Non-disclosure of drug injection practices as a barrier to HCV testing: results from the PrebupIV community-based research study.

BACKGROUND: Hepatitis C virus (HCV) infection prevalence is particularly high in people who inject drugs (PWID), a population that faces many barriers to HCV testing and care. A better understanding of the determinants of access to HCV testing is needed to improve their engagement in the HCV care cascade. We used data from a cross-sectional survey of people who inject drugs, mainly opioids, to identify factors associated with recent HCV testing. METHODS: Self-reported data on HCV antibody testing were analyzed for 550 of the 557 PWID enrolled in PrebupIV, a French cross-sectional community-based survey which assessed PWID acceptability of injectable buprenorphine as a treatment. Factors associated with recent (i.e., in the previous six months) HCV antibody testing were identified performing multivariable logistic regression. RESULTS: Among the study sample, 79% were men and 31% reported recent HCV antibody testing. Multivariable analysis found that PWID who did not disclose their injection practices to anyone (aOR [95% CI] 0.31 [0.12,0.82], p = 0.018), older PWID (aOR [95% CI] 0.97 [0.95,1.00], p = 0.030) and employed respondents (aOR [95% CI] 0.58 [0.37,0.92], p = 0.019) were all less likely to report recent HCV testing. No association was found between opioid agonist therapy and HCV testing. CONCLUSIONS: Our findings suggest that non-disclosure of injection practices, employment and age were all barriers to HCV antibody testing. Preventing stigma around injection practices, developing the HCV testing offer in primary care and addiction care services, and training healthcare providers in HCV care management could improve HCV testing and therefore, the HCV care cascade in PWID.

Outcome-dependent geographic and individual variations in the access to renal transplantation in incident dialysed patients: a French nationwide cohort study.

This study investigated geographical variations of access to renal transplantation using three outcomes (access to the transplant waiting list, access to renal transplantation after waitlisting and access to renal transplantation after dialysis start). Associations of patient-related and regional variables with the studied outcomes were assessed using a Cox shared frailty model and a Fine and Gray model. At the study endpoint (December 31, 2015), 26.3% of all 18-90-year-old patients who started dialysis in the 22 mainland and four overseas French regions in 2012 (n = 9312) were waitlisted and 15.1% received a kidney transplant. The geographical disparities of access to renal transplantation varied according to the studied outcome. Patients from the Ile-de-France region had the highest probability of being waitlisted, but were less likely to receive a kidney transplant. Two regional factors were associated with the access to the waiting list and to renal transplantation from dialysis start: the incidence of preemptive kidney transplantation and of ESRD. The use of different outcomes to evaluate access to kidney transplantation could help healthcare policy-makers to select the most appropriate interventions for each region in order to reduce treatment disparities.

Daily hemodialysis practices in Australia/New Zealand and in France: a comparative cohort study.

BACKGROUND: As patients on daily hemodialysis (DHD) have heterogeneous profiles, DHD benefit in terms of survival is still debated. The aim of this study was to compare DHD practices in France and in Australia and New Zealand. METHODS: This study was based on data from the French Renal Epidemiology and Information Network (REIN) and the Australian and New Zealand Dialysis and Transplant Registry (ANZDATA). All incident patients from both registries who underwent DHD (i.e., 5-6 sessions/week, including short daily hemodialysis and long nocturnal hemodialysis) at least once during their trajectories were included, and their characteristics and care trajectories were compared. For survival analyses, one French patient was matched to one Australian or New Zealand patient, based on age, sex and year of dialysis start. Survival was assessed using the Cox proportional hazards model, and access to renal transplantation was evaluated using the Fine & Gray model to take into account death as competing risk. RESULTS: Between 2003 and 2012, 523 patients from the AZNDATA and 753 from the REIN registry started DHD. ANZDATA patients were younger (54.8 vs 64.0 years, p < 0.001) and had comorbidities more frequently than French patients. In both registries, one third of patients were on early DHD (i.e., DHD started less than one year after dialysis initiation). Long nocturnal hemodialysis was more frequent in the ANZDATA than in the REIN cohort (20.8 and 3%, respectively). Comparison of the matched subgroups showed comparable survival rates between French and Australian/New Zealand patients (HRadjusted = 1.08; 95%CI: 0.78-1.50). Access to renal transplantation also was similar between matched groups (SHRadjusted = 1.30, 95%CI: 0.86-1.97). CONCLUSIONS: Our study shows that, despite differences in terms of patients' characteristics and DHD regimens, the mortality risk and access to renal transplantation are similar in France and Australia and New Zealand.

