Incidence and risk factors of herpes zoster among adult renal transplant recipients receiving universal antiviral prophylaxis.

BACKGROUND: Herpes zoster (HZ) is a significant cause of morbidity and complications in adult renal transplant recipients. We determined the incidence, complications and risk factors for the development of HZ after renal transplantation in a setting using universal antiviral prophylaxis. METHODS: The medical files of all adult renal transplants, performed between 2004 and 2008, were retrospectively reviewed to assess the clinical characteristics and risk factors of HZ. Incident cases of HZ were determined and the probability of developing post-transplant HZ for all subjects was calculated using the Kaplan Meier method. A multivariable Cox proportional hazards model was applied to assess the risk factors associated with the development of HZ. RESULTS: A total of 450 patients were eligible with a median follow up of 38 months. Twenty nine subjects (6.4%) developed HZ, the median time to onset was 18 months, only three of them (10.3%) required hospitalization, and none developed disseminated or visceral disease and death directly attributed to zoster. However, high rates of post-herpetic neuralgia (48.7%) were observed. Overall incidence was calculated at 20.6 cases per 1000 patient-years of follow-up. Following multivariate analysis, increased age ≥ 60 years old, positive pre-transplant history of varicella related disease and administration of rejection treatment conferred an increased risk of 4.00-fold (CI: 1.79-8.92), 16.00-fold (CI: 4.62-55.52), and 5.57-fold (CI: 1.56-19.84) respectively, for the development of post-transplant zoster. CONCLUSIONS: HZ remains a common complication after renal transplantation in adults under current immunosuppession protocols and universal antiviral prophylaxis.

Individualized scheme of immunoadsorption for the recurrence of idiopathic focal segmental glomerulosclerosis in the graft: a single center experience.

OBJECTIVES: To explore the role of immunoadsorption (IA) for the treatment of idiopathic focal segmental glomerulosclerosis (FSGS) recurrence in the renal allograft, if applied in a personalized manner. METHODS: We studied patients with end-stage renal disease (ESRD) due to idiopathic FSGS, transplanted between 2001 and 2010. Patients with FSGS recurrence were treated with daily sessions of IA for the first week, followed by an every other day scheme and then individualized tapering until discontinuation. Complete remission was defined as a reduction of 24-h proteinuria to ≤ 0.5 g/day and partial remission as a reduction of 24-h proteinuria to 50% or more from baseline. RESULTS: Of the 18 renal transplant recipients with ESRD due to idiopathic FSGS, 12 (66.7%) experienced disease recurrence in a mean time of 0.75 months post-transplantation (KTx), with a mean proteinuria of 8.9 g/day at the time of recurrence. The mean recipient age was 30.8 years; the mean donor age was 47.4 years, while living related donors provided the allograft in seven cases. Four of the patients received therapy with rituximab in addition to IA. During a mean time of follow-up of 48.3 months, seven patients (58.3%) achieved complete remission, and five (41.7%) partial remission. At the end of follow-up, eight patients (66.7%) had functioning grafts, being in sustained remission, in contrast to four patients (33.3%), who ended up in ESRD because of FSGS recurrence. CONCLUSIONS: IA was shown efficacious in a small series of patients with recurrent FSGS in the graft. Renal function remained stable in eight of the 12 patients with FSGS recurrence.

Valproate-induced hyperammonemic encephalopathy in a renal transplanted patient.

Neurological complications after renal transplantation constitute an important cause of morbidity and mortality. Their differential diagnosis is difficult and essential for subsequent patient's management. Valproate-induced hyperammonemic encephalopathy is an uncommon but serious effect of valproate treatment. Here, we describe the case of a 15-year-old girl who was on a long-term therapy with valproate due to epilepsy and revealed impaired consciousness with hyperammonemia 12 days after renal transplantation. After withdraw of valproate, patients' symptoms resolved within 24 h. Clinicians should increase their awareness for potential complication of valproate, especially in transplanted patients.

Kidney transplantation outcomes from expanded criteria donors, standard criteria donors or living donors older than 60 years.

