Morrell M. Avram

Markers for survival in dialysis: A seven-year prospective study

Serum biochemical markers suggestive of undernutrition are directly correlated with mortality in hemodialysis and peritoneal dialysis patients. In particular, serum albumin is the most powerful predictor of survival. We have prospectively examined the relationship of single baseline measurements of serum albumin, cholesterol, creatinine, apoproteins, and prealbumin in 250 hemodialysis patients and 140 patients maintained on continuous ambulatory peritoneal dialysis (CAPD) monitored up to 7 years (1987 to 1994). Other variables studied included age, race, gender, diabetes, and number of months on dialysis. Observed survival was computed by the Kaplan-Meier method. Coxs proportional hazards model was used to determine independent predictors of mortality risk. Age, diabetes, prior months on dialysis, and low levels of serum albumin, creatinine, and cholesterol were important and independent predictors of mortality risk in hemodialysis patients. For peritoneal dialysis patients, the independent predictors of mortality risk were age, diabetes, and low serum albumin and serum creatinine. Prealbumin, a serum protein with rapid turnover and relatively small pool, was an important and independent risk predictor in both hemodialysis and CAPD patients. In addition, prealbumin was more highly correlated with other nutritional markers than was albumin. In summary, these findings suggest that biochemical measures associated with visceral and somatic protein depletion are predominant long-term mortality risk factors in patients maintained on hemodialysis and CAPD.

Predictors of Survival in Continuous Ambulatory Peritoneal Dialysis Patients: The Importance of Prealbumin and Other Nutritional and Metabolic Markers

Serum markers of visceral and somatic protein status are directly correlated with the survival of hemodialysis patients. We prospectively examined the relationship of single baseline levels of serum albumin, cholesterol, creatinine, and urea to prognosis in 80 continuous ambulatory peritoneal dialysis patients monitored for up to 33 months. Other variables tested included age, race, gender, diabetes, cause of end-stage renal disease, and number of months on dialysis. The Cox proportional hazards model was used to determine independent predictors of mortality risk. In a subgroup of 33 patients followed for up to 21 months, the predictive value of single measurements of baseline serum prealbumin also was tested. Overall, 29 patients died during the study. Independent predictors of mortality risk included serum albumin (P = 0.024) and creatinine (P = 0.006), diabetes (P < 0.06), prior months on dialysis (P < 0.05), and older age (P = 0.18). In a subgroup of 33 patients with prealbumin measurements, there were nine deaths over 21 months. A serum prealbumin level less than 30 mg/dL was associated with an increased mortality rate compared with higher prealbumin values (odds ratio, 3.8; P = 0.09). We conclude that markers of visceral and somatic nutrition are important and independent predictors of mortality risk in continuous ambulatory peritoneal dialysis patients. We are unable to suggest whether the relationship is causal or causative. However, the predictive value of these single baseline markers were valid for up to 33 months. We also note that patients with diabetes are at an increased risk even after adjusting for somatic and visceral protein status.

Prealbumin is the best nutritional predictor of survival in hemodialysis and peritoneal dialysis

Patients undergoing dialytic therapy for end-stage renal disease (ESRD) have greater morbidity and mortality than age-matched individuals with similar demographics in the general population. Risk factors for early death during treatment for ESRD include advanced age, diabetes, hypertension, and malnutrition. We questioned whether the level of serum prealbumin at the start of uremia therapy might serve as a marker of subsequent survival in patients treated with maintenance hemodialysis (HD) and peritoneal dialysis (PD). Study cohorts included 111 HD and 78 PD patients followed for up to 5 years. Selected demographic characteristics and biochemical variables were tested for correlation with survival in each cohort. Variables evaluated included age, race, gender, diabetic status, and serum concentrations of albumin, creatinine, cholesterol, and prealbumin. For comparison, expected survival was calculated with Cox proportional hazards analysis, which accounts for confounding variables. We found that a higher relative risk (RR) of death in HD patients correlated with older age, the diagnosis of diabetes, and a serum prealbumin < 30 mg/dL. In PD patients, older age and the presence of diabetes correlated with a higher RR of death than in the standard population. When nutritional variables were analyzed separately, prealbumin < 30 mg/dL was the strongest variable that predicted mortality in HD patients (RR = 2.64, P = 0.002) and also predicted increased risk of mortality in PD patients (RR = 1.8, P = 0.035). Observed and expected survival was significantly higher in patients with enrollment prealbumin greater than 30 mg/dL in both HD and PD. The serum prealbumin level correlated significantly with other measures of nutrition, including serum albumin, serum creatinine, and serum cholesterol, in both HD and PD patients. Among tested markers of nutritional status, prealbumin level appears to be the single best nutritional predictor of survival in ESRD patients.