Association between daily haemodialysis, access to renal transplantation and patients' survival in France.

AIM: Daily haemodialysis improves patients' quality of life and blood purification, but its effect on survival remains controversial. The aim of this study was to analyze the association between daily haemodialysis and renal transplantation and survival in France. METHODS: This was an observational cohort study based on the French REIN registry. All incident patients ≥18 years old who started daily haemodialysis in France between 2003 and 2012 were included. Using a propensity score, 575 patients on daily haemodialysis were matched with 1696 patients receiving thrice-weekly haemodialysis. Survival analysis was performed using the Cox model. Access to the renal transplant waiting list and renal transplantation were analyzed using the Fine and Gray model. RESULTS: Daily haemodialysis was not independently associated with reduced access to transplant waiting list, whereas, major comorbidities remained associated with restricted waitlisting after multivariate analysis adjusted for confounding factors. After being waitlisted, the cumulative incidence of renal transplantation was lower for the daily haemodialysis than for the thrice-weekly haemodialysis group (SHR = 0.72, 95%CI: 0.56-0.91). The risk of death was significantly higher in the daily haemodialysis group (HRadjusted  = 1.58, 95%CI: 1.4-1.8). Major comorbidities were associated with higher risk of death and lower likelihood of receiving a renal transplant during the follow-up period. CONCLUSION: Our study showed that in France, the likelihood of undergoing renal transplantation after being waitlisted was lower for patients on daily haemodialysis than those on thrice-weekly haemodialysis. Moreover, daily haemodialysis was associated with higher risk of death, even after taking into account age and all major comorbidities.

Correction to: Deleterious effects of dialysis emergency start, insights from the French REIN registry.

Following publication of the original article [1], the authors reported that all of the authors' names were processed incorrectly so that their given and family names were interchanged.

Deleterious effects of dialysis emergency start, insights from the French REIN registry.

BACKGROUND: Emergency start (ES) of dialysis has been associated with worse outcome, but remains poorly documented. This study aims to compare the profile and outcome of a large cohort of patients starting dialysis as an emergency or as a planned step in France. METHODS: Data on all patients aged 18 years or older who started dialysis in mainland France in 2012 or in 2006 were collected from the Renal Epidemiology and Information Network and compared, depending on the dialysis initiation condition: ES or Planned Start (PS). ES was defined as a first dialysis within 24 h after a nephrology visit due to a life-threatening event. Three-year survival were compared, and a multivariate model was performed after multiple imputation of missing data, to determine the parameters independently associated with three-year survival. RESULTS: In 2012, 30.3% of all included patients (n = 8839) had ES. Comorbidities were more frequent in the ES than PS group (≥ 2 cardiovascular diseases: 39.2% vs 28.8%, p < 0.001). ES was independently associated with worse three-year survival (57% vs. 68.2%, p = 0.029, HR 1.10, 95% CI 1.01-1.19) in multivariate analysis. Among ES group, a large part had a consistent previous follow-up: 36.4% of them had ≥3 nephrology consultations in the previous year. This subgroup of patients had a particularly high comorbidity burden. ES rate was stable between 2006 and 2012, but some proactive regions succeeded in reducing markedly the ES rate. CONCLUSION: ES remains frequent and is independently associated with worse three-year survival, demonstrating that ES deleterious impact is never overcome. This study shows that a large part of patients with ES had a previous follow-up, but high comorbidity burden that could favor acute decompensation with life-threatening conditions before uremic symptoms appearance. This suggests the need of closer end-stage renal disease follow-up or early dialysis initiation in these high-risk patients.

