Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound   Target Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound

---

Query: EC:3.1.3.16 (calcineurin)
17,112 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Transplantation of kidneys from older donors is followed by an increase in delayed graft function (DGF) and acute rejection episodes (ARE). In these circumstances, induction treatment, whether with antithymocyte globulin or with interleukin-2 receptor blockers, may delay the introduction of calcineurin inhibitors (CNI) with effective prevention of ARE. We examined the efficacy and safety of induction treatment with 2 low doses of thymoglobulin compared with 2 doses of basiliximab. A group of 27 patients were treated with thymoglobulin and another 36 with basiliximab. CNI introduction was delayed until day 3 posttransplantation. The thymoglobulin group received 2 doses of 1.25 mg/kg on alternate days and the basiliximab group 2 doses of 20 mg. A trend to a lower incidence of DGF was observed in the thymoglobulin group (33% vs 55.6%; P = .08), with lower levels of serum creatinine on days 7 (P = .02) and 14 (P = .02) posttransplantation. No patient in the thymoglobulin group experienced ARE, but 11 patients (30.6%) in the basiliximab group did (P < .001), and 5 needed rescue treatment with thymoglobulin. We found no differences in the incidence of cytomegalovirus (CMV) disease (P = .945), admission due to infections (P = .274), or neoplasia (P = .340), or differences in graft (P = .69) and patient (P = .21) survivals at 1 and 3 years. Low-dose thymoglobulin was more effective at preventing DGF and ARE in renal transplant recipients of organs from older donors, with no differences in infectious complications or graft and patient survivals.
...
PMID:Induction treatment with low-dose thymoglobulin or basiliximab in renal transplants from older donors. 1901 Jan 41

We present the 12-month results of a prospective trial of conversion from calcineurin inhibitors (CNI) to everolimus (EVL) in maintenance liver transplant (LT) recipients. Forty (M:F = 28:12; 54.9 +/- 11 years) patients were enrolled at a mean interval of 45.5 +/- 31.2 months from transplantation. Conversion was with EVL at a dosage of 0.75 mg b.i.d., withdrawal of antimetabolites, and a 50%-per-week reduction of CNI to a complete stop within 4 weeks. The treatment success was conversion to EVL monotherapy at 12 months while failure was presence of CNI, death, and graft loss. Indication to conversion was deteriorating renal function in 36 (90%). At 12 months, patient- and graft survival were 100% and the success rate was 75% (30/40). Ten patients (25%) were failures: four (10%) for acute rejection; three hepatitis C virus-RNA positive patients (7.5%) for hypertransaminasemia; one (2.5%) for acute cholangitis; and two (5%) due to persistent pruritus and oral ulcers. In patients on EVL monotherapy, at 12 months the mean change of calculated creatinine clearance (cCrCl) was 4.03 +/- 12.6 mL/min and the only variable correlated with the probability of improvement was baseline cCrCl (P < 0.0001). Conversion from CNI to EVL is feasible in 75% of the cases and associated with improvement in renal function for patients with higher baseline cCrCl.
...
PMID:Conversion to everolimus monotherapy in maintenance liver transplantation: feasibility, safety, and impact on renal function. 1905 83

Reports on the use of sirolimus (SRL) in pancreas transplantation are still limited. The aim of this study was to evaluate the outcome of SRL conversion in pancreas transplant patients. Among 247 patients undergoing simultaneous kidney-pancreas or solitary pancreas transplantation, 33 (13%) were converted to SRL. The reasons for conversion were calcineurin inhibitors (CNI) nephrotoxicity (n = 24; 73%), severe neurotoxicity owing to CNI (n = 1; 3%), severe and/or recurrent acute rejection episodes (n = 7; 21%), gastrointestinal (GI) side effects of mycophenolate mofetil (MMF; n = 5; 15%), and hyperglycemia (n = 4; 12%). Before conversion, all patients were maintained on a CNI, MMF, and low-dose steroids. They were gradually converted to SRL associated with either CNI or MMF withdrawal. Sixty-three percent (n = 15) of patients who were converted owing to CNI nephrotoxicity, showed stable or improved renal function. At 12 months after conversion, serum creatinine levels were significantly decreased in this group (2.2 +/- 0.5 vs 1.6 +/- 0.3 mg/dL; P = .001) and C-peptide values increased (2.9 +/- 1.1.1 vs 3.1 +/- 1.3 nmol/L; P = .018). The only patient with leucoencephalopathy showed improved neurologic status after SRL conversion. All patients converted to SRL because of GI side effects of MMF showed improvements, and none of those converted because of hyperglycemia experienced improvement. There were no episodes of acute rejection after conversion. We concluded that conversion to SRL in pancreas transplantation should be considered an important alternative strategy, particularly for CNI nephrotoxicity and neurotoxicity, and in cases of severe diarrhea due to MMF.
...
PMID:Conversion to sirolimus in kidney-pancreas and pancreas transplantation. 1910 Apr 48

