Jonathan H. Segal

Intradialytic hypotension: frequency, sources of variation and correlation with clinical outcome.

Intradialytic hypotension (IH) is a frequent complication of hemodialysis (HD) and is associated with increased patient mortality and cardiovascular events. We studied IH to determine its variability, correlates, and clinical impact in 13 outpatient HD facilities. Blood pressure was captured by machine download. IH was defined as >30 mmHg decrease in systolic blood pressure to <90 mmHg. Risk factors were assessed by logistic regression and hospitalization by Poisson regression. Time to death and first hospitalization were assessed using Kaplan–Meier analysis in patients completing >20 HD treatments. We studied IH in 44,801 treatments (Tx) in 1137 patients. IH was frequent (17.2% of treatments) and highly variable by patient (0–100% Tx) and dialysis facility (11.1–25.8% Tx). 25.1% of patients had no IH (0% Tx) and 16.2% had IH on >35% Tx. Increased IH frequency was associated with age, female gender, diabetes, Hispanic origin, longer end stage renal disease vintage, higher body mass index, higher ultrafiltration volume, the second and third weekly Tx, lower pre‐HD systolic blood pressure, higher difference between prescribed and achieved post‐HD weight, and higher dialysate temperature. Dialysis facility was an independent predictor of IH frequency. Patients with >35% IH treatments had poorer survival (P = 0.036), and more frequent and longer hospitalization (P = 0.04, P = 0.002, respectively) than patients without IH. In conclusion, IH frequency was highly variable, associated with individual facilities, patient and treatment characteristics, and correlated with mortality and hospitalization. Identifying practice patterns associated with IH coupled with routine reporting of IH will facilitate medical management and may result in the prevention of IH, decreased mortality, and decreased hospitalization.

Vascular access outcomes using the transposed basilic vein arteriovenous fistula

BACKGROUND Although the transposed basilic vein arteriovenous fistula (TBAVF) is increasingly performed for hemodialysis vascular access in patients lacking adequate superficial veins, little is known about the long-term patency or risk factors for failure. METHODS A retrospective analysis was conducted for 99 patients who had a TBAVF created between April 1997 and October 2001. Primary outcomes were unassisted and assisted patency rates and primary failure rates. RESULTS This was the first access procedure in 46% of patients, mean age was 55 years, and 46% were men. Unassisted and assisted patency rates were 47% and 64% at 1 year and 41% and 58% at 2 years, respectively. Primary access failure occurred in 23% of cases. Unassisted access patency was significantly worse in patients with a previous access (relative risk [RR], 2.04; confidence interval [CI], 1.09 to 3.85; P = 0.03) or an ipsilateral central venous catheter (RR, 2.92; CI, 1.34 to 6.38; P < 0.01). Primary access failure was affected by older age (RR, 2.0; CI, 1.20 to 3.38; P < 0.01), obesity (RR, 7.1; CI, 1.65 to 30.1; P < 0.05), and a previous vascular access (RR, 6.4; CI, 1.49 to 27.6; P = 0.01). Steal syndrome requiring intervention occurred in 5% of cases. CONCLUSION In summary, the TBAVF provides a viable option for vascular access; however, certain patient characteristics seem to affect long-term patency and should be considered when exploring access options.

Effects of Citrate Acid Concentrate (Citrasate ) on Heparin N Requirements and Hemodialysis Adequacy: A Multicenter, Prospective Noninferiority Trial

