End-stage renal disease (ESRD) causes premature ageing of the immune system. However, it is not known whether hemodialysis (HD) and peritoneal dialysis (PD) similarly affect the T cell system.
The ...aim of our study was to analyse whether dialysis modality may mitigate ESRD-induced immune senescence. We explored a large population of patients (675 ESRD patients) and both confirmed and refined the results in a second cohort (84 patients).
HD patients exhibited higher inflammatory monocytes counts (44/mm
(1-520) vs 36/mm
(1-161);
= 0.005). Patients on HD also had higher frequency of CD8 T cells (24% (7-61) vs 22% (8-42);
= 0.003) and reduced CD4/CD8 ratio. Such results were confirmed in the second cohort. Moreover, both CD4 + CD57 + CD28- (3.25% (0-38.2) vs 1.05% (0-28.5);
= 0.068) and CD8 + CD57 + CD28- (38.5% (3.6-76.8) vs 26.1 (2.1-46.9);
= 0.039) T cells frequencies were increased in HD patients. Telomere length did not differ according to dialysis modality, but was inversely related to ferritin levels (
= - 0.33; p = 0.003). There was a trend towards higher telomerase activity in PD patients (11 ± 13 vs 6 ± 11;
= 0.053). Thymic function was not different in PD and HD patients. Patients on PD before transplantation had a higher risk of acute rejection after kidney transplantation (HR, 1.61; 95%CI, 1.02 to 2.56;
= 0.041).
More pronounced inflammation with hemodialysis may induce premature aging of the immune system. This observation correlates with a lower risk of acute kidney rejection in patients previously on HD. Clinical consequences in patients maintained on dialysis should be determined.
Trial registration: NCT02843867, registered July 8, 2016.
Primary membranous nephropathy (pMN) is an autoimmune kidney disease and a common cause of nephrotic syndrome in adults. Rituximab is becoming a first line therapy for patients with persistent ...nephrotic syndrome with proven safety and efficacy, achieving remission in 60%-80% of cases. For the remaining 20%-40% of patients there is an urgent need to identify early biomarkers of resistance to rituximab to adapt therapeutic management. In nephrotic patients, rituximab is found in the blood more transiently than in other autoimmune diseases without proteinuria, due to rituximab wasting in the urine. However, rituximab immunomonitoring is not routinely performed. We evaluated the predictive value of serum rituximab levels in patients with pMN three months after rituximab injection (month-3) on clinical remission rates six months (month-6) and 12 months (month-12) after injection and investigated predictive factors for serum rituximab levels at month-3. Sixty-eight patients treated with rituximab between July 2015 and January 2020 from two French nephrology centers were included. We identified residual rituximab levels at month-3 as a novel early predictor of remission at month-6 (
<0.0001) and month-12 (
= 0.001). Reduced likelihood of remission in patients with undetectable rituximab at month-3 was associated with lower serum albumin and higher anti-PLA2R1 titers at baseline and with lower serum albumin, higher proteinuria, higher CD19
counts and higher anti-PLA2R1 titers during follow-up. In multivariate analysis, high baseline proteinuria and undetectable rituximab levels at month-3 were independent risk factors for treatment failure at month-6 and high baseline weight and undetectable rituximab levels at month-3 were independent risk factors for treatment failure at month-12. We identified serum albumin at baseline as a predictive factor for serum rituximab levels at month-3. Patients with serum albumin below 22.5 g/L at baseline had an 8.66-fold higher risk of having undetectable rituximab levels at month-3. Therefore, rituximab immunomonitoring in pMN patients treated with rituximab would allow the detection of patients at risk of treatment failure as early as month-3. Studies are needed to assess whether patients with low residual rituximab levels at month-3 may benefit from an early additional course of rituximab.
