Safety and efficacy of iron sucrose in patients sensitive to iron dextran: North American clinical trial.

Sensitivity to iron dextran is a potent obstacle to maintaining optimum iron status in patients with dialysis-associated anemia. As part of the North American clinical trials for iron sucrose injection, we examined the effect of intravenous (IV) iron sucrose in 23 hemodialysis patients with documented sensitivity to iron dextran, ongoing epoetin alfa therapy, and below-target-range hemoglobin (Hgb) levels (<11.0 g/dL). We assigned patients to treatment groups according to whether reactions they had experienced to iron dextran were judged to be mild (n = 16; group A) or severe (n = 7; group B). We prospectively examined adverse events and vital signs after administering 100 mg of IV iron sucrose in each of 10 consecutive dialysis treatment sessions and compared results with those recorded in each of three consecutive dialysis sessions without iron treatment. We administered iron sucrose by IV push over 5 minutes to group A patients and by IV push over 5 minutes or IV infusion over 15 to 30 minutes to group B patients. We did not administer a test dose. Results showed no serious adverse drug reactions after a total of 223 doses of iron sucrose (184 doses by IV push, 39 doses by IV infusion). Intradialytic blood pressure changes after IV iron sucrose injection did not differ from those recorded during dialysis sessions without treatment. An increase in values for Hgb, hematocrit, transferrin saturation, and ferritin, coupled with no significant change in epoetin dose and a decrease in total iron-binding capacity, confirmed the efficacy of iron sucrose injection in managing anemia. We conclude that iron sucrose injection is safe and effective in the management of anemia in patients sensitive to iron dextran and can be administered without a test dose by IV push or infusion.

Design and baseline characteristics for the aminoguanidine Clinical Trial in Overt Type 2 Diabetic Nephropathy (ACTION II).

Advanced glycosylation endproduct (AGE) formation has been implicated in the development and progression of nephropathy in type 2 diabetes mellitus. In diabetic animals, aminoguanidine inhibits AGE-mediated cross-linking of proteins in vascular and renal tissue and slows the progression of renal disease. ACTION II is a randomized, double-blind, placebo-controlled trial comparing two dose levels of aminoguanidine with placebo on the progression of nephropathy in 599 type 2 diabetic patients with renal disease from 84 centers in the United States and Canada. The primary endpoint is time to doubling of serum creatinine concentration. Secondary endpoints include the effect of aminoguanidine on time to all-cause mortality, end-stage renal disease (ESRD), cardiovascular morbidity and mortality, rate of change in indices of renal function (iothalamate, Cockcroft and Gault [C&G] calculated creatinine and measured creatinine clearances), proteinuria, retinopathy, circulating and urinary AGE levels, and estimation of the relationship between plasma aminoguanidine concentrations and primary and secondary efficacy endpoints and adverse events. Progression of macrovascular disease was monitored and fundus photography performed. Type 2 diabetic patients aged 30 to 70 years were eligible for the trial if their blood pressure was < or =180 mm Hg systolic and < or =120 mm Hg diastolic, serum creatinine concentration > or =1.0 mg/dL (in women) or > or =1.2 mg/dL (in men), C&G clearance > or =40 mL/min, and proteinuria > or =500 mg/d with diabetic retinopathy or diabetic nephropathy on renal biopsy. Recruitment began in July 1995 and terminated in December 1996. The trial randomized a total of 599 subjects. At baseline, the mean (standard deviation [SD]) age was 58 (7.7) years, diabetes duration 16.5 (7.5) years, body mass index 32 kg/m2 (10-90% range 2642), arterial blood pressure 105 (12) mm Hg, C-peptide concentration 2.55 (1.71) ng/mL, serum glucose concentration 201 (89) mg/dL, hemoglobin A1c 8.7% (1.6), serum creatinine concentration 1.6 (0.5) mg/dL, iothalamate clearance 52 (25) mL/min/1.73 m2, proteinuria 4.1 (4.2) g/d, triglycerides 259 (214) mg/dL, and LDL cholesterol 144 (40) mg/dL. Patients are 72% male, 68% white, 16% black, and 16% Asian American and Native American. At baseline, 76% were receiving concomitant angiotensin-converting enzyme (ACE) inhibitors and 43% lipid-lowering agents. Follow-up in ACTION II was scheduled to continue through December 1998, so that follow-up was to be 2 years after the date of randomization of the final enrolled patient. The trial in fact ended in March 1998. This trial will contribute to our understanding of the natural history of type 2 diabetes mellitus-associated nephropathy and determine whether aminoguanidine will slow the progression of established diabetic renal disease.

