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M N Peraldi

Publications and source records attributed to M N Peraldi.

At least 19 recordsLinked to original sources
PubMed2001

Prognostic value of plasminogen activator inhibitor type 1 mRNA in microdissected glomeruli from transplanted kidneys.

BACKGROUND: Plasminogen activator inhibitor type 1 (PAI-1) exerts antifibrinolytic and profibrotic activities. Inside the glomerulus, PAI-1 is mainly synthesized by mesangial cells. We hypothesized that thrombin, via its receptor protease activated receptor type 1 (PAR-1), present on the membrane of glomerular cells, is an important mediator of PAI-1 synthesis. METHODS: Using the technique of Peten et al., we microdissected the glomeruli of 23 kidney transplanted patients admitted in our department from 1993 to 1997, and we followed-up these patients for up to 5 years, with sometimes iterative renal biopsies. With this technique, we also microdissected the glomeruli of three patients who have had a nephrectomy for cancer (control patients). We investigated mRNA expression of the PAI-1, the thrombin receptor PAR-1, the alpha2 chain of type IV (alpha2 IV) collagen, and of a housekeeping gene (cyclophilin) by reverse transcription-polymerase chain reaction. The results were correlated with the renal function and the histological findings classified into acute rejection (9 biopsies), chronic rejection (22 biopsies), or normal (8 biopsies). RESULTS: A significant up-regulation of PAI-1 and alpha2 IV collagen mRNA was observed in acute rejection (P<0.05) when compared to normal kidneys. A positive correlation exists between alpha2 IV collagen mRNA level and the degree of cellular infiltration. A negative correlation was found between the level of mRNA of PAR-1 and the degree of vascular thrombosis (P=0.005) and glomerulosclerosis (P=0.04). A positive correlation was found between the degradation of renal function and the mRNA level of PAI-1 at the time of the renal biopsy (P<0.05). CONCLUSIONS: These results suggest that glomerular PAI-1 mRNA may be predictive of the long-term renal graft function.

Adolescent↗
PubMed2001

Characteristics of sirolimus-associated interstitial pneumonitis in renal transplant patients.

BACKGROUND: Sirolimus, a promising new immunosuppressive drug for organ transplantation, is currently associated with side effects, such as thrombocytopenia and hyperlipidemia. METHODS: Eight renal transplant recipients, who developed unexplained interstitial pneumonitis during sirolimus therapy, were extensively re-screened for all causes of pneumonitis. RESULTS: Interstitial pneumonitis was constantly characterized by bilateral interstitial infiltrates on chest x-rays and lung computed tomography scans, with marked general symptoms in all patients but one. Bronchoalveolar lavage (BAL) disclosed lymphocytic alveolitis (mainly of the CD4 type) in seven patients and alveolar hemorrhage in one. Transbronchial lung biopsies, performed in two patients, showed bronchiolitis obliterans with organizing pneumonia combined with lymphocytic interstitial pneumonitis. Pulmonary infections were ruled out by specific stainings and cultures of BAL, bronchial aspirates, and blood cultures. After the elimination of all possible causes, sirolimus-induced pneumonitis was considered probable. Discontinuation of sirolimus in seven cases and dose reduction in the remaining case dramatically improved clinical and radiological status within a few weeks and led to complete resolution within 3 months. CONCLUSIONS: Sirolimus is very probably responsible for interstitial pneumonitis on the following grounds: (a) occurrence of pneumonitis during sirolimus therapy; (b) absence of any other causes; and (c) resolution within 3 months of sirolimus discontinuation or dose reduction. Sirolimus should now be added to the list of possible causes of pulmonary complications after renal transplantation. Discontinuation or dose reduction of sirolimus led to complete and lasting resolution of symptoms.

Aged↗
PubMed1999

Human herpes virus-8 and other risk factors for Kaposi's sarcoma in kidney transplant recipients. Groupe Cooperatif de Transplantation d' Ile de France (GCIF).

BACKGROUND: The exact reasons for the high incidence of Kaposi's sarcoma (KS) after kidney transplantation are still unknown. Immunosuppression is classically considered as the main risk factor, but the relative risk contributed by the patient's geographic origin and by human herpes virus (HHV)-8 infection still has to be determined. METHODS: We carried out a retrospective and a prospective study among kidney transplant recipients (TP) to identify the risk factors for posttransplantation KS. Each of 30 KS patients was matched with two controls to investigate the association with geographic origin, immunosuppressive regimen, HHV-8 antibodies before and after transplantation, and other infections. Among TP with new onset of KS, we prospectively evaluated HHV-8 serology and viremia in response to decreased immunosuppression. RESULTS: African and Middle East origins, past infection with hepatitis B, hemoglobin level <12 g/dl, lymphocyte count <750/mm3 at the time of diagnosis and initial use of polyclonal antilymphocyte sera were risk factors for KS. After multivariate analysis, origin in Africa or Middle East and use of antilymphocyte sera for induction remained as independent risk factors. Sixty-eight percent (17/25) of TP with HHV-8 antibodies before or after transplantation developed KS compared with 3% (1/33) of seronegative TP (P<0.00001). HHV-8 DNA was detectable in seven of nine peripheral blood mononuclear cells (PBMC) and in six of six KS lesions at diagnosis; it became negative in PBMC in three of five patients in parallel with tumor regression. CONCLUSION: African and Middle East geographic origins, HHV-8 infection before and after kidney transplantation, and initial use of polyclonal antilymphocyte sera were independent risk factors for KS. The presence of HHV-8 antibodies before or after transplantation was highly predictive of the emergence of posttransplantation KS and conferred a 28-fold increased risk of KS (odds ratio=28.4; 95% confidence interval: 4.9-279). Detection of HHV-8 DNA within PBMC and KS lesions seems related to tumor burden and evolution.

