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Biomedical subjects

Tom Greene

Publications and source records attributed to Tom Greene.

At least 37 records · Page 2Linked to original sources
PubMed2005

The effect of a lower target blood pressure on the progression of kidney disease: long-term follow-up of the modification of diet in renal disease study.

BACKGROUND: Hypertension is a risk factor for progression of chronic kidney disease. The optimal blood pressure to slow progression is unknown. OBJECTIVE: To evaluate the effects of a low target blood pressure on kidney failure and all-cause mortality. DESIGN: Long-term follow-up of the Modification of Diet in Renal Disease Study, a randomized, controlled trial conducted from 1989 to 1993. SETTING: 15 outpatient nephrology practices. PARTICIPANTS: 840 persons with predominantly nondiabetic kidney disease and a glomerular filtration rate of 13 to 55 mL/min per 1.73 m2. INTERVENTION: A low target blood pressure (mean arterial pressure < 92 mm Hg) or a usual target blood pressure (mean arterial pressure < 107 mm Hg). MEASUREMENTS: After the randomized trial was completed, kidney failure (defined as initiation of dialysis or kidney transplantation) and a composite outcome of kidney failure or all-cause mortality were ascertained through 31 December 2000. RESULTS: Kidney failure occurred in 554 participants (66%), and the composite outcome occurred in 624 participants (74%). After Cox proportional hazards modeling and intention-to-treat analysis, the adjusted hazard ratios were 0.68 (95% CI, 0.57 to 0.82; P < 0.001) for kidney failure and 0.77 (CI, 0.65 to 0.91; P = 0.0024) for the composite outcome in the low target blood pressure group compared with the usual target blood pressure group. Evidence was insufficient to conclude that the benefit of a low target blood pressure differed according to the cause of kidney disease, baseline glomerular filtration rate, or degree of proteinuria. LIMITATIONS: The exact mechanism underlying the benefit of a low target blood pressure is unknown. CONCLUSIONS: Assignment to a low target blood pressure slowed the progression of nondiabetic kidney disease in patients with a moderately to severely decreased glomerular filtration rate.

Adolescent↗
PubMed2005

Dialysis dose as a determinant of adequacy.

The intent-to-treat analyses of all patients in the HEMO trial suggested that increases in dose of dialysis as measured by urea Kt/V were of marginal or no benefit when dialysis was provided in a 3 times/wk schedule. The as-treated analysis in the HEMO trial pointed to markedly increased mortality when the delivered dose decreased even slightly below the targeted dose, evidence of a dose-targeting bias. The intent-to-treat HEMO study results suggested a potential interaction between sex and the dose-mortality relationship, and this also has been found in some cross-sectional studies, the cause of which remains unexplained. Whether dialysis dose should continue to be targeted based on urea distribution volume (V), or targeted to a body size measure that is a lower power of body weight (such as body surface area), remains an open question. The lack of benefit of increasing the dialysis dose in a 3 times/wk setting is more understandable if one looks at measures of equivalent continuous solute removal, such as the standard Kt/V. Differences in standard Kt/V in the 2 dose arms of the HEMO trial, for example, were only about 15%. Without going into removal of very large solutes (eg, beta-2-microglobulin), which is discussed elsewhere in this issue, or protein-bound uremic solutes, the only way to provide significantly more dialysis dose may be to move to more frequent dialysis schedules and/or to very long session lengths. Here, benefit may be related as much to better control of salt and water balance as to better removal of uremic toxins.

Female↗
PubMed2005

Factors associated with lipoprotein(a) in chronic kidney disease.