Effect of angiotensin-converting enzyme inhibitors on response to erythropoietin therapy in chronic dialysis patients.

BACKGROUND: Erythropoietin (EPO) therapy is a common and effective treatment for the correction of anemia in patients with end-stage renal disease. Simultaneous treatment with angiotensin-converting enzyme (ACE) inhibitors for the control of hypertension and/or heart failure is often necessary. Recent reports in the literature have raised concern about a potential interaction between these drugs, with a resultant decreased EPO efficacy. METHODS: To investigate whether this interaction occurs in chronic dialysis patients, we retrospectively reviewed the records of 175 patients receiving chronic dialysis. All study patients were treated with EPO for at least 3 months, and had normal iron indices. Patients were treated with ACE inhibitors for at least 3 months, at a constant daily dose for at least 1 month (group 1, n = 32), or did not receive ACE inhibitors (group 2, n = 143). Patients with infections or overt iron deficiency were excluded. Total weekly EPO doses and hematocrit (Hct)/hemoglobin (Hgb) values in the two groups were compared. Variables known to affect response to EPO were compared, including ferritin, transferrin saturation, dialysis dose and serum aluminum. RESULTS: Total weekly EPO dose was 17,358 +/- 6,871 units in group 1 and 17,612 +/- 7,744 units in group 2 (p = 0.854). The achieved Hct was 32.1 +/- 4.4% (group 1) and 30.5 +/- 4.0% (group 2) (p = 0.079). Similarly, Hgb, ferritin, transferrin saturation, Kt/V, and serum aluminum were not different. The dose or duration of ACE inhibitor therapy did not affect Hgb or Hct. Thus, ACE inhibitor therapy does not appear to affect response to EPO in chronic dialysis patients.

Potential angiotensin-converting enzyme inhibitor-epoetin alfa interaction in patients receiving chronic hemodialysis.

We compared epoetin alfa (EPO) dose requirements and hematocrit response in 17 patients receiving chronic hemodialysis at baseline and after 3 and 12 months of therapy with angiotensin-converting enzyme (ACE) inhibitors (12 enalapril, 5 captopril). No acute processes were present (infection, hemorrhage, inflammation) at time of starting ACE inhibitor therapy. Mean (+/- SD) intravenous EPO dosages at zero, 3, and 12 months were 6012 +/- 2575, 5800 +/- 2026, and 5660 +/- 2285 U 3 times/week (p=0.56), and mean differences were -212 U for 0-3 months (95% CI -1310 to 886) and -713 U for 0-12 months (95% CI -2142 to 716). Mean +/- SD hematocrits were 30.5 +/- 3.9%, 31.6 +/- 3.2%, and 34.2 +/- 3.1% (p=0.01, zero vs 12 mo), and mean differences were 1.7% for 0-3 months (95% CI -1.41 to 4.81) and 3.85% for zero-12 months (95% CI 0.71-7). Our results indicate that ACE inhibitors do not increase EPO dose requirements or reduce hematocrits in these patients.

Cholesterol crystal embolization-associated renal failure after therapy with recombinant tissue-type plasminogen activator.

We report the occurrence of renal failure due to cholesterol crystal embolization following thrombolytic therapy with intravenous recombinant tissue-type plasminogen activator (t-PA). No invasive vascular procedure had been performed. Although there is one case report of cholesterol crystal embolization following t-PA therapy with only extrarenal manifestations (N Engl J Med 321:1270, 1989), this is the first reported case of atheroembolic acute renal failure following t-PA therapy.

Dialysis adequacy in hypoalbuminemic continuous ambulatory peritoneal dialysis patients.

