Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: EC:3.1.3.16 (calcineurin)
 17,112 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

This prospective study assesses over a period of 6 months, the variations in glomerular filtration rate (GFR) and safety parameters within a cohort of 44 cadaveric renal-transplant (RT) patients presenting with moderate renal insufficiency. They were progressively switched from calcineurin inhibitors (CNIs) based- to sirolimus (SRL) based-therapies aiming SRL troughs at levels approximately 8 ng/ml (range 6-10). All the patients were receiving in addition mycophenolate mofetil. The intent-to-treat (ITT) patient and graft survivals were 100%. Thirty-four patients, i.e. 77.3% completed the study. Overall, there was a significant improvement in the calculated GFR (Nankivell formula) from day 0 to month 6, i.e. from 45.98 (+/-16.3) to 53.07 (+/-12.68) ml/mn (P=0.03). However, renal function improved in only 20 cases (group I), and deteriorated in the others (group II). Groups I and II did not significantly differ with respect to time between transplantation and drug switch, GFR, serum creatinine, and proteinuria at baseline. There was only one case of steroid-sensitive acute rejection. Overall, there was a significant increase in proteinuria from 0 (0-3.15) to 0.57 (0-4.85) g/day (P=0.002). Finally, the conversion was associated with a significant increase in lipids, and a significant decrease in hemoglobin levels.
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PMID:Evaluation of the efficacy and safety of a slow conversion from calcineurin inhibitor- to sirolimus-based therapies in maintenance renal-transplant patients presenting with moderate renal insufficiency. 1723 20

The mTOR (mammalian target of rapamycin) inhibitors sirolimus (SRL) and everolimus (EVL) are potent immunosuppressive agents, which allow reducing the dose of the nephrotoxic calcineurin inhibitors cyclosporin and tacrolimus (TAC) in solid organ transplant recipients. However, there is evidence that mTOR inhibitors may lead to myelosuppression and dyslipidemia/hyperlipidemia. We therefore performed a retrospective analysis in heart transplant recipients with renal insufficiency, who received 3.0 mg/d SRL (SRL group; n = 28) or 1.5 mg/d EVL (EVL group; n = 27) each in combination with a reduced TAC dose for at least one yr. Fewer cardiac rejections, but a similar rate of infections occurred in the EVL group compared with the SRL group indicating that the administered EVL dose resulted in a potent immunosuppression. Serum triglyceride and total cholesterol concentrations rose significantly in the SRL group but not in the EVL group. In the SRL group only, the frequency of statin use increased significantly during follow-up. The EVL group showed a significant rise in HDL cholesterol levels during follow-up. There was a slight transient fall in haemoglobin concentrations in the SRL group but not in the EVL group. Leucocyte counts fell significantly in both study groups. However, no cases of leucopenia and also no cases of thrombopenia occurred. In summary, we could demonstrate that in heart transplant recipients with renal insufficiency the introduction of 1.5 mg/d EVL in combination with a reduced TAC dose is effective in preventing cardiac rejections and has less adverse effects on lipid metabolism than the usually prescribed SRL dose, whereas both therapy regimens are not associated with major haematological side-effects.
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PMID:Comparison of sirolimus and everolimus in their effects on blood lipid profiles and haematological parameters in heart transplant recipients. 1764 16

