John C. Van Stone

Intravenous versus subcutaneous dosing of epoetin alfa in hemodialysis patients.

Hemodialysis patients were studied to determine whether the dose of recombinant human erythropoietin (Epoetin alfa; Amgen Inc, Thousand Oaks, CA) required to maintain a therapeutic hematocrit level changed when the route of administration was switched from intravenously (IV) three times per week to subcutaneously (SC) three times per week. Thirteen to 16 weeks after patients were changed from IV three times per week to SC three times per week treatment, the Epoetin alfa requirement was reduced by 18.5% +/- 3.8% (P < 0.001; n = 72), and after 21 to 24 weeks of SC treatment the mean dosage had decreased from the IV dose by 26.5% +/- 4.2% (P < 0.001; n = 41). Sixty-one percent (44 of 72) of patients experienced maintenance-dose reductions over 13 to 16 weeks of treatment and 80% (33 of 41) were maintained on lower weekly doses after 21 to 24 weeks of treatment than at baseline (IV). There was interpatient variability, however: 26% of the patients required greater doses SC than IV following 13 to 16 weeks of SC treatment, and 15% required greater doses SC than IV following 21 to 24 weeks. On completing the initial SC three-times-per-week stage of the study, patients were randomized to one of three SC dosing strategies for an additional 12 weeks: (1) once per week, (2) three times per week Epoetin alfa diluted 1:2 with bacteriostatic saline to mitigate stinging at the injection site, or (3) continued three times per week with undiluted Epoetin alfa. Patients who were switched to administration of SC once per week undiluted Epoetin alfa (n = 20) had their total weekly dose lowered by 18.0% +/- 9.4% (P > 0.05), but the mean hematocrit for this cohort also decreased, from 34.3% +/- 3.0% to 32.4% +/- 3.9% (P > 0.05), rendering dose comparison between the two schedules ambiguous. The maintenance dose for patients who received Epoetin alfa diluted 1:2 with bacteriostatic saline (n = 23) did not differ from the undiluted three times per week dose at the end of stage 1. The third cohort of patients (n = 24), who continued to receive undiluted Epoetin alfa on the same SC three-times-per-week schedule, did not require a significant change in dosage over the ensuing 12 weeks. Comparison of SC three times per week mean dosage after an average of 32 weeks following the switch from IV three times per week for this latter cohort revealed a decrease of 23.5% +/- 6.5% (P < 0.001).(ABSTRACT TRUNCATED AT 400 WORDS)

Effect of hemodialysis on left ventricular performance. Analysis of echocardiographic subsets

To assess the effect of hemodialysis on left ventricular performance, we performed M-mode echocardiography on 31 patients with end-stage renal disease prior to and immediately following 4-hour chronic maintenance hemodialysis. Overall, hemodialysis produced a significant increase in mean heart rate and the mean velocity of circumferential fiber shortening (mean Vcf), a significant decrease in mean stroke index and no significant change in mean cardiac index. Hemodialysis resulted in a significant increase in mean Vcf in the subset of patients with reduced mean Vcf prior to dialysis, but produced no significant change in mean Vcf in the group with normal predialysis mean Vcf. Hemodialysis resulted in a significant increase in mean Vcf in the subset of patients with normal left ventricular end-diastolic volume prior to dialysis, but produced no significant change in mean Vcf in the group with increased predialysis left ventricular end-diastolic volume. The presence of left ventricular hypertrophy appeared to blunt the expected increase in mean Vcf in the group with reduced mean Vcf prior to hemodialysis. These results suggest that predialysis left ventricular volume, wall thickness and contractility are important determinants of the effect of hemodialysis on left ventricular performance.

The Effect of Dialysate Sodium Concentration on Body Fluid Compartment Volume, Plasma Renin Activity and Plasma Aldosterone Concentration in Chronic Hemodialysis Patients

