Biomedical subjects
P Goldwasser
Publications and source records attributed to P Goldwasser.
URR, weight, and mortality.
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Prediction equation for glomerular filtration rate.
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Rise in serum albumin and creatinine in the first half year on hemodialysis.
UNLABELLED: Rise in serum albumin and creatinine in the first half year on hemodialysis. BACKGROUND: Serum albumin and creatinine have been reported to rise in new hemodialysis patients; however, these trends have not been quantitated in a stable cohort, and their determinants and prognostic value are unknown. METHODS: This study examined the changes in monthly values of serum albumin and creatinine over the first half year of hemodialysis in 115 patients who survived to the start of the sixth month. After verifying that the trends were approximately linear, we calculated the rates of rise (slope) of six predialysis values of serum albumin (months 1 through 6) and of creatinine (months 2 through 7) and examined their associations with age, diabetes, race, baseline 24-hour urine protein and creatinine excretion, and survival during the latter half of the first year. RESULTS: Serum albumin rose by 13% over months 1 through 6 [0.08 +/- 0.12 (SD) g/dl/month, P < 10-9 vs. zero slope]. Patients who survived the entire year had higher mean values for both serum albumin (month 1, P < 0.003; months 3 through 6, P < 10-3) and rate of rise of albumin (0.09 +/- 0.11 g/dl/month vs. 0.01 +/- 0.13 g/dl/month, P < 0.005) than patients who died during months 6 through 12, but the slope was not an independent predictor of survival after adjusting for serum albumin concentration. Baseline proteinuria correlated inversely with serum albumin measured at the first and second months (P < 0.005) and directly with the albumin slope (r = 0.49, P < 10-5). Serum creatinine rose by 12% between months 2 through 7 (0.12 +/- 0.47 mg/dl/month, P < 0.02). Survivors had a significantly higher mean baseline creatinine excretion (P < 0. 03) and serum creatinine (month 2, P < 0.03; months 3 through 7, P < 0.01) but only a marginally higher rate of rise of serum creatinine (0.16 +/- 0.47 mg/dl/month vs. -0.07 +/- 0.48 mg/dl/month, P < 0.06) than patients who died during the second half of the year. Baseline urinary creatinine excretion correlated directly with serum creatinine at month 2 (P < 0.01) and more strongly at months 3 through 7 (P < 10-3), as well as correlating with the creatinine slope (r = 0.26, P < 0.03). CONCLUSIONS: Serum albumin and creatinine rose by 12 to 13% during the first half year of hemodialysis in a stable cohort. The slope of serum albumin versus time predicted survival, but it was not as predictive as the absolute albumin concentration. The pattern of correlations of baseline urinary protein and creatinine excretion with the respective monthly serum values of albumin and creatinine and their slopes is consistent with the hypothesis that as residual renal function declines, progressive retention of protein and creatinine contributes to the respective rises in serum albumin and creatinine.
Race and creatinine excretion in chronic renal insufficiency.
Black race and the absence of diabetes are associated with higher levels of serum creatinine in patients with end-stage renal disease. We examined whether these factors have a similar influence on creatinine excretion in men with chronic renal insufficiency. The hypotheses were tested in one sample (group A, n = 35) and the findings replicated in a second, independent sample (group B, n = 66). Creatinine excretion normalized to weight (UCr/kg) was compared by race and diabetic status. UCr/kg and creatinine clearance also were compared with the values predicted by the Cockcroft-Gault (CG) formula (based on the regression equation, UCr/kg = 28 - age/5). In each sample, mean UCr/kg was significantly higher in black patients than in nonblack patients (group A, P = 0.004; group B, P = 0.029), and UCr/kg and creatinine clearance were significantly underestimated by the CG predictions in black patients (group A, P < or = 0.004; group B, P < or = 0.019), but not in nonblack patients. Diabetes did not significantly influence UCr/kg. The analysis also was performed at two age levels (< 50 years or > or = 50 years) using groups A and B combined. For black patients younger than 50 (n = 10), observed UCr/kg (P = 0.059) and creatinine clearance (P = 0.025) exceeded the values predicted by the CG formula; the analysis of nonblack patients younger than 50 years was limited by sample size (n = 1). For patients aged 50 years and older (black, n = 32; nonblack, n = 58), mean UCr/kg was significantly higher in black patients (P = 0.034), and UCr/kg and creatinine clearance were significantly underestimated by the CG predictions in black patients (P < or = 0.002) but not in nonblack patients. In multiple regression analysis of all patients aged 50 years and older, UCr/kg was independently influenced by both race (P < 0.05) and age (P < 0.04) (overall model, multiple R = 0.31; P = 0.012). The prediction equation was UCr/kg (mg/kg) = 23.6 - age/8.3 + 1.9 x race (race = 0 if nonblack; race = 1 if black). We conclude that the creatinine excretion rate was strongly affected by race but not diabetes in men with chronic renal insufficiency. The CG formula significantly underestimated UCr/kg and therefore creatinine clearance in black patients. These findings may reflect differences between black and nonblack subjects in body composition, muscle metabolism, or diet, and the interaction of these factors with chronic renal insufficiency.
