Search

Background: Malignancies and lymphoma are common complications after kidney transplantation. However, no link has been made between the incidence of malignancies and hepatitis C virus (HCV) infection in this setting. This case-controlled study compared the incidence of malignancies, including lymphoma, between kidney transplant (KT) patients with or without HCV replication., Patients and Methods: A total of 99 HCV-positive RNA-positive KT patients were matched with 198 (1:2) anti-HCV-negative patients according to age, gender, and date of transplantation, and were followed for 145.8±78.4 months., Results: During the follow-up period, 28 HCV-positive (28%) cases developed at least one cancer, and 64 (32%) patients developed cancer in the HCV-negative group (P=not significant [ns]). Survival without a cancer was similar between both groups. Thirteen HCV-positive patients (13%) developed at least one solid cancer vs 29 (15%) HCV-negative patients (P=ns). Survival without a solid cancer was similar between both groups. Three patients from the HCV-positive and 4 from the HCV-negative group developed a lymphoma. Only 2 patients from the HCV group died from hepatocellular carcinoma. Survival without a skin cancer was similar between both groups. Patient and death-censored graft survival rates were significantly lower in the HCV group., Conclusion: The incidences and types of malignancies were similar in the HCV-positive and HCV-negative KT patients., (© 2017 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

There is no approved therapy for hepatitis C virus (HCV) infection after kidney transplantation, and no data regarding the use of new-generation direct antiviral agents (DAAs) have been published so far. The aims of this pilot study were to assess the efficacy and safety of an interferon-free sofosbuvir-based regimen to treat chronic HCV infection in kidney transplant recipients. Twenty-five kidney transplant recipients with chronic HCV infection were given, for 12 (n = 19) or 24 weeks (n = 6), sofosbuvir plus ribavirin (n = 3); sofosbuvir plus daclatasvir (n = 4); sofosbuvir plus simeprevir, with (n = 1) or without ribavirin (n = 6); sofosbuvir plus ledipasvir, with (n = 1) or without ribavirin (n = 9); and sofosbuvir plus pegylated-interferon plus ribavirin (n = 1). A rapid virological response, defined by undetectable viremia at week 4 after starting DAA therapy, was observed in 22 of the 25 patients (88%). At the end of therapy, HCV RNA was undetectable in all patients. At 4 and 12 weeks after completing DAA therapy, all had a sustained virological response. The tolerance to anti-HCV therapy was excellent and no adverse event was observed. A significant decrease in calcineurin inhibitor levels was observed after HCV clearance. New-generation oral DAAs are efficient and safe to treat HCV infection after kidney transplantation., (© Copyright 2015 The American Society of Transplantation and the American Society of Transplant Surgeons.)

Fibrosing cholestatic hepatitis (FCH) is a classical but rare and severe form of recurrent hepatitis C virus (HCV) after liver transplantation. Classical anti-HCV therapy, that is pegylated-interferon (peg-interferon) and ribavirin, has been shown to have limited efficacy in treating FCH. Herein, we report on the first case of successful use of peg-interferon, ribavirin, plus sofosbuvir to treat HCV-induced FCH in a combined liver-kidney transplant patient. Antiviral therapy was given for 24 weeks. HCV clearance occurred within 4 weeks after starting therapy and was maintained until 4 weeks after the end of therapy. Antiviral tolerance was good. We conclude that the use of sofosbuvir-based anti-HCV therapy can be successfully used to treat FCH after a liver or combined kidney-liver transplantation., (© 2014 Steunstichting ESOT.)

