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Rituximab (RTX) therapy for primary focal segmental glomerulosclerosis recurrence after kidney transplantation (KT) has been extensively debated. We aimed to assess the benefit of adding RTX to plasmapheresis (PP), corticosteroids, and calcineurin inhibitors (standard of care, SOC). We identified 148 adult patients who received KT in 12/2004-12/2018 at 21 French centers: 109 received SOC (Group 1, G1), and 39 received immediate RTX along with SOC (Group 2, G2). In G1, RTX was introduced after 28 days of SOC in the event of failure (G1a, n = 19) or PP withdrawal (G1b, n = 12). Complete remission (CR) was achieved in 46.6% of patients, and partial remission (PR) was achieved in 33.1%. The 10-year graft survival rates were 64.7% and 17.9% in responders and nonresponders, respectively. Propensity score analysis showed no difference in CR+PR rates between G1 (82.6%) and G2 (71.8%) (p = .08). Following the addition of RTX (G1a), 26.3% of patients had CR, and 31.6% had PR. The incidence of severe infections was similar between patients treated with and without RTX. In multivariable analysis, infection episodes were associated with hypogammaglobulinemia

Kidney transplant recipients (KTRs) are frequently infected with chronic hepatitis C virus (HCV), which can increase the risk of graft loss. Active HCV infections among KTRs are associated with shorter survival times. The emergence of very efficient interferon-free treatments (direct-acting antivirals [DAAs]) has revolutionized prognoses for chronic viral hepatitis. We performed a multicenter study where HCV (+)/RNA (+) KTRs were followed up and either received DAAs (group A) or not (group B) according to the transplant center. The aim was to assess, in a real-life setting, the impact of DAA therapy and to compare these results with those from HCV RNA (+) KTRs where HCV infection was not treated during the same period.This study included 66 patients from 11 centers: 44 patients (66.7%; group A) received DAAs, whereas 22 patients did not (group B); the 2 groups were comparable according to baseline data. Most patients (88.6%) received sofosbuvir, 50% received ledipasvir, and 34.7% received daclatasvir. The duration of treatments ranged from 8 to 24 weeks.HCV RNA clearance (ie, a sustained virologic response) was observed in 95.4% of treated patients. Eradication of HCV led to a significant decrease in liver enzymes (50% reduction for alanine aminotransferase [P ≤ .001] and 41% for gamma glutamyl transpeptidase [P .001]). Conversely, liver enzymes did not decrease in group B. Death occurred significantly more frequently in nontreated than treated patients (3 in group B vs none in group A, P = .003). Of the 10 treated patients with severe renal impairment before DAA therapy, 6 experienced graft loss.DAAs are very effective at treating chronic HCV and have an excellent tolerance profile.

Background Belatacept (bela) rescue therapy seems to be a valuable option for calcineurin inhibitor chronic toxicity in kidney transplantation. Nevertheless, the risk of infection associated with bela is not well reported. Methods We report the rate of opportunistic infections (OPI) after a switch to bela in a multicentric cohort of 280 kidney transplant patients. Results Forty-two OPI occurred in 34 patients (12.1%), on average 10.8 ± 11.3 months after the switch. With a cumulative exposure of 5128 months of bela treatment, we found an incidence of 0.008 OPI/month of exposure, and 9.8 OPI/100 person-years. The most common OPI was cytomegalovirus (CMV) disease in 18/42 OPI (42.9%) and pneumocystis pneumonia in 12/42 OPI (28.6%). Two patients presented a progressive multifocal leucoencephalopathy and two patients developed a cerebral Epstein–Barr virus-induced post-transplant lymphoproliferative disease. OPI led to death in 9/34 patients (26.5%) and graft failure in 4/34 patients (11.8%). In multivariate analysis, estimated glomerular filtration rate Conclusions The risk of OPI is significant post-conversion to bela and may require additional monitoring and prophylactic therapy, particularly regarding pneumocystis pneumonia and CMV disease. These data need to be confirmed in a larger case–control study.

International audience; We reported 3 kidney transplant patients with PTLD who developed mixed AR following IS treatment minimization. AR episodes were treated with extracorporeal photopheresis (ECP), methylprednisolone and IVIG. In all patients, graft function improved under ECP and stabilized in the long term. These observations suggest that ECP is safe and efficient for treatment of AR in the context of PTLD.

De novo donor-specific antibodies (DSAs) are associated with antibody-mediated rejection (AMR) and allograft loss. Whether monitoring of de novo DSA (dnDSA) paired with systematic kidney biopsy should become routine remains to be established.A retrospective multicentric study (9 French kidney transplant units of the Spiesser group) included patients without graft dysfunction biopsied because of the presence of dnDSA (One Lambda, mean fluorescence intensity [MFI],1000).One hundred twenty-three patients (85 male/38 female; mean age, 49.5 ± 13.1 y old) were biopsied after the detection of a dnDSA, 65.3 months (median) after kidney transplantation. Graft function was stable within 3 months before biopsy (estimated glomerular filtration rate, 55.3 ± 18.9 mL/min/1.73 m). Fifty-one subclinical AMRs (sAMRs) (41.4%) were diagnosed, of which 32 (26%) active and 19 (15.5%) chronic active sAMR. Seventy-two biopsies revealed no AMR (58.5%). Predictive factors associated with the diagnosis of active sAMR were MFI of immunodominant DSA4000, MFI of the sum of DSA6300, age of the recipient45 years old, and the absence of steroids at biopsy. The presence of proteinuria200 mg/g was predictive of chronic active sAMR. The decrease of estimated glomerular filtration rate at 5 years post-biopsy was significantly higher in patients with acute sAMR (-25.2 ± 28.3 mL/min/1.73 m) and graft survival significantly lower.Performing a kidney graft biopsy for the occurrence of dnDSA without renal dysfunction leads to the diagnosis of a sAMR in over 40% of cases. Nevertheless, we did not observe any effect of standard treatment in acute sAMR.

