Pyomyositis in a Patient with IgA Nephropathy and Kidney Transplant.

Infections are among the most common complications transplant physicians face when dealing with solid organ transplant recipients. We present a case of pyomyositis caused by Staphylococcus aureus in a patient with IgA nephropathy and a kidney transplant, under treatment with mTOR inhibitors and prednisone. This entity is a rare intramuscular infection, given the resistance of healthy muscle to colonization. We review the most frequent agents, the diagnostic algorithm, and therapeutic alternatives. We also comment on the role of mTOR inhibitors in this case as possible predisposing factor for the infection.

Association of Brain-Dead Donors' Terminal Inflammation With Delayed Graft Function in Kidney Transplant Recipients.

BACKGROUND: Systemic inflammation affects kidney function in a wide range of diseases. Even in kidney transplant recipients, higher levels of C-reactive protein (CRP) are invariably associated with both worse short- and long-term graft outcomes. However, little is known about systemic inflammation in kidney donors and, notably, brain death causes a strong systemic inflammatory response. OBJECTIVE: To analyze the role of systemic inflammation of brain-dead donors on short-term kidney graft outcomes (ie, delayed graft function [DGF], defined as the need of dialysis during the first week after transplantation). MATERIALS AND METHODS: Retrospective analysis of clinical and biochemical characteristics of all brain-dead kidney donors generated in the Hospital Clínic of Barcelona in the 2006 to 2015 period (n = 194). Donors who were tested for CRP in the 24 hours before BD declaration were included (n = 97, 50% of initial population). Clinical and biochemical features of their respective recipients (n = 165) were analyzed, comparing recipients who developed DGF (n = 30) with recipients who did not (n = 135). RESULTS: Donors whose recipients later developed DGF had much higher CRP values (10.58 [5.1-18.21] vs 4.81 [1.42-12.2] mg/dL, P = .025). Other characteristics associated with the development of DGF were renal biopsy score and recipient dialysis vintage (P = .025 and P = .002, respectively). In logistic regression analysis, PCR maintained significance in the non-expanded criteria donor (ECD) group (odds ratio [OR], 1.102; P = .027), but it lost significance in the ECD group (P = .67). CONCLUSIONS: Terminal donor CRP was associated with DGF in kidney transplant recipients and proved to be mostly significant in younger donors.

Relationship Between Vitamin D Blood Levels and Cancer Development in Renal Transplant Patients: A Case-Control Study.

BACKGROUND: Malignancy is one of the most common long-term complications in renal transplant patients, often related to immunosuppressive treatment although other factors could be considered. Vitamin D plays an important role in reducing cancer risk. After kidney transplantation (KT), 25-hydroxyvitamin D (25OH-D, or calcidiol) insufficiency concerns >85%. The main aim of the present study was to determine the relationship between calcidiol blood levels and cancer development in KT recipients. METHODS: This was a retrospective observational case-control study including patients who received transplants in our hospital from 2003 to 2009 with a follow-up period to 2015. A total of 738 patients were included; 94 of them developed malignancy process, 80 of whose tumor data were analyzed in the cancer group, and the rest composed the control group. At the moment of cancer presentation, age, sex, primary kidney disease, time after surgery, immunosuppressant schedule, and 25OH-D blood levels were collected. RESULTS: The mean patient age was 57 years. The percentages of man and women were 59.5% and 41.5%. The predominant etiology of kidney disease was chronic glomerulonephritis in 31.9%. There were no significant differences between sex, primary kidney disease, immunosuppressant schedule, or incidence of neoplasm in each group of patients. There were no significant differences in 25OH-D blood levels. The incidence of cancer was 7.1%-13.7% per year. The mean time between the graft surgery and the event was 5.6 years. CONCLUSIONS: In patients with functioning KT, we found no correlation between blood levels of calcidiol and the incidence of cancer.

Inhibition of JAK3 and PKC via Immunosuppressive Drugs Tofacitinib and Sotrastaurin Inhibits Proliferation of Human B Lymphocytes In Vitro.

