Biomedical subjects

Tom Greene

Publications and source records attributed to Tom Greene.

At least 55 records · Page 3Linked to original sources

PubMed2004

Effects of hemodialysis dose and membrane flux on health-related quality of life in the HEMO Study.

BACKGROUND: It has been widely supposed that high dose and high flux hemodialysis would affect the quality as well as the length of life of patients treated by maintenance hemodialysis. The HEMO Study examined changes in health-related quality of life as a secondary study outcome. Specific hypotheses were that study interventions would affect physical functioning, vitality, Short Form-36 Health Survey (SF-36) physical and mental component summary scores, symptoms and problems associated with kidney disease, and sleep quality. METHODS: At baseline and annually, subjects responded to both the Index of Well-Being and the Kidney Disease Quality of Life-Long Form questionnaires. The interventions were assessed on the basis of their average effects over 3 years. RESULTS: At baseline, the SF-36 physical component summary score was lower than in healthy populations, but the mental component score was nearly normal. Over 3-year follow-up, physical health continued to decline; mental health and kidney disease-targeted scores remained relatively stable. The high dose hemodialysis intervention was associated with significantly less pain (4.49 points, P < 0.001) and higher physical component scores (1.23 points P= 0.007), but these effects were small compared to the natural variability in scores. High flux membranes were not associated with statistically significant differences in health-related quality of life. CONCLUSION: The HEMO Study results demonstrate the marked burden of chronic kidney failure and hemodialysis treatment on daily life. In this trial among patients undergoing maintenance three times a week hemodialysis, the SF-36 physical component summary score and pain scale showed significant but very small clinical effects favoring the higher dialysis dose. No clinically meaningful benefits or either the dose or flux interventions were observed for other indices of health-related quality of life.

Aged↗

PubMed2004

Kinetics of urea and beta-microglobulin during and after short hemodialysis treatments.

BACKGROUND: Daily short hemodialysis (HD) is often prescribed by simply doubling treatment frequency and halving treatment time; however, the effect of this prescription approach on the equilibrated HD dose (urea eKt/V) and whole body clearance for beta(2)-microglobulin has not been established. METHODS: We compared urea and beta(2)-microglobulin kinetics during and 60 minutes after a short HD treatment and a conventional HD treatment in a crossover study on 22 maintenance HD patients: 16 male and 6 female, 61 +/- 18 (mean +/- standard deviation) years of age. One patient in each treatment modality was excluded from certain analyses because of missing data. Short and conventional HD treatments were essentially identical, except for treatment times, which were 116 +/- 14 and 241 +/- 27 minutes, respectively. Blood samples were collected at regular intervals during and after treatments, and additional blood and dialysate samples were collected at 60 minutes of treatment to evaluate dialyzer clearances. RESULTS: Plasma water urea clearances measured directly across the dialyzer during short and conventional HD treatments were not different (255 +/- 23 mL/min and 255 +/- 28 mL/min, respectively). The 60-minute postdialysis blood urea nitrogen concentration rebounded more (P < 0.01) after short HD than conventional HD (5.9 +/- 3.1 vs. 4.0 +/- 1.5 mg/dL, respectively). Calculated urea eKt/V values using the Daugirdas-Schneditz rate equation were not different from those measured during conventional HD using the 60-minute postdialysis concentration but significantly overestimated measured urea eKt/V values during short HD. Postdialysis rebound of beta(2)-microglobulin concentrations was variable but similar after short and conventional HD treatments (0.1 +/- 3.4 vs. 0.7 +/- 1.8 mg/L, respectively). Whole body clearances of beta(2)-microglobulin calculated from predialysis and immediate (10-second) postdialysis serum concentrations during short and conventional HD treatments were not different from each other (42.9 +/- 24.1 vs. 41.9 +/- 22.4 mL/min, respectively). CONCLUSION: These observations show that the Daugirdas-Schneditz rate equation is accurate in predicting urea eKt/V during conventional, but not during short, HD. In contrast, whole body clearances of beta(2)-microglobulin during short and conventional HD treatments were similar. We conclude that calculation of accurate estimates of urea eKt/V, but not clearances of beta(2)-microglobulin, differ during short and conventional HD treatments.

Blood Urea Nitrogen↗

PubMed2003

High urine volume and low urine osmolality are risk factors for faster progression of renal disease.

