bluuebunny/crossref_metadata_2025 huggingface dataset:
Modeling the Dose of Home Dialysis
Authors: Gotch Frank A.
Published: September 2016

The growing interest in daily dialysis and combined continuous and intermittent dialysis treatments has created the need for a dialysis dosing model that is valid over a wide range of dosing frequency and intensity. Three models have been described for this purpose and are reviewed here. They have in common the concept of a continuous clearance value which is equivalent to the summed intermittent dialysis prescribed. The continuous clearance models all define a point on the saw‐toothed blood urea nitrogen (BUN) concentration profile and calculate the continuous clearance required to achieve this at the same urea generation rate. The points modeled are the peak predialysis concentration (pkKt/V), the average Co (standard Kt/V, stdKt/V), and time‐averaged urea concentration (TAC), which is termed equivalent renal clearance (EKRt/V). At the present time the only data for evaluation of clinical relevance of the three models is continuous ambulatory peritoneal dialysis (CAPD) outcome. The stdKt/V predicts that optimal CAPD outcome requires weekly stdKt/V 2.0, while the pkKt/V and EKRt/V models predict optimal doses of 1.8 and 3.0. These results suggest that the stdKt/V is the most realistic model, but data over much higher levels of therapy are not yet available to judge generalizability. The stdKt/V model was used to assess dose in two hemodialysis studies with 5 to 6 dialyses per week and showed that in one study the stdKt/V was only 2.0, while in the second study it was 5.6. These results show that dose can vary widely with a similar number of dialyses per week and point to the need for a generalized dosing model to guide and compare studies of daily home dialysis.
Global ESRD Costs Associated with a Short Daily Hemodialysis Program in the United States
Authors: Ting George , Carrie Brian , Freitas Terri , Zarghamee Shahrzad
Published: September 2016

In spite of the growing evidence that daily hemodialysis (DHD) improves clinical outcomes and quality of life, the additional dialysis costs are not currently reimbursed in the United States. Nor have there been reports of the effects of DHD on end‐stage renal disease (ESRD) global costs, which would help predict the financial impact of DHD on the ESRD program. Since 1996, 22 patients (20 in‐center, 2 home) have switched from conventional thrice‐weekly dialysis to short, daily dialysis with six treatments per week. Eighteen patients started for medical indications, and four started for nonmedical reasons. Causes of ESRD were the following: diabetes mellitus (6), hypertension (4), glomerulonephritis (6), hereditary (2), and other (4). Mean age was 56 ± 16 years. Patients had an average of 3.3 major comorbidities. Weekly conventional HD dialysis times were divided into six DHD treatments, each 2.0 ± 0.3 hours. Weekly Kt/V remained unchanged. Twenty‐two patients were followed on DHD for 220 patient‐months: 7 patients died after 1.8 ± 1.3 months, 2 were transplanted at 4.3 ± 3.2 months, and 2 discontinued DHD at 3.6 ± 4.8 months. Eleven patients remain on DHD at 17.4 ± 8.3 months. Actual costs per extra dialysis session are as follows: $14.30 for supplies and $3.20 for labor for setup/cleanup time (15 minutes at $12.80/hour). Annualized DHD savings are based on comparison of doses of epoetin alpha (Epogen) and blood pressure medication at the start and after 12 months of DHD. Hospitalization rates include all enrolled patients, comparing rates for the 12 months prior to DHD with the first year on DHD, or annualized rates for those on DHD less than one year. Cost assumptions are $9/ 1000 U Epogen, $1/blood pressure pill, and $1200/per day of hospitalization. Extra transportation costs were covered by the patients. No increased access problems were observed. For patients on short DHD longer than 12 months, supply and labor costs increased to $2733/patient/year; however, Epogen use was reduced 55%, and blood pressure medications were reduced 40%. For all patients who switched to DHD, hospitalization rates were reduced 24%. This resulted in a net savings of about $4241/patient/ year after 12 months on DHD. Overall ESRD costs were substantially decreased on DHD. These cost savings must be passed on to providers before DHD becomes more widely available.
Evolution of Daily Hemodialysis in Acute Renal Failure: From the Korean War to the Present
Authors: Teschan Paul E.
Published: September 2016

Over half a century of hemodialysis therapy has brought significant progress in technology and in our approach to its use. This brief review has three objectives: (1) to describe what dialysis was like in the beginning, 50 years ago; (2) to review the origins and interval evolution of the paradigm of daily hemodialysis; and (3) to introduce some vistas for the future.
A Proposed Peritoneal‐Based Wearable Artificial Kidney
Authors: Roberts M. , Lee D.B.N.
Published: September 2016

Ideally, an artificial kidney should simulate the normal kidney in providing continuous metabolic control, removal of toxins, and unrestricted patient freedom. Of the dialysis procedures available, continuous ambulatory peritoneal dialysis (CAPD) comes the closest to this ideal but provides inadequate dialysis and fails to remove protein‐bound toxins.

