Effects of diet and exercise on adipocytokine levels in patients with moderate to severe chronic kidney disease.

BACKGROUND AND AIMS: Obesity is a pro-inflammatory risk factor for progression of CKD and cardiovascular disease. We hypothesized that implementation of caloric restriction and endurance exercise would improve adipocytokine profiles in patients with moderate to severe CKD. METHODS AND RESULTS: We enrolled patients with moderate to severe CKD through a multi-center pilot randomized trial of diet and exercise in a 4-arm design (dietary restriction of 10%-15% reduction in caloric intake, exercise three times/week, combined diet and exercise, and control) (NCT01150851). Adipocytokines (adiponectin and leptin) were measured at the beginning and end of the study period as secondary outcomes. Treatment effect was analyzed in a multivariable model adjusted for baseline outcome values, age, gender, site and diabetes. A total of 122 participants were consented, 111 were randomized (42% female, 25% diabetic, and 91% hypertensive), 104 started intervention and 92 completed the study (Figure 1). Plasma adiponectin levels increased significantly in response to diet by 23% (95% CI: 0.2%, 49.8%, p = 0.048) among participants randomized to the caloric restriction and usual activity arm but not to exercise, whereas circulating leptin did not change by either treatment. CONCLUSION: Our data suggest that dietary caloric restriction increases plasma adiponectin levels in stage 3-4 CKD patients, with limited effect on leptin levels. These findings suggest the potential for improving the metabolic milieu of CKD with moderate calorie restriction.

Angiotensin receptor blocker vs ACE inhibitor effects on HDL functionality in patients on maintenance hemodialysis.

BACKGROUND AND AIMS: Angiotensin receptor blockers (ARB) and angiotensin converting enzyme inhibitors (ACEI) reduce cardiovascular events in the general population. Maintenance hemodialysis (MHD) patients are at high cardiovascular risk but few studies have directly addressed the comparative efficacy of these drugs. MHD disrupts the normally atheroprotective actions of high density lipoprotein (HDL), therefore, we compared ACEI or ARB treatment on HDL functions in MHD. METHODS AND RESULTS: HDL was isolated at the starting point (pre) and 3-6 months later (post) in 30 MHD randomly assigned to placebo, ramipril or valsartan. Outcomes included cholesterol efflux, inflammatory cytokine response, effects on Toll-like receptors (TLR), superoxide production, methylarginine and serum amyloid A (SAA) levels. HDL from ARB- or ACEI-treated subjects was more effective in maintaining efflux than HDL of placebo. HDL from ARB- or ACEI-treated subjects but not placebo lessened cellular superoxide production. In contrast, neither ARB nor ACEI improved HDL anti-inflammatory effect. Indeed, HDL of ACEI-treated subjects potentiated the cytokine responses in association with activation of TLR but did not alter the HDL content of methylarginines or SAA. CONCLUSION: Both ACEI and ARB stabilized HDL cholesterol acceptor function and sustained cellular anti-oxidative effects but not anti-inflammatory effects, and ACEI-treatment instead amplified the HDL inflammatory response. The findings reveal possible utility of antagonizing angiotensin actions in MDH and suggest a possible mechanism for superiority of ARB vs ACEI in the setting of advanced kidney disease.

Higher protein intake is associated with increased risk for incident end-stage renal disease among blacks with diabetes in the Southern Community Cohort Study.