Independent association of PD-L1 expression with noninactivated VHL clear cell renal cell carcinoma-A finding with therapeutic potential.

Clear cell renal cell carcinoma (ccRCC) is an aggressive tumor that is characterized in most cases by inactivation of the tumor suppressor gene VHL. The VHL/HIF/VEGF pathway thus plays a major role in angiogenesis and is currently targeted by anti-angiogenic therapy. The emergence of resistance is leading to the use of targeted immunotherapy against immune checkpoint PD1/PDL1 that restores antitumor immune response. The correlation between VHL status and PD-L1 expression has been little investigated. In this study, we retrospectively reviewed 98 consecutive cases of ccRCC and correlated PD-L1 expression by immunohistochemistry (IHC) with clinical data (up to 10-year follow-up), pathological criteria, VEGF, PAR-3, CAIX and PD-1 expressions by IHC and complete VHL status (deletion, mutation and promoter hypermethylation). PD-L1 expression was observed in 69 ccRCC (70.4%) and the corresponding patients had a worse prognosis, with a median specific survival of 52 months (p = 0.03). PD-L1 expression was significantly associated with poor prognostic factors such as a higher ISUP nucleolar grade (p = 0.01), metastases at diagnosis (p = 0.01), a sarcomatoid component (p = 0.04), overexpression of VEGF (p = 0.006), and cytoplasmic PAR-3 expression (p = 0.01). PD-L1 expression was also associated with dense PD-1 expression (p = 0.007) and with ccRCC with 0 or 1 alteration(s) (non-inactivated VHL tumors; p = 0.007) that remained significant after multivariate analysis (p = 0.004 and p = 0.024, respectively). Interestingly, all wild-type VHL tumors (no VHL gene alteration, 11.2%) expressed PD-L1. In this study, we found PD-L1 expression to be associated with noninactivated VHL tumors and in particular wild-type VHL ccRCC, which may benefit from therapies inhibiting PD-L1/PD-1.

French patients on daily hemodialysis: clinical characteristics and treatment trajectories.

BACKGROUND: Increasing the weekly frequency of hemodialysis sessions has positive effects, on the control of several biological data of patients. However, knowledge about Daily HemoDialysis (DHD) practices is limited in France. The aim of the present study was to describe the characteristics and treatment trajectories of all French patients undergoing DHD. METHODS: All patients older than 18 years who started DHD between 2003 and 2012 in France were included and followed until December 31, 2013. The patients' demographic and clinical characteristics and treatment modalities were extracted from the French Renal Epidemiological and Information Network (REIN) registry. RESULTS: During the inclusion period, 753 patients started DHD in France. Based on their median age (64 years), patients were classified in two groups: "old" group (≥64 years) and "young" group (<64 years). Patients in the old group had more comorbidities than in the young group: 48 % had diabetes (vs 29 % in the young group), 17 % an active malignancy (vs 10 %) and 80 % ≥1 cardiovascular disease (vs 41 %). Concerning patients' treatment trajectories, 496 (66 %) patients started with another dialysis before switching to DHD and 257 (34 %) directly with DHD. At the end of the follow-up, 69 % of patients in the old group were dead (27.4 % in the young group) and kidney transplantation was more frequent in the young group (30.4 % vs 0.5 %). CONCLUSION: In France, DHD is proposed not only to young in rather good clinical conditions and waiting for kidney transplantation, but also to old and frail patients with higher mortality.

Pneumococcal vaccination coverage at the initiation of chronic dialysis, and its association with mortality during the first year.