Association of serum albumin and mortality risk.
Reduced levels of serum albumin concentration, a routine blood test, within the "normal" range have been reported to be associated with mortality risk. The literature is reviewed, with a focus on cohort studies meeting specified criteria, and findings are summarized. In studies of many populations, comprising healthy subjects and patients with acute or chronic illness, serum albumin concentration is inversely related to mortality risk in a graded manner over its entire range; the estimated increase in the odds of death ranges from 24% to 56% for each 2.5 g/l decrement in serum albumin concentration. The association predicts overall and cause-specific mortality including cardiovascular mortality. It is likely that albumin concentration is a highly sensitive indicator of preclinical disease and disease severity. A direct protective effect of the albumin molecule is suggested by the persistence of the association after adjustment for other known risk factors and preexisting illness, and after exclusion of early mortality. Although biologically plausible, there is no direct evidence for this hypothesis. Serum albumin concentration is an independent predictor of mortality risk and could be useful in the quantification of risk in a broad range of clinical and research settings.
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.
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.
Serum ferritin, hematocrit and mean corpuscular volume in hemodialysis.
Prior to beginning to administration erythropoietin (EPO) in 1989, we examined the relationships of hematocrit (HCT), mean corpuscular volume (MCV), and serum ferritin (FER) in one group of hemodialysis patients (group A, n = 117) and replicated the findings in a second group (group B, n = 73). The groups had similar mean (+/- SD) HCT (A: 25.7 +/- 5.3%; B: 25.2 +/- 5.1%), MCV (A: 83.3 +/- 6.5 fl; B: 83.5 +/- 7.5 fl) and FER (A: 607 +/- 1446 micrograms/l; B: 374 +/- 601 micrograms/l). For group A, iron stores [log (FER)] correlated inversely with HCT (r = -0.44, p < 10(-4)) and directly with MCV (r = 0.32, p < 10(-3)). After dividing group A into octiles by the FER level, the lowest octile (mean FER 17.8 +/- 6.2 micrograms/l) had the highest mean HCT (29.5 +/- 6.4%) and lowest mean MCV (80.8 +/- 7.1 fl), while the highest octile (mean FER 3,312 +/- 3,005 micrograms/l) had the lowest mean HCT (21.9 +/- 2.8%) and the second-highest mean MCV (86.4 +/- 4.9 fl). The trends were similar in group B. We conclude that increased erythropoiesis appeared to cause or, at least, unmask iron deficiency in HD patients even prior to the advent of EPO therapy. Variations in the level of erythropoiesis among these patients (presumably due to variation in EPO levels, chronic inflammation) strongly influenced the determinants of iron stores (i.e., marrow utilization of iron, transfusion need); iron stores, in turn, influenced MCV.
The observed correlation between PCRN and KT/V is not a mathematical artifact?
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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)
Predictors of mortality in hemodialysis patients.
Serum biochemical measures suggestive of undernutrition have been reported to correlate with 1-yr mortality risk in prevalent groups of hemodialysis patients. The predictive power of these variables has not been reported in newly diagnosed patients or in patients whose dialysis prescription is guided by urea kinetics. The relationship of these predictors to mortality over periods of longer than 1 yr is also unreported. Therefore, the survival of 184 hemodialysis patients was examined for up to 44 months (1987 to 1991) with the Cox proportional hazards model. Baseline demographic, clinical, and biochemical parameters were used as independent variables. To adjust for bias in patient selection, the survival of patients with 12 months or less of prior dialysis at the time of enrollment ("new cases") was analyzed separately from that of patients with more than 1 yr of prior treatment ("long-standing cases"). Serum albumin was less than 3.5 g/dL in 31% of new cases and in 12% of long-standing cases. Adjusting for the other variables, low serum albumin was the strongest mortality risk predictor in both new and long-standing cases. Low serum cholesterol was an independent risk predictor in both groups. Diabetes and race were not significant predictors. Mean age at enrollment was nearly a decade higher for nonsurvivors than for survivors, in both new and long-standing groups. Yet, age was not an independent risk predictor in the Cox model for the new group because of an unexpectedly high death rate among young black men. Female gender, which was confounded by increased age, took the place of age in the model for the new group. For each model, there was good agreement between observed and predicted mortality for up to 24 months. To assess the influence of dialysis treatment time and dose (measured as pre-to-post treatment urea ratio) on risk, survival was examined in a subset of 139 patients monitored for up to 22 months, from 1989 to 1991, a period when the urea ratio was used routinely. Adjusting for the other variables, low serum albumin and cholesterol again independently increased risk. The urea ratio was also a significant independent predictor. The pattern of mortality by urea ratio was U shaped, with minimum risk for values between 2.5 and 3.4 Treatment time did not influence risk. It was concluded that baseline serum values of albumin and cholesterol strongly influence survival for up to 2 yr in new and long-standing hemodialysis patients.(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)
Effect of urine chemistry on red cells.
