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      Lymphocyte Drug Sensitivity Is Useful for Prediction of the Antiproteinuric Effect and Relapse Rate in Cyclosporine Treatment for Frequent-Relapse Minimal Change Nephrotic Syndrome

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          Background/Aims: The therapeutic effect of cyclosporine A (CsA) in combination with steroids varies greatly for frequent-relapse minimal change nephrotic syndrome (FRMCNS). The association between the sensitivity of peripheral blood lymphocytes (PBLs) to CsA in vitro and the therapeutic effect of CsA in FRMCNS were investigated. Methods: The sensitivity of PBLs in vitro and the therapeutic effect of CsA in 23 FRMCNS patients were compared. The length of time to complete remission (CR) and the number of relapses were compared using the 50% inhibitory concentration (IC<sub>50</sub>) of CsA in the presence of a T-cell mitogen. Results: FRMCNS patients were divided into 2 groups: a low sensitivity group with an IC<sub>50</sub> of >14.8 ng/ml (GII, n = 10), and a high sensitivity group with an IC<sub>50</sub> of <14.8 ng/ml (GI, n = 13). Comparison of the length of time to CR between the 2 groups showed that GI reached CR earlier than GII (p < 0.01). GI had significantly fewer relapses than GII when CsA was administered for 12 months or longer (p < 0.01). Conclusion: Lymphocyte sensitivity to CsA has the potential to be an important clinical indicator of the antiproteinuric effect and relapse rate in FRMCNS.

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          Suppression of dialysis patients' lymphocyte IL-2R expression by glucocorticoids and cyclosporine.

          Previous studies have shown interindividual heterogeneity in the suppressive effects of glucocorticoids and cyclosporine (CsA) on the proliferation responses of dialysis patients' peripheral blood mononuclear cells (PBMC). In addition, methylprednisolone (MP) was shown to be significantly more suppressive than prednisolone (P), and PBMC from patients on peritoneal dialysis (PD) were found to be more sensitive to both glucocorticoids than those from patients on haemodialysis (HD). In order to begin to explore the cellular mechanism(s) underlying these observations, the differential suppressive effects of these drugs on lymphocyte interleukin 2 receptor (IL-2R) expression by mitogen-stimulated PBMC from 23 PD and 30 HD were determined. The mean+/-SD concentrations (ng/ml) of steroid causing 50% inhibition (IC50) of cell proliferation was significantly lower for PD than HD PBMC with both P (94+/-93 vs 148+/-105, P<0.05) and MP (21+/-25 vs 35+/-31, P<0.05). MP was significantly (P<0.001) more suppressive than P of IL-2R expression in both PD and HD. PD IL-2R expression was significantly (P<0.05) more suppressed by CsA alone and by 400 ng/ml CsA+10(-7) MP than was HD IL-2R expression. CsA+10(-7) M MP was significantly (P<0.001) more suppressive of IL-2R expression than the other drugs, alone or in combination, in both groups of patients. In conclusion, these results support the notion that at least one mechanism underlying the significantly greater efficacy of MP compared to P in suppressing PBMC proliferation is its significantly greater suppression of lymphocyte IL-2R expression, either alone or in combination with CsA. Thus, use of MP following allograft transplantation may result in more effective immunosuppression for many recipients.
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            Clinical impact of cyclosporine cellular pharmacodynamics in minimal change nephrotic syndrome

             T HIRANO (2000)

              Author and article information

              Kidney Blood Press Res
              Kidney and Blood Pressure Research
              S. Karger AG
              December 2005
              27 December 2005
              : 28
              : 4
              : 226-229
              aRenal Unit, Department of Internal Medicine, Hachioji Medical Center, Tokyo Medical University, and bDepartment of Clinical Pharmacology, School of Pharmacy, Tokyo University of Pharmacy and Life Science, Tokyo, Japan
              87768 Kidney Blood Press Res 2005;28:226–229
              © 2005 S. Karger AG, Basel

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              Figures: 1, Tables: 3, References: 6, Pages: 4
              Self URI (application/pdf): https://www.karger.com/Article/Pdf/87768
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