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“Selectivity” of protein excretion in theurine as an expression of the severity of the nephrotic syndrome in children
400
Abstracts
tissue was fixed in bicarbonate-buffered osmium or in buffered glutaraldehyde with postfixation in osmium, then embedded in Epon 812 after dehydration. Ultrathin sections were studied with a Philips 300 electron microscope. With the light microscope mild, nonspecific changes were seen in the mucosal architecture, consisting of some blunting of the apices of the villi, darker staining of the epithelial cells in this region, and absence of scalloping of the sides of the villi. Migrant cells were frequently observed in increased numbers between the villous epithelial cells. T h e electron microscope revealed severe alterations of the microvilli of the brush border at the villous apices. These abnormalities tended to be minimal or absent in the cells at the base of the villi. Lysosomes and free ribosomes were increased in number in the supranuclear cytoplasm. T h e basement Iamella was thin and indistinct. It had freqnent breaches, some of them very extensive. T h e histologic and fine structural alterations of the villi and intestinal epithelium probably represent evidences of nonspecific damage due to the prolonged, severe protein deprivation. On the other hand, it is likely that tile alterations of the basement lamella are a manifestation at the ultrastructural level of the disturbance in mucoprotein metabolism that is evidenced, among other biochemical changes, by increased urinary excretion of hydroxyproline. I n contrast to what has been reported by Platt and co-workers, our pigs did not have a flattened mucosa. It is possible that this may be explained by the fact that our animals were started on a protein-deficient diet at a later age than Platt's, and that under circumstances of greater metabolic maturity the capacity of the intestinal mucosa to respond to a protein-deficient diet may have changed.
Heparin treatment oJ the hemolytic-uremic syndrome Margarita Vitaeco, Julio S~nehez Avalos, and Carlos A. Gianantonio, Hospital de Nifios and Instituto de Investigaciones M6dicas, Buenos Aires, Argentina. Previous studies have demonstrated that intravascular coagulation is an intermediary mechanism of importance in the pathogenesis of hemolytic-uremic syndrome ( H U S ) . Even though the possibility of treating these patients wich anticoagulants has been suggested, the experience accumulated thus far is limited. Thirteen patients with severe forms of H U S were included in the present study. Their oliguric period ranged from 7 to 52 days, and prominent neurologic signs were present. Heparin administra:. tion was added to the usual therapeutic measures. Anticoagulant therapy was initiated 1 to t 7 days after the onset of oliguria, and 12 hours to 4 days after the appearance of neurologic signs.
The Journal o[ Pediatrics August 1972
Twelve children had thrombocytopenia. Goagulation studies were performed in 11 of these, 4 of whom h a d low values of several factors (V, II, V I I I , and fibrinogen) with fibrinogen degradation products in their sera. In the other 7 patients the levels of these coagulation factors were normal or high. Heparin was administered in doses varying from 2 to 10 nag. per kilogram per 24 hours for periods of 3 to 16 days. Dextran in a dose of 500 rag. per kilogram per 24 hours was also used in 8 children. T h e effectiveness of anticoagulant therapy was evaluated by comparing the course of these 13 patients with a group of 20 children who had H U S of the same clinical severity but who did not receive heparin. Six of the treated children died; their mortality rate was higher than t h a t of the nontreated group. In only 2 of the patients who recovered was clinical improvement evident during anticoagulant therapy; the apparent response of the other 5 children to anticoagulation was poor or nil. The return of coagulation factors to normal did not always correspond with clinical improvement in either the heparinized children or the control group. The results showed that heparin treatment is not effective in severe cases of HUS. The failure could be attributed in some patients to the irreversibility of the initial injury; in others, earlier administration of the anticoagulant might conceivably have contributed to a more favorable outcome. O n the other hand, definitive evaluation of heparin therapy is hindered by the existence of spontaneous recovery from HUS, even in severe cases not treated with anticoagulants.
"Selectivity" of protein excretion in the urine as an expression of the severity o[ the nephrotic syndrome in children E. T. Sojo, G. Feldman, A. Castro, and M. Vitacco, Secci6n de Nefrolog~a y Centro de Estudios Pedis Hospital de Nifios de Buenos Aires, Buenos Aires, Argentina. The histologic lesions of the glomeruli observed in renal biopsies, together with certain clinical features such as age of onset, sex, response to steroid therapy, hematuria, hypertension, and renal failure, are the parameters on which assessment of the severity and prognosis of the nephrotic syndromes is based at the present time. Several authors have proposed different methods to determine the "selectivity" of protein excretion by the kidney, with the thought t h a t study of this characteristic might help to define the severity of the affection. I n an attempt to evaluate these factors, 25 patients with the nephrotic syndrome due to a variety of causes were studied. T h e i r ages at onset ranged from I m o n t h t o 2 3 years. T h e duration of the disease prior to the time of study was between 4 months and 1 0 ~ years.
