Effects of dietary lecithin on hormonal and neurobehavioral profiles in normal subjects.

Four normal subjects received lecithin supplements sufficient to elevate serum choline levels 3-fold. Despite persistent hypercholinemia over 48 hours of close observation, no increase was observed in serum ACTH, cortisol, and insulin concentrations, or in free urinary catecholamine excretion. Screening of a large group of other pituitary and gonadal hormones also failed to reveal any influence of lecithin supplements. EEG patterns and results of psychometric tests were also unaltered.

Electroencephalographic and other neurophysiological abnormalities in uremia.

1) Neurophysiological abnormalities in patients with renal failure are being investigated because a) it is the nervous system which preeminently produces the phenomena of clinical uremia that dialysis affects and b) objective quantitative measures of such functions are generally lacking and are needed to provide objective evidence for adequacy of dialysis and other treatment measures in uremic patients. Accordingly, the attempt is warranted to measure in objective terms what renal failure, alternatively maintenance dialysis, does to the patient's nervous system in the comprehensive terms and the several modalities by which the nervous system serves the patient. 2) It is clear from the foregoing presentation that electroencephalographic phenomena including some aspects of the spontaneous EEG and certain event-related potentials can be readily reduced to quantitative terms. Some of these are abnormal in the presence of renal failure, are improved by dialysis treatment, may vary with the frequency of dialysis treatment and are often normalized by renal transplantation. Apparently similar EEG changes may be induced by other intercurrent influences occasionally operating in patients with renal failure. These can usually be readily detected but appear at this time to limit the potential usefulness of the EEG in those instances. However, especially using successive determinations in individual patients, the quantitative measure of slow-wave-associated EEG power is a reasonable candidate-measure of adequacy of dialysis. Other measures should be explored. 3) Quantitative measures of EEG phenomena appear to be superior in speed and objectivity to conventional, descriptive reporting of electroencephalograms, especially for the repetitive comparisons which are necessary for clinical patient monitoring. 4) The data system so far employed to transform EEG phenomena into clinically useful data (Fig. 1) will be greatly simplified as soon as the most informative, sensitive and specific measures are selected from among those being explored. Dedicated micro-processing equipment, for example, can then be expected to replace the much more expensive, multipurpose computer system which is necessary for the initial investigation.

Neurotoxicity in uremia.

The dialysis patient is aware that his behavior evokes reciprocal and complicating responses from important people in his environment. These interactions are perceived and conducted by neurochemical mechanisms which may be impaired in the abnormal chemical environment imposed in renal failure. It is the behaviors we comprehend as indicators of disordered nervous mechanisms. Therefore, it is logical that neurophysiological and neurobehavioral phenomena should be measured quantitatively in order 1) to estimate objectively the patients' success in achieving the goal of maintenance dialysis treatment, 2) to assess the comparative adequacy of dialysis regimens and 3) to provide objective endpoint measures which are relevant to uremia for further investigations of the etiology and pathogenesis of these critically significant uremic manifestations. Our experimental results illustrate that: 1) measures of conduction velocity, distal latency and response amplitudes, as employed by us, were relatively insensitive in the patients and circumstances studied; 2) several neurophysiological measures, i.e., the spontaneous EEG, VER latency and, perhaps, photic stimulation, on the other hand, are highly correlated with the severity of renal failure; 3) behavioral measures of sustained attention and alertness (TMT), of short-term memory (ASTM) and of cognitive manipulation of symbols (AR) are also highly correlated with the severity of renal failure; 4) some measured abnormalities improve following dialysis, but not always to normal--three residual impairments may indicate dialysis in adequacy; 5) several of these measures can provide objective evidence for adequacy of dialysis and other clinical and treatment effects in patients with renal failure.

Urinary tract calculous disease after renal transplantation.

We report 3 cases of a series of 372 (0.8 per cent) renal transplant recipients in whom urinary tract calculi developed as a complication of the procedure. In each patient symptoms were minimal and not classic of calculous disease. We disagree with the contention that all such patients have either hypercalcemia, infection, or tubular acidosis, although thorough evaluation is indicated. We believe this entity should be considered in problematic renal transplantation patients. Conservative therapy is advocated when the situation permits.

Effect of a ketoacid-aminoacid-supplemented very low protein diet on the progression of advanced renal disease: a reanalysis of the MDRD feasibility study.