OBJECTIVES: Pneumococcal immunization is recommended in dialysis patients. We aimed to estimate pneumococcal vaccination coverage among patients who initiate dialysis in France, and its association with mortality. METHODS: Data were extracted from two prospective national databases, merged using a deterministic linkage method: renal epidemiology and information network (REIN) registry, which includes all patients on dialysis and kidney transplants recipients in France, and the national health insurance information system (SNIIRAM) which collects individual data on health expenditure reimbursement, including vaccines. We enrolled all patients who initiated chronic dialysis in 2015. Data on health status at dialysis initiation, dialysis modalities, and pneumococcal vaccine prescribed from 2 years before to 1 year after dialysis start were collected. Univariate and multivariate Cox proportional hazard models were used to assess one-year all-cause mortality. RESULTS: Among the 8,294 incident patients included, 1,849 (22.3 %) received at least one pneumococcal vaccine before (n = 542, 6.5 %), or after (n = 1,307, 15.8 %) dialysis start, as follows: 13-valent pneumococcal conjugated vaccine (PCV13) followed by 23-valent pneumococcal polysaccharide vaccine (PPSV23), n = 938 (50.7 %); only PPSV23, n = 650 (35.1 %); or only PCV13, n = 261 (14.1 %). Vaccinated patients were younger (mean, 66.5 ± 14.8 years vs. 69.0 ± 14.9 years, P ≤ 0.001), more likely to suffer from glomerulonephritis (17.0 % vs. 11.0 %, P ≤ 0.001), and less likely to start dialysis in emergency (27.2 % vs. 31.1 %, P = 0.001). On multivariate analysis, patients who received PCV13 and PPSV23, or only PCV13 were less likely to die (respectively, HR = 0.37; 95 %CI 0.28-0.51, and HR = 0.35; 95 %CI 0.19-0.65). CONCLUSIONS: Pneumococcal immunization with PCV13 followed by PPSV23, or with PCV13 alone, but not with PPSV23 alone, is independently associated with decreased one year-mortality in patients who start dialysis.

Systemic sclerosis and end-stage renal disease: study of patient characteristics, follow-up and outcomes in France.

BACKGROUND: Scleroderma renal crisis (SRC), the most frequent renal complication of Systemic Sclerosis (SSc), can lead to end-stage renal disease (ESRD), most frequently, but not exclusively, because of scleroderma renal crisis (SRC). METHODS: The main objectives of our study using data extracted from the French renal epidemiology and information network (REIN) registry, were to describe the characteristics and outcomes in an incident French cohort of SSc patients requiring renal replacement therapy (RRT) compared with a matched RRT patient sample. RESULTS: Between 2002 and 2014, 120 incident SSc patients started RRT in France. SSc was significantly associated with higher mortality (HR 1.95; 95% CI 1.41-2.71; p = 0.001) in comparison with matched controls. Among SSc patients in dialysis, besides age, the only risk factor independently associated with mortality was the inability to walk without help (HR 2.34, CI 95% 1.37-4.02, p = 0.002). Dialysis withdrawal was reported for 22 (18.3%) of the SSc patients compared to 15 (6.3%) for the controls. Patients with SSc have less access to transplantation waiting list (HR 0.21; CI 95% 0.11-0.41, p < 0.001) and to kidney transplantation (KTR) (HR 0.22; 95% CI 0.12-0.43; p < 0.001). During the follow-up, 6 of the 27 patients (22.2%) registered on KTR waiting list died compared to 69 of the 93 (74.2%) patients who were not on the waiting list. CONCLUSIONS: The prognosis for SSc patients requiring RRT is still poor, with a significantly higher mortality and lower registration on kidney transplant waiting-list compared to matched controls.

[Prolonged hemodialysis: Rationale, practical organization, results]. / Hémodialyse longue : rationnel, organisation pratique, résultats.

In France, long nocturnal dialyses, eight hours three-times a week, are sparsely proposed. However, numerous studies reported that this specific type of dialysis is associated to better blood pressure control, better cardiac remodeling, better mineral and nutritional balance as well as better life quality and survival rate. MATERIAL AND METHODS: In this study, we aimed at quantifying the benefits, risks and obstacles of developing night dialysis and at describing the results of a program that took place in Rennes from 2002 to 2019. Data were collected between 2008 and 2014 for eighteen case-patients and were compared to thirty-six controls that underwent conventional dialysis. Patients were paired according sex, age and year of dialysis start. RESULTS: The median age for dialysis start was 47.5 years [27-60] with a male prevalence (5/1). After six months, a significant difference was reported for postdialytic, systolic and diastolic pressure (respectively 126±15 vs 139±21 [P=0.04] and 72±9 vs 81±14 [P=0.02]) despite an antihypertensive reduction ranging from 2.4±1.4 to 1.3±0.9 per day at six months and 0.7±0.9 at one year (P=0.02). An increase of nPCR was evidenced at 6 and 9 months (P=0.02). At the end of the study, the phosphate level was maintained for both cohorts at the expense of an increased consumption of phosphate binder for the long nocturnal dialysis group (P=0.025). As a whole, 61% of the patients that pursued long night dialysis maintained a professional activity compared to only 30% for the controls (P=0.04). This highlights the advantages of night dialysis for maintaining employment but also the bias that represents the employment status in observational study on this specific topic.