Volume 81 Number 2
Abstracts
Renal biopsy was performed and the tissue prepared with periodic acid-Schiff, hematoxylin and eosin, methenamine silver, and triehrome stains; at the same time the following laboratory determinations were made: glomerular filtration rate, quantitative urinary protein output, cellulose acetate electrophoresis of serum and urine proteins (Veronal buffer at pH 8.6) with quantification of fractions by reflection densitometry, urinary eq/a2globulin ratio, transferrin clearance, and IgG clearance (Mancini's radial immunodiffusion using Behrlng's specific antisera). From these studies there emerged four criteria for the evaluation of the selectivity of urinary protein excretion: semiquantitative determination of urinary protein fractions, ~l,/a.~u-globulln rela(IgG~ x tionship, IgG/transferrin clearance ratio \ I g G , Transf~ - , and "urinary protein selectivity index" TransfJ
_ql IgG
X
I
) x I00.
In all patients with minimal glomerular lesions
a~,/a2~ was greater than 1.0, while patients with severe lesions had ratios between 1.0 and 0.1. In patients with minimal gtomerular lesions Chgo/C1T.... ~ was less than 0.09; in those with moderate to severe lesions ratios were greater than 0.13, although some patients had lower values. Correlation with the severity of the pathologic lesion was best expressed by the "selectivity index." Study of the selective excretion of proteins in the urine affords useful data that do not substitute for, but rather complement, biopsy findings and clinical criteria in the assessment of the severity of the nephrotic syndrome.
Chemical analysis of bone in patients dead of chronic renal failure or acute renal failure of more than two weeks' duration Maria Gracia Calet'ti, Sofia G. de Liapchuc, and Margarita Vitacco, Hospital de Nifios de Buenos Aires, Buenos Aires, Argentina. The skeleton participates in the response of the body to chronic renal failure (CRF) through adaptive metabolic and hormonal changes. These changes were investigated in 7 children (4 boys
40 1
and 3 girls) 4 to 19 years old with CRF of 2 to 12 years' duration, and a 6-month-old boy and a 13-month-old girl with acute renal failure of 2 and 4 weeks' duration, respectively. T h e subjects had had clinical, radiologic, and biochemical studies, the last including acid-base balance; serum Na, K, Mg, Ca, P, alkaline phosphatase, urea, and protein; urinary Na, K, Mg, Ca, P, and hydroxyproline; and endogenous creatinine clearance and tubular phosphate reabsorption. After death of the patients, bone samples were taken from the second lumbar vertebral body (trabeeular bone) and the proximal tiblal metaphysis (compact bone). Part of each sample was examined histologically; the remainder was maintained at -20 ~ C. pending biochemical analysis. Eight infants (4 boys and 4 girls) 3 to 7 months of age, who were known by clinical course and postmortem examination to have died of causes other than renal disease, served as control subjects. The following determinations were carried out on each bone sample: density (picnometry), dry weight, water content, ash content, Na and K (flame photometry), Ca and Mg (atomic absorption), PO4 (Fiske and Subbarow), CO3 (Van Slyke), and hydroxyproline (Proekop and associates). The bone of the uremic patients had significantly tess ash, lower dry weight, and more water than that of the control subjects (Table I). Bone density was less in the uremic subjects than in the control subjects (Table I ) , but the difference was not significant. The Mg and PO4 content in the uremic patients was significantly higher than in the control subjects. There were no significant differences in Na, K, Ca, and hydroxyproline content. The correlation between histologlc and biochemical findings was good. The foregoing observations suggest that renal osteodystrophy in children is not simply an expression of secondary hyperparathyroidism, but must represent redistribution of bone mineral content, as well as alteration of t h e composition of bone crystal.
Renal excretion of acid in dehydrated infants with acidosis G. Sperotto, F. R. Carrazza, E. Mareondes, and R. A. Abdalla, Laboratbrio de Investiga~'5o da Cllnica Pediittrica, Hospital das Cllnicas, Siio Paulo, Brazil.
