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M. Coulthard1, M. Kalra1, A. Nelson2, T. Smith2, J. Perry2. 1Royal Victoria Infirmary, Newcastle, UK; 2Freeman Hospital, Newcastle, UK
ObjectivesTo determine the best urinary bacterial concentration to diagnose urinary infections.
DesignProspective quantitative culture of serially diluted paired urines from 203 children aged 2 weeks to 17.7 years.
Results36/203 children had a urinary tract infection (UTI), with the same likely uropathogen cultured at concentrations within 25‐fold in both urines (E coli in 32). The colony counts were mean 1.7×107/ml, range 106 to >108/ml. Among the 167 children without a UTI, 12 (7%) had positive cultures on the first sample according to standard criteria (likely uropathogen, 105/ml), but had a UTI excluded because the second sample was sterile (7), or had a colony count more than 25‐fold different (5) (contaminated pairs had 11× greater variation in colony counts than infected pairs, p<0.0001, CI 4–36). All 9 (5%) children who had a mixed culture with 105/ml of a uropathogen (heavy mixed growth) in the first sample, had a urine infection excluded by the second sample.
ConclusionDiagnosing a UTI as 105 bacteria/ml gives a false‐positive rate of 7.2%. Using 106/ml would require changes in laboratory techniques, but would correctly diagnose all the UTIs, and reduce the false‐positives to 4.8%. Using 106/ml in 2 urine samples would reduce it to 0.6%. Urines with heavy mixed growths should be considered to be contaminated.
I. Verber. University Hospital of North Tees, Stockton on Tees, UK
IntroductionThe link between early childhood urinary tract infections (UTIs) and renal scarring is well recognised. Although much effort, using imaging techniques, has gone into detecting children with risk factors the only strategies effective in reducing scarring in a population are those aimed at early recognition and treatment. Young children with UTI present with non‐specific symptoms; conversely not all children with dysuria have an infection. In the community delay in diagnosis will lead to unacceptable delays in treatment initiation. A high index of suspicion is necessary but a reliable near patient diagnostic test is then needed.
AimsUrine microscopy (UM) can be used to make an early diagnosis but its accuracy is not established. Previous studies have been flawed by the lack of a gold standard. Culture can give false negatives (if boric acid tubes are used or antibiotics are being prescribed) and false positives (due to contamination). We have therefore used prepared cultures of urinary pathogens, sterile urine and urine with added cells to assess our accuracy using UM.
MethodsThe microbiology lab prepared 5 specimens on five occasions over two years. Paediatric medical staff were asked to microscope the specimens and record their results. A Fuchs‐Rosenthal counting chamber was used with a phase contrast binocular microscope. The results were analysed by the lab who were blinded to the name and status of the staff.
Results116 microscopies were carried out by 4 consultants, 10 SpRs and 12 SHOs. Microscopy had a sensitivity of 0.8 in detecting cells (specificity 0.95) although distinguishing RBCs and WBCs was difficult. Bacterial detection was 0.85 sensitive (specificity 1.0) but for bacilli improved to 0.9 (see table). Slide preparation method did not affect accuracy but disposable counting chambers performed poorly. Inter observer variability which was accounted for by training differences and not by seniority.
ConclusionsGiven approriate training UM is a sensitive way of detecting common urinary pathogens. This will allow earlier diagnosis of UTI and thus earlier effective treatment especially among ambulant children.
M. Shenoy, M. Bradbury, M. Lewis, N. Webb. Royal Manchester Children's Hospital, Manchester, UK
AimsTo look at the long‐term outcome of all children with severe Henoch–Schönlein purpura nephritis (HSN) treated with long‐term immunosuppression in a single centre over a 10‐year period.
Patients and MethodsWe retrospectively reviewed the records of 27 children (19 male) with ISKDC grade 3b, 4, 5 and 6 HSN managed at our institution from 01/01/92 to 31/12/01.
ResultsThe mean age at presentation was 9.8 years (range 3.6–15.8 years). The median estimated glomerular filtration rate (eGFR) at presentation was 91.3 ml/min/1.73 m2 (IQR 51.5–96.6) and urine protein: creatinine ratio (UP:UC) was 556 mg/mmol (IQR 292–1363). The median serum albumin was 23 g/l (IQR 18–29). The indication for biopsy was nephrotic syndrome in 9, nephrotic range proteinuria in 7, sub‐nephrotic range proteinuria in 3, acute nephritis in 6 and nephritic‐nephrotic syndrome in 2. On renal biopsy, the ISKDC grading was as follows: 16 grade 3b, 6 grade 4, 2 grade 5 and 3 grade 6. The median cellular crescent percentage was 25% (IQR 10–50). A total of 25 patients were treated with weaning dose of steroids, of whom 22 were also commenced on long‐term azathioprine (mean duration 8.9 months). 18 of these children received an 8–12 week course of oral cyclophosphamide (2–3 mg/kg/day) prior to azathioprine therapy (2–3 mg/kg/day).
