Metabolic Evaluations Research Articles

Acetazolamide Is an Effective Adjunct for Urinary Alkalization in Patients With Uric Acid and Cystine Stone Formation Recalcitrant to Potassium Citrate

Acetazolamide has been proposed as a treatment adjunct for patients with cystine and uric acid stone formation recalcitrant to standard alkalization therapy. We evaluated the effect of acetazolamide in urinary alkalization in patients with uric acid and cystine stone formation recalcitrant to potassium citrate alone. An institutional review board-approved, retrospective chart review identified 12 patients at 2 sites who had been prescribed acetazolamide as a treatment adjunct to potassium citrate for uric acid or cystine stones from 1997 to 2007. We evaluated the urine studies, metabolic evaluations, surgical interventions, and stone recurrence or growth. The mean follow-up was 46.1 months (range 11-86). Ten patients (83%) were categorized as compliant. Of the 2 patients excluded from the study, 1 was noncompliant with the medication, and the other was lost to follow-up. Of the 10 patients who were compliant with the treatment, 5 (50%) developed adverse effects from the medication requiring discontinuation. Of the remaining 5 patients (50%) who tolerated the medication and remained compliant, 3 (60%) were stone free at a mean follow-up of 42 months. Two patients continued to form stones, including one who developed calcification of an existing uric acid stone. Both patients required surgical intervention. The mean urinary pH before treatment was 5.9 (range 5-7) and after treatment was 7.2 (range 6.5-8.5; P = .001). Acetazolamide was effective in increasing the urinary pH in patients with uric acid and cystine stone formation who were already taking potassium citrate. Caution must be taken when prescribing acetazolamide, because it could be poorly tolerated and can induce calcium phosphate stone formation.

Urinary Metabolic Evaluations in Solitary and Recurrent Stone Forming Children

We have previously reported a high rate of urinary metabolic abnormalities in stone forming children compared to normal controls. At our institution a 24-hour urine evaluation is initiated after the first stone episode in children, to measure stone risk indices. The purpose of this study was to determine which children are at the greatest risk for recurrent stone formation. A retrospective cohort study was performed to assess urinary metabolic profiles in children with urolithiasis. In all patients 24-hour urine collections were performed and evaluated elsewhere. Urine chemistry assessments such as calcium and citrate were adjusted for creatinine and weight. Calcium oxalate supersaturation was measured. Patients were stratified as solitary or recurrent stone formers based on review of the medical record. Univariate analysis between means was performed with a 2-tailed t test. A total of 148 samples from 88 solitary stone formers and 84 samples from 51 recurrent stone formers were evaluated. Age and gender were well matched between the 2 groups. Timed urinary calcium levels referenced to creatinine and citrate were significantly higher in patients with recurrent stones. Supersaturation levels of calcium oxalate were higher in recurrent stone formers but did not reach statistical significance. There are significant differences in 24-hour urinary calcium levels between solitary and recurrent calcium stone forming children. A patient with increased urinary calcium indices on a 24-hour specimen may benefit from more aggressive initial dietary and pharmacological treatment to prevent stone recurrence.

Intellectual disability: definition, etiological factors, classification, diagnosis, treatment and prognosis

ETIOLOGY AND CLASSIFICATION: Causal factors related with cognitive disability are multiples and can be classified as follows: Genetic, acquired (congenital and developmental), environmental and sociocultural. Likewise, in relation to the classification, cognitive disability has as a common denominator a subnormal intellectual functioning level; nevertheless, the extent to which an individual is unable to face the demands established by society for the individuals age group has brought about four degrees of severity: Mild, moderate, severe and profound. The clinical history must put an emphasis on healthcare during the prenatal, perinatal and postnatal period and include the results of all previous studies, including a genealogical tree for at least three generations and an intentional search for family antecedents of mental delay, psychiatric illnesses and congenital abnormalities. The physical exam should focus on secondary abnormalities and congenital malformations, somatometric measurements and neurological and behavioral phenotype evaluations. If it is not feasible to establish a clinical diagnosis, it is necessary to conduct high-resolution cytogenetic studies in addition to metabolic clinical evaluations. In the next step, if no abnormal data are identified, submicroscopic chromosomal disorders are evaluated. Intellectual disability is not curable; and yet, the prognostic in general terms is good when using the emotional wellbeing of the individual as a parameter. Intellectual disability should be treated in a comprehensive manner. Nevertheless, currently, the fundamental task and perhaps the only one that applies is the detection of the limitation and abilities as a function of subjects age and expectations for the future, with the only goal being to provide the support necessary for each one of the dimensions or areas in which the persons life is expressed and exposed.

