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Biomedical subjects

Pierre Bedossa

Publications and source records attributed to Pierre Bedossa.

At least 37 records · Page 2Linked to original sources
PubMed2005

Frozen sectioning of the pancreatic cut surface during resection of intraductal papillary mucinous neoplasms of the pancreas is useful and reliable: a prospective evaluation.

OBJECTIVE: To prospectively evaluate the accuracy of frozen sectioning (FS) of the pancreatic transection margin and its influence on surgery during resection of intraductal papillary and mucinous neoplasms (IPMNs). SUMMARY BACKGROUND DATA: Preoperative assessment of IPMN extension is difficult and transection margin is frequently tumoral on the surgical specimen. PATIENTS AND METHODS: FS was performed in 127 patients who underwent partial pancreatectomy for IPMN from 1996 to 2004, corresponding to 90 pancreaticoduodenectomies (1-4 successive FS; total = 132), 25 distal pancreatectomies (1-2 FS; total = 27), and 12 medial pancreatectomies (2-4 FS; total = 29). Dysplasia was graded in both main (MD) and branch ducts (BD), and pancreatectomy was extended if FS revealed at least IPMN adenoma on the MD or borderline IPMN on BD (defined as "significant" lesions). RESULTS: The 188 FS revealed that MD and BD epithelium comprised significant noninvasive lesions in 49 and 13 cases, respectively, and infiltrating carcinoma in 4 other ones. Definitive examination corroborated FS in 176 of 188 cases (94%). Altogether, 54 of 188 (29%) FS comprised significant lesions that resulted in 46 additional resections in 38 patients (30%). Eight patients did not have additional resection because of either high operative risk or preoperative diagnosis of noncurable infiltrating carcinoma. The 134 FS without significant lesions were associated with 7 additional resections mainly because of macroscopic suspicion of another tumor location. Conflicting results between FS and definitive examination resulted in inadequate extent of pancreatectomy in 4 patients (3%). CONCLUSIONS: Results of FS of the transection margin are confirmed by definitive examination in 94% of cases. According to our protocol, FS changes the extent of resection in 30% of patients and allows adequate resection in 97% of patients.

Adenocarcinoma, Mucinous↗
PubMed2004

Changes in renal function in patients with familial amyloid polyneuropathy treated with orthotopic liver transplantation.

BACKGROUND: Familial amyloid polyneuropathy (FAP) is an autosomal dominant disease caused by a point mutation in the gene encoding transthyretin, which is secreted by the liver. Orthotopic liver transplantation (OLT) has been proposed to prevent disease progression. Little is known about long-term changes in renal function and lesions after OLT. METHODS: The renal function of 33 patients with FAP was evaluated (proteinuria, serum creatinine, creatinine clearance) before OLT and over a period of at least 5 years afterwards. A pre-transplantation renal biopsy was performed in 14 patients and a follow-up biopsy in eight patients. RESULTS: Before transplantation, mean serum creatinine concentration was 86 micromol/l (47-126 micromol/l) and creatinine clearance was 71.9+/-31.6 ml/min/1.73 m(2). Proteinuria was detected in 54% of patients (0.3-4 g/day). Pre-transplant renal biopsies (n = 14) revealed glomerular, tubular and vascular amyloid deposits in 90, 58 and 66% of patients, respectively. Eleven patients (33%) died after OLT. Death occurred most frequently in patients having weight losses >7 kg (P<0.05). After transplantation, 25 patients (76%) suffered acute renal failure but only one required dialysis. One month after transplantation, the mean serum creatinine concentration was 134.1+/-73 micromol/l and remained constant during follow-up. Eight patients underwent a second renal biopsy 2 years after transplantation. No significant changes in deposits or renal toxicity due to calcineurin inhibitors were detected. CONCLUSION: Although liver transplantation in FAP does not affect existing renal amyloid deposits, it prevents the progression of renal disease.

Adult↗
PubMed2004

Reversibility of hepatitis C virus-related cirrhosis.

