Biomedical subjects

Lesley Rees

Publications and source records attributed to Lesley Rees.

At least 19 recordsLinked to original sources

PubMed2007

Nutrition in children with CRF and on dialysis.

The objectives of this study are: (1) to understand the importance of nutrition in normal growth; (2) to review the methods of assessing nutritional status; (3) to review the dietary requirements of normal children throughout childhood, including protein, energy, vitamins and minerals; (4) to review recommendations for the nutritional requirements of children with chronic renal failure (CRF) and on dialysis; (5) to review reports of spontaneous nutritional intake in children with CRF and on dialysis; (6) to review the epidemiology of nutritional disturbances in renal disease, including height, weight and body composition; (7) to review the pathological mechanisms underlying poor appetite, abnormal metabolic rate and endocrine disturbances in renal disease; (8) to review the evidence for the benefit of dietetic input, dietary supplementation, nasogastric and gastrostomy feeds and intradialytic nutrition; (9) to review the effect of dialysis adequacy on nutrition; (10) to review the effect of nutrition on outcome.

Adolescent↗

PubMed2007

Effect of haemodialysis on markers of bone turnover in children.

'Intact' parathyroid hormone (iPTH) assays are used to measure serum PTH levels in haemodialysis patients to diagnose and monitor secondary hyperparathyroidism and consequent renal osteodystrophy (ROD); these assays exhibit cross-reactivity with long carboxyl-terminal PTH fragments (C-PTH) that accumulate in end stage renal failure (ESRF) and antagonise the biological activity of the whole molecule, 1-84 PTH. The effects of haemodialysis on C-PTH are not known. We investigated how haemodialysis affects serum concentrations of calcium, iPTH, 1-84 PTH, C-PTH, and other markers of bone turnover; bone-specific alkaline phosphatase (BALP) and type 1 collagen cross-linked telopeptide (CTx). Fifteen patients, mean (range) age 13.9 (4.3-17.6) years, haemodialysed for a median of 16.3 (4-41) months, had pre- and post-dialysis serum samples collected for routine biochemistry, BALP, CTx, iPTH and 1-84 PTH assays. Changes to serum concentrations and relationships between these biochemical surrogate markers of ROD were investigated. Serum phosphate and PTH levels (measured by both assays) fell significantly during dialysis, whereas serum calcium, C-PTH, the 1-84 PTH: C-PTH ratio and BALP and CTx concentrations were not significantly changed. 1-84 PTH levels were related to pre but not post dialysis serum calcium levels and changes to 1-84 PTH levels during dialysis were related to changes in serum calcium levels. 1-84 PTH and iPTH were reduced by haemodialysis, whereas levels of BALP and CTx remained stable post-dialysis. The relationship between BALP and CTx and bone histology requires investigation to determine whether they are more useful markers of bone turnover in this patient group.

Adolescent↗

PubMed2006

Predictors of long-term outcome of children with idiopathic focal segmental glomerulosclerosis.

Clinical and histological data of children presenting with steroid-resistant nephrotic syndrome and renal biopsy showing focal and segmental glomerulosclerosis from 1980 with a follow-up of over 10 years were reviewed. There were 66 patients; 38 male and 28 female. Age at onset ranged from 0.4-14.1 years (mean 6.4). Tubular atrophy was present at first biopsy in 50/66, capsular adhesions in 35/66, glomerular tip lesions in 8/66 and mesangial expansion in 31/66 patients. In 51 children, cyclophosphamide was prescribed as the first cytotoxic agent, while 15 received cyclosporine A and complete remission was induced in 43 and 40% of the children, respectively. Complete and stable remission was maintained in 35 children, while 22 had reduction of proteinuria with symptomatic relief. Nine were refractory to cytotoxic therapy. Of the 35 patients who entered complete and stable remission, the renal survival was over 90%, while in the 31 non-responders it was 48% in 10 years. The multivariate analysis using unconditional logistic regression method identified the presence of mesangial expansion (p=0.011) and tip lesions (p=0.005) as the independent predictors of favourable response to cytotoxic therapy and the presence of renal impairment (p=0.008) and extensive focal segmental sclerosis (p=0.025) as independent predictors of unfavourable response.

