Search

Background In the recent years, an increased use of marginal donors and grafts and a growing prevalence of peripheral arterial disease in the recipients have been observed. Meanwhile, the open surgical technique for kidney transplantation has not changed. The aim of this study is to analyze all surgical complications occurring in the first year after kidney transplant and to determine potential predictive risk factors. Method Data of the 399 patients who underwent kidney transplant in our University Hospital between January 2006 and December 2015 were retrospectively reviewed. The primary endpoint was the overall rate of vascular, parietal and urological complications at 1 year following kidney transplantation. The secondary outcomes were graft and patient’ survival rates, and the identification of predictive factors of the surgical complications. Results Twenty-four percent of patients developed 134 complications. Vascular complication represented 39% of all complications and resulted in 9 graft losses. Parietal and urological complications represented 46% and 15% of all complications, respectively, No parietal or urological complications were associated with graft loss. Five patients died during the first year, none of these cases was associated with graft loss. The graft survival rate reached 96% at 1 year, including patients still alive. The occurrence of surgical complication was associated with reduced graft survival at 1 year. Using a multivariate analysis, 4 predictive factors were identified: age, deceased donor, operative time and dyslipidemia. Conclusion Surgical complications after kidney transplantation remained frequent and age, deceased kidney donors, and operative time were identified as risk factors. As vascular complications were a major cause of early graft loss, efforts should aim to reduce their occurrence to increase graft survival.

Fluid overload has been associated with a high prevalence of sleep apnea (SA) in patients with end-stage kidney disease (ESKD). In this prospective study, we hypothesized that improvement in kidney function and hydration status after kidney transplantation (Tx) may result in an improvement in SA severity. A total of 196 patients on the kidney Tx waiting list were screened for SA using home nocturnal polysomnography (PSG) to measure the apnea-hypopnea index (AHI) and underwent bioimpedance to assess body composition. Of 88 participants (44.9%) with SA (AHI ≥ 15/h), 42 were reassessed 6 months post-Tx and were compared with 27 control patients. There was a significant, but small, post-Tx improvement in AHI (from 44.2 ± 24.3 to 34.7 ± 20.9/h, P = .02) that significantly correlated with a reduction in fluid overload (from 1.8 ± 2.0 to 1.2 ± 1.2 L, P = .02) and body water (from 54.9% to 51.6%, P = .003). A post-Tx increase in body fat mass (from 26% to 30%, P = .003) possibly blunted the beneficial impact of kidney Tx on SA. All parameters remained unchanged in the control group. In conclusion, SA is a frequent condition in ESKD patients and partially improved by kidney Tx. We suggest that SA should be systematically assessed before and after kidney Tx. ClinicalTrials.gov Identifier: NCT02020642.

Improved glycemic control with a bionic pancreas and recent safety data of a wearable artificial pancreas may be relevant for kidney transplant recipients with type 1 diabetes [1, 2]. Diabetes is a major risk factor for end-stage renal disease, and the DCCT trial showed that tight glycemic control is superior to conventional insulin therapy to prevent complications of type 1 diabetes, including diabetic nephropathy [3]. Moreover, continuous subcutaneous insulin pump infusion partially prevented early diabetic nephropathy in native kidneys in another 3-year follow-up study which included kidney biopsies [4]. In kidney allografts, the risk of recurrent biopsy-proven diabetic nephropathy is almost 100 % after 10 years of follow-up, and histological diabetic lesions can be observed as soon as 2 years after transplant [5]. Kidney– pancreas transplantation with its associated euglycemia can prevent recurrent diabetic nephropathy in the allograft [6, 7]. However, kidney–pancreas transplantation is associated with significant morbidity, and donor organ shortage limits its widespread application [8]. Islet after kidney transplantation can also potentially reduce long-term diabetic complications; however, the rate of insulin independence after islet transplantation remains significantly lower as compared to full pancreas transplantation [9].

Titre Variations et anomalies nephrologiques, vasculaires et urologiques chez les candidats au don vivant renal. Introduction Cette etude consiste a determiner I.a prevalence des variations anatomiques (renales, vasculaires et urologiques) ainsi que des pathologies renales acquises dans une population de candidats au don vivant de rein (CDVR). Materiel et methodes Il s'agit d'une etude retrospective de tous les CDVR referes dans notre centre en vue d'une transplantation renale entre avril 2003 et se pt embre· 2014. Sur les 491 CDVR, 189 ont ete initialement exclus pour des raisons medicales (n=140) ou autres (n=49), sans avoir effectue de bilan radiologique. 302 ont beneficie d'un bilan radiologique (angio-CT ou IRM) en prevision du don et 226/302 (73.5%) ont pu donner un rein. Resultats Une ou plusieurs variations anatomiques et/ou anomalies acquises ont ete constatees chez 178/302 (58.9%) des CDVR, dont les plus frequentes concernaient les anomalies et variations arterielles (arteres multiples, fibrodysplasie, anevrisme, stenose 70%), presentes chez . 39.3% des CDVR, suivies par les variations veineuses (27.8%). Des calculs ont ete observes chez 5.6% des C:DVR et les anomalies des voies urinaires (duplicite/bifidite ureterale) ont concerne 3.0% des CDVR. Aucune tumeur maligne n'a ete diagnostiquee alors que 4 tumeurs benignes (1.3%) ont ete identifiees, dont un cas necessitant des investigations supplementaires. Conclusion Nous constatons une haute prevalence de variations anatomiques et anomalies acquises dans une population de CDVR. Cependant, ces variantes et anomalies constatees ont conduit a exclure seulement 4 % des candidats. Ceci soit parce que les anomalies ne contre­ indiquaient pas le prelevement, soit parce que dans la majorite des cas le. rein controlateral a pu etre utilise.

