Risk of Acute Kidney Injury Following Contrast-enhanced CT in a Cohort of 10 407 Children and Adolescents.

Background Previous studies have challenged the concept of contrast material-induced acute kidney injury (AKI) in adults; however, limited data exist for children and adolescents. Purpose To calculate the incidence and determine the risks of AKI in patients who received intravenous iodinated contrast media for CT. Materials and Methods This retrospective study was performed at a children's hospital from January 2008 to January 2018 and included patients aged 0-17 years in whom serum creatinine levels were measured within 48 hours before and after CT with or without contrast media. The incidence of AKI was measured according to the AKI Network guidelines. A subgroup analysis with propensity score matching of cases with control patients was performed. Differences before and after stratification based on estimated glomerular filtration rate (eGFR) were explored. Adjusted risk models were developed using log-binomial generalized estimating equations to estimate relative risk (RR). Results From a total of 54 000 CT scans, 19 377 scans from 10 407 patients (median age, 8.5 years; IQR, 3-14; 5869 boys, 4538 girls) were included in the analysis. Incidence rate of AKI for the entire sample was 1.5%; it was 1.4% (123 of 8844) in the group that underwent contrast-enhanced CT and 1.6% (171 of 10 533) in the group that did not (P = .18). In the contrast-enhanced CT group, AKI incidence was higher in the group with eGFR of at least 60 mL/min/1.73 m2 and in the group with eGFR lower than 60 mL/min/1.73 m2 (1.3% and 8.5%, respectively; P < .001) compared with the noncontrast group (0.1% and 2.7%, respectively; P < .001). Age was found to be a protective factor against AKI, with an RR of 0.96 (95% CI: 0.94, 0.99; P = .01), and contrast media increased risk in the subgroup analysis, with an RR of 2.19 (95% CI: 1.11, 4.35; P = .02). Conclusion The overall incidence of acute kidney injury after contrast-enhanced CT in children and adolescents was very low, and exposure to contrast media did not increase the risk consistently for acute kidney injury among different groups and analyses. © RSNA, 2022 See also the editorial by McDonald in this issue.

Management of Lupus Nephritis in Children.

Lupus nephritis affects 50-75% of all children with systemic lupus erythematosus with a higher prevalence in Asians. It remains a major contributor to morbidity and mortality in childhood onset lupus. Proliferative lupus nephritis (class III and class IV) warrants aggressive treatment to prevent progression to end stage renal disease. Newer immunosuppressive agents available in the last decade offer more options to treat lupus nephritis. Despite guidelines from professional bodies, there remains a lack of consensus on the treatment of refractory disease and duration of maintenance therapy. We review the treatment options for pediatric patients with lupus nephritis based on studies and published guidelines in the last decade, and highlight opportunities for continued improvement in care.

Elucidation of the anticancer potential and tubulin isotype-specific interactions of ß-sitosterol.

Beta-sitosterol (ß-SITO), a phytosterol present in many edible vegetables, has been reported to possess antineoplastic properties and cancer treatment potential. We have shown previously that it binds at a unique site (the 'SITO-site') compared to the colchicine binding site at the interface of α- and ß-tubulin. In this study, we investigated the anticancer efficacy of ß-SITO against invasive breast carcinoma using MCF-7 cells. Since 'isotypes' of ß-tubulin show tissue-specific expression and many are associated with cancer drug resistance, using computer-assisted docking and atomistic molecular dynamic simulations, we also examined its binding interactions to all known isotypes of ß-tubulin in αß-tubulin dimer. ß-SITO inhibited MCF-7 cell viability by up to 50%, compared to vehicle-treated control cells. Indicating its antimetastatic potential, the phytosterol strongly inhibited cell migration. Immunofluorescence imaging of ß-SITO-treated MCF-7 cells exhibited disruption of the microtubules and chromosome organization. Far-UV circular dichroism spectra indicated loss of helical stability in tubulin when bound to ß-SITO. Docking and MD simulation studies, combined with MM-PBSA and MM-GBSA calculations revealed that ß-SITO preferentially binds with specific ß-tubulin isotypes (ßII and ßIII) in the αß-tubulin dimer. Both these ß-tubulin isotypes have been implicated in drug resistance against tubulin-targeted chemotherapeutics. Our data show the tubulin-targeted anticancer potential of ß-SITO, and its potential clinical utility against ßII and ßIII isotype-overexpressing neoplasms.

