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The immunogenicity of the severe acute respiratory syndrome-coronavirus 2 (SARS-CoV-2) vaccine was improved by the administration of a third dose. The aim of our retrospective study was to assess the evolution of binding and neutralizing antibody concentration until 3 months after the third dose in a large cohort of solid organ transplant (SOT) patients (n = 872). At 1 month after the third dose, anti-SARS-CoV-2 antibodies were detected by means of enzyme-linked immunosorbent assay tests in 578 patients (66.3%). In a subgroup of patients, 70% (180 out of 257) had anti-SARS-CoV-2 antibody concentrations ranging from 1.2 to 18 411 binding antibody units (BAU)/ml and 48.5% (115 out of 239) had a neutralizing antibodies titer that can confer clinical protection against SARS-CoV-2. Three-hundred ninety-three patients out of the 416 (94.5%) who were seropositive at month 1 and were tested at 3 months after vaccination remained seropositive. Between months 1 and 3 after vaccination, binding and neutralizing antibodies concentrations decreased significantly. The proportion of protected patients against the SARS-CoV-2 also slightly decreased. In conclusion, this study shows that although two-third of SOT develop anti-SARS-CoV-2 antibodies after three doses, one-third of them remain weak or non-protected. It is important to measure anti-SARS-CoV-2 antibodies to define the strategy that can optimize SOT protection against SARS-CoV-2.

BACKGROUND Preventive strategies for invasive aspergillosis (IA) have still not been determined in heart transplant recipients whereas IA leads to a high mortality rate at 12 months posttransplantation. The use of voriconazole or echinocandins was proposed but can favor emergence of Aspergillus or Candida sp. resistant strains or promote neurological and liver disorders in some patients. OBJECTIVES To assess whether universal prophylaxis with weekly high-dose of liposomal amphotericin-B (L-AmB) can safely prevent IA in heart transplant recipients. PATIENTS/METHODS Retrospective before/after study that included 142 patients who received heart transplantation between 2010 and 2019 at the University Hospital of Toulouse (France). Weekly high dose of L-AmB (7.5 mg/kg/week) was used as universal prophylaxis from 2016 because of high environmental exposure to Aspergillus sp. and high incidence of IA. RESULTS Cumulative 1-year incidence of IA decreased from 23% to 5% after introduction of L-Amb prophylaxis. Multivariate analysis (Cox model) identified L-AmB prophylaxis as a protective factor against IA (hazard ratio [HR] 0.21 [95% confidence interval 0; 0.92], p = .04), whereas postoperative renal replacement therapy was associated with IA (HR 3.6 [95% confidence interval 1.38; 9.3], p = .001), after correction for confounding effects (induction regimen, methylprednisolone pulses and history of hematological malignancy). The incidence of acute kidney injury requiring renal replacement therapy was similar in the two groups, suggesting a low risk of kidney toxicity when L-AmB is used weekly. No patient developed severe kidney electrolyte loss nor L-AmB-related anaphylaxis. CONCLUSIONS Once-weekly high-dose L-AmB is safe and may prevent the development of IA after heart transplantation.

International audience; Scedosporiosis/lomentosporiosis is a devastating emerging fungal infection. Our objective was to describe the clinical pattern and to analyze whether taxonomic grouping of the species involved was supported by differences in terms of clinical presentations or outcomes. We retrospectively studied cases of invasive scedosporiosis in France from 2005 through 2017 based on isolates characterized by polyphasic approach. We recorded 90 cases, mainly related to Scedosporium apiospermum (n = 48), S. boydii/S. ellipsoideum (n = 20), and Lomentospora prolificans (n = 14). One-third of infections were disseminated, with unexpectedly high rates of cerebral (41%) and cardiovascular (31%) involvement. In light of recent Scedosporium taxonomic revisions, we aimed to study the clinical significance of Scedosporium species identification and report for the first time contrasting clinical presentations between infections caused S. apiospermum, which were associated with malignancies and cutaneous involvement in disseminated infections, and infections caused by S. boydii, which were associated with solid organ transplantation, cerebral infections, fungemia, and early death. The clinical presentation of L. prolificans also differed from that of other species, involving more neutropenic patients, breakthrough infections, fungemia, and disseminated infections. Neutropenia, dissemination, and lack of antifungal prescription were all associated with 3-month mortality. Our data support the distinction between S. apiospermum and S. boydii and between L. prolificans and Scedosporium sp. Our results also underline the importance of the workup to assess dissemination, including cardiovascular system and brain. Lay Summary Scedosporiosis/lomentosporiosis is a devastating emerging fungal infection. Our objective was to describe the clinical pattern and to analyze whether taxonomic grouping of the species involved was supported by differences in terms of clinical presentations or outcomes.

International audience; The first cases of Severe Acute Respiratory Syndrome coronavirus 2 (SARS‐CoV‐2) occurred in France in early February and in our region (Southwest France) in early March 2020.

International audience; Objectives: To characterize the clinical presentation and outcomes of invasive mold infections (IMI) in solid organ transplant (SOT) recipients.Methods: Inclusion of all SOT recipients with IMI diagnosed between 2008 and 2016 at a referral center for SOT. Univariable analyses identified factors associated with death at one year, and logistic regression models retained independent predictors.Results: Of the 1739 patients that received a SOT during this period, 68 developed IMI (invasive aspergillosis [IA] in 58). Cumulative incidence of IMI at 1 year ranged from 1.2% to 18.8% (kidney and heart transplantation, respectively). At baseline, compared with other IMI, the need for vasoactive drugs was more frequent in patients with IA. During follow-up, 35 patients (51%) were admitted to the ICU and required mechanical ventilation (n = 27), vasoactive drugs (n = 31), or renal replacement therapy (n = 31). The need for vasoactive drugs (OR 7.34; P = .003) and a positive direct examination (OR 10.1; P = .004) were independently associated with the risk of death at 1 year in patients with IA (n = 33; 57%) CONCLUSIONS: Characteristics of IMI at presentation varied according to the underlying transplanted organ and the mold species. Following IA, one-year mortality may be predicted by the need for hemodynamic support and initial fungal load

Belatacept (BTC) is indicated for prophylaxis of graft rejection in adults receiving a renal transplant (Tx). This retrospective observational study (three centers) included all heart transplant recipients receiving BTC between January 2014 and October 2018. Forty EBV+ patients mean GFR 35 ± 20 mL/min/m2 were identified, among whom belatacept was initiated during the first 3 months after transplantation in 12 patients, and later in 28 patients. Several patients were multiorgan transplant recipients. Study outcomes were GFR, safety, and changes in immunosuppressive therapy. The main reason for switching to BTC was to preserve renal function, resulting in discontinuation of CNI and changes in immunosuppressive therapy in 76% of cases. At study closeout, 24/40 patients were still on BTC therapy. GFR was improved (+59%, P = .0002*) within 1 month, particularly in the early group. More episodes of rejection were observed among "late" patients (1 death). Sixteen treatment discontinuations were recorded: GFR recovery (n = 4), DSA no longer detectable (n = 1), compliance issues (n = 3), poor venous access (n = 2), multiple infections (n = 1), 1 death (fungal lung infection), and treatment failure (n = 4). Median follow-up was 24 months. Four patients developed de novo DSA (MFI

Background Minimal-change nephrotic syndrome (MCNS) is a common cause of steroid sensitive nephrotic syndrome (NS) with frequent relapse. Although steroids and calcineurin inhibitors (CNIs) are the cornerstone treatments, the use of rituximab (RTX), a monoclonal antibody targeting B cells, is an efficient and safe alternative in childhood. Methods Because data from adults remain sparse, we conducted a large retrospective and multicentric study that included 41 adults with MCNS and receiving RTX. Results Complete (NS remission and withdrawal of all immunosuppressants) and partial (NS remission and withdrawal of at least one immunosuppressants) clinical responses were obtained for 25 and 7 patients, respectively (overall response 78%), including 3 patients that only received RTX and had a complete clinical response. After a follow-up time of 39 months (6-71), relapses occurred in 18 responder patients [56%, median time 18 months (3-36)]. Seventeen of these received a second course of RTX and then had a complete (n = 13) or partial (n = 4) clinical response. From multivariate analysis, on-going mycophenolate mofetil (MMF) therapy at the time of RTX was the only predictive factor for RTX failure [HR = 0.07 95% CI (0.01-0.04), P = 0.003]. Interestingly, nine patients were still in remission at 14 months (3-36) after B-cell recovery. No significant early or late adverse event occurred after RTX therapy. Conclusions RTX is safe and effective in adult patients with MCNS and could be an alternative to steroids or CNIs in patients with a long history of relapsing MCNS.