BACKGROUND: Increased fluid intake slows renal disease progression in animal models. The relevance of these findings to human renal disease is not clear, although increased fluid intake often is recommended to patients with chronic renal insufficiency. This study tested the hypothesis that urine volume, urine osmolality (Uosm), or both are significantly associated with glomerular filtration rate (GFR) decline in patients with chronic renal insufficiency. METHODS: This is a retrospective analysis of Modification of Diet in Renal Disease (MDRD) study A patients with (N = 139) and without polycystic kidney disease (PKD; N = 442). The key outcome measure was GFR slope in relation to mean 24-hour urine volume and Uosm during follow-up in study A (mean, 2.3 years). RESULTS: The regression of GFR slope on mean follow-up 24-hour urine volume (adjusted for body surface area and MDRD diet and blood pressure group) showed that the greater the urine volume, the faster the GFR decline in patients both with and without PKD. For example, the difference in GFR slope for those with a mean follow-up 24-hour urine volume of 2.4 versus 1.4 L was -1.01 mL/min/y (confidence interval, -0.27 to -1.75) for patients without PKD and -1.20 mL/min/y (confidence interval, -0.06 to -2.34) for those with PKD. A similar but inverse relationship was shown between GFR decline and mean 24-hour Uosm in patients with (P = 0.01) and without PKD (P = 0.001). These associations remained significant after adjustment for 13 relevant baseline and follow-up covariates. CONCLUSION: Sustained high urine volume and low Uosm are independent risk factors for faster GFR decline in patients with chronic renal insufficiency. Thus, high fluid intake does not appear to slow renal disease progression in humans. We suggest that until better evidence becomes available, patients with chronic renal insufficiency should generally let their thirst guide fluid intake. The advice to avoid "pushing fluids" might be particularly important for patients with PKD.

Disease Progression↗

PubMed2003

Relationship between C-reactive protein, albumin, and cardiovascular disease in patients with chronic kidney disease.

BACKGROUND: C-Reactive protein (CRP) level is elevated in kidney failure and may be related to malnutrition and cardiovascular disease (CVD). Data are limited regarding relationships between CRP levels and glomerular filtration rate (GFR), nutritional indices, and CVD in patients with earlier stages of kidney disease. METHODS: CRP was assayed from samples from the Modification of Diet in Renal Disease (MDRD) Study (n = 801). CRP distributions were compared between the MDRD Study and National Health and Nutrition Examination Survey (NHANES; 1999 to 2000). Associations between CRP level and GFR, nutritional indices, serum albumin levels, and CVD risk factors were examined in the MDRD Study. RESULTS: Geometric means of CRP, adjusted for age and sex, were similar in NHANES (0.23 mg/dL) and the MDRD Study (0.22 mg/dL). In the MDRD Study, CRP level was related directly to measures of body fat and CVD risk factors, inversely with serum albumin level and energy intake, and unrelated to GFR. In multivariable analysis adjusting for other determinants of serum albumin level, high CRP level (>0.6 mg/dL) was associated with a 0.07-g/dL (0.7-g/L; 95% confidence interval [CI], 0.03 to 0.12) lower mean serum albumin level. After adjusting for traditional CVD risk factors, the odds of CVD were 1.73 (95% CI, 1.07 to 2.78) times greater in subjects with a high CRP level. CONCLUSION: GFR level does not appear to influence CRP level in the earlier stages of chronic kidney disease. CRP levels are independently associated with serum albumin level and CVD prevalence. Inflammation may be involved in the pathophysiological state of malnutrition and CVD in the earlier stages of predominantly nondiabetic kidney disease.

Adolescent↗

PubMed2003

Anthropometrically estimated total body water volumes are larger than modeled urea volume in chronic hemodialysis patients: effects of age, race, and gender.

