The effect of an exercise program during hemodialysis on dialysis efficacy, blood pressure and quality of life in end-stage renal disease (ESRD) patients.

AIM: We wished to determine if an 8-week program of exercise during dialysis in end-stage renal disease (ESRD) patients would increase urea removal (enhance dialysis efficacy) with subsequent improvements in work performance and perception of quality of life, and/or alterations in cardiovascular status. METHODS: Self-care hemodialysis patients (EX, n = 6) performed cycle ergometry exercise 3 times per week during their dialysis session at 40-50% maximal work capacity for 15 min during each of the first 3 hours of dialysis and were matched for age, protein catabolism rate, and WLmax with a CON group (n = 7). Dialysis efficacy was measured using serum urea clearance (Kt/V) and dialysate urea clearance (DUC) during the first 2 hours of dialysis. Resting blood pressure was monitored on a sessional basis, pre- and postdialysis and during exercise in the EX group. QOL, measured using the SF-36 questionnaire, and WLmax were determined prior to and at 4 and 8 weeks of the exercise program. RESULTS: DUC was significantly elevated in the EX group at the end of the exercise program, but was of insufficient magnitude to result in an overall increase in Kt/V. DUC decreased in the CON group but Kt/V remained unchanged. No changes in resting blood pressure occurred in either group over the course of the study, however, pulse pressure tended to increase in the CON group but decrease in the EX group, indicating a potential beneficial adaptation of the cardiovascular system in patients undergoing an exercise program. The exercise program had no effect on QOL scores and this was most likely due to the short duration of the exercise program and high-functioning level of the population studied as compared to normative data for this patient population. We also found that 33% of the exercise sessions in the 3rd hour of dialysis were not performed due to hypotensive events. CONCLUSION: Exercise during dialysis enhanced dialysate urea removal but not serum urea clearance. Alterations in the modality and the timing of exercise during dialysis may be required to elicit increases in serum urea clearance. It is also recommended that exercise during dialysis be performed during the first 2 hours of dialysis.

Elevated levels of serum creatinine: recommendations for management and referral.

BACKGROUND: The potential benefits of earlier referral to a nephrologist of patients with elevated levels of serum creatinine include identifying and treating reversible causes of renal failure, slowing the rate of decline associated with progressive renal insufficiency, managing the coexisting conditions associated with chronic renal failure and facilitating efficient entry into dialysis programs for all patients who might benefit. METHODS: A subcommittee of the Canadian Society of Nephrology, which included representatives from family practice and internal medicine, conducted a MEDLINE search for the period 1966 to 1998 using the key words referral and consultation, dialysis, hemodialysis, peritoneal dialysis, renal replacement therapy and kidney diseases. Where published evidence was lacking, conclusions were reached by consensus. GUIDELINES: Earlier referral to nephrologists of patients with elevated creatinine levels is expected to lead to better health care outcomes and lower costs for both the patients and the health care system. All patients with newly discovered renal insufficiency (as evidenced by serum creatinine elevated to a level above the upper limit of the normal range of that laboratory, adjusted for age and height in children) must undergo investigations to determine the potential reversibility of disease, to evaluate the prognosis and to optimize planning of care. All patients with an established, progressive increase in serum creatinine level should be followed with a nephrologist. Adequate preparation for dialysis or transplantation (or both) requires at least 12 months of relatively frequent contact with a renal care team. Nephrologists should provide consultation in a timely manner for any patient with an elevated serum creatinine level. In addition, they should provide advice about what aspects of the condition require particularly urgent or emergency assessment. SPONSORS: This clinical practice guideline has been endorsed by the Canadian Society of Nephrology and the College of Family Physicians of Canada. Meeting, teleconference and travel expenses of the Referral Guideline Subcommittee were covered by The Momentum Program, a collaboration between Baxter Corp. and Janssen-Ortho Inc. However, the authors are solely responsible for the editorial content of this article.

The pathophysiology and management of renal bone disease in dialysis patients.

