Deborah P. Jones

Rickets Secondary to Phosphate Depletion: A Sequela of Antacid Use in Infancy

Two infants presented with growth failure and were found to have generalized osteomalacia (rickets) due to phosphate depletion from prolonged administration of an aluminum-containing antacid given for the symptoms of colic. One of the infants developed bilateral proptosis due to craniosynostosis related to the underlying metabolic bone disease. The chronic use of aluminum-containing antacids in infants has potential risk for the growing skeleton and is not innocuous. Therefore, antacid therapy should be used in low doses and very cautiously, with routine monitoring of serum calcium and phosphorus in children taking medications which reduce gastrointestinal phosphate absorption.

Short-term outcomes of Thymoglobulin induction in pediatric renal transplant recipients

Abstract. No data are currently available that describe the clinical outcomes associated with Thymoglobulin (rabbit polyclonal anti-thymocyte globulin) induction in pediatric renal transplant recipients. We report the outcomes of 17 pediatric renal transplant recipients (mean age 10.1±5.2xa0years) transplanted between 1 August 1999 and 31 July 2001. Eleven patients (65%) were Caucasian and 6 (35%) were African-American. Eleven (65%) recipients received cadaveric allografts. Two patients (12%) were second allograft recipients. One patient had primary allograft non-function secondary to vascular thrombosis. Two patients (12%) had delayed allograft function. Immunosuppression consisted of Thymoglobulin induction (mean number of doses 6±1.7) with tacrolimus (62%) or cyclosporine A (38%), mycophenolate mofetil, and prednisone. One year post transplant, patient and graft survival was 100% and 93%, respectively. No acute rejection episodes occurred during the first 6xa0months after transplantation in any of the recipients. Additionally, no rejection episode occurred among the 14 patients followed for 1xa0year after transplant. The incidences of asymptomatic cytomegalovirus (CMV) and Epstein-Barr virus (EBV) seroconversion at 1xa0year in seronegative recipients with a seropositive donor were 100% of 4 patients and 0% of 4 patients, respectively. No symptomatic CMV or EBV infections and no post-transplant lymphoproliferative disease have occurred in any patient. These short-term data suggest that Thymogobulin induction is safe and effective in combination with triple immunosuppressive therapy for preventing early rejection in pediatric renal transplant recipients.

Acute Renal Failure Following Amoxicillin Overdose

Departments of 1 Pediatrics and 2Pathology, LeBonheur Children’s Medical Center and Center for Pharmacokinetics/Therapeutics, The Health Science Center, University of Tennessee College of Medicine, Memphis, Tennessee; 3Department of Pediatrics, Bryner Clinic, Intermountain Pediatric Adolescent Renal Disease Program; 4Texas Children’s Hospital, Houston, Texas; 5Department of Pediatrics, State University of New York at Buffalo, Children’s Hospital, Buffalo, New York

Characteristics of Taurine Transport in Cultured Renal Epithelial Cell Lines: Asymmetric Polarity of Proximal and Distal Cell Lines

Taurine transport was determined in two continuous, renal epithelial cell lines: LLC-PK1 derived from the proximal tubule of the pig, and the Madin-Darby canine kidney cell (MDCK) from the distal tubule of the dog. In LLC-PK1, taurine transport is maximal at the apical surface, whereas in MDCK cells, transport is greatest at the basolateral surface. Transport is highly dependent on both sodium and chloride in the external medium, and is specific for beta-amino acids. The apical and basolateral surfaces of both cell lines show an adaptive response to extracellular taurine concentration, but only the basolateral surface of the MDCK cell responds to hyperosomolality by increased taurine accumulation. Thus, differential control of the beta-amino acid transport system by substrate and external tonicity exists. The role of the beta-amino acid transport system may differ according to the origin of the cell: in the proximal renal tubular cell, net transepithelial reabsorption of filtered taurine increases the body pool. By contrast, taurine accumulation by distal tubular cells may form a mechanism of cell volume regulation in response to osmotic stress.

Regulation of Expression of Taurine Transport in Two Continuous Renal Epithelial Cell Lines and Inhibition of Taurine Transporter by a Site-Directed Antibody

