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Biomedical subjects

E A Friedman

Publications and source records attributed to E A Friedman.

At least 55 records · Page 3Linked to original sources

Parathyroidectomy does not correct hypertension in patients on maintenance hemodialysis.

Both hypertension and secondary hyperparathyroidism (2 degrees HPT) are common features of the uremic syndrome. It has been suggested that 2 degrees HPT causes hypertension in end-stage renal disease (ESRD). We compared predialysis blood pressure (BP), weight and dose of antihypertensive medications (AHM) prescribed in 19 hemodialysis patients 1 month before total parathyroidectomy (PTx), during the first month after PTx, and long-term (mean 16 months) in 12 of 19 patients. At the time of PTx, study patients had a mean age of 47 +/- 9 years, mean duration of ESRD was 112 +/- 57 months, and mean intact parathyroid hormone (PTH) level of 1,181 +/- 552 pg/ml. Mean BP and predialysis weight were equivalent during the month before and the month after PTx. Of 12 patients followed long term, 8 (67%) were receiving AHM before PTx; after PTx; 3 (36%) of 8 discontinued AHM within 1 year, 2 (25%) of 8 required more AHM, while 2 (25%) of 8 continued on their original AHM, and 1 patient who was not on AHM prior to PTx required initiation of AHM after PTx. There was a clinically significant increase in predialysis weight at 1 year after PTx (median 13 lb) and over time (r = 0.7; slope = 0.5; p = 0.07). However, there was neither a clinically nor statistically significant change in either systolic (r = -0.18; slope = -0.01; p = 0.61) or diastolic (r = -0.6; slope = -0.24; p = 0.12) BP over time. We conclude that PTx fails to correct hypertension in hemodialysis patients with 2 degrees HPT.

Adult↗

Predictive value of functional status for mortality in patients on maintenance hemodialysis.

In patients receiving maintenance hemodialysis, laboratory indices (such as serum albumin concentration) are predominantly utilized to assess well-being, while measures of functional status are rarely applied. However, the serum albumin concentration declines with advancing age, and the mean age of patients starting maintenance hemodialysis is now over 63 years. Using a 14-level modified Karnofsky activity scale, we measured baseline functional status in 522 randomly selected hemodialysis patients and prospectively monitored them for 3 years to determine the predictive value of our modified Karnofsky score for mortality. At onset of study, serum albumin and creatinine concentrations as well as hematocrit were measured and the comorbid conditions documented. At baseline, the 522 subjects (270 women and 252 men) included 327 blacks (63%), 154 whites (29%), 31 Hispanics (6%), and 10 Asians (2%) of mean age 59 +/- (SD) 15 years. The mean duration of end-stage renal disease was 4 +/- 3.6 years, and the mean serum albumin concentration was 3.7 +/- 0.4 g/dl. 166 (32%) of the patients died during the observation period. Cox regression analysis revealed inverse relations between mortality and both our modified Karnofsky score (p = 0.0001) and serum albumin concentration (p = 0.001). The predictive value of a low modified Karnofsky score for mortality persisted after analysis of subjects stratified according to serum albumin concentration (< 4 g/dl, n = 382, p = 0.0001 vs. > or = 4 g/dl, n = 140, p = 0.008). With a modified Karnofsky score (< 70 vs. > or = 70), the relative risk of death during the 3-year follow-up period was 1.44 (95% confidence interval 1.236, 1.675; p < 0.0001). Forward stepwise Cox regression analysis showed that advanced age (p = 0.0005), white race (p = 0.0009), diabetes mellitus (p = 0.01), and a low serum albumin concentration (p = 0.003) were independently associated with an increased risk of mortality during follow-up after adjustment for other factors. A modified Karnofsky score (p = 0.14) did not predict survival in the Cox model when other independent variables were included. We conclude that in patients with end-stage renal disease sustained on maintenance hemodialysis, a poor functional status (measured on a modified Karnofsky activity scale) is associated with early mortality. Periodic measurement of modified Karnofsky score is a simple, low-cost, and reliable means of identifying patients on dialysis at risk for early death.

Adult↗

Timing of initiation of uremia therapy and survival in patients with progressive renal disease.