BACKGROUND: Kidney transplantation increases the chances for pregnancy and live birth for women with end-stage kidney disease. The aims of this study were to describe the outcomes of pregnancies in women with a kidney transplant and to evaluate the impact on anti-human leucocyte antigen (HLA) alloimmunization. METHODS: We analysed 61 pregnancies that occurred in 46 patients after having excluded 10 miscarriages during the first trimester and 10 other pregnancies from which important data were missing. Anti-HLA antibodies were screened using the Luminex assay. RESULTS: Overall, the live birth rate was 83% (94% after exclusion of miscarriages during the first trimester). Pre-eclampsia and gestational diabetes occurred in 26 and 21% of cases, respectively. The use of tacrolimus was an independent predictive factor for gestational diabetes. Twenty-four newborns (42%) were premature (

OBJECTIVES Scarce data exist regarding the effect of acute graft pyelonephritis on kidney histology after a kidney transplant. This study sought to assess the kidney histology at 1 month, and kidney function at 1 year, after acute graft pyelonephritis in kidney transplant patients. MATERIALS AND METHODS All kidney transplant patients with acute graft pyelonephritis between October 2006, and December 2008, underwent a kidney biopsy 1 month later (n=28). Histologic findings were compared with those observed in a control group (n=28) who underwent a protocol kidney biopsy at 1 year posttransplant and did not present with acute graft pyelonephritis. Patients were matched according to age, sex, and immunosuppressive regimen. RESULTS Kidney function was impaired by the acute graft pyelonephritis episodes at the time of biopsy. In 40% of patients, the estimated glomerular filtration rate did not return to baseline by 1 month after acute graft pyelonephritis and remained impaired thereafter. Three patients had features of acute rejection. Tubulitis was seen more frequently in the acute graft pyelonephritis group, especially in patients in whom estimated glomerular filtration rate did not completely recover by 1 month after acute graft pyelonephritis. Patients with acute graft pyelonephritis who had inflammatory infiltrate of > 20% 1 month after acute graft pyelonephritis had worse kidney function 1 year later. CONCLUSIONS After transplant, when kidney function remains impaired 1 month after acute graft pyelonephritis, kidney biopsies allowed graft rejection diagnosis and predicted kidney function recovery.

Within the last few years, anti-human leukocyte antigen detection assays have significantly improved. This study asked, using the Luminex single-antigen assay, whether an allograft nephrectomy allowed donor-specific alloantibodies to appear that were not previously detected in the serum when the failed kidney was still in place.After losing the kidney allograft and stopping immunosuppressive therapy, the proportions of donor-specific alloantibodies and nondonor-specific alloantibodies were compared in patients who had (n=48; group I) and had not (n=21; group II) undergone an allograft nephrectomy. Allograft nephrectomies were performed at 150 days after kidney allograft loss, and the time between allograft nephrectomy and last follow-up was 538 ± 347 days.At kidney allograft loss, donor-specific alloantibodies were detected in three group II patients (14.2%) and six group I patients (12.5%). At last follow-up, donor-specific alloantibodies were detected in 11 patients (52.4%) without and 39 patients (81%) with an allograft nephrectomy (P=0.02). Anti-human leukocyte antigen class I donor-specific alloantibodies were positive in 23.8% of group II and 77% of group I patients (P0.001); anti-human leukocyte antigen class II donor-specific alloantibodies were positive in 42.8% of group II and 62.5% of group I patients. Independent predictive factors for developing donor-specific alloantibodies after losing kidney allograft and stopping immunosuppressants were number of anti-human leukocyte antigen A/B mismatches at transplantation (zero versus one or more) and allograft nephrectomy.The development of donor-specific alloantibodies was significantly greater in patients with a failed kidney who had undergone an allograft nephrectomy compared with those patients who had not undergone allograft nephrectomy.

Background. Tenofovir therapy has been found to be efficient in treating hepatitis B virus (HBV) in nontransplant patients. However, in the setting of solid-organ transplantation, the efficacy of tenofovir has not been tested. The aim of this pilot study was to assess the clinical and biologic response and tolerance to tenofovir therapy in HBV-positive organ transplant recipients. Methods. Seven patients, three kidney, three liver, and one cardiac transplant recipients, with chronic HBV infection were partial responders to adefovir (n=7), lamivudine (n=7), or entecavir (n=5) therapy. Consequently, they were placed on tenofovir therapy (245 mg daily, which was adapted to renal function) alone (n=4) or in combination with lamivudine (n=3). Tenofovir therapy was assessed at 1, 3, 6, and 12 months postinitiation or at the last follow-up. Results. HBV DNA viral load (4.16 [2.03–5.56] log10 copies/mL at baseline) became significantly decreased to 3.15 (1.08–5.17), 2.88 (1.3–4.3), 3.53 (1.3–5.75), 3.33 (1.3–7.57), and 2.31 (1.3–4.81) log copies/mL at 1, 3, 6, and 12 months posttenofovir initiation and at last follow-up, respectively (P=0.02). Three patients were HBV DNA negative at the last follow-up. Liver enzyme levels did not change significantly throughout the follow-up period. Clinical and biologic tolerance was excellent. Conclusions. Even though HBV DNA clearance was not achieved in all patients, the results of this pilot study are encouraging and demonstrate that tenofovir therapy is safe and efficacious in treating HBV-positive organ transplant patients. However, a larger trial is needed to confirm these preliminary results.

After kidney transplantation, occurrence of anemia in the early post-transplant period (1 month) is high and arises out of issues that are multifactorial. We performed a retrospective single-center study to assess whether delivery of high doses of erythropoietin-stimulating agents (ESA) within the first week of kidney transplantation, translates at 1 month post-transplant, in to causing less anemia and whether it has an impact on allograft function. Ninety-nine patients were not given ESA (group I), whereas 82 were (250 IU/kg/week; group II). All patients had similar pretransplant and baseline (day 0) variables. Similar numbers of group II patients were still receiving ESA by day 14 (97.5%) and day 30 (89%). Respective figures for group I were 27% and 27%. Independent factors for anemia at 1 month post-transplant included: being male subject, treatment for hypertension at pretransplant, anemia at transplant, a higher mean corpuscular volume at transplant, and an induction therapy using antithymocyte globulins. Independent predictive factors for lower creatinine clearance included being female subjects, having a donor aged50 years, being a recipient aged50 years, not treated for hypertension at pretransplant, and no post-transplant ESA therapy. High doses of ESA within the first month of kidney transplantation have no impact on anemia or renal function by 1 month post-transplant.