BACKGROUND: It is unclear whether lipoprotein(a) (Lp[a]) levels in patients with chronic kidney disease (CKD) are elevated as a result of reduced glomerular filtration rate (GFR) or other factors associated with CKD. The goal of this study is to describe the association of Lp(a) level with GFR in the context of apoprotein(a) (apo[a]) isoform size, race, and other kidney disease-related factors, such as proteinuria, serum albumin level, C-reactive protein (CRP) level, and serum lipid levels. METHODS: Lp(a) and apo(a) isoforms were measured in serum samples obtained at baseline from 804 participants in the Modification of Diet in Renal Disease study (GFR range, 13 to 55 mL/min/1.73 m2). The cross-sectional association between Lp(a) level and GFR, apo(a) isoform size, race, and other variables was analyzed in univariate and multivariate linear regression. RESULTS: Median Lp(a) level was greater in blacks than whites (97.5 versus 28.1 nmol/L; P < 0.001). Those with a low-molecular-weight apo(a) isoform size had greater Lp(a) levels than those with a high-molecular-weight apo(a) isoform size (57.5 versus 21.3 nmol/L; P < 0.001). Lp(a) level was not associated with GFR. Low-molecular-weight apo(a), black race, and greater levels of proteinuria, CRP, and triglycerides were independently associated with greater Lp(a) levels. CONCLUSION: In this population with CKD stages 3 to 4, GFR was not associated with Lp(a) level, whereas other factors related to CKD, such as proteinuria, CRP level, and triglyceride level, as well as genetic factors such as apo(a) isoform size and race, were associated with Lp(a) level.

Adolescent↗
PubMed2005

Performance of the Cockcroft-Gault and modification of diet in renal disease equations in estimating GFR in ill hospitalized patients.

BACKGROUND: Estimating glomerular filtration rate (GFR) in severely ill inpatients is clinically important for therapeutic interventions and prognosis, but notoriously difficult to do accurately. The Modification of Diet in Renal Disease (MDRD) equation and Cockcroft-Gault (CG) formula are widely used to estimate renal function in sick hospitalized patients; however, neither method has been validated in this setting. METHODS: Iodine 125-iothalamate clearances (iGFR) performed in 107 sick inpatients with renal dysfunction were compared with estimated GFRs (eGFRs) from the 6- and 4-variable MDRD (MDRD eGFR) and CG (CG eGFR) equations. RESULTS: Mean serum creatinine (SCr) level was 3.5 +/- 2.0 mg/dL (309 +/- 177 micromol/L), and mean iGFR was 17.1 +/- 17.9 mL/min/1.73 m2 (0.29 +/- 0.30 mL/s/1.73 m2). Six-variable MDRD eGFR was 22.5 +/- 17.4 mL/min/1.73 m2 (0.38 +/- 0.29 mL/s/1.73 m2), 4-variable MDRD eGFR was 23.9 +/- 16.3 mL/min/1.73 m2 (0.40 +/- 0.27 mL/s/1.73 m2), and CG eGFR was 26.0 +/- 17.1 mL/min/1.73 m2 (0.43 +/- 0.29 mL/s/1.73 m2). Blood urea nitrogen (BUN)/SCr ratios greater than 20 were seen in 58% of patients. Overall, the CG and MDRD equations overestimated iGFR, with poor agreement. Overestimation of at least 25% of measured iGFR was seen in 63%, 67%, and 70% of all inpatients when using the 6-variable MDRD, 4-variable MDRD, and CG equations, respectively. Accuracy of eGFR within 50% of measured iGFR was 55% for the 6-variable MDRD equation, 49% for the 4-variable MDRD equation, and 40% for the CG formula. The performance of both methods deteriorated further in patients with a BUN/SCr ratio greater than 20. CONCLUSION: Estimation equations are performed poorly compared with iGFR and are not reliable measures of actual level of function in sick hospitalized patients, especially those with a high BUN/SCr ratio. Although use of the 6-variable MDRD equation provides a better estimation of GFR, it still is unsuitable for clinical application in this population.

Adult↗
PubMed2005

Relationship of phosphorus and calcium-phosphorus product with mortality in CKD.