Background: Data on individualized immunosuppressive protocols for the pediatric heart recipients are missing in Europe. To contribute to this very small but specialized field, we describe the use of induction therapy (IT) in pediatric heart transplant patients in Switzerland and the retrospective outcomes. Method: This is a retrospective national database analysis of children

Introduction et but de l'etude Le traitement de choix lors d'insuffisance renale terminale est la transplantation. Malgre un faible taux de complications operatoires, des perturbations hemodynamiques peuvent evoquer une perte de greffon. Les principales complications vasculaires sont des erreurs techniques ou un mauvais positionnement du rein ou de ses vaisseaux, pouvant mener a une perte du greffon, dramatique d'autant plus lors de transplantation a donneur vivant. Le benefice de l'echographie precoce a la recherche de problemes vasculaires a deja ete demontre, mais son role en intra- operatoire reste peu clair. Le but de cette etude etait d'evaluer d'eventuelles differences de complications post-operatoires avec et sans utilisation systematique de l'ultrasonographie Doppler per-operatoire, lors de transplantation renale a donneur vivant. L'objectif secondaire etait d'etablir une valeur seuil ou un index de resistance predictif, motivant une reprise chirurgicale. Materiel et methode Sur une periode de 10 ans, 108 greffes renales consecutives ont ete realisees a partir de donneurs vivants dans notre etablissement. Deux groupes ont ete crees selon l'utilisation ou non de l'echographie per- operatoire. Dans le groupe 1 (n=67), une echographie Doppler a ete systematiquement realisee avec mesure de l'indice de resistance intra- parenchymateux, alors que dans le groupe 2 (n=41), aucune echographie n'a ete realisee. Dans le groupe 1, nous avons recherche les donnees de l'echographie intra-operatoire, les index de resistance et les eventuelles modifications chirurgicales immediates. Le taux de complications vasculaires et non-vasculaires, de re-operations et de rejets aigus ont ete compares dans les deux groupes. Resultats Nos analyses ne montrent pas de differences sur le taux de complications postoperatoires globales, ni la survie du greffon ou du patient entre les deux groupes. Cependant, le taux de complications vasculaires (10% vs 0%, p = 0,02) est significativement plus eleve dans le groupe 2. Le taux de rejets aigus est egalement plus eleve (37% vs 10%) dans le groupe 2. Nous proposons une valeur seuil pour l'index de resistance inferieur a 0,5 pour justifier une revision chirurgicale immediate. Conclusion Cette etude est le premier rapport demontrant les avantages de l'echographie Doppler intra-operatoire systematique sur les complications postoperatoires dans la transplantation renale a donneurs vivants. D'apres nos resultats, une revision chirurgicale est recommandee lors d'index de resistance inferieur a 0,5.

Background To describe the optical coherence tomography angiograhy (OCTA) of drusenoid pigment epithelial detachments (PEDs) in a woman affected by Complement 3 (C3) glomerulopathy, which represents a spectrum of glomerular diseases characterized on fluorescent microscopy by C3 accumulation with absent, or scanty, immunoglobulin deposits. It is due to acquired or genetically defective alternative pathway control and is generally associated with drusen-like deposits in Bruch’s membrane, as well as choriocapillaris. These retinal lesions can be associated with choroidal neovascularization and central serous chorioretinopathy (CSCR). OCTA is useful to detect neovascularization without injecting a contrast product, particularly in these patients who may have renal insufficiency. Case presentation A 28-year-old woman affected by C3 glomerulpathy was diagnosed with asymptomatic multiple bilateral PEDs during a routine ophthalmologic consultation. To better characterize the lesions, multimodal imaging was performed and included: optic coherence tomography (OCT), en-face OCT, OCTA, fluorescence and indocyanine angiography. The OCTA clearly identified vascular network rarefaction with decreased choriocapillary vascularization. It confirmed that PEDs associated with C3 glomerulonephritis are not vascularized, but rather of serous type. Conclusions Patients affected by C3 glomerulopathy can develop neovascular membranes as retinal complications of pigment epithelial detachments. Optical coherence angiography may be indicated to identify this complication, without injecting any contrast product that could produce further kidney damage.