OBJECTIVES: To evaluate outcomes in kidney allograft recipients from donors with expanded criteria (ECD) versus standard criteria (SCD) or living donors (LD) >60 years. METHODS: We studied all patients who received a kidney between 2005 and 2011, focusing in recipients of kidneys from deceased ECD, SCD and LD >60 years. ECD was any deceased donor >60 years or >50 years with two of the following: hypertension (HTN), stroke as the cause of death, or serum creatinine >1.5 mg/dL. We recorded characteristics of the transplant procedure, patient, graft survival and renal function 1 year after transplantation and at the end of follow-up. RESULTS: Six-hundred and five patients were transplanted between 2005 and 2011 in our department. There were 142 (25.1%) transplantations from ECD, 192 (33.98%) from SCD and 96 (16.99%) from LDs older than 60 years. In a mean follow-up time of 36.4 months, graft survival rates were similar for all groups. Calculated GFR was found statistically different between the ECD and SCD groups, but still satisfactory at first year, and at end of follow-up time. Comparison of the patients, who received transplants from ECD, even older than 70 years, and those from LD >60 years revealed equivalent renal function in short and long term. CONCLUSIONS: Utilization of marginal kidneys effectively doubled our deceased transplant volume in the period 2005-2011. Patients' and graft survival were shown similar at the end of follow-up for all groups. Renal outcomes were shown equivalent between the ECD and LD >60 years groups, and although significantly lower between the ECD and the SCD group, were still very satisfactory.

Multiple bilateral oncocytomas of the native kidneys following renal transplantation: report of a rare case and review of the literature.

Renal oncocytomas are benign tumors of the kidneys, which are usually diagnosed postoperatively, due to differential diagnostic problems, from a sample of a renal cell carcinoma. The development of a renal oncocytoma in the native kidneys following renal transplantation is a very rare condition and only a few cases have been published in the world literature. In this case report we present a unique case of bilateral multifocal renal oncocytomas of the native kidneys in a female transplant recipient 6 years after renal transplantation. The patient's postoperative clinical course was uneventful and no local recurrence or distant metastasis has been found so far. The pathology, clinical characteristics, and treatment of renal oncocytomas are also reviewed.

Impact of Primary Disease Nature in the Development of De Novo Donor-Specific Antibodies After Kidney Transplant and the Risk of Acute Rejection.

OBJECTIVES: In this study, we explored the effect of the primary disease nature on development of de novo donor-specific antibodies after kidney transplant. MATERIALS AND METHODS: We retrospectively studied kidney transplant recipients based on their primary disease. Patients were divided according to autoimmune and nonautoimmune diseases. The frequency of de novo donor-specific antibodies posttransplant and the incidence of acute rejection were estimated. De novo donor-specific antibodies were determined by the Luminex (LAB Screen products, One Lambda, Inc., Canoga Park, CA, USA) assay. RESULTS: Our study included 228 patients: 92 with autoimmune diseases and 136 with nonautoimmune diseases. Similar rates of de novo donor-specific antibodies (10.9% vs 11.8%; P = .835) were shown in the 2 groups over a mean (standard deviation) follow-up of 56.5 (27.8) months. In the nonautoimmune group, presence of de novo donor-specific antibodies was associated with higher rates of biopsy-proven acute rejection (37.5% vs 8.3%; odds ratio = 6.6; 95% confidence interval, 1.985-21.945; P = .002) versus that shown in patients of the same group without de novo donor-specific antibodies. In the autoimmune group, biopsy-proven acute rejection rates were similar between patients with and without de novo donor-specific antibodies. Mean fluorescence intensity titers of de novo donor-specific antibodies were significantly higher in patients with nonautoimmune primary disease (P = .003).Overall, graft loss was shown to be significantly higher in patients with autoimmune than in patients with nonautoimmune diseases (P < .001), although not different between patients with de novo donor-specific antibody formation (P = .677). CONCLUSIONS: No associations were shown between the frequency of de novo donor-specific antibody development after kidney transplant and the nature of the primary disease (autoimmune vs nonautoimmune). Detection of de novo donor-specific antibodies was associated with higher rates of biopsy-proven acute rejection among patients with nonautoimmune primary disease.

Primary Hepatic Burkitt Lymphoma in a Kidney Transplant Recipient.

