Abstract
Background
Patients with chronic kidney disease (CKD) are more prone to develop premature age-related diseases. Data on immune senescence are scarce in CKD populations, except in end-stage ...renal disease and dialysis. We designed a longitudinal prospective study to evaluate immune senescence at different CKD stages and its influence on CKD patient outcomes.
Methods
Clinical and biological data collections were performed on 222 patients at different CKD stages 1–2 (n = 85), 4 (n = 53) and 5 (n = 84). Immune senescence biomarkers were measured by cytometry on T cells (CD28, CD57, CD45RA, CD31, γH2A.X) or by quantitative polymerase chain reaction relative telomere length (RTL) on peripheral blood mononuclear cells and analysed according to CKD stages and outcomes.
Results
CKD was associated with an increase in immune senescence and inflammation biomarkers, as follows: low thymic output (197 ± 25 versus 88 ± 13 versus 73 ± 21 CD4+CD45RA+CD31+ T cells/mm3), an increased proportion of terminally differentiated T cells (CD8+CD28−CD57+) (24 ± 18 versus 32 ± 17 versus 35 ± 19%) restricted to cytomegalovirus-positive patients, telomere shortening (1.11 ± 0.36 versus 0.78 ± 0.24 versus 0.97 ± 0.21 telomere:single copy ratio) and an increase in C-reactive protein levels median 2.9 (range 1.8–4.9) versus 5.1 (27–9.6) versus 6.2 (3.4–10.5) mg/L. In multivariate analysis, shorter RTL was associated with death {hazard ratio HR 4.12 95% confidence interval (CI) 1.44–11.75}. Low thymic output was associated with infections HR 1.79 (95% CI (1.34–9.58) and terminally differentiated CD8+ T-cell expansion with a risk of cardiovascular events CEs; HR 4.86 (95% CI 1.72–13.72).
Conclusion
CKD was associated with premature immune ageing. Each of these alterations increased the risk of specific age-related diseases, such as RTL and death, thymic function and infections and terminally differentiated CD8+ T-cell expansion and CEs.
Post-transplant diabetes is a frequent complication after transplantation. Moreover, patients suffering from post-transplant diabetes have increased cardiovascular morbidity and reduced survival. ...Pathogenesis mainly involves beta-cell dysfunction in presence of insulin resistance. Both pre- and post-transplant risk factors are well-described, and some of them may be corrected or prevented. However, the frequency of post-transplant diabetes has not decreased in recent years. We realized a critical appraisal of preventive measures to reduce post-transplant diabetes.
Antithymocyte globulins (ATGs) are part of the immunosuppression arsenal currently used by clinicians to prevent or treat acute rejection in solid organ transplantation. ATG is a mixture of ...non-specific anti-lymphocyte immunoglobulins targeting not only T cell subsets but also several other immune and non-immune cells, rendering its precise immunoglobulin composition difficult to appreciate or to compare from one preparation to another. Furthermore, several mechanisms of action have been described. Taken together, this probably explains the efficacy and the side effects associated with this drug. Recent data suggest a long-term negative impact on allograft and patient outcomes, pointing out the need to better characterize the potential toxicity and the benefit-risk balance associated to this immunosuppressive therapy within large clinical trials.
The French Renal Epidemiology and Information Network (REIN) registry collect dialysis initiation context for each patient starting dialysis with a flawed definition of urgent start dialysis (USD). ...The main objective of this study was to identify factors associated with USD in patients regularly followed-up by a nephrologist using a classification of USD considering the preparation to renal replacement therapy.
This retrospective cohort study included adult patients who started dialysis between 2012 and 2018 in the Franche-Comté region of France after a minimum of two nephrology consultations. We classified dialysis initiation context as follows: USD for patients with no dialysis access (DA) created or planned, unplanned non urgent start dialysis (UNUSD) for patients starting with a recent or non-functional DA and planned start dialysis (PSD) for those starting with a functional and mature DA.
