Evaluation of a delayed liver transplantation strategy for patients with HCC receiving bridging therapy: the DELTA-HCC study.

INTRODUCTION: To maximize utility and prevent premature liver transplantation (LT), a delayed LT strategy (DS) was adopted in France in 2015 in patients listed for any single HCC treated with resection or thermal-ablation during waiting phase, postponing LT until recurrence. The purpose of this study was to evaluate DS to make sure that it did not hamper pre and post-LT outcomes in DS patients. PATIENTS AND METHODS: Patients listed for HCC in France between 2015 and 2018 were studied. After data extraction from the national LT database, 2,025 patients were identified and classified according to 6 groups: single tumor entering DS, single tumor not entering DS, multiple tumors, no curative treatment, untreatable HCC or T1 tumors. 18-months Kaplan-Meier estimates of drop-out for death, too sick to be transplanted or tumor progression before LT, 5-year post-LT HCC recurrence and post LT-survival rates were compared. RESULTS: Median waiting-time in DS group was 910 days. Pre-LT drop-out probability was significantly lower in DS compare to other groups (13% vs 19%, p=0.0043) and significantly higher in the T1 group (25.4%, p=0.05). Post-LT HCC-recurrence rate in multiples nodules group was significantly higher (19.6%, p= 0.019) and post-LT 5-year survival did not differ among groups with 74% in DS group (p=0.22). CONCLUSION: The DELTA HCC study shows that DS does not negatively impact neither pre- nor post-LT patients 'outcomes, and has the potential to redistribute organs to patients in more urgent need of LT. It can reasonably be proposed and pursued. The unexpected high risk of drop out in T1 patients seems related to the MELD-based driving rules underserving this subgroup, calling for revision of allocation rules. IMPACTS AND IMPLICATIONS: To maximize utility and prevent premature liver transplantation (LT), a delayed LT strategy (DS) was adopted in France in 2015. It consists in postponing LT until recurrence in patients listed for any single HCC curatively treated by surgical resection or thermal ablation. The DELTA HCC study was conducted to evaluate this nationwide strategy. It shows in a non-US, European LT program that DS:- does not negatively impact pre- nor post-LT patients 'outcome,- concerns up to 20% of LT candidates-has therefore the potential to redistribute organs to patients in more urgent need of LT. Such a delayed strategy can reasonably be pursued and extended to other LT programs. Of note, an unexpected high risk of drop out in T1 patients, seemingly related to MELD-based offering rules which underserve these patients, calls for further scrutinization and revision of allocation rules in this subgroup.

Study of the association between serum levels of kynurenine and cardiovascular outcomes and overall mortality in chronic kidney disease.

Background: Kynurenine is a protein-bound uremic toxin. Its circulating levels are increased in chronic kidney disease (CKD). Experimental studies showed that it exerted deleterious cardiovascular effects. We sought to evaluate an association between serum kynurenine levels and adverse fatal or nonfatal cardiovascular events and all-cause mortality in CKD patients. Methods: The CKD-REIN study is a prospective cohort of people with CKD having an estimated glomerular filtration rate (eGFR) <60 ml/min/1.73 m². Baseline frozen samples of total and free fractions of kynurenine and tryptophan were measured using a validated liquid chromatography tandem mass spectrometry technique. Cause-specific Cox models were used to estimate hazard ratios (HRs) for each outcome. Results: Of the 2406 included patients (median age: 68 years; median eGFR: 25 ml/min/1.73 m2), 52% had a history of cardiovascular disease. A doubling of serum-free kynurenine levels was associated with an 18% increased hazard of cardiovascular events [466 events, HR (95%CI):1.18(1.02,1.33)], independently of eGFR, serum-free tryptophan level or other uremic toxins, cardioprotective drugs, and traditional cardiovascular risk factors. Serum-free kynurenine was significantly associated with non-atheromatous cardiovascular events [HR(95%CI):1.26(1.03,1.50)], but not with atheromatous cardiovascular events [HR(95%CI):1.15(0.89,1.50)]. The association of serum-free kynurenine with cardiovascular mortality was also independently significant [87 events; adjusted HR(95%CI):1.64(1.10,2.40)]. However, the association of serum-free kynurenine with all-cause mortality was no more significant after adjustment on serum-free tryptophan [311 events, HR(95%CI):1.12(0.90, 1.40)]. Conclusions: Our findings imply that serum-free kynurenine, independently of other cardiovascular risk factors (including eGFR), is associated with fatal or nonfatal cardiovascular outcomes, particularly non-atheromatous cardiovascular events; in patients with CKD. Strategies to reduce serum kynurenine levels should be evaluated in further studies.