Background: Kidney transplantation increases the chances for pregnancy and live birth for women with end-stage kidney disease. The aims of this study were to describe the outcomes of pregnancies in women with a kidney transplant and to evaluate the impact on anti-human leucocyte antigen (HLA) alloimmunization., Methods: We analysed 61 pregnancies that occurred in 46 patients after having excluded 10 miscarriages during the first trimester and 10 other pregnancies from which important data were missing. Anti-HLA antibodies were screened using the Luminex assay., Results: Overall, the live birth rate was 83% (94% after exclusion of miscarriages during the first trimester). Pre-eclampsia and gestational diabetes occurred in 26 and 21% of cases, respectively. The use of tacrolimus was an independent predictive factor for gestational diabetes. Twenty-four newborns (42%) were premature (<37 weeks). The median birth weight was 2720 (1040-3730) g. Nine newborns (15%) had low birth weights (<2.5 kg). At least one severe complication occurred in 56% of pregnancies. A high glomerular-filtration rate (GFR) before pregnancy was the sole independent protective factor that avoided a severe complication. Death-censored kidney-allograft survival was 80.4% at 6 years. De novo donor-specific anti-HLA antibodies were detected after only 5.9% of pregnancies: for two women, the father had the same HLA antigens as those from the deceased organ donor. The determination of the HLA of the father before pregnancy can better inform the woman about the possible impact of pregnancy on her kidney-allograft function., Conclusions: Despite many complications, the outcomes for pregnancy and kidney allografts are good. The risk of anti-HLA alloimmunization was low., (© The Author 2014. Published by Oxford University Press on behalf of ERA-EDTA. All rights reserved.)

Background and Objectives: Within the last few years, anti-human leukocyte antigen detection assays have significantly improved. This study asked, using the Luminex single-antigen assay, whether an allograft nephrectomy allowed donor-specific alloantibodies to appear that were not previously detected in the serum when the failed kidney was still in place., Design, Setting, Participants, & Measurements: After losing the kidney allograft and stopping immunosuppressive therapy, the proportions of donor-specific alloantibodies and nondonor-specific alloantibodies were compared in patients who had (n=48; group I) and had not (n=21; group II) undergone an allograft nephrectomy. Allograft nephrectomies were performed at 150 days after kidney allograft loss, and the time between allograft nephrectomy and last follow-up was 538 ± 347 days., Results: At kidney allograft loss, donor-specific alloantibodies were detected in three group II patients (14.2%) and six group I patients (12.5%). At last follow-up, donor-specific alloantibodies were detected in 11 patients (52.4%) without and 39 patients (81%) with an allograft nephrectomy (P=0.02). Anti-human leukocyte antigen class I donor-specific alloantibodies were positive in 23.8% of group II and 77% of group I patients (P<0.001); anti-human leukocyte antigen class II donor-specific alloantibodies were positive in 42.8% of group II and 62.5% of group I patients. Independent predictive factors for developing donor-specific alloantibodies after losing kidney allograft and stopping immunosuppressants were number of anti-human leukocyte antigen A/B mismatches at transplantation (zero versus one or more) and allograft nephrectomy., Conclusions: The development of donor-specific alloantibodies was significantly greater in patients with a failed kidney who had undergone an allograft nephrectomy compared with those patients who had not undergone allograft nephrectomy.

Introduction: The occurrence of de novo anti-human leukocyte antigen (HLA) antibodies and donor-specific antibodies (DSAs) after early graft loss is not well known. The aims of this single-center study were to evaluate the incidence of de novo DSAs and non-DSA anti-HLA antibodies after allograft nephrectomy for early graft loss and to seek the predictive factors for the development of DSAs., Materials and Methods: Thirty-two patients, who experienced an early graft loss (<3 months after transplantation) and required an allograft nephrectomy, and who were considered for retransplantation, were included in the study. Anti-HLA antibodies were assessed, using the Luminex assay, before transplantation, on day 15 and at months 1, 3, 6, and 9 after the nephrectomy, and then every 3 to 6 months until the last follow-up., Results: The median time between transplantation and allograft nephrectomy was 2.5 (0-81) days. The median follow-up was 335 (30-1441) days. At month 9, postallograft nephrectomy, the incidence of DSAs was 56.6% (17/30). Anti-HLA class I and class II DSAs were detected, respectively, in 33.3% (10/30) and 30% (9/30) of patients. The incidence of de novo non-DSA anti-HLA antibodies was 64% (19/30): of these, 83.3% reacted to the donors' epitopes. Induction therapy (type and dose) and the time between transplantation and allograft nephrectomy did not influence the incidence of DSAs. No independent predictive factor for the development of DSAs was identified., Conclusion: Even after a short transplantation period, DSAs and non-DSA anti-HLA antibodies may develop in more than 50% of patients whose immunosuppression has been stopped after an allograft nephrectomy.