Acute Hypocalcemia and Metabolic Alkalosis in Children on Cation-Exchange Resin Therapy.

BACKGROUND: Sodium polystyrene sulfonate (SPS) is a chelating agent used for the treatment of hyperkalemia. SPS has a wide range of exchange capacity requiring close monitoring of serum electrolytes. We observed two patients who developed acute hypocalcemia and increased metabolic alkalosis after initiating SPS therapy. We report these cases to draw attention to the potential risk of this medication in pediatric patients. CASE DIAGNOSIS/TREATMENT: Two children with chronic kidney disease on dialysis were started on SPS for hyperkalemia. Within a week after initiation of the medication, both patients developed hypocalcemia on routine labs without overt clinical manifestations. The hypocalcemia was rapidly corrected with oral supplementation and discontinuation of SPS. CONCLUSIONS: Severe hypocalcemia can develop after SPS therapy. The metabolic alkalosis in these patients associated with the hypocalcemia put them at increased risk for complications. Hence, careful attention must be paid to the state of calcium metabolism in all patients receiving SPS. Often calcium supplementation is required to maintain normal calcium levels.

Effect of Intravenous Administration of Contrast Media on Serum Creatinine Levels in Neonates.

Purpose To assess the effect of intravenous contrast media on renal function in neonates. Materials and Methods Institutional review board approval was obtained with waiver of consent. Electronic health records from January 2011 to April 2013 were reviewed retrospectively. Measures of renal function were obtained in inpatient neonates who underwent magnetic resonance (MR) imaging or computed tomography (CT) and for whom serum creatinine (Cr) levels were obtained within 72 hours before imaging and at least one time after imaging (>1 day after administration of contrast material). A total of 140 neonates who received contrast material (59 who underwent CT with iohexol or iodixanol and 81 who underwent MR imaging with gadopentetate dimeglumine) were identified. These neonates were frequency matched according to sex, gestational and postnatal age, and preimaging serum Cr levels with neonates who underwent unenhanced MR imaging or CT. Cr levels and glomerular filtration rates (GFRs) were grouped according to when they were obtained (before imaging, 1-2 days after imaging, 3-5 days after imaging, 6-9 days after imaging, 10-45 days after imaging, and more than 45 days after imaging). Serum Cr levels and GFRs for each time period were compared between groups by using hierarchic regressions or χ2 or Fisher exact tests and with repeated-measures analysis of variance to compare groups on the rate of change in serum Cr levels and GFRs from before to after imaging. Results Cr levels decreased and GFRs increased in both groups from before to after imaging (CT group, P ≤ .01; MR imaging group, P ≤ .01). The neonates who underwent contrast material-enhanced imaging and the neonates who underwent unenhanced imaging showed similar serum Cr levels at all examined time periods. Groups also did not differ in the proportion of neonates with serum Cr levels higher than the reference range (>0.4 mg/dL) at any time point (iodine- [P > .12] or gadolinium-based [P > .13] contrast material). Similar findings were observed for GFRs. None of the neonates developed nephrogenic systemic fibrosis. Conclusion In the absence of known renal failure, neonates receiving standard inpatient care do not appear to be at increased risk for developing renal toxicity due to administration of intravenous iodine- and gadolinium-based contrast material. © RSNA, 2017.

An Atypical Presentation of a Male with Oral-Facial-Digital Syndrome Type 1 Related Ciliopathy.

