Robert L. Benz

Health-related quality of life associated with recombinant human erythropoietin therapy for predialysis chronic renal disease patients

The investigators evaluated the impact of recombinant human erythropoietin (r-HuEPO) therapy on health-related quality of life (HRQL) in predialysis chronic renal disease patients with anemia. Eighty-three patients were entered into a randomized, parallel-group, open-label clinical trial with follow-up evaluations over 48 weeks. Forty-three patients were assigned to r-HuEPO treatment, and 40 patients were assigned to an untreated control group. Hematocrit levels were measured at baseline and monthly. HRQL was assessed at baseline and at weeks 16, 32, and 48. The HRQL assessment included measures of physical function, energy, role function, health distress, cognitive function, social function, home management, sexual dysfunction, depression, and life satisfaction. Significant improvements in hematocrit levels were observed in the r-HuEPO-treated group (P < 0.0001), and no changes were seen in the untreated group. Correction of anemia (hematocrit > or = 36) occurred in 79% of r-HuEPO-treated patients and 0% of control patients. Significant improvements in assessments of energy (P < 0.05), physical function (P < 0.05), home management (P < 0.05), social activity (P < 0.05), and cognitive function (P < 0.05) were found for the r-HuEPO-treated group. No changes were observed in the control group, except for a decrease in physical function (P < 0.05). Between-group differences favoring the r-HuEPO-treated group were found for energy (P < 0.05) and physical functioning (P < 0.05). In patients receiving r-HuEPO, significant improvements were seen in hemotocrit levels, and these increases resulted in improvements in HRQL.

Potential novel predictors of mortality in end-stage renal disease patients with sleep disorders.

Patients with end-stage renal disease (ESRD) have an annual mortality rate exceeding 20%, although some survive many years. The ESRD population has a high incidence of sleep disorders, including sleep apnea and periodic limb movements in sleep (PLMS). Sleep disorders result in sleep deprivation, which can negatively affect immune function and cardiovascular-related outcomes, common causes of death in patients with ESRD. This study examined predictors of mortality in patients with ESRD with sleep problems. Twenty-nine consecutive patients with ESRD reporting disrupted sleep or daytime sleepiness were studied by all-night polysomnography. All patients were followed up until death, transplantation, or study termination. Among the variables studied, including such previously reported predictors as serum albumin level, urea reduction ratio, and hematocrit, only the PLMS index (PLMSI), arousing PLMSI (APLMSI), and total number of arousals per hour of sleep significantly predicted mortality. The 20-month survival rate with a PLMSI less than 20 was greater than 90% versus 50% for a PLMSI of 20 or greater (exact log-rank, P = 0.007). For the deceased versus survivor groups, mean PLMSI was 119.1 versus 19.8 (P = 0.01) and APLMSI was 48.1 versus 7.8 (P = 0.00006), with a mean survival of 10.3 versus greater than 25.5 months, respectively (P = 0.001). Median survival of patients with a PLMSI greater than 80 was only 6 months. PLMSI, APLMSI, and total arousals per hour of sleep were strongly associated with mortality in patients with ESRD with sleep disorders independent of other factors and may be novel predictors of near-term mortality.

A preliminary study of the effects of correction of anemia with recombinant human erythropoietin therapy on sleep, sleep disorders, and daytime sleepiness in hemodialysis patients (The SLEEPO study)

End-stage renal disease (ESRD) is commonly associated with complaints of disturbed sleep and sleep disorders, frequently related to periodic limb movements in sleep (PLMS) or sleep apnea that may result in daytime sleepiness and other sequelae. Improvements in quality of life, including subjective sleep quality, have been reported in ESRD patients treated with recombinant human erythropoietin (rHuEPO). We investigated the objective effects of normalizing hematocrit on sleep disorders, sleep patterns, and daytime ability to remain awake in ESRD patients. Ten hemodialysis patients with sleep complaints while on rHuEPO therapy were studied by polysomnography while moderately anemic (mean hematocrit, 32.3%) and again when hematocrit was normalized (mean hematocrit, 42.3%) by increased rHuEPO dosing. Sleep patterns and associated parameters were monitored. Delivered dialysis dose and iron storage factors were monitored. Maintenance of Wakefulness Testing (MWT) was performed to assess daytime alertness/sleepiness. All 10 subjects experienced highly statistically significant reductions in the total number of arousing PLMS (P = 0.002). Nine of 10 subjects showed reductions in both the Arousing PLMS Index (P < 0.01) and the PLMS Index (P = 0.03) when hematocrit was normalized. Measures of sleep quality showed trends to improved quality of sleep. MWT demonstrated significant improvement in the length of time patients were able to remain awake (9.7 versus 17.1 minutes; P = 0.04). RHuEPO therapy with full correction of anemia reduces PLMS, arousals from sleep, and sleep fragmentation while allowing for more restorative sleep and improved daytime alertness. These findings may explain one mechanism for the improved quality-of-life parameters reported in ESRD patients treated with rHuEPO.

