Frank A. Krumlovsky

Putative atherogenic factors in patients with chronic renal failure

HIS review analyzes several factors which may initiate and sustain atherosclerosis in patients with chronic renal failure. These factors are examined within the framework of the “injury” theory of atherogenesis, which postulates that repeated cycles of endothelial cell injury, platelet deposition, and smooth muscle cell proliferation lead to the formation of typical atherosclerotic plaques. Thus, in the patient with chronic renal failure, endothelial cell damage may be due to hypertension, immunologic injury, or cigarette smoking. Platelet adherence to the damaged vessel wall may be facilitated by the increased levels of the factor VIII/van Willebrand factor found in these patients. Platelets activated during hemodialysis can release growth factors which stimulate vascular smooth muscle cell proliferation. Discrete areas of proliferating smooth muscle cells may preferentially incorporate cholesterol, which then accumulates in the tissues because the transfer of tissue cholesterol to plasma is impaired as a result of reduced or abnormal plasma high density lipoprotein. Ultimately, intimal thickening may occlude the vessel lumen, producing end-organ damage. As the treatment of chronic renal failure enters upon another decade of continued progress and the life span of affected patients lengthens, atherosclerosis and its complications are emerging as significant problems in these patients. In 1974, Lindner et al’ reported a mortality rate of 56 percent in a group of 39 patients with chronic renal failure treated by maintenance hemodialysis. These patients had a mean age of 37 years and were initially free of vascular or other systemic disease. Careful follow-up over a 13-year period disclosed that 14 (16 percent) of the deaths were due to complications of atherosclerosis; coronary heart disease was confirmed by necropsy in most cases. The mortality rates for this group were five times those seen in age matched subjects with hypertension, and were similar to those noted in familial hypercholesterolemia.’ The data suggest that atherosclerosis develops often and progresses with great rapidity in these individuals. Studies of larger numbers of patients have confirmed the high rate of complications due to cardiovascular disease.3*4 There is disagreement, however, as to whether this “accelerated atherosclerosis” is due to dialysis per se or is explainable by the high prevalence of major risk factors in these patients. 5-g Nicholls et al” presented evidence that the disease is already established in these patients when they come to dialysis. They observed that the morbidity and mortality due to atherosclerosis was most prominent in newly recognized patients with chronic renal failure, and that the incidence of new atheromatous disease did not increase during dialysis. Nevertheless, 9 of their 32 patients who died and were autopsied had severe occlusive arterial disease, and the average age of these patients was only 47 years. In another series,’ the de novo incidence of ischemic heart disease in 382 patients on chronic hemodialysis was 10.2%. In this review, we will examine several factors

Hemoperfusion for methotrexate removal.

Removal of methotrexate by Amberlite XAD‐4 hemoperfusion was determined in a patient with metastatic breast carcinoma. During 4 hr of hemoperfusion the plasma concentration of methotrexate fell from 5.5 × 10−7 M to 3.1 × 10−7 M. After hemoperfusion methotrexate concentration increased as a consequence of multicompartmental pharmacokinetics to 5.5 × 10−7 M and then slowly declined. Plasma methotrexate clearance decreased from 79 mllmin 30 min into hemoperfusion to 28 mllmin at the conclusion. In vitro clearance of methotrexate by 17 artificial kidneys. Amberlite XAD‐4. and uncoated charcoal was determined. Uncoated charcoal had the greatest clearance of methotrexate of all the devices tested. We conclude that: (1) Amberlite XAD‐4 transiently reduces plasma methotrexate concentration; (2) in vitro. charcoal hemoperfusion is more effective than XAD‐4 in removing methotrexate; (3) as a consequence of the multicompartmental pharmacokinetics of methotrexate a postperfusion rebound in plasma methotrexate concentration is to be expected.

Hemodialysis for severe procainamide toxicity: clinical and pharmacokinetic observations.

A 67‐yr‐old woman who ingested approximately 7 gm procainamide developed severe hypotension, renal insufficiency, and life‐threatening cardiac toxicity, Hemodialysis doubled the rate of procainamide elimination and increased fourfold the clearance of NA PA , the N‐acetylated metabolite of procainamide. Observations of procainamide and N‐acetylprocainamide (NAPA) plasma levels during the patients recovery suggest that lethargy and profound hypotension can be expected when these levels total 60 µg/ml and that severe cardiac toxicity should be anticipated with levels totaling 42 µg/ml or more. Hemodialysis also permitted investigation of the effects of hypotension on the pharmacokinetics of these compounds. The apparent volume of procainamide distribution was reduced from a normal value of 2 L/kg to 0.76 L/kg, and that of NAPA from 1.4 L/kg to 0.63 L/kg. The elimination t½ of procainamide was prolongedfrom the normal of 3 hr to 10.5 hr, and that of NAPA from 6 to 35.9 hr. Procainamide absorption was also slowed in this clinical setting, causing procainamide plasma levels to continue rising for some time after toxicity was first recognized.