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Lipid abnormalities in black renal patients.
Racial differences in lipoprotein (LP) and cardiovascular (CV) abnormalities have been noted in the general population and in the population of patients on dialysis. Few studies have investigated the interaction of race and LP and CV disturbances in other renal disease groups. We studied lipid profiles and risk ratios (total cholesterol (TC)/high density lipoprotein-cholesterol) (HDL-C) and apolipoprotein (apo) A-I/apo B (A-I/B)) and the influence of race across a spectrum of renal disease groups (normal renal function (NRD), nephrotic range proteinuria (NS), hemodialysis (HD), continuous ambulatory peritoneal dialysis (CAPD), post-transplant (TR), renal insufficiency (RI)). We also performed a longitudinal study of lipid profiles in patients with end stage renal disease (ESRD) and the relationship of these profiles to race and other variables. There was a general tendency towards a better CV risk profile for blacks than whites in all the groups. Blacks tended to have lower TC, higher HDL-C, lower TC/HDL-C, higher apo A-I, lower apo B, and higher A-I/B. We analyzed four yearly cross-sections of the HD and CAPD populations using ANOVA with adjustment for appropriate covariates. Whites had lower HDL-C and a higher TC/HDL-C risk ratio than blacks. HD patients had lower TC, TC/HDL-C, apo A-I, and apo B than CAPD patients, and women had higher TC than men. When lipid profiles were studied longitudinally by yearly intervals, no consistent significant changes were seen, but over two years, levels of apo B fell and A-I/B rose. Race had no significant effect on any of the longitudinal data.(ABSTRACT TRUNCATED AT 250 WORDS)
Urinary red cell size: diagnostic value and determinants.
Urinary red blood cells (RBC) are usually small and morphologically abnormal in glomerular (GN) hematuria, and slightly enlarged and morphologically normal in nonglomerular (NG) hematuria. This study was performed to evaluate the diagnostic value of urinary red cell size and morphology and to investigate the mechanism of the alteration in cell size. In 34 consecutive patients with hematuria we examined the urinary RBC size distribution and mean corpuscular volume (MCV) by electronic sizing of suspensions of RBC in an isotonic medium and, in 28 cases, compared it with the presence of 50% or greater dysmorphia. In 15 consecutive cases, we correlated MCV values with urine chemistries. In two GN cases we recorded the urine MCV serially during a furosemide-induced diuresis. In vitro incubations of peripheral or urinary RBC in various electrolyte solutions prior to sizing were also performed. The MCVs were significantly lower in GN (p less than 10(-6)) and probable GN (p less than 10(-4)) than NG hematuria. A cutoff of 72 fl completely separated GN and probable GN from NG cases. Fifty percent or more 'dysmorphic' RBC were seen in 12 of 13 GN, 3 of 4 probable GN but in no NG sediments. In patients with NG hematuria, the ratio of urinary to peripheral MCV tended to be greater than unity and correlated strongly with pH (r = -0.97; p less than 0.002). The effect of pH was confirmed in vitro. Furosemide diuresis induced a partial correction of the microcytosis of GN RBC, which correlated with the changes in urine composition. Furosemide had no effect on GN cells in vitro.(ABSTRACT TRUNCATED AT 250 WORDS)
Cholesterol and lipid disturbances in renal disease: the natural history of uremic dyslipidemia and the impact of hemodialysis and continuous ambulatory peritoneal dialysis.
Lipid abnormalities have been postulated to contribute to renal insufficiency by a mechanism that is analogous to atherogenesis. The majority of patients treated for chronic renal failure die of cardiovascular complications. Lipid abnormalities in this group are thought to contribute to this high mortality. Proving a causal association between dyslipidemia and accelerated atherosclerosis in the end-stage renal disease population has been confounded by the presence of other pro-atherogenic conditions in this population. The current study compiles the lipid data we have accumulated from our renal population for the years 1987 to 1989. The report is divided into three main parts: The first is a survey of lipid levels and atherogenicity indicators in groups with different types of renal disease or modalities of treatment. The second is a multivariate analysis of the relationship of clinical and biochemical variables (and their interactions) to the serum lipid and apolipoprotein levels and their ratios and their change over time in a large dialysis population. In the third study, we quantitate the peritoneal clearances of apolipoproteins A-I and B in patients undergoing continuous ambulatory peritoneal dialysis and assess the relationship of these clearances to serum lipid and lipoprotein levels and risk ratios.