BACKGROUND: The modeled volume of urea distribution (Vm) in intermittently hemodialyzed patients is often compared with total body water (TBW) volume predicted from population studies of patient anthropometrics (Vant). METHODS: Using data from the HEMO Study, we compared Vm determined by both blood-side and dialysate-side urea kinetic models with Vant as calculated by the Watson, Hume-Weyers, and Chertow anthropometric equations. RESULTS: Median levels of dialysate-based Vm and blood-based Vm agreed (43% and 44% of body weight, respectively). These volumes were lower than anthropometric estimates of TBW, which had median values of 52% to 55% of body weight for the three formulas evaluated. The difference between the Watson equation for TBW and modeled urea volume was greater in Caucasians (19%) than in African Americans (13%). Correlations between Vm and Vant determined by each of the three anthropometric estimation equations were similar; but Vant derived from the Watson formula had a slightly higher correlation with Vm. The difference between Vm and the anthropometric formulas was greatest with the Chertow equation, less with the Hume-Weyers formula, and least with the Watson estimate. The age term in the Watson equation for men that adjusts Vant downward with increasing age reduced an age effect on the difference between Vant and Vm in men. CONCLUSION: The findings show that kinetically derived values for V from blood-side and dialysate-side modeling are similar, and that these modeled urea volumes are lower by a substantial amount than anthropometric estimates of TBW. The higher values for anthropometry-derived TBW in hemodialyzed patients could be due to measurement errors. However, the possibility exists that TBW space is contracted in patients with end-stage renal disease (ESRD) or that the TBW space and the urea distribution space are not identical.

Black or African American↗

PubMed2003

Prescribing an equilibrated intermittent hemodialysis dose in intensive care unit acute renal failure.

BACKGROUND: Prospective, formal, blood-side, urea kinetic modeling (UKM) has yet to be applied in intermittent hemodialysis for acute renal failure (ARF). Methods for prescribing a target, equilibrated Kt/V (eKt/V) are described for this setting. METHODS: Serial sessions (N= 108) were studied in 28 intensive care unit ARF patients. eKt/V was derived using delayed posthemodialyis urea samples and formal, double-pool UKM (eKt/Vref), and by applying the Daugirdas-Schneditz venous rate equation to pre- and posthemodialysis samples (eKt/Vrate). Individual components of prescribed and delivered dose were compared. Prescribed eKt/V values were determined using in vivo dialyzer clearance estimates and anthropometric (Watson and adjusted Chertow) and modeled urea volumes. RESULTS: eKt/Vref (mean +/- SD = 0.91 +/- 0.26) was well-approximated by eKt/Vrate (0.92 +/- 0.25), R= 0.92. Modeled V exceeded Watson V by 25%+/- 29% (P < 0.001) and Adjusted Chertow V by 18%+/- 28% (P < 0.001), although the degree of overestimation diminished over time. This difference was influenced by access recirculation (AR) and use of saline flushes. The median % difference between Vdprate and Watson V was reduced to 1% after adjusting for AR for the 22 sessions with < or =1 saline flush. The median coefficients of variation for serial determinations of Adjusted Chertow V, modeled V, urea generation rate, and eKt/Vref were 2.7%, 12.2%, 30.1%, and 16.4%, respectively. Because of comparatively higher modeled urea Vs, delivered eKt/Vref was lower than prescribed eKt/V, based on Watson V or Adjusted Chertow V, by 0.13 and 0.08 Kt/V units. The median absolute errors of prescribed eKt/V vs. delivered therapy (eKt/Vref) were not large and were similar in prescriptions based on the Adjusted Chertow V (0.127) vs. those based on various double-pool modeled urea volumes (approximately 0.127). CONCLUSION: Equilibrated Kt/V can be derived using formal, double-pool UKM in intensive care unit ARF patients, with the venous rate equation providing a practical alternative. A target eKt/V can be prescribed to within a median absolute error of less than 0.14 Kt/V units using practical prescription algorithms. The causes of the increased apparent volume of urea distribution appear to be multifactorial and deserve further investigation.

Acute Kidney Injury↗

PubMed2003

Prevalence of chronic kidney disease and decreased kidney function in the adult US population: Third National Health and Nutrition Examination Survey.

