Erythropoietin deficiency causes anemia in nephrotic children with normal kidney function.

Anemia in persistent nephrotic syndrome (NS) has been described in a few case reports but has not been studied systematically. We present a group of 19 children with NS who developed anemia before the deterioration of kidney function. The aim of our study is to determine whether erythropoietin (EPO) and/or iron deficiency are causative factors and to evaluate the effect of EPO replacement therapy. Serum EPO levels, iron status, and vitamin B(12) concentrations were measured in nephrotic patients with anemia (NS-A) and compared with those of nephrotic children with normal hemoglobin (Hb) levels (NS-NHb; n = 13). Two control groups consisted of age-matched patients without kidney disease or hypoxemia with either iron deficiency anemia (IDA; n = 19) or normal Hb concentrations (NHb; n = 16). Most NS-A patients experienced persistent steroid-resistant NS, whereas most NS-NHb children had steroid-responsive NS. Although serum iron, ferritin, and B(12) levels were significantly lower in NS-A children, appropriate replacement therapy that resulted in normalization of ferritin and/or cobalamin levels did not lead to correction of the anemia. NS-A patients had greater EPO levels than those without anemia (21.6 +/- 3.3 versus 5.5 +/- 0.8 IU/L; P: < 0.001), but their response to anemia was inappropriately low compared with IDA children (EPO, 94.6 +/- 15.1 IU/L) despite similar Hb concentrations. EPO therapy for 4 to 9 months in 6 NS-A children with Hb levels less than 9 g/dL led to resolution of the anemia. In conclusion, anemia is a common feature of persistent NS that develops before the deterioration of kidney function. Depletion of iron stores may contribute to the development of anemia, but iron replacement therapy is ineffective. Nephrotic patients have EPO deficiency with a blunted response to anemia. The EPO deficiency is amenable to EPO therapy, which is recommended for this group of patients.

Case series: hyponatremia associated with moderate exercise.

Exercise-induced hyponatremia is commonly believed to be associated only with extraordinary physical efforts, or particularly strenuous exercise. Hyponatremia complicating moderate exercise has not been described previously. The authors describe the characteristics of seven patients with life-threatening hyponatremia associated with mild to moderate exercise. All patients suffered from nausea, vomiting, agitation, and confusion, appearing during or after moderate physical activity. Grand mal convulsions occurred in five of the patients. In laboratory results, hyponatremia was as low as 115 mEq/L, with a relatively high sodium concentration in the urine. High serum creatine kinase activity levels were found in most of the patients. All patients were discharged in good condition, without neurologic sequela. The authors conclude that hyponatremia is a possible complication of moderate exercise, and not only of endurance sports, and that exercise-induced hyponatremia can produce severe neurologic manifestations. The mechanism of the hyponatremia is unclear, but may be due to a hemodynamically inappropriate stimulus for antidiuretic hormone secretion.

[Acetaminophen toxicity in children as a "therapeutic misadventure"].

Acetaminophen toxicity after repeated administration of amounts that only moderately exceed recommended doses, is being increasingly reported in alcoholic or fasting adults. Pediatric experience with this pattern of acetaminophen toxicity is sparse. We present 2 children who developed severe hepatic damage, with renal insufficiency as well in 1, after 15-20 mg/kg of acetaminophen, given at 4-hour intervals for 3-4 days during an intercurrent febrile illness. When given in doses as low as 20 mg/kg at frequent intervals for a number of days, the drug puts children who are vomiting or have sharply reduced caloric intakes at increased risk for severe toxicity. Increased caution and awareness of the toxic effects of acetaminophen are needed, and it should be dispensed with appropriate package-label warnings.

Uptake of aggregated immunoglobulin by the mouse kidney. I. Effect of endotoxin.

Endotoxin (ET) pretreatment of mice resulted in increased liver and spleen uptake and decreased circulating levels of aggregated IgC (AggIgG) compared to control animals. ET had no effect upon the uptake of AggIgG by lung or whole kidney cortex. However, immunofluorescent microscopy revealed increased localization of AggIgG in the mesangium of ET mice at 1 but not at 2 or 16 h after administration of AggIgG. These studies show that mesangial macromolecular uptake is not solely dependent upon blood levels, but appears to be influenced by unknown and probably complex variables.

Uptake of aggregated immunoglobulin by the mouse kidney. II. Effect of hydrocortisone.

The uptake of radiolabelled (125I) aggregated human IgG (AggIgG) by the renal cortex, liver, spleen and lung was evaluated quantitatively in mice treated with hydrocortisone (HC) (25 mg) 72 h previously. AggIgG was administered in a dose of 1.5 or 3.5 mg/g body wt i.v.; tissue and blood were obtained at 1, 4 and 24 h. Renal cortical and mesangial uptake of AggIgG was significantly increased in HC animals. A rise in blood level was also observed in association with decreased splenic uptake, normal or slightly increased hepatic uptake and unchanged lung uptake. A significant increase in the kidney:lung and kidney:spleen ratios of AggIgG was induced by hydrocortisone, suggesting a relatively greater rate of loss from the spleen and liver than the renal cortex. The increased mesangial uptake may be a consequence of higher blood levels of AggIgG, as well as a direct effect of HC on the mesangium.

