M.J. Keir

New renal scarring in children who at age 3 and 4 years had had normal scans with dimercaptosuccinic acid : follow up study

Abstract Objective: To determine up to what age children remain at risk of developing a new renal scar from a urinary tract infection. Design: Follow up study. Families of children who had normal ultrasound scans and scanning with dimercaptosuccinic acid (DMSA) after referral with a urinary tract infection when aged 3 (209) or 4 (220) were invited to bring the children for repeat scans 2-11 years later. A history of infections since the original scan was obtained for children not having a repeat scan. Setting: Teaching hospital. Subjects: Children from three health districts in whom a normal scan had been obtained at age 3-4 years in 1985-1992 because of a urinary tract infection. Main outcome measure: Frequency of new renal scars in each age group. Results: In each group, about 97% of children either had repeat scanning (over 80%) or were confidently believed by their general practitioner or parent not to have had another urinary infection. The rate of further infections since the original scan was similar in the 3 and 4 year old groups (48/176 (27%) and 55/179 (31%)). Few children in either group known to have had further urinary infections did not have repeat scanning (3/209 (1.4%) and 4/220 (1.8%)). In the 3 year old group, 2.4% (5/209) had one or more new kidney scars at repeat scanning (one sided 95% confidence interval up to 5.0%), whereas none of the 4 year olds did (one sided 95% confidence interval up to 1.4%). The children who developed scars were all aged under 3.4 years when scanned originally. Conclusions: Children with a urinary tract infection but unscarred kidneys after the third birthday have about a 1 in 40 risk of developing a scar subsequently, but after the fourth birthday the risk is either very low or zero. Thus the need for urinary surveillance is much reduced in a large number of children. Key messages Urinary tract infections can cause renal scars in young children that may lead to hypertension or renal failure, often years later Scars can be detected immediately on scanning with dimercaptosuccinic acid (DMSA) but may not be apparent for years if only intravenous urography is used Previous studies based on intravenous urography have suggested that new scars may develop in children up to the age of 10 years This study, which used DMSA scanning, shows that there is little or no risk of new renal scars developing in children aged 4 and older

Reflux nephropathy in kidney transplants, demonstrated by dimercaptosuccinic acid scanning

Background. This study determines why kidney transplants develop new focal defects. Methods. Thirty children at a U.K. pediatric nephrology department receiving kidney transplants had early and late dimercaptosuccinic acid (DMSA) scans to detect acquired focal defects, and their presence correlated with possible risk factors. Associations between clinical events and focal DMSA lesions appearing in grafts were measured. Results. Of the 30 early DMSA scans (within 2 weeks of function), one child with a thrombosed polar artery had a focal defect. On rescanning later, 11 (37%) had acquired segmental defects; five were multiple, and their glomerular filtration rates were 20 ml/min/1.73m2 lower (95% CI 7–34). Histology in one case showed pyelonephritic scarring. Reflux into the transplant ureter occurred in 19/27 (70%) of children tested (by radiological or indirect radionuclide cystography). Nine of 13 children (69%) who had a combination of reflux and a urine infection had acquired scars, whereas only 1/14 (7%) did without this combination (P=0.001). Scarring was not associated with the age or sex of the donor or recipient, rejection episodes, renal biopsy, or drug-induced nephrotoxicity. Conclusion. Kidney transplants are at high risk of developing segmental pyelonephritic scars if infected urine refluxes into the graft, either early through a transanastomotic stent or later from vesicoureteric reflux. These scars may reduce the renal function and are readily seen on DMSA, but not ultrasound scans. Consideration should be given to more effective antireflux surgery for transplants, with subsequent testing for reflux, urinary antibiotic prophylaxis, and prompt treatment of urine infections.

Inaccuracy of glomerular filtration rate estimation from height/plasma creatinine ratio.

Use of a height/plasma creatinine formula to estimate glomerular filtration rate (GFR) is simpler and less invasive than renal or plasma clearance methods. The aim of this study was to determine whether these formulas enabled accurate prediction of GFR measured from the plasma clearance of 51Cr labelled ethylenediaminetetra-acetic acid (51Cr-EDTA). Thirty nine patients underwent GFR measurement at least six months after potentially nephrotoxic chemotherapy. Altman-Bland analysis was performed on the measured GFR and that estimated simultaneously using the original and a modified Counahan-Barratt formula and the Schwartz formula. The limits of agreement of the estimated GFR with the measured GFR were unacceptably wide in each case, despite highly significant correlation coefficients. The bias was smallest for the modified Counahan-Barratt formula. Use of these formulas to estimate GFR in children is insufficiently accurate for research purposes and has limitations in clinical practice. Furthermore, use of correlation coefficients to evaluate different methods of measuring GFR is inappropriate.