Renal disease associated with toxic epidermal necrolysis (Lyell's disease)

Abstract A woman with toxic epidermal necrolysis and severe renal involvement is described. Serial renal biopsies were compatible with membranoproliferative glomerulonephritis. The pathophysiology and renal manifestations of toxic epidermal necrolysis are reviewed, and several previously unreported cases of toxic epidermal necrolysis with renal involvement are discussed. In several cases, changes were consistent with membranous or membranoproliferative glomerulonephritis, lending support to the concept of toxic epidermal necrolysis as an immunologic disease.

Low-dose prazosin in patients with muscle cramps during hemodialysis

Sympathetic nervous system response to volume stress is more marked in patients with frequent hemodialysis‐associated skeletal muscle cramps than in most patients who cramp infrequently. Accordingly, we conducted a double‐blind, randomized, and balanced trial in which five patients with frequent hemodialysis‐associated cramps were given either placebo or a prazosin dose (ranging from 0.25 to 1.0 mg) at the start of 16 dialysis sessions. These low doses of prazosin appeared to reduce cramp frequency in four of the five patients, and patient‐stratified multiple logistic regression analysis indicated an aggregate 58% reduction in cramp frequency (p = 0.030). On the other hand, prazosin therapy was associated with an increased incidence of hypotension that required therapeutic intervention both during (p = 0.033) and after (p = 0.010) hemodialysis. Our findings support the hypothesis that sympathetic activation plays a pathogenetic role in hemodialysis‐associated skeletal muscle cramps and suggest that pharmacologic attenuation of this response may be of therapeutic benefit.

Dialysis in Treatment of Neomycin Overdosage

Abstract A 39-year-old woman developed severe nephrotoxicity secondary to neomycin overdosage. A moderately high dialysance of neomycin was demonstrated. Hemodialysis is an effective method of ther...

Electrophysiological studies on uremic patients-comparison of peritoneal dialysis and hemodialysis.

Introduction Electrophysiological studies on uremic patients, whose symptoms typically reflect brain dysfunction, have shown abnormalities in the EEG (1-7), visual evoked responses (810) and photic driving responses(11). Most of these studies have emphasized changes of only one of these physiological indices. By contrast, in the present study all three types of measures were investigated in each patient. Furthermore, since controversy still exists regarding the relative benefits of different types of dialysis, our patients were paired according to the two kinds of dialytic therapy used, i.e., peritoneal dialysis and hemodialysis. Therefore, the goal of this project was to compare the quantified and computerized (1) EEG, (2) visual evoked and (3) photic driving responses of these paired patients, especially to investigate the possibility that different neurophysiological effects may be produced by these two kinds of dialysis.

Maintenance dialysis for diabetic nephropathy with uremia.

Abstract Fourteen patients, aged 28–61 yr, with diabetic nephropathy and uremia were observed on maintenance dialysis for a total of 156.5 dialysis patient months (range: 1.5–30 months per patient). Clinical course on dialysis was eventful in most cases, though nitrogen retention and acidosis were readily controlled. Bouts of circulatory congestion and severe fluid retention were frequent in nine patients, six of whom died of acute myocardial infarction or intractable heart failure. Septic complications and hepatitis caused or contributed to the demise of four patients, and thromboembolic complications to that of one patient. Rehabilitation on dialysis was limited in nine cases, and five remained disabled. Retinopathy was not improved. Emotional problems were common in nine patients, five of whom required psychiatric care. Ten patients died between 1.5 and 21 months after the start of dialysis, and only one survived over 30 months. Three patients underwent renal transplantation 6 to 18 months after inception of dialysis. They all died 10 days to 3 months after surgery of overwhelming septic complications. Survival rate on maintenance dialysis for the whole group was 54.8 per cent at 1 yr, and 16.4 per cent at 2 yr.

Effect of autonomic hyperreflexia on plasma benin

Four patients with paroxysmal hypertension related to spinal cord injury (autonomic hyperreflexia) were studied to determine if the plasma renin became elevated in relation to a sympathetic stimulus. Using bladder distention to produce the autonomic hyperreflexia, renin determinations were made during and after the hypertensive episode. None of the patients demonstrated elevation of the plasma renin after this event.

Renin activity in acute renal failure.

our respondents. Secondly, we based our 50-item questionnaire on verbatim attitude and opinion statements derived from interviews with members of the various hospital staff groups under study. While we would agree that it is important to stress the positiveness of attitudes to psychiatry, we consider it equally if not more important to define the areas of prejudice that still exist and which at least up to date defy change. For such prejudice might seriously hamper the further integration of psychiatry in the general hospital and yet go undetected. The fuller analysis of our findings should help to clarify what attitudes still require change and hence lead to a more rational teaching programme for all general hospital staff. Finally, we would hope our results will encourage research into methods of teaching by which such prejudices can be overcome.-We are, etc.,