BACKGROUND: Abnormalities of mineral metabolism are prevalent in patients with kidney failure and are associated with increased risk for cardiovascular events. There are limited data investigating relationships of phosphorus and calcium-phosphorus product with outcomes in patients with chronic kidney disease (CKD) stages 3 to 4. METHODS: Serum phosphorus and calcium were measured at baseline in 840 participants from the randomized cohort of the Modification of Diet in Renal Disease Study. Survival status until December 31, 2000, was obtained from the National Death Index. Cox models were performed to assess the relationship of serum phosphorus level and calcium-phosphorus product with all-cause and cardiovascular disease (CVD) mortality. RESULTS: Mean serum phosphorus level was 3.8 +/- 0.7 mg/dL (1.23 +/- 0.23 mmol/L), calcium-phosphorus product was 34.7 +/- 6.3 mg2/dL2, and glomerular filtration rate (GFR) was 33 +/- 12 mL/min/1.73 m2 (0.55 +/- 0.20 mL/s/1.73 m2). All-cause and CVD mortality rates were 25% and 15%. Serum phosphorus level was not related to all-cause mortality in multivariable models (P = 0.46). In unadjusted analysis, serum phosphorus level was associated with (hazard ratio [HR] per 1 mg/dL increase, 1.34; 95% confidence interval [CI], 1.05 to 1.71; P = 0.02) increased risk for CVD mortality, but this association was partly attenuated and not statistically significant after adjustment for GFR and other confounders (HR, 1.27; 95% CI, 0.94 to 1.73; P = 0.12). Calcium-phosphorus product was not associated with all-cause mortality in unadjusted (P = 0.23) or multivariate analysis (P = 0.35). Calcium-phosphorus product was related to CVD mortality in unadjusted (HR per 10 mg2/dL2 increase, 1.30; 95% CI, 1.01 to 1.69; P = 0.04) analysis, but this association was not statistically significant after adjustment for GFR and other confounders (HR, 1.22; 95% CI, 0.89 to 1.66; P = 0.23). CONCLUSION: In the Modification of Diet in Renal Disease Study cohort, serum phosphorus level and calcium-phosphorus product were not statistically associated with all-cause or CVD mortality after adjustment for GFR; however larger studies with additional statistical power are needed to evaluate these relationships, especially in the context of current practice patterns in patients with CKD.

Adult↗
PubMed2005

Homocysteine in chronic kidney disease: Effect of low protein diet and repletion with B vitamins.

BACKGROUND: Data are limited on the determinants of homocysteine (tHcy) and its relationship with nutritional indices, and dietary protein intake, in the earlier stages of chronic kidney disease (CKD). METHODS: Levels of tHcy were assayed at baseline (N= 804) and 1 year postrandomization (N= 678) in the Modification of Diet in Renal Disease (MDRD) Study [study A, glomerular filtration rate (GFR) 25 to 55 mL/min/1.73 m(2) and study B GFR 13 to 24 mL/min/1.73 m(2)]. Participants were randomly assigned to different blood pressure targets and protein diets and all subjects received a multivitamin supplement containing 1 mg of folic acid, 10 mg pyridoxal 5'-phosphate (PLP) and 6 mug of vitamin B(12). Multivariable analyses were used to evaluate determinants of tHcy at baseline and 1 year. RESULTS: The prevalence of hyperhomocysteinemia (tHcy >15 mumol/L) at baseline was 56% in study A and 85% in study B. Baseline tHcy was negatively correlated with measures of body fat and dietary protein intake. Folate, vitamin B(12), and GFR were the major determinants of tHcy levels. Of the patients with hyperhomocysteinemia at baseline, 49% and 24% reduced their tHcy levels at 1 year to < or =15 micromol/L in study A and study B, respectively. There was no association between dietary protein intake and odds of developing hyperhomocysteinemia at 1 year in study A (P= 0.94) or study B (P= 0.10). CONCLUSION: Hyperhomocysteinemia is partly amenable to correction by vitamin supplementation in CKD stages 3 and 4. There is insufficient evidence to suggest that low tHcy is associated with poor nutritional status in the MDRD Study cohort. B vitamins and GFR, but not dietary protein, are the major determinants of tHcy in this patient population.