We examined the interrelationship between hypoalbuminemia (HA) and the normalized protein catabolic rate (NPCR; g/kg/day) in the face of adequate Kt/V and weekly creatinine clearances in 40 end-stage renal disease patients on long-term continuous ambulatory peritoneal dialysis (CAPD). We also evaluated serum albumin (SA) levels as an additional marker of nutritional status of the PD patients receiving adequate dialysis therapy in terms of Kt/V greater than 1.5 per week. Twenty-three of 40 patients had normal serum albumin (NSA; > or = 3.4 g/dL) and 17 had HA (< g/dL). A correlation between NPCR and SA levels was observed. Also, the NPCR values in patients with NSA (0.98 +/- 0.31) differ significantly (p < 0.0005) from patients with HA (0.80 +/- 0.13). Urea kinetic parameters for adequacy of dialysis, that is, Kt/V, blood urea nitrogen (BUN), and weekly creatinine clearance, did not reveal any statistically significant difference between patients with NSA and HA. These data suggest that low values of NPCR may be seen in hypoalbuminemic CAPD patients despite adequate dialysis therapy and indicate further investigation for associated morbid conditions or supplemental nutrition.

Dialysis adequacy versus metabolic factors in the clinical assessment of CAPD.

We performed a cross sectional study of our continuous ambulatory peritoneal dialysis (CAPD) patients (n = 98) to examine the relation between parameters of adequacy of dialysis [KT/V, weekly creatinine clearance (Ccr)], urea kinetics (PCR), biochemical parameters (serum albumin), and clinical status of these patients. We also investigated the predictive value of these parameters in the determination of clinical outcomes. The clinical status of each patient was assessed by patient self-assessment and objectively by physicians and nurses. On this basis a total clinical assessment score was assigned. Individuals with a score of 3 or less were judged to be clinically stable (group 1, n = 61), while a score of 4 or more was considered "not doing well" (group 2, n = 37). A good correlation (r = 0.7) between subjective and objective assessments was observed. No correlation between total clinical assessment score and KT/V, PCRN (normalized protein catabolic rate), or Ccr was obtained, while serum albumin levels correlated inversely (r = -0.30; p < 0.003), suggesting that parameters of dialysis adequacy (weekly KT/V, Ccr) and urea kinetics (PCRN) are not predictive of clinical outcome in CAPD patients, in contrast with hemodialysis (HD) patients. Serum albumin levels were observed to be correlated with clinical outcome in CAPD patients. Hypoalbuminemia was observed in group 2 patients, despite statistically insignificant different values of KT/V, Ccr, and PCRN in the two groups. Therefore, clinical assessment and parameters such as serum albumin must be considered when determining the total well-being of CAPD patients.

Impact of epoetin beta on dialyzer clearance and heparin requirements.

The present studies were undertaken to determine whether treatment with recombinant human erythropoietin (epoetin beta [Marogen Sterile Powder, Chugai-Upjohn, Rosemont, IL] ) necessitates an alteration in dialysis prescription or in heparin requirements. All patients had end-stage renal disease (ESRD), were on chronic hemodialysis (either high-flux or conventional) for more than 3 months, and had participated in large-scale, multicenter epoetin beta clinical trials. Nine patients were entered into the clearance study. Blood chemistry values, dialyzer clearances, and hematocrit values were determined before beginning epoetin beta administration and after approximately 40 weeks of treatment. The mean hematocrit value at the beginning of the study was 0.229 (22.9%); by week 40, it averaged 0.313 (31.3%). The mean percent change in urea clearance was -1.9%, and a mean percent change of +12.7% in blood urea nitrogen (BUN) was noted. The mean percent change in creatinine clearance was -15.3, while the mean percent change in serum creatinine was +0.2%. The mean percent change in phosphate clearance was -10.1%, and the mean percent change in serum phosphate was +44.1%. Heparin profiling was performed for nine patients (four participated in the clearance study). Seven patients showed increased requirements for heparin, with a mean percent change of +24.3%. These results underscore the necessity for careful attention to the changing status of the dialysis patient on epoetin beta. While epoetin beta treatment does not, in general, adversely affect either clearance or blood chemistry values, these values may fluctuate in individual patients in response to the increasing hematocrit values and to dietary changes that result from an increased sense of well-being.(ABSTRACT TRUNCATED AT 250 WORDS)

Transfusion therapy: associated risks and alternative approaches.