Background: Citrasate®, citric acid dialysate (CD), contains 2.4 mEq of citric acid (citrate), instead of acetic acid (acetate) as in standard bicarbonate dialysate. Previous studies suggest CD may improve dialysis adequacy and decrease heparin requirements, presumably due to nonsystemic anticoagulant effects in the dialyzer. Methods: We prospectively evaluated 277 hemodialysis patients in eight outpatient facilities to determine if CD with reduced heparin N (HN) would maintain dialyzer clearance. Subjects progressed through four study periods [baseline (B): bicarbonate dialysate + 100% HN; period 1 (P1): CD + 100% HN; period 2 (P2): CD + 80% HN; period 3 (P3): CD + 66.7% HN]. The predefined primary endpoint was noninferiority (margin –8%) of the percent change in mean dialyzer conductivity clearance between baseline and P2. Results: Subjects were 57.4% male, 41.7% white, 54.3% black, and 44.4% diabetic; mean age was 59 ± 14.4 years; mean time on dialysis was 1,498 ± 1,165 days; 65.7% had arteriovenous fistula, 19.9% arteriovenous graft, 14.4% catheters, and 27.8% used antiplatelet agents. Mean dialyzer clearance increased 0.9% (P1), 1.0% (P2), and 0.9% (P3) with CD despite heparin reduction. SpKt/V remained stable (B: 1.54 ± 0.29; P1: 1.54 ± 0.28; P2: 1.55 ± 0.27; P3: 1.54 ± 0.26). There was no significant difference in dialyzer/dialysis line thrombosis, post-HD time to hemostasis, percent of subjects with adverse events (AEs), or study-related AEs. Conclusions: CD was safe, effective, and met all study endpoints. Dialyzer clearance increased approximately 1% with CD despite 20–33% heparin reduction. Over 92% of P3 subjects demonstrated noninferiority of dialyzer clearance with CD and 33% HN reduction. There was no significant difference in dialyzer clotting, bleeding, or adverse events.

Intradialytic Administration of Daptomycin in End Stage Renal Disease Patients on Hemodialysis

BACKGROUND AND OBJECTIVES Infusion of intravenous antibiotics after hemodialysis (HD) may delay initiation of treatment for the next HD shift. Intradialytic administration of drugs such as vancomycin during the final hour of HD obviates these delays. Daptomycin has potent activity against Gram-positive bacteria, but the manufacturer recommends that the dose be infused after HD ends. This study determined the pharmacokinetics of intradialytically dosed daptomycin in patients with ESRD. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS This prospective crossover study compared single-dose daptomycin (6 mg/kg, 30-min intravenous infusion) pharmacokinetics administered after HD versus during the last part of HD with high-permeability (HP) and low-permeability (LP) dialyzers to seven patients who had ESRD and were on thrice-weekly HD. Serial blood samples were collected to determine daptomycin serum concentrations and protein binding. Statistical analysis was done using linear mixed model analysis. RESULTS The maximum serum concentration observed with a 6 mg/kg post-HD dose was 61.1 +/- 7.6 microg/ml with a mean protein binding of 89.2%. Intradialytic daptomycin administration resulted in reduced maximum serum concentration and area under the curve values that were approximately 12 to 20% lower when administered during HD with LP dialyzers and approximately 35% lower with HP dialyzers. CONCLUSIONS Intradialytic daptomycin administration during the last 30 min of HD is feasible, provided that larger dosages are used to compensate for intradialytic drug loss. On the basis of our findings, intradialytic doses of approximately 7 mg/kg (LP) or approximately 9 mg/kg (HP) theoretically should be bioequivalent to 6 mg/kg infused after HD. The calculated dosages are mathematically driven and must be validated in prospective clinical trials.

A Successful Approach to Fall Prevention in an Outpatient Hemodialysis Center

BACKGROUND AND OBJECTIVES Hemodialysis patients are at high risk both for falling and for serious complications associated with falls, but few fall studies have specifically focused on this population. Falls occurring in an outpatient dialysis unit were reviewed to identify contributing factors and implement interventions designed to reduce fall risk. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS A root cause analysis of all fall incidents occurring at an outpatient hemodialysis center during a 4-year period was conducted. A targeted intervention program to reduce falls was then implemented. Risk of falls in the postintervention period was compared with that of the baseline period. RESULTS In the baseline period, a total of 22 falls occurred involving 14 patients and 8 staff members or visitors (incidence of 50 falls per 100,000 dialysis treatments). Root cause analyses identified staff educational deficits and environmental hazards as the most significant risk factors for fall incidents. After an interventional period that focused on formal staff education and environmental modifications, a total of only 3 additional falls (2 patients and 1 staff member) during 21 months of follow-up (14 falls per 100,000 dialysis treatments, P = 0.01) were observed. CONCLUSIONS Several modifiable risk factors for falls occurring in the high-risk setting of an outpatient hemodialysis unit were identified as a result of this formal analysis of fall incidents. Through a targeted series of interventions, a marked reduction in fall risk was achieved.