Urinary Reference Values for Stone Risk Factors in Children

Reference values for stone risk factors in 24-hour urine samples for nonstone forming children are limited. We measured urinary stone risk factors in healthy children 3 to 18 years old, and sought to determine whether the risk factors are affected by age. A total of 48 healthy subjects with no history of stone disease, endocrine abnormalities or urological surgery were recruited from the Naval Medical Center in San Diego. Subjects were then further divided into 4 age groups, each separated by 5 years. A single outpatient 24-hour urine sample was obtained and analyzed. Urine chemistries were adjusted for urinary creatinine and body weight. After excluding under collected samples 46 urine samples were analyzed. Urinary pH and volume decreased with increasing age, although the difference in pH did not reach statistical significance. Unadjusted urinary parameters failed to show statistical difference among the age groups. When adjusted for urinary creatinine and body weight all urinary parameters (calcium, oxalate, uric acid, citrate, magnesium, sodium, phosphorus and potassium) decreased with increasing age (statistically significant except for calcium). Stone risk factors in 24-hour urine samples decrease with increasing age in healthy, nonstone forming children. Normative data, derived by adjustment with urinary creatinine or body weight and stratified according to quintiles of age, should be useful in defining abnormal stone risk factors in children with stones.

Retinol binding protein 4, low birth weight-related insulin resistance and hormonal contraception

It has been recently reported that increased serum levels of retinol binding protein 4 (RBP4), a molecule secreted by adipocytes and liver, could be an early marker of insulin resistance (IR). We determined whether serum RBP4 was increased in low birth weight (LBW)-young women as a model of early-onset IR, through a historical prospective study. The study-population included 35 LBW and 35 born at term appropriate for gestational age (term AGA) young women. Metabolic evaluations included the composite-insulin sensitivity index (composite ISI). Serum RBP4 was measured with a competitive enzyme-linked immunosorbent assay (ELISA). RBP4 levels were similar in LBW and term AGA women, while composite ISI was significantly lower in the former group. With multivariate logistic regression analysis hormonal contraception (HC) use but not birth weight, diabetes in either parents and body mass index was significantly associated with higher RBP4 levels: odds ratio = 10.6; 95% confidence interval (CI) = 2.4-76.6. In spite of higher RBP4 levels in women under HC, composite ISI was similar in women with or without HC. Women under HC also exhibited significantly higher levels of sex hormone binding globulin (SHBG), triglycerides, cholesterol, and C-reactive protein (CRP), and all of them, but not composite ISI, were significantly correlated with RBP4 levels. In conclusion, RBP4 serum level was not a marker of IR but, for the first time, it is documented a sustained increase of serum RBP4 under HC. Pathophysiological and clinical significance of this novel finding requires further investigations.

Pharmacokinetic Drug‐Drug Interaction Potentials for Therapeutic Monoclonal Antibodies: Reality Check

A formal assessment of the drug-drug interaction potential of any investigational drug product often requires multiple metabolic and pharmacokinetic evaluations. In contrast to a small-molecule drug, investigating the drug-drug interaction potential of a monoclonal antibody is inherently complicated. High molecular weight monoclonal antibodies are often genetically engineered to demonstrate strong specificity for a particular human antigen target. Consequently, monoclonal antibodies usually have few clinically relevant animal models--other than nonhuman primates--in which to conduct appropriate nonclinical studies. Likewise, clinical drug-drug interaction studies of monoclonal antibodies with long elimination half-lives pose definite operational challenges as conventional crossover studies with adequate washout periods are difficult to conduct. Furthermore, the current regulatory guidance on the design and conduct of in vitro and in vivo drug-drug interaction studies applies more readily to small-molecule drugs than protein-based biologics. Nevertheless, a certain amount of clinically useful information has begun to emerge from the published literature on drug-drug interaction potentials of therapeutic monoclonal antibodies. This article provides a systematic review of the current literature and offers some practical considerations for the design and conduct of pharmacokinetic drug-drug interaction assessments involving novel monoclonal antibodies. Ideally, these evaluations should be performed throughout all stages of drug development. In particular, pharmacokinetic interaction studies with any marketed drugs that are likely to be coadministered with the monoclonal antibody will yield the most clinically useful information for practitioners and patients alike.

