OBJECTIVE: Estrogen is a major regulator/modulator of bone metabolism, and bone loss in estrogen deficiency is associated with increased bone turnover, But the mechanism for estrogen action on bone metabolism is still unknown. Recent studies have suggested that the increase in bone loss induced by estrogen deficiency is mediated by increased paracrine production of bone resorbing cytokines. Among cytokines, 1nterleukin-6(IL-6) is released from osteoblasts in estrogen deficiency and increases bone resorption by stimulation of osteoclastic activities and recruitment. Thus we performed this study to evaluate the effect of ovariectomies on bone mineral density and IL-6 in cultured monocytes of peripheral blood and bone marrow. METHODS: The experimental animals were 13 female Sprague-Dawley rats that were 8 weeks of age and weighed an average of 188.5 gram at the beginning of the study. Bilateral ovariectomies were performed in all rats from a ventral approach. Bone mineral density(BMD) of the total body, spine and level of IL-6 of cultured monocytes of peripheral blood and bone marrow were measured before and 8 weeks after ovariectomy. RESULTS: 1) BMD of total body and spine were lower after ovariectomy(0.257+/-0.069g/cm2, 0,208+/-0.005g/cm2) than before ovariectomy (0.276+/-0.005g/cm2, 0.229+/-0.011g/cm2), respectively (P<0.01). 2) Although IL-6 level of cultured monocytes in peripheral blood tended to be higher after ovariectomy than before ovariectomy, this difference was not statistically significant (P>0.05). 3) IL-6 level of cultured monocytes in bone marrow was higher after ovariectomy(82.78+/-4.99pg/ml) than before ovariectomy(48.85+/-2.42pg/ml)(P<0.05). CONCLUSION: It is possible that increased production of IL-6 in estrogen deficiency induced by ovariectomy occurs in the local environment of bone or bone marrow rather than in the pheripheral blood and stimulates bone resorption.
Animals ; Bone Density* ; Bone Marrow ; Bone Resorption ; Cytokines ; Estrogens ; Female ; Humans ; Interleukin-6* ; Metabolism ; Monocytes ; Osteoblasts ; Osteoclasts ; Ovariectomy* ; Rats* ; Rats, Sprague-Dawley ; Spine

PURPOSE: Tacrolimus (FK506) is a new potent immunosuppressive agent which has been used as a primary immunosuppressive agent and rescue therapy for refractory rejection in kidney transplantation. In vitro, on a molecular basis, tacrolimus is 10 to 100 times more potent than cyclosporine. Complications associated with tacrolimus are similar to those seen in cyclosporine, including nephrotoxicity. An early marker of tacrolimus-induced nephropathy is tubular vacuolization, whereas long-term administration of tacrolimus is associated with striped interstitial fibrosis and arteriolar hyalinosis. However, morphological changes and pathogenesis of fibrosis in chronic tacrolimus-induced nephropathy remain poorly understood. Transforming growth factor (TGF)-beta1 has been implicated in the fibrosis of a number of chronic diseases of the kidney and other organs. This study was designed to clarify the ultrastructural changes of tacrolimus-induced nephropathy, and to evaluate the relationship between tacrolimus- induced nephropathy and expression of TGF-beta1. METHODS: Male ICR mice received tacrolimus daily at a dose of 2.5 mg/kg by intraperitoneal route for 12 weeks and sacrified 1, 4, 8, 10, and 12 weeks after the initiation of the study, respectively. The kidneys were removed, the cortex is carefully dissected from the medulla, and the tissues are processed for evaluation by light microscopy, electron microscopy, immunohistochemistry and RT-PCR for RNA analysis. RESULTS: Characteristic histological changes of tacrolimus-induced nephropathy were peritubular capillary and intraglomerular capillary congestions, vacuolizations of the tubular epithelium, pericapillary focal fibrosis, and tubular atrophy. Tacrolimus- treated kidneys had a progressive increase in the expression of TGF-beta1, especially in the glomerular and interstitial capillary endothelial cells and atrophied tubular epithelial cells. TGF-beta1 mRNA is expressed persistently in tacrolimus- treated mice for 12 weeks. CONCLUSION: It can be concluded that TGF-beta1 may be involved in the fibrogenesis in the tacrolimus-induced nephropathy.
Animals ; Atrophy ; Capillaries ; Chronic Disease ; Cyclosporine ; Endothelial Cells ; Epithelial Cells ; Epithelium ; Estrogens, Conjugated (USP) ; Fibrosis ; Humans ; Immunohistochemistry ; Kidney ; Kidney Transplantation ; Male ; Mice ; Mice, Inbred ICR ; Microscopy ; Microscopy, Electron ; RNA ; RNA, Messenger ; Tacrolimus ; Transforming Growth Factor beta1 ; Transforming Growth Factors

