A study of the extracorporeal rate of blood flow and blood pressure during hemodialysis.

Hemodynamic instability is a common problem during hemodialysis (HD). The effect of blood flow rate (BFR) on blood pressure (BP) during HD has not been previously evaluated. Subjects receiving HD for the treatment of renal failure were enrolled (n=34). For each patient, during the last hour of 2 consecutive HD sessions the BFR was set at 200 mL/min for 30 min and at 400 mL/min for 30 min, during which period the fluid removal rate was kept constant. The order of the BFR alterations was randomized. The study procedure was repeated during the next HD session but with reversal of the order of the altered BFR. During each 30-min period, BP was recorded at baseline and subsequently every 10 min. During the BFR of 400 mL/min, subjects had a higher systolic BP by an average of 4.1 mmHg compared with the BFR of 200 mL/min (95% confidence interval [CI] 0.22-7.98; p=0.038). Similarly, during the BFR of 400 mL/min, subjects had a higher diastolic BP by an average of 3.04 mmHg compared with the BFR of 200 mL/min (95% CI 0.55-5.53; p=0.017). Likewise, during the BFR of 400 mL/min, subjects had a higher mean arterial pressure by an average of 3.44 mmHg (95% CI 0.77-6.11; p=0.012). The findings suggest that during HD, BPs are maintained higher at higher BFRs as compared with lower BFRs.

Predictors of hospitalization in patients on peritoneal dialysis: the Missouri experience.

BACKGROUND: We analyzed a large number of demographic and biochemical variables to identify predictors of hospitalization in subjects on peritoneal dialysis (PD). METHODS: All patients initiated on PD at our center from January 1990 through December 1999 were included. The following variables at the initiation of PD were included: demographics, clinical data, nutritional and adequacy parameters, transport characteristics, and various co-morbidities. Co-morbidities were graded for severity using a modified version of the Index of Coexistent Disease. Variables included during the course of PD consisted of weighted time average of a number of laboratory, adequacy, and nutritional parameters along with the number of peritonitis episodes per year. Stepwise linear regression was used following a univariate screening procedure to identify independent predictors of the outcome of hospitalization days per month on PD. RESULTS: The subject population consisted of 191 subjects (105 men, 86 women; 180 Caucasians, 10 African-American, 1 Asian). The mean age was 61 +/- 13 (SD) years and mean duration of follow-up was 21 +/- 18 months. The baseline variable analysis revealed that the presence of partner to perform PD predicted increased hospitalization (p < 0.0001). Additionally, the presence and severity of peripheral vascular disease and residual renal Kt/V at baseline (negative association) predicted increased hospitalization. In the analyses of ongoing variables, stepwise linear regression solely identified weighted time average albumin as a strong negative predictor of hospitalization (p < 0.0001). CONCLUSION: A comprehensive analysis of a large number of variables revealed that serum albumin during the course of PD (negative association) and the need for partner to perform PD strongly predicted increased hospitalization in PD subjects.

Subnormal rise of erythropoietin in patients receiving interferon and ribavirin combination therapy for hepatitis C.

OBJECTIVES: Anemia is a common complication during interferon-ribavirin therapy for hepatitis C. While normally a fall in hematocrit in results in an exponential compensatory rise in erythropoietin, such that the correlation between hematocrit and erythropoietin is sharply negative, the erythropoietin response during interferon-ribavirin combination therapy is not known. METHODS: We measured the hematocrit and erythropoietin levels before and after about 4 weeks of interferon-ribavirin therapy for hepatitis C (n = 43), and compared their relation to the normal human response to anemia. RESULTS: The hematocrit fell from an average pre-treatment level of 43.7 +/- 3.7% to 36.9 +/- 5 (P < 0.0001). The erythropoietin level rose from 14.5 +/- 15.1 to 58.5 +/- 94.1 units/L (P < 0.0001), indicating there was an adequate stimulus for erythropoietin release. The rise of erythropoietin was severely impaired in relation to the normal human response to a fall in hematocrit. Using the normal human response to anemia as the population line, for our population there was a significant difference in the slope of hematocrit (x) versus log10 erythropoietin (y) (-8.7 vs. -3.098 respectively, P < 0.001) and y-intercept (4.609 vs. 2.753 respectively, P < 0.001). The Bonferroni adjusted "p" value was derived to be <0.002. There was an approximate 2 log10 reduction in maximal achievable erythropoietin level in subjects exposed to interferon-ribavirin combination. CONCLUSION: There is a subnormal rise of erythropoietin after interferon-ribavirin combination therapy for hepatitis C.

Discrepancy in the epidemiology of nondiabetic chronic renal insufficiency and end-stage renal disease in black and white Americans: the third National Health and Nutrition Examination Survey and United States Renal Data System.