Adolescent↗

PubMed2006

Long-term outcome of paediatric renal transplantation: follow-up of 300 children from 1973 to 2000.

BACKGROUND/AIM: To report our experience of paediatric renal transplantation at Great Ormond Street and Royal Free Hospitals since the inception of the programme. METHODS: Retrospective review of the patient and transplant survival and influencing factors in the 300 children transplanted between 1973 and 2000. RESULTS: 300 children had received a total of 354 transplants; 56 were living-related donations. The median age at transplantation was 10.3 (range 1.4-17.9) years. Forty-four percent had congenital structural abnormalities of the urinary tract. Forty-six children required a second and 8 a third transplant before transfer to an adult unit. The overall patient survival at 5, 10, and 20 years was 97, 94, and 72%, respectively. In the overall cohort, the donor type (deceased donor or living-related donor) did not affect mortality, nor did age at transplantation, but those transplanted before 5 years of age had a significantly shorter post-transplant survival time (p < 0.0001). Transplant survival (first transplant) for deceased and living-related donors was 66 and 87% at 5 years (p < 0.01), 51 and 54% at 10 years, and 36% at 20 years (deceased-donor transplants only). Although the overall transplant survival was inferior in children transplanted before 2 years of age (p < 0.03), in the most recent cohort (1990-2000), age did not affect the outcome. On multiple regression analysis, the only predictor of transplant survival was the era of transplantation (p < 0.001). The median final height was within the normal range for males and females; 7 patients received growth hormone after transplantation. CONCLUSIONS: The outlook for successful transplantation is improving, and in the last decade was unaffected by age at transplantation. The survival of living-related donor transplants is superior to deceased-donor transplants for the first 5 years. From the above data, we can predict that a 10-year-old child receiving a renal transplant in 2000 and on ciclosporin-based immunosuppression can expect a transplant half-life of 13.1 years from a living-related donor and one of 10.8 years from a deceased-donor transplant.

Adolescent↗

PubMed2006

Growth and PTH in prepubertal children on long-term dialysis.

Growth failure is an important complication for children on dialysis. One possible influence on growth is renal bone disease. We reviewed the case notes of 35 children (23 boys), mean (range) age at inclusion 2.8 (0.25-8.9) years (17 children age <2 years), on dialysis for 2.0 (1-4.8) years, for growth, PTH, calcium and phosphate levels and medications. Data collection ended at age 10 years, commencement of growth hormone (rhGH) or renal transplantation. The mean (range) height standard deviation score (HtSDS) at the start of dialysis was -2.06 (-5.90 to 0.63). No change in HtSDS per year was observed; the median was -0.06 (-1.07 to 2.39). Children aged <2 years showed catch-up growth in the first year on dialysis; median change in HtSDS was 0.31 (-0.78 to 3.13). Mean plasma calcium and ionised calcium were approximately at the mid-point and phosphate just above the mid-point of the respective normal ranges. The median PTH level was 1.52 times the upper limit of normal and levels did not correlate with growth. Our results indicate that intensive nutritional therapy and phosphorus control aiming to keep PTH within the normal range prevents further loss of HtSDS in short children on dialysis. In some children under 2 years of age catch-up growth can be observed in the first dialysis year.

Child↗

PubMed2006

Bone mineral density in children with chronic renal failure.

Bone mineral density (BMD) is important in children and adolescents because of its relationship to long-term skeletal health, and because, in adults with chronic renal failure (CRF), a relationship between low BMD and vascular calcification has been suggested. To investigate the relationship between BMD and manipulable factors that might affect it, i.e. plasma calcium, phosphate and parathyroid hormone (PTH), 64 patients with a median glomerular filtration rate (GFR) of 31 (range 7-60) ml min(-1) 1.73 m(-2) and median age of 10.0 (4.1-16.9) years were followed over 1.3 (0.7-1.7) years at an average of 5 (3-14) clinic visits. At one visit, BMD of the lumbar spine was measured by dual energy X-ray absorptiometry. The mean BMD Z-score was normal (=0.0). Overall mean calcium, phosphate and PTH levels were in their respective normal ranges. The majority of the patients (72%) were treated with calcium carbonate, mean dose 65 mg kg(-1) day(-1); prescription was positively related to serum calcium levels and calcium-phosphate product (P=0.012 and P<0.01 respectively). Almost all patients (98%) were treated with alfacalcidol, mean dose 12 ng kg(-1) day(-1); prescription was not related to investigated factors. Patients grew well; there was no change in height standard deviation score (DeltaHtSDS=0.0). Normal BMD Z-score for age and sex can be achieved in children with CRF managed with the aim of maintaining normal PTH levels by dietary phosphate restriction, calcium-based phosphate binders and small doses of alfacalcidol. Further investigation of the underlying bone by the use of biopsy and histomorphometry is required to determine actual bone health.