We conducted a prospective cohort study to detect any relationships between specific clinical features and laboratory indices at initiation of hemodialysis and long-term survival. One hundred and thirty-nine consecutive patients with chronic renal failure hospitalized to start maintenance hemodialysis between January 1990 and December 1994 were enrolled, and follow-up was completed through December 1995. At baseline, subjects were assigned to one of five groups based on their major indication for initiation of hemodialysis. The indications were: (a) nausea and vomiting; (b) severe weakness; (c) no major symptom (dialysis started because of 'high' serum creatinine and blood urea nitrogen concentrations); (d) volume overload, and (e) miscellaneous (angina, pericarditis, seizure, pruritus, and hyperkalemia). Blood urea nitrogen, serum creatinine and serum albumin concentrations were measured once before the first dialysis. The main outcome measure was death. The 139 study subjects included 77 women and 62 men comprising 116 Blacks (83%), 15 Hispanics (11%), and 8 Whites (6%) of mean age 54 +/- 15 years. Mean length of follow-up was 39 months. At baseline, mean blood urea nitrogen concentration was 121 +/- 38 mg/dl, mean serum creatinine concentration was 12.6 +/- 5.2 mg/dl, and mean serum albumin concentration was 3.5 +/- 0.62 g/dl. Forty-two subjects (30%) died during follow-up. Cox regression analysis showed that there was no significant association between mortality and any of the indicators evaluated (indication for initiation of dialysis (p = 0.2), serum creatinine concentration (< 10 vs. > or = 10 mg/dl) (p = 0.8), blood ure nitrogen concentration (< 100 vs. > or = 100 mg/dl) (p = 0.68) and serum albumin concentration (< 4 vs. > or = 4 g/dl) (p = 0.62). All analyses included adjustment for age and diabetes. We conclude that in patients with chronic renal failure, the clinical features and laboratory indices used as guidelines for initiation of renal replacement therapy do not correlate with survival. Objective parameters that will permit initiation of dialysis at a time that will maximize survival in patients with chronic renal failure are needed.

Female↗

Effect of increased hemodialysis dose on endogenous erythropoietin production in end-stage renal disease.

We investigated 20 patients (12 men and 8 women) with end-stage renal disease sustained on hemodialysis to determine the effect of 6 weeks of increased dialysis dose on endogenous erythropoietin production. Increased dialysis dose was achieved by increasing thrice-weekly dialysis treatment time from 4 to 4.5 h and switching from an MCA 160 dialyzer to an F80 dialyzer. The mean age of the study subjects was 51 +/- 13.8 years, and the mean duration of end-stage renal disease prior to the study was 31.4 +/- 55.5 months. All subjects were receiving recombinant erythropoietin for at least 4 months prior to the study. The dialysis dose was increased from a mean reduction of urea of 60.7 to 72%. At baseline, the group's mean hematocrit was 28.4 +/- 3.4%, the mean predialysis endogenous erythropoietin level was 9.1 +/- 4.5 (range 2.5-18.4) mU/ml, the mean reduction of urea was 60.7 +/- 4%, and the mean transferrin saturation was 22.6 +/- 15.5%. Mean thrice-weekly recombinant erythropoietin injections were administered intravenously after dialysis to each patient at a dose of 51 +/- 19 U/kg body weight. After 6 weeks of an increased dialysis dose, the mean hematocrit increased from 28.4 +/- 3.4 to 32.3 +/- 3.3% (p = 0.0001), while the mean serum endogenous erythropoietin level decreased from 9.1 +/- 4.5 (range 2.5-18.4) mU/ml to 6.1 +/- 3.2 (range 2.5-13.4) mU/ml (p = 0.0001). We conclude that the serum endogenous erythropoietin levels decrease with increased dialysis dose and that the increase in hematocrit following increased dialysis dose is probably not mediated by changes in endogenous erythropoietin.

Adult↗

Aminoguanidine prolongs survival in azotemic-induced diabetic rats.

Toxic effects of hyperglycemia-induced advanced glycosylated end products (AGEs) may explain some vasculopathic complications of diabetes. Aminoguanidine, a known inhibitor of AGE formation, was administered by gavage to Sprague-Dawley streptozotocin-induced diabetic rats made azotemic by surgical reduction of renal mass. All rats became hyperglycemic. Renal ablation caused renal insufficiency, as evidenced by markedly reduced endogenous creatinine clearances at days 7 and 14. Aminoguanidine-treated rats had significantly (P < 0.04) superior survival to that of untreated azotemic diabetic rats. We infer from the extended life in a rat model of uremia in diabetic nephropathy that aminoguanidine may prove beneficial in human diabetes.