A continuous, wearable, peritoneal‐based artificial kidney is proposed in which the spent peritoneal dialysate is regenerated using a REDY sorbent cartridge one‐tenth the size of the present cartridge, with the urease chemically bound to an inert support to eliminate the possibility of its displacement by protein in the spent dialysate. To simplify the flow path and to increase clearance, the dialysate flow will be through the peritoneal cavity using a dual lumen catheter instead of the traditional in/outflow through a single catheter. At a flow rate of 4 L/hour through the peritoneal cavity, of which 2 L/hour will pass through the sorbent cartridge, it is estimated that the weekly Kt/V will be 6.5 and the creatinine clearance will be 250 L. In addition, any protein in the spent peritoneal dialysate will be stripped of toxins by the sorbents and returned to the patient, thereby minimizing protein loss. The only disposables will be the sorbent cartridge and infusate, which will be changed every 8 hours.
Outpatient High‐Dose Urokinase Infusion Improves Dialysis Catheter Longevity: A Prospective Observational Study
Authors: Saran Rajiv , Venkataraman Vijaya , Leavey Sean F. , Usovsky Ron , Usha Kumari , Twardowski Zbylut J.
Published: September 2016

Catheter thrombosis is a major limiting factor affecting catheter survival in hemodialysis (HD). A previous retrospective study highlighted the utility of outpatient intradialytic high‐dose urokinase (HDU) infusion in the treatment of HD catheter thrombosis. The present study was designed to prospectively evaluate the effectiveness of 250 000 IU urokinase given as a 3‐hour infusion during HD. The infusion would follow detection of a drop in blood flow thought to be secondary to thrombosis [a "thrombotic event" (TE)] after exclusion of nonthrombotic causes of drop in blood flow [a "nonthrombotic event" (NTE)], such as systemic hypotension or suboptimal position of the catheter on x ray. An “event” was defined as a drop in pump blood flow by greater than or equal to 20% of the prescribed blood flow. Twenty patients (mean age 57.7 years; 13 males) with documented or potentially long‐term catheters were recruited (total catheters used, 30) from an outpatient HD unit. A variety of catheter types were used. Catheter position was confirmed on x ray. Hemodialysis sessions were monitored for 6 months or until catheter removal (whichever was earlier). Thrombotic and NTEs (mostly related to drop in blood flow) were noted. The use of intradialytic HDU infusions was monitored. Improvement was defined as reestablishment of blood flow to within 10% of prescription.

There were 24 TEs in 11 patients and 15 NTEs in 7 patients. Twenty‐one of 22 (95%) TEs responded to HDU, with complete restoration of blood flow; in 1/22 HDU‐treated instances there was a partial response. For 2/24 TEs the patients underwent catheter stripping with good results. Twelve of 15 NTEs occurred in the first 2 weeks of catheter placement versus 6/24 TEs (p = 0.001, chi‐square). Catheter survival was longer than 24 weeks in 12/30 catheters. Nine catheters were lost to NTEs. No catheter was lost secondary to a TE. It is therefore concluded that intradialytic outpatient HDU is useful for the treatment of HD catheter thrombosis. It may obviate/reduce the need for catheter stripping or replacement. Randomized controlled trials with this approach are needed. A higher proportion of NTEs tended to occur earlier after catheter placement compared to TEs.
Stepwise Anticoagulation with Warfarin for Prevention of Intravenous Catheter Thrombosis
Authors: Twardowski Zbylut J.
Published: September 2016

Warfarin is the most commonly used anticoagulant for prevention and therapy of thrombosis. Warfarin is a vitamin K antagonist and inhibits synthesis of clotting factors II, VII, IX, and X, and anticoagulant proteins C and S. Whereas there is extensive information about the efficacy of warfarin and target International Normalized Ratio (INR) for patients with artificial heart valves, atrial fibrillation, pulmonary emboli, deep venous thrombosis, and lupus anticoagulant, there is little in the literature on the role of warfarin in maintaining the patency of hemodialysis catheters. Much more is reported about the value of minidose warfarin in maintaining the patency of infusion catheters. Many centers have tried low‐dose warfarin (1 mg per day), and found this not to be effective in preventing catheter thrombosis in many patients. Although most support the use of warfarin following catheterproblems, individual units have their own guidelines, with doses ranging from 2 mg per day (normal INR) to formal systemic anticoagulation with INR from 1.5 to 3.0.

Stepwise anticoagulation with warfarin is emerging as useful in preventing catheter‐associated thrombosis. With this method, patients are placed on low‐dose warfarin after the first clotting episode. With each subsequent episode, the dose is increased, raising INR by 0.5 until clotting episodes do not recur. Warfarin doses similar to those in patients with artificial heart valves have been used in selected patients (target INR 3.0 – 4.0) to prevent clotting.
Blood Access Outcomes Associated with Short Daily Hemodialysis
Authors: Ting George
Published: September 2016

