Nephrotic Children Research Articles

PHYSIOLOGIC RESPONSES ASSOCIATED WITH STEROID-INDUCED DIURESIS IN THE NEPHROTIC SYNDROME.

Abstract The physiologic changes during development of steroid-induced diuresis were examined in nephrotic children to determine the relationship between urinary aldosterone excretion and other responses. The earliest alterations occurred before diuresis and consisted of progressive decrements in urinary excretion of protein and aldosterone. In contrast, levels of serum albumin and of serum colloid osmotic pressure were not significantly altered until diuresis had begun. Plasma volume measurements, performed in a limited number of subjects, did not change consistently. The data are consistent with the interpretation that changes in aldosterone excretion during diuresis in the nephrotic syndrome are independent of serum albumin levels and, perhaps, of total circulating albumin. The findings suggest that excretion of edema fluid in this disease may be more significantly related to declining levels of aldosterone than to changes in serum albumin concentrations, serum colloid osmotic pressure, or total circulating albumin.

Steroids in Nephrotic Syndrome-Reply

To the Editor:— In answer to Dr. Rugstad's comments, I do agree with him that the rate of recovery from the nephrotic syndrome in children can, to a certain extent, be determined by the duration of the disease process. In fact, the data of our publication in question seem to support this contention for the first time. To shorten the duration of this variable disease has thus been our aim. How else could this be achieved today than by earlier institution of intensive long-term steroid administration? I do not assume that 29 of 34 nephrotic children given a placebo within 3 months after onset of their disease would be free of any detectable renal pathology over several years of observation. All available data up to 1954, when long-term, intensive regimen of steroid treatment of the nephrotic syndrome was first started in the United States, speak against such a possibility.

Studies on the pathogenesis of nephrotic edema: With particular emphasis upon changes in renal hemodynamics andthe metabolism of electrolyte and proteins

Summary Some physiologic and biochemical observationson children with the nephrotic syndrome and on rats with an experimental nephrotic syndrome are summarized. Particular reference is made to renal function, including some estimates of renal thermodynamics associated with the secretion of potassium by the edematous nephrotic child. Electrolyte balances illustrate the accumulation and diuresis of nephrotic edema fluid with particular reference to the effect of sodium restriction and sodium loading in nephrotic children. The balance data suggest that edema is asoociated with a decreased intracellular potassium content, as well as an accumulation of Na and Cl extracellularly. Studies of the composition of muscle from a nephrotic child support this thesis. It is suggested that some of the discrepancies in estimating the retention and distribution of Na and Cl by Balance measurements may be explained by correction for the retention of sodium, chloride, and water in skin and skeleton. A technique for such correction is illustrated. The skin appears to be the principal tissue reservor of edema fluid according to such calculations, and some evidence for this is provided by analyses of skin from rats with the experimental nephrotic syndrome. In the edenmatous skins of these animals, sodium and chloride are retained in excess of their anticipated distribution in the extracellular and intracellular fluids. It is suggested that the “excess” sodium and choride might be contained by loose electrostatic apposition to charged polar-end groups in the collagen fibril. Analytical data are given for “excess” Na and Cl of normal human skin, which are consistent with the above concept. Recent studies of cell composition of rats with an experimental nephrotic syndrome indicate a deficit of magnesium and organic phosphate as well as the accumulation of intracellular sodium and decreased concentration of potassium previously described. An attempt has been made to integratethese observations with others taken from the available literature and other studies by our group upon plasma protein metabolism in the nephrotic syndrome, to construc a tentative, hypothetical schema for the pathogenesis of nephrotic edema.

The effects of intermittent doses of adrenocortical steroids on the statural growth of nephrotic children

Summary The linear growth patterns of two groups of children with nephrosis were studied. One group received prolonged intermittent corticosteroid therapy to maintain remission and the other group (control) did not. Although the growth increments of each group were accelerated just prior to and following remission, those of the patients receiving intermittent corticosteroid therapy were significantly lower than the growth increments of the control group. These differences in growth rates were no longer significantly different when intermittent corticosteroid therapy was discontinued in the first group. Several aspects of growth changes occurring during the nephrotic syndrome are discussed.