Objectives: This retrospective single-center study evaluated long-term renal function after conversion from calcineurin inhibitors to sirolimus-based immunosuppression in kidney transplant recipients., Materials and Methods: From 2001 to 2009, one hundred fifty kidney transplant recipients were converted from calcineurin inhibitors to sirolimus at least 3 months after transplant., Results: After a mean follow-up of 171 weeks, 56.7% of converted patients remained on sirolimus. The 5-year survival rate of the patients (including intent-to-treat) and grafts was 85.5% and 83.6%. Patients on sirolimus showed significant improvement in renal function with a creatinine clearance of 50.9 ± 20.7 and 52.9 ± 20.8 mL/minute at month 0 and month 24. Independent predictive factors associated with a stable estimated glomerular filtration rate at the last follow-up of sirolimus patients were (1) having a living donor, (2) absence of anti-HLA alloantibodies at month 0, and (3) cyclosporine versus tacrolimus used before conversion. Adverse effects were reported in 134 patients (89.3%). They included (1) hospitalization for infection (n=52), (2) de novo proteinuria (n=40), and (3) eight patients with biopsy-proven acute rejection. Sirolimus was stopped and replaced by calcineurin inhibitors in 37 patients after a mean of 16 months treatment. After stopping sirolimus, renal-allograft function remained stable at 2 years., Conclusions: Conversion of calcineurin inhibitors to sirolimus in kidney transplant recipients was associated with improved renal function. The reintroduction of calcineurin inhibitors was safe in patients who were withdrawn from sirolimus owing to adverse effects.

After kidney transplantation, occurrence of anemia in the early post-transplant period (<1 month) is high and arises out of issues that are multifactorial. We performed a retrospective single-center study to assess whether delivery of high doses of erythropoietin-stimulating agents (ESA) within the first week of kidney transplantation, translates at 1 month post-transplant, in to causing less anemia and whether it has an impact on allograft function. Ninety-nine patients were not given ESA (group I), whereas 82 were (250 IU/kg/week; group II). All patients had similar pretransplant and baseline (day 0) variables. Similar numbers of group II patients were still receiving ESA by day 14 (97.5%) and day 30 (89%). Respective figures for group I were 27% and 27%. Independent factors for anemia at 1 month post-transplant included: being male subject, treatment for hypertension at pretransplant, anemia at transplant, a higher mean corpuscular volume at transplant, and an induction therapy using antithymocyte globulins. Independent predictive factors for lower creatinine clearance included being female subjects, having a donor aged >50 years, being a recipient aged >50 years, not treated for hypertension at pretransplant, and no post-transplant ESA therapy. High doses of ESA within the first month of kidney transplantation have no impact on anemia or renal function by 1 month post-transplant.

Rituximab off-label use includes organ transplantation. We review the occurrence of infectious disease and its outcome after rituximab therapy. Between April 2004 and August 2008, 77 kidney-transplant patients received rituximab therapy [2-8 courses (median 4) of 375 mg/m2 each] for various reasons. Their results were compared with a control group (n=902) who had received no rituximab. After a median follow-up of 16.5 (1-55) months for rituximab patients and 60.9 (1.25-142.7) months for control patients, the incidence of infectious disease was 45.45% and 53.9% (ns), respectively. The incidence of bacterial infection was similar between the two groups, whereas the viral-infection rate was significantly lower, and the rate of fungal infection was significantly higher in the rituximab group. Nine out of 77 patients (11.68%) died after rituximab therapy, of which seven deaths (9.09%) were related to an infectious disease, compared to 1.55% in the controls (p=0.0007). In the whole population, the independent predictive factors for infection-induced death were the combined use of rituximab and antithymocyte-globulin given for induction or anti-rejection therapy, recipient age, and bacterial and fungal infections. After kidney transplantation, the use of rituximab is associated with a high risk of infectious disease and death related to infectious disease.