OutcomeAfter a mean follow‐up period of 7 years (range 3.6–13.7 years) following presentation, 10 (37%) have made a complete recovery (normal eGFR with no proteinuria or hypertension), 11 (40.7%) have persistent proteinuria (UP:UC 20–200 mg/mmol) but normal eGFR, 2 (7.4%) have persistent proteinuria and are on antihypertensive therapy with normal eGFR and 4 (14.8%) have progressed to ESRD. Older age at presentation was the only independent risk factor for poor outcome (12.8 years v 8.9 years, p=0.005). Although all four children who progressed to ESRD had nephrotic range proteinuria and 50% cellular/fibro cellular crescents on initial renal biopsy, the degree of proteinuria or crescent % did not correlate with outcome.
ConclusionsDespite treatment with cyclophosphamide, long‐term steroids and azathioprine, a majority of children with HSN grade 3b on initial biopsy have persistent renal abnormalities on long‐term follow‐up. Only older age at presentation was associated with poor outcome.
V. Belostotsky1, M. Z. Mughal2, J. Berry2, N. J. A. Webb1. 1Royal Manchester Children's Hospital, Manchester, UK; 2St Mary's Hospital, Manchester, UK
AimsTo describe the prevalence of vitamin D deficiency in South Asian and white UK children with renal disease. To establish how decreased levels of vitamin D affect PTH in patients with a normal glomerular filtration rate (GFR).
Methods143 children aged 1–18 years were enrolled in the study: 99 were of white UK origin, 38 of S Asian origin and 6 of other ethnic origin or mixed race. 18 were on dialysis, 18 had chronic renal failure, 46 had various renal disorders with normal GFR (>80 ml/min/1.73 m2), 61 had a renal transplant (42 with a normal GFR). Blood samples were collected to establish the levels of 25‐Hydroxyvitamin D (25OHD): a measure of an individual's vitamin D stores); PTH; creatinine. 25OHD concentration <10 ng/ml was defined as vitamin D deficiency; levels between 10–20 ng/ml as vitamin D insufficiency. Serum PTH of 0.8–3.9 pmol/l was defined as normal;
ResultsValues in parentheses indicate the number of children with serum PTH >3.9 pmol/l. The prevalence of vitamin D deficiency was higher in S Asian than White children (p<0.0001). Of the 88 (28 S Asian, 56 White and 4 other) with normal GFR 17/28 S Asian and 28/56 White children had serum PTH concentrations >3.9 pmol/l. Of these 12/17 S Asian and 11/28 white children had low levels of 25OHD (p=0.04). Of 19 transplant patients with reduced GFR, 11 of 14 with a high PTH had low 25OHD levels, compared with 1 of 5 with a normal PTH (p=0.04).
ConclusionsMany S Asian children attending our renal clinic are vitamin D deficient/insufficient and the prevalence of this problem is significantly higher than that in the white population. High PTH values in the setting of a normal GFR can often be explained by vitamin D deficiency and should result in serum 25OHD levels being measured.
N. Dunne1, M. Fitzpatrick2, P. Callery1. 1The University of Manchester, Manchester, UK; 2Leeds Teaching Hospital Trust, Leeds, UK
AimThe aim of the study was to examine indicators of adherence in children aged 5–18 years of White British and South Asian ethnicity on Renal Replacement Therapy RRT (peritoneal and haemodialysis).
MethodsChildren were recruited from 7 paediatric dialysis centres in the UK. Physical and biochemical indicators of RRT effectiveness were collected once a month for six months. Three categories of proxies for adherence were examined: potassium and phosphate levels for diet; interdialytic weight gain and blood pressure for fluid; phosphate levels for medication. Data were collected prospectively, although in 9 cases retrospective data were collected to complete the 6‐month period.
ResultsSeventy nine children were recruited (male, 31; female, 48; 5–11 age group, 40; 12–18, 39; South Asian, 22, White British 57). Only 7/79 children were within therapeutic range for all three proxies over the 6‐month period. 31/79 children were out of therapeutic range for a proxy for 1 month. 41/79 (52%) were out of therapeutic range for a proxy for 2 or more of the 6 months. Children on haemodialysis were significantly more often out of therapeutic range for proxy measures of diet than those on peritoneal dialysis (p<0.001). There were significant differences for proxy measures for medication between centres (p<0.05). A greater proportion of children aged 5–11 were out of range for fluid for 5 of the 6 months, although this was only statistically significant in 1 month (p<0.01). A greater proportion of South Asian children were out of range for fluid in 5 of the 6 months, this was also only statistically significant in 1 month (p<0.05). There were no significant differences between the sexes.