International audience; Background Atypical hemolytic uremic syndrome (HUS) is associated with high recurrence rates after kidney transplant, with devastating outcomes. In late 2011, experts in France recommended the use of highly individualized complement blockade-based prophylaxis with eculizumab to prevent post-transplant atypical HUS recurrence throughout the country.Methods To evaluate this strategy's effect on kidney transplant prognosis, we conducted a retrospective multicenter study from a large French nationwide registry, enrolling all adult patients with atypical HUS who had undergone complement analysis and a kidney transplant since January 1, 2007. To assess how atypical HUS epidemiology in France in the eculizumab era evolved, we undertook a population-based cohort study that included all adult patients with atypical HUS (n=397) between 2007 and 2016.Results The first study included 126 kidney transplants performed in 116 patients, 58.7% and 34.1% of which were considered to be at a high and moderate risk of atypical HUS recurrence, respectively. Eculizumab prophylaxis was used in 52 kidney transplants, including 39 at high risk of recurrence. Atypical HUS recurred after 43 (34.1%) of the transplants; in four cases, patients had received eculizumab prophylaxis and in 39 cases they did not. Use of prophylactic eculizumab was independently associated with a significantly reduced risk of recurrence and with significantly longer graft survival. In the second, population-based cohort study, the proportion of transplant recipients among patients with ESKD and atypical HUS sharply increased between 2012 and 2016, from 46.2% to 72.3%, and showed a close correlation with increasing eculizumab use among the transplant recipients.Conclusions Results from this observational study are consistent with benefit from eculizumab prophylaxis based on pretransplant risk stratification and support the need for a rigorous randomized trial.

The diagnosis of disseminated intravascular coagulation (DIC) is often considered to be a contraindication to organ donation. The aim of this study was to evaluate the impact of DIC+ donors on kidney recipient (KR) evolution. We identified 169 KRs with DIC+ donation after brain death donors between January 1996 and December 2012 in 6 French transplant centers. Individuals were matched using propensity scores to 338 recipients with DIC- donors according to donor age and sex, whether expanded criteria for the donor existed, graft year, and transplantation center. After kidney transplantation, delayed graft function was observed in 28.1% of DIC+ KRs and in 22.8% of DIC- KRs (NS). Renal allograft survival at 1, 5, and 10 years was 94.5%, 89.3%, and 73.9% and 96.2%, 90.8%, and 81.3% in DIC+ KRs and DIC- KRs, respectively (NS). The median estimated glomerular filtration rate (eGFR) was similar between DIC+ and DIC- KRs at 3 months, 1 year, and 10 years: 45.9 vs 48.1 mL/min, 42.1 vs 43.1 mL/min, and 33.9 vs 38.1 mL/min, respectively. Delayed calcineurin inhibitor introduction or induction had no impact on delayed graft function rate or eGFR evolution at 10 years after transplantation in DIC+ KRs. Donor DIC did not seem to affect initial outcome, long-term graft function, or allograft survival.

Immune checkpoint inhibitors are new therapeutic options for metastatic melanoma, but few data are available in organ transplant recipient populations. Six French patients, three men and three women, mean age 66 years (range 44-74), all kidney transplant recipients, received ipilimumab (CTLA-4 inhibitor) for metastatic melanoma. At diagnosis of advanced melanoma, immunosuppressive therapy had been minimized in all but one. Adverse effects included one case of grade 1 diarrhea and one of grade 1 pruritus. One patient had acute T cell-mediated rejection confirmed by histology after the first injection of ipilimumab. After a median follow-up of 4.5 (3-20) months, one patient achieved partial response, one had stable disease, and four had disease progression. All the patients died, five from melanoma, one from another cause. In this series and in the literature, ipilimumab proved to be safe and possibly active. The acute rejection we encountered was probably related to both a rapid, drastic reduction of immunosuppression and the use of ipilimumab. Our safety data on ipilimumab contrast with the organ transplant rejections already reported with PD-1 inhibitors. We consider that immunosuppression should not be minimized, as the impact on metastatic disease control is probably small.

BackgroundThe increased survival of patients with multiple myeloma (MM) raises the question of kidney transplantation (KT) in patients with end-stage renal disease (ESRD).MethodsWe included 13 patients with MM or smoldering myeloma (SMM) and ESRD transplanted between 2007 and 2015, including 7 MM with cast nephropathy, 3 with MM-associated amyloid light chain amyloidosis or light chain deposition disease and 3 SMM and compared them with 65 control-matched kidney-transplanted patients. Nine of the MM patients with KT were also compared with 63 matched MM patients on haemodialysis.ResultsPre-transplantation parameters were comparable, except for the duration of renal replacement therapy (57.8 versus 37.0 months; P = 0.029) in MM versus control patients, respectively. The median follow-up post-KT was 44.4 versus 36.4 months (P = 0.40). The median MM graft and patient survival were 80.1 and 117.2 months, respectively, and were not significantly different from control patients, although mortality tended to be higher in the 10 symptomatic MM patients (P = 0.059). MM patients had significantly more viral and fungal infections and immunosuppressive maintenance therapy modifications while they received lower induction therapy. Two MM patients relapsed and two SMM cases evolved to MM after KT. Three cast nephropathies occurred, two of them leading to ESRD. Moreover, survival of MM with KT increased relative to control haemodialysed patients (P = 0.002).ConclusionsSelected MM patients may benefit from KT but need careful surveillance in the case of KT complications and MM evolution.

The aim of this study was to estimate the incidence of COVID-19 disease in the French national population of dialysis patients, their course of illness and to identify the risk factors associated with mortality. Our study included all patients on dialysis recorded in the French REIN Registry in April 2020. Clinical characteristics at last follow-up and the evolution of COVID-19 illness severity over time were recorded for diagnosed cases (either suspicious clinical symptoms, characteristic signs on the chest scan or a positive reverse transcription polymerase chain reaction) for SARS-CoV-2. A total of 1,621 infected patients were reported on the REIN registry from March 16th, 2020 to May 4th, 2020. Of these, 344 died. The prevalence of COVID-19 patients varied from less than 1% to 10% between regions. The probability of being a case was higher in males, patients with diabetes, those in need of assistance for transfer or treated at a self-care unit. Dialysis at home was associated with a lower probability of being infected as was being a smoker, a former smoker, having an active malignancy, or peripheral vascular disease. Mortality in diagnosed cases (21%) was associated with the same causes as in the general population. Higher age, hypoalbuminemia and the presence of an ischemic heart disease were statistically independently associated with a higher risk of death. Being treated at a selfcare unit was associated with a lower risk. Thus, our study showed a relatively low frequency of COVID-19 among dialysis patients contrary to what might have been assumed., Graphical abstract

