PAI-1 donor polymorphism influences long-term kidney graft survival.

International audienceBACKGROUND: The type 1 plasminogen activator inhibitor (PAI-1) is involved in the development of fibrosis, and its intrarenal expression is increased in interstitial fibrosis and tubular atrophy (IFTA). Moreover, a 4G/5G polymorphism of the PAI-1 gene has been described associating 4G haplotype with higher PAI-1 plasma activity. We investigated the relationship between the donor and recipient PAI-1 polymorphism and kidney graft survival. METHODS: The PAI-1 genotype was determined for both the 304 donors and the 337 corresponding recipients. In recipients, PAI-1 antigen levels were also determined. We compared 4G/4G donors versus donors with other genotypes. RESULTS: Donor or recipient genotype did not influence the PAI-1 plasma level in recipients. Actuarial kidney graft survival was significantly reduced in the 4G/4G donor group (107 months versus 147.5 months, P = 0.013), while recipient PAI-1 genotype did not show any influence on graft survival. Moreover, graft loss due to IFTA proved significantly higher in the 4G/4G donor group (13% versus 6%, P = 0.03). Multivariate analysis showed that the significant independent variables associated with graft loss were the donor 4G/4G genotype, acute clinical rejection and donor age. CONCLUSION: Our study suggests that donor PAI-1 polymorphism influences kidney graft survival and that the donor 4G/4G genotype is an independent risk factor for graft loss. Prospective studies are needed to confirm these results

Donor P-gp polymorphisms strongly influence renal function and graft loss in a cohort of renal transplant recipients on cyclosporine therapy in a long-term follow-up.: Donor's P-gp polymorphisms and graft loss

International audienceCyclosporin A (CsA) is a substrate for cytochrome P450 3A and the efflux transporter P-glycoprotein (P-gp; ABCB1), both abundantly expressed in the kidney. In a long-term follow-up of a cohort of patients who had received kidney transplants between the years 1990 and 2005, we retrospectively investigated the effect of CYP3A4, CYP3A5, and ABCB1 polymorphisms in kidney graft donors on recipients' renal function and risk of subsequent graft loss. DNA samples from 227 donors and clinical data from the 259 respective recipients were analyzed. Graft loss was significantly associated with the presence of the ABCB1 variant haplotype 1236T/2677T/3435T in the donor (1236T/2677T/3435T vs. other haplotypes: hazard ratio = 9.346; 95% confidence interval (CI) (2.278-38.461); P = 0.0019) and with previous episodes of acute organ rejection (hazard ratio = 3.077; 95% CI (1.213-7.812); P = 0.0178). The variant haplotype was also associated with a greater decrease in renal function (homozygotes for TTT -3.047 mlxmin(-1)/year; heterozygotes for TTT -4.435 mlxmin(-1)/year; others -2.186 mlxmin(-1)/year; P = 0.0240). The study showed that the presence of ABCB1 polymorphisms in donors influences long-term graft outcome adversely with decrease in renal function and graft loss in transplant recipients receiving CsA

Bordetella holmesii bacteremia in a renal transplant recipient: emergence of a new pathogen.

International audienceBordetella holmesii is a gram-negative rod that was initially identified in 1995. It causes bacteremia, pneumonia, and endocarditis mostly in patients with anatomical or functional asplenia. We report here, to the best of our knowledge, the first case of B. holmesii bacteremia in a renal transplant recipient following rituximab therapy for recurrence of membranoproliferative glomerulonephritis

HEMO 2 life® improves renal function independent of cold ischemia time in kidney recipients: A comparison with a large multicenter prospective cohort study

International audienceM101 is an extracellular hemoglobin isolated from a marine lugworm and is present in the medical device HEMO2 life®. The clinical investigation OXYOP was a paired kidney analysis (n = 60) designed to evaluate the safety and performance of HEMO2 life® used as an additive to preservation solution in renal transplantation. The secondary efficacy endpoints showed less delayed graft function (DGF) and better renal function in the HEMO2 life® group but due to the study design cold ischemia time (CIT) was longer in the contralateral kidneys

Eight-Year Results of the Spiesser Study, a Randomized Trial Comparing de Novo Sirolimus and Cyclosporine in Renal Transplantation

International audienceWe present the results at 8 years of the Spiesser study, a randomized trial comparing de novo sirolimus and cyclosporine in kidney transplant recipients at low immunologic risk. We assessed estimated glomerular filtration (eGFR), graft, patient, and death-censored graft survival (log-rank compared), de novo DSA appearance, risk of malignancy, post-transplant diabetes mellitus (PTDM), and anemia. Intent-to-treat and on-treatment analyses were performed. Graft survival was similar in both groups (sirolimus: 73.3%, cyclosporine: 77.7, P = 0.574). No difference was observed between treatment groups concerning patient survival (P = 0.508) and death-censored graft survival (P = 0.858). In conditional intent-to-treat analysis, mean eGFR was greater in sirolimus than in cyclosporine group (62.5 ± 27.3 ml/min vs. 47.8 ± 17.1 ml/min, P = 0.004), in particular because graft function was excellent in patients maintained under sirolimus (eGFR = 74.0 ml/min). Importantly, no detrimental impact was observed in patients in whom sirolimus has been withdrawn (eGFR = 49.5 ml/min). Overall, 17 patients showed de novo DSAs, with no difference between the two groups (P = 0.520). Malignancy did not differ by treatment. An initial maintenance regimen based on sirolimus provides a long-term improvement in renal function for kidney transplant patients, especially for those maintained on sirolimus

A lack of significant effect of POR*28 allelic variant on tacrolimus exposure in kidney transplant recipients

International audienceBACKGROUND: POR*28 is a recently newly described allelic variant of the cytochrome P450 oxydoreductase (POR) which might be associated with an increased metabolic activity of P450 cytochromes (CYP) 3A5 and 3A4. Consequently, carriers of at least one allele of this polymorphism could require increased calcineurin inhibitors doses to reach the target residual concentrations (Co). The objective of this study is to test whether the allelic variant of POR, which is associated with an increased metabolic activity of CYP3A, impacts Tacrolimus (Tac) pharmacokinetics. METHODS: We tested this hypothesis in a population of 229 kidney transplant recipients (KTR) from a large, multicenter, prospective and randomized study. We have analyzed the association between POR*28 genotype and the proportion of individuals reaching the target Tac residual concentration (Tac Co) 10 days after transplantation. We have also measured the association between POR*28 and the Tac Co, and adjusted Tac Co (Tac Co/Tac dose) over time using generalized mixed linear models. RESULTS: Ten days after transplantation, there was no difference of frequencies of KTR within the target range of Tac Co (Co 10-15 ng/ml) according to the POR*28 genotype (p=0.8). The mean Tac Co at day 10 in the POR*1/*1 group was 15.3±9.7 ng/ml compared with 15.7±7.8 ng/ml in the POR*1/*28 group and 14.2 ±6.8 ng/ml, in the POR*28/*28 group, p=0.8. The adjusted Tac Co was not associated with POR*28 genotype over time (random effects model, p=0.9). When restricted to KTR expressing CYP3A5, POR*28 gentoype did not impact the proportion of individuals within the Tac Co target range neither the adjusted Tac Co (random effects model, p=0.1). CONCLUSIONS: POR*28 does not significantly influence Tac pharmacokinetic parameters in a large cohort of KTR. This study does not confirm recent findings indicating that POR*28 carriers require more Tac to reach target C

Occurrence of severe COVID-19 in vaccinated transplant patients

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