Urgent-start dialysis in patients referred early to a nephrologist-the CKD-REIN prospective cohort study.

BACKGROUND: The lack of a well-designed prospective study of the determinants of urgent dialysis start led us to investigate its individual- and provider-related factors in patients seeing nephrologists. METHODS: The Chronic Kidney Disease Renal Epidemiology and Information Network (CKD-REIN) is a prospective cohort study that included 3033 patients with CKD [mean age 67 years, 65% men, mean estimated glomerular filtration rate (eGFR) 32 mL/min/1.73 m2] from 40 nationally representative nephrology clinics from 2013 to 2016 who were followed annually through 2020. Urgent-start dialysis was defined as that 'initiated imminently or <48 hours after presentation to correct life-threatening manifestations' according to the Kidney Disease: Improving Global Outcomes 2018 definition. RESULTS: Over a 4-year (interquartile range 3.0-4.8) median follow-up, 541 patients initiated dialysis with a known start status and 86 (16%) were identified with urgent starts. The 5-year risks for the competing events of urgent and non-urgent dialysis start, pre-emptive transplantation and death were 4, 17, 3 and 15%, respectively. Fluid overload, electrolytic disorders, acute kidney injury and post-surgery kidney function worsening were the reasons most frequently reported for urgent-start dialysis. Adjusted odds ratios for urgent start were significantly higher in patients living alone {2.14 [95% confidence interval (CI) 1.08-4.25] or with low health literacy [2.22 (95% CI 1.28-3.84)], heart failure [2.60 (95% CI 1.47-4.57)] or hyperpolypharmacy [taking >10 drugs; 2.14 (95% CI 1.17-3.90)], but not with age or lower eGFR at initiation. They were lower in patients with planned dialysis modality [0.46 (95% CI 0.19-1.10)] and more nephrologist visits in the 12 months before dialysis [0.81 (95% CI 0.70-0.94)] for each visit. CONCLUSIONS: This study highlights several patient- and provider-level factors that are important to address to reduce the burden of urgent-start dialysis.

Adverse outcomes of proton pump inhibitors in patients with chronic kidney disease: The CKD-REIN cohort study.

AIMS: Long-term use of proton pump inhibitors (PPIs) has been associated with adverse kidney events in the general population, but their impact among chronic kidney disease (CKD) patients is unclear. We studied the prevalence and incidence (new users) of PPI prescriptions and their relation to kidney outcomes and mortality in CKD patients. METHODS: We collected drug prescriptions prospectively in a cohort of 3023 nephrology outpatients with CKD stages 2-5 at inclusion. Hazard ratios (HR, 95% confidence intervals [95% CI]) for acute kidney injury (AKI), end-stage kidney disease (ESKD), and mortality associated with new PPI prescriptions as a time-dependent variable were estimated with cause-specific Cox models in 1940 non-users with eGFR ≥ 15 mL/min/1.73 m2 at baseline, adjusted for comorbidities, laboratory data and drugs. RESULTS: There were 981/3023 (32%) prevalent users (67 ± 13 years, 65% men) at baseline, and 366/3023 (12%) were prescribed PPI (new users) over a median follow-up of 3.9 years (interquartile range, 3-4.2). Among these new users, their median cumulative duration of prescription was 1 year (interquartile range: 0.4-2.3). During follow-up, 354 patients developed ESKD and 216 died before ESKD. The adjusted HRs associated with PPI prescription were 1.74 (95% CI, 1.26-2.40) for ESKD and 2.42 (95% CI, 1.73-3.39) for all-cause mortality. Over the first 3 years of follow-up, 211 AKI events had occurred. The adjusted HR for AKI associated with PPI prescription was 2.89 (95% CI, 1.91-4.38). CONCLUSIONS: Long-term PPI prescription was common in CKD patients. Our results call attention to its potential risks of both acute and chronic kidney failure.

