This study shows that the mTORC pathway is central to the antiphospholipid syndrome. Among patients with kidney transplants and antiphospholipid syndrome, 70% of those treated with sirolimus had ...long-term functioning allografts versus 12% of those not treated with sirolimus.
The antiphospholipid syndrome is an autoimmune disease characterized by the presence of circulating antiphospholipid antibodies that result in vascular thrombosis and obstetrical complications.
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The syndrome may be isolated or may occur in association with autoimmune disorders, such as systemic lupus erythematosus. Thrombotic events represent the major complication of the antiphospholipid syndrome,
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and to date, long-term anticoagulation has been the only treatment shown to reduce vascular complications. However, that regimen does not prevent organ deterioration and death in high-risk patients, particularly those in whom catastrophic antiphospholipid syndrome develops.
In addition to the thrombotic complications, vascular cellular infiltrates and fibrosis of the . . .
•Patient presented with constitutional signs without skin involvement.•The serological tests for Bartonella species were negative.•Celiac lymph node biopsy confirmed the diagnosis of bacillary ...angiomatosis.•This is the first case reported in a kidney transplant recipient on belatacept.•Prolonged antibiotherapy and immunosuppression minimization prevent relapses.
Bacillary angiomatosis is a disseminated vascular proliferative disease caused by aerobic gram-negative bacilli Bartonella henselae or Bartonella quintana. Bacillary angiomatosis is mostly described in immunosuppressed patients with HIV infection and organ transplant recipients. We describe the case of a female aged 75 years who is a kidney transplant recipient who was admitted for a 3-month history of intermittent fever, chills, vomiting, and a 12-kg weight loss. The maintenance immunosuppression was based on prednisone, mycophenolate, and monthly infusions of belatacept. Physical examination was unremarkable. Laboratory investigations revealed elevated blood acute phase proteins but all blood cultures were negative. Serological tests for Bartonella were negative. Thoracoabdominal computed tomography scan and transesophageal echocardiography were normal. A Positron Emission Tomography scan showed a hypermetabolic mass in the duodenopancreatic region, with multiple hepatic and splenic lesions. Histological findings of spleen and pancreatic biopsies were not conclusive. The histopathological examination of a celiac lymph node biopsy finally demonstrated bacillary angiomatosis. The diagnosis of bacillary angiomatosis in immunocompromised patients is most often delayed in the absence of skin involvement. A high index of clinical suspicion is needed when interpreting negative results.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
The contribution of memory B cells in alloreactive humoral responses remains poorly understood. Here we tested the presence of circulating alloreactive memory B cells in 69 patients with end-stage ...renal disease under renal replacement therapy, using an in vitro memory B cell–stimulation assay combined with identification of IgG human leukocyte antigen (HLA) antibodies in culture supernatant. HLA antibody–producing memory B cells were evidenced only in patients carrying serum HLA antibodies following multiple classical HLA-immunizing events. In patients with a previous renal allograft, alloreactive memory B cells could be detected ranging from 6 to 32 years (mean 13.2 years) after transplantation. HLA antibodies produced by memory B cells were also detected in the corresponding sera and showed a restricted reactivity, targeting only a few epitopes shared by several HLA antigens. In contrast, serum HLA antibodies, not associated with the detection of specific memory B cells, showed a broader pattern of specificities. Thus, expansion and survival of alloreactive memory B cells is alloantigen driven, and their frequency is related to the ‘strength’ of HLA immunization.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
Diarrhea of unspecified cause frequently occurs after renal transplantation and is usually ascribed to mycophenolic acid toxicity. Norovirus (NoV) and sapovirus (SaV) have been sporadically reported ...to cause chronic diarrhea in immunocompromised patients.
We undertook a retrospective study (2008-2009) to examine the clinical and epidemiologic significance of NoV and SaV infections in adult renal transplant recipients hospitalized for acute or chronic diarrhea.
