De novo once-monthly darbepoetin alpha treatment for the anemia of chronic kidney disease using a computerized algorithmic approach.

BACKGROUND: Anemia of chronic kidney disease (CKD) has been traditionally treated by erythropoiesis-stimulating agents (ESAs) and/or iron following manual determination of dose. We hypothesized that once-monthly (QM) algorithmically dosed darbepoetin α (DA) and iron administration would successfully treat anemia of CKD in ESA-naïve CKD subjects. METHODS: QM DA and iron doses were determined via a computerized program targeting a hemoglobin (Hb) of 10.5 - 12.5 g/dl in anemic, ESA-naïve, CKD Stages 3 - 5 subjects. Six consecutive QM doses were administered. Hb, ferritin, and transferrin saturation were recorded. Data are presented as means ± standard deviation. RESULTS: Anemia was identified in 133 subjects, with a mean follow-up of 188 days. DA doses and Hb were significantly greater at Months 3 and 6 compared to baseline (p < 0.05); DA doses were 109 ± 68 µg and 118 ± 91, respectively, at Months 3 and 6. Hemoglobin levels were correspondingly 11.3 ± 1.1 g/dl and 11.3 ± 1.0. 78% of patients achieved the target Hb by 6 months of therapy. The elevation of Hb was greater in non-proteinuric than proteinuric subjects at 6 months of treatment (11.6 ± 0.8 g/dl vs. 11.0 ± 1.1; p < 0.05), despite lower DA dose (96 ± 76 µg vs. 139 ± 98; p < 0.05). CONCLUSION: Successful treatment of the anemia of CKD by QM DA based upon a computerized dosing program was achieved by 6 months in 78% of ESA-naïve, CKD subjects.

Comparison of long-term actual renal allograft survival in mycophenolate mofetil and azathioprine-based triple drug immunosuppression protocols.

INTRODUCTION: The use of mycophenolate mofetil (MMF) in renal transplantation results in a 50% lower incidence of acute rejection compared to azathioprine (AZA). However, the graft survival reports are conflicting: the European trial and US database analysis suggest better survival with MMF, an observation that was not seen in the US and tricontinental studies. METHODS: We retrospectively reviewed our single-center experience (60% African-Americans) comparing the serum creatinine (SCr) values and 3-year actual graft survival with MMF versus AZA-based immunosuppression. Group I included patients transplanted between January 1990 and December 1992 on cyclosporine (CSA), AZA, and steroids; group II subjects, from January 1996 to December 1998 on CSA, MMF, and steroids. We analyzed SCr and all causes of graft losses at 3, 6, 12, 18, 24, and 36 months posttransplantation. RESULTS: The patient demographics were similar in both groups as was the mean SCr values at different times. The time-group interaction for SCr, the Kruskal-Wallis test for SCr for different categories (<1.5, 1.5 to 2.0, 2.0 to 2.5, and >2.5 mg/dL) and the all-cause graft loss between the two groups were not significantly different. CONCLUSION: Our results failed to show better long-term actual graft survival despite the 6-year interval between the two groups. These findings agree with the results of the United States and the tricontinental studies. A lower incidence of acute rejection early after transplantation observed with MMF may not always translate into a long-term benefit, possibly due to the influence of nonimmunological factors, such as hypertension, calcineurin inhibitor toxicity, more frequent cytomegalovirus infections, and increased attempts to withdraw steroids using MMF-based protocols.

Increased urea kinetic modeling volume. Possible mechanisms and its significance.

The presence of access recirculation reduces delivered urea clearance and produces an increased volume/weight (V/M) ratio in three-point kinetic modeling. We measured R in 20 patients receiving conventional hemodialysis and correlated results with normalized intra-access venous pressure (PIA) and with angiographic or color-flow Doppler studies. Twenty patients were equally divided into those with and without persistently elevated modeled V/W ratios (0.64 vs 0.53), and subdivided into those with native and synthetic bridge graft accesses. Kinetic modeling parameters (Kt/V) and P1A did not differ between the two V/W groups. Modeled volume was quite accurately predicted by the equations in the normal group but deviated by 7.3 +/- 2.1 L in the high V/W ratio group. Three of 10 native and 4 of 10 graft accesses had trivial and hemodynamically insignificant abnormalities by color-flow Doppler or angiography. Recirculation was independent of V/W group and when measured by the slow flow/clamp technique was negligible (< 2.0%). Access flow always exceeded prescribed dialyzer blood flow by more than 300 ml/ min. Therefore, access recirculation was unlikely. In many of the high V/W patients, alternative explanations for falsely high modeled volume were found on follow-up modeling. Only one patient appeared to have a true high volume. The authors conclude that high urea volumes during kinetic modeling are unlikely to occur from access recirculation, but arise from other factors affecting the delivered urea clearance.

Single center success with a high risk peritoneal dialysis population.

