Increased intracranial pressure in a patient with Congenital Heart Defect and Ectodermal Dysplasia (CHDED): Extension of phenotype and review of literature.

Congenital heart defect (CHD) is a birth defect that affects the structure of the heart. Although CHD is often multifactorial, it can also be inherited as part of a Mendelian disorder such as in congenital heart defect and ectodermal dysplasia (CHDED). This disorder is caused by de novo variants in PRKD1. Here, we describe a patient with a novel de novo variant of PRKD1 with phenotypic features consistent with CHDED. Previously unreported features were noted including high intracranial pressure (ICP), partial anomalous pulmonary venous return (PAPVR), and bifid uvula. We suggest that these features may be associated with CHDED.

Acadian variant of Fanconi syndrome is caused by mitochondrial respiratory chain complex I deficiency due to a non-coding mutation in complex I assembly factor NDUFAF6.

The Acadian variant of Fanconi Syndrome refers to a specific condition characterized by generalized proximal tubular dysfunction from birth, slowly progressive chronic kidney disease and pulmonary interstitial fibrosis. This condition occurs only in Acadians, a founder population in Nova Scotia, Canada. The genetic and molecular basis of this disease is unknown. We carried out whole exome and genome sequencing and found that nine affected individuals were homozygous for the ultra-rare non-coding variant chr8:96046914 T > C; rs575462405, whereas 13 healthy siblings were either heterozygotes or lacked the mutant allele. This variant is located in intron 2 of NDUFAF6 (NM_152416.3; c.298-768 T > C), 37 base pairs upstream from an alternative splicing variant in NDUFAF6 chr8:96046951 A > G; rs74395342 (c.298-731 A > G). NDUFAF6 encodes NADH:ubiquinone oxidoreductase complex assembly factor 6, also known as C8ORF38. We found that rs575462405-either alone or in combination with rs74395342-affects splicing and synthesis of NDUFAF6 isoforms. Affected kidney and lung showed specific loss of the mitochondria-located NDUFAF6 isoform and ultrastructural characteristics of mitochondrial dysfunction. Accordingly, affected tissues had defects in mitochondrial respiration and complex I biogenesis that were corrected with NDUFAF6 cDNA transfection. Our results demonstrate that the Acadian variant of Fanconi Syndrome results from mitochondrial respiratory chain complex I deficiency. This information may be used in the diagnosis and prevention of this disease in individuals and families of Acadian descent and broadens the spectrum of the clinical presentation of mitochondrial diseases, respiratory chain defects and defects of complex I specifically.

Natural killer cell response to BK virus infection in polyoma virus-associated nephropathy of renal transplant recipients.

The mechanisms of injury and advantage secured by opportunistic infection with polyoma virus in renal transplant patients are not completely known. Patient virus-specific T cells play a large role in elimination of reactivated polyoma virus. Natural killer (NK) cells are early responders in antiviral response. Inflammatory NK-cell antiviral responses involve activation receptors such as killer-cell immunoglobulin-like receptors (KIRs) interacting with host-cell major histocompatibility complex class I molecules, altering cell sensitivity to lysis by NK cells.

A novel rearrangement of occludin causes brain calcification and renal dysfunction.

Pediatric intracranial calcification may be caused by inherited or acquired factors. We describe the identification of a novel rearrangement in which a downstream pseudogene translocates into exon 9 of OCLN, resulting in band-like brain calcification and advanced chronic kidney disease in early childhood. SNP genotyping and read-depth variation from whole exome sequencing initially pointed to a mutation in the OCLN gene. The high degree of identity between OCLN and two pseudogenes required a combination of multiplex ligation-dependent probe amplification, PCR, and Sanger sequencing to identify the genomic rearrangement that was the underlying genetic cause of the disease. Mutations in exon 3, or at the 5-6 intron splice site, of OCLN have been reported to cause brain calcification and polymicrogyria with no evidence of extra-cranial phenotypes. Of the OCLN splice variants described, all make use of exon 9, while OCLN variants that use exons 3, 5, and 6 are tissue specific. The genetic rearrangement we identified in exon 9 provides a plausible explanation for the expanded clinical phenotype observed in our individuals. Furthermore, the lack of polymicrogyria associated with the rearrangement of OCLN in our patients extends the range of cranial defects that can be observed due to OCLN mutations.