Effects of Recombinant Human Erythropoietin on Renal Function in Chronic Renal Failure Predialysis Patients

A study was undertaken to ascertain the effects of recombinant human erythropoietin (r-HuEPO) on renal function in chronic renal failure predialysis patients. The effect of improvement of anemia by r-HuEPO on the rate of decline in renal function in predialysis patients has not been previously studied prospectively in a large number of patients using reliable measures of glomerular filtration rate (GFR). To investigate the efficacy, safety, and impact of r-HuEPO therapy in chronic renal insufficiency patients, a 48-week, randomized, open-label, multicenter study was initiated in 83 anemic, predialysis (serum creatinine 3 to 8 mg/dL) patients. Serial GFRs were measured using 125I-iothalamate clearance. Forty patients were randomized to the untreated arm and 43 patients to the treatment arm (50 U/kg r-HuEPO subcutaneously three times weekly). Baseline characteristics were comparable for the r-HuEPO-treated and untreated groups. During this 48-week study, GFR, mean arterial blood pressure, and daily protein intake were not significantly different between the two groups. There was a statistically significant increase in hematocrit for the r-HuEPO-treated group that was not associated with acceleration of deterioration in residual renal function. This was demonstrated by the lack of a significant (P = 0.376) between-group difference in mean change in GFR from baseline to last available value for the r-HuEPO-treated (-2.1 +/- 3.2 mL/min) and untreated (-2.8 +/- 3.5 mL/min) groups. This study concludes that r-HuEPO therapy improves anemia in predialysis patients and does not accelerate the rate of progression to end-stage renal disease.

Carpal Tunnel Syndrome in Dialysis Patients: Comparison Between Continuous Ambulatory Peritoneal Dialysis and Hemodialysis Populations

Carpal tunnel syndrome (CTS) has been reported with increased frequency in hemodialysis (HD) patients. A comparative study of patients on continuous ambulatory peritoneal dialysis (CAPD) has not been previously reported. To delineate the significance of dialytic modality and access-related risk factors, this study investigated the incidence and patient characteristics of CTS in CAPD v HD populations. One hundred and fifty one patients (HD n = 90, CAPD n = 61) were evaluated by questionnaire, physical examination, and nerve conduction studies. Age, gender, renal diagnosis, access, diabetic history, and duration of dialysis were determined. Eight of 57 CAPD and 15/83 HD patients had CTS. chi 2 testing revealed no significant difference in incidence (P = 0.7). It is concluded that CTS occurs with similar incidence in CAPD and HD populations. Dialytic modality and access are not likely to be factors in the development of CTS. Rather, CTS is a metabolic complication of end-stage renal failure.

Bias in Assessment of Health-Related Quality of Life in a Hemodialysis Population: A Comparison of Self-Administered and Interviewer-Administered Surveys in the HEMO Study

ABSTRACT. Examined is the relationship of patient-reported health-related quality of life (HRQOL) to the mode of survey administration in the Hemodialysis Study. In addition to self-administered surveys to assess HRQOL, interviewer-administered surveys were made available to include patients with poor vision, decreased manual dexterity, or strong preference. For examining the predictors of participation by self-administration of the survey, multiple logistic regression was performed. For examining the relationship of HRQOL results to mode of survey administration, adjusted differences between the self-administered and interviewer-administered groups were obtained from multiple linear regression models accounting for sociodemographic and case-mix factors. A total of 978 of the first 1000 subjects in the Hemodialysis Study completed the survey by interview (n = 427) or by self-administration (n = 551). The interviewer-administered group was older, was more likely black, had longer duration of ESRD, had a higher prevalence of diabetes, and had more severe comorbidity (all P < 0.01). After adjustment for these differences, patients in the interviewer-administered group had higher scores on scales that measured Role-Physical, Role-Emotional, and Effects of Kidney Disease (all P < 0.001). Dialysis studies that restrict HRQOL measurement to patients who are able to complete surveys without assistance will not accurately represent the health of the overall hemodialysis population. Clinical studies and clinical practices using HRQOL as an outcome should include interviewer administration or risk a selection bias against subjects with older age, minority status, and higher level of comorbidity. Future investigation should include research of survey modalities with a low response burden such as telephone interview, computer-assisted interview, and proxy administration.

