Isaac Teitelbaum

Pill burden, adherence, hyperphosphatemia, and quality of life in maintenance dialysis patients.

BACKGROUND AND OBJECTIVES Dialysis patients have a high burden of co-existing diseases, poor health-related quality of life (HR-QOL), and are prescribed many medications. There are no data on daily pill burden and its relationship to HR-QOL and adherence to therapy. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS Two hundred and thirty-three prevalent, chronic dialysis patients from three units in different geographic areas in the United States underwent a single, cross-sectional assessment of total daily pill burden and that from phosphate binders. HR-QOL, adherence to phosphate binders, and serum phosphorus levels were the three main outcome measures studied. RESULTS The median daily pill burden was 19; in one-quarter of subjects, it exceeded 25 pills/d. Higher pill burden was independently associated with lower physical component summary scale scores on HR-QOL on both univariate and multivariate analyses. Phosphate binders accounted for about one-half of the daily pill burden; 62% of the participants were nonadherent. There was a modest relationship between pill burden from phosphate binders and adherence and serum phosphorus levels; these associations persisted on multivariate analyses. There was no relationship between adherence and serum phosphorus levels. CONCLUSIONS The daily pill burden in dialysis patients is one of the highest reported to date in any chronic disease state. Higher pill burden is associated with lower HR-QOL. There are many reasons for uncontrolled serum phosphorus levels; increasing the number of prescribed pills does not seem to improve control and may come at the cost of poorer HR-QOL.

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.

Systematic Barriers to the Effective Delivery of Home Dialysis in the United States: A Report From the Public Policy/Advocacy Committee of the North American Chapter of the International Society for Peritoneal Dialysis

Home dialysis, currently underused in the United States compared with other industrialized countries, likely will benefit from the newly implemented US prospective payment system. Not only is home dialysis less expensive from the standpoint of pure dialysis costs, but overall health system costs may be decreased by more subtle benefits, such as reduced transportation. However, many systematic barriers exist to the successful delivery of home dialysis. We organized these barriers into the categories of educational barriers (patient and providers), governmental/regulatory barriers (state and federal), and barriers specifically related to the philosophies and business practices of dialysis providers (eg, staffing, pharmacies, supplies, space, continuous quality improvement practices, and independence). All stakeholders share the goal of delivering home dialysis therapies in the most cost- and clinically effective and least problematic manner. Identification and recognition of such barriers is the first step. In addition, we have suggested action plans to stimulate the kidney community to find even better solutions so that collectively we may overcome these barriers.

Epidermal growth factor-stimulated phosphoinositide hydrolysis in cultured rat inner medullary collecting tubule cells. Regulation by G protein, calcium, and protein kinase C.

Epidermal growth factor (EGF) exhibits specific saturable binding to cultured rat inner medullary collecting tubule cells and stimulates inositol trisphosphate (IP3) production by these cells in a dose-dependent fashion. EGF-stimulated IP3 production is enhanced by GTP gamma s or AIF4- and is inhibited by GDP beta s or pertussis toxin. Alterations in extracellular Ca2+ have no effect on either basal or EGF-stimulated IP3 production. Similarly, treatment with EGTA which decreases cytosolic Ca2+ is without effect. In contrast, treatment with ionomycin which increases cytosolic Ca2+ has no effect on basal IP3 production but enhances the response to EGF. Activation of protein kinase C inhibits IP3 production in response to either EGF or AIF4-. These studies demonstrate the occurrence of EGF-stimulated phospholipase C activity in the rat inner medullary collecting duct. Stimulation by EGF is transduced by a pertussis toxin-sensitive G protein, unaffected by alterations in extracellular Ca2+, insensitive to a decrement in cytosolic Ca2+, enhanced by an increase in cytosolic Ca2+, and inhibited by protein kinase C.

Effects of calcium on vasopressin-mediated cyclic adenosine monophosphate formation in cultured rat inner medullary collecting tubule cells. Evidence for the role of intracellular calcium.