Analysis of Variance↗
PubMed2005

C-reactive protein and albumin as predictors of all-cause and cardiovascular mortality in chronic kidney disease.

BACKGROUND: High C-reactive protein (CRP) and hypoalbuminemia are associated with increased risk of mortality in patients with kidney failure. There are limited data evaluating the relationships between CRP, albumin, and outcomes in chronic kidney disease (CKD) stages 3 and 4. METHODS: The Modification of Diet in Renal Disease (MDRD) Study was a randomized controlled trial conducted between 1989 and 1993. CRP was measured in frozen samples taken at baseline. Survival status and cause of death, up to December 31, 2000, were obtained from the National Death Index. Multivariable Cox models were used to examine the relationship of CRP [stratified into high CRP > or =3.0 mg/L (N= 414) versus low CRP<3.0 mg/L (N= 283)], and serum albumin, with all-cause and cardiovascular mortality. RESULTS: Median follow-up time was 125 months, all-cause mortality was 20% (N= 138) and cardiovascular mortality was 10% (N= 71). In multivariable analyses adjusting for demographic, cardiovascular and kidney disease factors, both high CRP (HR, 95% CI = 1.56, 1.07-2.29) and serum albumin (HR = 0.94 per 0.1 g/dL increase, 95% CI = 0.89-0.99) were independent predictors of all-cause mortality. High CRP (HR 1.94, 95% CI 1.13-3.31), but not serum albumin (HR 0.94, 95% CI 0.87-1.02), was an independent predictor of cardiovascular mortality. CONCLUSION: Both high CRP and low albumin, measured in CKD stages 3 and 4, are independent risk factors for all-cause mortality. High CRP, but not serum albumin, is a risk factor for cardiovascular mortality. These results suggest that high CRP and hypoalbuminemia provide prognostic information independent of each other in CKD.

Adolescent↗
PubMed2005

Are nutritional status indicators associated with mortality in the Hemodialysis (HEMO) Study?

BACKGROUND: The purpose of this study was to determine if indicators of nutritional status were associated with subsequent mortality in hemodialysis patients. METHODS: Twelve selected nutrition indicators were measured prior to randomization in the Mortality and Morbidity in Hemodialysis (HEMO) Study. Relative risks (RR) of mortality were assessed at <6 months and >6 months of follow-up using Cox regression after controlling for case mix, comorbidity, and treatment assignment (high vs. standard Kt/V and high vs. low membrane flux). RESULTS: Low values of most nutritional status indicators were associated with increased RR of mortality. RRs were greatest over the short term (<6 months) and diminished with increasing follow-up (>6 months). Increases in body mass index (BMI) at lower levels (e.g., < or =25 kg/m(2)) and increases in serum albumin at any level were associated with reduced short-term RR, even after adjusting for case mix, treatment assignment, and for the joint effects of equilibrated normalized protein catabolic rate, total cholesterol, and serum creatinine. For >6 months' follow-up, increases in values among those with lower levels of BMI and serum albumin (< or =3.635 g/dL) and increases in all serum creatinine levels were associated with lower RR. CONCLUSION: Nutrition indicators are associated with subsequent mortality in a time-dependent manner, with greatest effects at <6 months of follow-up. The RR for these indicators may also vary within different ranges of values.

Body Mass Index↗
PubMed2005

What did we learn from the HEMO Study? Implications of secondary analyses.