An epidemiologic study of the nephrotic syndrome

Epidemiologic methods were used for a survey of nephrotic children admitted to the hospitals in the Greater Buffalo area. The incidence was found to be 2.1 cases per 100,000 children 0 through 9 years old per year. A higher incidence was found among nonwhite children. The sex ratio of nephrotic children living inside the city limits was very significantly different from that of nephrotic children living outside the city limits. On the basis of this study, a disease-producing factor is suspected in the patients' environment to which boys between 1 and 2 years old are exposed more often than girls who live within the city of Buffalo, while boys and girls are exposed equally often when they live in the suburbs or smaller towns.

Treatment of edema with cation exchange resins, including certain hormonal observations.

Excerpt The use of ion exchange resins was suggested by Segal et al.2for control of gastric acidity and by Dock3for treatment of cardiac edema. The background and theory of ion exchange by resins i...

CORTICOSTEROIDS AND ANTIDIURETIC SUBSTANCE IN NEPHROTIC CHILDREN

The role of tubular reabsorption in the pathogenesis of nephrotic edema led the authors to study the participation of antidiuretic hormone and adrenal steroids in regard to changes in renal hemodynamics and tubular function during different clinical events that may induce an increase or a decrease of urinary flow in nephrotic children. Formaldehydogenic steroids in urine, plasma and ascitic fluid and serum antidiuretic substance were simultaneously studied with clearance tests, electrolyte excretion and plasma constituents through 10 different periods of observations. From previous and present studies on renal function it was found that changes in renal hemodynamics and tubular transport mechanisms are responsible for variations in urinary flow leading to accumulation or disappearance of edema in the nephrotic syndrome. An increase in urinary flow was seen to occur with no change in the GFR but with a marked decrease in the U/P inulin and potassium ratio. Serum antidiuretic substance appeared to correlate closely with antidiuresis. Injection of nephrotic sera into peritoneal cavity of rats was followed by an antidiuretic effect similar to that produced by pitressin and posterior pituitary hormone. Antidiuretic factor seemed to be present in the globulin fraction of plasma proteins. No such effect was seen with intraperitoneal injections of plasma albumin, protein-free filtrate and ascitic fluid. An increase in titer of antidiuretic substance was observed during initial doses of ACTH and the reverse at the onset of diuretic response. Urinary excretion of formaldehydogenic steroids depended partly on diuresis in nephrotic children; this was not so in control cases. The influence of tubular function was suggested by the relationship found between urinary excretion of steroids and the V/Cin and V/Cth ratio and between clearance of steroids and diuresis. The influence of renal functional disturbance prevented a correct evaluation of adrenal activity by estimation of urinary steroids in nephrotic children. During the edematous-oliguric stage of nephrosis and in the absence of any stimulating or depressing effect upon the elaboration of adrenal steroids their urinary excretion was not significantly different from that seen in control cases. Formaldehydogenic steroids did not seem to have a direct role in producing variations of urine flow in nephrotic children. Increase and decrease in diuresis occurred simultaneously with an increase and a decrease in urinary and plasma steroids and vice versa. Formaldehydogenic material was found in variable amounts in the ascitic fluid suggesting an appreciable retention in the increased extracellular fluid during the oliguricedematous stage of the nephrotic syndrome. This material appears to be mostly true adrenal steroids. Potassium excretion was related to urinary steroids in nephrotic children but not in control cases. Potassium clearance was related to glomerular filtration in both control and nephrotic children. At the present time it remains a matter of some speculation of the role that steroids present in extracellular fluids may play in the physiologic and morphologic changes known to occur in the course of the nephrotic syndrome and experimentally reproduced by injection of DOCA to animals.