Oral Losartan After Limited Mandibulectomy for Treatment of Desmoid-Type Fibromatosis.

Desmoid-type fibromatosis (DF) is a rare soft tissue lesion with an annual incidence of 2 to 4 per million population and peak incidence occurring at approximately 4.5 years of age. While benign, the tumor has a locally aggressive infiltrative growth pattern and a high rate of recurrence. Given the functional and aesthetic implications of excision and reconstruction in the facial skeleton, novel medical treatment options are highly desirable. We describe the case of a 3-year-old boy who presented with an enlarging, asymptomatic mass involving the left mandible. Biopsy revealed an immunohistochemical profile consistent with DF. Despite the high likelihood of recurrence, conservative, mandible-sparing en bloc resection and limited mandibulectomy were performed. Pathological and immunohistochemical analysis of the resection specimen revealed DF with grossly positive margins and elevated expression of angiotensin II type 1 receptor. Postoperative medical treatment with the angiotensin receptor blocker losartan was initiated. The patient remains medically stable and disease progression-free on repeat imaging at 20 months post-resection. We describe for the first time the successful use of the angiotensin blocker losartan following conservative surgery for management of DF.

Optimal Sequencing of Deceased Donor and Live Donor Kidney Transplant Among Pediatric Patients With Kidney Failure.

Importance: In the US, live donor (LD) kidney transplant rates have decreased in pediatric recipients. Pediatric patients with kidney failure will likely need more than 1 kidney transplant during their lifetime, but the optimal sequence of transplant (ie, deceased donor [DD] followed by LD or vice versa) is not known. Objective: To determine whether pediatric recipients should first receive a DD allograft followed by an LD allograft (DD-LD sequence) or an LD allograft followed by a DD allograft (LD-DD sequence). Design, Setting, and Participants: This decision analytical model examined US pediatric patients with kidney failure included in the US Renal Data System 2019 Report who were waiting for a kidney transplant, received a transplant, or experienced graft failure. Interventions: Kidney transplant sequences of LD-DD vs DD-LD. Main Outcomes and Measures: Difference in projected life-years between the 2 sequence options. Results: Among patients included in the analysis, the LD-DD sequence provided more net life-years in those 5 years of age (1.82 [95% CI, 0.87-2.77]) and 20 years of age (2.23 [95% CI, 1.31-3.15]) compared with the DD-LD sequence. The net outcomes in patients 10 years of age (0.36 [95% CI, -0.51 to 1.23] additional life-years) and 15 years of age (0.64 [95% CI, -0.15 to 1.39] additional life-years) were not significantly different. However, for those aged 10 years, an LD-DD sequence was favored if eligibility for a second transplant was low (2.09 [95% CI, 1.20-2.98] additional life-years) or if the LD was no longer available (2.32 [95% CI, 1.52-3.12] additional life-years). For those aged 15 years, the LD-DD sequence was favored if the eligibility for a second transplant was low (1.84 [95% CI, 0.96-2.72] additional life-years) or if the LD was no longer available (2.49 [95% CI, 1.77-3.27] additional life-years). Access to multiple DD transplants did not compensate for missing the LD opportunity. Conclusions and Relevance: These findings suggest that the decreased use of LD kidney transplants in pediatric recipients during the past 2 decades should be scrutinized. Given the uncertainty of future recipient eligibility for retransplant and future availability of an LD transplant, the LD-DD sequence is likely the better option. This strategy of an LD transplant first would not only benefit pediatric recipients but allow DD kidneys to be used by others who do not have an LD option.