Carbamazepine and the active epoxide metabolite are effectively cleared by hemodialysis followed by continuous venovenous hemodialysis in an acute overdose

Hemodialysis (HD) and continuous venovenous hemodialysis (CVVHD) have an unproven role in the management of carbamazepine overdose. Albumin‐enhanced CVVHD may accelerate carbamazepine (CBZ) clearance, but no pharmacokinetic data has been reported for traditional CVVHD without albumin enhancement. In addition, it is unclear whether the active CBZ‐epoxide metabolite is removed with either mode of dialysis. We present a case of CBZ intoxication successfully managed with sequential HD and CVVHD. The CBZ half‐life during CVVHD was 14.7 hours, compared with the patients endogenous half‐life of 30.8 hours. The CBZ‐epoxide half‐life was 3.2 hours during HD. We conclude that HD and CVVHD provide effective clearance of CBZ and the epoxide metabolite and should be considered in the management of an acute toxic ingestion.

Invited Manuscript Poster on Renal-Related Education American Society of Nephrology, Nov. 16–21, 2010 Adolescents with Chronic Kidney Disease and Their Need for Online Peer Mentoring: A Qualitative Investigation of Social Support and Healthcare Transition

Abstract Adolescents with chronic kidney disease (CKD) tend to be isolated from peers who also have CKD, develop non-adherent behavior with treatment recommendations, and consequently are at higher risk for poor health outcomes such as transplant rejection. At the same time, patients in this age group tend to be technologically savvy and well-versed in using Internet-based communication tools to connect with other people. In this study, we conducted semi-structured interviews among adolescents with CKD to assess their information needs and their interest in using a CKD-oriented peer-mentoring website that we are developing, kTalk.org. We interviewed 17 adolescents with CKD, ages 14–18 years old, to learn about (1) any concerns regarding transition from pediatric to adult care teams; and (2) their interest in using the Internet as a source for disease-related information and as a social networking tool for finding and interacting with their peers. The interviews were digitally recorded, transcribed, and qualitatively analyzed. Results showed that (1) the adolescent participants are commonly concerned about transitioning to an adult clinic; (2) they are isolated from peers with the same medical condition who are of similar age; (3) they are frequent Facebook users and are highly interested in exploring the possibility of using an online community website, such as kTalk.org, to discover and communicate with peers and peer mentors; and (4) there exist divergent opinions regarding if an online community of adolescent CKD patients should be open to the public.

Prevention of peritonitis in peritoneal dialysis.

Reducing the frequency of peritonitis for patients undergoing peritoneal dialysis (PD) continues to be a challenge. This review focuses on recent updates in catheter care and other patient factors that influence infection rates. An experienced nursing staff plays an important role in teaching proper PD technique to new patients, but nursing staff must be cognizant of each patients unique educational needs. Over time, many patients become less adherent to proper dialysis technique, such as washing hands or wearing a mask. This behavior is associated with higher risk of peritonitis and is modifiable with re‐training. Prophylactic antibiotics before PD catheter placement can decrease the infection risk immediately after catheter placement. In addition, some studies suggest that prophylaxis against fungal superinfection after antibiotic exposure is effective in reducing fungal peritonitis, although larger randomized studies are needed before this practice can be recommended for all patients. Over time, exit site and nasal colonization with pathogenic organisms can lead to exit‐site infections and peritonitis. For patients with Staphylococcus aureus colonization, exit‐site prophylaxis with either mupirocin or gentamicin cream reduces clinical infection with this organism. Although there are limited data for support, antibiotic prophylaxis before gastrointestinal, gynecologic, or dental procedures may also help reduce the risk of peritonitis.

