ABSTRACT
The subcutaneous administration of recombinant human erythropoietin is effective in the treatment of anemia of end-stage renal disease. Single-dose pharmacokinetic studies suggest the possibility of less frequent dosing via the subcutaneous route. In this study, dosing once-weekly was as effective as thrice-weekly subcutaneous dosing in maintaining the corrected hematocrit in a group of children receiving continuous cycling peritoneal dialysis. This regimen was preferred by and beneficial to both patients and their parents.
Subject(s)
Anemia/drug therapy , Erythropoietin/administration & dosage , Kidney Failure, Chronic/therapy , Peritoneal Dialysis/methods , Anemia/blood , Anemia/etiology , Child , Drug Administration Schedule , Erythropoietin/therapeutic use , Female , Hematocrit , Humans , Injections, Subcutaneous , Kidney Failure, Chronic/complications , Male , Prospective Studies , Recombinant Proteins/administration & dosage , Recombinant Proteins/therapeutic useABSTRACT
Although a cellular immune pathogenesis is suspected in idiopathic nephrotic syndrome of childhood (INS), there is scant direct evidence of in vivo immune activation. In order to investigate cytokine cascade activation in INS, soluble interleukin-2 receptor (sIL-2R) in plasma and urine was characterized and its levels measured in INS patients during relapse. Immunochemically detectable sIL-2R had a molecular mass of 35-46 kDa in both serum and urine and the molecule appears to be excreted intact; the pI was 5.05. INS patients had elevated serum sIL-2R levels compared with adult normal controls (845 +/- 97 vs. 373 +/- 47 U/ml, P = 0.001) and were significantly higher than previously published age-matched controls. Urinary excretion of sIL-2R was 47.2 +/- 13 U/mg creatinine in patients. Both the sIL-2R excretion rate and the fractional excretion of sIL-2R were positively correlated with the excretion of albumin (P = 0.02 and 0.002, respectively). These increased serum and urine levels occurred whether relapse was or was not associated with an intercurrent illness. We conclude that: (1) despite increased sIL-2R excretion during INS relapse, serum levels are significantly elevated; (2) while the elevated urinary levels could result from enhanced intrarenal production, they more likely reflect the increased serum levels; (3) the elevated sIL-2R levels support an immune pathogenesis in INS.
Subject(s)
Nephrotic Syndrome/blood , Nephrotic Syndrome/urine , Receptors, Interleukin-2/analysis , Adolescent , Child , Child, Preschool , Creatinine/blood , Creatinine/urine , Electrophoresis, Polyacrylamide Gel , Enzyme-Linked Immunosorbent Assay , Female , Humans , Isoelectric Point , Male , Molecular Weight , Nephrotic Syndrome/immunology , Serum Albumin/analysis , SolubilityABSTRACT
The use of recombinant human erythropoietin (rhEPO) for the treatment of renal anemia is well accepted. However, the lowest effective dose for subcutaneous (SC) administration has not been determined. This study documents that a dose of 50 U/kg administered three times a week was effective in 10 children (age range, 13 days to 18.6 years) receiving continuous cycling peritoneal dialysis (CCPD) for a period ranging from 0.25 to 23.5 months. Their hematocrit (hct) increased at an average rate of 0.26% points per day from a baseline of 19.8% +/- 3.1% to a value of at least 30% after a mean of 7.4 +/- 2.5 weeks of treatment. When compared with other studies, this response was more rapid than what has been observed with the same dose administered intravenously (IV). This response was similar to that seen with larger IV doses. Hypertension and functional iron deficiency were the most common complications. Two patients with previously controlled hypertension developed elevation in blood pressure that was easily controlled by oral antihypertensives. Six patients required IV iron dextran to reestablish treatment response. A SC rhEPO dose less than 50 U/kg three times a week may be effective in children and should be investigated.
Subject(s)
Erythropoietin/administration & dosage , Kidney Failure, Chronic/therapy , Peritoneal Dialysis, Continuous Ambulatory , Adolescent , Anemia/blood , Anemia/etiology , Anemia/therapy , Blood Pressure , Child , Child, Preschool , Erythropoietin/adverse effects , Erythropoietin/therapeutic use , Female , Ferritins/blood , Hematocrit , Humans , Infant , Infant, Newborn , Injections, Subcutaneous , Kidney Failure, Chronic/complications , Kidney Failure, Chronic/physiopathology , Male , Recombinant ProteinsABSTRACT
An unusual case of severe hypercholesterolemia and hypertriglyceridemia is described in a child with nephrotic syndrome. The severe hyperlipidemia in this patient was most likely induced by multiple interacting factors which included the metabolic abnormalities of nephrotic syndrome, steroid therapy, the underlying genetic predisposition of ApoE-2 homozygosity as well as diet and diuretic therapy. The result of these factors was an extremely severe type III hyperlipoproteinemia. The pathogenesis of hyperlipidemia in this setting is discussed.
