Michael A. Kraus

Efficacy and Safety of Renal Tubule Cell Therapy for Acute Renal Failure

The mortality rate for patients with acute renal failure (ARF) remains unacceptably high. Although dialysis removes waste products and corrects fluid imbalance, it does not perform the absorptive, metabolic, endocrine, and immunologic functions of normal renal tubule cells. The renal tubule assist device (RAD) is composed of a conventional hemofilter lined by monolayers of renal cells. For testing whether short-term (up to 72 h) treatment with the RAD would improve survival in patients with ARF compared with conventional continuous renal replacement therapy (CRRT), a Phase II, multicenter, randomized, controlled, open-label trial involving 58 patients who had ARF and required CRRT was performed. Forty patients received continuous venovenous hemofiltration + RAD, and 18 received CRRT alone. The primary efficacy end point was all-cause mortality at 28 d; additional end points included all-cause mortality at 90 and 180 d, time to recovery of renal function, time to intensive care unit and hospital discharge, and safety. At day 28, the mortality rate was 33% in the RAD group and 61% in the CRRT group. Kaplan-Meier analysis revealed that survival through day 180 was significantly improved in the RAD group, and Cox proportional hazards models suggested that the risk for death was approximately 50% of that observed in the CRRT-alone group. RAD therapy was also associated with more rapid recovery of kidney function, was well tolerated, and had the expected adverse event profile for critically ill patients with ARF.

Effect of Daily Hemodialysis on Depressive Symptoms and Postdialysis Recovery Time: Interim Report From the FREEDOM (Following Rehabilitation, Economics and Everyday-Dialysis Outcome Measurements) Study

BACKGROUND Clinical depression and postdialysis fatigue are important concerns for patients with kidney failure and can have a negative impact on quality of life and survival. STUDY DESIGN The FREEDOM (Following Rehabilitation, Economics and Everyday-Dialysis Outcome Measurements) Study is an ongoing prospective cohort study investigating the clinical and economic benefits of daily (6 times per week) hemodialysis (HD). In this interim report, as part of an a priori planned analysis, we examine the long-term impact of daily HD on depressive symptoms, measured using the Beck Depression Inventory (BDI) survey, and postdialysis recovery time, measured using a previously validated questionnaire. SETTING & PARTICIPANTS Adult patients initiating daily HD with a planned 12-month follow-up. OUTCOMES & MEASUREMENTS The BDI survey and postdialysis recovery time question were administered at baseline, and changes were assessed at months 4 and 12. RESULTS 239 participants were enrolled (intention-to-treat cohort) and 128 completed the study (per-protocol cohort). Mean age was 52 years, 64% were men, 55% had an arteriovenous fistula, and 90% transitioned from in-center HD therapy. In the per-protocol cohort, there was a significant decrease in mean BDI score over 12 months (11.2 [95% CI, 9.6-12.9] vs 7.8 [95% CI, 6.5-9.1]; P<0.001). For robustness, the intention-to-treat analysis was performed, yielding similar results. The percentage of patients with depressive symptoms (BDI score>10) significantly decreased during 12 months (41% vs 27%; P=0.03). Similarly, in the per-protocol cohort, there was a significant decrease in postdialysis recovery time over 12 months (476 [95% CI, 359-594] vs 63 minutes [95% CI, 32-95]; P<0.001). The intention-to-treat analysis yielded similar results. The percentage of patients experiencing prolonged postdialysis recovery time (>or=60 minutes) also significantly decreased (81% vs 35%; P=0.001). LIMITATIONS Observational study with lack of control arm. CONCLUSIONS Daily HD is associated with long-term improvement in depressive symptoms and postdialysis recovery time.

At-home short daily hemodialysis improves the long-term health-related quality of life

Patients with chronic kidney disease treated by in-center conventional hemodialysis (3 times per week) have significant impairments in health-related quality of life measures, which have been associated with increased morbidity and mortality. FREEDOM is an ongoing prospective cohort study measuring the potential benefits of at-home short daily (6 times per week) hemodialysis. In this interim report we examine the long-term effect of short daily hemodialysis on health-related quality of life, as measured by the SF-36 health survey. This was administered at baseline, 4 and 12 months after initiation of short daily hemodialysis to 291 participants (total cohort), of which 154 completed the 12-month follow-up (as-treated cohort). At the time of analysis, the mean age was 53 years, 66% were men, 58% had an AV fistula, 90% transitioned from in-center hemodialysis, and 45% had diabetes mellitus. In the total cohort analysis, both the physical- and mental-component summary scores improved over the 12-month period, as did all 8 individual domains of the SF-36. The as-treated cohort analysis showed similar improvements with the exception of the role-emotional domain. Significantly, in the as-treated cohort, the percentage of patients achieving a physical-component summary score at least equivalent to the general population more than doubled. Hence, at-home short daily hemodialysis is associated with long-term improvements in various physical and mental health-related quality of life measures.