With the growing number of reports that daily hemodialysis (DHD) improves clinical outcomes and quality of life, there has been increased interest in the effects of more frequent venipunctures on blood accesses. Since 1996, we have converted 30 patients (27 in‐center, 3 home) from conventional 3/week dialysis to short, daily, 6/week dialysis (sDHD). Twenty‐five patients started for medical indications. End‐stage renal disease (ESRD) causes were diabetes mellitus (in 7), hypertension (6), glomerulonephritis (8), hereditary nephritis (2), and other (7). Mean (±SD) age was 57 ± 16 years. Patients had an average of 3.8 major comorbidities in addition to ESRD. Thirty patients were followed on sDHD for 388 patient‐months: 9 patients died after 4.2 ± 6.7 months, 3 were transplanted at 5.4 ± 2.2 months, and 3 were disenrolled at 9.3 ± 10.5 months. Fifteen patients remain on sDHD at 20.4 ± 14.1 months. Access problems for the 12 months prior to sDHD were compared to those that occurred while the patient was on sDHD. Problems were tracked by access type. There were 40 different accesses in 30 patients with a cumulative 28.07 access‐years pre‐DHD; 24 of these accesses were artificial bridge grafts (ABG) of either polytetrafluoroethylene or bovine material. There were 27 access problems pre‐DHD, or 0.962 problems per access‐year. On sDHD these same 30 patients had 41 accesses for 34.44 access‐years; 23 of these were ABGs. There were 31 access problems or 0.900 problems per access‐year. There were no significant differences in access problems comparing pre‐DHD with on‐sDHD, either in aggregate or when analyzed by access type. After 39 months of observation, there does not appear to be an increase in blood access problems when patients are converted from conventional dialysis to sDHD.
Why Our Patients Like Daily Hemodialysis
Authors: Piccoli Giorgina B. , Bechis Francesca , Iacuzzo Candida , Anania Patrizia , Iadarola Anna M. , Mezza Elisabetta , Vischi Margherita , Gai Massimo , Martino Barbara , Garofletti Yara , Jeantet Alberto , Segoloni Giuseppe P.
Published: September 2016

The option of daily hemodialysis (HD) was discussed in November 1998 with a group of 35 HD patients on home or self‐care/limited‐care HD in a single, freestanding unit. After the meeting, 3 patients on home HD chose to switch to daily HD. The clinical success of the first patient and the immediate followers was one of the main reasons for further extension of this experience. At the time of this writing (February 2000), 10 patients were on a daily HD program (8 at home and 2 in a self‐care/limited‐care center) and one was in training for home daily HD. One further patient who tried 1 month of daily HD dropped out for logistic reasons. On daily HD, patients are dialyzed 2 – 3 hours/day, 6 days/ week, with blood flow of 270 – 300 mL/min, on bicarbonate dialysate with individually determined levels of Na and K. The schedule is flexible and a switch to 3 – 4 dialyses/week is occasionally allowed for working needs or for vacation. In addition to the well‐known clinical advantages (better well‐being, blood pressure control, nutrition, etc.), some patients preferred daily HD because of easier organization of daily activities, including work schedule. Patients initially feared frequent needle punctures and excessive burden on partners, but those concerns proved to be less a problem than anticipated. All current patients are willing to continue daily HD; only a nursing shortage limits further extension of the program in the self‐care/limited‐care center.
The Case for Every‐Other‐Day Dialysis
Authors: Scribner Belding H. , Twardowski Zbylut J.
Published: September 2016

Until daily dialysis becomes widely available, we believe that hemodialysis patients would benefit enormously from every‐other‐day dialysis (EODD), which may be implemented both by home patients and in centers. Benefits of EODD over the routine, three‐times‐weekly schedule would include decreased mortality after the weekend interval without dialysis; increased weekly dose of dialysis, resulting in better rehabilitation; and improved blood pressure control.
What Went Wrong with Home Hemodialysis in the United States and What Can Be Done Now?
Authors: Blagg Christopher
Published: September 2016

In 1973, almost 40% of the more than 10 000 dialysis patients were treated by home hemodialysis. Today, with more than a quarter of a million dialysis patients in the United States, fewer than 2000 are on home hemodialysis. A number of factors have contributed to this change. First, many nephrologists and administrators who were developing new dialysis units had little or no practical experience with dialysis for chronic renal failure. Second, more elderly and diabetic patients were admitted to treatment. Home hemodialysis was more difficult for such patients, and often their helpers were themselves were elderly. Third, hemodialysis machines were difficult to learn and operate. Fourth, following publication of the results of the National Cooperative Dialysis Study, there developed the erroneous concept that a Kt/V equal to 1.0 was “adequate dialysis.” As bigger dialyzers became available, there was a widespread shortening of dialysis time. This decrease in time was embraced by for‐profit dialysis facilities and inadequately educated patients, and assembly‐line dialysis became generally accepted. Finally, continuous ambulatory peritoneal dialysis, with its simplicity and short training time, began to fill the need of many patients for home dialysis and independence, at least temporarily.

Fortunately, the trend is now reversing. Two developments clearly have benefits for home hemodialysis. The first is an increasing interest in the use of more frequent dialysis. The second is the development of new equipment designed specifically for use by the patient, and requiring a minimum of effort on the patient's part.
Volume Control in Hemodialysis Patients
Authors: Charra Bernard , Chazot Charles , Hurot Jean-Marc , Jean Guillaume , Terrat Jean-Claude , Vanel Thierry , Laurent Guy
Published: September 2016

Cardiovascular disease is the main cause of the high mortality of dialysis patients and is largely due to poor control of blood pressure. Establishing and maintaining normal extracellular volume (ECV) is required to achieve normotension. The dry weight concept links ECV and blood pressure by a simple clinical relationship. Dry weight is the ideal postdialysis weight that allows a constantly normal blood pressure to be maintained without using antihypertensive medications.

Maintenance of normal ECV requires control of salt intake to reduce interdialytic weight gain ( i.e., saline overload) combined with the diffusive and convective removal of salt and water from the body during dialysis sessions.