Optimizing anemia management in hospitalized patients with end-stage renal disease

Objective: To review available literature on the use of erythropoiesis-stimulating agents (ESAs) in patients with end-stage renal disease (ESRD) who require hospitalization and to provide recommendations for ESA use in this setting. Data Sources: Primary articles were identified by English-language MEDLINE search (1966–October 2008) using the MeSH headings: kidney failure (chronic), anemia, erythropoietin, darbepoetin, hospitalization, and hematinics. Relevant data presented at recent nephrology scientific meetings (2004–October 2008) were also identified. Study Selection and Data Extraction: Identified studies were reviewed and information regarding hospitalization, ESA use, and patient outcomes was evaluated. Data Synthesis: Studies demonstrate that hospitalized patients with ESRD usually experience a decline in hemoglobin values. Contributing factors include infection, inflammation, and untreated iron deficiency. ESAs are used inconsistently during hospitalization, with less than 50% of hospitalized patients with ESRD receiving ESA therapy in some reports. Some controversy exists regarding optimal hemoglobin targets for ESA therapy in nonhospitalized patients with ESRD, and no targets are defined for hospitalized patients. Clinical trials examining in-hospital ESA use have primarily involved the intensive care population and excluded ESRD patients. Following the patients hospitalization, lower hemoglobin values may persist for 6 months, despite increased ESA dosing. Variability exists in frequency of hemoglobin monitoring and ESA dose changes. To date, no clinical trials have evaluated different approaches to anemia management in hospitalized patients with ESRD, and there are no published guidelines in this area. Based on published observations and clinical experience, we offer recommendations for anemia management around the time of hospitalization in an attempt to define a more rational approach to ESA therapy in this population. Conclusions: Trials are needed to define optimal ESA dosing strategies and hemoglobin targets in hospitalized patients with ESRD.

Reverse Epidemiology of Blood Pressure in Peritoneal Dialysis Associated with Dynamic Deterioration of Left Ventricular Function.

♦ Background: Reverse epidemiology of blood pressure (BP) in end-stage kidney disease (ESKD) is manifested as higher mortality at lower blood pressure. We hypothesize that this phenomenon is partially mediated by deterioration of cardiac structure and function. ♦ Methods: Seventy-seven prevalent ESKD patients starting renal replacement therapy on peritoneal dialysis (PD) from 2007 to 2012 were evaluated for the primary outcome of all-cause mortality. Longitudinal data were obtained from 1,930 patient-encounters including monthly clinic BP and serial echocardiograms. Generalized linear mixed models using data from the last observation moving backward, and time-to-event analysis using time-varying Cox-survival models to estimate mortality risk at different blood pressure categories were applied. ♦ Results: There were 39 males (50.6%). Mean age was 51 years (standard deviation [SD] = 15). During follow-up, 20 patients (25%) died. As compared to systolic blood pressure (SBP) of 140 – 159 mmHg, unadjusted risk of mortality was 7.3 (95% confidence interval [CI]: 1.5 – 35.7, p = 0.008) at level < 120 mmHg. Systolic BP trended down to an average of 117 mmHg prior to death in non-survivors as compared to 141 mmHg in survivors (p < 0.05). In non-survivors, percentage with concentric left ventricular hypertrophy (LVH) decreased by 20% at the expense of a 20% reciprocal increase in eccentric hypertrophy associated with a 30% increase in percentage with low ejection fraction (EF) (< 50%). After adjusting for EF, risk of mortality at SBP < 120 mmHg attenuated to 3.4 (95% CI: 0.7 – 17.7, p = 0.14). ♦ Conclusion: We conclude that higher mortality associated with lower BP may be mediated in part by worsening heart function in ESKD patients receiving PD.