This is a case of a renal transplant recipient who developed a primary hepatic Burkitt lymphoma a few years after kidney transplantation. The past medical history of the patient was significant for anti-HCV positivity with liver histopathology showing minimal changes of grades 0 and 1, stage 0. She received a graft from a deceased donor, with rabbit antithymocyte globulin and methyl-prednisolone, as induction therapy, and was maintained on azathioprine, cyclosporine, and low dose methyl-prednisolone with normal renal function. Four years after KTx she presented with fatigue, hepatomegaly, and impaired liver function and the workup revealed multiple, variable-sized, low density nodules in the liver, due to diffuse monotonous infiltration of highly malignant non-Hodgkin lymphoma of B-cells, which turned out to be a Burkitt lymphoma. Bone marrow biopsy and spinal fluid exam were free of lymphoma cells. At time of lymphoma diagnosis she was shown to be positive for Epstein-Barr virus polymerase chain reaction. She received aggressive chemotherapy but died due to sepsis, as a result of toxicity of therapy.

Prevalence of human herpesvirus 8 DNA sequences in human immunodeficiency virus-negative individuals without Kaposi's sarcoma in Greece.

BACKGROUND: It has already been established that the prevalence of human herpes virus 8 (HHV8) in the general population varies among different geographical areas. The objective of this study was to evaluate the prevalence of HHV8 infection in the Greek population. MATERIALS AND METHODS: Eight hundred blood samples were collected consecutively from human immunodeficiency virus (HIV)-negative individuals without evidence of Kaposi's sarcoma (KS). All individuals were Greeks and were classified according to gender, age and geographic origin. HHV8 DNA sequences were detected by nested-PCR. RESULTS: An overall HHV8 positivity rate of 9.6% was found. Analysis of the KS330 region within ORF-26 revealed that the HHV8 strains were distributed to the C1, C3 or A1 subtypes. Logistic regression showed no association between HHV8 presence and geographic regions in Greece. The results indicate that very few individuals (4.3%) were exposed to HHV8 before 15 years of age. The infection rate peaked (16.4%) between the ages of 31 and 40. Females and males showed similar prevalence of HHV8. CONCLUSION: The data suggest that HHV8 is spread in Greece, but to a lesser extent than that observed in other Mediterranean countries. The fact that HHV8 was also found in individuals under 15 years of age indicates that a small percent of HHV8 transmission could occur through non-sexual contacts.

Excellent long term patient and renal allograft survival after ABO-incompatible kidney transplantation: Experience of one center.

AIM: To investigate the long-term results of ABO-incompatible (ABOi) kidney transplantation in a single center in Greece. METHODS: Thirty consecutive ABOi kidney transplantations were performed from June 2005 to December 2013. All patients received rituximab one month prior to transplantation. Immunoadsorption therapy was performed for the removal of anti-A/B IgG antibodies until the titer was ≤ 1:16. Additional apheresis sessions were performed post-operatively. Intravenous immunoglobulin and oral immunosuppression consisting of tacrolimus (TAC) in combination with either everolimus or mycophenolate acid was administered. We compared the long term results of our ABOi group to those of a matched group of 30 ABO compatible (ABOc) living kidney recipients with similar baseline characteristics. The ABOc recipients received an immunosuppressive regimen consisting of TAC and mycophenolate acid. All patients in both groups received induction therapy with Basiliximab or Daclizumab, whereas corticosteroids were instituted on the day of surgery. During the follow-up period, indication biopsies were performed and interpreted by an experienced nephropathologist. The parameters we analyzed included the following: Donor/recipient age, gender, blood type, human leukocyte antigen mismatches, panel reactive antibodies, primary cause of renal failure, mean time on dialysis, immunosuppressive regimen, patient survival, graft outcome, incidence of rejections, surgical and infectious complications. RESULTS: The mean follow-up period was 6 years (range 1 to 9 years). A mean of 5.0 ± 3.0 (range 0-14) pre-transplant immunoadsorptions were required in order to reach the target titer. Patient survival in ABOi group in comparison to ABOc group at 1, 3, 5 and 8 years did not differ significantly (100% vs 100%, 96% vs 100%, 92% vs 100% and 92% vs 100%, P = ns). Additionally, graft survival was similar in the two groups at the same time points (100% vs 100%, 96% vs 96%, 92% vs 96% and 81% vs 92%, P = ns). The mean serum creatinine and the estimated glomerular filtration rate by the modification of diet in renal disease formula at 1, 3, 5 and 8 years did not differ significantly between ABOi and ABOc group. None of the patients in the ABOi group developed acute or chronic antibody-mediated rejection evidenced by histological signs. Four patients (13.3%) in the ABOi group and 3 (10%) in the ABOc group experienced acute cellular rejection, which was treated successfully in all cases. Bacterial and viral infections were also similar between the two groups. CONCLUSION: ABOi kidney transplantation is a safe and effective alternative that enables kidney transplantation in countries with unacceptably long deceased-donor waiting lists.