932: Urinary Metabolic Evaluations in Solitary and Recurrent Stone-Forming Children

You have accessJournal of UrologyModerated Poster 27, Monday, May 21, 2007, 1:00 - 3:00 pm1 Apr 2007932: Urinary Metabolic Evaluations in Solitary and Recurrent Stone-Forming Children William R. Defoor, Eugene Minevich, Elizabeth Jackson, Pramod Reddy, Curtis Clark, Curtis A. Sheldon, and John R. Asplin William R. DefoorWilliam R. Defoor More articles by this author , Eugene MinevichEugene Minevich More articles by this author , Elizabeth JacksonElizabeth Jackson More articles by this author , Pramod ReddyPramod Reddy More articles by this author , Curtis ClarkCurtis Clark More articles by this author , Curtis A. SheldonCurtis A. Sheldon More articles by this author , and John R. AsplinJohn R. Asplin More articles by this author View All Author Informationhttps://doi.org/10.1016/S0022-5347(18)31160-1AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookLinked InTwitterEmail "932: Urinary Metabolic Evaluations in Solitary and Recurrent Stone-Forming Children." The Journal of Urology, 177(4S), p. 309 © 2016 by American Urological AssociationFiguresReferencesRelatedDetails Volume 177Issue 4SApril 2007Page: 309 Advertisement Copyright & Permissions© 2016 by American Urological AssociationMetricsAuthor Information William R. Defoor More articles by this author Eugene Minevich More articles by this author Elizabeth Jackson More articles by this author Pramod Reddy More articles by this author Curtis Clark More articles by this author Curtis A. Sheldon More articles by this author John R. Asplin More articles by this author Expand All Advertisement PDF downloadLoading ...

Efficacy of Standard Diet Therapy for Patients with Urolithiasis

Purpose: To determine the effectiveness of standard diet therapy as a preventive measure against urinary stone recurrence, we compared the metabolic parameters before and after diet recommendation in the patients with urolithiasis. Materials and Methods: A total of 40 stone formers participated in this study and none of them had other metabolic disorders. The dietary recommendations for them included the following: large amounts of water and fruit juice, and restriction of animal protein, salt and oxalate-rich foods. Simplified metabolic evaluations were performed before and after the dietary therapy and compared using the Wilcoxon signed rank test and McNemar’s test. The urinary volume and creatinine differences between the two tests were also considered for determining the patients' compliance and appropriate 24-hour urine collection. Results: There was no significant change in the patients blood chemistry before and after the diet therapy. Among the urinary parameters, the excretion of citrate (p=0.005) was significantly increased, but the rest of the parameters remained unchanged. With respect to occurrence of urinary metabolic abnormalities, only the frequency of hypocitraturia showed a statistically significant decrease after diet therapy (p=0.039). The results concerning the changes in the urinary volume and creatinine level showed no difference before and after the therapy. Conclusions: The standard diet therapy applied to the patients with urolithiasis showed a favorable effect on the excretion of urinary citrate, which is an important protective factor against stone formation. However, we could not found any significant changes in the other urinary lithogenic parameters during this short-term evaluation. (Korean J Urol 2007;48: 608-614) 󰠏󰠏󰠏󰠏󰠏󰠏󰠏󰠏󰠏󰠏󰠏󰠏󰠏󰠏󰠏󰠏󰠏󰠏󰠏󰠏

Prolonged Rate-Corrected QT Interval and Other Electrocardiogram Abnormalities in Girls With Turner Syndrome

