Helen L. MacLaughlin

Nonrandomized trial of weight loss with orlistat, nutrition education, diet, and exercise in obese patients with CKD: 2-year follow-up.

BACKGROUND Obesity increases the comorbidity-adjusted relative risk of developing end-stage renal disease. Body mass index (BMI) > 30 kg/m(2) was a contraindication for transplant in our renal unit until 2008. STUDY DESIGN Open-label prospective nonrandomized intervention. SETTING & PARTICIPANTS All men and women aged 18-75 years with chronic kidney disease (CKD) and BMI > 30 or > 28 kg/m(2) with diabetes, hypertension, or dyslipidemia and otherwise suitable for kidney transplant if on dialysis therapy were eligible to enroll in the weight-management program. 64 patients were referred; 44 agreed to participate in the intervention group and 20 did not wish to take part and constitute the usual-care group. INTERVENTION 24-month weight-management program that included a low-fat renal-specific diet, exercise, and orlistat, 120 mg, 3 times daily. OUTCOMES Body weight, blood pressure (BP), kidney transplant wait listing. MEASUREMENTS Body weight, BP, estimated glomerular filtration rate (eGFR; calculated using the 4-variable Modification of Diet in Renal Disease [MDRD] Study equation). RESULTS 32 patients (73%) in the weight-management program group completed the follow-up evaluation. Baseline mean BMI was 35.7 +/- 4.5 (SD) kg/m(2) in the weight-management program group and 34.1 +/- 4.2 kg/m(2) in the usual-care group. 12 (38%) patients in the weight-management program and 9 (45%) in usual care had stages 3-4 CKD, with the remainder in stage 5 CKD on dialysis therapy. There were no differences in body weight, BP, or eGFR between groups at baseline. After 24 months, mean body weight was 94.6 +/- 16.1 kg in the weight-management program group versus 101.0 +/- 26.8 kg in the usual-care group (P < 0.001), and eGFR was 43 mL/min in the weight-management program group versus 18 mL/min in the usual-care group (P < 0.001). 9 of 26 (35%) otherwise eligible patients in the weight-management program and 1 of 18 (6%) patients in usual care were accepted for kidney transplant listing, with 3 transplants performed in the weight-management program group and 1 in the usual-care group. LIMITATIONS Nonrandomized trial, small number of participants. CONCLUSIONS The weight-management program group showed significant weight loss and weight-loss maintenance in obese patients with CKD and potentially enables obese patients with CKD to undergo kidney transplant.

Unintentional Weight Loss Is an Independent Predictor of Mortality in a Hemodialysis Population

OBJECTIVE This study investigated common components of classification of nutrition screening risk in the prediction of clinical end-points (mortality and morbidity) in hemodialysis patients over a 3-year period (2005 to 2008). DESIGN This was a retrospective cohort study. SETTING This study was conducted at a Hemodialysis centre. PARTICIPANTS The study included patients on maintenance hemodialysis in June 2005. INTERVENTION Assessment of nutrition risk was carried out using components of Protein-Energy Wasting criteria. MAIN OUTCOME MEASURE Clinical outcome at the 3-year follow-up (June 2008) was measured as mortality and morbidity (as unplanned hospital admissions). Risk of mortality was investigated independent of comorbidities, age, gender, ethnicity, and dialysis vintage using Cox proportional hazards model. RESULTS A total of 217 patients met the inclusion criteria (143 male [66%]; age, 60.5 ± 15.6 years). Patients who lost ≥5% body weight in the 6 months before the study commenced, had a 3-fold (Hazard Ratio = 3.0; 95% confidence interval: 1.2 to 7.5) independent greater risk of death (P = .02). Low serum albumin (<38 g/L) resulted in higher morbidity and mortality; however, this was not statistically significant when adjusted for confounders. Body mass index was only available in 64% (138 of 217) of the cohort at baseline, and was not related to clinical outcome at the 3-year follow-up. CONCLUSION Unintentional weight loss is independently predictive of clinical outcome in this cohort of dialysis patients. It is recommended that nutrition screening tools include weight loss as a key component in classification of risk and for prioritizing patient care.

Risk for chronic kidney disease increases with obesity: Health Survey for England 2010.

