The Experts below are selected from a list of 312 Experts worldwide ranked by ideXlab platform
Marek Drozdzik - One of the best experts on this subject based on the ideXlab platform.
-
TGF-β1 gene polymorphism in renal transplant patients with and without gingival overgrowth
Oral Diseases, 2011Co-Authors: Malgorzata Kozak, Mateusz Kurzawski, Anna Wajda, Joanna Lapczuk, Mariusz Lipski, Krzysztof Dziewanowski, Marek DrozdzikAbstract:BACKGROUND: The incidence of gingival overgrowth among renal transplant patients treated with Cyclosporine A ranges from 13 to 84.6%, and the overgrowth is not only esthetic but also medical problem. The study was aimed at determination of association between TGF- β1 gene (TGFB1) polymorphism and gingival overgrowth in kidney transplant patients medicated with cyclosporin A. METHODS: 84 kidney transplant patients with gingival overgrowth and 140 control transplant patients without overgrowth were enrolled into the case control study. TGFB1 polymorphism was determined using the PCR-RFLP assay for +869T>C in codon 10 and +915G>C in codon 25 as well as TaqMan real-time PCR assays for promoter −800G>A and −509C>T SNPs. RESULTS: In kidney transplant patients suffering from gingival overgrowth mean score of gingival overgrowth was 1.38±0.60, whereas in control subjects was 0.0. The patients with gingival overgrowth were characterized by similar distribution of TGFB1 genotypes and allele in comparison to subjects without gingival overgrowth. Among 16 potentially possible haplotypes of TGFB1 gene, only four were observed in the studied sample of kidney transplant patients: G_C_T_G, G_T_C_G, G_C_C_C, and A_C_T_G, with similar frequency in patients with and without gingival overgrowth. CONCLUSION: No association between the TGFB1 gene polymorphism and gingival overgrowth was revealed in kidney transplant patients administered Cyclosporine A.
T D Dubose - One of the best experts on this subject based on the ideXlab platform.
-
Mannitol-induced acute renal failure.
Journal of the American Society of Nephrology : JASN, 1997Co-Authors: P Visweswaran, E K Massin, T D DuboseAbstract:The osmotic diuretic mannitol may be used in diverse clinical settings, such as providing "renal protection" in patients at risk for acute renal failure, decreasing intracranial pressure in patients with intracranial trauma, and preventing the dialysis-disequilibrium syndrome. Mannitol is commonly used after cardiac catheterization, cardiovascular surgery, and exposure to intravenous contrast dyes. This study presents a case in which a long-term renal transplant recipient receiving Cyclosporine therapy concomitantly developed acute renal failure after the administration of high-dose mannitol in an attempt to induce an osmotic diuresis. The diagnosis of "osmotic nephrosis" was confirmed by renal biopsy, and the condition was reversed by cessation of the agent. Studies in experimental animals indicate that cyclosporin A can potentiate the tubular toxicity of mannitol, but such an association has not been verified in humans. Numerous studies confirm the nephrotoxic potential of high-dose mannitol, especially in patients with renal insufficiency. The clinical utility of the osmolar gap in preventing mannitol nephrotoxicity is emphasized.
Russ B Altman - One of the best experts on this subject based on the ideXlab platform.
-
pharmgkb summary Cyclosporine and tacrolimus pathways
Pharmacogenetics and Genomics, 2013Co-Authors: Julia M Barbarino, Raman Venkataramanan, Christine E Staatz, Teri E Klein, Russ B AltmanAbstract:Tacrolimus (FK506) and Cyclosporine (cyclosporin A, CsA) are cornerstone immunosuppressive agents administered to solid organ transplant recipients to prevent and treat allograft rejection. The discovery of Cyclosporine in the 1970s, and its entry into the collection of immunosuppressants in the early 1980s, was a major breakthrough in medicine. Cyclosporine was the most successful antirejection drug to date, and it radically improved the chance of survival for transplant recipients. In 1994, the Food and Drug Administration (FDA) approved tacrolimus, an effective alternative to Cyclosporine [1]. Since then, tacrolimus and Cyclosporine have become the principal immunosuppressive drugs for solid organ transplantation. The United States Organ Procurement and Transplantation Network and the Scientific Registry of Transplant Recipients showed that in 2011, 86% of the 16 055 patients who received a kidney transplant were prescribed tacrolimus upon discharge, and 2.4% were prescribed Cyclosporine. One year after transplant, 84 and 4% of patients received tacrolimus and Cyclosporine therapy, respectively [2]. Global differences exist in the usage of tacrolimus and Cyclosporine: 2008 figures from the Australia and New Zealand Dialysis and Transplant Registry show that 61% of the 391 Australian patients who received a deceased kidney donor graft were prescribed tacrolimus, and 35% were prescribed Cyclosporine. At 1-year post-transplant, these numbers changed to 55 and 33% for tacrolimus and Cyclosporine, respectively [3]. Both drugs are also prescribed for liver, intestinal, lung, and heart transplant recipients [2], and can be used to manage severe autoimmune conditions, such as atopic dermatitis [4,5] and rheumatoid arthritis [6,7]. Tacrolimus and Cyclosporine differ in their chemical structure: Cyclosporine is a cyclic endecapeptide [8], whereas tacrolimus is a macrocyclic lactone [9]. However, they act in a similar manner. Both are calcineurin inhibitors; their main mechanism of action involves inhibition of this important phosphatase [1]. Tacrolimus exhibits similar effects to Cyclosporine, but at concentrations 100 times lower [10]. Despite these differences in potency, tacrolimus and Cyclosporine both show excellent survival rates for grafts across many comparative studies (summarized in