Absorptiometry, Photon↗

PubMed2006

An association of tubular dysfunction, cortical macrocysts and chronic kidney disease.

We present an unusual combination of kidney disorders in a boy born to consanguineous parents. He presented in the first year of life with dehydration and urosepsis and was subsequently found to have hyposthenuria and distal renal tubular acidosis, with normal appearance of the kidneys, by ultrasound examination. By 4 years of age he had developed multiple large cysts in both kidneys, and his nephropathy eventually progressed so that at 17 years of age he is approaching end-stage renal disease (ESRD). The association of initial tubular dysfunction followed by the development of multiple cysts may represent a new form of kidney disease.

Acidosis, Renal Tubular↗

PubMed2005

Long-term outcome of chronic dialysis in children.

We describe the outcome since 1984 of all children receiving chronic dialysis in our centre for >3 months with a minimum follow-up of 5 (median 7.2) years. There were 98 children (61 boys), with a median age at the start of dialysis of 4.2 (range: birth to 16.2) years. Twenty-one children started dialysis at <1 year of age and 54 under <5 years. Thirty children had significant comorbidity. The median time on dialysis was 1.4 (0.3 to 14.4) years, giving a total dialysis experience of 296 patient-years. Fifty-three children received a renal transplant as their first change of treatment modality, but 31 switched between PD and HD, with a total of 54 changes of dialysis modality pre-transplantation. Twenty-one of the transplanted patients (39%) returned to dialysis. There were a total of 115 transplants in 88 patients. There was a positive increase for both the weight and height SDS for all the age groups while on dialysis, but this did not reach statistical significance. There were 17 deaths over the 20-year study period; of these, 10 died on dialysis. The overall patient survival was 83%. The mortality rate was 2.7 times greater in children who required renal replacement therapy under the age of 5 years. Of the deaths, 76% were in association with comorbid conditions. In conclusion, both a younger age at the start of renal replacement therapy and comorbidity are significant risk factors for death. The number of returnees to dialysis highlights the importance of conserving dialysis access.

Adolescent↗

PubMed2005

Childhood thin GBM disease: review of 22 children with family studies and long-term follow-up.

Thin glomerular basement membrane (GBM) disease is generally known to have a good renal prognosis, although renal insufficiency has sometimes been reported and the overlap with Alport syndrome implies that a good prognosis cannot be guaranteed. In order to shed light on long-term prognosis of thin GBM disease we have retrospectively evaluated 22 children with persistent haematuria and biopsy-proven thin GBM. Mean follow up was 7 years (range 2-17 years), mean age at onset was 7 years (range 1.5-15). Biopsies were performed a mean of 3.8 years after detection of hematuria. The light microscopy (LM) and immunofluorescence (IF) findings were essentially unremarkable in all of the children, while electron microscopy (EM) showed thinning of the GBM in all cases and no changes characteristic of Alport syndrome. The family history was positive for renal disease in 17 (77.3%) patients with hematuria in 8 (36.3%) families, and hematuria with renal failure (RF) or deafness in 9 (40.9%). It was completely negative for renal disease in 4 (18.2%) and unavailable in 1 (4.5%). Four patients (18%) showed a decline in renal function after 6, 8, 9 and 12 years of follow-up, and 1 of these also developed hearing impairment. None developed hypertension. Our study suggests that thin GBM disease is not always benign and a child with thin GBM should never be assigned such a prognosis, especially if there is a family history of renal impairment or deafness, where careful follow-up is needed due to the risk of late onset renal failure.

