Artificial Orgatis 10(4):301-305, Raven Press, New York 0 1986 International Society for Artificial Organs

Nutrition in Renal Failure

Paul E. Teschan

Departments of Medicine, Urology, and Biomedical Engineering, Vanderbilt University School of Medicine, Nashville, Tennessee, U.S.A.

Contemporary concerns about nutrition in renal failure derive from the development of artificial organs, preeminently represented in dialyzers and dialysis. Use of artificial hearts, lungs, and related techniques of assisted circulation and ventilation often permits the survival of patients who also de- velop acute renal failure and require nutritional therapy in intensive care units. “Since the begin- ning” of these developments, Dr. George Schreiner has contributed as both observer and recorder as Editor of the Transactions-American Society for Artificial Internal Organs (ASAIO), and as a clini- cian-researcher has himself contributed to the evolution of dialysis techniques and instrumenta- tion. Thus, under George Schreiner’s leadership, the Transactions-ASAZO represents an authorita- tive chronicle of the developments that lend to the issues of “renal nutrition” their currently credible urgency.

The initial reports that presaged the general use of artificial kidneys described dialysis in patients with acute renal failure (1,2) using the rotating- drum dialyzer designed by Dr. Willem J. Kolff (3). Recommended management of these patients in 1947 and through the 1950s differed sharply from current practice in at least two ways: (a) Dialysis was usually applied often as a “last resort” to sick uremic patients when clinical symptoms (such as drowsiness, anorexia, nausea, and vomiting) and chemical imbalances (such as potassium intoxica- tion and metabolic acidosis) became severe and progressive despite “conservative” medical treat- ment; and (b) nutrition was limited to 100 g glu- cose/24 h i.v., i.e., the amount that produced max- imal suppression of protein catabolism per gram of

Received April 1986. Address correspondence and reprint requests to Dr. P. E. Tes-

chan at Department of Medicine, B-2214 MCN, Vanderbilt Uni- versity School of Medicine, Nashville, TN 37232, U.S.A.

glucose administered in fasting normal subjects, and that could be administered within the fluid volume restriction in oliguric patients at concentra- tions that did not usually produce immediate occlu- sive phlebitis in peripheral veins. These recom- mended usages derived from studies summarized by Gamble (4), the signal formulations by Strauss (3, and the general recognition that the recurrent nausea and vomiting of these patients would usually preclude oral intake. However, both Borst (6) and Kolff (7) reported the value of dietary pro- tein restriction and of much higher, even forced, ca- loric intakes (i.e., concentrated fat and carbohy- drate) by mouth or by intragastric tube feeding. Rates of urea accumulation were reduced and nausea was ameliorated in some patients by such dietary means alone, or a dialysis treatment re- duced the nausea sufficiently to permit a subse- quent high-caloric intake. On the other hand, these authors also cited the catabolic and symptomatic impact of sepsis, trauma, and nitrogen loading by blood transfusions, findings that were vividly en- countered in military casualties in the Korean War (8,9) and reported at the first meeting of the ASAIO in 1955 (10).

A chemical analysis of the catabolic reaction of oliguric patients was reported at the second ASAIO meeting in 1956 in a study by Doolan et al. (1 1) of 19 individual amino acid concentrations (by means of individual microbiological assays) in plasmas of six patients on the eighth to tenth day of oliguric acute renal failure, both before and after dialysis. Next, in 1958, the Transactions recorded a panel discussion on the “Nature of the Uremic State” (12), in which themes about the mainly “neuropsy- chiatric” symptoms and about concurrent blood c he mica1 abnormalities were interwoven with themes concerning the responses of both (symp- toms and solutes) to dialysis. The discussion in- cluded speculations about possible relationships

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302 P. E. TESCHAN

FIG. 1. Seated left to right: G. E. Schreiner, H. L. Conn, E. G. Herndon, P. D. Doolan, L. W. Bluernle, G. M. Bull, W. J. Kolff. Standing left to right: P. E. Teschan, J. E. Kiley, A. D. Mason, J. P. Merrill, G. Richet, M. E. Rubini.

between uremic symptoms and solute concentra- tions as well as their potential origins in the course of exogenous dietary protein loading, endogenous protein catabolism, or disordered intermediary me- tabolism. Needs for data are cited that are still largely unmet in some areas nearly 30 years later.