OBJECTIVE Studies of the relationship between obesity and chronic kidney disease (CKD) in nationally representative population samples are limited. Our study aimed to determine if overweight and obesity were independently associated with the risk for CKD in the 2010 Health Survey for England (HSE). DESIGN The HSE is an annually conducted cross-sectional study. In 2010 serum creatinine was included to determine the incidence of CKD in the population. CKD was defined as estimated glomerular filtration rate (eGFR) <60 ml/min per 1.73 m2 using the Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) formula. Multivariable logistic regression models were developed to calculate odds ratios and 95% confidence intervals for CKD risk by BMI (reference category: BMI=18.5-24.9 kg/m2) and adjusted for age, gender, ethnicity, smoking, diabetes and hypertension. SETTING A random sample of nationally representative households in England. SUBJECTS Adults (n 3463) with calculable eGFR and BMI were included. RESULTS The prevalence of CKD was 5.9%. The risk of CKD was over 2.5 times higher in obese participants compared with normal-weight participants in the fully adjusted model (BMI=30.0-39.9 kg/m2: adjusted OR=2.78 (95% CI 1.75, 4.43); BMI ≥ 40.0 kg/m2: adjusted OR=2.68 (95% CI 1.05, 6.85)). CONCLUSIONS Obesity is associated with an increased risk of CKD in a national sample of the UK population, even after adjustment for known CKD risk factors, which may have implications for CKD screening and future national health service planning and delivery.

Compliance With a Structured Weight Loss Program Is Associated With Reduced Systolic Blood Pressure in Obese Patients With Chronic Kidney Disease

BACKGROUND The effectiveness of lifestyle-based weight loss programs in obese patients with chronic disease has not been widely studied. This study examined the effectiveness of a weight management program (WMP), and sought to determine factors associated with successful weight loss in obese patients with chronic kidney disease (CKD). METHODS In this prospective cohort study, all patients with a body mass index (BMI) of >30 kg/m(2) referred to our clinic from January 2005 to December 2008 and who commenced a structured WMP of an energy-reduced renal diet, exercise, and pharmacotherapy were included in the analyses. Changes in body weight and associated variables up to 24 months were assessed with intention-to-treat mixed linear models and predictors of weight loss were identified with multiple linear regression. RESULTS One hundred and thirty-five patients (56% male), of mean age 52.2 years and BMI 36.4 kg/m(2) commenced the WMP. Significant weight loss was achieved for all patients at 6, 12, 18, and 24 months. Weight loss at 12 months was predicted by compliance and age, but not by baseline BMI, blood pressure (BP), stage of CKD or pharmacotherapy use. Greater compliance was associated with decreased systolic BP, with no change in mean antihypertensive medication dose. CONCLUSIONS Significant weight loss was achieved, demonstrating the effectiveness of the WMP, and compliance with a structured program improved weight loss and systolic BP.

Obesity and iron deficiency in chronic kidney disease: the putative role of hepcidin

Hepcidin is a 25-amino acid peptide with a defensinlike structure that is primarily synthesized in hepatocytes [1, 2]. It was independently isolated ~10 years ago by two groups seeking peptides with antimicrobial activity in urine [3] and plasma [4]. Hepcidin was originally shown to have a weak selective antimicrobial activity against certain bacteria; thus, its name reflected the site of major tissue expression (‘hep’ for hepatocyte) and its antimicrobial properties (‘cidin’) [1, 2]. However, soon after its isolation, independent studies suggested an important role of hepcidin in iron regulation [5, 6]; currently, a large body of evidence strongly supports the role of hepcidin as the ‘master regulator’ of iron homeostasis [2, 7]. Hepcidin reduces the efflux of recycled iron from both splenic and hepatic macrophages and also inhibits iron absorption from the gut [1, 2] (Figure 1). The cellular mechanisms of hepcidin action seem to be tissue specific. In reticuloendothelial macrophages, hepcidin was previously shown to bind to the cellular iron export channel ferroportin, inducing its internalization and subsequent degradation [8, 9]. Recent data suggest that in intestinal 50 Nephrol Dial Transplant (2012): Editorial Reviews

Nutrition and Exercise Rehabilitation in Obesity hypoventilation syndrome (NERO): a pilot randomised controlled trial