Transfusion therapy has been the mainstay for treating the anemia of end-stage renal disease (ESRD). Recently, several factors, including the awareness of associated risks, especially the transmission of blood-borne diseases and the transient treatment effect with regard to reversal of anemic symptoms, have caused a reassessment of transfusion therapy. Recombinant human erythropoietin (epoetin) has emerged as the alternative treatment, capable of sustained reversal of anemia without the associated risks of transfusions. The result of epoetin therapy has been marked improvement in the quality of life of ESRD patients. However, the advent of this therapy has also changed the nurse's role in caring for ESRD patients, as new medical management issues are identified and supportive care is tailored to the individual patient.

Effect of long-term epoetin beta therapy on the quality of life of hemodialysis patients.

Differences in quality of life were observed using two separate patient populations with end-stage renal disease who were on maintenance hemodialysis. The first population (91 patients) received epoetin beta (Marogen Sterile Powder, Chugai-Upjohn, Inc., Chicago, Ill.) for an average of 18 months. The second population (96 patients) did not receive this therapy. The measured quality of life parameters included a number of global and psychological well-being measurements and the Sickness Impact Profile (SIP), as well as energy, activity levels, appetite, work, and sexual function. When adjusted for covariates (health status and demographics), 16 of 26 parameters were significantly higher (p less than .05) in patients receiving epoetin beta. All mean scores for global measurements were significantly higher. Significantly higher scores were also obtained for total SIP and total psychosocial subscale, as well as for sleep, home management, recreation, emotional behavior, social interaction, ability to work, and energy. While not statistically significant, all of the remaining measurements were higher for epoetin beta than for untreated patients.

EPO--one year later: a look at rehabilitation. The impact of long-term epoetin beta therapy on ESRD patient quality of life.

Long-term observational studies such as the one reported here represent the best chance for measuring the effects of epoetin treatment on quality of life as compared with conventional treatment. When scores were adjusted for between-group differences, patients receiving epoetin beta for an average of 18 months demonstrated significantly better quality of life in 16 of the 26 parameters reported. These measures included all global measurements, psychological well-being as measured by IGA, sleep, rest, energy, SIP psychosocial subscale, and total SIP score. While differences were not significant, remaining measurements were higher in the epoetin beta group. On the basis of this study, epoetin beta treatment has a beneficial effect on energy, the ability to work, and participation in activities such as home management, recreation, and pastimes. While the mean score for ability to work was significantly higher in the epoetin beta-treated patients, the work category of the SIP was not significantly different from the untreated population. The fact that the latter scale was completed by only the small proportion of the patients who were actually working may have contributed to this insignificant finding. The current study demonstrates sustained benefit form epoetin beta compared with conventional therapy, even after 18 months. These long-term results validate previously published results of benefits seen during shorter-term epoetin therapy.

Subclavian vein stenosis as a complication of subclavian catheterization for hemodialysis.

Thirteen patients had placement of a subclavian vein catheter for temporary vascular access for hemodialysis. Peripheral venography was performed within two to six weeks of catheter placement. Forty-six percent (six of 13 patients) developed subclavian vein narrowing, which resolved in two patients. The duration of catheter placement had no impact on the incidence of this complication. Subclavian vein catheterization can frequently lead to subclavian vein stenosis, which often will resolve spontaneously. Consideration should be given to placement of subclavian lines on the contralateral side of a planned permanent vascular access.

Comparison of eosinophilia in patients undergoing peritoneal dialysis and hemodialysis.

Eosinophilia (E) has been noted in hemodialysis (HD) patients, but its etiology is not clear. In an effort to clarify this phenomenon, we prospectively studied patients initiating dialysis in our outpatient HD and peritoneal dialysis programs. Rate of E was greatest for a small group of four continuous cycling peritoneal dialysis patients (75%), less for 63 HD patients (41%), and least for 66 continuous ambulatory peritoneal dialysis (CAPD) patients (21%, P less than .05, HD v CAPD). Increasing E rates among the groups paralleled increased frequency of tubing changes. There were no differences in etiology of renal disease, medications, types of dialyzers, types of access, or transfusion frequency that could account for the E. IgE levels did not correlate with E. The data suggest that the dialysis procedure or the tubing changes may be causing the E, but the possibility that uremia, itself, is important in the pathogenesis of dialysis E is also discussed.

