Seropositivity for hepatitis C virus (HCV) predicts lower patient and graft survival after renal transplantation (RT). However, the influence of viral replication at transplantation on long-term ...outcome remains to be determined.
This was a retrospective study conducted in four Spanish hospitals, from 1997 to 2006. Data of all patients with RT, who displayed HCV+ (enzyme-linked immunosorbent assay), and with negative viremia at RT (NEG group) were collected (n=41). For each NEG patient enrolled, data of two patients with RT nearest in time, HCV+, and positive viremia (POS group) were also collected (n=78).
The POS group showed a higher incidence of long-term liver disease (56.4% vs. 24.4%, P=0.0009) and episodes of transaminase elevation (38.5% vs. 7.3%, P=0.0003) and worse renal function (serum creatinine sCr, 3.0 2.7 vs. 1.9 1.6 mg/dl, P=0.032; glomerular filtration rate, 43.7 22.4 vs. 56.9 27.9 ml/min, P=0.075). Noteworthy, 24.4% of NEG patients reactivated after RT, showing a worse patient survival (P=0.039). Active viral replication at RT and dialysis requirement in the first week remained as independent predictors of lower graft survival (death censored): hazards ratio, 3.11 (95% confidence interval, 1.34-7.19; P=0.009) and hazards ratio 3.13 (95% confidence interval, 1.53-6.37; P=0.002).
This study shows that active viral replication at transplantation is an independent risk factor for graft failure in patients with positive serology for HCV.
Background. The contribution of mammalian target of rapamycin (mTOR) inhibitors to proteinuria is controversial. The aim was to analyse proteinuria in suboptimal kidney calcineurin inhibitor-(CNI) ...free de novo immunosuppression. Methods. All patients from our centre with donors >60 years and CNI-free treatment were included (n = 108). Patients were divided into two groups: (i) SRL group: sirolimus (SRL) + prednisone + mycophenolate mofetil (MMF) + antiCD25; (ii) MMF group: prednisone + MMF w/ or w/o antiCD25 (n = 75). Follow-up was 12 months. Results. Donors were slightly younger in the SRL group (68 vs 71 years; P < 0.05), receptor age (67 vs 65 years) was not significantly different. Patient survival in the MMF group was 88 vs 94% in the SRL group, however, these differences did not reach statistical significance. One-year graft survival censored for death was 83% in the MMF group and 94% in the SRL group. Acute rejection rate was 45% in the MMF and 15% in the SRL group (P < 0.01). The incidence of CNI introduction was higher in the MMF-group (35 vs 5; P < 0.05). The intention-to-treat analysis revealed significant differences of proteinuria SRL vs MMF at 12 months: 461 (163–6988) vs 270 (53–3029) mg/day, which did not exist in the on-therapy (OT) analysis SRL vs MMF at 12 months: 357 (199–1428) vs 279 (53–3029) mg/day. New onset nephrotic range proteinuria seemed to occur slightly more frequently in SRL patients (3/33 vs 1/75; P = 0.049), however, all four cases occurred in a context of recurrent disease, or previous drug-independent damage or non-adherence. All of these patients were converted to CNI. Conclusion. SRL-based compared with MMF-based treatment in kidney transplantation with advanced age donors is associated with an acceptable outcome, however, with increased proteinuria in the intention-to-treat analysis. A large subgroup of the patients in the MMF group experienced acute rejection and required conversion to CNI.
The aim was to evaluate feasibility and safety of calcineurin inhibitor-free immunosuppression in high-risk donor kidney transplantation with sequential sirolimus introduction. Kidney transplant ...patients (n=76) with a donor aged >60 years, donor with acute renal failure, or a nonheartbeating donor were included. Immunosuppression consisted of antithymocyte globulin or basiliximab, mycophenolate mofetil, prednisone, and sequential introduction of sirolimus. One-year patient survival was 96.2% and 95.8%; graft survival was 94.2% and 91.7%; acute rejection rates were 21.2% and 12.4%; delayed graft function was 21.2% and 66.7%; and creatinine clearance was 58+/-20 mL/min and 56+/-21 mL/min for the brain-dead donor group and the nonheartbeating donor group, respectively. Most adverse events were infections, but also three lymphoceles, three urinary fistulas, three wound seromas. Sequential sirolimus introduction in high-risk donor kidney transplantation was found to lead to good patient and graft survival and incidence of acute rejection and delayed graft function.