Generalized infestation of a 3 1/2-year-old girl with the pubic louse.

A 3 1/2-year-old girl had a Pthirus pubis infestation of the scalp, neck, eyelashes, back, and pubic area. The child's body, including the scalp, was treated with a 1% permethrin cream rinse formulation for 10 minutes. The treatment was repeated after 10 days. The eyelashes were treated by application of the permethrin solution with a cotton-tip swab.

Effect of bicarbonate and phosphate on renal phosphate leak in experimental Fanconi syndrome.

The role of acidosis in the renal phosphate leak in Fanconi syndrome (FS) was studied in maleate-induced FS in rats. Clearance studies were performed in the following groups: 1) intact rats served as control, 2) rats with maleate-induced FS, 3) rats with FS receiving intravenous bicarbonate (HCO3-), 4) intact rats receiving intravenous 0.03 N HCl (inducing acidosis similar to that of Group 2), 5) rats with FS receiving intravenous phosphate buffer and NaCl, and 6) rats with FS receiving intravenous phosphate buffer and bicarbonate similar to Group 3. In Group 2 serum pH and fractional excretion of phosphate (CP/GFR) averaged 7.31 +/- 0.08 (mean +/- SE) and 1.00 +/- 0.06, respectively, and differed significantly from Group 1, in which the corresponding values were 7.41 +/- 0.01 and 0.12 +/- 0.02, respectively. In Group 3, intravenous HCO3- corrected pH to 7.43 +/- 0.01 and reduced CP/GFR to 0.33 +/- 0.05, both results were different from the corresponding rates in Group 2 (P less than 0.0005). In Group 4, intravenous HCl reduced serum pH to 7.31 +/- 0.02 (P not significant as compared with Group 2) and increased CP/GFR to 0.186 +/- 0.030, the latter was higher than CP/GFR in control rats (P less than 0.01) but was lower than that in HCO3- -treated FS rats. In Group 5 serum pH was 7.31 +/- 0.021, similar to Group 2. CP/GFR was 0.84 +/- 0.031, significantly lower than in Group 2 (P less than 0.05). In Group 6 serum pH was 7.43 +/- 0.013 and CP/GFR was 0.86 +/- 0.044.(ABSTRACT TRUNCATED AT 250 WORDS)

Regulation of parathyroid cell gene expression in experimental uremia.

The secondary hyperparathyroidism of renal failure is an important component of renal osteodystrophy. We studied PTHmRNA levels and their regulation in control and subtotal nephrectomized (5/6 NX) rats at 3 wk, as well as levels of the 1,25(OH)2D3 receptor mRNA in parathyroids. Serum 1,25(OH)2D levels were decreased in 5/6 NX, whereas PTHmRNA levels were increased (7 +/- 0.7 OD U, N = 4) compared to controls (2.1 +/- 1.2, P less than 0.01); both decreased after 1,25(OH)2D3 (100 pmol/100 g body weight). Similar results were found in 5/6 NX rats after 3 months. There was no change in actin mRNA levels. PTHmRNA levels were highest in 5/6 NX rats with the most severe renal failure. The parathyroid gland 1,25(OH)2D3 receptor mRNA levels were not different between 5/6 NX rats and controls and were not affected by 1,25(OH)2D3 (100 pmol/100 g body weight daily) at 1 or 3 days. PTHmRNA levels of 5/6 NX rats did not increase when the serum calcium was decreased from 2.8 +/- 0.05 mmol/L to 0.9 +/- 0.15 mmol/L at 3 or 5 h, which contrasted with the marked increase in PTHmRNA in normal rats after hypocalcemia. As in normal rats, after hypercalcemia (4.8 mmol/L at 1 h) there was no change in the 5/6 NX rats' PTHmRNA levels. These results show that 5/6 NX rats have increased PTHmRNA levels that are normally regulated by injected 1,25(OH)2D3 but not by calcium. Parathyroid gland 1,25(OH)2D receptor mRNA levels are not increased in 5/6 NX in contrast to the increased PTHmRNA, which reflects the larger glands of uremia. 1,25(OH)2D receptor mRNA levels were not regulated by 1,25(OH)2D3.(ABSTRACT TRUNCATED AT 250 WORDS)

Thiazide therapy for ACTH-induced hypercalciuria and nephrolithiasis.

A one-year-old boy presented with hypercalciuria and nephrolithiasis following a course of ACTH therapy for infantile spasms. After a successful cystolithotripsy, therapy with chlorothiazide was followed by regression of the hypercalciuria within 42 months. Neither nephrolithiasis nor nephrocalcinosis recurred. Therapy with thiazides to prevent hypercalciuria caused by ACTH is proposed.

IgM nephropathy: morphological study related to clinical findings.