The interleukin-6-174 promoter polymorphism is associated with a risk of development of Kaposi's sarcoma in renal transplant recipients.

BACKGROUND: Kaposi's sarcoma (KS), an angio-proliferative inflammation lesion, is frequently secondary to clinical immunosuppression such as after renal transplantation. KS growth is promoted by the inflammatory cytokine interleukin-6 (IL-6) and is also correlated with human herpesvirus-8 (HHV-8) infection. MATERIALS AND METHODS: In a sample of 15 renal transplant patients with KS and 40 patients without KS, we explored the influence of genetic differences in the production of IL-6 by promoter polymorphisms G-174C as well as the correlation with HHV-8 DNA. RESULTS: The G allele homozygotes, which are associated with increased IL-6 production, had increased KS incidence (p=0.008). Therefore increased IL-6 production constitutes a risk factor which should be considered in clinical immunosuppression. CONCLUSION: In addition to the HHV-8 infection, the interleukin-6 promoter polymorphism G-174C is associated with a risk of development of KS in renal transplant recipients.

Mycotic pseudoaneurysms complicating renal transplantation: a case series and review of literature.

INTRODUCTION: Kidney transplantation can be complicated by infection and subsequent development of mycotic aneurysm, endangering the survival of the graft and the patient. Management of this condition in five cases is discussed, accompanied by a review of the relevant literature. CASE PRESENTATIONS: Five patients, three men 42-, 67- and 57-years-old and two women 55- and 21-years-old (mean age of 48 years), all Caucasians, developed a mycotic aneurysm in the region of the anastomosis between renal graft artery and iliac axes. Four patients presented with systemic fever and iliac fossa pain and one presented with hemorrhagic shock. Morphologic investigation by color doppler ultrasonography revealed a pseudoaneurysm at the anastomotic site. A combination of antibiotic therapy, surgery and interventional procedures was required as all kidney transplants had to be removed. No recurrence was recorded during the follow-up period. CONCLUSIONS: A high index of suspicion is required for the timely diagnosis of a mycotic aneurysm; aggressive treatment with cover stents and/or surgical excision is necessary in order to prevent potentially fatal complications.

Optimal utilization of expanded criteria deceased donors for kidney transplantation.

BACKGROUND: The utilization of kidney grafts from expanded criteria donors (ECDs) needs to be evaluated within the context of critical organ shortage and graft function and survival. The impact of donor risk variables on kidney transplantation (KTx) outcome was investigated. METHODS: A retrospective review of 75 KTxs from ECDs over a 5-year period was performed. Donor risk factors were analyzed separately and correlated with recipients graft function and survival. RESULTS: Sixty-four recipients out of 75 (85.3%) had functioning grafts 5 years post-transplant. The overall actuarial graft survival rates at 1 through 5 years were 87.5, 68.1, 57.3, 55.4, and 47.3%, respectively. Forty-seven kidneys (62.7%) had early function with actuarial survival of 100.0, 88.3, 75.8, 75.8, and 68.4% at 1-5 years post-transplant, and 28 (37.3%) grafts presented delayed function with substantially decreased actuarial survival, ranging from 66.7 to 23.2%. KTxs from elderly donors had remarkable actuarial survival rates ranging from 100.0 to 67.0%, at 1-5 years, being the best graft survival rates among KTxs from other donor categories. The other donor risk variables when associated with old age had an adverse effect on recipient graft function and survival, but none alone or a combination of the two, showed any significant statistical variability. CONCLUSION: ECDs significantly increased the kidney pool and can be utilized safely if adequate measures are taken.

Nonmelanoma skin cancer after renal transplantation: a single-center experience in 1736 transplantations.