ConclusionThis study suggests that younger children have greater difficulty adhering to the fluid allowance. In contrast to previous studies, teenagers were at no greater risk of non‐adherence than younger children. Some differences were detected between ethnic groups.
R. Subramaniam, A. Turner, G. Kousidis, D. Thomas, S. Feather. St James's University Hospital, Leeds, UK
AimsTo assess the influence of gender on the manifestations of vesicoureteric reflux (VUR) and outcomes of endoscopic correction (EC).
MethodsChildren who underwent EC were included in this prospective study. Indications for EC included children with dilating reflux (Grade 3+) and symptomatic children with VUR irrespective of grade.
ResultsSixty children with VUR were identified, 27 males and 33 females. A quarter had hydronephrosis on antenatal scans, of which 80% were male. Urine infections (UTI) occurred in 83% of the cases, with 97% of girls and 67% of boys being affected. The symptoms in girls were predominantly lower tract related in terms of dysuria, urgency, offensive urine and incontinence. Boys presented with febrile UTI. There was no significant difference in VUR severity between boys and girls, nor was VUR significantly worse with respect to laterality. EC with Deflux was carried out at a mean age of 2.8 years in boys and 6.4 years in girls. Mean time to follow‐up was 5 and 7 months in girls and boys respectively. In patients with follow‐up data available, 81% of refluxing units were cured in females after one Deflux treatment compared to 53% in males. After two treatments, cure rate increased in females only, to 92%. In bilateral cases, where both refluxing units were treated, cure rate was 85% in females after one treatment rising to 100% after two. In boys, cure rate was 31% after one treatment. In girls who were largely symptomatic, 84% were clinically improved on follow‐up and had no UTI after one Deflux treatment. In boys with UTI preoperatively, 91% had clinically improved.
ConclusionsVUR is a different problem in boys compared to girls. The algorithm of VUR is changing. EC should have an essential role in the management options along with conservative management and invasive surgery. Girls with VUR respond significantly better than boys to EC.
S. Rhodes, A. Watson. Nottingham University Hospitals, Nottingham, UK
IntroductionA single kidney is one of the commonest renal abnormalities in the general population. Concerns remain about long‐term outcomes with a reduced nephron mass and hence intensity of investigations and duration of follow‐up.
MethodsWe identified 52 cases with unilateral renal agenesis (URA) (ectopic and pelvic kidneys excluded) from the Trent Nephrourology database between 1985 and 2006.
ResultsThirty eight (73%) occurred in males and 25 (48%) had left URA. 27 (52%) were detected antenatally with 12/27 (44%) recognised in the last 2 years with no change in antenatal ultrasound (USS) procedures. Median age of detection for postnatal URA was 7 months (range 0.25–179 months) with UTI (29%) as the main indication for USS. Overall 60% patients were classified as simple URA with no associated urinary tract abnormalities and 40% as complex with clinically significant problems such as vesicoureteric reflux (VUR), hydronephrosis or scarring necessitating long‐term follow‐up. All cases reviewed had USS which showed compensatory hypertrophy in 25/52 (48%). 29/52 (56%) had DMSA scan and 24/52 (46%) micturating cystogram. Of those antenatally detected single kidneys with normal initial USS none had VUR, scarring, hypertension or proteinuria. These patients were discharged from follow‐up at the median age of 6 months (range 1–122 months). Overall, VUR was the single commonest abnormality (21%), with grade IV VUR in 15%. All had abnormalities on the initial USS which also detected pelviureteric junction obstruction, ureteroceles and scarring. All complex cases have continued under follow‐up.
ConclusionsOur data suggest that the incidence of antenatally detected URA may be increasing. Investigations need to be individualised depending upon the initial USS findings and the value of routine DMSA and MCUG in simple cases is questioned. Most of these patients can be discharged after adequate documentation of compensatory hypertrophy of the normal kidney, absence of proteinuria, normal blood pressure and renal function.
R. Lennon, A. Singh, G. Welsh, L. Ni, P. Mathieson, M. Saleem. Academic Renal Unit, Southmead Hospital, Bristol, UK
IntroductionHemopexin (HPX) is an abundant plasma protein and a very effective heme scavenging molecule. It has serine protease activity and infusing HPX induces reversible proteinuria in rats. Interestingly although total HPX is reduced in children with minimal change nephrotic syndrome (MCNS) the remaining HPX has increased serine protease activity.
