tacrolimus and Constriction--Pathologic

Atherosclerotic renal artery stenosis is one of the risk factors for cardiovascular death and can lead to the ischemic nephropathy. In this report, we describe the successful management of ischemic nephropathy that developed in a kidney transplant recipient with graft artery stenosis. The 52-year-old male patient had diabetes and hypertension and was a nonsmoker with hypothyroidism on replacement therapy. He had a history of recurrent urinary tract infection due to vesicoureteric reflux before starting hemodialysis in July 2009. In November 2020, he received a deceased donor renal allograft and showed slow graft function. He received thymoglobulin as induction and steroid, tacrolimus, and mycophenolate mofetil as maintenance therapy. He was discharged with nadir creatinine around 130 μmol/L. His diabetes was controlled by intensive insulin regimen. Later, he presented with graft dysfunction with partially controlled hypertension and suspected graft artery stenosis by Doppler ultrasonography but no evidence of obstruction. His tacrolimus level was adequate, and his echocardiography was unremarkable. He received empirical pulse steroid. A graft biopsy showed severe acute tubular necrosis, suspicious T-cell-mediated rejection, and negative C4d and positive SV40 stain, suggesting BK nephropathy. His BK viremia (500 copies/mL) and viruria (885 billion copies/mL) improved after immunosuppression minimization, although he remained dependent on dialysis. A repeated Doppler ultrasonogram showed flattening of the systolic wave. Computed tomographic angiography revealed diffusely attenuated graft arteries. The patient received graft artery angioplasty and stenting of the 2 arteries. The patient showed good response, with same-day urine production and Doppler showing good systolic wave. His graft function started to improve, and he was discharged with stable graft function. His immunosuppressive regimen was subsequently tailored to steroid and low-dose tacrolimus. In conclusion, we found that ischemic nephropathy could be reversed if properly managed, even in presence of other comorbidities.

Topics: BK Virus; Constriction, Pathologic; Graft Rejection; Humans; Hypertension; Immunosuppressive Agents; Kidney Transplantation; Male; Middle Aged; Polyomavirus Infections; Renal Artery Obstruction; Tacrolimus; Treatment Outcome

A 15-year-old Asian girl with severe atopic dermatitis was referred for dupilumab-associated blepharoconjunctivitis. Medical history was significant for severe atopic dermatitis. She was started on prednisolone acetate 1% ophthalmic suspension three times daily, and dupilumab injections were withheld after the initial visit. The patient was noted to have right lower eyelid ectropion, cicatricial occlusion, and severe punctal stenosis 6 weeks later. She was started on 0.03% tacrolimus ointment to the eyelid margin. Resolution of ectropion and restoration of punctal patency with residual stenosis were observed 4 weeks later. This is the first reported adolescent case of dupilumab-associated ectropion and punctal stenosis successfully treated with topical tacrolimus ointment.

Topics: Adolescent; Constriction, Pathologic; Dermatitis, Atopic; Ectropion; Female; Humans; Immunosuppressive Agents; Lacrimal Apparatus Diseases; Ointments; Tacrolimus; Treatment Outcome

Nodular regenerative hyperplasia is a histopathological diagnosis characterized by the diffuse transformation of the liver parenchyma into regenerative nodules associated with rheumatologic and hematologic disorders, azathioprine immunosuppression or vascular injuries. The authors report the case of a 60-year-old female patient with a diagnosis of familial systemic paramyloidosis submitted to liver transplantation complicated by a hepatic artery thrombosis. A second liver transplant was performed and after 6 months she developed ascites and peripheral edema. The abdominal computed tomography (CT) showed an inferior vena cava stenosis. She underwent balloon angioplasty and an endovascular prosthesis was placed. The patient remained asymptomatic under immunosuppression with tacrolymus for 4 years, when she complained of peripheral edema and ascites. Laboratory work-up showed anemia and hypoalbuminemia with liver chemistry within the normal range. The ascites fluid analysis revealed a serum ascites albumin gradient superior to 1.1 g/L. Abdominal Doppler ultrasound and abdominopelvic CT angiogram confirmed endovascular prosthesis permeability. A percutaneous hepatic biopsy specimen was taken and histologic analysis showed, with reticulin stain, focal regenerative nodules of hyperplastic hepatocytes and internodular hepatocyte atrophy, compatible with the diagnosis of nodular regenerative hyperplasia. The case described is of particular interest as the nodular regenerative hyperplasia occurred after liver transplantation complicated with inferior vena cava stenosis, which might have contributed in a crucial way to liver parenchyma transformation.