UNLABELLEDnThe renal tubular epithelium adapts to changes in the sulfur amino acid composition of the diet, particularly in terms of reabsorption of taurine. The adaptive response is expressed by enhanced or decreased NaCl-dependent taurine transport by rat renal brush border membrane vesicles (BBMV). Taurine transport activity in two cultured renal epithelial cell lines (MDCK and LLC-PK1) is up- or down-regulated by extracellular taurine concentration as the result of reciprocal changes in the Vmax of the transporter. In MDCK cells, abundance of taurine transporter mRNA (pNCT mRNA) was up- or down-regulated after incubation in media containing 0, 50, or 500 microM taurine. Decreased mRNA was observed in both cell lines after 12 h, and it was appreciably reduced after 72 h exposure to 500 microM taurine. Northern blot analysis of mRNA from LLC-PK1 cells using pNCT cDNA as a riboprobe showed that two transcripts, 9.6 kb and 7.2 kb, were expressed; the abundance of mRNA was increased or decreased after incubation in taurine-free or high taurine medium, respectively. Down-regulation was observed primarily in the 7.2 kb transcript after 24 h incubation. Rapid up-regulation occurred in the 9.6 kb transcript within 12 h of transfer from high to low taurine. Nuclear run-off assays showed that the gene for pNCT is induced at the transcriptional level by taurine. Regulation of expression of the taurine transporter was also studied by injection of pNCT cRNA into Xenopus laevis oocytes. Expression of transport activity was significantly reduced (64%) when oocytes were incubated in 50 microM taurine as compared to 0 microM taurine. Transport activity was totally blocked when pNCT cRNA-injected oocytes were exposed to an active phorbol ester, PMA (10(-6) M). Inhibition of uptake was reversed by staurosporine, an inhibitor of protein kinase C activity. An inactive phorbol ester, 4 alpha-phorbol, had no effect on taurine transport. A polyclonal antibody directed a highly conserved intracellular segment between homologous transmembrane domains VI and VII inhibited taurine transport activity in both pNCT cRNA-injected oocytes and BBMV. Incubation of oocytes with 10 micrograms/ml antibody (Ab) reduced taurine uptake to 46% of control, and 20-80 micrograms/ml Ab reduced uptake to 20% of control. In BBMV, active taurine uptake (10 microM) was inhibited approximately 30% by 10 pg Ab/mg protein, whereas none specific IgG had no significant effect. Proline uptake (20 microM) by BBMV was not inhibited by the Ab, nor was GABA uptake (50 microM). Two pNCT proteins, approximately 70 kD and approximately 30 kD, were detected by Western blot, and the abundance of both was regulated by medium taurine.nnnIN CONCLUSIONn(i) regulation of taurine transport activity in LLC-PK1 cells by medium taurine occurs at a level of mRNA transcription; (ii) regulation of pNCT occurs at both transcriptional and translational levels; (iii) pNCT expression is regulated by protein kinase C-dependent phosphorylation; and (iv) the intracellular segment between domains VI and VII may be required for activation of the taurine transporter; this segment may function as a gate in taurine transport.

Urinary N-acetyl-beta-glucosaminidase as a screening technique for vesicoureteral reflux.

OBJECTIVEnTo determine if urinary N-acetyl-beta-glucosaminidase (NAG) assays could be applied as a screening test for early detection of vesicoureteral reflux.nnnMETHODSnTwo hundred eighty-eight urine samples from children undergoing voiding cystourethrography (VCU) for a variety of urologic problems were assayed for N-acetyl-beta-glucosaminidase using spectrophotofluorimeter techniques. Sample creatinine levels were also determined using an auto analyzer. The urinary NAG to creatinine ratio for each patient was then compared to their VCU results, which were interpreted independently of the assay values and graded according to the International Reflux Classification system. The NAG to creatinine ratios were then classified according to their grade of reflux, and the mean NAG levels, plus one standard deviation, were calculated for each as well as for the nonrefluxing controls. Statistical analysis was done with P values obtained by Students t-test.nnnRESULTSnA total of two hundred thirty-two specimens were evaluable with ninety (38.8%) samples collected from refluxing patients and one hundred forty-two (61.2%) samples from nonrefluxers. The NAG levels standardized to urine creatinine revealed a mean value among refluxers of 15.514 mumol/g creatinine. This compared with a mean value of 14.611 mumol/g creatinine in the nonrefluxing group, with the difference being insignificant. When the mean NAG levels were compared for each grade of reflux to the nonrefluxing controls, only grade V had a significant elevation (44.561 mumol/g creatinine) above the nonrefluxers (P = 0.0001).nnnCONCLUSIONSnWith the exception of grade V vesicoureteral reflux, urinary NAG levels do not reliably detect the presence of reflux and therefore cannot be accurately applied as a screening test for detection of this common urologic problem.

Regulation of Taurine Transport by External Taurine Concentration and Medium Osmolality in Renal Tubular Cells in Culture

Taurine is actively transported into the renal tubular cell by a Na+ — and Cl−-dependent system specific for this β-amino acid and structural analogs (14). The proximal epithelial transport system regulates the urinary excretion of taurine. Taurine transport is regulated by the dietary intake of taurine in the rat (1), by extracellular taurine concentration in kidney cells in culture (7), and by medium osmolality in MDCK cells (11). We have previously demonstrated that taurine transport in both MDCK and LLC-PK1 cells is increased following incubation of cell monolayers in taurine-free medium and in decreased following incubation of cells in high extracellular taurine (8). The LLC-PK1 is a porcine cell line of proximal tubular origin and the MDCK (Madin Darby Canine Kidney) cell line is from the collecting duct of the dog.

Genetics of Urolithiasis

Urolithiasis is a major worldwide health problem that primarily afflicts adults, although children are not immune from the disorder. In the United States, nearly 15% of adults suffer from urinary stones; in other geographic regions (i.e., Southeast Asia), urinary calculi are endemic and the incidence is even greater. In some patients, environmental factors, such as diet, climate, composition of drinking water, or fluid intake, may be responsible for the formation of urinary stones. On the other hand, a genetic basis of urolithiasis is present in many patients in whom no exogenous explanation for calculus formation is found. Certainly, a genetic basis for specific metabolic disorders that lead to urolithiasis, such as cystinuria and oxaluria, is well established. Few comprehensive reviews of the genetic basis of urolithiasis are available.

An unusual etiology of hypertension in a 5-year-old boy

Abstract. Ganglioneuromas are rare benign tumors of neural crest origin, arising from ganglia of the sympathetic nervous system and adrenal medulla. These masses are usually detected during the first 2xa0decades of life and are generally discovered incidentally. We present a 5-year-old boy with sickle β-thalassemia whose hypertension is caused by a perihilar ganglioneuroma encasing the right renal artery and distorting the right renal vein. The tumor was resected and the childs blood pressure subsequently normalized.