Adolescent↗

PubMed2005

Growth hormone for children with chronic renal failure and on dialysis.

We studied all children with CRF who received recombinant human growth hormone (rhGH) for more than a year (mean+/-SD duration of therapy 3.7+/-2.5 years) over an 11-year period. There were 32 children. Twenty-one children were conservatively managed, with a mean glomerular filtration rate (GFR) of 24+/-12 mL min(-1)/1.73 m2 at the start of rhGH. Their height standard deviation score improved from -2.5+/-1.4 to -2.1+/-0.7 at 1 year (P=0.3), -2.0+/-0.7 at 2 years (P=0.01), and -1.6+/-0.6 at 3 years (P=0.001). After that there was no improvement. Eleven children were on dialysis, six on haemodialysis (HD) and five on peritoneal (PD). Ht SDS improved from -2.7+/-0.5 to -2.3+/-0.5 at 1 year (P=0.02). Thereafter there was no further improvement. RhGH was stopped because of transplantation in 29 patients at a mean+/-SD age of 12.1+/-4.0 years. Mean Ht SDS was -1.8+/-0.8 at transplant and there was no change over the following 5 years. In conclusion, treatment with rhGH resulted in improvement in Ht SDS in conservatively managed CRF for up to 3.0 years and for 1 year in children on dialysis. Discontinuation of rhGH after transplantation resulted in little change in Ht SDS.

Adolescent↗

PubMed2005

Parathyroid hormone and growth in children with chronic renal failure.

BACKGROUND: In pediatric chronic renal failure (CRF) optimal parathyroid hormone (PTH) concentrations that minimize renal osteodystrophy and maximize growth are unknown. The search for optimum concentrations has been complicated as currently used "intact" PTH (iPTH) assays cross-react with long carboxyl-terminal PTH fragments (C-PTH), which antagonize the biologic actions of 1-84 PTH. The purpose of this study was to investigate the relationship between PTH, the 1-84 PTH:C-PTH ratio and growth rate in children with CRF. METHODS: A total of 162 patients, median (range) age 9.9 years (0.3 to 17.1 years), were recruited: 136 with a glomerular filtration rate (GFR) <60 mL/min/1.73 m(2)[96 managed conservatively (CRF group) and 40 transplanted patients], and 26 dialysis patients. Over a median (range) period of 1.1 years (0.5 to 1.7 years), children attended five (three to 15) clinics at which iPTH, cyclase-activating PTH (CAP-PTH), and height were measured. RESULTS: Mean PTH concentrations were within the normal range for both assays for the CRF group and up to twice the upper limit of normal for the dialysis group; CAP-PTH 24.8 pg/mL and 59.9 pg/mL (normal range 5 to 39 pg/mL), iPTH 37.1 pg/mL, and 102.6 pg/mL, respectively (normal range 14 to 66 pg/mL). The patients grew normally (change in height standard deviation score per year (DeltaHtSDS) =-0.01). There was no relationship between PTH concentrations and DeltaHtSDS in any patient group. The 1-84 PTH:C-PTH ratio was lower in dialyzed patients (P= 0.003), with worsening renal function (P= 0.047) and with PTH concentrations outside the normal range (P= 0.01). There was a weak correlation between the 1-84 PTH:C-PTH ratio and the DeltaHtSDS (r= 0.2, P= 0.01). CONCLUSION: Normal range PTH concentrations are appropriate, allowing normal growth in children with CRF managed conservatively. C-PTH may be of clinical significance.

Adolescent↗

PubMed2004

Differences between "intact" PTH and 1-84 PTH assays in chronic renal failure and dialysis.