Canadian Society of Nephrology Commentary on the Kidney Disease Improving Global Outcomes 2017 Clinical Practice Guideline Update for the Diagnosis, Evaluation, Prevention, and Treatment of Chronic Kidney Disease-Mineral and Bone Disorder.

PURPOSE OF REVIEW: (1) To provide commentary on the 2017 update to the Kidney Disease Improving Global Outcomes (KDIGO) 2017 Clinical Practice Guideline Update for the Diagnosis, Evaluation, Prevention, and Treatment of Chronic Kidney Disease-Mineral and Bone Disorder (CKD-MBD); (2) to apply the evidence-based guideline update for implementation within the Canadian health care system; (3) to provide comment on the care of children with chronic kidney disease (CKD); and (4) to identify research priorities for Canadian patients. SOURCES OF INFORMATION: The KDIGO 2017 Clinical Practice Guideline Update for the Diagnosis, Evaluation, Prevention, and Treatment of CKD-MBD. METHODS: The commentary committee co-chairs selected potential members based on their knowledge of the Canadian kidney community, aiming for wide representation from relevant disciplines, academic and community centers, and different geographical regions. KEY FINDINGS: We agreed with many of the recommendations in the clinical practice guideline on the diagnosis, evaluation, prevention, and treatment of CKD-MBD. However, based on the uncommon occurrence of abnormalities in calcium and phosphate and the low likelihood of severe abnormalities in parathyroid hormone (PTH), we recommend against screening and monitoring levels of calcium, phosphate, PTH, and alkaline phosphatase in adults with CKD G3. We suggest and recommend monitoring these parameters in adults with CKD G4 and G5, respectively. In children, we agree that monitoring for CKD-MBD should begin in CKD G2, but we suggest measuring ionized calcium, rather than total calcium or calcium adjusted for albumin. With regard to vitamin D, we suggest against routine screening for vitamin D deficiency in adults with CKD G3-G5 and G1T-G5T and suggest following population health recommendations for adequate vitamin D intake. We recommend that the measurement and management of bone mineral density (BMD) be according to general population guidelines in CKD G3 and G3T, but we suggest against routine BMD testing in CKD G4-G5, CKD G4T-5T, and in children with CKD. Based on insufficient data, we also recommend against routine bone biopsy in clinical practice for adults with CKD or CKD-T, or in children with CKD, although we consider it an important research tool. LIMITATIONS: The committee relied on the evidence summaries produced by KDIGO. The CSN committee did not replicate or update the systematic reviews.

JUSTIFICATION: (1) Commenter les recommandations du KDIGO 2017 (Kidney Disease Improving Global Outcomes) sur les bonnes pratiques cliniques pour le diagnostic, l'évaluation et le traitement des troubles du métabolisme minéral osseux associés aux maladies rénales chroniques (TMO-MRC); (2) appliquer les lignes directrices actualisées et fondées sur les données probantes en vue de leur mise en œuvre dans le système de soins de santé canadien; (3) commenter les soins prodigués aux enfants atteints d'insuffisance rénale chronique (IRC) et (4) définir les priorités de recherche des patients Canadiens. SOURCES: Les recommandations du KDIGO 2017 (Kidney Disease Improving Global Outcomes) sur les bonnes pratiques cliniques pour le diagnostic, l'évaluation et le traitement des troubles du métabolisme minéral osseux associés aux maladies rénales chroniques (TMO-MRC). MÉTHODOLOGIE: Les coprésidents du comité ont sélectionné les membres potentiels sur la base de leur connaissance du secteur de la santé rénale au Canada, tout en visant une bonne représentation de toutes les disciplines concernées, des centres universitaires et communautaires et des différentes régions géographiques. PRINCIPAUX COMMENTAIRES: Nous approuvons un grand nombre des recommandations du KDIGO. Cependant, compte tenu de la rareté des anomalies du calcium et du phosphate et de la faible probabilité d'anomalies graves de la PTH (hormone parathyroïde), nous déconseillons le dépistage et la surveillance des taux de calcium, de phosphate, de PTH et de phosphatase alcaline chez les adultes atteints d'IRC de stade G3. Nous suggérons de mesurer ces paramètres chez les adultes de stade G4 et nous le recommandons pour les patients de stade G5. Chez les enfants, nous appuyons la recommandation de commencer la surveillance des TMO-MRC dès le stade G2, mais nous suggérons de mesurer le calcium ionisé plutôt que les taux de calcium total ou de calcium corrigé en fonction de l'albumine. En ce qui concerne la vitamine D, nous déconseillons le dépistage de routine des carences chez les adultes atteints d'IRC de stade G3 à G5 et G1T à G5T; nous suggérons plutôt de suivre les recommandations visant la population générale pour un apport adéquat en vitamine D. Nous recommandons que la mesure et la prise en charge de la densité minérale osseuse (DMO) se fassent en suivant les recommandations pour la population générale chez les adultes atteints d'IRC de stade G3 et G3T, mais nous déconseillons les tests de DMO de routine chez les adultes de stades G4-G5 et G4T-G5T, de même que chez les enfants atteints d'IRC. En raison de données insuffisantes, nous déconseillons également la pratique systématique d'une biopsie osseuse chez les adultes atteints d'IRC ou d'IRC-TMO, ainsi que chez les enfants atteints d'IRC, bien que nous la considérions comme un important outil de recherche. LIMITES: Le comité s'est appuyé sur le résumé des preuves rédigé par le KDIGO. Le comité de la SCN n'a pas reproduit ou mis à jour les revues systématiques.