The aim of this retrospective study was to determine the potential reversibility of hepatitis C virus (HCV) cirrhosis with the combined antifibrotic effects of interferon-alpha and the increasing frequency of sustained virologic response. Sixty-four HCV-cirrhotic immunocompetent patients who underwent antiviral therapies (interferon-alpha with or without ribavirin) and pretreatment and posttreatment liver biopsies were included (group 1). Resolution of cirrhosis was defined as a decrease in the fibrosis score from 4 to 2 or less by the Metavir score after blinded analysis by 2 independent pathologists. An additional group of 4 HCV-infected dialysis patients (group 2) who had received antiviral treatment, among whom 3 underwent a combined renal and liver transplantation allowing the analysis of the whole liver, was also studied. In 5 (all stage Child A) of the 64 cirrhotic patients (7.8%), the final biopsy showed only F2 to portal and periportal fibrosis with rare fibrous septa without nodule formation. Four of these 5 were complete sustained responders (negative PCR and normal ALT), and 1 was a relapser. In group 2, reversibility of cirrhosis was observed in 3 of the 4 patients and was clearly shown in 2 patients by the analysis of the whole-liver examination at the time of the hepatectomy preceding the transplantation. In conclusion, long-lasting suppression of the necroinflammatory activity of liver disease and/or antifibrogenetic effects of interferon-alpha may allow regression of cirrhosis.

Adult↗
PubMed2004

Telangiectatic focal nodular hyperplasia: a variant of hepatocellular adenoma.

BACKGROUND & AIMS: "Telangiectatic focal nodular hyperplasia" designate atypical lesions considered as variants of focal nodular hyperplasia (FNH). However, because "telangiectatic FNH" share several morphologic patterns with hepatocellular adenomas, classification of such lesions deserve further clarification. Therefore, the aim of the present study was to reconsider the classification of telangiectatic FNH with the help of a molecular approach. METHODS: Ten telangiectatic FNH, 6 typical FNH, and 6 hepatocellular adenomas were studied. DNA, RNA, and protein from each lesion were extracted. Clonality was assessed by the study of the X chromosome inactivation pattern (HUMARA assay). Angiopoietin (ANGPT-1 and ANGPT-2) mRNA, genes the expression of which is typically modified in FNH, were quantified by a real-time RT-PCR procedure. Protein profiles were analyzed by SELDI-TOF PROTEINCHIP (Cyphergen Biosystem, Inc., Fremont, CA) technology. RESULTS: Although all informative cases of FNH (5 of 6) and hepatocellular adenomas (6 of 6) were polyclonal and monoclonal, respectively, clonal analysis showed a nonrandom pattern of X chromosome inactivation consistent with a monoclonal lesion in 6 of 8 cases of telangiectatic FNH. The mean value of the ANGPT-1/ANGPT-2 mRNA ratio was 21.4 in FNH, 2.6 in adenomas, and 2.1 in telangiectatic FNH (P <or = 0.001 in telangiectatic FNH vs. FNH). SELDI-TOF PROTEINCHIP profiling and hierarchical clustering analysis showed that all except 1 telangiectatic FNH clustered within the group of hepatocellular adenomas. CONCLUSIONS: These results show that telangiectatic FNH display a molecular pattern closer to that of hepatocellular adenomas than to FNH and suggest that these lesions should instead be referred to as "telangiectatic hepatocellular adenomas."

Adenoma, Liver Cell↗
PubMed2003

Measurement of telomere length on tissue sections using quantitative fluorescence in situ hybridization (Q-FISH).

Loss of telomere repeat sequences occurs after each cell division and telomere shortening has been implicated in cellular senescence. The measurement of telomere length might therefore assess the lifespan of a cell. The aim of this study was to set up and validate a technique enabling the assessment of telomere length on tissue sections. Quantitative fluorescence in situ hybridization (Q-FISH) with telomeric probes was performed on smears and sections from cell preparations or human tissues. The mean fluorescence intensity of telomere spots (FI/spot) was automatically quantified by image analysis. Telomeric restriction fragment (TRF) length was assessed by Southern blotting. There was a positive significant correlation between telomere length, as assessed by Q-FISH, and TRF length determined by Southern blotting in corresponding samples (p < 0.01, r = 0.6 for tissue and p < 0.01, r = 0.79 for cells). FI/spot was higher on smears than on sections, but pairwise comparison showed a significant correlation both for cells and for tissues (r = 0.77, p < 0.001 for cells and p < or = 0.01, r = 0.64 for tissue). Finally, since telomere length is expected to shorten with age, FI/spot was assessed in liver samples according to the age of patients: a negative correlation was demonstrated (r = 0.76, p < 0.01). Inter-assay variation was 7% for Q-FISH performed on tissue sections and 12% on touch preparations. This study shows that Q-FISH can be performed with confidence on fixed frozen tissue sections in order to assess telomere length. It is an easy, accurate, and reproducible in situ method for assessing telomeres in the context of cell type and tissue architecture.

