BACKGROUND:Taste loss may contribute to the loss of appetite in children with chronic kidney disease (CKD) and other serious medical conditions that result in malnutrition. Traditional methods for measurement of taste loss commonly use aqueous tastant solutions that can induce nausea, vomiting, or even pain in the mouth. An alternative is to measure fungiform papillae density on the anterior tongue since this correlates with taste sensitivity. Here we aimed to develop a non-invasive method for assessing papillae density on the anterior tongue and to use the method to determine if CKD patients [estimated glomerular filtrate (eGFR < 60 ml/min/1.73 m(2))] have a lower density than clinical controls (CC)(eGFR > 89 ml/min/1.73 m(2)). METHODS:Thirty-five healthy adults participated in the development of a method, which was assessed by 24 children, 12 of whom were CKD patients and 12 were clinical controls. RESULTS:Similar papillae densities were found using invasive and non-invasive methods (F(1,34) = 0.647, p = 0.427). The CKD group had a significantly lower papillae density (X(2) = 7.17, p = 0.007) and poorer taste sensitivity than the CC group (p = 0.0272), and the density correlated significantly with eGFR (r = 0.56, p < 0.01). CONCLUSIONS:Loss of taste in children with CKD is due to the reduced number of papillae and their taste-sensing receptor cells.

Aims: This study aims to characterise the timing of referral to a paediatric nephrology unit of children who develop end‐stage kidney disease (ESKD). This study also aims to determine whether late referral (LR) influences outcomes and to explore factors that may lead to LR.Methods: A retrospective case review of all incident patients with ESKD who received renal replacement therapy (RRT) at a single paediatric centre. Time between referral to a paediatric nephrologist and commencement of RRT, demographic and clinical data were collated. Estimated glomerular filtration rate (eGFR) at referral was calculated using height and creatinine. LR was defined as having an eGFR ≤30 mL/min/1.73 m2 when first seen by a paediatric nephrologist.Results: RRT was initiated for 74 patients <18 years of age between 1988 and 2010. The median age at referral was 2.0 years (birth–15.9 years) and age at RRT was 10.0 years (6 days–17.4 years). Children referred before age 1 year (41%) had a more prolonged course before ESKD. Median (interquartile range) eGFR at referral of children >1 year was 27.2 (9.0–52.0) mL/min/1.73 m2. Twenty‐two (55%) of these children were referred late (LR) with an eGFR ≤30 mL/min/1.73 m2. LR patients were more likely to have glomerulonephritis or haemolytic uraemic syndrome and to live in a remote or outer regional area. LR patients had higher urea, lower haemoglobin and were more likely to receive haemodialysis via a vascular catheter.Conclusions: A significant proportion of children who develop ESKD are referred late to nephrology units with potentially preventable complications. Aetiology of renal disease and geographic isolation contribute to LR.

Most cases of facial nerve paresis are idiopathic (Bell's palsy). However, rare and potentially dangerous conditions may present in this manner. We report 2 children presenting with unilateral lower motor neuron facial nerve palsy and hypertension. A diagnosis of Guillain-Barre syndrome was made in both; literature linking facial nerve palsy in childhood with hypertension and Guillain-Barre syndrome is reviewed.

Loss of appetite and poor growth are common in children with chronic kidney disease (CKD), and changes in smell and/or taste function may be responsible, but the hypothesis has not been proven. This aims of this prospective age- and gender-controlled study were to determine whether: (1) changes in smell and taste function occur in children with CKD; (2) smell or taste dysfunction are associated with estimated glomerular filtration rate (eGFR); (3) there is an association between smell or taste loss and body mass index (BMI). The study cohort consisted of 72 children of whom 20 were CKD stage 3–5 patients, 12 were CKD stage 2 patients, 20 were clinical controls (CC) and 20 were healthy children (HC). The CKD patients and clinical controls were recruited from Sydney Children’s Hospital and The Children’s Hospital, Westmead, and healthy controls were recruited from a local school. Scores for each group from taste and smell chemosensory function tests were compared, and their relationship with renal function and BMI investigated. The CKD stage 3–5 group had a significantly lower taste identification score (85.6%, P < 0.001) than the CC (94.8%) and HC (94.8%) groups, with almost one third of the children in the CKD stage 3–5 group exhibiting taste loss. Decreased taste function was associated with decreased eGFR (r = 0.43, P < 0.01), but no association between BMI and taste function was found (r = 0.001, P > 0.9). Odour identification scores were not different; however, there was a positive relationship with BMI (r = 0.427, P = 0.006). We conclude that a loss of taste can occur in children with CKD and that when it occurs, it worsens as eGFR declines and is found early in kidney disease.