Topics: Amyloidosis, Familial; Angioplasty, Balloon; Biopsy; Constriction, Pathologic; Female; Focal Nodular Hyperplasia; Hemodynamics; Humans; Immunosuppressive Agents; Liver Transplantation; Middle Aged; Phlebography; Risk Factors; Tacrolimus; Tomography, X-Ray Computed; Treatment Outcome; Vascular Diseases; Vena Cava, Inferior

The aim of the present investigation was to describe a new model of liver regeneration in growing rats with reduced portal flow. In addition, it was studied whether tacrolimus and insulin could have any pro-regenerative effect under such conditions. Ninety-five rats were divided into five groups: Group 1 (sham), abdominal incision without intervention; Group 2, 70% hepatectomy; Group 3, 70% hepatectomy + PV stenosis; Group 4, 70% hepatectomy + portal vein stenosis + insulin; and Group 5, 70% hepatectomy + portal vein stenosis + tacrolimus. The remnant liver lobes were harvested for analyses. The liver weight decreased in the PV stenosis group and it increased with the use of insulin and tacrolimus. The mitotic activity was higher in the hepatectomy, insulin and tacrolimus groups and this parameter was reduced by portal stenosis. Levels of interleukin 6 (IL-6) were higher in the hepatectomy group compared to the sham and PV stenosis groups. The expression of IL-6 and Ki67 was significantly increased in the insulin and tacrolimus groups compared to the portal stenosis group. A highly reproducible model was standardized to study liver regeneration with portal blood inflow reduction in weaning rats. It was demonstrated that insulin or tacrolimus administration may partially reverse the harmful effects of PV stenosis.

Topics: Animals; Calcineurin Inhibitors; Constriction, Pathologic; Immunohistochemistry; Insulin; Interleukin-6; Liver; Liver Regeneration; Male; Models, Animal; Polymerase Chain Reaction; Portal Vein; Rats; Rats, Wistar; Regional Blood Flow; RNA; Tacrolimus

We developed a novel sustained drug-eluting device using tacrolimus-eluting biodegradable nanofiber to prevent anastomotic stricture and evaluated the effects in a rat abdominal aortic anastomosis model.. In vitro and in vivo tacrolimus release tests for tacrolimus-eluting biodegradable nanofiber were performed to confirm its sustained release. To verify the prevention of anastomotic stricture, tacrolimus-eluting biodegradable nanofiber was placed around the end-to-end anastomosis of abdominal aorta in rats. Five rats were allocated to the following 5 groups: (1) control without tacrolimus-eluting biodegradable nanofiber, (2) 5 mg of nanofiber only (0 wt% of tacrolimus), (3) 5 mg of tacrolimus-eluting biodegradable nanofiber containing 0.04 wt% of tacrolimus, (4) 5 mg of tacrolimus-eluting biodegradable nanofiber containing 0.1 wt% of tacrolimus, and (5) 5 mg of tacrolimus-eluting biodegradable nanofiber containing 1.0 wt% of tacrolimus. Morphometric and histologic analyses including immunohistochemistry were performed in each of the groups 2 weeks after the operation.. The tacrolimus-eluting biodegradable nanofiber gradually released tacrolimus for at least 1 month in vitro and in vivo. The ratio of intimal area was significantly reduced in the 1.0 wt% tacrolimus-eluting biodegradable nanofiber group compared with the other groups (0.26, 0.24, 0.25, 0.21, and 0.08 in control, 0 wt%, 0.04 wt%, 0.1 wt%, and 1.0 wt%, respectively, P < .05). The cells, which constitute intimal hyperplasia, were positive for smooth muscle actin and SMemb, and factor VIII revealed that endothelial cells covered the surface of the aortic lumen even in the 1.0 wt% tacrolimus-eluting biodegradable nanofiber group in immunohistochemistry.. Tacrolimus-eluting biodegradable nanofiber reduced neointimal hyperplasia and preserved endothelialization. This device may be useful in the prevention of anastomotic stricture.

Topics: Anastomosis, Surgical; Animals; Aorta, Abdominal; Aortic Diseases; Biocompatible Materials; Constriction, Pathologic; Models, Animal; Nanostructures; Postoperative Complications; Rats; Rats, Wistar; Tacrolimus

To evaluate the outcome of pediatric patients who underwent liver transplantation between Oct. 2002 and May 2005 in the Pediatric Hospital.. Eight cases aged from 4 to 67 months who underwent liver transplantation were analyzed retrospectively. Four of the patients were boys and 4 girls, whose body weight at the time of liver transplantation was 6-19 kg. The underlying diseases were biliary atresia, congenital cholestasis, drug-induced cholestatic cirrhosis and cryptogenic cirrhosis. These patients had been followed up for blood routine examinations, liver and renal function, serum electrolytes and blood concentration of tacrolimus for 16 to 43 months after liver transplantation. Results of serological studies for viral etiology, liver biopsy, growth and mental development were also recorded.. One-year survival rate was 75.0% with the longest survival time being 43 months after transplantation. One patient died from renal failure due to postoperative bleeding 24 hours after the surgery and another case died of variceal hemorrhage 8 months after transplantation. Posttransplantation complications included acute cellular rejection, viral infection and hypoalbuminemia. Viral infections included cytomegalovirus infection in 3 cases, Epstein-Barr virus infection in 1 and hepatitis B virus infection in 1. Surgical complications of portal vein thrombosis and stenosis of inferior vena cava and hepatic vein occurred in 2 cases respectively. Side effects of tacrolimus including hypertension, renal damage, liver damage and diarrhea were observed. Significant growth-retardation was not often seen. A self-reported high quality of life was common.. Close follow-up and management of patients after liver transplantation may significantly increase the survival rate and improve quality of life in children with end-stage liver diseases.