BACKGROUND: Recently developed clinical practice guidelines and calibration of the Third National Health and Nutrition Examination Survey (NHANES III) serum creatinine assay provide a basis for estimating the prevalence and distribution of chronic kidney disease (CKD) in the United States using standardized criteria based on estimated glomerular filtration rate (GFR) and persistent albuminuria. METHODS: A nationally representative sample of 15,625 noninstitutionalized adults aged 20 years and older from the NHANES III was analyzed. Kidney function (GFR), kidney damage (albuminuria), and stages of CKD (GFR and albuminuria) were estimated from calibrated serum creatinine level, spot urine albumin level, age, sex, and race. GFR was estimated using the simplified Modification of Diet in Renal Disease Study equation and compared with the Cockcroft-Gault equation for creatinine clearance (CCr). RESULTS: The prevalence of CKD in the US adult population was 11% (19.2 million). By stage, an estimated 5.9 million individuals (3.3%) had stage 1 (persistent albuminuria with a normal GFR), 5.3 million (3.0%) had stage 2 (persistent albuminuria with a GFR of 60 to 89 mL/min/1.73 m(2)), 7.6 million (4.3%) had stage 3 (GFR, 30 to 59 mL/min/1.73 m(2)), 400,000 individuals (0.2%) had stage 4 (GFR, 15 to 29 mL/min/1.73 m(2)), and 300,000 individuals (0.2%) had stage 5, or kidney failure. Aside from hypertension and diabetes, age is a key predictor of CKD, and 11% of individuals older than 65 years without hypertension or diabetes had stage 3 or worse CKD. Compared with GFR estimates, CCr estimates showed a steeper decline with age and were lower in non-Hispanic blacks. CONCLUSION: CKD is common and warrants improved detection and classification using standardized criteria to improve outcomes. Am J Kidney Dis 41:1-12.

Adult↗

PubMed2003

Longitudinal and cross-sectional effects of C-reactive protein, equilibrated normalized protein catabolic rate, and serum bicarbonate on creatinine and albumin levels in dialysis patients.

BACKGROUND: Loss of muscle mass and hypoalbuminemia each may result in part from either malnutrition, inflammation, or a combination of both. Short-term acidosis increases muscle protein catabolism and inhibits albumin synthesis. METHODS: We analyzed albumin and creatinine levels as outcome variables and their association with C-reactive protein (CRP) level, equilibrated normalized protein catabolic rate (enPCR), and serum bicarbonate level as independent variables from laboratory data obtained from patients in the Hemodialysis Study. Analyses controlled for race, sex, age, body mass index, and randomized treatment group. RESULTS: Albumin level correlated with both enPCR and CRP level, but not serum bicarbonate level, in both cross-sectional and longitudinal analyses. Effects of CRP level and enPCR were not linear. Albumin level correlated positively with enPCR for an enPCR less than 1.0 g/kg/d, but not for a greater enPCR, and correlated inversely with CRP level for a CRP level greater than 13 mg/L. Similarly, creatinine level correlated with both enPCR and CRP level. As in the case of albumin level, effects were not linear. Creatinine level correlated positively with enPCR for values less than 1.0 g/kg/d, but not for greater enPCR values. In contrast to albumin level, creatinine level correlated negatively with serum bicarbonate level, even when adjusted for enPCR. CONCLUSION: Albumin and creatinine levels are independently associated with nutrition (enPCR) and inflammation (CRP level). The cross-sectional relationship with enPCR is apparent only at values less than 1.0 g/kg/d. CRP level is associated with reduced albumin and creatinine values when increased to values greater than 5.6 mg/dL. CRP may be increased to levels associated with increased cardiovascular risk with little or no effect on either serum albumin or creatinine level. Thus, a normal albumin level does not exclude elevated CRP levels.

Acidosis↗

PubMed2003

Design and statistical aspects of the African American Study of Kidney Disease and Hypertension (AASK).

The African American Study of Kidney Disease and Hypertension (AASK) is a multicenter randomized clinical trial designed to test the effectiveness of three anti-hypertensive drug regimens and two levels of BP control on the progression of hypertensive kidney disease. Participants include African-American men and women aged 18 to 70 yr who have hypertensive kidney disease and GFR between 20 and 65 ml/min per 1.73 m(2). The three anti-hypertensive drug regimens include an angiotensin converting enzyme inhibitor (ramipril), a dihydropyridine calcium channel blocker (amlodipine) or a beta-blocker (metoprolol) as initial therapy. The BP control levels are a lower goal (mean arterial pressure, </=92 mmHg) and a usual goal (mean arterial pressure, 102 to 107 mmHg inclusive). The primary outcome is rate of change in renal function as measured by GFR, assessed by (125) I-iothalamate clearance. The main secondary patient outcome is a composite including the following events: (1) reduction in GFR by 50%, (2) end-stage renal disease, or (3) death.

Adolescent↗

PubMed2003

The rationale and design of the AASK cohort study.