BACKGROUND AND AIMS: Diabetes, a risk factor for end-stage renal disease (ESRD), is associated with impaired protein metabolism. We investigated whether protein intake is associated with ESRD and whether the risk is higher among blacks with diabetes. METHODS AND RESULTS: We conducted a nested case-control study of ESRD within the Southern Community Cohort Study, a prospective study of low-income blacks and whites in the southeastern US (2002-2009). Through 2012, 1057 incident ESRD cases were identified by linkage with the United States Renal Data System and matched to 3198 controls by age, sex, and race. Dietary intakes were assessed from a validated food frequency questionnaire at baseline. Odds ratios (ORs) and 95% confidence intervals (CIs) were computed from logistic regression models that included matching variables, BMI, education, income, hypertension, total energy intake, and percent energy from saturated and polyunsaturated fatty acids. Mean (±SD) daily energy intake from protein was higher among ESRD cases than controls (15.7 ± 3.3 vs. 15.1 ± 3.1%, P < 0.0001). For a 1% increase in percent energy intake from protein, the adjusted ORs (95% CIs) for ESRD were 1.06 (1.02-1.10) for blacks with diabetes, 1.02 (0.98-1.06) for blacks without diabetes, 0.99 (0.90-1.09) for whites with diabetes and 0.94 (0.84-1.06) for whites without diabetes. Protein intake in g/kg/day was also associated with ESRD (4th vs. 1st quartile OR = 1.76; 95% CI: 1.17-2.65). CONCLUSION: Our results raise the possibility that among blacks with diabetes, increased dietary protein is associated with increased incidence of ESRD. Studies on how protein intake and metabolism affect ESRD are needed.

A proposed nomenclature and diagnostic criteria for protein-energy wasting in acute and chronic kidney disease.

The recent research findings concerning syndromes of muscle wasting, malnutrition, and inflammation in individuals with chronic kidney disease (CKD) or acute kidney injury (AKI) have led to a need for new terminology. To address this need, the International Society of Renal Nutrition and Metabolism (ISRNM) convened an expert panel to review and develop standard terminologies and definitions related to wasting, cachexia, malnutrition, and inflammation in CKD and AKI. The ISRNM expert panel recommends the term 'protein-energy wasting' for loss of body protein mass and fuel reserves. 'Kidney disease wasting' refers to the occurrence of protein-energy wasting in CKD or AKI regardless of the cause. Cachexia is a severe form of protein-energy wasting that occurs infrequently in kidney disease. Protein-energy wasting is diagnosed if three characteristics are present (low serum levels of albumin, transthyretin, or cholesterol), reduced body mass (low or reduced body or fat mass or weight loss with reduced intake of protein and energy), and reduced muscle mass (muscle wasting or sarcopenia, reduced mid-arm muscle circumference). The kidney disease wasting is divided into two main categories of CKD- and AKI-associated protein-energy wasting. Measures of chronic inflammation or other developing tests can be useful clues for the existence of protein-energy wasting but do not define protein-energy wasting. Clinical staging and potential treatment strategies for protein-energy wasting are to be developed in the future.

Acute kidney injury: changing lexicography, definitions, and epidemiology.

In recent years, there have been numerous advances in understanding the molecular determinants of functional kidney injury after ischemic and/or toxic exposure. However, translation of successful novel therapies designed to attenuate kidney functional injury from animal models to the clinical sphere has had modest results. This lack of translatability is at least in part due to lack of sufficient standardization in definitions and classification of cases of acute kidney injury (AKI), an incomplete understanding of the natural history of human AKI, and a limited understanding of how kidney injury interacts with other organ system failure in the context of systemic metabolic abnormalities. A concerted effort is now being made by nephrologists and intensivists to arrive at standardized terminology and classification of AKI. There have also been dramatic advances in our understanding of the epidemiology and natural history of AKI, particularly in the hospital and intensive care unit setting. Promising strategies are now being developed which may ultimately lead to improved outcomes for patients at risk for or who have developed AKI, which should be readily testable in the coming decade.

Exercise improves albumin fractional synthetic rate in chronic hemodialysis patients.

OBJECTIVE: To determine whether exercise augments the improvements in fractional synthetic rate (FSR) of albumin observed with nutrition alone. DESIGN: Randomized crossover study. Each patient randomly participated in two protein metabolism kinetic studies using primed-constant infusion of (13C) leucine 2 h before, during and 2 h after hemodialysis. Plasma enrichments of (13C) leucine and (13C) ketoisocaproate were examined to determine the FSR of albumin. SETTING: General Clinical Research Center at Vanderbilt University Medical Center. SUBJECTS: Five chronic hemodialysis (CHD) patients. INTERVENTIONS: Intra-dialytic parenteral nutrition (IDPN) with or without exercise. RESULTS: Exercise performance during hemodialysis significantly improves the FSR of albumin beyond what is observed with IDPN alone (26.2+/-3.1% per day versus 17.7+/-1.9% per day, P<0.05). CONCLUSION: Exercise improves albumin fractional synthetic rate beyond what is observed with IDPN alone in the acute setting in CHD patients.

