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This study addresses mechanisms of the clinical, encephalopathic uremic illness and its suppression by dialysis. Renoprival rats were treated with peritoneal dialysis (8 exchanges per day, 30 min dwell), or untreated (attrition group), and their EEG's were automatically sampled overnight and subjected to power spectrum analysis as an index of encephalopathy. As in man the background rhythm of the quantified EEG (Q.EEG) in the attrition group slowed with time as extracellular fluid composition became increasingly abnormal; these changes were normalized by therapeutic dialysis (TD) using standard, commercial dialysate. However, Q.EEG slowing was only partially normalized by solute-specific dialysis using "mock uremic dialysate" (M-UD), prepared from laboratory chemicals to equal plasma concentrations in preterminal uremic rats of urea, creatinine, potassium, phosphorus, calcium, magnesium, bicarbonate, sodium, and chloride. When only phosphate was added to TD, the Q.EEG slowed to the same level achieved after M-UD. We conclude that uremic encephalopathy in this model is produced by an unknown neurotoxin and augmented by one or more of the M-UD solutes, phosphate being a likely candidate. To localize the encephalopathic effect, regional brain glucose uptake was estimated in 20 discrete brain areas. Significance of reduced uptake in three areas is discussed.

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.

It has been recognized for over 30 years that increased renal dysfunction results in increased slow wave activity in the EEG generally prior to the clinical appearance of disabling, dialysis-responsive encephalopathic symptoms of clinical uremia. This paper describes computerized methods that have been used to quantify this slow wave activity and the results of studies that have employed such computerized techniques. Practical information is furnished to guide those who wish to use these methods in their own research and practice. A survey of the limitations and pitfalls inherent in the various techniques is given. A prospectus outlines possible future directions in the field.

Fifty-three samples in 26 patients were analyzed for aliphatic amines (DMA and TMA), and the levels correlated with 2 neurophysiological tests, choice reaction time (CRT), and electroencephalogram (EEG). A significant correlation was found between TMA and CRT and EEG (p less than 0.001 and 0.003, respectively) and between DMA and CRT (p less than 0.01). These amines reflect part of the spectrum of toxic compounds which accumulate in uremia. Dissociation of neurophysiological functions may be helpful in evaluating various classes of potentially toxic compounds found in renal failure, as exemplified by short-chain aliphatic amines.

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.