Kamyar Kalantar-Zadeh

Body mass index and mortality in heart failure: A meta-analysis

BACKGROUND In patients with chronic heart failure (CHF), previous studies have reported reduced mortality rates in patients with increased body mass index (BMI). The potentially protective effect of increased BMI in CHF has been termed the obesity paradox or reverse epidemiology. This meta-analysis was conducted to examine the relationship between increased BMI and mortality in patients with CHF. METHODS We searched the Cochrane Central Register of Controlled Trials, MEDLINE, EMBASE, Scopus, and Web of Science to identify studies with contemporaneous control groups (cohort, case-control, or randomized controlled trials) that examined the effect of obesity on all-cause and cardiovascular mortality. Two reviewers independently assessed studies for inclusion and performed data extraction. RESULTS Nine observational studies met final inclusion criteria (total n = 28,209). Mean length of follow-up was 2.7 years. Compared to individuals without elevated BMI levels, both overweight (BMI approximately 25.0-29.9 kg/m(2), RR 0.84, 95% CI 0.79-0.90) and obesity (BMI approximately > or =30 kg/m(2), RR 0.67, 95% CI 0.62-0.73) were associated with lower all-cause mortality. Overweight (RR 0.81, 95% CI 0.72-0.92) and obesity (RR 0.60, 95% CI 0.53-0.69) were also associated with lower cardiovascular mortality. In a risk-adjusted sensitivity analysis, both obesity (adjusted HR 0.88, 95% CI 0.83-0.93) and overweight (adjusted HR 0.93, 95% CI 0.89-0.97) remained protective against mortality. CONCLUSIONS Overweight and obesity were associated with lower all-cause and cardiovascular mortality rates in patients with CHF and were not associated with increased mortality in any study. There is a need for prospective studies to elucidate mechanisms for this relationship.

Associations between Changes in Hemoglobin and Administered Erythropoiesis-Stimulating Agent and Survival in Hemodialysis Patients

Although treating anemia of chronic kidney disease by erythropoiesis-stimulating agents (ESA) may improve survival, most studies have examined associations between baseline hemoglobin values and survival and ignored variations in clinical and laboratory measures over time. It is not clear whether longitudinal changes in hemoglobin or administered ESA have meaningful associations with survival after adjustment for time-varying confounders. With the use of time-dependent Cox regression models, longitudinal associations were examined between survival and quarterly (13-wk averaged) hemoglobin values and administered ESA dose in a 2-yr (July 2001 to June 2003) cohort of 58,058 maintenance hemodialysis patients from a large dialysis organization (DaVita) in the United States. After time-dependent and multivariate adjustment for case mix, quarterly varying administered intravenous iron and ESA doses, iron markers, and nutritional status, hemoglobin levels between 12 and 13 g/dl were associated with the greatest survival. Among prevalent patients, the lower range of the recommended Kidney Disease Quality Outcomes Initiative hemoglobin target (11 to 11.5 g/dl) was associated with a higher death risk compared with the 11.5- to 12-g/dl range. A decrease or increase in hemoglobin over time was associated with higher or lower death risk, respectively, independent of baseline hemoglobin. Administration of any dose of ESA was associated with better survival, whereas among those who received ESA, requiring higher doses were surrogates of higher death risk. In this observational study, greater survival was associated with a baseline hemoglobin between 12 and 13 g/dl, treatment with ESA, and rising hemoglobin. Falling hemoglobin and requiring higher ESA doses were associated with decreased survival. Randomized clinical trials are required to examine these associations.

Fluid retention is associated with cardiovascular mortality in patients undergoing long-term hemodialysis.

Background— Patients with chronic kidney disease (stage 5) who undergo hemodialysis treatment have similarities to heart failure patients in that both populations retain fluid frequently and have excessively high mortality. Volume overload in heart failure is associated with worse outcomes. We hypothesized that in hemodialysis patients, greater interdialytic fluid gain is associated with poor all-cause and cardiovascular survival. Methods and Results— We examined 2-year (July 2001 to June 2003) mortality in 34 107 hemodialysis patients across the United States who had an average weight gain of at least 0.5 kg above their end-dialysis dry weight by the time the subsequent hemodialysis treatment started. The 3-month averaged interdialytic weight gain was divided into 8 categories of 0.5-kg increments (up to ≥4.0 kg). Eighty-six percent of patients gained >1.5 kg between 2 dialysis sessions. In unadjusted analyses, higher weight gain was associated with better nutritional status (higher protein intake, serum albumin, and body mass index) and tended to be linked to greater survival. However, after multivariate adjustment for demographics (case mix) and surrogates of malnutrition-inflammation complex, higher weight-gain increments were associated with increased risk of all-cause and cardiovascular death. The hazard ratios (95% confidence intervals) of cardiovascular death for weight gain <1.0 kg and ≥4.0 kg (compared with 1.5 to 2.0 kg as the reference) were 0.67 (0.58 to 0.76) and 1.25 (1.12 to 1.39), respectively. Conclusions— In hemodialysis patients, greater fluid retention between 2 subsequent hemodialysis treatment sessions is associated with higher risk of all-cause and cardiovascular death. The mechanisms by which fluid retention influences cardiovascular survival in hemodialysis may be similar to those in patients with heart failure and warrant further research.

