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.
Prolonged CD4 T cell lymphopenia after administration of polyclonal anti-thymocyte globulins increases the rate of posttransplantation morbidity, but whether impaired immune reconstitution affects survival is unknown. We studied the effect of CD4 T cell lymphopenia on survival in 302 consecutive prevalent renal transplant recipients and the role of thymic function in CD4 T cell reconstitution and posttransplantation outcomes in 100 consecutive incident renal transplant recipients. We followed the prevalent cohort for a mean duration of 92 months. Of these 302 patients, 81 (27%) had persistent CD4 T cell counts Ͻ300/mm 3 and 36 (12%) died during follow-up. We observed a higher death rate in patients with CD4 T cell lymphopenia persisting for Ͼ1 year (24.1 versus 7.6%; P Ͻ 0.001). Furthermore, in Cox regression analysis, CD4 T cell lymphopenia associated with a nearly five-fold risk for death (adjusted hazard ratio [HR] 4.63; 95% confidence interval [CI] 1.91 to 10.65; P ϭ 0.001). In the incident cohort, we estimated thymic function by T cell receptor excision circles (TRECs) per 150,000 CD3 ϩ cells, which predicted efficient CD4 T cell reconstitution. Higher pretransplantation TREC values associated with lower risks for cancer (adjusted HR 0.39; 95% CI 0.15 to 0.97; P ϭ 0.046) and infection (HR 0.29; 95% CI 0.11 to 0.78; P ϭ 0.013). In summary, prolonged polyclonal anti-thymocyte globulin-induced CD4 T cell lymphopenia is an independent risk factor for death. Determination of pretransplantation thymic function may identify patients at higher risk for CD4 T cell lymphopenia and posttransplantation morbidity, including cancer and infections. Broad T cell depletion by polyclonal anti-thymocyte globulins (ATG) has been used for many years as a part of immunosuppressive treatment in transplantation. These polyclonal antibodies are a complex mixture of antibodies with multiple specificities directed to both T and non-T cells. 1,2 These antibodies produce profound T cell depletion via complement-dependent lysis and Fas/Fas ligand-mediated apoptosis. 3,4 Although T cell regeneration generally occurs in the months after ATG administration, Muller et al. 5 reported that ATG may induce persistent changes in T cell subsets characterized by a low CD4 T cell count and a CD8 T cell expansion.
CD4 cell depletion is associated with skin cancer in long-term renal transplant recipients.
Background: Rhabdomyolysis is a life-threatening disease that can lead to severe hyperkalemia, acute kidney injury (AKI) and hypovolemic shock. The predictive factors of AKI and acute to chronic kidney disease (CKD) transition remain poorly described. Methods: This multicenter retrospective study enrolled 387 patients with severe rhabdomyolysis (CPK > 5000 U/L). Primary end-point was the development of severe AKI, defined as stage 2 or 3 of KDIGO classification. Secondary endpoints included the incidence of AKI to CKD transition. Results: Among the 387 patients, 315 (81.4%) developed AKI, including 171 (44.1%) with stage 3 AKI and 103 (26.6%) requiring RRT. Stage 2-3 AKI was strongly correlated with serum phosphate, potassium and bicarbonate at admission, as well as myoglobin over 8000 U/L and the need for mechanical ventilation. 42 patients (10.8%) died before day 28. In the 80 patients with available eGFR values both before and 3 months after the rhabdomyolysis, the decrease in eGFR (greater than 20 mL/min/1.73 m 2 in 23 patients; 28.8%) was correlated to the severity of the AKI and serum myoglobin levels > 8000 U/L at admission. Conclusions: Severe rhabdomyolysis leads to AKI in most patients admitted to an ICU. Mechanical ventilation and severity of the rhabdomyolysis, including myoglobin level, are associated with the risk of stage 2-3 AKI. The long-term renal decline is correlated to serum myoglobin at admission.
In elderly patients, transplantation with an ECD kidney was associated with higher survival rates than remaining on the waiting list. This result suggests that the identification and use of ECD kidney grafts should be optimized, given changes in the characteristics of potential donors and recipients.
