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Biomedical subjects

L Rostaing

Publications and source records attributed to L Rostaing.

At least 91 records · Page 5Linked to original sources
PubMed1997

[HCV RNA clearance after treatment with interferon-alpha in chronic hemodialysis patients with or without coinfection by HGV/HGBV-C].

Patients on maintenance hemodialysis are frequently infected with hepatitis C virus (HCV). The long-term effect of alpha interferon therapy has not yet been assessed, or the influence of co-infection with the newly discovered hepatitis G/hepatitis GB virus-C (HGV/HGBV-C) upon therapy outcome. Eleven anti-HCV and HCV RNA-positive hemodialysis patients, 3 of whom had HGV/HGBV-C infection were given 3 mega-units of alpha 2b recombinant interferon subcutaneously 3 times weekly for six months. The mean follow-up after cessation of therapy was 24 +/- 8 months (range: 18-30 months). Sustained serum HCV RNA clearance, as assessed by PCR analysis, occurred in 5/11 patients (45.5%). Two had received a cadaveric kidney transplant at 16 and 18 months post-treatment and were treated by immunosuppressive therapy; HCV RNA remained undetectable in both serum and a liver biopsy. HCV was eradicated in 3 of the 6 patients infected with HCV genotype 1b, which is less sensitive to alpha-interferon than other HCV genotypes. Among the 3 patients infected with both HCV and HGV/HGBV-C, alpha-interferon cleared the HCV RNA from one patient, but not the HGV/HGBV-C RNA. In view of the high rate of HCV eradication after alpha-interferon therapy and its fair tolerance, we suggest that HCV RNA-positive dialysis patients should be treated before transplantation, regardless of their aminotransferase levels or liver histological score, since alpha interferon therapy after renal allografting is associated with an unacceptable rate of renal failure. Our preliminary data indicate that HGV/HGBV-C does not interfere with sustained HCV RNA clearance.

Adult↗
PubMed1996

Epidemiology of HCV infection: disease and renal transplantation.

We studied the prevalence of HCV infection in a cohort of 346 patients who received renal transplantation between January 1989 and April 1994. Assessments were made at the time of surgery, one year later and at the last follow-up visit. The hepatic consequences of HCV infection were also studied. The prevalence of HCV infection at the time of surgery was 21.4% (74/346). The risk factors associated with the presence of anti-HCV antibodies were: duration of haemodialysis, the number of transfusions and the number of previous renal transplantations. The incidence of HCV infection was 3% (8/272) and was accompanied by either transient (n = 4) or chronic (n = 3) hepatic cytolysis; five patients underwent liver biopsy which revealed persistent chronic hepatitis (n = 2) or active chronic hepatitis (n = 3). Seroconversion always occurred within one year following transplantation. In the long-term, 91% of HCV+ patients remained viraemic. The HCV genotype was predominantly 1b. Fifty-six per cent (56%) of HCV+ patients had normal ALAT at the time of transplantation, which remained normal on follow-up in two-thirds of cases. After transplantation, 39 HCV+ patients underwent liver biopsy. ALAT were normal in 13 of those; liver biopsy elicited either normal liver (n = 1) or chronic persistent hepatitis (CPH) (n = 8) or chronic active hepatitis (CAH) (n = 4). ALAT were chronically elevated in 26 patients; liver histology revealed: 7 CPH, 19 CAH including 12 cases with bridging fibrosis. No deleterious effect of azathioprine on liver histology was found. Lastly, four patients were co-infected with HBV: all had elevated ALAT; liver biopsy always revealed severe chronic active hepatitis. Post-transplantation hepatitis C is a worrying problem. Liver enzymes are not correlated with the severity of histological disorders, which are frequent. Interferon-alpha therapy should be proposed to HCV+ patients before renal transplantation.

Adult↗
PubMed1996

Serological markers of autoimmunity in renal transplant patients before and after alpha-interferon therapy for chronic hepatitis C.