Ninety-six renal transplant recipients were hospitalized for diarrhea at our institution during a 16-month period, 87 of whom were included in the study, including 46 patients with chronic diarrhea. Among 41 patients with unexplained diarrhea, 20 patients were screened for NoV/SaV, 16 of whom were positive. Fifteen of them (94%) had chronic diarrhea. When compared with bacterial and parasitic infections, NoV/SaV infections were associated with a greater weight loss at the time of admission, a 8.7-fold longer duration of symptoms and a more frequent need for mycophenolic acid dosage reduction. Eighty-one percent of patients hospitalized for NoV/SaV-associated diarrhea experienced acute renal failure. Five and one patients subsequently had biopsy-diagnosed active graft rejection and oxalate nephropathy, respectively. Ten of the 14 patients who underwent a longitudinal study of NoV/SaV stool's clearance exhibited a prolonged viral shedding period with a median time of 289 days (107-581 days).
Our study indicates that NoV/SaV infection causes posttransplant chronic diarrhea potentially complicated by severe kidney graft impairment.
Summary
During the past 10 years, minimization strategies have been legitimately initiated to decrease the many toxicities of calcineurin inhibitors, especially nephrotoxicity which was considered to ...be responsible for the majority of graft losses. Even though CNI‐induced nephrotoxicity is undeniable, we have learned in the past 10 years that DSAs detected with solid‐phase assays are excellent prognostic biomarkers in kidney transplantation (and in other organ transplantations as well) and that chronic antibody‐mediated rejection has become the leading cause of graft loss. In this review, we will focus on the immunological risks linked to various strategies aiming at decreasing CNI doses either at time of transplantation or later in the course of follow‐up. Some of these interventions are associated with an increase in acute cellular rejection rates but also with an improvement in renal function. The effects on antibody‐mediated rejection and occurrence of de novo donor‐specific antibodies are still under‐reported. We are currently missing long‐term data to appreciate the influence of these minimization strategies on graft and patient survival. This then leads to a cautious attitude regarding reducing immunosuppression.
Coronavirus disease 2019 (COVID-19) represents a serious threat to patients on maintenance dialysis. The clinical setting, mortality rate, and prognostic factors in these patients have not been well ...established.
We included all dialyzed patients with COVID-19 referred to our dialysis center between March 11 and April 11, 2020. Data were obtained through the review of the medical records and were censored at the time of data cutoff, on May 11, 2020.
Forty-four patients on maintenance dialysis with COVID-19 were referred to our dialysis unit during the COVID-19 epidemic. Median age was 61 years (interquartile range IQR: 51.5–72.5); 65.9% were men. Comorbidities included hypertension (97.7%), diabetes mellitus (50%), and chronic cardiac (38.6%) and respiratory (27.3%) diseases. Initial symptoms were fever (79.5%), shortness of breath (29.5%), cough (43.2%), and diarrhea (13.6%). Three profiles of severity were distinguished based on the World Health Organization (WHO) progression scale. Forty-one (93.2%) were hospitalized and only 3 were maintained on outpatient hemodialysis. Thirty-three (75%) patients required oxygen therapy, including 15 (45.5%) who were referred to the intensive care unit. Overall, 27.3% of patients died, and 58.5% were discharged from hospital, including only 2 (13.3%) of those admitted to the intensive care unit. By multivariate analysis, cough, thrombopenia <120 g/l, lactate dehydrogenase (LDH) level greater than 2 times the upper limit of normal, and blood C-reactive protein (CRP) >175 mg/l were significantly associated with death.
A major outbreak of COVID-19 occurred in the Paris region, and spread among dialyzed patients. Our study underscores the severity of COVID-19 in these patients and identified prognostic markers.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
We report our experience regarding the profile and screening process of potential recipients (R) and their live donors (D) in our Uterus transplantation (UTx) trial from 2014 to 2020. The initial ...screening was performed using medical questionnaires and consultations. The second step of the screening consisted of two individual interviews with an independent multidisciplinary committee. Then, a complete medical, biological and imaging assessment of the directed living D, the R, and her partner was performed over a two-day hospitalization. A total of 239 women contacted our department: 165 potentials R and 74 potentials D. During the first step of screening, 141 R and 45 D were excluded. Only 12 R/D pairs were pursued. During inclusion, 10 R/D pairs were excluded. One R/D pair is still under evaluation. Finally, only 1 R/D pair was definitively included (0.6%), which led us to perform the first French UTx in March 2019 with a successful graft. The primary limiting factors of inclusion were due to very strict criteria and difficulty of having a suitable directed living D. The International Society of UTx (ISUTx) guidelines based on worldwide results of trials can help ease our inclusion criteria in the future while remaining safe for patients.