To assess the burden over time of renal dysfunction in pediatric heart transplant patients using an objective measure on an annual basis for serial comparison. GFR was measured at regular interval by nuclear medicine scintigraphy. Results were analyzed in relation to age, time post-transplantation, gender, and average calcineurin-inhibitor dose for the first two months post-transplantation. Results were compared with cGFR using the Schwartz equation. A total of 91 patients (56 males) transplanted between 1990 and 2004 underwent 373 GFR measurements. Median age at transplantation was 3.3 yr (birth - 17.8). Median first GFR at 0.7 yr (0.1-4.1) post-transplant was normal (94 mL/kg/1.73 m(2)). Freedom from at least mild renal insufficiency was 84% and 33% at one and five years post-transplant. Females had better renal function early post-transplant (GFR 105 mL/min/1.73 m(2)) but an increased probability of an abnormal GFR over time. Higher calcineurin inhibitor dose in the first two months post-transplantation was associated with an increasing probability of an abnormal GFR over time. The cGFR overestimated the measured GFR by 33 +/- 26 mL/kg/1.73 m(2). Renal insufficiency is an important morbidity after pediatric transplantation with the majority of patients experiencing at least mild renal dysfunction. Calculated GFR significantly underestimates the burden of renal insufficiency in this patient population.
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PMID:The profile of renal function over time in a cohort of pediatric heart transplant recipients. 1809 86

The purpose of this study is to review the clinical experience with sirolimus immunosuppression in liver transplant patients with calcineurin inhibitor-induced chronic renal insufficiency. The study design is a case-control retrospective series. Fifty-seven liver transplant patients with renal insufficiency that were started on sirolimus at greater than 90 days postoperatively and treated for more than 90 days were identified. A control group of 57 patients maintained on low-dose calcineurin inhibitors, matched for gender, year of transplant, and baseline creatinine clearance, was also identified. There were no significant differences in the absolute creatinine clearance values between the sirolimus and control groups from 6 months before sirolimus conversion to 12 months after sirolimus conversion. Patients exposed to calcineurin inhibitors for more than 5 years or those with an initial creatinine clearance of less than 30 mL/minute who were converted to sirolimus did worse than control patients maintained on low-dose calcineurin inhibitors. Progression to renal replacement therapy, episodes of acute and chronic rejection, and death were similar between the sirolimus and control groups. The overall prevalence of side effects was significantly higher in the sirolimus group compared with the control group, although these were generally tolerable in most patients. In conclusion, this study suggests that conversion to sirolimus in liver transplant patients with chronic renal insufficiency is associated with stabilization of renal function but confers no additional benefit to low-dose calcineurin inhibitor regimens and may in fact be disadvantageous in patients with a creatinine clearance of less than 30 mL/minute.
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PMID:Sirolimus in liver transplant recipients with renal dysfunction offers no advantage over low-dose calcineurin inhibitor regimens. 1843 68

Focal and segmental glomerular sclerosis (FSGS) is a heterogeneous disease from a clinical, etiological and clinical point of view. FSGS may be idiopathic, usually associated with nephrotic syndrome, which requires an ''etiological'' treatment approach. In addition, hereditary and secondary forms of FSGS have been described. The response to therapy, including steroids, cytotoxic drugs and calcineurin inhibitors, is considered the best clinical indicator of outcome. Many uncertainties exist regarding the best therapeutic approach to FSGS in patients presenting with chronic renal failure. In this setting, before planning any treatment, the physician should always assess the presence of superimposed functional renal insufficiency and evaluate the severity of the renal impairment, the histological picture, previous immunosuppressive treatments, and the individual patient's risk for side effects. Keeping in mind these considerations and in the absence of appropriate studies, we can formulate the following suggestions: 1. there is no absolute contraindication to the use of full-dose prednisone as initial therapy, although the likelihood of a good response is low; 2. the use of cytotoxic drugs is not recommended unless the patient presents with a steroid-responsive form of the disease; 3. in patients with a glomerular filtration rate of less than 40 mL/min, the use of calcineurin inhibitors should be avoided.
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PMID:[Choosing the right treatment approach in focal and segmental glomerular sclerosis with chronic renal failure]. 1904 92