ALBUMIN THERAPY IN NEPHROSIS

Twelve nephrotic children were treated with intravenous injections of low-sodium concentrated human plasma albumin. Favorable response, as judged by the decrease in weight and edema and the increase in diuresis, was only seen in five cases. Lack of therapeutic effect on nephrotic edema was due in the majority of cases to the great urinary loss of injected albumin and to the inability of the kidney to excrete the edema fluid mobilized into the circulation by the osmotic effect of albumin.

Influence of sodium salicylate and sodium gentisate on proteinuria of lipemic nephrosis.

Abstract The effect of sodium salicylate on nephrotoxic nephrosis was studied in fifteen rats. Renal disease was induced by the intravenous injection of nephrotoxic sera obtained from rabbits. Twenty-five to one hundred milligrams of sodium salicylate per 100 grams of body weight were given daily by mouth for one to nine weeks. Proteinuria was suppressed in five, quantitatively reduced in six, and remained unaffected in four animals. Relapse occurred in all but two rats. Sodium gentisate was given in doses of 100 to 250 mg. per 100 grams of body weight to nine nephrotic rats for three to four weeks. This agent was without effect in all animals. Sodium salicylate was given orally to three nephrotic children. Two of these patients had evidence of glomerular lesions. They were treated with increasing doses of sodium salicylates for twenty-two and twenty-three days respectively and their plasma-salicylate concentration rose to 250 and 350 γ per cubic centimeter. The proteinuria decreased in both children to half of the pretreatment level. No further benefit was noted. The third child suffered from lipemic nephrosis without apparent glomerular involvement. Salicylates were given for thirty-seven days and a plasma level of 200 to 300 γ per cubic centimeter was maintained for nineteen days. Complete elimination of edema and ascites occurred, the proteinuria stopped, the blood chemistry and sedimentation rate returned to normal, and this patient has thus far remained free of symptoms for over nine months. Application in younger children was not possible because of toxic reactions to salicylates in the dosages required.

Lipemic nephrosis

Lipemic nephrosis

MINIMAL NITROGEN REQUIREMENTS OF CHILDREN WITH THE NEPHROTIC SYNDROME

The appetite of patients with the nephrotic syndrome is notoriously poor. In addition to lacking a desire for food these patients are peculiarly subject to gastrointestinal upsets, which may be induced or exacerbated by forced feeding. It is especially important that nephrotic patients be maintained in nitrogen equilibrium to offset the severe malnutrition characteristic of the syndrome. Previous studies from this clinic on the capacity of nephrotic children similar in age to those used in this study to assimilate dietary protein indicated that maximum assimilation of nitrogen occurred with a diet containing 3.2 Gm. of protein per kilogram of ideal body weight (accepted average weight for height and age) when the caloric intake was liberal.¹No data were available regarding the ability of nephrotic children to maintain themselves in nitrogen equilibrium on minimum caloric and nitrogen intakes. Unpublished observations on the incidence of nephrotic crises, with and without accompanying

The comparative nutritive efficiency of intravenous amino acids and dietary protein in children with the nephrotic syndrome

Summary 1. Nitrogen balance studies of ten weeks' duration have been reported on four children with the nephrotic syndrome. 2. Replacement of 33 to 57 per cent of dietary protein nitrogen with nitrogen furnished by casein hydrolysate given intravenously increased slightly the efficiency of nitrogen utilization in these patients and within this range of substitution indicated that casein hydrolysate completely replaced dietary protein. 3. Intravenous administration to four nephrotic children of 30 to 42 Gm. of casein hydrolysate daily during alternate weeks for four injection periods was not followed by consistent increases in the concentration of plasma amino acids or plasma proteins. No adverse effects were noted. 4. Reactions encountered were limited to flushing of the skin, a sensation of warmth, abdominal cramps, nausea, and vomiting. The latter two reactions could generally be completely avoided by reducing the rate of administration. 5. Some of the physiologic effects following intravenous administration of casein hydrolysate were discussed. 6. We recommend the intravenous administration of casein hydrolysate as the primary therapeutic procedure in the treatment of nephrotic crises particularly when complicated by bacteriemia.