We recently reported that electrocardiographic abnormalities are common in adults with monosomy X (Turner syndrome), but this issue has not been investigated in girls with Turner syndrome. We analyzed electrocardiograms in 78 girls with Turner syndrome and 50 age-matched control girls. The girls with Turner syndrome had additional cardiac and metabolic evaluations. Girls with Turner syndrome were more likely to demonstrate > or = 1 electrocardiographic findings including right axis deviation, right ventricular hypertrophy, accelerated atrioventricular conduction, T-wave abnormalities, and a prolonged rate-corrected QT interval. The right-sided findings were associated with partial anomalous pulmonary venous connection, but the etiology of the other findings remains unknown. The rate-corrected QT interval was significantly longer in girls with Turner syndrome (431 +/- 22 vs 407 +/- 21 milliseconds). Twenty-eight girls with Turner syndrome but only 2 controls had a rate-corrected QT interval above the reference range. We found no correlation between body habitus, cardiac dimensions, or metabolic parameters and the rate-corrected QT interval duration in girls with Turner syndrome. Cardiac conduction and repolarization abnormalities seem to affect both young girls and adults with Turner syndrome equally, suggesting that electrophysiologic defects are intrinsic to the syndrome and indicating that electrocardiogram analysis should be included in evaluating and monitoring even the youngest patients with Turner syndrome. Attention to the rate-corrected QT interval is important, because some common medications may further prolong this interval and increase the risk of arrhythmias.

Urinary Metabolic Evaluations in Normal and Stone Forming Children

Urinary stone disease is relatively rare in children and urinary metabolic evaluations have been the standard in our practice. We have previously reported a high rate of urinary metabolic abnormalities in stone forming children. We compared urinary chemistry values in normal and stone forming children. A prospective study was performed to assess urinary metabolic profiles in children with no history or a family history of urinary calculi. The 24-hour urine collections were performed and evaluated at an outside central laboratory. Urine chemistry studies were adjusted for creatinine. The data were compared to those on a historical cohort of calcium stone forming children. A total of 58 samples from normal children and 142 from stone forming children were evaluated. Mean age was 10 years in normal children and 12 years in stone forming children. of the normal and stone forming children 45% and 51%, respectively, were female. Supersaturation levels of calcium oxalate as well as calcium to creatinine levels were significantly higher in children with stones. No data confounding by age or sex was identified by stratification. There are significant differences in urinary metabolic evaluations between normal and stone forming children. This may allow more precise treatment to prevent recurrent stone episodes. We continue to perform metabolic evaluations in all children with documented urolithiasis.

Testosterone effects on avian basal metabolic rate and aerobic performance: Facts and artefacts

We examined the effects of cage size and testosterone (T) levels on basal and peak metabolic rates (BMR and PMR, respectively) and on pectoral and leg muscle masses of male house sparrows ( Passer domesticus). Birds were housed either in small birdcages or in flight aviaries for at least 2 weeks prior to the initial metabolic evaluations. They were then implanted with either empty or T-filled silastic capsules and remeasured 5–6 weeks later. Birds treated with single T implants achieved breeding levels (4–6 ng/mL) and one group given double implants reached 10 ng/mL. There was no effect of T on BMR or PMR in any group studied, but there was an effect of caging. Caged birds showed significant reductions in PMR over the course of captivity, whereas PMR in aviary-housed birds were indistinguishable from their free-living counterparts. Testosterone treatment significantly increased leg muscle mass in caged birds, but had no effect on muscle mass in aviary-housed sparrows. We conclude that testosterone has no direct effect on sparrow metabolic rate or muscle mass, but may interact with cage conditions to produce indirect changes to these variables.

Hepatic Infantile Hemangioendothelioma with Unusual Manifestations

Hepatic Infantile Hemangioendothelioma with Unusual Manifestations

Épilepsies néonatales et erreurs innées du métabolisme

Metabolic disorders constitute an important cause of neurologic disease, including neonatal epilepsy. Epilepsy rarely dominates the clinical presentation, which is more frequently associated with other neurologic symptoms, such as hypotonia and/or vigilance disturbances. In most cases, epilepsy secondary to inherited metabolic disorders presents with polymorphic clinical and electrographic features that are difficult to classify into precise epileptic syndromes. However, specific types of seizures, such as myoclonic seizures or distinctive electroencephalographic patterns, such as suppression burst patterns, epileptic syndrome or early myoclonic encephalopathy, may suggest a specific metabolic disease. The aim of this article is to help clinicians in reviewing potential metabolic diagnoses and approaching metabolic evaluations.