Nutritional recommendations for the management of sarcopenia.

The Society for Sarcopenia, Cachexia, and Wasting Disease convened an expert panel to develop nutritional recommendations for prevention and management of sarcopenia. Exercise (both resistance and aerobic) in combination with adequate protein and energy intake is the key component of the prevention and management of sarcopenia. Adequate protein supplementation alone only slows loss of muscle mass. Adequate protein intake (leucine-enriched balanced amino acids and possibly creatine) may enhance muscle strength. Low 25(OH) vitamin D levels require vitamin D replacement.

Similar Outcomes With Hemodialysis and Peritoneal Dialysis in Patients With End-Stage Renal Disease

BACKGROUND The annual payer costs for patients treated with peritoneal dialysis (PD) are lower than with hemodialysis (HD), but in 2007, only 7% of dialysis patients in the United States were treated with PD. Since 1996, there has been no change in the first-year mortality of HD patients, but both short- and long-term outcomes of PD patients have improved. METHODS Data from the US Renal Data System were examined for secular trends in survival among patients treated with HD and PD on day 90 of end-stage renal disease (HD, 620 020 patients; PD, 64 406 patients) in three 3-year cohorts (1996-1998, 1999-2001, and 2002-2004) for up to 5 years of follow-up using a nonproportional hazards marginal structural model with inverse probability of treatment and censoring weighting. RESULTS There was a progressive attenuation in the higher risk for death seen in patients treated with PD in earlier cohorts; for the 2002-2004 cohort, there was no significant difference in the risk of death for HD and PD patients through 5 years of follow-up. The median life expectancy of HD and PD patients was 38.4 and 36.6 months, respectively. Analyses in 8 subgroups based on age (<65 and ≥65 years), diabetic status, and baseline comorbidity (none and ≥1) showed greater improvement in survival among patients treated with PD relative to HD at all follow-up periods. CONCLUSION In the most recent cohorts, patients who began treatment with HD or PD have similar outcomes.

Effect of malnutrition-inflammation complex syndrome on EPO hyporesponsiveness in maintenance hemodialysis patients.

BACKGROUND Elements of malnutrition-inflammation complex syndrome (MICS) may blunt the responsiveness of anemia of end-stage renal disease (ESRD) to recombinant human erythropoietin (EPO). METHODS The authors examined cross-sectional associations between the required dose of EPO within a 13-week interval as prescribed by practicing nephrologists who were blind to the study and several laboratory values known to be related to nutrition and/or inflammation, as well as the malnutrition-inflammation score (MIS), which is a fully quantitative assessment tool based on the subjective global assessment of nutrition. RESULTS A total of 339 maintenance hemodialysis (MHD) outpatients, including 181 men, who were aged 54.7 +/- 14.5 years (mean +/- SD), who had undergone dialysis for 36.3 +/- 33.2 months, were selected randomly from 7 DaVita dialysis units in Los Angeles South/East Bay area. The average weekly dose of administered recombinant human EPO within a 13-week interval was 217 +/- 187 U/kg. Patients were receiving intravenous iron supplementation (iron gluconate or dextran) averaging 39.5 +/- 47.5 mg/wk. The MIS and serum concentrations of high-sensitivity C-reactive protein, interleukin 6 (IL-6), tumor necrosis factor-alpha, and lactate dehydrogenase had positive correlation with required EPO dose and EPO responsiveness index (EPO divided by hemoglobin), whereas serum total iron binding capacity (TIBC), prealbumin and total cholesterol, as well as blood lymphocyte count had statistically significant but negative correlations with indices of refractory anemia. Most correlations remained significant even after multivariate adjustment for case-mix and anemia factors and other relevant covariates. Similar associations were noticed across EPO per body weight tertiles via analysis of variance and after estimating odds ratio for higher versus lower tertile via logistic regression after same case-mix adjustment. CONCLUSION The existence of elements of MICS as indicated by a high MIS and increased levels of proinflammatory cytokines such as IL-6 as well as decreased nutritional values such as low serum concentrations of total cholesterol, prealbumin, and TIBC correlates with EPO hyporesponsiveness in MHD patients.

Etiology of the Protein-Energy Wasting Syndrome in Chronic Kidney Disease: A Consensus Statement From the International Society of Renal Nutrition and Metabolism (ISRNM)

Protein-energy wasting (PEW), a term proposed by the International Society of Renal Nutrition and Metabolism (ISRNM), refers to the multiple nutritional and catabolic alterations that occur in chronic kidney disease (CKD) and associate with morbidity and mortality. To increase awareness, identify research needs, and provide the basis for future work to understand therapies and consequences of PEW, ISRNM provides this consensus statement of current knowledge on the etiology of PEW syndrome in CKD. Although insufficient food intake (true undernutrition) due to poor appetite and dietary restrictions contribute, other highly prevalent factors are required for the full syndrome to develop. These include uremia-induced alterations such as increased energy expenditure, persistent inflammation, acidosis, and multiple endocrine disorders that render a state of hypermetabolism leading to excess catabolism of muscle and fat. In addition, comorbid conditions associated with CKD, poor physical activity, frailty, and the dialysis procedure per se further contribute to PEW.

