Low incidence of acute rejection within 6 months of kidney transplantation in HIV-infected recipients treated with raltegravir: the Agence Nationale de Recherche sur le Sida et les Hépatites Virales (ANRS) 153 TREVE trial.

Objectives: High rates of clinical acute rejection after kidney transplantation have been reported in people living with HIV (PLHIV), probably as a consequence of drug interactions. We therefore investigated the incidence of acute rejection within 6 months of transplantation in HIV-infected recipients treated with a protease-inhibitor-free raltegravir-based regimen.

Methods: The Agence Nationale de Recherche sur le Sida et les Hépatites Virales (ANRS) 153 TREVE (NCT01453192) study was a prospective multicentre single-arm trial in adult PLHIV awaiting kidney transplantation, with viral load < 50 HIV-1 RNA copies/mL, CD4 T-cell count > 200 cells/μL, and HIV-1 strains sensitive to raltegravir, aiming to demonstrate 6-month clinical acute rejection rates < 30%.

Anticardiolipin antibodies and 12-month graft function in kidney transplant recipients: a prognosis cohort survey.

Background: In kidney transplant recipients, anticardiolipin (ACL) antibodies without antiphospholipid syndrome (APS) are found in up to 38% of patients and could be associated with thrombotic events (TEs). However, the prognostic role of ACL regarding kidney transplant and patients outcomes have still not been well defined.

Methods: We conducted an observational, monocentric, retrospective cohort study including 446 kidney transplant recipients and standardized follow-up: 36-month allograft and patient survival, 12-month estimated glomerular filtration rate (eGFR) and 3- and 12-month screening biopsies.

C1q binding is not an independent risk factor for kidney allograft loss after an acute antibody-mediated rejection episode: a retrospective cohort study.

After kidney transplantation, C4d is an incomplete marker of acute antibody-mediated rejection (AMR) and C1q-binding donor-specific antibodies (DSA) have been associated with allograft survival. However, the impact on allograft survival of C1q+ DSA after clinical AMR has not been studied yet. We analysed retrospectively in clinical AMR C4d staining and C1q-binding impact on allograft survival.

Development and validation of a prognostic index for allograft outcome in kidney recipients with transplant glomerulopathy.

We studied 92 patients with transplant glomerulopathy to develop a prognostic index based on the risk factors for allograft failure within five years of diagnosis (Development cohort). During 60 months (median) follow-up, 64 patients developed allograft failure. A chronic-inflammation score generated by combining Banff ci, ct and ti scores, serum creatinine and proteinuria at biopsy, were independent risk factors for allograft failure.

Membranous Nephropathy Associated With Immunological Disorder-Related Liver Disease: A Retrospective Study of 10 Cases.

The association between membranous nephropathy (MN) and immunological disorder-related liver disease has not been extensively investigated, and the specific features of this uncommon association, if any, remain to be determined.We retrospectively identified 10 patients with this association. We aimed to describe the clinical, biological, and pathological characteristics of these patients and their therapeutic management.

Th-17 Alloimmune Responses in Renal Allograft Biopsies From Recipients of Kidney Transplants Using Extended Criteria Donors During Acute T Cell-Mediated Rejection.

Although renal transplantation using expanded criteria donors has become a common practice, immune responses related to immunosenescence in those kidney allografts have not been studied yet in humans. We performed a retrospective molecular analysis of the T cell immune response in 43 kidney biopsies from patients with acute T cell-mediated rejection including 25 from recipients engrafted with a kidney from expanded criteria donor and 18 from recipients grafted with optimal kidney allograft. The clinical, transplant and acute T cell-mediated rejection characteristics of both groups were similar at baseline.

Minimal change nephrotic syndrome associated with non-Hodgkin lymphoid disorders: a retrospective study of 18 cases.

Few studies have examined the occurrence of minimal change nephrotic syndrome (MCNS) in patients with non-Hodgkin lymphoma (NHL). We report here a series of 18 patients with MCNS occurring among 13,992 new cases of NHL. We analyzed the clinical and pathologic characteristics of this association, along with the response of patients to treatment, to determine if this association relies on a particular disorder.

APOL1 polymorphisms and development of CKD in an identical twin donor and recipient pair.