Recovery from acute kidney injury requires regeneration of tubule cells. Because calcineurin induces nuclear transport of NFATc proteins, whose expression pattern correlates with the nephron segments injured by calcineurin inhibitors, we hypothesized that NFATc1 plays a role in modifying epithelial regeneration after injury. To test this, we induced proximal tubular cell (PTC) injury in Balb/c mice and Nfatc1(+/-) mice with mercuric chloride; the PTCs of Nfatc1(+/-) mice demonstrated increased apoptosis, sustained injury, and delayed regeneration. To attenuate NFATc1 activity further, we injected cyclosporin A daily. Cyclosporin A-treated Nfatc1(+/-) mice demonstrated rapid and severe injury after administration of mercuric chloride, with increased serum creatinine, increased apoptosis, decreased PTC proliferation, and increased mortality compared with similarly treated wild-type mice. Using a novel NFATc1 transgenic line that reports activation of an NFATc1 enhancer domain critical for NFATc1 autoamplification, we demonstrated accentuated NFATc1 expression in a PTC subpopulation after mercuric chloride-induced injury. In addition, NFATc1-labeled, apoptosis-resistant PTCs proliferated to repair the damaged proximal tubule segment. These data provide evidence for a resident progenitor PTC population and suggest a role for NFATc1 in the regeneration of injured proximal tubules.
...
PMID:NFATc1 identifies a population of proximal tubule cell progenitors. 1911 53

We assessed the efficacy and outcome of low through level of calcineurin inhibitors (CNI) and introducing mycophenolate mofetil (MMF) in liver transplant (LT) patients with CNI-related renal dysfunction. Thirty LT patients were converted to combined therapy and compared with 30 patients used as a contemporary control group receiving CNI only. The two groups were matched for sex, age, months after LT, immunosuppressive treatment, creatinine level, presence of diabetes and calculated glomerular filtration rate (GFR) via Cockroft-Gault method. After two years, in the MMF serum creatinine decreased from 1.65 mg/dL (range 1.33-3.5) to 1.4 mg/dL (range 0.9-4.7) (p = 0.002) and GFR increased from 51 mL/min (range 18.9-72.2) to 57.6 mL/min (range 16-92.2) (p < 0.001), whereas the controls not showed any improvement. The logistic regression models employing improvement of creatinine and GFR of at least 10% with respect to baseline as dependent variables showed the use of MMF (p = 0.004 and p = 0.019, respectively) as the only statistically significant parameter. Multiple linear regression analysis identified only MMF as independent predictor of Deltacreatinine and DeltaGFR (p = 0.002 and p < 0.001, respectively). No rejection episode was observed (three in controls). This study demonstrates the medium-term efficacy and safety of MMF plus low dose CNI in reducing nephrotoxicity in LT recipients.
...
PMID:Two yr mycophenolate mofetil plus low-dose calcineurin inhibitor for renal dysfunction after liver transplant. 1921 May 25

Posterior reversible encephalopathy syndrome (PRES) is one of the serious adverse side effects of calcineurin inhibitors, which are used for the prophylaxis of graft-versus-host disease (GVHD) after allogeneic stem cell transplantation (allo-SCT). We retrospectively analyzed 12 patients who developed PRES after allo-SCT aiming to clarify the clinical features, risk factors, and prognosis of PRES. Median onset of PRES is 17 days after allo-SCT. The most frequent primary symptom was high blood pressure, followed by headache and visual disturbance. Nine of our patients subsequently developed systemic seizure. Sites of PRES by MRI were detected in the frontal, temporal, and parietal lobes, basal ganglia, and brain stem in addition to occipital lobe. Serum creatinine that had increased two-fold from the baseline value was identified as the only risk factor for developing PRES after allo-SCT. The incidence of acute GVHD (grade II-IV) in patients with PRES and those without were 88.9% and 48.7%; respectively (P<0.001), and most of these patients died of GVHD or GVHD-related causes. The 2-year overall survival of patients with PRES and those without were 16.7% and 72.4%, respectively (P<0.001). These data suggested the importance of early intervention for PRES and exploitation of optimal GVHD prophylaxis after developing PRES.
...
PMID:[Retrospective analysis of posterior reversible encephalopathy syndrome after allogeneic stem cell transplantation]. 1922 23

