Joel D. Kopple

NUTRITIONAL STATUS AS A PREDICTOR OF MORBIDITY AND MORTALITY IN MAINTENANCE DIALYSIS PATIENTS

Many epidemiologic studies indicate that protein-energy malnutrition is a strong predictor of morbidity and mortality in maintenance hemodialysis and chronic peritoneal dialysis patients. Those parameters of protein-energy malnutrition that have been most clearly associated with morbidity or mortality include serum albumin, dietary protein intake as indicated by the protein equivalent of total nitrogen appearance (PNA, also referred to as PCR), and the predialysis serum urea nitrogen. In large scale clinical surveys, low predialysis serum creatinine, cholesterol, potassium, phosphorus, calcium, and bicarbonate also correlate with increased mortality rates in maintenance hemodialysis patients. These correlations may reflect an association between dietary intake and mortality. The paucity of data correlating energy intake or body composition (e.g., total body protein or nitrogen, skeletal muscle mass, total body fat) with clinical outcome may reflect the difficulty of obtaining these data in large scale prospective or retrospective analyses. The correlation between protein-energy malnutrition and increased morbidity and mortality rates does not prove that a higher protein and/or energy intake or a more optimal body composition will improve the patients outcome. Prospective, randomized studies will be necessary to examine this question. However, two retrospective analyses of the effect of intradialytic parenteral nutrition on mortality rates in maintenance hemodialysis patients are consistent with the thesis that increased nutrient intake will reduce mortality in maintenance hemodialysis patients. Methods for assessing protein-energy nutritional status are discussed. There are essentially no data indicating that the more complicated and expensive techniques for nutritional assessment have important advantages over the more simple methods for the clinical management of maintenance dialysis patients.

Circulating somatomedin activity and sulfate levels in adults with normal and impaired kidney function

Circulating somatomedin activity was measured by porcine cartilage bioassay in 52 men with normal and impaired renal function. Serum somatomedin activity correlated inversely with serum creatinine and urea nitrogen, and was significantly decreased in nondialyzed patients with advanced renal failure. Somatomedin activity was even lower in subjects undergoing maintenance hemodialysis, but increased significantly during a single dialysis. Serum inorganic sulfate was elevated in uremic individuals, correlated directly with creatinine and urea nitrogen, and fell with dialysis. Since somatomedins measured by radioassay are reported to be elevated in uremia and do not change during hemodialysis, it seems likely that bioassayable somatomedin activity is depressed because of the accumulation of dialyzable inhibitors. Since somatomedins have broad anabolic properties, impaired somatomedin action may contribute to poor growth and wasting in uremia.

Thyroid function in patients undergoing maintenance hemodialysis: Unexplained low serum thyroxine concentration☆

Thyroid function was studied in 55 patients undergoing maintenance hemodialysis who were all judged to be clinically euthyroid. The dialysis patients, in comparison to normal control subjects, had significantly lower mean values for serum T4 (4.0 +/- 1.4 [SD] microgram/dl versus 7.9 +/- 1.5 microgram/dl, p less than 0.001), T3 (118 +/- 31 ng/dl versus 147 +/- 28 ng/dl, p less than 0.001), free T4 measured by equilibrium dialysis (1.22 +/- 0.38 ng/dl versus 2.15 +/- 0.67 ng/dl, p less than 0.001), free T3, free T4 index, and free T3 index. Serum TBG, measured by radioimmunoassay, was similar to that of the controls and serum TSH, 2.2 +/- 1.3 micromicron/ml, was also similar to that of control values, 2.0 +/- 1.1 micromicron/ml. The serum PBI did not change during the dialysis procedure, but serum inorganic iodine fell slightly from 2.1 +/- 1.1 microgram/dl before dialysis to 1.2 +/- 0.6 microgram/dl after dialysis (p less than 0.05). The marked reduction in serum total T4 and free T4 concentrations and the moderate reduction in serum total T3 and free T3 levels in apparently euthyroid patients undergoing hemodialysis has not been explained. The normal serum TSH levels in the face of these low concentrations of thyroid hormone suggests an abnormality in the control of TSH secretion in these patients.

Time perception and hemodialysis.

Subtle alterations in neurological function are often difficult to identify and even harder to quantitate. The identification of a neurotoxic state existing before overt behavioral changes occur has eluded quantification. It was hypothesized that a challenging signal-detection procedure would be used to assess neurological function of dialysis patients and other subjects, the degree of uremic toxicity occuring during an interdialytic interval, and the effects of neuroactive drugs. A vigilance task demanding the detection of an irregularly flashing light from a matrix of regularly flashing lights was administered to 3 groups of 15 men: patients undergoing maintenance hemodialysis, patients with chronic illness and no kidney disease, and healthy subjects. The procedure was found to yield a reliable measure; average test-retest correlation was 0.93, which differentiated not only within the hemodialysis cycle (p less than 0.001), between groups (p less than 0.001), but was also related to the recency of neuroactive drugs ingested (p less than 0.01).

Low-Protein Diets and the Nondialyzed Uremic Patient

It is accepted that in patients with chronic renal failure, dietary control of salt and water balance and diuretics should be used to prevent depletion or excessive retention of salt and water.1 Similarly, there is little argument concerning the need to control dietary potassium, phosphorus, and magnesium intake, to provide calcium and vitamin supplements, and to use phosphate binders in such patients.1,2 Thus the controversy concerning the value of dietary therapy in chronic uremia relates to the management of protein intake to postpone dialysis therapy and optimize nutritional status.

Activities of ornithine aminotransferase and ornithine decarboxylase in chronically uremic rats

Abstract The activities of two enzymes mediating different pathways of ornithine catabolism were measured in liver and kidney of chronically uremic rats and their pair-fed controls. Two months following partial nephrectomy hepatic ornithine aminotransferase (OAT) activity tended to be lower in uremic rats and was correlated with urea clearance and with carbamoyl phosphate synthetase activity. Renal OAT activity in uremic rats was also correlated with urea clearance. When uremic rats were maintained for five months, OAT activity was significantly decreased in liver but not in kidney and the activity of ornithine decarboxylase (ODC), the enzyme regulating polyamine biosynthesis, was reduced in both liver and kidney. In cross-over experiments, evidence was obtained for a factor in uremic kidney cytosol which inhibited renal ODC activity.

Monoamine and diamine oxidase activities in uremic rats

Abstract The activities of monoamine and diamine oxidases in various organs and tissues and the amine levels in plasma and urine were determined in chronically uremic and pair-fed control rats. Plasma amine levels were elevated in uremic animals while the urinary excretion of amines was decreased. In uremic as compared to control animals, monomaine oxidase activity was decreased in kidney and muscle, increased in heart and plasma and not altered in liver and cerebrum. Diamine oxidase activity in uremic rats was decreased in kidney, increased in plasma and unchanged in liver and muscle. These alterations of amine oxidase activities in renal failure may affect the metabolism of many amines and thus contribute to the pathogenesis of the uremic syndrome.

Nutritional Needs for the Elderly Hemodialysis Patient

Virtually no data have been published concerning the specific nutritional problems and nutritional requirements of the elderly maintenance dialysis patient. There is, however, substantial information concerning the nutritional status and needs of the nonuremic elderly patient. The data suggest that nutritional requirements and nutritional status change with aging, and that many diseases commonly associated with aging are influenced by the individual’s nutritional intake. Since these phenomenae also may apply to the elderly dialysis patient, the data will be reviewed briefly.