THE DONOR The 9-year-old donor had been febrile and probably had a seizure on the day of a submersion injury. He was declared brain dead after 60 hr of sedation, ventilation, and cooling. He did not have evidence of significant respiratory illness, was not immunized against influenza, and had not received antiviral agents. After allocation of kidneys, liver, and lungs, the organ procurement center was notified by the donor hospital that a donor nasopharyngeal aspirate demonstrated influenza B virus by immunofluorescence. Positive status was later confirmed by nested reverse- transcription polymerase chain reaction (RT-PCR) and cultures. At the time of notification, the lung recipient had native lung removal in progress. Organ recipient centers for liver and kidneys were notified of this risk and accepted the organs. Recipient clinical management details and investigative workup are summarized in Table 1.TABLE 1: Summary of the progress and management of all organ recipientsRENAL TRANSPLANT—KIDNEY 1 The recipient of kidney 1 was a 14-year-old boy with end-stage kidney disease secondary to hypoplastic kidneys. He had not received the 2008 seasonal influenza vaccine. This retrieved kidney was biopsied and was positive for influenza B RNA by RT-PCR. Initially, standard immunosuppression of basiliximab, mycophenolate, tacrolimus, and methylprednisone was used. A pretransplant dose of oseltamivir was given. After transplant, there was delayed graft function requiring peritoneal dialysis at 18 hr. Oseltamivir was administered daily. At 30-hr posttransplant, the patient developed severe respiratory distress and fever. By day 4, ventilation was required. A chest x-ray demonstrated widespread interstitial infiltrates (see Figure 1A, Supplemental Digital Content 1,https://links.lww.com/TP/A203). Because of delayed graft function, and this severe possibly infective illness, immunosuppression other than methylprednisone was withdrawn. Multiple RT-PCRs for influenza B RNA were performed on blood and tracheal aspirate samples. By day 6, oseltamivir was ceased as all investigations were negative. All other cultures and immunofluoresence studies were also negative. By day 6, the patient was extubated. A nonidentified infectious agent or an acute drug hypersensitivity reaction was proposed as a cause of the respiratory illnesses. On day 14, a renal biopsy, performed because of continued oliguria, demonstrated acute cellular rejection. Influenza B RNA was not detected in this biopsy. Following muro monah-CD3 (OKT3) and methylprednisone, renal function improved. Six months posttransplant, the patient's creatinine level was 67 μmol/L. Follow- up influenza serology did not demonstrate an increase in titers. LUNG TRANSPLANT The lung transplant recipient was a 17-year-old girl with end-stage lung disease because of neonatal onset pulmonary fibrosis. She had received yearly seasonal influenza vaccine. Induction therapy comprised steroids alone. After transplant, she received standard immunosuppression with cyclosporine, azathioprine, and methylprednisolone. Given the donor's influenza B status, oseltamivir was prescribed daily for 10 days in addition to routine broad spectrum antibiotic and inhaled antifungal therapy. The patient was noted to have widespread crackles on chest auscultation on postoperative day 0. Chest x-ray demonstrated diffuse bilateral interstitial infiltrates (see Figure 1B, Supplemental Digital Content 1,https://links.lww.com/TP/A203). During bronchoscopy, the airway anastomoses and distal bronchial tree were macroscopically normal, but bronchoalveolar lavage was tested positive for influenza B virus on direct immunofluorescence and culture on postoperative days 0 and 1 but negative by day 10. She was extubated successfully on day 6 and