No abstract available.
Retroperitoneal Fibrosis*

BACKGOUND: On-line hemodiafiltration (HDF) is a technique that relies on the re-injection of pyrogen-free substitution fluid obtained by cold filtration of dialysate. Therefore, safety of this therapy depends on the quality of dialysate and, mainly, on the integrity of the ultrafilters employed. Paired hemodiafiltration (PHF) is a new technique where re-infusion takes place inside the dialyzer by means of dialysate backfiltration. METHODS: To assess safety and feasibility, we carried out prospective cross-over trial comparing PHF with hemodialysis (HD) in five stable HD patients RESULTS: All PHF sessions were well tolerated. No pyrogenic reactions were observed during the study period. No significant difference was found in the incidence of intradialytic hypotension. PHF led to significantly higher small and middle molecule clearance than HD. The reduction rates of urea, creatinine and beta2-M were significantly higher in PHF than in HD, while no difference was found for phosphate. The serum beta2-M levels fell progressively from the HD value of 29 mg/L to 17 mg/L at the end of 3 months's PHF treatment. CONCLUSION: In conclusion, PHF is a feasible and safe convective therapy to increase beta2-M removal compared with HD. Long-term, prospective multicenter clinical studies are mandatory to assess the clinical outcome of this new on-line technique of HDF.
Creatinine ; Filtration ; Hemodiafiltration* ; Humans ; Hypotension ; Incidence ; Prospective Studies ; Renal Dialysis ; Urea

PURPOSE: Posttransplant diabetes mellitus (PTDM) is one of the feared complications of the immunosuppressive agents following renal transplantation. Despite advances of immunosuppressive therapy, including the introduction of the steroid- sparing calcineurin inhibitors, cyclosporine and tacrolimus, the incidence rate remains greater than 10~30%. METHODS: This prospective study investigated the influence of tacrolimus on glucose metabolism before and after transplantation for twenty patients without known glucose metabolism abnormalities. RESULTS: The overall incidence of PTDM was 30% and was developed within 3 months after renal transplantation in majority of cases. During tacrolimus administration, fasting blood glucose increased from a median of 87.0 mg/dL to 103.5 mg/dL (P<0.05), and Insulin sensitivity decreased in 15 of 20 patients, from a median of 1.6 mg/dL/min to 1.2 mg/dL/min (P<0.05). Insulin secretion decreased from 1918.3 microUx min/mL to 1018.2micro Ux min/mL (P<0.05), whereas insulin resistance did not change. CONCLUSION: These results indicate that diminished insulin secretion response to a glucose load rather than insulin resistance was proved as the main pathogenesis of PTDM in renal transplant recipients treated with tacrolimus. Higher tacrolimus trough level, older age, and higher weight were more frequently seen in the PTDM group than normal group, although the difference failed to reach statistical significance. Further prospective studies with a greater number of patients are needed to define the risk factor for PTDM.
Blood Glucose ; Calcineurin ; Cyclosporine ; Diabetes Mellitus ; Fasting ; Glucose* ; Humans ; Immunosuppressive Agents ; Incidence ; Insulin ; Insulin Resistance ; Kidney Transplantation* ; Metabolism* ; Prospective Studies ; Risk Factors ; Tacrolimus* ; Transplantation

