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There have now been many studies on the effects of growth hormone (GH) on renal function. Chronically elevated GH levels, such as occur in acromegaly, are associated with an increase in renal plasma flow (RPF), glomerular filtration rate (GFR) and kidney size. When GH falls in these individuals (such as, after hypophysectomy in acromegalic patients), RPF, GFR and renal size decrease. A rapid increase in plasma GH in normal or growth hormone deficient adults, such as occurs after GH injection, causes an increase in RPF and GFR. However, these effects on renal function are delayed, occurring between 5.5 and 23 hours after the GH injection and in association with an elevation in the plasma concentrations of insulin-like growth factor I (IGF-I). These observations suggest that IGF-I may mediate the GH stimulated increase in RPF and GFR. We evaluated this question in rats starved for three days. A 20 minute infusion of IGF-I causes an increase in RPF and GFR in these animals. This effect could be blocked by indomethacin but not by somatostatin. These findings suggest that: 1) GH injection does increase RPF and GFR; 2) this effect on GH, which is delayed for several hours seems to be mediated by IGF-I; and 3) a 20-minute IGF-I infusion itself increases RPF and GFR in starved rats. The effect of IGF-I on renal function seems to require the presence of eicosanoids. Further studies will be necessary to examine whether IGF-I is a physiological regulator of renal function.

The enzyme, diamine oxidase, is present in many tissues and plays a role in the metabolism of certain amines, some of which may be toxic. In renal failure, plasma diamine oxidase activity was found to be increased in chronically uremic patients and before and after dialysis therapy in patients undergoing maintenance hemodialysis. Diamine oxidase activity was decreased in urine of the chronically uremic patients as compared to normal subjects. In chronically uremic rats, diamine oxidase activity was observed to be increased in plasma and reduced in urine as compared to sham-operated, pair-fed control rats. In the uremic rats diamine oxidase activity was also decreased in kidney and unchanged in liver and muscle. Total amine levels were elevated in plasma and reduced in urine of patients and rats with chronic renal failure. Although the clinical significance of abnormal diamine oxidase activity in renal failure is not clear, it is possible that this enzyme may have a pathophysiologic role in uremia.

Thirty-six patients aged 1.6 to 18.8 years with end-stage renal disease (ESRD) underwent continuous, ambulatory peritoneal dialysis (CAPD) between August, 1980, and May, 1982. With four or five exchanges daily, the mean serum urea and creatinine levels were 75 +/- 24 mg/dl and 9.2 +/- 3.1 mg/dl, respectively, hypertension was controlled in 34 of 36 patients without antihypertensive medications, and transfusion requirements were minimal in nephric patients (0.20 U/month). Despite added energy intake from dialysate glucose absorption, the total energy intake was suboptimal in most patients. The mean growth velocity was only 0.35 cm/month and only 4 of 17 patients observed for more than 6 months exhibited normal growth velocity. The incidence of peritonitis was one episode every 12.5 patient months. Rehabilitation was excellent with all patients engaged in age-appropriate activities. CAPD appears to be an acceptable therapeutic modality for children with ESRD.

Recent studies suggest that patients undergoing continuous ambulatory peritoneal dialysis (CAPD) may be prone to develop protein depletion. This paper reviews data concerning glucose uptake, protein and amino acid losses, and nitrogen and mineral balances in clinically stable adult CAPD patients. Approximately 70% of the glucose instilled with dialysate was absorbed, and the glucose absorbed provided approximately 8 kcal/kg/day to the patient. Serum total protein and albumin losses into dialysate averaged 8.8 +/- (SEM) 0.5 and 5.7 +/- 0.4 g/day, respectively. The quantity of free amino acids removed with dialysis was less, 3.4 +/- 0.3 g/day. The balance studies suggest that a safe dietary protein allowance for clinically stable CAPD patients who are ingesting high energy diets is 1.2 to 1.3 g/kg/day. Tentative dietary allowances for other nutrients in clinically stable CAPD patients are proposed.