"Intact" parathyroid hormone (iPTH) assays overestimate actual PTH as they cross-react with non (1-84) PTH fragments (C-PTH) that accumulate in renal failure. New assays that measure just 1-84 PTH (CAP-PTH) are now available. It has been suggested that there is a linear relationship between the two assays; however, increased C-PTH levels are found as glomerular filtration rate (GFR) declines and in patients on dialysis. We investigated the relationship between iPTH and CAP-PTH in children with chronic renal failure (CRF) managed conservatively and on dialysis. We investigated 241 children, 156 with a GFR <60 ml/min per 1.73 m(2) managed conservatively, 49 post renal transplant (and GFR <60 ml/min per 1.73 m(2)) and 36 on dialysis, by measuring PTH levels by iPTH and CAP-PTH assays. Multiple regression analysis comparing differences between PTH levels in each patient group was performed. Correlation slopes between iPTH and CAP-PTH assays differed between CRF and dialysis patients (P=0.001). These assays perform differently in CRF and dialysis patient groups. Studies investigating the correlation between newer assays and bone histology are required to determine whether these more-specific PTH assays are superior surrogate markers of bone turnover.

Adolescent↗

PubMed2004

The effect of heparin on graft thrombosis in pediatric renal allografts.

Graft thrombosis is an important cause of early (<4 weeks) renal graft loss. Reports show that heparin reduces the incidence of early renal allograft thrombosis. Routine peri-operative administration of unfractionated heparin was introduced in our unit in 1994. We conducted a retrospective study of 254 transplants, undertaken in children, between 1987 and 2000. There were 126 children who did not receive heparin (group 1) and 128 who did (group 2). Recipient characteristics and immunosuppression were similar in both groups. The incidence of graft loss secondary to thrombosis was compared between the groups. Variables previously identified with increased risk of graft loss, including donor age, recipient age, cold ischaemia time (CIT), multiple donor vessels, surgical complications, and side of graft donation, were examined using logistic regression. Thrombosis occurred in 14 grafts in group 1 and 11 grafts in group 2 (odds ratio 0.7, 95% confidence interval 0.3-1.6, P=not significant). The mean time to graft loss was similar in groups 1 and 2 (6.6, SD 3.9, range 2-12 days and 7.9, SD 4.4, range 1-14 days, respectively) ( P=0.445). Young recipient age ( P=0.006), young donor age ( P=0.009), increasing CIT ( P=0.007), and surgical complications ( P=0.002) increased the risk of graft thrombosis. A reduction in the incidence of early renal allograft thrombosis upon introduction of heparin was not demonstrated.

Adolescent↗

PubMed2004

The post-transplant lymphoproliferative disorder-a literature review.

The Epstein-Barr virus (EBV)-induced post-transplant lymphoproliferative disorder (PTLD) affects 1%-10% of all paediatric renal transplant recipients. This is a heterogeneous group of conditions characterised by EBV-driven proliferation of B-lymphocytes in the face of impaired T-cell immune surveillance. The risk factors predisposing to PTLD are becoming better understood, but its pathogenesis and myriad of clinical and histological features remain poorly defined. While new treatment modalities are being tried with variable success, regular EBV surveillance and carefully monitored reduction of immunosuppression remain the mainstay of treatment. In this review, we have presented the current knowledge of this increasingly common complication in renal transplant recipients.

Adult↗

PubMed2003

Catch-up growth with normal parathyroid hormone levels in chronic renal failure.

The optimum range for parathyroid hormone (PTH) levels in children with chronic renal failure (CRF) remains undefined. We aimed to determine growth velocity in children with CRF managed with normal PTH levels. We performed a retrospective case note review of 99 children (77 boys), with a glomerular filtration rate (GFR) <41 ml/min per 1.73 m(2), who had at least 2 years of 3-monthly follow-up. The age range at entry was 0.5-6.0 years; data collection was continued until 10 years of age or the commencement of growth hormone or renal replacement therapy. The median GFR was 22 ml/min per 1.73 m(2); over the study period mean serum calcium and phosphate levels were approximately equal to the mid-point of the respective normal ranges. Median PTH levels were equal to the upper limit of the normal range. Height standard deviation score (Ht SDS) at entry was -1.73. During the study period the overall mean change in Ht SDS was +0.3, significantly greater than the no change expected of a normal population ( P=0.004). The median dose of calcium carbonate was 150 mg/kg per day and 1-alpha calcidol 0.015 microg/kg per day. The growth rate was independent of all parameters, including age, PTH levels, the use of enteral feeds, and 1-alpha calcidol prescription. Our results indicate that catch-up growth can occur in infants and children with CRF when medical therapy is aimed at normalizing PTH levels.