Does prompt treatment of urinary tract infection in preschool children prevent renal scarring: mixed retrospective and prospective audits

Objective To test whether active management of urinary tract infections (UTI) in young children by general practitioners can reduce kidney scarring rates. Design A comparison of two audits in Newcastle, of children aged <8 years, presenting with UTIs ; a retrospective audit of conventional management during 1992–1995 (1990s) versus a prospective audit of direct access management during 2004–2011 (2000s). Main outcome measures Kidney scarring rates, and their relationship with time-to-treat. Results Children with a first UTI in the 2000s compared to those in the 1990s, were referred younger, were half as likely to have a renal scar (girls OR 0.47, 95% CI 0.29 to 0.76; boys 0.35, 0.16 to 0.81), and were about 12 times more likely to have vesicoureteric reflux without scarring (girls 11.9, 4.3 to 33.5; boys 14.4, 4.3 to 47.6). In the 2000s, general practitioners treated about half the children at first consultation. Children who were treated within 3 days of their symptoms starting were one-third as likely to scar as those whose symptoms lasted longer (0.33, 0.12 to 0.72). Interpretation Most kidney defects seen in children after UTIs, are acquired scars, and in Newcastle, active management in primary care has halved this rate.

Do systemic symptoms predict the risk of kidney scarring after urinary tract infection

Background and aims: In the NICE guideline on childhood urinary tract infection (UTI), it is assumed that the presence or severity of systemic symptoms, especially fever, predicts for renal scarring, and different management is recommended accordingly. We aimed to test this hypothesis by retrospective case note analysis. Design and subjects: Notes of children aged under 5 years referred with a first UTI who were assessed for scarring were reviewed. Main outcome criteria: Ability to predict for single or multiple scarring from age, sex, fever, vomiting or anorexia or malaise, or need for hospitalisation, within the age bands used by NICE. Results: There were 51 (65% girls) scarred and 140 (69% girls) unscarred children. Fever, systemic symptoms and hospitalisation were all commoner among younger children (<6 months vs 6 months–3 years vs >3 years; fever 0.67 vs 0.38 vs 0.38; systemic symptoms 0.78 vs 0.62 vs 0.43; hospitalisation 0.67 vs 0.29 vs 0.19; p<0.001 for all). Having vomiting, anorexia or malaise at presentation correlated weakly with single or multiple renal scarring (R2 = 0.03; p = 0.02), but sex, age, fever or hospitalisation did not (p>0.5 for all). Sensitivity and specificity data, and plots of proportionate reduction of uncertainty showed that none of these variables was useful for predicting any scarring in children aged <3 years and that they were only weakly predictive in older children. Conclusions: Clinical signs at presentation in childhood UTI cannot be used to predict for mild or multiple scarring, and should not be used to guide management. NICE’s recommendation to do so is not justified.

Estimation of glomerular filtration rate in paediatric cancer patients using 51CR-EDTA population pharmacokinetics.

Estimation of glomerular filtration rate (GFR) using the clearance of chromium 51 EDTA (51Cr-EDTA) (or other radiolabelled isotopes) is reliable, but invasive and not always practicable. Mathematical models have been devised for estimating GFR using readily obtainable patient characteristics. Unfortunately, these models were developed using various patient populations and may not provide the optimal prediction of GFR in children with cancer. The current study uses population pharmacokinetics to determine the relationship between 51Cr-EDTA clearance, and patient covariates in 50 paediatric cancer patients. These models were validated using a separate group of 43 children and were compared with previously published models of renal function. Body size was the major determinant of 51Cr-EDTA clearance and inclusion of weight or surface area reduced the residual variability between individuals (coefficient of variation) from 61 to 32%. Serum creatinine was the only other parameter that significantly improved the model. Mean percentage error values of –5.0 and –1.1% were observed for models including weight alone or weight and creatinine, respectively, with precision estimates of 21.7 and 20.0%. These simple additive models provide a more rationale approach than the use of complex formulae, involving additional parameters, to predict renal function.

Preparation of the colon for double-contrast barium enema: comparison of Picolax, Picolax with cleansing enema and Citramag (2 sachets)--a randomized prospective trial.

