Mycophenolate sodium-induced hepatotoxicity: first report.
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Acute Disease↗
Biomedical subjects
Frank Martinez
Publications and source records attributed to Frank Martinez.
Comparison of sequential protocol using basiliximab versus antithymocyte globulin with high-dose mycophenolate mofetil in recipients of a kidney graft from an expanded-criteria donor.
This retrospective pilot study investigated use of high-dose mycophenolate mofetil with biological induction and sequential introduction of low-dose cyclosporine in recipients of expanded criteria donor (ECD) kidneys. Fifty-four patients received mycophenolate mofetil 3 g/day for 45 days, cyclosporine 4 mg/kg/day, prednisolone, and rabbit antithymocyte globulin (rATG, n=14) or basiliximab (n=40). Acute rejection incidence was 11.3% (7.1% with rATG, 12.6% with basiliximab). Delayed graft function was observed in 31 patients (54%). At one year, measured glomerular filtration rate was 54+/-4 ml/min, with no significant differences between induction therapies. Thirty patients (55%) required > or =1 MMF dose reduction within month 1 due to adverse events (gastrointestinal symptoms, 67%; leucopenia 33%). Leucopenia was more frequent with rATG, while gastrointestinal symptoms were more frequent with basiliximab. Cytomegalovirus replication occurred in three patients (23%) with rATG and 3 (8%) with basiliximab. In conclusion, high-dose MMF, corticosteroids, delayed low-dose cyclosporine and induction therapy offers an excellent risk-to-benefit ratio in patients receiving an ECD allograft.
Antibodies, Monoclonal↗
The impact of the built environment on children's school conduct grades: the role of diversity of use in a Hispanic neighborhood.
A population-based study examined the relationship between diversity of use of the built environment and teacher reports of children's grades. Diversity of use of the built environment (i.e., proportion of a block that is residential, institutional, commercial and vacant) was assessed for all 403 city blocks in East Little Havana, Miami-a Hispanic neighborhood. Cluster analysis identified three block-types, based on diversity of use: Residential, Mixed-Use, and Commercial. Cross-classified hierarchical linear modeling was used to examine the impact of diversity of use, school, gender, and year-in-school on academic and conduct grades for 2857 public school children who lived in these blocks. Contrary to popular belief, mixed-use blocks were associated with optimal outcomes. Specifically, follow-up analyses found that a youth living on a residential block had a 74% greater odds of being in the lowest 10% of conduct grades (conduct GPA <2.17) than a youth living on a mixed-use block. In fact, an analysis of the population attributable fraction suggests that if the risk associated with residential blocks could be reduced to the level of risk associated with mixed-use blocks, a 38% reduction in Conduct GPAs <2.17 could be achieved in the total population. These findings suggest that public policy targeting the built environment may be a mechanism for community-based interventions to enhance children's classroom conduct, and potentially related sequelae.
Achievement↗
Tacrolimus-induced alopecia in female kidney-pancreas transplant recipients.
BACKGROUND: Immunosuppressive drugs given to solid organ transplant recipients may be responsible for cosmetic side effects which can endanger patient compliance. Cyclosporine is associated with hirsutism whereas tacrolimus has been associated with rare cases of alopecia. Since 1998, we have included tacrolimus within the immunosuppressive regimen following kidney-pancreas transplantation. The aim of this study was to evaluate the incidence of alopecia in this population and possible risk factors. METHODS: Between January 1, 1995 and October 31, 2003, 59 consecutive simultaneous kidney-pancreas (SPK) transplants were performed in 58 recipients (27 females and 31 males). The immunosuppressive regimen comprised corticosteroids, calcineurin inhibitor (cyclosporine, n=11; or tacrolimus, n=40) and a purine inhibitor (azathioprine or mycophenolate mofetil). RESULTS: Clinically significant alopecia occurred in 13 patients (28.9%) receiving tacrolimus versus none receiving cyclosporine (P<0.001). Of those who experienced alopecia, 11 were female and two were male (P=0.02). The mean delay between transplantation and alopecia was 422 days (range 100-1,567). Other causes of alopecia were excluded. Treatment of alopecia with topic minoxidil was successful in all cases but one, which required conversion from tacrolimus to cyclosporine. CONCLUSIONS: Alopecia is a frequent complication in women receiving tacrolimus therapy following SPK transplantation. Its pathogenesis is unknown. This cosmetic complication must be discussed with patients before transplantation to minimize the risk of noncompliance.
Alopecia↗
Benefits of erythropoietin in renal transplantation.