Insulin resistance is associated with skeletal muscle protein breakdown in non-diabetic chronic hemodialysis patients.

Deranged protein metabolism is known to complicate uremia. Insulin resistance is evident in chronic hemodialysis (CHD) patients. We hypothesized that the degree of insulin resistance would predict protein catabolism in non-diabetic CHD patients. We examined the relationship between Homeostasis Model Assessment (HOMA) and fasting whole-body and skeletal muscle protein turnover in 18 non-diabetic CHD patients using primed-constant infusions of L-(1-(13)C) leucine and L-(ring-(2)H(5)) phenylalanine. Mean+/-s.d. fasting glucose and body mass index were 80.6+/-9.8 mg/dl and 25.4+/-4.4 kg/m(2), respectively. Median (interquartile range) HOMA was 1.6 (1.4, 3.9). Mean+/-s.e.m. skeletal muscle protein synthesis, breakdown, and net balance were 89.57+/-11.67, 97.02+/-13.3, and -7.44+/-7.14 microg/100 ml/min, respectively. Using linear regression, a positive correlation was observed between HOMA and skeletal muscle protein synthesis (R(2)=0.28; P=0.024), and breakdown (R(2)=0.49; P=0.001). An inverse association between net skeletal muscle protein balance and HOMA was also noted (R(2)=0.20; P=0.066). After adjustment for C-reactive protein, only the relationship between HOMA and skeletal muscle protein breakdown persisted (R(2)=0.49; P=0.006). There were no significant associations between components of whole-body protein turnover and HOMA. This study demonstrates that insulin resistance is evident in non-diabetic dialysis patients, is associated with skeletal muscle protein breakdown, and represents a novel target for intervention in uremic wasting.

Mortality after acute renal failure: models for prognostic stratification and risk adjustment.

To adjust adequately for comorbidity and severity of illness in quality improvement efforts and prospective clinical trials, predictors of death after acute renal failure (ARF) must be accurately identified. Most epidemiological studies of ARF in the critically ill have been based at single centers, or have examined exposures at single time points using discrete outcomes (e.g., in-hospital mortality). We analyzed data from the Program to Improve Care in Acute Renal Disease (PICARD), a multi-center observational study of ARF. We determined correlates of mortality in 618 patients with ARF in intensive care units using three distinct analytic approaches. The predictive power of models using information obtained on the day of ARF diagnosis was extremely low. At the time of consultation, advanced age, oliguria, hepatic failure, respiratory failure, sepsis, and thrombocytopenia were associated with mortality. Upon initiation of dialysis for ARF, advanced age, hepatic failure, respiratory failure, sepsis, and thrombocytopenia were associated with mortality; higher blood urea nitrogen and lower serum creatinine were also associated with mortality in logistic regression models. Models incorporating time-varying covariates enhanced predictive power by reducing misclassification and incorporating day-to-day changes in extra-renal organ system failure and the provision of dialysis during the course of ARF. Using data from the PICARD multi-center cohort study of ARF in critically ill patients, we developed several predictive models for prognostic stratification and risk-adjustment. By incorporating exposures over time, the discriminatory power of predictive models in ARF can be significantly improved.

Adiponectin level is reduced and inversely correlated with the degree of proteinuria in type 2 diabetic patients.