Maes and Vanrenterghem [11]). However, several studies have shown that use of tacrolimus is associated with a lower allograft rejection rate compared with Cyclosporine [12-14]. The principal adverse effects associated with tacrolimus and Cyclosporine treatment are neurotoxicity, nephrotoxicity, hypertension, hyperglycemia, gastrointestinal disturbances, infections, and malignancy [15]. Although the two drugs have similar side-effect profiles, they may differ in the frequency of effects. For example, tacrolimus is more likely to cause alopecia [16], tremors [17], and new-onset diabetes mellitus [12], whereas Cyclosporine is associated with hyperlipidemia [18], hypertrichosis, and gingival hyperplasia [19]. The idea that tacrolimus is less nephrotoxic than Cyclosporine remains controversial [20], particularly as most studies of renal injury are based on evaluations in renal transplant patients, making it difficult to discriminate between drug-induced organ damage and other causes of organ dysfunction [21]. A recent study in pancreatic transplant recipients examined baseline kidney biopsies and 5-year post-transplant biopsies, and reported that the chronic nephrotoxic effects of tacrolimus and Cyclosporine were similar [20]. Despite the success of both drugs, treatment is complicated by narrow therapeutic indices and large intrapatient and interpatient pharmacokinetic variability [22,23]. Although adequate exposure is essential to prevent rejection, overexposure can lead to toxicities that reduce tolerability and affect long-term allograft and patient survival [24]. Therapeutic drug monitoring (TDM), therefore, is mandatory for both drugs. However, because individual transplant recipients respond differently to similar immunosuppressant concentrations, achieving the recommended therapeutic target range does not guarantee absence of drug toxicity or complete immunosuppressant efficacy. A mechanistic understanding of the underlying factors affecting the pharmacokinetics and pharmacodynamics of calcinuerin inhibitors may prove useful in being able to further personalize these therapies. This review aims to provide a broad overview of recently published literature on the pharmacokinetics, pharmacodynamics, and pharmacogenetics of tacrolimus and Cyclosporine in transplant patients, with the goals of clarifying current understanding and identifying areas of future research. In doing so, this review builds on the work of others in this field [1,8,24-27]. A particular emphasis is given to pharmacogenetics, as developments in this area may provide a way to optimize treatment with these drugs, potentially avoiding negative side effects while still maintaining efficacy.
Malgorzata Kozak - One of the best experts on this subject based on the ideXlab platform.
-
TGF-β1 gene polymorphism in renal transplant patients with and without gingival overgrowth
Oral Diseases, 2011Co-Authors: Malgorzata Kozak, Mateusz Kurzawski, Anna Wajda, Joanna Lapczuk, Mariusz Lipski, Krzysztof Dziewanowski, Marek DrozdzikAbstract:BACKGROUND: The incidence of gingival overgrowth among renal transplant patients treated with Cyclosporine A ranges from 13 to 84.6%, and the overgrowth is not only esthetic but also medical problem. The study was aimed at determination of association between TGF- β1 gene (TGFB1) polymorphism and gingival overgrowth in kidney transplant patients medicated with cyclosporin A. METHODS: 84 kidney transplant patients with gingival overgrowth and 140 control transplant patients without overgrowth were enrolled into the case control study. TGFB1 polymorphism was determined using the PCR-RFLP assay for +869T>C in codon 10 and +915G>C in codon 25 as well as TaqMan real-time PCR assays for promoter −800G>A and −509C>T SNPs. RESULTS: In kidney transplant patients suffering from gingival overgrowth mean score of gingival overgrowth was 1.38±0.60, whereas in control subjects was 0.0. The patients with gingival overgrowth were characterized by similar distribution of TGFB1 genotypes and allele in comparison to subjects without gingival overgrowth. Among 16 potentially possible haplotypes of TGFB1 gene, only four were observed in the studied sample of kidney transplant patients: G_C_T_G, G_T_C_G, G_C_C_C, and A_C_T_G, with similar frequency in patients with and without gingival overgrowth. CONCLUSION: No association between the TGFB1 gene polymorphism and gingival overgrowth was revealed in kidney transplant patients administered Cyclosporine A.
P Visweswaran - One of the best experts on this subject based on the ideXlab platform.
-
Mannitol-induced acute renal failure.
Journal of the American Society of Nephrology : JASN, 1997Co-Authors: P Visweswaran, E K Massin, T D DuboseAbstract:The osmotic diuretic mannitol may be used in diverse clinical settings, such as providing "renal protection" in patients at risk for acute renal failure, decreasing intracranial pressure in patients with intracranial trauma, and preventing the dialysis-disequilibrium syndrome. Mannitol is commonly used after cardiac catheterization, cardiovascular surgery, and exposure to intravenous contrast dyes. This study presents a case in which a long-term renal transplant recipient receiving Cyclosporine therapy concomitantly developed acute renal failure after the administration of high-dose mannitol in an attempt to induce an osmotic diuresis. The diagnosis of "osmotic nephrosis" was confirmed by renal biopsy, and the condition was reversed by cessation of the agent. Studies in experimental animals indicate that cyclosporin A can potentiate the tubular toxicity of mannitol, but such an association has not been verified in humans. Numerous studies confirm the nephrotoxic potential of high-dose mannitol, especially in patients with renal insufficiency. The clinical utility of the osmolar gap in preventing mannitol nephrotoxicity is emphasized.
