Late Cytomegalovirus Infection in Kidney Transplant Recipients after a Six-Month Prevention Protocol.

BACKGROUND: Despite a reduction in the incidence of cytomegalovirus (CMV) infections after kidney transplantation, less is known about late CMV infection in kidney transplant recipients. OBJECTIVE: To assess incidence of CMV infection in a cohort of patients under a high surveillance CMV prevention protocol and identify factors associated with late CMV infection. METHODS: Analysis of a consecutive cohort of 181 kidney allograft recipients between January 2012 and Aug 2015. CMV prevention-protocol consisted of 6-month universal prophylaxis and pre-emptive therapy for high-risk group (D+/R- or patients submitted to lymphocyte-depleting agent for induction or rejection treatment) and pre-emptive therapy for standard-risk group (D±/R+). Stopping valganciclovir was followed by CMV screening in the next two appointments. RESULTS: CMV infection was identified in 73 of 181 patients; the rate in high-risk group and standard-risk group was similar (p=0.443). However, in the latter group, the infection occurred mostly in the first 6 months. Late CMV infection occurred in 25 of 181 patients (5 of standard-risk group and 20 of high-risk group), after a median (IQR) of 253 (230.3-312.3) days after transplantation and 55 (41-89.5) days after the protocol period. Screening for CMV after valganciclovir discontinuation revealed 56% of late CMV infections. In high-risk group, D+/R- was associated with late CMV infection (HR 2.7, p=0.039) and in standard-risk group; lower age was associated with late CMV infection (HR 0.89, p=0.02). CONCLUSION: The incidence of CMV infection was similar to that reported in the literature. In high-risk patients, antigenemia surveillance during prophylaxis did not appear to reduce late CMV infections. Antigenemia screening after valganciclovir had limited results in the diagnosis of late CMV infection. D+/R- was associated to late CMV infection in high-risk group. Lower age appeared to influence late CMV infection in standard-risk group.

Intravenous Immunoglobulin and Rituximab in HLA Highly Sensitized Kidney Transplant Recipients.

INTRODUCTION: HLA-sensitized patients are penalized both in the access to kidney transplantation (KT) and, once transplanted, in the incidence of rejections and long-term allograft survival despite aggressive induction and maintenance therapy. METHODS: This study retrospectively evaluates the impact of combining T- and B-cell-depleting agents and intravenous immunoglobulin for induction therapy in 45 highly sensitized KT patients (anti-panel reactive antibodies >60%, positive flow cytometry crossmatch or donor specific antibodies at the time of transplantation). The outcome data included the occurrence of biopsy-proven acute rejection, new-onset proteinuria, development of leukopenia, incidence of poliomavirus infection (BK or JC virus), fungal or bacterial infection after KT, de novo neoplasia, graft function, graft loss, or death with functioning KT. RESULTS: The average panel reactive antibody was 62.5%; 41 patients (91.1%) had ≥3 HLA mismatches with the donor and 91.1% of patients had class I or II anti-HLA antibodies. Fourteen patients (31.1%) presented pre-KT donor-specific antibodies and 6 patients (13.3%) had a positive flow cytometry cross-match at the time of transplantation. The incidence of acute rejection in the first 6 months was 24.4% and the cumulative incidence was 37.8%. Two patients were diagnosed with leukopenia in the first 6 months after KT. Two patients (4.5%) had cytomegalovirus disease, 17 patients (37.8%) were diagnosed with bacterial infections. Cutaneous neoplasms were identified in 5 patients (11.1%) and solid tumors in 4 (8.9%). The death-censored graft survival was 100% in the first 6 months and 93.5% at the last evaluation. Patient survival in the same periods was 97.8% and 93.3%, respectively. CONCLUSIONS: Induction immunosuppressive therapy with intravenous immunoglobulin and rituximab is effective; outcomes demonstrate an excellent patient and allograft survival and allograft function over the follow-up period.

Hepatitis C Virus Eradication in Kidney Transplant Recipients: A Single-Center Experience in Portugal.

INTRODUCTION: Hepatitis C (HCV) is a major cause of liver impairment post-kidney transplantation (KT). Anti-HCV direct-acting antivirals (DAA) made viral eradication possible. METHODS: We performed a retrospective review of KT patients (n = 23) who received DAA at our hospital. Sustained viral response (SVR) was defined as absence of viral detection 12 weeks after cessation of therapy. RESULTS: From 1985 to September 2017, 1440 patients underwent transplantation at Hospital Santa Cruz. From a total of 32 HCV RNA+ KT recipients on follow-up, we describe the first 23 patients treated with DAA. They were 56.7 ± 9.1 years old; 22 were white, 52.2% were males, they underwent transplantation 18.8 ± 9.0 years ago, and 13 had genotype 1B, 21 were naïve, and 9 had stages F3/F4. All but 2 patients, treated with grazoprevir/elbasvir, received sofosbuvir (18 with ledispasvir, 2 with daclastavir, and 4 with simultaneous ribavirin). Pretreatment, intra-treatment, and post-treatment creatinine clearances were 61.4, 60.6, and 60.7 mL/min/1.73 m2, respectively (not significant [NS]). Cyclosporine A was the basis of immunosuppression in the majority [(n = 14); pretreatment and intra-treatment levels were 79.5 ± 23.0 and 91.8 ± 26.0 ng/mL, respectively (P = .08)]; tacrolimus (n = 8) and mammalian target of rapamycin (mTOR) levels (n = 5) were also similar. One patient interrupted ribavirin after 7 weeks due to anemia; all other patients completed the treatment course without major side effects. Only 3 patients presented positive viral RNA at the fourth week of treatment and SVR was achieved in 100% of the patients 12 weeks after treatment. CONCLUSIONS: DAA therapy was well tolerated and effective in 100% of our treated patients, without significant impact on the renal function or on the immunosuppression.