Homocyst(e)inaemia is closely related to renal function and folate concentration in renal-transplant recipients. CsA does not seem to have direct effects on homocysteine metabolism. Hyperhomocyst(e)inaemia is associated with cardiovascular disease in renal-transplant recipients. Prospective placebo-controlled homocysteine-lowering therapy studies are required in this patient category.
Summary Perforin (P), Granzyme B (GB) and Fas‐Ligand (FAS‐L) are cytotoxic molecules involved in acute rejection (AR) after renal transplantation. A noninvasive diagnostic test to monitor AR and other complications could improve clinical management. We investigated the predictive and diagnostic interest of target mRNA measurements, with a quantitative PCR assay, in AR, as well as in other clinical complications recurrent in kidney transplantation. One hundred and sixty‐two urine specimens from 37 allograft recipients were investigated. Clinical settings were AR, urinary tract infection (UTI), cytomegalovirus infection (CMVi) or disease (CMVd), chronic allograft nephropathy (CAN), delayed graft function (DGF) and stable graft course (controls). In the case of AR, mRNA levels of all three molecules were significantly higher than in recipients not showing any clinically evident signs of complication. Indeed, it was observed that expression levels of P, GB and Fas‐L mRNA also increase in other clinical situations such as UTI, CMV and DGF. Finally, kinetic studies in three patients with AR revealed that increased P, GB and Fas‐L mRNA levels could precede or were concomitant with increased serum creatinin levels. P, GB and Fas‐L gene expression in urine specimens were upregulated in AR episodes but also in UTI, CMV infection and DGF. Therefore, this technique would appear to be of limited clinical value as a noninvasive method of diagnosing AR.
Tubulointerstitial nephritis and uveitis (TINU) syndrome is a rare disease, defined by the association of idiopathic acute TINU. The aim of our work was to determine the characteristics of adult TINU syndrome in France, and to assess factors (including treatment) influencing medium-term prognosis.We conducted a nationwide study including 20 French hospitals. Clinical, laboratory, and renal histopathologic data of 41 biopsy-proven TINU syndromes were retrospectively collected. The patients were diagnosed between January 1, 1999 and December 1, 2015.Twenty-five females and 16 males were included (F/M ratio: 1.6:1). The median age at disease onset was 46.8 years (range 16.8–77.4) with a median serum creatinine level at 207 μmol/L (range 100–1687) and a median estimated glomerular filtration rate (eGFR) at 27 mL/min per 1.73 m2 (range 2–73). Twenty-nine patients (71%) had a bilateral anterior uveitis and 24 (59%) had deterioration in general health at presentation. Moderate proteinuria was found in 32 patients (78%) (median proteinuria 0.52 g/24 h; range 0.10–2.10), aseptic leukocyturia in 25/36 patients (70%). The evaluation of renal biopsies revealed 41 patients (100%) with an acute tubulointerstitial nephritis, 19/39 patients (49%) with light to moderate fibrosis and 5 patients (12%) with an acute tubular necrosis. Thirty-six patients (88%) were treated with oral corticosteroids. After 1 year of follow-up, the median eGFR was 76 mL/min per 1.73 m2 (range 17–119) and 32% of the patients suffered from moderate to severe chronic kidney disease. Serum creatinine (P < 0.001, r = −0.54), serum bicarbonate and phosphate levels (respectively, P = 0.01, r = 0.53; and P = 0.04, r = 0.46), and age (P = 0.03, r = −0.37) at the 1st symptoms were associated with eGFR after 1 year. During the 1st year 40% of patients had uveitis relapses. The use of oral corticosteroids was not associated with a better kidney function but was associated with fewer uveitis relapses (P = 0.44 and 0.02, respectively).In our study, 32% of patients were suffering from moderate to severe chronic kidney disease after 1 year of follow-up, and 40% had uveitis relapses during this follow-up. This work also suggests that oral corticosteroids are effective for the treatment of TINU syndrome's uveitis.
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