Six stable chronic hemodialysis patients received six hemodialysis treatments: two each with the dialysate sodium concentration (DNa) 7% greater than serum sodium concentration, two with a DNa equal to serum sodium concentration and two with the DNa 7% less than the serum sodium concentration. During one treatment with each dialysate 2 kg of fluid was removed and during the other treatments the patients weight was kept constant. Total body water (TBW), intracellular water (ICW), extracellular water (ECW), plasma volume (PV), plasma renin activity (PRA), aldosterone (ALDO), Na, BUN and osmolality were determined before and after each treatment. Fluid removal during dialysis had no effect on ICW with essentially all the fluid removed during dialysis coming from ECW. ICW increased with low DNa and decreased with high DNa. The effect of DNa on ECW and PV was the opposite of that on ICW. PRA increased and ALDO decreased during dialysis. Predialysis ALDO directly correlated with PRA (r = 0.68, p less than 0.001) but not with serum potassium concentration. Post dialysis ALDO was not significantly correlated with either PRA or potassium. Fluid removal and low DNa increased both PRA and ALDO. These studies indicate that water shifts from the extracellular space into intracellular space when DNa is lower than serum Na and the reverse is true when DNa exceeds serum Na. Plasma aldosterone decreases during dialysis despite an increase in PRA, possibly related to the decrease in serum potassium concentration. The effect of fluid removal and low DNa on PRA and ALDO may be related to a reduction in ECW and/or PV.

Detection of hemodialysis access outlet stenosis by measuring outlet resistance

Stenosis of the outflow segment of hemodialysis access grafts frequently leads to thrombosis and loss of the access. Previous studies have shown that early detection and correction of the stenosis can prevent graft failure. The purpose of the present study was to compare four methods of detecting outflow segment stenosis: measurement of the pressure in the venous line during dialysis, measurement of the pressure in the distal portion of the access graft, measurement of the relative resistance of the outflow segment of the graft relative to the total resistance of the graft, and measurement of recirculation of venous dialysis blood into the dialysis arterial line. The graft pressure was determined by measuring the pressure in the dialysis venous line with the blood pump turned off. The relative resistance of the outflow segment was determined by dividing the graft blood flow-induced pressure decrease across this segment by the difference between mean systemic arterial and venous pressures. Sixty-eight chronic hemodialysis patients were followed prospectively for 11 months. Sixty-nine complications occurred in 31 accesses in 24 patients. Outlet obstruction was present in 21 of the 31 accesses. Relative graft resistance and recirculation rate measurement were found to be most useful in detecting hemodialysis access outlet obstruction.

Effects of nicotinic acid and lovastatin in renal transplant patients: a prospective, randomized, open-labeled crossover trial.

Lipid abnormalities are seen frequently in renal transplant patients. Cardiovascular disease is an important cause of morbidity and mortality in these patients. We assessed the efficacy and safety of the lipid-lowering drugs, nicotinic acid (short acting) and lovastatin, the 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitor. Twelve renal transplant patients who had persistent hyperlipidemia despite 6 weeks of dietary treatment participated in this prospective, randomized, open-labeled crossover trial. At 16 weeks, when compared with control values, nicotinic acid (> or = 1.5 g twice a day) significantly reduced the total cholesterol (from 312 +/- 18 [+/- SEM] mg/dL to 229 +/- 19 mg/dL; P = 0.03) and the low-density lipoprotein cholesterol (from 218 +/- 15 mg/dL to 142 +/- 13 mg/dL; P = 0.03) and significantly increased the high-density lipoprotein cholesterol (from 44 +/- 3 mg/dL to 58 +/- 5 mg/dL; P = 0.03). The triglyceride level was reduced from 255 +/- 40 mg/dL to 150 +/- 23 mg/dL (P = 0.09). At 16 weeks, lovastatin therapy (40 mg/d) significantly reduced the total cholesterol (from 285 +/- 13 mg/dL to 233 +/- 10 mg/dL; P = 0.005) and the low-density lipoprotein cholesterol (from 201 +/- 11 mg/dL to 147 +/- 7 mg/dL; P = 0.001). There were no significant changes in the triglyceride and high-density lipoprotein cholesterol levels. Although flushing developed in 67% of patients treated with nicotinic acid, this was not a reason for any of the study dropouts. During this short-term study period no adverse biochemical effects were noted with either of the drugs.(ABSTRACT TRUNCATED AT 250 WORDS)

Benign Intracranial Hypertension: A Complication of Subclavian Vein Catheterization and Arteriovenous Fistula

Thrombosis of the right innominate vein occurred in a patient on maintenance hemodialysis following repeated subclavian vein catheterization. The patient had a functional right brachial arteriovenous fistula for blood access that resulted in a massive retrograde blood flow into the cerebral venous system with the development of the benign intracranial hypertension. The symptoms and signs of intracranial hypertension abated following ligation of the arteriovenous fistula. This unusual association of benign intracranial hypertension with an arteriovenous fistula and innominate vein thrombosis has not been reported previously. Pertinent literature dealing with benign intracranial hypertension and complications of subclavian vein catheterization is reviewed.

