Shubho R. Sarkar

Methods and Reproducibility of Measurement of Resistivity in the Calf Using Regional Bioimpedance Analysis

The usefulness of regional bioimpedance analysis (RBIA) in determining the dry weight in dialysis patients is currently being investigated. The aim of this study was to evaluate the reproducibility of measurement of resistivity in the calf. Methods: Twenty-five normal subjects and 10 patients undergoing regular hemodialysis were studied. Four electrodes inserted into a blood pressure cuff were placed on the calf. Bioimpedance was continuously measured over 3- to 5-min periods (Xitron Hydra). After a resting period of 1 min, cuff pressure was increased to above the systolic blood pressure (SBP) for a few seconds to expel excess ECF fluid and then deflated. The effect on recordings of moving the electrodes 2 cm higher and then 2 cm lower than the normal position was studied in 8 normal subjects. In a second study of reproducibility, post-dialysis measurements were made twice in 10 patients who maintained the same post-dialysis target weight throughout the study period. Results: The mean resting resistivity (ρ₀) in normal subjects was 532.6 ± 95 Ω·cm rising to 583.9 ± 99.7 Ω·cm when cuff pressure was applied (ρp). The average values of ρ₀ and ρp in patients post-dialysis were 489 ± 74 and 537 ± 77 respectively showing that there were no significant differences in ρ₀ and ρp between normal subjects and patients post-dialysis. The mean values of change in resistivity when the electrodes were shifted between the lowest and highest positions on the calf were –3.66 ± 4.45 and –1.44 ± 3.82%, respectively. Repeat measurement of resistivity in patients post-dialysis varied by 2.04 ± 2.29% while post-dialysis body weight varied by 0.17 ± 0.47%. Conclusion: In this study, resistivity measurement by RBIA at the calf showed similar levels of fluid loading in patients post-dialysis as in normal subjects. This study also showed that change in electrode position resulted in a mean change in resistivity of <5% and repeated measurements showed a change in resistivity <3% while body weight changes were <0.2%. This technique appears to have an acceptable level of reproducibility for its application to the assessment of patient hydration.

Relationship between adiposity and cardiovascular risk factors in prevalent hemodialysis patients.

OBJECTIVE Increased body mass index (BMI) is associated with reduced all-cause and cardiovascular (CV) mortality in hemodialysis (HD) patients, whereas CV risk increases with BMI in the general population. In the general population, obesity is associated with inflammation, decreased high-density lipoprotein (HDL) cholesterol, increased low-density lipoprotein (LDL) cholesterol, and triglycerides (TGs), all risk factors for CV disease. Low-density lipoprotein cholesterol does not predict CV risk in HD, whereas increased C-reactive protein and interleukin-6 (IL-6), low HDL and apolipoprotein (apo) AI, and increased fasting TGs do predict risk. Renal failure is associated with dyslipidemia and inflammation in normal-weight patients. We hypothesized that the effects of obesity may be obscured by renal failure in HD. METHODS We explored the relationship between adipose tissue pools and distribution, i.e., subcutaneous adipose tissue (SAT) and visceral adipose tissue (VAT) (measured by magnetic resonance imaging) and measures of inflammation (C-reactive protein, IL-6, ceruloplasmin, and alpha1 acid glycoprotein), HDL and LDL cholesterol, total TGs, apo AI, apo B, apo CII (an activator of lipoprotein lipase), apo CIII (an inhibitor of lipoprotein lipase), and the adipokines, leptin and adiponectin, in 48 patients with prevalent HD. RESULTS AND CONCLUSIONS Total TG concentrations were positively correlated with VAT controlled for age, sex, and weight. Both apo CII and apo CIII were correlated only with VAT. Adiponectin was inversely correlated with VAT, and leptin was positively associated with SAT. C-reactive protein and alpha1 acid glycoprotein were weakly associated with SAT, whereas ceruloplasmin was strongly associated with VAT according to multiple regression analysis. In contrast, apo B, LDL, apo AI, HDL, and IL-6 were not correlated with any measure of body composition, potentially mitigating the effects of obesity in HD.