Adverse Drug Reactions in Patients with CKD.

BACKGROUND AND OBJECTIVES: Little is known about the burden of adverse drug reactions in CKD. We estimated the incidence of overall and serious adverse drug reactions and assessed the probability of causation, preventability, and factors associated with adverse drug reactions in patients seen by nephrologists. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: The Chronic Kidney Disease-Renal Epidemiology and Information Network cohort included 3033 outpatients (65% men) with CKD and eGFR<60 ml/min per 1.73 m2, with follow-up for 2 years. Adverse drug reactions were identified from hospitalization reports, medical records, and participant interviews and finally assessed for causality, preventability, and immediate therapeutic management by experts in pharmacology. RESULTS: Median (interquartile range) age was 69 (60-76) years old; 55% had eGFR≥30 ml/min per 1.73 m2, and 45% had eGFR<30 ml/min per 1.73 m2. Participants were prescribed a median (range) of eight (five to ten) drugs. Over 2 years, 536 patients had 751 adverse drug reactions, 150 (in 125 participants) classified as serious, for rates of 14.4 (95% confidence interval, 12.6 to 16.5) and 2.7 (95% confidence interval, 1.7 to 4.3) per 100 person-years, respectively. Among the serious adverse drug reactions, 32% were considered preventable or potentially preventable; 16 caused death, directly or indirectly. Renin-angiotensin system inhibitors (15%), antithrombotic agents (14%), and diuretics (10%) were the drugs to which the most adverse drug reactions were imputed, but antithrombotic agents caused 34% of serious adverse drug reactions. The drug was discontinued in 71% of cases, at least temporarily. Adjusted hazard ratios for serious adverse drug reaction were significantly higher in patients with eGFR<30 versus ≥30 ml/min per 1.73 m2 (1.8; 95% confidence interval, 1.3 to 2.6), in those prescribed more than ten versus less than five medications (2.4; 95% confidence interval, 1.1 to 5.2), or in those with poor versus good adherence (1.6; 95% confidence interval, 1.4 to 2.4). CONCLUSIONS: Adverse drug reactions are common and sometimes serious in patients with CKD. Many serious adverse drug reactions may be preventable. Some specific pharmacologic classes, particularly antithrombotic agents, are at risk of serious adverse drug reactions. CLINICAL TRIAL REGISTRY NAME AND REGISTRATION NUMBER: Chronic Kidney Disease-Renal Epidemiology and Information Network (CKD-REIN), NCT03381950.

Should we use liver grafts repeatedly refused by other transplant teams?