Adult↗
PubMed2003

Liver extracellular matrix in health and disease.

Liver fibrosis is the hallmark of every chronic liver disease. It is also the major factor of morbidity and mortality due to the development of cirrhosis and its complications including hepatocellular carcinoma. But even at the beginning of the process of liver fibrosis and due to the strategic position of the extracellular matrix at the interface between blood flow and epithelial compartment, any quantitative or qualitative modification of extracellular matrix will rapidly affect structure and function of the liver. The development of several animal models of liver fibrosis as well as isolation and cultivation of hepatic stellate cells, the major fibrogenic cell type in the liver, led to the gathering of recent knowledge on the mechanism of liver fibrosis. Activation of hepatic stellate cells is a key event in this process and many details on this finely tuned mechanism are now available. In addition to these experimental data, experience from chronic hepatitis C now allows the development of new concepts and perspectives such as liver fibrosis regression and antifibrotic therapies.

Antibodies, Monoclonal↗
PubMed2003

Respective roles of porto-septal fibrosis and centrilobular fibrosis in alcoholic liver disease.

In alcoholic liver disease, fibrosis classically begins around the centrilobular veins, while portal tract fibrosis is described as inconstant and septal fibrosis is a late event. The aim of this study was to compare the roles of centrilobular fibrosis (CLF) and portal tract/septal fibrosis (PTF) especially in alcoholic chronic liver disease. One hundred and sixty patients with alcoholic chronic liver disease and 83 controls with viral chronic hepatitis were included. The PTF score, derived from the Metavir score, CLF and the area of fibrosis, assessed by image analysis, were evaluated on liver biopsies in addition to blood markers of fibrosis. The correlation between the PTF score and the area of fibrosis was higher in alcoholic liver disease (r = 0.87, p < 10(-4)) than in viral chronic hepatitis (r = 0.66, p < 10(-4)). The PTF score correlated with the CLF score (r = 0.92, p < 10(-4)), serum hyaluronate (r = 0.76, p < 10(-4)), and the prothrombin index (r = -0.77, p < 10(-4)). Multiple regression analyses showed that the area of fibrosis was explained only by the PTF score and not by the CLF score. PTF appears more frequent than CLF in alcoholic chronic liver disease, suggesting that PTF may precede CLF. PTF is more responsible for the amount of fibrosis than CLF. The results of this study also validate the use of the Metavir fibrosis score in alcoholic chronic liver disease.

Biomarkers↗
PubMed2003

Quantitative RT-PCR in cirrhotic nodules reveals gene expression changes associated with liver carcinogenesis.

Cirrhosis is considered to be the precursor of most hepatocellular carcinomas. To gain insight into the early molecular mechanisms of liver carcinogenesis, this study compared, using real-time quantitative reverse transcriptase-polymerase chain reaction (RT-PCR), the expression levels of 31 selected genes in normal livers, cirrhotic nodules, and hepatocellular carcinomas. Since cirrhosis is composed of a mixture of polyclonal and monoclonal nodules, gene expression levels were also compared according to the clonal status of the cirrhotic nodules. The expression of eight of the 31 genes studied was significantly increased (NEGF2, ANGPT1, ARF, KRT19, SFN, CLDN4, MMP7, and ETV4) in cirrhotic nodules compared with normal liver, while only one was decreased (LYVE1). The same trend of variation was observed in cirrhosis and hepatocellular carcinomas for all of these genes except KRT19. When gene expression variation was compared according to the clonal status of cirrhotic nodules, only the LYVE1 expression level was significantly different. The LYVE1 gene expression level decreased progressively from polyclonal cirrhotic nodules to monoclonal cirrhotic nodules (polyclonal nodules 0.39 +/- 0.25; monoclonal nodules 0.20 +/- 0.14; p < 0.05) and to hepatocellular carcinoma (0.07 +/- 0.1). In conclusion, this study highlights the fact that among genes strongly dysregulated in hepatocellular carcinoma, some are already abnormally expressed in cirrhosis. The decrease in the expression level of one of these genes, LYVE1, was associated with monoclonality in cirrhotic nodules.

Adult↗
PubMed2003

Sampling variability of liver fibrosis in chronic hepatitis C.