Prealbumin and Lipoprotein(a) in Hemodialysis: Relationships With Patient and Vascular Access Survival

The high morbidity and mortality of hemodialysis patients has led to a search for early markers of risk. Because cardiovascular and nutritional risk are prevalent in this population, we examined the prognostic value of the serum levels of two markers of risk in the general population: (1) lipoprotein(a) [Lp(a)], a low-density lipoprotein-like particle linked to myocardial infarction and coronary bypass stenosis, and (2) prealbumin, a marker of visceral protein status, with a shorter half-life than that of serum albumin. Baseline demographics, clinical information, dialysis prescription, and serum biochemistry measurements of 125 hemodialysis patients followed for up to 14 months were recorded on enrollment. Vascular access events and deaths were recorded prospectively. The hypotheses tested were that increased serum Lp(a) levels would predict cardiovascular mortality and vascular access stenosis and thrombosis, and that reduced serum prealbumin levels would predict mortality risk independently of established risk predictors. Cross-sectional analysis of serum Lp(a) demonstrated a skewed distribution with a median value of 38.3 mg/dL (upper tertile, > or = 57 mg/dL). Lipoprotein(a) was significantly higher in black patients (P < 0.001) and was significantly correlated (P < 0.005) with total cholesterol and apoprotein B (apoB), but not with a history of prior coronary disease. Serum prealbumin was strongly correlated with serum albumin (r = 0.49, P < 0.001). However, prealbumin correlated (P < 0.001) more strongly with other serum nutrition markers (total cholesterol, apoB, creatinine, urea) than did serum albumin. Fourteen-month cumulative survival was 80%. Age, diabetes, and serum levels of albumin, prealbumin, creatinine, total cholesterol and apoB, but not Lp(a), were correlated with survival in univariate analysis. Using the Cox proportional hazards model, independent predictors of mortality risk were prealbumin less than 15 mg/dL versus higher values (relative risk [RR] = 4.48, P < 0.01), apoB (RR = 0.97 per 1 mg/dL increase, P < 0.02), creatinine less than 10 mg/dL versus higher values (RR = 3.51, P = 0.04), and age (RR = 1.04 per year, P = 0.10). Thirty-eight patients experienced at least one vascular access thrombosis (n = 33) or stenosis (n = 5) during the study. Patients with Lp(a) > or = 57 mg/dL had decreased vascular access event-free survival compared with patients with Lp(a) less than 57 mg/dL (56% v 73%, P < 0.06). This trend was increased in magnitude and statistically significant for white and Hispanic patients (31% v 79%, P < 0.01).(ABSTRACT TRUNCATED AT 400 WORDS)

The Uremic Dyslipidemia: A Cross-Sectional and Longitudinal Study

Patients on maintenance hemodialysis (HD) and continuous ambulatory peritoneal dialysis (CAPD) exhibit numerous disturbances of serum lipids and apoproteins that may contribute to their high cardiovascular mortality. Cross-sectional studies have found that lipid levels are inversely related to time on dialysis. However, it is not known whether this association is the result of the attrition of hyperlipidemic patients or a decrease in lipid levels over time in all patients. Additionally, few studies have investigated the effect of dialysis modality on the lipoprotein disturbances of uremia adjusting for the confounding influences of demographics, or nutritional and endocrine status. To address these issues, we undertook a cross-sectional and longitudinal study of lipids, apoproteins, and atherogenic risk ratios in patients maintained on HD and CAPD. Patients were enrolled in annual cohorts from 1987 to 1990 and monitored until 1991. A total of 196 HD and 77 CAPD patients were studied. Total cholesterol (TC), high-density lipoprotein cholesterol (HDL-C), apoprotein (apo) A-I, and apo B were measured on enrollment and remeasured annually in survivors through 1990. Using multivariate methods, we examined the relationship of the lipids, apoproteins, their respective ratios, and their changes over time, to a broad range of clinical factors and to mortality. Compared with HD patients, CAPD patients had significantly higher TC, apo A-I, and apo B, and a significantly lower apo A-I/apo B ratio. Serum albumin correlated directly with TC and apo B and inversely with apo A-I/apo B. For patients with normal serum albumin (> or = 3.5 g/dL [35 g/L]), CAPD patients had a significantly higher TC/HDL-C than HD patients; otherwise the ratios were similar for CAPD and HD. Independent influences on lipoprotein levels in HD and CAPD patients were also demonstrated for race, gender, and diabetes, but not for parathyroid hormone (PTH) levels. For both dialysis modalities, patients who died had significantly lower TC and apo B, and significantly higher apo A-I/apo B throughout their entire courses compared with survivors. In the subset of patients followed longitudinally for 2 or more years, apo B tended to decrease with time, but TC, HDL-C, and apo A-I were stable. The longitudinal changes in lipoproteins did not correlate with outcome or other factors. In conclusion, CAPD patients have more atherogenic lipoprotein profiles than HD patients. Improved visceral protein nutritional status, as defined by serum albumin level, is associated with hyperlipidemia and, especially vor CAPD, worsened atherogenic risk ratios.(ABSTRACT TRUNCATED AT 400 WORDS)

