Ingrid Masson

MDRD versus CKD-EPI equation to estimate glomerular filtration rate in kidney transplant recipients.

Background The new Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) creatinine-based equation was developed to address the systematic underestimation of the glomerular filtration rate (GFR) by the Modification of Diet in Renal Disease (MDRD) Study equation in patients with a relatively well-preserved kidney function. The performance of the new equation for kidney transplant recipients is discussed. Methods We analyzed the performances of the CKD-EPI equation in comparison with the MDRD Study equation in 825 stable kidney transplant recipients. Bias, precision, and accuracy within 30% of true GFR were determined. GFR was measured by urinary clearance of inulin (n=488) and plasma clearance of 51Cr-EDTA (n=337). Results Mean measured GFR (mGFR) was 50±19 mL/min/1.73 m2. On the whole cohort, bias was significantly lower for MDRD Study equation compared with CKD-EPI creatinine. This superiority translates into a better accuracy (80% and 74% for the MDRD and CKD-EPI creatinine, respectively). The best performance of the MDRD Study equation is confirmed both in the subgroups of patients with mGFR <60 mL/min/1.73 m2 and between 60 and 90 mL/min/1.73 m2. For mGFR >90 mL/min/1.73 m2, there were no significant differences between the two equations in terms of performance. Conclusions The CKD-EPI creatinine equation does not offer a better GFR prediction in renal transplant patients compared with the MDRD Study equation, even in the earlier CKD stages.

Venovenous haemodiafiltration for the management of dabigatran overdose in intensive care unit

Dabigatran is a direct thrombin inhibitor indicated for thromboembolism prophylaxis in patients with non-valvular atrial fibrillation. The procedure to manage dabigatran-associated haemorrhages is not well formalized. Conventional haemodialysis has been evaluated with good results. Patients with dabigatran-associated bleeding may be unstable and convective techniques like venovenous haemodiafiltration (HDF) can be interesting. We report the case of a 74-year-old, critically ill patient with haemorrhagic shock and dabigatran overexposure due to acute kidney injury. He underwent HDF and dabigatran blood concentrations decreased from 325.3 ng/mL to 160.5 ng/mL. We report here key pharmacokinetics parameters (half-life, extraction coefficient, clearance).

Protein A-Based Immunoadsorption Is More Efficient Than Conventional Plasma Exchange to Remove Circulating Anti-HLA Antibodies

We retrospectively evaluated the ability of protein-A immunoadsorption (IA) as compared to that of conventional plasma exchanges (PE) in reducing the mean fluorescence intensity (MFI) of anti-HLA antibodies assessed by the single antigen assay in sensitized renal transplant recipients. Change in MFI of 441 anti-HLA antibodies was measured after 1 single session of IA or after 3 consecutive daily PE sessions. While both strategies were able to significantly lower the amount of anti-HLA antibodies, the relative reduction in MFI was higher after IA as compared to PE (-69 vs. -58%, respectively, p = 0.003). This better efficacy of IA was observed despite a lower total volume of treated plasma (105 ± 6 vs. 160 ± 16 ml/kg after IA and after PE, respectively). Our data suggest a higher efficiency of IA over conventional PE sessions to remove anti-HLA antibodies and call for a larger evaluation of IA to confirm its potential added value in desensitization protocols.

KDIGO Guidelines and Kidney Transplantation: Is the Cystatin-C Based Recommendation Relevant?

The KDIGO guidelines propose a new approach to diagnose chronic kidney disease (CKD) based on estimated glomerular filtration rate (GFR). In patients with a GFR value comprised between 45 and 59 mL/min/1.73 m2 as estimated by the CKD‐EPI creatinine equation (eGFRcreat), it is suggested to confirm the diagnosis with a second estimation using the CKD‐EPI cystatin C‐based equations (eGFRcys/eGFRcreat‐cys). We sought to determine whether this new diagnostic strategy might extend to kidney transplant recipients (KTR) and help to identify those with decreased GFR. In 670 KTR for whom a measured GFR was available, we simulated the detection of CKD using the two‐steps approach recommended by the guidelines in comparison to the conventional approach relying on creatinine equation. One hundred forty‐five patients with no albuminuria had eGFRcreat between 45 and 59 mL/min/1.73 m2. Among them, 23% had inulin clearance over 60 mL/min/1.73 m2 and were thus incorrectly classified as CKD patients. When applying the Kidney Disease: Improving Global Outcomes (KDIGO) strategy, 138 patients were confirmed as having a GFR below 60 mL/min with eGFRcreat‐cys. However, 21% of them were misclassified in reference to measured GFR. Our data do no not support the use of cystatin C as a confirmatory test of stage 3 A CKD in KTR.