Fibrosis is a common endpoint of clinical trials in chronic hepatitis C, and liver biopsy remains the gold standard for fibrosis evaluation. However, variability in the distribution of fibrosis within the liver is a potential limitation. Our aim was to assess the heterogeneity of liver fibrosis and its influence on the accuracy of assessment of fibrosis with liver biopsy. Surgical samples of livers from patients with chronic hepatitis C were studied. Measurement of fibrosis was performed on the whole section by using both image analysis and METAVIR score (reference value). From the digitized image of the whole section, virtual biopsy specimens of increasing length were produced. Fibrosis was assessed independently on each individual virtual biopsy specimen. Results were compared with the reference value according to the length of the biopsy specimen. By using image analysis, the coefficient of variation of fibrosis measurement with 15-mm long biopsy specimens was 55%; and for biopsy specimens of 25-mm length it was 45%. By using the METAVIR scoring system, 65% of biopsies 15 mm in length were categorized correctly according to the reference value. This increased to 75% for a 25-mm liver biopsy specimen without any substantial benefit for longer biopsy specimens. Sampling variability of fibrosis is a significant limitation in the assessment of fibrosis with liver biopsy. In conclusion, this study suggests that a length of at least 25 mm is necessary to evaluate fibrosis accurately with a semiquantitative score. Sampling variability becomes a major limitation when using more accurate methods such as automated image analysis.

Biopsy↗
PubMed2003

Molecular profiling of hepatocellular carcinomas (HCC) using a large-scale real-time RT-PCR approach: determination of a molecular diagnostic index.

The aim of this study was to develop and validate a molecular index for the diagnosis of hepatocellular carcinoma (HCC) based on genes whose specificity and level of expression are the most discriminating for the diagnosis of HCC. The level of expression of 219 genes was assessed with a real-time reverse transcription-polymerase chain reaction approach in a training set of samples including normal livers (15), cirrhosis (12), and HCC (16). The most informative genes were selected for the molecular index. This index was prospectively validated in a new set of 40 samples (testing set) and in a set of 45 cirrhotic macronodules. 44 out of the 219 genes were differentially expressed in HCC. 13 out of these 44 genes were finally selected for the molecular index according to their diagnostic performance and after exclusion of most redundant genes. Using this index, 42 out of 43 samples of the training set and 39 out of the 40 samples of the testing set were correctly ranked as HCC or not HCC (normal liver or cirrhosis). The index also enabled correct ranking of 44 out of 45 cirrhotic macronodules into 2 groups: benign (including macroregenerative and dysplastic macronodules) and malignant macronodules. This molecular diagnostic index is an efficient tool both for identification of overt HCC as well as minute lesions (cirrhotic macronodules). It might be useful to correctly diagnose borderline lesion or small well-differentiated hepatocellular carcinomas whose diagnosis is often difficult on a histopathological basis.

Adolescent↗
PubMed2003

Long-term results of renal transplantation using kidneys harvested from non-heartbeating donors: a 15-year experience.

PURPOSE: To expand the pool of suitable organ donors we developed an organ procurement program of non-heartbeating donors during the last 15 years. We compare graft survival in patients receiving renal transplants procured from non-heartbeating with recipients of kidneys from heartbeating donors. MATERIALS AND METHODS: From 1986 to 1999, 60 renal transplantations were performed with kidneys harvested from non-heartbeating donors (Mastrich category IV). Kidneys were procured using a double balloon triple lumen catheter inserted into the femoral artery. The 60 kidneys were selected from 70 non-heartbeating donors based on age younger than 50 years, warm ischemia less than 30 minutes, creatinine less than 200 micromol./l., and no hypertension or major histological lesions. Long-term results of graft survival and complications were compared with a series of 1,065 renal transplantations performed during the same period with kidneys procured from heartbeating donors. RESULTS: Mean age of the recipients was statistically different as non-heartbeating donors were older. However, the 10-year graft survival rates were similar in both groups (50% versus 53%). Incidence of ureteral stenosis and fistula, arterial stenosis and thrombosis was not statistically different in both groups. On the other hand, delay graft function was more frequent in non-heartbeating donors (60% versus 40%, p = 0.01). CONCLUSIONS: Despite a high rate of acute tubular necrosis, kidneys harvested from non-heartbeating donors had the same graft survival rates as those procured from heartbeating donors. Surgical complications were not different. Transplantation of selected kidneys procured from non-heartbeating donors should be promoted as a response to organ shortage.

Adult↗
PubMed2003

The role of replicative senescence in chronic allograft nephropathy.