discharged on day 20. Spirometry improved from a forced expiratory volume in 1 sec/forced vital capacity (FVC) of 0.84/0.88 preoperatively to 1.89/2.04 by 6 months at which stage she was well and attending school. OTHER ORGAN RECIPIENTS The other kidney recipient showed no symptoms to suggest a donor-derived influenza infection. The liver recipient's posttransplant course was also unaltered by this donor-derived influenza risk. RESULTS OF INFLUENZA B VIRUS IDENTIFICATION Typing of influenza B virus in the explant kidney of recipient 1 and the lung recipient showed that the donor was B/Florida/4/2006 type (Table 1). Phylogenetic analysis based on partial nonstructural gene showed that the kidney and lung recipient strains were closely related with 98.9% amino acid identity across the partial nonstructural gene (see Figure 2, Supplemental Digital Content 2,https://links.lww.com/TP/A204). The strains shared more than 97.8% amino acid identity with B/Florida/4/2006, the influenza B-like strain in the Australian 2008 to 2009 influenza virus vaccine. DISCUSSION This case unfolded before the novel influenza A/H1N1 pandemic and the publication of recommendations for preventing donor-derived influenza infection (both seasonal and pandemic) (1, 2). Donor-derived influenza infection, however, has been documented rarely, with one reported case of influenza A transmission (3). To our knowledge, our case is the first report of influenza B transmission through lung transplantation. Although the recipient survived and is currently well, it is acknowledged that the outcome could have been different. Apart from acute risks, transplant- associated respiratory virus infection leading to bronchiolitis obliterans syndrome and graft dysfunction has been proposed as a potential longer term issue. However, there is no clear data to support influenza specifically as a causative agent in bronchiolitis obliterans syndrome (4). Given theoretical high likelihood of influenza transmission through lung transplantation, and potentially more significant recipient risk, a general recommendation by the transplantation society has been to defer a lung transplant in such a risk setting (1). Another approach, as recommended by The Australian Organ and Tissue Donation and Transplantation Authority, especially to be considered where recipient organ need is dire, is an individual case risk benefit analysis with informed consent (2). In our report, a donor kidney was shown to harbor influenza B virus during implantation, and although the recipient developed a respiratory illness, this was not related to influenza B. The presence of influenza in solid organs has been reported by authors in nontransplant settings (5). As far as we are aware, however, there are no reports of solid organ transplant transmission of influenza. This transmission risk remains to be clarified. Current guidelines recommend a cautious consideration to transplant in this risk setting (1, 2). Recognition of potentially influenza- infected donors, early donor screening, and antiviral use are the key initial steps in managing donor transmission risk of influenza viruses. If donation is to be considered, informed recipient consent is vital, with use of donor and recipient neuraminidase inhibitors (oseltamivir or zanamivir). This approach should be used in any donor influenza risk setting, regardless of subtype. Amelia K. Le Page1 Gad Kainer1 Allan R. Glanville2 Elise Tu3 Deepak Bhonagiri4 William D. Rawlinson3 1Department of Nephrology Sydney Children's Hospital Randwick, Australia 2The Lung Transplant Unit St. Vincent's Hospital Darlinghurst, Australia 3Virology Department of Microbiology SEALS, Prince of Wales Hospital Randwick, Australia 4NSW Organ and Tissue Donation Service St George Hospital Kogarah, Australia