Durability of the medical management of cystinuria.

Cystinuria is an autosomal recessive disorder of dibasic amino acid transport in the kidney that leads to an abundance of cystine in the urine. This molecule is poorly soluble in urine and it is prone to crystallization and stone formation at concentrations above 300 mg./l. Medical treatment in these patients has incorporated increasing urine volumes, alkalinization and thiol medications that decrease the availability of free cystine in urine. Despite a reasonable prognosis for reduced stone formation we and others have noted difficulties in patients complying with medical management recommendations. Therefore, we evaluated the durability of treatment success in our patients with cystinuria. A retrospective chart review was performed in all patients with cystinuria referred to the comprehensive kidney stone center at our institution for an 8-year period. Medical therapy, stone recurrence rates, compliance with medications and scheduled followup, and the results of metabolic evaluations via 24-hour urine collections were reviewed. The average concentrations of urinary cystine in initial and followup 24-hour samples were compared in patients compliant and noncompliant with medical treatment. In addition, each patient was mailed a 1-page questionnaire to assess the self-perception of medical compliance. We identified 26 patients with a mean age of 32 years at referral (range 13 to 67) who were followed an average of 38.2 months (range 6 to 83). Females represented 58% of those with cystinuria. Overall compliance with medical recommendations was poor with a short duration of success. Of the 26 patients followed at our stone center only 4 (15%) achieved and maintained therapeutic success, as defined by urine cystine less than 300 mg./l. An additional 11 patients (42%) achieved therapeutic success but subsequently had failure at an average of 16 months (range 6 to 27). Of these patients 7 (64%) regained therapeutic success at an average of 9.4 months (range 4 to 20). Five patients (19%) never achieved therapeutic success, while an additional 6 (23%) failed to present to followup appointments or provide subsequent 24-hour urine studies despite referral to a tertiary care center. Patient self-assessment of medical compliance was uniformly high regardless of physician perceptions or treatment results. CONCLUSIONS The durability of medically treating patients with cystinuria is limited with only a small percent able to achieve and maintain the goal of decreasing cystine below the saturation concentration. Greater physician vigilance in these complicated stone formers is required to achieve successful prophylactic management. Furthermore, these patients require better insight into the own disease to improve compliance.

RESULTS OF A PROSPECTIVE TRIAL TO COMPARE NORMAL URINE SUPERSATURATION IN CHILDREN AND ADULTS

Urinary stone disease is relatively rare in children but is often due to metabolic abnormalities. Urinary supersaturation (SS) indices have been suggested as more precise predictors of stone recurrence. We previously reported urinary metabolic evaluations in stone-forming children using adult references. We now assess normal SS values in children. A prospective trial was performed to assess urinary metabolic profiles in children with no personal or family history of urinary calculi. The 24-hour urine collections were performed and evaluated at an outside central laboratory. Urine chemistries were adjusted for urine creatinine. Urine pH and SS for calcium oxalate, calcium phosphate and uric acid were also assessed. The data were compared to a cohort of normal adults. A total of 168 samples from 168 adults (58% males) and 51 samples from 30 children (59% males) were evaluated. The mean age of the children was 8.8 years (range 5 to 18). Calcium oxalate SS was similar between children and adults, and urine pH was the major cause of differences seen in the calcium phosphate and uric acid SS indices. Children had a much higher excretion of calcium, oxalate and citrate when adjusted for creatinine. There are significant differences in the normal ranges of urine chemistries in children and adults. An understanding of normal supersaturation values may allow metabolic abnormalities in stone-forming children to be more precisely diagnosed and treated.