BACKGROUND: The HEMO Study was a randomized clinical trial designed to determine whether increasing hemodialysis dose above current standards, or using high-flux membranes, would improve patient outcome. The primary results of the trial showed no statistically significant effects of either dialysis dose or membrane flux on the primary outcome of mortality. METHODS: This report examines the implications of secondary analyses involving subgroups and secondary outcome measures for the overall interpretation of the trial. RESULTS AND CONCLUSIONS: The secondary analyses of the HEMO Study do not alter the conclusions of the primary analysis: In the context of conventional three times per week hemodialysis, neither the high-flux nor high-dose interventions substantially improved patient outcome compared to low-flux and standard-dose levels. However, certain secondary results from the trial are consistent with the hypothesis of subtle effects that may be magnified by more intensive therapies that extend beyond the limits of conventional three times per week dialysis. This hypothesis will be addressed by a pair of new randomized trials sponsored by the National Institute of Digestive and Kidney Disease (NIDDK), which will compare six times per week daily and nocturnal therapies with conventional three times per week dialysis.

Body Size↗
PubMed2005

Design of the Dialysis Access Consortium (DAC) Aggrenox Prevention Of Access Stenosis Trial.

BACKGROUND: Surgically created arteriovenous (AV) grafts are the most common type of hemodialysis vascular access in the United States, but fail frequently due to the development of venous stenosis. The Dialysis Access Consortium (DAC) Aggrenox Prevention of Access Stenosis Trial tests the hypothesis that Aggrenox (containing dipyridamole and aspirin) can prevent stenosis and prolong survival of arteriovenous grafts. METHODS: This is a multicenter, randomized, double-blind, placebo-controlled trial that will enroll 1056 subjects over four years with one-half year follow-up. Subjects undergoing placement of a new AV graft for hemodialysis are randomized to treatment with Aggrenox or placebo immediately following access surgery. The primary outcome is primary unassisted patency defined as the time from access placement until thrombosis or an access procedure carried out to maintain or restore patency. The major secondary outcome is cumulative access patency. Monthly access flow monitoring is incorporated in the study design to enhance detection of a hemodynamically significant access stenosis before it leads to thrombosis. RESULTS: This paper describes the key issues in trial design, broadly including: 1) ethical issues surrounding the study of a clinical procedure that, although common, is no longer the clinical intervention of choice; 2) acceptable risk (bleeding) from the primary intervention; 3) inclusion of subjects already receiving a portion of the study intervention; 4) inclusion of subjects with incident rather than prevalent qualifying clinical conditions; 5) timing of the study intervention to balance safety and efficacy concerns; and 6) the selection of primary and secondary study endpoints. CONCLUSIONS: This is the first, large, multicenter trial evaluating a pharmacologic approach to prevent AV graft stenosis and failure, an important and costly problem in this patient population. Numerous design issues were addressed in implementing the trial and these will form a roadmap for future trials in this area.

Algorithms↗
PubMed2005

Design of the Dialysis Access Consortium (DAC) Clopidogrel Prevention of Early AV Fistula Thrombosis Trial.

BACKGROUND: The Dialysis Access Consortium (DAC) was developed to investigate interventions to improve hemodialysis vascular access outcomes. The autogenous arteriovenous fistula created by direct connection of native artery to vein is the recommended vascular access for hemodialysis. However, it fails frequently due to clotting after surgery. PURPOSE: The DAC Early AV Fistula Thrombosis Trial tests the hypothesis that clopidogrel can prevent early fistula failure and increase the number of fistulas that ultimately become usable for hemodialysis access. This is one of two initial and concurrent trials being performed by the DAC. The companion trial investigates pharmacologic approaches to prevent venous stenosis leading to AV graft failure. METHODS: This is a multicenter, randomized, double-blind, placebo-controlled trial that will enroll 1,284 patients over four years. Patients undergoing creation of a new native arteriovenous (AV) fistula are randomized to treatment with clopidogrel or placebo for six weeks following fistula creation surgery. The primary outcome is fistula patency at six weeks. The major secondary outcome is fistula suitability for dialysis. RESULTS: This paper examines key aspects of this study that have broad relevance to trial design including: 1) the selection of an intermediate event as the primary outcome, 2) timing of the intervention to balance efficacy and safety concerns, 3) ethical considerations arising from required modifications of concomitant drug therapy, and 4) choosing an efficacy or effectiveness evaluation of the intervention. CONCLUSIONS: This is the first, large, multicenter trial evaluating a pharmacologic approach to prevent early AV fistula failure and promote more usable fistulas for hemodialysis. The methodologic challenges identified and addressed during the development of this trial should help to inform the design of future vascular access trials, and are relevant to clinical trials addressing a wide range of questions.