Cardiovascular (CVS) death accounts for almost a quarter of paediatric and young adult end stage kidney disease deaths (1) and traditional CVS risk factors are often evident at an early age in children with chronic kidney disease (CKD). Endothelial dysfunction is a precursor of atherosclerosis (2) and it has been documented to be present by the first decade of life in children with CKD. (3). Given that endothelial dysfunction occurs very early in the timeline of atherosclerosis, it would seem to be an attractive target for therapeutic intervention (4). There is some evidence that statins may improve endothelial dysfunction in nephrotic syndrome (5), and in adults with raised (6,7) and borderline raised (8) lipid levels. We therefore designed an intervention trial in children with CKD to determine whether we could improve endothelial dysfunction by using an HMG CoA reductase inhibitor (statin). Patients were included if lipid levels were ‡50th percentile (rather than the more conventional 95th percentile) because the risk of hyperlipidaemia seems to be continuous, evidenced by an almost linear correlation between increasing lipid levels and decreasing arterial distensibility in normal children (9). The objective of this study was to assess the effect of statin-associated cholesterol lowering on endothelial function, lipoprotein levels, C reactive protein (CRP), blood pressure (BP) and renal function in mildly hyperlipidaemic children with CKD stages 3–4 [estimated glomerular filtration rate (GFR) (10) <60 mL ⁄ min ⁄ 1.73 m]. A prospective, randomized double-blinded placebo controlled, crossover trial of atorvastatin 10 mg daily for 8 weeks in children (5–17 years of age; n = 8) with serum lipoprotein levels >50th percentile was conducted (i.e. each patient was studied before and after 8 weeks of placebo and atorvastatin with a 4-week washout period between treatment arms). Seven of eight children were taking Angiotensin Converting Enzyme Inhibitors (ACE-inhibitors) for renoprotection (not hypertension). Endothelial function was measured non-invasively by studying brachial artery reactivity by vascular ultrasound (ATL HDI 5000 Phillips, Bothell, Washington, DC, USA) (11). Change in brachial artery endothelium-dependent flow-mediated dilatation (FMD) was the primary end-point. It was estimated that in a crossover design with scans before and after intervention, 10 patients would detect a significant change in FMD of 3.6% (11) to provide 80% power at the 5% significance level. Unfortunately, placebo expiry and recruitment difficulty led to only eight patients participating in a pilot study. Patients were recruited from the renal clinic of Sydney Children’s Hospital and South Eastern Area Health and Central Sydney Ethics Committees approved the study. Total cholesterol and LDL significantly decreased during treatment by a mean of 1.3 ± 0.3 mmol ⁄ L p < 0.0001 and 1.1 ± 0.3 mmol ⁄ L respectively p < 0.0001 (paired student t test) (Table 1). Baseline FMD was normal with a mean of 9.75 ± 0.39% (SEM) and did not significantly alter after 8 weeks of atorvastatin (8.04 ± 1.02% p = 0.18) (Table 2). No significant change was seen in creatinine, BP, CRP, liver function tests, or creatinine kinase levels with atorvastatin. There was no significant correlation (Pearson) between vascular reactivity studies and serum creatinine or estimated GFR. There was no correlation between lipid concentrations, BP, BMI and FMD or glyceryl trinitrate (GTN) studies. Atorvastatin therapy for 8 weeks did not alter endothelial function in children with CKD despite a dose which achieved a significant reduction in LDL cholesterol. We postulate this may be attributable to the FMD results that Acta Pædiatrica ISSN 0803–5253

