Outcome-related reimbursement will not improve patient care.
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Humans↗
Biomedical subjects
T I Steinman
Publications and source records attributed to T I Steinman.
Transplantation--who delivers the care in what setting?
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Delivery of Health Care↗
Dialysis of plasma soluble lipofuscins in patients with end-stage renal failure.
Fluorescence spectrophotometry demonstrates that the levels of plasma soluble lipofuscins (SL) in patients with end-stage renal failure, undergoing continuous ambulatory peritoneal dialysis (CAPD) or haemodialysis (HD), remain significantly higher than in normal subjects. Plasma samples from these patients show the presence of SL generated from 3-hydroxy-anthranilic acid [excitation (ex) at approximately 324 nm and emission (em) at approximately 413 nm] and of other SL generated from dopa, catecholamines, 3-hydroxykynurenine and from structurally related precursors (ex at approximately 345 nm, em at approximately 445 nm). These precursors form the melanin components, which are approximately 3 wt % of SL. The fluorescence of SL appears to originate mainly from the melanin components. Peaks and shoulders at these wavelengths are found in the spectra of all dialysates. Based on intensity measurements at 413 nm and 445 nm, the weekly clearance rates with HD are in general greater than those with CAPD. The saponified cellulose ester membrane used in HD passes only lower-molecular-weight SL and/or components of SL. After HD, the greatest reductions in plasma intensities are found at approximately 324 nm and approximately 413 nm. The clearance rates (l/week) are always greater at 413 nm [means HD: 18.47 +/- 4.44 standard deviation (SD), n = 8; CAPD: 12.50 +/- 2.47, n = 4] than at 445 nm (HD: 10.94 +/- 3.86; CAPD: 7.95 +/- 1.75) both with HD and CAPD. In CAPD, the membrane also permits the passage of large amounts of albumin and other high-molecular-weight substances.(ABSTRACT TRUNCATED AT 250 WORDS)
Adult↗
Health care reform: a new approach.
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Delivery of Health Care↗
Magnetic resonance imaging: a reliable test for the evaluation of proximal atherosclerotic renal arterial stenosis.
Symptomatic renal artery stenosis is a significant and treatable clinical problem. A reliable and accurate noninvasive method of screening for renal artery stenosis has not yet been found. We used magnetic resonance imaging to study 37 patients who had undergone recent renal angiography. Fourteen patients had normal renal arteries by angiography. In 23 patients either unilateral or bilateral stenosis or occlusion was present. The disease process in all patients appeared to be atherosclerosis. The average age of the 37 patients was 68 years. The magnetic resonance scans and angiograms were read independently by two different radiologists, each of whom was blinded to the clinical history and the results of the other study. Renal arterial stenoses found on angiogram and magnetic resonance scans were graded as absent (0% to 24%), mild (25% to 49%), moderate (50% to 74%), or severe (75% to 99%). The magnetic resonance imaging results concurred with the angiographic findings in 70 of 77 arteries (91%). Magnetic resonance imaging predicted the presence of a greater than 50% stenosis of the renal artery with a sensitivity of 100% and a specificity of 94%. Magnetic resonance imaging may prove to be the best noninvasive screening test for proximal atherosclerotic renal arterial stenosis.
Adult↗
Utility of radioisotopic filtration markers in chronic renal insufficiency: simultaneous comparison of 125I-iothalamate, 169Yb-DTPA, 99mTc-DTPA, and inulin. The Modification of Diet in Renal Disease Study.
Assessment of glomerular filtration rate (GFR) with inulin is cumbersome and time-consuming. Radioisotopic filtration markers have been studied as filtration markers because they can be used without continuous intravenous (IV) infusion and because analysis is relatively simple. Although the clearances of 99mTc-diethylenetriamine-pentaacetic acid (DTPA), 169Yb-DTPA, and 125I-iothalamate have each been compared with inulin, rarely has the comparability of radioisotopic filtration markers been directly evaluated in the same subject. To this purpose, we determined the renal clearance of inulin administered by continuous infusion and the above radioisotopic filtration markers administered as bolus injections, simultaneously in four subjects with normal renal function and 16 subjects with renal insufficiency. Subjects were studied twice in order to assess within-study and between-study variability. Unlabeled iothalamate was infused during the second half of each study to assess its effect on clearances. We found that renal clearance of 125I-iothalamate and 169Yb-DTPA significantly exceeded clearance of inulin in patients with renal insufficiency, but only by several mL.min-1.1.73m-2. Overestimation of inulin clearance by radioisotopic filtration markers was found in all normal subjects. No differences between markers were found in the coefficient of variation of clearances either between periods on a given study day (within-day variability) or between the two study days (between-day variability). The true test variability between days did not correlate with within-test variability. We conclude that the renal clearance of 99mTc-DTPA, 169Yb-DTPA, or 125I-iothalamate administered as a single IV or subcutaneous injection can be used to accurately measure GFR in subjects with renal insufficiency; use of the single injection technique may overestimate GFR in normal subjects.