Several problems are to be faced when using the dry weight method. Clinical evaluation must take into account the following confounding factors: weight varies with nutrition, clinical symptoms are unspecific and sometimes discordant, and there is a lag time between ECV and blood pressure changes. On the other hand, achievement of dry weight is hampered by dialysis times that are too short (and weight gains that are too high), by antihypertensive medications, and by poor heart conditions. A longer session time allows for a slower, easier, and more comfortable ultrafiltration.
Thrombolytic Agents
Authors: Green David
Published: September 2016

Thrombus dissolution is dependent on activators of plasminogen, the principal enzyme of fibrinolysis, reaching plasminogen bound to the surface of fibrin, and overcoming the many inhibitors of clot lysis present in the plasma milieu. In dialysis patients with occluded catheters and grafts, three activators — streptokinase, urokinase, and tissue plasminogen activator (tPA) — have been used. Streptokinase has fallen out of favor because of its adverse effect profile; urokinase has been the mainstay of therapy. Urokinase has been used alone and in conjunction with mechanical methods for clearance of thrombi from arteriovenous grafts. It has also been instilled into occluded central venous catheters, but often is more effective if given systemically during dialysis in order to lyse the fibrin sheath that surrounds the catheter tip. Due of manufacturing problems, urokinase is no longer available and management with tPA is being actively investigated. One small trial showed that recombinant tPA was significantly more effective than urokinase for restoring catheter patency, but the drug is not yet approved for this purpose by the FDA, and current packaging is not optimal. The problems with thrombolytic agents may be obviated in the future by better methods of prevention of thrombus formation, monitoring flow to anticipate occlusion, and early mechanical interventions to restore patency.
Central Venous Catheters for Hemodialysis: How to Overcome the Problems
Authors: Davenport Andrew
Published: September 2016

The use of central venous dialysis catheters is increasing in clinical practice. These devices, although relatively easy to insert, do have problems. Catheter size limits the amount of dialysis that can be delivered. Central venous hemodialysis catheters minimize cardiopulmonary recirculation, but have increased potential for access recirculation compared to native or artificial arteriovenous (AV) fistulas and grafts. Developments in catheter design and optimal positioning have improved the amount of dialysis that can be delivered. Similarly, infection rates are improving with careful attention to peri‐insertion care and the use of topical antiseptics and antibiotics. Although catheter thrombus remains a problem, the introduction of recombinant tissue plasminogen activator and mechanical dislodgement with an endoluminal brush have improved patency rates, but some patients may require long‐term warfarin therapy.
Tunneled Catheter–Associated Atrial Thrombi: Successful Treatment with Chronic Anticoagulation
Authors: Kung Shiang-Cheng , Aravind Bonapally , Morse Stephen , Jacobs Larry E. , Raja Rasib
Published: September 2016

Tunneled dialysis catheter–associated right atrial thrombus (RAT) is a rarely reported complication. We reviewed hospital records of 10 patients from a teaching hospital dialysis unit, in whom RAT was diagnosed by trans‐esophageal echocardiography (TEE). Patients were treated with chronic anticoagulation (heparin followed by warfarin) and followed over time. The group included 7 women; 6 patients were African American, 3 were Caucasian, and 1 was Hispanic. The average age was 52.1 ± 15.3 years. The most common presenting symptom was poor catheter flow on hemodialysis followed by fever and chills. On average, the patients had had 3.4 ± 2.7 catheter insertions before diagnosis of RAT, and the tunneled dialysis catheter (TC) had been in place for a mean of 91 ± 89.4 days when the thrombi were diagnosed. Trans‐thoracic echocardiography (2‐D echo) was done in 4 patients, but it identified RAT in only 1 patient. The catheter tip was at the junction of the superior vena cava and right atrium (SVC/RA) in most patients.

Thrombolysis (unsuccessful) was attempted with urokinase in 3 patients, complicated in 2 patients by hemorrhage. After anticoagulation, 90% of the RAT resolved on repeated TEE. One patient had persistent RAT for 23 weeks and underwent surgical thrombolysis, but died postoperatively.

We conclude that RAT is a frequently missed complication of a TC. Positioning the tip of the TC at the SVC/RA junction may not prevent RAT. Trans‐esophageal echocardiography is a more sensitive diagnostic tool than 2‐D echo and should be obtained early. Most patients can be successfully treated with anticoagulation alone. Thrombolytic therapy and surgical thrombolysis have high morbidity and mortality.
A Comparative Study of C‐Reactive Protein Plasma Levels in Patients on Hemodialysis and Peritoneal Dialysis
Authors: Fernández–Reyes M. José , Hevia Covadonga , Bajo M. Auxiliadora , Peso Gloria Del , Costero Olga , Diez Juan J. , Selgas Rafael
Published: September 2016

In dialysis patients, C‐reactive protein (CRP), a well‐recognized marker of inflammation, predicts mortality. Higher levels have been described in hemodialysis (HD) patients as compared with peritoneal dialysis (PD) patients. Our aim was to determine, based on CRP plasma levels, the degree of inflammation in HD patients using low‐permeability polysulfone membranes and relatively pure dialysate, and that in PD patients. A secondary objective was to study factors associated with hypoalbuminemia and inflammation in both populations.

We studied 69 stable patients on dialysis (32 on HD and 37 on PD). The mean age was 69.9 ± 8.2 years, and the mean time on dialysis was 27 months. The two populations were comparable for overall and cardiovascular comorbidities. Nephelometry was used to measure CRP plasma levels (normal levels < 0.6 mg/dL). The Kt/Vurea, corrected for residual renal clearance, and the equivalent of protein nitrogen appearance (PNA) were also calculated.