Meanwhile a pivotal development occurred in October 1957 at the Brooke Army Medical Center when a “think tank” or “consensus conference” (Fig. 1) documented high mortality rates in all acute renal failure populations treated by means of the then-standard, largely empiric medical measures plus “dialysis-on-clinical-or-chemical-indication” -by which was usually meant significant uremic illness andor potassium intoxication. Fluid volume overload did not become an indication for use of the dialyzer until its configuration permitted ultra- filtration. The average mortality in the pooled series of 1,044 patients was 49% and varied from 30% in 270 patients with postpartum acute renal failure to 66% in 242 patients with posttraumatic acute renal failure.

The consensus regarding nutrition (in a session chaired by Dr. John P. Merrill) was that wasting is severe in acute renal failure, that oral intake is not predictably tolerated, and that hypertonic glucose should be infused into large central veins by in- dwelling polyethylene catheters within the limits of volume restriction. Again, needs for data were cited that.might lead to better treatment. At this session Dr. Schreiner commented that patients who happen to tolerate oral intake should be fed a diet of natural foods that are low in sodium, potassium, and protein and high in carbohydrate and fat con- tent.

Clues for one such improved treatment appeared

in the foregoing experiences, i.e., that “conven- tional’’ dialysis could restore alertness and appetite in clinically ill, uremic patients. The next logical step was stated by O’Brien et al. [(13) p. 771, at the 1959 ASAIO meeting: “We have been working on methods that would enable us to treat these pa- tients with hemodialysis early and frequently to see whether we might prevent prophylactically the de- velopment of the clinical uremic state instead of trying to modify it after it has developed.” The “new” treatment was called “prophylactic daily hemodialysis” [(13) p. 791, and the report states in part: “Clinically these patients remained almost entirely free of the usual symptoms of uremia throughout the oliguric and diuretic periods. . . . Appetites varied, but all seven patients were eating three small- to moderate-sized, unrestricted meals per day by the middle of their oliguric period and showed a gradual improvement thereafter con- tinuing through diuresis.” In essence dialysis was performed with no indications present at all. It was reasoned that uremic symptoms, like all oif its other manifestations, are signals from maifunctioning cells, tissues, or organs, and that in reversing such indications as the agitated depression derived from a malfunctioning cerebrum, dialyses somehow re- lieve the brain of a toxic burden. The interesting conceptual nuance was that the same materials might also be toxic to other cells, such as those concerned with wound repair, the local defense against infection, the production of antibody, or the enzymatically controlled balance between anabo- lism and catabolism, including the rates of multipli- cation and death involved in cell turnover in all tissues and organs.

These initial clinical findings were confirmed and

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extended at the ASAIO meeting in 1960 in an up- date by Teschan (14), in a report on continuous he- modialysis by Scribner et al. (15), and especially in the twin papers by Quinton et al. (16) on chronic vessel cannulation and by Scribner et al. (17) on the treatment of chronic uremia by intermittent hemo- dialysis. Chemical, metabolic, and nutritional con- sequences in patients with prolonged oliguria and treated with intermittent hemodialysis were also carefully set forth by Maher et al. (18), calling our attention from preoccupations with dialysis tech- niques to the basic medical and nutritional mainte- nance of these patients. Thus, 1959 and 1960 were the years in which the field of “nutrition in renal failure” was placed on a much more promising, practicable, and hopeful footing by the technolog- ical advances in dialyzers, vascular access, and re- gional heparinization and the favorable responses of patients to the (then) daring and unprecedented changes in treatment methods.

In 1962 Boen et al. (19) reported favorable effects on symptoms, nutrition (caloric intake and weight gain), strength, and activity level when periodic peritoneal dialysis was applied in patients with low levels of residual renal function (creatinine clear- ance of ~ 2 . 0 ml/min) by means of the first auto- matic peritoneal dialysate-cycling machine. Home peritoneal dialysis was envisioned and soon re- ported by Tenckhoff et al. (20). Despite symptom- atic improvements, weight loss and malnutrition were periodically reported in patients treated by ei- ther hemodialysis or peritoneal dialysis together with abnormalities revealed by assays of vitamins (21) and amino acids in plasma in relation to dial- ysis and transplantation (22). This tendency to un- dernutrition began to receive documentation, as in a study of serum albumin concentrations and of al- bumin turnover (usually accelerated in the presence of lower serum albumin concentrations) in chroni- cally hemodialyzed patients (23). In careful balance studies in 23 dialyzed outpatients, Kopple et al. (24) recorded improvements in body weight and serum albumin at two levels of prescribed dietary protein intake (0.75 and 1.25 g/kg/day) together with caloric intakes exceeding 35 kcal/kg/day. Anemia was not improved and “uremic” symptom scores were slightly more abnormal at higher protein intakes, in the face of twice-weekly 11-h dialyses using Kiil di- alyzers. Similar findings of protein-calorie under- nutrition were rediscovered in the course of the National Cooperative Dialysis Study (25) that ap- peared to be independent of the blood urea nitrogen levels or dialysis times employed in the protocol. Nitrogen balance studies in six patients treated

