Effects of a novel rice-based diabetes-specific formula on postprandial glucose and gastrointestinal hormones: a double-blinded multi-arm randomized crossover trial.

Introduction: We developed a novel rice-based medical food for diabetes (MFDM) powder formula, using locally available ingredients in Thailand, which can potentially improve patient access to diabetes-specific formula (DSF) by reducing cost and improving availability. Purpose: The goals of our studies were to 1) measure the glycemic index (GI) and glycemic load (GL) of the MFDM powder formula in healthy individuals, and 2) assess postprandial glucose, insulin, satiety, hunger, and gastrointestinal (GI) hormone responses in adults with prediabetes or early type 2 diabetes after consuming MFDM in comparison with a commercially available standard formula (SF) and a DSF. Methods: In Study 1, glycemic responses were assessed using the area under the curve (AUC), which was used to calculate GI and GL. Study 2 was a double-blinded multi-arm randomized crossover trial enrolling participants with either prediabetes or type 2 diabetes of ≤6 years. At each study visit, participants consumed either MFDM, SF, or DSF which contained 25 g of carbohydrates. Hunger and satiety were assessed using a visual analog scale (VAS). Glucose, insulin, and GI hormones were assessed using AUC. Results: All participants tolerated the MFDM well with no adverse events. In Study 1, the measured GI was 39 ± 6 (low GI) and GL was 11 ± 2 (medium GL). In Study 2, glucose and insulin responses were significantly lower after MFDM compared with SF (p-value<0.01 for both), however, those responses were similar between MFDM and DSF. MFDM suppressed hunger, promoted satiety, stimulated active GLP-1, GIP, and PYY, and suppressed active ghrelin although these changes were similar to SF and DSF. Conclusions: MFDM had a low GI and a low-to-medium GL. In people with prediabetes or early type 2 diabetes, MFDM elicited reduced glucose and insulin responses when compared with SF. Rice-based MFDM may be an option for patients who are at risk for postprandial hyperglycemia. Clinical Trial Registration: https://www.thaiclinicaltrials.org/show/TCTR20210731001, identifier TCTR20210731001; https://www.thaiclinicaltrials.org/show/TCTR20210730007, identifier TCTR20210730007.

Development of a protein energy malnutrition screening tool for older Thais in public residential homes.

OBJECTIVE: This study aimed to develop and validate protein energy malnutrition (PEM) screening tool for older adults in public residential homes, and to test its practicality. DESIGN: This cross-sectional study consisted of two phases: tool development/validation and tool practicality evaluation. In Phase 1, the questionnaire was developed based on literature review and tested for content validity. Older residents were interviewed using this questionnaire to identify potential PEM risk factors. A 24-h recall was used to collect dietary data, and body composition and serum albumin were measured. In Phase 2, practicality of new PEM screening tool was evaluated by intended users. Data were analysed by χ2 test, Fisher's exact test, t-test, Mann-Whitney U test and multiple logistic regression. Akaike Information Criterion (AIC) was used to estimate the best fit model. SETTING: Four public residential homes in central region, Thailand. PARTICIPANTS: 249 older residents residing in public residential homes and eight intended users. RESULTS: 26·9 % had PEM (serum albumin <3·5 g/dl). According to multiple logistic regression and AIC values, PEM predictors were having pressure ulcer, experiencing significant weight loss and taking ≥ 9 types of medicine daily. These predictors were included in PEM screening tool. Regarding the tool performance test, area under the ROC curve was 0·8 (P < 0·001) with sensitivity and specificity of 83·9 and 45·5 %, respectively. For its practicality, eight intended users reported that it was useful and easy to use. CONCLUSIONS: New screening tool may be capable of identifying PEM in older residents, and further testing is required before being recommended for use.

Dietary Iron Intake and Availability in Hill Tribe and Urban Women, Chiang Rai Province, Northern Thailand.