MethodsWe studied the effects of HPX on conditionally immortalised human podocytes.
ResultsWild type podocytes (WTP) showed dramatic reorganisation of actin within 30 minutes of HPX treatment. Actin reorganised from stress fibres to cytoplasmic aggregates and membrane ruffles. In nephrin mutant podocytes there was no actin reorganisation, similarly there were no changes in other cells which do not express nephrin namely 3t3 fibroblasts and glomerular endothelial cells (GEC). These results suggest that HPX causes podocyte structural change in a nephrin dependent manner. Furthermore we found the HPX effects on WTPs were reversible within 4 hours and were blocked by preincubating cells with 10% human plasma. HPX treatment of WTPs also caused activation of protein kinase B and RhoA, two proteins involved in the signalling cascade leading to actin reorganisation. Finally, we found that HPX caused increased passage of FITC‐labelled albumin across a mono layer of GEC. Exploring this further, we demonstrated a reduction in the sugar moieties of glycocalyx on both GEC and WTP, the two cell types which make up the glomerular filtration barrier.
ConclusionsActive HPX in MCNS may cause direct podocyte injury and increase permeability of the filtration barrier. Both of these mechanisms could cause or contribute to proteinuria.
R. Shroff1, R. McNair2, N. Figgs2, A. Donald1, J. Deanfield1, L. Rees1, C. Shanahan2. 1Great Ormond Street Hospital and Institute of Child Health, London, UK; 2University of Cambridge, Cambridge, UK
BackgroundCalcification of the arterial media occurs in chronic kidney disease (CKD) and its severity links to adverse cardiovascular outcome. Using intact human vessels we studied the phenotypic changes when vessels are exposed to elevated concentrations of calcium (Ca) and phosphate (PO4). These were related to patients' biochemical parameters and carotid intima‐media thickness (IMT), aortic pulse‐wave velocity and coronary calcification.
MethodsWith full ethical approval medium‐sized muscular arteries were retrieved during insertion of PD catheters or at transplantation from 29 children (dialysis n=21, CKD n=8) and 5 age‐matched controls. Vessel rings were incubated in serum‐free tissue culture medium with graded concentrations of Ca and PO4 (1 mM PO4+1.8 mM Ca, 2 mM PO4+1.8 mM Ca, 3 mM PO4+1.8 mM Ca, 2 mM PO4+2.7 mM Ca) for 7, 14 or 21 days. Ca content in vessels was measured by cresolphtalein complexone chemistry and von Kossa staining.
ResultsVessels from patients with CKD or on dialysis had higher baseline levels of vessel wall calcium and alkaline phosphatase activity compared with normal controls. When these vessels are exposed in vitro to raised extracellular calcium and/or phosphate to mimic uraemic conditions, vessels from dialysis patients showed significantly greater calcification than those from controls or CKD patients. In the presence of elevated PO4 even a small increase in Ca concentration significantly increased calcification (p<0.001). Calcification was associated with increased apoptosis and increased annexin‐6 deposition in the vessel, consistent with a vesicle‐mediated calcification process. In vitro baseline calcification correlated with the time on dialysis (p=0.04), CaxPO4 product (p=0.018) and carotid IMT (p=0.03).
ConclusionsThese observations imply that vascular damage induced by elevated Ca‐PO4 over time as well as factors specific to dialysis primes vessels for rapid progression of medial calcification. This work will lead to an improved understanding of the process of vascular calcification and to further studies aimed at its prevention.
L. Krischock, A. Gullett, D. Bockenhauer, L. Rees, R. S. Trompeter, S. D. Marks. Great Ormond Street Hospital, London, UK
AimsTo determine if paediatric patients receiving mycophenolate mofetil (MMF) and prednisolone for long‐term immunosuppression following renal transplantation have an improved estimated GFR (eGFR) without an increased rate of acute rejection when compared to those receiving MMF, prednisolone and a calcineurin inibitor (CNI).
MethodsRetrospective review of paediatric patients who received MMF in combination with steroids with or without a CNI as part of their immunosuppressive drug regimen for renal transplantation in a single UK centre from 1995 to 2002. Patients were included if follow‐up data were available for at least 12 months following commencement of MMF.
