Christian Combe

Intradialytic Parenteral Nutrition Does Not Improve Survival in Malnourished Hemodialysis Patients: A 2-Year Multicenter, Prospective, Randomized Study

Although intradialytic parenteral nutrition (IDPN) is a method used widely to combat protein-calorie malnutrition in hemodialysis patients, its effect on survival has not been thoroughly studied. We conducted a prospective, randomized trial in which 186 malnourished hemodialysis patients received oral nutritional supplements with or without 1 year of IDPN. IDPN did not improve 2-year mortality (primary end point), hospitalization rate, Karnofsky score, body mass index, or laboratory markers of nutritional status. Instead, both groups demonstrated improvement in body mass index and the nutritional parameters serum albumin and prealbumin (P < 0.05). Multivariate analysis showed that an increase in prealbumin of >30 mg/L within 3 months, a marker of nutritional improvement, independently predicted a 54% decrease in 2-year mortality, as well as reduced hospitalizations and improved general well-being as measured by the Karnofsky score. Therefore, although we found no definite advantage of adding IDPN to oral nutritional supplementation, this is the first prospective study demonstrating that an improvement in prealbumin during nutritional therapy is associated with a decrease in morbidity and mortality in malnourished hemodialysis patients.

Renal diffusion and BOLD MRI in experimental diabetic nephropathy

To investigate the possibility of using combined blood oxygen level‐dependent (BOLD) imaging and diffusion‐weighted imaging (DWI) to detect pathological and physiological changes in renal tissue damage of the kidney induced by chronic renal hyperfiltration.

Renal diffusion and BOLD MRI in experimental diabetic nephropathy. Blood oxygen level-dependent.

To investigate the possibility of using combined blood oxygen level‐dependent (BOLD) imaging and diffusion‐weighted imaging (DWI) to detect pathological and physiological changes in renal tissue damage of the kidney induced by chronic renal hyperfiltration.

Outbreak of Shiga Toxin–Producing Escherichia coli O104:H4 Associated With Organic Fenugreek Sprouts, France, June 2011

BACKGROUND On 22 June 2011, 8 patients with hemolytic uremic syndrome (HUS) or bloody diarrhea were reported in France. All 8 were attendees of a community center event on 8 June near Bordeaux. Three Escherichia coli cases were confirmed by isolation of Shiga toxin-producing E. coli O104:H4 stx2 aggR producing a cefotaximase (CTX-M) β-lactamase (STEC O104:H4); the same rare serotype caused the outbreak in Germany in May-July 2011. An investigation was initiated to describe the outbreak, identify the vehicle for infection, and guide control measures. METHODS We conducted a retrospective cohort study among all adults attending the event, including food handlers. A standardized questionnaire was administered to participants. A case was an attendee who developed HUS or diarrhea between 8 and 24 June. Cases were confirmed by isolation of STEC O104:H4 or O104 serology. Relative risks (RRs) and 95% confidence intervals (CIs) by exposure were calculated using a Poisson regression model. RESULTS Twenty-four cases were identified (14% attack rate). Of these, 18 (75%) were women, 22 (92%) were adults, 7 (29%) developed HUS, 5 (21%) developed bloody diarrhea, and 12 (50%) developed diarrhea. Ten (42%) cases were confirmed. Fenugreek was the only sprout type with an independent association to illness (RR, 5.1; 95% CI, 2.3-11.1) in multivariable analysis. CONCLUSIONS This investigation identified a point-source STEC O104:H4 outbreak associated with consumption of fenugreek sprouts. Comparison of results from French and German STEC O104:H4 outbreak investigations enabled identification of a common food vehicle, fenugreek sprouts, and resulted in implementation of Europe-wide control measures in July 2011.

The Associations of Social Support and Other Psychosocial Factors with Mortality and Quality of Life in the Dialysis Outcomes and Practice Patterns Study

BACKGROUND AND OBJECTIVES This study aimed to investigate the influence of social support and other psychosocial factors on mortality, adherence to medical care recommendations, and physical quality of life among hemodialysis patients. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS Data on 32,332 hemodialysis patients enrolled in the Dialysis Outcomes and Practice Patterns Study (1996 to 2008) in 12 countries were analyzed. Social support and other psychosocial factors related to ESRD and its treatment were measured by patient self-reports of health interference with social activities, isolation, feeling like a burden, and support from family and dialysis staff. Cox regression and logistic regression were used to examine associations of baseline social support and other psychosocial factors with all-cause mortality and with other measured outcomes at baseline, adjusting for potential confounders. RESULTS Mortality was higher among patients reporting that their health interfered with social activities, were isolated, felt like a burden, and were dissatisfied with family support. Poorer family support and several psychosocial measures also were associated with lower adherence to the prescribed hemodialysis length and the recommended weight gain between sessions. Some international differences were observed. Poorer self-reported social support and other psychosocial factors were associated with poor physical quality of life. CONCLUSIONS Poorer social support and other psychosocial factors are associated with higher mortality risk, lower adherence to medical care, and poorer physical quality of life in hemodialysis patients. More research is needed to assess whether interventions to improve social support and other psychosocial factors will lengthen survival and enhance quality of life.