As renal function declines, changes in mineral metabolism occur including phosphate retention, calcitriol deficiency, and the development of secondary hyperparathyroidism. Renal bone disease related to disordered mineral metabolism may result in increased patient morbidity and mortality. Uncontrolled parathyroid hormone (PTH) secretion will result in osteitis fibrosa, a high turnover bone disease. The use of calcium and aluminum-based phosphate binders and vitamin D sterols may contribute to the development of low turnover bone diseases such as osteomalacia and aplastic bone disease. Prevention and control of renal bone disease is an important goal for the interdisciplinary health care team. This paper discusses disordered mineral metabolism and its relationship to renal bone disease. Case studies illustrate the development and treatment of renal bone disease related to secondary hyperparathyroidism and aluminum intoxication.

Reducing complications during hemodialysis using gradient ultrafiltration with gradient sodium dialysate.

The objective of this study was to determine if patient complications and nursing interventions during hemodialysis could be reduced using gradient ultrafiltration and gradient sodium dialysate. Twenty outpatients who had been on hemodialysis for at least 3 months, and using gradient sodium dialysate for at least 1 month, participated. Patients received either ultrafiltration at a constant hourly rate or gradient ultrafiltration, in which the ultrafiltration rate was set higher initially, then decreased step-wise mid-dialysis. Patients received each protocol for 3 months, using a randomized cross-over design. Both protocols used gradient sodium dialysate (150 mEq/L x 3 hrs, 140 mEq/L x 1 hr). There were significantly fewer complications and interventions using gradient ultrafiltration, as compared to constant ultrafiltration. No differences were found in interdialytic weight gain, intradialytic weight loss, or orthostatic blood pressure. These results indicate that gradient ultrafiltration combined with gradient sodium dialysate enhances patient well-being and reduces nursing interventions during hemodialysis.

Tissue plasminogen activator (t-PA) efficacy in the restoration of hemodialysis catheter function.

Thrombus formation within hemodialysis catheters contributes to inadequate dialysis and adverse patient outcomes. A thrombolytic agent may be required to restore patency and improve blood flow. This study evaluates the efficacy of instilling low dose (1 mg/ml) t-PA in catheter lumens to restore patency in malfunctioning catheters. t-PA was utilized to treat suspected catheter thrombus over a four-month period. Seventeen patients with 21 catheters (12 temporary, 9 permanent) received 40 doses of t-PA. Catheter function was restored in 39 of 40 cases (97.5%). Significant improvement in blood flow was confirmed by paired t-test (p < 0.001). Sustained improvement in blood flow was confirmed by ANOVA (p < 0.001). The mean primary patency of all catheters was 29.7 days (SD = 27.0 days). No adverse patient effects were noted. These results demonstrate that t-PA can safely and effectively restore blood flow and extend patency in hemodialysis catheters.

Urokinase efficacy in the restoration of hemodialysis catheter function.

Thrombus formation is a common cause of hemodialysis catheter malfunction. When thrombus or fibrin sheath restrict the flow of blood through one or both lumens, the catheter may need to be replaced. A less invasive, potentially lower cost option may be the instillation of low dose urokinase to degrade fibrin and restore catheter function. This study examines the efficacy of urokinase in improving blood flow and maintaining catheter patency. In a one-year period, urokinase was utilized in 25 dual lumen hemodialysis catheters (20 temporary, five permanent) in 22 patients. Blood flow and arterial and venous pressures were monitored before and after instillation. Urokinase administration successfully restored function in 20 catheters (80%). Paired t-tests demonstrated a significant improvement in blood flow and arterial pressure (p < 0.01) following urokinase. Catheter patency was extended for a mean of 18.0 days (range 0-90 days). The cost effectiveness of urokinase was evaluated in terms of direct costs, such as the cost of urokinase or materials to replace catheters, and indirect costs such as nursing and physician time and delays in dialysis scheduling. The results of this study suggest that judicious use of urokinase is a cost-effective, non-invasive method of restoring blood flow and extending patency in hemodialysis catheters.