BACKGROUND: Antibody-mediated response in solid organ transplantation is critical for graft dysfunction and loss. The use of immunosuppressive agents partially inhibits the B-lymphocyte response leading to a risk of acute and chronic antibody-mediated rejection. This study evaluated the impact of JAK3 and PKC inhibitors tofacitinib (Tofa) and sotrastaurin (STN), respectively, on B-cell proliferation, apoptosis, and activation in vitro. METHODS: Human B cells isolated from peripheral blood of healthy volunteers were cocultured with CD40 ligand-transfected fibroblasts as feeder cells in the presence of interleukin (IL) 2, IL-10, and IL-21. The cocultures were treated with immunosuppressants Tofa, STN, and rapamycin (as a control), to analyze the proliferation and apoptosis of B cells by means of Cyquant and flow cytometry, respectively. CD27 and IgG staining were applied to evaluate whether treatments modified the activation of B cells. RESULTS: Tofa and STN were able to inhibit B-cell proliferation to the same extent as rapamycin, without inducing cell apoptosis. After 6 days in coculture with feeder cells, all B cells showed CD27 memory B-cell phenotype. None of the immunosuppressive treatments modified the proportion between class-switched and non-class-switched memory B cells observed in nontreated cultures. The high predominance of CD27+CD24+ phenotype was not modified by any immunosuppressive treatment. CONCLUSIONS: Our results show that Tofa and STN can suppress B-cell antibody responses to an extent similar to rapamycin, in vitro; therefore these compounds may be a useful therapy against antibody-mediated rejection in transplantation.

Desensitization Before Living Donor Kidney Transplantation in Highly HLA-Sensitized Patients: A Single-Center Study.

BACKGROUND: Renal transplantation in highly sensitized patients represents a major clinical challenge leading to long periods on the waiting list. When a living donor is available, the use of different strategies to desensitize recipients with preformed human leukocyte antigen antibodies can allow a successful transplantation. METHODS: We performed a retrospective observational study including all living donor kidney transplantation (LDKT) with desensitization (DS) from 2008 to 2014 in our transplant unit. The rates of rejection and graft survival were evaluated. DS consisted of plasma exchange (PE), rituximab (RTX), and intravenous immunoglobulin (IVIG) induction with thymoglobulin and maintenance immunosuppression with tacrolimus, corticosteroids, and mycophenolate mofetil. RESULTS: From 2008 to 2014, we performed 368 LDKT, with 31 receiving desensitization. Seven cases from a clinical trial were excluded. Demographic data and outcomes were recorded. All of the patients received RTX + PE + IVIG. DS was performed for positive complement-dependent cytotoxicity cross-match (4.2%), T-cell- and/or B-cell-positive flow cytometry cross-match (87.5%) and presence of donor-specific antibodies alone (8.3%). We identified 23 episodes of rejection in 12 patients (50%); 79% were antibody-mediated rejections (AMR). Graft failure was 12.5%, with a mean time to graft loss of 229 ± 203 days. Mean follow-up was 37 ± 27 months, and graft survival was 91% and 86% at 1 and 5 years, respectively. CONCLUSIONS: Desensitization in LDKT appears to offer an acceptable option for highly sensitized patients. In our series, 41% presented an AMR and 12.5% showed transplant glomerulopathy in protocol and/or indication biopsies. However, short-term outcomes and graft survival were satisfactory.

Desensitization in ABO-Incompatible Kidney Transplantation With Low ABO Iso-Agglutinin Titers.

BACKGROUND: In ABO-incompatible (ABOi) kidney transplantation (KT) with low iso-agglutinin (IG) titers (IGT), standard pre-conditioning treatment might be excessive. To try to answer this question, we evaluated the pre-conditioning requirements of a group of ABOi KT with low ABO IGT in our center. Our main objective was to assess desensitization requirements for ABOi KT with low IGT (<16) at Hospital Clinic of Barcelona from 2006 to 2014. METHODS: A retrospective study of desensitization (rituximab and plasma exchange [PE]) requirements for ABOi KT with IGT <16 was conducted. RESULTS: One and 5 years after KT, patient survival was 100%. Renal graft survival was 90% at 1 and 5 years after KT. Mean PE performed before KT was 1.7 (standard deviation [SD], 1.703); 50% of the patients did not receive PE after transplantation, 30% received 2 sessions of PE, and 20% received only 1. The average is 0.8 (SD, 0.91).Follow-up IG determinations remained with low titers (≤8/8). No rebounds of titers were observed during the first 4 to 6 months after transplantation. CONCLUSIONS: Recipients with IGT ≤8 required none or only 1 PE session to reach acceptable titers (titers ≤4) to perform ABOi KT safely. This information is useful to assess the possibility of a minimized desensitization protocol in ABOi KT donors with low titers of IG to reduce adverse effects, reduce cost, and simplify pre-transplant logistics.