Strong evidence suggests that replicative senescence is involved in vivo because senescent cells have been detected in human tissues associated with physiological and pathological aging processes. Chronic allograft nephropathy (CAN) appears to be a major determinant of long-term survival in kidney transplantation. Several mechanisms are potentially involved; the aim of this study was to assess the impact of replicative senescence in CAN. Replicative senescent cells were detected on renal tissue cryosection using expression of a specific marker, senescence-associated beta-galactosidase (SA-beta-Gal) at pH 6. A total of 80 frozen renal samples (67 cases of CAN and 13 controls) were studied. To validate this marker, we measured in situ telomere length in cells expressing or not expressing SA-beta-Gal using a validated quantitative fluorescence in situ hybridization technique. The presence of senescent cells was correlated with clinicopathologic data. Telomere length was significantly lower in cells expressing SA-beta-Gal than in cells that did not. Replicative senescence was present in 45 out of 67 (67%) biopsy specimens and was significantly associated with the severity of CAN. No correlation with the notion of a previous episode of acute tubular necrosis, acute rejection, extrarenal epuration, duration of cold ischemia, and the delay between transplantation and biopsy was observed. However, the age of the donor, but not that of the recipient, was correlated with the occurrence of senescent cells. These results suggest that replicative senescence is a mechanism that might be involved in the development of CAN. The age of the donor appears to be the major determinant factor in replicative senescence.

Adult↗
PubMed2003

A comparison of fibrosis progression in chronic liver diseases.

BACKGROUND/AIMS: No study has compared the liver fibrosis progression rates among chronic liver diseases and the risk factors in order to better organize screening strategies. METHODS: A total of 4852 patients were retrospectively studied (chronic hepatitis C (HCV) [n=2313], human immunodeficiency virus (HIV)-HCV co-infection (HIV-HCV [n=180]), hepatitis B (HBV [n=777]), alcoholic liver disease (ALD [n=701]), primary biliary cirrhosis (PBC [n=406]), genetic hemochromatosis (GH [n=383]) auto-immune hepatitis (AIH [n=57]) and delta hepatitis (n=35). The fibrosis progression rates were estimated from birth and from the date of exposure, when known, to the first biopsy. RESULTS: There were highly significant differences in the rates of fibrosis progression, the most rapid being HIV-HCV co-infection (50% cirrhosis percentile at 52 years of age) and the slowest being PBC (50% cirrhosis percentile at 81 years). There was an acceleration of fibrosis progression with aging. Fibrosis progression was slower in females compared with males for HCV, HBV, GH, and PBC. In contrast, in ALD, the fibrosis progression was more rapid in females. CONCLUSIONS: Rates of fibrosis progression differ markedly between the predominant causes of chronic liver disease, and according to age and gender. Patients with HIV-HCV co-infection are at particularly high risk of fibrosis progression.

Adult↗
PubMed2003

Approaches for treatment of liver fibrosis in chronic hepatitis C.

In the past 20 years, the elucidation of the mechanisms responsible for liver fibrogenesis has provided many potential targets for antifibrotic treatments. Difficulty has arisen, however, from the fact that fibrogenesis is part of a general beneficial wound healing process. To be successful, an antifibrotic treatment of HCV might need to be delivered selectively to the hepatic site of fibrogenesis or targeted precisely at an HCV-specific regulatory mechanism. It is likely that in the future, besides viral eradication, another treatment goal in chronic HCV infection will be to reverse existing fibrosis, but considerable work is necessary before making this a reality.

Animals↗
PubMed2003

Inhibitors of swelling-activated chloride channels increase infarct size and apoptosis in rabbit myocardium.

Apoptosis is a significant contributor to myocardial cell death during ischemia-reperfusion and swelling-activated chloride channels (I(Cl,swell)) contribute to apoptosis. However, the relationship between I(Cl,swell) ischemia-reperfusion and apoptosis remains unknown. To further investigate this, New Zealand rabbits underwent a 20-min coronary artery occlusion (CAO) followed by 72 h of coronary artery reperfusion (CAR). Two I(Cl,swell) blockers, 5-nitro-2-[3-phenylpropylamino]benzoic acid (NPPB) and indanyloxyacetic acid 94 (IAA-94) (both 1 mg/kg), were administered prior to CAO and throughout the 72 h CAR. Infarct size (IS) was increased with NPPB and IAA-94 compared with control (vehicle) rabbits (51 +/- 2% and 48 +/- 3% and vs. 35 +/- 2%, respectively, P < 0.05). Similar results were found when NPPB was administered only during the reperfusion period. The percentage of TUNEL-positive nuclei in the border zone of the infarct was increased with NPPB compared with control (37 +/- 2% vs. 25 +/- 31%, P < 0.05) as well as the number of cytoplasmic histone-associated DNA fragments (0.45 +/- 0.06 vs. 0.33 +/- 0.04 absorbance units, P < 0.05). These findings support the concept that I(Cl,swell) channels play an important role in the determination of myocardial infarct size and apoptosis during ischemia-reperfusion.