Conversion from calcineurin-inhibitors (CNIs) to belatacept can help kidney-transplant (KT) recipients avoid CNI-related nephrotoxicity. The risk of associated opportunistic infections (OPIs) is ill-defined. We conducted a multicentric cohort study across 15 French KT-centers in a real-life setting. Between 07-2010 and 07-2019, 453 KT recipients were converted from CNI- to belatacept-based therapy at 19 [0.13&ndash, 431] months post-transplantation. Most patients, i.e., 332 (79.3%), were converted after 6-months post-transplantation. Follow-up time after conversion was 20.1 +/&minus, 13 months. OPIs developed in 42(9.3%) patients after 14 +/&minus, 12 months post-conversion. Eight patients (19%) had two OPI episodes during follow-up. Incidences of CMV DNAemia and CMV disease were significantly higher in patients converted before 6-months post-KT compared to those converted later (i.e., 31.6% vs. 11.5%, p &lt, 0.001, and 11.6% vs. 2.4%, p &lt, 0.001, respectively). Cumulative incidence of OPIs was 6.5 OPIs/100 person&ndash, years. Incidence of CMV disease was 2.8/100 person&ndash, years, of pneumocystis pneumonia 1.6/100 person&ndash, years, and of aspergillosis 0.2/100 person&ndash, years. Multivariate analyses showed that estimated glomerular filtration (eGFR) &lt, 25 mL/min/1.73 m2 at conversion was independently associated with OPIs (HR = 4.7 (2.2 &minus, 10.3), p &lt, 0.001). The incidence of EBV DNAemia was 17.3 events /100 person&ndash, years. At 1-year post-conversion, mean eGFR had significantly increased from 32.0 +/&minus, 18 mL/min/1.73 m2 to 42.2 +/&minus, 18 mL/min/1.73 m2 (p &lt, 0.0001). Conversion to belatacept is an effective strategy with a low infectious risk.

International audience; The treatment of active antibody-mediated rejection (ABMR) is still a matter of debate, the place of rituximab remaining controversial. The French multicenter double-blind RITUX-ERAH study included 38 patients with ABMR in the first year of renal transplantation. All patients received plasma exchanges, intravenous immunoglobulins, and corticosteroids and were randomly assigned rituximab or placebo infusion at day 5. Additional rituximab infusions were allowed. In the intention-to-treat analysis, 12-month graft survival and renal function were not different between the rituximab and placebo groups. Long-term data are needed to conclude. Evaluation of the 7-year outcomes of the RITUX-ERAH study patients according to the rituximab or placebo treatment received. Eleven patients received placebo and 27 at least one infusion of rituximab. Seven years after ABMR, death-censored kidney allograft survival and renal function were not different between the groups. The evolution of anti-HLA sensitization was similar. There was no statistically significant difference in the incidence of infectious or neoplastic complications, but to be noted, seven cancers developed in six patients treated with rituximab (mean period of 44~months post-ABMR). In this cohort, there was no benefit 7~years after ABMR of rituximab in addition to plasma exchanges, intravenous immunoglobulins, and steroids.

BACKGROUND Renal cancer accounts for 3% of adult malignancies; renal cell carcinoma (RCC) represents 80% of all renal cancers, and is characterized by late recurrences. Recurrences after kidney transplantation are associated with a high mortality rate. We aimed to determine if recurrences are linked to tumor characteristics and to delays between diagnosis and transplantation. METHODS We retrospectively analyzed data from French kidney-transplanted patients with medical histories of pretransplant renal cancer, focusing on the most common histological subtypes: clear cell and papillary cancers. Characteristics of the tumors, patients, and kidney transplantations were documented, and posttransplant patient survival was analyzed. RESULTS Of 143 patients, 13 experienced cancer recurrence after kidney transplantation. The mean delay in recurrence was 3 ± 2.3 years posttransplantation, and the cumulative incidences of recurrence were 7.7% at 5 years and 14.9% at 10 years. The risk of recurrence was higher in patients with clear cell RCC (13% vs 0%, P = 0.015). There was no correlation between posttransplant recurrence and the interval before transplantation. Factors associated with a higher risk of cancer recurrence were histological clear cell RCC (P = 0.025), tumor stage pT2 (P = 0.002), and Fuhrman grade IV (P < 0.001). Recurrences were associated with a high mortality rate; 76.9% of patients with recurrences had died by the end of the follow-up period. CONCLUSIONS Recurrences of clear cell RCC are not uncommon after kidney transplantation and are associated with very poor prognoses. These results should be considered before listing patients with a history of renal cancer for transplantation.

BACKGROUND: Although anti-HLA antibodies (Abs) cause most antibody-mediated rejections of renal allografts, non-anti-HLA Abs have also been postulated to contribute. A better understanding of such Abs in rejection is needed.METHODS: We conducted a nationwide study to identify kidney transplant recipients without anti-HLA donor-specific Abs who experienced acute graft dysfunction within 3 months after transplantation and showed evidence of microvascular injury, called acute microvascular rejection (AMVR). We developed a crossmatch assay to assess serum reactivity to human microvascular endothelial cells, and used a combination of transcriptomic and proteomic approaches to identify non-HLA Abs.RESULTS: We identified a highly selected cohort of 38 patients with early acute AMVR. Biopsy specimens revealed intense microvascular inflammation and the presence of vasculitis (in 60.5%), interstitial hemorrhages (31.6%), or thrombotic microangiopathy (15.8%). Serum samples collected at the time of transplant showed that previously proposed anti-endothelial cell Abs-angiotensin type 1 receptor (AT1R), endothelin-1 type A and natural polyreactive Abs-did not increase significantly among patients with AMVR compared with a control group of stable kidney transplant recipients. However, 26% of the tested AMVR samples were positive for AT1R Abs when a threshold of 10 IU/ml was used. The crossmatch assay identified a common IgG response that was specifically directed against constitutively expressed antigens of microvascular glomerular cells in patients with AMVR. Transcriptomic and proteomic analyses identified new targets of non-HLA Abs, with little redundancy among individuals.CONCLUSIONS: Our findings indicate that preformed IgG Abs targeting non-HLA antigens expressed on glomerular endothelial cells are associated with early AMVR, and that in vitro cell-based assays are needed to improve risk assessments before transplant.

Background - Extracorporeal photopheresis (ECP) has shown encouraging results in the prevention of allograft rejection in heart transplantation. However, the role of ECP in kidney transplant (KT) rejection needs to be determined. Methods - This multicentre retrospective study included 33 KT recipients who were treated with ECP for allograft rejection (23 acute antibody-mediated rejections (AMRs), 2 chronic AMRs and 8 acute cellular rejections (ACRs)). The ECP indications were KT rejection in patients who were resistant to standard therapies (n = 18) or in patients for whom standard therapies were contraindicated because of concomitant infections or cancers (n = 15). Results - At 12 months (M12) post-ECP, 11 patients (33%) had a stabilization of kidney function with a graft survival rate of 61%. The Banff AMR score (g + ptc + v) was a risk factor for graft loss at M12 (HR 1.44 [1.01-2.05], p 0.05). The factorial mixed data analysis identified 2 clusters. Patients with a functional graft at M12 tended to have cellular and/or chronic rejections. Patients with graft loss at M12 tended to have acute rejections and/or AMR; higher serum creatinine levels; DSA levels and histologic scores of AMR; and a longer delay between the rejection and ECP start than those of patients with functional grafts. Conclusions - ECP may be helpful to control ACR or moderate AMR in KT recipients presenting concomitant opportunistic infections or malignancies when it is initiated early.