BACKGROUND & AIMS: In France, liver grafts that have been refused at least 5 times can be "rescued" and allocated to a centre which chooses a recipient from its own waiting list, outside the patient-based allocation framework. We explored whether these "rescued" grafts were associated with worse graft/patient survival, as well as assessing their effect on survival benefit. METHODS: Among 7,895 candidates, 5,218 were transplanted between 2009 and 2014 (336 centre-allocated). We compared recipient/graft survival between patient allocation and centre allocation, considering a selection bias and the distribution of centre-allocation recipients among the transplant teams. We used a propensity score approach and a weighted Cox model using the inverse probability of treatment weighting method. We also explored the survival benefit associated with centre-allocation grafts. RESULTS: There was a significantly higher risk of graft loss/death in the centre allocation group compared to the patient allocation group (hazard ratio 1.13; 95% CI 1.05-1.22). However, this difference was no longer significant for teams that performed more than 7% of the centre-allocation transplantations. Moreover, receiving a centre-allocation graft, compared to remaining on the waiting list and possibly later receiving a patient-allocation graft, did not convey a poorer survival benefit (hazard ratio 0.80; 95% CI 0.60-1.08). CONCLUSIONS: In centres which transplanted most of the centre-allocation grafts, using grafts repeatedly refused for top-listed candidates was not detrimental. Given the organ shortage, our findings should encourage policy makers to restrict centre-allocation grafts to targeted centres. LAY SUMMARY: "Centre allocation" (CA) made it possible to save 6 out of 100 available liver grafts that had been refused at least 5 times for use in the top-listed candidates on the national waiting list. In this series, the largest on this topic, we showed that, in centres which transplanted most of the CA grafts, using grafts repeatedly refused for top-listed candidates did not appear to be detrimental. In the context of organ shortage, our results, which could be of interest for any country using this CA strategy, should encourage policy makers to reassess some aspects of graft allocation by restricting CA grafts to targeted centres, fostering the "best" matching between grafts and candidates on the waiting list.

Effects of the dialysate calcium concentrations and mineral bone disease treatments on mortality in The French Renal Epidemiology and Information Network (REIN) registry.

BACKGROUND: In patients on hemodialysis (HD), the various chemical elements in the dialysate may influence survival rates. In particular, calcium modifies mineral and bone metabolism and the vascular calcification rate. We studied the influence of the dialysate calcium concentration and the treatments prescribed for mineral bone disease (MBD) on survival. METHODS: All patients in REIN having initiated HD from 2010 to 2013 were classified according to their exposure to the different dialysate calcium concentrations in their dialysis unit. Data on the individual patients' treatments for MBD were extracted from the French national health database. Cox proportional hazard models were used to estimate mortality hazard ratios (HR) associated with time-dependent exposure to dialysate calcium concentrations and MBD therapies, adjusted for comorbidities, laboratory and technical data. RESULTS: Dialysate calcium concentration of 1.5 mmol/L was used by 81% of the dialysis centers in 2010 and in 83% in 2014. Most centers were using several formulas in up to 78% for 3 formulas in 2010 to 86% in 2014. In full adjusted Cox survival analyses, the percentage of calcium >1.5 mmol/L and <1.5 mmol/l by center and the number of formula used per center were not associated with survival. Depending on the daily dose used, the MBD therapies were associated with survival improvement for calcium, native vitamin D, active vitamin D, sevelamer, lanthanum and cinacalcet in the second and third tertiles of dose. CONCLUSION: No influence of the dialysate calcium concentration was evidenced on survival whereas all MBD therapies were associated with a survival improvement depending on the daily dose used.

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.

Trends and Outcomes with Kidney Failure from Antineoplastic Treatments and Urinary Tract Cancer in France.