Arteriovenous Shunt, Surgical↗
PubMed2005

Low-level environmental lead exposure and children's intellectual function: an international pooled analysis.

Lead is a confirmed neurotoxin, but questions remain about lead-associated intellectual deficits at blood lead levels < 10 microg/dL and whether lower exposures are, for a given change in exposure, associated with greater deficits. The objective of this study was to examine the association of intelligence test scores and blood lead concentration, especially for children who had maximal measured blood lead levels < 10 microg/dL. We examined data collected from 1,333 children who participated in seven international population-based longitudinal cohort studies, followed from birth or infancy until 5-10 years of age. The full-scale IQ score was the primary outcome measure. The geometric mean blood lead concentration of the children peaked at 17.8 microg/dL and declined to 9.4 microg/dL by 5-7 years of age; 244 (18%) children had a maximal blood lead concentration < 10 microg/dL, and 103 (8%) had a maximal blood lead concentration < 7.5 microg/dL. After adjustment for covariates, we found an inverse relationship between blood lead concentration and IQ score. Using a log-linear model, we found a 6.9 IQ point decrement [95% confidence interval (CI), 4.2-9.4] associated with an increase in concurrent blood lead levels from 2.4 to 30 microg/dL. The estimated IQ point decrements associated with an increase in blood lead from 2.4 to 10 microg/dL, 10 to 20 microg/dL, and 20 to 30 microg/dL were 3.9 (95% CI, 2.4-5.3), 1.9 (95% CI, 1.2-2.6), and 1.1 (95% CI, 0.7-1.5), respectively. For a given increase in blood lead, the lead-associated intellectual decrement for children with a maximal blood lead level < 7.5 microg/dL was significantly greater than that observed for those with a maximal blood lead level > or = 7.5 microg/dL (p = 0.015). We conclude that environmental lead exposure in children who have maximal blood lead levels < 7.5 microg/dL is associated with intellectual deficits.

Child↗
PubMed2004

Performance of the modification of diet in renal disease and Cockcroft-Gault equations in the estimation of GFR in health and in chronic kidney disease.

The performance of the Modification of Diet in Renal Disease (MDRD) and the Cockcroft-Gault (CG) equations as compared with measured (125)I-iothalamate GFR (iGFR) was analyzed in patients with chronic kidney disease (CKD) and in potential kidney donors. All outpatients (n = 1285) who underwent an iGFR between 1996 and 2003 were considered for analysis. Of these, 828 patients had CKD and 457 were potential kidney donors. Special emphasis was put on the calibration of the serum creatinine measurements. In CKD patients with GFR <60 ml/min per 1.73 m(2), the MDRD equation performed better than the CG formula with respect to bias (-0.5 versus 3.5 ml/min per 1.73 m(2), respectively) and accuracy within 30% (71 versus 60%, respectively) and 50% (89 versus 77%, respectively). Similar results are reported for 249 CKD patients with diabetes. In the kidney donor group, the MDRD equation significantly underestimated the measured GFR when compared with the CG formula, with a bias of -9.0 versus 1.9 ml/min per 1.73 m(2), respectively (P < 0.01), and both the MDRD and CG equations overestimated the strength of the association of GFR with measured serum creatinine. The present data add further validation of the MDRD equation in outpatients with moderate to advanced kidney disease as well as in those with diabetic nephropathy but suggest that its use is problematic in healthy individuals. This study also emphasizes the complexity of laboratory calibration of serum creatinine measurements, a determining factor when estimating GFR in both healthy individuals and CKD patients with preserved GFR.

Adult↗
PubMed2004

Factors that affect postdialysis rebound in serum urea concentration, including the rate of dialysis: results from the HEMO Study.