Table I. Composition of bone
Subjects Renal failure Control
Average weight (Gin.) Dry Ash weight Water 39.73 53.25
163.40 168.40
22.61 19.60
Average density 1.85 1.88
Electrolytes per gram dry weight (Average + S. D,) Mg (#g) [ PO~ (rag.) 253 -+ 67.23 191 + 30.45
10.39 + 0.91 9.29 "+ 0.46
Abstracts
tissue was fixed in bicarbonate-buffered osmium or in buffered glutaraldehyde with postfixation in osmium, then embedded in Epon 812 after dehydration. Ultrathin sections were studied with a Philips 300 electron microscope. With the light microscope mild, nonspecific changes were seen in the mucosal architecture, consisting of some blunting of the apices of the villi, darker staining of the epithelial cells in this region, and absence of scalloping of the sides of the villi. Migrant cells were frequently observed in increased numbers between the villous epithelial cells. T h e electron microscope revealed severe alterations of the microvilli of the brush border at the villous apices. These abnormalities tended to be minimal or absent in the cells at the base of the villi. Lysosomes and free ribosomes were increased in number in the supranuclear cytoplasm. T h e basement Iamella was thin and indistinct. It had freqnent breaches, some of them very extensive. T h e histologic and fine structural alterations of the villi and intestinal epithelium probably represent evidences of nonspecific damage due to the prolonged, severe protein deprivation. On the other hand, it is likely that tile alterations of the basement lamella are a manifestation at the ultrastructural level of the disturbance in mucoprotein metabolism that is evidenced, among other biochemical changes, by increased urinary excretion of hydroxyproline. I n contrast to what has been reported by Platt and co-workers, our pigs did not have a flattened mucosa. It is possible that this may be explained by the fact that our animals were started on a protein-deficient diet at a later age than Platt's, and that under circumstances of greater metabolic maturity the capacity of the intestinal mucosa to respond to a protein-deficient diet may have changed.
Heparin treatment oJ the hemolytic-uremic syndrome Margarita Vitaeco, Julio S~nehez Avalos, and Carlos A. Gianantonio, Hospital de Nifios and Instituto de Investigaciones M6dicas, Buenos Aires, Argentina. Previous studies have demonstrated that intravascular coagulation is an intermediary mechanism of importance in the pathogenesis of hemolytic-uremic syndrome ( H U S ) . Even though the possibility of treating these patients wich anticoagulants has been suggested, the experience accumulated thus far is limited. Thirteen patients with severe forms of H U S were included in the present study. Their oliguric period ranged from 7 to 52 days, and prominent neurologic signs were present. Heparin administra:. tion was added to the usual therapeutic measures. Anticoagulant therapy was initiated 1 to t 7 days after the onset of oliguria, and 12 hours to 4 days after the appearance of neurologic signs.
The Journal o[ Pediatrics August 1972
Twelve children had thrombocytopenia. Goagulation studies were performed in 11 of these, 4 of whom h a d low values of several factors (V, II, V I I I , and fibrinogen) with fibrinogen degradation products in their sera. In the other 7 patients the levels of these coagulation factors were normal or high. Heparin was administered in doses varying from 2 to 10 nag. per kilogram per 24 hours for periods of 3 to 16 days. Dextran in a dose of 500 rag. per kilogram per 24 hours was also used in 8 children. T h e effectiveness of anticoagulant therapy was evaluated by comparing the course of these 13 patients with a group of 20 children who had H U S of the same clinical severity but who did not receive heparin. Six of the treated children died; their mortality rate was higher than t h a t of the nontreated group. In only 2 of the patients who recovered was clinical improvement evident during anticoagulant therapy; the apparent response of the other 5 children to anticoagulation was poor or nil. The return of coagulation factors to normal did not always correspond with clinical improvement in either the heparinized children or the control group. The results showed that heparin treatment is not effective in severe cases of HUS. The failure could be attributed in some patients to the irreversibility of the initial injury; in others, earlier administration of the anticoagulant might conceivably have contributed to a more favorable outcome. O n the other hand, definitive evaluation of heparin therapy is hindered by the existence of spontaneous recovery from HUS, even in severe cases not treated with anticoagulants.
"Selectivity" of protein excretion in the urine as an expression of the severity o[ the nephrotic syndrome in children E. T. Sojo, G. Feldman, A. Castro, and M. Vitacco, Secci6n de Nefrolog~a y Centro de Estudios Pedis Hospital de Nifios de Buenos Aires, Buenos Aires, Argentina. The histologic lesions of the glomeruli observed in renal biopsies, together with certain clinical features such as age of onset, sex, response to steroid therapy, hematuria, hypertension, and renal failure, are the parameters on which assessment of the severity and prognosis of the nephrotic syndromes is based at the present time. Several authors have proposed different methods to determine the "selectivity" of protein excretion by the kidney, with the thought t h a t study of this characteristic might help to define the severity of the affection. I n an attempt to evaluate these factors, 25 patients with the nephrotic syndrome due to a variety of causes were studied. T h e i r ages at onset ranged from I m o n t h t o 2 3 years. T h e duration of the disease prior to the time of study was between 4 months and 1 0 ~ years.
