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Renal biopsy, the introduction of immunohistologic methods and electron microscopy have allowed the differentiation of clinicopathologic entities associated to nephrotic syndrome. Two main categories must be differentiated: in the first, diffuse lesions of the glomerulus, including those secondary to specific diseases the same as those that are apparently primary, are responsible for the increased permeability of glomerular capillaries. Any one of the following clinical signs suggests this category: acute onset with nephritic syndrome, moderate nephritic syndrome, moderate nephrotic syndrome, gross hematuria, persistent hypertension and/or renal failure, poor selectivity of proteinuria and drop in complement serum levels (C3). In the second category, known as idiopathic nephrotic syndrome, the mechanism of disorder of the glomerular capillary is unknown and the nephrotic syndrome is more marked. In most cases with idiopathic nephrotic syndrome, minimal glomerular lesions (MGL) are present. The clinicopathologic correlation among these three types of lesions shows that the type with MGL is characterized by selective proteinuria, absence of hematuria, good response to corticosteroids and good outlook; whereas in types with diffuse mesangial proliferation (DMP) and segmentary sclerosis, proteinuria is frequently non selective, hematuria shows in 50 to 75% of the patients; prognosis is poor. However, MGL, DMP and focal segmentary glomerular sclerosis are not different entities, but represent variants of the same disease. Considering that corticosensitive nephrosis to this moment is the most common cause of the nephrotic syndrome, especially in children under 8 years, renal biopsy should be done only under two circumstances: a) when the clinical symptoms suggest diffuse glomerular lesions and b), when resistance to corticosteroids becomes evident.

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.

The effects of long-term indomethacin therapy were studied in rats with chronic nephrosis induced by puromycin of aminonucleoside (PAN). Fifteen PAN rats received indomethacin (2 mg/kg/d) administered by daily gavages, and fifteen received glucose. A control group received indomethacin but no PAN. Three to five animals per group were sacrificed monthly. Proteinuria was similar in both PAN rat groups. Renal function and histology were normal in the control rats. In the PAN animals, renal failure developed earlier in the treated rats than in the others. Histological examination revealed in all PAN rats early tubulo-interstitial lesions and progressive glomerular damage. The pattern of the lesions was identical in both PAN rats, but the glomerular changes developed earlier, were more diffuse and more severe in the indomethacin treated rats. Thus, indomethacin resulted in an accelerated destruction of the glomeruli in experimental nephrosis. Such a deleterious effect remains unexplained, and its relevance to human disease is not demonstrated.

The glomerular filtration rate (GF) of each nephron can vary, with increases being caused by stimuli such as nephron reduction and ingestion of proteins. This "functional reserve" (FR), detectable by protein load tests, may be lost in extensive renal destruction where the remaining nephrons are in a permanent state of maximal stimulation. If this hypothesis is true, FR determinations would be of greater value than baseline GFR measurements for evaluating the condition of the remaining parenchyma. A very large number of studies have addressed the FR in normal subjects and have used either diets containing variable amounts of proteins or acute loads given orally (approximately 1 g/kg cooked meat) or intravenously (amino acids). All these studies have evidenced increases in the GFR after the load, regardless of its type, but with major variations across studies and patients. Subjects with a single healthy kidney seem to retain a FR whose magnitude is equal to or smaller than the FR in normal subjects. Conflicting data have been reported in more extensive destruction of the parenchyma, where the FR has been shown to either disappear or persist with no change in percentage. Thus, the practical value of GFR determinations after protein loads has not as yet been established and should be specified using better standardized methods that do not rely on creatinine clearance, at least during oral load tests where serum creatinine levels increases and is no longer stable.

Uremic children have low energy intakes, with little appetite for sweet foods. Likewise, sucrose-rich diets are poorly accepted by uremic rats, which suggests that uremia causes a relative aversion for sucrose. Hemodialyzed children (no. = 39, mean age = 160 mo) and healthy controls (no. = 25, mean age = 122 mo) were compared for perception of sweet taste intensity in two familiar foods (soft white cheese and apple sauce) and for preference for sweetness. The food stimuli were prepared in five sucrose concentrations: 1%, 5%, 10%, 15%, and 20% for cheese; 10%, 20%, 30%, 40%, and 60% for apple sauce. Children were presented with pairs of stimuli of adjacent concentrations and asked, in a forced choice, to identify the sweeter stimulus and to express their preferences. The hemodialyzed children made more mistakes (19%) than the controls (5%) when asked to rank sweetness in the soft cheese (i.e., with low concentrations). Both groups made an equal number of mistakes when asked to rank sweetness in the apple sauce. Preferences for sweetness were markedly different. In cheese, the highest sucrose concentration was preferred by 21.9% of the hemodialyzed children vs 41% of the controls. The lowest sucrose concentration was selected by 15.6% of the hemodialyzed children vs 4.6% of the controls. Similar preference trends were observed for apple sauce. We conclude that abnormally low preferences for sweet foods can contribute to insufficient caloric intake in uremic children.

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.

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.

Rats progressively develop proteinuria and glomerular sclerosis with age. These physiologic and histologic changes are accelerated by subtotal renal mass ablation. Alterations in the glomerular basement membrane (GBM), such as thickening and decreased anionic site density, occur during senescence. This study examines the ultrastructural alterations of the GBM affecting remnant glomeruli. Six week-old male Wistar rats underwent a subtotal nephrectomy (70%) and were compared with sham operated rats. Rats were fed a standard diet, and physiologic measurements were performed every 3 weeks. Rats were killed 6 and 12 weeks after surgery. Anionic sites were labeled by polyethyleneimine perfusion before killing. Kidneys were processed for light and electron microscopy. Nephrectomized rats had higher protein-uria than the controls and developed glomerular sclerosis. The GBM of nephrectomized rats were significantly thinner and anionic sites were less numerous 12 weeks after nephrectomy, especially in the lamina densa (LD) of the GBM. The number and distribution of anionic sites were similar to those observed in sham operated rats killed 6 weeks after surgery. These results indicate that glomerular sclerosis and GBM thickening are unrelated phenomena. They also suggest that the number and density of anionic sites in LD are not a prominent factor for increasing proteinuria after subtotal nephrectomy.

While a diet deficient in phosphorus has a protective effect against kidney deterioration in uraemic rats, this effect, in fact, is more closely related to the reduction of food intake than tho the phosphorus load itself, even though the latter influenced the pattern of the renal lesions.