Quantity of dialysis: quality of life--what is the relationship?

Health related quality of life (HRQOL) is increasingly being used to evaluate physical and psychosocial parameters in patients receiving dialysis. In patients with chronic illness, these indices are important adjuncts to biochemical measurements. Inadequate dialysis with low urea clearance (Kt/Vurea) has been linked to adverse outcomes in dialysis patients. Little is known about the relationship between dialysis adequacy and patient reported HRQOL. We evaluated HRQOL in 55 hemodialysis and 60 peritoneal dialysis patients using the RAND 36 Item Health Survey 1.0, measuring the following: physical functioning; role limitations (physical); role limitations (emotional); social functioning; emotional well being; pain; energy; and general health perceptions. Kt/V was also calculated for each patient. Mean HD Kt/V was 1.44 +/- 0.31 (range, 0.5-2.0); mean weekly PD Kt/V was 2.28 +/- 0.90 (range, 1.13-6.02). The relationship between Kt/V and HRQOL was tested using Pearson's correlation. No significant association was found for either treatment group between Kt/V and any of the domains of HRQOL. Thus, HRQOL seems to be influenced by factors other than dialysis adequacy, enhancing its role as an independent measure of patient problems otherwise undetected by traditional objective parameters.

Self-delivery of hemodialysis care: a therapy in itself.

Patient autonomy, sense of control, and well-being are thought to be enhanced by self-care hemodialysis as a therapy for end-stage renal disease. Dialysis in a satellite setting reduces travel time and can diminish therapy intrusiveness. Health-related quality of life (HRQOL), in terms of functional status and well-being, was measured in a group of patients trained for self-care, and then measured again after these patients were transferred to a satellite unit. Comparison was made with an age- and comorbidity-matched cohort of full-care patients. Patients trained for self-care tended to score higher than the full-care patients in the psychosocial domains of HRQOL, such as role function, social function, and emotional well-being, before and after transfer to the satellite unit. Physiological measurements did not differ significantly between groups at any time during the study, indicating that differences in HRQOL were not attributable to differences in metabolic stability. We conclude that patients trained for self-care hemodialysis experience better subjective quality of life than their full-care counterparts. This study highlights both the usefulness of measuring HRQOL as an outcome of hemodialysis therapy and the potential benefits of therapies such as self-care and satellite dialysis.

A comparison of continuous arteriovenous hemofiltration and intermittent hemodialysis in acute renal failure patients in the intensive care unit.

Our experience with high flow CAVH (1-2 L/hr) and intermittent hemodialysis in our combined medical-surgical tertiary care intensive care unit was reviewed. During a 16 month period, 12 patients received CAVH and 23 patients received hemodialysis (3-7 days/week). Mean CAVH treatment duration was 5.5 days (0.5-18 days). Hemodialysis patients received a mean of 4.3 treatments (1-16). CAVH patients had a mean age of 44.5 +/- 16.4 years (19-68), whereas the hemodialysis patients had a mean age of 60.9 +/- 14 years (34-82) (p = 0.004). Mean admission APACHE II score was 21.3 (11-29) for the CAVH group and 25.5 (10-39) for the hemodialysis group (p = NS). Peak ICU APACHE II score did not differ between groups (CAVH 26.2 [11-37], HD 28 [10-40]; p = NS). There were 4 deaths in the CAVH group (25%) and 19 deaths in the HD group (82%) (p = 0.006: chi-squared test). Although age was significantly different between groups, APACHE II scores were similar. Mortality rate was significantly higher in the hemodialysis group. This supports the hypothesis that CAVH may be the renal replacement therapy of choice in the ICU.

Plasma disposition and hemodynamic effects of a single oral dose of isosorbide dinitrate in human males and females.