Chronic hepatitis C is the major cause of chronic liver disease after successful cadaveric renal transplantation. The aims of this prospective, open study were to assess in such a population, firstly the prevalence of different organ-specific and nonspecific antibodies and related disorders, and secondly their outcome after inteferon-alpha therapy as well as the incidence of new immunologic disorders under and after this therapy. In 15 cadaveric renal transplant patients (10 men, 5 women, ages 29-65 years) with chronic hepatitis C and histological features of chronic active hepatitis, undergoing chronic immunosuppression (ciclosporine A with or without steroid and azathioprine) and treated with recombinant alpha 2b-interferon (IFN alpha) (mean duration 142 +/- 35 days), we assessed before and after this therapy the serum levels of cryoglobulinemia, rheumatoid factors (RF), thyroid-stimulating hormone (TSH), free thyroxine (fT4), and antinuclear (ANA), antismooth muscle (ASMA), antimitochondrial (AMA), anti-LKM1, antimicrosomal thyroid (MCA), antithyroglobulin (TGA) autoantibodies. At the start of IFN alpha therapy, 14 of 15 patients had detectable autoantibodies (RF: 9; ANA > 1/50: 8; ASMA > 1/50: 4; other autoantibodies: 0); 1 had cryoglobulinemia. At the end of therapy the cryoglobulinemia had disappeared, the preexisting autoantibodies remained present in all patients but 2; 3 patients had developed MCA without evidence of clinical or biological thyroid abnormalities and 3 others had developed either RF (1) or ANA (1) or ASMA (1), without any related symptoms. One patient developed transient type II diabetes mellitus without anti-Langerhans beta-cell antibodies. Finally, the occurrence of autoantibodies in our patients was associated either with HLA DR3 or DR4 or DR7 phenotypes. We found that the prevalence of extrahepatic immunologic abnormalities was high in renal transplant patients with chronic hepatitis C and no exacerbation was observed during of after IFN alpha therapy. The most frequent autoantibody appearing after IFN alpha therapy was MCA although without thyroid abnormalities.

Adult↗
PubMed1996

Acute renal failure in kidney transplant patients treated with interferon alpha 2b for chronic hepatitis C.

Sixteen kidney transplant (KT) patients (10 men, 6 women, aged 49 +/- 10 years) with chronic hepatitis C alpha-interferon (IFN-alpha) therapy (Intron A, Schering Plough) at a dose of 3 x 10(6) units subcutaneously 3 times a week. The treatment was scheduled for 24 consecutive weeks. Each patient had had stable renal function for at least 12 months prior to IFN-alpha therapy (mean serum creatinine, SCr, 121 +/- 38 mmol/l). Fourteen patients were receiving cyclosporin-A (CsA)-based immunosuppression and 2 patients were on conventional therapy. The patients' SCr was checked every 2 weeks while on IFN-alpha, or weekly if it increased more than 15% from baseline. IFN-alpha was withdrawn if SCr increased more than 25% from baseline, in which case a kidney biopsy was performed. Six patients experienced either acute (n = 5) or subacute (n = 1) renal failure within 7-24 weeks after the onset of IFN-alpha therapy. Their mean SCr increased from 105 +/- 31 to 207 +/- 63 mmol/l (p = 0.02) with de novo proteinuria in 1 case (1 g/day) and an increase in preexisting proteinuria in 2. The other 3 patients did not develop proteinuria. In each case, histological study showed diffuse interstitial edema associated with dilation of the peritubular capillaries, whereas mild inflammatory infiltrates were present in only 3 cases and mild glomerular lesions were not always found (glomerular ischemia, mesangial hypertrophy). There were no vascular lesions. IFN-alpha was withdrawn in these 6 patients, in association with methylprednisolone pulses in 5 cases. Renal function improved in 2 cases, stabilized in 1 and progressed to end-stage renal failure in 3 within 4-12 months. Four of these patients had iterative renal biopsies which showed diffuse interstitial fibrosis in each case. The patients who developed renal failure did not statistically differ at the start of the study from those who did not, with respect to the following: baseline immunosuppression, HLA matching, total peripheral blood lymphocyte count or peripheral blood lymphocyte subtypes. IFN-alpha therapy was associated with acute or subacute renal failure in 37% of the patients. The most prominent histological finding was diffuse interstitial edema of rapid onset, without signs of cellular or vascular rejection. In conclusion, we do not recommend IFN-alpha therapy for KT patients with chronic hepatitis C, until the mechanisms of the subsequent renal failure are better understood.

Acute Kidney Injury↗
PubMed1996

Renal functional reserve in kidney and heart transplant recipients.