Kennedy, S E.1; Mackie, F E.1,2; Kainer, G1; Craig, E1; Rosenberg, A R.1,2 Author Information

Journal of Paediatrics and Child HealthVolume 44, Issue 5 p. 305-307 Tubulointerstitial nephritis: Drugs are not always to blame Fiona E Mackie, Corresponding Author Fiona E Mackie Department of Nephrology, Sydney Children's Hospital and University of NSW, NSW, AustraliaDr. Fiona Mackie, Department of Nephrology, Sydney Children's Hospital, High St, Randwick 2031, NSW, Australia. Fax: +61293821580; email: f.mackie@unsw.edu.auSearch for more papers by this authorAndrew R Rosenberg, Andrew R Rosenberg Department of Nephrology, Sydney Children's Hospital and University of NSW, NSW, AustraliaSearch for more papers by this authorGad Kainer, Gad Kainer Department of Nephrology, Sydney Children's Hospital andSearch for more papers by this author Fiona E Mackie, Corresponding Author Fiona E Mackie Department of Nephrology, Sydney Children's Hospital and University of NSW, NSW, AustraliaDr. Fiona Mackie, Department of Nephrology, Sydney Children's Hospital, High St, Randwick 2031, NSW, Australia. Fax: +61293821580; email: f.mackie@unsw.edu.auSearch for more papers by this authorAndrew R Rosenberg, Andrew R Rosenberg Department of Nephrology, Sydney Children's Hospital and University of NSW, NSW, AustraliaSearch for more papers by this authorGad Kainer, Gad Kainer Department of Nephrology, Sydney Children's Hospital andSearch for more papers by this author First published: 15 April 2008 https://doi.org/10.1111/j.1440-1754.2008.01303.xCitations: 4Read the full textAboutPDF ToolsRequest permissionExport citationAdd to favoritesTrack citation ShareShare Give accessShare full text accessShare full-text accessPlease review our Terms and Conditions of Use and check box below to share full-text version of article.I have read and accept the Wiley Online Library Terms and Conditions of UseShareable LinkUse the link below to share a full-text version of this article with your friends and colleagues. Learn more.Copy URL Share a linkShare onFacebookTwitterLinked InRedditWechat Citing Literature Volume44, Issue5May 2008Pages 305-307 RelatedInformation

A renal length discrepancy (RLD) of more than 10 mm by ultrasound (US) is accepted as a potential indicator of an underlying renal pathology; however, there are few supporting data for this in children. Our objective was to determine a cutoff at which RLD on US is a reliable predictor of dimercaptosuccinate acid (DMSA) scan abnormality. We present data from 90 patients who had both renal US and a DMSA scan, as well as DMSA scan results compared with bipolar RLD by US. Positive (PPV) and negative (NPV) predictive values were calculated for renal RLD from 6 to >10 mm. The left kidney was longer in 56%, whereas the right kidney was longer in 37%; their lengths were equal in 8%. For children at all ages, a left kidney longer than the right by ≥10 mm or a right kidney longer than the left by ≥7 mm gave a PPV for DMSA abnormality of 79% and 100%, respectively. In children older than 4 years, if the right kidney was longer by ≥7 mm or if the left kidney was longer by ≥10 mm, the PPVs for DMSA abnormality were 100% and 63%, respectively. In children younger than 4 years, when the right kidney was longer by ≥6 mm or the left was kidney longer by ≥10 mm, the PPV were 86% and 100%, respectively. Thus, children with a right kidney longer than the left by even <10 mm is a reliable predictor of an abnormal DMSA scan.

Moyamoya disease (MMD) is an idiopathic progressive disorder associated with stenosis or occlusion of the cerebral vasculature with particular involvement of the circle of Willis and the arteries that feed it. Renal artery lesions and renovascular hypertension (RVH) in MMD have been described by many authors. Captopril renography is a sensitive screening investigation for RVH in adults and children. Basal/acetazolamide stress brain perfusion SPECT with Tc-99m HMPAO performed, in MMD can disclose regions of decreased cerebral perfusion and cerebrovascular reserve, which can be improved by revascularization surgery.

OBJECTIVES:Hypertension in children may be defined by blood pressure elevated above the 95th percentile according to sex and age. Population data for ambulatory blood pressure provide different age-related and sex-related threshold limits to office-derived data. We sought to determine whether, when using ambulatory blood pressure monitoring in a clinical setting, changing 95th percentile threshold limit sets from office-derived to ambulatory blood pressure-derived would lead to different diagnostic decisions. METHODS:Three nephrologists who were blinded as to patient identity and limit setting method reported on 42 ambulatory blood pressure records from a mixed group of patients aged 5-18 years by using both office-derived threshold limits for the 95th centile of blood pressure and ambulatory blood pressure-derived limits. Decisions regarding the presence or absence of hypertension were compared for each patient according to the limit set. RESULTS:Thirty-five (83%) patients were considered to be hypertensive when office-derived threshold limits were used and 20% (P=0.005) fewer records were reported as showing hypertension when ambulatory blood pressure-derived threshold limits were used. When ambulatory blood pressure limits were applied, there were fewer records with an awake systolic blood pressure load >50% (P=0.004) and the average awake systolic blood pressure load was significantly lower (P<0.001). CONCLUSION:Ambulatory blood pressure normative data tend to provide higher blood pressure limits for age and sex. Consequently, when ambulatory blood pressure data are used to set threshold limits, clinical decisions based on ambulatory blood pressure may be different than when office limits are used. These findings demonstrate the importance of using the most appropriate limit sets to analyze ambulatory blood pressure and when interpreting ambulatory blood pressure-based research.

