A pilot study of cyclosporine withdrawal in stable renal transplant recipients after azathioprine-mycophenolate mofetil conversion.
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Biomedical subjects
Publications and source records attributed to D Ducloux.
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BACKGROUND: Cyclosporine A (CsA) nephrotoxicity is a nonimmunologic factor of chronic allograft dysfunction (CAD) in kidney transplant recipients. Mycophenolate mofetil (MMF) may allow CsA dosage reduction or even complete withdrawal in selected populations with CsA nephrotoxicity or CAD. The aim of the present study was to evaluate the efficacy and safety of CsA withdrawal after azathioprine (AZA)-MMF conversion in a population of stable renal transplant recipients. METHODS: Twenty-eight first cadaver kidney recipients were included. AZA was then discontinued, MMF was introduced and after 4 months CsA was completely withdrawn. All patients underwent inuline clearance measurement and renal biopsy at inclusion and at the end of the follow-up (40 wk). RESULTS: CsA was completely discontinued in 20 patients. No patient lost his graft during the study period, but 1 patient experienced a reversible acute rejection episode. Inuline clearance improved significantly in the whole series. At the end of follow-up, histological worsening was observed in 50% of patients without any specific risk factor. In these patients, inuline clearance did not improve. Systolic blood pressure, the need for anti-hypertensive drugs and HDL cholesterol improved. CONCLUSION: In stable kidney transplant recipients, CsA withdrawal after AZA replacement by MMF switch was safe with regard to acute rejection. It improved blood pressure and the lipid profile, but, in 50% of patients was associated with histologic deterioration.
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UNLABELLED: The aim of this study was to determine the prevalence of secondary hypertension in a population of refractory hypertension without initial clinical or biological findings suggesting identifiable causes of hypertension. METHODS: A survey included 200 consecutive hypertensive patients referred to hypertension specialists for refractory hypertension (BP > 140/90 mmHg on at least two antihypertensive drugs). Prior inclusion, the permanent elevation of blood pressure was confirmed by ambulatory monitoring. In each subject an extensive work-up was performed to detect a secondary cause for hypertension. RESULTS: An essential hypertension was confirmed in 61% of this cohort. A secondary hypertension was detected in 20% of the patients; 8.5% with a primary hyperaldosteronism, 8% with a reno-vascular hypertension and 3% with a nephropathy. Moreover, 18.5% had a low renin hypertension. Thus, 27% of these patients had an abnormality of the renin-aldosterone axis. CONCLUSION: Patients with refractory hypertension should be explored to detect secondary hypertension even without findings suggesting such causes. This additional diagnostic procedure must include at least renovascular investigations and plasma renin/aldosterone level determinations in appropriate conditions.
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BACKGROUND: The prevalence and clinical significance of antiphospholipid antibodies (APAs) have not been extensively studied in non-systemic lupus erythematosus (non-SLE) renal transplant recipients. METHODS: To further define the prevalence and clinical significance of APAs in non-SLE renal transplant recipients and the appearance of dialysis-related APAs after renal transplantation, we conducted a retrospective study on 178 renal transplant recipients. Documentation of anticardiolipin antibodies (ACAs) and lupus anticoagulant in non-SLE renal transplant recipients, retrospective documentation of ACAs on pretransplant frozen plasma and standardized collection of demographic characteristics and posttransplant history of thrombosis were assessed. RESULTS: Fifty of 178 patients (28.1%) had APAs. Transplant duration was shorter and hemodialysis duration was longer in patients with APAs. A posttransplant history of both venous and arterial thrombosis was more frequent in patients with posttransplant APAs (respectively, 18% vs. 6.2% [P<0.001] and 8% vs. 2.3% [P<0.001]). Pretransplant sera were available from 55 patients. Most of patients with posttransplant ACAs had ACAs in the pretransplant period (85%). Pretransplant ACAs were associated with a posttransplant history of venous thrombosis (P<0.001). CONCLUSIONS: Our study demonstrates a high prevalence of APAs in non-SLE renal transplant recipients. Most of them have been acquired in the pretransplant period. Both pretransplant ACAs and posttransplant APAs are associated with posttransplant episodes of thrombosis. Further studies are required to determine the interest of prophylactic measures.