Conversion from calcineurin inhibitors (CNI) to proliferation signal inhibitors (PSI), such as sirolimus or everolimus (EV), may improve the course of chronic allograft nephropathy. Herein we have presented a case of a kidney recipient with chronic cyclosporine (CsA) nephrotoxicity who was converted from CsA to EV at 5.5 years posttransplantation. There were no significant changes in immunofluorescence (IFL) or in electron microscopy (EM) in the preconversion biopsy. Two months after conversion, proteinuria and creatinine increased. The biopsy showed focal, segmental necrosis of the glomerular tuft with the formation of segmental cellular crescents and increased endocapillary cellularity. IFL showed granular deposits of IgG, IgM, and C3 mostly along the capillary walls; it was negative for C4d. EM revealed electron-dense deposits within the glomerular basement membrane (GBM) and in the subendothelial region with significant reduction in the capillary lumina due to GBM reduplication and widening of lamina rara interna with the formation of fibrillary structures therein: focal, segmental glomerulosclerosis. EV was withdrawn and we administered tacrolimus and steroid pulses with improvement. Five months after the withdrawal of EV, a third graft biopsy showed remission of the necrotizing glomerulonephritis. However, the patient demanded dialysis at 17 months after conversion to EV. We concluded that necrotizing glomerulonephritis with immune complex deposition in a renal allograft was possibly induced by late conversion from CNI to EV. Reconversion to CNI may be recommended in cases of PSI-associated posttransplantation glomerulonephritis but the long-term prognosis is uncertain.
...
PMID:Late conversion to everolimus complicated with necrotizing glomerulonephritis in a renal allograft recipient: case report. 1924 76

Sirolimus (SRL) is a non-nephrotoxic immunosuppressive drug blocking T-cell proliferation through mTOR inhibition. SRL can be used as (1) an early drug in a calcineurin inhibitor-free protocol in the first 3 months after transplantation, (2) in the early and late conversion protocols as suggested by the multicenter randomized CONVERT trial, and (3) in recipients from marginal donors, because calcineurin inhibitors can increase the preexisting renal damage induced by age, hypertension, and diabetes that are frequent in elderly cadaveric donors. In any case, SRL should be used in patients with a cutoff of proteinuria (<or=800 mg/24 hr) or proteinuria-to-creatinine ratio less than 0.11.
...
PMID:Review of symposium. Sirolimus in kidney transplantation. 1938 85

Concomitant cyclosporine interacts with mycophenolic acid (MPA) through inhibition of the biliary excretion of its glucuronide (MPAG). The aim of this study was to evaluate the influence of calcineurin inhibitors on the plasma disposition and urinary excretion of MPA and MPAG in kidney transplant recipients. Twelve recipients treated with tacrolimus and 18 treated with cyclosporine at 30 days after transplantation were enrolled. AUC from 0 to 12 hours (AUC(0-12)) of MPA was significantly higher in tacrolimus-treated than in cyclosporine-treated recipients. In contrast, there was no significant difference in MPAG AUC(0-12) between calcineurin inhibitor medications. Unbound fractions of MPA and MPAG did not change significantly in a comparison between the tacrolimus and cyclosporine treatments (0.90% vs 1.27% in MPA; 20.0% vs 19.3% in MPAG). The ratio of renal clearance to creatinine clearance (CL(R)/CL(Cr)) of MPA was significantly lower in tacrolimusthan in cyclosporine-treated recipients (0.054 vs 0.100). In contrast, no significant difference was observed in the CL(R)/CL(Cr) of MPAG between the tacrolimus and cyclosporine treatments (0.19 vs 0.18). In conclusion, concomitant calcineurin inhibitors influenced the urinary excretion of MPA but not MPAG in kidney transplant recipients. The results suggest the presence of renal tubular secretion in the urinary excretion process of MPA.
...
PMID:Impact of calcineurin inhibitors on urinary excretion of mycophenolic acid and its glucuronide in kidney transplant recipients. 1945 5

Enteric-coated mycophenolate sodium (EC-MPS) is a formulation of mycophenolic acid (MPA) that releases the active molecule in the intestine reducing drug-related gastrointestinal (GI) side effects. The aim of present work was to summarize the use of EC-MPS for one-way conversion from mycophenolate mofetil (MMF) due to GI side effects and for de novo administration in a stable liver transplant population. In 10 patients on MMF and low-dose calcineurin inhibitors (CNI), significant GI side effects suggested drug conversion to ameliorate subjective symptoms. In 5 patients, EC-MPS was initiated de novo together with reduction of CNI for prevention of long-term renal failure. Conversion was carried out at equivalent MMF/EC-MPS dosages. Reevaluation at 2 months after conversion showed that no episode of rejection or infection occurred, and white blood cell count, CNI levels and doses, and creatinine clearance did not vary significantly. In 70% of converted patients there was a reduction of GI symptoms, especially diarrhea. Eighty percent suspended proton pump inhibitors. The de novo-treated patients showed no significant GI side effects. In conclusion, conversion from MMF to EC-MPS demonstrated significant GI symptom relief and de novo drug administration was well tolerated.
...
PMID:Enteric-coated mycophenolate sodium: one-way conversion from mycophenolate mofetil and de novo use in stable liver transplant recipients. 1946 May 41


<< Previous 1 2 3 4 5 6 7 8 9 10

---