Srinivasan Beddhu

Effects of Body Size and Body Composition on Survival in Hemodialysis Patients

It is unclear whether increased muscle mass or body fat confer the survival advantage in hemodialysis patients with high body-mass index (BMI). Twenty-four-hour urinary creatinine (UCr) excretion was used as a measure of muscle mass. The outcomes of hemodialysis patients with high BMI and normal or high muscle mass (inferred low body fat) and high BMI and low muscle mass (inferred high body fat) were studied to study the effects of body composition on outcomes. In 70,028 patients who initiated hemodialysis in the United States from January 1995 to December 1999 with measured creatinine clearances reported in the Medical Evidence form, all-cause and cardiovascular mortality were examined in Cox and parametric survival models. When compared with normal BMI (18.5 to 24.9 kg/m(2)) group, patients with high BMI (> or = 25 kg/m(2)) had lower hazard of death (hazard ratio [HR], 0.85; P < 0.001). However, when compared with normal BMI patients with UCr >25th percentile (0.55 g/d), high BMI patients with UCr >0.55 g/d had lower hazard of all-cause (HR, 0.85; P < 0.001) and cardiovascular death (HR, 0.89; P < 0.001), and high BMI patients with UCr < or =0.55 g/d had higher hazard of all-cause death (HR, 1.14; P<0.001) and cardiovascular death (HR, 1.19; P <0.001). Both BMI and body composition are strong predictors of death. The protective effect conferred by high BMI is limited to those patients with normal or high muscle mass. High BMI patients with inferred high body fat have increased and not decreased mortality.

Weight Loss Interventions in Chronic Kidney Disease: A Systematic Review and Meta-analysis

BACKGROUND AND OBJECTIVES Obesity is an independent risk factor for development and progression of chronic kidney disease (CKD). We conducted a systematic review to assess the benefits of intentional weight loss in patients with non-dialysis-dependent CKD and glomerular hyperfiltration. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS We searched MEDLINE, SCOPUS, and conference proceedings for randomized, controlled trials and observational studies that examined various surgical and nonsurgical interventions (diet, exercise, and/or antiobesity agents) in adult patients with CKD. Results were summarized using random-effects model. RESULTS Thirteen studies were included. In patients with CKD, body mass index (BMI) decreased significantly (weighted mean difference [WMD] -3.67 kg/m(2); 95% confidence interval [CI] -6.56 to -0.78) at the end of the study period with nonsurgical interventions. This was associated with a significant decrease in proteinuria (WMD -1.31 g/24 h; 95% CI -2.11 to -0.51) and systolic BP with no further decrease in GFR during a mean follow-up of 7.4 mo. In morbidly obese individuals (BMI >40 kg/m(2)) with glomerular hyperfiltration (GFR >125 ml/min), surgical interventions decreased BMI, which resulted in a decrease in GFR (WMD -25.56 ml/min; 95% CI -36.23 to -14.89), albuminuria, and systolic BP. CONCLUSIONS In smaller, short-duration studies in patients with CKD, nonsurgical weight loss interventions reduce proteinuria and BP and seem to prevent further decline in renal function. In morbidly obese individuals with glomerular hyperfiltration, surgical interventions normalize GFR and reduce BP and microalbuminuria. Larger, long-term studies to analyze renal outcomes such as development of ESRD are needed.

Lipoprotein Metabolism and Lipid Management in Chronic Kidney Disease

Dyslipidemia is an established cardiovascular (CV) risk factor in the general population. In chronic kidney disease (CKD), however, epidemiologic studies ([1][1]–[3][2]) and clinical trials ([4][3]–[12][4]) have raised uncertainties regarding the impact of dyslipidemia on clinical outcomes and,

Impact of Dialysis Dose and Membrane on Infection-Related Hospitalization and Death: Results of the HEMO Study