Creatinine↗
Adaptation to low-protein diets in renal failure: leucine turnover and nitrogen balance.
In normal subjects, short to intermediate responses to dietary protein restriction include decreased amino acid oxidation and protein degradation plus increased utilization of amino acids for protein synthesis; these responses are activated to improve amino acid utilization and nitrogen balance. To assess whether chronic renal failure (CRF) impairs the adaptive responses to a low-protein diet, we measured nitrogen balance and the kinetics of infused L-(15N,1-13C)leucine during fasting and feeding. In six adult CRF and four control (C) subjects, 0.6 (LP) and 1.0 (HP) g protein kg-1 day-1 diets were compared. LP reduced feeding stimulated oxidation of leucine by 26% in CRF and 33% in C (P = NS). During fasting, oxidation was unaffected by diet or CRF. For both groups, feeding suppressed protein degradation to the same extent; leucine incorporation into protein did not change. Nitrogen balance during the two diets was the same with C and CRF, as was protein balance estimated from results of measured leucine kinetics. Thus, patients with CRF can activate appropriate adaptive responses to LP inasmuch as reduced amino acid oxidation occurring with feeding and estimates of protein balance did not differ from control.
Adaptation, Physiological↗
Hemodialysis and red cell cation transport in uremia: role of membrane free fatty acids.
Active and facilitated cation transport in erythrocytes of uremic patients may be improved acutely by hemodialysis, although the mechanisms remain unknown. As nonesterified fatty acids (NEFA) can affect Na+ pump activity in vitro, changes in plasma and red cell membrane NEFA content following a single hemodialysis procedure were examined and compared with acute changes in erythrocyte cation flux rates in 34 hemodialysis patients. In nonsodium-loaded cells, small changes in Na+ pump flux with dialysis did correlate with changes in intracellular Na+ content (r = 0.59; N = 17; P less than 0.01). On average, neither maximal Na+ pump activity nor Na+/Li+ counter-transport flux improved with dialysis, but Na+/K+/Cl- cotransport rates rose 25% post-dialysis (P less than 0.02). Plasma NEFA levels rose 87% following hemodialysis but erythrocyte membrane NEFA content declined by 23% (P less than 0.001). Importantly, 24 of the 34 subjects studied had a decrease in erythrocyte membrane NEFA content of greater than 10%, and in these patients, the fall in membrane NEFA correlated with an increase in ouabain-sensitive Na+ efflux (r = 0.564; P less than 0.01). The effects of hemodialysis on both erythrocyte NEFA content and Na+ pump flux could be reproduced by incubating pre-dialysis cells in fatty acid-free albumin. We conclude that acute changes in membrane NEFA may modulate active cation transport in uremic erythrocytes.
Aged↗
Nutritional status of patients with different levels of chronic renal insufficiency. Modification of Diet in Renal Disease (MDRD) Study Group.
This study evaluated the nutritional status of 95 patients with chronic renal insufficiency who participated in the feasibility phase of the NIH funded Modification of Diet in Renal Disease (MDRD) Study. All patients were seen monthly by a physician and dietitian. After a baseline period, the patients were randomly assigned either to a mildly protein-restricted control diet or to one of three low protein, low phosphorus diets. Patients with clear evidence for protein-calorie malnutrition were excluded from the study. Patients were followed for an average of 12.4 months (range, 0 to 22 months). The glomerular filtration rate (GFR) at the commencement of the experimental diets ranged from 8 to 56 ml/min/1.73 m2. Assessment of the nutritional parameters indicated that none of the four diet treatment groups developed protein-calorie malnutrition. At the end of treatment with the experimental diets, most nutritional parameters were normal and few had worsened. Nonetheless, the following observations indicated that some patients had developed subtle evidence for protein-calorie malnutrition. There were positive correlations between the GFR and the serum transferrin and creatinine:height ratio. In men, arm muscle area and, at the onset of the experimental diets, the % standard body weight also correlated with the GFR. In women, GFR correlated with dietary energy intake. When patients were grouped according to their GFR level, those with the lowest GFR also tended to have lower energy intakes, serum transferrin levels and creatinine:height ratios. Patients with a GFR of 24 ml/min/1.73 m2 or lower tended to lose body mass during the study. In all groups of patients, the estimated actual energy intake was significantly lower than the prescribed intake. On the other hand, in the patients assigned to one of the three low protein, low phosphorus diets, nitrogen intake was above the prescribed level. The low energy intake of those patients with the lower GFR levels may contribute to their propensity to become malnourished.