Understanding Sources of Dietary Phosphorus in the Treatment of Patients with Chronic Kidney Disease

In individuals with chronic kidney disease, high dietary phosphorus (P) burden may worsen hyperparathyroidism and renal osteodystrophy, promote vascular calcification and cardiovascular events, and increase mortality. In addition to the absolute amount of dietary P, its type (organic versus inorganic), source (animal versus plant derived), and ratio to dietary protein may be important. Organic P in such plant foods as seeds and legumes is less bioavailable because of limited gastrointestinal absorption of phytate-based P. Inorganic P is more readily absorbed by intestine, and its presence in processed, preserved, or enhanced foods or soft drinks that contain additives may be underreported and not distinguished from the less readily absorbed organic P in nutrient databases. Hence, P burden from food additives is disproportionately high relative to its dietary content as compared with natural sources that are derived from organic (animal and vegetable) food proteins. Observational and metabolic studies indicate nutritional and longevity benefits of higher protein intake in dialysis patients. This presents challenges to providing appropriate nutrition because protein and P intakes are closely correlated. During dietary counseling of patients with chronic kidney disease, the absolute dietary P content as well as the P-to-protein ratio in foods should be addressed. Foods with the least amount of inorganic P, low P-to-protein ratios, and adequate protein content that are consistent with acceptable palatability and enjoyment to the individual patient should be recommended along with appropriate prescription of P binders. Provision of in-center and monitored meals during hemodialysis treatment sessions in the dialysis clinic may facilitate the achievement of these goals.

Association of Activated Vitamin D Treatment and Mortality in Chronic Kidney Disease

BACKGROUND Treatment of secondary hyperparathyroidism (SHPT) with activated vitamin D analogues is associated with better survival in patients receiving dialysis. It is unclear whether such a benefit is present in patients with predialysis chronic kidney disease (CKD). METHODS We examined the association of oral calcitriol treatment with mortality and the incidence of dialysis in 520 male US veterans (mean [SD] age, 69.8 [10.3] years; 23.5% black) with CKD stages 3 to 5 and not yet receiving dialysis (mean [SD] estimated glomerular filtration rate, 30.8 [11.3]). Associations were examined by the Kaplan-Meier method and in Poisson regression models with adjustment for age, race, comorbidities, smoking, blood pressure, body mass index, use of phosphate binders, estimated glomerular filtration rate, proteinuria, white blood cell count, percentage of lymphocytes, and levels of parathyroid hormone, calcium, phosphorus, albumin, bicarbonate, and hemoglobin. RESULTS Two hundred fifty-eight of 520 subjects received treatment with calcitriol, 0.25 to 0.5 microg/d, for a median duration of 2.1 years (range, 0.06-6.0 years). The incidence rate ratios for mortality and combined death and dialysis initiation were significantly lower in treated vs untreated patients (P < .001 for both in the fully adjusted models). Treatment with calcitriol was associated with a trend toward a lower incidence of dialysis. These results were consistent across different subgroups. CONCLUSIONS Treatment with the activated vitamin D analogue calcitriol appears to be associated with significantly greater survival in patients with CKD not yet receiving dialysis. Randomized clinical trials are required to verify the causality of these associations and to examine whether similar associations are seen with different activated vitamin D analogues.

Risk factor paradox in wasting diseases.

Purpose of reviewEmerging data indicate that conventional cardiovascular risk factors (e.g. hypercholesterolemia and obesity) are paradoxically associated with better survival in distinct populations with wasting. We identify these populations and review survival paradoxes and common pathophysiologic mechanisms. Recent findingsA ‘reverse epidemiology’ of cardiovascular risk is observed in chronic kidney disease, chronic heart failure, chronic obstructive lung disease, cancer, AIDS and rheumatoid arthritis, and in the elderly. These populations apparently have slowly progressive to full-blown wasting and significantly greater short-term mortality than the general population. The survival paradoxes may result from the time differential between the two competing risk factors [i.e. over-nutrition (long-term killer but short-term protective) versus undernutrition (short-term killer)]. Hemodynamic stability of obesity, protective adipokine profile, endotoxin–lipoprotein interaction, toxin sequestration of fat, antioxidation of muscle, reverse causation, and survival selection may also contribute. SummaryThe seemingly counterintuitive risk factor paradox is the hallmark of chronic disease states or conditions associated with wasting disease at the population level. Studying similarities among these populations may help reveal common pathophysiologic mechanisms of wasting disease, leading to a major shift in clinical medicine and public health beyond the conventional Framingham paradigm and to novel therapeutic approaches related to wasting and short-term mortality.