Animals↗

Uremia therapy in patients with end-stage renal disease and human immunodeficiency virus infection: has the outcome changed in the 1990s?

We conducted a cross-sectional survey to determine the relative course of patients with end-stage renal disease (ESRD) and human immunodeficiency virus (HIV) infection sustained on maintenance hemodialysis. All 34 patients with ESRD and HIV infection receiving hemodialysis in one hospital-based and three community-based outpatient hemodialysis facilities in Brooklyn, NY, were studied. We documented their known duration of HIV infection, duration of ESRD, and hemodialysis prescription, and noted the presence of clinical acquired immunodeficiency syndrome (AIDS). Total CD4 count, serum albumin concentration, and percent reduction of urea (predialysis blood urea nitrogen minus postdialysis blood urea nitrogen, divided by predialysis blood urea nitrogen x 100) were measured. The 34 study subjects (26 men and eight women) included 31 blacks (91%) and three Hispanics (9%) with a mean age of 42 +/- 7.5 years, 29 (85%) of whom had AIDS. Twenty subjects (59%) had a history of intravenous drug abuse. Only six subjects (18%) were receiving an antiretroviral drug (zidovudine = five, dideoxyinosine = one). In 23 subjects (68%), AIDS was diagnosed prior to ESRD and was presumed to be the cause of renal failure (HIV-associated nephropathy). The mean known duration of HIV infection was 50.5 +/- 34 months (median, 48 months); the mean duration of ESRD was 57 +/- 50 months, the mean total CD4 count was 140 +/- 150 cells/microL (median, 70 cells/microL), the mean hematocrit was 28% +/- 5%, and the mean serum albumin concentration was 3.5 +/- 0.37 g/dL. All subjects were receiving erythropoietin for anemia correction. The mean length of the prescribed thrice-weekly hemodialysis sessions was 3.5 +/- 0.4 hours. Our results suggest that the survival of many ESRD patients with HIV infection receiving hemodialysis has improved compared with the uniformly dismal survival rate reported in the 1980s. Decisions on whether to initiate renal replacement therapy in patients with AIDS and advanced renal failure should be individualized because the combination of ESRD and HIV infection does not necessarily signal near-term death.

AIDS-Associated Nephropathy↗

Unemployment in inner-city renal transplant recipients: predictive and sociodemographic factors.

Studies of dialysis patients report unemployment rates of 60% to 75%; however, it is generally believed that following transplantation, improvement in well-being and removal of time constraints imposed by the dialytic regimen afford improvement in employment status. We studied 58 stable renal transplant recipient attending an outpatient transplant clinic by questionnaire, administered anonymously. Only 25 (43%) of the patients were currently employed. Employed and unemployed patients did not differ when compared for age, gender, race, cause of renal disease, type of transplant or prior dialysis, time on dialysis or time since transplantation, years of education, or prestige score or classification ("blue collar" v "white collar") of prior job. In the employed group, 24 (96%) patients had worked before developing kidney disease compared with 23 (70%) patients in the unemployed group (P < 0.05). While on dialysis, 19 (79%) of the employed patients continued working compared with 10 (30%) of the unemployed patients (P < 0.005). Major reasons for discontinuing work after starting dialysis for both groups were subjective illness (feeling too sick, 51%), followed by interference of the dialysis regimen with time necessary for work (32%). Only 15% of the previously employed patients did not work after transplantation because of feeling too sick. By multiple logistic regression, the strongest predictors of employment posttransplant were being more than 1 year posttransplant (odds ratio, 2.35; 95% confidence interval, 1.01 to 5.5) and having been employed before transplantation (odds ratio, 3.79; 95% confidence interval, 1.60 to 9.02). Over half of the unemployed patients (20 [61%]) expressed interest in job training. Eighty percent to 90% of patients in both groups were insured by Medicare, with the second greatest number insured by Medicaid. Of the 15 unemployed patients insured by Medicaid, 67% reported that their decision not to work was related to fear of losing Medicaid benefits because they could not afford medications without it. Despite no difference in actual type of insurance carried, 17 (51%) of the unemployed patients believed their health insurance coverage was inadequate compared with four (12%) of the employed patients (P = 0.005, chi-squared test). Unemployment remains a significant problem for our population of inner-city renal transplant recipients. Attention to job retention or retraining during the early renal disease and dialysis therapy period may promote better rehabilitation following transplantation. However, for this population, with limited employment opportunities, removal of disincentives to work, including loss of Insurance and Inability to pay for medications, will be necessary before we can provide optimal rehabilitation for renal transplant recipients from all social strata.