Renal functional impairment paradoxically often seems less severe in kidney than in heart-transplant recipients (KTR and HTR, respectively) when both are submitted to cyclosporine therapy. Renal functional reserve (RFR), elicited by a 3-h intravenous amino acid infusion, was examined in 12 KTR and 13 HTR at 7 to 8 months, appropriately compared with either eight one-kidney or 12 two-kidney healthy control subjects (1K.C and 2K.C, respectively). Baseline GFR was 54 +/- 4 mL/min in KTR and 71 +/- 4 mL/min in HTR (P < 0.05). During amino acid infusion, the maximum increase in GFR (which represented RFR) was 17 +/- 3 mL/min in both KTR and HTR (P < 0.001). RFR in KTR was 96 +/- 18% of that in 1K.C, whereas RFR in HTR was only 59 +/- 9% of that in 2K.C. Effective RPF increased (41 +/- 8 mL/min, P < 0.001), and renal vascular resistances decreased (48 +/- 17 mm Hg/L per min, P < 0.05) in KTR but not in HTR. These results demonstrate that both KTR and HTR possess a renal reserve but that the single renal graft in KTR retains a proportionally higher baseline GFR and a better ability to exhibit a RFR than the two native kidneys in HTR. This dissimilar impairment could result from slightly higher cyclosporine dosage, activation of the intact renal sympathetic innervation accentuated by cardiac denervation, renal consequences of former heart failure and potential alterations in the cardiac graft function, and/or higher prevalence of hypertension and additive therapies in HTR.

Adult↗
PubMed1996

Treatment of chronic hepatitis B and C with alpha interferon in a renal transplant patient.

We report the case of a 51-year-old renal transplant patient, treated by interferon alpha (5MUI, three times a week) since he presented a coinfection by hepatitis B (HBV) and hepatitis C (HCV) virus for more than 7 years, associated with a chronic increase in serum alanine aminotransferase (ALT) levels and a chronic active hepatitis. The 4-month treatment was associated with a sustained normalization of ALT, a disappearance of HBV replication and a transient clearance of HCV viremia. Side effects were moderate and included thrombopenia (90,000/mm3), leucopenia (2200/mm3), an increase in serum creatinine (178 mumol/l). The withdrawal of alpha interferon was associated with the correction of these parameters. No rejection was observed on kidney biopsy. Meanwhile, liver histology was not affected by the treatment. To date, nineteen months after the end of alpha interferon therapy HBV DNA was still negative; ALT remained normal despite the early recurrence of HCV viremia; this emphasized the fact that HBV infection was certainly the most important factor involved in the patient's chronic hepatitis. It is concluded that alpha interferon therapy is able to decline HBV replication for a prolonged period in renal transplant patient although its use should be performed with caution due to the potential renal side effects.

Dose-Response Relationship, Drug↗
PubMed1996

[Acute renal insufficiency in renal transplants treated with interferon-alpha for chronic hepatitis C].

Sixteen renal transplant (RT) patients (10 men, 6 women, aged 49 +/- 10 years) with chronic hepatitis C received alpha interferon (IFN alpha) therapy (Intron A, Schering Plough) at a dose of 3 x 10(6) units s.c. 3 times a week, scheduled for 24 consecutive weeks. At the beginning of the study all had a stable renal function since at least 12 months (mean serum creatinine -SCr- 121 +/- 38 mmol/l). Fourteen patients were receiving cyclosporin A (CsA) either alone (1) or in combination with steroids and/or azathioprine -AZA- (double therapy: 8; triple therapy: 5); two patients were on conventional therapy. The mean daily doses of CsA were 2.6 mg/kd i.e. a mean whole blood trough level of 104 ng/ml. Six patients experienced renal failure either acute (5) or subacute (1) within 7 to 24 weeks after the start of IFN alpha therapy. Their mean SCr increased from 105 +/- 31 mmol/l to 207 +/- 63 mmol/l (p = 0.02) with de-novo proteinuria in one case (1 g/d) and an increase in pre-existing proteinuria in 2; 3 remained without proteinuria. The histological study showed in all cases a diffuse interstitial edema associated with dilatation of peritubular capillaries; mild inflammatory infiltrates were present in only 3 cases; mild glomerular lesions were not always found (glomerular ischemia, mesangial hypertrophy). There was no vascular lesions IFN alpha was withdrawn in these 6 patients, associated with methylprednisolone pulses in 5 cases. Renal function improved in two cases, stabilized in one and progressed to end stage renal failure in 3 within 4 to 12 months. Four patients had iterative renal biopsies showing in all cases diffuse interstitial fibrosis. This subgroup of patients did not statistically differ at the start of the study from those who did not develop renal failure according to baseline immunosuppression, HLA matching, total peripheral blood lymphocyte (PBL) count. PBL subtypes. INF alpha therapy was associated with acute or subacute renal failure in 37% of patients. The most prominent histological finding was a diffuse interstitial edema of rapid onset, without signs of cellular or vascular rejection. Thus we do not recommend to use IFN alpha therapy in RT patients with chronic hepatitis C, until the mechanisms of the subsequent renal failure be more understood.

