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Children with chronic renal failure (CRF) show a reduced appetite for sweet foods. Sensory responses to sweet stimuli were investigated in 45 children with CRF, 39 dialyzed patients (HD) and 25 controls(C). Two familiar foods were prepared in 5 sucrose concentrations: 1, 5, 10, 15, 20% for soft white cheese (SWC): 10, 20, 30, 40, 60% for apple sauce (AS). When identifying the sweeter of two SWC samples, CRF(15%) and HD (18%) made more mistakes than C (5%). When testing AS, mistakes were comparable between groups (25, 21, 19%). Preferences differed according to diagnosis group. The sweetest SWC was preferred by 40% of CRF and C and by only 22% HD; the least sweet SWC was preferred by 5% of C, 10% of CRF and 16% of HD. In AS, the highest concentrations were preferred by CRF and C, median concentration by HD. Plasma zinc had no clear effect on taste. Altered preferences for sweet foods in patients suggest post-ingestive adverse effects of sucrose resulting from an altered sucrose metabolism.

The effects of chronic metabolic acidosis (CMA) on zinc (Zn) bone content and urinary excretion were examined in the presence of normal or reduced renal function together with some aspects of calcium (Ca) metabolism. Four groups of rats were compared. All were fed a 30% protein and 9 mg Zn/100 g diet. Two were uremic (U): The first developed acidosis (UA), which was suppressed in the other (UNA) by NaHCO3 supplement. Two other groups had normal renal function: One was normal (CNA), and the other had NH4Cl in the drinking water and acidosis (CA). Femur total Zn and Ca content was markedly reduced by CMA and was not affected by uremia. Zn urinary excretion was increased by CMA and unaltered by uremia. Ca urinary excretion was markedly reduced in uremic rats, but was enhanced in both acidotic conditions. Urinary Ca and Zn showed a strong correlation in uremic and in control rats. Plasma parathormone and 1,25(OH)2D3 were unchanged by CMA. These data are in agreement with a direct primary effect of CMA on bone in releasing buffers. CMA induces bone resorption and a parallel decrease of mineral bone components, such as Ca and Zn, with little or no role of PTH, 1,25(OH)2D3 and of uremia itself.

A few of the many reports of experimental chronic renal failure have been summarized. Anorexia and food selection have been studied in experimental uremia and the findings are comparable with those observed in uraemic children. The optimal dietary protein content for growth is close to the minimal requirement for "optimal" growth. Protein excess leads to growth retardation and renal deterioration in uraemic rats, at least with the commonly used dry diets. The increased water requirement may be more critical for growth than the blood urea level or acidosis, although this requires further investigation. Reduction of the dietary protein by 50% and supplementation with essential amino acids (EAA) results in growth similar to that of the 100% protein diet. There is no growth improvement despite low blood urea levels, but the renal parenchymal is preserved. Supplementation with nitrogen-free analogues is more frequently associated with defective growth; the optimal mixture remains to be defined, and to date, when nutrition is identical, nitrogen-free analogues offer no benefit for renal preservation compared with EAA. Sucrose-rich diets have adverse effects on uraemia. These effects are associated with fructose intolerance and with reduced energy storage in the liver. The precise metabolic alteration remains to be defined.

The many published studies of experimental chronic renal failure (CRF) include a few findings which are similar to those reported in children with the naturally occurring disease. Experimental CRF has proved a useful model for investigating changes in eating behaviors: lack of appetite for sweet foods and selection of foods with high protein contents was comparable to behaviors exhibited by children. Optimal protein intake was found to be close to the minimum recommended intake for "optimal" growth (different from maximum growth in rats). Excessive protein intake had detrimental effects on renal function and growth with conventional dehydrated feeds, but water intake may have a greater impact than blood urea nitrogen and acidosis. A 50% reduction in protein intake with adequate amounts of essential amino acids ensured normal growth and slowed progression of renal lesions. Replacement of protein by mixtures of ketoanalogs was more likely to be responsible for growth failure; where similar growth rates were achieved, there was no evidence of a beneficial effect on renal lesions. Diets with high sucrose contents were poorly tolerated by CRF rats and were associated with fructose "intolerance" and reduced liver energy stores.