Previous studies have suggested that postdialysis urea rebound is related to K/V, the rate of dialysis, but a systematic analysis of factors that affect rebound has not been reported. With the use of 30-min and, in a subset, 60-min postdialysis samples, postdialysis urea rebound was measured to (1) determine how well previously proposed equations based on the rate of dialysis (K/V) predict rebound in a large sample of patients with varying characteristics, (2) determine whether other factors besides K/V affect rebound, and (3) estimate more precise values for coefficients in prediction equations for rebound. Rebound was calculated relative to both immediate and 20-s postdialysis samples to study early components of rebound unrelated to access recirculation. The equilibrated Kt/V (eKt/V) computed by fitting the two-pool variable volume model to the 30-min postdialysis sample agreed well with eKt/V based on the 60-min postdialysis sample. Using the pre-, post-, and 30-min postdialysis samples for 1245 patients with arteriovenous (AV) accesses, the median intercompartmental mass transfer coefficient (Kc) was 797 ml/min for rebound computed relative to the 20-s postdialysis samples and 592 ml/min relative to the immediate postdialysis samples. K/V was the strongest predictor of rebound among 22 factors considered. Other factors associated with greater rebound for 1331 patients using AV accesses or venous catheters included access type, black race, male gender, absence of congestive heart failure, greater age, ultrafiltration rate, and low predialysis or intradialysis systolic BP. Equations of the form eKt/V = single-pool Kt/V - B x (K/V) were fit to the data. With AV access, the optimum values for the slope term (B) were 0.39 and 0.46 (in h(-1)) for single-pool Kt/V calculated based on 20-s postdialysis or immediate postdialysis samples, respectively. For patients using venous catheters, the respective values for B were 0.22 and 0.29. Postdialysis urea rebound can be predicted with acceptable accuracy from a postdialysis sample using a zero-intercept, K/V-based rate equation. Several patient or treatment-specific factors predict enhanced or reduced rebound. Rate equation slope coefficients for K/V of 0.39 (AV access) and 0.22 (venous access) are proposed when a 15- to 20-s slow-flow method is used to draw the postdialysis blood. Slightly higher K/V slope coefficients (0.46 and 0.29, respectively) should be used if a shorter (e.g., 10 s) slow-flow period is used.

Female↗
PubMed2004

A comparison of iothalamate-GFR and serum creatinine-based outcomes: acceleration in the rate of GFR decline in the African American Study of Kidney Disease and Hypertension.

In renal clinical trials, both slope-based and time-to-event renal outcomes have been used. These outcomes are typically based on estimates of GFR obtained using creatinine or iothalamate GFR (iGFR). The African American Study of Kidney Disease and Hypertension (AASK) was a trial in 1094 African Americans with hypertensive nephrosclerosis, which examined the effects of two levels of BP control and three antihypertensive regimens. This study compared the effects of the AASK interventions on outcomes based on serum creatinine with corresponding outcomes based on iGFR using 9742 matched pairs of iGFR and serum creatinine measurements. The iGFR-based outcomes included (1) a time-to-event composite outcome including a 50% GFR decline, ESRD, or death; (2) a composite outcome including a 50% GFR decline or ESRD; (3) mean decline in GFR in the first 3 mo after randomization (acute slope); (4) mean decline in GFR starting 3 mo after randomization (chronic slope); and (5) mean decline in GFR from baseline (total slope). The corresponding creatinine-based outcomes were (1) a composite of doubling of serum creatinine, ESRD, or death and (2) a composite of doubling of serum creatinine or ESRD and acute, chronic, and total slopes defined by the mean change in estimated GFR (eGFR), where eGFR was estimated from a regression equation for GFR depending primarily on serum creatinine and developed in AASK enrollees. Mean changes in iGFR and eGFR were also compared under extended models that allowed for the possibility that the rate of GFR decline may change over time during the chronic phase. an apparent acceleration in rate of decline of renal function over time was found. Subtle differences were observed between effects of the interventions on some of the creatinine and iGFR slope-based outcomes, but the main conclusions of the trial were similar for the serum creatinine and iothalamate-based measurements. This has important implications for the design of clinical trials with renal outcomes.