We report an occurrence of progressive loss of transplant function and ultimately transplant failure after living related kidney transplantation involving monozygotic twin brothers of Afro-Caribbean origin who were both heterozygous for the G1 and G2 kidney disease risk alleles in the APOL1 gene, which encodes apolipoprotein L-I. A 21-year-old man with end-stage kidney disease of unknown cause received a kidney from his brother, who was confirmed as a monozygotic twin by microsatellite analysis. Thirty months after transplantation, the patient presented with proteinuria and decreased estimated glomerular filtration rate; a biopsy of the transplant showed typical focal segmental glomerulosclerosis lesions.

Clinicopathological study of glomerular diseases associated with sarcoidosis: a multicenter study.

Background: The association between sarcoidosis and glomerular diseases has not been extensively investigated in a large series and the potential features of this uncommon association remain to be determined.

Methods: We retrospectively identified 26 patients with biopsy-proven glomerular lesions that occurred in a sarcoidosis context. Potential remission of glomerular disease and sarcoidosis under specific treatment (steroid and/or immunosuppressive agents) was recorded for all patients.

Upregulation of c-mip is closely related to podocyte dysfunction in membranous nephropathy.

Membranous nephropathy is a glomerular disease typified by a nephrotic syndrome without infiltration of inflammatory cells or proliferation of resident cells. Although the cause of the disease is unknown, the primary pathology involves the generation of autoantibodies against antigen targets on the surface of podocytes. The mechanisms of nephrotic proteinuria, which reflect a profound podocyte dysfunction, remain unclear.

[Kidney involvement in sarcoidosis].

Sarcoidosis is a chronic multisystemic inflammatory disorder of unknown etiology, characterized by the presence of non-necrotizing epithelioid and giant cell granulomas. Various renal manifestations have been reported in patients with sarcoidosis. Disorders of bone and mineral metabolism related to the overexpression of 25-hydroxyvitamin-D1α-hydroxylase by alveolar and granuloma macrophages are frequently associated with sarcoidosis.

c-mip down-regulates NF-κB activity and promotes apoptosis in podocytes.

The mechanisms of podocyte disorders in cases of idiopathic nephrotic syndrome (INS) are complex and remain incompletely elucidated. The abnormal regulation of NF-κB may play a key role in the pathophysiology of these podocyte diseases, but at present, NF-κB has not been thoroughly investigated. In this study, we report that induction of c-mip in podocytes of patients with INS is associated with a down-regulation of RelA, a potent antiapoptotic factor that belongs to the NF-κB family.

Acute interstitial nephritis with predominant plasmacytic infiltration in patients with HIV-1 infection.

We describe a new form of acute interstitial nephritis with predominant plasmacytic infiltration in 2 patients with active human immunodeficiency virus 1 (HIV-1) infection. Clinical features included acute kidney injury and proteinuria, but no sicca syndrome. Acute kidney injury was characterized by a high serum creatinine level and nephrotic syndrome with no hematuria or leukocyturia.

Intrarenal IFN-γ mRNA expression differentiates clinical and subclinical glomerulitis in renal transplant recipients.

Background: Transplant glomerulitis, characterized by mononuclear cell infiltration of glomeruli, is likely to occur during clinical or subclinical antibody-mediated rejection.

Methods: To determine whether T-cell phenotype influences the clinical presentation of this pathologic condition, we used reverse transcription quantitative polymerase chain reaction to analyze expression of Treg cells (Foxp3), cytotoxic CD8 T cells (Granzyme B), Th1 cells (INF-γ,T Bet), Th2 cells (GATA3, IL-4), and Th17 pathway (IL-17). Our study included 20 renal transplant recipients exhibiting subclinical glomerulitis (SG) diagnosed after a routine 3-month posttransplant biopsy.

Renal transplantation in patients with sarcoidosis: a French multicenter study.

Background And Objectives: Sarcoidosis is a multisystem disorder of unknown etiology. The outcome of renal transplantation on patients with sarcoidosis is not well known. A few case reports have described recurrence of sarcoidosis after transplant.

T-cell phenotype in protocol renal biopsy from transplant recipients treated with belatacept-mediated co-stimulatory blockade.

Background: Belatacept is thought to disrupt the interaction between CD80/86 and CD28, thus preventing T-cell activation by blocking the co-stimulatory second signal. However, the consequences on the T-cell profile in human renal transplant cases have not been determined.

Methods: In this study, we analysed intra-graft levels of the mRNAs for Treg (FOXP3), cytotoxic CD8 T cells (Granzyme B), Th1 (INFγ, Tbet), Th2 (GATA3) and Th17 (RORγt and IL-17) in protocol biopsies obtained 12 months after renal transplantation in recipients treated with Belatacept or calcineurin inhibitor (CNI).

c-mip impairs podocyte proximal signaling and induces heavy proteinuria.