Topics: Biliary Atresia; Child; Child, Preschool; Constriction, Pathologic; Female; Graft Rejection; Hepatitis B; Herpesvirus 4, Human; Humans; Hypertension; Immunosuppressive Agents; Liver Cirrhosis; Liver Failure; Liver Transplantation; Male; Pediatrics; Postoperative Complications; Survival Rate; Tacrolimus; Treatment Outcome; Vena Cava, Inferior; Venous Thrombosis

1. Tumour necrosis factor (TNF-alpha) is a pleiotropic cytokine which is deeply involved in the pathogenesis of splanchnic artery occlusion (SAO) shock. Tacrolimus, formerly known as FK506, is a macrolide antibiotic, that blocks the transcription of several proinflammatory cytokines including TNF-alpha. 2. Male anaesthetized rats were subjected to clamping of the splanchnic arteries for 45 min. This surgical procedure resulted in an irreversible state of shock (SAO shock). Sham operated animals were used as controls. SAO shocked rats had a decreased survival rate (0% at 4 h of reperfusion, while sham shocked rats survived more than 4 h), enhanced serum TNF-alpha concentrations (415+/-12 U ml(-1)), decreased mean arterial blood pressure (MAP), leukopenia and increased ileal leukocyte accumulation studied by means of myeloperoxidase activity (MPO=7.5+/-0.3 U g(-1) tissue). Moreover aortic rings from shocked rats showed a marked hyporeactivity to phenylephrine (PE, 1 nM - 10 microM), reduced responsiveness to acetylcholine (ACh, 10 nM - 10 microM) and increased staining for intercellular adhesion molecule-1 (ICAM-1). Furthermore increased mRNA for TNF-alpha was observed in peritoneal macrophages of SAO shocked rats. 3. Tacrolimus (100 microg kg(-1), 5 min after splanchnic arteries occlusion) increased survival rate (SAO + Tacrolimus = 100% at 4 h of reperfusion), reverted the marked hypotension, reduced serum TNF-alpha (15+/-3 U ml(-1)), ameliorated leukopenia, reduced ileal MPO (0.9+/-0.01 U g(-1) tissue), restored to control values the hyporeactivity to PE. improved the reduced responsiveness to ACh and blunted the enhanced immunostaining for ICAM-1 in the aorta. Finally tacrolimus suppressed cytokine mRNA levels in peritoneal macrophages. 4. The data suggest that tacrolimus may represent a new therapeutic approach in circulatory shock.

Topics: Animals; Blood Pressure; Constriction, Pathologic; Endothelium, Vascular; Immunohistochemistry; Immunosuppressive Agents; Leukocyte Count; Macrophages; Male; Muscle Contraction; Muscle, Smooth, Vascular; Peroxidase; Rats; Rats, Sprague-Dawley; Reverse Transcriptase Polymerase Chain Reaction; RNA, Messenger; Shock; Splanchnic Circulation; Survival Analysis; Tacrolimus; Tumor Necrosis Factor-alpha

Cardiac hypertrophy is a fundamental adaptive response to hemodynamic overload; how mechanical load induces cardiac hypertrophy, however, remains elusive. It was recently reported that activation of a calcium-dependent phosphatase, calcineurin, induces cardiac hypertrophy. In the present study, we examined whether calcineurin plays a critical role in pressure overload-induced cardiac hypertrophy.. Pressure overload produced by constriction of the abdominal aorta increased the activity of calcineurin in the rat heart and induced cardiac hypertrophy, including reprogramming of gene expression. Treatment of rats with a calcineurin inhibitor, FK506, inhibited the activation of calcineurin and prevented the pressure overload-induced cardiac hypertrophy and fibrosis without change of hemodynamic parameters. Load-induced expression of immediate-early-response genes and fetal genes was also suppressed by the FK506 treatment.. The present results suggest that the calcineurin signaling pathway plays a pivotal role in load-induced cardiac hypertrophy and may pave the way for a novel pharmacological approach to prevent cardiac hypertrophy.

Topics: Animals; Aorta, Abdominal; Atrial Natriuretic Factor; Blood Volume; Body Weight; Calcineurin; Calcineurin Inhibitors; Cardiomegaly; Constriction, Pathologic; Disease Models, Animal; Echocardiography; Fibrosis; Gene Expression; Genes, Immediate-Early; Heart Rate; Immunosuppressive Agents; Male; Myocardium; Proto-Oncogene Proteins c-fos; Proto-Oncogene Proteins c-jun; Rats; Rats, Wistar; Signal Transduction; Tacrolimus