Volume 81 Number 2
Abstracts
Renal biopsy was performed and the tissue prepared with periodic acid-Schiff, hematoxylin and eosin, methenamine silver, and triehrome stains; at the same time the following laboratory determinations were made: glomerular filtration rate, quantitative urinary protein output, cellulose acetate electrophoresis of serum and urine proteins (Veronal buffer at pH 8.6) with quantification of fractions by reflection densitometry, urinary eq/a2globulin ratio, transferrin clearance, and IgG clearance (Mancini's radial immunodiffusion using Behrlng's specific antisera). From these studies there emerged four criteria for the evaluation of the selectivity of urinary protein excretion: semiquantitative determination of urinary protein fractions, ~l,/a.~u-globulln rela(IgG~ x tionship, IgG/transferrin clearance ratio \ I g G , Transf~ - , and "urinary protein selectivity index" TransfJ
_ql IgG
X
I
) x I00.
In all patients with minimal glomerular lesions
a~,/a2~ was greater than 1.0, while patients with severe lesions had ratios between 1.0 and 0.1. In patients with minimal gtomerular lesions Chgo/C1T.... ~ was less than 0.09; in those with moderate to severe lesions ratios were greater than 0.13, although some patients had lower values. Correlation with the severity of the pathologic lesion was best expressed by the "selectivity index." Study of the selective excretion of proteins in the urine affords useful data that do not substitute for, but rather complement, biopsy findings and clinical criteria in the assessment of the severity of the nephrotic syndrome.
Chemical analysis of bone in patients dead of chronic renal failure or acute renal failure of more than two weeks' duration Maria Gracia Calet'ti, Sofia G. de Liapchuc, and Margarita Vitacco, Hospital de Nifios de Buenos Aires, Buenos Aires, Argentina. The skeleton participates in the response of the body to chronic renal failure (CRF) through adaptive metabolic and hormonal changes. These changes were investigated in 7 children (4 boys
40 1
and 3 girls) 4 to 19 years old with CRF of 2 to 12 years' duration, and a 6-month-old boy and a 13-month-old girl with acute renal failure of 2 and 4 weeks' duration, respectively. T h e subjects had had clinical, radiologic, and biochemical studies, the last including acid-base balance; serum Na, K, Mg, Ca, P, alkaline phosphatase, urea, and protein; urinary Na, K, Mg, Ca, P, and hydroxyproline; and endogenous creatinine clearance and tubular phosphate reabsorption. After death of the patients, bone samples were taken from the second lumbar vertebral body (trabeeular bone) and the proximal tiblal metaphysis (compact bone). Part of each sample was examined histologically; the remainder was maintained at -20 ~ C. pending biochemical analysis. Eight infants (4 boys and 4 girls) 3 to 7 months of age, who were known by clinical course and postmortem examination to have died of causes other than renal disease, served as control subjects. The following determinations were carried out on each bone sample: density (picnometry), dry weight, water content, ash content, Na and K (flame photometry), Ca and Mg (atomic absorption), PO4 (Fiske and Subbarow), CO3 (Van Slyke), and hydroxyproline (Proekop and associates). The bone of the uremic patients had significantly tess ash, lower dry weight, and more water than that of the control subjects (Table I). Bone density was less in the uremic subjects than in the control subjects (Table I ) , but the difference was not significant. The Mg and PO4 content in the uremic patients was significantly higher than in the control subjects. There were no significant differences in Na, K, Ca, and hydroxyproline content. The correlation between histologlc and biochemical findings was good. The foregoing observations suggest that renal osteodystrophy in children is not simply an expression of secondary hyperparathyroidism, but must represent redistribution of bone mineral content, as well as alteration of t h e composition of bone crystal.
Renal excretion of acid in dehydrated infants with acidosis G. Sperotto, F. R. Carrazza, E. Mareondes, and R. A. Abdalla, Laboratbrio de Investiga~'5o da Cllnica Pediittrica, Hospital das Cllnicas, Siio Paulo, Brazil.
Table I. Composition of bone
Subjects Renal failure Control
Average weight (Gin.) Dry Ash weight Water 39.73 53.25
163.40 168.40
22.61 19.60
Average density 1.85 1.88
Electrolytes per gram dry weight (Average + S. D,) Mg (#g) [ PO~ (rag.) 253 -+ 67.23 191 + 30.45
10.39 + 0.91 9.29 "+ 0.46