To evaluate outcomes and post-donation kidney function of older living kidney donors (LKD). Retrospective analysis of prospective database including all consecutive LKD undergoing laparoscopic nephrectomy in a single center (09/1998-12/2013). LKD aged ≥60 years were compared to younger LKD. Renal function assessed by creatinine levels and estimated glomerular filtration rates (eGFR). Surgical complications classified according to the Clavien-Dindo classification. Bivariate and multivariate analyses using linear mixed effect models were performed to determine factors (age, gender, hypertension status, BMI, choice of better functioning kidney for donation) that might impinge on renal function after donation. 213 LKD were identified: 49 older (median age: 66 years, range: 60-79) and 164 younger (median age: 46, range: 25-59). Mean operative time (149 vs. 152 min, p = 0.69), conversion to laparotomy (n = 1 vs. 3, p = 0.92), grade III-IV complications (n = 4 vs. 2, p = 0.36) were similar. Older had more grade I-II complications (n = 18 vs. 4, p < 0.001). Despite similar pre-donation eGFR (80 vs. 84 ml/min/1.73 m 2 ), older donors presented significantly lower eGFR during inpatient period (46 vs. 51 ml/min/1.73 m 2 , p = 0.0003), at 1 month (51 vs. 58 ml/min/1.73 m 2 , p = 0.002) and at 1 year (54 vs. 62 ml/min/1.73 m 2 , p = 0.001). Multivariate analysis adjusted to gender, hypertension status, BMI and choice of better functioning kidney for donation showed that at 1 year, age ≥60 affected renal function by a coefficient of 0.91 (p < 0.001). Despite renal function improvement after discharge, LKD ≥ 60 years presented lower eGFR than younger at one year and had more grade I-II surgical complications.

Pretransplant anti-HLA donor-specific antibodies (DSA) are recognized as a risk factor for acute antibody-mediated rejection (AMR) in kidney transplantation. The predictive value of C4d-fixing capability by DSA or of IgG DSA subclasses for acute AMR in the pretransplant setting has been recently studied. In addition DSA strength assessed by mean fluorescence intensity (MFI) may improve risk stratification. We aimed to analyze the relevance of preformed DSA and of DSA MFI values.280 consecutive patients with negative complement-dependent cytotoxicity crossmatches received a kidney transplant between 01/2008 and 03/2014. Sera were screened for the presence of DSA with a solid-phase assays on a Luminex flow analyzer, and the results were correlated with biopsy-proven acute AMR in the first year and survival.Pretransplant anti-HLA antibodies were present in 72 patients (25.7%) and 24 (8.6%) had DSA. There were 46 (16.4%) acute rejection episodes, 32 (11.4%) being cellular and 14 (5.0%) AMR. The incidence of acute AMR was higher in patients with pretransplant DSA (41.7%) than in those without (1.6%) (p0.001). The median cumulative MFI (cMFI) of the group DSA+/AMR+ was 5680 vs 2208 in DSA+/AMR- (p=0.058). With univariate logistic regression a threshold value of 5280 cMFI was predictive for acute AMR. DSA cMFI's ability to predict AMR was also explored by ROC analysis. AUC was 0.728 and the best threshold was a cMFI of 4340. Importantly pretransplant DSA5280 cMFI had a detrimental effect on 5-year graft survival.Preformed DSA cMFI values were clinically-relevant for the prediction of acute AMR and graft survival in kidney transplantation. A threshold of 4300-5300 cMFI was a significant outcome predictor.

Metabolic syndrome after transplantation is a major concern following solid organ transplantation (SOT). The CREB-regulated transcription co-activator 2 (CRTC2) regulates glucose metabolism. The effect of CRTC2 polymorphisms on new-onset diabetes after transplantation (NODAT) was investigated in a discovery sample of SOT recipients (n1=197). Positive results were tested for replication in two samples from the Swiss Transplant Cohort Study (STCS, n2=1294 and n3=759). Obesity and other metabolic traits were also tested. Associations with metabolic traits in population-based samples (n4=46'186, n5=123'865, n6>100,000) were finally analyzed. In the discovery sample, CRTC2 rs8450-AA genotype was associated with NODAT, fasting blood glucose and body mass index (PcorrectedA was significantly associated with several metabolic abnormalities. CRTC2 rs8450G>A appears to have an important role in the high prevalence of metabolic traits observed in patients with SOT. A weak association with metabolic traits was also observed in the population-based samples.The Pharmacogenomics Journal advance online publication, 8 December 2015; doi:10.1038/tpj.2015.82.