Contribution of medico-administrative data to the development of a comorbidity score to predict mortality in End-Stage Renal Disease patients.

Comorbidity scores to predict mortality are very useful to facilitate decision-making for personalized patient management. This study aim was to assess the contribution of medico-administrative data in addition to French Renal Epidemiology and Information Network (REIN) data to the development of a risk score to predict the 1-year all-cause mortality in patients with End Stage Renal Disease (ESRD), and to compare it with previous scores. Data from a derivation sample (n = 6336 patients who started dialysis in 2015 in France) obtained by linking the REIN and the French National Health Insurance Information System databases were analyzed with multivariate Cox models to select risk factors to establish the score. A randomly chosen validation sample (n = 2716 patients who started dialysis in 2015) was used to validate the score and to compare it with the comorbidity indexes developed by Wright and Charlson. The ability to predict one-year mortality of the score constructed using REIN data linked to the medico-administrative database was not higher than that of the score constructed using only REIN data (i.e., Rennes score). The Rennes score included five comorbidities, albumin, and age. This score (AUC = 0.794, 95%CI: 0.768-0.821) outperformed both the Wright (AUC = 0.631, 95%CI: 0.621-0.639; p < 0.001) and Charlson (AUC = 0.703, 95%CI: 0.689-0.716; p < 0.001) indexes. Data from the REIN registry alone, collected at dialysis start, are sufficient to develop a risk score that can predict the one-year mortality in patients with ESRD. This simple score might help identifying high risk patients and proposing the most adapted care.

Cancer risk in dialyzed patients with and without diabetes.

BACKGROUND: The risk of cancer is higher in patients with renal diseases and diabetes compared with the general population. The aim of this study was to assess in dialyzed patients, the association between diabetes and the risk to develop a cancer after dialysis start. METHODS: All patients who started dialysis in the French region of Poitou-Charentes between 2008 and 2015 were included. Their baseline characteristics were extracted from the French Renal Epidemiology and Information Network and were linked to data relative to cancer occurrence from the Poitou-Charentes General Cancer Registry using a procedure developed by the INSHARE platform. The association between diabetes and the risk of cancer was assessed using the Fine & Gray model that takes into account the competing risk of death. RESULTS: Among the 1634 patients included, 591 (36.2 %) had diabetes and 91 (5.6 %) patients developed a cancer (n = 24 before or at dialysis start, and n = 67 after dialysis start). The risk to develop a cancer after dialysis initiation was lower in dialyzed patients with diabetes than without diabetes (SHR = 0.54; 95 %CI: 0.32-0.91). Moreover, compared with the general population, the cancer risk was higher in dialyzed patients without diabetes, but not in those with diabetes. CONCLUSION: The risk of developing a cancer in the region of Poitou-Charentes is higher in dialyzed patients without diabetes than with diabetes.

Geographic Variations in the Risk of Emergency First Dialysis for Patients with End Stage Renal Disease in the Bretagne Region, France.

