Early Prediction of Graft Outcomes After Kidney Transplantation From Donors After Circulatory Death: Biomarkers and Transplantation Characteristics.

BACKGROUND: This study aimed to identify transplantation characteristics and biomarkers that predict outcomes for kidney transplant (KT) patients from donors after circulatory death (DCDs). METHODS: Consecutive patients receiving a KT from a DCD in our center between 2014 and 2016 were included; the reference population was recipients with a living donor KT. The urinary tubular injury biomarker-to-creatinine ratio and serum lactate dehydrogenase (LDH) were measured at post-transplant days 1 and 3. The primary outcome was the occurrence of delayed graft function (DGF). Descriptive and receiver operating characteristic analyses were performed. RESULTS: Forty-one patients were included in the analysis: 15 (36.59%) DCD KTs (9 of which suffered from DGF) and 26 (63.41%) living donor KTs. For the primary endpoint, neutrophil gelatinase-associated lipocalin, N-acetyl-beta-D-glucosaminidase, urinary tubular injury biomarker-to-creatinine ratio, and LDH areas under the curve were 1 and 0.96 (95% confidence interval: 0.84-1.0), 1 and 0.92 (95% confidence interval: 0.73-1.0), respectively. Among the transplant characteristics, only the 30-minute resistive index on the perfusion machine was significantly higher in DCD KTs with DGF vs those without DGF (0.26 mm Hg/mL/min [0.20; 0.32] vs 0.14 mm Hg/mL/min [0.12; 0.16], P = .05). Median 3-month creatinine clearance among DGF DCD KTs was 49 mL/min/1.73 m2 [IQR: 42; 65] and 65 mL/min/1.73 m2 [IQR: 62; 66] among DCD KTs without DGF (P = .22). CONCLUSION: In the DCD KT population, clinical and biological markers were identified that provided predictive tools for DGF. Thus, systematic measurement of these biomarkers, particularly LDH, could improve the management of kidney graft recipients' immunosuppressive therapy.

Circulating Klotho Associates With Cardiovascular Morbidity and Mortality During Hemodialysis.

Background: Klotho gene was identified as an aging suppressor. In animals, klotho overexpression extends life span, and defective klotho results in rapid aging and early death. The kidney is the main contributor to circulating klotho levels, and, during chronic kidney disease, renal klotho gene expression is drastically reduced in animals and humans as well. Objective: We aimed to determine the consequences of a serum klotho (seKL) defect on cardiovascular morbidity and mortality during chronic dialysis. Design: The ARNOGENE study was designed to prospectively follow a cohort of hemodialysis patients for 2 years without specific intervention. A total of 769 patients was recruited and followed from the end of 2008 until January 2011. A total of 238 patients was analyzed due to a technical sample conservation issue with other samples. Results: The median seKL was markedly reduced, 360.4 ng/L (interquartile range 176.5) as compared with nondialysis chronic kidney disease patients or healthy volunteers. Patients with a seKL above the first quartile (≥280 ng/L) had a significantly reduced occurrence of outcome combining cardiovascular events and cardiovascular death [odds ratio (OR) = 0.39; 0.19 to 0.78, P = 0.008] compared with patient with klotho <280 ng/L. This effect persisted (OR = 0.86; 0.76 to 0.99, P = 0.03) after adjustment on age, sex, diabetes, cardiac insufficiency, dialysis vintage, and serum hemoglobin, albumin, fibroblast growth factor-23, phosphate, and calcium. Conclusions: These results suggest that, during chronic hemodialysis, conservation of seKL >280 ng/L is associated with a better 2-year cardiovascular protection. Thus, a preserved klotho function supports cardiovascular protection and may represent a prognostic tool and therapeutic target for cardiovascular disease.

Impact of BMI Variations on Survival in Elderly Hemodialysis Patients.