De novo donor-specific antibodies (dnDSA) are associated with antibody-mediated rejection (ABMR) and allograft loss. We tested Immucor* (IM) Luminex Single-antigen beads (LSAB) assay and C3d-fixing antibodies in the setting of dnDSA and subclinical (s) ABMR. This retrospective multicentric study included 123 patients biopsied because of the presence of subclinical de novo DSA detected by One Lamda* Labscreen (MFI > 1000). In 112 patients, sera of the day of the biopsy were available and tested in a central lab with IM Lifecodes LSAB and C3d fixing antibodies assays. In 16 patients (14.3%), no DSA was detected using Immucor test. In 96 patients, at least one DSA was determined with IM. Systematic biopsies showed active sABMR in 30 patients (31.2%), chronic active sABMR in 17 patients (17.7%) and no lesions of sABMR in 49 KT recipients (51%). Intensitity criteria (BCM, BCR and AD-BCR) of DSA were not statistically different between these 3 histological groups. The proportion of patients with C3d-fixing DSA was not statistically different between the 3 groups and did not offer any prognostic value regarding graft survival. Performing biopsy for dnDSA could not be guided by the intensity criteria of IM LSAB assay. C3d-fixing DSA do not offer added value.

In 2012, an expert working group from the French Transplant Health Authority recommended the use of hypothermic machine perfusion (HMP) to improve kidney preservation and transplant outcomes from expanded criteria donors, deceased after brain death. This study compares HMP and cold storage (CS) effects on delayed graft function (DGF) and transplant outcomes. We identified 4,316 kidney transplants from expanded criteria donors (2011-2014) in France through the French Transplant Registry. DGF occurrence was analyzed with a logistic regression, excluding preemptive transplants. One-year graft failure was analyzed with a Cox regression. A subpopulation of 66 paired kidneys was identified: one preserved by HMP and the other by CS from the same donor. Kidneys preserved by HMP (801) vs CS (3515) were associated with more frequent recipient comorbidities and older donors and recipients. HMP had a protective effect against DGF (24% in HMP group and 38% in CS group, OR = 0.49 [0.40-0.60]). Results were similar in the paired kidneys (OR = 0.23 [0.04-0.57]). HMP use decreased risk for 1-year graft failure (HR = 0.77 [0.60-0.99]). Initial hospital stays were shorter in the HMP group (P < 0.001). Our results confirm the reduction in DGF occurrence among expanded criteria donors kidneys preserved by HMP.

International audience; Magnesium (Mg) status has recently drawn close attention in chronic kidney disease and in kidney transplant recipients. This review aims to evaluate the body of evidence linking hypomagnesemia to clinical consequences in these specific populations. After a brief summary of the main mechanisms involved in Mg regulation and of Mg status in end-stage renal disease, the review focuses on the relationship between hypomagnesemia and cardiovascular risk in kidney transplant recipients. A body of evidence in recent studies points to a negative impact of hypomagnesemia on post-transplant diabetes mellitus (PTDM) and cardiovascular risk, which currently represent the main threat for morbidity and mortality in kidney transplantation. Deleterious biological mechanisms induced by hypomagnesemia are also discussed. While data analysis enables us to conclude that hypomagnesemia is linked to the development of PTDM, studies prospectively evaluating the impact of hypomagnesemia correction after kidney transplantation are still lacking and needed.

International audience; Background: The differential pathogenicity of anti-HLA donor-specific antibodies (DSAs) is not fully understood. The presence of complement-binding DSAs helps in better defining the prognosis of acute antibody-mediated rejection (ABMR). The evolution of these antibodies after the treatment of ABMR is unknown.Methods: We included patients from the French multicenter RITUX ERAH study diagnosed with acute ABMR within the first year of renal transplantation, with circulating anti-HLA DSAs and treated randomly by rituximab or placebo (and intravenous immunoglobulins, plasma exchange). We centrally analyzed serum samples at the time of ABMR, 3 and 6 months after ABMR, with anti-HLA DSAs specificities and C1q-binding capacity assessment.Results: Twenty-five patients were included: 68% had C1q-binding DSAs at the time of ABMR. The presence of C1q-binding DSAs was associated with a poorer evolution of chronic glomerulopathy at 6 months (P = 0.036). The persistence of C1q-binding DSAs at 3 and/or 6 months after ABMR was associated with more severe chronic glomerulopathy (P = 0.006), greater C4d score deposition score at 6 months after ABMR (P = 0.008), and graft loss 5 years after ABMR (P = 0.029). C1q-binding capacity was associated with the DSA MFI but 5 C1q-binding DSAs in 4 patients had low MFI values without a prozone effect.Conclusion: The presence and persistence of anti-HLA C1q-binding DSAs after ABMR is a detrimental marker, leading to transplant glomerulopathy and graft loss. Assessment of the complement-binding capacities of DSAs could help decide treatment intensification.

International audience; IgA nephropathy (IgAN), the most frequent primary glomerulonephritis, affects young patients and is associated with a high risk of progression to end-stage renal disease. Consequently, patients with IgAN constitute an important proportion of candidates for kidney transplantation. Several studies showed a significant risk of IgAN recurrence on kidney graft, but the risks factors for recurrence remain to be accurately evaluated. Indeed, early identification of at risk patients may allow the optimization of treatment and the reduction of recurrence rate on the graft. In the present work, we studied the relationship between post-transplant serum IgA (sIgA) levels and the risk of IgAN recurrence after kidney transplantation. Recipients with IgAN had higher levels of sIgA as compared to patients with other nephropathies (p

Background: Total artificial heart (TAH) device is sometimes necessary to treat end stage heart failure (HF). After surgery, renal impairment can occur with the need of renal replacement therapy. Method: We report the case of a 51-year-old man who was treated with conventional hemodialysis (HD) while on support with TAH. Results: The patient underwent HD while on TAH support during 14 months. He benefited from conventional HD, 6 sessions per week. HD sessions were well tolerated, and patient's condition and quality of life improved significantly. The main difficulty was to maintain red blood cell level because of chronic hemolysis due to TAH, which required repetitive blood transfusions, resulting in a high rate of human leukocyte antigen sensitization. Unfortunately, the patient died of mesenteric ischemia due to anticoagulation under dosing. Conclusion: We conclude that HD treatment is possible despite TAH and should be considered in patients with both end stage renal and HF.