Early conversion from twice-daily tacrolimus to once-daily extended formulation in renal transplant patients before hospital discharge.

BACKGROUND Although the once-daily formulation of tacrolimus (ADVAGRAF) is approved in renal transplantation to be used immediately after surgery, conventional twice-daily formulation offers better flexibility to adjust the dosage of tacrolimus during the initial period of transplantation. MATERIAL AND METHODS We retrospectively report here our initial experience with a strategy of an early conversion from PROGRAF to ADVAGRAF before hospital discharge. RESULTS Forty-eight de novo renal transplant recipients were started on PROGRAF and then switched to ADVAGRAF after a median time of 11 days and 4.5 days, respectively, before discharge. In terms of tacrolimus exposure, great inter-individual heterogeneity was noted, with 56% of patients experiencing a clinically significant modification in post-switch tacrolimus blood trough levels. Modification in post-switch drug exposure was poorly predicted by change in tacrolimus daily dosage. Six-month post-transplant outcome was similar in patients converted to ADVAGRAF to that of patients who had remained on PROGRAF during the same period of time. Our data suggest that an early conversion from PROGRAF to ADVAGRAF during the hospital stay may be safely undertaken, provided tacrolimus exposure is tightly monitored in patients. CONCLUSIONS This strategy might represent an alternative to the immediate post-transplant introduction of ADVAGRAF and needs to be clinically validated in large-scale controlled trials.

Serum cystatin C is a determinant of central pressure augmentation index measured by oscillometric method in renal transplant recipients

BackgroundSerum cystatin C (ScysC) may help predicting cardiovascular outcome not only through its ability to detect renal dysfunction but also through its potential connection to others factors that are directly related to cardiovascular diseases. We explored the potential association of ScysC with arterial stiffness - a major contributor to cardiovascular disease - in renal transplant recipients (RTR).MethodsTraditional and non-traditional cardio-vascular risk factors were collected from 215 stable RTR whom arterial stiffness was evaluated by the measure of the augmentation index of central pressure (AIx) determined by the arteriograph device. Serum creatinine and ScysC were measured the same day using standardized methods. Association between ScysC and AIx was examined in univariate and multivariate linear regression analysis.ResultsIn univariate analysis, ScysC was strongly associated with AIx. This relationship was not confounded by age, gender, length of time spent on dialysis and transplantation vintage. Adjustment on the level of GFR estimated by the MDRD Study equation attenuated but did not abolish the association between ScysC and AIx.ConclusionsIn conclusion, ScysC is an independent predictor of AIx in RTR. Our data suggest that arterial stiffness may partially mediate the association between ScysC and cardiovascular risk in renal transplantation.

Single nucleotidic polymorphism 844 A->G of FCAR is not associated with IgA nephropathy in Caucasians

BACKGROUND IgA nephropathy is characterized by a high heterogeneity of clinical expression with 10-30% of patients progressing to end-stage renal failure. The gene of the FcαRI or CD89 presents a single-nucleotide polymorphism responsible for a proinflammatory phenotype of neutrophils in vitro and ex vivo. The aim of our study was to assess whether this CD89 polymorphism 844 A->G is (i) a marker of disease susceptibility and/or (ii) associated with a more severe prognosis. METHODS All patients diagnosed with IgA nephropathy and for whom DNA frozen sample was available were included in this European monocentric retrospective analysis and compared to a cohort of healthy volunteers. Allelic discrimination was performed by real-time quantitative polymerase chain reaction (Applied Biosystems™). We first compared the distribution of A and G alleles between patients and volunteers and then studied the relationships between alleles and renal survival, histological score, proteinuria and renal function at diagnosis. RESULTS Seven hundred and twenty-six patients were analyzed for the study of susceptibility and 425 in the association study. The presence of the G allele was not associated with the occurrence of IgA nephropathy (χ(2) test 0.57, ns). Likewise, renal survival and the criteria for disease activity at time of diagnosis were not affected by the presence of the G allele. CONCLUSIONS No significant association between 844 A->G CD89 polymorphism and the expression of the IgA nephropathy in Caucasians exists. This result does, however, not preclude the implication of other CD89 polymorphisms neither the possibility for a role of CD89 in the pathogenesis of IgA nephropathy.