Data were collected as part of a cross-sectional study. The objectives were to compare dietary intakes of iron and enhancers and inhibitors of non-heme iron absorption in hill tribe and urban women of Chiang Rai province, northern Thailand, and compare iron- and vitamin C- containing foods sold in markets in both settings. Dietary data were collected using three 24- hour recalls from 128 women aged 19-50 years (hill tribe: n = 65; urban n = 63), and proportions of low-, medium- and high-iron/vitamin C containing foods were surveyed in local markets. Hill tribe women consumed less iron, animal protein, vitamin C and calcium, but market availability of iron/vitamin C foods was similar. Future interventions should focus on food choice modification, to improve intakes of iron and foods that enhance its absorption, especially among hill tribe women.

Food Consumption and Accessibility in Hill Tribe and Urban Women, Chiang Rai Province, Northern Thailand.

This analytical cross-sectional study aimed to examine the associations between setting and food consumption and accessibility in two districts of Chiang Rai province, northern Thailand. 128 women (65 in hill tribe setting and 63 in urban setting) were surveyed using an interviewer-administered questionnaire. Traditional and mobile markets were well utilized in both settings, in spite of the growth of multinational retailers. Consumption of ready-to-eat food and home-grown/reared or wild foods was associated with socioeconomic status. Fewer hill tribe women had eaten ready-to-eat food, although some reported fairly regular consumption. Consumption of home-grown/reared or wild foods was more evident in the hill tribe group, showing their continued utilization of traditional food resources.

A Social Ecological Approach to Develop a Nutrition Education Program for Preventing Iron Deficiency Anemia in Young Children in Rural Pakistan.

Inappropriate feeding practices puts infants and young children at risk of iron deficiency anemia. Maternal complementary feeding (CF) behavior is determined by influences at various levels, including knowledge and attitude about feeding, inter-personal interaction with family/friends, community norms and support. The aim of this study is to understand the various influences on maternal CF behavior in order to develop a culturally appropriate nutrition education program to improve iron status of children aged 9-24 months. Using a social ecological approach, in-depth interviews with stakeholders revealed restraining factors that prevented behavior change. Culturally appropriate nutrition education messages were developed to address these constraints.

Dietary iron intake and availability are related to maternal education level in overweight/obese adolescents.

PURPOSE: To compare intakes of dietary iron and enhancers and inhibitors of iron absorption between overweight/obese (OW/OB) adolescents and their normal weight (NW) peers, and between parental education levels stratified by weight status. METHODS: This was a comparative cross-sectional study of adolescents (n 121 OW/OB and n 102 NW) aged 12-14 years, attending a secondary school in Nonthaburi province, Thailand. Socio-demographic data were obtained from participants' parents using a questionnaire. Participants recorded their intakes for 3 non-consecutive days, using a prospective food record. RESULTS: Compared with NW adolescents, OW/OB adolescents consumed more total protein and animal protein after adjustment for energy intake (both p = 0.047). OW/OB adolescents whose mothers were less educated consumed more total iron and available iron after adjustment for energy intake, compared with their OW/OB peers whose mothers were more educated (p = 0.045 and p = 0.040). NW adolescents with more highly educated mothers had higher absolute and energy-adjusted fibre intakes (both p = 0.047). However, NW adolescents of mothers with a high-intermediate level of education consumed less calcium, after adjustment for energy intake (p = 0.028). CONCLUSIONS: OW/OB adolescents with less educated mothers had higher energy-adjusted intakes of iron and available iron. Dietary differences in OW/OB adolescents relative to maternal education, and other socioeconomic indicators, should be explored in a nationally representative data set.

A review of iron studies in overweight and obese children and adolescents: a double burden in the young?