Idiopathic nephrotic syndrome comprises several podocyte diseases of unknown origin that affect the glomerular podocyte, which controls the permeability of the filtration barrier in the kidney to proteins. It is characterized by the daily loss of more than 3 g of protein in urine and the lack of inflammatory lesions or cell infiltration. We found that the abundance of c-mip (c-maf inducing protein) was increased in the podocytes of patients with various acquired idiopathic nephrotic syndromes in which the podocyte is the main target of injury.

Predominant Th1 and cytotoxic phenotype in biopsies from renal transplant recipients with transplant glomerulopathy.

Transplant glomerulopathy (TGP) appears to be a pathogenic feature of chronic antibody-mediated rejection, but the pathogenesis of this histologic entity is still poorly understood. Previous studies suggest the involvement of lymphocytes but the phenotypes of these cells have never been analyzed. Here, we report the first study of mRNAs for specific markers of CD4+ T cells including Th1 (T-bet and INFgamma), Th2 (IL4 and GATA3), Treg (Foxp3) and Th17 (IL-17 and RORgammat) subsets, cytotoxic CD8 T cells (Granzyme B) and B-cell markers (CD20) in renal biopsies from renal transplant recipients suffering interstitial fibrosis and tubular atrophy (IF/TA) with or without TGP but with a similar inflammatory score and controls including transplant recipients with normal renal function.

Arteriolar hyalinization predicts delayed graft function in deceased donor renal transplantation.

Delayed renal graft function (DGF) remains a largely unpredictable and burdensome consequence of deceased donor renal transplantation. There is growing evidence that histologic and molecular analyses of baseline donor kidney biopsies can predict both short- and long-term graft outcome. We performed histologic analyses of 172 preimplantation kidney biopsies to determine reliable histologic risk factors for DGF.

Intragraft levels of Foxp3 mRNA predict progression in renal transplants with borderline change.

The optimal therapeutic management of borderline lymphocytic infiltrates in renal allografts, described by Banff criteria, is unknown, largely because of the inability to predict clinical outcome in these cases. For determination of molecular factors that may predict outcome in cases of borderline change histology, mRNA levels of Foxp3, Granzyme B, IFN-gamma, IL-23, and RORgammat were measured in renal tissue from 46 untreated patients. Twenty-five patients were considered "nonprogressive," defined by a serum creatinine that remained <110% of baseline during the 40 d after biopsy.

A 59-kD renal antigen as a new target for rapidly progressive glomerulonephritis.

Anti-glomerular basement membrane (anti-GBM) antibodies are the hallmark of anti-GBM disease, which is characterized by rapidly progressive glomerulonephritis. We describe the case of a 58-year-old woman who presented with rapidly progressive glomerulonephritis with typical anti-GBM staining found by means of direct immunofluorescence microscopy, associated with linear immunoglobin G deposits on tubules. Serum analysis showed circulating anti-tubular basement membrane antibodies, but failed to detect anti-GBM antibodies.

The regulatory/cytotoxic graft-infiltrating T cells differentiate renal allograft borderline change from acute rejection.

The interpretation of cellular infiltrate from renal transplant recipients with borderline (BL) changes is still a challenging problem. To analyze the immune phenotype of such infiltrate, we quantified the mRNA expression of Foxp3 and interleukinL-10 and granzyme B (GB) in 15 kidney biopsies with BL changes. Controls were patients presenting type IA acute rejection and nonrejecting patients.

Renal allograft biopsies with borderline changes: predictive factors of clinical outcome.

The clinical outcome and appropriate management for patients showing 'borderline changes' on allograft biopsy after renal transplantation is still controversial. In an attempt to identify predictive factors of clinical outcome of patients with such lesions, we reviewed the clinical course of 91 patients with borderline changes. Multivariate analysis revealed significant and independent effects of histological stage (i + t < or = or > 2) and time to borderline changes (< or = or > 3 months after transplant) on serum creatinine levels at 1 year from borderline changes episodes (respectively, p = 0.

Risk factors and outcome of focal and segmental glomerulosclerosis recurrence in adult renal transplant recipients.

Background: Recurrence of nephrotic syndrome (NS) after renal transplantation for primary focal segmental glomerulosclerosis (FSGS) is a frequent and still unpredictable complication. However, risk factors for recurrence have not yet been clearly identified.

Methods: Data from 33 patients who underwent 35 renal transplantations for FSGS in two French centres are reported.