Background: In the setting of kidney transplantation, cinacalcet has been given, mainly, once daily, but also twice daily. The aims of this prospective study were to assess the acute pharmacodynamic effect of cinacalcet administrated once or twice daily to kidney transplant patients with normal renal function and persisting hypercalcaemia due to hyperparathyroidism and to evaluate 1-year efficacy and tolerance of cinacalcet given at a dose of 30 mg b.i.d., Methods: Eleven patients, who received a transplant 6 (6-59) months previously, were included in the study. A first kinetic was done after administration of 60 mg of cinacalcet at 8 a.m. After a washout period of 1 week, the second kinetic was performed with cinacalcet given at 30 mg b.i.d within a 12-h period., Results: During both kinetics, serum calcium (sCa), ionized calcium (sCa(2+)), albumin-corrected Ca and parathyroid hormone (PTH) levels decreased significantly. At 24 h after the second kinetic, sCa(2+) was significantly lower. After 1 year of cinacalcet treatment, given at the dose of 30 mg b.i.d., there was a significant decrease in sCa, sCa(2+), PTH levels and calcium x phosphorus (Ph) product. In contrast, Ph levels increased significantly. There was no significant change in renal function., Conclusion: Once- or twice-daily acute administration of cinacalcet to kidney-transplant patients has similar efficacy. One-year administration of cinacalcet, given as two daily doses, is safe and efficient.

The aim of our study was to assess the efficacy and safety of entecavir in kidney- and liver-transplant recipients with chronic hepatitis B virus (HBV) infection. Ten male transplant patients with chronic HBV infection (eight kidney- and two liver-transplant patients), who have become adefovir (n=9) or lamivudine-resistant (n=1) were given entecavir at 0.5 to 1 mg/d. All patients were HBs Ag positive: six were HBe Ag(-)/HBe Ab(+), and four were HBe Ag(+)/HBe Ab(-). After a median follow-up of 16.5 months, entecavir therapy was associated with a significant decrease in HBV DNA viral load, that is, 3.86 (2.71-6.46) log10 copies/mL at baseline down to 2.94 (2.15-4) log10 copies/mL at last follow-up (P=0.004). Rate of HBV DNA clearance was 50% in both HBeAg(+) and HBeAg(-) patients. There were no significant changes in renal function or hematological parameters. This study demonstrates that entecavir therapy is safe and efficient in HBV(+) organ-transplant patients.

The aims of this prospective, open-label, single-center pilot study were to assess the efficacy and safety of human cytomegalovirus (HCMV) prophylaxis using valganciclovir in HCMV- seropositive kidney-transplant patients to prevent HCMV infection and disease. Fifty-one HCMV seropositive kidney-transplant patients recipients who received transplants between 1 December 2005 and 30 November 2006 were included in the study. Valganciclovir was given from transplantation up to 114 (37-329) days, and was adapted to renal function, i.e., 900 mg/d if calculated creatinine clearance was >60 ml/min, or 450 mg/day if it was <60 ml/min. HCMV DNAemia was assessed every 2 weeks during prophylaxis, and on the same basis for 3 months post-prophylaxis. Immunosuppression was based on calcineurin inhibitors (ciclosporine A=22; tacrolimus=11), with mycophenolate mofetil (n=51), and low-dose steroids. Eighteen patients received no calcineurin-inhibitors, but Belatacept instead. During valganciclovir prophylaxis, asymptomatic HCMV DNAemia was observed in one patient, and no case of HCMV disease occurred. Within 252 days (45-425) post-valganciclovir prophylaxis, HCMV DNAemia was detected in 23.5% (n=12) of patients, of whom two had two or more consecutive HCMV DNAemias. Valganciclovir prophylaxis in HCMV-seropositive kidney-transplant patients is effective for preventing cytomegalovirus disease.