ResultsTwenty three children (70% male) aged 2.1–15.3 (median 10.3) years received MMF and prednisolone as part of their immunosuppressive regimen, with 10 (43%) of these children receiving a CNI. Follow‐up was for 12–96 (median 36) months post MMF commencement, and the MMF was commenced at 3–78 (median 37) months post transplantation. A greater improvement in median eGFR was seen by final follow‐up in those treated without CNI (13.8 ml/min/1.73 m2 improvement compared to 5.9 ml/min/1.73 m2 in those remaining on a CNI). There was no statistical difference in the number of acute rejection episodes between the two groups.
ConclusionWithdrawal of CNI in paediatric renal transplant recipients receiving MMF and prednisolone improves renal allograft function without increasing acute rejection rates.
M. Muorah, P. Brogan, R. Trompeter, N. Sebire, S. Marks. Great Ormond Street Hospital for Sick Children and UCL Institute of Child Health, London, UK
BackgroundSome recent studies have suggested adverse outcome for renal allograft rejection associated with dense CD20 lymphocyte infiltrates.
AimsTo evaluate the association between renal allograft function and survival and the density of B‐cell infiltrates from CD20 immunohistochemical staining of renal transplant biopsies in children with suspected rejection.
MethodsWe performed a retrospective review of demographic factors, histopathology and CD20 immunohistochemistry of all renal transplant biopsies for acute and chronic allograft dysfunction in our unit over 3.5 years with review of initial and subsequent treatment. Clinical and laboratory data at the time of transplant, biopsy and follow‐up were recorded. Patients' biopsies were divided in terms of the B‐cell density seen per high power field (hpf) classified into either few (ie, 300 cells/hpf) or dense B cells (ie, >300 B‐cells/hpf).
ResultsFifty renal transplant biopsies were performed for investigation of acute or chronic allograft dysfunction in 48 children aged 2.1–17.5 (median 13.1) years, at 0–155 (median 22) months post‐transplantation who were followed up for 0–62 (median 24) months post‐biopsy. 17 (35%) graft losses occurred at 0–36 (median 8) months post‐biopsy, and 1–163 (median 49) months post‐transplantation. There was a statistically significant increase in renal allograft loss in those with dense (>300 cells per high power field) CD20+ lymphocyte infiltrates at the end of follow‐up (p=0.046). Dense B‐cell infiltrates were also associated with increased glucocorticoid requirement to treat acute rejection episodes. There were no significant differences in age, sex, HLA mismatches, EBV or CMV viral loads or baseline immunosuppressive regimens between those with few or dense CD20 infiltrates.
ConclusionsWe confirm previous suggestions that demonstration of dense CD20 lymphocyte infiltrates in renal transplant biopsies is associated with adverse clinical outcome. Dense CD20 lymphocyte infiltrates could be an important factor in stratifying patients with rejection as high risk for renal allograft loss, thereby necessitating more intensive therapy. B‐cell depletion therapy with rituximab may be worthy of further study in this clinical context.
S. Waller1, A. Freemont2, L. Rees1. 1Institute of Child Health and Great Ormond Street Hospital, London, UK; 2Osteo‐Articular Pathology, The Medical School, Manchester University, Manchester, UK
IntroductionThe importance and relevance of renal osteodystrophy (ROD) has increased with improving patient survival. Little is known of the bone health in children prior to starting renal replacement therapy (RRT).
AimTo estimate the prevalence of renal osteodystrophy and investigate the relationship between skeletal abnormalities and parathyroid hormone (PTH) levels in children starting RRT.
MethodsFollowing bone labelling with tetracycline 11 patients with chronic renal insufficiency, median age 14.6 (range 9.2–17.1) years, underwent bone biopsy at the time of insertion of dialysis access or transplantation. PTH levels were recorded for an average of 1.0 (0.5–1.9) years pre‐biopsy.
ResultsAll patients demonstrated abnormal bone histology. Three patients (27%) had low turnover disease, including two approaching an adynamic classification. Mean PTH levels pre‐biopsy were 1.7, 4.0 and 6.5 pmol/l (normal range 0.7–5.6 pmol/l). Two patients (18%) had mixed osteodystrophy; mean PTH levels pre‐biopsy were just above the upper limit of the normal range (ULN); 7.5 and 7.6 pmol/l. The remaining six patients (54%) had changes indicative of hyperparathyroid ROD; all these patients had raised PTH levels. In three patients PTH levels were 1–3 times ULN (11.4, 16.0 and 16.0 pmol/l). In the remaining three patients PTH levels were about four times ULN or greater (21.5, 27.1 and 28.8 pmol/l).
ConclusionThe presence of ROD was ubiquitous in children with severe chronic renal insufficiency. Lower levels of PTH were associated with low turnover bone disease and higher PTH levels with high turnover disease.