Simvastatin Improves Hyperandrogenism, Hyperandrogenemia, LH and Lipid Profile in Women With PCOS: A Randomized, Cross-over Study

Simvastatin Improves Hyperandrogenism, Hyperandrogenemia, LH and Lipid Profile in Women With PCOS: A Randomized, Cross-over Study

Metabolic abnormalities associated with weight loss during chemoirradiation of head-and-neck cancer

Weight loss caused by acute mucositis and dysphagia is common during concurrent chemoirradiation (chemo-RT) of head-and-neck (HN) cancer. The metabolic consequences of weight loss during chemo-RT were investigated. Ninety-six patients with locally advanced HN cancer were treated from 1995 to 2001 on protocols that consisted of 1 to 2 cycles of induction cisplatin/5-fluorouracil followed by irradiation (70 Gy over 7 weeks) concurrent with cisplatin (100 mg/m2 every 3 weeks). Body weights and metabolic evaluations were obtained before and during induction chemotherapy and chemo-RT. Greatest percent changes in weight and in the laboratory values were calculated for each phase of therapy. During induction chemotherapy, significant changes were found in BUN, BUN:creatinine ratio, HCO3, Mg, and albumin, but not in creatinine, Na, K, or weight. During chemo-RT, significant additional changes were observed in all parameters measured, including increases in BUN, creatinine, BUN: creatinine ratio, and HCO3 and decreases in Mg, albumin, Na, K, and weight. The magnitude of most of these changes was significantly greater during chemo-RT than during induction chemotherapy. During chemo-RT, 35% of the patients had more than 10% body weight loss and 6 patients had an increase in creatinine of more than 100%, including 5 patients with Grade 2 nephrotoxicity, all of whom had weight loss 10% or more. Significant correlations were found between weight loss and creatinine (p < 0.0001) or BUN (p = 0.0002) rises, but not with BUN:creatinine ratio or other metabolic changes. Age, gender, tobacco history, hypertension, and diabetes mellitus were not significant predictors of nephrotoxicity. Weight loss during cisplatin-containing chemo-RT was found to be associated with reduced kidney function. These findings do not establish cause-effect relationships; however, they highlight the importance of intensive supportive measures of nutrition and hydration beyond standard hydration during cisplatin administration. These intensive measures should be enacted before a 10% weight loss is reached.

METABOLIC RISK FACTORS AND THE IMPACT OF MEDICAL THERAPY ON THE MANAGEMENT OF NEPHROLITHIASIS IN OBESE PATIENTS

Previous studies have demonstrated that obesity can increase the risk of stone formation as well as recurrence rates of stone disease. Yet appropriate medical management can significantly decrease the risk of recurrent stone disease. Therefore, we analyzed our obese patient population, assessing the risk factors for stone formation and the impact of selective medical therapy on recurrent stone formation. A retrospective chart review was performed to identify obese patients with stone disease from our Stone Center. Metabolic risk factors for stones were identified as well as patient response to medical therapy. A similar analysis was performed on a group of age and sex matched nonobese stone formers. Of 1,021 patients 140 (14%) were identified as obese (body mass index greater than 30). Of these patients complete metabolic evaluations were available in 83 with an average followup of 2.3 years. The most common presenting metabolic abnormalities among these obese patients included gouty diathesis (54%), hypocitraturia (54%) and hyperuricosuria (43%), which presented at levels that were significantly higher than those of the nonobese stone formers (p <0.05). Stone analysis was available in 32 obese patients with 63% having uric acid calculi. After initiating treatment with selective medical therapy obese and nonobese patients demonstrated normalization of metabolic abnormalities, resulting in an average decrease in new stone formation from 1.75 to 0.15 new stones formed per patient per year in both groups. Obesity, as a result of dietary indiscretion, probable purine gluttony and possible type II diabetes, appears to have a significant role in recurrent stone formation. Appropriate metabolic evaluation, institution of medical therapy and dietary recommendations to decrease animal protein intake can significantly improve the risk of recurrent stone formation in these often difficult to treat patients.

P0267 HEPATIC VENO-OCCLUSIVE DISEASE AND HHV-7 IN BRUTON???S AGAMAGLOBULINEMIA.