The goal of the present work was to determine the plasma disposition and hemodynamic effects of isosorbide dinitrate (ISDN) in human males and females. Fourteen healthy human volunteers took part in the study; seven males, 21.7 +/- 2.5 y (SD), and seven females, 20.7 +/- 3.4 y. Measurements of forearm blood flow (FBF), vascular conductance (FVC), and venous capacitance (Cv) were obtained by venous occlusion plethysmography, whereas blood pressure was measured by automatic sphygmomanometry. Blood samples were taken through a catheter placed in the antecubital vein at 0, 15, 30, 45, 60, 90, 120, 360, 480, 720, and 1440 min following a single 10 mg oral dose of ISDN. Plasma concentrations of ISDN and its mononitrate metabolites, isosorbide-2-mononitrate (2-ISMN) and isosorbide-5-mononitrate (5-ISMN), were determined by large bore capillary column gas-liquid chromatography. Hemodynamic measurements were made at corresponding experimental times up to 480 min. No differences were observed in the disposition of ISDN, 2-ISMN or 5-ISMN between the male and female volunteers. In addition, the plasma concentrations of ISDN and its mononitrate metabolites did not consistently correlate with the hemodynamic changes of the individual subjects. Diastolic blood pressure was significantly decreased for a 0.5 h period starting at 30 min, which was the time at which plasma ISDN concentrations peaked, and which preceded the time when the plasma concentrations of 2-ISMN and 5-ISMN were maximal. These observations indicate that, for a single 10 mg oral dose of ISDN, there were no gender-dependent differences in the plasma disposition of the parent drug or its mononitrate metabolites, and the vascular changes responsible for the decrease in diastolic blood pressure in these volunteers occurred in vascular beds other than those of skeletal muscle as represented by forearm blood flow.

Response of plasma prorenin and active renin to chronic and acute alterations of renin secretion in normal humans. Studies using a direct immunoradiometric assay.

We employed a novel immunoradiometric assay to measure plasma levels of active renin and prorenin in physiologic and pharmacologic studies designed to characterize renin biosynthesis and processing in response to both chronic and acute stimuli of renin secretion in normal human subjects. Stimulation of renin secretion with prolonged dietary sodium restriction or amiloride resulted in marked increases in the plasma levels of prorenin, active renin, and plasma renin activity (PRA); suppression of renin secretion with indomethacin resulted in parallel decreases in prorenin, active renin, and PRA. In contrast, acute stimulation with upright activity or administration of an angiotensin-converting enzyme inhibitor, which increased active renin and PRA from 2- to 15-fold, had no effect on prorenin levels. Based on studies in cultured human juxtaglomerular tumor cells, it has been proposed that prorenin is secreted constitutively whereas active renin is stored in and released from secretory granules through a regulated pathway. Our studies are consistent with such a model: the parallel changes in active renin and prorenin with experimental maneuvers of long duration suggest that both the constitutive and regulated pathways are altered under these conditions. The increase in active renin levels in the absence of a change in prorenin that occurs in response to acute stimuli presumably represents the release of preformed active enzyme that is stored in secretory granules.

Plasma exchange in thrombotic thrombocytopenic purpura.

Three patients were recently treated for thrombotic thrombocytopenic purpura (TTP). One presented with toxic shock syndrome; TTP developed but promptly responded to a regimen of antiplatelet agents, steroids and plasma exchange. In another the manifestations of TTP developed after presentation with hypertension and abdominal pain. This patient responded to a similar regimen but required extended treatment before remission could be maintained with medications alone. In the third patient the full TTP syndrome appeared after several days of plasma exchange treatment for hemolyticuremic syndrome. He did not respond. It is suggested that TTP may present in many forms initially, that microangiopathic hemolysis may be a late manifestation and that the optimal therapy is not known.

Erythrocyte life-span in dystrophic hamsters.

[3H]Diisopropylfluorophoshate was used to label erythrocytes from normal and dystrophic hamsters. The mean erythrocyte life-span in dystrophic animals was 57.3 +/- 0.7 days whereas in normal animals it was 50.1 +/- 1.6 days.