Fluid dynamics during hemodialysis in relationship to sodium gradient between dialysate and plasma.

Fluid shifts during hemodialysis involve changes in both extracellular and intracellular volumes. This study aimed to determine the effect of intradialytic sodium gradients (GNa+), that is, the difference between dialysate and serum sodium concentration, on dynamics of extracellular and intracellular volumes in a group of maintenance hemodialysis patients. Extracellular volume change (deltaECV) between predialysis and postdialysis periods was determined by whole-body bioimpedance spectroscopy; intracellular volume change (deltaICV) was indirectly derived as the difference between deltaECV and the change in body weight, corrected for intradialytically given fluids. A total of 200 bioimpedance measurements were performed in 32 dialysis patients. Extracellular and intracellular volume changes were −2.6 ± 0.9 L (range: −4.7 to −0.5 L) and −0.2 ± 0.7 L (range: −2.5 to +1.5 L), respectively. There was a significant correlation between deltaICV and GNa+; deltaICV = −0.12 * GNa+ + 0.26 (p < 0.001). In contrast, GNa+ was not correlated with deltaECV. We conclude that the sodium gradient between dialysate and plasma has a significant effect on the ICV during dialysis. Hemodialysis with GNa+ = 0 mmol/L should be sought to prevent ICV shrinking or swelling and to prevent excessive thirst, consequently high interdialytic weight gains, and ultrafiltration rates.

Basic Science and Dialysis: Nitric Oxide and Hemodialysis

Nitric oxide (NO), previously thought of as a noxious gas, is now recognized as an important mediator of vascular responsiveness. Soon after its discovery, it was realized that the actions of NO are similar to the previously described endothelium‐derived relaxing factor (EDRF). It is synthesized in the vascular endothelium utilizing the enzyme nitric oxide synthase (NOS) and diffuses in the adjacent vascular media, where it has a vasodilatory action. Opposing actions of NO and vasoconstrictor agents (such as endothelin‐1, angiotensin ΙΙ, and others) maintain the vascular tone of the renal arteries. The same balance at the level of the macula densa maintains glomerular filtration rate (GFR) during varying levels of salt excretion. Lack of NO can result in disruption of this fine balance, with resultant vasoconstriction and disease progression, hypertension, and accelerated atherosclerosis. In addition, hypertension may result from positive salt balance that occurs when macula densa NOS is inhibited. While most investigators report low levels of NO in uremic subjects, the levels in hemodialysis (HD) patients have not been characterized adequately. This is primarily because HD patients are exposed to both stimulatory and inhibitory factors for NO synthesis. Retention of inhibitors of NOS tends to decrease NO levels, whereas production of NO will be increased by cytokines generated during blood‐dialyzer interaction. There is less disagreement, however, over the finding of elevated levels in those with dialyzer reactions and dialysis‐induced hypotension. Recent developments in the isolation of inducible and constitutive forms of NOS makes understanding of its pathophysiologic effects more complete. Newer treatment directed at inhibiting only the inducible forms of NOS (sparing the constitutive forms) may soon be found useful for the treatment and prevention of hypotension and dialyzer reactions in HD patients.

Fellows' Forum in Dialysis: Interdialytic Weight Gain: Implications in Hemodialysis Patients

Interdialytic weight gain (IDWG) is an easily measurable parameter in the dialysis unit, routinely assessed at the beginning of the dialysis session. It is used along with clinical symptoms and signs and predialysis blood pressure readings to make decisions regarding the amount of fluid removal during a dialysis session. IDWG is also used as a basis for fluid and salt intake recommendations. However, advising fluid and salt restriction based solely on IDWG may not be appropriate because of its status as a nutritional indicator, as well. Very few studies have been designed to determine the direct effect of IDWG on morbidity and mortality. Any such effect is confounded by residual renal function and various comorbidities, the effects of which might be difficult to separate from those of IDWG. Most attempts to control IDWG have concentrated on requiring patients to reduce fluid and dietary salt intake. Although there does not seem to be a consensus at this point, it is likely that within the lower values of IDWG (less than 5.7% of dry weight), tighter control of fluid and salt intake might not be warranted since these values may reflect higher protein and calorie intake, indicating better nutritional status.