Impact of Short Daily Hemodialysis on Restless Legs Symptoms and Sleep Disturbances

BACKGROUND AND OBJECTIVES Restless legs syndrome (RLS) and sleep disturbances are common among in-center hemodialysis patients and are associated with increased morbidity/mortality. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS The FREEDOM study is an ongoing prospective cohort study investigating the benefits of home short daily hemodialysis (SDHD) (6 times/week). In this interim report, we examine the long-term effect of SDHD on the prevalence and severity of RLS, as measured by the International Restless Legs Syndrome (IRLS) Study Group rating scale, and sleep disturbances, as measured by the Medical Outcomes Study sleep survey. RESULTS 235 participants were included in this report (intention-to-treat cohort), of which 127 completed the 12-month follow-up (per-protocol cohort). Mean age was 52 years, 55% had an arteriovenous fistula, and 40% suffered from RLS. In the per-protocol analysis, among patients with RLS, the mean IRLS score improved significantly at month 12, after adjustment for use of RLS-related medications (18 versus 11). Among patients with moderate-to-severe RLS (IRLS score ≥15), there was an even greater improvement in the IRLS score (23 versus 13). The intention-to-treat analysis yielded similar results. Over 12 months, there was decline in the percentage of patients reporting RLS (35% versus 26%) and those reporting moderate-to-severe RLS (59% versus 43%). There was a similar and sustained 12-month improvement in several scales of the sleep survey, after adjustment for presence of RLS and use of anxiolytics and hypnotics. CONCLUSIONS Home SDHD is associated with long-term improvement in the prevalence and severity of RLS and sleep disturbances.

Randomized Comparison of High-Flow versus Conventional Hemodialysis Catheters

PURPOSE To evaluate short-term flow rates achieved with a new split-tip polyurethane hemodialysis catheter. PATIENTS AND METHODS This was a prospective, randomized, nonblinded study. Patients referred for a tunneled-dialysis catheter received either a conventional silicone (Bard Hickman 13.5 F) if randomized to the control group, or a split-tip, high-flow polyurethane (MedComp AshSplit 14.5 F) catheter if randomized to the study group. Effective flow rates (QbEff) and recirculation were measured with use of ultrasonic dilution at pump settings (Qb) of 200, 300, 350 and 400 mL/min, as well as maximum Qb (QbMax, up to 500 mL/min) sustainable for at least 3 minutes. Measurements were repeated weekly for 6 weeks. Procedure times and initial and late complications were recorded. RESULTS Twelve patients were enrolled in each group, 11 and eight completed the study in the test and control groups, respectively. Insertion complications, limited to the split-tip group, included asymptomatic air embolus (n = 1), prolonged tunnel bleeding (n = 2), and kinking (n = 2). Recirculation in both groups was low (mean < 6% at all flow rates). QbMax was 499 mL/min in the Ash group and 470 mL/min in the Hickman group. A repeated measures analysis of variance was used. Adjusted (for week) mean effective flow rates (Qbeff, mL/min) were as follows: at Qb = 200, Ash = 211, Bard = 211, P = .93; at Qb = 300, Ash = 301, Bard = 292, P = .28; at Qb = 350, Ash = 341, Bard = 314, P = .03; at Qb = 400, Ash = 375, Bard = 329, P = .01; at QbMax, Ash = 422, Bard = 359, P = .0005. CONCLUSION Both catheters delivered flows within the acceptable range indicated by the Dialysis Outcomes Quality Initiative. The split-tip catheter is capable of higher flow rates (Qb and QbEff) compared with the conventional catheter, which may allow more efficient dialysis. Insertion complications appear to be higher with the new design.

Effects of Dialysis Membrane on Intradialytic Vancomycin Administration

Study Objective. To quantify the influence of hemodialyzers on vancomycin removal when the drug was infused during hemodialysis.