Anemia is a common complication in patients with chronic kidney diseases (CKD), including transplanted patients. Recent studies have found a prevalence of anemia of about 30%, whereas less than 10% of these patients received recombinant human erythropoietin. Factors explaining this high incidence of anemia in renal transplant recipients include delayed and impaired graft function and use of drugs inhibiting the action of angiotensin II and preventing rejection. Like in CKD patients, chronic anemia may impact on the cardiovascular system and finally on the high mortality of these patients. Recent data suggest also that anemia may be a factor of progression of renal dysfunction in kidney transplant recipients. A French randomized multicenter study was designed to answer this question.
Anemia↗
Kidney transplant in black recipients: are African Europeans different from African Americans?
Despite recent improvement, significant racial disparities in outcome still persist after renal transplantation among African American patients in the United States. This study evaluated the association of race and ethnicity with allograft outcomes in a French population of 952 Caucasian (Cauc) patients and 140 African European (AE) patients who underwent renal transplantation in our center between 1987 and 2003. Demographic characteristics were similar for the two cohorts other than cause of end-stage renal failure (more hypertension among AE and more polycystic kidney disease among Cauc) and cold ischemia time (significantly longer for AE). Immunosuppressive treatment was comparable between groups. There were no significant differences between AE and Cauc in the incidence of acute rejection (31% vs. 30%). At 5 years post-transplant, patient survival (93% vs. 92%), graft survival (83% in both groups) and graft function (creatinine clearance 48 mL/min vs. 45 mL/min) were also similar among the AE and Cauc patients. We demonstrate that ethnic origin does not affect outcome after renal transplantation in France. Therefore, differences observed in the United States cannot be only related to immunologic or pharmacologic factors. The results of renal transplantation in patients of African origin could be improved with universal immunosuppressive drug coverage.
Adult↗
Complications of protocol renal biopsy.
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Acute Kidney Injury↗
High dose chemotherapy in light chain or light and heavy chain deposition disease.
BACKGROUND: Conventional chemotherapy for myeloma yield unsatisfactory results in light and/or heavy chain deposition disease [(H)CDD] Because of the well-established dose-response effect of high dose melphalan in multiple myeloma, aiming to dramatically reduce the pathogenic monoclonal immunoglobulin (MIg) level, high dose therapy is a tempting alternative approach. METHODS: We treated 11 young patients with L(H)CDD by high dose therapy with the support of autologous blood stem cell transplantation. All had renal symptoms, including four who required dialysis and seven who had various, mainly cardiac, extrarenal manifestations. RESULTS: No toxic deaths occurred. A decrease in the MIg level was observed in eight patients, with complete disappearance from serum and urine in six cases. Improvement in manifestations related to MIg deposits were observed in six patients, including renal, cardiac, and hepatic responses in 4/11, 4/4, and 2/2 cases, respectively. Histologic regression of MIg deposits was documented in cardiac, hepatic, and skin biopsies. In contrast, examination of the kidney still showed light chain deposits in one patient who had renal transplantation 3 years after high dose therapy, at a time when he was in persisting remission. Within a median follow-up of 51 months, three patients were retreated because of multiple myeloma relapse, of whom one died and one required hemodialysis, and renal function secondarily deteriorated in a patient who had resistant multiple myeloma. Otherwise, no manifestations related to MIg deposits occurred or recurred in any patient. CONCLUSION: Present results of this retrospective study argue in favor of a benefit of high dose therapy with stem cell support in young patients with L(H)CDD.
Adult↗
Benefit-risk assessment of ciclosporin withdrawal in renal transplant recipients.
Ciclosporin is associated with significant toxicity, including nephrotoxicity, and with an increased risk of cardiovascular events. Many attempts have been made to wean patients from ciclosporin. Before the availability of new immunosuppressive drugs, the acute rejection rate observed after ciclosporin withdrawal did not permit the widespread use of withdrawal regimens even though meta-analysis did not show that they adversely affected patient or graft survival. Nevertheless, maintenance therapy with azathioprine and corticosteroids has not become routine practice. The introduction of mycophenolate mofetil and subsequently sirolimus has increased the number of clinical studies of the effects of ciclosporin withdrawal. In stable patients, this withdrawal is associated with a small but significant increase in the incidence of acute rejection episodes. Declining renal function and other forms of ciclosporin-related toxicity have improved. However, this improvement was also observed when ciclosporin was only reduced (and not withdrawn), which did not increase the risk of acute rejection. More precise definition of the patients who could benefit from ciclosporin-withdrawal may help to optimise the immunosuppressive regimen in this setting. In patients with chronic allograft deterioration, ciclosporin withdrawal together with mycophenolate mofetil introduction has been shown to improve renal function significantly in many small studies, and a large prospective randomised study. For the time being, ciclosporin withdrawal is a good therapeutic option for patients with declining renal function and signs of chronic ciclosporin nephrotoxicity on renal biopsy. Finally, recent preliminary studies have reported the results of complete avoidance of calcineurin inhibitors after renal transplantation. These results are promising as regards the incidence of acute rejection, renal function and safety, but need confirmation in larger trials with a longer follow-up. Nevertheless, it has become clear that the concept of an immunosuppressive regimen with little or no nephrotoxicity after renal transplantation is more and more important and plays a crucial part in tailoring immunosuppression to the needs of specific patient populations.
