Onyekachi Ifudu

Excess morbidity in patients starting uremia therapy without prior care by a nephrologist

Many inner-city residents with progressive renal disease do not receive specialist care from a nephrologist, and often arrive in the emergency room manifesting life-threatening uremic symptoms requiring emergency rescue dialysis. We examined the relationship between the quality of medical care received during progression to end-stage renal disease, and the clinical condition and morbidity at initiation of renal replacement therapy. During a 5-year period (January 1990 to December 1994), we prospectively studied 139 consecutive inner-city residents with a confirmed diagnosis of chronic renal failure who were starting uremia therapy. At onset of study, subjects were sorted into one of three groups depending on the extent of medical care received during the 3 years immediately preceding initiation of hemodialysis: nephrologist, nonnephrologist (physician), or no medical care. Information obtained from each subject included length of hospital stay during the admission for initiation of dialysis therapy and the type of hemodialysis vascular access used for first dialysis treatment (permanent v temporary). Predialysis blood urea nitrogen concentration, serum creatinine concentration, serum albumin concentration, and serum bicarbonate concentration were measured once immediately before the first dialysis. The 139 study subjects (62 men and 77 women) comprised 116 blacks (83%), 15 Hispanics (11%), and eight whites (6%), and had a mean age of 56 +/- 15 years (+/-SD). Only 59 (43%) subjects received prior specialist nephrologist care, and their mean length of hospital stay (12 +/- 23 days) was shorter than that of subjects who received nonnephrologist care (n = 63 [45%]; 25 +/- 21 days) or those who received no prior medical care (n = 17 [12%]; 29 +/- 23 days) (P = 0.002). Temporary hemodialysis vascular access was used for the first dialysis in all 17 (100%) of the subjects with no prior medical care, in 56 (89%) of the 63 subjects who received prior care from a nonnephrologist, and in 21 (36%) of the 59 subjects who received prior care from a nephrologist (P = 0.0001). Subjects who received prior care from a nephrologist had a lower mean serum creatinine concentration at initiation of dialysis (11 +/- 4.4 mg/dL) than did either the subjects who received nonnephrologist care (13 +/- 5.4 mg/dL) or no medical care (16 +/- 5.7 mg/dL) (P = 0.003). In addition, subjects who received prior care from a nephrologist had less severe metabolic acidosis than the subjects in the other two groups (P = 0.04). We infer that initiation of uremia therapy is delayed in inner-city residents with progressive renal failure who do not receive specialist nephrologic care, and that as a consequence these patients suffer excess short-term morbidity.

Delayed referral of black, Hispanic, and older patients with chronic renal failure

Delayed referral (defined as a serum creatinine concentration > 4 mg/dL at referral) of patients with chronic renal failure to the nephrologist is common in the United States. We retrospectively examined the records of 220 consecutive patients referred to an urban teaching hospital nephrology division for evaluation of chronic renal failure from January 1987 to December 1994 to detect any relationship between race, renal diagnosis, or age and the timing of referral of medically-insured patients with chronic renal failure. We documented serum creatinine concentration and hematocrit at referral, length of time under the care of a nephrologist (interval from referral to initiation of dialysis), and total number of clinic visits. The 220 study subjects (120 women, 100 men) included 139 blacks (63%), 61 whites (28%), 16 Hispanics (7%), and 4 Asians (2%) aged 51.7 +/- 1.06 years (mean +/- standard error of the mean) at referral. At referral, nonwhites (black and Hispanic patients) had a greater mean serum creatinine concentration than whites (4.3 +/- 0.38 v 3 +/- 0.24 mg/dL; P = 0.001), as well as a lower mean hematocrit (31.7% +/- 1.3% v 34.7% +/- 0.9%; P = 0.001). Mean length of time under the care of a nephrologist was shorter in nonwhites (13 +/- 0.8 months) than whites (43.5 +/- 4.8 months; P = 0.001). Delayed referral was almost six times more likely in nonwhites than whites (odds ratio, 5.6; 95% confidence interval [CI], 1.52 to 20; P = 0.008) and five times more likely in those aged older than 55 years than in those 55 years or younger (odds ratio, 4. 7; 95% CI, 1.37 to 16; P = 0.01). The greater the serum creatinine concentration at referral, the greater the odds of receiving less than 12 months of nephrologic care before initiation of dialysis (odds ratio, 1.8; 95% CI, 1.04 to 3.13; P = 0.03). We conclude that even among those patients with health insurance, delayed referral to the nephrologist is more likely in black, Hispanic, and older patients with chronic renal failure than in their white or younger counterparts.