Background. Townes-Brocks syndrome (TBS) is a rare autosomal dominant disease, resulting from mutation in the developmental gene SALL1. The phenotype encompasses malformations of limbs (triphalangeal thumbs and pre-axial polydactyly), intestine (anal stenosis) and ears (dysplastic ear with perception hearing loss). Renal involvement (hypo-dysplasia, multicystic kidneys or unilateral absence) is observed in almost half of patients and may progress to end-stage renal failure in childhood. Methods. Herein, we report two adult patients diagnosed with TBS at age 28 and 35. Results. Both exhibited severe chronic renal failure and kidney hypodysplasia by imaging studies while focal and segmental glomerulosclerosis (FSGS) was demonstrated in one case. Conclusion. Regular assessment of glomerular filtration rate is mandatory throughout life in all TBS patients.

International audience; Hepatitis E virus (HEV) is considered an agent responsible for acute hepatitis that does not progress to chronic hepatitis. We identified 14 cases of acute HEV infection in three patients receiving liver transplants, nine receiving kidney transplants, and two receiving kidney and pancreas transplants. All patients were positive for serum HEV RNA. Chronic hepatitis developed in eight patients, as confirmed by persistently elevated aminotransferase levels, serum HEV RNA, and histologic features of chronic hepatitis. The time from transplantation to diagnosis was significantly shorter and the total counts of lymphocytes and of CD2, CD3, and CD4 T cells were significantly lower in patients in whom chronic disease developed.

Background Anemia, frequent in post-transplant patients, has been associated with cardiovascular outcomes. Although recombinant human erythropoietin (rHuEPO) is used in post-transplant anemic patients, little information is available concerning the use of darbepoetin-alfa (DA) in this population. Methods Eligible patients had been recipients of a kidney graft for > 3 months, had anemia and chronic renal failure, but no iron deficiency. 38 patients, not previously treated by rHuEPO (Group 1), were given DA, and 35 rHuEPO-treated patients (Group 2) were switched to DA according to European Summary of Product Characteristics. Only the subcutaneous route was used. Dose adjustments were done to maintain Hb at 11 - 13 g/dl. Hb levels and DA dosage were assessed at baseline, and at Months 3 and 6. Results Mean age (A+/- SD) of patients was 47.7 (A+/- 13.4) years (53% male). Mean duration of transplantation was 8.5 (A+/- 5.5) years and mean creatinine clearance was 42.5 (A+/- 19.8) ml/min. In Group 1, mean Hb became increased by +1.27 g/dl (95% CI 0.61, 1.94) and mean DA dose was decreased by 44% between baseline and M6. In Group 2, mean Hb and DA dose remained stable between baseline and M6. Hb response to DA appeared faster in patients who had received a transplant for less than 3 years, and lower in patients who had received a transplant more than 12 years previously. Conclusions DA effectively corrected anemia in renal-transplant patients, in previously treated patients and in EPO-naive patients. DA was also found to be well-tolerated.

The aims of the present study were to assess the incidence of cytomegalovirus (CMV) reactivation, and to determine the predictive factors for CMV reactivation in CMV seropositive kidney-transplant patients. One hundred ninety CMV seropositive kidney-transplant patients were included in this study; of these, 39 patients had received CMV prophylaxis. CMV DNAemia was assessed by real-timepolymerase chain reaction assay every 2 weeks until day 120, then every 3–4 weeks until day 180, and then every month until day 365. One hundred seven patients (56.3%) had at least one positive CMV DNAemia within the first year. The time between renal transplantation and the first positive CMV DNAemia was 59 ± 5 days. The number of positive CMV DNAemia/patient was 3.28 ± 0.22. CMV viral load at first positive CMV DNAemia was 704 (10–742,000) copies/ml. The donor CMV seropositivity, the absence of CMV prophylaxis, and the occurrence of acute rejection before CMV reactivation were independent factors associated with CMV reactivation within the first year after kidney transplantation. Hence, CMV reactivation is frequent after kidney transplantation. CMV prophylaxis in CMV seropositive kidney-transplant patients should be offered to avoid CMV-related side-effects. J. Med. Virol. 80:1012–1017, 2008. © 2008 Wiley-Liss, Inc.

A pilot study was performed on eight consecutive renal-transplant (RT) patients presenting with acute humoral rejection (AHR) to assess the efficacy of monoclonal anti-B cell antibodies, such as rituximab (375 mg/m weekly) for 3 to 5 consecutive weeks, in addition to plasma exchange (PE), steroids, mycophenolate mofetil, and tacrolimus. AHR was associated with increased serum creatinine, the appearance of donor-specific alloantibodies (DSA), and the presence of C4d in a transplant biopsy. After a follow-up of 10 months (range 7-23), patient and graft survivals were 100% and 75%, respectively. Renal function improved in six cases in which serum creatinine decreased from 297+/-140 to 156+/-53 micromol/L (P=0.015); graft loss occurred in two cases; and four patients had infectious complications. At last follow-up, DSA had disappeared or decreased in four cases. Rituximab therapy, in addition to PE, might be of benefit for RT patients presenting with AHR.

Background: Primary focal segmental glomerular sclerosis (FSGS) recurs in 20 - 40% of patients after kidney transplantation. Rituximab has been used to treat several glomerular diseases. Patients and results: We treated two renal-transplant patients with recurrence of FSGS with rituximab. Despite a prophylactic perioperative therapy of plasma-pheresis (PE) and i.v. cyclosporine A, Patient 1 developed significant proteinuria, at 1 day after his first kidney transplantation. After two infusions of rituximab (375 mg/m 2 ) he had complete remission. A second relapse, which occurred on Day 40, was also successfully treated by PE and one additional infusion of rituximab. 10 months after transplantation, he still has complete remission from recurrent nephrotic syndrome. Patient 2 also developed significant proteinuria, but 1 day after a second kidney transplantation. Nephrotic syndrome persisted despite 27 sessions of PE and cyclophosphamide therapy. At 13 months after transplantation, he received four infusions of rituximab (375 mg/m 2 ), but this was ineffective. Conclusion: There is a need to demonstrate whether or not rituximab therapy is of interest to prevent and to treat nephritic syndrome in renal-transplant patients who suffer from FSGS.

Ribavirin is efficient at treating chronic hepatitis E virus infection in solid-organ transplant patients. However, the early kinetics of viral replication under therapy and the impact of immunosuppressant regimens on viral replication are unknown: thus, determining the aim of our study.Thirty-five patients with a solid-organ transplant and chronic hepatitis E virus infection were given ribavirin for 3 months. The hepatitis E virus (HEV) RNA concentrations were determined before treatment, at days 7, 15, and 21 and at months 1, 2, and 3 during therapy and after ribavirin cessation.A sustained virological response (SVR) occurred in 63%. Decreased viral concentration within the first week post-ribavirin therapy was an independent predictive factor for SVR, and a decreased HEV concentration of 0.5 log copies/mL or greater had an 88% positive predictive value. No correlation between ribavirin trough level on day 7 or at month 2 with a virological response or an SVR was observed. Before therapy, HEV RNA concentration was significantly greater in patients receiving mechanistic target of rapamycin inhibitor-based immunosuppression compared to patients given calcineurin inhibitors. The use of mycophenolic acid did not impact on the response to ribavirin.An early response to ribavirin can be used to define the optimal duration of therapy in the setting of HEV infection.

