The dialysis outcomes and practice patterns study (DOPPS): how can we improve the care of hemodialysis patients?

Outcomes among dialysis patients vary considerably internationally and across regions within the United States. The Dialysis Outcomes and Practice Patterns Study (DOPPS) is a large, prospective, observational study of representative samples of hemodialysis patients in France, Germany, Italy, Japan, Spain, the United Kingdom, and the United States. The DOPPS collects a wealth of data regarding the patients' demographic characteristics, medical histories, laboratory values, prescriptions, dialysis unit practices, and outcomes. The study seeks to clarify which dialysis practices contribute to improved mortality rates, hospitalization rates, health related quality of life, and vascular access outcomes, after adjusting for the effects of comorbid disease and demographic variables. Over 18,000 patients have been enrolled to date. This paper describes the initial findings and outlines the plans to expand the trial.

A calcimimetic agent lowers plasma parathyroid hormone levels in patients with secondary hyperparathyroidism.

BACKGROUND: The calcimimetic agent R-568 lowers plasma parathyroid hormone (PTH) levels in hemodialysis patients with mild secondary hyperparathyroidism, but its efficacy in those with more severe secondary hyperparathyroidism has not been studied. METHODS: Twenty-one patients undergoing hemodialysis three times per week with plasma PTH levels between 300 and 1200 pg/mL were randomly assigned to 15 days of treatment with either 100 mg of R-568 (N = 16) or placebo (N = 5). Plasma PTH and blood ionized calcium levels were measured at intervals of up to 24 hours after oral doses on days 1, 2, 3, 5, 8, 11, 12, and 15. RESULTS: Pretreatment PTH levels were 599 +/- 105 (mean +/- SE) and 600 +/- 90 pg/mL in subjects given R-568 or placebo, respectively, and values on the first day of treatment did not change in those given placebo. In contrast, PTH levels fell by 66 +/- 5%, 78 +/- 3%, and 70 +/- 3% at one, two, and four hours, respectively, after initial doses of R-568, remaining below pretreatment values for 24 hours. Blood ionized calcium levels also decreased after the first dose of R-568 but did not change in patients given placebo. Despite lower ionized calcium concentrations on both the second and third days of treatment, predose PTH levels were 422 +/- 70 and 443 +/- 105 pg/mL, respectively, in patients given R-568, and values fell each day by more than 50% two hours after drug administration. Predose PTH levels declined progressively over the first nine days of treatment with R-568 and remained below pretreatment levels for the duration of study. Serum total and blood ionized calcium concentrations decreased from pretreatment levels in patients given R-568, whereas values were unchanged in those given placebo. Blood ionized calcium levels fell below 1.0 mmol/L in 7 of 16 patients receiving R-568; five patients withdrew from study after developing symptoms of hypocalcemia, whereas three completed treatment after the dose of R-568 was reduced. CONCLUSIONS: The calcimimetic R-568 rapidly and markedly lowers plasma PTH levels in patients with secondary hyperparathyroidism caused by end-stage renal disease.

Hematocrit stability following intravenous versus subcutaneous administration of epoetin alfa to dialysis patients: a post hoc analysis.

UNLABELLED: BACKGROUND, SUBJECTS AND METHODS: A previous study of epoetin alfa dose requirements [Paganini et al. 1995] among hemodialysis patients who were switched from thrice weekly intravenous (i.v.) to thrice weekly subcutaneous (s.c.) administration showed that the weekly epoetin alfa dose requirement decreased by 18.5% after 13 to 16 weeks s.c. treatment and 26.5% after 21 to 24 weeks, without significant change in hematocrit. There was patient-to-patient variation in response, however, and 39% of the patients required the same or greater doses of epoetin alfa after the change from i.v. to s.c. administration. The present study reexamines the database to compare hematocrit stability between the two routes of administration. RESULTS: During 4 weeks of i.v. epoetin alfa administration, the pooled standard deviation (SD) for the patients' (n = 72) weekly hematocrit measurements was 1.40, compared with weeks 13 to 16 of s.c. epoetin alfa administration when the SD was 1.66 (p < 0.01). Among 41 patients who completed 24 weeks of s.c. therapy, the pooled SD for the 4 weeks of i.v. treatment was 1.37 compared with 2.02 during weeks 21-24 of s.c. treatment (p < 0.01). Sixty-eight percent of patients had lower hematocrit SD during 4 weeks of i.v. therapy than during the 4 weeks of s.c. therapy (p = 0.03). CONCLUSION: These data suggest that hematocrits may be more stable when epoetin alfa is administered i.v. rather than s.c. to patients on dialysis. These results would be expected since 100% of i.v.-administered epoetin alfa reaches the systemic circulation compared with 18% to 80% bioavailability of s.c.-administered epoetin alfa. Within-patient variation in s.c. epoetin alfa absorption may be related to non-uniformity of adipose tissue, blood supply, lymphatic drainage, and other factors at sequential injection sites, and may explain the variability in hematocrit after s.c. administration.