Pneumococcus peritonitis in nephrotic and non-nephrotic children: A comparative clinical and pathologic study with a brief review of the literature

<h2>Summary</h2> A study of twenty-nine children with pneumococcus peritonitis observed in the last nineteen years is presented. The cases are divided into two groups, seventeen with nephrosis, and twelve without nephrosis. The clinical features of the disease are briefly described. The bacteriologic findings in the two groups differ. Pneumococcus Type I prevails in non-nephrotic cases, and Type VI, in patients with nephrosis. Various factors affecting the prognosis are considered, the mortality in the cases with nephrosis being 76 per cent, as compared with 41 per cent in the non-nephrotic group. From a discussion of surgical and conservative measures of treatment, one reaches the conclusion that at the present time most of the patients without nephrosis are operated upon and that little evidence can be found to show the efficacy of serotherapy alone. Sulfapyridine offers brighter therapeutic prospects. Operative and post-mortem examination of the pelvic and abdominal organs casts no light upon the role of these organs in the pathogenesis of the disease.

The intravenous administration of small doses of casein hydrolysate to nephrotic children and its effect upon the nitrogen balance and plasma amino acid level

The intravenous administration of small doses of casein hydrolysate to nephrotic children and its effect upon the nitrogen balance and plasma amino acid level

HYPOAMINOACIDEMIA IN CHILDREN WITH NEPHROTIC CRISES

The failure of children with the nephrotic type of Bright's disease to regenerate plasma protein when fed a diet approximately optimal for the assimilation of nitrogen cannot be attributed solely to loss of protein in the urine in all cases; sometimes severe hypoalbuminemia occurs with but slight loss of urinary protein.¹Further, rapid regeneration of plasma protein during recovery is, within wide limits, independent of the protein content of the diet. In observing nephrotic children in this clinic we have also noted that acute febrile episodes with peritoneal symptoms were most frequent in patients with a plasma albumin content below 1 Gm. per hundred cubic centimeters. Sometimes these episodes were accompanied by pneumococcic bacteremia and peritonitis, but often an episode ran its course without such infection. It was suggested in a previous study that when bacterial invasion occurs it may be secondary to acute disturbances in metabolism which cause

ASSIMILATION OF PROTEIN BY YOUNG CHILDREN WITH THE NEPHROTIC SYNDROME

Previous observations of the effect of dietary protein, 1 fat and carbohydrate 2 on the nitrogen balance of young children with the nephrotic syndrome revealed the fact that protein intakes above the optimum of 3 Gm. daily per kilogram of body weight tended to produce a less positive or even a negative nitrogen balance in these children. There still remained unexplained fluctuations in the nitrogen balance unrelated to diet and in the absence of infection. It is well known that nephrotic children are susceptible to acute infections, particularly pneumococcic peritonitis. MacLeod and Farr 3 found that these attacks are usually due to infection not by freshly acquired organisms but by organisms which have been carried for some time. The infections appear to result primarily from some metabolic disturbance, as a result of which resistance is lowered and a previously harmless organism invades the blood and the peritoneal fluid. Since publication

Amino Acid Nitrogen in Urine of Children with the Nephrotic Syndrome Following Intravenous Amino Acids

SummaryThere was no significant immediate increase in the urinary excretion per minute of non-protein nitrogen, urea plus ammonia nitrogen nor amino acid nitrogen, by 4 nephrotic children 5 to 7 years of age who had received intravenously 5 g of an amino acid mixture from casein hydrolyzed by enzymes. Therefore it appears probable that the injected amino acids are utilized for the nutritional needs of the patients.