AIMS: Adiponectin seems to be an important modulator for metabolic and vascular diseases. We aimed to measure plasma adiponectin levels in type 2 diabetic patients and investigate any association with the severity of proteinuria. METHODS: 80 patients (mean age, 46.9 +/- 5.1 years; body mass index (BMI), 25.8 +/- 1.98 kg/m2) and 47 healthy volunteers (mean age, 46.1 +/- 5.5 years; BMI 26.74 +/- 2.23 kg/m2) were included. Plasma adiponectin concentration, insulin levels, homeostasis model assessment (HOMA) indices, calculated glomerular filtration rate (GFR), high sensitive C reactive protein (hsCRP) and biochemistry panel were determined in all subjects. The association between adiponectin concentration and proteinuria was evaluated. Additionally, the relationship between adiponectin and hsCRP and calculated GFR were also investigated. RESULTS: Adiponectin levels in patients were significantly lower than those of controls (n = 80; 8.76 +/- 4.50 microg/ml for patients, n = 47; 24.27 +/- 5.59 microg/ml for controls, p < 0.001). Plasma adiponectin levels in patients with proteinuria were significantly lower than those without proteinuria (n = 43; 6.81 +/- 2.82 microg/ml for proteinuria, n = 37; 11.98 +/- 3.32 microg/ml for no proteinuria, p < 0.001). There was a significant negative correlation between plasma adiponectin concentrations and the degree of proteinuria (r = -0.433, p < 0.001). There were also significant negative correlations between adiponectin concentrations and insulin levels as well as HOMA index in the patient group (r = -0.322, p = 0.004; r = -0.301, p = 0.032). Additionally there was a significant negative correlation between adiponectin and hsCRP levels in the patient group (r = -0.872, p < 0.001). CONCLUSION: The results show that adiponectin is lower in patients with type 2 diabetes and the levels are negatively correlated with the severity of proteinuria.

Plasma F2-isoprostane levels are elevated in chronic hemodialysis patients.

AIMS: Cardiovascular mortality has been reported to be 10- to 20-fold higher in chronic dialysis patients than in the age-matched general population. It has been suggested that increased oxidant stress and resulting vascular wall injury due to uremia and the hemodialysis procedure may be one of the mechanisms predisposing to these cardiovascular complications. Further, hemodialysis membrane bioincompatibility can contribute to increased oxidative stress and prevalence of inflammation. MATERIALS: We studied 18 chronic hemodialysis (CHD) patients (age 62.8 +/- 14.7 years, 39% male, 61% African-American, 44% insulin-dependent diabetic, 61% smokers, 61% with documented coronary artery disease) during hemodialysis with 2 membranes with different flux and complement activating properties. METHODS: We have measured free and phospholipid-bound F2-isoprostane (F2-IsoP) levels, a sensitive marker of oxidative stress, in CHD patients and compared them to levels in healthy subjects. We have also examined the acute effects of the hemodialysis procedure using both biocompatible and bioincompatible membranes on F2-IsoP levels. RESULTS: The results indicated that, compared to controls, both free (96.2 +/- 48.8 pg/ml versus 37.6 +/- 17.2 pg/ml) and bound F2-IsoP (220.4 +/- 154.8 pg/ml versus 146.8 +/- 58.4 pg/ml) levels were significantly higher (p < 0.05 for both). There was a statistically significant decrease in free F2-IsoP concentrations at 15 and 30 minutes of HD, which rebounded to baseline levels at the completion of the procedure. There were no significant differences in F2-IsoP concentrations between the 2 study dialyzers at any time point. Age, smoking status, diabetes mellitus and presence of cardiovascular disease were also not correlated with F2-IsoP levels in this patient population. There was a significant association between predialysis F2-IsoP and C-reactive protein concentrations. CONCLUSION: Using a sensitive and specific assay for the measurement of F2-IsoP, we demonstrated that CHD patients are under increased oxidative stress. During a single hemodialysis treatment, the hemodialysis membrane appears to have no discernable effect on oxidative stress status. Measurement of F2-isoprostanes may be a useful biomarker of oxidative stress status as well as in developing new therapeutic strategies to ameliorate inflammatory and oxidative injury in this patient population.

Recombinant human growth hormone in patients with acute renal failure.