with two to three dialyses per week (120- 160 L di- alysate/week) were reported by Lindner and Tenck- hoff (26) and revealed an average value of dialysate protein loss at 16.4 g/dialysis that was compensated for by average protein intakes of 1.51 g/kg/day to achieve an average nitrogen balance of + 3.28 giday in these patients. Protein binding of various sub- stances including vitamins and essential amino acids was reported by Farrell et al. (27) and by Kopple et al. (28), while the potential for vitamin C deficiency was explored by Sullivan et al. (29). In like manner, reports of abnormal lipid metabolism in patients with renal failure and dialysis also ap- peared, e.g., by Dombeck et al. (30) who reported frequent findings of hypertriglyceridemia and Type IV lipoprotein electrophoretic patterns that were unaffected by dialysis or dialysate glucose levels. A glucose-free dialysate produced reductions in cho- lesterol and triglycerides in some patients, how- ever, as reported by Swamy et al. (31). The ab- normal triglycerides were fractionated by Samar et al. (321, revealing predominance of the very low density lipoprotein fraction. A 58% incidence of Type 111 hyperlipoproteinemia was reported by Wada et al. (33), while Lamberth and Oates (34) also emphasized reduced amounts of polyunsatu- rated fatty acids in the various lipid fractions. Bag- dade et al. (35) suggested that part of the lipid ab- normality was attributable to peripheral very low density lipoprotein catabolism and to a qualitative defect in lipoprotein lipase in uremic patients.

Meanwhile, instrumentation for hemofiltration and diafiltration and dialyzers with higher ultrafil- tration rates helped clinicians to cope further with the special problems of nutrition in oliguric pa- tients, often with multiple organ failure, in intensive care units. As a result, both volume and composi- tional abnormalities imposed by total parenteral and even enteral nutritional support could be more effectively controlled, e.g., by daily dialysis and/or filtration techniques (35- 38). Concurrent develop- ment of highly porous filtration membranes (e.g., permitting passage of solutes up to 10,000 daltons) faciliated the technique of continuous arteriove- nous hemofiltration, which accommodated the large fluid loads of total parenteral nutrition and other fluids in patients in the intensive care unit while avoiding the circulatory assault of hemodial- ysis in such critically ill and often hypotensive pa- tients (39,40). Amino acid losses during dialysis and continuous arteriovenous hemofiltration (41) and the nutritional benefit of amino acid supplementa- tion in chronic hernodialysis patients (42) were re- ported, exemplifying increasing concern for nutri-

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304 P . E. TESCHAN

tion as solute and fluid loads could be more effec- tively removed by the newer techniques.

Two further developments bore significantly on our understanding of nutritional issues in renal failure: (a) the use of urea kinetics in dialysis pa- tients as advanced by Gotch and Sargent (25) to es- timate the protein catabolic rate (which equals the daily protein intake in clinically steady-state condi- tions) and to qualify estimates of the desirable bal- ance between dietary solute intake and dialytic solute removal; and (b) the demonstration that it was technically feasible to quantify caloric expen- ditures in patients including those undergoing he- modialysis (43), i.e., to obtain a quantified target for caloric intakes by which otherwise frequent, cu- mulating negative caloric balances could be avoided (44,45). Thus, guidelines for optimal nutri- tional management for patients in intensive care units began to emerge (46,47).

COMMENT

This presentation deliberately focused on the link between renal failure, on the one hand, and the his- torical evolution of dialyzer instrumentation and of concepts and styles of dialysis treatment, on the other, as often originally reported in the Transac- tions-ASAZO. Important collateral developments and much information published elsewhere were therefore necessarily omitted as beyond the scope of this article. The cited developments, however, sustain the thesis that by virtue of these technolo- gies patients survived, and in their dialysis-depen- dent state presented nephrologists with new med- ical problems, including those of nutritional mainte- nance. Thus, “nutrition in renal failure” became a plausible topic for investigation, and spawned a new literature embracing biochemical and meta- bolic aspects, series of conferences (48), and a number of national and international cooperative studies, including some that are currently un- der way.

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