Merging health literacy with computer technology: Self-managing diet and fluid intake among adult hemodialysis patients

OBJECTIVE The Dietary Intake Monitoring Application (DIMA) is an electronic dietary self-monitor developed for use on a personal digital assistant (PDA). This paper describes how computer, information, numerical, and visual literacy were considered in development of DIMA. METHODS An iterative, participatory design approach was used. Forty individuals receiving hemodialysis at an urban inner-city facility, primarily middle-aged and African American, were recruited. RESULTS Computer literacy was considered by assessing abilities to complete traditional/nontraditional PDA tasks. Information literacy was enhanced by including a Universal-Product-Code (UPC) scanner, picture icons for food with no UPC code, voice recorder, and culturally sensitive food icons. Numerical literacy was enhanced by designing DIMA to compute real-time totals that allowed individuals to see their consumption relative to their dietary prescription. Visual literacy was considered by designing the graphical interface to convey intake data over a 24-h period that could be accurately interpreted by patients. Pictorial icons for feedback graphs used objects understood by patients. PRACTICE IMPLICATIONS Preliminary data indicate the application is extremely helpful for individuals as they self-monitor their intake. If desired, DIMA could also be used for dietary counseling.

Starting a home hemodialysis program

Home hemodialysis is not a new therapy; rather it is a therapy in which interest has been rekindled due to both the continually growing end‐stage renal disease population and concern about poor outcomes in patients on conventional thrice‐weekly in‐center dialysis. The practical issues to be considered when starting a home hemodialysis center are presented, including the choice of equipment, patient selection and training, home set‐up, dialysis prescription, and patient follow‐up. We outline the steps required to start a program that will be successful for patients, caretakers, and providers alike.

Solute control by extracorporeal therapies in acute renal failure

Abstract A clear relationship between dialysis dose and outcome in chronic hemodialysis patients has been demonstrated. Recent data suggest renal replacement therapy (RRT) dose or intensity may affect outcome in critically ill acute renal failure (ARF) patients also. This review addresses the factors influencing small solute removal by extracorporeal RRTs in ARF. Methods to quantify and compare small solute removal by intermittent and continuous therapies in ARF are also presented. Finally, studies demonstrating a link between therapy intensity and outcome are assessed. To improve the management of critically ill ARF patients, the effect of delivered RRT dose on ARF outcome requires additional analysis.

Intensive Hemodialysis, Blood Pressure, and Antihypertensive Medication Use.

Hypertension is a cardinal feature of end-stage renal disease (ESRD). Hypertensive nephropathy is the primary cause of ESRD for nearly 30% of patients, and the prevalence of hypertension is >85% in new patients with ESRD. In contemporary hemodialysis (HD) patients, mean predialysis systolic blood pressure (SBP) is nearly 150mmHg, and about 70%, 50%, and 40% use β-blockers, calcium channel blockers, and renin-angiotensin system inhibitors, respectively. Predialysis SBP generally exhibits a U-shaped association with mortality risk. Interdialytic ambulatory SBP is more strongly associated with risk. Hypertension is multifactorial; key causes include persistent hypervolemia and elevated peripheral resistance. With 3 HD sessions per week, blood pressure (BP) climbs during the interdialytic interval, in step with interdialytic weight gain, particularly among elderly patients and those with higher dry weight. Elevated peripheral resistance can be attributed to inappropriate activation of the sympathetic nervous system due to higher plasma norepinephrine concentrations. Multiple randomized clinical trials show that intensive HD reduces BP and the need for oral medications indicated for hypertension. In the first 2 months of the Frequent Hemodialysis Network trial, the short daily schedule reduced predialysis SBP by 7.7mmHg, whereas the nocturnal schedule reduced predialysis SBP by 7.3mmHg, both relative to 3 sessions per week. Improvements were sustained after 12 months. Both schedules reduced antihypertensive medication use relative to 3 sessions per week. In FREEDOM (Following Rehabilitation, Economics, and Everyday-Dialysis Outcome Measurements), a prospective cohort study of short daily HD, the mean number of prescribed antihypertensive agents decreased from 1.7 to 1.0 in 1 year, whereas the percentage of patients not prescribed antihypertensive agents increased from 21% to 47%. Nocturnal HD appears to markedly reduce total peripheral resistance and plasma norepinephrine and restore endothelium-dependent vasodilation. In conclusion, intensive HD reduces BP and the need for antihypertensive medications.