The role of nutrition in the care of children with renal insufficiency.
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Biomedical subjects
Publications and source records attributed to S J Wassner.
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The relative contributions of skeletal muscle, gastrointestinal tract, and skin to urinary N tau-methylhistidine (MH) excretion were estimated during in vitro studies using the rat hemicorpus preparation. After 0.5 h of perfusion, MH release into the perfusate was linear for 3 h and averaged 29.8 nmol . h-1 . 100 g hemicorpus-1. In vivo, 24-h urinary MH excretion averaged 37.3 nmol . h-1 . 100 g body wt-1. The ratio of soft tissue to skin weight is equal (3.2:1) in the whole rat and in the hemicorpus. The gastrointestinal tract released 16.0 nmol . h-1 . 100 g body wt-1 or approximately 41% of the total urinary MH excretion. Preparations perfused with or without skin showed modest differences in the rate of MH release that were not statistically significant. Skeletal muscle contains 89.8% of total body MH content, whereas gastrointestinal tract and skin contain 3.8 and 6.4%, respectively. Gastrointestinal tract actomyosin turns over rapidly with a fractional catabolic rate of 24%/day versus 1.4%/day for skeletal muscle actomyosin.
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The rate of myofibrillar protein degradation was measured by 3-methylhistidine (3MH) release in moderately uremic and sham-operated control rats. The rats were studied in the fed state or after 24 and 48 hours of fasting. When fed, both uremic and control rats gained weight at the same rate. During 48 hours of fasting, the uremic animals lost more weight (17.1%) than the shams (13.2%). The ratio of gastrocnemius muscle protein per gram of wet weight was not significantly different under any conditions. When fed and 48-hour fasted animals are compared, urinary excretion of 3MH rose from 0.81 to 1.32 moles per 24 hr per 100 g of initial body wt shams and from 0.90 to 1.30 moles per 24 hr per 100 g of initial body wt in the uremics. When ratio of 3MH to creatinine excretion in the urine was compared, there was no change in 3MH excretion between 0 and 24 hours, but there was an increase between 24 and 48 hours. Analysis of serum and muscle samples from fed and 48-hours fasted animals revealed that the concentrations of 3MH increased in both groups during fasting, with the uremic rats having a large increase in the total body 3MH pool. Myofibrillar degradation rates calculated from the sum of urinary excretion plus the changes in body 3MH pool size revealed that with moderate fasting, degradation rates increased in both sham and uremic rats with a larger increase being seen in the uremic group. After 48 hours of fasting, the increased amount of 3MH released from muscle of uremic rats was comparable to their larger percentage weight loss.
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Six malnourished patients were studied during intravenous nutrition therapy to compare the efficiency of essential and general amino acids when given as the sole nitrogen source during intravenous nitrogen therapy. A cross-over design was used so that each patient received both essential amino acids plus arginine and histidine and a general amino acid solution in random order. Glucose provided the remainder of the energy and both infusions contained 2 g of amino acid per 100 kcal. Each patient's daily urea nitrogen production was greater during infusion of the general amino acid solution. Consequently, nitrogen intake minus urea nitrogen production was significantly greater when the essential amino acid solution was infused. Plasma amino acid levels were determined on each patient during both essential and general amino acid infusion. Abnormalities tend to reflect the composition of the amino acid solutions as well as their administration directly into the systemic circulation bypassing the portal circulation.
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Degradation rates of muscle proteins were determined in young rats allowed access to standard rat chow 12 h/day. degradation was assessed by determination of 3-methylhistidine (3MH) excretion rates. 3MH is a nonreutilized amino acid produced almost exclusively within the actin and myosin of skeletal and cardiac muscle. Because plasma levels of 3MH are low and renal clearance is high, excretion reflects myofibrillar degradative rates. Excretion of 3MH was determined for 4-h periods beginning 12 and 20 h after initiation of feeding and after 24-and 48-h fasts. Excretion of 3MH per 4-h period increased with time after the last feeding. Because creatinine excretion is a function of muscle mass dividing 3MH excretion by creatinine excretion represents myofibrillar degradation per unit muscle mass, the fractional degradative rate. Degradation rates rose from 4.6 to 14.5%/day between 12 and 16 and 60 and 64 h after the beginning of the last meal. These results support the presence of a diurnal pattern of protein degradation as well as increased muscle degradation during starvation.
Thyroid function was evaluated in 24 children (aged 4-18 years) with chronic renal failure either before institution of hemodialysis or after more than 3 months of hemodialysis. 22 patients were clinically euthyroid and 2 were hypothyroid; in one case hypothyroidism was secondary to cystinosis and in the other it followed radiation therapy. The 2 hypothyroid patients had subnormal levels of T4, T3, FTI and FT4 as well as elevated serum TSH levels. Mean values for T4, T3, FTI and FT4 for the remaining 22 patients were within the normal range, but were significantly decreased, (all p values less than 0.01) when compared to controls. TSH and TBG levels were not significantly different from those of the normal population. Eleven of the euthyroid patients (50%) had either T3 or FT4, but not both, below the normal range without elevation of their TSH levels. These findings suggest that in the absence of other causes of hypothyroidism, children with chronic renal failure are able to maintain a clinically euthyroid state with either normal FT4 or T3 serum levels and can respond to primary gland failure with elevated TSH secretion.
The use of phenobarbital and diphenylhydantoin in transplant recipients is associated with reduced cadaver allograft survival when compared to transplant recipients not receiving anticonvulsant medication. An attempt was made to overcome the adserve effect on allograft survival by either discontinuing the anticonvulsants (2 patients) or maintaining the dose of prednisone at greater than 1 mg/kg/day (2 patients). Discontinuation of phenobarbital was successful after transplantation, with subsequent stabilization of allograft function. Of the 2 patients receiving greater than 1 mg/kg/day of prednisone, renal function is normal in one patient; however, the second is undergoing chronic rejection. Neither patient appears cushingoid. Anticonvulsant medication should be discontinued prior to transplantation. If the patient has an active seizure disorder, prednisone dosage should be maintained at a higher level.
Administration of anticonvulsant medication to recipients of cadaver renal allografts appears to be associated with decreased allograft survival. The one-and two-year actuarial graft survival rates for 20 index grafts was significantly lower than for 92 control grafts. Since phenobarbital and diphenylhydantoin increase the metabolism of corticosteroids, it is proposed that renal allograft recipients receiving these anticonvulsants may have ineffective immunosuppression, leading to a higher incidence of graft failure.
Secondary hyperparathyroidism is commonly present in patients with chronic renal failure. It has been suggested that elevated levels of parathyroid hormone (PTH) may be responsible for the glucose, amino acid and protein turnover abnormalities present in uremia. We utilized an in vitro muscle perfusion system to explore this possibility in more detail. We measured glucose uptake, muscle alanine and glutamine release, protein synthesis and both total and myofibrillar degradation rates, in the presence and absence of exogenous PTH and/or insulin. The addition of PTH either in the presence or absence of insulin had no effect on glucose uptake, protein synthesis or degradation or amino acid release by peripheral muscle tissue. Measurement of PTH revealed that 84% of the initial dose of immunoreactive hormone was still present at the end of the perfusion period. Our results suggest that PTH has no effect on skeletal muscle glucose or protein metabolism.