Chronic active antibody-mediated rejection (caAMR) is a major cause of allograft loss after kidney transplantation (1). The BANFF 2013 classification redefined caAMR by the presence of donor-specific anti-HLA antibodies (DSA) together with immuno-histopathological evidence for active vascular lesions of the endothelium (C4d deposits, glomerulitis, peritubular capillaritis) as well as evidence of chronic tissue injury (transplant glomerulopathy, peritubular capillary basement membrane multilayering or arterial intimal fibrosis) (2,3). Humoral immunity, detected by the presence of DSA, and B cells are considered pivotal in the development of caAMR. Gosset et al. showed that circulating DSA are responsible for accelerated allograft fibrosis independently of acute AMR (1). This article is protected by copyright. All rights reserved.

New-onset diabetes mellitus after transplantation (NODAT) is a complication following solid organ transplantation (SOT) and may be related to immune or inflammatory responses. We investigated whether single nucleotide polymorphisms (SNPs) within 158 immune- or inflammation-related genes contribute to NODAT in SOT recipients. The association between 263 SNPs and NODAT was investigated in a discovery sample of SOT recipients from the Swiss Transplant Cohort Study (STCS, n 1 = 696). Positive results were tested in a first STCS replication sample (n 2 = 489) and SNPs remaining significant after multiple test corrections were tested in a second SOT replication sample (n 3 = 156). Associations with diabetic traits were further tested in several large general population-based samples (n > 480 000). Only SP110 rs2114592C>T remained associated with NODAT in the STCS replication sample. Carriers of rs2114592-TT had 9.9 times (95% confidence interval [CI]: 3.22-30.5, P = .00006) higher risk for NODAT in the combined STCS samples (n = 1184). rs2114592C>T was further associated with NODAT in the second SOT sample (odds ratio: 4.8, 95% CI: 1.55-14.6, P = .006). On the other hand, SP110 rs2114592C>T was not associated with diabetic traits in population-based samples, suggesting a specific gene-environment interaction, possibly due to the use of specific medications (ie, immunosuppressants) in transplant patients and/or to the illness that may unmask the gene effect.

Objectives To determine whether valganciclovir 450 mg every 48 h for cytomegalovirus (CMV) prophylaxis provides appropriate ganciclovir exposure in solid organ transplant recipients during continuous renal replacement therapy (CRRT). Patients and methods Ganciclovir pharmacokinetics was intensively studied in two lung transplant recipients under valganciclovir 450 mg every 48 h over one dosing interval. In vitro experiments using blank whole blood spiked with ganciclovir further investigated exchanges between plasma and erythrocytes. Results Ganciclovir disposition was characterized by apparent total body clearance of 3.3 and 5.8 L/h, terminal half-life of 16.9 and 14.1 h, and apparent volume of distribution of 60.3 and 104.9 L in Patients 1 and 2, respectively. The observed sieving coefficient was 1.05 and 0.96, and the haemofiltration clearance was 3.3 and 3.1 L/h. In vitro experiments confirmed rapid efflux of ganciclovir from red blood cells into plasma, increasing the apparent efficacy of haemofiltration. Conclusions A valganciclovir dosage of 450 mg every 48 h appears adequate for patients under CRRT requiring prophylaxis for CMV infection, providing concentration levels in the range reported for 900 mg once daily dosing outside renal failure.

Background: Lack of adherence to medication is a trigger of graft rejection in solid-organ transplant (SOT) recipients. Objective: This exploratory study aimed to assess whether a biopsychosocial evaluation using the INTERMED instrument before transplantation could identify SOT recipients at risk of suboptimal post-transplantation adherence to immunosuppressant drugs. We hypothesized that complex patients (INTERMED>20) might have lower medication adherence than noncomplex patients (INTERMED≤20). Methods: Each patient eligible for transplantation at the University Hospital of Lausanne, Switzerland, has to undergo a pre-transplantation psychiatric evaluation. In this context the patient was asked to participate in our study. The INTERMED was completed pre-transplantation, and adherence to immunosuppressive medication was monitored post-transplantation by electronic monitors for 12 months. The main outcome measure was the implementation and persistence to two calcineurin inhibitors, cyclosporine and tacrolimus, according to the dichotomized INTERMED score (>20 or ≤20). Results: Among the 50 SOT recipients who completed the INTERMED, 32 entered the study. The complex (N=11) and noncomplex patients (N=21) were similar in terms of age, sex and transplanted organ. Implementation was 94.2% in noncomplex patients versus 87.8% in complex patients (non-significant p-value). Five patients were lost to follow-up: one was non-persistent, and four refused electronic monitoring. Of the four patients who refused monitoring, two were complex and withdrew early, and two were noncomplex and withdrew later in the study. Conclusion: Patients identified as complex pre-transplant by the INTERMED tended to deviate from their immunosuppressant regimen, but the findings were not statistically significant. Larger studies are needed to evaluate this association further, as well as the appropriateness of using a nonspecific biopsychosocial instrument such as INTERMED in highly morbid patients who have complex social and psychological characteristics.