BACKGROUND: Epidemiologic data regarding the prevalence of chronic renal insufficiency (CRI) [from the third National Health and Nutrition Examination Survey (NHANES III)] and the incidence of end-stage renal disease (ESRD) [from the United States Renal Data System (USRDS)] are available. However, reconciliation of these separate particulars has not been performed objectively. The present work examines the epidemiology of CRI of nondiabetic etiology and ESRD in black and white Americans aged 20 years or greater. METHODS: Based on the incidence of ESRD in the study population (USRDS), the numbers of subjects with decreased Modification of Diet in Renal Disease (MDRD) glomerular filtration rate (GFR) <80 ml/min/1.73 m(2), <60 ml/min/1.73 m(2) and <30 ml/ min/1.73 m(2) in 1991 (on December 31 1991) were mathematically obtained based on a linear model of GFR decline. Similarly, the corresponding estimated prevalence figures of CRI were derived based on analyses of NHANES III data and the 1991 census counts of black and white Americans (aged 20 years or more). Unadjusted and adjusted (correcting for calibration differences between the NHANES III and MDRD laboratory) prevalences were calculated. Subsequently, the prevalence of different degrees of CRI based on the incidence of ESRD (USRDS) was compared to the corresponding figures of the estimated prevalence of CRI (NHANES III). RESULTS: By analyses of USRDS data, on December 31 1991, the prevalence of different degrees of reduced GFR in the study population was estimated to be as follows: 396,863 subjects with GFR <80 ml/min/1.73 m(2); 272,932 subjects with GFR <60 ml/min/1.73 m(2), and 115,065 subjects with GFR <30 ml/min/1.73 m(2). Using actual NHANES III creatinine values, the prevalence of different degrees of CRI in the study population was estimated as follows: 92,595,211 people with GFR <80 ml/min/1.73 m(2); 20,754,099 people with GFR <60 ml/min/1.73 m(2), and 415,082 people with GFR <30 ml/min/1.73 m(2). The data suggest that approximately 0.43% of subjects with GFR <80 ml/min/1.73 m(2), 1.32% of subjects with GFR <60 ml/min/1.73 m(2) and 27.72% of subjects with GFR <30 ml/ min/1.73 m(2) reached ESRD (USRDS). Using adjusted NHANES III creatinine values (downwardly correcting the NHANES III creatinine values to account for calibration differences with the MDRD measurements), the prevalence of different degrees of CRI in the study population was estimated as follows: 28,512,939 people with MDRD GFR <80 ml/min/1.73 m(2) (17.86%); 5,364,136 people with MDRD GFR <60 ml/min/1.73 m(2) (3.36%), and 255,435 people with MDRD GFR <30 ml/min/1.73 m(2) (0.16%). Of these, about 1.39% of the people with MDRD GFR <80 ml/min/1.73 m(2), 5.09% of the people with MDRD GFR <60 ml/min/1.73 m(2) and 45.07% of the people with MDRD GFR <30 ml/min/1.73 m(2) in 1991 reached ESRD. CONCLUSION: There is a major discrepancy in the epidemiology of nondiabetic CRI and ESRD amongst black and white Americans. The reasons for this need further study.

A randomized prospective trial to assess the role of saline hydration on the development of contrast nephrotoxicity.

Though simple and attractive, the role of hydration for the prophylaxis of contrast nephrotoxicity has not been definitively established. We prospectively evaluated the role of deliberate saline hydration in patients undergoing nonemergency cardiac catheterization. Patients (n = 53) were randomized on the day prior to scheduled catheterization to one of two groups - group 1 (n = 27) received normal saline for 24 h (at a rate of 1 ml/kg/h) beginning 12 h prior to scheduled catheterization, and group 2 (n = 26) were allowed unrestricted oral fluids. Serum creatinine measured 24 and 48 h postcardiac catheterization was compared to the pre-randomization baseline value. The mean baseline calculated creatinine clearance was 79.6 +/- 31.9 ml/min and the mean baseline creatinine was 106 +/- 28 micromol/l. An increase in serum creatinine by at least 44.2 micromol/l (0.5 mg/dl), within 48 h of contrast exposure, was considered to represent clinically significant acute renal insufficiency. Ten subjects (18.9%) developed acute renal insufficiency. The incidence of acute renal insufficiency was significantly lower in group 1 (1 out of 27) as compared to group 2 (9 out of 26; p = 0.005 for comparison between groups; relative risk 0.11, 95% confidence interval 0.015 to 0.79). Twenty-four hours after contrast exposure, the mean increase in creatinine was less in group 1 vs. group 2 (8 +/- 11 vs. 20 +/- 21 micromol/l, p = 0.02). The increase in creatinine was not significantly different in group 1 vs. group 2 48 h after contrast exposure (12 +/- 21 vs. 29 +/- 40 micromol/l, p = 0.17). Deliberate saline hydration decreases the incidence of contrast-related acute renal failure and the severity of contrast-induced renal dysfunction in patients undergoing non-emergency cardiac catheterization.