OBJECTIVE: The objective of this study is to determine the impact of recombinant human growth hormone (rhGH) on metabolic and nutritional parameters in malnourished patients with acute renal failure. DESIGN: The design is an open-labeled pilot trial examining the effects of rhGH administration in a small group of highly catabolic, malnourished patients with acute renal failure. Each patient served as his or her own control. SETTING: An intensive care unit in a tertiary care medical institution. PATIENTS: Five patients with established acute renal failure in a critical care unit. Entry criteria included clinical evidence of malnutrition: a serum albumin level of <3.2 g/dL, a prealbumin level of < or = 20 mg/dL, and an insulin-like growth factor IGF 1 level <200 ng/mL. The study consisted of 3 periods: phase I, 3 day baseline; phase II, 6 day treatment; and phase III, 3 day washout. During the entire study, blood and urine samples were obtained daily to calculate normalized protein catabolic rate, total nitrogen appearance rate (TNA), and nitrogen balance. Additional data were collected to measure metabolic and inflammatory parameters. INTERVENTION: The intervention consisted of administering 100 microg/kg/d of rhGH for 6 days. RESULTS: There were significant changes in TNA, normalized protein catabolic rate, and nitrogen balance during the 3 study phases. TNA decreased from 43.3 +/- 24.4 g/d in phase I, to 25.2 +/- 16.5 g/d during phase II (P <.001). There was a further decrease in TNA to 16.2 +/- 8.3 g/d during phase III (P <.001 v phase I). Nitrogen balance improved from - 31.8 +/- 21.4 g/d during phase I, to - 12.9 +/- 10.3 g/d during phase II (P <.001), and further improved to - 4.1 +/- 4.0 g/d in phase III (P <.001 v phase I). Significant changes were also noted in levels of blood urea nitrogen, phosphorous, serum growth hormone, IGF-1, and serum leptin levels after growth hormone administration. A statistically significant increase in serum albumin was noted in phase III (3.1 g/dL) versus phase I (2.7 +/- 0.7 g/dL). CONCLUSIONS: Administration of rhGH to critically ill patients with acute renal failure resulted in improvements in negative nitrogen balance and a significant decrease in total nitrogen appearance rate. These changes corresponded to increases in serum growth hormone, IGF-1, IGF-1 binding protein 3, and leptin levels after growth hormone administration.

Vascular access blood flow monitoring reduces access morbidity and costs.

BACKGROUND: Vascular access morbidity results in suboptimal patient outcomes and costs more than $8000 per patient-year at risk, representing approximately 15% of total Medicare expenditures for ESRD patients annually. In recent years, the rate of access thrombosis has improved following the advent of vascular access blood flow monitoring (VABFM) programs to identify and treat stenosis prior to thrombosis. To define further both the clinical and financial impact of such programs, we used the ultrasound dilution method to study the effects of VABFM on thrombosis-related morbid events and associated costs, compared with both dynamic venous pressure monitoring (DVPM) and no monitoring (NM) in arteriovenous fistulas (AVF) and grafts. METHODS: A total of 132 chronic hemodialysis patients were followed prospectively for three consecutive study phases (I, 11 months of NM; II, 12 months of DVPM; III, 10 months of VABFM). All vascular access-related information (thrombosis rate, hospitalization, angiogram, angioplasty, access surgery, thrombectomy, catheter placement, missed treatments) was collected during the three study periods. RESULTS: During the three study phases, graft thrombosis rate was reduced from 0.71 (phase I), to 0.67 (phase II), to 0.16 (phase III) events per patient-year at risk (P < 0.001 phase III vs. phases I and II). Similarly, hospital days, missed treatments, and catheter use related to thrombotic events were significantly reduced during phase III compared to phases I and II. Hospital days related to vascular access morbidity and adjusted for patient-year at risk were 1.8, 1.6, and 0.4 and missed dialysis treatments were 0.98, 0.86, and 0.26 treatments per patient-year at risk for phases I, II, and III, respectively (P < 0.001 for phase III vs. phases I and II). Catheter use was also significantly reduced during phases II and III, from 0.29 (phase I) to 0.17 and further to 0.07 catheters per patient-year at risk, respectively (P < 0.05 for phase III vs. phase I). Percutaneous angioplasty procedures increased during phases II and III from 0.09 to 0.32 to 0.54 procedures per patient-year at risk for phases I, II, and III, respectively (P < 0.01 for phase III vs. phase I). When the total cost of treatment for thrombosis-related events for grafts was estimated, it was found that during phase III, the adjusted yearly billed amount was reduced by 49% versus phase I and 54% versus phase II to $158,550. Similar trends in reduced thrombosis-related morbid events and cost were observed for AVFs. CONCLUSIONS: VABFM for early detection of vascular access malfunction coupled with preventive intervention reduces thrombosis rates in both polytetrafluoroethylene (PTFE) grafts and native AVFs. While there was a significant increase in the number of angioplasties done during the flow monitoring phase, the comprehensive cost is markedly reduced due to the decreased number of hospitalizations, catheters placed, missed treatments, and surgical interventions. Vascular access blood flow monitoring along with preventive interventions should be the standard of care in chronic hemodialysis patients.