Renal disease is a major cause of mortality and morbidity in systemic lupus erythematosus. Among the histological classes of lupus nephritis, membranous nephropathy comprises only one-fifth of all cases. Reported survival and rates of end-stage renal disease in membranous lupus nephropathy (MLN) vary considerably, because of substantial heterogeneity among the published studies. The risk of progression from MLN to renal failure is generally reduced in the absence of proliferative lesions, but patients are, nevertheless, at risk of thromboembolic complications. The optimal therapy for MLN remains elusive because of a lack of controlled trials; however, cardiovascular protection and blockade of the renin-angiotensin system should be instituted early in all patients. Mixed membranous and proliferative lupus nephritis should be treated in the same way as pure proliferative lupus nephritis. If MLN is not accompanied by proliferative lesions but is associated with clinically relevant proteinuria, renal insufficiency or failure to respond to supportive therapies, immunosuppressive treatment is indicated. Treatment options include glucocorticoids combined with azathioprine, calcineurin inhibitors or alkylating agents. The efficacy of mycophenolate mofetil in MLN remains to be confirmed. Controlled trials to compare existing immunosuppressive agents and experimental modalities such as sirolimus, rituximab and infliximab should be undertaken in the future.
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PMID:Membranous nephropathy in systemic lupus erythematosus: a therapeutic enigma. 1932 86

There is evidence that treatment with m-TOR inhibitors can be beneficial in cases of chronic renal allograft dysfunction. However, some authors have reported poor outcomes of renal function if the switch to m-TOR inhibitors is made in the presence proteinuria > 0.8 g/d. The present study sought to provide a retrospective analysis of the clinical outcome of 63 kidney recipients diagnosed with chronic allograft dysfunction whose therapy was converted to rapamycin including 35 subjects with renal biopsy-proven chronic allograft nephropathy. At the time of conversion, patients were divided into three groups: group I (negative proteinuria), group II (proteinuria between 0.3 and 0.8 g/d), and group III (proteinuria > 0.8 g/d). On conversion, 21 recipients had no proteinuria (group I). After a follow-up of 24.6 +/- 12.8 months, they showed a significant improvement in renal function (previous MDRD4 = 39.9 +/- 11.5 mL/m/1.73 m(2), current MDRD4 50.3 +/- 13.3 mL/m/1.73 m(2), P < .05). Fifteen patients (71.4%) developed proteinuria, which was generally mild (0.8 +/- 0.7 g/d) and controlled with angiotensin-converting enzyme inhibitors (42.8%). In group II (n = 18), renal function clearly stabilized after a follow-up of 23.2 +/- 14.4 months (previous MDRD4 = 30 +/- 8.8 mL/m/1.73 m(2), current MDRD4 = 37 +/- 12.2 mL/m/1.73 m(2), NS), although there was a progressive deterioration of previous proteinuria levels (previous proteinuria 0.4 +/- 0.15 g/d, current proteinuria 1.2 +/- 2 g/d, P < .05), which was more frequent and intense in patients whose treatment with calcineurin inhibitors (CNIs) was suspended (with CNI 0.9 +/- 1.7 g/d, without CNI 1.6 +/- 2.2 g/d, P < .05). Group III (n = 24) had a greater degree of renal insufficiency and a worse outcome after 25.9 +/- 18 months of follow-up, with a frank and progressive deterioration in renal function (previous MDRD4 = 38 +/- 17 mL/m/1.73 m(2), current MDRD4 = 32.5 +/- 19.2 mL/m/1.73 m(2), P < .05) and proteinuria (previous proteinuria = 1.5 +/- 0.7 g/d, current proteinuria = 2.5 +/- 2.2 g/d, P < .05) after conversion. Again, the deterioration in proteinuria was more intense in the patients whose previous CNIs were suspended (with CNI = 1.1 +/- 0.9 g/d, without CNI = 4.2 +/- 2.3 g/d, P < .05). In conclusion, for patients with chronic allograft dysfunction who do not present with proteinuria or whose proteinuria is less than 0.8 mg/d, switching to rapamycin is useful, since it clearly improves or stabilizes renal function, although there may be a discrete increase in proteinuria in the second case. However, among patients with proteinuria greater than 0.8 mg/d accompanied by a greater degree of renal insufficiency, conversion to rapamycin leads to deterioration of proteinuria levels and renal function. These data show that conversion to rapamycin in cases of chronic allograft dysfunction must be made early when there is no proteinuria or it is minimal, and that proteinuria is a predictor of the outcome of allograft function.
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PMID:Clinical implications of proteinuria in renal transplant recipients switching to rapamycin for chronic allograft dysfunction. 1971 16

