CD4+CD25+ T regulatory cells in renal transplantation.

The immune response to an allograft activates lymphocytes with the capacity to cause rejection. Activation of CD4+CD25+Foxp3+T regulatory cells (Treg) can down-regulate allograft rejection and can induce immune tolerance to the allograft. Treg represent <10% of peripheral CD4+T cells and do not markedly increase in tolerant hosts. CD4+CD25+Foxp3+T cells include both resting and activated Treg that can be distinguished by several markers, many of which are also expressed by effector T cells. More detailed characterization of Treg to identify increased activated antigen-specific Treg may allow reduction of non-specific immunosuppression. Natural thymus derived resting Treg (tTreg) are CD4+CD25+Foxp3+T cells and only partially inhibit alloantigen presenting cell activation of effector cells. Cytokines produced by activated effector cells activate these tTreg to more potent alloantigen-activated Treg that may promote a state of operational tolerance. Activated Treg can be distinguished by several molecules they are induced to express, or whose expression they have suppressed. These include CD45RA/RO, cytokine receptors, chemokine receptors that alter pathways of migration and transcription factors, cytokines and suppression mediating molecules. As the total Treg population does not increase in operational tolerance, it is the activated Treg which may be the most informative to monitor. Here we review the methods used to monitor peripheral Treg, the effect of immunosuppressive regimens on Treg, and correlations with clinical outcomes such as graft survival and rejection. Experimental therapies involving ex vivo Treg expansion and administration in renal transplantation are not reviewed.

Chronic kidney disease is independently associated with alterations in left atrial function.

BACKGROUND: Chronic kidney disease (CKD) is associated with increased cardiovascular morbidity and mortality; hence detection of early cardiovascular involvement in CKD is important to prevent future adverse cardiovascular events. Left atrial (LA) enlargement and dysfunction has been reported in end stage renal disease. However, there is a paucity of published data regarding the evaluation of LA function in CKD using noninvasive imaging parameters. In this study, we evaluated biplane LA volume as well as LA function (LA global systolic strain (GS) and strain rate [SR]) in stage 3 CKD patients (eGFR 30-59 mL/min per 1.73 m(2) ) to determine if LA function parameters are more significantly altered by the presence of CKD in addition to changes due to hypertension alone. METHODS: Thirty-three CKD patients (eGFR 30-59 mL/min per 1.73 m(2) ) with hypertension were compared to 33 normal controls and 34 hypertensive (HT) subjects with normal renal function; all participants underwent a detailed transthoracic echocardiogram. Indexed biplane LA volume (LAVI), LA segmental function, and GS and SR (systolic, early, and late diastole) derived from tissue Doppler imaging (TDI) were measured. Univariate predictors of LA strain were determined. Multiple logistic regression analysis was used to examine the effect of patient group (i.e. CKD) on GS and SR as well as LAVI. RESULTS: Left atrial volume indexed was significantly increased in both the HT and CKD with HT group compared to normal controls (28 ± 9 mL/m(2) vs. 28 ± 9 mL/m(2) vs. 23 ± 5 mL/m(2) , respectively, P = 0.02). However, LAVI was similar in the HT and CKD with HT group (28 ± 9 mL/m(2) vs. 28 ± 9 mL/m(2) ; P = NS). LA GS and SR were reduced in both the CKD with HT and HT group, compared to controls. However, a significantly lower LA GS was present in the CKD with HT group (Controls vs. HT vs. CKD with HT: 54.9 ± 14.5% vs. 34.5 ± 6.2% vs. 25.7 ± 9.3%, respectively; P = 0.001). To examine the effect of group, (i.e. presence of CKD) multiple logistic regression analysis was performed with univariate predictors including indexed left ventricular mass (LVMI), LV diastolic grade, LAVI, peak A-wave velocity, ß-blocker therapy, GS and SR; this demonstrated that CKD had an independent effect on LA GS and SR (systolic, early, and late diastole). GS demonstrated moderate correlation with systolic blood pressure (r = -0.5, P = 0.01), diastolic grade (r = -0.5, P = 0.01), E' velocity (r = 0.6, P = 0.0001), peak A velocity (r = -0.5, P = 0.004), and LAVI (r = -0.6, P = 0.002). CONCLUSIONS: Left atrial dysfunction is evident in stage 3 CKD with associated LA enlargement. This study demonstrates that LA GS and SR were reduced in the CKD group despite similar LAVI in the CKD with HT and HT group. Hence LA GS and SR may be a more sensitive noninvasive tool to detect cardiovascular involvement in CKD.

High-sensitivity troponin as a predictor of cardiac events and mortality in the stable dialysis population.

BACKGROUND: High-sensitivity cardiac troponin T (hs-cTnT) is a biomarker used in diagnosing myocardial injury. The clinical utility and the variation of this biomarker over time remain unclear in hemodialysis (HD) and peritoneal dialysis (PD) patients. We sought to determine whether hs-cTnT concentrations were predictive of myocardial infarction (MI) and death and to examine hs-cTnT variability over a 1-year period. METHODS: A total of 393 nonacute HD and PD patients (70% HD and 30% PD) were followed in a prospective observational study for new MI and death. RESULTS: Median hs-cTnT was 57 ng/L (interquartile range, 36-101 ng/L) with no observed difference between HD and PD patients (P = 0.11). Incremental increases in mortality (P = 0.024) and MI (P = 0.001) were observed with increasing hs-cTnT quartiles. MI incidence increased significantly across quartiles in both HD and PD patients (P = 0.012 and P = 0.025, respectively), whereas mortality increased only in HD patients (P = 0.015). For every increase of 25 ng/L in hs-cTnT, the unadjusted hazard ratio (HR) was 1.10 for mortality in the whole group (95% CI, 1.04-1.16, P = 0.001) and 1.16 for MI (95% CI, 1.08-1.23, P < 0.001). Adjusted HR for mortality was 1.07 (95% CI, 1.01-1.15, P = 0.04) and 1.14 for MI (95% CI, 1.06-1.22, P < 0.001). Changes in hs-cTnT from baseline concentrations after 1 year were minimal (55 ng/L vs 53 ng/L, P = 0.22) even in patients who had an MI (P = 0.53). CONCLUSIONS: hs-cTnT appears to have a useful role in predicting MI and death in the dialysis population. Over a 1-year period concentrations remained stable even in patients who sustained a new cardiac event.