OBJECTIVES: In elderly hemodialysis patients, protein-energy wasting is associated with poor outcome; however, the association between body mass index (BMI) changes over time, and survival has been seldom studied in this particularly frail population. DESIGN AND METHODS: This prospective study recruited 502 hemodialysis patients aged ≥75 years from the French cohort ARNOS and followed them from 2005 to 2009. BMI changes over time were modeled by individual linear regression models. Survival analyses used frailty Cox models. RESULTS: The population average age was 80.9 years. Forty-one percent of the patients died during follow-up. A 1 kg/m(2) lower baseline BMI was associated with a 4% increase in the risk of death over the study period (hazard ratio [HR] 1.04, 95% confidence interval [1.01-1.08], P = .02). A 5% BMI loss per year was associated with a 52% increase in the risk of death (HR 1.52, 95% confidence interval [1.32-1.75], P < .001). In patients who lost weight (>5% BMI loss per year), the lower was the baseline BMI, the higher was the HR for death. There was a similar trend in the patients with stable weight (5% BMI loss-5% BMI gain per year). In patients who gained weight, the HR was unexpectedly higher than in those with stable weight. CONCLUSIONS: In elderly hemodialysis patients, the impact of the BMI percent change on survival was stronger than that of the baseline BMI. Patients with stable weight had longer survivals than patients who lost or gained weight. Thus, in this population, BMI changes should be regularly assessed. Further studies should assess the safety of weight gain strategies.

A simple protein-energy wasting score predicts survival in maintenance hemodialysis patients.

OBJECTIVE: Nutritional status is a powerful predictor of survival in maintenance hemodialysis patients but remains challenging to assess. We defined a new Protein Energy Wasting (PEW) score based on the nomenclature proposed by the International Society of Renal Nutrition and Metabolism in 2008. DESIGN AND METHODS: This score, graded from 0 (worse) to 4 (best) was derived from 4 body nutrition compartments: serum albumin, body mass index, a normalized serum creatinine value, and protein intake as assessed by nPNA. SUBJECTS: We applied this score to 1443 patients from the ARNOS prospective dialysis cohort and provide survival data from 2005 until 2008. MAIN OUTCOME MEASURE: Patients survival at 3.5 year. RESULTS: Survival ranged from 84%-69% according to the protein-energy wasting score. There was a clear-cut reduction in survival (5%-7%; P < 0.01) for each unit decrement in the score grade. There was a 99% survival at 1 year for patients with the score of 4. In addition, the 6-month variation of this PEW score also strongly predicted patients' survival (P < 0.01). CONCLUSION: A new simple and easy-to-get PEW score predicts survival in maintenance hemodialysis patients. Furthermore, increase of this nutritional score over time also indicates survival improvement, and may help to better identify subgroups of patients with a high mortality rate, in which nutrition support should be enforced.

[Higher dialysate calcium is not associated with mortality in hemodialysis patients: results from the French ARNOS study]. / Les concentrations élevées du calcium du dialysat ne sont pas associées à la mortalité chez les patients hémodialysés : les résultats de l'étude ARNOS.

Finding the optimal dialysate calcium (DCa) in haemodialysis (HD) patients remains a therapeutic challenge. Besides, the Dialysis Outcomes and Practice Pattern Study (DOPPS) has reported a greater mortality rate using higher DCa doses. The objective was to assess the impact of DCa prescription on survival. Baseline DCa prescriptions were recorded using a cross-sectional analysis of HD patients from the regional ARNOS French cohort. A prospective 42-month survival analysis study was performed. In July 2005, 1294 HD patients were included in this study. DCa at doses of 1.25, 1.5, and 1.75 mmol/L was prescribed in 13.6%, 74.1%, and 12.3% patients, respectively. Using a Cox proportional model adjusted for several parameters, DCa was found to be not significantly associated with survival. Patients receiving 1.75 mmol/L DCa were more frequently treated with online haemodiafiltration, cinacalcet, and shorter dialysis sessions; they had a more frequent history of parathyroidectomy and lower calcium levels. The DCa prescription remained stable after 12 months in 80% of cases. This is an observational study; therefore, only baseline data were recorded for analysis. Higher DCa concentration is not associated with mortality, in contrast to the findings by DOPPS. Prescribing DCa on an individual basis according to various mineral metabolism parameters and treatments appears to be safe irrespective of the DCa dosage.

Calcium carbonate, but not sevelamer, is associated with better outcomes in hemodialysis patients: results from the French ARNOS study.