The pesticide adjuvant, Toximul, alters hepatic metabolism through effects on downstream targets of PPARalpha.

Previous studies demonstrated that chronic dermal exposure to the pesticide adjuvant (surfactant), Toximul (Tox), has significant detrimental effects on hepatic lipid metabolism. This study demonstrated that young mice dermally exposed to Tox for 12 days have significant increases in expression of peroxisomal acyl-CoA oxidase (mRNA and protein), bifunctional enzyme (mRNA) and thiolase (mRNA), as well as the P450 oxidizing enzymes Cyp4A10 and Cyp4A14 (mRNA and protein). Tox produced a similar pattern of increases in wild type adult female mice but did not induce these responses in PPARalpha-null mice. These data support the hypothesis that Tox, a heterogeneous blend of nonionic and anionic surfactants, modulates hepatic metabolism at least in part through activation of PPARalpha. Notably, all three groups of Tox-treated mice had increased relative liver weights due to significant accumulation of lipid. This could be endogenous in nature and/or a component(s) of Tox or a metabolite thereof. The ability of Tox and other hydrocarbon pollutants to induce fatty liver despite being PPARalpha agonists indicates a novel consequence of exposure to this class of chemicals, and may provide a new understanding of fatty liver in populations with industrial exposure.

Two formulations of the agricultural pesticide adjuvant, Toximul, reduce the glycogen content of HepG2 cells.

Young mice exposed dermally to the Toximul (Tox) class of agricultural pesticide adjuvants have reduced levels of hepatic glycogen, a marker of subclinical toxicity. The present study determined whether these effects on glycogen also occurred in cultured HepG2 cells. Exposure (3 hr) to Tox resulted in significant, concentration-dependent glycogen reductions (up to 70%) relative to control values (76 +/- 3 microg glycogen/mg protein). These reductions did not appear to be due to loss of cell viability, and were reversible with Tox removal. Two different formulations of Tox (3409F and MP-A) differed significantly in the magnitudes of glycogen reduction in the HepG2 cells.

Paradoxical cyclosporine A requirements in pediatric renal transplants receiving high-dose steroids.