The effects of normal as compared with low hematocrit values in patients with cardiac disease who are receiving hemodialysis and epoetin.

BACKGROUND: In patients with end-stage renal disease, anemia develops as a result of erythropoietin deficiency, and recombinant human erythropoietin (epoetin) is prescribed to correct the anemia partially. We examined the risks and benefits of normalizing the hematocrit in patients with cardiac disease who were undergoing hemodialysis. METHODS: We studied 1233 patients with clinical evidence of congestive heart failure or ischemic heart disease who were undergoing hemodialysis: 618 patients were assigned to receive increasing doses of epoetin to achieve and maintain a hematocrit of 42 percent, and 615 were assigned to receive doses of epoetin sufficient to maintain a hematocrit of 30 percent throughout the study. The median duration of treatment was 14 months. The primary end point was the length of time to death or a first nonfatal myocardial infarction. RESULTS: After 29 months, there were 183 deaths and 19 first nonfatal myocardial infarctions among the patients in the normal-hematocrit group and 150 deaths and 14 nonfatal myocardial infarctions among those in the low-hematocrit group (risk ratio for the normal-hematocrit group as compared with the low-hematocrit group, 1.3; 95 percent confidence interval, 0.9 to 1.9). Although the difference in event-free survival between the two groups did not reach the prespecified statistical stopping boundary, the study was halted. The causes of death in the two groups were similar. The mortality rates decreased with increasing hematocrit values in both groups. The patients in the normal-hematocrit group had a decline in the adequacy of dialysis and received intravenous iron dextran more often than those in the low-hematocrit group. CONCLUSIONS: In patients with clinically evident congestive heart failure or ischemic heart disease who are receiving hemodialysis, administration of epoetin to raise their hematocrit to 42 percent is not recommended.

Effects of Epoetin alfa on hemostasis in chronic renal failure.

Epoetin alfa is the cornerstone of anemia therapy in patients with end-stage renal disease. In addition to stimulating erythropoiesis, Epoetin alfa has been demonstrated to affect hemostasis. Such effects may be important because patients with chronic renal failure have a bleeding diathesis that is multifactorial in origin. Therefore, a computer literature search on the relationship between Epoetin alfa therapy for anemia in patients with end-stage renal disease and platelets, coagulation, coagulation inhibitors, and fibrinolysis was performed. All articles and abstracts reporting original data in the English language on Epoetin alfa and its effect on hemostasis were reviewed. The literature suggests that the effects of Epoetin alfa on the coagulation cascade are of minimal clinical importance. However, Epoetin alfa transiently increases the number of circulating platelets and improves platelet function, and these effects are associated with a return of the bleeding time towards normal.

Intravenous versus subcutaneous dosing of epoetin alfa in hemodialysis patients.

Hemodialysis patients were studied to determine whether the dose of recombinant human erythropoietin (Epoetin alfa; Amgen Inc, Thousand Oaks, CA) required to maintain a therapeutic hematocrit level changed when the route of administration was switched from intravenously (IV) three times per week to subcutaneously (SC) three times per week. Thirteen to 16 weeks after patients were changed from IV three times per week to SC three times per week treatment, the Epoetin alfa requirement was reduced by 18.5% +/- 3.8% (P < 0.001; n = 72), and after 21 to 24 weeks of SC treatment the mean dosage had decreased from the IV dose by 26.5% +/- 4.2% (P < 0.001; n = 41). Sixty-one percent (44 of 72) of patients experienced maintenance-dose reductions over 13 to 16 weeks of treatment and 80% (33 of 41) were maintained on lower weekly doses after 21 to 24 weeks of treatment than at baseline (IV). There was interpatient variability, however: 26% of the patients required greater doses SC than IV following 13 to 16 weeks of SC treatment, and 15% required greater doses SC than IV following 21 to 24 weeks. On completing the initial SC three-times-per-week stage of the study, patients were randomized to one of three SC dosing strategies for an additional 12 weeks: (1) once per week, (2) three times per week Epoetin alfa diluted 1:2 with bacteriostatic saline to mitigate stinging at the injection site, or (3) continued three times per week with undiluted Epoetin alfa. Patients who were switched to administration of SC once per week undiluted Epoetin alfa (n = 20) had their total weekly dose lowered by 18.0% +/- 9.4% (P > 0.05), but the mean hematocrit for this cohort also decreased, from 34.3% +/- 3.0% to 32.4% +/- 3.9% (P > 0.05), rendering dose comparison between the two schedules ambiguous. The maintenance dose for patients who received Epoetin alfa diluted 1:2 with bacteriostatic saline (n = 23) did not differ from the undiluted three times per week dose at the end of stage 1. The third cohort of patients (n = 24), who continued to receive undiluted Epoetin alfa on the same SC three-times-per-week schedule, did not require a significant change in dosage over the ensuing 12 weeks. Comparison of SC three times per week mean dosage after an average of 32 weeks following the switch from IV three times per week for this latter cohort revealed a decrease of 23.5% +/- 6.5% (P < 0.001).(ABSTRACT TRUNCATED AT 400 WORDS)