Normoalbuminuric Renal-Insufficient Diabetic Patients: A lower-risk group

OBJECTIVE—About 20% of diabetic patients with chronic kidney disease (CKD) detected from the new American Diabetes Association recommendations (albumin excretion rate >30 mg/24 h or estimated glomerular filtration rate [GFR] <60 ml/min per 1.73 m2) may be normoalbuminuric. Do the characteristics and outcome differ for subjects with and without albuminuria? RESEARCH DESIGN AND METHODS—A total of 89 patients with diabetes and a modification of diet in renal disease (MDRD) estimated GFR (e-GFR) <60 ml/min per 1.73 m2 underwent a 51Cr-EDTA B-isotopic GFR determination and were followed up for 38 ± 11 months. RESULTS—The mean MDRD e-GFR (41.3 ± 13.1 ml/min per 1.73 m2) did not significantly differ from the i-GFR (45.6 ± 29.7). Of the subjects, 15 (17%) were normoalbuminuric. Their i-GFR did not differ from the albuminuric rate and from their MDRD e-GFR, although their serum creatinine was lower (122 ± 27 vs. 160 ± 71 μmol/l, P < 0.05): 71% would not have been detected by measuring serum creatinine (sCr) alone. They were less affected by diabetic retinopathy, and their HDL cholesterol and hemoglobin were higher (P < 0.05 vs. albuminuric). None of the CKD normoalbuminuric subjects started dialysis (microalbuminuric: 2/36, macroalbuminuric: 10/38) or died (microalbuminuric: 3/36, macroalbuminuric: 7/38) during the follow-up period (log-rank test: P < 0.005 for death or dialysis), and their albumin excretion rate and sCr values were stable after 38 months, whereas the AER increased in the microalbuminuric patients (P < 0.05), and the sCr increased in the macroalbuminuric patients (P < 0.01). CONCLUSIONS—Although their sCr is usually normal, most of the normoalbuminuric diabetic subjects with CKD according to an MDRD e-GFR below 60 ml/min per 1.73 m2 do really have a GFR below 60 ml/min per 1.73 m2. However, as expected, because of normoalbuminuria and other favorable characteristics, their risk for CKD progression or death is lower.

Factors influencing survival in hemodialysis patients aged older than 75 years: 2.5-year outcome study

The incidence of malnutrition is widely held to be greater in the elderly, but this specific factor has not been extensively studied in elderly dialysis patients. In a 30-month follow-up prospective study, we evaluated the role of nutrition on the outcome of 290 stable hemodialysis (HD) outpatients aged older than 75 years followed up in 20 French HD centers (167 men, 123 women; age, 79.8 +/- 4.2 years; previous time on dialysis, 41 +/- 38 months). On the same day in January 1996, predialysis and postdialysis blood samples were collected according to recommended procedures for dialysis quantification. Normalized protein catabolic rate, dialysis adequacy parameters, and estimation of lean body mass (LBM; expressed as observed/expected LBM values [obs/exp LBM]) were computed from predialysis and postdialysis urea and creatinine levels. Overall survival rates were 80% and 65% after 1 and 2 years of follow-up, respectively, and were significantly less in patients with the lower quartile of obs/exp LBM. In univariate analysis using the Cox proportional hazards model, survival was significantly influenced by age, albumin level, prealbumin level, body mass index, and diabetes, but not by sex, Kt/V, duration of dialysis, cholesterol level, hemoglobin level, or obs/exp LBM. In multivariate analysis, no variable remained significant. Cardiovascular mortality accounted for 52.1% of the patient deaths. We conclude that in elderly HD patients, malnutrition influences overall survival despite adequate dialysis treatment.

C-reactive protein and prediction of 1-year mortality in prevalent hemodialysis patients.