New-onset diabetes after transplantation (NODAT) is a frequent condition associated with a poor outcome. In kidney transplantation, hypomagnesemia is a frequent posttransplant complication and has been associated with calcineurin inhibitors use. Previous studies have analyzed the relationship between posttransplant hypomagnesemia and the risk of NODAT and provided conflicting conclusions. We conducted an observational study to analyze the relationship between pretransplant magnesemia (Mg) and the risk of NODAT within the first year of kidney transplantation.A cohort study was conducted to determine the risk conferred by pretransplant magnesium level on development of NODAT within 1 year posttransplant. First time kidney transplant recipients between January 2005 and December 2010 with more than 6 months of follow-up were included. Mg was measured within the 24 hours preceding kidney transplantation. NODAT was defined according to the American Diabetes Association criteria.Among the 154 patients analyzed, 28 (18.2%) developed NODAT at year 1. NODAT patients had lower levels of pretransplant Mg as compared with non-NODAT patients (P0.02). When patients were divided into tertiles of Mg level, NODAT developed more frequently in patients in the lower tertile (Mg2 mg/dL) as compared with patients in the higher tertile (Mg2.3 mg/dL) (log rank, P0.05). A multivariate analysis after adjustment to several variables demonstrated pretransplant Mg to be an independent risk factor of NODAT.This study supports that a low pretransplant Mg level is an independent risk factor of NODAT in kidney transplant recipients.

Introduction Avec le vieillissement de la population, la biopsie renale est de plus en plus frequemment indiquee chez des patients âges voire tres âges [1] . Cependant, les etudes concernant les indications et l’interet de la biopsie renale chez ces patients sont rares. Patients/materiels et methodes Tous les patients consecutifs de plus de 65 ans chez lesquels une biopsie de rein natif a ete realisee entre 2004 et 2016 dans notre centre ont ete inclus. Les donnees des patients de plus de 80 ans (tres âges) ont ete comparees a celles des patients dont l’âge etait compris entre 65 et 80 ans (âges). La survie a long terme des patients tres âges a egalement ete etudiee. Resultats Deux cent six biopsies ont ete analysees chez 199 patients, 153 patients âges et 46 patients tres âges. L’insuffisance renale aigue et le syndrome nephrotique etaient les principales indications de la biopsie renale. Il n’a pas ete observe de difference significative entre les deux groupes concernant : la presentation clinique, les diagnostics histologiques et le taux de complication du geste. La glomerulonephrite extra-membraneuse et la nephroangiosclerose etaient les diagnostics les plus representes chez les patients tres âges avec 13 % et 15 % des diagnostics respectivement, sans difference avec les patients âges (p = 0,59 et p = 0,8 respectivement). La survie des patients tres âges etait de 73,1 %, 50,6 % et 21,8 % a 2, 4 et 6 ans apres la biopsie. La survenue d’un deces precoce etait associee a un rapport proteinurie/creatininurie plus eleve (p = 0,036). Parmi les patients tres âges, 67,4 % presentaient une nephropathie potentiellement accessible a un traitement et 40 % ont debute un traitement immunosuppresseur. La survie des patients presentant une nephropathie potentiellement accessible a un traitement semblait meilleure bien que de facon non significative (p = 0,065). Conclusion La biopsie renale est une technique fiable et utile pour etablir un diagnostic nephrologique chez les patients tres âges. Nos resultats suggerent que la biopsie permet de mettre en evidence des pathologies renales accessibles a un traitement specifique et d’eviter ainsi une evolution irreversible vers l’insuffisance renale terminale ou le deces.

Thrombotic microangiopathies (TMAs) can be due to inherited or acquired ADAMTS13 deficiency. Acquired deficiency is mainly associated with autoantibodies directed to ADAMTS13, including drug-induced forms. A few cases of TMA have been reported in association with interferon-alpha treatment and more rarely with interferon-beta. We report the case of a 52-year-old male with TMA-associated severe renal failure secondary to severe ADAMTS13 deficiency due to an anti-ADAMTS13 IgG antibody which developed after interferon-beta treatment for multiple sclerosis. Treatment included interferon-beta discontinuation, immediate plasma exchange therapy, corticosteroids, and hemodialysis. After an initial hematologic improvement, early hemolysis relapse led us to introduce rituximab allowing durable hematologic recovery. This is the first reported case of interferon-beta-induced TMA due to acquired ADAMTS13 deficiency that was treated by rituximab.

Anti-tumor necrosis factor-α (TNFα) therapy has improved the prognosis of many chronic inflammatory diseases. It appears to be well-tolerated by liver-transplant patients. However, their use and their safety in kidney-transplant patients have yet to be determined. In this retrospective study, we identified 16 adult kidney-transplant patients aged 46.5 years (34–51.8) who received anti-TNFα therapy from 7 kidney transplantation centers. The indications for this treatment included: chronic inflammatory bowel disease (n = 8), inflammatory arthritis (n = 5), AA amyloidosis (n = 1), psoriasis (n = 1), and microscopic polyangiitis (n = 1). Anti-TNFα therapies resulted in a clinical response in 13/16 patients (81%). Estimated glomerular filtration rates (MDRD-4) were similar on day 0 and at 24 months (M24) after anti-TNFα treatment had been initiated (41 [12–55] and 40 [21–53] mL/min/1.73 m2, respectively). Two allograft losses were observed. The 1st case was due to antibody-mediated rejection (M18), while the 2nd was the result of AA amyloidosis recurrence (M20). There were several complications: 8 patients (50%) developed 23 serious infections (18 bacterial, 4 viral, and 1 fungal) and 4 developed cancer. Five patients died (infection n = 2, cardiac AA amyloidosis n = 1, intraalveolar hemorrhage following microscopic polyangiitis n = 1, and acute respiratory distress syndrome n = 1). On univariate analysis, recipient age associated with death (P = 0.009) and infection development (P = 0.06). Using anti-TNFα therapies, remission can be achieved in chronic inflammatory diseases in kidney-transplant patients. However, concommitant anti-TNFα and immunosuppresive therapies must be used with caution due to the high risk of infection, particularly after the age of 50.