Emergency first dialysis start considerably increases the risk of morbidity and mortality. Our objective was to identify the geographic variations of emergency first dialysis risk in patients with end-stage renal disease in the Bretagne region, France. The spatial scan statistic approach was used to determine the clusters of municipalities with significantly higher or lower risk of emergency first dialysis. Patient data extracted from the REIN registry (sociodemographic, clinical, and biological characteristics) and indicators constructed at the municipality level, were compared between clusters. This analysis identified a cluster of municipalities in western Bretagne with a significantly higher risk (RR = 1.80, p = 0.044) and one cluster in the eastern part of the region with a significantly lower risk (RR = 0.59, p < 0.01) of emergency first dialysis. The degree of urbanization (the proportion of rural municipalities: 76% versus 66%, p < 0.001) and socio-demographic characteristics (the unemployment rate: 11% versus 8%, p < 0.001, the percentage of managers in the labor force was lower: 9% versus 13% p < 0.001) of the municipalities located in the higher-risk cluster compared with the lower-risk cluster. Our analysis indicates that the patients' clinical status cannot explain the geographic variations of emergency first dialysis incidence in Bretagne. Conversely, where patients live seems to play an important role.

[Is cancer incidence different between type 2 diabetes patients compared to non-diabetics in hemodialysis? A study from the REIN registry]. / Patients en hémodialyse : l'incidence de cancer est-elle différente entre les diabétiques de type 2 comparés aux non-diabétiques ? Une étude du registre REIN.

BACKGROUND AND OBJECTIVES: In France, diabetes mellitus is now the second cause of end stage renal disease. In a large previous French national study, we observed that dialyzed diabetics have a significant lower risk of death by cancer. This first study was focused on cancer death but did not investigate cancer incidence. In this context, the aim of this second study was to compare the incidence of cancer in diabetic dialyzed patients compared to non-diabetic dialyzed patients in a French region. METHODS: This epidemiologic multicentric study included 588 diabetic and non-diabetic patients starting hemodialysis between 2002 and 2007 in Bretagne. Data were issued from REIN registry and cancer incidence were individually collected from medical records. Diabetics and non-diabetics were matched one by one on age, sex and year of dialysis initiation. RESULTS: During the follow-up, we observed 28 cancers (9.4%) in diabetic patients and 26 cancers (8.9%) in non-diabetics patients. The cumulative incidence to develop a cancer 2 years after the dialysis start was approximately 6% in both diabetics and non-diabetics patients. In univariate Fine and Gray analysis, BMI, hemoglobin, statin use had P-value<0.2. However, in the adjusted model, these variables were not significantly associated with cancer incidence. CONCLUSION: This study lead on a little number of dialyzed patients did not show any significant difference on cancer incidence between diabetic and non-diabetic patients after hemodialysis start.

Synchronous Metastatic Clear-Cell Renal Cell Carcinoma: A Distinct Morphologic, Immunohistochemical, and Molecular Phenotype.

INTRODUCTION: Clear cell renal cell carcinomas (ccRCCs) are highly metastatic tumors with metastases detected at diagnosis (synchronous) or during follow-up (metachronous). To date, there have been no reports comparing primary ccRCC of patients with synchronous and metachronous metastases, who are different in terms of prognosis. Determining whether there is a phenotypic difference between these 2 groups could have important clinical implications. PATIENTS AND METHODS: In a retrospective consecutive cohort of 98 patients with ccRCC, 48 patients had metastases, including 28 synchronous and 20 metachronous presentations, with a follow-up of 10 years. For each primary tumor in these metastatic patients, pathologic criteria, expression of vascular endothelial growth factor, partitioning-defective 3, CAIX, and programmed death ligand 1 as detected by immunohistochemistry, and complete VHL status were analyzed. Univariate analysis was performed, and survival was assessed using Kaplan-Meier curves compared by log-rank test. RESULTS: Compared with primary ccRCC in patients with metachronous metastases, primary ccRCC in patients with synchronous metastases were significantly associated with a poorer Eastern Cooperative Oncology Group performance (P = .045), higher pT status (P = .038), non-inactivated VHL gene (P = .01), sarcomatoid component (P = .007), expression of partitioning-defective 3 (P = .007), and overexpressions of vascular endothelial growth factor (> 50%) (P = .017) and programmed death ligand 1 (P = .019). Patients with synchronous metastases had a worse cancer-specific survival than patients with metachronous metastases even from metastatic diagnosis (median survival, 16 months vs. 46 months, respectively; P = .01). CONCLUSION: This long-term study is the first to support the notion that synchronous m-ccRCC has a distinct phenotype. This is probably linked to the occurrence of oncogenic events that could explain the worse prognosis. These particular patients with metastases could benefit from specific therapy.