BACKGROUND: Patients with end-stage renal diseases (ESRD) have an increased risk of sleep problems such as daytime sleepiness, insomnia, restless legs syndrome (RLS), and obstructive sleep apnea syndrome (OSAS). However, presently there is limited data available, particularly in Asia. METHODS: To investigate the prevalence of sleep complaints in ESRD patients, 100 patients at the maintenance hemodialysis (HD) and 100 patients at the continuous ambulatory peritoneal dialysis (CAPD) were surveyed using a specific questionnaire. RESULTS: Patients had a mean age of 50.58+/- 14.03 years, with a mean body mass index (BMI) of 21.8+/-3.5 kg/m2. The mean duration of dialysis was 44.56 +/-49.74 months. Fifty-six percent of the dialysis patients were poor sleepers. Daytime sleepiness occurred in 24% to 34% of the patients, and insomnia occurred in 35% of the patients, while restless legs syndrome was reported in 44% of the patients. The higher BMI group had a lower risk for insomnia when compared to the lower BMI group (OR=0.11, 95% CI=0.03-0.46). The OR of depression for insomnia was 2.8 (95% CI=1.02-7.69). There was no difference in the prevalence of sleep disturbances between the HD and CAPD patients groups. CONCLUSIONS: Complaints of sleep disturbance and daytime somnolence are very common in dialysis patients and likely contribute to the impaired quality of life experienced by many of these patients. Identifying and treating the sleep complaints in dialysis patients could contribute significantly to their quality of life and avoid potential side effects of nonspecific sedatives.
Asia ; Body Mass Index ; Depression ; Dialysis* ; Humans ; Hypnotics and Sedatives ; Kidney Failure, Chronic* ; Peritoneal Dialysis ; Peritoneal Dialysis, Continuous Ambulatory ; Prevalence ; Quality of Life ; Surveys and Questionnaires ; Renal Dialysis ; Restless Legs Syndrome ; Sleep Apnea, Obstructive ; Sleep Wake Disorders* ; Sleep Initiation and Maintenance Disorders

BACKGROUND: Patients with end-stage renal diseases (ESRD) have an increased risk of sleep problems such as daytime sleepiness, insomnia, restless legs syndrome (RLS), and obstructive sleep apnea syndrome (OSAS). However, presently there is limited data available, particularly in Asia. METHODS: To investigate the prevalence of sleep complaints in ESRD patients, 100 patients at the maintenance hemodialysis (HD) and 100 patients at the continuous ambulatory peritoneal dialysis (CAPD) were surveyed using a specific questionnaire. RESULTS: Patients had a mean age of 50.58+/- 14.03 years, with a mean body mass index (BMI) of 21.8+/-3.5 kg/m2. The mean duration of dialysis was 44.56 +/-49.74 months. Fifty-six percent of the dialysis patients were poor sleepers. Daytime sleepiness occurred in 24% to 34% of the patients, and insomnia occurred in 35% of the patients, while restless legs syndrome was reported in 44% of the patients. The higher BMI group had a lower risk for insomnia when compared to the lower BMI group (OR=0.11, 95% CI=0.03-0.46). The OR of depression for insomnia was 2.8 (95% CI=1.02-7.69). There was no difference in the prevalence of sleep disturbances between the HD and CAPD patients groups. CONCLUSIONS: Complaints of sleep disturbance and daytime somnolence are very common in dialysis patients and likely contribute to the impaired quality of life experienced by many of these patients. Identifying and treating the sleep complaints in dialysis patients could contribute significantly to their quality of life and avoid potential side effects of nonspecific sedatives.
Asia ; Body Mass Index ; Depression ; Dialysis* ; Humans ; Hypnotics and Sedatives ; Kidney Failure, Chronic* ; Peritoneal Dialysis ; Peritoneal Dialysis, Continuous Ambulatory ; Prevalence ; Quality of Life ; Surveys and Questionnaires ; Renal Dialysis ; Restless Legs Syndrome ; Sleep Apnea, Obstructive ; Sleep Wake Disorders* ; Sleep Initiation and Maintenance Disorders