HCV-infected Renal Transplant Recipients: Our Experience before the Availability of New Antiviral Drugs.

BACKGROUND: Natural history of HCV-infected renal transplant recipients is about to change with the invention of new drugs available for the treatment of HCV. OBJECTIVE: To analyze the evolution of renal transplant recipients infected with HCV in 30 years of activity of a Renal Transplantation Unit. METHODS: We studied 1334 patients who underwent renal transplantation between 1985 and 2015. RESULTS: 189 (14.2%) of these 1334 were found HCV seropositive. 60 were HCV RNA-positive for >6 months. 5 died with a functioning graft; 19 lost their graft and resumed dialysis. Most of the rejections occurred within the first year of the transplantation and none resulted in immediate loss of the graft. In post-transplantation period, 14 patients developed clinical hepatic disease, 10 manifested new-onset diabetes after transplantation, and 4 had de novo neoplasia, none of them had hepatocellular carcinoma. The outcomes of the different variables analyzed were similar between patients with HCV-infection and those with HCV and HBV co-infection. The median survival time was 13.4 (95% CI: 10.7-16.1) years; the median survival time of patients without HCV infection was 14.6 (95% CI: 13.8-15.4) years (p=0.23). CONCLUSION: In the era before the availability of new anti-HCV drugs, our experience with HCV-infected renal transplant recipients revealed similar post-transplantation complications, graft and patient survival as those not infected with HCV.

Kidney Graft Leiomyosarcoma: A Case Report.

BACKGROUND: Kidney transplant (KT) recipients have a higher incidence of malignancy than the general population. Smooth muscle tumors (SMT), including leiomyosarcoma, are rare in kidney transplant recipients, and most cases are associated with Epstein-Barr virus (EBV) infection. CASE REPORT: A 57-year-old man received a deceased donor kidney transplant at the age of 53 years, with 5 human leukocyte antigen (HLA) mismatches. Before the transplantation, the patient was IgG positive for EBV viral capsid antigen (VCA), negative for IgM EBV VCA, and also negative for IgG EBV nuclear antigen (EBNA), suggesting a prior EBV infection. He received immunosuppressive induction with basiliximab, and maintenance with tacrolimus, mycophenolate mofetil, and prednisolone. Two years after transplantation, he had an acute cellular rejection episode treated with methylprednisolone. An increased graft size was found 4 years after transplantation. A computed tomographic scan showed 3 solid tumors involving the renal graft with extension to the perinephric fat; no secondary localizations were found. A nephrectomy of the graft was performed. The histologic diagnosis was a high-grade leiomyosarcoma. In situ hybridization for EBV was negative. Nine months after nephrectomy, local recurrence was diagnosed. The surgical approach was unsuccessful, and the patient died after a brief period. CONCLUSION: Kidney leiomyosarcoma is a very rare clinical condition. Most of these neoplasms that arise in transplanted recipients are associated with EBV in tumor tissue. Only one case of renal graft leiomyosarcoma without EBV RNA in the tumor has been previously reported.

JC polyomavirus nephropathy confirmed by using an in-house polymerase chain reaction method.

We report the case of an isolated JC virus (JCV) infection, without co-infection by polyoma BK virus (BKV), associated with nephropathy 4 years after kidney transplantation. Clinical suspicion followed the observation of a decrease in estimated glomerular filtration rate (eGFR) and a renal allograft biopsy revealing polyomavirus-associated tubulointerstitial nephritis and positivity for SV40. An in-house real-time polymerase chain reaction assay, targeting the presence of JCV and the absence of BKV in biopsy tissue, confirmed diagnosis. Thirteen months after diagnosis, and following therapeutic measures, eGFR remains stable.

New law of renal transplantation in Portugal associated with more acute rejection episodes and higher costs.

The new law implemented in August 2007 changed the criteria to select renal transplantation (RT) candidates in Portugal, favoring hyperimmunized subjects and those on the waiting list for a longer time, making human leukocyte antigen (HLA) compatibilities less important. The authors compared patients who received a deceased donor kidney between 2005 and 2010. Patients were divided in group A who underwent transplantation before August 2007 (n = 132) and group B (n = 125) after that date. We considered a value of P < .05. Overall mean age at RT was 46.6 ± 13.9 years with 58.8% men, 88% on hemodialysis (HD), with a mean dialysis time of 82.8 ± 119 months. Also, 10.5% of patients underwent a previous transplantation. The mean follow-up was 35 ± 17.1 months. Group B showed significant adverse differences, including dialysis time (50.9 vs. 117 months), length of hospitalization (14.4 vs. 23.2 days), need for HD (1 vs. 3.4 days), HLA match (3.3 vs. 1.4 compatibilities), previous sensitization (4.4% vs. 21.7%), acute rejection episodes in the 1st year (23% vs. 37%), greater use of immunosuppressive drugs, higher costs of induction therapy (2790 vs 4360ϵ), and greater costs of drugs during first hospitalization (3456 vs. 7144ϵ). Among the 16 subjects who lost their grafts, 7 were in group A (3 in the first year) and 9 in group B all in the first year. There was a 5.1% decrease in graft survival at 12 months (P = .07). Univariate analysis showed an association of acute rejection episodes with HLA mismatches, hyperimmunized patients, absence of immediate graft function, hospitalization time, longer HD need, and higher creatinine level at months 1, 2, 3, and 6. Multivariate analysis revealed acute rejection episodes to be associated with a lower number of HLA compatibilities (odds ratio = 0.65; 95% confidence interval, [0.46-0.9]). Application of the law has led to a greater number of acute rejection episodes in the first year and increased costs.