Adult↗

Severity of AIDS and the response to EPO in uremia.

To determine the factors that govern their response to erythropoietin (EPO), we conducted a cross-sectional study of all patients in four outpatient hemodialysis facilities in Brooklyn, NY, who had end-stage renal disease (ESRD) and human immunodeficiency virus (HIV) infection and were receiving recombinant EPO. We also compared the hematocrit and EPO requirements of these patients to those of a control group of hemodialysis patients without HIV infection. We documented known duration of HIV infection, and total CD4 count was measured once. In both groups, hematocrit was measured weekly for 5 weeks and a mean value calculated for each subject. Transferrin saturation was measured twice and a mean value calculated for each subject. Intensity of hemodialysis was assessed by measuring both percent reduction of urea and serum albumin concentration twice; mean values were calculated for each subject. Twenty-nine (88%) of 33 study subjects had acquired immunodeficiency syndrome. Mean known duration of HIV infection was 49 +/- 32.5 months (median, 48 months), and mean total CD4 count was 143 +/- 152.4 cells/mm3 (median, 72 cells/mm3). Mean hematocrit in the study subjects was 27.4% +/- 4.7% compared with 27.6% +/- 3.7% in the controls (P = 0.69). Mean thrice-weekly EPO dose was higher in the study subjects (90 +/- 52 U/kg body weight) than in the controls (62 +/- 36 U/Kg body weight) (P = 0.001). Among the study subjects, hematocrit had direct univariate correlations with serum albumin concentration (r = 0.43; P = 0.02), transferrin saturation (r = 0.4; P = 0.03), and percent reduction of urea (r = 0.4; P = 0.02), but not with total CD4 count (r = -0.05; P = 0.8) or known duration of HIV infection (r = -0.11; P = 0.55). There was an inverse correlation between hematocrit and dose of EPO (r = -0.5; P = 0.003). Multiple regression analysis showed that transferrin saturation (P = 0.01) and percent reduction of urea (P = 0.003) had direct correlations with hematocrit after adjustment for other factors. There was an inverse relationship between hematocrit and dose of EPO (P = 0.0006). We conclude that in patients with ESRD and HIV infection receiving hemodialysis, the response to EPO (hematocrit) is modulated by the dose of EPO, quantity of hemodialysis, and transferrin saturation, but not by the severity of HIV disease. Hemodialysis patients infected with HIV receive a higher dose of EPO than those without HIV infection.

Adult↗

Determinants of type of initial hemodialysis vascular access.

Vascular access thrombosis is more common with polytetrafluoroethylene (PTFE) grafts than with native arteriovenous fistulae (AVF). Recent studies report an unexplained excess vascular access morbidity in women on hemodialysis. We studied 92 consecutive end-stage renal disease (ESRD) patients receiving their first permanent hemodialysis vascular access at initiation of hemodialysis to identify variables that determine assignment of either a PTFE graft or a native AVF. Independent variables included: age, gender, race, etiology of ESRD, and whether or not access surgery was electively planned before need for dialytic therapy. The 51 women and 41 men included 65 blacks, 13 Hispanics, 11 whites, and 3 Orientals aged 50 +/- (SD) 16 years. Of the 92 subjects, 54 (59%) received an AVF, while 38 (41%) received a PTFE graft. 36 (94%) of 38 PTFE grafts were placed in the upper arm as compared with 9 (17%) of 54 AVF (p = 0.0001). Also, 45 (83%) of 54 AVF were placed in the forearm as compared with only 2 (6%) of 38 PTFE grafts (p = 0.0001). Women were more likely to receive a PTFE graft - 28 (55%) of 51 - than men - 10 (24%) of 41 (p = 0.003). By contrast, men were more likely to get an AVF - 31 (76%) of 41 - than women - 23 (45 %) of 51 (p = 0.003). The log linear analysis confirmed that this finding was significant (p = 0.0018) for the coefficient of interaction between gender and type of vascular access. No other independent variable had a significant relationship with type of vascular access. We conclude that women with ESRD are more likely to receive a PTFE graft for hemodialysis, while men are more likely to get an AVF. These findings may explain, in part, the reported excess vascular access morbidity in women on hemodialysis.