Erythropoietin therapy in pre-dialysis patients with chronic renal failure: lack of need for parenteral iron.

BACKGROUND: During erythropoietin therapy, scant information exists regarding the optimal target percent saturation of transferrin (TSAT), ferritin and the mode and amount of iron supplementation in pre-dialysis patients with anemia due to chronic kidney disease (CKD). HYPOTHESIS: Pre-dialysis CKD patients may have different needs for iron supplementation than end-stage renal disease subjects during erythropoietin therapy. METHODS: Retrospective analysis of pre-dialysis CKD subjects (n = 31) treated with erythropoietin at our institution. RESULTS: In this population our results showed that target hematocrit (33-36%) was achievable with erythropoietin (mean subcutaneous dose 86 +/- 17 [SD] units/kg/week) without parenteral iron therapy. The hematocrit increased from a mean baseline value of 28.4 +/- 2.7 to 33.6 +/- 3.4% at time 1 (4-9 weeks, p < 0.0001), and to 37.7 +/- 4.5% at time 2 (10-20 weeks, p < 0.0001). The hemoglobin concentration increased from 9 +/- 0.9 g/dl at baseline to 10.7 +/- 1.1 g/dl at time 1 (p < 0.0001) and to 12 +/- 1.5 g/dl at time 2 (p < 0.0001). Subgroup analyses of patients prescribed <200 mg oral elemental iron per day (n = 10), those with TSAT <20% and/or ferritin <100 ng/ml (n = 19), and those prescribed erythropoietin <80 units/kg/week (n = 12), all showed a significant increase in hematocrit and hemoglobin. CONCLUSIONS: Our data show that pre-dialysis CKD subjects respond adequately to erythropoietin at or lower than recommended erythropoietin doses without parenteral iron. This response extends even to subgroups with TSAT and/or ferritin levels deemed to indicate iron deficiency in CKD subjects, and may be due to lack of existence of functional iron deficiency in this group of patients.

Slowing the progression of chronic renal failure: economic benefits and patients' perspectives.

Because of the predicted increase in end-stage renal disease (ESRD) incidence (projected increase from 1998 to 2010; 86,825 to 172,667), prevalence (projected increase from 1998 to 2010; 326,217 to 661,330), and cost (total cost based on 1998 ratio of Medicare versus non-Medicare cost; $16.74 billion in 1998 to $39.35 billion in 2010), a cohesive national effort is needed to develop strategies to slow the progression of chronic renal failure (CRF). The question arises to how much reduction in the progression of CRF would lead to a meaningful decrease in the prevalence and cost of ESRD. There are no objective data that show the economic impact of slowing the progression of CRF. We developed a mathematical model to assess the economic impact of decreasing the progression of CRF by 10%, 20%, and 30%. US Renal Data System (USRDS) projections were used to model the rate of increase in ESRD incidence and prevalence. Glomerular filtration rate (GFR) at the initiation of ESRD therapy and cost per patient-year were based on USRDS data. The average decline in GFR in subjects with CRF was estimated to be 7.56 mL/min/y. All dollar savings reflect 1998 costs, discounted for the future at 3% per annum. We also determined how much slowing of the progression of CRF is important from patients' perspectives by means of a written questionnaire (which inquired about willingness to go on a restricted diet, take six extra medications per day, and make six extra office visits per year) and calculation of the pre-ESRD time gained for different degrees of reduction in the progression of CRF. If the rate of decline in GFR decreased by 10%, 20%, and 30% after December 31, 1999, in all patients with GFRs of 60 mL/min or less, cumulative direct healthcare savings through 2010 would equal approximately $18.56, $39.02, and $60.61 billion, respectively. For a 10%, 20%, and 30% decrease in the rate of decline in GFR in all patients with a GFR of 30 mL/min or less, estimated cumulative savings through 2010 equal $9.06, $19.98, and $33.37 billion, respectively. Responses to the questionnaire showed that approximately 79% of subjects with CRF (n = 113) perceived a few weeks' dialysis-free period significant (P < or = 0.0001), a period corresponding to a 10% reduction in the rate of decline in GFR. Our data suggest that the cumulative economic impact of slowing the progression of CRF, even by as little as 10%, would be staggering. They provide strong support for the development and implementation of intensive reno-protective efforts beginning at the early stages of chronic renal disease and continued throughout its course.