We explored the effects of alterations in extracellular and intracellular calcium concentration on arginine vasopressin (AVP)-stimulated cAMP formation in cultured rat inner medullary collecting tubule cells. cAMP formation remains constant at extracellular calcium concentrations between 0.5 and 4.0 mM, which did not change intracellular calcium. Maneuvers that alter intracellular calcium concentration are associated with marked changes in cAMP generation. EGTA decreases intracellular calcium and enhances AVP-stimulated cAMP formation, while increasing cellular calcium with 2 microM A23187 decreases AVP-stimulated cAMP formation in the presence, but not in the absence, of extracellular calcium. The changes in cAMP formation observed when intracellular calcium is altered are associated with reciprocal changes in prostaglandin E2 (PGE2) synthesis. Despite greater than 95% inhibition of PGE2 synthesis with 5 microM meclofenamic acid, the changes in cAMP formation accompanying alterations in intracellular calcium concentration are still evident. These studies suggest that intracellular calcium critically influences AVP-stimulated cAMP formation. It does so by a mechanism independent of PG that is probably mediated by a direct effect of the cation on the adenylate cyclase complex.

Mortality Associated with Dose Response of Erythropoiesis-Stimulating Agents in Hemodialysis versus Peritoneal Dialysis Patients

Background: Several studies have shown an association between erythropoietin-stimulating agent (ESA) responsiveness and mortality in chronic kidney disease (CKD) patients. In our present study, we examined the association between prescribed ESA dose and mortality in peritoneal dialysis (PD) and hemodialysis (HD) patients. We hypothesized that PD patients received lower ESA dose for the same achieved hemoglobin compared to HD patients and that ESA dose-mortality associations were different between PD and HD patients. Methods: We compared the prescribed doses of ESA between 139,103 HD and 10,527 PD patients treated in DaVita dialysis clinics from 7/2001 through 6/2006 using adjusted Poisson regression and examined mortality-predictability of prescribed ESA dose and ESA responsiveness index (ESA/hemoglobin) in PD and HD with follow-up through 6/2007 using Cox regression models. Results: Poisson adjusted ratio of ESA dose of HD to PD was 3.6 (95% CI 3.5–3.7). In PD patients, adjusted all-cause death hazard ratios (HR) for ESA doses of 3,000–5,999, 6,000–8,999 and ≧9,000 U/week (reference <3,000 U/week) were 0.97 (0.87–1.07), 0.85 (0.76–0.95) and 1.08 (0.98–1.18), respectively; whereas in HD patients across commensurate ESA dose increments of 10,000–19,999, 20,000–29,999 and ≧30,000 U/week (reference <10,000 U/week) were 1.14 (1.11–1.17), 1.54 (1.50–1.58) and 2.15 (2.10–2.21), respectively. In PD and HD patients, the adjusted death HR of the 4th to 1st quartile of ESA responsiveness index were 1.14 (1.04–1.26) and 2.37 (2.31–2.43), respectively. Conclusions: Between 2001 and 2006, most PD patients received substantially lower ESA dose for same achieved hemoglobin levels, and low ESA responsiveness was associated with higher mortality in both HD and PD patients.

Strategies for Improving Long-Term Survival in Peritoneal Dialysis Patients

The incidence and prevalence of ESRD in the United States continues to increase. Currently there are over 26,000 patients maintained on peritoneal dialysis. Mortality rates have fallen over the past several years, but long-term survival remains poor, with only 11% of peritoneal dialysis patients surviving past 10 years. Cardiovascular disease accounts for most deaths, and dialysis patients have many traditional and nontraditional cardiovascular risk factors. Lowering of these risk factors has not resulted in reduced cardiovascular morbidity and mortality in dialysis patients. Maneuvers to improve long-term peritoneal dialysis patient survival must therefore focus on modifiable risk factors including residual renal function, peritoneal membrane integrity, rate of infections, and peritoneal dialysis center size. This article reviews strategies for preserving residual renal function and peritoneal membrane integrity as well as strategies for reducing the rate of infections to enhance long-term survival in peritoneal dialysis patients.