Serum transferrin and serum prealbumin are early predictors of serum albumin in chronic hemodialysis patients.

Protein-calorie malnutrition is a known risk factor for increased morbidity and mortality in maintenance hemodialysis patients (MHD). Serum albumin is the most commonly measured nutritional index in MHD patients because of its easy routine availability and association with outcomes of interest. However, its long half-life of approximately 20 days makes it a late index of nutritional status, and its exclusive use may delay implementation of appropriate nutritional interventions. Serum prealbumin and transferrin have been proposed as earlier nutritional markers. However, the temporal associations among these indices and serum albumin have not been well documented. To assess the ability of serum prealbumin and serum transferrin to predict changes in serum albumin over time, we prospectively analyzed these parameters in 105 MHD patients every month for 6 consecutive months. The mixed model analysis showed that early changes in either serum transferrin or prealbumin predicted and were significantly associated with changes in serum albumin (P<.0001). Using a prototype equation, a change of 0.12 g/dL in serum albumin concentration can be predicted by a 10% change in the same direction of serum transferrin and prealbumin. We conclude that clinically significant changes in albumin can be reliably predicted by earlier changes in serum transferrin and prealbumin.

Quantitating urea removal in patients with acute renal failure: lost art or forgotten science?

A 67-year-old woman is admitted to the surgical service with a high fever, a painful and distended abdomen, jaundice, and almost complete anuria. A urinalysis revealed dark red-brown urine notable for albuminuria, erythrocytes, leukocytes, and casts. The patient was treated with antibiotics, but continued to have oligoanuria. On the eighth day of hospitalization, the following laboratory tests were obtained: serum potassium, 13.7 mEq/L; BUN, 396 mg/dl. At this time the patient was noted to be encephalopathic with deteriorating clinical condition. Renal replacement therapy was initiated. The characteristics of the initial dialysis treatment are described in Table 1. After the initial dialysis treatment, the patient went on to become nonoliguric, followed by gradual recovery of urea clearance. She survived her acute illness, left the hospital, and at 7 months posthospitalization was doing quite well.

Transforming growth factor-beta is involved in the pathogenesis of dialysis-related amyloidosis.