We sought to determine the prevalence and predictive factors for posttransplant anemia within the first year after orthotopic liver transplant (OLT) among 97 consecutive patients. Anemia was defined at months 6 and 12 according to the WHO criteria, that is, a hemoglobin (Hb) level of12 g/dL for women and13 g/dL for men. Immunosuppression relied on tacrolimus and steroids, with or without mycophenolate mofetil. Anemia was present in 64.5%, 50%, and 52.8% of patients pre-OLT versus 6 and 12. Thirty-three percent (month 6) and 30.3% (month 12) of anemic patients received recombinant erythropoietin therapy. A multivariate analysis revealed that the independent predictive factors for anemia at month 6 were mean corpuscular volume (85 fL) at day 7, daily steroid dosage (0.3 mg/kg), serum creatinine (130 mumol/L), and Hb level (11 g/dL) at month 1. Independent predictive factors for anemia at month 12 were daily steroid dosage at month 1 (0.3 mg/kg), hematocrit at month 1 (33%), red blood cell count at month 6 (3.75 T/L), daily dosage at month 1 of cyclosporine or tacrolimus, and etiology of end-stage liver disease other than alcohol abuse. We concluded that anemia was highly prevalent within the first year of post-OLT. This observation deserves further investigation and appropriate treatment.

The aim of our study was to determine the prevalence and predictive factors for post-transplant anemia (PTA) at 6 (M6) and 12 (M12) months after orthotopic liver-transplant (OLT) in a cohort of 97 consecutive patients.Anemia was defined at M6 and M12 according to the World Health Organization criteria, i.e., a hemoglobin level of12 g/dL for women and13 g/dL for men. Immunosuppression relied on tacrolimus and steroids with or without mycophenolate mofetil.Anemia was present in 64.5%, 50%, and 52.8% of patients before OLT and at M6 and M12, respectively. Of the anemic patients, 33% (M6) and 30.3% (M12) received recombinant erythropoietin therapy. In multivariate analysis, the independent predictive factors for anemia at M6 were mean corpuscular volume (85 fl) at day 7, daily steroid dosage (0.3 mg/kg), serum creatinine (130 micromol/L), and hemoglobin level (11 g/dL) 1 month after OLT (M1). Independent predictive factors for anemia at M12 were daily steroid dosage at M1 (0.3 mg/kg), hematocrit at M1 (33%), red blood cell count at M6 (3.75 T/L), daily dosage at M1 of cyclosporine and tacrolimus, and OLT for causes other than alcohol abuse.Anemia is highly prevalent within the first year post-OLT. This deserves further investigation and appropriate treatment.

Background. Type II or III cryoglobulins are fairly prevalent in renal-transplant (RT) patients, and are often related to chronic hepatitis C virus (HCV) infection. However, they rarely result in graft dysfunction. They are sustained by proliferation of oligoclonal B-cells. Systemic B-cell depletion and clinical remission of the systemic effects of cryoglobulins have been achieved in HCV-positive immunocompetent patients with a human/mouse chimeric monoclonal antibody that specifically reacts with the CD20 antigen (i.e., rituximab). Thus, this provides the rationale to use rituximab for cryoglobulin-related graft dysfunction in RT patients. Methods. Three RT patients, of whom one was HCV-positive, developed renal-function impairment long after transplantation, as well as de novo nephrotic syndrome (n=2) and severe hypertension (n=2). This latter case was related to type III cryoglobulinemia and was associated with membranoproliferative glomerulonephritis. In addition to their baseline standard immunosuppression, the patients were given weekly rituximab infusions of 375 mg/m2 (two infusions in patient and four infusions for the other two cases). Results. This treatment resulted in a dramatic improvement in renal parameters, particularly in a sustained remittence of nephrotic syndrome, a sustained clearance of cryoglobulins in two cases, but also in severe infectious complications in two cases. Conclusion. We conclude that rituximab therapy is highly effective in cryoglobulin-related renal dysfunction in RT patients; however, due to chronic immunosuppression, this is at the expense of infectious complications.

International audience; The incidence and consequences of de novo donor-specific anti-HLA antibodies (DSAs) after liver transplantation (LT) are not well known. We investigated the incidence, risk factors, and complications associated with de novo DSAs in this setting. A total of 152 de novo liver-transplant patients, without preformed anti-HLA DSAs, were tested for anti-HLA antibodies, with single-antigen bead technology, before, at transplantation, at 1, 3, 6 and 12 months after transplantation, and thereafter annually and at each time they presented with increased liver-enzyme levels until the last follow-up, that is, 34 (1.5-77) months. Twenty-one patients (14%) developed de novo DSAs. Of these, five patients had C1q-binding DSAs (24%). Younger age, low exposure to calcineurin inhibitors, and noncompliance were predictive factors for de novo DSA formation. Nine of the 21 patients (43%) with de novo DSAs experienced an acute antibody-mediated rejection (AMR). Positive C4d staining was more frequently observed in liver biopsies of patients with AMR (9/9 vs. 1/12, P < 0.0001). Eight patients received a B-cell targeting therapy, and one patient received polyclonal antibodies. Only one patient required retransplantation. Patient- and graft-survival rates did not differ between patients with and without DSAs. In conclusion, liver-transplant patients with liver abnormalities should be screened for DSAs and AMR.

Proteinuria is an expected complication in transplant patients treated with mammalian target of rapamycin inhibitors (mTOR-i). However, clinical suspicion should always be supported by histological evidence in order to investigate potential alternate diagnoses such as acute or chronic rejection, interstitial fibrosis and tubular atrophy, or recurrent or de novo glomerulopathy. In this case we report the unexpected diagnosis of amyloidosis in a renal-transplant patient with pre-transplant monoclonal gammapathy of undetermined significance who developed proteinuria after conversion from tacrolimus to everolimus.

Few data regarding viral replication in patients receiving belatacept are available. The aim of this single-center study was to compare the incidence of viral infections (cytomegalovirus, Epstein Barr virus, BK virus, and JC virus), in 62 de novo kidney transplant patients enrolled in the BENEFIT studies, receiving either belatacept (n=42) or cyclosporine (n=20).By means of polymerase chain reaction, belatacept-treated patients were tested for cytomegalovirus, Epstein-Barr virus, BK virus, and JC virus infections monthly for 36 months, monthly for the first 6 months, and then quarterly for 36 months in cyclosporine-treated patients. Additional samples were obtained when a viral infection was suspected.The number of positive cytomegalovirus, BK virus, or JC virus viremias over the number of polymerase chain reactions performed through all 3 years was similar in both groups. Conversely, over the 3-year study, the number of positive Epstein-Barr virus viremias over the number of Epstein-Barr virus polymerase chain reactions performed was significantly higher in the belatacept group (76% vs 50%; P = .047). The number of Epstein-Barr virus primary infection was similar in both groups, while the number of Epstein-Barr virus reactivation was higher in the belatacept group.Epstein-Barr virus replication occurs more often in patients receiving belatacept, than it does in those receiving cyclosporine.

Linezolid is a recent oral antibiotic used in drug-resistant Gram-positive cocci infection. We herein report on the first two cases of linezolid-related pancytopenia in organ-transplant patients. Both patients had methicillineresistant Staphylococcus aureus infections. Pancytopenia, i.e. aregenerative anemia, neutropenia and thrombopenia, developed 3 weeks and 5 weeks after initiating linezolid therapy at a conventional dosage (600 mg bid). There were no other confounding causes of pancytopenia, which resolved promptly after withdrawing linezolid. Because of the potential hazards of pancytopenia in immunosuppressed organ-transplant patients, we advocate the cautious use of linezolid for transplant patients.