Acute Kidney Injury↗
PubMed1995

Treatment of chronic hepatitis C with recombinant interferon alpha in kidney transplant recipients.

Chronic hepatitis C is a common cause of viral liver disease in kidney transplant (KT) recipients. To assess the efficacy and safety of therapy with interferon alpha we conducted a prospective study where 14 cadaveric KT recipients with chronic hepatitis C received recombinant interferon alpha-2b (IFNa) 3 million units three times weekly (scheduled) for 6 months (group A). 14 KT recipients with chronic hepatitis C were not treated and served as controls for the study period (group B). All the patients in both groups had had stable renal function for at least one year. All patients in both groups had a positive HCV viremia at the beginning of the study. Patients of group A were treated for 142 +/- 34.8 days (range 65-168); elevated serum aminotransferase (ALT) levels decreased rapidly and significantly from 100.3 +/- 48.9 to 37.7 +/- 13.9 IU/L (P = 0.001); 10 patients (77%) were "responders," whereas the others experienced a decrease in ALT values but without reaching the normal ranges. With a mean follow-up of twelve months after discontinuation of IFNa therapy, 8 responders--i.e., 80%--relapsed within 1-20 weeks. Only 4 patients had no detectable HCV viremia at the end of the IFNa; two of them already have abnormal values of ALT. Moreover HCV viremia was present in all patients one month after the cessation of IFNa treatment. Side effects of IFNa (fatigue, anorexia, weight loss) were frequent, and 3 patients decided to drop out of the treatment. The hematological tolerance was good although there was a significant decrease in hemoglobin (11.9 +/- 1.7 vs. 13.4 +/- 1.7 g/dl; P = 0.0044). In group B, serum ALT levels did not significantly decrease (84.2 +/- 47.6 vs. 105.2 +/- 68.8 IU/L). At the end of the study period serum ALT levels were significantly lower in group A than in group B (37.7 +/- 13.9 vs. 84.2 +/- 47.6 IU/L, P = 0.013). The major concern in group A was the occurrence of 5 renal failures. Kidney transplant biopsies showed edema, no significant tubulitis, scarcely scattered interstitial inflammatory cellular infiltration, and mesangial thickening. Four patients received methylprednisolone pulses but renal function improved in only two cases. We were not able to discover predictive factors of renal failure. We conclude that IFNa therapy is effective in controlling disease activity--i.e., reducing amino-transferase levels in KT patients with chronic hepatitis C, although relapse and detection of HCV RNA after the cessation of treatment were observed, respectively, in 80% and 100% of patients.(ABSTRACT TRUNCATED AT 400 WORDS)

Adult↗
PubMed1995

Renal functional reserve in calcium channel blocker-treated hypertensive recipients of kidney transplant.

Renal functional reserve during infusion of an amino acid solution was examined in 12 cyclosporin-treated kidney recipients at 1 (T1) and 8 months (T2) after transplantation. Patients were retrospectively divided into six normotensive (NT) and six hypertensive recipients (HT) maintained on monotherapy with a calcium channel blocker. Baseline glomerular filtration rates (GFR) were similar in NT and HT at T1 and T2. Renal functional reserve was identical in NT and HT at T1 (15 +/- 7 vs 18 +/- 13 ml/min/1.73 m2) but significantly greater in HT at T2 (11 +/- 5 vs 23 +/- 10 ml/min/1.73 m2; P < 0.05). At T2, baseline proximal tubule outflow (lithium clearance) was greater in HT (26 +/- 8 vs 16 +/- 3 ml/min/1.73 m2; P < 0.05), whereas fractional proximal reabsorption was less (54 +/- 11% vs 67 +/- 5%; P < 0.05). These results indicate that: (i) hypertensive recipients on calcium channel blocker therapy do not exhibit permanent glomerular hyperfiltration until 8 months after transplantation, and have a reduced proximal reabsorption; (ii) measurement of amino acid-stimulated GFR and renal functional reserve is a more sensitive method than that of baseline GFR for evaluating renal function and the effects of therapy in kidney recipients.

Adult↗
PubMed1995

Preliminary results of treatment of chronic hepatitis C with recombinant interferon alpha in renal transplant patients.