Zidovudine Is Beneficial in Human Immunodeficiency Virus Associated Nephropathy

Human immunodeficiency virus associated nephropathy (Hivan) is a distinct renal disease described in patients infected with the human immunodeficiency virus (HIV). Hivan is characterized by a nephrotic syndrome, enlarged kidneys, a histologic finding of focal and segmental glomerulosclerosis, and a very rapid progression to end-stage renal disease (ESRD). No therapeutic intervention has been shown, in a prospective evaluation, to either alter the course of established Hivan or to influence the emergence of Hivan in HIV-infected patients. We conducted a prospective study on 23 consecutively selected patients seen between 1989 and 1992 who were infected with the HIV, 14 (61%) of whom had significant proteinuria (> or = 2+). Percutaneous kidney biopsy was performed in 5 (36%) of the 14 subjects who had significant proteinuria, and histologic examination of the kidney tissue revealed focal and segmental glomerulosclerosis in all 5 cases. Of the 14 subjects with proteinuria, 8 (57%) also had azotemia (serum creatinine level > or = 1.3 mg/dl). Nine (39%) of 23 subjects admitted intravenous drug use, while 9 (39%) of 23 subjects have had an opportunistic infection before enrollment in the study. The known duration of HIV infection before initiation of zidovudine therapy was 10.3 +/- (SD) 8 months. The mean CD4 count before zidovudine therapy was 195.9 +/- 117 (range 21-654) cells/mm3. The mean dose of zidovudine administered was 543 +/- 117 (range 400-800) mg daily for a period of 20.4 +/- 11 (range 6-38) months.(ABSTRACT TRUNCATED AT 250 WORDS)

Gouty Arthritis in End-Stage Renal Disease: Clinical Course and Rarity of New Cases

We studied 201 end-stage renal disease (ESRD) patients sustained on maintenance hemodialysis (MD) (n = 164) and chronic ambulatory peritoneal dialysis (CAPD) (n = 37) to determine (1) the frequency of acute attacks of gouty arthritis (GA) in those ESRD patients who had GA before dialytic therapy, and (2) the incidence of new-onset GA in hyperuricemic long-term (> 12 years) ESRD patients on MD. The 2-month mean of predialysis serum uric acid levels was calculated for each subject and the prevalence of hyperuricemia ascertained. There were 25 patients on MD for more than 12 years, and this group was evaluated and analyzed separately from those patients on dialytic therapy for less than 12 years; the mean of each of their predialysis uric acid values was calculated for each subject for at least 60% of the time they have been on dialysis. Patients who had GA before or after initiation of dialytic therapy were identified, and the frequency of acute attacks of GA determined. The presence of treated hypertension in each subject was noted. Thirteen of 201 patients had clinically active GA before commencing dialytic therapy, and each recalled a minimum of two painful attacks of GA per year before the initiation of ESRD therapy. Mean duration of ESRD for these 13 patients was 25 +/- 3.8 months; painful attacks of GA have not recurred in nine patients (70%), and the frequency of attacks declined by 50% in the remaining four patients (30%), despite persistent hyperuricemia in all 13.(ABSTRACT TRUNCATED AT 250 WORDS)

Parathyroidectomy Does Not Correct Hypertension in Patients on Maintenance Hemodialysis

Both hypertension and secondary hyperparathyroidism (2° HPT) are common features of the uremic syndrome. It has been suggested that 2° 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° HPT.

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.

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.

Effect of Missed Hemodialysis Treatments on Mortality in Patients with End-Stage Renal Disease

This article is also accessible online at: http://BioMedNet.com/karger Dear Sir, Investigators have attributed the excess mortality of American dialysis patients to a higher frequency of noncompliance than in their European counterparts [1]. We enumerated missed dialysis treatments among 430 randomly selected hemodialysis patients over a 10-week period and prospectively monitored them for 3 years to determine whether a relationship existed between missed dialysis treatments and mortality. Information obtained from subjects at onset of study included age, gender, race, cause of end-stage renal disease (ESRD), duration of ESRD, and an inventory of comorbid conditions. The predialysis serum albumin concentration was measured once. All study subjects were on a three times weekly dialysis schedule of 3.5–4 h duration. At the onset of the study, the 430 subjects (215 women, 215 men) comprised 280 (65%) blacks, 114 (27%) whites, 27 (6%) Hispanics, and 9 (2%) Asians with a mean age of 56 B14 (range 21–92) years. One hundred and fifty-seven patients (36.5%) had diabetes mellitus, while 273 (63.5%) had not. Forthy-three (10%) of 430 patients missed a total of 96 treatments. 132 (31%) of the 430 patients died during the follow-up period. Fourteen (33%) of 43 subjects who missed a dialysis treatment died during follow-up as compared with 118 (30%) of 387 patients who did not miss a treatment (p by chisquare = 0.79). Cox regression analysis with continuing survival as the outcome variable and missed dialysis treatment as the only independent variable did not reveal any statistically significant relationship (p = 0.79). Cox regression analysis with adjustment for other key variables, also failed to detect a statistically significant relationship between missed dialysis treatments and mortality (p = 0.47). A low serum albumin level (p = 0.007), white race (p = 0.001), advancing age (p = 0.05), and diabetes mellitus (p = 0.018) were risk factors for mortality (table 1). Our study showed that in patients with ESRD receiving hemodialysis missed dialysis treatments were not associated with shortened survival. However, other previously established risk factors for early death such as a low serum albumin level and diabetes mellitus were associated with shortened survival in our study subjects [2]. We wish to emphasize that the nondetection of a clinically or statistically significant relationship between missed dialyses treatment and mortality in this study does not rule out any effect that noncompliance over a longer period of time may have on mortality. A potential reason for the failure to detect any relationship between missed dialysis treatment and mortality is that missed dialysis treatments were more likely in younger