Pre-Emptive Retransplantation in Patients With Chronic Kidney Graft Failure.

INTRODUCTION: The aim of this study was to compare the group of patients receiving a new kidney transplant before starting dialysis again (pre-reTR) with a group of patients receiving a new kidney transplant after restarting dialysis (reTR). METHODS: This retrospective cohort included all the kidney retransplantations (second transplantations) between 2000 and 2012 performed at our center and their follow-up until July 2014. We analysed graft and patient survival, rejection rates, and immunologic parameters of these patients. RESULTS: We studied 18 patients who had pre-reTR and 83 who had reTR. In the pre-reTR group no patient had panel-reactive assay (PRA) >10% at any time. In the reTR group 26.5% had PRA >10% at the time of transplantation (P = .014) and 54.2% had a historical highest PRA >10% (P < .001). The rejection rate was 11.1% in the pre-reTR group and 27.7% in the reTR group during the first year post-retransplantation (P = .227). Patient survival rate was 100% in the pre-reTR group at 5 years of follow-up, whereas in the reTR group at 1 year it was 95.2% and 85.9% at 5 years after retransplantation. Allograft survival at 1 and 5 years was 88% and 89%, respectively, in the pre-reTR group. On the other hand, in the reTR group it was 89% after the first year and 65% at 5 years post-retransplantation. CONCLUSION: Pre-emptive renal retransplantation is a feasible option that should be assessed in patients with kidney graft failure and may help to minimize the morbidity associated with dialysis reinitiation.

Economic analysis of the treatment of end-stage renal disease treatment: living-donor kidney transplantation versus hemodialysis.

INTRODUCTION: End-stage renal disease (ESRD) is a major public health problem in the Spanish health system. Kidney transplantation is the treatment of choice, offering better survival and cost-effectiveness than other alternatives. This study aimed to compare the cost of living-donor kidney transplantation (LDKT) during the first year after transplantation with that of hemodialysis (HD). METHOD: A prospective, descriptive study of cost and efficacy was performed in the Hospital Clinic in Barcelona from January to December 2011. We included 106 patients (57 undergoing HD and 49 receiving a LDKT). The costs of LDKT (donor and recipient) and HD were calculated based on our economic database program. RESULTS: The mean age of recipients and donors was 46 ± 15 and 52 ± 10 years, respectively, and 67% of the recipients were men. In HD patients, the mean age was 67 ± 11 years and 62% were men. The total cost of LDKT was €29,897.91 (€8,128.44 for donors and €21,769.47 for recipients). The total cost of HD was €43,000.88 (€37,917 for HD and related procedures plus €5,082 for transport). LDKT represented a savings of €13,102.97 per patient/year and the payback period was less than 1 year. Quality-adjusted life years were higher in LDKT than in HD patients. CONCLUSION: LDKT is cost effective during the first year after transplantation and is associated with enhanced quality of life. From both the medical and economic points of view, pre-emptive LDKD should be encouraged in Spain to reduce the health budget for ESRD.

Polyclonal versus monoclonal induction therapy in a calcineurin inhibitor-free immunosuppressive therapy in renal transplantation: a comparison of efficacy and costs.

BACKGROUND: Induction therapy in renal transplantation reduces the incidence of acute rejection (AR) in expanded criteria donation (ECD) and donation after cardiac death (DCD). We compared the efficacy of Thymoglobulin (Sanofi-Aventis, Spain), ATG Fresenius (ATG-Fresenius, Spain), and Simulect (Novartis Farm, Spain) in a calcineurin-free protocol in ECD and DCD renal transplantation by evaluating patient survival, graft survival, and AR at 1 year and overall costs. METHODS: An observational retrospective study was performed using our database of 289 consecutive cadaveric ECD renal transplant recipients (n = 178) and DCD recipients (n = 111) from April 1999 to December 2011. Induction therapy consisted of Simulect, Thymoglobulin, and ATG Fresenius. Calcineurin-inhibitor (CNI)-free maintenance therapy consisted of mycophenolate mofetil or sodium and steroids. RESULTS: There were no differences in the patients' demographic characteristics or patient and graft survival. One-year AR rates were equivalent (ECD: 10%, 19.1%, 17.7% versus DCD: 14.3%, 7.1%, 16.7%). Leukopenia and thrombopenia were significantly more frequent in the ECD group treated with polyclonal induction. The average total cost of transplantation was higher in the ECD group but there were no significant differences in the average total cost between ECD and DCD: 39,970.31 ± 7,732€ versus 35,058.34 ± 6,801€ (P = NS). CONCLUSION: Our study shows the same efficacy with polyclonal and monoclonal antibody induction and a CNI-free treatment regimen in ECD and DCD renal transplantation with no differences in overall costs at 1 year after transplantation.