Biomarkers↗

PubMed2003

Parathyroid hormone and its fragments in children with chronic renal failure.

Parathyroid hormone (PTH) immunoradiometric assays (IRMA) exhibit cross-reactivity between 1-84 PTH and long carboxyl-terminal-PTH (C-PTH) molecules. C-PTH antagonizes the biological actions of 1-84 PTH and circulates in excess in chronic renal failure (CRF), partially explaining why supra-physiological PTH levels are recommended to maintain bone turnover. Furthermore, the ratio 1-84 PTH/C-PTH may be related to bone turnover. This study characterizes the 1-84 PTH/C-PTH ratio in children with varying severity of CRF and levels of PTH. Two hundred and forty-one children with CRF, managed with the aim of preventing the development of hyperparathyroidism, had PTH measured by 'intact' IRMA and a new more specific Cyclase-Activating-PTH (CAP) IRMA. C-PTH levels were calculated by subtracting CAP-IRMA from 'intact' IRMA. Fifty-three controls with normal renal function were also recruited. Mean 'intact' IRMA correlated with CAP-IRMA ( r=0.98), but was higher ( P<0.001). The mean 1-84 PTH/C-PTH ratio was lower than controls in dialysis patients ( P=0.022) and those with a glomerular filtration rate <30 ml/min per m(2 )( P=0.033). This ratio was comparable to controls when the PTH level was normal, but was lower with PTH levels outside the normal range ( P<0.01). These data suggest that CAP-IRMA gives a more accurate assessment of actual PTH levels than 'intact' IRMA in CRF. Maintenance of normal PTH levels throughout the course of CRF permits the maintenance of a normal 1-84 PTH/C-PTH ratio, the clinical significance of which requires further investigation in children.

Child↗

PubMed2003

The use of steroid-sparing agents in steroid-sensitive nephrotic syndrome.

Childhood nephrotic syndrome (NS) is frequently characterized by a relapsing course. There is no uniform agreement about the precise stage at which a steroid-sparing agent should be introduced to control the disease. In order to evaluate the treatment strategies and outcome of steroid-sensitive NS over the last 2 decades, a retrospective notes review was undertaken in a cohort of children treated at Great Ormond Street Children's Hospital between 1980 and 2000. From a population of 863 children with NS referred, 509 had frequently relapsing or steroid-dependent disease and 261 children received at least one steroid-sparing agent. Cyclophosphamide was the first choice in 178 patients and in 114 no further steroid-sparing agent was needed. Levamisole was prescribed as the first steroid-sparing agent for 65 children and disease control was achieved in 30%. Cyclosporin A was prescribed in 61 children and sustained remission was induced in 69%. It is concluded that cyclophosphamide is a potent agent in inducing sustained remission in steroid-sensitive NS. Levamisole and cyclosporin A have emerged as attractive steroid-sparing agents. Complications and major side effects of treatment are infrequent but occasionally fatal.

Adolescent↗

PubMed2003

BK virus-associated renal problems--clinical implications.

BK virus (BKV), a human polyomavirus, infects most of the human population, but clinically relevant infections are usually limited to individuals who are immunosuppressed. After primary infection, BKV remains latent in the kidneys and can be reactivated in immune deficiency conditions, including transplantation. As primary infection occurs in childhood, BKV may be particularly important in the pediatric transplant population. BKV is associated with tubulointerstitial nephritis and ureteric stenosis in renal transplant recipients and hemorrhagic cystitis in bone marrow transplant recipients. There are increasing reports of BKV causing nephropathy and cystitis in non-renal solid organ transplant recipients and other immunodeficiency diseases. This might be related to the use of more potent immunosuppressive regimens or increasing awareness of BKV as an important pathogen. Diagnosis of BKV disease is by biopsy. Histopathological changes in renal biopsy specimens may mimic rejection or drug toxicity, but BKV nuclear inclusions can be seen. Treatment is by reduction of immunosuppression. Antiviral agents such as cidofovir are showing promise. BKV DNA polymerase chain reaction in blood or biopsy may be helpful in monitoring therapy. The impact of BKV disease in children is not well understood and prospective studies are needed to elucidate this further. This article reviews the current understanding of BKV-associated renal problems.

BK Virus↗