BACKGROUND: Advanced glycation end product-modified beta2-microglobulin (AGE-beta2m) is an important component of dialysis-related amyloidosis (DRA). Its presence induces monocyte chemotaxis and the release of the proinflammatory cytokines through macrophage activation. Transforming growth factor-beta (TGF-beta) is a multifunctional cytokine that also has chemotactic activity for monocytes at very low (0.1 to 10 pg/mL) concentrations and inhibits proinflammatory cytokine production of macrophages. In this study, we investigated the role of TGF-beta in the pathogenesis of DRA. METHODS: We performed an immunohistochemical study of DRA tissues (8 cases) to confirm the existence of TGF-betas and their receptors; we also performed a chemotaxis assay of human monocytes as well as enzyme-linked immunosorbent assay (ELISA) of TGF-beta1, tumor necrosis factor-alpha (TNF-alpha), interleukin-1beta (IL-1beta), and interleukin-1 receptor antagonist (IL-1Ra) in the supernatant of human monocyte-derived macrophage cell culture under varying conditions of incubation with TGF-beta1, AGE-beta2m, and TGF-beta1 antibody additions. RESULTS: There was positive staining for TGF-betas (types 1, 2, and 3) and their receptors (types I, II, and III) in infiltrated macrophages (CD68+), synovial lining cell, as well as vascular walls around amyloid deposition. AGE-beta2m also induced TGF-beta1 production by macrophages in a dose-dependent manner (410 +/- 80 pg/mL at 12.5 microg/mL, 621 +/- 62 pg/mL at 25 microg/mL, and 776 +/- 62 pg/mL at 50 microg/mL of AGE-beta2m). AGE-beta2m induced significant TNF-alpha and IL-1Ra production by macrophage. The addition of exogenous TGF-beta1 (0.1 to 10 ng/mL) decreased AGE-beta2m-induced TNF-alpha production and increased IL-1Ra production in a dose-dependent fashion. IL-1beta production was not effected by any experimental conditions. In chemotaxis assay, anti-TGF-beta1 antibody (0.1 to 10 microg/mL) attenuated AGE-beta2m-induced monocyte chemotaxis. CONCLUSIONS: These results provide the first evidence to our knowledge for the presence of TGF-beta in DRA tissue, as well as the stimulatory action of AGE-beta2m on tissue macrophages. In turn, TGF-beta suppresses the proinflammatory activation of macrophages, suggesting a dual role for TGF-beta in the inflammatory process of DRA. These observations may provide a pathophysiologic link between TGF-beta and DRA.

Intradialytic serial vascular access flow measurements.

Hemodialysis vascular access failure represents a major source of morbidity and mortality in chronic hemodialysis (CHD) patients. Serial vascular access blood flow (VABF) measurements are being used as a screening method at an increasing rate. There are limited data on the changes in VABF throughout the hemodialysis session, which may potentially affect the validity of VABF measurement. This study is performed to evaluate the trend in VABF during a given hemodialysis session by serial VABF measurements, along with potential factors that may affect VABF. Thirty-two CHD patients had serial VABF measurements performed during a hemodialysis session. Each patient had three serial VABF measurements during a hemodiaysis treatment (within 30, 90, and 150 minutes from the start of hemodialysis). Mean arterial blood pressure (MAP), ultrafiltration rate, and patient symptoms were recorded simultaneously. The mean VABF was 1,344 +/- 486 mL/min within 30 minutes of hemodialysis and decreased to 1,308 +/- 532 and 1,250 +/- 552 mL/min after 90 and 150 minutes, respectively. This trend was statistically significant (P = 0.03). There was a strong correlation between VABF measurements and MAP, which was more pronounced after 90 minutes of initiation of hemodialysis (r = 0.68; P < 0.001). Using multivariate analysis, it can be predicted that after 90 minutes of hemodialysis, each 10% decrease in MAP would result in an expected decrease of 8% in VABF. There was no effect of type of vascular access, baseline VABF, or amount of ultrafiltration on VABF changes. In conclusion, VABF measurements can be performed up to 2 to 2(1/2) hours from the start of hemodialysis in the majority of patients. The major determinant of VABF changes is MAP. In a subset of patients with a decrease MAP greater than 15%, it is advisable to perform VABF measurement either at the first 90 minutes of hemodialysis or postpone it to another treatment session, when MAP is more stable.

Association of morbidity with markers of nutrition and inflammation in chronic hemodialysis patients: a prospective study.