The aims of the present study were to assess the incidence of cytomegalovirus (CMV) reactivation, and to determine the predictive factors for CMV reactivation in CMV seropositive kidney-transplant patients. One hundred ninety CMV seropositive kidney-transplant patients were included in this study; of these, 39 patients had received CMV prophylaxis. CMV DNAemia was assessed by real-timepolymerase chain reaction assay every 2 weeks until day 120, then every 3-4 weeks until day 180, and then every month until day 365. One hundred seven patients (56.3%) had at least one positive CMV DNAemia within the first year. The time between renal transplantation and the first positive CMV DNAemia was 59 +/- 5 days. The number of positive CMV DNAemia/patient was 3.28 +/- 0.22. CMV viral load at first positive CMV DNAemia was 704 (10-742,000) copies/ml. The donor CMV seropositivity, the absence of CMV prophylaxis, and the occurrence of acute rejection before CMV reactivation were independent factors associated with CMV reactivation within the first year after kidney transplantation. Hence, CMV reactivation is frequent after kidney transplantation. CMV prophylaxis in CMV seropositive kidney-transplant patients should be offered to avoid CMV-related side-effects.

A pilot study was performed on eight consecutive renal-transplant (RT) patients presenting with acute humoral rejection (AHR) to assess the efficacy of monoclonal anti-B cell antibodies, such as rituximab (375 mg/m weekly) for 3 to 5 consecutive weeks, in addition to plasma exchange (PE), steroids, mycophenolate mofetil, and tacrolimus. AHR was associated with increased serum creatinine, the appearance of donor-specific alloantibodies (DSA), and the presence of C4d in a transplant biopsy. After a follow-up of 10 months (range 7-23), patient and graft survivals were 100% and 75%, respectively. Renal function improved in six cases in which serum creatinine decreased from 297+/-140 to 156+/-53 micromol/L (P=0.015); graft loss occurred in two cases; and four patients had infectious complications. At last follow-up, DSA had disappeared or decreased in four cases. Rituximab therapy, in addition to PE, might be of benefit for RT patients presenting with AHR.

Objective: The aim of this study was to assess the effects of tacrolimus in combination with either sirolimus (n = 10) or mycophenolate mofetil (n = 7) on renal function and renal histopathologic factors 6 and 12 months after kidney transplantation., Materials and Methods: Renal function was assessed by the glomerular filtration rate (as measured by the inulin clearance rate) and by determining renal functional reserve. A renal allograft biopsy was performed at the time of transplantation and 6 and 12 months later., Results: Serum creatinine levels tended to be higher in the sirolimus group 12 months after transplantation. In contrast, inulin clearance and renal functional reserve were similar in both groups 6 and 12 months after transplantation. With respect to histopathologic findings, only mononuclear-cell interstitial inflammation was significantly higher in the sirolimus group than in the mycophenolate mofetil group 12 months after transplantation. However, the progression of tubular atrophy, interstitial fibrosis, and vascular fibrous intimal thickening within the first postoperative year was significantly greater in the sirolimus group., Conclusions: In the long term, the addition of sirolimus to treatment with tacrolimus in de novo renal transplant patients might more adversely affect renal allograft survival than might the addition of mycophenolate mofetil to tacrolimus therapy.

Objective: Mycophenolic acid dose modifications after renal transplantation seem to adversely affect renal allograft outcome. The aim of this retrospective study was to examine the effect of mycophenolic acid dose modifications on renal function 1 year after transplantation and to determine the factors predictive of those dose modifications within the first year after renal transplantation., Patients and Methods: All 130 patients at our institution who were treated de novo between January 2002 and April 2003 with either a mycophenolate mofetil-based or an enteric-coated mycophenolate sodium-based therapy and who had a functioning renal allograft 1 month after transplantation were included in this study., Results: Fifty-seven patients (43.8%) underwent a dose modification during the first year after transplantation. One, 3, 6, and 12 months after transplantation, renal function was significantly improved in the patients who did not receive a dose modification. A mycophenolic acid dose that 1 year after transplantation was less than the initial dose received just after transplantation was an independent factor associated with deteriorating renal function. Sirolimus immunosuppression, Cytomegalovirus infection, and pretransplant lymphocyte counts were independent factors associated with mycophenolic acid dose modifications within the first year after kidney transplantation., Conclusions: Modification of the mycophenolic acid dose may adversely affect renal function 1 year after transplantation.