Hypertensive kidney disease commonly progresses. The primary objective of the AASK (African American Study of Kidney Disease and Hypertension) Cohort Study is to determine prospectively the course of kidney function and risk factors for kidney disease progression in African Americans with hypertensive kidney disease who receive recommended anti-hypertensive therapy. The AASK Cohort Study is a prospective, observational study that is an extension of the AASK trial. The AASK trial tested the effects of three medications used as initial anti-hypertensive therapy (ramipril, metoprolol, and amlodipine) and two levels of BP control. Of the 1094 trial participants, approximately 650 to 700 individuals who have not reached ESRD will likely enroll in the Cohort Study. Risk factors to be studied include environmental, genetic, physiologic, and socioeconomic variables. The primary renal outcome is a composite clinical outcome defined by doubling of serum creatinine, ESRD, or death. Medication treatment for hypertension, beginning with the angiotensin converting enzyme inhibitor ramipril, is offered to all participants. In this fashion, the study directly controls two of the major determinants of kidney disease progression: treatment of hypertension and use of renoprotective, anti-hypertensive medication. The minimum duration of follow-up in the Cohort Study is 5 yr (total of 9 to 12 yr, including the period of the AASK trial). Ultimately, data from the AASK Cohort Study should enhance our understanding of the risk factors and processes that determine the progression of kidney disease. Such results might eventually lead to new strategies that delay or prevent ESRD.

Adolescent↗

PubMed2003

Effects of high-flux hemodialysis on clinical outcomes: results of the HEMO study.

Among the 1846 patients in the HEMO Study, chronic high-flux dialysis did not significantly affect the primary outcome of the all-cause mortality (ACM) rate or the main secondary composite outcomes, including the rates of first cardiac hospitalization or ACM, first infectious hospitalization or ACM, first 15% decrease in serum albumin levels or ACM, or all non-vascular access-related hospitalizations. The high-flux intervention, however, seemed to be associated with reduced risks of specific cardiac-related events. The relative risks (RR) for the high-flux arm, compared with the low-flux arm, were 0.80 [95% confidence interval (CI), 0.65 to 0.99] for cardiac death and 0.87 (95% CI, 0.76 to 1.00) for the composite of first cardiac hospitalization or cardiac death. Also, the effect of high-flux dialysis on ACM seemed to vary, depending on the duration of prior dialysis. This report presents secondary analyses to further explore the relationship between the flux intervention and the duration of dialysis with respect to various outcomes. The patients were stratified into a short-duration group and a long-duration group, on the basis of the mean duration of dialysis of 3.7 yr before randomization. In the subgroup that had been on dialysis for >3.7 yr, randomization to high-flux dialysis was associated with lower risks of ACM (RR, 0.68; 95% CI, 0.53 to 0.86; P = 0.001), the composite of first albumin level decrease or ACM (RR, 0.74; 95% CI, 0.60 to 0.91; P = 0.005), and cardiac deaths (RR, 0.63; 95% CI, 0.43 to 0.92; P = 0.016), compared with low-flux dialysis. No significant differences were observed in outcomes related to infection for either duration subgroup, however, and the trends for beneficial effects of high-flux dialysis on ACM rates were considerably weakened when the years of dialysis during the follow-up phase were combined with the prestudy years of dialysis in the analysis. For the subgroup of patients with <3.7 yr of dialysis before the study, assignment to high-flux dialysis had no significant effect on any of the examined clinical outcomes. These data suggest that high-flux dialysis might have a beneficial effect on cardiac outcomes. Because these results are derived from multiple statistical comparisons, however, they must be interpreted with caution. The subgroup results that demonstrate that patients with different durations of dialysis are affected differently by high-flux dialysis are interesting and require further study for confirmation.

Female↗

PubMed2002

Effect of dialysis dose and membrane flux in maintenance hemodialysis.

