Low-Density Lipoprotein Adsorption Therapy Can Restore Drug Sensitivity for Immunosuppressants Via Inhibitory Effects Upon MDR-1 Gene Expression

• Published in: Therapeutic apheresis and dialysis Vol. 15; no. 5; pp. 499 - 503
• Main Authors: Ueda, Satoshi, Sugimoto, Keisuke, Yanagida, Hidehiko, Fujita, Shinsuke, Miyazawa, Tomoki, Sakata, Naoki, Okada, Mitsuru, Takemura, Tsukasa
• Format: Journal Article
• Language: English
• Published: Melbourne, Australia Blackwell Publishing Asia 01.10.2011
• Subjects: Adsorption; ATP-Binding Cassette, Sub-Family B, Member 1 - genetics; Blood Component Removal - methods; Child, Preschool; Corticosteroid sensitivity; Cyclosporine - pharmacology; Cyclosporine - therapeutic use; Drug Resistance; Focal segmental glomerulosclerosis; Gene expression; Gene Expression Regulation; Glucocorticoids - pharmacology; Glucocorticoids - therapeutic use; Humans; Immunosuppressive Agents - pharmacology; Immunosuppressive Agents - therapeutic use; Lipoproteins, LDL - blood; Low-density lipoprotein adsorption therapy; Male; Minimal change disease; Multiple drug resistant gene-1; Nephrotic Syndrome - drug therapy; Remission
• ISSN: 1744-9979; 1744-9987
• DOI: 10.1111/j.1744-9987.2011.00984.x

In two patients with steroid‐resistant nephrotic syndrome (SRNS), we investigated the relationship between clinical findings during immunosuppressive therapy and multiple drug resistant gene‐1 (MDR‐1) expression. MDR‐1 was detected by real‐time polymerase chain reaction (PCR). In a boy who initially developed SRNS at 3 years, we observed MDR‐1 expression over 3 years. Maximal and minimal MDR‐1 expression were 90 000 and 7800 copies/µg RNA, respectively. In a 4‐year‐old boy who initially developed SRNS at 3 years, we determined MDR‐1 expression over 2 years. Maximal and minimal MDR‐1 expression were 42 000 and 6900, respectively. MDR‐1 evaluation requires determination of MDR‐1 expression at several time points in a clinical course. Establishment of a normal expression may be needed for each individual patient. Increasing MDR‐1 during remission was followed soon by recurrences, an observation that may be a guide for therapeutic choice. LDL influences a humoral factor involved in MDR‐1 expression. Both patients responded to LDL adsorption therapy because of elevated LDL levels. While cyclosporine A therapy gradually decreased MDR‐1 expression, LDL adsorption therapy decreased expression sharply. Based on the results of the present study, LDL adsorption therapy could contribute to the amelioration of drug sensitivity for immunosuppressants including corticosteroids via inhibitory effects on MDR‐1 expression.