Of the patients studied, 53% showed CRP plasma levels higher than 0.6 mg/dL; in 36%, the levels were higher than 1 mg/dL. No significant differences in these percentages were noted between the two dialysis groups. Patients with CRP levels higher than 1 mg/dL showed lower serum albumin, iron, hemoglobin, and transferrin levels, and higher ferritin values and leukocyte counts. Under logistic regression analysis, CRP levels higher and lower than 1 mg/dL were significantly associated with serum albumin [p = 0.01; odds ratio (OR): 0.15], iron (p = 0.006; OR: 0.96), transferrin (p = 0.004; OR: 0.97), and hemoglobin (p = 0.02; OR: 0.67). Serum albumin levels were significantly lower in PD patients. Under regression analysis, serum albumin levels correlated with cholesterol (r: 0.25; p = 0.04), serum iron (r: 0.5; p = 0.0001), transferrin (r: 0.3; p = 0.015), ultrafiltration capacity (r: 0.42; p = 0.008), and CRP values above 0.6 mg/dL (r: –0.65; p = 0.001).

In conclusion, the frequent elevation of CRP plasma levels observed in both HD and PD patients suggests the presence of a silent inflammatory state. Hemodialysis performed with biocompatible, low‐permeability membranes is not associated with higher CRP plasma levels than those seen in PD. In both groups, hypoalbuminemia is related to CRP level. Levels of serum albumin, slightly lower in PD patients, are also related to peritoneal ultrafiltration capacity.
Arterial Hypertension Is Associated with Increased Serum Lipoprotein(a) Levels in End‐Stage Renal Disease Patients
Authors: Fytili Christina I. , Passadakis Ploumis S. , Progia Euaggelia G. , Kambouromiti Georgia L. , Panopoulou Maria I. , Sombolos Kostas I. , Vargemezis Vassilis A.
Published: September 2016

In addition to disorders in lipoprotein metabolism, several other factors are involved in the development of atherosclerotic changes in end‐stage renal disease (ESRD) patients. One of these is arterial hypertension.

We evaluated serum lipids—total cholesterol (TC), triglycerides (TG), apolipoproteins (AI , A II , B, E), lipoprotein(a) [Lp(a)]—in 109 ESRD patients on dialysis [46 on hemodialysis (HD); 63 on continuous ambulatory peritoneal dialysis (CAPD)] and in 45 hyperlipidemic patients without renal failure (HL group). Dialysis patients were divided in two groups. Group A included 42 hypertensive patients (mean age: 62.3 ± 15.5 years) whose blood pressure (BP) was satisfactorily controlled with anti‐hypertensive medications. Group B included 67 non hypertensive patients (mean age: 66.6 ± 11.9 years).

Levels of Lp(a) were significantly higher in both the HD (p = 0.001) and the CAPD (p < 0.05) patients as compared with the HL group. When the HD and CAPD groups were divided into hypertensive and non hypertensive patients, Lp(a) levels were significantly higher in the hypertensive patients; this difference was not observed among non renal failure patients.

These results indicate that arterial hypertension is associated with elevated Lp(a) serum levels in ESRD patients undergoing either HD or CAPD.
Mechanism and Clinical Presentation of Heparin‐Induced Thrombocytopenia
Authors: Fischer Karl-Georg
Published: September 2016

Heparin‐induced thrombocytopenia (HIT) is a potentially life‐threatening complication of heparin anticoagulation, occurring in approximately 3% of patients treated with unfractionated heparin.

Heparin and platelet factor 4 (PF4) are capable of forming multimolecular complexes. Given stoichiometric concentrations of heparin and platelet factor 4 (PF4), heparin may induce conformational changes in the PF4 molecule, rendering it antigenic. The subsequent immune response generates antibodies against heparin–PF4 complexes (HIT antibodies). Binding of these antibodies to FcγIIA receptors on the surface of platelets results in potent platelet activation. Binding of HIT antibodies to heparan sulfate–PF4 complexes on the surface of endothelial cells (ECs) causes EC activation with subsequent expression of tissue factor. Activation of platelets and of ECs together leads to marked thrombin generation, resulting in the hypercoagulable state in HIT.

Clinically, HIT presents with two major sequelae: thrombocytopenia and thrombosis. Thrombocytopenia—that is, a platelet count below 150×10 9 /L—is present in 85% – 90% of HIT patients and typically occurs between day 5 and day 10 of heparin treatment. The mean platelet count nadir is approximately 60×10 9 /L. Alternatively, HIT may be associated with a marked fall in platelet count (≥50% of the initial value) whose nadir is not below 150×10 9 /L. Despite the low platelet count, thrombosis rather than bleeding predominates. In HIT, the risk for thrombosis is 5% – 10% in the first 2 days; the 30‐day cumulative risk is approximately 50%. Thromboses most often occur in deep veins of the lower limbs, frequently leading to pulmonary embolism. If thrombosis is severe or if it is detected in an unusual location in heparintreated patients, HIT should be suspected.
Management of Heparin‐Induced Thrombocytopenia During Renal Replacement Therapy
Authors: Davenport Andrew
Published: September 2016

Awareness is increasing concerning the development of antibodies to heparin–platelet factor 4 complex in both regular hemodialysis patients and those treated with continuous forms of renal replacement therapy. Although the development of antibodies does not result in thrombocytopenia or thrombosis in some patients, most patients present with thrombocytopenia, premature platelet activation, and clotting of the extracorporeal circuit. When systemic anticoagulation is also required to treat venous thrombosis, then synthetic heparinoids or recombinant hirudin will be the agents of choice. However, neither the synthetic heparinoids nor hirudin are without problems. A few patients may have cross‐reacting antibodies against the currently available heparinoids. Similarly, antibodies may develop against recombinant hirudin, leading to a potentiation of anticoagulant activity and increased risk of hemorrhage.