Pervasive Failed Rehabilitation in Center-Based Maintenance Hemodialysis Patients

At its inception in 1972, the end-stage renal disease (ESRD) program was conceived with a set of assumptions about cost, rate of growth, and treatment outcomes in its client population. Despite the potential to correct anemia with recombinant erythropoietin (EPO) introduced in 1987 and improved survival, the level of physical activity among some segments of the hemodialysis population remains suboptimal. This study was undertaken, among other reasons, to identify correlates of poor functional status as measured by a modified Karnofsky scale. Using a modified Karnofsky scale, we measured the functional status of 430 patients who had been treated by hemodialysis for at least 1 year and some of whom were also receiving concomitant treatment with EPO. Patients studied were randomly selected from eight dialysis units in urban New York and suburban New Jersey. A Karnofsky score of less than 70 indicated frank disability--the subject was unable to perform routine living chores without assistance. In addition, current vocational activity was ascertained, and comorbid conditions were quantified. The necessity for wheelchair dependence was noted for each patient. The mean age (+/- SD) of the study population was 56 +/- 14 years (range, 21 to 92 years). Subjects had been on maintenance hemodialysis for 4.09 +/- 3.8 years (range, 1 to 23 years). The study group included 215 men and 215 women, of whom 65% were black, 27% white, 6% Hispanic, and 2% Asian; 36.5% had diabetes mellitus. Although 376 members (87%) of the study group were under treatment with EPO, the mean hematocrit of the study population was only 29% +/- 4.5%.(ABSTRACT TRUNCATED AT 250 WORDS)

Correlates of Vascular Access and Nonvascular Access-Related Hospitalizations in Hemodialysis Patients

Four hundred and thirty randomly selected hemodialysis patients, aged 20 years and over, were studied to identify risk factors for vascular access and nonvascular access-related hospitalizations in the immediately preceding 1 year. Risk estimates for hospitalization were assessed using a multinominal logistic analysis model. We measured functional status, utilizing a 14-point Karnofsky scale, and in a separate analysis of covariance, in which Karnofsky score was the outcome, we examined the relationships of age, gender, ethnicity, renal diagnosis, and hospitalization. Individual comparisons were adjusted for multiple comparison bias by Tukeys Honest Difference method. There were a total of 508 hospitalizations of which 322 (63%) lasted > or = 1 week. Two hundred and sixty (60%) patients were hospitalized at least once; 105 (24.4%) for access problems only, 115 (27%) for a nonaccess problem only, and 40 for access and nonaccess-related problems. Access-related problems, accounted for 48% of all hospitalizations. The risk of hemodialysis vascular access morbidity was increased in women (p < 0.028) and white (p < 0.048) hemodialysis patients. Neither diabetic nor elderly hemodialysis patients were at greater risk for access hospitalization than their respective counterparts, though a greater proportion of the access hospitalizations in the elderly (> or = 64 years) lasted > or = 1 week (p < 0.0006). More access-related hospitalizations in blacks (64.5%), lasted for > or = 1 week than in whites (40.6%) (p < 0.001). Hispanics (p < 0.043), whites (p < 0.002), and the older patients (p < 0.054) were at greater risk for nonaccess hospitalization than blacks and younger patients, respectively. Even after adjusting for age, race, and diabetes, each decrease of one unit in the modified Karnofsky score was associated with a 3-4% increased risk for all types of hospitalization (p < 0.001)--poor functional status is associated with increased risk for all hospitalizations. We conclude that the risk for hemodialysis vascular access morbidity is increased in women and white hemodialysis patients. Poor functional status is associated with increased risk for all hospitalizations.