Animals↗
PubMed2003

A quantitative gene expression study suggests a role for angiopoietins in focal nodular hyperplasia.

BACKGROUND AND AIMS: Although the pathogenesis of focal nodular hyperplasia (FNH) of the liver remains unclear, a vascular mechanism has been suspected. To gain insight into the pathogenesis of FNH, we performed a large-scale quantitative study of gene expression in FNH. METHODS: Quantitative expression level of 209 selected genes was assessed using real-time reverse-transcription polymerase chain reaction in 14 cases of FNH and compared with their expression level in 13 cases of liver cirrhosis, 4 adenomas, and 15 hepatocellular carcinomas. RESULTS: Among the 7 genes, the expression of which was significantly up-regulated or down-regulated in FNH, the most informative markers for the diagnosis of FNH as assessed using the receiving operative curve and area under the curve (AUC) were angiopoietin-1 (Ang-1; AUC, 0.82) and angiopoietin-2 (Ang-2; AUC, 0.80). These 2 genes are involved in the regulation of vasculogenesis. In FNH, Ang-1 was significantly up-regulated, Ang-2 was down-regulated, and the Ang-1/Ang-2 ratio was highly and specifically increased in FNH compared with normal liver or other groups of lesions (FNH, 15.2-fold increase; HCC, 2.78; adenoma, 2.28; cirrhosis, 1.92; P < 0.01 for FNH vs. all groups, analysis of variance). Tie-2 messenger RNA, the receptor of Ang-1 and Ang-2, was detected at the same level in FNH as in normal liver. Ang-1 protein was detected on Western blot of FNH and expressed by endothelial cells of dystrophic vessels and sinusoids as shown by immunohistochemistry. CONCLUSIONS: A specific increase of Ang-1/Ang-2 ratio in FNH, in the presence of the functional Tie-2 receptor, might be involved in the formation of hyperplastic and dystrophic vessels of FNH.

Adenoma↗
PubMed2003

The long-term effect of switching from cyclosporin A to mycophenolate mofetil in chronic renal graft dysfunction compared with conventional management.

BACKGROUND: To overcome toxicity of calcineurin inhibitors, recent trials have proposed substituting cyclosporin (CysA) with mycophenolate mofetil (MMF). No data concerning the long-term side effects and long-term renal outcome of this strategy have been published. METHODS: We retrospectively compared 39 renal transplant patients with chronic graft dysfunction who were subjected to CysA to MMF substitution (group 1) with 39 matched renal transplant patients who were continued on conventional management (group 2). The mean serum creatinine and the slope of deterioration of renal function before the date of the therapeutic intervention (T(0)) were similar in both groups. Follow-up in both groups was 76 +/- 42 months before T(0) and 44 +/- 11 months after T(0). RESULTS: In group 1, conversion was associated with a decrease of mean serum creatinine concentrations from 192 to 172 micro mol/l at 1 year (P = 0.004) and 159 micro mol/l at 3 years (P < 0.003) after T(0), whereas it remained unchanged in group 2. The systolic blood pressure decreased in group 1 from 155 mmHg before T(0) to 145 mmHg at 1 year (P < 0.01) and 133 mmHg at 3 years (P < 0.001) without any increase of the antihypertensive drug, whereas it did not change in group 2. Lipid profile tended to improve in group 1 after T(0) and was unchanged in group 2. None of the patients in group 1 developed acute rejection after T(0), whereas two acute rejections occurred in group 2. Graft survival, however, was similar in both groups. In group 1, several side effects occurred related to MMF treatment, and led to its discontinuation in two cases and the reduction of its dose for 18 patients (64%). CONCLUSION: CysA/MMF substitution improves renal function and blood pressure in chronic allograft dysfunction when compared with conventional management. However, CysA/MMF substitution is associated with a high rate of MMF-related side effects, requiring modulation of its dose.

Adult↗