A comparative study of continuous ambulatory peritoneal dialysis and center hemodialysis. Efficacy, complications, and outcome in the treatment of end-stage renal disease.

We retrospectively compared 92 patients treated with center hemodialysis (CHD) and 72 patients receiving continuous ambulatory peritoneal dialysis (CAPD) over a 26-month period. The groups were comparable with respect to underlying disease and demographic characteristics. Biochemical control was also similar, with higher bicarbonate levels and hematocrits in patients receiving CAPD, despite fewer transfusions and minimal administration of anabolic steroid and iron therapy. Hospitalization rates were also similar (1.58 +/- 2.89 vs 1.43 +/- 3.35 days per patient month for patients receiving center hemodialysis vs CAPD, respectively). Access complications were the most frequent cause of hospitalization in both groups, but cardiovascular causes were more frequent among patients receiving CHD. Diabetic patients had significantly higher hospitalization rates, which were similar in both groups. Twenty-nine percent of the peritonitis episodes necessitated hospitalization. Mortality and dropout rates were virtually identical in the two groups, with a 70% retention rate during the 26-month study. Continuous ambulatory peritoneal dialysis is comparable with CHD with regard to biochemical results, complications, hospitalization rates, and outcome. It is widely applicable, as 44% of our new patients with end-stage renal disease are being sent home receiving this treatment.

Nondilated obstructive nephropathy.

Three patients had renal failure due to obstructive nephropathy associated with processes that prevented dilatation of the collecting systems. Thus, various radiologic procedures, including renal sonography, angiography, and isotope renography, all failed to identify an obstructing process. Because of the high index of clinical suspicion, surgical exploration and nephrostomy were performed on each patient. This confirmed the presence of obstructive nephropathy and led to marked improvement of renal function in each case. When renal failure develops in a setting with a high probability of ureteral obstruction, this diagnosis should be vigorously pursued despite normal radiologic results.

Percutaneous transluminal dilatation for vascular access.

The application of percutaneous transluminal angioplasty to vascular access stenosis is described. These access problems were discovered by the technique of retrograde venous fistulography. 13 dilatations were attempted in 12 patients. Functional success was achieved in seven attempts. This resulted in a significant prolongation of access survival in these patients. Angioplasty is recommended as a nonsurgical approach to vascular access stenosis.

Continuous ambulatory peritoneal dialysis: establishment and growth of a program in a large metropolitan area.

We describe our experience at the Booth Memorial Medical Center with the development and growth of a Continuous Ambulatory Peritoneal Dialysis program. This initial experience includes the training and close follow-up of 41 patients with End Stage Renal Disease over a period of 15 months. The status of our program with respect to medical complications encountered and their management is described. Our results, in terms of biochemical control, success with training, and patient satisfaction with CAPD are outlined.

Eosinophilic peritonitis.

The development of cloudy peritoneal dialysis effluent is of great concern to the patient undergoing therapy with Continuous Ambulatory Peritoneal Dialysis. As described in this study, not all cloudy fluid represents bacterial infection. We describe the occurrence of cloudy fluid in eight patients in whom culture of the dialysate did not yield any growth, and whose cell count was characterized by the presence of significant numbers of the eosinophiles. As outlined, the entity of eosinophilic peritonitis has a characteristic presentation which allows for its distinction from the more common bacterial peritonitis.

Technique for implantation of the Toronto-Western catheter at the Booth Memorial Medical Center.

The proper placement of the chronic peritoneal dialysis catheter is pivital to the early, as well as continued success of dialysis therapy with Continued Ambulatory Peritoneal Dialysis. We describe our current technique for the implantation of the Toronto-Western catheter. The success of any particular technique is dependent upon the incidence of complications. The latter is described elsewhere in this symposium.