Bone marrow transplant nephropathy (BMTN) classically presents more than 100 days after transplantation as an acute nephritis with hypertension, azotaemia and anemia that usually results in end stage renal failure (ESRF). The risk of developing BMTN may be greater with the use of more intensive chemotherapy and higher total body and tumor bed irradiation. Cis-retinoic acid (RA) may further increase the risk of developing BMTN. Here, we report the cases of two children who developed typical clinical and biochemical features of BMTN. They were both treated for stage IV neuroblastoma with chemotherapy, bone marrow transplant (BMT) conditioning that included total body irradiation and RA therapy after BMT, although the patient in case 1 had established renal insufficiency prior to the commencement of RA. Renal biopsy of these children showed classical BMTN histology, and the renal manifestations progressed quickly; the patient in case 1 became dialysis dependent by 1 year post-bone marrow transplant. Recently, RA has been added to the post-BMT therapy in children with stage IV neuroblastoma. The occurrence of BMTN in two children treated with RA in our unit is unlikely to be coincidental. Although RA has been shown to confer a significant survival advantage in this disease, animal studies and a previous case report have suggested it could increase the toxic effects of chemotherapy and renal irradiation. It is likely that RA contributed to the deterioration in renal function in these patients.

The use of ambulatory blood pressure monitoring (ABPM) can improve the accuracy of paediatric BP measurement and may better correlate with end-organ injury than office BP measurement. However, the interpretation of ABPM may be influenced by several variables. We sought to ascertain the agreement among three paediatric nephrologists when reporting 92 ABPM sessions performed on patients aged 5 to 18 years. All three nephrologists were in agreement on the presence or absence of hypertension in 64% of cases. They were less likely to concur about records where hypertension was borderline or if the ABP record contained fewer BP readings. These results highlight the need for evidence-based consensus regarding the interpretation of ABPM in children.

Collection of urine under paraffin is routinely used in clinical practice for urine pH evaluation. To examine whether the accuracy of pH measurement is adversely influenced by the method of collection and storage, we divided each urine specimen and sent one aliquot to the laboratory under paraffin and another in a sealed 5-ml plastic syringe. In another experiment we evaluated the stability of urine pH measurement in a clinical setting. Urine collected under paraffin was tested immediately for pH; an aliquot from the same specimen was stored in a capped 5-ml syringe at 4 degrees C and tested after 24 h. We found no appreciable difference in measured pH between samples sent to the laboratory under paraffin or in a capped plastic syringe.

The objective of this prospective study was to determine the prevalence of hyperlipidemia in our pediatric renal transplant patients and to treat those with persistently elevated cholesterol and/or low-density lipoprotein (LDL) levels. All patients with a functioning renal allograft for greater than 6 months were studied (n = 18). Patients with cholesterol and/or LDL levels greater than the 95th percentile (n = 9) were commenced on an HMG-CoA reductase inhibitor, Atorvastatin and monitoring was performed for efficacy and adverse effects. Total serum cholesterol was elevated in 11 of 18 (61%) and triglyceride (TG) was elevated in 12 of 18 (67%) patients. Atorvastatin treatment was effective with a mean percentage reduction of total cholesterol of 41 +/- 10% (p < 0.01 vs. before treatment), LDL 57 +/- 7% (p < 0.01 vs. before treatment) and TG 44 +/-25% (p = 0.05 vs. before treatment). No adverse effects on allograft function or cyclosporin levels were experienced. Hyperlipidemia is a common problem and Atorvastatin is a safe and effective treatment in pediatric renal transplant recipients.