Une patiente dialysée chronique depuis trois ans a développé une anémie normocytaire arégénérative apparue hors de tout contexte médical particulier. La réalisation du myélogramme a révélé une ...carence en cuivre, cause rare d’anémie dans la population générale et a fortiori dans la population hémodialysée. La supplémentation en cuivre a permis de corriger l’anémie avec une nette diminution des besoins transfusionnels et des doses d’agents stimulant l’érythropoïèse (ASE). Cette observation suggère qu’une carence en cuivre doit être évoquée en cas de syndrome myélodysplasique associé à un déficit neurologique, notamment en présence de vacuolisations des précurseurs granuleux et érythrocytaires sur le frottis médullaire. Le bilan étiologique d’une anémie réfractaire en dialyse doit comporter un dosage des oligo-éléments.
We reported the case of a female in chronic dialysis since 3years who developed a normocytic a regenerative anemia with no evident etiology. A bone marrow smear revealed a copper deficiency, a rare cause of anemia in general and dialyzed populations. Copper supplementation improved anemia with a decrease in transfusions rate and erythropoietin dosage. This case suggests that a copper deficiency has to be considered when a myelodysplastic syndrome is associated with neurologic symptoms and granulocytes precursors vacuolization identified in bone marrow smear. A blood titration of trace elements should be considered in front of a refractory anemia with no evident etiology.
Immune checkpoint inhibitors (ICIs) dramatically improve the prognosis of many malignancies but at the cost of numerous side effects, which may limit their benefits. Acute kidney injury associated ...with immune checkpoint inhibitors most frequently are acute tubulointerstitial nephritis (ATIN), but various cases of glomerulonephritis have also been reported. Herein, we report a case of severe IgA nephropathy (IgAN) associated with ICIs and carry out a literature review. IgAN was diagnosed in a median time of 5 months (range 1-12 months) after the initiation of ICIs, with heterogeneous severity, and usually treated by corticosteroid and discontinuation of ICIs. In contrast to our case, renal outcomes in literature were often favorable, with recovery of renal function and a reduction in proteinuria on treatment. Although IgAN related to ICIs is a much rarer complication than ATIN, it may still be underdiagnosed. Careful questioning and screening for asymptomatic hematuria should be performed before using ICIs.
Immune senescence is associated with age-related diseases (i.e. infectious disease, cardiovascular diseases and cancers). Chronic kidney disease patients die prematurely when compared with general ...population, because of a higher occurrence of infections, cardiovascular events and cancer. These diseases are commonly observed in the elderly population and frequently associated with immune senescence. Indeed, chronic kidney disease causes a premature aging of the T lymphocyte compartment, widely related to a decrease in thymic function, a phenomenon that plays a key role in the onset of age-related diseases in chronic kidney disease patients. The degree of immune senescence also influences patients' outcome after renal transplantation, particularly the risk of acute rejection and infections. Partial reversion of pre-transplant immune senescence is observed for some renal transplant patients. In conclusion, to reduce the increasing incidence of morbidity and mortality of chronic kidney disease patients, a better knowledge of uremia-induced immune senescence would help to pave the way to build clinical studies and promote innovative therapeutic approaches. We believe that therapeutic reversion and immune senescence prevention approaches will be part of the management of chronic kidney disease patients in the future.
Accelerated thymic involution is a main feature of end-stage renal disease (ESRD)-associated immune senescence. Recent evidences suggest that ESRD-associated immune senescence is associated with ...adverse outcomes in dialysis patients. However, no study focused on the association between pre-transplant thymic function and patient survival after transplantation. We conducted a prospective, multicenter study to assess whether pre-transplant thymic function measured by recent thymic emigrants (RTE) may predict death after first kidney transplantation. Results were tested in a validation cohort. Nine hundred and sixty-seven incident kidney transplant recipients were included in the prospective study. Mean follow up was 5.1 + 2.9 years. Eighty two patients (8.5%) died during follow up. Lower RTE levels were associated with a higher risk of death (2.53; 95%CI, 1.54-4.39 for each decrease of 1 log in RTE;
< 0.001). Cancer-related death was particularly increased in patients with low RTE levels (4.23; 95%CI, 1.43-12.13;
= 0.007). One hundred and thirty-six patients having received a first kidney transplantation were included in the validation cohort. Lower TREC levels were associated with higher risk of death (1.90; 95%CI, 1.11-3.51 for each decrease of 1 log in RTE;
= 0.025). RTE were not associated with death-censored graft loss. Pre-transplant thymic function is strongly associated with death after transplantation. Attempt to reverse ESRD-related thymic loss may prevent premature death.
