Damien Thibaudin

Predicting glomerular filtration rate in kidney transplantation: are the K/DOQI guidelines applicable?

The kidney disease outcomes quality initiative (K/DOQI) guidelines introduced a classification of chronic kidney disease (CKD) based on the level of kidney function. In order to predict the glomerular filtration rate (GFR), they specifically recommended the use of the modification of diet in renal disease (MDRD) study and Cockcroft–Gault (C–G) equations.

Significant Risk Factors for Occurrence of Cancer After Renal Transplantation: A Single Center Cohort Study of 1265 Cases

Occurrence of cancer after renal transplantation remains a major problem, and the second cause of death. We performed a retrospective analysis of first cancer, first skin cancer, and first organ cancer (including posttransplant lymphoproliferative disease [PTLD]) among 1265 cases from 1979 to 2006. The occurrence of cancer was clearly a time-dependent event justifiying the use of Kaplan-Meier survival and Cox regression methods. The 10-year cumulative incidences of first cancer, first skin cancer, and first organ cancer were 24.6%, 14.5%, and 14.5%, respectively. Recipient age was a major, independent risk factor for the 3 endpoints with a 6% increased relative risk for each year increment (P < .0001). Female gender was also a major, independent risk factor, but only for skin cancer (P = .0002). We could not demonstrate any difference between the immunosuppressive drugs used for induction or maintenance therapy, especially between antithymocyte globulin (ATG) vs anti-CD25, cyclosporine vs tacrolimus, and azathioprine vs mycophenolate mofetil. Large cohorts are needed with strict stratifications for recipient age and gender to detect any difference, if any, among the drugs.

Hypertension after renal transplantation and polymorphism of genes involved in essential hypertension: ACE, AGT, AT1R and ecNOS

BACKGROUND Arterial hypertension (HT), secondary to cyclosporine A (CsA) used as main immunosuppressive treatment in renal transplantation (RTx), is very frequent (70%), usually severe and explained mostly by vasoconstriction of the glomerular afferent arteriole with secondary sodium and water retention. MATERIAL AND METHODS In a retrospective study, we have analyzed 294 consecutive recipients receiving a first renal cadaveric allograft and all treated with CsA (the majority with triple therapy). We studied, by molecular biology, the polymorphism of genes previously implicated in essential HT such as: angiotensin-converting enzyme (ACE: II, ID and DD), angiotensinogen (AGT: MM, MT and TT), angiotensin II type 1 receptor (AT1-R: AA, AC and CC) and endothelial constitutive nitric oxide synthase (ecNOS: aa, ab and bb), and correlated the data to the prevalence and severity of post-Tx HT. This cohort included 195 (66%) males and 99 females with a mean age of 42 years at time of Tx. The presence and severity of post-Tx HT were indicated by initial persistent blood pressure over 140/90 mmHg with the need for at least one anti-hypertensive drug and by the number of anti-HT medications required to achieve its control. RESULTS The distribution of the specific alleles and genotypes for ACE, AGT, AT1-R, and ecNOS was not different in transplant recipients compared to 181 controls. At 5 years post-Tx, the prevalence of HT was 72% (169 out of 235) among functioning grafts. There was no significant difference for ACE, AGT, AT1R and ecNOS genotypes distribution between hypertensive vs non-HT recipients. The number of anti-hypertensive drugs prescribed was not different among ACE, AGT, and AT1-R genotypes. However, the a allele and the non-bb genotype (aa + ab) for ecNOS were significantly (p = 0.001) associated with a less severe HT, needing fewer anti-HT drugs. At 10 years post-Tx, the HT prevalence remained high 78% (67 out of 86) among functioning Tx. However, the limited numbers did not allow further correlation. CONCLUSIONS This study produced mainly negative results except for ecNOS-a allele, which seems to protect against severe hypertension. The explanation remains speculative but probably relates to the known cyclosporine-induced upregulation of ecNOS gene and enzyme activity.

Results of the HepZero study comparing heparin-grafted membrane and standard care show that heparin-grafted dialyzer is safe and easy to use for heparin-free dialysis.