In the future, thrombin inhibitors such as recombinant hirudin and the arginine derivative argatroban will probably be the agents most widely used to prevent thromboembolic complications. However, anti‐platelet agents used alone or in combination with hirudin or synthetic heparinoids may provide adequate treatment by inhibiting both platelet and clotting cascade activation.
Dialysis Disequilibrium Syndrome Revisited
Authors: Sahani Mandeep M. , Daoud Tarek M. , Sam Ramin , Andrews Jerry , Cheng Yuk Lun , Kjellstrand Carl M. , Ing Todd S.
Published: September 2016

An aggressive dialysis in a grossly azotemic patient, especially one with severe metabolic acidosis, can lead to dialysis disequilibrium syndrome (DDS). Mild forms present as nausea, vomiting, restlessness, and headache. Severe manifestations include seizures, obtundation, coma, and even death.

This clinical picture is caused by cerebral edema induced by one or more of the following mechanisms:

“Reverse urea effect” ‐ Dialysis removes urea faster from the blood than from the brain; consequently, water enters the brain.

“Cerebrospinal fluid acidosis” ‐ Correction of systemic acidosis engenders the condition due to a lowering of brain pH.

“Idiogenic osmoles” ‐ As a response to blood hyperosmolar state, osmoles are produced in the brain. As blood osmolality decreases under relatively quick dialysis, idiogenic osmoles tend to induce brain edema.

Because the symptoms of DDS can be life‐threatening, preventive measures in patients with severe uremia are important. The first strategy relies on raising blood osmolality by introducing solutes (osmoles) into the blood. The second approach, which is the most common, decreases the efficiency of the dialysis treatment by shortening the duration of a dialysis run to 25% – 30% of normal, by lowering dialyzer blood flow or dialysate flow rate, by using a less efficient dialyzer, or by a combination of these maneuvers. Dialysis frequency is increased instead. Anticonvulsant drugs are needed in cases where the preventive measures have not been used or have been unsuccessful.
Peritoneal Dialysis and Hemodialysis in Pregnancy
Authors: Krane N. Kevin
Published: September 2016

Management of women who require dialysis during pregnancy is an unusual and challenging clinical problem for both the nephrologist and the obstetrician. More than 200 pregnancies have been reported in women requiring hemodialysis, and more than 50 pregnancies in women on peritoneal dialysis. Surveys from several countries of pregnancy in dialysis patients provide data regarding management and outcomes. Conception rates are significantly lower in women on dialysis, and when these women do become pregnant, the spontaneous abortion rate usually exceeds 40%. However, in the pregnancies that continue, as many as 71% result in surviving infants.

Pregnant women require longer, more intense hemodialysis, and enough experience has been reported to support the use of peritoneal dialysis as well as hemodialysis during pregnancy. The patients typically experience anemia, hypertension, and premature delivery. Most infants are small for gestational age, and the stillbirth rate is as high as 12%. While the potential problems are many, sufficient data has been accumulated to provide clinicians with guidelines to help them manage pregnant women on dialysis and to achieve successful outcomes.
Cardioprotection in the ESRD Population: How Do We Get There?
Authors: Petrulis Alice Stollenwerk , Holmes Kristen J. , Weber Rachel E. , Harris Meghan B.
Published: September 2016

Cardiovascular mortality for end‐stage renal disease (ESRD) patients is about 30 times the risk in the general population. About 30% of ESRD patients have hyperlipidemia. The 1998 National Kidney Foundation Task Force on Cardiovascular Disease recommends implementation of effective measures to prevent and treat cardiovascular disease in this population.

Our intent was to evaluate the extent of use of cardioprotective drugs in ESRD patients through a quality improvement project. Twenty‐eight dialysis facilities throughout Ohio volunteered for this project. Data regarding use of angiotensin‐converting enzyme inhibitors (ACE‐I) and angiotensin receptor blockers (ARB) in heart failure, beta‐blockers in myocardial infarction (MI), aspirin in coronary artery disease, and 3‐hydroxy‐3‐methylglutaryl coenzyme A (HMG‐CoA) reductase inhibitors (statins) were collected using chart abstraction for the period March through May 2000. The results were compared to Ohio hospital discharges from July through September 2000. This latter population was comprised of non‐‐ESRD patients. Dialysis facilities were visited and interviews were conducted with staff members. Information was gathered regarding facility infrastructure, quality improvement process, and existing protocols.

27% of ESRD patients with a history of heart failure were on ACE‐I, compared to 75.7% of non‐ESRD patients. 34.8% of ESRD patients with a previous MI were taking beta‐blockers, compared with 68.0% of non‐ESRD patients with a prior MI. Aspirin use in ESRD patients with a previous MI was 52.8%, compared to 88% in non‐ESRD patients with a prior MI. 17.3% of ESRD patients were on statins. Hyperlipidemia is found in 30% to 50% of ESRD patients.