The aim of this study (NCT01744470) was to determine the efficacy and safety of two different doses of extended-release tacrolimus (TacER) in kidney transplant recipients (KTR) between 4 and 12 months post-transplantation. Stable steroid-free KTR were randomized (1:1) after 4 months: Group A 50%-reduction in TacER dose with targeted TacERC0>3μg/L; Group B no change in TacER dose (TacERC0=7-12μg/L). The primary outcome was eGFR at 1 year. Of 300 patients, intent-to-treat analysis included 186 patients (Group A 87, Group B 99). TacERC0 were lower in Group A than in Group B at 6 (4.1±2.7 vs 6.7±3.9μg/L, p 0: 21.4% vs. 8.8%, p=0.047; t>0: 19.6% vs. 8.7%, p=0.076, i+t: 1.14±1.21 vs 0.72±1.01, p=0.038). DSA appeared only in Group A (6 patients vs. 0, p=0.008). TacERC0 should be maintained above 7μg/L during the first year post-transplantation in low immunological risk steroid-free KTR receiving moderate dose of MPA. This article is protected by copyright. All rights reserved.

Background Recent data have outlined a link between hypogammaglobulinemia (HGG) and infection risk and suggested that HGG correction may decrease post-transplant infections. Methods We analyzed the risk factors of HGG and the relationship between HGG and the risk of severe infection in a cohort of 318 kidney transplant recipients (KTR) who were transplanted between 2003 and 2013. Immunoglobulin (Ig) concentration was measured prospectively at day 15 (D15), month 6 (M6), month 12 (M12), and month 24 (M24) post transplant. Results The prevalence of IgG HGG was 56% and 36.8% at D15 and M6 respectively. Age was the sole identified risk factors for D15 IgG HGG (odds ratio [OR] 1.02, P = 0.019). Risk factors for M6 IgG HGG were the presence of D15 IgG HGG (OR 6.41, P

Background Adult Henoch-Schonlein purpura (HSP) has been associated with poor outcome and end-stage renal disease in >20% of cases. Although the benefit of adding another immunosuppressant to steroids in severe adult HSP has not been shown, the benefit of plasma exchange (PE) therapy has been poorly evaluated. Study Design Case series. Setting & Participants 11 consecutive patients with severe and newly diagnosed HSP since 1988 who were treated with steroids and PE. Outcome & Measurement Patients' characteristics and outcome were analyzed. Birmingham Vasculitis Activity Score (BVAS), estimated glomerular filtration rate (eGFR), and proteinuria were measured at baseline, at the end of PE treatment, at months 6 and 12, and at the last visit. Side effects of corticoid treatment and PE were recorded. Results 11 patients were identified in 1988-2010. Patients received intravenous corticoid pulses in 64% of cases, followed by oral prednisone for a median of 6.6 months. They received a median of 12 PE sessions. BVAS, eGFR, and proteinuria improved significantly between baseline and the last PE at a median of 2 months. PE sessions were well tolerated, except in one patient who developed central catheter–associated septicemia. One patient required dialysis therapy 15 days after HSP diagnosis and did not recover kidney function. At the last medical evaluation at a mean follow-up of 6 years, median eGFR and proteinuria were 83 ± 22 mL/min/1.73 m 2 and protein excretion of 140 ± 10 mg/d, respectively. 3 women had pregnancy without complications. Limitations This case series did not have a control group. Conclusions The combination of PE and corticoid therapy in severe forms of HSP was associated with fast improvement and good long-term outcome.

Introduction Les infections a CytoMegaloVirus (CMV) constituent une complication infectieuse majeure en transplantation renale. Le principal facteur de risque reste le « mismatch » serologique, lorsque le receveur non immunise contre le CMV recoit un greffon d’un donneur immunise. Les patients greffes renaux immunises avant la greffe, dits CMV R+, se situent a un risque intermediaire et doivent beneficier, selon les recommandations de 2012, d’un traitement antiviral prophylactique ou d’une strategie preemptive. L’administration de serum anti-lymphocytaire en traitement d’induction est un facteur de risque independant de reactivation a CMV. Il est donc difficile de considerer les CMV R+ comme un groupe homogene en terme de risque de reactivation CMV mais aucune etude n’a jamais separe les patients en fonction du type d’induction recue. Nous nous sommes interesses specifiquement aux CMV R+ sans induction depletante, consideres a risque moins eleve de maladie a CMV. Patients/Materiels et methodes Cette etude retrospective multicentrique a inclus les patients CMV R+, greffes dans 6 centres francais entre janvier 2012 et avril 2015 et ayant recu une induction non depletante par basiliximab ou une absence d’induction. Les patients beneficiant d’une strategie preemptive ont ete exclus. L’objectif de l’etude etait d’evaluer la non-inferiorite de l’absence de traitement preventif par rapport a une prophylaxie par 3 mois de valganciclovir. Le critere de jugement principal etait la survenue d’une maladie a CMV. Observation/Resultats Ont ete inclus 372 patients (57,8 % d’hommes), d’âge moyen 57,2 ans. A un an, 5/222 patients (2,25 %) avec prophylaxie et 9/150 (6 %) sans prophylaxie ont presente une maladie a CMV sans difference significative en non-inferiorite (difference + 3,7 ; IC95 % −0,5 a 8 ; p = 0,002). A un an, les taux de rejets, de survenue d’autres infections et la fonction du greffon etaient similaires. Il y avait moins de neutropenies severes dans le groupe sans prophylaxie (4,7 % contre 11,3 %, p Discussion/Conclusion Notre etude est la premiere a evaluer le risque de maladie a CMV specifiquement chez les patients CMV R+ ne recevant pas d’induction depletante. L’absence de prophylaxie n’apparait pas deletere quant au risque de maladie a CMV, mais egalement sur les effets indirects du CMV (taux de rejets et survie du greffon). Par contre, en l’absence de prophylaxie, les patients font moins de leuconeutropenies. Le benefice est egalement economique puisque 3 mois de traitement par Valganciclovir coutent 3500 euros.

Malakoplakia is a rare inflammatory disorder that affects predominantly the urinary tract and kidneys. Isolated renal parenchymal involvement occurs in 16% of all cases [1]. Urinary tract and digestive malakoplakia have been reported in transplant recipients but involvement in transplant tissue is rare. We report a case of renal allograft parenchymal malakoplakia and present a brief review of kidney transplant malakoplakia cases from the literature.

The aim of this study was to compare the outcomes of kidney transplants from uncontrolled DCD (uDCD) with kidney transplants from extended (ECD) and standard criteria donors (SCD). In this multicenter study, we included recipients from uDCD (n = 50), and from ECD (n = 57) and SCD (n = 102) who could be eligible for a uDCD program. We compared patient and graft survival, and kidney function between groups. To address the impact of preservation procedures in uDCD, we compared in situ cold perfusion (ICP) with normothermic regional perfusion (NRP). Patient and graft survival rates were similar between the uDCD and ECD groups, but were lower than the SCD group (P < 0.01). Although delayed graft function (DGF) was more frequent in the uDCD group (66%) than in the ECD (40%) and SCD (27%) groups (P = 0.08 and P < 0.001), graft function was comparable between the uDCD and ECD groups at 3 months onwards post-transplantation. The use of NRP in the uDCD group (n = 19) was associated with a lower risk of DGF, and with a better graft function at 2 years post-transplantation, compared to ICP-uDCD (n = 31) and ECD. In conclusion, the use of uDCD kidneys was associated with post-transplantation results comparable to those of ECD kidneys. NRP preservation may improve the results of uDCD transplantation.