BACKGROUND: We reanalyzed the data of the Modification of Diet in Renal Disease (MDRD) feasibility study to ascertain the effects of ketoacid- and aminoacid-supplemented very low protein diets. METHODS: Sixty-six patients with advanced renal disease (Study B, baseline glomerular filtration rate (GFR) 7.5-24 ml/min/1.73 m2) were randomly assigned to a low protein diet (L, 0.575 g/kg/d), or a very low protein diet (0.28 g/kg/d) supplemented either with a ketoacid-aminoacid mixture (diet K) or with a mixture of essential aminoacids (diet J). Thirty patients with moderate renal disease (Study A, baseline GFR 25-80 ml/min/1.73 m2) were randomly assigned to a usual protein diet (M, 1.2 g/kg/d), diet L, or diet K. Mean follow-up was 14 months. RESULTS: In Study B, GFR decline differed among the three diets (p = 0.028). Pairwise comparisons showed that the mean +/- SE GFR decline in ml/min/mo in diet K [-0.250+/-0.072] was slower than in diet J [-0.533+/-0.074] (p = 0.008) despite similar achieved protein intakes. The mean GFR decline in diet L [-0.394+/-0.068] was intermediate between, and did not differ significantly from the rates of decline in the other two groups. In Study A, consistent with a hemodynamic effect, the mean GFR decline varied directly with the reduction in protein intake in diets M, L and K (p = 0.028) during the first four months of follow-up, but thereafter did not differ among the diet groups (p = 0.76). CONCLUSION: The study suggests that supplementation of a very low protein diet with the ketoacid-aminoacid mixture used in this feasibility study slowed the progression of advanced renal disease more than supplementation with an amino acid mixture.

Long-term hemodialysis for patients over 50.

Hemodialysis can hodl end-state renal failure at bay and enable patients to lead a relatively normal life-regardless of their age. In a 10 year retrospective study of 574 patients, the 154 patients over 50 had about the same survival rates as younger persons for the first three years of dialysis. After that, the older patients had higher mortality. Patients who dialyzed themselves at home-with a relative or friend to help-had much better results than those who were dialyzed at the center. This in part reflects the selection process, since patients with severe medical problems usually weren't allowed to try self-dialysis. Older patients did particularly well on home dialysis, which was attributed to their maturity and dependability. Older patients with cardiac instability may require carefully monitored dialysis at the center and frequent blood transfusions. In general, though, patients over 50 needed fewer transfusions and fewer days in the hospital than younger patients.

Acute renal failure during the Korean War.

Oliguric ARF occurred in 0.5% of battle casualties who reached the field medical care system and raised their mortality expectancy from less than 5% to nearly 90%, due primarily to fluid volume overload and/or myocardial potassium intoxication. For their effective treatment the Renal Insufficiency Center with laboratory and a Brigham-Kolff rotating drum dialyzer began operations in 1952, as depicted in a videotape prepared for this presentation from motion picture footage filmed in early 1953. Our Surgical Research Team's major findings relevant to ARF were: (1) Renal function was depressed in most battle casualties in proportion to the severity of their wounds and blood loss. (2) Among the more severely wounded some developed nonoliguric; others, oliguric ARF. (3) Oliguria lasted from 3 days to 3 weeks without a discernible peak frequency of beginning diuresis at 10 days. (4) During oliguria, posttraumatic catabolism greatly accelerated extracellular accumulations of nitrogen, potassium, phosphate, and hydrogen ion with rapid, concurrent clinical deterioration. (5) Dialysis "on indication" produced an oscillating clinical and chemical course. (6) ARF was then revealed as a wasting disease complicated by infections, poor wound healing until diuresis occurred, anemia and bleeding, and hypertension during dialyses and in early diuresis. (7) The overall mortality rate was reduced.

Kolff's credo: new ways of thinking!

Dr. Willem J. Kolff's imaginative venturesomeness in adopting "new ways of thinking" has served as an encouraging model for this author's research career. In appreciation of his leadership and beginning with the favorable results that attended the initial use of the Brigham-Kolff artificial kidney at a renal center in the Korean war, this presentation summarizes four experiences to illustrate how "new ways of thinking" produced new results and new research, namely, the concept and use of prophylactic daily hemodialysis; the use of a model of acute renal failure in rats to examine mechanisms of pathogenesis and means of prevention; the recognition of patients' uremic illness as an encephalopathy that can be quantified by appropriate measures; and the use of daily peritoneal dialysis and quantified EEGs in rats to explore relationships between dialysis-induced concentrations of potentially toxic solutes, quantified indices of symptomatic uremic encephalopathy, and concurrent, localized metabolic abnormalities in the brain. The results of these "new ways of thinking" suggest that we may ultimately come to understand the clinical uremic illness and its response to dialysis.