Background. Oral-facial-digital syndrome type 1 (OFD1) is a rare condition with X-linked dominant inheritance caused by mutations in the Cxorf5 (OFD1) gene. This gene encodes the OFD1 protein located within centrosomes and basal bodies of primary cilia. Approximately 15-50% of patients with OFD1 progress to end-stage kidney disease following development of polycystic changes within the kidneys. This condition almost always causes intrauterine lethality in males. Description of Case Diagnosis and Treatment. A Caucasian male aged 9 years and 9 months presented with increased urinary frequency, increased thirst, and decreased appetite. Physical examination demonstrated short stature, hearing loss, photophobia, murmur, and hypogonadism. He had no other dysmorphic features. Laboratory results revealed anemia, renal insufficiency, and dilute urine with microscopic hematuria but no proteinuria. Ultrasound showed small kidneys with increased echogenicity but no evidence of cystic changes. A Ciliopathy Panel showed a novel and likely pathogenic deletion, approximately 7.9 kb, in the OFD1 gene encompassing exons 16, 17, and 19 (c.1654+833_2599+423del). Brain MRI did not demonstrate typical OFD1 findings. He is currently on chronic hemodialysis awaiting transplant from a living donor. Conclusions. We present a male patient with OFD1 mutation who lacks the classic OFD1 phenotype who presented with end-stage renal disease without evidence of polycystic changes within the kidneys.

A quality improvement initiative to increase pneumococcal vaccination coverage among children after kidney transplant.

Pneumococcal vaccination rates among children receiving a kidney transplant remain suboptimal. Current practice guidelines in the United States recommend giving the PPSV23 after priming with the PCV13. We conducted a QI initiative to increase pneumococcal vaccine rates in our kidney transplant recipients by developing an age-based vaccine algorithm, obtaining vaccine records, and generating reminders for patients and clinicians. A monthly report from the EHR tracked outcomes. The process metric was missed vaccine opportunities, and the overall objective was to improve coverage with both the PCV13 and PPSV23. Over the first six months, we increased the percentage of visits where the vaccine was given from a baseline of 4% to 33%. However, by the end of the 12-month period, the percentage of eligible visits where the vaccine was given decreased to 8.7%. Nevertheless, over the 12-month observation period, we were able to increase the percentage of transplant patients receiving the PCV13 and PPSV23 from 6% to 52%. Utilizing an age-based algorithm and the electronic medical record, vaccine champions can track both missed visit opportunities and the number of vaccinated patients to improve pneumococcal immunization coverage for these high-risk patients.

Claudin 19-based familial hypomagnesemia with hypercalciuria and nephrocalcinosis in a sibling pair.

BACKGROUND: Familial hypomagnesemia with hypercalciuria and nephrocalcinosis (FHHNC) is a rare, autosomal recessive condition caused by mutations in CLDN16 or CLDN19, which encode for tight junction proteins, claudin-16 and claudin-19, respectively. This condition often has a delayed diagnosis in patients with no prior family history due to a lack of specific clinical symptoms. Description of case, diagnosis, and treatment: A 4-year, 10-month-old Caucasian boy presented with failure to thrive, developmental delay, and ocular findings consisting of horizontal nystagmus, bilateral macular staphylomas, and high myopia. Laboratory studies revealed hypercalciuria, hypomagnesemia, and renal insufficiency. Renal ultrasound showed bilateral small kidneys with medullary nephrocalcinosis. Candidate gene sequencing performed at age 7 years identified a novel, homozygous, frameshift mutation c.140_141delAT (p.Tyr47Stop) within CLDN19, confirming the molecular diagnosis of FHHNC. Due to rapid renal progression, the proband underwent renal transplant at age 10 years, 10 months. FHHNC was prenatally diagnosed in the proband's sister, who was found at birth to have ocular findings and hypomagnesemia. In addition, she had feeding intolerance and persistent hypoglycemia with hyperinsulinism that has required chronic diazoxide therapy. CONCLUSIONS: Although rare, FHHNC should be suspected in patients who present with nephrocalcinosis in the setting of congenital eye anomalies..

Heart Retransplant Recipients Have Better Survival With Concurrent Kidney Transplant Than With Heart Retransplant Alone.