Posterior reversible encephalopathy syndrome (PRES) was originally used to describe a reversible, predominantly posterior leukoencephalopathy in patients who had renal insufficiency, hypertension, or who received immunosuppressive therapy. Since PRES is prevalent in children with kidney diseases, awareness and understanding of it is important for practicing pediatric nephrologists. A comprehensive approach to the diagnosis of PRES includes thorough determination of predisposing factors, clinical symptoms, and mandatory appropriate imaging. Unfortunately, the pathophysiology of PRES is still obscure and specificity of radiological examination has not yet been established. Two major predisposing factors, namely hypertension and calcineurin inhibitors, are well recognized. In addition, nephrotic syndrome is a common underlying condition for development of PRES. Frequent symptoms include altered consciousness (coma, stupor, lethargy, confusion), seizure, headache, and visual disturbance. Most of these symptoms usually develop abruptly and resolve within a few weeks after proper management. Cranial magnetic resonance (MR) imaging is the first-line modality of imaging studies for detecting PRES. Diffusion-weighted imaging with quantification of apparent diffusion coefficient (ADC) values by ADC mapping may provide more accurate and specific images in the future.
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PMID:Posterior reversible encephalopathy syndrome in children with kidney diseases. 2155 18

It remains elusive what factors affect posterior reversible encephalopathy syndrome (PRES). Eleven PRES children, all with acute glomerulonephritis, Alport syndrome, and lupus nephritis, 5 with nephrosis, and 3 renal transplant recipients, were studied. PRES recurred in 1 patient. Neurological symptoms were graded as 1: mild (headache, nausea/vomiting, or tremor), 2: moderate (vision change), and 3: severe (mental dysfunction, cerebellar symptoms, seizures, recurrence of seizures, and coma). Magnetic resonance imaging was graded as 1: subtle change, 2: abnormal large areas, and 3: complete involvement of the regions. The common symptoms were seizures (100%), headache (82%), nausea/vomiting (73%), coma (55%), and vision change (46%). Seizures recurred in 7 (64%). All but one (91%) developed hypertension and 7 (64%) received calcineurin inhibitors (CNI). Edema occurred in 7 (64%) and renal insufficiency/end-stage renal disease (ESRD) in 4 (36%). Seizures recurred frequently in younger patients. Symptoms were severe in girls. Duration or severity of the condition with predisposing factors (hypertension, CNI, nephrosis or renal insufficiency/ERSD) did not make a difference in the symptoms and neuroimaging. Two patients developed chronic epilepsy. Age and gender may affect PRES symptoms. Our results are limited by small sample size and should be determined using larger numbers of patients.
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PMID:Age and gender may affect posterior reversible encephalopathy syndrome in renal disease. 2182 8

Vitamin D is a steroid hormone that, in addition to its actions on calcium and bone metabolism, exhibits a plethora of regulatory effects on growth, proliferation, apoptosis and function of the cells of the immune system that are relevant to the pathophysiology of systemic lupus erythematosus (SLE). Hypovitaminosis D is highly prevalent in SLE as a result of avoidance of sunshine, photoprotection, renal insufficiency and the use of medications such as glucocorticoids, anticonvulsants, antimalarials and the calcineurin inhibitors, which alter the metabolism of vitamin D or downregulate the functions of the vitamin D receptor. Low levels of vitamin D correlate with disease activity, and is associated with osteoporosis, fatigue and certain cardiovascular risk factors in SLE patients. This review updates the recent evidence on the relationship between vitamin D status and the onset, activity and complications of SLE, and summarizes the recommendations for vitamin D supplementation.
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PMID:Vitamin D and systemic lupus erythematosus: an update. 2363 33


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