Estimation of Adipose Pools in Hemodialysis Patients From Anthropometric Measures

OBJECTIVE Adiposity, measured as increased body mass index (BMI), is associated with reduced all-cause and cardiovascular (CV) mortality in hemodialysis (HD) patients, whereas CV risk increases with BMI in the general population. A major limitation of BMI as a measure of adiposity is its failure to distinguish muscle and fat compartments. In addition, the biology of different adipose compartments is not the same. The visceral adipose tissue (VAT) mass is especially biologically active, secreting a variety of cytokines and adipokines. Alternate methods of estimating body composition were found to have a greater association with CV risk factors than BMI in several populations. We measured total adipose tissue, subcutaneous adipose tissue, and VAT in 48 prevalent HD patients, using magnetic resonance imaging. METHODS AND RESULTS Based on these measurements, we developed parsimonious multiple-regression models to estimate these adipose compartments using age, sex, BMI, weight, maximum abdominal circumference (MAC), and race. The parsimonious models for VAT included only age, race, and MAC (adjusted r(2) = 0.776, P < .0001), whereas the subcutaneous adipose tissue model included sex, weight, age, and BMI (adjusted r(2) = 0.91, P < .0001) rather than MAC. The total adipose tissue model included BMI, sex, weight, and age (adjusted r(2) = 0.905, P < .0001). CONCLUSION We propose that measurements of MAC, in addition to height and weight, be included in studies relating body composition to outcomes, because this measure provides a better estimate of the metabolically active VAT pool.

Editorials: Quest for V: Body Composition Could Determine Dialysis Dose

Since the demonstration that dialysis patients with lower body weight have a higher mortality than larger patients, there has been much interest in determining possible mechanisms and any possible relationships to the dialysis dose. Arguments have been made against using Kt/Vurea as the basis for dialysis prescription. Efforts have been made to determine a parameter of dialysis delivery independent of body size. An emerging area of intense research interest has explored the body composition determinants of resting metabolic rate. Based on the knowledge of in vitro organ tissue energy production, newer high‐resolution imaging methods have been applied as a means of establishing the sources of resting energy production in chronic kidney disease (CKD) patients. However, the linkages between resting energy expenditure (REE), body composition, and survival have not received much attention despite various studies exploring the effect of renal dysfunction and of the hemodialysis process on REE. We explore possible mechanisms leading to a higher mortality in smaller (lower body mass index) patients. The hypothesis of Morton and Singer is discussed. We have hypothesized that delivery of dialysis based on visceral organ volume (Vorgan), which could be the appropriate representation of uremic toxin generation, would be more logical than the current practice. This retains the concept of Kt/V but suggests that instead of the total V, a component related to major metabolic activity might represent the volume of interest. As per our hypothesis, smaller dialysis patients would need relatively a higher dialysis dose delivery, as expressed by current Kt/V, in order to achieve the same level of clearance of uremic toxins as in larger patients.