Monoclonal immunoglobulins (molg) have repeatedly been described in organ and bone marrow transplantation. Although their exact significance is not known, their occurrence is often associated with intensive immunosuppression. We investigated whether molg reflect T-cell immune defect and B-cell activation in renal transplant recipients. Immunofixations and lymphocyte subset analysis (CD4, CD8, CD19) were performed in 182 renal transplant recipients. Soluble CD23 concentrations were measured in patients with molg and in control transplant patients without molg. Monoclonal immunoglobulins were identified in 54 patients (29.6 %). Transplant endurance was shorter (62 +/- 53 months vs 81 +/- 47 months; P < 0.02) and age was older (53 +/- 13 years vs 46 +/- 13 years; P < 0.005) in patients with molg. Maintenance immunosuppression did not differ between patients with and without molg. Mean CD4-cell count was significantly lower in patients with molg (387 +/- 286/mm(3) vs 538 +/- 341/mm(3); P < 0.005). Both CD8- and CD19-cell counts were similar for the 2 groups. Soluble CD23 concentrations were higher in patients with abnormal immunoglobulin values than in patients with normal immunofixation (12.8 +/- 8 vs 1.9 +/- 1.8 microg/l; P < 0. 005). Our study provides new evidence that molg reflect T-cell immune defect in renal transplant recipients. Further studies are required to determine whether CD4-cell count and sCD23 may help to predict the risk of lymphoma in transplant patients with molg.
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INTRODUCTION: Determinants of hyperhomocysteinaemia in peritoneal dialysis patients have been recently reported but there is still conflicting data on the influence of dialysis adequacy on homocysteine (Hcy). METHODS: We studied 46 consecutive new continuous ambulatory peritoneal dialysis (CAPD) patients to determine the variation of Hcy before and 1 and 6 months after dialysis. The variation in Hcy was analysed with respect to dialysis adequacy, factors known to influence its metabolism, and Hcy peritoneal clearance. RESULTS: Hcy was 31.9+/-9 micromol/l before dialysis. It was significantly higher before dialysis than 1 month after the onset of PD (31.9+/-9 micromol/l vs 23.2+/-6.9 micromol/l, P < 0.0005). Weekly PD Hcy clearance was 14.3+/-5.4 1. There was no relationship between pre-dialysis Hcy and 1 month post-dialysis Hcy (r=0.176, P=0.15). There was a strong relationship between PD Hcy clearance and both PD creatinine clearance (r=0.502, P<0.005) and Kt/V (r=0.42, P<0.005). There was no relationship between Hcy and PD creatinine clearance (r= -0.221, P=0.11). In contrast, the decrease in tHcy at 1 month was related to PD Hcy clearance (r=0.487, P<0.01), to PD creatinine clearance (r= 0.349, P<0.02) and to Kt/V (r=0.32, P<0.02). Multivariate analysis confirmed the relationship between the decrease in Hcy and dialysis adequacy. Eleven patients (24%) experienced arteriosclerotic complications. Fasting Hcy concentrations in this population were significantly higher before and 1 month-post-dialysis than in patients without cardiovascular complications. CONCLUSIONS: We observed a significant and prolonged reduction in Hcy concentrations by peritoneal dialysis in end-stage renal disease patients. The decrease in Hcy concentration was positively related to dialysis adequacy. This study suggests the possibility that dialysis adequacy may influence arteriosclerotic outcomes through an Hcy-lowering effect.
BACKGROUND: Insulin resistance with compensatory hyperinsulinaemia has been reported in adult polycystic kidney disease (APKD) patients. Diabetes mellitus is a common complication following transplantation and previous studies have demonstrated that inadequate insulin secretion was a prerequisite for the development of post-transplant diabetes mellitus (PTDM). We conducted a retrospective study to determine whether APKD is a risk factor for PTDM. METHODS: Twenty-six consecutive patients transplanted because of end-stage renal disease due to APKD were studied. A control patient matched for age, gender, immunosuppressive therapy and transplant year was selected for each APKD patient. PTDM was defined by fasting glycaemia exceeding 7.8 mmol/l and the need for insulin or oral antidiabetic therapy. RESULTS: Age, renal function, immunosuppressive regimen, number of acute rejection, cumulative dose of steroids and haemodialysis duration before transplantation were similar in both groups. PTDM occured in 10 APKD patients and four controls (34.6% vs 15.3%; P < 0.005). Among diabetic patients, six APKD patients and two controls required insulin therapy (60% vs 50%; P = n.s.). Diabetic patients were significantly older (55.8 +/- 7 years vs 50.2 +/- 11 years; P < 0.05). CONCLUSION: Although retrospective, this study suggests that APKD confers an increased risk of PTDM.