Living donor psychosocial assesment/follow-up practices in the partners' countries of the ELIPSY project.

BACKGROUND: Living donor (LD) transplantation has increased recently, but psychosocial aspects of living donation have not been well characterized, as risk factors for the donors. ELIPSY is a project confunded by EAHC, seeking to develop a common methodology for all EU countries for LD assessment/follow-up in the psychosocial sphere (www.eulivingdonor.eu). OBJECTIVE: To evaluate current psychosocial LD assessment/follow-up practices among European centers for key aspects and differences between kidney and liver programs. METHODS: Within a timeline of 30 months, this phase of the project sought to identify current LD psychosocial assessment/follow-up practices. The final survey concerned two versions focused on the kidney and on liver transplant program. The survey took place in ELIPSY partner centers under their own responsibility. Each of the centers sent the survey to other ones performing LD in their country. Partners in the EULID project includes ones in the United Kingdom, Poland, and Romania. The results were analyzed separately for each program seeking to compare and define differences among them. RESULTS: The survey took place in 10 European countries including 65 centers with LD programs. Positive answers regarding psychosocial assessment/follow-up practices were obtained for 26 (42%) kidney and nine (38%) liver centers. Some centers perform several psychosocial follow-ups but did not explain their tools, whereas the centers that did explain the tools used the same ones for both programs.

Preemptive use of Mammalian target of rapamycin inhibitors in living donor transplantation.

UNLABELLED: Sirolimus (SRL) has demonstrated beneficial impacts on the development of chronic allograft dysfunction (CAD). In living donor transplantation, strategies mostly seek to prevent graft dysfunction and respond to a decline in renal function. The present study focused on proactive, preemptive SRL administration for patients with repeated renal transplantations and those engrafted with an extended criteria donor organ. MATERIAL AND METHODS: This retrospective, monocenter study describes 7 renal transplant recipients with stable graft function receiving SRL within the first year posttransplantation and 3 recipients of second transplantations who started SRL treatment before obtaining their repeat grafts. RESULTS: A proactive use of SRL revealed stable renal function parameters at 1 year after SRL introduction: Creatinine 1.33 ± 0.21 mg/dL; Modification of Diet in Renal Disease (MDRD) equation glomerular filtration rate, 57 ± 19 mL/min; PU 452 ± 338 mg/24 hours. Cell counts, hemoglobin concentrations, as well as triglyceride and total cholesterol levels did not differ over the 1-year follow-up. SRL administration before retransplantation provided good graft survival and renal function with a creatinine of 1.2 ± .32 mg/dL, MDRD of 60 ± 28 mg/dL, and PU 502 ± 432 mg/24 hour. Cell counts, hemoglobin concentrations, as well as triglyceride and total cholesterol levels did not differ over 1-year follow-up. CONCLUSION: Preemptive SRL-induction before signs of graft deterioration or chronic injury may be a useful approach to prevent CAD.

Third and fourth kidney transplant: still a reasonable option.