Cyclosporine↗
Tenofovir-related nephrotoxicity in human immunodeficiency virus-infected patients: three cases of renal failure, Fanconi syndrome, and nephrogenic diabetes insipidus.
We report 3 cases of renal toxicity associated with use of the antiviral agent tenofovir. Renal failure, proximal tubular dysfunction, and nephrogenic diabetes insipidus were observed, and, in 2 cases, renal biopsy revealed severe tubular necrosis with characteristic nuclear changes. Patients receiving tenofovir must be monitored closely for early signs of tubulopathy (glycosuria, acidosis, mild increase in the plasma creatinine level, and proteinuria).
Acidosis↗
The expanding spectrum of renal diseases associated with antiphospholipid syndrome.
BACKGROUND: The association of thrombotic events and/or pregnancy complications with circulating antiphospholipid antibodies defines antiphospholipid syndrome (APS). In previous reports, renal involvement in APS consisted mainly of thrombotic vascular complications involving large vessels or intrarenal small-sized vessels (APS nephropathy). We report 9 cases of glomerulonephritis associated with APS. These cases are characterized by predominant pathological features distinct from vascular APS nephropathy. METHODS: We reviewed consecutive renal biopsies examined in 2 French university hospitals between 1980 and 2002 and identified renal biopsies performed in patients with primary APS. RESULTS: We identified 29 biopsies performed in patients with APS. Twenty biopsies showed characteristic features of APS nephropathy. In 9 cases, predominant pathological features distinct from vascular APS nephropathy were noted: membranous nephropathy (3 cases), minimal change disease/focal segmental glomerulosclerosis (3 cases), mesangial C3 nephropathy (2 cases), and pauci-immune crescentic glomerulonephritis (1 case). In 7 cases, the presentation of renal symptoms was subacute or chronic. Two patients experienced episodes of acute renal failure. At referral, median creatinine clearance was 50 mL/min (0.83 mL/s) (range, 18 to 117 mL/min [0.30 to 1.95 mL/s]). Proteinuria was noted in all cases (range, 1.5 to 15 g/d), with nephrotic syndrome in 4 cases. Lupus anticoagulant was present in all cases, and anticardiolipin antibodies, in 8 cases. Anti-DNA antibodies repeatedly were negative in all cases. Treatment consisted of antihypertensive therapy (6 cases), anticoagulant drugs (5 cases), steroids (4 cases), and antiplatelet drugs (3 cases). At last follow-up, renal function remained stable in 7 patients. Of 2 patients presenting with acute renal failure, 1 patient recovered normal renal function, whereas the other patient progressed to end-stage renal failure. CONCLUSION: The cases reported here represent a new aspect of the expanding spectrum of renal diseases encountered in association with APS.
Adrenal Cortex Hormones↗
Spontaneous rupture of non-tumoral kidneys in patients with end stage renal failure: risks and management.
OBJECTIVES: To determine the risks and treatment modalities of spontaneous subcapsular or perinephric bleeding in end stage renal patients. METHODS: 8 patients with end stage renal failure developed a spontaneous hemorrhage of one of their native kidneys and were referred to our institution. They were all men. Six of them presented an acquired renal cystic disease. Symptoms included sudden abdominal pain in 7 patients, vomiting in 2 and hematuria in 1. Symptoms were always associated with a hemoglobin decrease. Four patients were receiving oral anticoagulants for various reasons and one had thrombopenia. Bleeding was confirmed by computerized tomography and nephrectomy undertaken in all cases. RESULTS: 3 patients died in the immediate post-operative period. Histologic findings confirmed bleeding and did not find any other abnormality than those related to renal insufficiency (cysts and atrophy). CONCLUSION: Renal rupture should be considered in case of unexplained distress or sudden fall of the hemoglobin especially when patients are on anticoagulants. Surgery is our preferred treatment because of the frequency of unrevealed tumours and the potential mortality of massive hematomas.
Adult↗
Mesenteric ischaemia in haemodialysis patients: a case/control study.