The potent immunosuppressant cyclosporine A (CyA) is a mainstay of treatment in the renal transplant population. During episodes of acute allograft rejection, therapy also includes the pulse administration of high-dose steroids such as prednisone or methylprednisolone. Both steroids and CyA are metabolized by the CYP3A4 isoenzyme of the cytochrome P450 catalytic system. On a theoretical basis, high steroid concentrations during a rejection episode could competitively inhibit CyA metabolism, increasing its systemic concentration and decreasing its dose requirements. A database was compiled consisting of pediatric patients who had undergone an acute renal rejection event during the years 1993 to 2003. The severity of rejection events, as well as the CyA and prednisone dosing regimens used during rejection, were assessed using a comprehensive chart analysis. The presence or absence of additional medications that could potentially interact with CyA was also examined. Although some patients responded in the predicted manner, the authors also found that a subgroup of pediatric patients placed on highdose pulse steroid therapy for acute graft rejection required increased amounts of CyA to maintain therapeutic concentrations. The authors recommend monitoring of patients on high-dose steroids for paradoxical CyA requirements intermittently during high-dose steroid treatment to individualize CyA therapy appropriately during renal allograft rejection and thereby maximize efficacy while minimizing potential toxic side effects of CyA such as under-immunosuppression and organ rejection.

Phenotypic heterogeneity in pediatric autosomal dominant polycystic kidney disease at first presentation: a single-center, 20-year review.

BACKGROUND: The presentation of autosomal dominant polycystic kidney disease (ADPKD) in childhood provides an insight into comorbidities and potential areas for interventions and investigation. METHODS: Phenotypic heterogeneity at the time of first presentation was studied with respect to age of diagnosis, mode of presentation, parental inheritance pattern, renal function, associated hypertension, and hyperlipidemia. Fifty-five children (median age of presentation, 8.7 years; 27% < 1 year) with ADPKD from 44 families followed up between March 1983 and March 2003 were reviewed. The diagnosis was based on family history and ultrasound confirmation of cysts. Progression of renal disease was followed over the study period (mean duration of follow-up, 4.9 years). RESULTS: A family history of ADPKD was known at presentation in 89%, which precipitated the screening diagnostic imaging in 59% of these children. Maternal inheritance was displayed in 51%, whereas 5% had no known family history of ADPKD. Bilateral renal findings were present in 78%. Hypertension (>95(th) percentile for age) was present in 22%, and hyperlipidemia was present in 54%. Renal function was not significantly diminished in 98% of patients with creatinine clearance > or =3rd percentile for age, and 7% had persistent proteinuria (>150 mg/d). No subjects had hepatic, splenic, or pancreatic cysts on ultrasound scan. A subpopulation of 10 patients had features of ADPKD dating back to prenatal ultrasound scans. All prenatal cases were characterized by bilateral renal findings, 90% had a known family history of ADPKD at the time of presentation, and 89% of these patients displayed maternal inheritance. Follow-up studies showed a persistence of hyperlipidemia despite pharmacotherapeutic treatment of hypertension, infrequent proteinuria, and sustained renal function in most patients. CONCLUSION: The results of this study show that many children at the time of first presentation have a significant prevalence of modifiable risk factors: hypertension, proteinuria, and hyperlipidemia, in the face of normal renal function. The results also show a unique presentation existing in prenatal subjects.

Effects of insulin-like growth factor-type 1 on weight gain and hepatic glycogen during early development in a surfactant/virus mouse model of acute liver failure: correlation with mortality.

Acute liver failure (ALF) was reproduced in young mice exposed daily for 12 days to the industrial surfactant, Toximul 3409F (Tox), and infected on postnatal day (P) 14 with sublethal doses of mouse-adapted human influenza B (Lee) virus (FluB). Combined Tox + FluB treatment potentiated mortality due to non-necrotic ALF. This study tested the hypothesis that mortality would decline if the known losses in energy production due to compromised fatty-acid beta-oxidation were compensated by pharmacological manipulation of hepatic glycogen stores. Glycogen levels, body weights, and mortality were determined without and with injections of insulin-like growth factor-1 (IGF-1). On P25, 13 days after Tox exposure ceased, glycogen levels (mg/100mg) were: 4.0 (control), 1.7 (Tox), 4.3 (FluB), and 2.9 (Tox + FluB). Corresponding cumulative mortalities were 0, 14, 2, and 38%. Following daily IGF-1 injections from P12 to P17, liver glycogen levels on P25 were: 3.5 (IGF-1), 3.9 (IGF-1 + Tox), 12.3 (IGF-1 + FluB), and 5.6 (IGF-1 + Tox + FluB). Unexpectedly, IGF-1 treatment increased mortality to 67% (IGF-1), 89% (IGF-1 + Tox), 63% (IGF-1 + FluB), and 81% (IGF-1 + Tox + FluB). For all groups there was a significant correlation between mortality and poor weight gain. This is the first report of persistent glycogen reductions after surfactant exposure and withdrawal. Their role in potentiating FluB-induced mortality remains to be established.