Systemic B-cell depletion and clinical remission of the systemic effects of cryoglobulins have been achieved in hepatitis C virus-positive immunocompetent patients with rituximab, a human/mouse chimeric monoclonal antibody that specifically reacts with the CD20 antigen. Thus, this provides a rationale for the use of rituximab for type III cryoglobulin-related graft dysfunction in renal-transplant patients. Seven patients, of whom five were hepatitis C positive, developed renal function impairment long after transplantation, as well as de novo nephrotic syndrome (n = 5), severe hypertension (n = 5), nephritic syndrome (n = 1), and increased serum creatinine (n = 1). This type III cryoglobulinemia was associated with membranoproliferative glomerulonephritis and with thrombi within the glomeruli in one case. In addition to their baseline standard immunosuppressive medications, the patients were given weekly rituximab infusions: 375 mg/m(2) for 2 weeks in four cases, for 3 weeks in one case, and for 4 weeks in two cases. This treatment resulted in a dramatic improvement in all renal parameters, particularly a sustained remission of nephrotic syndrome in three cases, the disappearance of nephritic syndrome in one patient, and improved nephrotic syndrome in two cases, as well as a sustained clearance of cryoglobulins in six cases. However, it also resulted in severe infectious complications in two cases. We concluded that rituximab therapy is effective in cryoglobulin-related renal dysfunction in renal transplant patients but, due to chronic immunosuppression, this may be achieved at the expense of infectious complications.

Background: Type II or III cryoglobulins are fairly prevalent in renal-transplant (RT) patients, and are often related to chronic hepatitis C virus (HCV) infection. However, they rarely result in graft dysfunction. They are sustained by proliferation of oligoclonal B-cells. Systemic B-cell depletion and clinical remission of the systemic effects of cryoglobulins have been achieved in HCV-positive immunocompetent patients with a human/mouse chimeric monoclonal antibody that specifically reacts with the CD20 antigen (i.e., rituximab). Thus, this provides the rationale to use rituximab for cryoglobulin-related graft dysfunction in RT patients., Methods: Three RT patients, of whom one was HCV-positive, developed renal-function impairment long after transplantation, as well as de novo nephrotic syndrome (n=2) and severe hypertension (n=2). This latter case was related to type III cryoglobulinemia and was associated with membranoproliferative glomerulonephritis. In addition to their baseline standard immunosuppression, the patients were given weekly rituximab infusions of 375 mg/m (two infusions in patient and four infusions for the other two cases)., Results: This treatment resulted in a dramatic improvement in renal parameters, particularly in a sustained remittence of nephrotic syndrome, a sustained clearance of cryoglobulins in two cases, but also in severe infectious complications in two cases., Conclusion: We conclude that rituximab therapy is highly effective in cryoglobulin-related renal dysfunction in RT patients; however, due to chronic immunosuppression, this is at the expense of infectious complications.

Objective: The aim of our study was to identify independent factors that might predict anemia at 6 months' (M6) and 12 (M12) months' posttransplantation. Postrenal transplant anemia was defined as a hemoglobin (Hb) level below 13 g/dL for men, and below 12 g/dL for women. We included 99 renal transplants performed in our department in 2001, for whom the graft was still functioning at 1 year., Results: Anemia was observed in 78%, 35.5%, and 25% on day (D) 0, and at M6, and M12, respectively. Iron deficiency was observed in 14% of patients at D0, and 13% at M12. During the postoperative period, 59.8% of patients received at least one blood transfusion, whereas 37% of patients were prescribed recombinant erythropoietin (rEpo) therapy within the first few months posttransplantation. By multivariate analysis the independent predictive factors for anemia at M6 were rEpo therapy at D0, initial nephropathy, posttransplantation rEpo therapy, hematocrit at M3, platelets at D7 and sirolimus therapy. The independent predictive factors for anemia at M12 were rEpo therapy at D0 and platelets at D7, delayed graft function (DGF), serum creatinine, and creatinine clearance at M12, and Hb level at M6 were also checked., Conclusion: The prevalence of anemia is 25% at M12; DGF, renal function at M12, and anemia at M6 were independent risk factors of anemia at M12.