BACKGROUND: Mesenteric ischaemia is not uncommon in dialysis patients and seems to have been increasing in the last decade. However, the risk factors for mesenteric ischaemia are unclear and prognosis of patients after this type of ischaemic accident is not well defined. METHODS: From January 1988 to June 1999, 15 haemodialysis patients (0.3% per patient-year) from a single institution presented with mesenteric ischaemia and the clinical, biological and radiological aspects of the ischaemia were described. To identify risk factors for mesenteric ischaemia, each ischaemic patient (case) was matched with two other haemodialysis patients not having ischaemia (controls). Survival curves were then established for the two groups. RESULTS: A marked hypotensive episode was present in seven out of 15 case patients (47%) during dialysis sessions that preceded mesenteric ischaemia. Abdominal pain, guarding, fever and hyperleucocytosis were all present in 13 out of 15 patients (87%). An abdominal computerized tomography scan with opaque enema enabled a rapid diagnosis for six patients. The caecum was the most frequently (47%) affected segment. Twelve patients were surgically treated and the remaining three were given medical support. The two groups (case and control) were not different in cardiovascular risk factors, comorbidity, administered drugs or main haemodialysis characteristics. The median survival of the case group was 600 days, whereas 80% of the control group survived beyond this period (P=0.0132). Eleven case patients survived >3 months after mesenteric ischaemia and had a median survival of 1500 days, which was identical to their matched control patients. CONCLUSIONS: Mesenteric ischaemia should be systematically suspected in patients experiencing abdominal pain during or after dialysis sessions. Prompt diagnosis and treatment usually allow for a favourable prognosis.
Aged↗
Pharmacokinetic interaction between corticosteroids and tacrolimus after renal transplantation.
BACKGROUND: Tacrolimus is an immunosuppressive drug that is a substrate of cytochrome P450 3A (CYP3A) enzymes and P-glycoprotein (P-gp). After transplantation, many pharmacological interactions have been described. Corticosteroids induce both CYP3A and P-gp activity. This study was designed to investigate the presence of a clinically significant interaction between steroids and tacrolimus after renal transplantation. METHODS: We studied 83 renal transplant recipients receiving tacrolimus after transplantation. Patients were divided into three groups, according to steroid dose (low: 0-0.15 mg/kg/day; intermediate: 0.16-0.25 mg/kg/day; and high: >0.25 mg/kg/day). All other medications, including those known to interact with CYP3A and/or P-gp, were recorded. Steroid dosage, tacrolimus dosage, tacrolimus trough concentration (C0) and tacrolimus concentration/dose ratio [C0 divided by the 24 h dosage (mg/kg)] were assessed for each dosage group after 1 and 3 months of tacrolimus treatment. RESULTS: The three groups were not different as regards the use of non-immunosuppressive treatments or clinical events. At 1 and 3 months, the tacrolimus doses and concentration/dose ratios differed significantly in the three steroid dosage groups. With the higher doses, higher tacrolimus doses were needed to achieve the blood tacrolimus targeted trough level. CONCLUSIONS: We demonstrated that pharmacokinetic interaction occurs between steroids and tacrolimus in renal transplant patients. The higher the steroid dosage, the higher the dosage of tacrolimus needed to achieve target trough levels in these patients. The most likely interaction mechanism is specific enzymatic induction of CYP3A and/or P-gp. Interaction is present, even when the steroid dosage is low. The clinical events liable to occur during steroid sparing or tapering must be taken into account because it may be associated with episodes of tacrolimus-related nephrotoxicity.
Adult↗
Factors affecting outcome and prognosis in membranous lupus nephropathy.
BACKGROUND: This study was designed to review the prognosis and the predictors of renal outcome in patients with membranous lupus nephropathy (MLN) with no or mild mesangial proliferation. METHODS: The medical records of patients (n=66) with biopsy-proven MLN, WHO class VA, and class VB without any past history of proliferative lupus nephropathy (PLN) were reviewed retrospectively. RESULTS: The mean follow-up was 6.9+/-0.2 years and renal survival at 5 and 10 years was 97+/-2 and 88+/-6%. Twenty-nine patients underwent a second renal biopsy during follow-up. Fourteen of these patients (21%) had lesions of PLN. Among them, four reached end-stage renal disease (ESRD) despite immunosuppressive treatment. The probability of a transition from MLN to PLN at 10 years was 35+/-8%. Two other patients reached ESRD but did not have repeat renal biopsies and two had biopsy-proven progression to fibrosis. Independent risk factors associated with the doubling of creatinine were transition into PLN and the occurrence of a thrombosis during follow-up. The only predictor of ESRD was the haemoglobin level. PLN was not a predictor of ESRD but the efficient treatment of this form of lupus nephritis prevented that outcome. CONCLUSIONS: With a long follow-up, our study noted a high frequency of transition into PLN in a large cohort of patients with MLN. Steroid usage was not predictive of outcome and did not affect renal survival, a result that must be qualified in light of the highly variable duration of treatments with steroids. The early screening and treatment of PLN is the main benefit of the close follow-up of patients with MLN. Progression to ESRD with only fibrosis remains a rare event.
Adult↗
Alpha-interferon-associated thrombotic microangiopathy: a clinicopathologic study of 8 patients and review of the literature.
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Adult↗