Hydrothorax in Continuous Ambulatory Peritoneal Dialysis: Successful Treatment With Intrapleural Tetracycline and a Review of the Literature

Recurrent hydrothorax complicating peritoneal dialysis has been considered a contraindication to continuing peritoneal dialysis. In the continuous ambulatory peritoneal dialysis (CAPD) population this problem has generally required a change of dialytic modality. Talc poudrage has been attempted to ameliorate the problem but has met with limited success. We report a successful case of intrapleural instillation of tetracycline to induce a pleural symphysis and prevent recurrence of peritoneal dialysis-related hydrothorax in a patient who refused any alternative mode of dialysis. We also review the literature, pathophysiology, epidemiology, diagnosis, and management of this compromising problem.

Sleep Disorders Associated with Chronic Kidney Disease

Twenty-six million American adults have Chronic Kidney Disease (CKD). Chronic Kidney Disease is defined as kidney damage for 3 or more months with or without decreased GFR. Chronic Kidney Disease is divided into five stages, from Stage 1 to Stage 5. End-Stage renal disease is the 5th stage of CKD when dialysis is needed to sustain life. Sleep disorders are common and under recognized in advanced stages of Chronic Kidney Disease. Sleep disorders affect the quality of life and may also increase cardiovascular morbidity and mortality.

Suppression of Renal vein Renin Profiles by Mannitol Prophylaxis: Implications in the Evaluation of Renovascular Hypertension

Renal arteriography with concomitant renal vein renin profiling remains the diagnostic standard for evaluating the anatomic and physiologic significance of stenotic renal artery lesions in hypertensive patients. False-negative renal vein renin profiles with failure of lateralization in patients with anatomically apparent high-grade stenosis complicate the diagnostic process. Mannitol is frequently administered prophylactically to minimize the risk of dye nephropathy in these patients. Yet, the potential effects of mannitol on renal vein renin profiling in man have not been previously reported. Seven patients with renovascular hypertension were studied prospectively to determine changes in renal vein renin profiles before and after mannitol prophylaxis. Despite captopril stimulation, all patients demonstrated significant renin suppression leading to the loss of renin lateralization in patients with unilateral renovascular hypertension. In 60% of the patients, renal vein renin ratios fell to below the standard 1.5 to 1 ratio after mannitol infusion. In patients with bilateral renovascular disease, the least stenotic side suppressed completely, while the more stenotic side suppressed partially. Percent suppression analysis showed a mean suppression of 56.8% on the stenotic side versus 8.2% on the noninvolved side (P less than 0.002). In every study, suppression equaled or exceeded 32% on the involved side and was less than this on the noninvolved side. Thus, the degree of renin suppression following mannitol infusion may prove to be an important tool in the diagnosis of clinically significant stenotic lesions. The mechanism of mannitol-induced suppression remains undefined, but appears independent of volume expansions or dilutional effects. The inhibitory effects of mannitol on renin profiles can obscure the diagnosis of underlying renovascular hypertension.

What Will Be the Impact of Erythropoietin on Chronic Dialysis

The anemia of uremia is largely the result of a relatively inadequate erythropoietin response. As demonstrated by Car0 et al. (1) the committed red blood cell precursors, the colony-forming units erythroid (CFU-E), are reduced in uremic marrow. Erythropoietin corrects this anemia by stimulation of the CFU-E population. Eschbach and others (2) have demonstrated that the hematocrit can be restored to normal in hemodialysis patients. We have had similar results in predialysis end-stage renal failure (ESRD) patients. In both groups a typical doseresponse curve can be demonstrated with either intravenous or subcutaneous recombinant human erythropoietin (r-HuEP) administration. The overall impact of correcting anemia in ESRD patients remains to be defined, but a reasonable prediction can be formulated from early publications and current work in progress. Our discussion will include the potential disadvantages as well as the considerable benefits associated with r-HuEP therapy for both the chronic dialysis population and the dialytic community.