Posttransplant diabetes mellitus, a complication due to corticosteroids and the calcineurin inhibitors, cyclosporine and tacrolimus, is commonly regarded as a form of type 2 diabetes mellitus. Diabetes ketoacidosis, which requires relative insulin deficiency to impair fatty acid metabolism, is a complication of type 1 diabetes mellitus. We report two patients who presented with diabetic ketoacidosis after kidney transplantation. Two patients presented with severe hyperglycemia, significant ketosis and metabolic acidosis of variable severity. One patient was treated with a cyclosporine-based regimen, and the other with a tacrolimus-based regimen. Both were found to have moderate to high serum levels of calcineurin inhibitors on presentation. Our experience suggests that post-transplant diabetes mellitus, in association with calcineurin inhibitor, may result in ketoacidosis either secondary to relative beta cell dysfunction, peripheral insulin resistance, or a combination of the two effects. Post transplant diabetes mellitus can be an atypical form of adult-onset diabetes with features of both type 1 and type 2 diabetes mellitus.
Acidosis ; Adrenal Cortex Hormones ; Calcineurin ; Cyclosporine ; Diabetes Mellitus ; Diabetes Mellitus, Type 1 ; Diabetes Mellitus, Type 2 ; Diabetic Ketoacidosis ; Humans ; Hyperglycemia ; Insulin ; Insulin Resistance ; Ketosis ; Kidney Transplantation ; Metabolism ; Tacrolimus

Posttransplant diabetes mellitus, a complication due to corticosteroids and the calcineurin inhibitors, cyclosporine and tacrolimus, is commonly regarded as a form of type 2 diabetes mellitus. Diabetes ketoacidosis, which requires relative insulin deficiency to impair fatty acid metabolism, is a complication of type 1 diabetes mellitus. We report two patients who presented with diabetic ketoacidosis after kidney transplantation. Two patients presented with severe hyperglycemia, significant ketosis and metabolic acidosis of variable severity. One patient was treated with a cyclosporine-based regimen, and the other with a tacrolimus-based regimen. Both were found to have moderate to high serum levels of calcineurin inhibitors on presentation. Our experience suggests that post-transplant diabetes mellitus, in association with calcineurin inhibitor, may result in ketoacidosis either secondary to relative beta cell dysfunction, peripheral insulin resistance, or a combination of the two effects. Post transplant diabetes mellitus can be an atypical form of adult-onset diabetes with features of both type 1 and type 2 diabetes mellitus.
Acidosis ; Adrenal Cortex Hormones ; Calcineurin ; Cyclosporine ; Diabetes Mellitus ; Diabetes Mellitus, Type 1 ; Diabetes Mellitus, Type 2 ; Diabetic Ketoacidosis ; Humans ; Hyperglycemia ; Insulin ; Insulin Resistance ; Ketosis ; Kidney Transplantation ; Metabolism ; Tacrolimus

Cytomegalovirus (CMV) remains an important pathogen in organ transplant recipients, and ganciclovir has been the antiviral agent of choice both for prevention and treatment of CMV disease. Recently ganciclovir-resistant cytomegalovirus has been reported with increasing frequency in organ transplant recipient and is an emerging clinical problem in transplant recipients. Ganciclovir-resistant CMV infection has been associated with clinical progression of CMV disease and high mortality even with foscarnet therapy. We report here a case of disseminated ganciclovir-resistant CMV disease in a 34-year-old renal transplant recipient, who died of multiorgan failure despite treatment with both ganciclovir and foscarnet.
Adult ; Cytomegalovirus Infections* ; Cytomegalovirus* ; Foscarnet ; Ganciclovir ; Humans ; Kidney Transplantation* ; Mortality ; Transplantation ; Transplants