A large end stage renal failure population treated by chronic ambulatory peritoneal dialysis (CAPD) was examined for rates of infection, CAPD modality failure and patient survival (N = 347). Nearly half were considered high risk for survival for reasons of age (39% older than 60 years), diabetes mellitus (33%), hemodialysis access failure (10%), poor cardiopulmonary reserve (16%) or technical challenges (30% had morbid obesity, history of abdominal aortic aneurysm repair or multiple abdominal surgeries). Hence, CAPD was often initiated by default rather than choice in the 347 patients studied (mean age: 51 +/- 17 years). Infections greatly outnumbered technical failures as grounds for cessation of CAPD. Over 5521 patient-months, 51% of patients developed infection with peritonitis predominating (80%) when compared to exit site infections (20%). The frequency of infections was 1.9 mean episodes per patient; however, 55% of these patients had only one episode of peritonitis. A rate of 0.75 infections per patient per year was seen with an average interval of 16 months between infections. Technique and patient survival rates at 4 years were 50% and 61% respectively. High risk status does not preclude successful CAPD and should not preclude its implementation.

Introduction, demography, and general methods.

The International Cooperative Biocompatibility Study was planned to analyse the symptomatic and laboratory response to seven different dialysers studied in five centres in four countries. The dialysers used were the G10-3N, G120 M, CD 4000, T 150, Duo-Flux, F 60, and Filtral (see below for full description). A total of 37 patients in the Veterans Administration Lakeside Medical Center, Chicago; Henry Ford Hospital, Detroit; Osaka City University Hospital, Osaka; Wilhelm Pieck University Hospital, Rostock; and Huddinge University Hospital, Stockholm were studied. All patients had been dialysed for a minimum of 6 months, were non-diabetic, stable, and compliant; and most were middle-aged and male. Patients were treated three times per week for 2 weeks with each new dialyser with random assignment to one of four orders of dialyser use. The same manufacturing lot of each dialyser, blood line sets and needles were used by all centres. Delivery systems were volumetric controlled except for some patients in Osaka treated with negative-pressure equipment. Individual patient prescriptions (Kt/Vs for urea), in use prior to the study, were continued. Kt/Vs for all treatments were derived from reported blood flows and blood water corrected mass transfer coefficients multiplied by dialyser surface area. Clinical data were measure pre-, intra- and postdialysis. Hourly signs, symptoms, drugs, and nursing interventions were recorded using the identical treatment record at all centres. In addition, patients completed a questionnaire form (translated into the appropriate language) at least weekly, relating symptoms experienced with each dialyser. Laboratory investigations were performed during the sixth consecutive treatment.(ABSTRACT TRUNCATED AT 250 WORDS)

Relationship between dialyser type and signs and symptoms.

A crossover study to compare the effects of seven different dialysers on intradialytic symptoms in 37 patients during dialysis with acetate-containing dialysate was performed at five centres in four countries. The same manufacturing lot of each dialyser and of blood line sets were used by all centres. The same clinical data (duration of dialysis, blood pressure, weights, temperature, drugs, symptoms, and treatments) and technical data (blood flow, dialyser clearance, and ultrafiltration rate) were collected. Kt/V for urea was used to determine dialysis prescribed. Intradialytic symptoms and signs were measured hourly or when observed by staff using the haemodialysis treatment form (see Introduction). After each week of treatment with a particular dialyser, patients completed a questionnaire relating to the presence and severity of symptoms. (Only presence or absence of symptoms are presented.) Wide differences in dialysis duration and blood flow between centres were noted. These may have contributed to the differences between centres in relationship to staff reported responses to different dialyser: Dialysers with the lowest incidence of both signs and symptoms and of chest pain, back pain, and itching (arbitrarily designated bioincompatibility symptoms) were the Duo-Flux and Filtral, with the G120 M, the CD 4000, and the T 150 having the highest incidence. By patient questionnaire the most biocompatible dialysers were the T 150, F 60, and the Filtral, with the most symptom producing being the G120 M and the G10-3N. Perceptions of symptoms between patients and staff differed substantially overall and between centres. Hypersensitivity reactions were noted in two patients, both occurring with cuprammonium cellulose hollow-fibre dialysis, despite adherence to manufacturers' instructions concerning saline priming and removal. Both patients showed antibody titres greater than 1:160 against ethylene oxide-HSA. Ethylene oxide was not detected (limit of detection 1 part per million) in dialysers, blood line sets, or fistula needles. The study suggests that dialysis symptom reporting is complicated by individual perceptions, staff reactions, and the efficiency of recording. In this study ethnic and cultural differences must be added to the haemodynamic differences and other prescription-related elements in influencing symptoms. Despite these problems a hierarchy of dialyser-related symptoms and signs could be discerned which largely paralleled laboratory findings of biocompatibility. Future comparative studies relating symptomatology to membrane and dialyser structure should consider the variables identified as influencing symptoms and their reporting.

An evaluation of the standard bubble time technique for the measurement of extracorporeal blood flow.

Manual BT is the standard technique to use when measuring Qb for dialysis. An electro-optical system (QB-1) was devised for the measurement of BT and its relationship to real Qb. We investigated the accuracy of standard manual timing methods, the roller pump induced effects of high amplitude low frequency pulses (HALFP), the fundamental pulse of flow (Lp), and the effect of hematocrit (HCT) on BT. Blood with 15, 24, and 38 HCT was used. During dialysis, BT's were measured manually and by QB-1. With Qb greater than 200 ml/min, variations in length became insignificant. HCT did not influence BT at the values studied. In conclusion, 1) QB-1 is more accurate than manual measurements of BT, especially at higher Qb. 2) Qb greater than 200 ml/min dampens the effects of HALFP at any length of tubing. 3) HCT has no effect on BT.