Several experimental studies have shown that the development of glomerular sclerosis during aging in rats is related to nutritional factors: it is impeded by overall food restriction, as well as by reduction of the protein, carbohydrate or sodium intake. It is enhanced by high protein or high sodium diets. In remnant kidneys, lesions develop that are similar to those in aging kidneys and that seem to be influenced by the same factors. Through several experiments, we have shown that the rapidity of the deterioration of renal function after subtotal nephrectomy is closely related to the protein intake and that the length of survival can be reduced by a high protein diet or increased by a low protein diet. The influence of protein intake remains clearly apparent when the intake of all other nutrients, particularly minerals, and of calories is strictly controlled. Low protein diets supplemented with essential amino acids resulting in increased appetite are of little benefit for survival, suggesting that the calorie intake or growth-related factors may be of significance. Prolonged survival observed with phosphorus (P) deficient diets compared to low or normal P diets is mainly due to decreased appetite. The optimal supply of protein, energy, sodium and other nutrients should be determined according, not only to nutritional status, but also to effects on the renal parenchyma.

The renal effects of carbohydrates (CHO) were studied in two experiments. 1) The effects of CHO-energy restriction was evaluated by comparing uremic growing rats (initial weight: 80 g) fed "ad lib" (L rats) or CHO-restricted (starch and glucose) but receiving identical amounts of all other nutrients (R rats). R rats showed reduced growth, slower increase in plasma creatinine, lower mortality rate, and less histological renal damage than L rats. 2) Two types of CHO restriction, low glucose (R1 rats) or low starch (R2 rats) were compared to "ad lib" feeding (L1 rats) in adult rats (initial weight: 130 g). Growth was identically reduced in R1 and R2 rats. Mean plasma creatinine levels at week four was lower in R1 than in L1 rats. The overall rate mortality was higher for L1 and R2 than in R1 rats (79%, 81%, 53%) but included deaths from other causes than renal failure. Actuarial survival excluding these deaths was 27%, 83% and 10% in L1, R1 and R2 rats, respectively. Diffuse renal lesions were found in 25 of 30 L1, 5 of 15 R1, and 12 of 15 R2 rats (R1 vs. R1 and R2, P less than 0.01). The results show that CHO restriction may preserve the renal parenchyma, and suggest that restriction of "simple" rather than "complex" CHO restriction may be beneficial, a finding which could be of clinical importance if confirmed by further investigations.

In order to evaluate the role of calorie and protein intake in growth impairment due to chronic renal failure (CRF), a subtotal nephrectomy was performed in weanling Wistar rats. A two-thirds reduction of renal function was obtained, which induced a marked growth retardation. Growth retardation was identical in nephrectomized and in pair-fed controls, and thus appeared to be entirely due to a deficient food intake. Using low protein diets, administration of a supplement with small amounts of essential amino acids (EAA) resulted in accelerated growth associated with a higher calorie intake, a better utilization of ingested calories for growth and a greater fall of blood urea nitrogen concentration.

Plasma and muscle free amino acid analyses have been performed on four groups of children with different levels of renal failure. Mean plasma creatinine of the groups 1 to 4 was respectively 1.3, 2.3, 3.3, and 4.9 mg/100 ml. Significant but different alterations of plasma and muscle amino acid pattern were found in the four groups of patients. In plasma, aspartic acid, citrulline, OH-proline, 1- and 3-methyl histidine were regularly increased, while threonine, valine, phenylalanine, isoleucine, leucine, tryptophane, tyrosine, and tyrosine/phenylalanine ratio were generally decreased. In muscle, glutamine was usually increased and alanine, valine and valine/glycine ratio decreased; significant increase of total amino acid content was only noted in group 4. Some amino acid alterations became worse with renal failure such as 3-methylhistidine increase or tyrosine/phenylalanine decrease, but group 3 patients had the greatest number of individual amino acid alternations. This group of patients also had the highest protein intake. Relationship between growth velocity and muscle amino acid pattern was found, a poor growth rate was associated with an increase of nonessential and essential amino acids with the exception of valine.