Heparin is used to prevent clotting during hemodialysis, but heparin-free hemodialysis is sometimes needed to decrease the risk of bleeding. The HepZero study is a randomized, multicenter international controlled open-label trial comparing no-heparin hemodialysis strategies designed to assess non-inferiority of a heparin grafted dialyzer (NCT01318486). A total of 251 maintenance hemodialysis patients at increased risk of hemorrhage were randomly allocated for up to three heparin-free hemodialysis sessions using a heparin-grafted dialyzer or the center standard-of-care consisting of regular saline flushes or pre-dilution. The first heparin-free hemodialysis session was considered successful when there was neither complete occlusion of air traps or dialyzer, nor additional saline flushes, changes of dialyzer or bloodlines, or premature termination. The current standard-of-care resulted in high failure rates (50%). The success rate in the heparin-grafted membrane arm was significantly higher than in the control group (68.5% versus 50.4%), which was consistent for both standard-of-care modalities. The absolute difference between the heparin-grafted membrane and the controls was 18.2%, with a lower bound of the 90% confidence interval equal to plus 7.9%. The hypothesis of the non-inferiority at the minus 15% level was accepted, although superiority at the plus 15% level was not reached. Thus, use of a heparin-grafted membrane is a safe, helpful, and easy-to-use method for heparin-free hemodialysis in patients at increased risk of hemorrhage.

Treatment tolerance and patient-reported outcomes favor online hemodiafiltration compared to high-flux hemodialysis in the elderly

Large cohort studies suggest that high convective volumes associated with online hemodiafiltration may reduce the risk of mortality/morbidity compared to optimal high-flux hemodialysis. By contrast, intradialytic tolerance is not well studied. The aim of the FRENCHIE (French Convective versus Hemodialysis in Elderly) study was to compare high-flux hemodialysis and online hemodiafiltration in terms of intradialytic tolerance. In this prospective, open-label randomized controlled trial, 381 elderly chronic hemodialysis patients (over age 65) were randomly assigned in a one-to-one ratio to either high-flux hemodialysis or online hemodiafiltration. The primary outcome was intradialytic tolerance (day 30-day 120). Secondary outcomes included health-related quality of life, cardiovascular risk biomarkers, morbidity, and mortality. During the observational period for intradialytic tolerance, 85% and 84% of patients in high-flux hemodialysis and online hemodiafiltration arms, respectively, experienced at least one adverse event without significant difference between groups. As exploratory analysis, intradialytic tolerance was also studied, considering the sessions as a statistical unit according to treatment actually received. Over a total of 11,981 sessions, 2,935 were complicated by the occurrence of at least one adverse event, with a significantly lower occurrence in online hemodiafiltration with fewer episodes of intradialytic symptomatic hypotension and muscle cramps. By contrast, health-related quality of life, morbidity, and mortality were not different in both groups. An improvement in the control of metabolic bone disease biomarkers and β2-microglobulin level without change in serum albumin concentration was observed with online hemodiafiltration. Thus, overall outcomes favor online hemodiafiltration over high-flux hemodialysis in the elderly.

Éruption et syndrome néphrotique, penser à la syphilis

Resume Introduction Parmi les manifestations cliniques de la syphilis secondaire figure la nephropathie, comme en temoigne cette observation. Observation Chez un homme de 63 ans, a l’occasion d’une syphilis secondaire confirmee par les examens serologiques, est survenu un syndrome nephrotique correspondant a une glomerulonephrite extra-membraneuse de type 1 a la biopsie renale. Commentaires La glomerulonephrite extra-membraneuse est une complication immunologique de la syphilis secondaire. D’evolution presque toujours favorable sous traitement, elle est souvent associee a des manifestations pouvant orienter a tort vers une connectivite.

Identifying Hemodialysis Patients With the Highest Risk of Staphylococcus aureus Endogenous Infection Through a Simple Nasal Sampling Algorithm