Body Weight↗
The long-term outcome of hepatitis B infection in hemodialysis patients.
Little information on the long-term outcome of hepatitis B virus (HBV) infection in hemodialysis patients is available. We studied 49 hemodialysis patients, seen at three centers between 1969 and 1985, who developed HBV infection. Patients were studied retrospectively and followed for up to 10 years (mean 52 +/- 5 months). Only 20% (n = 10) of patients converted to hepatitis B surface antigen (HBsAg) negative, the majority of whom did so within 6 months of becoming HBsAg positive. Twenty-nine percent (n = 14) of patients developed chronic elevation of liver enzymes which remitted in one patient. Only one patient died from liver disease. We conclude that HBV infection in hemodialysis patients more often results in persistent antigenemia and chronic elevation of liver enzymes than is the case in patients without kidney disease. However, the risk of death from liver disease is low.
Alanine Transaminase↗
Elevated levels of plasma lipofuscins in patients with chronic renal failure.
The fluorescence excitation and emission spectra observed in plasma from patients with chronic renal failure were reproduced by the generation of soluble lipofuscins in normal plasma samples by incubation with mixtures of L-dopa, dopamine, L-norepinephrine, L-epinephrine, 3-hydroxy-DL-kynurenine and 3-hydroxy-anthranilic acid for 24 h at 37 degrees C. Relative fluorescence intensity measurements consistently showed elevated plasma levels of the soluble lipofuscins in chronic renal failure: the means (n = 27) were 73.9 +/- 33.4 (SD) and 71.1 +/- 14.8 at emissions 413 nm and 445 nm respectively, in contrast to those of normal plasma samples (n = 11), 18.2 +/- 5.3 and 23.1 +/- 5.6. The maximum or shoulder at approximately 413 nm represents soluble lipofuscin that can be generated from 3-hydroxyanthranilic acid and the maximum or shoulder at approximately 445 nm represents soluble lipofuscins derived from the precursors listed above and probably from other related precursors. Gravimetric measurements also showed elevated levels of melanins in the plasma samples of patients with chronic renal failure: 2.72 +/- 0.38 mg/ml (n = 16), as compared to normal values: 1.70 +/- 0.10 mg/ml (n = 6). In individual patients haemodialysis reduced the fluorescence intensities to a range of 65-99% and the melanin levels to a range of 86-99% of the pre-dialysis values.
Adolescent↗
Increased levels of serum lipofuscin derived from 3-hydroxyanthranilic acid in patients with chronic renal failure.
Normal Caucasian male sera incubated with 3-hydroxyanthranilic acid to generate soluble lipofuscin were studied together with unincubated serum samples from uremic Caucasian males, using the methods of Schwertner & Hawthorne in order to identify a fluorescent substance found by them to increase in uremic sera. Ethanol extracts of uremic sera, of normal sera containing this soluble lipofuscin and of same normal serum blanks were prepared. Reversed-phase thin-layer chromatograms of the extracts developed with methanol-water (40:60, v./v.), displayed one significant spot per sample, with RF values of 0.89 +/- 0.02. The spots showed blue fluorescence in 366 nm ultraviolet light. Aqueous solutions of the spots from uremic sera and from 3-hydroxyanthranilic acid-incubated normal sera produced closely similar fluorescence excitation shoulders and maxima at approximately 321 nm and emission maxima at 402 +/- 3 nm with significantly higher intensities than the normal. Thin-layer chromatograms of the ethanol extracts were also prepared on silica gel G developed with ethanol. The uremic, the 3-hydroxyanthranilic acid-incubated normal sera and the normal blank sera showed identical patterns in 366 nm light. The findings demonstrate that serum lipofuscin derived from 3-hydroxyanthranilic acid either in vivo or in vitro yields the fluorescent substance or component separated by ethanol extraction and reversed-phase thin-layer chromatography and that this serum lipofuscin present at low concentration in normal sera increases in uremic sera.