BACKGROUND: The effects of the dose of dialysis and the level of flux of the dialyzer membrane on mortality and morbidity among patients undergoing maintenance hemodialysis are uncertain. METHODS: We undertook a randomized clinical trial in 1846 patients undergoing thrice-weekly dialysis, using a two-by-two factorial design to assign patients randomly to a standard or high dose of dialysis and to a low-flux or high-flux dialyzer. RESULTS: In the standard-dose group, the mean (+/-SD) urea-reduction ratio was 66.3+/-2.5 percent, the single-pool Kt/V was 1.32+/-0.09, and the equilibrated Kt/V was 1.16+/-0.08; in the high-dose group, the values were 75.2+/-2.5 percent, 1.71+/-0.11, and 1.53+/-0.09, respectively. Flux, estimated on the basis of beta2-microglobulin clearance, was 3+/-7 ml per minute in the low-flux group and 34+/-11 ml per minute in the high-flux group. The primary outcome, death from any cause, was not significantly influenced by the dose or flux assignment: the relative risk of death in the high-dose group as compared with the standard-dose group was 0.96 (95 percent confidence interval, 0.84 to 1.10; P=0.53), and the relative risk of death in the high-flux group as compared with the low-flux group was 0.92 (95 percent confidence interval, 0.81 to 1.05; P=0.23). The main secondary outcomes (first hospitalization for cardiac causes or death from any cause, first hospitalization for infection or death from any cause, first 15 percent decrease in the serum albumin level or death from any cause, and all hospitalizations not related to vascular access) also did not differ significantly between either the dose groups or the flux groups. Possible benefits of the dose or flux interventions were suggested in two of seven prespecified subgroups of patients. CONCLUSIONS: Patients undergoing hemodialysis thrice weekly appear to have no major benefit from a higher dialysis dose than that recommended by current U.S. guidelines or from the use of a high-flux membrane.

Adult↗

PubMed2002

Effect of blood pressure lowering and antihypertensive drug class on progression of hypertensive kidney disease: results from the AASK trial.

CONTEXT: Hypertension is a leading cause of end-stage renal disease (ESRD) in the United States, with no known treatment to prevent progressive declines leading to ESRD. OBJECTIVE: To compare the effects of 2 levels of blood pressure (BP) control and 3 antihypertensive drug classes on glomerular filtration rate (GFR) decline in hypertension. DESIGN: Randomized 3 x 2 factorial trial with enrollment from February 1995 to September 1998. SETTING AND PARTICIPANTS: A total of 1094 African Americans aged 18 to 70 years with hypertensive renal disease (GFR, 20-65 mL/min per 1.73 m(2)) were recruited from 21 clinical centers throughout the United States and followed up for 3 to 6.4 years. INTERVENTIONS: Participants were randomly assigned to 1 of 2 mean arterial pressure goals, 102 to 107 mm Hg (usual; n = 554) or 92 mm Hg or less (lower; n = 540), and to initial treatment with either a beta-blocker (metoprolol 50-200 mg/d; n = 441), an angiotensin-converting enzyme inhibitor (ramipril 2.5-10 mg/d; n = 436) or a dihydropyridine calcium channel blocker, (amlodipine 5-10 mg/d; n = 217). Open-label agents were added to achieve the assigned BP goals. MAIN OUTCOME MEASURES: Rate of change in GFR (GFR slope); clinical composite outcome of reduction in GFR by 50% or more (or > or =25 mL/min per 1.73 m2) from baseline, ESRD, or death. Three primary treatment comparisons were specified: lower vs usual BP goal; ramipril vs metoprolol; and amlodipine vs metoprolol. RESULTS: Achieved BP averaged (SD) 128/78 (12/8) mm Hg in the lower BP group and 141/85 (12/7) mm Hg in the usual BP group. The mean (SE) GFR slope from baseline through 4 years did not differ significantly between the lower BP group (-2.21 [0.17] mL/min per 1.73 m2 per year) and the usual BP group (-1.95 [0.17] mL/min per 1.73 m2 per year; P =.24), and the lower BP goal did not significantly reduce the rate of the clinical composite outcome (risk reduction for lower BP group = 2%; 95% confidence interval [CI], -22% to 21%; P =.85). None of the drug group comparisons showed consistent significant differences in the GFR slope. However, compared with the metoprolol and amlodipine groups, the ramipril group manifested risk reductions in the clinical composite outcome of 22% (95% CI, 1%-38%; P =.04) and 38% (95% CI, 14%-56%; P =.004), respectively. There was no significant difference in the clinical composite outcome between the amlodipine and metoprolol groups. CONCLUSIONS: No additional benefit of slowing progression of hypertensive nephrosclerosis was observed with the lower BP goal. Angiotensin-converting enzyme inhibitors appear to be more effective than beta-blockers or dihydropyridine calcium channel blockers in slowing GFR decline.

Adrenergic beta-Antagonists↗

PubMed2002

Successful blood pressure control in the African American Study of Kidney Disease and Hypertension.