Adult↗

Relative contributions of body iron status and uremia severity to anemia in patients with advanced chronic renal failure.

Anemia in chronic renal failure is predominantly caused by diminished erythropoietin synthesis by diseased kidneys. While iron deficiency is often stated as a cause of anemia in chronic renal failure prior to end-stage renal disease, its relative contribution is debated. It is speculated that rather than frank 'iron deficiency', many patients with chronic renal failure may indeed have impaired utilization of iron. We analyzed 139 consecutive patients with chronic renal failure starting maintenance hemodialysis to determine the relationship between hematocrit, measures of renal function (blood urea nitrogen and serum creatinine concentration), and measures of iron availability (serum transferrin saturation, serum iron level and serum ferritin). The 139 study subjects (60 men, 79 women) comprised 116 blacks (83%), 15 hispanics (11%), and 8 whites (6%) of a mean age 56 +/- 15 years. Only 23 (17%) of 139 subjects had positive hemoccult stool test for blood. Their mean hematocrit was 24 +/- 4.5%, mean blood urea nitrogen concentration was 121 +/- 38, mean serum creatinine concentration was 12.6 +/- 5.2 mg/dl, mean serum transferrin saturation was 22 +/- 14%, mean serum ferritin level was 235 +/- 194 U/l, mean serum iron level was 55 +/- 40 U/l, and mean total iron binding capacity was 254 +/- 93%. Multiple regression analysis with hematocrit as the outcome variable, and blood urea nitrogen level, serum creatinine concentration, serum albumin concentration, serum transferrin saturation, and serum ferritin level as the independent variables, showed an inverse correlation between hematocrit and serum creatinine concentration (p = 0.002). We conclude that in patients with chronic renal failure starting uremia therapy, anemia does not correlate with any of the commonly measured indices of body iron stores. We infer that impaired utilization of iron may be a significant factor in the anemia of chronic renal failure.

Adult↗

Severe hyperparathyroidism associated with prolonged hungry bone syndrome in a renal transplant recipient.

Although widely believed to resolve within 6 to 12 months of successful renal transplantation, hyperparathyroidism may persist or develop after renal transplantation and eventually require parathyroidectomy. Avid calcium retention by demineralized bones (hungry bone syndrome) is well-recognized after parathyroidectomy and usually resolves after a few weeks. This report documents the case of a renal transplant recipient with persistent hyperparathyroidism who developed a pathological fracture of the pelvis and required parathyroidectomy 1 year after transplant and then manifested severe and prolonged hungry bone syndrome lasting for more than 20 months postoperatively. The clinical features and treatment of hyperparathyroidism in renal transplant recipients are discussed, as are diagnosis, pathogenesis, and management of hungry bone syndrome. Recognition of renal transplant recipients at greater risk for severe hungry bone syndrome should permit earlier and more aggressive management of this sometimes protracted complication of parathyroid surgery.

Adult↗

Anemia following renal transplantation: erythropoietin response and iron deficiency.

To define the etiology of anemia post-renal transplantation, we assessed hematologic parameters and EPO levels in 38 anemic and 16 non-anemic control renal transplant recipients (RTRs) with varying degrees of allograft function at periods > 3 months post-transplantation. Significant differences between the two groups were found for serum creatinine (Cr) 291.7 +/- 26.5 vs. 203.3 +/- 26.5 mumol/l, p < 0.01; iron 9.3 +/- 0.92 vs. 13.6 +/- 1.7 mumol/l, p < 0.05; and ferritin 345.5 +/- 90.8 vs. 91.1 +/- 18.5 micrograms/l, p < 0.01. Serum EPO levels were inappropriately low in anemic patients with no significant correlation between EPO and Cr or hematocrit (Hct) levels. Serum iron was the only predictive factor for anemia on regression analysis (p < 0.05). Ferritin levels did not correlate with serum iron or Hct, and may be falsely elevated in iron deficient RTRs. Iron deficiency, poor renal function and inappropriately low EPO levels are major contributors to the 12% of our outpatient renal transplant population who are anemic.

Anemia↗