BACKGROUND: Heart retransplant (HRT) recipients represent a growing number of transplant patients. The impact of concurrent kidney transplants (KTs) in this population has not been well studied. We tested the hypothesis that recipients of HRT with concurrent KT (HRT-KT) would have worse survival than recipients of HRT alone. METHODS AND RESULTS: A retrospective analysis of the United Network of Organ Sharing database was performed for all patients undergoing HRT from 1987 to 2011. There were 1660 HRT patients, of which 116 (7%) received concurrent KT. Those who received HRT-KT had older age, longer wait-list time, worse kidney function, and more known diabetes. Survival among recipients of HRT-KT was significantly better than that of recipients of HRT alone (P=0.005). A subgroup of 323 HRT patients with severe kidney dysfunction (estimated glomerular filtration rate <30 mL/min per 1.73 m(2) or on dialysis) was studied in more detail, and 76 (24%) received concurrent KT. Those on dialysis at the time of HRT had better survival with versus without concurrent KT (P<0.0001). On multivariable analysis, concurrent KT was independently associated with better outcomes for all patients with HRT and for the subgroup of patients with severe kidney dysfunction. CONCLUSIONS: Recipients of HRT-KT have better survival than recipients of HRT alone. Further research is needed to determine which HRT patients may benefit the most from concurrent KT.

Probing differentiation in cancer cell lines by single-cell micro-Raman spectroscopy.

Single-cell micro-Raman spectroscopy has been applied to explore cell differentiation in single, live, and malignant cells from two tumor cell lines. The spectra of differentiated cells exhibit substantial enhancement primarily in the intensities of protein peaks with concomitant decrease in intensities of O−P−O asymmetric stretching peaks in DNA/RNA. Principal component analyses show that the spectral score of differentiated cells tends to asymptotically approach that of spectra obtained from normal neural stem cells/progenitors. This lends credence to the notion that the observed spectral changes are specific to differentiation, since upon differentiation, malignant cells become less malignant and tend toward benignity.

Preclinical model for identification of therapeutic targets for CML offers clues for handling imatinib resistance.

Success of imatinib in chronic myeloid leukemia (CML) therapy has undoubtedly proved utility of signalling molecules as therapeutic targets. However, development of imatinib resistance and progression to blastic crisis are the current challenges in clinics. To develop therapeutic alternatives for CML, understanding of signalling events downstream of bcr-abl might be helpful. Current CML cell lines do not give comprehensive picture of signalling events involved in pathogenesis of CML. Hence, there is a major unmet need for a better preclinical model for CML. Here, we report on development of RIN9815/bcr-abl, a novel cell line model that mimics signalling events in CML PMNL. Studies on crucial signalling molecules i.e., ras, rac, rhoA and actin in this cell line identified rhoA as the key regulator involved in CML cell function as well as proliferation of both, imatinib sensitive and resistant cells. Hence, RIN9815/bcr-abl could serve as the unique preclinical model in understanding pathogenesis of CML and in drug development.

Neonatal atypical hemolytic uremic syndrome from a factor H mutation treated with eculizumab.

BACKGROUND: Atypical hemolytic uremic syndrome (aHUS) results from an inherited dysregulation of the alternative complement pathway leading to thrombotic microangiopathy consisting of hemolytic anemia, thrombocytopenia, and renal injury. The complement inhibitor eculizumab is an approved treatment, but its reported use in neonates - who have an inherently high risk of infection - is limited. CASE DIAGNOSIS/TREATMENT: A 28-day-old female presented with gross hematuria and hypertension. aHUS was suspected based on anemia with schistocytes, thrombocytopenia, low C3, and acute kidney injury requiring peritoneal dialysis. A septic work-up initiated on day 2 for hypothermia and respiratory failure was negative. There was no improvement after 6 days of plasma therapy. Despite being < 6 weeks old she was vaccinated with pneumococcal-13 conjugate, meningococcal (groups C and Y) polysaccharide, and Haemophilus b tetanus toxoid conjugate vaccines and started on penicillin prophylaxis. After 1 dose of eculizumab 300 mg, dialysis was discontinued and her hematological parameters improved. Genetic testing revealed a complement factor H mutation. After 11 months of follow-up, she remains on eculizumab and penicillin without recurrence of aHUS or any infectious complications. CONCLUSIONS: Eculizumab is a safe and effective treatment option for aHUS even in neonates at high risk for infection.

