Brendan P. Teehan

Serum β-2 Microglobulin Levels Predict Mortality in Dialysis Patients: Results of the HEMO Study

In the randomized Hemodialysis (HEMO) Study, chronic high-flux dialysis, as defined by higher beta-2 microglobulin (beta(2)M) clearance, compared with low-flux dialysis did not significantly alter all-cause mortality in the entire cohort but was associated with lower mortality in long-term dialysis patients. This analysis examined the determinants of serum beta(2)M levels and the associations of serum beta(2)M levels or dialyzer beta(2)M clearance with mortality. In a multivariable regression model that examined 1704 patients, baseline residual kidney urea clearance and dialyzer beta(2)M clearance were strong predictors of predialysis serum beta(2)M levels at 1 mo of follow-up, with regression coefficients of -7.21 (+/-0.69 SE) mg/L per ml/min per 35 L urea volume (P < 0.0001) and -1.94 (+/-0.30) mg/L per ml/min (P < 0.0001),respectively. In addition, black race and baseline years on dialysis correlated positively whereas age, diabetes, serum albumin, and body mass index correlated negatively with serum beta(2)M levels (P < 0.05). In time-dependent Cox regression models, mean cumulative predialysis serum beta(2)M levels but not dialyzer beta(2)M clearance were associated with all-cause mortality (relative risk = 1.11 per 10-mg/L increase in beta(2)M level; 95% confidence interval 1.05 to 1.19; P = 0.001), after adjustment for residual kidney urea clearance and number of prestudy years on dialysis. This association is supportive of the potential value of beta(2)M as a marker to guide chronic hemodialysis therapy.

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.

Effects of High-Flux Hemodialysis on Clinical Outcomes: Results of the HEMO Study

Among the 1846 patients in the HEMO Study, chronic high-flux dialysis did not significantly affect the primary outcome of the all-cause mortality (ACM) rate or the main secondary composite outcomes, including the rates of first cardiac hospitalization or ACM, first infectious hospitalization or ACM, first 15% decrease in serum albumin levels or ACM, or all non-vascular access-related hospitalizations. The high-flux intervention, however, seemed to be associated with reduced risks of specific cardiac-related events. The relative risks (RR) for the high-flux arm, compared with the low-flux arm, were 0.80 [95% confidence interval (CI), 0.65 to 0.99] for cardiac death and 0.87 (95% CI, 0.76 to 1.00) for the composite of first cardiac hospitalization or cardiac death. Also, the effect of high-flux dialysis on ACM seemed to vary, depending on the duration of prior dialysis. This report presents secondary analyses to further explore the relationship between the flux intervention and the duration of dialysis with respect to various outcomes. The patients were stratified into a short-duration group and a long-duration group, on the basis of the mean duration of dialysis of 3.7 yr before randomization. In the subgroup that had been on dialysis for >3.7 yr, randomization to high-flux dialysis was associated with lower risks of ACM (RR, 0.68; 95% CI, 0.53 to 0.86; P = 0.001), the composite of first albumin level decrease or ACM (RR, 0.74; 95% CI, 0.60 to 0.91; P = 0.005), and cardiac deaths (RR, 0.63; 95% CI, 0.43 to 0.92; P = 0.016), compared with low-flux dialysis. No significant differences were observed in outcomes related to infection for either duration subgroup, however, and the trends for beneficial effects of high-flux dialysis on ACM rates were considerably weakened when the years of dialysis during the follow-up phase were combined with the prestudy years of dialysis in the analysis. For the subgroup of patients with <3.7 yr of dialysis before the study, assignment to high-flux dialysis had no significant effect on any of the examined clinical outcomes. These data suggest that high-flux dialysis might have a beneficial effect on cardiac outcomes. Because these results are derived from multiple statistical comparisons, however, they must be interpreted with caution. The subgroup results that demonstrate that patients with different durations of dialysis are affected differently by high-flux dialysis are interesting and require further study for confirmation.

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.

A proposed glossary for dialysis kinetics

Quantification of the dialysis dose and assessment of nutritional status and response to nutritional therapy have become standard parts of the management of the chronic dialysis patient. Although advances in these areas have led to a more rational basis for therapy, certain misconceptions and points of confusion appear to have occurred. Recognizing the importance of a standard nomenclature to the development of concepts and the communication of research findings, we have attempted to compile a list of terms that are commonly used in the field of dialysis. New terms have been proposed for current ones that do not seem adequate. In addition, we have discussed potential methodologies for obtaining more accurate data for dialysis kinetics and for precise monitoring of nutritional intake and status. It is hoped that this glossary will stimulate discussion that will lead to refinements in terminology and concepts that will, in turn, improve research and practice in nephrology. It is anticipated that many of these definitions and recommendations will be modified or superseded as the management of patients with renal failure continues to advance.

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.