Adolescent↗
PubMed2004

Dialysis dose and the effect of gender and body size on outcome in the HEMO Study.

BACKGROUND: Gender and body size have been associated with survival in hemodialysis populations. In recent observational studies, overall mortality was similar in men and women and higher in small patients. The effect of dialysis dose in each of these subgroups has not been tested in a clinical trial. METHODS: The HEMO Study was a controlled trial of dialysis dose and membrane flux in 1846 hemodialysis patients followed up for 6.6 years in 15 centers throughout the United States. We examined the effect of dialysis dose on mortality and on selected secondary outcomes in subgroups of patients. RESULTS: Adjusting for age only, overall mortality was lower in patients with higher body weight (P < 0.001), higher body mass index (P < 0.001), and higher body water content determined by the Watson formula (Vw) (P < 0.001), but was not associated with gender (P= 0.27). The RR of mortality comparing the high dose with the standard dose group was related to gender (P= 0.014). Women randomized to the high dose had a lower mortality rate than women randomized to the standard dose (RR = 0.81, P= 0.02), while men randomized to the high dose had a nonsignificant trend for a higher mortality rate than men randomized to the standard dose (RR = 1.16, P= 0.16). Analysis of both genders combined showed no overall dose effect (R = 0.96, P= 0.52), as reported previously. Vw was greater than 35 L in 84% of men compared with 17% of women. However, the RR of mortality for the high versus standard dose remained lower in women than in men after adjustment for the interaction of dose with Vw or with other size parameters, including weight and body mass index. Conversely, the dose effect was not significantly related to size parameters after controlling for the relationship of the dose comparison with gender. CONCLUSION: The data suggest that mortality and morbidity might be reduced by increasing the dialysis dose above the current standard in women but not in men. This effect was not explained by differences between men and women in age, race, or in several indices of body size. Because multiple comparisons were considered in this analysis, the role of gender on the effect of dialysis dose is suggestive and invites further study.

Black People↗
PubMed2004

The effect of dialysis dose and membrane flux on nutritional parameters in hemodialysis patients: results of the HEMO Study.

BACKGROUND: The effect of standard or high dialysis dose and low or high dialysis flux on nutritional status was ascertained in 1846 maintenance hemodialysis patients enrolled in the HEMO Study. METHODS: Serum albumin levels, equilibrated protein catabolic rate, and postdialysis weight were obtained monthly, while adjusted protein and energy intake, self-reported appetite assessment, upper arm circumference, and calf circumference were obtained yearly. To account for patient attrition due to death or transfer, three statistical models were used to test the effects of the study interventions on longitudinal changes in nutritional parameters. RESULTS: During the first 3 years of follow-up, neither mean serum albumin levels, which declined by 0.21 g/dL, nor mean postdialysis weight, which declined by 2.7 kg, were significantly affected by either study intervention. Mean levels of all anthropometric measures declined during follow-up. For years 1, 2, and 3, the mean +/- SE declines in upper arm and calf circumferences were 0.35 +/- 0.16 cm (P= 0.031) and 0.31 +/- 0.13 (P= 0.015) cm less, respectively, in the high flux compared to the low flux group. Appetite scores and mean equilibrated protein catabolic rate also declined in all randomized groups; however, the average decline in equilibrated protein catabolic rate during years 1, 2, and 3 was 0.019 +/- 0.007 g/kg/day less in the high dose than the standard dose group (P= 0.007). There was no significant change in either mean energy or protein intake from diet records over time, and neither parameter was affected by the study interventions. CONCLUSION: Although the dose and flux interventions may subtly influence certain nutritional parameters, neither intervention prevented deterioration in nutritional status over time.

Adult↗