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Mycophenolate mofetil (MMF) is a new immunosuppressant developed for the prevention and treatment of acute renal rejection after transplantation. Diarrhea is the most frequent side effect observed during treatment with MMF. Its pathogenic mechanisms remain unknown. We describe a case of severe diarrhea due to villous atrophy in a renal transplant recipient during treatment with MMF. The patient was free of symptoms before MMF. Villous atrophy disappeared a few months after MMF withdrawal.
BACKGROUND: There is a great concern over cyclosporine (CsA) nephrotoxicity in renal transplant recipients, and the effects of conversion from CsA to azathioprine (AZA) remain controversial. Large studies have demonstrated that mycophenolate mofetil (MMF), the morpholinoethyl ester of mycophenolic acid, is superior to AZA as a posttransplant immunosuppressant. METHODS: Six patients with isolated biopsy-proven CsA nephrotoxicity were converted from CsA-AZA to MMF. RESULTS: Mean follow-up was 12+/-2 months. No patient experienced acute rejection. The mean serum creatinine concentration decreased from 225+/-58 to 159+/-66 micromol/L (P<0.0005). Hyperlipidemia and blood pressure improved after CsA withdrawal. CONCLUSION: In a selected transplant population with biopsy-proven CsA nephrotoxicity, CsA withdrawal with a concomitant switch from AZA to MMF seems to be safe and allows a significant improvement of renal function.
BACKGROUND: Recurrence of hemolytic-uremic syndrome (HUS) in the allograft is associated with a very poor renal prognosis. Meta-analysis of previous trials may allow us to better estimate its real frequency, to identify risk factors for recurrence, and to predict the outcome of patients with definite recurrence. METHODS: An exhaustive search was conducted of HUS recurrence in renal transplantation from January 1977 to June 1997 using MEDLINE. RESULTS: Ten studies comprising 159 grafts in 127 patients were identified. The rate of recurrence was 27.8%. One-year graft survival was 76.6% in patients without recurrence and 33.3% in patients with recurrence (P<0.001). Older age at onset of HUS (16.96+/-7.6 years vs. 9.95+/-6.55 years; P<0.02), shorter mean interval between HUS and transplantation (2.51+/-2.7 years vs. 6.03+/-6.4 years; P<0.01), shorter mean interval between HUS and end-stage renal disease (0.79+/-0.39 years vs. 2.78+/-2.47 years; P<0.01), living-related donors, and the use of calcineurin inhibitors were associated with recurrence. CONCLUSION: Risk factors for HUS recurrence in renal transplantation could be identified through this meta-analysis.
BACKGROUND: Renal transplant recipients are at increased risk of developing skin cancer. It remains difficult to establish the actual influence of overimmunosuppression in the development of skin cancers. We investigated whether lymphocyte subset count may predict the risk of developing skin cancer in long-term renal transplant recipients. METHODS: One hundred fifty long-term renal transplant recipients were followed for a mean period of 26 months. Each patient was examined at least annually by a dermatologist. Lymphocyte subsets were measured annually. RESULTS: Fifteen patients exhibited skin cancers. Patients with and without skin cancer did not differ in age, gender, transplant duration, hemodialysis duration before transplantation, immunosuppressive regimen, and serum creatinine concentration. CD4 cell counts were significantly lower in patients with skin cancers (330+/-179/mm3 vs. 503+/-338/mm3; P<0.01), whereas total lymphocyte and CD8 and CD19 cell counts were similar between the two groups. CONCLUSIONS: CD4 cell depletion is associated with skin cancer in long-term renal transplant recipients.
Post-transplant erythrosis (PTE) develops in 9%-22% of all renal transplant recipients. Defined as a persistently elevated hematocrit (> 0.51), it occurs most commonly during the first 2 years post-transplantation in hypertensive males with excellent allograft function. Several studies have focused on a major role for angiotensin II in PTE pathogenesis, and some case reports have suggested that losartan is an effective treatment for PTE. Nevertheless, its long-term safety and efficiency have not been reported in renal transplant recipients suffering from PTE. We describe four patients successfully treated with losartan for PTE. Hematocrit remained normal for 21, 18, 15, and 15 months, respectively, after the beginning of losartan therapy. Mean erythropoietin concentration was not modified by treatment (17 +/- 3.7 mU/ml vs 17 +/- 3.8 mU/ml) and serum creatinine concentration remained stable. We conclude that losartan is a safe and effective long-term treatment for PTE.