Urinalysis interpretation for pediatricians.

CME EDUCATIONAL OBJECTIVES: 1.Cost-effectively evaluate microscopic hematuria and proteinuria.2.Recognize important conditions associated with isolated microscopic hematuria.3.Review important conditions associated with asymptomatic proteinuria.

RhoA: a therapeutic target for chronic myeloid leukemia.

BACKGROUND: Chronic Myeloid Leukemia (CML) is a malignant pluripotent stem cells disorder of myeloid cells. In CML patients, polymorphonuclear leukocytes (PMNL) the terminally differentiated cells of myeloid series exhibit defects in several actin dependent functions such as adhesion, motility, chemotaxis, agglutination, phagocytosis and microbicidal activities. A definite and global abnormality was observed in stimulation of actin polymerization in CML PMNL. Signalling molecules ras and rhoGTPases regulate spatial and temporal polymerization of actin and thus, a broad range of physiological processes. Therefore, status of these GTPases as well as actin was studied in resting and fMLP stimulated normal and CML PMNL. METHODS: To study expression of GTPases and actin, Western blotting and flow cytometry analysis were done, while spatial expression and colocalization of these proteins were studied by using laser confocal microscopy. To study effect of inhibitors on cell proliferation CCK-8 assay was done. Significance of differences in expression of proteins within the samples and between normal and CML was tested by using Wilcoxon signed rank test and Mann-Whitney test, respectively. Bivariate and partial correlation analyses were done to study relationship between all the parameters. RESULTS: In CML PMNL, actin expression and its architecture were altered and stimulation of actin polymerization was absent. Differences were also observed in expression, organization or stimulation of all the three GTPases in normal and CML PMNL. In normal PMNL, ras was the critical GTPase regulating expression of rhoGTPases and actin and actin polymerization. But in CML PMNL, rhoA took a central place. In accordance with these, treatment with rho/ROCK pathway inhibitors resulted in specific growth inhibition of CML cell lines. CONCLUSIONS: RhoA has emerged as the key molecule responsible for functional defects in CML PMNL and therefore can be used as a therapeutic target in CML.

Radiologically placed tunneled hemodialysis catheters: a single pediatric institutional experience of 120 patients.

PURPOSE: To report the outcome of tunneled dialysis catheter insertion in 120 patients. MATERIALS AND METHODS: A retrospective review of the interventional radiology database and electronic medical records of 120 patients who had tunneled dialysis catheters inserted from April 1997 to July 2010 was performed with institutional review board approval. There were 61 female patients and 59 male patients, with a mean age of 13.3 years (range, 0.2-28.5 y). A total of 193 primary insertions and 330 salvage procedures were performed. RESULTS: The technical success rate for primary catheter insertions was 100%. Immediate complications included self-limiting tract bleeding and air embolism in two of 193 insertions each (1.03%). Mean indwell duration for primary insertions was 66 catheter-days (range, 1-765 d), compared with a total mean of 159.4 catheter-days (range, 1-1,034 d). Rates of infection and mechanical complications were 0.21 and 0.9 per 100 total catheter-days, respectively. Mechanical and infections complications were increased in children younger than 9 years of age and weighing less than 20 kg. The catheter removal rates for infection and mechanical complications were 0.084 and 0.081 per 100 catheter-days, respectively. Medical salvage procedures, ie, intracatheter thrombolytic agent use or antibiotic therapy (52.1%) and interventional radiologic catheter salvage procedures (47.1%), increased catheter survival by an average of 54.8 days (range, 0-959 d). CONCLUSIONS: Radiologic placement of tunneled hemodialysis catheters is a safe and technically successful procedure in pediatric patients. However, there is a high rate of infectious and mechanical complications, particularly in younger and smaller patients.

