Pre-transplant end-stage renal disease-related immune risk profile in kidney transplant recipients predicts post-transplant infections.

BACKGROUND: End-stage renal disease (ESRD) is associated with premature aging of the T-cell system. Nevertheless, the clinical significance of pre-transplant ESRD-related immune senescence is unknown. METHODS: We studied whether immune risk phenotype (IRP), a typical feature of immune senescence, may affect post-transplant infectious complications. A total of 486 patients were prospectively studied during the first year post transplant. IRP was defined as positive cytomegalovirus serology with at least 1 of the following criteria: CD4/CD8 ratio <1 and/or CD8 T-cell count >90th percentile. RESULTS: We found that 47 patients (9.7%) had pre-transplant IRP. IRP+ patients did not differ from IRP- patients for any clinical characteristics, but exhibited more pronounced immune senescence. Both opportunistic infections (43% vs. 6%, P < 0.001) and severe bacterial infection (SBI) (40% vs. 25%, P = 0.028) were more frequent in IRP(+) patients. In multivariate analysis, IRP was predictive of both opportunistic infection (hazard ratio [HR] 2.97 [95% confidence interval {CI} 1.53-5.76], P = 0.001), and SBI (HR 2.33 [95% CI 1.34-3.92], P = 0.008). Acute rejection rates were numerically much lower in IRP+ patients. A total of 418 patients (86%) had biological evaluation 1 year post transplant. Among 41 IRP+ patients, 35 (85%) remained IRP+ 1 year post transplant. CONCLUSION: Pre-transplant IRP is associated with an increased risk of post-transplant infection.

ATG-induced accelerated immune senescence: clinical implications in renal transplant recipients.

Persistent ATG-induced CD4(+) T cell lymphopenia is associated with serious clinical complications. We tested the hypothesis that ATG induces accelerated immune senescence in renal transplant recipients (RTR). Immune senescence biomarkers were analyzed at transplant and one-year later in 97 incident RTR -62 patients receiving ATG and 35 receiving anti-CD25 mAb (α-CD25). This consisted in: (i) thymic output; (ii) bone marrow renewal of CD34(+) hematopoietic progenitor cells (CD34(+) HPC) and lymphoid (l-HPC) and myeloid (m-HPC) progenitor ratio; (iii) T cell phenotype; and (iv) measurement of T cell relative telomere length (RTL) and telomerase activity (RTA). Clinical correlates were analyzed with a 3 year follow-up. Thymic output significantly decreased one-year posttransplant in ATG-treated patients. ATG was associated with a significant decrease in l-HPC/m-HPC ratio. Late stage differentiated CD57(+) /CD28(-) T cells increased in ATG-treated patients. One-year posttransplant T cell RTL and RTA were consequently lower in ATG-treated patients. ATG is associated with accelerated immune senescence. Increased frequency of late differentiated CD4(+) T cell frequency at transplantation tended to be predictive of a higher risk of subsequent opportunistic infections and of acute rejection only in ATG-treated patients but this needs confirmation. Considering pretransplant immune profile may help to select those patients who may benefit from ATG to prevent severe infections and acute rejection.

Polycystic kidney size and outcomes on peritoneal dialysis: comparison with haemodialysis.

BACKGROUND: For many nephrologists, patients with polycystic kidney disease (PKD) have an increased risk of complications and technique failure on peritoneal dialysis (PD) due to enlarged kidneys. The literature showed that PD can be as good a therapeutic option as haemodialysis (HD) for patients with PKD. However, no study has focused on the impact of polycystic kidney size on outcomes for patients on PD. METHODS: This is a retrospective monocentric study. Fifty-eight patients with PKD started dialysis between January 2000 and December 2010: 24 on PD and 34 on HD. Kidney size assessed by abdominal computed tomography scans was available for 45 patients (19 on PD and 26 on HD). PD technique survival, specific PKD complications and mechanical and infectious PD complications, as need for pre-transplant nephrectomy and kidney transplantation, were considered. RESULTS: The two cohorts were similar in terms of age and body surface area. The median kidney size was not significantly different between PD and HD patients [19.1 cm (12.5-32.5) versus 16.5 cm (11.8-33.8), respectively, P = 0.13]. However, we identified an increased number of PD patients with larger kidneys [(>25 cm) (27.8% on PD versus 7.7% on HD (P = 0.07)]. Neither cystic (infection or haemorrhage) nor mechanical complications (hernias and leaks) were different in PD or HD. Ten patients experienced PD-related peritonitis, mainly due to non-enteric bacterial pathogens. The main reason for stopping PD and HD was transplantation. Six PD patients underwent nephrectomy in order to access the transplant programme. Among them, five were maintained on PD after surgical procedure with good adequacy dialysis criteria. CONCLUSIONS: We observed no deleterious impact of kidney size on outcomes on PD when compared with HD. A large kidney size in patients with PKD is not a contraindication to PD. Patients for whom a pre-transplant nephrectomy is mandatory can also safely opt for PD as a dialysis method.

[Atypical progressive multifocal leukoencephalopathy (PML) in a patient with pulmonary sarcoidosis]. / Leucoencéphalopathie multifocale progressive atypique chez un patient atteint de sarcoïdose médiastinopulmonaire.

INTRODUCTION: Progressive multifocal leukoencephalopathy (PML) is a demyelinating disease of central nervous system due to the JC virus. PML generally occurs in immunocompromised hosts and has a fatal outcome. OBSERVATION: We report a case of an atypical PML in a patient with pulmonary sarcoidosis: MRI showed multifocal and punctate contrast enhancements. The diagnostic was made by brain biopsy. CONCLUSION: The pathophysiology of this association is probably related to the immunodepression induced by sarcoidosis.