BACKGROUND We assessed the impact of a preemptive strategy after discontinuation of antiviral prophylaxis in the prevention of late-onset cytomegalovirus (CMV) disease in a cohort of kidney transplant recipients. METHODS Patients undergoing kidney transplantation at the University Hospital of Lausanne (CHUV) between November 2003 and November 2007 were included if they were donor or recipient (D/R) seropositive for CMV. All patients received 3 months of prophylaxis with valganciclovir, followed by monitoring of CMV DNAemia by polymerase chain reaction (PCR) every 15 days during 3 additional months. Valganciclovir was restarted if CMV PCR was more than or equal to 10,000 copies/mL. The primary endpoint of the study was the incidence of late-onset CMV disease. RESULTS.: Eighty-six kidney transplant recipients were included; 30 patients were D+/R- and 56 patients were R+ for CMV. At 6 months posttransplant, CMV DNAemia had occurred in 31 of 86 (36%) patients: 13 of 30 (43%) in the D+/R- group and 18 of 56 (32%) in the R+ group (P = 0.35). In the D+/R- group, among the 13 patients with CMV DNAemia, 7 (54%) patients developed late-onset CMV disease, simultaneously to the first positive viral load (n = 5) or after detection of low-grade viremia (n = 2). Only two patients received a preemptive treatment. In the R+ group, all positive PCR results were below the established cutoff. Thus, these 18 patients were not treated, and none of them developed late-onset CMV disease (R+ vs. D+/R-: P < 0.001). CONCLUSIONS Within the limitations of a noncontrolled study, our data indicate that a preemptive strategy after 3 months of valganciclovir prophylaxis for CMV is not useful in R+ kidney transplant recipients. In D+/R- patients, this approach should be further evaluated.

Background. Few data are available regarding the immunogenicity and safety of the pandemic influenza vaccine in immunocompromised patients. We evaluated the humoral response to the influenza A H1N1/09 vaccine in solid-organ transplant (SOT) recipients, in patients with human immunodeficiency virus (HIV) infection, and in healthy individuals. Methods. Patients scheduled to receive the pandemic influenza vaccine were invited to participate. All participants received the influenza A H1N1/09 AS03-adjuvanted vaccine containing 3.75 μg of hemagglutinin. SOT recipients and HIV-infected patients received 2 doses at 3-week intervals, whereas control subjects received 1 dose. Blood samples were taken at day 0, day 21, and day 49 after vaccination. Antibody responses were measured with the hemagglutination inhibition assay (HIA) and a microneutralization assay. Results. Twenty-nine SOT recipients, 30 HIV-infected patients, and 30 healthy individuals were included in the study. Seroconversion measured by HIA was observed in 15 (52%) of 29 SOT recipients both at day 21 and day 49; in 23 (77%) of 30 at day 21 and 26 (87%) of 30 at day 49 in HIV-infected patients, and in 20 (67%) of 30 at day 21 and in 23 (77%) of 30 at day 49 in control subjects (P = .12 at day 21 and P = .009 at day 49, between groups). Geometric means of antibody titers were not significantly different between groups at day 21 or at day 49. Conclusions. Influenza A H1N1/09 vaccine elicited a similar antibody response in HIV-infected individuals and in control subjects, whereas SOT recipients had an overall lower response. A second dose of the vaccine only moderately improved vaccine immunogenicity in HIV-infected patients.

Valganciclovir (VGC) is an oral prodrug of ganciclovir (GCV) recently introduced for prophylaxis and treatment of cytomegalovirus infection. Optimal concentration exposure for effective and safe VGC therapy would require either reproducible VGC absorption and GCV disposition or dosage adjustment based on therapeutic drug monitoring (TDM). We examined GCV population pharmacokinetics in solid organ transplant recipients receiving oral VGC, including the influence of clinical factors, the magnitude of variability, and its impact on efficacy and tolerability. Nonlinear mixed effect model (NONMEM) analysis was performed on plasma samples from 65 transplant recipients under VGC prophylaxis or treatment. A two-compartment model with first-order absorption appropriately described the data. Systemic clearance was markedly influenced by the glomerular filtration rate (GFR), patient gender, and graft type (clearance/GFR = 1.7 in kidney, 0.9 in heart, and 1.2 in lung and liver recipients) with interpatient and interoccasion variabilities of 26 and 12%, respectively. Body weight and sex influenced central volume of distribution ( V 1 = 0.34 liter/kg in males and 0.27 liter/kg in females [20% interpatient variability]). No significant drug interaction was detected. The good prophylactic efficacy and tolerability of VGC precluded the demonstration of any relationship with GCV concentrations. In conclusion, this analysis highlights the importance of thorough adjustment of VGC dosage to renal function and body weight. Considering the good predictability and reproducibility of the GCV profile after treatment with oral VGC, routine TDM does not appear to be clinically indicated in solid-organ transplant recipients. However, GCV plasma measurement may still be helpful in specific clinical situations.