Protein synthesis and degradation and net uptake and release of amino acids and minerals were investigated in the perfused hemicorpus of acutely uremic and sham-operated control Sprague-Dawley rats. Rats underwent bilateral nephrectomy or sham surgery and were studied 30 hours after surgery. The uremic rats displayed greater urea nitrogen appearance (net urea generation), lower plasma and muscle intracellular concentrations of most amino acids, and increased protein degradation in the hemicorpus as compared with control animals. Muscle protein synthesis was slightly but not significantly decreased in the uremic animals as compared with controls. There was greater net release of phenylalanine, tyrosine, alanine, total nonessential amino acids, total amino acids, potassium, and phosphorus from the perfused hemicorpus of uremic rats and greater release of citrulline from sham rats. Muscle ATP, creatine phosphate, and cyclic AMP, and muscle cathepsin B1, cathepsin D, and alkaline protease activities were not different in the uremic and control rats. These data provide evidence that acutely uremic rats have increased muscle protein wasting which is due to enhanced protein degradation. The cause of the increased muscle protein degradation is unknown.

This study was undertaken to assess the clinical and metabolic responses to total parenteral nutrition (TPN) in patients with acute renal failure who could not be nourished adequately through the enteral tract. The TPN provided either about 21 g/day of essential amino acids (EAA) or a larger quantity of essential and nonessential amino acids (ENAA); the ratio of essential to nonessential amino acids in the latter preparation was 1.0:1.0. Attempts were made to give sufficient ENAA nitrogen to equal or slightly exceed the urea nitrogen appearance (UNA). Five patients were randomly assigned to receive TPN with EAA (2.3 g of nitrogen per day) and six patients to receive ENAA (11.3 g of nitrogen per day). Hypotension with trauma or infarcted intestine was the cause of acute renal failure in 10 of the 11 patients. Three of the five patients receiving EAA recovered renal function, and two survived. In the patients receiving ENAA, as compared with those given EAA, UNA was significantly greater (14 +/- 7.4 [SD] vs. 7.5 +/- 3.0 g/day; P less than 0.01), and nitrogen balance, estimated from the difference between intake nitrogen and UNA was slightly, but not significantly, less negative (-3.0 +/- 4.0 vs. -5.2 +/- 2.9 g of nitrogen per day). These preliminary findings suggest that in comparison to TPN with EAA, there is no advantage to larger amounts of ENAA (76 +/- 13 g/day). Studies are indicated to assess whether a multifaced approach using TPN with ENAA and possibly a larger proportion of the branched-chain amino acids, higher energy intakes, anabolic agents, and continuous arterio-venous hemofiltration will improve morbidity and mortality in patients with acute renal failure.

This study evaluated the nutritional status of 95 patients with chronic renal insufficiency who participated in the feasibility phase of the NIH funded Modification of Diet in Renal Disease (MDRD) Study. All patients were seen monthly by a physician and dietitian. After a baseline period, the patients were randomly assigned either to a mildly protein-restricted control diet or to one of three low protein, low phosphorus diets. Patients with clear evidence for protein-calorie malnutrition were excluded from the study. Patients were followed for an average of 12.4 months (range, 0 to 22 months). The glomerular filtration rate (GFR) at the commencement of the experimental diets ranged from 8 to 56 ml/min/1.73 m2. Assessment of the nutritional parameters indicated that none of the four diet treatment groups developed protein-calorie malnutrition. At the end of treatment with the experimental diets, most nutritional parameters were normal and few had worsened. Nonetheless, the following observations indicated that some patients had developed subtle evidence for protein-calorie malnutrition. There were positive correlations between the GFR and the serum transferrin and creatinine:height ratio. In men, arm muscle area and, at the onset of the experimental diets, the % standard body weight also correlated with the GFR. In women, GFR correlated with dietary energy intake. When patients were grouped according to their GFR level, those with the lowest GFR also tended to have lower energy intakes, serum transferrin levels and creatinine:height ratios. Patients with a GFR of 24 ml/min/1.73 m2 or lower tended to lose body mass during the study. In all groups of patients, the estimated actual energy intake was significantly lower than the prescribed intake. On the other hand, in the patients assigned to one of the three low protein, low phosphorus diets, nitrogen intake was above the prescribed level. The low energy intake of those patients with the lower GFR levels may contribute to their propensity to become malnourished.