Effect of dialyzer reprocessing methods on complement activation and hemodialyzer-related symptoms.

The effects of different dialyzer processing methods and of reuse on complement activation and dialyzer-related symptoms were studied in 96 maintenance hemodialysis patients. New dialyzers were either unprocessed (Group 1) or machine-washed with bleach and stored in formaldehyde (Group 2). Reused dialyzers were manually cleansed using the combination of bleach and formaldehyde (Group 3), or machine-washed in formaldehyde (Group 4) or peracetic acid (Group 5). Prewashed new dialyzers (Group 2) were associated with greater complement activation during dialysis when compared with unprocessed, new dialyzers (Group 1) (p less than 0.05). Reused, unbleached but formaldehyde-treated or peracetic acid-treated dialyzers (Groups 4 and 5) were associated with reduced complement activation (p less than 0.05). Complement activation was not reduced when bleach was used for reprocessing (Group 3). The percentage of patients without symptoms during dialysis was significantly greater with reused dialyzers than with new dialyzers (Groups 3 through 5 versus Groups 1 and 2; 39 versus 25%; p = 0.035). The severity of total symptoms correlated significantly (p = 0.0004) with complement activation. Our results suggest that total symptoms during dialysis are correlated with the degree of complement activation. However, trends in the data pertaining to chest pain suggest that factors other than complement activation may be important in the pathogenesis of some dialyzer-related symptoms.

A practical algorithm for blood pressure (BP) monitoring and control during hemodialysis.

A system such as described here is technically feasible, allows for adequate BP monitoring and control, thus providing safe and efficient hemodialysis while maintaining cost effective patient care.

Clinical experience with short-time hemodialysis.

After at least 6 months on conventional hemodialysis (cellulosic dialyzers, acetate dialysate, and a 3- to 4-hour treatment time), 56 patients were changed to short-time hemodialysis (less than 180 minutes) using polysulfone dialyzers and bicarbonate-containing dialysate. Treatment time decreased (191 +/- 5 v 147 +/- 5 min; P = 0.001), while Kt/V (1.22 +/- 0.04 v 1.29 +/- 0.06; P = NS) and normalized protein catabolic rate (pcr) (1.10 +/- 0.05 v 1.10 +/- 0.07 g/kg/d; P = NS) remained constant. When compared with the conventional period, 30 months of short-time hemodialysis resulted in no changes in predialysis blood pressure (BP) (151 +/- 2/84 +/- 1 v 151 +/- 2/86 +/- 1 mm Hg), postdialysis BP (144 +/- 2/81 +/- 1 v 143 +/- 3/84 +/- 1 mm Hg), interdialytic weight gain (2.4 +/- 0.1 v 2.7 +/- 0.2 kg), or blood urea nitrogen (BUN) (26.1 +/- 0.71 v 25.3 +/- 1.07 mmol/L [73 +/- 2 v 71 +/- 3 mg/dL]). Shorter treatment times were not associated with an increase in intradialytic complications. Actually, the frequency (%) of dialysis treatments associated with nausea (5.94 +/- 1.33 v 2.21 +/- 0.52), vomiting (3.12 +/- 0.87 v 0.54 +/- 0.14; P less than 0.05), headaches (5.60 +/- 1.13 v 2.03 +/- 0.52; P less than 0.05), and back pain (0.91 +/- 0.25 v 0.05 +/- 0.05; P less than 0.05) was decreased.(ABSTRACT TRUNCATED AT 250 WORDS)

Effect of cooled dialysate on serum catecholamines and blood pressure stability.

In the current study dialysis at 34 degrees C resulted in improved vascular stability in a group of patients who developed hypotension on conventional dialysis at 37 degrees C. Side effects of dialysate cooling were not noteworthy. The stability of blood pressure during cool dialysis may at least in part be due to an increase in plasma norepinephrine concentrations not observed during warm dialysis. Although pathogenesis of dialysis induced hypotension has not been clearly elucidated, a reduced vasoconstrictor and catecholamine response may be an important mechanism.

The effect of cooled dialysate on thermal energy balance in hemodialysis patients.

The authors have monitored extracorporeal thermal energy balance using continuous in-line arterial and venous temperature and blood flow measurements. Use of dialysate at 37 degrees C resulted in a mean heat energy gain of 83 +/- 61 cal/min, whereas dialysate at 34 degrees C produced a loss of 463 +/- 121 cal/min. Monitoring extracorporeal thermal energy balance during cooled-dialysate hemodialysis will facilitate the use of feedback loops for dialysate temperature control in order to maximize hemodynamic stability while reducing discomfort. This methodology also may be helpful in assessing the metabolic effects of protein intake, high flux dialysis, membrane biocompatibility, and adequacy of dialysis in relation to thermal energy balance.