This study describes 10 cases of IgM nephropathy in whom the main morphological findings consisted of diffuse mesangial deposition of IgM and varying degrees of mesangial cell proliferation. In addition, focal segmental sclerosis was present in 1 patient and global sclerosis in another. An ill-defined electron-dense deposit was seen within the mesangial area in 1 case. Except for 1 patient, who had hematuria only, all suffered from nephrotic syndrome without deterioration of renal function. In view of the constant and characteristic finding of a diffuse mesangial IgM deposition, it is suggested that this form of nephropathy constitutes an entity separate from focal glomerulosclerosis or minimal change disease.

Nephrogenic diabetes insipidus, cystinosis, and vitamin D.

We describe a patient with early diagnosed cystinosis who presented with nephrogenic diabetes insipidus in addition to proximal tubular dysfunction. Another feature in this patient was abnormally low serum concentration of 24,25 dihydroxy vitamin D3 (24,25(OH)2D3) with normal 25 hydroxy vitamin D3 (25(OH)D3) and relatively low 1,25 dihydroxy vitamin D3 (1,25(OH)2D3).

Combined cyclophosphamide and corticosteroid-induced remission in severe glomerulopathy associated with systemic vasculitis.

Three patients with systemic vasculitis and severe renal disease as major manifestations are reported. In 2 cases, rapidly progressive glomerulonephritis presented as oliguric renal failure. In the third case, the clinical picture was severe nephrotic syndrome with decreased renal function. Combined cyclophosphamide and corticosteroid treatment resulted in dramatic improvement of renal function and remission of nephrotic syndrome. In 2 cases, histological improvement was documented by repeated kidney biopsy. The optimal duration of cyclophosphamide therapy has to be determined.

Vitamin D-dependent rickets types I and II. Diagnosis and response to therapy.

The diagnostic value of measuring serum vitamin D metabolites is demonstrated in the present study in which two patients with vitamin D-dependent rickets (VDDR) Types I and II are reported. The patient with sporadic VDDR Type I was severely disabled and unable to walk. Her serum 1,25(OH)2D level was low (32 pg/ml, normal 30 to 60) and she responded dramatically to 1 microgram of 1 alpha-hydroxyvitamin D3 daily. The VDDR Type II patient had an autosomal recessive inheritance and total alopecia. His serum 1,25(OH)2D level was greater than 500 pg/ml, compatible with end-organ refractoriness to 1,25(OH)2D. He did not respond to daily doses of 1 microgram 1 alpha-hydroxyvitamin D3. These cases demonstrate the striking difference in 1,25(OH)2D levels and therapeutic response to 1,25(OH)2D in these two conditions.

Multiple hornet stings with features of Reye's syndrome.

Hornet's venom is known to possess a variety of toxic effects. A 19-mo-old girl who developed a Reye-like syndrome following multiple stings by the Oriental hornet (Vespa orientalis) is described. She presented with encephalopathy associated with hepatomegaly, elevated transaminase levels, low prothrombin time, and hyperammonemia. Liver biopsy demonstrated microvesicular fatty infiltration and diffuse mitochondrial changes. Additional features were acute renal tubular necrosis and massive hemolysis.

Genetic polymorphisms of the renin-angiotensin system and the outcome of focal segmental glomerulosclerosis in children.

BACKGROUND: The clinical course of primary focal segmental glomerulosclerosis (FSGS) in children is variable, with some patients having a much more rapidly progressing course than others. The purpose of our study was to compare the frequency of three polymorphisms of the renin-angiotensin system (RAS) in children with FSGS with that in healthy controls of matching ethnic groups, and to determine whether the clinical outcome of FSGS was associated with different RAS genotypes. METHODS: Three RAS genotypes were examined in 47 Jewish and Arab children with biopsy-proven primary FSGS and in a large control group: the ACE insertion/deletion polymorphism in intron 16, the M235T mutation in the angiotensinogen gene, and the A1166C in the angiotensin II type 1 receptor gene (AT1R). RESULTS: Arab patients showed a greater tendency towards progressive renal disease than their Jewish counterparts (12 of 21 vs. 9 of 26, P = 0.05) and were less likely to achieve remission (3 of 21 vs. 11 of 26, P < 0.04), despite similar clinical presentation, medical management and follow-up. The RAS allele prevalence was similar among patients and controls of matching ethnic backgrounds, and no difference in allele frequency was found between Arabs and Jews. Homozygotes for the ACE insertion genotype (II) were significantly less likely to have progressive renal disease than patients with the other genotypes (ID and DD; 0 of 6 vs. 21 of 41; P < 0.022). The other RAS polymorphisms were not associated with variations in the clinical course of childhood FSGS. CONCLUSIONS: Homozygosity for the ACE insertion allele may have a protective effect in children with FSGS and can serve as a positive prognostic indicator at diagnosis. The D allele may exert a detrimental dominant effect on outcome. Neither the ACE gene polymorphism nor the other RAS polymorphisms studied are associated with disease prevalence. The AT1R and angiotensinogen gene polymorphisms are not associated with progression of renal disease in FSGS. Ethnic differences in the clinical course of the disease are not linked to these polymorphisms.