Scarce data exist regarding the incidence of donor-specific antibodies (DSAs) in kidney transplant patients receiving everolimus-based immunosuppression without calcineurin inhibitors (CNIs). The aim of this retrospective case-control study was to compare the incidence of de novo DSAs in patients converted to an everolimus-based regimen without CNIs with that seen in patients maintained on CNIs. Sixty-one DSA-free kidney transplant patients who had been converted to an everolimus-based regimen (everolimus group) were compared to 61 other patients maintained on CNIs-based regimen (control group). Patients were matched according to age, gender, induction therapy, date of transplantation, and being DSA-free at baseline. At last follow-up, the incidence of DSAs was 9.8% in the everolimus group and 5% in the control group (p = ns). In the everolimus group, the increased incidence of DSAs between baseline and last follow-up was statistically significant. Antibody-mediated rejection occurred in 6.5% in the everolimus group and 0% in the CNIs group. The incidence of DSAs is numerically increased in kidney transplant patients treated with an everolimus-based without CNIs. A study including a larger number of patients is required to determine whether a CNI-free everolimus-based immunosuppression significantly increases DSAs formation.

International audience; Histological renal lesions observed after liver transplantation are complex, multifactorial, and interrelated. The aims of this study were to determine whether kidney lesions observed at five yr after liver transplantation can predict long-term kidney function. Ninety-nine liver transplant patients receiving calcineurin inhibitor (CNI)-based immunosuppression, who had undergone a kidney biopsy at 60 ± 48 months post-transplant, were included in this follow-up study. Kidney biopsies were scored according to the Banff classification. Estimated glomerular filtration rate (eGFR) was assessed at last follow-up, that is, 109 ± 48 months after liver transplantation. eGFR decreased from 92 ± 33 mL/min at transplantation to 63 ± 19 mL/min after six months, to 57 ± 17 mL/min at the kidney biopsy, to 54 ± 24 mL/min at last follow-up (p < 0.0001). At last follow-up, only three patients required renal replacement therapy. After the kidney biopsy, 13 patients were converted from CNIs to mammalian target of rapamycin inhibitors, but no significant improvement in eGFR was observed after conversion. Elevated eGFR at six months post-transplant and a lower fibrous intimal thickening score (cv) observed at five yr post-transplant were the two independent predictive factors for eGFR ≥60 mL/min at nine yr post-transplant. Long-term kidney function seems to be predicted by the kidney vascular lesions.

Objectives This retrospective single-center study evaluated long-term renal function after conversion from calcineurin inhibitors to sirolimus-based immunosuppression in kidney transplant recipients. Materials and methods From 2001 to 2009, one hundred fifty kidney transplant recipients were converted from calcineurin inhibitors to sirolimus at least 3 months after transplant. Results After a mean follow-up of 171 weeks, 56.7% of converted patients remained on sirolimus. The 5-year survival rate of the patients (including intent-to-treat) and grafts was 85.5% and 83.6%. Patients on sirolimus showed significant improvement in renal function with a creatinine clearance of 50.9 ± 20.7 and 52.9 ± 20.8 mL/minute at month 0 and month 24. Independent predictive factors associated with a stable estimated glomerular filtration rate at the last follow-up of sirolimus patients were (1) having a living donor, (2) absence of anti-HLA alloantibodies at month 0, and (3) cyclosporine versus tacrolimus used before conversion. Adverse effects were reported in 134 patients (89.3%). They included (1) hospitalization for infection (n=52), (2) de novo proteinuria (n=40), and (3) eight patients with biopsy-proven acute rejection. Sirolimus was stopped and replaced by calcineurin inhibitors in 37 patients after a mean of 16 months treatment. After stopping sirolimus, renal-allograft function remained stable at 2 years. Conclusions Conversion of calcineurin inhibitors to sirolimus in kidney transplant recipients was associated with improved renal function. The reintroduction of calcineurin inhibitors was safe in patients who were withdrawn from sirolimus owing to adverse effects.

INTRODUCTION The occurrence of de novo anti-human leukocyte antigen (HLA) antibodies and donor-specific antibodies (DSAs) after early graft loss is not well known. The aims of this single-center study were to evaluate the incidence of de novo DSAs and non-DSA anti-HLA antibodies after allograft nephrectomy for early graft loss and to seek the predictive factors for the development of DSAs. MATERIALS AND METHODS Thirty-two patients, who experienced an early graft loss (

Background Hepatitis E virus (HEV) infection is an emerging disease in industrialized countries. Few data regarding genotype 3 HEV extrahepatic manifestations exist. Methods We assessed kidney function and histology in solid-organ transplant patients during HEV infection. In all, 51 cases of genotype 3 HEV infections were diagnosed (34 kidney, 14 liver, and 3 kidney-pancreas transplant patients). Of these, 43.2% were cleared of the virus spontaneously within 6 months of infection, whereas 56.8% evolved to chronic hepatitis. Twelve of these patients completed a 3-month antiviral therapy and were followed up for 6 months posttreatment. Kidney function (estimated glomerular filtration rate [eGFR] obtained by the Modification of Diet in Renal Disease equation) and proteinuria were assessed before infection, during HEV infection and during follow-up. Kidney biopsies were obtained from patients with high proteinuria and decreased eGFR levels. Results During HEV infection, there was a significant decrease in eGFR in both kidney- and liver-transplant patients. Glomerular diseases were observed in kidney biopsies obtained during the acute and chronic phases. This included membranoproliferative glomerulonephritis and relapses in IgA nephropathy. The majority of patients had cryoglobulinemia that became negative after HEV clearance. Kidney function improved and proteinuria decreased after HEV clearance. Conclusion HEV-associated glomerulonephritis seems to be an HEV-related extrahepatic manifestation. Further studies are required to confirm these observations.

New-onset diabetes mellitus after transplantation (NODAT) is an important complication after kidney transplantation, responsible for increased mortality mainly related to cardiovascular events and infections. It has been also identified as an independent risk factor associated with graft loss. The varying definitions of diabetes used in the literature, and the prevalence and incidence of NODAT, are difficult to establish: it varies from 2 to 50% in the kidney transplant population. However, using the World Health Organization and the American Diabetes Association criteria, it occurs in ~15% of transplant recipients at 1 year in the USA, and ~5-10% in Europe. The main recipient-related risk factors include old age, high body weight and high body mass index (BMI) before transplantation, Afro-American or Hispanic ethnicity, hepatitis C virus (HCV) infection, and impaired fasting glucose level before transplantation. The other significant risk factors include male donor, acute rejection episodes, cytomegalovirus (CMV) infection and the immunosuppressive regimen, especially the use of tacrolimus (FK506), steroids, or mammalian target for rapamycin inhibitors. While some risk factors cannot be modified, others, such as recipient body weight, BMI, HCV or CMV infection, and immunosuppressive regimen can be controlled with an appropriate diet or treatment. Screening for impaired fasting glucose should be done before transplantation in dialysis or end-stage renal disease patients to identify patients at risk for NODAT. In patients with increased BMI, weight loss before transplantation reduces the risk of NODAT. HCV infection should be treated before transplantation. Prolonged anti-CMV prophylaxis may be used. Cyclosporine A is preferred to tacrolimus in patients at high risk of NODAT. A steroid-free regimen or early steroid withdrawal is encouraged to reduce the risk of NODAT.