BK virus infection, replication, and diseases in pediatric kidney transplantation.

Polyomavirus-associated nephropathy is diagnosed in 2-8% of pediatric renal transplants and often precedes renal allograft dysfunction. Without intervention, however, significant graft dysfunction is observed in more than 50% of cases, although progressive early graft loss is reported in only three of 32 (9%) of cases. No specific treatment is available, but early decrease in immunosuppression is followed by declining human polyomavirus type 1 (BK virus) replication and improved outcome. The data suggest differences between pediatric and adult kidney transplantation. Possibly, pediatric patients might be able to mount a more vigorous BK virus-specific immune response than adult patients under similar modulation of immunosuppression. Also the role of cidofovir and leflunomide is still unresolved in pediatric patients. Larger prospective trials are needed to better define the impact of BK virus immunity for replication and disease as well as the role of reducing immunosuppression with or without cidofovir or leflunomide in pediatric transplant patients.

Polyoma virus in pediatric renal transplantation.

Renal transplantation is the treatment of choice for children with end-stage renal disease. Patient survival and allograft survival have improved with better immunosuppressant regimes to reduce acute allograft rejection but post-transplant infections have been exacerbated. An emerging problematic virus in the past decade is the polyoma virus BKV. The features of BKV including the clinical features in the general and immune compromised population are reviewed and correlated with pediatric studies in the post-transplant population. These features are placed in context with lessons learned about BKV in relevant adult studies.

Brain cyclosporin A levels are determined by ontogenic regulation of mdr1a expression.

Cyclosporin A (CyA) toxicity is a common occurrence in pediatric organ transplant patients. We hypothesized that reduced mdr1a expression in newborn and developing mice would affect CyA accumulation within organs and/or toxicity. For functional studies, CyA was administered (5 mg kg(-1) i.p.) to 1-, 12-, and 19-day, and adult male and female mdr1a+/+ and mdr1a-/- mice. Peak blood CyA was lower in 1-, 12-, and 19-day-old (1000 ng ml(-1)) versus adult (1500 ng ml(-1)) mice but was similar in mdr1a+/+ and mdr1a-/- mice. Kidney mdr1a expression (measured by quantitative polymerase chain reaction) increased 2.5-fold in 19-day-old male and female mice and increased another 4-fold in adult females compared with adult males. Liver mdr1a expression increased 6-fold by day 12 compared with neonatal mice. Thereafter, maintenance of hepatic mdr1a expression in females and a reduction to neonatal levels in males was observed. Kidney/blood (8- to 9-fold) and liver/blood (12- to 15-fold) CyA levels were highest on days 12 and 19 and were not dependent on maturational changes in mdr1a mRNA levels. Adults had higher brain expression of mdr1a mRNA (3-fold), a corresponding 5-fold increase in immunodetectable P-glycoprotein, and 80% lower brain accumulation of CyA compared with 1-day-old mice. Conversely, in mdr1a-null mice, brain/blood CyA was similar in newborn and adult mice. A similar pattern was observed for the brain accumulation of the mdr1a substrate 3H-digoxin. We conclude that the risk for central nervous system drug toxicity could be higher in neonates or young children as a consequence of underdeveloped P-glycoprotein.

Pamidronate distribution in pediatric renal and rheumatologic patients.