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.

Hemodialysis immediately after acute myocardial infarction

Acute myocardial infarction (AMI) is common in patients who have end-stage renal disease. However, the prudent interval after AMI until resuming hemodialysis is unknown. Also incidence and severity of intradialytic morbid events during the initial dialysis treatment after AMI have not been determined. We conducted a retrospective analysis of the course of hemodialyses performed immediately after AMI in 13 maintenance hemodialysis patients (group 1) hospitalized with AMI over the 5-year period 1988-1992. For comparison, the incidence of intradialytic morbid events (hypotension--systolic blood pressure < 90 or diastolic blood pressure < 60 mm Hg or a fall in systolic or diastolic blood pressure of > 30 mm Hg--with and without symptoms, arrhythmias, and unplanned termination of hemodialysis was extracted from the charts of 9 maintenance hemodialysis patients (group 2) admitted during the same period with angina but no AMI, and in 13 stable ambulatory hemodialysis patients (group 3) dialyzed during the same period who had no evidence of heart disease. Patients in groups 1 and 2 were sorted by time interval from onset of chest pain to initiation of hemodialysis (< 12, 12-24, and > 24 h). In group 1, we examined the relationship of anatomic location of AMI, number of antihypertensive medications, predialysis left ventricular systolic ejection fraction, and various other clinical and laboratory parameters to the incidence intradialytic morbid events. The mean (+/- SD) age of the study subjects was 67 +/- 7.5 years in group 1, 57 +/- 3.7 in group 2, and 60 +/- 11 years in group 3 (p = 0.6). Arrhythmias and early termination of dialysis did not occur in any patient. Intradialytic hypotension (IDH) was recorded in 5 (38%) of 13 patients in group 1, in 3 (33%) of 9 in group 2, and in 2 (15%) of 13 patients in group 3 (p = 0.47). 4 (80%) of 5 patients in group 1 had multiple episodes of IDH. There were 0.92 +/- 1.4 episodes of IDH per patient in group 1 as compared with a rate of 0.44 +/- 0.68 per patient in group 2, and of 0.15 +/- 0.36 per patient in group 3 (p = 0.2). IDH responded to 0.9% normal saline replacement in all cases. Group 1 patients who had IDH (n = 5) were older (68 +/- 3 vs. 58 +/- 7 years, p = 0.01), had a lower diastolic blood pressure at the start of hemodialysis (59 +/- 13 vs. 83 +/- 13 mm Hg; p = 0.01), had a lower post-AMI left ventricular systolic ejection fraction (42 +/- 19 vs. 62 +/- 10%; p = 0.04), and also had a lower predialysis serum albumin level (3.6 +/- 0.4 vs. 4.1 +/- 0.4 g/dl; p = 0.09) than those who did not have IDH (n = 8). All 5 group 1 patients who had IDH (100%) had had prior AMI as compared with 2 (25%) of 8 of those who did not have IDH (p = 0.02). AMI involved the inferior myocardial wall in more (4 of 5; 80%) of the group 1 patients who had IDH as compared with those who did not have IDH (2 of 8; 25%; odds ratio = 9.5; p = 0.08; 95% confidence interval = 0.7-341.0). In group 1 patients, the time from onset of chest pain to hemodialysis did not affect the risk of IDH (p = 0.4). We conclude that a low diastolic blood pressure at onset of hemodialysis prior myocardial infarction, inferior myocardial wall involvement, advanced age, and a low predialysis serum albumin level are risk factors for the development of hypotension during the first hemodialysis session after AMI.