Chronic hepatitis C is a common cause of viral liver disease in kidney transplant recipients. To assess the efficacy and the safety of therapy with interferon alpha (IFN alpha) in such a population we conducted a prospective study where 16 kidney transplant recipients with chronic hepatitis C received recombinant IFN alpha 3 million units three times weekly scheduled for 24 consecutive weeks. All the patients had stable renal function for at least 1 year (mean serum creatinine 125.4 +/- 41 mumol/l). Fifteen patients had a positive HCV viraemia at the beginning of the study. In 15 patients serum alanine aminotransferase (ALT) levels decreased rapidly and normalized (48 +/- 44 vs 98.5 +/- 46 IU/l; P = 0.0044). ALT remained in the normal range as long as IFN alpha was continued. Serum levels of gamma glutamyl transpeptidase decreased from 129.75 +/- 111.2 to 88 +/- 85 IU/l; P = 0.012). After discontinuation of IFN alpha therapy seven responders relapsed within 1-9 weeks. HCV viraemia assessed 1 month after the end of IFN alpha therapy remained positive in all the patients who scored positive at the beginning, i.e. 15. Side effects of IFN alpha (fatigue, anorexia, weight loss) were frequent leading to four patients dropping out of the study. The haematological tolerance was moderate. The major concern was the increase in serum creatinine (162.5 +/- 57.6 vs 125.4 +/- 41 mumol/l; P < 0.05). In fact only six patients experienced renal failure occurring 45-168 days after the beginning of IFN alpha. Kidney transplant biopsies showed oedema, scarce scattered interstitial inflammatory cellular infiltration and moderate mesangial hypertrophy.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1995

Calciphylaxis in a chronic hemodialysis patient with protein S deficiency.

Vascular calcifications are common in uremic patients whereas calciphylaxis is rare. We report the case of a 45-year-old woman on chronic hemodialysis since 1977. She had a subtotal parathyroidectomy in 1985, aortic and mitral valve replacement in 1986, and has been treated since then with nicoumalone. In June 1991, she presented with repeated, painful cutaneous necrosis suggesting panniculitis. A skin biopsy showed lobular panniculitis and evidence of calciphylaxis. There was an obvious biological hyperparathyroidism. Protein C functional level was in the normal range whereas protein S functional level was low, i.e. 42%. The patient underwent cervical surgery to remove two parathyroid glands, and daily hemodialysis sessions. Despite this treatment, cutaneous necrosis progressed with superinfection. A few weeks later, the patient died from a septic shock after a myocardic infarction. Necropsy was not performed.

Calciphylaxis↗
PubMed1995

Correction of post-renal transplant erythrocytosis by enalapril.

We studied whether post-renal transplant erythrocytosis (PRTE) could be corrected by enalapril with minimal side-effects, thus avoiding iterative phlebotomies or bilateral nephrectomy of native kidneys. From our renal transplant patients, 12 presented a true PRTE as defined by a 51-Cr red blood cell mass (RBCM) above 32 ml/kg for women and above 36 ml/kg for men. Secondary polycythemia was ruled out: all the patients had a normal renal artery pulsed ultrasonography; in all cases the blood arterial 02 saturation was above 96%. Bone marrow aspiration and histology were performed for each patient: none of them showed evidence of Vaquez disease. All of them had stable renal function i.e. the mean serum creatinine was 112.8 +/- 26.3 mumol/l. They all received the same immunosuppression: azathioprine; ciclosporine A; methylprednisolone. PRTE occurred within the first year post transplant (median 7.5 months; range: 2-34). Their mean RBCM was 37.38 +/- 2.7 ml/kg. Their mean serum value of Epo was 17.41 +/- 13.5 mU/ml (range: 9.1-54). After informed consent, all patients received enalapril starting with 5 mg/day, progressively increased to 20 mg/day, if necessary, in order to maintain the hematocrit below 45%. The mean daily dosage of enalapril was 13.75 +/- 6.1 mg (range: 5-20). The mean follow-up was 14.8 months (range: 3.5-29.5). There was no change in renal function (mean serum creatinine: 126.3 +/- 35 mumol/l). A successful response to enalapril was obtained with a median of 40 days (range: 20-120). 11 patients out of 12 responded to enalapril with a decrease of Hb (14 +/- 2 g/dl vs 16.8 +/- 1.04 g/dl; p = 0.0006) and Ht (41.9 +/- 6.17% vs 51.14 +/- 2%; p = 0.0002) without a significant decrease of Epo (8.1 +/- 3.87; p = 0.1). One patient did not respond to enalapril nor to captopril, but did respond to a combined treatment of enalapril and theophilline. Moreover, all PRTE patients but two did not have Epo levels, before enalapril, above the normal range, suggesting mechanisms other than Epo overproduction by native kidneys i.e. erythropoiesis dysregulation. In conclusion, all patients but one were successfully treated by enalapril without side effects. The treatment was effective as early as 3 weeks from the start and avoided the need for iterative phlebotomies and nephrectomy of native kidneys.

Adult↗