Background Polyomavirus-associated nephropathy (PVAN) is a serious complication and cause of graft loss in kidney transplant recipients. In the absence of specific antiviral drugs, early detection of the disease and reduction of immunosuppressive regimen is the cornerstone of therapy. Cidofovir, a nucleoside analogue, has been found to inhibit BK virus (BKV) replication in vitro and has been proposed as treatment of refractory PVAN at low doses; however, its efficacy has never been demonstrated in randomized controlled trials. Methods Cidofovir therapy (0.5 mg/kg at a 2-week interval for eight consecutive doses) was initiated in two patients with biopsy-proven PVAN and persistent BKV DNA viraemia (≥10,000 copies/ml despite sustained reduction of the immunosuppressive regimen). In addition to these two case reports, we performed a critical review of the literature on the use of cidofovir in PVAN. Results No significant decrease of BKV viral load in blood was observed during cidofovir therapy and in follow-up of the two patients treated with cidofovir. Our literature review identified 21 publications reporting the use of cidofovir for the treatment of PVAN. All were case reports or small series. The efficacy of cidofovir therapy could not be assessed in 17 of these publications because of lack of data or concomitant reduction of immunosuppressive regimen. The four remaining publications were case reports. Conclusions In vitro and clinical data to support the efficacy of cidofovir in the treatment of PVAN are currently lacking. More promising compounds should be identified for further clinical studies.

We analyzed data from all consecutive kidney transplant patients at our institution between April 2003 and October 2006. We found 15 cases of late-onset cytomegalovirus (CMV) infection, two of which developed concurrent post-transplant diabetes mellitus (PTDM). In these two cases, PTDM was transient and normal glucose tolerance was achieved after an eight-wk therapeutic course of oral valganciclovir. These findings suggest that CMV infection after organ transplantation may be associated with concurrent PTDM. The distinct causative relationship is yet to be determined.

In the general population, renal cell carcinoma (RCC) is a relatively common neoplasm; however, the papillary RCC subtype is infrequent and represents only 10 to 15% of all RCC. Angiomyolipoma is a well-known common benign tumor. The occurrence of RCC in association with angiomyolipoma is a rare event, with only approximately 50 cases reported in the nontransplantation setting. In transplant recipients, RCC can develop in native kidneys, but its occurrence "de novo" in the renal allograft is very rare with an estimated incidence of less than 0.5%. We report here the case of a 39-year-old woman who underwent cadaveric renal transplantation in 1990. No lesion was observed in the allograft during the pre- and perioperative period or on early postoperative ultrasounds. No graft rejection occurred under a standard triple immunosuppressive therapy. Thirteen years later, during a routine ultrasonography, 2 solid masses were discovered in the allograft, both of them richly vascularized. She underwent allograft nephrectomy and the histologic findings revealed that one of the tumors was a chromophilic (type 1) papillary RCC (2.5 cm in diameter) and the other, an angiomyolipoma (1.5 cm). Microsatellite analysis of the allograft, as compared with the recipient peripheral blood leukocytes, demonstrated that the 2 tumors (1 malignant and 1 benign) were of donor origin. To our knowledge, this is the first report of de novo concurrent papillary RCC and angiomyolipoma in a renal allograft.

The calcineurin inhibitors (CNIs) cyclosporine and tacrolimus have been the cornerstones of immunosuppressive strategies in clinical transplantation. Currently, regimens that are most widely used for induction and maintenance therapy include CNIs. However, many clinical trials aiming at reducing or eliminating CNIs have been performed in recent years. Here, we review and discuss current and future immunosuppressive strategies with a special emphasis on the role of CNIs, in the light of recent studies in the field of kidney transplantation. In the current era, CNIs still play an important role.

Sirolimus is a new immunosuppressive agent used to prevent rejection in renal allograft recipients in order to reduce the need of potentially nephrotoxic calcineurin inhibitors (cyclosporine, tacrolimus). The cutaneous side effects of sirolimus are not well known and they may have been underestimated. We report 2 cases of follicular acneiform eruptions induced by sirolimus in renal allograft recipients. This dermatologic complication was severe and difficult to treat, and resolved only after discontinuation of sirolimus.