Background Respiratory management of obesity hypoventilation syndrome (OHS) focusses on the control of sleep-disordered breathing rather than the treatment of obesity. Currently, there are no data from randomised trials of weight loss targeted rehabilitation programmes for patients with OHS. Intervention A 3-month multimodal hybrid inpatient–outpatient motivation, exercise and nutrition rehabilitation programme, in addition to non invasive ventilation (NIV), would result in greater per cent weight loss compared with standard care. Methods A single-centre pilot randomised controlled trial allocated patients to either standard care or standard care plus rehabilitation. Primary outcome was per cent weight loss at 12 months with secondary exploratory outcomes of weight loss, exercise capacity and health-related quality of life (HRQOL) at the end of the rehabilitation programme to assess the intervention effect. Results Thirty-seven patients (11 male, 59.8±12.7 years) with a body mass index of 51.1±7.7 kg/m2 were randomised. At 12 months, there was no between-group difference in per cent weight loss (mean difference −5.9% (95% CI −14.4% to 2.7%; p=0.17)). At 3 months, there was a greater per cent weight loss (mean difference −5% (95% CI −8.3% to −1.4%; p=0.007)), increased exercise capacity (6 min walk test 60 m (95% CI 29.5 to 214.5) vs 20 m (95% CI 11.5 to 81.3); p=0.036) and HRQL (mean difference SF-36 general health score (10 (95% CI 5 to 21.3) vs 0 (95% CI −5 to 10); p=0.02)) in the rehabilitation group. Conclusion In patients with OHS, a 3-month comprehensive rehabilitation programme, in addition to NIV, resulted in improved weight loss, exercise capacity and QOL at the end of the rehabilitation period, but these effects were not demonstrated at 12 months, in part, due to the limited retention of patients at 12 months. Trial registration number Pre-results; NCT01483716.

Altered Protein Composition of Subcutaneous Adipose Tissue in Chronic Kidney Disease

Introduction Loss of renal function is associated with high mortality from cardiovascular disease (CVD). Patients with chronic kidney disease (CKD) have altered circulating adipokine and nonesterified fatty acid concentrations and insulin resistance, which are features of disturbed adipose tissue metabolism. Because dysfunctional adipose tissue contributes to the development of CVD, we hypothesize that adipose tissue dysfunctionality in patients with CKD could explain, at least in part, their high rates of CVD. Therefore we characterized adipose tissue from patients with CKD, in comparison to healthy controls, to search for signs of dysfunctionality. Methods Biopsy samples of subcutaneous adipose tissue from 16 CKD patients and 11 healthy controls were analyzed for inflammation, fibrosis, and adipocyte size. Protein composition was assessed using 2-dimensional gel proteomics combined with multivariate analysis. Results Adipose tissue of CKD patients contained significantly more CD68-positive cells, but collagen content did not differ. Adipocyte size was significantly smaller in CKD patients. Proteomic analysis of adipose tissue revealed significant differences in the expression of certain proteins between the groups. Proteins whose expression differed the most were α-1-microglobulin/bikunin precursor (AMBP, higher in CKD) and vimentin (lower in CKD). Vimentin is a lipid droplet−associated protein, and changes in its expression may impair fatty acid storage/mobilization in adipose tissue, whereas high levels of AMBP may reflect oxidative stress. Discussion These findings demonstrate that adipose tissue of CKD patients shows signs of inflammation and disturbed functionality, thus potentially contributing to the unfavorable metabolic profile and increased risk of CVD in these patients.

The nutrition impact symptoms (NIS) score detects malnutrition risk in patients admitted to nephrology wards