BACKGROUND AND OBJECTIVES: Cancer survival is improving along with an increase in the potential for adverse kidney effects from antineoplastic treatments or nephrectomy. We sought to describe recent trends in the incidence of kidney failure related to antineoplastic treatments and urinary tract cancers and evaluate patient survival and kidney transplantation access. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: We used the French Renal Epidemiology and Information Network registry to identify patients with kidney failure related to antineoplastic treatments or urinary tract cancer from 2003 to 2015. We identified 287 and 1157 cases with nephrotoxin- and urinary tract cancer-related kidney failure, respectively. The main study outcomes were death and kidney transplantation. After matching cases to two to ten controls (n=11,678) with other kidney failure causes for age, sex, year of dialysis initiation, and diabetes status, we estimated subdistribution hazard ratios (SHR) of each outcome separately for patients with and without active malignancy. RESULTS: The mean age- and sex-adjusted incidence of nephrotoxin-related kidney failure was 0.43 (95% CI, 0.38 to 0.49) per million inhabitants and 1.80 (95% CI, 1.68 to 1.90) for urinary tract cancer-related kidney failure; they increased significantly by 5% and 2% annually, respectively, during 2006-2015. Compared with matched controls, age-, sex-, and comorbidity-adjusted SHRs for mortality in patients with nephrotoxin-related kidney failure were 4.2 (95% CI, 3.2 to 5.5) and 1.4 (95% CI, 1.0 to 2.0) for those with and without active malignancy, respectively; for those with urinary tract cancer, SHRs were 2.0 (95% CI, 1.7 to 2.2) and 1.1 (95% CI, 0.9 to 1.2). The corresponding SHRs for transplant wait-listing were 0.19 (95% CI, 0.11 to 0.32) and 0.62 (95% CI, 0.43 to 0.88) for nephrotoxin-related kidney failure cases and 0.28 (95% CI, 0.21 to 0.37) and 0.47 (95% CI, 0.36 to 0.60) for urinary tract cancer cases. Once on the waiting list, access to transplantation did not differ significantly between cases and controls. CONCLUSIONS: Cancer-related kidney failure is slowly but steadily increasing. Mortality does not appear to be increased among patients without active malignancy at dialysis start, but their access to kidney transplant remains limited.

Risk profile, quality of life and care of patients with moderate and advanced CKD: The French CKD-REIN Cohort Study.

Background: The French Chronic Kidney Disease-Renal Epidemiology and Information Network (CKD-REIN) cohort study was designed to investigate the determinants of prognosis and care of patients referred to nephrologists with moderate and advanced chronic kidney disease (CKD). We examined their baseline risk profile and experience. Methods: We collected bioclinical and patient-reported information from 3033 outpatients with CKD and estimated glomerular filtration rates (eGFRs) of 15-60 mL/min/1.73 m2 treated at 40 nationally representative public and private facilities. Results: The patients' median age was 69 (60-76) years, 65% were men, their mean eGFR was 33 mL/min/1.73 m2, 43% had diabetes, 24% had a history of acute kidney injury (AKI) and 57% had uncontrolled blood pressure (BP; >140/90 mmHg). Men had worse risk profiles than women and were more likely to be past or current smokers (73% versus 34%) and have cardiovascular disease (59% versus 42%), albuminuria >30 mg/mmol (or proteinuria > 50) (40% versus 30%) (all P < 0.001) and a higher median risk of end-stage renal disease within 5 years, predicted by the kidney failure risk equation {12% [interquartile range (IQR) 3-37%] versus 9% [3-31%], P = 0.008}. During the previous year, 60% of patients reported one-to-two nephrologist visits and four or more general practitioner visits; only 25% saw a dietician and 75% were prescribed five or more medications daily. Physical and mental quality of life (QoL) were poor, with scores <50/100. Conclusions: The CKD-REIN study highlights high-risk profiles of cohort members and identifies several priorities, including improving BP control and dietary counselling and increasing doctors' awareness of AKI, polypharmacy and QoL. Trial registration: ClinicalTrials.gov identifier: NCT03381950.

Optimization of heart allocation: The transplant risk score.

The new French heart allocation system is designed to minimize waitlist mortality and extend the donor pool without a detrimental effect on posttransplant survival. This study was designed to construct a 1-year posttransplant graft-loss risk score incorporating recipient and donor characteristics. The study included all adult first single-organ recipients transplanted between 2010 and 2014 (N = 1776). This population was randomly divided in a 2:1 ratio into derivation and validation cohorts. The association of variables with 1-year graft loss was determined with a mixed Cox model with center as random effect. The predictors were used to generate a transplant-risk score (TRS). Donor-recipient matching was assessed using 2 separate recipient- and donor-risk scores. Factors associated with 1-year graft loss were recipient age >50 years, valvular cardiomyopathy and congenital heart disease, previous cardiac surgery, diabetes, mechanical ventilation, glomerular filtration rate and bilirubin, donor age >55 years, and donor sex: female. The C-index of the final model was 0.70. Correlation between observed and predicted graft loss rate was excellent for the overall cohort (r = 0.90). Hearts from high-risk donors transplanted to low-risk recipients had similar survival as those from low-risk donors. The TRS provides an accurate prediction of 1-year graft-loss risk and allows optimal donor-recipient matching.