Valganciclovir (VGC) has proved efficacious and safe for the prophylaxis against cytomegalovirus (CMV) in high-risk transplant recipients and for the treatment of CMV retinitis in AIDS patients. We used VGC for the treatment of CMV infection (viremia without symptoms) or disease (CMV syndrome or tissue-invasive disease) in kidney, heart, and lung transplant recipients. Fourteen transplant recipients were treated: five for asymptomatic CMV infection and nine for CMV disease. VGC was administered in doses adjusted to renal function for 4 to 12 weeks (induction and maintenance therapy). Clinically, all nine patients with CMV disease responded to treatment. Microbiologically, treatment with VGC turned blood culture negative for CMV within 2 weeks in all patients and was associated with a ≥2 log decrease in blood CMV DNA within 3 weeks in 8 of 8 tested patients. With a follow-up of 6 months (n = 12 patients), asymptomatic recurrent CMV viremia was noted in five cases, and CMV syndrome noted in one case (all cases in the first 2 months after the end of treatment). VGC was clinically well tolerated in all patients; however, laboratory abnormalities occurred in three cases (mild increase in transaminases, thrombocytopenia, and pancytopenia). This preliminary experience strongly suggests that therapy with VGC is effective against CMV in organ transplant recipients; however, the exact duration of therapy remains to be determined: a longer course may be necessary to prevent early recurrence.

Introduction: Double transplantation is one possible answer to the shortage of donor organs. While each donor kidney would be unsuitable when considered as a single allograft, use of both kidneys should provide sufficient nephron mass for effective glomerular filtration. Case report: This is the first Swiss report of a dual adult transplant of marginal kidneys in a 46-year-old man, who was transplanted for the fourth time. Follow-up at 6 months is excellent without acute rejection. Conclusion: Recent analysis of dual marginal versus single ideal transplant outcomes, found a comparable 1-yr graft survival in both of the procedures. Long term results are still lacking and guidelines to decide between single, double or no transplantation are emerging.

Some experimental studies have suggested a beneficial effect of the mammalian target of rapamycin (mTOR) inhibitor use on hepatic and renal cyst growth in patients with autosomal dominant polycystic kidney disease (ADPKD). However, the results of clinical studies are conflicting and the role of mTOR inhibitors is still uncertain. We report the case of a patient with ADPKD who underwent deceased kidney transplantation because of an end-stage renal disease. The evolution was uneventful with an excellent graft function under cyclosporine (CsA) monotherapy. Some years later, the patient developed a symptomatic hepatomegaly due to growth of cysts. CsA was replaced by sirolimus, an mTOR inhibitor, in order to reduce or control the increase in the cyst and liver volume. Despite the switch, the hepatic volume increased by 25% in two years. Finally sirolimus was stopped because of the lack of effect on hepatic cyst growth and the presence of sirolimus side effects. The interest of our case resides in the followup by MRI imaging during the mTOR inhibitor treatment and 15 months after the restart of the initial immunosuppressive therapy. This observation indicates that mTOR inhibitors did not have significant effect on cyst-associated hepatic growth in our patient, which is consistent with some results of recent large clinical studies.

A 59-year-old man was referred by his family doctor for progressive renal failure. He was on lithium sulfate therapy since 32 years for bipolar disorder. The medical history revealed polyuria and polydypsia, which was persistent since several years. Family history was negative for hereditary nephropathies. Laboratory findings revealed a blood urea nitrogen concentration of 7.0 mmol/l and a serum creatinine concentration of 168 μmol/l, corresponding to an estimated glomerular filtration rate of 38 ml/min per 1.73 m2 according to the Modification of Diet in Renal Disease formula. There was no electrolyte anomaly. Urinalysis demonstrated a pH of 7.0, and a specific gravity of 1005, without protenuria nor hematuria. A chronic lithium nephropathy (CLN) was suspected and a renal biopsy proposed, but was refused by the patient.

A 59-year-old kidney recipient was diagnosed with a late onset of severe chronic inflammatory demyelinating polyradiculoneuropathy and almost fully recovered after stopping tacrolimus and one course of intravenous immunoglobulin treatment. Unique features of this patient are the unusually long time lapse between initiation of tacrolimus and the adverse effect (10 years), a strong causality link and several arguments pointing toward an inflammatory etiology. When facing new neurological signs and symptoms in graft recipients, it is important to bear in mind the possibility of a drug-induced adverse event. Discontinuation of the suspect drug and immunomodulation are useful treatment options.

