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Abstract Background Chronic kidney disease (CKD) is age-related disease, and decreased renal function is associated with the premature aging of T cells and increased incidence of other age-related diseases. However, the relationship between T cell senescence and CKD progression remains unclear. Here, we investigated the relationship between T cell senescence, as indicated by decreased thymic output and increased proportion of highly differentiated CD28− T cells, and CKD progression. Results A total of 175 patients with non-dialysis-dependent CKD were enrolled in this study. Thymic output was assessed based on the CD45RA+CD31+CD4+ cell (recent thymic emigrant [RTE]) counts (RTEs) (/mm3) and the proportion of RTE among CD4+ T cells (RTE%). Highly differentiated T cells were assessed based on the proportion of CD28− cells among CD4+ T cells (CD28−/CD4+) and CD28− cells among CD8+ T cells (CD28−/CD8+). The primary outcome was estimated glomerular filtration rate (eGFR) decline of ≥40% or initiation of renal replacement therapy. The association between T cell senescence and renal outcomes was examined using Cox proportional hazards models and restricted cubic splines. The median age was 73 years, 33% were women, and the median eGFR was 26 mL/min/1.73 m2. The median RTEs, RTE%, CD28−/CD4+, and CD28−/CD8+ were 97.5/mm3, 16.2, 5.3, and 49.7%, respectively. After a median follow-up of 1.78 years, renal outcomes were observed in 71 patients. After adjusting for age, sex, eGFR, proteinuria, diabetes, and cytomegalovirus seropositivity, decreased RTEs, which corresponded to decreased thymic output, significantly and monotonically increased the risk of poor renal outcome (p = 0.04), and decreased RTE% and increased highly differentiated CD28−/CD4+ T cells also tended to monotonically increase the risk (p = 0.074 and p = 0.056, respectively), but not CD28−/CD8+ T cells. Conclusions Decreased thymic output in CKD patients, as well as increased highly differentiated CD4+ T cells, predicted renal outcomes. Thus, the identification of patients prone to CKD progression using T cell senescence, particularly decreased RTE as a biomarker, may help to prevent progression to end-stage kidney disease.

Abstract Premature immune ageing, including thymic atrophy, is observed in patients with chronic kidney disease (CKD). Parathyroid hormone (PTH) and fibroblast growth factor 23 (FGF23), which are mineral and bone disorder (MBD)-related factors, affect immune cells and possibly cause thymic atrophy. We examined the cross-sectional association between thymic atrophy, evaluated as the number of CD3+CD4+CD45RA+CD31+ cells [recent thymic emigrants (RTE)/μL], and MBD-related factors [(serum PTH, FGF23, and alkaline phosphatase (ALP) level] in 125 patients with non-dialysis dependent CKD. Median estimated glomerular filtration rate (eGFR) was 17 mL/min/1.73 m2. Older age (r = −0.46), male sex (r = −0.34), lower eGFR (r = 0.27), lower serum-corrected calcium (r = 0.27), higher PTH (r = −0.36), and higher ALP level (r = −0.20) were identified as determinants of lower number of RTE. In contrast, serum concentrations of FGF23 and phosphorus were not correlated with RTE. Multivariate non-linear regression analysis indicated a negative association between serum PTH and log-transformed RTE (P = 0.030, P for non-linearity = 0.124). However, the serum levels of FGF23 and ALP were not associated with RTE. In patients with CKD, serum PTH concentrations were related to thymic atrophy which contributes to immune abnormality.

BackgroundImmunoglobulin (Ig)A nephropathy (IgAN) is the most common form of primary glomerulonephritis in the world. Some bacteria were reported to be the candidate of the antigen or the pathogenesis of IgAN, but systematic analysis of bacterial flora in tonsil with IgAN has not been reported. Moreover, these bacteria specific to IgAN might be candidate for the indicator which can predict the remission of IgAN treated by the combination of tonsillectomy and steroid pulse.Methods and findingsWe made a comprehensive analysis of tonsil flora in 68 IgAN patients and 28 control patients using Denaturing gradient gel electrophoresis methods. We also analyzed the relationship between several bacteria specific to the IgAN and the prognosis of the IgAN. Treponema sp. were identified in 24% IgAN patients, while in 7% control patients (P = 0.062). Haemophilus segnis were detected in 53% IgAN patients, while in 25% control patients (P = 0.012). Campylobacter rectus were identified in 49% IgAN patients, while in 14% control patients (P = 0.002). Multiple Cox proportional-hazards model revealed that Treponema sp. or Campylobactor rectus are significant for the remission of proteinuria (Hazard ratio 2.35, p = 0.019). There was significant difference in remission rates between IgAN patients with Treponema sp. and those without the bacterium (p = 0.046), and in remission rates between IgAN patients with Campylobacter rectus and those without the bacterium (p = 0.037) by Kaplan-Meier analysis. Those bacteria are well known to be related with the periodontal disease. Periodontal bacteria has known to cause immune reaction and many diseases, and also might cause IgA nephropathy.ConclusionThis insight into IgAN might be useful for diagnosis of the IgAN patients and the decision of treatment of IgAN.

Background. Erythropoietin (EPO) has been reported to slow the decline of renal function in predialysis chronic kidney disease (CKD) patients. On the contrary, in the recent large-scale randomized controlled trial (RCT), CREATE and CHOIR, which aimed to keep a higher haemoglobin (Hb) level than former trials, the renoprotective effect of EPO was not observed. Today, the renoprotective effect of EPO has become controversial. In order to test the hypothesis that the usage of EPO in predialysis CKD patients may ameliorate the progression of renal disease, we conducted a macro-level observational study dealing with all Japanese predialysis CKD patients. Methods. Annually since 1982, the Japanese Society for Dialysis Therapy reports the number of patients that have entered maintenance dialysis in each prefecture of Japan. Based on the 2002–2004 data, we calculated the annual incidence of end-stage renal disease (ESRD) in each of the 47 prefectures. The annual amounts paid for EPO by each prefecture, presumably corresponding to the amounts used, corrected for the estimated predialysis CKD patients, were calculated. We examined the relationship between the incidence of new dialysis and the usage of EPO in each prefecture. Furthermore, the usage of EPO was compared with that of antihypertensive agents including angiotensin converting enzyme inhibitor (ACE-I), and that of statin. Results. There were prefectural differences in the annual incidence of ESRD from 2002 to 2004. We also found prefectural differences in the usage of EPO for the three consecutive years. The usage of EPO in predialysis patients was negatively correlated with the incidence of ESRD on linear and multiple regression analyses. At the same time, the usage of EPO had strong positive correlations with the usage of antihypertensive agents including ACE-I and with that of statin. Conclusion. Our nationwide epidemiologic study revealed that a higher use of EPO was associated with a decreased incidence of new dialysis in daily clinical practice. In addi- tion, there were strong correlations among the usage of EPO, antihypertensive agents and statin. These data are supportive of, but do not prove, the hypothesis that EPO may be renoprotective, when used in combination with other strategies. [ABSTRACT FROM AUTHOR]