A favorable survival effect of phosphate binders (PBs) on incident hemodialysis (HD) patients was recently reported, but no definitive advantages of calcium-based or noncalcium-based PBs have been demonstrated. The aim of this study was to assess the impact of the prescription of PBs using calcium carbonate (CaCO(3) ) or sevelamer HCl (SV) on survival. Baseline PB prescription was recorded using a cross-sectional analysis of prevalent HD patients from the regional Association Régionale des Néphrologues OStéodystrophie French cohort. A prospective 42-month survival analysis study was performed. In July 2005, 1347 HD patients were included. CaCO(3) , SV, and mixed PBs were prescribed in 55%, 42%, and 24% of cases, respectively, and 26% were not prescribed PBs. Using a Cox proportional model adjusted for several parameters, CaCO(3) use was found to be associated with less mortality (HR, 0.64 [0.4-0.78]), but not in the case of SV use (HR, 1.13 [0.92-1.3]). SV prescription was associated with higher mortality than CaCO(3) (HR, 1.46 [1.1-1.9]). CaCO3, but not sevelamer prescription, is associated with a favorable effect on survival in a French HD population. This novel result can be partly accounted for by the differences in mineral metabolism disorder management that exist between randomized controlled trials and "real life" conditions.

Serum creatinine improves body mass index survival prediction in hemodialysis patients: a 1-year prospective cohort analysis from the ARNOS study.

OBJECTIVE: This study sought to better characterize the relationships between body mass index (BMI) and lean body mass (LBM) as assessed by serum creatinine (SCr) and mortality. DESIGN: The data were collected from a prospective prevalent cohort in maintenance hemodialysis patients. SETTING: The study was carried out in 25 dialysis units in Rhônes Alpes area (France and Switzerland). PATIENT: A total of 1,205 patients were followed up for 1-year, starting July 1, 2005. OUTCOME: Mortality as well as clinical and biological routine parameters were recorded. Kaplan-Meier, Cox model, Log rank test were used for the statistical analysis. RESULTS: We found that SCr was a strong predictor of mortality (P < .001), whereas BMI was not. Additionally, higher BMI lost its protective effect when it was associated with low SCr. Survival was strongly reduced in patients having a predialysis SCr <717 µmol/L in patients with a BMI >23 (P < .001). CONCLUSION: BMI should not be used by itself but in conjunction with SCr as a surrogate of LBM to improve its morbid-mortality predictive power. LBM should also be taken into account in further survival studies carried out in hemodialysis patients.

[Dialin: infection surveillance network for haemodialysis patients. First results]. / Présentation de Dialin : réseau de surveillance des infections chez les patients hémodialysés en centre. Premiers résultats.

AIM AND BACKGROUND: To show results of the first year of an infection surveillance network for haemodialysis patients (Dialin). In order to improve the security and quality of care, six haemodialysis centers have organized an infection watching network. The purpose of the network is to compare of the watching results between centers. This comparison includes vascular access infection (VAI), bacteraemia and C viral hepatitis. The heterogeneous pattern has been also taken into account. SURVEY TYPE: Multicenter prospective permanent survey. POPULATION: Six hundred and sixty-four haemodialyzed chronic patients, followed during one year (2005), in six voluntary haemodialysis centers. This survey has based on 71,688 treatment sessions corresponding to 6257.5 months of haemodialysis (HM). METHODS: As with the heterogeneity among centers, the acquired infection standardized ratios (observed/expected) (AISR) and 95% confidence interval are computed with Cox model which includes confounding factors found in literature or in the preliminary stage of the survey. RESULTS: VAI crude rate was 0.47 per 100HM, 0.10 per 1000 native fistulae utilisation days, 0.45 per 1000 days of prosthetic graft utilisation and 0.44 per 1000 days of catheter utilisation. Bacteraemia crude incidence rate was 0.69 per 100HM, 0.02 per 1000 days of native fistulae utilisation, 0.00 per 1000 days of prosthetic graft utilisation and 0.39 per 1000 days of catheter utilisation. No new case of C viral hepatitis was found. Prevalence rate at the beginning of the survey was 5.3% (35 over 664). Two centers had a significantly high AISR for VAI and two centers had a significantly low AISR for VAI. One center had a significantly high AISR for bacteraemia and one center had a significantly low AISR for bacteraemia. CONCLUSIONS: The first year of Dialin running demonstrates the importance of standardised surveillance method in VAI and bacteraemia surveillance but not for viral hepatitis.