Persistent diarrhea is commonly observed after solid organ transplantation (SOT). A few cases of mycophenolate mofetil (MMF)-induced duodenal villous atrophy (DVA) have been previously reported in kidney-transplant patients with chronic diarrhea. Herein, we report on the incidence and characteristics of DVA in SOT patients with chronic diarrhea. One hundred thirty-two SOT patients with chronic diarrhea underwent an oesophago-gastroduodenoscopy (OGD) and a duodenal biopsy after classical causes of diarrhea have been ruled out. DVA was diagnosed in 21 patients (15.9%). It was attributed to mycophenolic acid (MPA) therapy in 18 patients (85.7%) (MMF [n = 14] and enteric-coated mycophenolate sodium [n = 4]). MPA withdrawal or dose reduction resulted in diarrhea cessation. The incidence of DVA was significantly higher in patients with chronic diarrhea receiving MPA compared to those who did not (24.6% vs. 5.1%, p = 0.003). DVA was attributed to a Giardia lamblia parasitic infection in two patients (9.5%) and the remaining case was attributed to azathioprine. In these three patients, diarrhea ceased after metronidazole therapy or azathioprine dose reduction. In conclusion, DVA is a frequent cause of chronic diarrhea in SOT recipients. MPA therapy is the most frequent cause of DVA. An OGD should be proposed to all transplant recipients who present with persistent diarrhea.

Chronic kidney disease is a common complication after liver transplantation. However, few reports regarding kidney histology exist for this setting.Inulin clearance was measured and a kidney biopsy was performed in 99 patients at 60 ± 48 months after liver transplantation. Kidney biopsies were scored according to the Banff classification, and interstitial fibrosis was measured by a computerized quantitative method.There was a steep decrease in kidney function within the first 6 months following transplantation, but this lessened thereafter. At kidney biopsy, inulin clearance and estimated glomerular filtration rate (eGFR) (using the abbreviated Modification of Diet in Renal Disease equation) were highly correlated (r(2) = 0.47, P0.0001). A decrease in eGFR at 6 months post-transplant was the sole predictive factor for inulin clearance of60 mL/min/1.73 m(2) at 5 years post-transplant. Few patients had a specific pattern of kidney histopathology and all patients had complex primary lesions. Lowered eGFR at 6 months post-transplant was a predictive factor for50% sclerotic glomeruli on the kidney biopsy. The duration of tacrolimus therapy, as compared to cyclosporine A, was a protective factor for20% interstitial fibrosis on the kidney biopsy.In the setting of liver transplantation, this is the largest kidney-histology study to confirm that histological kidney lesions are complex, multiple and interrelated. Kidney function at 6 months post-transplant can predict long-term kidney function and histology.

Background Castleman disease (CD), or angiofollicular lymph-node hyperplasia, is an atypical lymphoproliferative disorder with heterogeneous clinical manifestations. Renal involvement in CD has been described in only single-case reports, which have included various types of renal diseases. Methods Nineteen patients with histologically documented CD and renal biopsies available were included. Clinical features and renal histological findings were reviewed, and the available samples were immunolabelled with anti-vascular endothelial growth factor (VEGF) antibody. Results Nineteen CD cases were identified: 89% were multicentric, and 84% were of the plasma-cell or mixed type. Four cases (21%) were associated with human immunodeficiency virus (HIV) infection. Among HIV-negative patients, two main patterns of renal involvement were found: (i) a small-vessel lesions group (SVL) (60%) with endotheliosis and glomerular double contours in all patients and with superimposed glomerular/arteriolar thrombi or mesangiolysis in most; and (ii) AA amyloidosis (20%). Renal histology was more heterogeneous among HIV-positive patients. Decreases in glomerular VEGF were observed only in some patients with SVL, whereas VEGF staining was normal in all other histological groups. Interestingly, glomerular VEGF loss associated with SVL was correlated with plasma C-reactive protein levels, a marker of CD activity. Conclusions Small-vessel lesions are the most frequent renal involvement in CD, whereas loss of glomerular VEGF is correlated with CD activity and could have a role in SVL pathophysiology.

Therapeutic drug monitoring of mycophenolate mofetil (MMF) was found to be beneficial in preventing acute rejection after kidney transplantation. The aim of this pilot prospective study was to evaluate the efficacy of MMF dose adjustment in de novo liver transplant patients receiving MMF at fixed versus concentration-controlled doses [ie, adapted to mycophenolic acid (MPA) AUC0-12h] and tacrolimus during the first 12 months posttransplant. Twenty-nine patients received steroids only up to day 10, induction therapy by lymphoglobulins followed by tacrolimus and MMF. In all patients, MPA AUC0-12h were measured on posttransplant days 7 and 14 and at months 1, 2, 3, 6, and 12. From March 2006 to March 2007, 15 patients received MMF at a fixed dose of 1 g twice a day for 12 months. From April 2007 to December 2007, MMF was given to 14 patients at a dose of 1 g twice a day until day 7 and was then adapted to reach an MPA AUC0-12h target of 30-60 mg x h/L. The proportion of MPA AUC0-12h values within the target range was similar in both groups. The proportion of patients with MPA AUC0-12h below 30 mg x h/L tended to be higher in the fixed dose group within the first month posttransplant. However, MMF dose did not differ significantly between the 2 groups at any period except month 1. MPA AUC0-12h tended to be higher in the concentration-controlled group at day 14 and month 2 and was significantly so at month 1. Tacrolimus trough concentrations tended to be lower in the concentration-controlled group at all study periods and was significantly so at month 3. At 12 months posttransplant, patient and graft survivals, acute rejection rate, and adverse events were similar in both groups. We concluded that adapting the dose of MMF resulted in a significant increase in MPA AUC0-12h at month 1. There was a trend toward a lower proportion of patients with MPA AUC0-12h below 30 mg x h/L in the concentration-controlled group. No difference in outcome was found between both groups.

Darbepoetin alfa is used to treat renal anemia; however, little information is available concerning its use during the posttransplant period, especially in HCV-positive patients treated with ribavirin for active hepatitis C.This study investigated the efficacy and safety of using darbepoetin alfa in this population during a 6-month treatment period. All anemic patients were HCV/RNA-positive, treated with ribavirin, and had impaired renal function. Patients (n=7) who had not been treated previously with recombinant human erythropoietin (rHuEPO) were placed in "group no rHuEPO." Patients previously with recombinant human erythropoietin (n=16; "group rHuEPO") were switched to darbepoetin alfa according to the European summary of product characteristics.Seventy-three percent of the patients were men. The mean creatinine clearance at baseline was 58.7 -/+ 21.5 mL/min. All patients received an immunosuppressive treatment. Although mean hemoglobin levels remained stable in group no rHuEPO and increased in group rHuEPO, the difference was not statistically significant. Also, the median darbepoetin-alfa-weighted dose in group no rHuEPO increased while it remained stable in group rHuEPO, as did the median daily dosage of ribavirin; however, these differences were not statistically significant. Creatinine levels and creatinine clearance levels remained stable throughout the study. No significant medical events related to the treatment were reported during the study.Darbepoetin alfa was found to be efficient and well tolerated in correcting renal anemia in transplant recipients treated with ribavirin for active hepatitis C.

