tacrolimus and Vitamin-D-Deficiency

Focal segmental glomerulosclerosis (FSGS) is a pathologic condition that represents many disease entities. The goals of therapy are to cure the disease. When this is not possible, the secondary goals are to reduce proteinuria to avoid the complications of nephrotic syndrome and to delay progression of kidney disease. Proteinuria remission is one of the most important independent predictors of kidney survival. Children with FSGS who do not achieve partial or complete remission have a 50% risk of progression to ESRD within 5 years whereas those who enter complete remission have a 5-year kidney survival rate of 90%. Treatment of idiopathic FSGS commonly involves immune-based and nonimmunologic therapy options. This manuscript will review the current state of FSGS therapy for children.

Topics: Adrenal Cortex Hormones; Angiotensin II Type 1 Receptor Blockers; Angiotensin-Converting Enzyme Inhibitors; Antibodies, Monoclonal, Murine-Derived; Antihypertensive Agents; Child; Cyclosporine; Glomerulosclerosis, Focal Segmental; Humans; Hypertension; Immunosuppressive Agents; Mycophenolic Acid; Obesity; Rituximab; Tacrolimus; Treatment Outcome; Vitamin D Deficiency

Transplantation is an established therapy for end-stage diseases of kidney, lung, liver, and heart among others. Osteoporosis and fragility fractures are serious complications of organ transplantation, particularly in the first post-transplant year. Many factors contribute to the pathogenesis of osteoporosis following organ transplantation. This review addresses the mechanisms of bone loss that occurs both in the early and late post-transplant periods, including the contribution of the immunosuppressive agents as well as the specific features to bone loss after kidney, lung, liver, cardiac, and bone marrow transplantation. Prevention and treatment for osteoporosis in the transplant recipient are also discussed.

Topics: Animals; Bone Marrow Transplantation; Glucocorticoids; Heart Transplantation; Humans; Hyperparathyroidism, Secondary; Immunosuppressive Agents; Kidney Transplantation; Liver Transplantation; Lung Transplantation; Organ Transplantation; Osteoporosis; Osteoporotic Fractures; Tacrolimus; Vitamin D Deficiency

What are the pregnancy outcomes after the OPtimization of Thyroid function, Immunity, and Uterine Milieu (OPTIMUM) treatment strategy in patients with repeated implantation failure (RIF)?. The 116 women with RIF after the OPTIMUM treatment strategy were 38.3 ± 3.8 years old and had an implantation failure history over 5 (3-19) ET cycles. Implantation testing identified impaired intrauterine circumstances in 75 women (64.7%), an aberrant elevated Th1/Th2 cell ratio in 56 women (48.3%), and thyroid abnormalities in 33 women (28.4%). Cumulative ongoing pregnancy rates including spontaneous pregnancy in the patients aged < 40 and ≥ 40 years were 72.7% and 45.5% within two ET cycles, respectively. The pregnancy outcomes in the OPTIMUM group were significantly higher than those in the control.. The OPTIMUM treatment strategy improved pregnancy outcomes in patients with RIF.

Topics: Adult; Anti-Bacterial Agents; Anticoagulants; Aspirin; Autoantibodies; Embryo Implantation; Endometritis; Female; Humans; Immunosuppressive Agents; Infertility, Female; Pregnancy; Pregnancy Outcome; Pregnancy Rate; Retrospective Studies; Risk Factors; Tacrolimus; Th1 Cells; Th2 Cells; Thrombophilia; Thyroid Diseases; Thyrotropin; Thyroxine; Vitamin D; Vitamin D Deficiency; Vitamins

Vitiligo is a pigmentary disorder and autoimmune pathogenesis seems most likely. Decreased vitamin D levels have been related to several autoimmune diseases. Little is known about the association of vitiligo and vitamin D. We aimed to evaluate serum 25-hydroxyvitamin D [25(OH)D] levels in children with vitiligo and to determine the efficacy of oral vitamin D therapy on the repigmentation of vitamin D deficient patients.. Thirty patients aged 6-17 years with vitiligo and 30 sex- and age-matched apparently healthy controls were included in this prospective study. Size of the vitiligo representative area was estimated using the point counting method and blood samples were obtained at the beginning and month six. By the end of the study, all patients treated with topical tacrolimus for six months and the patients who were vitamin D deficient (n = 14) had been on combination treatment of oral vitamin D and topical tacrolimus. A dose of 1500 IU/day vitamin D was given if the serum 25(OH)D levels <20 ng/ml and 3000 IU/day was given if the levels <10 ng/ml for six months. Serum 25(OH)D levels were measured by high-performance liquid chromatography.. Serum 25(OH)D levels of patients and controls were not significantly different (p > 0.05). Lesion size decreased from 66.1 ± 58.3 cm. Although we did not determine decreased serum 25(OH)D levels in children with vitiligo, we showed that combination treatment with oral vitamin D and topical tacrolimus is more effective in reaching repigmentation than topical tacrolimus alone. Oral vitamin D supplementation might be useful for children with vitiligo who are also deficient in vitamin D.