A randomized prospective trial was undertaken on 196 consecutive patients referred for double-contrast barium enema examination to assess the relative efficacy of three colon cleansing regimes: Citramag (2 sachets), Picolax and Picolax with a preliminary cleansing enema. Each of the regimes was preceded by a 5 day low residue diet. The radiographs from the examinations were assessed on a double-blind basis. The quality of bowel preparation was significantly poorer (P < 0.001) in the group receiving the preliminary cleansing enema, notably with respect to mucosal coating, compared with the other two groups. The quality of the preparation was slightly better in the group receiving Picolax alone than in the Citramag group (P < 0.01), the difference being most apparent in the proximal colon. The laxatives were equally well tolerated. The study has formed the basis of a departmental audit. As a result, the bowel preparation has been standardized to a 5 day period of dietary restriction followed by 2 Picolax sachets. This measure has improved efficiency within the department with no sacrifice in quality.

Investigating suspected acute pulmonary embolism - what are hospital clinicians thinking?

AIMS To assess local clinical knowledge of the appropriate investigation of suspected acute pulmonary embolism (PE) and this compare with the 2003 British Thoracic Society (BTS) guidelines as a national reference standard. METHODS A clinical questionnaire was produced based on the BTS guidelines. One hundred and eight-six participants completed the questionnaires at educational sessions for clinicians of all grades, within a single NHS Trust. The level of experience amongst participants ranged from final year medical students to consultant physicians. RESULTS The clinicians were divided into four groups based on seniority: Pre-registration, Junior, Middle, and Senior. Forty-six point eight percent of all the clinicians correctly identified three major risk factors for PE and 25.8% recognized the definition of the recommended clinical probability score from two alternatives. Statements regarding the sensitivity of isotope lung imaging and computed tomography pulmonary angiography (CTPA) received correct responses from 41.4 and 43% of participants, respectively, whilst 81.2% recognized that an indeterminate ventilation-perfusion scintigraphy (V/Q) study requires further imaging. The majority of clinicians correctly answered three clinical scenario questions regarding use of D-dimers and imaging (78, 85, and 57.5%). There was no statistically significant difference between the four groups for any of the eight questions. CONCLUSIONS The recommended clinical probability score was unfamiliar to all four groups of clinicians in the present study, and the majority of doctors did not agree that a negative CTPA or isotope lung scintigraphy reliably excluded PE. However, questions based on clinical scenarios received considerably higher rates of correct responses. The results indicate that various aspects of the national guidelines on suspected acute pulmonary embolism are unfamiliar to many UK hospital clinicians. Further research is needed to identify methods to improve this situation, as both clinicians and radiologists have a duty to ensure that patients are appropriately investigated.

Estimation of renal function and its potential impact on carboplatin dosing in children with cancer

Renal function-based carboplatin dosing is used routinely in paediatric oncology clinical practice. It is important that accurate assessments of renal function are carried out consistently across clinical centres, a view supported by recently published British Nuclear Medicine Society (BNMS) guidelines for measuring glomerular filtration rate (GFR). These guidelines recommend the use of a radioisotope method for GFR determination, with between two and five blood samples taken starting 2 h after radioisotope injection and application of the Brochner-Mortensen (BM) correction factor. To study the likely impact of these guidelines, we have investigated current practices of measuring GFR in all 21 Childrens Cancer and Leukaemia Group (CCLG) paediatric oncology centres in the United Kingdom. This information was used to evaluate the potential impact on renal function-based carboplatin dosing using raw 51Cr-EDTA clearance data from 337 GFR tests carried out in children with cancer. A questionnaire survey revealed that between two and four samples were taken after isotope administration, with BM and Chantler corrections used in 38% (8/21) and 28% (6/21) of centres, respectively. A change from Chantler to BM correction, based on the BNMS guidelines, would result in a >10% decrease in carboplatin dose in at least 15% of patients and a >25% decrease in 2% of patients. A greater proportion of patients would have an alteration in carboplatin dose when centres not using any correction factor implement the BM correction. The increase in estimated 51Cr-EDTA half-life observed by omitting the 1 h sample decreases carboplatin dose by >10% in 23–52% of patients and by >25% in 3% of patients. This study highlights current variations in renal function measurement between clinical centres and the potential impact on carboplatin dosing. A standard methodology for estimating GFR should be followed to achieve uniform dosing in children with cancer.

Critical analysis of the use of skeletal surveys in patients with chronic renal failure

Skeletal radiology and bone histopathology were compared in 82 patients with renal failure. The performance of radiology in detecting lesions was assessed using interobserver studies which showed disappointing levels of agreement probably reflecting the subjective nature of the radiological signs. Radiology was very insensitive in detecting and grading hyperparathyroidism even when histology and serum biochemistry were floridly abnormal. The most useful radiographs for monitoring subperiosteal erosions and vascular and soft tissue calcification are identified.