BACKGROUND: The African American Study of Kidney Disease and Hypertension (AASK) is an ongoing trial to evaluate the effect of blood pressure and choice of antihypertensive drug on the rate of decline of renal function. OBJECTIVE: To present the success of the AASK in achieving the trial's rigorous blood pressure goals in an extremely challenging patient population. METHODS: The AASK participants included African American patients with hypertension (n = 1094), aged 18 to 70 years, with glomerular filtration rates between 20 and 65 mL/min per 1.73 m(2) and no other identified causes of renal insufficiency. Participants were randomized to a goal mean arterial blood pressure (MAP) of either 102 to 107 mm Hg (usual MAP goal) or 92 mm Hg or less (low MAP goal). Participants in each of these groups were also randomized (double-blind) to a regimen containing metoprolol succinate, ramipril, or amlodipine besylate. Additional agents were added, if required, in the following recommended order: furosemide, doxazosin mesylate, clonidine hydrochloride, or hydralazine hydrochloride (or minoxidil, if needed). RESULTS: In participants randomized to the low MAP goal, the percentage of participants who achieved a blood pressure of less than 140/90 mm Hg increased from a baseline of 20.0% to 78.9% by 14 months after randomization. For usual MAP goal participants, the corresponding percentages increased from 21.5% to 41.8%. The difference in median levels of MAP between the 2 MAP goal groups increased and remained at approximately 12 mm Hg. Blood pressure reduction was similar regardless of age, sex, body mass index, education, insurance or employment status, income, or marital status. CONCLUSION: The blood pressure goals set and achieved in AASK participants clearly demonstrate that adequate blood pressure control can be achieved even in hypertensive populations whose blood pressure is the most difficult to control.

Adolescent↗

PubMed2002

Serum C-reactive protein and leptin as predictors of kidney disease progression in the Modification of Diet in Renal Disease Study.

BACKGROUND: In vitro and in vivo data suggest that markers of inflammation and nutritional status may be risk factors for the progression of chronic kidney disease. METHODS: We investigated whether higher levels of C-reactive protein (CRP) and leptin were risk factors for progression of chronic kidney disease in the Modification of Diet in Renal Disease (MDRD) Study. Frozen samples were assayed for high sensitivity C-reactive protein (CRP) or leptin in 804 patients. CRP and leptin were then evaluated as risk factors for glomerular filtration rate (GFR) decline using univariate and multivariable analyses. RESULTS: At baseline, the mean (median) CRP in Study A (GFR between 25 and 55 mL/min/1.73 m2) and Study B (GFR between 13 and 24 mL/min/1.73 m2) were 0.48 (0.25) and 0.46 (0.20) mg/dL, respectively, while the mean (median) leptin in Study A and Study B were 15.2 (9.80) and 15.1 (7.80) ng/mL, respectively. Mean follow-up time was 2.2 years. The mean GFR decline was -4.33 and -3.65 mL/min/year in Study A and B, respectively. There was no significant association between the rate of GFR decline with the level of CRP or leptin in multivariable analysis in Study A [0.08 (-0.14, 0.30) mL/min/year slower GFR decline per twofold increase in CRP level; and 0.14 (-0.13, 0.40) mL/min/year slower GFR decline per twofold increase in leptin level], or in multivariable analysis in Study B [-0.05 (-0.28, 0.18) mL/min/year faster GFR decline per twofold increase in CRP level; and -0.12 (-0.42, 0.19) mL/min/year faster GFR decline per twofold increase in leptin level]. CONCLUSIONS: Higher serum levels of CRP and leptin are not independent risk factors for progression of non-diabetic kidney disease.

Adolescent↗

PubMed2002

Calibration and random variation of the serum creatinine assay as critical elements of using equations to estimate glomerular filtration rate.

Equations using serum creatinine level, age, sex, and other patient characteristics often are used to estimate glomerular filtration rate (GFR) in both clinical practice and research studies. However, the critical dependence of these equations on serum creatinine assay calibration often is overlooked, and the reproducibility of estimated GFR is rarely discussed. We address these issues in frozen samples from 212 Modification of Diet in Renal Disease (MDRD) study participants and 342 Third National Health and Nutrition Examination Survey (NHANES III) participants assayed for serum creatinine level a second time during November 2000. Variation in serum creatinine level was assessed in 1,919 NHANES III participants who had serum creatinine measured on two visits a median of 17 days apart. Linear regression was used to compare estimates. Calibration of serum creatinine varied substantially across laboratories and time. Data indicate that serum creatinine assays on the same samples were 0.23 mg/dL higher in the NHANES III than MDRD study. Data from the College of American Pathologists suggest that a difference of this magnitude across laboratories is not unusual. Conversely, serum creatinine assays an average of 2 weeks apart have better precision (SD of percentage of difference in estimated GFR, 15%; 90% of estimates within 21%). Errors in calibration make little difference in estimating severely decreased GFR (<30 mL/min/1.73 m2), but result in progressively larger differences at higher GFRs. Both clinical and research use of serum creatinine or equations to estimate GFR require knowledge of the calibration of the serum creatinine assay.