Four hundred and sixty-five patients met inclusion criteria. According to REIN registry, 94 (20.3%) patients were urgent starters (US) whereas with our classification 80 (17.2%) and 73 (15.7%) where respectively US and unplanned non urgent starters (UNUS). The factors independently associated with USD in our classification were: stroke (odds ratio(OR) = 2.76, 95% confidence interval (95%CI)=1.41-5.43), cardiac failure (OR = 1.78, 95%CI=1.07-2.96) and the number of nephrology consultations prior dialysis onset (OR = 0.73, 95%CI=0.64-0.83). Thirty-one patients died during the first year after dialysis start. According to our classification, we observed significantly different survival probabilities: 95.7%, 89.5% and 83.4% respectively for planned starters, UNUS and US (p = 0.001).
The two factors independently associated with USD were cardiac failure and stroke.
Background
Red blood cell (RBC) transfusions are frequently required in the early period after kidney transplantation. However, the consequences of RBC transfusions on long-term outcomes are largely ...unrecognized.
Methods
We conducted a nationwide French cohort study involving all 31 French kidney transplant centers. Patients having received a first kidney transplant between January 1, 2002 and December 31, 2008 were identified through the national registry of the French BioMedecine Agency (
Agence de BioMédecine
). Number and date of RBC transfusions were collected from the national database of the French transfusion public service. The primary endpoint was transplant failure defined as graft loss or death with a functional graft.
Results
Among 12,559 patients included during the study period, 3,483 (28%) were transfused during the first 14 days post-transplant. Median follow-up was 7.6 (7.5-7.8) years. Multivariable analysis determined that post-transplant RBC transfusion was associated with an increased risk in transplant failure (HR 1.650, 95%CI 1.538;1.771 p<0.0001). Both sensitivity and propension score analyses confirmed the previous result.
Conclusions
Early red blood cell transfusion after kidney transplantation is associated with increased transplant failure.
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.
We assessed incidence, predictors, and impact on 6-month mortality of contrast-induced acute kidney injury (CI-AKI) after coronary angiography with or without percutaneous coronary intervention in ...patients with acute coronary syndrome (ACS), according to 3 different CI-AKI definitions.
Serum creatinine (sCr) was assessed at baseline and 48 to 72 hours after procedure to classify patients into 3 CI-AKI groups: Group 1: increase in sCR ≥25% over baseline but absolute increase <0.5 mg/dl; Group 2: absolute increase ≥0.5 mg/dl; Group 3: absolute increase ≥0.3 mg/dl or ≥50% over baseline. The association between CI-AKI and all-cause 6-month mortality was assessed using multivariate Cox regression. Among 1,002 patients included, median age was 68 57 to 79 years. The sample had the following characteristics: 70% men, 25% diabetics, 22% had a history of myocardial infarction, 21% had baseline estimated glomerular filtration rate (as calculated by the Modification of Diet in Renal Disease) <60 ml/min/1.72 m2, 34% had ST-segment elevation myocardial infarction, 61% underwent percutaneous coronary intervention, and 43% had multivessel disease. Based on changes in sCr, 89 patients (8.9%) were classified in Group 1; 69 (6.9%) in Group 2; and 157 (15.7%) in Group 3, whereas sCr did not increase >25% in the remaining 844 (84.2%). CI-AKI was significantly associated with 6-month all-cause mortality using the definitions for Group 2 (hazard ratio 3.1, 95% confidence interval CI 1.5 to 6.6, p = 0.002) and Group 3 (hazard ratio 2.03, 95% CI 1.03 to 4.0, p = 0.04), but not Group 1. In conclusion, based on the definition used for CI-AKI, CI-AKI is observed in 6% to 15.7% of patients. An increase of 25% over baseline sCr does not identify high-risk patients. CI-AKI defined as an increase in sCr >0.3 mg/dl identifies 15.7% of the population at 2-fold higher risk of mortality.
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.
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