Longitudinal relations between obesity and hypertension following pediatric renal transplantation.

Obesity and hypertension frequently complicate renal transplantation (RTxp). The objective was to assess relations among obesity, hypertension, and glucocorticoids in pediatric RTxp recipients. A retrospective cohort study was carried out in 141 RTxp recipients, 2-21 years of age, with >or=12 months of follow-up. Body mass index Z-score (BMI-Z), systolic and diastolic blood pressure Z-scores (SBP-Z and DBP-Z), and medications at 1, 3, 6, and 12 months and annually thereafter were recorded. Quasi-least squares regression analysis was used. The prevalence of obesity (BMI>or=95th percentile) increased from 13% at baseline to >30% from 3 months onward. Greater glucocorticoid exposure (mg/kg/day) was associated with greater increases in BMI-Z (p<0.001). This association was greater in males, younger recipients, and those with lower baseline BMI-Z (all interactions p<0.02). The prevalence of systolic hypertension (SBP>or=95th percentile) was 73% at 1 month and >or=40% at all follow-up visits. Greater glucocorticoid exposure (p<0.001) and increases in BMI-Z (p=0.005) were independent determinants of SBP-Z over time. Cyclosporine (versus tacrolimus) was independently associated with greater SBP-Z and DBP-Z (p=0.001). Sustained obesity and hypertension frequently complicated pediatric RTxp. Obesity was an independent determinant of systolic hypertension. Strategies are needed to prevent obesity and its impact on hypertension, cardiovascular disease, and allograft survival.

USB drives for communication of medical information in a pediatric dialysis unit.

We evaluated the feasibility of using universal serial bus (USB) drives for communicating medical information between parents of children receiving dialysis and medical personnel during clinical encounters. When surveyed, parents and pediatric resident physicians supported the use of USB drives and were willing to use the devices. The utilization rate of USB drives was 57%.

Successful deceased donor renal transplant in a sensitized pediatric recipient with the use of plasmapheresis.

Sensitization following renal transplant is a significant barrier to repeat transplantation in children. We report a successful DD renal transplant, with the use of PP, in an 11-yr-old girl who became highly sensitized following a prior failed transplant. She received PP treatments after failure of high-dose IVIg (Gamimune). We established the effectiveness of PP by attaining a 0% PRA and negative cross-matches after five PP treatments. Subsequently, our patient underwent a second round of scheduled PP. When the PRA was 0%, unacceptable antigens were removed from the UNOS wait list, PP was continued, and a kidney became available within 10 days. The final flow cytometry cross-match with the eventual donor was negative. This success demonstrates that coordination of desensitization by PP and advanced laboratory monitoring techniques with recent policies regarding allocation of organs to pediatric patients provides new opportunities for children awaiting transplantation. Since the transplant, our patient sustained a low-titer increase of anti-HLA antibodies. However, she has had no episodes of acute rejection and has maintained excellent graft function more than 17 months later.

Early use of plasmapheresis for recurrent post-transplant FSGS.

Recurrence of focal segmental glomerulosclerosis (FSGS) in an allograft is a challenging clinical situation because it frequently results in graft loss. We report our experience with early use of plasmapheresis in recurrent FSGS. Of the 18 (33%) children with biopsy-proven FSGS (in their native kidneys) transplanted at our institution, 6 had recurrence (elevated urine protein/creatinine ratios) post transplant and were treated with plasmapheresis. Patients who received treatment within 1 day of the recurrence (4/6) went into remission after 5-13 plasmapheresis treatments, within 5-27 days of starting treatment. Patients who did not respond to plasmapheresis (2/6) were treated 7 and 17 days after onset of proteinuria; 1 of these had acute tubular necrosis and acute rejection leading to graft loss and the other developed acute rejections, ongoing proteinuria, and subsequent graft loss. All 4 patients who went into remission have maintained good graft function, 22-53 months post transplant. In our experience early institution of plasmapheresis for recurrent post-transplant proteinuria in FSGS is effective.