Actuarial Analysis of Patient Survival and Dropout With Various End-Stage Renal Disease Therapies

Life table analyses were applied to experiences at the University of Missouri over a 5-year period with center hemodialysis, home hemodialysis, continuous ambulatory peritoneal dialysis (CAPD), living related donor transplantation, and cadaveric transplantation. Patient survival, graft survival, and persistence on therapy were analyzed. Mean ages and the percentage of insulin-treated diabetics were not similar in all groups; many factors influenced the choice of therapy by patient and physician. Nevertheless, the results show the net outcomes of these different therapies at an institution that has offered them all over the 5-year period analyzed. Patient survival and persistence on therapy for CAPD fell within the range of the other forms of therapy. Based on predictions of patient survival from published experiences with end-stage renal disease (ESRD) populations, observed survivals in CAPD were close to those predicted for the age of the population. At 2 years, persistence on therapy (technique survival) was similar for center hemodialysis and CAPD. However, 88% of the nondeath dropouts from center hemodialysis were for kidney transplantation, while 12% were related to technique problems. In contrast, in CAPD only 14% of the nondeath dropouts were for a kidney transplantation, 10% were based on recovery of renal function, and 76% were related to dialysis therapy problems. Nondeath dropouts from home hemodialysis were more similar to those in CAPD, with only 33% for kidney transplantation and 67% for therapy problems. These results cannot be assumed to indicate that the choice of therapy influences outcome. They show net outcomes in a single program are most likely based on multiple factors (age, diabetes mellitus, cardiac status, patient selection bias, physician selection bias, and perhaps the therapy per se) that influence these indices of success. To our knowledge these are the first comparisons of the net outcomes of all these forms of therapy at a single institution over the same period of time.

The amount of sodium removed by hemodialysis.

The amount of sodium removed by hemodialysis was estimated, without using radioisotopes, as the change in total osmotically active cations, which is the product of the serum sodium concentration and urea-space. The extracellular and total body fluid volumes were measured using 35SO4 and 3H2O, respectively, in five stable hemodialysis patients under four different conditions. Urea-space determined, based on urea kinetics, was consistent with total body fluid volume measured by 3H2O. The amount of sodium removal, estimated as the change in the product of the serum (Na+) and urea-space, was equal to the change in the sodium content, which is the product of the serum (Na+) and extracellular fluid volume measured by 35SO4. Sodium removal may be divided into two components, diffusion and ultrafiltration.

Controlling Thirst in Dialysis Patients

Thirst is a sensation that many if not most dialysis patients are all too familiar with. Giovannetti and coworkers found that 86% of chronic hemodialysis patients have excessive thirst (1). Many peritoneal dialysis patients also complain of increased thirst. This analysis reviews factors which affect thirst with particular emphasis on those of particular importance in ESRD patients. There are at least six major factors affecting thirst: plasma sodium concentration, potassium depletion, angiotensin 11, acute increases in plasma urea, hyperglycemia and psychological factors. In spite of the importance that many ESRD patients attach to thirst there has been a paucity of research done in this area in these patients.

Effect of Hemodialysis on Left Ventricular Systolic Function in the Presence and Absence of Beta-Blockade: Influence of Left Ventricular Mass

To assess the effect of hemodialysis on the left ventricular (LV) systolic function in the presence and absence of beta blockade, we performed echocardiography just prior to and immediately after 4-hour maintenance hemodialysis in 38 patients with end-stage renal disease. The LV systolic function was assessed in subgroups with normal and increased LV mass in both the beta blockade group (n = 19) and the non-beta blockade group (n = 19). There was a significant negative correlation between LV mass and the dialysis-induced change in the mean velocity of LV circumferential fiber shortening (mean Vcf) in both the beta blockade group (r = -0.93; p less than 0.0005) and in the non-beta blockade group (r = -0.82; p less than 0.0005). The mean dialysis-induced change in mean Vcf in the subgroup with increased LV mass in the beta blockade group (-0.02 +/- 0.11 circumferences/s) was significantly lower than the mean dialysis-induced change in mean Vcf in the non-beta blockade group (+0.12 +/- 0.04 circumferences/s; p less than 0.0005). Thus, the coexistence of increased LV mass and beta blockade significantly impedes the expected improvement of LV systolic function associated with hemodialysis.