Abdullah Sakarcan

Systemic lupus erythematosus in a child receiving long-term interferon therapy

Systemic lupus erythematosus (SLE) developed in a 10 1/2-year-old white boy with juvenile laryngeal papillomatosis who had been treated with interferon alfa-n1 for 7 years. His age, gender, and fast recovery after discontinuation of interferon therapy and institution of appropriate treatment for SLE are compatible with a diagnosis of drug-induced SLE. Autoimmune disorders may occur as a complication of interferon therapy.

Hyperphosphatemia in tumor lysis syndrome: the role of hemodialysis and continuous veno-venous hemofiltration.

We report a 4-year-old boy who developed tumor lysis syndrome complicated by severe hyperphosphatemia and acute renal failure, following chemotherapy for T-cell acute lymphoblastic leukemia. Despite successful treatment of hyperphosphatemia with hemodialysis, there was an immediate rebound in the high serum phosphorus level. The patient underwent a second treatment with hemodialysis which was then followed by continuous veno-venous hemofiltration (CVVH). CVVH maintained his serum phosphorus at a stable level until his renal function improved. CVVH can be used in conjunction with hemodialysis to successfully treat the hyperphosphatemia associated with tumor lysis syndrome.

125Iodine-iothalamate clearance in children. A simple method to measure glomerular filtration

Glomerular filtration rate (GFR) is the most widely used test to evaluate renal function. Several clearance markers have been used to measure GFR in adults. In children, however, a simple and reliable method to measure GFR is not available. Renal125iodine (I)-iothalamate clearance, after a single subcutaneous injection, is a simple and accurate test to measure GFR in adults. The validity of unlabelled iothalamate, as a marker for measurement of GFR in children, was reported recently. Unfortunately, the unlabelled iothalamate assay is arduous. We report our experience with a single subcutaneous injection of125I-iothalamate to measure GFR in normal children and those with renal disease. A weight-adjusted dosing regimen was adopted. This regimen resulted in sufficient above-background radioactivity in both blood and urine for reproducible measurement of GFR. Intra-test variability for GFR was not affected by the degree of renal insufficiency. The test was well tolerated with only 2 patients developing mild headache during the procedure. Our study showed that renal clearance of125I-iothalamate is reproducible, simple, and practical in healthy children and those with mild and advanced renal disease.

Reversible idiopathic acute renal failure in children with primary nephrotic syndrome.

We describe the clinical features of four pediatric patients (20 months to 10 years of age) in whom reversible idiopathic acute renal failure (RIARF) developed during the course of primary nephrotic syndrome (PNS). All patients had severe PNS and were in relapse at the onset of RIARF. This complication of PNS was preceded by primary peritonitis in three of four patients. Renal biopsy done in the early phases of RIARF showed tubular epithelial changes similar to those observed in acute tubular ischemia. All patients required dialysis. Recovery of renal function followed fluid removal in three of four patients. The RIARF lasted from 12 days to 1 year and was followed by complete recovery of renal function in all patients. We conclude that (1) RIARF is a potential complication in children with severe PNS, (2) RIARF is associated with primary ischemic renal tubular injury, and (3) recognition of the reversibility of this complication of PNS could alter long-term plans for management of renal failure in these patients.

Intracellular cystine loading causes proximal tubule respiratory dysfunction : effect of glycine

ABSTRACT: The present study examined proximal tubular respiration in control proximal tubules and proximal tubules loaded with cystine using 2 mmol/L cystine dimethyl ester. Basal oxygen consumption was significantly less in cystine-loaded tubules (20.6 ± 0.5 versus 12.1 ± 0.6 nmol O2·min-1·mg protein-1, p < 0.001). In the presence of 10-4 mol/L ouabain, an inhibitor of the NaK ATPase, oxygen consumption was 10.2 ± 0.7 nmol O2·min-1·mg protein-1 in control tubules and 11.4 ± 1.0 nmol O2·min-1·mg protein-1 in cystine-loaded tubules. Thus, proximal tubular intracellular cystine loading specifically inhibits oxygen metabolism directed toward transport. Compared with control proximal tubules, cystine-loaded proximal tubules also had a lower rate of O2 consumption when the cells were permeabilized to sodium with nystatin and when mitochondrial respiration was uncoupled. Glycine, an amino acid that is cytoprotective to hypoxic proximal tubule injury, ameliorated the repiratory dysfunction observed in cystine-loaded tubules.

Intracellular distribution of cystine in cystine-loaded proximal tubules.

ABSTRACT: Cellular cystine loading with cystine dimethyl ester has been shown to inhibit transport in proximal convoluted tubules perfused in vitro and decrease the rate of oxygen consumption in suspensions of proximal tubules. The present study was designed to examine the intracellular distribution of cystine in this model of the Fanconi syndrome of cystinosis and to determine whether cystine or its degradation product, cysteine, is the cytotoxic agent in cystine-loaded rabbit proximal tubules. Tubules were incubated with 2 mmol/L cystine dimethyl ester for 10 min at 37°C and subjected to cellular fractionation. The intralysosomal cystine content (272 ± 125 nmol/mg protein) was significantly higher than that measured in the nucleus (8.7 ± 2.0 nmol/mg protein) and cytosol (9.8 ± 4.0 nmol/mg protein (p < 0.05). Electron micrographs of tubules loaded with cystine depicted huge swollen lysosomes. To determine whether cystine or its breakdown product, cysteine, was the cytotoxic agent in tubules incubated with cystine dimethyl ester, the intracellular cystine and cysteine contents were measured and found to be 86.5 ± 14.8 and 5.7 ± 1.7 nmol/mg protein, respectively. These tubules had a 50% decrease in the rate of O2 consumption. To examine whether the increased level of intracellular cysteine played a role in this decrease in O2 consumption, we loaded tubules with 2 mmol/L cysteine methyl ester for 10 min. Despite an intracellular cysteine concentration of 59.6 ± 5.8 nmol/mg protein, cysteine-loaded tubules had a rate of O2 consumption equal to that measured in control tubules. Thus, intracellular cystine loading significantly increases intralysosomal cystine content. The inhibition of tubular respiration with cystine dimethyl ester is due to cystine rather than its degradation product, cysteine.

Thyroxine and nifedipine reduce the generation of reactive oxygen species in an vitro model of anoxia and reoxygenization 1648

Reactive oxygen species have been reported to cause injury to various tissues exposed to reperfusion. This experiment was designed to create an in vitro model of anoxia-reoxygenization using a proximal tubule suspension obtained from renal cortex of New Zealand rabbits. Proximal tubules subjected to 15 min of anoxia followed by 45 min of reoxygenizaton generated 1454± 298 cpm/ mg protein of superoxide anion (Lucigenin chemiluminescence) vs 56 ± 21 in control tubules not exposed to anoxia-reoxygenization(p< 0.001,n=8) and 181 ± 64 vs 28 ± 6 cpm/ mg protein of reactive oxygen species measured by luminol cemiluminescence method, respectively (p< 0.001,n=8). Some proximal tubules exposed to anoxia-reoxygenization were pretreated with thyroxine and nifedipine.(Table).