The use of cardioprotective drugs in the Medicare ESRD patient is lower than in the Medicare non‐dialysis counterpart. Reasons for this are related to fragmentation of health care arising from communication and infrastructure issues. Until these issues are addressed and resolved, efforts at initiation of cardioprotective strategies will be slowed.
Comparison of Preventive Care Provided to Dialysis Patients by Nephrologists and to Patients Followed in General Medical Clinics: Compliance with American College of Physicians Guidelines
Authors: Hamad Abdullah , Lakshmi Kameswari , Khedr Mohammad , Ibrahim Hisham , Cantelmo Laurette , Ward Laurie
Published: September 2016

Most end‐stage renal disease (ESRD) patients do not have primary‐care providers, and preventive medicine often is provided by their nephrologists. Little has been written about their success in providing this care. We studied all patients on dialysis at our hospital and compared their preventive care to a control group followed in the general medical clinic. The general medical group showed higher compliance with Pap smears (89% vs 48%), mammography (87% vs 62%), fecal occult blood testing (75% vs 50%), and pneumococcal vaccination (55% vs 28%). The ESRD group had better compliance with influenza vaccination (70% vs 55%) and lipid profile (100% vs 75%).

When the subgroup of patients on hemodialysis (HD) was compared with patients on peritoneal dialysis (PD), it was shown that HD patients were more likely than PD patients to receive preventive care. We also compared diabetes‐specific care. The ESRD group had a higher rate of HbA 1C (100% vs 78%) and lipid monitoring (100% vs 76%), diabetes education (100% vs 84%), and podiatry visits (70% vs 38%). There was no difference in ophthalmologic examination or influenza vaccination. We found that nephrologists provide preventive care to ESRD patients with success approximately equal to primary‐care physicians in our institution, although in different parameters. Ready access to dialysis patients and their blood and unit‐specific policies contribute to compliance that is above national averages. Further improvements can be made by additional preventative measures policies, by physician and patient education, and by monitoring primary‐care compliance in the chart.
Pitfalls in the Use of Anticoagulants
Authors: Green David
Published: September 2016

Anticoagulants are in widespread use for the management of a variety of conditions, ranging from thrombus prevention to the treatment of arterial and venous occlusion. As with any effective therapy, recognition of adverse effects is critically important for the safe use of these drugs. Pitfalls in the use of heparins include dosing in close proximity to invasive procedures; not closely monitoring patients in whom dose adjustments may be required, such as the very obese, the elderly, and patients with renal or hepatic failure; failing to make dose adjustments during pregnancy; and not recognizing when patients are developing heparin‐induced thrombocytopenia or osteoporosis. Pitfalls in the use of unfractionated heparin include delays in achieving a therapeutic activated partial thromboplastin time (aPTT) and failure to consider the effects of protein binding in acutely ill patients. A pitfall in the use of low molecular weight heparin is giving prophylactic doses when therapeutic doses are indicated. Pitfalls in the use of warfarin are stopping heparin before the warfarin is fully effective; failing to maintain the International Normalized Ratio within the therapeutic range; failing to adjust the dose of warfarin because of changes in diet, renal or hepatic failure, and exposure to new drugs; failing to stop warfarin at an appropriate interval before an invasive procedure; and giving warfarin during pregnancy. Pitfalls in the use of thrombin inhibitors include using them with thrombolytic agents; giving them in proximity to invasive procedures; not adjusting the dose for renal or hepatic failure; and failing to consider the effect of these agents on the prothrombin time when initiating warfarin therapy.
Knowledge of Home Dialysis Among Inner‐City Satellite Hemodialysis Patients
Authors: Delano Barbara G. , Markell Marianna S. , Wolf Frieda , Ugova Ejiro , Friedman Eli A. , Salifu Moro O.
Published: September 2016

There is limited use of home renal replacement therapies in the U.S.A. One percent of dialysis patients are on home hemodialysis (HHD) and only 9% undergo peritoneal dialysis (PD). In an effort to better understand this, 161 satellite hemodialysis patients in 6 units in Brooklyn were surveyed. Forty‐eight percent of patients were women, 86% were black, 5% white, 8% Hispanic, and 1% other. Mean age was 49.4 years (range 22 – 69 years). Etiology of renal disease was hypertension (41%), diabetes mellitus (31%), polycystic kidney disease (3%), systemic lupus erythematosus (4%), and other or unknown (21%). Patients were queried about knowledge of and attitudes toward home therapies. Seventy‐nine percent of patients knew of home dialysis. The source of this information was the nephrologist (59%), the social worker (14%), a nurse (8%), other patients (4%), and other sources (15%). Only 10% of patients had ever considered HHD. Fifty‐four percent were afraid to do self‐care at home and 35% were not interested. Surprisingly, only 3% felt they had no reliable helper and 8% felt that their housing was not suitable. Similarly, 78% of patients had been spoken to about PD, but only 11% had considered it. Forty‐one percent were afraid of doing self‐care on PD, and 45% were not interested. We conclude that, although the majority of patients in six inner‐city dialysis units had heard of home dialysis, only a small number ever considered it. As many patients were afraid of doing home therapy, better education about the risks and benefits needs to be disseminated.
An alternative mode ofCD43 signal transduction activates pro‐survival pathways of T lymphocytes
Authors: Bravo‐Adame Maria Elena , Vera‐Estrella Rosario , Barkla Bronwyn J. , Martínez‐Campos Cecilia , Flores‐Alcantar Angel , Ocelotl‐Oviedo Jose Pablo , Pedraza‐Alva Gustavo , Rosenstein Yvonne
Published: September 2016