BACKGROUND: Numerous studies suggest a strong association between nutrition and clinical outcome in chronic hemodialysis (CHD) patients. Nevertheless, the pathophysiological link between malnutrition and morbidity remains to be clarified. In addition, recent evidence suggests that nutritional indices may reflect an inflammatory response, as well as protein-calorie malnutrition. In this study, we prospectively assessed the relative importance of markers of nutritional status and inflammatory response as determinants of hospitalization in CHD patients. METHODS: The study consisted of serial measurements of concentrations of serum albumin, creatinine, transferrin, prealbumin, C-reactive protein (CRP), and reactance values by bio-electrical impedance analysis (BIA) as an indirect measure of lean body mass every 3 months over a period of 15 months in 73 CHD patients. Outcome was determined by hospitalizations over the subsequent three months following each collection of data. RESULTS: Patients who required hospitalization in the three months following each of the measurement sets had significantly different values for all parameters than patients who were not hospitalized. Thus, serum albumin (3.93 +/- 0.39 vs. 3.74 +/- 0.39 g/dl), serum creatinine (11.0 +/- 3.7 vs. 9.1 +/- 3.5 mg/dl), serum transferrin (181 +/- 35 vs. 170 +/- 34 mg/dl), serum prealbumin (33.6 +/- 9.2 vs. 30.0 +/- 10.1 mg/dl), and reactance (50.4 +/- 15.6 vs. 43.0 +/- 13.0 ohms) were higher for patients not hospitalized, whereas CRP (0.78 +/- 0.89 vs. 2.25 +/- 2.72 mg/dl) was lower in patients who were not hospitalized. All differences were statistically significant (P < 0.05 for all parameters). When multivariate analysis was performed, serum CRP and reactance values were the only statistically significant predictors of hospitalization (P < 0.05 for both). When a serum CRP concentration of 0.12 mg/dl was considered as a reference range (relative risk 1.0), the relative risk for hospitalization was 7% higher (relative risk = 1.07) for a CRP concentration of 0.92 mg/dl and was 30% (relative risk = 1.30) higher for a CRP concentration of 3.4 mg/dl. When a reactance value of 70 ohms was considered as a reference range with a relative risk of 1.0, the relative risk of hospitalization increased to 1.09 for a reactance value of 43 ohms and further increased to 1.14 for a reactance value of 31 ohms. CONCLUSIONS: The results of this study strongly indicate that both nutritional status and inflammatory response are independent predictors of hospitalization in CHD patients. CRP and reactance values by BIA are reliable indicators of hospitalization. Visceral proteins such as serum albumin, prealbumin, and transferrin are influenced by inflammation when predicting hospitalization. When short-term clinical outcomes such as hospitalizations are considered, markers of both inflammation and nutrition should be evaluated.

Measurement of the delivery of dialysis in acute renal failure.

BACKGROUND: Recent studies in patients with acute renal failure (ARF) have shown a relationship between the delivered dose of dialysis and patient survival. However, there is currently no consensus on the appropriate method to measure the dose of dialysis in ARF patients. In this study, the dose of dialysis was measured by blood- and dialysate-based kinetic methods in a group of ARF patients who required intermittent hemodialysis. METHODS: Treatments were performed using a Fresenius 2008E volumetric hemodialysis machine with the ability to fractionally collect the spent dialysate. Single-, double-pool, and equilibrated Kt/V were determined from the pre-, immediate post-, and 30-minute post-blood urea nitrogen (BUN) measurements. The solute reduction index was determined from the collected dialysate, as well as the single- and double-pool Kt/V. RESULTS: Forty-six treatments in 28 consecutive patients were analyzed. The mean prescribed Kt/V (1.11 +/- 0.32) was significantly greater than the delivered dose estimated by single-pool (0.96 +/- 0.33), equilibrated (0.84 +/- 0.28), and double-pool (0.84 +/- 0.30) Kt/V (compared with prescribed, each P < 0.001). There was no statistical difference between the equilibrated and double-pool Kt/V (P = NS). The solute removal index, as determined from the dialysate, corresponded to a Kt/V of 0.56 +/- 0.27 and was significantly lower than the single-pool and double-pool Kt/V (each P < 0.001). CONCLUSION: Blood-based kinetics used to estimate the dose of dialysis in ARF patients on intermittent hemodialysis provide internally consistent results. However, when compared with dialysate-side kinetics, blood-based kinetics substantially overestimated the amount of solute (urea) removal.