Prediction of chronic kidney disease after acute kidney injury in ICU patients: study protocol for the PREDICT multicenter prospective observational study.

BACKGROUND: Acute kidney injury (AKI) is frequent and associated with poor outcome in intensive care unit (ICU) patients. Besides the association with short- and long-term mortality, the increased risk of chronic kidney disease (CKD) has been recently highlighted in non-ICU patients. This study aims to describe the incidence and determinants of CKD after AKI and to develop a prediction score for CKD in ICU patients. METHODS: Prospective multicenter (n = 17) observational study included 1200 ICU patients who suffered from AKI (defined by an AKIN stage ≥ 1) during their ICU stay and were discharged alive from ICU. Preexisting end-stage renal disease (ESRD) and immunosuppressant treatments are the main exclusion criteria. Patients will be monitored by a nephrologist at day 90 and every year for 3 years. The main outcome is the occurrence of CKD defined by a creatinine-based estimated glomerular filtration rate (eGFR) lower than 60 mL/min/1.73 m2 or renal replacement therapy for ESRD in patients whose eGFR will be normalized (≥ 60 mL/min/1.73 m2) at day 90. Secondary outcomes include albuminuria changes, eGFR decline slope and ESRD risk in patients with preexisting CKD, cardiovascular and thromboembolic events and health-related quality of life. DISCUSSION: This is the first study prospectively investigating kidney function evolution in ICU patients who suffered from AKI. Albuminuria and eGFR monitoring will allow to identify ICU patients at risk of CKD who may benefit from close surveillance after recovering from AKI. Major patient and AKI-related determinants will be tested to develop a prediction score for CKD in this population. Trial registration ClinicalTrials.gov, NCT03282409. Registered on September 14, 2017.

Anti-HLA sensitization after kidney allograft nephrectomy: changes one year post-surgery and beneficial effect of intravenous immunoglobulin.

The analysis of anti-HLA sensitization at the time of and following allograft nephrectomy may help clinicians to define better both the indications for nephrectomy and preventive therapeutic strategies. We carried out a retrospective analysis of anti-HLA antibodies in 63 clinically indicated nephrectomies (baseline and three and 12 months after) according to the time elapsed since transplantation (six months) and clinical background. An intervention study included 10 patients without donor-specific antibodies (DSA) at the time of nephrectomy treated with high-dose intravenous immunoglobulin (IVIG) (1.5 g/kg). Early nephrectomies were performed in 15 patients (24%). Among the late nephrectomies, 14 patients (22%) were asymptomatic and 34 (54%) had graft intolerance syndrome (GIS). At baseline, anti-HLA sensitization was significantly lower in the early and late asymptomatic groups than in the GIS group, but increased considerably within the three months following surgery. In the group of 10 patients treated with IVIG, only the number of class I non-DSA increased in the three months after surgery, whereas in the control group (N = 13), all anti-HLA variables increased significantly. All patients undergoing a clinically indicated allograft nephrectomy become highly sensitized within the 12 months after surgery. In patients without DSA before nephrectomy, high doses of IVIG may prevent anti-HLA sensitization.

Issues in the classification of disease instances with ontologies.