Background. Hepatitis C virus (HCV) infection represents an important problem for the dialysis population due to its high prevalence and the long-term development of chronic liver disease, ...particularly following renal transplantation. Methods. In order to assess the efficacy and tolerance of interferon (IFN) in the treatment of chronic hepatitis C in haemodialysis (HD) patients and their clinical course following renal transplantation, a multicentre, randomized, open-label study was conducted to compare IFN therapy vs a control group. Results. Nineteen HCV RNA-positive patients received 3×106 U of IFN s.c., three times a week (post-HD), and 17 HCV RNA-positive patients were assigned to the control group. Tolerance to IFN therapy was good in nine patients, while treatment was discontinued in the other 10 due to the occurrence of side effects. HCV RNA was negative at the end of treatment in 14 out of 19 patients (74%) receiving IFN and in one patient (5%) in the control group. Six out of the 14 patients who initially responded to IFN therapy had a virological relapse (43%). Eight patients (42%) remained HCV RNA-negative, three of them until the day that renal transplantation (RT) was performed (7, 12 and 27 months, respectively), as did five patients on HD during the follow-up (27±5 months). Eight out of the nine patients (89%) who completed therapy were HCV RNA-negative at the end of treatment, and seven of them (78%) remained HCV RNA-negative during the follow-up on dialysis (21±8 months). Mean transaminase (ALT) values were significantly decreased following IFN therapy, while no changes were observed during the follow-up period in the control group. Fifteen patients (10 in the treatment group and five in the control group) underwent RT. Three patients in the treatment group were HCV RNA-negative at RT, and one of them had a virological relapse 20 months after RT, while the other two remained HCV RNA-negative at 3 months and 24 months after RT, respectively. In contrast to the control group, transaminase (ALT) remained within normal limits in all patients in the treatment group. Finally, during the post-RT follow-up, the transaminase mean values were significantly lower in treated patients vs patients in the control group (P<0.05). Conclusions. It is concluded that the biochemical and virological response to IFN therapy is good in HD patients. In addition, IFN therapy appears to exert a beneficial effect on the course of liver disease following RT, regardless of the virological response. Despite the fact that IFN therapy was discontinued in 10 out of the 19 patients due to the occurrence of side effects, these disappeared following discontinuation of therapy. Therefore, IFN therapy is advisable for HCV-infected dialysis patients who are candidates for RT.
Increased plasma adrenomedullin levels in hemodialysis patients with sustained hypotension.
Sustained hypotension in end-stage renal disease patients is characterized, despite an overactivation of ...the sympathetic and renin-angiotensin systems, by decreased vascular resistance and a blunted vascular response to pressor stimuli. An increased production of one or more vasodilator substances might play a role in the reduced vascular resistance and response to pressor stimuli in these patients. We evaluated the possible role of an increased production of nitric oxide and/or adrenomedullin (ADM) in the pathophysiology of chronic hypotension in hemodialysis (HD) patients.
Three groups of hypotensive (N = 9), normotensive (N = 10), and hypertensive (N = 9) HD patients were included in the study. Plasma renin activity (PRA) and plasma levels of catecholamines, ADM, nitrite/nitrate (an estimator of nitric oxide production), tumor necrosis factor (TNF), and interleukin-1β (IL-1β) were measured. Plasma volume and left ventricular ejection fraction (LVEF) were also evaluated.
Plasma levels of nitrite/nitrate and ADM were elevated in HD patients with respect to the reference values in normal subjects. Plasma ADM levels, but not nitrite/nitrate levels, were higher in hypotensive (368.1 ± 25.4 pg/mL) than normotensive (225 ± 9.9 pg/mL) and hypertensive HD patients (278.2 ± 15.5 pg/mL, P < 0.01). When considering hypotensive and normotensive patients together, the mean blood pressure inversely correlated with time on HD (r = -0.53, P < 0.05) and plasma ADM levels (r = -0.78, P < 0.01).
Plasma ADM and nitrite/nitrate levels are increased in HD patients, but only ADM levels were higher in hypotensive than in normotensive and hypertensive HD patients. The higher plasma levels of this peptide in hypotensive patients and its inverse correlation with mean arterial pressure suggest that ADM may be involved in the pathophysiology of chronic hypotension in HD patients.
Hepatitis C virus (HCV) infection is a common problem in renal transplant patients, associated with an increase in morbidity and mortality. HCV infection is associated with a lower graft and patient ...survival. The problem of HCV infection is the increase in viral load and liver transaminases after renal transplantation secondary to immunosuppressive therapy. After renal transplantation, interferon therapy is not recommended because of the risk for acute rejection and acute nephritis. In this context, it is absolutely necessary to consider the evaluation and treatment of HCV infection during the dialysis period. Several studies have defined the benefits of interferon therapy in dialysis patients, with rates of maintenance response significantly higher than in the general population. The difference in the pharmacokinetic profile of interferon in dialysis patients could justify its higher efficacy.
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