Role of platelet-derived growth factor in osteoblast function and bone synthesis.

In vitro studies have shown that platelet-derived growth factor binds to specific receptors on osteoblasts and induces proliferation. Some reports also indicate that platelet-derived growth factor may inhibit differentiation of bone cells. Such findings are difficult to interpret, however, because many of these studies used impure platelet-derived growth factor extracted from platelets (rather than pure, recombinant platelet-derived growth factor), used mixed cell populations, and added serum to the culture media (likely introducing additional growth factors). In vivo studies also have yielded conflicting results regarding the effects of platelet-derived growth factor on bone formation. Platelet-derived growth factor may act in concert with insulin-like growth factor I to induce bone formation in a canine periodontal system. Other investigators, however, have shown that platelet-derived growth factor inhibits the effects of osteoinductive proteins such as osteogenin. No evidence of bone formation has been detected in patients receiving platelet-derived growth factor treatment of soft tissue wounds overlying bony prominences in clinical trials. Thus, despite the observations that osteoblasts can specifically bind and proliferate in response to platelet-derived growth factor in tissue culture, platelet-derived growth factor alone has not yet been proved to be osteoinductive in vivo. These observations suggest that in the presence of the many cytokines and multiple cell types found in wounds and fractures, the direct effects of platelet-derived growth factor on osteoblasts are eclipsed.

Dilutional acidosis.

Rapid, extreme expansion of the extracellular fluid with solutions devoid of acid or alkali theoretically can produce a metabolic acidosis, due to buffer dilution. This phenomenon has previously been demonstrated only in experimental animal studies. We have reported what we believe to be the first documented case of hypobicarbonatemia and metabolic acidosis consequent to massive saline infusion, other causes having been excluded.

An outpatient maneuver to treat bloody effluent during continuous ambulatory peritoneal dialysis (CAPD).

Asymptomatic episodes of grossly bloody effluent during continuous ambulatory peritoneal dialysis (CAPD) can be treated by following a simple therapeutic maneuver. The patient performs one to three rapid exchanges using unwarmed (room temperature), 1.5% dextrose-containing dialysate. No dwell time is employed. This treatment proves successful in a variety of clinical settings, and no adverse effects have been noted. Infusion of unwarmed dialysate likely induces peritoneal vasoconstriction and thus favors hemostasis. Bleeding of nonperitoneal etiology, such as renal cyst hemorrhage or retrograde menstruation, proves resistant.

Radiographic contrast medium--induced glossitis.

A new complication of intravenous radiographic contrast medium administration is recognized: severe glossitis. The pathophysiology of adverse reactions to contrast media is briefly reviewed.

The role of the anion gap in detecting and managing mixed metabolic acid-base disorders.

Mixed metabolic-respiratory acid-base disorders may be diagnosed when the respiratory compensation for a primary metabolic acidosis or alkalosis is inappropriate or when there is inappropriate metabolic compensation for a primary respiratory disorder. The magnitude of the primary change in HCO3 concentration (in metabolic disorders) defines the limits of compensation. We emphasized the importance of the equality of the increment in the anion gap (delta AG) and the decrement in the serum bicarbonate concentration (delta HCO3) in diagnosing a simple high AG metabolic acidosis. The close relationship between these two changes in simple high AG acidoses is reviewed. When the delta HCO3 is greater than the delta AG, we suggest that a mixed high AG and hyperchloraemic acidosis is present. Other possible interpretations of these chemical changes are discussed. When the delta HCO3 is less than the delta AG, a mixed metabolic alkalosis and metabolic acidosis is likely to be present, but other additional explanations of this combination are also reviewed. Thus, guidelines are presented as a basis for the use of the delta AG and delta HCO3 for diagnosing and managing mixed metabolic acid-base disorders.