CD43 is one of the most abundant co‐stimulatory molecules on a T‐cell surface; it transduces activation signals through its cytoplasmic domain, contributing to modulation of the outcome of T‐cell responses. The aim of this study was to uncover new signalling pathways regulated by this sialomucin. Analysis of changes in protein abundance allowed us to identify pyruvate kinase isozyme M2 (PKM2), an enzyme of the glycolytic pathway, as an element potentially participating in the signalling cascade resulting from the engagement ofCD43 and the T‐cell receptor (TCR). We found that the glycolytic activity of this enzyme was not significantly increased in response toTCR+CD43 co‐stimulation, but thatPKM2 was tyrosine phosphorylated, suggesting that it was performing moonlight functions. We report that phosphorylation of both Y105ofPKM2 and of Y705of signal transducer and activator of transcription 3 was induced in response toTCR+CD43 co‐stimulation, resulting in activation of the mitogen‐activated protein kinase kinase 5/extracellular signal‐regulated kinase 5 (MEK5/ERK5) pathway.ERK5 and thecAMPresponse element binding protein (CREB) were activated, and c‐Myc and nuclear factor‐κB (p65) nuclear localization, as well as Bad phosphorylation, were augmented. Consistent with this, expression of humanCD43 in a murine T‐cell hybridoma favoured cell survival. Altogether, our data highlight novel signalling pathways for theCD43 molecule in T lymphocytes, and underscore a role forCD43 in promoting cell survival through non‐glycolytic functions of metabolic enzymes.
The interaction of pillars in multi‐pillar pension systems: A comparison of Canada, Denmark, Netherlands and Sweden
Authors: Sørensen Ole Beier , Billig Assia , Lever Marcel , Menard Jean‐Claude , Settergren Ole
Published: September 2016

Canada, Denmark, the Netherlands and Sweden have advanced multi‐pillar pension systems. Using micro‐simulations, this article presents a close examination of the interaction of pillars in these countries. The relative importance and the role of the different pension pillars vary from country to country, and according to age, income, gender and socio‐economic dimensions as well as between generations. A further area of investigation is the mitigation capacity of the four pension systems. On the one hand, adverse labour careers lead to lower life‐time earnings and lower private pension accruals. On the other hand, these effects are mitigated through the design of pillars and their interaction. Mitigation is important to income security and stability in retirement and to post‐retirement income distribution. However, mitigation mechanisms come at the cost of incentives. Moreover, in many countries, the generosity of public benefits is set to decrease – increasing the importance of private pensions. This will shift risk and uncertainty from employers and pension institutions to individuals. Thus, risks and uncertainties related to private pensions will become more important, raising questions about the division of responsibilities between public and private pensions, and about the potential of mitigating such risk through pillar interaction. These concerns are further reinforced by labour market changes. Although a pension system free of distortions is inconceivable, this article seeks to contribute to addressing how mitigation should be designed, and how mitigation and risk sharing should be balanced against incentives, challenges which are as much political as technical.
What Oregon Psychologists Think and Know About Prescriptive Authority: Divided Views and Data‐Driven Change
Authors: Tompkins Tanya L. , Johnson Jenna D.
Published: September 2016

Following a veto of a prescriptive authority (RxP) bill in Oregon, 397 of 743 randomly selected psychologists were surveyed online regarding their attitudes and knowledge. Participants were randomly assigned to a control (n = 203) or education (n = 194) condition. After being exposed to information regarding access, training, and legislation, education participants completed post‐test measures. Evidence supporting proponents’ argument of improved access was not forthcoming. There was a division about scope expansion (43% support, 32% opposed, 25% undecided). Respondents’ knowledge of RxP was minimal, but education increased knowledge. Views were more stable, with attitudes shifting only in targeted areas. Using a “cultural cognition” framework, the discussion centers on exploring the need to evaluate RxP and use this information to educate psychologists about this issue.
Stability of core language skill across the first decade of life in children at biological and social risk
Authors: Bornstein Marc H. , Hahn Chun‐Shin , Putnick Diane L.
Published: September 2016

Background

Command of language is a fundamental skill, a cornerstone of multiple cognitive and socioemotional aspects of development, and a necessary ingredient of successful adjustment and functioning in society. Little is known about the developmental stability of language in at‐risk youth or which biological and social risk factors moderate stability.

Methods

This four‐wave 10‐year prospective longitudinal study evaluated stability of core language skill in 1,780 children in varying categories of biological and social risk in a multiage, multidomain, multimeasure, and multireporter framework.

Results

Structural equation modeling supported loadings of diverse age‐appropriate measures of child language on single latent variables of core language skill at 15 and 25 months and 5 and 11 years, respectively. Core language skill was stable over the first decade of life; significant and comparable stability coefficients were obtained for children with diverse biological and social risks, including poor health, welfare status, teen motherhood, ethnicity, gender, birth order, and families that changed in income and maternal education over the study period; stability in language was strong even accounting for child nonverbal intelligence and social competence, maternal education and language, and the family home environment.

Conclusions

Core language skill varies in stability with age but is robustly stable in children regardless of multiple biological and social risk factors.