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Provides information on a study that described the proper management of sodium and water removal by hypertonic peritoneal dialysis. Methodology of the study; Results and discussion on the 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.

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.

The Modification of Diet in Renal Disease (MDRD) Study examined the effects of dietary protein restriction and strict blood pressure control on the decline in glomerular filtration rate (GFR) in 840 patients with diverse renal diseases. We describe a systematic analysis to determine baseline factors that predict the decline in GFR, or which alter the efficacy of the diet or blood pressure interventions. Univariate analysis identified 18 of 41 investigated baseline factors as significant (P < 0.05) predictors of GFR decline. In multivariate analysis, six factors--greater urine protein excretion, diagnosis of polycystic kidney disease (PKD), lower serum transferrin, higher mean arterial pressure, black race, and lower serum HDL cholesterol--independently predicted a faster decline in GFR. Together with the study interventions, these six factors accounted for 34.5% and 33.9% of the variance between patients in GFR slopes in Studies A and B, respectively, with proteinuria and PKD playing the predominant role. The mean rate of GFR decline was not significantly related to baseline GFR, suggesting an approximately linear mean GFR decline as renal disease progresses. The 41 baseline predictors were also assessed for their interactions with the diet and blood pressure interventions. A greater benefit of the low blood pressure intervention was found in patients with higher baseline urine protein. None of the 41 baseline factors were shown to predict a greater or lesser effect of dietary protein restriction.

Patients with advanced renal disease randomized to the very low-protein diet group in the Modification of Diet in Renal Disease (MDRD) Study had a marginally (P = 0.066) slower mean glomerular filtration rate (GFR) decline compared with patients randomized to the low-protein diet group. The objective of these secondary analyses was to determine the relationship between achieved, in addition to prescribed, dietary protein intake and the progression of advanced renal disease. A randomized controlled trial was conducted in patients with chronic renal diseases of diverse etiology. The average follow-up was 2.2 years. Fifteen university hospital outpatient nephrology practices participated in the study, which comprised 255 patients aged 18 to 70 years with a baseline GFR 13 to 24 mL/min/1.73 m2 who participated in MDRD Study B. Patients with diabetes requiring insulin were excluded. The patients were given a low-protein (0.58 g/kg/d) or very low-protein (0.28 g/kg/d) diet supplemented with keto acids-amino acids (0.28 g/kg/d). Outcomes were measured by comparisons of protein intake from food or from food and supplement between randomized groups, and correlations of protein intake with rate of decline in GFR and time to renal failure or death. Comparison of the randomized groups showed that total protein intake from food and supplement was lower (P < 0.001) among patients randomized to the very low-protein diet (0.66 g/kg/d) compared with protein intake from food only in patients randomized to the low-protein diet (0.73 g/kg/d). In correlational analyses, we combined patients assigned to both diets and controlled for baseline factors associated with a faster progression of renal disease. A 0.2 g/kg/d lower achieved total protein intake (including food and supplement) was associated with a 1.15 mL/min/yr slower mean decline in GFR (P = 0.011), equivalent to 29% of the mean GFR decline. After adjusting for achieved total protein intake, no independent effect of prescription of the keto acid-amino acid supplement to slow the GFR decline could be detected. If the GFR decline is extrapolated until renal failure, a patient with a 29% reduction in the rate of GFR decline would experience a 41% prolongation in the time to renal failure. Additional analyses confirmed a longer time to renal failure in patients with lower total protein intake. In conclusion, these secondary analyses of the MDRD Study suggest that a lower protein intake, but not the keto acid-amino acid supplement, retards the progression of advanced renal disease. In patients with GFR less than 25 mL/min/1.73 m2, we suggest a prescribed dietary protein intake of 0.6 g/kg/d.

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.

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.

Photically driven EEGs were recorded from patients with renal disease using photic stimulation at integer rates between 3 and 12 flashes/sec. Changes in the structure of the power spectrum of the potentials produced by this stimulus paradigm are described as a function of a patient's clinical state. The basic overall findings are that (1) harmonic activity is attenuated while activity below the fundamental driving frequency is increased as a patient's clinical condition deteriorates, and (2) that these effects are substantially reversed and controlled by means of dialysis and renal transplantation.

Transient visually evoked cortical potentials (VECPs) were recorded from patients with renal disease. Changes in VECP latencies are described for undialyzed patients, patients receiving dialysis therapy, and patients who received kidney transplants. Characteristics of VECP latencies in these patient groups as well as examples of changes in latency values with respect to time for two individual patients are examined. The basic overall finding is that the VECP latencies increase as a patient's clinical condition deteriorates and normalize as the condition improves.

EEGs wre recorded from renal patients to determine if there are quantifiable characteristic changes in the EEG was quantified by calculating the percentage of spectral power in the bandwidth 3-7 c/sec referrred to a frequency range of 3-13 c/sec and by computing the mean frequency of the dominant rhythm in the EEG. Blood urea nitrogen and creatinine concentrations, as well as a self-assessment of the patient's clinical condition, were recorded. The general finding of this research is that EEG slowing, as evaluated by power spectral techniques, is correlated with uremia-associated variables. 1. In a non-dialyzed patient population with renal failure, slowing in the EEG was found to be directly corelated with increased creatinine concentrations. 2. Quantitative measures of slow wave activity computed using power spectral techniques were found to be highly corelated with an estimate of slowing made by an electroencephalographer. 3. Compared with undialyzed azotemic patients, malignant hypertensive patients with comparable serum creatinine concentrations typically displayed increased slow wave activity, while slowing was generally reduced in the dialyzed patient population. 4. A series of EEGs recorded from one patient during the first three dialyses of her life revealed that slow wave activity decreased during each successive dialysis. In another patient, all quantified EEG values recorded prior to renal transplantation significantly improved after transplantation...

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.

The disabling, dialysis-responsive symptoms of clinical uremia primarily represent impaired functions of the nervous system. Accordingly, these studies used several quantitative electrophysiologic and cognition-dependent probes of nervous system function: peripheral nerve-conduction velocity, response latency and amplitude; electroencephalographic (EEG) power-spectrum analysis; visual evoked response latency; EEG responses to photic driving; and measures of integrated behavioral performance that stressed sustained and selective attention, reaction time, speed of decision-making, short-term memory, and mental manipulation of symbols. Probes of quanitified central nervous system function consistently revealed impairments that varied directly with the degree of renal failure, that improved following onset of maintenance dialysis, and that improved still further after successful renal transplantation. In contrast, measures of peripheral nerve function were generally unchanged. Neurobehavioral measures that are relevant to uremic symptomatology provide quantitative estimates of the clinically significant, whole-organism biologic effects of renal failure and its several treatments. Applications of such measures in studies of symptomatic states other than uremia are indicated also.

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.