In order to design differential phase shifters (DPS) from metamaterial-based transmission lines, research had a long tradition of using balanced transmission lines which are a particular case of ...metamaterials, specifically characterized by a simplified equivalent circuit model. This paper presents an innovative way of designing DPS metamaterials by exploiting metamaterial properties more widely, using both balanced and unbalanced cases to obtain a broader set of solutions. These solutions are acquired through the dedicated method this paper expounds, and conceived with the help of a new use of metamaterials. For the sake of ensuring time efficiency and implementation easiness of this design method for industrial purpose, the full wave parametric optimization is reduced to its minimum by exploiting as much as possible in analytic parametric study. This method is illustrated by an application of 180degrees DPS on C-Band (5-6 GHz). Three prototypes were fabricated, and the measurements show that the best case of DPS has less than 9degrees of phase error over the targeted 20% bandwidth, with a return loss less than -14dB and insertion losses lower than 1dB.
End-stage renal disease (ESRD) patients exhibit clinical features of premature ageing, including frailty, cardiovascular disease, and muscle wasting. Accelerated ageing also concerns the immune ...system. Patients with ESRD have both immune senescence and chronic inflammation that are resumed in the so-called inflammaging syndrome. Immune senescence is particularly characterised by premature loss of thymic function that is associated with hyporesponsiveness to vaccines, susceptibility to infections, and death. ESRD-related chronic inflammation has multiple causes and participates to accelerated cardiovascular disease. Although, both characterisation of immune senescence and its consequences are relatively well-known, mechanisms are more uncertain. However, prevention of immune senescence/inflammation or/and rejuvenation of the immune system are major goal to ameliorate clinical outcomes of ESRD patients.
Abstract Compelling data suggest that lymphocyte depletion following T cell depleting therapy may induce prolonged CD4 T cell lymphopenia and trigger lymphocyte activation in some patients. These ...profound and non-reversible immune changes in T cell pool subsets are the consequence of both impaired thymic renewal and peripheral homeostatic proliferation. Chronic viral challenges by CMV play a major role in these immune alterations. Even when the consequences of CD4 T cell lymphopenia have been now well described, recent studies shed new light on the clinical consequences of immune activation. In this review, we will first focus on the mechanisms involved in T cell pool reconstitution after T cell depletion and further consider the clinical consequences of ATG-induced T cell activation and senescence in renal transplant recipients.
TAFRO syndrome was first described as a variant of multicentric Castleman’s disease with thrombocytopenia, anasarca, fever, renal dysfunction, and organomegaly. We report the case of a 25-year-old ...Caucasian male with diagnosis of TAFRO syndrome and present a literature review. The objective of the study was to compare TAFRO syndrome between Japanese and non-Japanese patients. Cases were included by searching the term “TAFRO” in the Medline database using PubMed between 2010 and 2016. The Student
t
test and Mann-Whitney
U
test were used to compare continuous variables. Fisher’s exact test was used for categorical variables. Statistical significance was set at
p
< 0.05. Forty-four cases were included. Thirty-two patients (73%) were of Japanese origin. Japanese patients were significantly older than non-Japanese ones (52.0 ± 13.6 years versus 36.9 ± 19.8 years,
p
= 0.0064) but there was no difference in gender. Creatinine level on admission was significantly higher in the non-Japanese group (1.87 ± 0.84 mg/dL versus 1.32 ± 0.57 mg/dL,
p
= 0.0347). There were no significant differences concerning lymphadenopathy, elevated number of megakaryocytes on bone marrow aspiration, autoimmune abnormalities, and the following parameters on admission: platelet count, hemoglobin, albumin, alkaline phosphatase (ALP). Corticotherapy was always used on induction for Japanese patients while it was only used in 75% of the cases on induction in non-Japanese patients (
p
= 0.0166). Our study was the first to compare TAFRO syndrome according to ethnicity. Japanese patients were significantly older and had a significantly lower creatinine level on admission than non-Japanese patients.
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