International audience; BACKGROUND: In the setting of kidney transplantation, cinacalcet has been given, mainly, once daily, but also twice daily. The aims of this prospective study were to assess the acute pharmacodynamic effect of cinacalcet administrated once or twice daily to kidney transplant patients with normal renal function and persisting hypercalcaemia due to hyperparathyroidism and to evaluate 1-year efficacy and tolerance of cinacalcet given at a dose of 30 mg b.i.d. METHODS: Eleven patients, who received a transplant 6 (6-59) months previously, were included in the study. A first kinetic was done after administration of 60 mg of cinacalcet at 8 a.m. After a washout period of 1 week, the second kinetic was performed with cinacalcet given at 30 mg b.i.d within a 12-h period. RESULTS: During both kinetics, serum calcium (sCa), ionized calcium (sCa(2+)), albumin-corrected Ca and parathyroid hormone (PTH) levels decreased significantly. At 24 h after the second kinetic, sCa(2+) was significantly lower. After 1 year of cinacalcet treatment, given at the dose of 30 mg b.i.d., there was a significant decrease in sCa, sCa(2+), PTH levels and calcium x phosphorus (Ph) product. In contrast, Ph levels increased significantly. There was no significant change in renal function. CONCLUSION: Once- or twice-daily acute administration of cinacalcet to kidney-transplant patients has similar efficacy. One-year administration of cinacalcet, given as two daily doses, is safe and efficient.

International audience; INTRODUCTION: The aims of our single-center study were to identify whether pretransplant diabetes had an impact on patient survival and, secondly, the predictive factors for development of new-onset diabetes mellitus (NODM) (as defined by American Diabetes Association/World Health Organization). PATIENTS AND METHODS: One hundred seventy-nine consecutive adult orthotopic liver-transplant patients were included in this study. Immunosuppression was based on calcineurin inhibitors with steroids, with or without mycophenolate mofetil, and with or without induction therapy. To evaluate the predictive factors for NODM, donor and recipient pre- and posttransplant data were included. RESULTS: At transplantation, 38 patients had diabetes (group I), and the 141 nondiabetic patients constituted group II. In group I, paternal history of diabetes was more frequent (P=0.03), as was length of exposure to smoking (P=0.03), higher pretransplant glycemia (P

Mycoplasma hominis has been incriminated in several genital and extragenital infections. Here, we report the first case of perihepatitis associated with a perinephric abscess in a woman who had received a kidney transplant. Four months after the transplant, the patient was admitted for perirenal allograft pain, fever, and elevated inflammatory parameters and liver enzyme levels. A renal ultrasonography found a collection of fluid. Results of blood and urine analyses were within normal limits. Fluid aspiration of the peritoneal cavity was performed, and the results of cultures for bacteria and fungi were negative. The patient was treated by surgical lavage of the peritoneal cavity. Her fever resolved 5 days later. Two months after surgical lavage of the peritoneal cavity, her liver enzyme levels returned to the normal range. Three months after surgical lavage, cultures of the perinephric fluid showed Mycoplasma hominis. We conclude that in patients who present with perinephric fluid suspected of being infected, bacteriologic analysis of the fluid (from surgical lavage of the peritoneal cavity) should be performed. Antibiotics active against intracellular bacteria should be administered.

Polyomavirus-associated nephropathy (PVAN) affects 1-10% of kidney-transplant (KT) patients, with graft failure/loss in approximately 90% of cases. Reducing immunosuppression is the key treatment option, but addition of leflunomide may improve BK Virus (BKV) clearance and graft survival. In a prospective open-labeled study, 12 KT patients with biopsy-proven PVAN were treated with reduced immunosuppression and leflunomide. BKV viremia and graft function were followed. PVAN was diagnosed at 6 months (3-192) post-transplant; median serum creatinine concentration (sCC) was 189 micromol/l (92-265). After 16 months (8-30) of follow-up, the sCC was 150 micromol/l (90-378, NS). Renal function improved in six cases (50%), remained stable in two (16.6%) and deteriorated in four (33.4%), with graft loss in two (17%). Clearance of BKV viremia was observed in five (42%) cases. Side effects included anemia in six cases leading to leflunomide withdrawal in two patients, and mild thrombocytopenia. In KT patients diagnosed with PVAN, leflunomide plus reduced immunosuppression improved graft function in 66.6%, cleared BKV viremia in 42%, and resulted in side effects in 17%. This limited efficacy contrasts with other reports and falls short of expectation. We conclude that active screening, earlier diagnosis and intervention remain the cornerstones of treatment.

Background; Many etiologies lead to thrombotic microangiopathy (TMA), amongst which are antineoplastic chemotherapies. Gemcitabine, a nucleoside analogue, has been approved for the treatment of bladder and advanced non-small cell lung carcinomas (NSCLC). The reported incidence of gemcitabine-associated TMA in the literature is low, ranging from 0.015 - 0.31%. Methods.-Herein, we describe the first reported case of gemcitabine-induced TMA in a renal transplant patient. This occurred in a 54-year-old male transplant recipient undergoing sirolimus-based immunosuppression. In February 2005, he was diagnosed to have NSCLC, for which he received dual chemotherapy, including carboplatin and gemcitabine. After the third cycle he developed TMA. Results. On admission, he presented with weakness, edema, normal blood pressure, leucopenia (2,440/mm 3 ), thrombopenia (11,000/mm 3 ), hemolytic anemia with hemoglobin at 8 g/dl, schistocytes between 18 - 33%o, increase in lactate dehydrogenase at 600 IU/1 (N < 380), and decreased haptoglobin at 0.29 g/1. Renal function was stable: serum creatinine was 1.3 mg/dl, albuminemia 30 g/1, proteinuria was present at 3 g/1 in association with microscopic hematuria, and sirolimus trough level was 6.4 ng/ml. Treatment included infusions of fresh frozen plasma, withdrawal of sirolimus, which was replaced by mycophenolate mofetil, and suspension of chemotherapy. He fully recovered from TMA within 4 weeks. The concomitant use of sirolimus, which inhibits vascular endothelial growth factor, plus gemcitabine may have resulted in TMA.

TCF2, the gene encoding for hepatocyte nuclear factor 1beta, is involved in early renal development. Mutations in TCF2 lead to heterogeneous renal phenotypes. Antenatal ultrasonography may show unilateral/bilateral hyperechogenic or enlarged cystic kidneys. In children or adults, cystic renal hypoplasia/dysplasia is a common feature, occasionally associated with maturity-onset diabetes of the young type 5 and genital tract abnormalities. We report an unusual presentation characterized by massively enlarged polycystic kidneys mimicking autosomal dominant polycystic kidney disease in monozygotic twins. Bilateral enlarged cystic kidneys were discovered in week 13 of a gemellic pregnancy. Postnatally, kidney size increased in both children, reaching 16 cm at 20 years. Nephromegaly was associated with bilateral cysts and a slowly decreasing glomerular filtration rate (40 mL/min/1.73 m(2) at 20 years). There was neither pancreatic nor genital malformation. Non-type 1 diabetes mellitus was diagnosed incidentally in both twins at 20 years. Knowledge of early-onset diabetes (at age 19 years) in their father prompted us to search for the TCF2 mutation. Genetic analysis showed complete TCF2 heterozygous whole-gene deletion in both twins. Genetic testing could not be performed in the father. Bilateral massively enlarged polycystic kidneys mimicking autosomal dominant polycystic kidney disease in young adults may be related to TCF2 mutation. Although uncommon, this new phenotype enlarges the clinical spectrum of kidney involvement associated with TCF2 mutation. In this case, maturity-onset diabetes of the young-type diabetes paved the way to accurate diagnosis.