Adequacy of Continuous Ambulatory Peritoneal Dialysis: Morbidity and Mortality in Chronic Peritoneal Dialysis

Mortality for hemodialysis patients tends to be in excess of 20% per year, and it is generally agreed that outcome for continuous ambulatory peritoneal dialysis patients is comparable. Several investigators have suggested recently that continuous ambulatory peritoneal dialysis, as commonly practiced, may not provide adequate therapy, especially for larger patients and for those with no residual renal function. Unfortunately, a dose-response curve relating the amount of dialysis delivered and clinical outcome for continuous ambulatory peritoneal dialysis patients has not been constructed. Several methods of quantifying the dose of peritoneal dialysis are described. Both cross-sectional and longitudinal studies are reviewed. The conclusions of these studies are of limited value, however, because of their retrospective nature and the limited number of patients enrolled. Nevertheless, in aggregate, these studies suggest that survival may be improved by higher doses of dialysis. They also suggest that while malnutrition is relatively common in this patient population, higher doses of Kt/V are associated with higher protein intake (as measured by protein catabolic rate). Serum albumin is recognized as a strong predictor of clinical outcome and the protein catabolic rate may correlate directly with Kt/V, but there are studies that support and others that refute a correlation between Kt/V and serum albumin. Definitive answers to these questions are likely to be available in the near future. Two large multicenter studies are currently under way. Preliminary results may be available in the near future.

Is Urea Kinetic Modeling the Best Measure of Adequacy in CAPD

In one form or another (urea reduction ratio, KT/ V, or traditional 3-point studies), urea kinetic analysis is an accepted standard of care in chronic hemodialysis patients. Although the application of urea kinetic analysis to continuous ambulatory peritoneal dialysis (CAPD) dates back to 1985 (I), some doubt remains regarding its role in this modality. Since then data have been presented suggesting that urea kinetic parameters, alone or in combination with other factors, are strong prelktors of clinical outcome in this patient population (2). For example, hospitalization rate, mortality rate, and transfusion requirement (in the pre-erythropoietin era) can be predicted using this approach. In addition, it has been shown that protein intake is a function of the dialysis dose, measured as KT/V urea (3, 4). Both protein intake and KT/V are major determinants of serum albumin, which, in turn, is a strong predictor of death in both CAPD (2) and hemodialysis patients (5 ) . Finally, Keshaviah et al. (6) and Nolph et al. (7) have presented a very plausible hypothesis suggesting that the difference in blood urea nitrogen (BUN) concentration profile between CAPD and hemodialysis may account for the well-being of CAPD patients in spite of lower overall urea clearance. It appears, therefore, that a number of urea kinetic indices (BUN, normalized protein catabolic rate (PCRN), KT/I/) influence clinical outcome in CAPD. A limited number of studies (8, 9), however, find no correlation between urea kinetics and clinical

Recommendations for Reducing the High Morbidity and Mortality of United States Maintenance Dialysis Patients

R ECENT epidemiologic studies have provided alarming evidence that the mortality rates of maintenance dialysis patients in the United States are very high: the gross annual mortality rate is approximately 24%. Moreover, the mortality rate of US maintenance hemodialysis patients is almost twice the mortality rate of comparable patients receiving chronic dialysis therapy in Europe and approximately three times that of similar patients in Japan. Mortality rates appear to be similarly high in chronic peritoneal dialysis patients. Since approximately 170,000 individuals in the United States receive chronic hemodialysis or peritoneal dialysis, this represents a serious public health problem. The National Kidney Foundation, recognizing the gravity of this situation, appointed a committee to review the potential causes for the increased morbidity and mortality among US maintenance dialysis patients and to recommend potential solutions. The possible causes for the high morbidity and mortality are summarized in the following reviews. The Committee offers in this document a series of recommendations that it is hoped will lead to a reduction in the high

Solute clearance in continuous venovenous hemodialysis : a comparison of cuprophane, polyacrylonitrile, and polysulfone membranes

Critically ill patients with ARF and MOSF were treated with continuous venovenous hemodialysis (CVVHD). The BSM 22 delivery system (CGH Medical, Denver, CO) and four different dialyzer membranes were used. Vascular access was achieved with a dual lumen catheter placed percutaneously into a large vein. Heparin was used for anticoagulation, and commercially available peritoneal dialysis fluid was used as dialysate. At a fixed blood flow rate of 100 ml/min, the dialysate inflow and outflow rates were regulated to control azotemia and fluid balance. Blood side and dialysate side clearances for urea nitrogen, creatinine, bicarbonate, and lactate were measured. All dialyzer membranes studied provided high urea nitrogen clearance approximating dialysate outflow rate and resulting in excellent control of azotemia. Some of the dialyzer membranes also had high creatinine and bicarbonate clearances. Bicarbonate loss was balanced by lactate uptake with all dialyzers. It is concluded that CVVHD is an efficient and safe therapy for acute renal failure, capable of maintaining nitrogen balance in patients with protein catabolic rates up to 2 g/kg/day. Urea nitrogen clearance is dependent upon dialysate outflow rate rather than the dialyzer membrane type or dialyzer flow geometry, and may prove to be the modality of choice for therapy of acute renal failure in unstable patients with MOSF.