BK virus (BKV) replication increases urinary chemokine C-X-C motif ligand 10 (uCXCL10) levels in kidney transplant recipients (KTRs). Here, we investigated uCXCL10 levels across different stages of ...BKV replication as a prognostic and predictive marker for functional decline in KTRs after BKV-DNAemia. uCXCL10 was assessed in a cross-sectional study (474 paired urine/blood/biopsy samples and a longitudinal study (1,184 samples from 60 KTRs with BKV-DNAemia). uCXCL10 levels gradually increased with urine (P-value < 0.0001) and blood BKV viral load (P < 0.05) but were similar in the viruria and no BKV groups (P > 0.99). In viremic patients, uCXCL10 at biopsy was associated with graft functional decline HR = 1.65, 95% CI (1.08-2.51), P = 0.02, irrespective of baseline eGFR, blood viral load, or BKVN diagnosis. uCXL10/cr (threshold: 12.86 ng/mmol) discriminated patients with a low risk of graft function decline from high-risk patients (P = 0.01). In the longitudinal study, the uCXCL10 and BKV-DNAemia trajectories were superimposable. Stratification using the same uCXCL10/cr threshold at first viremia predicted the subsequent inflammatory response, assessed by time-adjusted uCXCL10/cr AUC (P < 0.001), and graft functional decline (P = 0.03). In KTRs, uCXCL10 increases in BKV-DNAemia but not in isolated viruria. uCXCL10/cr is a prognostic biomarker of eGFR decrease, and a 12.86 ng/ml threshold predicts higher inflammatory burdens and poor renal outcomes.
Age per se should not be a contraindication to kidney transplantation. The first studies have shown a benefit for the survival of elderly eligible patients getting a kidney transplant compared to be ...maintained on the waiting list. However, more recent data suggest that this benefit is not as constant, notably with a significant early mortality period. The eligibility of elderly patients for transplantation must be based on the usual consideration of co-morbidities, but should also include, for some patients, a geriatric evaluation to detect clinical symptoms of frailty. The decision to transplant an elderly recipient must also integrate the characteristics of the donors, since the use of donors with increasingly expanding criteria can have a negative impact on the survival of these patients.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
L’âge ne constitue pas en soi une contre-indication à la transplantation rénale. Les premières études réalisées sur le sujet avaient montré un bénéfice de la transplantation rénale pour la survie des ...sujets âgés éligibles à la transplantation par rapport au maintien sur liste d’attente. Cependant, des données plus récentes suggèrent que ce bénéfice n’est pas aussi constant, avec notamment une période de surmortalité précoce étendue après transplantation. L’éligibilité des sujets âgés à la transplantation doit reposer sur l’habituelle prise en compte des comorbidités, mais doit aussi comporter pour certains patients une évaluation gériatrique, pour dépister d’éventuels signes de fragilité. La décision de transplanter un sujet âgé doit aussi intégrer les caractéristiques des donneurs, l’utilisation de donneurs de plus en plus à la marge pouvant avoir un impact négatif sur la survie de ces patients.
Age per se should not be a contraindication to kidney transplantation. The first studies have shown a benefit for the survival of elderly eligible patients getting a kidney transplant compared to be maintained on the waiting list. However, more recent data suggest that this benefit is not as constant, notably with a significant early mortality period. The eligibility of elderly patients for transplantation must be based on the usual consideration of co-morbidities, but should also include, for some patients, a geriatric evaluation to detect clinical symptoms of frailty. The decision to transplant an elderly recipient must also integrate the characteristics of the donors, since the use of donors with increasingly expanding criteria can have a negative impact on the survival of these patients.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
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