INTRODUCTION: At present, a second kidney transplant is considered an established therapeutic option for patients who have lost a previous graft. Second transplants show similar graft survival as first transplants. A debate exists about the benefit of submitting the patient to a third or fourth renal transplant, or to maintain dialysis. OBJECTIVE: We sought to analyze graft and patient survivals as well as associated variables and surgical complications of third and fourth transplantations. MATERIAL AND METHODS: From July 1985 to December 2008, we performed 74 third and 8 fourth transplantations among 2763 cases. We prospectively collected the variables of age, gender, graft origin, hyperimmunization, time on dialysis, location, bench surgery, acute rejection episodes, graft survival, and operative complications. RESULTS: Third and fourth trasplantations were performed in 49 men and 33 women, with an overall mean age of 40.26 years who were on dialysis for an average of 126.89 months before transplantation. Mean graft survivals of their first and second grafts were 35.6 and 50.1 months, respectively. Acute or chronic rejection was reason for renal failure in 71% and 75% of cases, respectively. Patient survivals at 1 and 5 years were 92.7% and 90.6%, for third and both 85.7% for the fourth transplantation. The third and fourth transplantations showed 1- and 5-year graft survivals of 88% and 76.4% and 71.4% and 42.9%, respectively. Sixty-eight cases underwent cadaveric donor and 14 living donor (mean age, 42.1 years) transplantations. Nine patients were hyperimmunized. In 60 cases, we used the left kidney. Orthotopic kidney transplantation was performed in 15 cases; heterotopic transplant to the right iliac fossa in 40 and in the left iliac fossa in 17 cases. Arterial bench surgery was necessary in 6 cases and venous in 3. We performed 3 hepatorenal and 1 cardiorenal transplantation. The complications included 29 cases (35.4%) of postoperative acute tubular necrosis, 14 of acute rejection episodes (17.1%); 12 of perirenal hematoma (14.6%); 1 urinary fistula (1.2%); 4 lymphocele (4.9%); 2 ureteral stenosis (2.4%); variables arterial kink requiring surgery (1.2%), and 1 venous thrombosis with graft loss (1.2%). The 4 patients who died in the perioperative period succumbed to intravascular disseminated coagulation (n = 1) cardiac failure (n = 2), and septic shock (n = 1). Induction antibody therapy, hyperimmunized status, or operative complications were not independent prognostic factors for patient or graft survival. CONCLUSIONS: Third or fourth renal transplantations constitute a valid therapeutic option with reasonable short- and long-term patient and graft survivals. Although orthotopic kidney transplantation was used in selected patients, we preferred an iliac fossa approach for most.

[ABO incompatible living donor kidney transplantation: a dream come true. Experience of Hospital Clínic of Barcelona]. / Trasplante renal ABO incompatible: de un sueño a una realidad. Experiencia del Hospital Clínic de Barcelona.

INTRODUCTION: During the last years the number of patients on waiting list for kidney transplantation has been stable. Living donor kidney transplantation is nowadays a chance to increase the pool of donors. However, there are a group of patients with ABO incompatibility, making impossible the transplant until now. The aim of the present study is to describe the experience of Hospital Clinic Barcelona on ABO incompatible living transplantation. METHODS: A retrospective- descriptive study was made based on 11 living donor kidney recipients with ABO incompatibility in Hospital Clinic of Barcelona from October'06 to January'09. Selective blood group, antibody removal with specific immunoadsortion, immunoglobulin and anti- CD 20 antibody were made until the immunoglobulin (IgG) and isoaglutinine (IgM) antibody titters were 1/8 or lower. Immunosuppressive protocol was adjusted to particular recipient characteristics. Isoaglutinine titters were set before, during and post desensitization treatment and two weeks after transplant. Immunological, medical and surgical evaluation was the standard in living donor kidney transplant program. RESULTS: Medium age of donors and recipients were 47.8 +/- 12.4 and 44.4 +/- 14.1 years, respectively. 90% of donors were females and 73% of recipients males. Follow-up time was 10.2 +/- 10.2 months. Siblings and spouses were the most frequent relation (n=4, 36.4%, respectively). Chronic glomerulonephritis, adult polycystic kidney disease and Alport syndrome, the most frequent cause of end-stage renal disease. All the patients acquire appropriate isoaglutinine titters pre transplant (< 1/8), requiring 5.54 +/- 2.6 immunoadsorption sessions pretransplant and 2.82 posttransplant. One patient didn t need any immunoadsorption session (incompatibility blood group B) and another patient plasma exchange instead of immunoadsorption for being hypersensitized with positive flow cytometry crossmatch. Posttransplant isoaglutinine titters remained low. Two patients had cellular acute rejection episode (type IA and IB of Banff classification) with good response to corticosteroid treatment. Patient and graft survival were 91% at first year and remain stable during the follow-up. A graft lost by death of patient in relation to haemorrhagic shock developed within the first 72 hours after transplantation. Renal graft function at first year was excellent with serum creatinine of 1.3 +/- 0.8 mg/dl, creatinine clearance of 62.6 ml/min/1.73 m2 and proteinuria of 244.9 mg/U-24h. CONCLUSION: ABO incompatible living donor kidney transplantation represent an effective and safe alternative in certain patients on waiting list for renal transplant, obtaining excellent results in patient and graft survival, with good renal graft function.