Efficacy and safety of universal valganciclovir prophylaxis combined with a tacrolimus/mycophenolate-based regimen in kidney transplantation.

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 <0.001). Overall, 30% of patients in period 1 were diagnosed with CMV infection/disease requiring antiviral treatment, compared with 11.4% in period 2 (p = 0.003). Late-onset CMV disease remained a problem in D+/R- patients in both periods. There was no difference in incidence of BK virus nephropathy, fungal infections, PTLD, graft loss or mortality. However, 4 cases (5.7%) of delayed transient asymptomatic agranulocytosis were observed in period 2. CONCLUSIONS: The present analysis indicates that the combined regimen introduced in period 2 improved clinical results with a significant decrease in acute rejection and in CMV infection/disease incidence. However, a unique syndrome of delayed transient agranulocytosis probably due to drug myelotoxicity was observed in a subset of patients

Case Report: A Rare Truncating Variant of the CFHR5 Gene in IgA Nephropathy.

IgA nephropathy (IgAN) is the most common primary glomerulonephritis worldwide. Despite appropriate therapy, 20-40% of affected-patients evolve toward end-stage kidney disease (ESKD). Mesangial IgA deposits are the hallmark of IgAN, and complement deposition (C3) seems to differentiate latent IgA mesangial deposits from active IgAN. Atypical hemolytic uremic syndrome (aHUS), another disease in which complement plays an important role, is caused by inherited or acquired deregulation of the alternative pathway (AP) of complement. A subgroup of IgAN shows thrombotic microangiopathy (TMA) lesions in kidney biopsies, the histological characteristic of aHUS. Genetic variants of complement Factor H (CFH), known to be present in aHUS, have been associated with rapidly progressive forms of IgAN and a clinical pattern of aHUS. Genome-wide association studies (GWAS) have confirmed that the 1q32 region, encoding for CFH and its related proteins, is an IgAN susceptibility locus. A 30 year-old man was admitted for seizures and malignant hypertension. The kidney biopsy showed IgAN associated with features of TMA. Despite five plasma exchanges, the patient remained dialysis-dependent, and ESKD was diagnosed. Functional and genetic complement analysis were performed. A monoallelic protein-truncating, likely loss-of-function variant was identified in the CFHR5 gene. Eculizumab is the treatment of aHUS. As it has been successfully used in a few cases of rapidly progressive IgAN, it was decided to administer eculizumab over a period of 12 months in addition to the usual immunosuppression for renal transplantation. After a follow-up of 3 years, there was no clinical disease recurrence. Systematic biologic and genetic screening of complement in individuals with IgAN might be useful to better delineate the role of the AP of complement in renal disease progression, and this may have therapeutic implications

Multimodal imaging of retinal pigment epithelial detachments in patients with C3 glomerulopathy: case report and review of the literature.

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. 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. 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

Rituximab as monotherapy for the treatment of chronic active antibody-mediated rejection after kidney transplantation.

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

Microangiopathie thrombotique et transplantation rénale

La survenue d'une microangiopathie thrombotique (MAT) chez un patient transplanté rénal peut correspondre soit à la récidive de la maladie Initiale sur le transplant, événement dont l'Incidence globale est estimée à 27,8%, soit à un phénomène « de novo », dont l'origine la plus fréquente (jusqu'à 14% des biopsies rénales effectuées sur des transplants) est une toxicité des inhibiteurs de la calcineurine. Pour illustrer ce sujet, trois cas de MAT associées à une toxicité de la clclosporine sont présentés. Le diagnostic se pose par biopsie rénale, motivée par une dégradation de la fonction rénale. Les manifestations extrarénales et les signes hématologiques d'hémolyse mécanique sont en effet rares. L'arrêt des Inhibiteurs de la calcineurine est la principale mesure thérapeutique. L'évolution est très variable: de la perte du greffon à une Insuffisance rénale aiguë complètement réversible

Hyperlipémie et maladie rénale : prévalence, mécanisme et approche thérapeutique

Les maladies cardiovasculaires représentent la cause principale de mortalité chez les patients atteints d'insuffisance rénale chronique et la prévalence de l'hyperlipémie est plus élevée chez tes patients par rapport à celle de la population générale. Le profil lipidique et la sévérité de la dyslipidémie varient en fanction de l'étiologie et de la sévérité de l'insuffisance rénale ainsi que du type de traitement d'épuration. L'élévation du cholestérol total et du LDL-cholestérol est plus marquée chez les patients souffrant d'un syndrome néphrotique, d'une insuffisance rénale chronique, en dialyse péritonéale et chez les transplantés rénaux. L'hypertriglycéridémie est présente chez moins de 50% de ces patients toutes catégories confondues. Ces patients doivent être considérés comme étant à haut risque pour une maladie cardiovasculaire et bénéficier d'un traitement conformément aux directives du groupe Lipides et Athérosclérose de la Société suisse de cardiologie 1999. Une diète est généralement insuffisante pour corriger le profil lipidique et un traitement hypolipémiant est indispensable

New treatments for acute humoral rejection of kidney allografts.

Acute antibody-mediated rejection (acute humoral rejection; AHR) of organ allografts usually presents as severe dysfunction with a high risk of allograft loss. Peritubular capillary complement C4d deposition with renal dysfunction, associated with circulating donor-specific anti-human leukocyte antigen alloantibodies, is diagnostic of AHR in kidney allografts. Removal of alloantibodies with suppression of antibody production and rejection reversal is now possible. Therapeutic strategies that include combinations of plasmapheresis (or immunoadsorption), tacrolimus, mycophenolate mofetil and/or intravenous immunoglobulins, as well as rituximab or splenectomy, have been recently used to successfully treat AHR. However, the optimal protocol to treat AHR still remains to be defined. Anti-CD20+ monoclonal antibody therapy (rituximab) aiming at depleting B cells and suppressing antibody production has been used as rescue therapy in some episodes of steroid- and antilymphocyte-resistant humoral rejection. Plasmapheresis and/or intravenous polyclonal immunoglobulin, as well as rituximab, have also been used to successfully desensitize selected high-immunological risk patients in anticipation of a previously cross-match positive (or ABO incompatible) kidney transplantation. In the near future, the possible role of new specific anti-B-cell approaches or, possibly, of new anti-T-cell activation approaches using selective agents such as belatacept should be assessed to further refine the present treatment of humoral rejection