Comparative Outcomes Between Continuous Ambulatory and Automated Peritoneal Dialysis: A Narrative Review

Automated methods for delivering peritoneal dialysis (PD) to persons with end-stage renal disease continue to gain popularity worldwide, particularly in developed countries. However, the endeavor to automate the PD process has not been advanced on the strength of high-level evidence for superiority of automated over manual methods. This article summarizes available studies that have shed light on the evidence that compares the association of treatment with continuous ambulatory PD or automated PD (APD) with clinically meaningful outcomes. Published evidence, primarily from observational studies, has been unable to demonstrate a consistent difference in residual kidney function loss rate, peritonitis rate, maintenance of euvolemia, technique survival, mortality, or health-related quality of life in individuals undergoing continuous ambulatory PD versus APD. At the same time, the future of APD technology appears ripe for further improvement, such as the incorporation of voice commands and expanded use of telemedicine. Given these considerations, it appears that patient choice should drive the decision about PD modality.

Prolonged Duration of Peritoneal Dialysis Catheter Embedment Does Not Lower the Catheter Success Rate

♦ Objective: Since 2000, we have used the Moncrief–Popovich technique as our standard method for peritoneal dialysis (PD) catheter insertion. The subcutaneous portion of the catheter is externalized immediately before initiation of PD. We undertook the present review to investigate whether duration of catheter embedment affects catheter or patient outcome. ♦ Methods: All catheters inserted beginning 1 January 2000 and externalized by 31 December 2008 were included. The primary outcome was catheter survival. Secondary outcomes were catheter patency (no fibrin plug or omental wrap) and complications within 90 days after externalization. A standard peritoneal equilibration test was used to classify peritoneal membrane transport status. Proportional hazards regression models were used to test whether duration of embedment affected catheter outcomes. The models treated embedment duration as both a continuous predictor and a categorical predictor categorized by tertile. ♦ Results: A total of 134 catheters were implanted and externalized. Twelve patients received 2 catheters each. To ensure statistical independence of the observations, 12 of the latter 24 catheters were excluded (1 chosen randomly from each patient), resulting in a useable sample size of 122 catheters. The total duration of observation was 2359 patient–months. The median duration of catheter embedment was 40.5 days (range: 2 – 788 days). After controlling for sex, race, age, and diabetes status, embedment duration did not have a significant effect on catheter survival as a continuous predictor or as a categorical predictor. Additionally, the 95% confidence interval for the 30-day effect of embedment duration ruled out a change of more than 20.6% in the hazard of catheter malfunction or infection. Of the studied catheters, 89.3% were patent and functioned properly immediately upon externalization. The remaining 13 catheters (10.7%) lacked patency on externalization because of fibrin plug or kinking (n = 10) or omental wrap (n = 3); however, 12 of the 13 non-patent catheters were corrected laparoscopically, and the patients resumed PD. Only 1 patient transferred to hemodialysis. Overall, 121 of 122 buried catheters (99.2%) were used for PD. Other complications within 90 days of catheter externalization included incision site and tunnel infection in 2 cases (1.6%), exit-site leak in 2 cases (1.6%), and coagulase-negative staphylococcal peritonitis in 1 case (0.8%). ♦ Conclusions: Duration of catheter embedment before externalization did not affect catheter survival and did not influence subsequent peritoneal membrane transport status. The overall effect of increasing embedment duration by 30 days is, at most, a 20.6% increase or decrease in the hazard of catheter failure, but the actual hazard may be much smaller or nonexistent. Larger studies are needed to further explore the ideal duration of embedment.

Bivalirudin versus unfractionated heparin for prevention of hemofilter occlusion during continuous renal replacement therapy.

Study Objective. To evaluate the safety and efficacy of bivalirudin compared with heparin for preventing hemofilter occlusion during continuous venovenous hemofiltration (CVVH).