The aim of dietary therapy of chronic renal failure is to reduce uremic symptoms while avoiding malnutrition. The possible toxic effects of the diet on the kidney are rarely taken into consideration. The present experiment compared the long-term effects of three low-protein diets in nephrectomized rats (UI, UII, UIII) and in controls: diet I containing 7.5% protein, diet II containing 7.5% protein + 1% EEAs, and diet III containing 14% protein. Nephrectomized rats gained less weight than corresponding controls. UI rats had a decrease in the rate of length gain as opposed to groups UII and UIII. UI, however, maintained a relatively constant GFR, whereas groups UII and UIII had severe reductions in renal function. There were no significant differences between either UII or UIII rats in terms of growth and survival, despite lower consumption not only of proteins but also of all nutrients in the former group measured in a previous study. Thus semisynthetic diet appeared of little benefit. A diet consistent with both normal growth and preservation of renal function remains to be defined.

Thirty-four children with severe kidney disease, either congenital (32 cases) or developing at birth, were followed until age 5 to 19 years. Overall growth retardation corresponded to -2.5 SD below the mean normal values. The retardation occurred almost exclusively before therapy for it was started. Fifteen children were first treated during infancy. In all of them except one, growth was dramatically improved following the first visit to our center, growth changing from slowed to normal rate, although catch-up growth was rare: the average change from normal mean height was -1.68 SD (or -5 SD per year) calculated for the infantile period up to the first visit to our clinic, followed by a change of +0.18 SD per year between first presentation and age 12 months, and +0.01 SD per year between first presentation and last observation at a mean age of 8.3 years. In the 19 patients who were treated after the first year of life, the mean change of height from birth to first presentation was -0.33 SD per year followed by a mean change of -0.04 SD per year up to the last observation (mean period, 7.3 years). Catch-up growth was exceptional. Five children entered puberty with a normal growth spurt. When GFR deteriorated, growth velocity was unchanged. Height calculated for corresponding bone maturity was reduced in half of the patients when first seen, but progressed to the same degree as height during follow-up, except in one patient. Mental development was normal in 31 of 34 patients. Conclusion. Normal growth rate and normal development is possible in children and even in infants with CRF chronic renal failure. The importance of instituting early conservative treatment to prevent height loss must be emphasized.

Binding sites for human GH (hGH) were studied in liver membranes of rats with chronic renal insufficiency (CRI) associated with marked growth retardation. A subtotal nephrectomy was performed in young female rats. One month after the nephrectomy, the animals with a plasma creatinine level 3 times or more that of controls were studied; their mean statural gain was 56% that of controls. The specific binding of [125I]hGH to microsomal membranes of rats with CRI was low (40% that of controls). The number of binding sites rather than the affinity of the binding was affected; both the lactogenic and somatotropic sites were decreased, as judged from the binding of ovine [125I]PRL and bovine [125I]GH. The binding sites of the plasma membranes as well as those of the Golgi fractions, were reduced. In plasma membranes of rats with CRI, the specific binding of glucagon was low, and the specific binding of insulin was elevated; these modifications were associated with a high plasma glucagon level and a decreased insulinemia in rats with CRI, but no modification of plasma GH and PRL levels was found. Thus, the hormone level does not appear to regulate the GH-binding sites in this system. The link between the growth defect and the decreased number of GH-binding sites in the liver membranes of rats with CRI remains to be established.

Several experiments have shown that deterioration of renal parenchyma after reduction of functional mass is affected by the protein content of the diet. The respective role of proteins and that of other nutrients particularly phosphorus which varies with proteins was never clearly separated. Three groups of 9 uremic rats U I, U II, U III, received three diets differing exclusively in their protein content, which was supplied by casein and was respectively 8%, 16% and 32%. Other nutrients were maintained identical, including energy and minerals. Food intake was similar in U I and U II rats and was lower in U III rats. Mortality rate remained closely related to protein intake. Of U III rats, 78% died within 10 weeks and 100% within 15 weeks. Of U II rats, 56% were dead at week 15, and 100% at week 30. Mortality occurred significantly later in U I rats fed the lowest protein diet. Histology of remnant kidneys showed severe glomerular and tubular damage, with no or little calcium deposits despite normal phosphorus diet and frequent hyperphosphoremia. In conclusion, protein intake influences survival by accelerating the renal damage in rats with reduced kidney mass independently of any other nutrient.