Polymorphism in programmed cell death 1 gene is strongly associated with lung and kidney allograft survival in recipients from CMV-positive donors.

BACKGROUND: Cytomegalovirus (CMV) has a role in chronic rejection and graft loss in kidney transplant (KTx) and lung transplant (LTx) recipients. In addition, donor CMV seropositivity is an independent risk factor for renal graft loss. The anti-CMV response might modulate this risk. Expression of programmed cell death 1 (PD-1), a receptor involved in viral-specific T-cell exhaustion, is influenced by a single nucleotide polymorphism called PD-1.3 (wild-type allele G, variant allele A). METHODS: We performed a retrospective study to assess the impact of PD-1.3 on graft outcome in donor CMV seropositive (D+) and donor CMV seronegative (D-) KTx and LTx. We also performed a case-control study to evaluate the anti-CMVpp65 response according to genotype. RESULTS: PD-1.3 was determined in 1,119 KTx and 181 LTx. In 481 D+ KTx, A allele carriers (24%) experienced significantly less graft failure compared with GG carriers (p = 0.001). Multivariate analysis showed that this association was independent of donor and recipient age, acute rejection episodes, and number of human leukocyte antigen mismatches (hazard ratio, 0.381; 95% confidence interval, 0.209-0.696; p = 0.002). Analysis in 85 D+ LTx showed similar results: A allele carriers had better survival (hazard ratio, 0.302; 95% confidence interval, 0.128-0.716; p = 0.006) and greater 6-month forced expiratory volume (71% ± 17% vs 54% ± 16%, p = 0.001). In D- recipients, PD-1.3 did not affect KTx or LTx outcome. Finally, AA recipients had a stronger anti-CMVpp65 T-cell response than matched GG recipients (p = 0.003). CONCLUSIONS: The A variant allele in PD-1.3 single nucleotide polymorphism improved graft survival in kidney and lung transplant recipients receiving grafts from CMV-positive donors.

Factors associated with albumin loss in post-dilution hemodiafiltration and nutritional consequences.

INTRODUCTION: Hemodiafiltration is currently one of the most effective techniques of extra-renal purification but results in an increase of albumin loss in dialysate. We aimed to determine the factors associated with albumin loss during post-dilution hemodiafiltration, compare an "automatic" mode of infusate flow control versus a "manual" control, and assess the potential nutritional impact. METHODS: This prospective observational study included all hemodialysis patients in our institution who underwent post-dilution hemodiafiltration 3 times a week on a Fresenius 5008 for at least 2 months. At each session, albumin content was measured in a representative effluent dialysate volume. The automatic mode of the Fresenius 5008 was used for automatic infusate flow control. RESULTS: In all, 18 patients (mean age 60.7 ± 15 years) underwent 85 post-dilution hemodiafiltration sessions. The mean albumin loss was 3134 ± 2450 mg/session. Albumin loss was significantly affected by infusate flow, infusate volume, transmembrane pressure and ultrafiltration volume. The loss was greater with Toraysulfone and FX 1000 membranes rather than FX 80 or FX 100 membranes. With AutoSub rather than manual control, infusate flow was greater (P<.001), transmembrane pressure was higher (P = .004), and the albumin loss was greater (P = .010). However, there was no correlation between albumin loss and nutritional variables. CONCLUSIONS: Albumin loss during post-dilution hemodiafiltration was correlated with increased transmembrane pressure and infusate flow, especially AutoSub flow control, and type of membrane. However, this loss, when moderate, did not seem to affect nutritional aspects and should not limit the use of hemodiafiltration.