3-Hydroxyanthranilic Acid↗
Treatment of progressive chronic renal failure. Implications for changing the composition of amino acid and ketoacid supplements.
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Amino Acids, Essential↗
Endogenous digitalis-like factors in hypertension and chronic renal insufficiency.
Endogenous digitalis-like factors have been implicated in the adaptations that accompany renal insufficiency and in the pathogenesis of hypertension. We recently described several fractions of normal human plasma that inhibit NaK-ATPase and exhibit apparent digoxin-like immunoreactivity. To determine if hypertension and/or renal insufficiency affect plasma levels of these factors, we examined four patient groups: normotensive controls; hypertensive subjects with normal renal function; hypertensives with moderate renal insufficiency; and chronic dialysis patients. Plasma levels of digoxin-like immunoreactivity and NaK-ATPase inhibitory activity were significantly increased in hypertensive patients with mild renal failure (7.6 +/- 1.1 ouabain equivalents, mean +/- SEM, N = 21 vs 4.1 +/- 1.1 in normotensive controls, N = 20, P less than 0.05). NaK-ATPase inhibitory activity tended to be higher in patients with primary hypertension and normal renal function (5.5 +/- 0.7 ouabain equivalents, P less than 0.07); in dialysis patients, it was not different from controls. There was no correlation between NaK-ATPase inhibitory activity and blood pressure in any group. There was a significant rise in plasma NaK-ATPase inhibitory activity during dialysis (+ 1.8 +/- 0.7 ouabain equivalents, N = 22, P less than 0.03). As we have found that NaK-ATPase inhibitory activity in the plasma of normal humans can be separated into three distinct fractions, EI1, EI2, and EI3, we analyzed the plasma of 10 dialysis patients further. The increase in NaK-ATPase inhibitory activity could be attributed to fractions EI1 and EI3. These results suggest that plasma NaK-ATPase inhibitors increase with chronic renal insufficiency, but not hypertension alone. Although hemodialysis may acutely raise plasma levels, long-term dialysis returns them to the normal range.
Adult↗
Ultraviolet phototherapy of uremic pruritus. Long-term results and possible mechanism of action.
The beneficial effect of sunburn-spectrum ultraviolet (UVB) phototherapy on uremic pruritus was studied. Seven patients were treated twice weekly for 4 weeks with UVB to one half of the body and placebo phototherapy to the other half. All patients noted generalized improvement without localization of benefit to the UVB side, suggesting a systemic effect of UVB. A comparison of three schedules varying from one to three treatments weekly showed that the percentage of patients responding was not influenced by frequency of UVB exposure, although patients treated more intensively improved faster. In three patients, improvement was delayed until 2 weeks after completion of a course of six treatments over 2 weeks, indicating a delayed onset of benefit in at least some patients. Overall 32 of 38 patients improved after a course of six or eight UVB exposures. Pruritus has recurred in 15 patients after a mean remission of 3 months. Sixteen patients are known to remain in remission for a mean of at least 10.6 months after the first or second course of treatment. The present evidence indicates a systemic mechanism of action for the long-lasting relief of uremic pruritus afforded by UVB phototherapy.
Adult↗
Gastric mucosal permeability and gastric acid secretion before and after hemodialysis in patients with chronic renal failure.
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Adult↗
Relief of uremic pruritus with ultraviolet phototherapy.
We studied the effect of ultraviolet-light phototherapy on severe persistent pruritus in 18 adult patients on hemodialysis. Patients were randomly assigned to one of two light sources. The experimental group received conventional sunburn-spectrum light in gradually increasing doses. The control group received time-matched exposures to long-wave ultraviolet light. All patients received eight exposures to the entire skin surface over a four-week treatment period. Nine of 10 patients in the sunburn-spectrum group reported marked decrease in pruritus as opposed to two of eight in the placebo group (P less than 0.01). of those responding to sunburn-spectrum light, improvement usually occurred two to three weeks into treatment. Mild sunburn, noted by some patients in this group, was the only side effect. The response to phototherapy was unaffected by the presence of secondary hyperparathyroidism. Ultraviolet phototherapy is a safe, convenient, inexpensive and effective treatment for uremic pruritus.
Adult↗