Adult↗

PubMed2002

Homocysteine, cysteine, and B vitamins as predictors of kidney disease progression.

BACKGROUND: Pathological similarities between atherosclerosis and glomerulosclerosis suggest that risk factors for the two processes may be similar. Elevated total homocysteine (tHcy) levels and low B vitamin levels are risk factors for atherosclerosis, but have not been evaluated sufficiently as risk factors for the progression of kidney disease. METHODS: Frozen samples from the Modification of Diet in Renal Disease Study were assayed for serum tHcy, cysteine, pyridoxal 5-phosphate (PLP), folate, and vitamin B12 levels in 804 participants. These factors were evaluated in both continuous and categorical analyses as risk factors for glomerular filtration rate (GFR) decline by using univariate and multivariable analyses. RESULTS: At baseline, mean tHcy levels in study A (GFR, 25 to 55 mL/min/1.73 m2) and study B (GFR, 13 to 24 mL/min/1.73 m2) were 16.9 micromol/L (median, 15.6 micromol/L) and 23.0 micromol/L (median, 20.5 micromol/L), respectively. Mean follow-up was 2.2 years. Mean GFR declines were -4.35 and -3.65 mL/min/y in studies A and B, respectively. There was no significant association between change in GFR with baseline level of tHcy in univariate (-0.26 mL/min/y per 1-SD unit increase in tHcy level; 95% confidence interval [CI], -0.67 to 0.15) or multivariable (-0.18 mL/min/y per 1-SD unit increase in tHcy level; 95% CI, -0.53 to 0.17) analysis in study A or univariate (0.07 mL/min/y per 1-SD unit increase in tHcy level; 95% CI, -0.36 to 0.51) or multivariable (0.24 mL/min/y per 1-SD unit increase in tHcy level; 95% CI, -0.16 to 0.64) analysis in study B. Similarly, higher cysteine levels and lower B vitamin levels were not associated with faster rates of GFR decline in multivariable analysis in either study. CONCLUSION: Higher tHcy or cysteine levels and lower folate, PLP, and vitamin B12 levels are not independent risk factors for progression of nondiabetic kidney disease.

Adolescent↗

PubMed2002

Seasonal variations in clinical and laboratory variables among chronic hemodialysis patients.

Seasonal variations in BP among chronic hemodialysis patients have been reported. It was hypothesized that other characteristics of these patients might also vary with the seasons. Twenty-one clinical and laboratory variables were examined for seasonal variations among 1445 patients enrolled in the Hemodialysis Study, sponsored by the National Institute of Diabetes and Digestive and Kidney Diseases. Mixed-effects models were applied to longitudinal changes (up to 45 mo) for individual patients for 19 of the 21 variables, which were measured at least twice each year, to determine the seasonal component of each variable. Seasonal variations in the other two variables, i.e., protein and energy intakes determined from annual dietary records, were assessed in cross-sectional comparisons of intakes of patients entering the study at different time points. Thirteen of the 21 variables examined demonstrated statistically significant (P < 0.01) seasonal components in their longitudinal variations. Predialysis blood urea nitrogen concentrations peaked in March, which coincided approximately with the peak protein catabolic rates, as well as protein and energy intakes (determined by dietary recall). Predialysis systolic and diastolic BP values were highest in winter and lowest in summer, corroborating previous reports. In addition, the lower predialysis BP values in summer were associated with higher outdoor temperatures and less interdialytic fluid gain. The mean predialysis hematocrit values were highest in July, which could not be attributed solely to the estimated changes in plasma volume. Seasonal variations in clinical and laboratory variables occur commonly among chronic hemodialysis patients. The reasons for most of these variations are not apparent and require further investigation. Nonetheless, failure to consider these variations might lead to biases in the interpretation of clinical studies. In addition, awareness of these variations might facilitate the interpretation of laboratory results and the clinical treatment of these patients.

Adult↗