Topics: Administration, Oral; Adolescent; Age Factors; Autoimmune Diseases; Blood Chemical Analysis; Body Mass Index; Child; Dietary Supplements; Female; Humans; Male; Prospective Studies; Sex Factors; Tacrolimus; Turkey; Vitamin D; Vitamin D Deficiency; Vitiligo

The aim of the study was to identify factors associated with 1,25(OH)2D3 concentrations in liver transplant recipients with emphasis on the renal function and catabolism. We also tested the hypothesis that tacrolimus increases 1,25(OH)2D3 concentrations. Serum 25(OH)D3, 1,25(OH)2D3, and 24,25(OH)2D3 were measured in 41 patients before, at 2 weeks and 3 months after transplantation. Dose-adjusted tacrolimus concentration was used as a surrogate marker of CYP3A4 activity. Factors associated with 1,25(OH)2D3 were identified using multivariate linear regression analysis. The median 1,25(OH)2D3 levels remained stable: 55 versus 46 pg/ml (P = 0.36) despite an increase in 25(OH)D3 from 18 ng/ml at baseline to 26 ng/ml (P = 0.03), serum albumin (34 to 41 g/l, P = 0.02), and comparable eGFR at baseline and month 3 (94 and 92 ml/min, respectively, P = 0.15). At 3 months 19 % of patients had 1,25(OH)2D3 < 25 pg/ml. Low eGFR and a low dose-adjusted tacrolimus concentration were both independently associated with 1,25(OH)2D3 at 3 months. Liver transplant recipients with impaired renal function or a low dose-adjusted tacrolimus concentration suggesting a high CYP3A4 are at risk of low 1,25(OH)2D3 concentrations. The use of tacrolimus does not lead to an increase in 1,25(OH)2D3 concentrations in a clinical setting.

Topics: Adult; Aged; Calcitriol; Calcium; Dose-Response Relationship, Drug; Female; Glomerular Filtration Rate; Humans; Immunosuppressive Agents; Kidney Function Tests; Liver Transplantation; Longitudinal Studies; Male; Middle Aged; Parathyroid Hormone; Prospective Studies; Tacrolimus; Vitamin D Deficiency; Young Adult

Osteoporosis is a major cause of morbidity in liver transplant recipients and is associated with multiple factors.. To evaluate bone mineral density (BMD), bone turnover and calcium-regulating hormones in 29 patients (17 men, 12 women) 2-12 yrs following liver transplantation for non-alcoholic liver diseases.. Fifteen patients (52%) were on immunosuppressive treatment with tacrolimus and 14 (48%) with cyclosporine. Eleven patients (38%) were currently on prednisone, 18 patients (62%) had stopped glucocorticoid treatment 6 months to 11 yrs prior to the study. Nineteen patients (65.5%) had decreased BMD according to WHO criteria, 17 (58.2%) at the femoral neck, 13 (44.8%) at the lumbar spine. Nineteen patients (65.5%) had a subnormal (<15 ng/mL) serum level of 25 (OH) D3. These patients had significantly lower BMD at the femoral neck (p = 0.02). Femoral neck BMD negatively correlated with serum parathyroid hormone level (p = 0.06, r = -0.35), length of the post-transplantation period (p = 0.025, r = -0.416) and duration of glucocorticoid treatment (p = 0.029, r = -0.406), regardless of its cumulative dose. Symptomatic fractures were less frequent in tacrolimus treated patients than in cyclosporine users (p = 0.03).. Decreased BMD is frequent following liver transplantation and is affected by vitamin D deficiency, cyclosporine use, and the duration of glucocorticoid therapy, but not by its cumulative dose. Achievement and maintenance of optimal vitamin D status and shortening of glucocorticoid treatment period may have a favorable effect on bone preservation.

Topics: Absorptiometry, Photon; Alkaline Phosphatase; Amino Acids; Bone Density; Bone Remodeling; Cyclosporine; Female; Glucocorticoids; Humans; Immunosuppressive Agents; Liver Transplantation; Male; Middle Aged; Osteoporosis; Parathyroid Hormone; Regression Analysis; Risk Factors; Statistics, Nonparametric; Tacrolimus; Time Factors; Vitamin D Deficiency