Adult↗
PubMed1999

Acute renal failure in the course of HIV infection: a single-institution retrospective study of ninety-two patients and sixty renal biopsies.

BACKGROUND: Acute renal failure syndromes are frequently encountered in patients with human immunodeficiency virus (HIV) infection. Most reported cases of acute renal failure are related to acute tubular necrosis, but many other causes of renal failure have been described in these patients. METHODS: The present work is a single-institution retrospective study of 92 HIV-infected patients with acute or rapidly progressing renal failure. In 60 cases, a renal biopsy was performed. For each patient we analysed clinical and pathological data, as well as the short-term prognosis. RESULTS: Ten different causes of acute or rapidly progressing renal failure were documented: (i) haemolytic uraemic syndrome (32 patients); (ii) acute tubular necrosis either of ischaemic-toxic origin (18 patients) or due to rhabdomyolysis (six patients); (iii) obstructive renal failure which was either extrinsic (two patients), drug-induced (13 patients) or secondary to paraprotein precipitation (one patient); (iv) HIV-associated nephropathy (14 patients); (v) acute interstitial nephritis (two patients); (vi) various glomerulonephritis (four patients). In most cases, renal failure was severe (the mean creatinine clearance at entry was 12 ml/min). Most patients had a significant improvement in renal function with only symptomatic treatment. Eighteen per cent of the patients died within 2 months of the diagnosis of renal failure. Renal biopsy seems important for the diagnosis but also for the prognosis, at least in the cases of haemolytic-uraemic syndrome, HIV-associated nephropathy and drug-induced micro-obstructive renal failure. CONCLUSION: Vascular and glomerular diseases are frequent causes of acute or rapidly progressing renal failure in HIV-infected patients. Renal biopsy appears to be safe and useful for the diagnosis and the prognosis of the renal failure. High mortality rate is only observed in patients with ischaemic/toxic causes of acute renal failure.

Acute Kidney Injury↗
PubMed1998

Tissue-type plasminogen activator activity in HIV-associated HUS.

BACKGROUND: In children, haemolytic uraemic syndrome (HUS) is associated with high plasma plasminogen activator inhibitor type 1 (PAI-1), which may contribute to the persistence of renal glomerular and arteriolar thrombi. HUS has been described in HIV-infected patients, but the pathophysiology of HUS in these patients is poorly understood. The aim of the study was to investigate plasma fibrinolytic activity in 18 patients with HIV-associated HUS. METHODS: We measured tissue type plasminogen activator (t-PA) and PAI-1 activities in the plasma of 18 HIV-infected patients with biopsy-proven HUS (HIV+/HUS+) and 48 HIV-infected patients without HUS (HIV+/HUS-). RESULTS: Patients with HUS had a significantly higher serum creatinine, a lower platelet count and an increased incidence of cytomegalovirus (CMV) infection (72% of patients HIV+/HUS+, vs 25% of patients HIV+/HUS-). Unexpectedly, plasma PAI-1 activity was similar in both groups. However, t-PA activity was significantly higher in HUS cases (11.5 vs 4.5 U/ml, P=0.001). Patients with CMV infection, with or without HUS, had significantly increased t-PA level (P=0.01). Multivariate analysis identified high t-PA (RR=9.21) and CMV infection (RR=3.36) as risk factors for HUS. CONCLUSION: This study provides evidence that HIV-infected patients with HUS have high plasma t-PA activity. PAI-1 plasma activity is not significantly increased, as opposed to non-HIV-associated HUS. Thus, in the setting of HIV infection, HUS cannot be attributed to decreased fibrinolytic activity.

Adult↗
PubMed1997

Retroperitoneal laparoscopic nephrectomy of native kidneys in renal transplant recipients.

BACKGROUND: The purpose of this study was to compare retroperitoneal laparoscopic nephrectomy in transplant recipients and in other patients scheduled for nephrectomy. METHODS: From February 1994 to July 1996, 15 transplant recipients and 17 other patients underwent a total of 36 retroperitoneal laparoscopic nephrectomies for various indications. Operative time, morbidity, and hospital stay were compared between the two groups. RESULTS: The average operating time for the 36 procedures was 95+/-38 min (range, 35-180 min). It was shorter in transplant recipients (81+/-32 min) than in other patients (100+/-39 min, P<0.05). There was one postoperative complication in the transplant recipient group. The average length of the postoperative hospitalization was 3.7+/-1.4 days (range, 2-8 days). CONCLUSIONS: The retroperitoneal laparoscopic approach for nephrectomy is as safe and effective in renal transplant recipients as in other patients. Postoperative stay and delay to resumption of oral immunotherapy are short. This approach has become our first-line approach for native nephrectomy in transplant recipients.

