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Large cohort studies suggest that high convective volumes associated with online hemodiafiltration may reduce the risk of mortality/morbidity compared to optimal high-flux hemodialysis. By contrast, intradialytic tolerance is not well studied. The aim of the FRENCHIE (French Convective versus Hemodialysis in Elderly) study was to compare high-flux hemodialysis and online hemodiafiltration in terms of intradialytic tolerance. In this prospective, open-label randomized controlled trial, 381 elderly chronic hemodialysis patients (over age 65) were randomly assigned in a one-to-one ratio to either high-flux hemodialysis or online hemodiafiltration. The primary outcome was intradialytic tolerance (day 30-day 120). Secondary outcomes included health-related quality of life, cardiovascular risk biomarkers, morbidity, and mortality. During the observational period for intradialytic tolerance, 85% and 84% of patients in high-flux hemodialysis and online hemodiafiltration arms, respectively, experienced at least one adverse event without significant difference between groups. As exploratory analysis, intradialytic tolerance was also studied, considering the sessions as a statistical unit according to treatment actually received. Over a total of 11,981 sessions, 2,935 were complicated by the occurrence of at least one adverse event, with a significantly lower occurrence in online hemodiafiltration with fewer episodes of intradialytic symptomatic hypotension and muscle cramps. By contrast, health-related quality of life, morbidity, and mortality were not different in both groups. An improvement in the control of metabolic bone disease biomarkers and β2-microglobulin level without change in serum albumin concentration was observed with online hemodiafiltration. Thus, overall outcomes favor online hemodiafiltration over high-flux hemodialysis in the elderly.

In this retrospective study, we evaluated the histological and biological predictors of long-term response of renal transplant (RT) patients treated with orthoclone OKT3 for steroid resistant acute rejection (AR). Seventy-three patients, aged 37 ± 12 years, were included in this study between March 1987 and December 1996. All the patients but one had received sequential quadruple immunosuppression (polyclonal antilymphocyte globulins; steroids; azathioprine, and cyclosporin A). OKT3 (5 mg/day for 10 days) was administered for biopsy-proven steroid resistant AR i.e., after 3 consecutive pulses of methylprednisolone (10 mg/kg each). This was the first AR in 46 cases, the second AR in 22 cases and the third AR in 4 cases. Renal histology (Banff) showed borderline (BL) changes in 18 patients, grade I AR in 28 patients; grade II AR in 22 patients, and grade III AR in 5 patients. When treatment with OKT3 commenced (107 ± 18 days post-transplantation) the mean serum creatinine (SCr) level was 325 ± 195 μmol/l; this had decreased to 191 ± 106 μmol/l by the end of OKT3 therapy. The immediate response to OKT3 therapy i.e., within the first month, was not dependent on the histological score. Twenty-six patients (35%) subsequently experienced at least one more AR episode of whom 4 were retreated with OKT3. The overall patient’s survival was 94.5% at last follow-up. The overall cumulative graft survival was 64.5% at 2 years, 52.5% at 5 years, and 40.5% at 8 years. The graft survival (5 years) tended to depend on the initial histological score, i.e. BL 30%; grade I 66%; grades II and III 55.5% (p = 0.08). In a multiple logistic regression analysis we tried to identify independent factors that would predict that a graft would still be functioning at least 2 years after OKT3 therapy. We therefore analyzed the following parameters: donor and recipient’s age; gender; cold ischemia time; HLA matching; panel reactive antibodies (PRA) prior to grafting; previous transplantation(s); total number of AR episodes; the time of onset of the AR treated by OKT3 compared to the other AR; the time of onset of the AR treated by OKT3; SCr levels at days 0, 10 and 30 after OKT3 therapy; histological score (Banff) i.e., the magnitude of AR and the presence or absence of chronic lesions. The only independent factors which would predict that a graft was still functioning 2 years after OKT3 therapy were: PRA