Introduction: Hepatobiliary disease is a common complication in primary hypogammaglobulinemia. In Bruton’s X-linked Agammaglobulinemia (BtAg), hepatitis virus infections acquired via intravenous immunoglobulin (IVIg) have been associated with the development of liver disease that may require liver transplantation. Hepatic veno-occlusive disease (VOD) is most commonly seen in association with patients following bone marrow transplantation but is also described in the setting of toxins, chemotherapeutic agents, radiation therapy, and metabolic disorders. We report an interesting case of progressive cirrhosis in a patient with BtAg who following liver transplantation was found to have VOD in the explanted liver. Methods: A 14 year old male with a history of BtAg was transferred to The Children’s Hospital in Denver, Colorado for evaluation of a two month history of cirrhosis, portal hypertension, and progressive ascites. BtAg was diagnosed in infancy and had been managed with monthly IVIg infusions. Two months prior to his transfer, he developed nausea, vomiting, fatigue and intermittent fevers. He was noted to have mildly elevated AST and ALT, and his clinical picture progressed to include jaundice and ascites. Protime was 25.4 seconds with an INR of 2.75. He underwent an extensive evaluation which included negative PCR testing for viral infections including hepatitis A, B, C, and E, EBV, CMV, parvovirus, enterovirus and adenovirus as well as negative metabolic and anatomic evaluations. Blood for human herpes virus 7 (HHV7) PCR was positive. Despite aggressive management, he developed intractable ascites and liver failure and underwent liver transplantation. Results: Evaluation of the explanted liver revealed advanced veno-occlusive lesions, including sinusoidal congestion, intimal fibroplasia, obliteration and recanalization of central venous lumina, and hepatocyte necrosis. There was an absence of giant cells, but portal inflammation and fibrosis were present, suggesting a possible infectious etiology. The patient is doing well fourteen months after liver transplantation on cyclosporin-based immunosuppression. Conclusion: This case demonstrates an interesting presentation in a boy with BtAg of subacute liver failure caused by hepatic VOD with HHV7 PCR positivity. Presumably the HHV7 was acquired through IVIg infusions. This unique case extends the spectrum of hepatic VOD and raises the possibility that HHV7 could be a hepatic pathogen in immunocompromised children.

Metabolic abnormalities associated with renal calculi in patients with horseshoe kidneys.

Horseshoe kidneys are a complex anatomic variant of fused kidneys, with a 20% reported incidence of associated calculi. Anatomic causes such as high insertion of the ureter on the renal pelvis and obstruction of the ureteropelvic junction are thought to contribute to stone formation via impaired drainage, with urinary stasis, and an increased incidence of infection. In this multi-institutional study, we evaluated whether metabolic factors contributed to stone development in patients with horseshoe kidneys. A retrospective review of 37 patients with horseshoe kidneys was performed to determine if these patients had metabolic derangements that might have contributed to calculus formation. Stone compositions as well as 24-hour urine collections were examined. Specific data points of interest were total urine volume; urine pH; urine concentrations of calcium, sodium, uric acid, oxalate, and citrate; and number of abnormalities per patient per 24-hour urine collection. These data were compared with those of a group of 13 patients with stones in caliceal diverticula as well as 24 age-, race-, and sex-matched controls with stones in anatomically normal kidneys. Eleven (9 men and 2 women) of the 37 patients (30%) with renal calculi in horseshoe kidneys had complete metabolic evaluations available for review. All patients were noted to have at least one abnormality, with an average of 2.68 abnormalities per 24-hour urine collection (range 1-4). One patient had primary hyperparathyroidism and underwent a parathyroidectomy. Low urine volumes were noted in eight patients on at least one of the two specimens (range 350-1640 mL/day). Hypercalciuria, hyperoxaluria, hyperuricosuria, and hypocitraturia were noted in seven, three, six, and six patients, respectively. No patients were found to have gouty diathesis or developed cystine stones. Comparative metabolic analyses of patients with renal calculi in caliceal diverticula or normal kidneys revealed a distinct profile in patients with horseshoe kidneys, with a higher incidence of hypocitraturia. All patients with renal calculi in horseshoe kidneys were noted to have metabolic abnormalities predisposing to stone formation. In this initial series of 11 patients, hypovolemia, hypercalcuria and hypocitraturia were most common metabolic defects. These findings suggest that metabolic derangements play a role in stone formation in patients with a horseshoe kidney. Patients with calculi in anatomically abnormal kidneys should be considered for a metabolic evaluation to identify their stone-forming risk factors in order to initiate preventative selective medical therapy and reduce the risk of recurrent calculus formation.