AbstractIn contrast to Staphylococcus aureus intermittent nasal carriers, persistent ones have the highest risk of infection. This study reports the usefulness of a simple nasal sampling algorithm to identify the S. aureus nasal carriage state of hemodialysis patients (HPs) and their subsequent risk of infection.From a cohort of 85 HPs, 76 were screened for S. aureus nasal carriage once a week during a 10-week period. The S. aureus nasal load was quantified by using either culture on chromogenic medium or fully automated real-time polymerase chain reaction assay. Molecular typing was used to compare strains from carriage and infection.The algorithm based on quantitative cultures was able to determine the status of S. aureus nasal carriage with a sensitivity of 95.8%, a specificity of 94.2%, a positive predictive value of 88.5%, and a negative predictive value of 98.0%. Of note, the determination of the S. aureus carriage state was obtained on the first nasal sample for all the 76 HPs, but 1 (98.7%). The algorithm based on quantitative polymerase chain reaction assay directly from the specimen yielded similar performances. During the 1-year follow-up after the last sampling episode, HPs classified as persistent nasal carriers with the algorithm were found to have a higher risk of S. aureus infection than those classified as nonpersistent carriers (P < 0.05), especially for infections of endogenous origin (P < 0.001).This simple algorithm is reliable for determining the S. aureus nasal carriage status in clinical practice and could contribute to characterize at an early stage of take-up patients with the highest risk of S. aureus infection.

Anti-phospholipase A2 receptor antibody levels at diagnosis predicts spontaneous remission of idiopathic membranous nephropathy

Abstract Background: The diagnostic role of circulating anti-phospholipase A2 receptor antibodies (anti-PLA2R Abs) is now well recognized in idiopathic membranous nephropathy (iMN). These Abs could also be interesting as predictors of clinical outcome. In this study, we explored the prognostic value of anti-PLA2R Abs measured in a cohort of iMN patients, with a special focus on their ability to detect patients achieving spontaneous remission. Methods: All adult patients with biopsy-proven iMN diagnosed between 1978 and 2007 were retrospectively screened in our centre. Using a validated enzyme-linked immunosorbent assay, levels of anti-PLA2R Abs were measured from serum samples obtained at the time of renal biopsy and stored at −80°C until processing. Clinical data on disease activity, treatments and outcomes were collected by reviewing patients’ medical records. The association between anti-PLA2R Ab titres and clinical activity/outcome was assessed by Cox proportional hazard and Kaplan–Meier methods. Results: In this retrospective study, 68 patients were included in the final analysis (median follow-up of 81 months). No significant association was found between anti-PLA2R Ab titres at diagnosis with baseline proteinuria, baseline estimated glomerular filtration rate or chronic kidney disease progression. Spontaneous remission was observed in 22% of patients. Ab titres were significantly and gradually correlated in a dose–response manner with the likelihood of spontaneous remission. Conclusions: While Ab titres measured at diagnosis were not found to predict the activity of iMN, evaluation of anti-PLA2R Ab titres might prove useful in the early identification of patients likely to achieve spontaneous remission.

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.

Spectrum of ANCA-Associated Disorders According to Serological Phenotype in Routine Care: Retrospective Case Series of 209 Patients

Objective : To summarize the experience of three years of positive ANCA (anti-neutrophil cytoplasmic antibodies) testing in a single university based hospital. We describe the clinical features according to ANCA phenotype of patients who did and did not have ANCA- associated vasculitis (AAV). Methods : We did a review of all samples tested for ANCA in a 3 year-period (2005-2007). Each sample was tested by indirect immunofluorescence (IIF) and enzyme-linked-immunosorbent assay (ELISA). Sera were considered as positive for ANCA testing if either IIF or ELISA for MPO or PR3 antigen specificity was positive. Patients were considered as having AAV on established diagnostic criteria and algorithms. Results : The positive ANCA population consisted in 209 patients, 54 were classified in the AAV group and 155 patients constituted the “Others” group. The typically most relevant ANCA phenotypes (C-ANCA/anti-PR3+ and P-ANCA/anti-MPO+) were detected in 90 % (49/54) of patients in the AAV group and only 10% (15/155) of the “Others” group (p < 0.001). Among the latter none developed AAV during follow-up. Positive IIF alone was found in 4% (2/54) of the AAV group and in 68% (105/155) of the “Others” group (p < 0.001). In patients without AAV, positive IIF alone or positive ELISA with negative IIF represented the main ANCA pattern. Conclusion : In routine clinical practice, most patients with positive ANCA testing do not have AAV. The typical ANCA pattern (C-ANCA/anti-PR3+ or P-ANCA/anti-MPO+) remains a strong predictor of AAV in patients with a high level of suspicion for systemic vasculitis. In other cases, ANCA positivity should be interpreted with extreme caution.