year post-transplantation was 43.0 ± 12.8 mL/min/1.73 m2 in the in situ perfusion group and 53.2 ± 12.8 mL/min/1.73 m2 in the normothermic recirculation group (p = 0.01). Estimated GFR levels were significantly higher in the normothermic recirculation group at 12 months (p = 0.01) and 24 months (p = 0.03) of follow-up. We did not find any difference between groups regarding patient and graft survival, delayed graft function, graft rejection, or interstitial fibrosis. CONCLUSIONS: Function of grafts preserved by normothermic recirculation was better at 1 year and the results suggest that this persists at 2 years, although no difference was found in short-term outcomes. Despite the retrospective design, this study provides an additional argument in favour of normothermic recirculation.

Profiling sirolimus-induced inflammatory syndrome: a prospective tricentric observational study.

BACKGROUND: The use of the immunosuppressant sirolimus in kidney transplantation has been made problematic by the frequent occurrence of various side effects, including paradoxical inflammatory manifestations, the pathophysiology of which has remained elusive. METHODS: 30 kidney transplant recipients that required a switch from calcineurin inhibitor to sirolimus-based immunosuppression, were prospectively followed for 3 months. Inflammatory symptoms were quantified by the patients using visual analogue scales and serum samples were collected before, 15, 30, and 90 days after the switch. RESULTS: 66% of patients reported at least 1 inflammatory symptom, cutaneo-mucosal manifestations being the most frequent. Inflammatory symptoms were characterized by their lability and stochastic nature, each patient exhibiting a unique clinical presentation. The biochemical profile was more uniform with a drop of hemoglobin and a concomitant rise of inflammatory acute phase proteins, which peaked in the serum 1 month after the switch. Analyzing the impact of sirolimus introduction on cytokine microenvironment, we observed an increase of IL6 and TNFα without compensation of the negative feedback loops dependent on IL10 and soluble TNF receptors. IL6 and TNFα changes correlated with the intensity of biochemical and clinical inflammatory manifestations in a linear regression model. CONCLUSIONS: Sirolimus triggers a destabilization of the inflammatory cytokine balance in transplanted patients that promotes a paradoxical inflammatory response with mild stochastic clinical symptoms in the weeks following drug introduction. This pathophysiologic mechanism unifies the various individual inflammatory side effects recurrently reported with sirolimus suggesting that they should be considered as a single syndromic entity.

Retreatment by antithymocyte globulin for second kidney transplantation: efficacy, tolerance and safety.

BACKGROUND: It is unknown whether kidney transplant patients who receive rabbit antithymocyte globulin (rATG) become immunized against rabbit antibodies, leading to reduced efficacy, or are at higher risk of cytomegalovirus infection or post-transplant lymphoproliferative disorder (PTLD) on retreatment. The efficacy and tolerance of rATG when used as induction for the second time in patients undergoing retransplantation have not been evaluated. METHODS: In a retrospective case-control study, 54 retransplanted patients who received rATG (Thymoglobulin) induction for the second time during 2004-2010 were compared to a matched cohort of 108 patients receiving rATG induction for a first kidney transplantation during the same period. Maintenance treatment was similar in both groups. RESULTS: Median follow-up was 45.8 months and 47.3 months in the second and first treatment groups, respectively. No differences were observed between the two groups in terms of leukocyte, lymphocyte or platelet depletion. Dose and duration of rATG treatment were similar in both groups, suggesting a similar tolerance profile. Cytomegalovirus infection (including primoinfection and reactivation) occurred in 4/54 retreated patients versus 22/108 controls (p=0.108). Use of cytomegalovirus prophylaxis was similar between groups. PTLD occurred in one control patient and no retreated patients. CONCLUSION: A second course of rATG induction results in similar lymphocyte depletion and is as well tolerated as a first course. The incidence of cytomegalovirus infection and post-transplant lymphoproliferative disease was not increased during retreatment. Further studies are required to evaluate specific T cell subpopulation depletion and compare long-term outcome in patients receiving a second induction with rATG.

Factors associated with chronic hepatitis in patients with hepatitis E virus infection who have received solid organ transplants.

BACKGROUND & AIMS: Hepatitis E virus (HEV) infection can cause chronic hepatitis in recipients of solid organ transplants. However, the factors that contribute to chronic infection and the outcomes of these patients are incompletely understood. We performed a retrospective analysis of data from 17 centers from Europe and the United States that described the progression, outcomes, and factors associated with development of chronic HEV infection in recipients of transplanted solid organs. METHODS: We studied data from 85 recipients of solid organ transplants who were infected with HEV. Chronic HEV infection was defined by the persistent increases in levels of liver enzymes and polymerase chain reaction evidence of HEV in the serum and/or stool for at least 6 months. RESULTS: Fifty-six patients (65.9%) developed chronic hepatitis. Univariate analysis associated liver transplant, shorter times since transplant, lower levels of liver enzymes and serum creatinine, lower platelet counts, and tacrolimus-based immunosuppressive therapy (rather than cyclosporin A) with chronic hepatitis. On multivariate analysis, the independent predictive factors associated with chronic HEV infection were the use of tacrolimus rather than cyclosporin A (odds ratio [OR], 1.87; 95% confidence interval [CI], 1.49-1.97; P = .004) and a low platelet count at the time of diagnosis with HEV infection (OR, 1.02; 95% CI, 1.001-1.1; P = .04). Of patients with chronic hepatitis, 18 (32.1%) achieved viral clearance after the dose of immunosuppressive therapy was reduced. No HEV reactivation was observed after HEV clearance. CONCLUSIONS: HEV infection causes chronic hepatitis in more than 60% of recipients of solid organ transplants. Tacrolimus therapy is the main predictive factor for chronic hepatitis. Dose reductions of immunosuppressive therapy resulted in viral clearance in more than 30% of patients.

Chronic humoral rejection mediated by anti-HLA-DP alloantibodies: insights into the role of epitope sharing in donor-specific and non-donor specific alloantibodies generation.

We report the case of a renal transplanted patient, in whom the detection of a unique anti HLA-DP antibody response preceded the development of chronic humoral rejection. In addition to donor-specific anti-DP alloantibodies, the patient displayed reactions against several non-donor-specific DP antigens (NDSA). Interestingly, we found that all the DP molecules recognized by the alloantibodies displayed the same amino-acid sequence suggesting that epitope sharing between unrelated HLA molecules was the mechanism underlying NDSA generation. This case highlights the pathogenicity of anti-DP alloantibodies and suggests that it could be more meaningful to match the epitopes than the HLA antigens for the prevention of rejection.

[Parathormone and chronic kidney disease]. / Parathormone et maladie rénale chronique.

The serum parathyroid hormone (PTH) rises in chronic kidney disease (CKD) and induces renal bone disease as well as other organ damage. The bone disease guidelines were released by the K-DOQI in 2003 in order to help physicians to improve bone management at all different CKD stages. However, many different PTH commercial assays are available today and some questions are raised concerning the interpretation, the validity and the practical choice of these different measurements. After reviewing PTH biosynthesis and metabolism, we will describe the regulation of different PTH fragments (particularly 1-84 and 7-84) and the various types of PTH assays. In compromised clinical situations, bone biopsy still remains the golden standard assessment of bone disease, and it will be helpful to clarify the interest of new 3rd generation PTH measurements. At present, we do not dispose of valid therapeutic recommendations using 3rd generation tests, as well as the relevance of the ratio PTH 1-84/7-84.