BACKGROUND AND OBJECTIVES Measurement of C-reactive protein (CRP) levels remains uncommon in North America, although it is now routine in many countries. Using Dialysis Outcomes and Practice Patterns Study data, our primary aim was to evaluate the value of CRP for predicting mortality when measured along with other common inflammatory biomarkers. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS We studied 5061 prevalent hemodialysis patients from 2005 to 2008 in 140 facilities routinely measuring CRP in 10 countries. The association of CRP with mortality was evaluated using Cox regression. Prediction of 1-year mortality was assessed in logistic regression models with differing adjustment variables. RESULTS Median baseline CRP was lower in Japan (1.0 mg/L) than other countries (6.0 mg/L). CRP was positively, monotonically associated with mortality. No threshold below which mortality rate leveled off was identified. In prediction models, CRP performance was comparable with albumin and exceeded ferritin and white blood cell (WBC) count based on measures of model discrimination (c-statistics, net reclassification improvement [NRI]) and global model fit (generalized R(2)). The primary analysis included age, gender, diabetes, catheter use, and the four inflammatory markers (omitting one at a time). Specifying NRI ≥5% as appropriate reclassification of predicted mortality risk, NRI for CRP was 12.8% compared with 10.3% for albumin, 0.8% for ferritin, and <0.1% for WBC. CONCLUSIONS These findings demonstrate the value of measuring CRP in addition to standard inflammatory biomarkers to improve mortality prediction in hemodialysis patients. Future studies are indicated to identify interventions that lower CRP and to identify whether they improve clinical outcomes.

ACID-BASE IN RENAL FAILURE: Acidosis and Nutritional Status in Hemodialyzed Patients

In a cross‐sectional study of more than 30% of French dialysis patients (N = 7,123), we evaluated the relationships between predialysis plasma bicarbonate concentration and nutritional markers. Data including age, gender, cause of end‐stage renal disease (ESRD), time on dialysis, body mass index (BMI), blood levels of midweek predialysis albumin, prealbumin, and bicarbonate were collected. Normalized protein catabolic rate (nPCR), dialysis adequacy parameters, and estimation of lean body mass (LBM) were computed from pre‐ and postbicarbonate‐dialysis urea and creatinine levels according to the classical formulas of Garred. Average values (±1 SD) were age 61 ± 16 years, BMI 23.3 ± 4.6 kg/m2, dialysis time 12.4 ± 2.7 h/week, HCO3 22.8 ± 3.5 mmol/L, albumin 38.7 ± 5.3 g/L, prealbumin 340 ± 90 mg/L, Kt/V 1.36 ± 0.36, nPCR 1.13 ± 0.32 g/kg BW/day, and LBM 0.86 ± 0.21% of ideal LBM. A highly significant negative correlation was observed between predialysis bicarbonate levels (within a range of 16–30 mmol/L, 95% of this population) and nPCR confirmed by analysis of variance using bicarbonate classes (p < 0.0001). Bicarbonate was also negatively correlated with albumin, prealbumin, BMI, and LBM. No relationship was noted between bicarbonate and Kt/V despite a positive correlation between Kt/V and nPCR. It is likely that a persistent acidosis observed despite standard bicarbonate dialysis was caused by a high dietary protein intake which results in an increased acid load, but also overcomes the usual catabolic effects of acidosis.

Outbreak of Escherichia coli O104:H4 haemolytic uraemic syndrome in France: outcome with eculizumab

Background An outbreak of haemolytic uraemic syndrome (HUS) due to Shiga toxin-secreting Escherichia coli (STEC) O104:H4 from contaminated fenugreek sprouts occurred in June 2011 near Bordeaux, France. In the context of this outbreak, all patients were treated with the monoclonal anti-C5 antibody, eculizumab. Methods The diagnosis of HUS was made based on haemolytic anaemia, low platelet count and acute kidney injury. Data were obtained from initial gastrointestinal symptoms to the end of follow-up 10 weeks after the start of eculizumab. Results Among 24 cases of STEC gastroenteritis, HUS developed in nine patients (eight adults and one child), 6 (median; range 3–12) days after digestive symptoms begun. The median (range) highest or lowest biological values were platelet count 26 (range 14–93) G/L; haemoglobin 6.6 (range 5–10.7) g/dL; LDH 1520 (range 510–2568) IU/L; creatinine 152 (range 48–797) µmol/L. All patients had extra-renal complications (liver 9, pancreas 5, brain 3 and heart 3). Two patients were dialysed, and one was ventilated. After failure of plasma exchange to increase platelets in the first three patients, eculizumab was administered in all nine patients, 0–4 days after HUS diagnosis (median 1 day). One patient with very severe neurological HUS received immunoadsorption. Outcome was favourable in all patients, with rapid normalization of haemoglobin, platelets, LDH levels, renal function and neurological improvement. There were no deaths and no serious adverse events related to eculizumab. Conclusions Early treatment of O104:H4 STEC-HUS by eculizumab was associated with a rapid and efficient recovery. Controlled prospective evaluation of eculizumab in STEC-HUS is warranted.