Enrollment Parathyroid Hormone Level Is a New Marker of Survival in Hemodialysis and Peritoneal Dialysis Therapy for Uremia

The relatively high morbidity and mortality during dialytic therapy for end-stage renal disease (ESRD) in the United States is the subject of current inquiry. Identified risk factors for excess mortality include advanced age, diabetes, and malnutrition exemplified by a low serum albumin level. Parathyroid hormone (PTH) has long been thought to contribute to the toxicity of the uremic syndrome. We reviewed the course of patients maintained by hemodialysis (HD) and peritoneal dialysis (PD) to detect any correlation between the level of PTH when beginning dialytic therapy and subsequent morbidity and mortality. Study cohorts consisted of 175 HD and 113 PD patients followed for up to 9 years. Demographic characteristics such as age, race, gender, diabetic status, and prior months on dialysis, as well as biochemical parameters including albumin, creatinine, cholesterol, intact PTH, calcium, and phosphorus levels at enrollment were evaluated for their effect on patient survival. Expected survival was calculated by Cox proportional hazards analysis. Older age and lower enrollment serum creatinine level were associated with increased mortality in both HD and PD patients, whereas low serum albumin and low serum cholesterol levels also predicted high mortality in HD patients. In both HD and PD, patients with enrollment PTH level of < or = 65 pg/mL had more than twice the mortality risk of those with PTH > or = 200 pg/mL. Both observed and expected survival of patients with low PTH were significantly lower than the survival in patients with higher PTH. Five-year HD survivors and four-year PD survivors had significantly higher PTH levels at initiation of dialytic therapy than did those with shorter survival. PTH level correlated with serum creatinine and serum albumin in HD but only with serum creatinine in PD, supporting the inference that patients with high enrollment PTH were better nourished than those with lower PTH.

Correlates of Vascular Access Occlusion in Hemodialysis

Vascular access occlusion results in significant morbidity in hemodialysis patients. Age, diabetes, and synthetic grafts (polytetrafluoroethylene [PTFE]) have been associated with vascular access occlusion in univariate analysis. However, the independent risk associated with each of these factors has not been assessed adjusting for confounding among the factors or by other variables, such as blood pressure (BP) or hematocrit. The influence of serum lipoprotein(a) [Lp(a)] and fibronectin on vascular access occlusion has not been widely studied despite their theoretical or demonstrated importance in vascular bypass occlusion. In a cohort study of 124 hemodialysis patients monitored for up to 14 months, we reported that Lp(a) values in the upper tertile (> or = 57 mg/dL) were associated with vascular access occlusion risk in white and Hispanic patients, but not in black patients. We now report an expanded analysis of this data set to determine the independent correlates of vascular access occlusion. Variables tested included age, race, gender, diabetes, access type (PTFE v endogenous), treatment time, systolic BP, hematocrit, heparin and erythropoietin dosage, and serum levels of Lp(a) and fibronectin. In univariate analysis, access occlusion was associated with age, diabetes, PTFE, Lp(a) > or = 57 mg/dL, serum fibronectin, and reduced BP. The independent correlates of first access occlusion were determined with the Cox proportional hazards model. Since the overall model included a significant race x Lp(a) interaction term, we stratified by race. In black patients, risk correlated directly with PTFE (P < 0.01) and inversely with systolic BP (P < 0.001), whereas for white and Hispanic patients, age (P = 0.04) and Lp(a) > or = 57 mg/dL (P = 0.05) were associated with increased risk. In summary, vascular access occlusion was found to be associated with a number of factors. Important independent correlates were PTFE and lower BP in black patients, and age and serum Lp(a) > or = 57 mg/dL in white and Hispanic patients. Diabetes mellitus and increased serum fibronectin may contribute additional risk.

Hemodialysis and the Elderly Patient: Potential Advantages as to Quality of Life, Urea Generation, Serum Creatinine, and Less Interdialytic Weight Gain

A total of 204 patients treated by maintenance hemodialysis or continuous ambulatory peritoneal dialysis (CAPD) were studied to ascertain how advancing age influences adaptation to uremia therapy. No difference in Karnofsky score was noted among patients over 70 years of age and two groups of patients, 16 to 59, and 60 to 69 years of age, respectively. In a subset of 33 hemodialysis patients studied midweek, it was noted that increasing age is associated with a lower serum creatinine concentration, lower interdialytic weight gain, and a lower urea generation rate. These three findings contribute to a relative ease in treating older uremia patients with hemodialysis or CAPD, as they tend to be stable and compliant relative to younger patients.