BACKGROUND Nutritional screening tools recommended for the general hospitalised population do not always adequately detect malnutrition risk in patients with kidney disease. The present study assessed the validity and reliability of the Nutrition Impact Symptoms (NIS) score as a nutrition screening tool for hospitalised inpatients prefer in nephrology wards. METHODS Nutritional status was classified using Subjective Global Assessment (SGA). NIS scores were calculated from the total score of responses to questions assessing symptoms impacting upon nutritional status from the patient-generated SGA. Concurrent validity of NIS score was assessed using a receiver operating characteristic curve to predict malnutrition risk against SGA. Predictive validity was examined against length of hospital stay (LOS) and 30-day re-admission using Poisson and logistic regression, respectively. Inter-rater reliability of NIS scoring between assessors was determined using intraclass correlation. RESULTS In 143 patients [90 males; mean (SD) age 57.8 (15.8) years], malnutrition prevalence was 38% (54/143) using SGA (rating B/C). Predicting malnutrition risk with an NIS score of ≥3 had a sensitivity of 0.89 and a specificity of 0.65 (area under the curve = 0.81 [95% confidence interval (CI) = 0.74-0.88]). For each 1-point increase in NIS score, the model predicted a 1.9% rise in the risk of an increased LOS (P = 0.002). Thirty-day re-admission was not associated with NIS score. Inter-rater reliability was moderate (mean difference = 0.53; intraclass correlation coefficient = 0.74; 95% CI = 0.57-0.85). CONCLUSIONS Nutrition impact symptoms score is a valid stand-alone nutrition screening tool for identifying malnutrition risk in nephrology inpatients and is associated with LOS.

Nutrition and Exercise Rehabilitation in Obesity hypoventilation syndrome (NERO)

Introduction We have previously shown that treatment of obesity hypoventilation syndrome (OHS) with non-invasive ventilation (NIV) results in weight reduction and an increase in physical activity (Murphy et al., 2012). We therefore hypothesised that a multi-modal rehabilitation programme, in addition to NIV, would lead to enhanced weight loss. Method We conducted a randomised controlled trial of NIV alone vs. NIV and a personalised rehabilitation programme in patients with OHS. Subjects in the intervention group received a bespoke diet and exercise regime, from a dietician and physiotherapist. All patients, in both groups, were reviewed monthly for 3 months. Anthropometrics, exercise capacity and health related quality of life (HQRL) were measured at baseline and at 3 months. The primary outcome measure at 3 months was weight loss. Secondary outcomes included: body mass index (BMI), neck circumference (NC), waist circumference (WC), hip circumference (HC) blood pressure (BP), rectus femoris cross-sectional area (RFCSA) and quadriceps maximal voluntary contraction (QMVC), 6 min walk distance (6MWD) and HRQL measures. Results 37 subjects were randomised with data from 30 patients analysed at 3 months (15 in each group). There were no differences between the groups in all parameters measured at baseline. The intervention group showed greater weight loss than the control group (-11.9 ± 6.7 vs. -2.4 ± 6.2 kg; p < 0.0001). There were also differences in NC, WC and HC (all p < 0.001, Table 1) with an improvement in BP observed in the intervention group (Table 1). In addition, there was an increase in weight corrected RFCSA and muscle strength (p < 0.0001, Table 1) with an increase in 6MWD in the intervention group (122 ± 161 vs. 46 ± 60 m; p = 0.005; Table 1). Finally, HRQL improved in the intervention group as evidenced by a greater reduction in Epworth sleepiness score, an increase in severe respiratory insufficiency questionnaire sum score and a greater decrease in the hospital and anxiety depression score (Table 1, all p < 0.0001).Abstract S30 Table 1 Changes in anthropometrics, blood pressure, peripheral muscle area, peripheral muscle strength and exercise capacity Conclusion In patients with OHS, the addition of a hospital-home hybrid personalised diet and exercise programme to standard NIV was shown to enhance weight loss as well as, skeletal muscle area and strength, exercise capacity and HRQL. Reference 1 Murphy PB, Davidson C, Hind MD, et al. Volume targeted versus pressure support non-invasive ventilation in patients with super obesity and chronic respiratory failure: a randomised controlled trial. Thorax. 2012;67:727–34

Contents Vol. 124, 2013

Chronic Kidney Disease and Hypertension A. Levin, Vancouver, B.C. R. Gansevoort, Groningen Acute Kidney Injury R. Mehta, San Diego, Calif. N. Kolhe, Derby Dialysis J. Daugirdas, Chicago, Ill. C. Hutchison, Hawkes Bay C. Fraansen, Groningen Patient Subjective Experience, Healthcare Delivery and Innovation in Practice R. Fluck, Derby E. Brown, London Crossover States with Non-Renal Organ Systems C. Chan, Toronto, Ont. T. Breidthardt, Basel N. Selby, Derby Transplantation A. Chandraker, Boston, Mass. A. Salama, London Editor-in-Chief