In this prospective randomized study including 28 patients, we show that, in cytomegalovirus (CMV)-seronegative renal transplant recipients (R-) receiving a CMV-seropositive graft (D+), high doses of acyclovir (ACV, i.e. 3,200 mg/day) during the first 3 months after transplantation were as efficient as hyperimmune CMV immunoglobulins (CMV Igs) plus high doses of ACV regarding the prophylaxis of CMV primoinfection. Fifty-four percent of the patients in the ACV arm and 50% in the other arm presented at least one episode of viremia (n.s.). The incidence of CMV disease was 31% in the ACV group and 20% in the ACV + CMV Ig group (n.s.). By comparison with historical controls (no prophylaxis), we found that ACV with or without CMV Ig significantly delayed and significantly decreased the rate of CMV disease, although the severity score was not statistically different. Moreover, high doses of ACV were far less expensive than their combination with hyperimmune CMV Igs. Thus, until oral ganciclovir is available for the prophylaxis of primary CMV infection in renal transplant patients, we recommend the use of high doses of ACV for the first 3 months after transplantation in high-risk renal transplant patients, i.e. D+/R-.

We studied the prevalence of hepatitis C virus (HCV) infection in 350 renal transplant (RT) patients with a functioning graft. The determination of HCV infection was based upon second-generation ELISA tests (ELISA-2, Abbott) confirmed by second-generation RIBA tests (RIBA-2, Chiron), including the proteins C22-3, C100-3, C33-C and 5-11. Three hundred and sixteen of these RT patients were on ciclosporin A (CsA) therapy with or without steroids (CS) and azathioprine (AZA); 34 received conventional immunosuppression. Eighty-seven RT patients were found to be HCV-positive (2.5%) when assessed by ELISA-2 tests; RIBA-2 was positive in 61 cases and 'indeterminate' in 26. Most of the HCV-positive patients had antibodies against C22-3 (94%), whereas antibodies against nonstructural antigens (C100-3, C33-C) were observed in 18 and 70% of cases, respectively. More than 88% of the HCV-positive patients were already HCV-positive before renal transplantation. Risk factors of developing HCV infection included: (i) the time on dialysis; (ii) the number of blood transufsions before transplantation, and (iii) the number of previous graft(s). There were significantly more HCV-positive patients among those on conventional immunosuppressive therapy (16 of 39) than among those on CsA (71 of 311; p0.02). Of those who where HCV-positive before transplantation, and for whom liver enzyme (LE) results were available (n = 68), 40 had either a normal or a transient increase in alanine aminotransferase (ALT) levels at that time, whereas 28 had a chronic increase in serum ALT +/- gamma-glutamyltranspeptidase levels. After transplantation, there was biochemical evidence of chronic liver disease in 33 patients (48.5%). Interestingly, 41 and 64% of those with respectively normal and increased LEs before transplantation presented with a biochemical chronic liver disease after RT. Surprisingly, 36% of those with a pretransplantation increase in ALT had normalized aminotransferase after transplantation. The daily doses of AZA, CS (i.e. prednisolone) were not statistically different between HCV-positive RT patients on conventional therapy (group A) and those on CsA (group B). Moreover, within each group, the daily doses of AZA, CS or CsA were not statistically different between those with a chronic increase in LEs and those with normal LEs. The percentage of HCV-positive RT patients with chronic abnormal LEs was not different between groups A and B. Surprisingly, the patients who were treated at least once for acute rejection with methylprednisolone pulses had a significantly lower incidence of chronic increases in LEs. Nine patients seroconverted for HCV after transplantation: 6 experienced a chronic increase in LEs. Finally, 7 of 87 patients were coinfected by HBV, all of them had a chronic increase in LEs. These results emphasize the fact that ALT alone cannot be used as a surrogate marker for chronic HCV infection in transplantation patients, thus a liver biopsy is required before and a few years after RT to assess liver damage in this population.

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.

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.