Adolescent↗
PubMed1997

Long-term prognosis of renal transplantation after preemptive treatment of cytomegalovirus infection.

A role for cytomegalovirus (CMV) infection in the etiologies of acute and chronic rejection in renal allograft recipients has been suggested. We previously reported that preemptive treatment of CMV infection with ganciclovir in kidney transplant patients was safe and effective. We now present a retrospective analysis of 169 consecutive renal transplant patients, of whom 87 (51.5%) received preemptive treatment with ganciclovir (CMV(+) group). No patient died of CMV infection. Actuarial graft and patient survival rates were not different between the CMV(+) and the CMV(-) groups (graft survival: 68% and 69%; patient survival: 89% and 88%, respectively). At the end of the study, the mean plasma creatinine levels were not statistically different between the two groups (185+/-13 and 166+/-12 micromol/L for the CMV(+) group and the CMV(-) group, respectively). These results suggest that preemptive treatment of CMV infection with ganciclovir may prevent the CMV-induced renal injury and graft loss.

Adolescent↗
PubMed1997

Thrombotic microangiopathy and cytomegalovirus disease in patients infected with human immunodeficiency virus.

Thrombotic microangiopathy (TMA) can occur during the course of human immunodeficiency virus (HIV) infection. Clinical and pathological data for 29 patients with TMA and HIV infection were recorded. In a retrospective case-control study, we analyzed the link between opportunistic infections or drug therapies and TMA. Twenty-five patients (mean CD4+ cell count +/- SD, 71.9 +/- 18.3/mm3) had renal impairment, and four had neurological dysfunction. In one-half the cases, the disease was progressive with isolated fragmentation anemia appearing several months before the clinical symptoms. The diagnosis of TMA was confirmed by histological examination of kidney biopsy specimens (18 cases). Endothelial cytomegalovirus (CMV) inclusions were associated with TMA in nine of 18 cases, whereas histological examination did not detect CMV in any control specimens (P < .001). The case-control study demonstrated a link between TMA and clinical CMV infection (odds ratio, 3.9; 95% confidence interval, 1.1-14). We conclude that TMA is a late complication of HIV infection and can be associated with systemic CMV infection in this setting.

AIDS-Related Opportunistic Infections↗
PubMed1997

Renal cell carcinoma of native kidneys: prospective study of 129 renal transplant patients.

PURPOSE: We evaluated the prevalence of renal cell carcinoma of the native kidneys in renal transplant recipients as well as possible risk factors. MATERIALS AND METHODS: A total of 129 consecutive renal transplant recipients underwent ultrasound examination of the native kidneys as part of a routine evaluation. A record was made of acquired cystic kidney disease, defined as 3 cysts or more, and of suspicious masses. When a malignancy was suspected radical nephrectomy was performed. RESULTS: The overall prevalence of renal cell carcinoma of the native kidney was 5 in 129 recipients (3.9%). All cancers were limited to the kidney. No significant relationship was detected between renal cell carcinoma occurrence and patient age, dialysis (when initiated, type and duration), transplantation, drug regimen or incidence of acquired cystic kidney disease. CONCLUSIONS: The risk of renal cell carcinoma, a clinically significant cancer, was approximately 100 times greater in our renal transplant patients than in the general population but no significant risk factor could be identified. Routine ultrasonography for early diagnosis in asymptomatic patients on immunosuppressive therapy is strongly recommended to improve prognosis.

Adult↗
PubMed1996

Long-term benefit of intravenous immunoglobulins in cadaveric kidney retransplantation.

Renal retransplantation can be hampered by the presence of anti-HLA alloantibodies. Previous studies have documented in vitro and in vivo suppression of these antibodies by intravenous immunoglobulins (IVIg). We conducted a randomized study in 41 patients, who have received a second cadaveric transplant between 1989 and 1994. They all were treated with a quadruple-immunosuppressive protocol. In addition, 21 patients received 0.4 g/kg/day of IVIg, on the first 5 days after transplantation. The two groups of patients were identical for age, sex, duration of the first graft, duration of cold ischemia, anti-HLA sensitization, HLA matching, the number of acute rejection episodes, and the incidence of cytomegalovirus infection. The 5-year survival rate was significantly higher in the group of patients treated with IVIg: 68% versus 50% in the control group. The only significant factor associated with IVIg infusion and better survival was a shorter delay of graft function (3.4 +/- 1.0 days versus 9.9 +/- 1.6 days). In conclusion, this randomized study demonstrates that IVIg treatment is associated with better long-term graft survival in retransplanted patients. This beneficial effect may be related to a long-lasting immunosuppressive effect of IVIg and/or to an early protective effect of the graft against ischemia.

Adult↗