Editorials: Quest for V: Body Composition Could Determine Dialysis Dose: BODY COMPOSITION AND DIALYSIS DOSE

Since the demonstration that dialysis patients with lower body weight have a higher mortality than larger patients, there has been much interest in determining possible mechanisms and any possible relationships to the dialysis dose. Arguments have been made against using Kt/Vurea as the basis for dialysis prescription. Efforts have been made to determine a parameter of dialysis delivery independent of body size. An emerging area of intense research interest has explored the body composition determinants of resting metabolic rate. Based on the knowledge of in vitro organ tissue energy production, newer high‐resolution imaging methods have been applied as a means of establishing the sources of resting energy production in chronic kidney disease (CKD) patients. However, the linkages between resting energy expenditure (REE), body composition, and survival have not received much attention despite various studies exploring the effect of renal dysfunction and of the hemodialysis process on REE. We explore possible mechanisms leading to a higher mortality in smaller (lower body mass index) patients. The hypothesis of Morton and Singer is discussed. We have hypothesized that delivery of dialysis based on visceral organ volume (Vorgan), which could be the appropriate representation of uremic toxin generation, would be more logical than the current practice. This retains the concept of Kt/V but suggests that instead of the total V, a component related to major metabolic activity might represent the volume of interest. As per our hypothesis, smaller dialysis patients would need relatively a higher dialysis dose delivery, as expressed by current Kt/V, in order to achieve the same level of clearance of uremic toxins as in larger patients.

Fellows' Forum in Dialysis: Interdialytic Weight Gain: Implications in Hemodialysis Patients: INTERDIALYTIC WEIGHT GAIN

Interdialytic weight gain (IDWG) is an easily measurable parameter in the dialysis unit, routinely assessed at the beginning of the dialysis session. It is used along with clinical symptoms and signs and predialysis blood pressure readings to make decisions regarding the amount of fluid removal during a dialysis session. IDWG is also used as a basis for fluid and salt intake recommendations. However, advising fluid and salt restriction based solely on IDWG may not be appropriate because of its status as a nutritional indicator, as well. Very few studies have been designed to determine the direct effect of IDWG on morbidity and mortality. Any such effect is confounded by residual renal function and various comorbidities, the effects of which might be difficult to separate from those of IDWG. Most attempts to control IDWG have concentrated on requiring patients to reduce fluid and dietary salt intake. Although there does not seem to be a consensus at this point, it is likely that within the lower values of IDWG (less than 5.7% of dry weight), tighter control of fluid and salt intake might not be warranted since these values may reflect higher protein and calorie intake, indicating better nutritional status.

Basic Science and Dialysis: Nitric Oxide and Hemodialysis: NITRIC OXIDE AND HEMODIALYSIS

Nitric oxide (NO), previously thought of as a noxious gas, is now recognized as an important mediator of vascular responsiveness. Soon after its discovery, it was realized that the actions of NO are similar to the previously described endothelium‐derived relaxing factor (EDRF). It is synthesized in the vascular endothelium utilizing the enzyme nitric oxide synthase (NOS) and diffuses in the adjacent vascular media, where it has a vasodilatory action. Opposing actions of NO and vasoconstrictor agents (such as endothelin‐1, angiotensin ΙΙ, and others) maintain the vascular tone of the renal arteries. The same balance at the level of the macula densa maintains glomerular filtration rate (GFR) during varying levels of salt excretion. Lack of NO can result in disruption of this fine balance, with resultant vasoconstriction and disease progression, hypertension, and accelerated atherosclerosis. In addition, hypertension may result from positive salt balance that occurs when macula densa NOS is inhibited. While most investigators report low levels of NO in uremic subjects, the levels in hemodialysis (HD) patients have not been characterized adequately. This is primarily because HD patients are exposed to both stimulatory and inhibitory factors for NO synthesis. Retention of inhibitors of NOS tends to decrease NO levels, whereas production of NO will be increased by cytokines generated during blood‐dialyzer interaction. There is less disagreement, however, over the finding of elevated levels in those with dialyzer reactions and dialysis‐induced hypotension. Recent developments in the isolation of inducible and constitutive forms of NOS makes understanding of its pathophysiologic effects more complete. Newer treatment directed at inhibiting only the inducible forms of NOS (sparing the constitutive forms) may soon be found useful for the treatment and prevention of hypotension and dialyzer reactions in HD patients.