Mycophenolic acid dose modifications after renal transplantation seem to adversely affect renal allograft outcome. The aim of this retrospective study was to examine the effect of mycophenolic acid dose modifications on renal function 1 year after transplantation and to determine the factors predictive of those dose modifications within the first year after renal transplantation.All 130 patients at our institution who were treated de novo between January 2002 and April 2003 with either a mycophenolate mofetil-based or an enteric-coated mycophenolate sodium-based therapy and who had a functioning renal allograft 1 month after transplantation were included in this study.Fifty-seven patients (43.8%) underwent a dose modification during the first year after transplantation. One, 3, 6, and 12 months after transplantation, renal function was significantly improved in the patients who did not receive a dose modification. A mycophenolic acid dose that 1 year after transplantation was less than the initial dose received just after transplantation was an independent factor associated with deteriorating renal function. Sirolimus immunosuppression, Cytomegalovirus infection, and pretransplant lymphocyte counts were independent factors associated with mycophenolic acid dose modifications within the first year after kidney transplantation.Modification of the mycophenolic acid dose may adversely affect renal function 1 year after transplantation.

Chronic renal failure (CRF) is increasingly prevalent in solid-organ-transplant patients. This is in part related to the long-term use of calcineurin inhibitor (CNI) agents. However, in orthotopic liver-transplant (OLT) patients, the effects of superimposed hepatitis C virus (HCV)-related renal lesions could also be a factor. The aim of this cohort study (February 2000 to September, 2003) was to identify the predictive factors at one year post-transplantation for CRF in OLT patients associated with induction therapies. CRF was defined as having a creatinine clearance (CC) lower than 60 mL/min. Of the 97 transplants performed during that period, 72 were still functioning after one year. Of these, 33 patients (45.8%) had CRF. In univariate analysis, the predicting factors for CRF were recipient sex (female), initial liver disease (HCV-related cirrhosis), pre-transplant CC (80 mL/mn), and post-transplant serum creatinine130 micromol/L at day 3 and months (M) 1, 3, and 6. In multivariate analysis, the independent predictive factors for CRF included female sex [OR: 11.5 (2.3-58.3); p = 0.003], HCV infection [OR: 5.01 (1.1-22.7); p = 0.03], pre-OLT CC80 mL/mn [OR: 5.4 (1.2-23.7); p = 0.025], and serum creatinine at M6 greater than 130 micromol/L [OR: 19.6 (3.7-102.5); p = 0.0004]. Among all of the predictive factors for post-OLT CRF, only one is modifiable: post-transplant serum creatinine, which could be, to some extent, related to the long-term use of CNIs.

BACKGROUND Switching from calcineurin inhibitors (CNIs) to sirolimus might improve renal function in chronic renal transplant patients. METHODS In a prospective study, we assessed long-term efficacy and safety parameters in 43 renal transplant recipients who were switched from a CNI (cyclosporin A, 65%; and tacrolimus, 35%) to sirolimus for either chronic allograft dysfunction (n = 38) or recurrent cutaneous cancers (n = 5). A kidney biopsy was done in 79% of patients prior to conversion, and showed either chronic allograft nephropathy (n = 26) or CNI nephrotoxicity (n = 7). Conversion was either abrupt or progressive, with CNI withdrawal over 3 weeks. All patients also received steroids with or without mycophenolate mofetil or azathioprin. Patient data were recorded at baseline (D0), at 1 (D30) and 6 months (D180), and at 1, 1.5 and 2 years post-conversion. RESULTS After a mean post-conversion follow-up of 27+/-1.5 months, 58% of the patients were still on sirolimus. The survival of intent to treat patients and grafts was 95.3 and 93%, respectively. Overall, there was significant improvement in renal function, creatinine clearance increasing from 49.4+/-14.9 to 53+/-16.3 ml/min at D30 (P = 0.01), and to 54.7+/-20 ml/min at D180 (P = 0.01). Thereafter, creatinine clearance was not different from baseline, i.e. 54.7+/-21.7, 52.8+/-20 and 51.7+/-20.3 ml/min at years 1, 1.5 and 2, respectively. We divided the patients into two groups: responders (n = 29), those with an increase in creatinine clearance at 6 months post-conversion compared with D0, and non-responders (n = 14), those with a decrease in creatinine clearance at 6 months post-conversion compared with D0. In univariate analysis, factors predictive of response included proteinuria at D0 and the magnitudes of the differences between D30 and D0 for serum creatinine and lactate dehydrogenase. The conversion was associated with (i) significant decreases in serum calcium, phosphorus and uric acid, and in haemoglobin levels; (ii) significant increases in serum alkaline phosphatase, total cholesterol, parathyroid hormone, and the number of patients on statin and recombinant erythropoietin therapies; and (iii) the appearance of de novo proteinuria of >1 g/day in 28% of patients (P 2 g/day in 12% of the entire cohort. Kidney biopsies in 17 patients 2 years after conversion showed the same Banff scores as observed at baseline. We identified three independent predictive factors for a renal response to the switch: absence of proteinuria, presence of antihypertensive therapy at D0 and serum lactate dehydrogenase level at D30. CONCLUSION Conversion from CNIs to sirolimus in renal transplant patients with chronic allograft nephropathy was associated with improved renal function; however, 33% of the patients developed overt proteinuria.

We report on the first case of acute renal failure related to obstructive urinary tract lithiasis involving sulfadiazine crystals in a kidney transplant recipient. This patient had disseminated toxoplasmosis which was treated by sulfadiazine (4 g/day) and pyrimethamine (50 mg/day). In the fourth week of anti-toxoplasmosis therapy, he presented with obstructive acute renal failure: the plasma creatinine level increased from 220 micromol/l to 547 micromol/l. Apercutaneous pyelography was conducted showing the presence of a lithiasis located at the junction between the graft ureter and the bladder. Six days later, he underwent surgery to retrieve an orange-colored, friable stone. Its spectrophotometric analysis confirmed that the stone consisted of N-acetyl sulfadiazine crystals.

To identify the predictive factors for acute renal failure (ARF) in a retrospective study of 100 orthotopic liver transplantations (OLT) performed in 94 patients between 2000 and 2003.Acute renal failure (ARF) was defined using the RIFLE criteria, i.e. injury when creatinine doubles or GFR halves, and failure when creatinine trebles or GFR decreases by75%. Patients on dialysis pre OLT (n = 3) were excluded from the study. Immunosuppression included steroids, calcineurin inhibitors (CNIs), with (n = 32) or without mycophenolate mofetil. A total of 85% of patients also received induction therapy with antithymocyte globulins (29%) or anti-CD25 monoclonal antibodies (56%).39 patients (41.5%) and 21 (22.3%) patients developed injury, and failure, respectively. Of these, 10 (10.6%) underwent dialysis. Univariate analysis revealed that acute renal dysfunction with a RIFLE scoreor = 3 was significantly associated with a pre-operative serum creatinine level of100 micromol/l, pre-operative creatinine clearance of75 ml/mn, need for a transfusion (10 red packed units), post-operative diuresis of100 ml/h, use of vasopressive drugs, times to aspartate (AST) and alanine (ALT) aminotransferase peaks of20 and24 hours, respectively, relaparotomy, CNIs transient discontinuation, and the use of lower daily dosage of CNIs at post-OLT Days 3, 5, 7 and 15. In multivariate analysis, failure was significantly associated with time to AST peak (20 h) (OR 6.35 (1.2 - 33.6), p = 0.029), post-operative diuresis (100 ml/h) (OR 9.8 (2.03 47.3), p = 0.004), post-operative use of vasopressive drugs (OR 9.91 (2.02 - 48.7), p = 0.004), and transient CNIs withdrawal (OR 51.08 (7.58-344.1), p0.0001). Finally, the occurrence of ARF was significantly associated with an increased number of days on mechanical ventilation, on stay-in intensive care unit (ICU), and on overall hospitalization time.ARF is quite common after OLT and significantly increases the post-operative time at the hospital, thereby increasing the OLT cost. Its independent predictive factors are mainly related to perioperative events.