Wild-type VHL Clear Cell Renal Cell Carcinomas Are a Distinct Clinical and Histologic Entity: A 10-Year Follow-up.

BACKGROUND: Clear cell renal cell carcinoma (ccRCC) is an aggressive tumor with 50% risk of metastases at initial diagnosis or at follow-up. An inactivation of the tumor-suppressor gene von Hippel-Lindau (VHL) is present in >70% of sporadic cases by two of three different mechanisms: locus deletion, gene mutation, or promoter hypermethylation. OBJECTIVE: To correlate the complete status of the VHL gene with clinical and pathologic criteria. DESIGN, SETTING, AND PARTICIPANTS: We retrospectively included 98 patients with ccRCC who underwent surgery between 2002 and 2005. VHL gene deletions (71 of 98; 72.4%), mutations (68 of 98; 69.4%), and promoter hypermethylations (13 of 98; 13.3%) were screened by gene copy analysis, gene sequencing, and methylation-specific multiplex ligation-dependent probe amplification, respectively. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: Relationships between VHL subgroups and the studied criteria were analyzed using chi-square and Student t tests. Survival was analyzed with the log-rank test and Kaplan-Meier curves. RESULTS AND LIMITATIONS: Compared with ccRCCs with two events (66.3%), tumors with no or one genetic event (33.6%) were associated with a higher nuclear grade IV (p=0.02), metastases (p=0.04), sarcomatoid component (p=0.01), dense lymphocyte infiltrate (p=0.013), and vascular endothelial growth factor overexpression (>30%) (p=0.003), which was also an independent factor after multivariate analysis. Furthermore, wild-type VHL tumors (no inactivating event, 11.2%) were associated with nodal involvement (p=0.019), and patients with this type of tumor had a specific survival of 33 mo compared with patients with ccRCCs having one or two VHL inactivating events (107 mo; p=0.016). The retrospective design with small number of wild-type tumors was a limitation of this work. CONCLUSIONS: This long-term study (10-yr clinical follow-up) confirms that ccRCCs with wild-type VHL are highly aggressive tumors that need to be formally identified. PATIENT SUMMARY: Among activated VHL tumors, the wild-type subgroup defines an aggressive phenotype with worse survival rates, suggesting that these tumors must be more thoroughly screened.

Type 1 and type 2 diabetes and cancer mortality in the 2002-2009 cohort of 39,811 French dialyzed patients.

End-stage renal disease is a chronic and progressive pathology associated with several comorbidities, particularly diabetes. Indeed, diabetes is the first cause of end-stage renal disease and, in France, 42% of incident patients had diabetes in 2012. In the general population, diabetes is associated with increased cancer risk. The aim of this study was to examine the association between risk of cancer death and diabetes in a large French cohort of patients with end-stage renal disease. Data on all patients with end-stage renal disease who initiated dialysis in France between 2002 and 2009 were extracted from the Renal Epidemiology Information Network registry. The risk of dying by cancer was studied using the Fine and Gray model to take into account the competing risk of death by other causes. We analyzed 39,811 patients with end-stage renal disease. Their mean age was 67.7±15 years, 39.4% had diabetes and 55.3% at least one cardiovascular disease. Compared with the non-diabetic group, patients with diabetes were older and had more cardiovascular and respiratory comorbidities when they started dialysis. Conversely, fewer diabetic patients had also a tumor at the beginning of the renal replacement therapy. Cancer was indicated as the cause of death for 6.7% of diabetic and 13.4% of non-diabetic patients. The Fine and Gray multivariate analyses indicated that diabetes (HR=0.72 95% CI: [0.68-0.95], p<0.001) and also female gender, peritoneal dialysis, cardio-vascular disease and kidney transplantation were associated with decreased risk of death by cancer. In this French cohort of patients with end-stage renal disease, diabetes was not associated with a significant increased risk of dying from cancer. Studies on the incidence of cancer in patients with ESRD are now needed to evaluate the potential association between diabetes and specific malignancies in this population.