OBJECTIVE: To evaluate the distribution and elimination of pamidronate in a population of pediatric patients with renal and rheumatologic disease. METHODS: Pamidronate whole blood levels were collected for the first 4 h after first exposure in 7 patients. The relationship between the rate of urinary excretion of pamidronate and bone formation or resorption was examined in 18 patients while receiving pamidronate at a total dose of 1 mg/kg/dose infused intravenously over a 4-h period. The urinary pamidronate clearances were correlated with renal function, calcium levels and measures of bone formation and resorption. RESULTS: Pamidronate levels reached steady state concentrations of 0.9-1.5 microg/ml within 30 min and the clearance of the drug (mean+/-SE) from blood was 180.0+/-64.2 ml/kg/h with an elimination half-life of less than 1 h. The mean urinary excretion of 31.5+/-2.2% of the administered dose indicated that about 68% of the drug was incorporated into bone, confirming the uptake of pamidronate into bone was similar in pediatric patients compared to that previously reported for adults. Bone specific alkaline phosphatase, which is a marker for bone growth and formation, had significant correlation with the uptake of pamidronate into bone (p=0.002). No correlation was demonstrated with a marker for bone resorption (urinary N-telopeptide/creatinine ratio), or with creatinine clearance or calciuria when assessed 2 months after treatment. CONCLUSION: Pamidronate at a dose of 1 mg/kg/dose every 2 months appears safe in the short term for pediatric patients, achieves relatively low whole blood pamidronate levels, and has similar skeletal uptake of pamidronate compared to adults.

Pamidronate treatment of pediatric fracture patients on chronic steroid therapy.

Pediatric nephrology and rheumatology patients with steroid-induced osteopenia are at risk of skeletal fracture. Bisphosphonate therapy has not been routinely advocated as a primary or secondary intervention for steroid-associated fractures in this population. This case control study evaluates the role of pamidronate therapy as a secondary fracture intervention. Children with symptomatic pathological fractures of the axial spine or ribs were treated with pamidronate 1 mg/kg/dose (n=17) IV at 60-day intervals for 1 yr (n=15) or 2 yr (n=2). Bone mineral density of L1-L4 (BMD) was assessed prior to treatment and at six-month intervals, and compared to 17 disease-age-gender-steroid dose-matched control patients. Alkaline phosphatase, calcium, phosphate, PTH, renal biochemistry, and 24-hr urine collections for CrCl, N-telopeptide/creatinine ratio, phosphate excretion, and calcium excretion were obtained every two months in the pamidronate population. Pamidronate caused a first exposure transient flu-like illness lasting <24 h in three patients and one patient had a new pathological fracture. No adverse events of hypocalcemia, allergic reaction or thrombophlebitis were noted. All patients reported improvement of skeletal pain. Despite ongoing steroid treatment, pamidronate significantly increased L1-L4 BMD Z-scores (mean+/-SE) relative to baseline (pamidronate vs control: 0-6 months: 0.27+/-0.14 vs -0.82+/-0.31; 0-12 months: 0.63+/-0.17 vs -0.46+/-0.27; 0-18 months: 0.55+/-0.32 vs 0.17+/-0.27; 0-24 months: 0.15+/-0.21 vs -0.23+/-0.22; 0-30 or 36 months: 0.77+/-0.71 vs -0.68+/-0.25) with repeated measures ANOVA assessment (F=11.27, p=0.0057). This study supports the safety and efficacy of pamidronate in steroid-induced fractures in pediatric nephrology and rheumatology patients.

Growth hormone therapy before and after pediatric renal transplant.

Children undergoing successful renal transplantation anticipate optimal growth and development. The use of rhGH pre- and post-Tx has been evaluated and supported by randomized control trials. Several strategies are required to maximize the potential benefit of this treatment in the renal population including provision of adequate nutrition intake, following bone parameters with appropriate interventions, and strategies to reduce steroid therapy including utilization of alternate day steroid treatment. Studies are required to further assess the impact of rhGH on renal allograft function, rejection risk, and allograft ultrastructural changes.