Infection is the second most common cause of death among hemodialysis patients. A predefined secondary aim of the HEMO study was to determine if dialysis dose or flux reduced infection-related deaths or hospitalizations. The effects of dialysis dose, dialysis membrane, and other clinical parameters on infection-related deaths and first infection-related hospitalizations were analyzed using Cox regression analysis. Among the 1846 randomized patients (mean age, 58 yr; 56% female; 63% black; 45% with diabetes), there were 871 deaths, of which 201 (23%) were due to infection. There were 1698 infection-related hospitalizations, yielding a 35% annual rate. The likelihood of infection-related death did not differ between patients randomized to a high or standard dose (relative risk [RR], 0.99 [0.75 to 1.31]) or between patients randomized to high-flux or low-flux membranes (RR, 0.85 [0.64 to 1.13]). The relative risk of infection-related death was associated (P < 0.001 for each variable) with age (RR, 1.47 [1.29 to 1.68] per 10 yr); co-morbidity score (RR, 1.46 [1.21 to 1.76]), and serum albumin (RR, 0.19 [0.09 to 0.41] per g/dl). The first infection-related hospitalization was related to the vascular access in 21% of the cases, and non-access-related in 79%. Catheters were present in 32% of all study patients admitted with access-related infection, even though catheters represented only 7.6% of vascular accesses in the study. In conclusion, infection accounted for almost one fourth of deaths. Infection-related deaths were not reduced by higher dose or by high flux dialyzers. In this prospective study, most infection-related hospitalizations were not attributed to vascular access. However, the frequency of access-related, infection-related hospitalizations was disproportionately higher among patients with catheters compared with grafts or fistulas.

Impact of Timing of Initiation of Dialysis on Mortality

Previous studies showed that sicker patients were initiated on dialysis at higher GFR as estimated by the Modification of Diet in Renal Disease (MDRD) formula. It was previously shown that patients with low creatinine production were malnourished and had low serum creatinine levels and creatinine clearances (CrCl) but high MDRD GFR at initiation of dialysis. Therefore, a propensity score approach was used to examine the associations of MDRD GFR and measured CrCl at the initiation of dialysis with subsequent mortality. Baseline data and outcomes were obtained from the Dialysis Morbidity Mortality Study Wave II. Propensity scores for early initiation derived by logistic regression were used in Cox models to examine mortality. Each 5-ml/min increase in MDRD GFR at initiation of dialysis in the entire cohort was associated with increased hazard of death in multivariable Cox model (hazard ratio [HR] 1.14; P = 0.002). In the subgroup of patients with reported CrCl, higher MDRD GFR was associated with increased risk of death (for each 5-ml/min increase, HR 1.27; P < 0.001) but not CrCl (for each 5-ml/min increase, HR 0.98; P = 0.81). These divergent results might reflect erroneous GFR estimation by the MDRD formula. Furthermore, these data do not support earlier initiation of dialysis. Therefore, for patients without clinical indications for initiation of dialysis, the appropriate GFR level for initiation of dialysis is unknown.

High dietary fiber intake is associated with decreased inflammation and all-cause mortality in patients with chronic kidney disease

Chronic kidney disease is considered an inflammatory state and a high fiber intake is associated with decreased inflammation in the general population. Here, we determined whether fiber intake is associated with decreased inflammation and mortality in chronic kidney disease, and whether kidney disease modifies the associations of fiber intake with inflammation and mortality. To do this, we analyzed data from 14,543 participants in the National Health and Nutrition Examination Survey III. The prevalence of chronic kidney disease (estimated glomerular filtration rate less than 60 ml/min per 1.73 m(2)) was 5.8%. For each 10-g/day increase in total fiber intake, the odds of elevated serum C-reactive protein levels were decreased by 11% and 38% in those without and with kidney disease, respectively. Dietary total fiber intake was not significantly associated with mortality in those without but was inversely related to mortality in those with kidney disease. The relationship of total fiber with inflammation and mortality differed significantly in those with and without kidney disease. Thus, high dietary total fiber intake is associated with lower risk of inflammation and mortality in kidney disease and these associations are stronger in magnitude in those with kidney disease. Interventional trials are needed to establish the effects of fiber intake on inflammation and mortality in kidney disease.

Creatinine Production, Nutrition, and Glomerular Filtration Rate Estimation

This study examined the validity and clinical implications of the assumption of the Modification of Diet in Renal Disease Study (MDRD) formula that age, gender, race, and BUN account for creatinine production (CP). The relationships of MDRD GFR, CP, and nutrition were examined in 1074 Dialysis Morbidity and Mortality Study Wave II patients with reported measured creatinine clearances at initiation of dialysis. Age, gender, race, BUN, and serum creatinine (Scr) were used to calculate MDRD GFR. The measured 24-h urinary creatinine was used to estimate CP. In linear regression, Scr positively correlated with CP independent of age, gender, race, and BUN. Compared with the highest CP quartile, the lowest CP quartile had lower creatinine clearance (5.8 +/- 2.9 versus 11.3 +/- 3.4 ml/min, P <.01) despite lower Scr (5.8 +/- 2.6 versus 8.6 +/- 3.1 mg%, P <.01). There was an excellent correlation between the reciprocal of Scr and the MDRD GFR (r = 0.90). As a result, the MDRD GFR was higher in the lowest CP quartile (10.9 +/- 4.6 versus 7.6 +/- 2.4 ml/min, P <.01). Malnutrition (48% versus 26%, P <.01) was more common in the lowest CP quartile. Each 5-ml/min increase in MDRD GFR was associated with 21% higher odds of malnutrition (P = 0.046) in a multivariable logistic regression, which was abolished by controlling for CP. The fundamental assumption of the MDRD formula is invalid in patients with advanced renal failure, and the use of this formula in these patients might introduce biases.