Background Valganciclovir, the oral prodrug of ganciclovir, has been demonstrated equivalent to iv ganciclovir for CMV disease treatment in solid organ transplant recipients. Variability in ganciclovir exposure achieved with valganciclovir could be implicated as a contributing factor for explaining variations in the therapeutic response. This prospective observational study aimed to correlate clinical and cytomegalovirus (CMV) viral load response (DNAemia) with ganciclovir plasma concentrations in patients treated with valganciclovir for CMV infection/disease. Methods Seven CMV D+/R- transplant recipients (4 kidney, 2 liver and 1 heart) were treated with valganciclovir (initial dose was 900-1800 mg/day for 3-6.5 weeks, followed by 450-900 mg/day for 2-9 weeks). DNAemia was monitored by real time quantitative PCR and ganciclovir plasma concentration was measured at trough (Ctrough) and 3 h after drug administration (C3h) by HPLC. Results Four patients presented with CMV syndrome, two had CMV tissue-invasive disease after prophylaxis discontinuation, and one liver recipient was treated pre-emptively for asymptomatic rising CMV viral load 5 weeks post-transplantation in the absence of prophylaxis. CMV DNAemia decreased during the first week of treatment in all recipients except in one patient (median decrease: -1.2 log copies/mL, range: -1.8 to 0) despite satisfactory ganciclovir exposure (AUC0-12 = 48 mg·h/L, range for the 7 patients: 40-118 mg·h/L). Viral clearance was obtained in five patients after a median of time of 34 days (range: 28-82 days). Two patients had recurrent CMV disease despite adequate ganciclovir exposure (65 mg·h/L, range: 44-118 mg·h/L). Conclusions Valganciclovir treatment for CMV infection/disease in D+/R- transplant recipients can thus result in variable viral clearance despite adequate ganciclovir plasma concentrations, probably correlating inversely with anti-CMV immune responses after primary infection.

Objectives:The aims of this study were to assess the 1-year cost-effectiveness of a new combined immunosuppressive and anti-infectious regimen in kidney transplantation to prevent both rejection and infectious complications.Methods:Patients (pts) transplanted from January 2000 to March 2003 (Group A) and treated with a conventional protocol were compared with pts submitted to a combined regimen including universal cytomegalovirus (CMV) prophylaxis between April 2003 and July 2005 (Group B). Costs were computed from the hospital accounting system for hospital stays, and official tariffs for outpatient visits. Patients with incomplete costs data were excluded from analysis.Results:Fifty-three patients were analyzed in Group A, and 60 in Group B. Baseline characteristics including CMV serostatus were not significantly different between the two groups. Over 12 months after transplantation, acute rejections decreased from 41.5 percent in Group A to 6.7 percent in Group B (p< .001), and CMV infections from 47 percent to 15 percent (p< .001). Overall, readmissions decreased from 68 percent to 55 percent (p= .160), and average hospital days from 28 ± 19 to 20 ± 11 days (p< .007). The average number of outpatient visits decreased from 49 ± 10 to 39 ± 8 (p< .001). Average 1-year immunosuppressive and CMV prophylaxis costs (per patient) increased from CHF20,402 ± 7,273 to 27,375 ± 6,063 (p< .001), graft rejection costs decreased from CHF4,595 ± 10,182 to 650 ± 3,167 (p= .005), CMV treatment costs from CHF2,270 ± 6,161 to 101 ± 326 (p= .008), and outpatient visits costs from CHF8,466 ± 1’721 to 6,749 ± 1,159 (p< .001). Altogether, 1-year treatment costs decreased from CHF39’957 ± 16,573 to 36,204 ± 6,901 (p= .115).Conclusions: The new combined regimen administered in Group B was significantly more effective, and its additional costs were more than offset by savings associated with complications avoidance.

Posttransplant cutaneous T cell lymphomas are rare and have been reported to have a poor prognosis. We report the case of a follicular mycosis fungoides in a lung transplant recipient who was successfully treated with topical mechlorethamine, prior to subsequent renal transplantation.

We describe the case of a kidney transplant recipient who developed meningococcemia, without meningeal signs, 2 months after transplantation. Plasma levels of complement components C3, C4, and CH 50 were within the normal range. However, using a method to screen for the functional activity of all 3 pathways of complement, no activation via the mannose-binding lectin (MBL) pathway could be detected (0%). A subsequent quantification of MBL pathway components revealed normal levels of MASP 2 but undetectable amounts of MBL. To our knowledge, this is the first report of meningococcal disease after organ transplantation in a patient with MBL deficiency.

BACKGROUND: Immunosuppressive and antiviral prophylactic drugs are needed to prevent acute rejection and infection after transplantation. We assessed the efficacy and safety of the introduction of universal valganciclovir prophylaxis in combination with a tacrolimus/mycophenolate-based regimen in kidney transplantation at our centre. METHODS: We reviewed all consecutive patients who underwent kidney transplantation over a 5.5-year period. Patients transplanted from January 2000 to March 2003 (period 1) were compared to patients from April 2003 to July 2005 (period 2). In period 1 patients were treated with basiliximab, cyclosporine, steroids and mycophenolate (or azathioprine). Prophylaxis with valacyclovir was prescribed in cytomegalovirus (CMV) D+/R- patients, while any R+ patients were managed with a preemptive approach. In period 2, immunosuppression consisted of basiliximab or thymoglobulin induction, tacrolimus, steroids and mycophenolate. Three-month CMV prophylaxis with valganciclovir was used in all at-risk patients. RESULTS: Data analysis included 73 patients (period 1) and 70 (period 2). Acute rejection was more frequent in period 1 than in period 2 (42% vs 7%, p