Ontologies define classes of entities and their interrelations. They are used to organize data according to a theory of the domain. Towards that end, ontologies provide class definitions (i.e., the necessary and sufficient conditions for defining class membership). In medical ontologies, it is often difficult to establish such definitions for diseases. We use three examples (anemia, leukemia and schizophrenia) to illustrate the limitations of ontologies as classification resources. We show that eligibility criteria are often more useful than the Aristotelian definitions traditionally used in ontologies. Examples of eligibility criteria for diseases include complex predicates such as ' x is an instance of the class C when at least n criteria among m are verified' and 'symptoms must last at least one month if not treated, but less than one month, if effectively treated'. References to normality and abnormality are often found in disease definitions, but the operational definition of these references (i.e., the statistical and contextual information necessary to define them) is rarely provided. We conclude that knowledge bases that include probabilistic and statistical knowledge as well as rule-based criteria are more useful than Aristotelian definitions for representing the predicates defined by necessary and sufficient conditions. Rich knowledge bases are needed to clarify the relations between individuals and classes in various studies and applications. However, as ontologies represent relations among classes, they can play a supporting role in disease classification services built primarily on knowledge bases.

New drugs for colorectal cancer (irinotecan, oxaliplatin, raltitrexed) meet expectations in routine practice: a single center's experience before and after their introduction.

BACKGROUND AND AIMS: Treatment of metastatic colorectal cancer with new drugs (NDs) as oxaliplatin and irinotecan had improved response and survival. In order to check whether the promising achievements of the trials are obtained in routine clinical practice, we have reviewed retrospectively our results for two periods, before (period A: 1993-1995, n=63) and after (period B:1998-2000 n=103) the introduction of these NDs. Patients characteristics, treatment modalities, survival, and prognostic factors were compared. PATIENTS: There were 74 women and 92 men, aged 60.8+/-11.6 yr, 7 patients received best supportive care only, 91 had synchronous metastasis. RESULTS: Period B patients were older, with WHO score>1 more often, more adjuvant treatment, more metachronous metastasis, and NDs used more frequently (24% vs 59%). Median survival was similar (16 vs 15 mo). But when looking at the population aged<75 years with WHO score<2, median survival was 13 mo (period A) vs 21 mo (period B); survival at 1, 2, and 3 yr were respectively 59.5+/-8%, 16.2+/-6 %, 13.5+/-6 % vs 69.8+/-6%, 49.6+/-7%, 29.8+/-7%, p<0.01). In multiparametric analysis, factors correlated with survival were the absence of elevated serum alkaline phosphatase, a unique metastatic organ, and administration of NDs. CONCLUSION: In our routine clinical experience the use of NDs for metastatic CRC has allowed a significant improvement in survival among patients with unresectable tumors.

Living with a functioning kidney transplant at 74 yr or older: a national epidemiological study.

The number of older patients living with a functioning kidney graft is increasing. However the safety of the immunosuppressive treatment and quality of life in this population have not yet been determined. All patients grafted in France since 1969, born before the January 1 1926 and living with a functioning graft on January 1 2000 were included in this national study including all 34 French transplant centers. Renal function, immunosuppressive treatment, comorbid conditions and quality of life were assessed. From the initial population of 446 patients, 113 (26.2%) were still alive in 2000 (study population). Mean age was 76 yr (range: 74-80) with a mean post-transplant follow-up of 9.9 yr (0.1-28.7). Average serum creatinine level was 129 micromol/L (55-286). Immunosuppression was heterogeneous and included triple therapy (18.6%), dual therapy (41.6%) and monotherapy (40.8%). A history of cancer was noted in 36 of the 113 patients (32.1%) whereas hypertension was the most frequent co-morbid condition (80.3%). Estimated quality of life using the Karnofsky scale was between 80 and 100 in 78.4% of the patients. The immunosuppressive regimen in older renal transplant recipients living with a functioning graft varied widely among the 34 French transplant centers. Renal function in this group of patients was good and quality of life seemed excellent. Cardiovascular disease and malignancies were the main co-morbid conditions.