BACKGROUND: Renal transplantation is associated with an increased incidence of nonmela-noma skin cancer (NMSC) caused by immunosuppression. Squamous cell carcinoma (SCC) and basal cell carcinoma (BCC), the two major histological types of NMSC, exhibit more aggressive biological and clinical courses in renal transplant recipients (RTRs), with higher rates of recurrence and mortality than in the general population. METHODS: We retrospectively analyzed our experience of NMSC in 1736 renal transplantations performed over a 25-year period. All cases of skin cancer after renal transplantation were included except those of skin cancer resulting from melanoma and mesenchymal skin tumors. RESULTS: In our series, the overall incidence of NMSC after transplantation was 2.2% (n = 39), and SCC represented the most frequent skin malignancy (64.1%), followed by BCC (17.9%), Bowen's disease (10.2%), basosquamous carcinoma (5.1%), and a rare case of invasive sebaceous carcinoma (2.6%). A shift to newer immunosuppressive regimens after the initial diagnosis of NMSC had been implemented in eight cases (20.5%). The recurrence rate after initial treatment was 41% (n = 16), and distant metastatic disease was diagnosed in 15.4% (n = 6) of NMSC patients. The NMSC-specific mortality rate was 25.6% (n = 10). CONCLUSIONS: Nonmelanoma skin cancer remains a significant source of morbidity and mortality in RTRs, and post-transplant surveillance should be increased.

De novo renal cell carcinoma in a kidney allograft 13 years after transplantation: a case report and review of the literature.

De novo carcinoma of the renal transplant is a rare but disastrous clinical entity. We report such a tumor developing 13 years after transplantation and describe its clinical presentation, diagnostic approach and therapy. The importance of a surveillance program allowing early detection of tumor developing in the renal transplant is emphasized.

Urgent superselective segmental renal artery embolization in the treatment of life-threatening renal hemorrhage.

INTRODUCTION: Renal hemorrhage is a major life-threatening condition that can be caused by trauma, operation, biopsy, as well as sudden spontaneous rupture of renal tumors or aneurysms. We report our experience with superselective segmental renal artery catheterization and embolization as therapeutic options for such cases. PATIENTS AND METHODS: Over the last 8 years, 28 patients with severe renal hemorrhage were admitted for evaluation and possible further treatment. Twenty of them had a history of previous biopsy (6 of them one of a transplanted kidney), 1 patient had a recent percutaneous nephrostomy, 4 patients presented with renal mass ruptures (2 patients renal cell carcinoma, 1 patient angiomyolipoma, 1 patient hemorrhagic cysts), 1 patient had rupture of a renal aneurysm during delivery, 1 patient suffered bleeding after partial nephrectomy, and 1 patient was hospitalized after a car accident. They all presented with clinical signs of hemodynamic instability. Angiographic investigation of the kidneys preceded further intervention in all cases. 26 out of the 28 patients underwent superselective embolization of the specific bleeding vessel with the use of microcoils and/or Gelfoam particles. RESULTS: All patients treated by superselective segmental renal artery embolization had a successful outcome, including a steady renal function and a stable clinical course. No complications occurred. CONCLUSION: Superselective segmental renal artery catheterization and embolization is a safe and efficient method for the treatment of patients with severe renal hemorrhage, preserving healthy renal parenchyma and renal function.

Clinicopathological aspects of 18 Kaposi's sarcoma among 1055 Greek renal transplant recipients.

The incidence of Kaposi's sarcoma (KS) in transplant recipients is 400-500 times greater than that in the general population, and is rising within the transplant population. In this study, between March 1983 and December 2001, 1055 cases were recorded where KS developed in 18 patients (1.7%) who were treated with AZA + CsA + MP, MMF + CsA + MP, MMF + Tac + MP, CsA + MP, or AZA + MP therapy (AZA, azathioprine; CsA, cyclosporine A; MP, methylprednisolone; MMF, mycophenolate mofetil; Tac, Tacrolimus). In the present study, 18 renal transplant recipients who developed KS and were followed and analyzed. Analysis revealed that a continuous state of immunodeficiency is important for the development of KS. Prognosis in patients with KS limited to the skin is favorable, while visceral involvement is associated with high mortality. Transplant function is well preserved in most of the cases. The association, previously described, between human herpesvirus 8 (HHV8) and transplant-associated KS also exists in the studied population.