Physical activity and mortality in chronic kidney disease (NHANES III).

BACKGROUND AND OBJECTIVES Chronic kidney disease (CKD) is associated with impaired physical activity. However, it is unclear whether the associations of physical activity with mortality are modified by the presence of CKD. Therefore, we examined the effects of CKD on the associations of physical activity with mortality. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS This was an observational study of 15,368 adult participants in the National Health and Nutrition Examination Survey III; 5.9% had CKD (eGFR < 60 ml/min per 1.73 m(2)). Based on the frequency and intensity of leisure time physical activity obtained by a questionnaire, participants were divided into inactive, insufficiently active, and active groups. Time to mortality was examined in Cox models, taking into account the complex survey design. RESULTS Inactivity was present in 13.5% of the non-CKD and 28.0% of the CKD groups (P < 0.001). In two separate multivariable Cox models, compared with the physically inactive group, hazard ratios (95% confidence intervals) of mortality for insufficiently active and active groups were 0.60 (0.45 to 0.81) and 0.59 (0.45 to 0.77) in the non-CKD subpopulation and 0.58 (0.42 to 0.79) and 0.44 (0.33 to 0.58) in the CKD subpopulation. These hazard ratios did not differ significantly between the CKD and non-CKD subpopulations (P > 0.3). CONCLUSIONS Physical inactivity is associated with increased mortality in CKD and non-CKD populations. As in the non-CKD population, increased physical activity might have a survival benefit in the CKD population.

Both low muscle mass and low fat are associated with higher all-cause mortality in hemodialysis patients

A higher body mass index is associated with better outcomes in hemodialysis patients; however, this index does not differentiate between fat and muscle mass. In order to clarify this, we examined the relationship between measures of fat and muscle mass and mortality in 1709 patients from the Hemodialysis Study. Triceps skin-fold thickness was used to assess body fat and mid-arm muscle circumference was used to assess muscle mass. Cox regression was used to evaluate the relationship between measures of body composition with all-cause mortality after adjustments for demographic, cardiovascular, dialysis, and nutrition-related risk factors. During a median follow-up of 2.5 years, there were 802 deaths. In adjusted models with continuous covariates, higher triceps skin-fold thickness and higher body mass index were significantly associated with decreased hazards of mortality, while higher mid-arm muscle circumference showed a trend toward decreased mortality. In adjusted models, lower quartiles of triceps skin-fold thickness, mid-arm muscle circumference, and body mass index were all significantly associated with higher all-cause mortality. These studies show that body composition in end-stage renal disease bears a complex relationship to all-cause mortality.

Higher serum bicarbonate levels within the normal range are associated with better survival and renal outcomes in African Americans

Recent studies suggest that correcting low serum bicarbonate levels may reduce the progression of kidney disease; however, few patients with chronic kidney disease have low serum bicarbonate. Therefore, we examined whether higher levels of serum bicarbonate within the normal range (20-30 mmol/l) were associated with better kidney outcomes in the African American Study of Kidney Disease and Hypertension (AASK) trial. At baseline and during follow-up of 1094 patients, the glomerular filtration rates (GFR) were measured by iothalamate clearances and events were adjudicated by the outcomes committee. Mean baseline serum bicarbonate, measured GFR, and proteinuria were 25.1 mmol/l, 46 ml/min per 1.73 m(2), and 326 mg/g of creatinine, respectively. Each 1 mmol/l increase in serum bicarbonate within the normal range was associated with reduced risk of death, dialysis, or GFR event and with dialysis or GFR event (hazard ratios of 0.942 and 0.932, respectively) in separate multivariable Cox regression models that included errors-in-variables calibration. Cubic spline regression showed that the lowest risk of GFR event or dialysis was found at serum bicarbonate levels near 28-30 mmol/l. Thus, our study suggests that serum bicarbonate is an independent predictor of CKD progression. Whether increasing serum bicarbonate into the high-normal range will improve kidney outcomes during interventional studies will need to be considered.