Impact of reduced exposure to calcineurin inhibitors on the development of de novo DSA: a cohort of non-immunized first kidney graft recipients between 2007 and 2014.

BACKGROUND: In low-immunological risk kidney transplant recipients (KTRs), reduced exposure to calcineurin inhibitor (CNI) appears particularly attractive for avoiding adverse events, but may increase the risk of developing de novo Donor Specific Antibodies (dnDSA). METHODS: CNI exposure was retrospectively analyzed in 247 non-HLA immunized first KTRs by taking into account trough levels (C0) collected during follow-up. Reduced exposure to CNI was defined as follows: C0 less than the lower limit of the international targets for ≥50% of follow-up. RESULTS: During a mean follow-up of 5.0 ± 2.0 years, 39 patients (15.8%) developed dnDSA (MFI ≥1000). Patients with DSA were significantly younger (46.6 ± 13.8 vs. 51.7 ± 14.0 years, p = 0.039), received more frequently poorly-matched grafts (59% with 6-8 A-B-DR-DQ HLA mismatches vs. 34.6%, p = 0.016) and had more frequently a reduced exposure to CNI (92.3% vs. 62.0%, p = 0.0002). Reduced exposure to CNI was associated with an increased risk of dnDSA (multivariable HR = 9.77, p = 0.002). Reduced exposure to CNI had no effect on patient survival, graft loss from any cause including death, or post-transplant cancer. CONCLUSIONS: Even in a low-immunological risk population, reduced exposure to CNI is associated with increased risk of dnDSA. Benefits and risks of under-immunosuppression must be carefully evaluated before deciding on CNI minimization.

[Idiopathic retroperitoneal fibrosis: a multicentric retrospective study of 30 French cases and follow-up of the renal function]. / Fibrose rétropéritonéale idiopathique : évolution à long terme du pronostic rénal dans une série rétrospective multicentrique de 30 cas.

PURPOSE: Idiopathic retroperitoneal fibrosis (IRF) is an inflammatory disorder, affecting the aorta and the surrounding vessels and tissues. The prognosis is mainly driven by the risks of chronic kidney disease and relapse. Our aim was to assess the prevalence of chronic kidney disease at follow-up. METHODS: We retrospectively reviewed the medical records of patients diagnosed for IRF in Seine-Saint-Denis (France) between 1987 and 2011. We collected informations about presentation, radiologic findings and follow-up. Diagnosis of IRF was confirmed when all the following criteria were met: infiltration of the infrarenal aorta or iliac vessels, absence of aneurysmal dilation, lack of clinical suspicion of malignancy. RESULTS: Thirty patients were identified, with a male/female ratio of 4.9. Mean age was 55±13 years old. The mean creatinine clearance was 66 mL/min/1.73 m(2) and the mean CRP was 45±36 mg/L. In 24 (80%) patients, the location of IRF was periaortic and periiliac. Eleven patients (37%) underwent a diagnostic biopsy, and 14 (47%) required an ureteral procedure. A mean follow-up of 63 months was available for 29 patients: 69% relapsed, 7 developed chronic renal disease (24%), and one died of urinary sepsis. Older age (P=0.023), diabetes (P=0.007), and initial renal insufficiency (P=0.05) were associated with a risk of chronic renal insufficiency. CONCLUSION: The high frequency of relapses and chronic renal disease emphasizes the need of close follow-up in patients diagnosed with IRF.

[Management of orbital inflammation in internal medicine: a retrospective case series of 29 patients]. / Prise en charge de l'inflammation orbitaire en médecine interne : à propos d'une série de 29 patients consécutifs.

PURPOSE: To describe a case series of patients investigated in internal medicine for an inflammation of the orbit and to clarify the clinical and pathological features of patients with idiopathic orbital inflammatory syndrome (IOIS). PATIENTS AND METHODS: Forty patients were consecutively referred by a specialized center where an orbital biopsy was performed in case of accessible lesion. Eleven patients were excluded because of missing data or diagnosis of lymphomas, periorbital xanthogranulomas, or Graves' disease. Patients with systemic disease (SD) or auto-immune disorder (AID) that validated the international criteria, or those having an IOIS in the absence of local or systemic etiology, were included. The clinicopathologic and immunologic characteristics of IOIS patients, their treatment and their evolutionary profiles are reported according to the histological types described by Mombaerts. RESULTS: Of the 29 patients enrolled, eight had a dacryoadenitis revealing a SD/AID, mainly a necrotizing vasculitis, seven patients had a presumed IOIS and 14 an IOIS histologically documented. The presentation of IOIS was dominated by a diffuse involvement of the orbit. Corticosteroids were administered alone or with an immunosuppressant in 57 and 24% of IOIS patients, respectively. The incidence of relapse/resistance was higher than that of remission, particularly in case of presumed IOIS or in its classical form. All four patients with a stage III-IV of Chisholm were relapsing or resistant. CONCLUSION: A dacryoadenitis may reveal some types of SD/AID. Unlike the severe sialadenitis, the form of sclerosing IOIS may not be a factor associated with relapse or resistance.

Recurrent dysphonia and acitretin.

We report the case of a woman complaining of dysphonia while she was treated by acitretin. Her symptoms totally regressed after drug withdrawal and reappeared when acitretin was reintroduced. To our knowledge, this is the first case of acitretin-induced dysphonia. This effect may be related to the pharmacological effect of this drug on mucous membranes.

Association of CYP2A6*1B genetic variant with the amount of smoking in French adults from the Stanislas cohort.

This study was designed in order to investigate the influence of the genetic polymorphism of CYP2A6 on the amount of smoking. In all, 463 French adults included in the Stanislas cohort were studied and underwent two examinations at 5 years distance (t0 and t(+5) years). Information on their smoking habits was collected. They were genotyped by RFLP for the CYP2A6*1A, CYP2A6*1B and CYP2A6*4 alleles. CYP2A6*1B and CYP2A6*4 allele frequencies were 32 and 4%, respectively. The subjects carrying the CYP2A6*1B allele oxidize nicotine to cotinine faster than subjects with the CYP2A6*1A allele. The number of cigarettes smoked per day was significantly higher in the CYP2A6*1B/*1B group as compared to the CYP2A6*1A/*1A group (P = 0.01 at t0; P = 0.001 t(+5) years), with a larger increase in their daily cigarettes consumption over the 5-year period (P = 0.006). No significant difference in the smoking status was observed according to the CYP2A6 genotype. These data suggest that the CYP2A6*1B is associated with the number of cigarettes smoked per day.