International audience; We present the results at 8 years of the Spiesser study, a randomized trial comparing de novo sirolimus and cyclosporine in kidney transplant recipients at low immunologic risk. We assessed estimated glomerular filtration (eGFR), graft, patient, and death-censored graft survival (log-rank compared), de novo DSA appearance, risk of malignancy, post-transplant diabetes mellitus (PTDM), and anemia. Intent-to-treat and on-treatment analyses were performed. Graft survival was similar in both groups (sirolimus: 73.3%, cyclosporine: 77.7, P = 0.574). No difference was observed between treatment groups concerning patient survival (P = 0.508) and death-censored graft survival (P = 0.858). In conditional intent-to-treat analysis, mean eGFR was greater in sirolimus than in cyclosporine group (62.5 ± 27.3 ml/min vs. 47.8 ± 17.1 ml/min, P = 0.004), in particular because graft function was excellent in patients maintained under sirolimus (eGFR = 74.0 ml/min). Importantly, no detrimental impact was observed in patients in whom sirolimus has been withdrawn (eGFR = 49.5 ml/min). Overall, 17 patients showed de novo DSAs, with no difference between the two groups (P = 0.520). Malignancy did not differ by treatment. An initial maintenance regimen based on sirolimus provides a long-term improvement in renal function for kidney transplant patients, especially for those maintained on sirolimus.

Learning Point for Clinicians Sarcoidosis may present as bilateral kidney pseudotumours. Clinical presentation of this form of renal sarcoidosis is quite unspecific and is usually associated with normal renal function. Its diagnosis relies on imagery [computed tomography (CT) scan] and kidney histology. The literature and the present case suggest the efficiency of corticosteroids. A 32-year-old male was referred to our department for bilateral kidney tumours. Past medical history included sarcoidosis with eyes and lung involvement that was diagnosed 10 years ago and successfully treated with oral corticosteroids for 3 months. Afterwards, he remained asymptomatic until recently when he developed a right renal colic. A CT scan revealed the presence of bilateral renal masses (Figure 1A). Infracentimetric retroperitoneal lymph nodes were detected and their association with the kidney tumours led to suspect the diagnosis of lymphomatous disease and the performance of biopsy of the kidney tumours. The histological analysis showed a granulomatous interstitial nephritis with typical multinucleated giant cells and a surrounding lymphocytic infiltrate. The interstitium was largely replaced by …

A 26-year-old woman presented to a local community hospital with fever and abdominal pain. Clinical examination showed mild abdominal and bilateral lumbar tenderness. Blood analysis showed C-reactive protein of 401 mg/l, leukocyte count of 15,340/mm3, and serum creatinine of 71 μmol/l. Chest radiograph and abdominal ultrasound were normal. She was diagnosed with pyelonephritis despite negative urinalysis and was discharged. Soon after, her condition worsened with 5 kg weight loss, myalgia, and arthralgia. Two months later, she was readmitted with severe left flank pain. Contrast-enhanced abdominal computed tomography (CT) showed a large subcapsular hematoma surrounding the left kidney (Figure 1). Multiple bilateral intrarenal aneurysms of variable diameter (1–14 mm) were detected during the arterial phase (Figure 1) with the appearance of bunch of grapes. Multiple bilateral wedge-shaped low-attenuation involving cortex and medulla suggesting kidney infarcts were also detected (Supplementary Figure 1 online). Urinalyses showed microscopic hematuria and proteinuria of 0.9 g/24 h. Comprehensive autoimmune including Anti-neutrophil cytoplasmic antibodies (ANCA) research and viral screenings were negatives.

Introduction Environ 1 % des lithiases urinaires sont d’origine medicamenteuse. Nous presentons un cas d’insuffisance renale aigue obstructive compliquant la prise de sulfadiazine, decouverte 12 jours apres l’initiation du traitement, avec identification des cristaux par analyse pharmacologique. Observation Il s’agit d’une patiente de 71 ans, presentant une myelodysplasie ayant necessite une allogreffe en juillet 2016. Les suites de la greffe ont ete marquees par une GVH corticoresistante traitee par ruxolitinib, puis par l’apparition en mars 2017 d’un syndrome confusionnel et de troubles mnesiques, faisant suspecter une toxoplasmose. Un traitement par pyrimethamine (50 mg/j)–sulfadiazine (1 g toutes les 4 heures) est initie. Le reste de son traitement comportait de l’amoxicilline 2 g/j, du valganciclovir 1800 mg/j (pour une reactivation CMV), prednisone 30 mg/j, ruxolitinib 20 mg/j, folinate de calcium 25 mg/j et l2 vetiracetam 1000 mg/j. Douze jours apres l’introduction de la sulfadiazine, elle presente une insuffisance renale aigue (IRA) avec une creatininemie a 176 μmol/L, associee a une microhematurie et une proteinurie moderee, motivant l’arret de la sulfadiazine, de la pyrimethamine et du valganciclovir. Trois jours plus tard, la creatininemie est controlee a 595 μmol/L. L’echographie renale retrouve une dilatation bilaterale des cavites pyelocalicielles. Le scanner confirme la presence de lithiases bilaterales legerement hyperdenses et de tonalite non calcique, faisant suspecter une lithiase d’origine medicamenteuse. Apres derivation par sondes JJ bilaterales, l’evolution est favorable sur le plan nephrologique. Une analyse pharmacologique urinaire a revele la presence de sulfadiazine et de son metabolite (N-4 acetylsulfadiazine). L’identification des cristaux objective la presence de cristaux de sulfadiazine, confirmant le diagnostic d’IRA obstructive secondaire a la prise de sulfadiazine. Conclusion La sulfadiazine est utilisee en premiere intention dans le traitement de certaines infections opportunistes, comme la toxoplasmose ou la nocardiose. Son elimination est essentiellement renale. L’apparition d’une insuffisance renale aigue chez un patient traite par sulfadiazine doit faire evoquer une etiologie obstructive, liee a la cristallisation de la molecule et de ses metabolites, responsable de la formation de lithiases. Elle peut etre prevenue par une hydratation adaptee avec alcalinisation.

