Brijesh Yadav

Differential alteration in peripheral T-regulatory and T-effector cells with change in P-glycoprotein expression in Childhood Nephrotic Syndrome: A longitudinal study.

INTRODUCTION Childhood Idiopathic Nephrotic Syndrome (INS) responds to glucocorticoid therapy, however, 60-80% of patients relapse and some of them become steroid non responsive. INS may occur because of T cell dysfunction, abnormal cytokines and podocytopathies which reverse on steroid treatment. The reason of relapses could be imbalances in T cells phenotypes and respective cytokines. Herein, we hypothesize that relapses in INS may occur due to imbalance in T-regulatory and T-effector cell with their respective cytokines and overexpression of P-gp on lymphocytes. METHODS The frequency of peripheral blood CD4(+)CD25(+)FoxP3(+) Treg, CD4(+)IFN-γ(+) Th1 and CD4(+)IL-4(+) Th2 lymphocytes and their respective cytokines and P-gp expression on peripheral blood lymphocytes (PBLs) were analyzed in INS patients at baseline (n=26), during remission (n=24) and at relapse (n=15). RESULTS Compared to baseline, the frequency of Tregs was significantly increased at remission and decreased during relapse. In contrast, the frequency of Th1 and Th2 lymphocytes was significantly decreased during remission and increased at the time of relapse. Similarly, expression of P-gp was significantly high at baseline and at the time of relapse as compared to remission. Levels of cytokines IL-10 and TGF-β in the supernatant of stimulated PBMCs was increased during remission and decreased during relapse. In contrast, levels of IFN-γ and IL-4 were decreased during remission and increased at the time of relapse. CONCLUSIONS Steroid therapy in INS induces decreased P-gp expression on PBLs along with increased frequency and cytokine response of T-regulatory cells, and reduced frequency and respective cytokine response of Th1 and Th2 cells during remission. However, reversal in the frequency and respective cytokines of T-regs, Th1 and Th2, and P-gp expression on PBLs occurs during relapses on follow-up.

Is basiliximab induction, a novel risk factor for new onset diabetes after transplantation for living donor renal allograft recipients?

It was found that, by affecting populations of T lymphocytes and regulatory T cells, basiliximab also indirectly affects pancreatic β‐cell function and glucose homeostasis.

Urinary Kidney injury molecule-1 can predict delayed graft function in living donor renal allograft recipients

Delayed graft function is an early complication leading to impaired creatinine clearance, urine formation and determinant of long term graft outcome. The aim of the present study was to determine the earliest predictive cut‐off value of uKIM‐1 level in patients with delayed graft function and acute tubular necrosis.

T-bet positive mononuclear cell infiltration is associated with transplant glomerulopathy and interstitial fibrosis and tubular atrophy

OBJECTIVES We aimed to study the role of T-bet-positive mononuclear cell infiltration in different compartments of kidney graft tissues in patients with chronic transplant glomerulopathy, interstitial fibrosis and tubular atrophy, and stable graft function. MATERIALS AND METHODS There were 80 living-related renal transplant recipients included (chronic transplant glomerulopathy, n = 28; interstitial fibrosis and tubular atrophy, n = 28; stable graft function, n = 24). Histologic characteristics and scoring for peritubular capillaritis, glomerulitis, interstitial fibrosis and tubular atrophy, and intimal arteritis were performed according to Banff 2007 classification and compared between the groups. Immunohistologic staining was performed for transcription factor T-bet, T-bet mononuclear cells were counted, and T-bet infiltration score was compared between groups. RESULTS Patients in different groups had similar clinical profiles and human leukocyte antigen mismatches, except the groups differed in serum creatinine and proteinuria. The prevalence and scoring of peritubular capillaritis and glomerulitis were significantly higher in chronic transplant glomerulopathy than interstitial fibrosis and tubular atrophy (P = .001) and stable graft function (P < .001). Tubulitis was observed in 6 patients (21.4%) with chronic transplant glomerulopathy but no patients with interstitial fibrosis and tubular atrophy. The C4d/donor-specific antibody was positive in 100% patients with chronic transplant glomerulopathy, 0% patients with interstitial fibrosis and tubular atrophy, and 4.1 % patients with stable graft function. Interstitial fibrosis and tubular atrophy was seen in 100% patients who had interstitial fibrosis and tubular atrophy; in patients who had chronic transplant glomerulopathy, 24 patients (85.7%) had interstitial fibrosis and 78.5% patients had tubular atrophy. The degree and severity of T-bet-positive cell infiltration were significantly higher in chronic transplant glomerulopathy than interstitial fibrosis and tubular atrophy or stable graft function; however, 85% patients with interstitial fibrosis and tubular atrophy also had T-bet-positive infiltration, suggesting a role of T-bet-positive cells in interstitial fibrosis and tubular atrophy. CONCLUSIONS Chronic transplant glomerulopathy is a consequence of chronic active immune-mediated injury. Interstitial fibrosis and tubular atrophy may be associated with T-bet-positive mononuclear cell infiltration in the peritubular region. The T-bet infiltration should be evaluated in patients with chronic allograft injury.