A prompt immunosuppressive treatment initiation is crucial in ANCA-associated vasculitis (AAV) to minimize organ injury. The aim of the present work was to analyze the accuracy of emergency ANCA screening to identify rapidly patients with AAV. In our Institution, emergency ANCA screening is based on a telephone call between a Clinician and a Biologist. Indirect immunofluorescence (IIF) for ANCA detection was performed using a commercial kit (Euroimmun(®) Granulocyte Mosaic 12). Positive serums for c- or p-ANCA at IIF are subsequently screened for antigenic specificity (MPO or PR3) by an immunodot technique (immunodot, D-Tek(®).) Positive samples with atypical c- or p-ANCA pattern at IIF are subsequently screened for antigenic specificity by ELISA. Data were retrieved from patients' medical records and confronted to emergency ANCA screening results. Between 2005 and 2012, 114 patients were screened. IIF was positive in 27.2% of patients, but c-/p-ANCA anti-MPO/-PR3 was detected in 13.2% of patients. The sensibility and specificity of IIF combined with immunodot for newly diagnosed AAV were 83.3 and 100%, respectively. Ten patients were newly diagnosed with AAV. In these patients, a specific AAV treatment was initiated less than 24 h following ANCA screening. Emergency ANCA screening based on a clinical gating policy was relevant to identify patients with AAV diagnosis, and was associated with a rapid treatment initiation.

Drug rash with eosinophilia and systemic symptoms (DRESS syndrome) is a rare and severe drug-induced hypersensitivity syndrome characterized by haematological abnormalities (hypereosinophilia and/or mononucleosis) and multiorgan involvement. Renal failure has been rarely described. We report the case of a 77-year-old female with sulphasalazine-induced DRESS syndrome who improved rapidly on corticosteroid treatment. After prednisone withdrawal, the patient developed renal failure that necessitated a session of haemodialysis. A kidney biopsy showed acute tubulointerstitial nephritis with an intense lymphocytic infiltrate and tubular necrosis. Kidney function normalized after a further 2 weeks of corticosteroid treatment. This is the first histologically proven case of acute tubulointerstitial nephritis in the setting of sulphasalazine-induced DRESS syndrome.

Primary lymphedema is a rare disease caused by a disorder of lymphangiogenesis. Clinical presentation and age at onset are variable. AA amyloidosis is usually due to chronic inflammatory diseases, malignant tumors or less frequently chronic infectious diseases. We report here the first two cases of AA amyloidosis present with renal failure and nephrotic syndrome in patients with primary lymphedema-induced chronic leg ulcers. The first patient was a 62-year-old female who presented with chronic untreated leg ulcers for 8 years secondary to primary lymphedema. A kidney biopsy done for nephrotic syndrome allowed the diagnosis of AA amyloidosis. The second patient was a 54-year-old male who presented with hereditary lymphedema and elephantiasis since the age of 12. A salivary gland biopsy allowed the diagnosis of AA amyloidosis. Renal function deteriorated progressively needing chronic haemodialysis. Chronic leg ulcers have been rarely reported to induce AA amyloidosis. Only five other cases have been reported in the literature, but none of them with chronic lymphedema. We believe that the relation between lymphedema, chronic leg ulcers and AA amyloidosis is underestimated.

International audience; Background: Recent studies have demonstrated the key role of the complement alternative pathway (cAP) in the pathophysiology of experimental ANCA-associated vasculitis (AAV). However, in human AAV the role of cAP has not been extensively explored. In the present work, we analysed circulating serum C3 levels measured at AAV onset and their relation to outcomes.Methods: We conducted a retrospective observational cohort study including 45 consecutive patients with AAV diagnosed between 2000 and 2014 with serum C3 measurement at diagnosis, before immunosuppressive treatment initiation. Two groups were defined according to the median serum C3 level value: the low C3 group (C3

International audience; Transient hypophosphatemia is frequently observed during the first months after renal transplantation and is usually asymptomatic. Phosphate diabetes is defined as inadequate tubular phosphorus reabsorption leading to persistent renal phosphorus wasting, which is an important but overlooked cause of osteodystrophy in the post-renal transplantation population. We report the case of a 58-year-old male who presented with severe multiple osteoarticular pains within 3 months after successful first kidney transplantation. Bone disease was attributed initially to mild hyperparathyroidism secondary to vitamin D deficiency. Despite the correction of the hyperparathyroidism, the withdrawal of corticosteroids, and the reduction of immunosuppressive treatment to tacrolimus-based monotherapy, the osteoarticular pains persisted. Skeletal investigations at month 9 post-transplantation demonstrated a significant bone mineral density loss associated with osteomalacia and osteoporosis on the bone biopsy. Laboratory data showed persistent hypophosphatemia, and phosphate diabetes was then diagnosed explaining the post-transplant bone disease. A tacrolimus-induced renal tubular disorder was suspected to contribute to the excessive renal phosphorus wasting. The replacement of tacrolimus by sirolimus, in addition to oral phosphorus and vitamin D supplementations, led to the disappearance of pains, the normalization of urinary and plasma phosphate level, and a significant improvement of bone mineralization.

Hyperoxaluria is a rare metabolic disorder characterized by calcium oxalate deposition in different tissues. It is caused either by an inherited disease of oxalate metabolism [primary hyperoxalurias (PH)] or by an acquired disturbance (secondary hyperoxaluria). We report here an atypical presentation of enteric hyperoxaluria-induced renal failure that occurred after liver transplantation. Despite adapted treatment and intensive haemodialysis, the patient did not recover. This case allows the reviewing of the multiple pathophysiological mechanisms involved in this disease. Oxalate nephropathy should be considered in the differential diagnosis of acute renal failure, especially when previous renal impairment and fat malabsorption are present. We suggest performing renal biopsy early to allow a prompt diagnosis and therapeutic intervention.

International audience; Cystic fibrosis (CF) is usually diagnosed during childhood by respiratory or gastro-intestinal symptoms. Hyponatremic hypochloremic dehydration with metabolic alkalosis is a rare but typical presentation of CF in infants. In contrast, only 3 cases have been described in adults. We report a case of CF in a 33-year-old Caucasian female presenting with a severe sodium and chloride depletion caused by inappropriate sweating. She experienced three episodes of severe dehydration before the diagnosis was suspected. Sweat chloride test was pathological and mild pulmonary involvement was found on CT scan. AF508 mutation and a rare mutation (3849+40 A/G) on the intron 19 of CFTR gene were found. Interestingly, our patient has a heterozygote twin sister, carrier of the same mutations of CFTR gene who also developed CF but with a different phenotype. We suspect modifier genes to be implicated in the differences observed between the two phenotypes. We discuss the physiopathology of electrolyte disturbance and review the other similar adults cases.