INTRODUCTION: The connection between iron and excessive adiposity has received much research interest. Although children and adolescents have unique developmental phases and nutritional demands, to date, reviews of iron in the overweight (OW) and obese (OB) have combined studies of children and adults or have focussed on adults. PURPOSE: The aim of this review was to critically evaluate studies of the relationship between iron and OW and obesity in children and adolescents, with emphasis on iron status, oral iron response, dietary intake and systemic inflammatory markers. METHODS: A PubMed search was conducted to identify relevant articles published up to December 2015. Combinations of the following keywords were used: iron, OW, OB, children, adolescents, diet, hepcidin, inflammation, fortification, supplementation, weight loss, trace elements, obesity, iron deficiency (ID), minerals. RESULTS AND CONCLUSION: A higher prevalence of ID, or risk of ID, among OW and OB children and adolescents has been consistently observed. Chronic inflammation caused by excessive adiposity offers a plausible explanation for this finding, rather than dietary factors. However, future studies must employ screening for the presence of both acute and chronic infections and inflammatory conditions and report other factors such as pubertal status. Intervention studies, although few, indicate that OW and OB children and adolescents have reduced response to oral iron. Further trials are needed to explore the connection between body fat mass, inflammatory proteins and iron absorption, together with the effect of weight loss on iron status in iron-deficient OW and OB children and adolescents.

Iron status is inversely associated with dietary iron intakes in patients with inactive or mildly active inflammatory bowel disease.

BACKGROUND: Patients with inflammatory bowel disease (IBD) frequently appear iron deplete but whether this is a reflection of dietary iron intakes is not known. METHODS: Dietary data were collected from 29 patients with inactive or mildly-active IBD and 28 healthy controls using a validated food frequency questionnaire that measured intakes of iron and its absorption modifiers. Non-haem iron availability was estimated using a recently developed algorithm. Subjects were classified for iron status based upon data from a concomitant and separately published study of iron absorption. Absorption was used to define iron status because haematological parameters are flawed in assessing iron status in inflammatory conditions such as IBD. RESULTS: Dietary intakes of total iron, non-haem iron and vitamin C were significantly greater in IBD patients who were iron replete compared to those who were iron deplete (by 48%, 48% and 94% respectively; p≤0.05). The predicted percentage of available non-haem iron did not differ between these groups (19.7 ± 2.0% vs 19.3 ± 2.0% respectively; p=0.25). However, because of the difference in iron intake, the overall amount of absorbed iron did (2.4 ± 0.8 mg/d vs 1.7 ± 0.5 mg/d; p=0.013). No such differences were observed in the healthy control subjects. CONCLUSIONS: In IBD, iron status is more closely related to the quality and quantity of dietary iron intake than in the general healthy population.

Dietary fortificant iron intake is negatively associated with quality of life in patients with mildly active inflammatory bowel disease.

BACKGROUND: Iron deficiency anaemia and oral iron supplementation have been associated negatively with quality of life, and with adverse effects, respectively, in subjects with inflammatory bowel disease (IBD). Hence, the risk-benefit ratio of oral iron is not understood in this patient group. The present case-control study investigated whether dietary iron intake impacts on quality of life in IBD patients. METHODS: Quality of life, habitual dietary iron intakes and iron requirements were assessed in 29 patients with inactive or mildly active IBD as well as in 28 healthy control subjects. RESULTS: As expected, quality of life was worse in IBD patients as a whole in comparison to healthy controls according to EuroQol score and EuroQol VAS percentage (6.9 ± 1.6 vs 5.3 ± 0.6; p< 0.0001 and 77 ± 14% vs 88 ± 12%; p=0.004 respectively). For IBD subjects, 21/29 were iron deplete based upon serum iron responses to oral iron but, overall, were non-anaemic with mean haemoglobin of 13.3 ± 1.5 g/dL, and there was no difference in their quality of life compared to 8/29 iron replete subjects (Hb 14.0 ± 0.8 g/dL). Interestingly, total dietary iron intake was significantly negatively associated with quality of life in IBD patients, specifically for non-haem iron and, more specifically, for fortificant iron. Moreover, for total non-haem iron the negative association disappeared when fortificant iron values were subtracted. Finally, further sub-analysis indicated that the negative association between (fortificant) dietary iron intake and quality of life in IBD patients is driven by findings in patients with mildly active disease rather than in patients with quiescent disease. CONCLUSIONS: Iron deficiency per se (i.e. without concomitant anaemia) does not appear to further affect quality of life in IBD patients with inactive or mildly active disease. However, in this preliminary study, dietary iron intake, particularly fortificant iron, appears to be significantly negatively associated with quality of life in patients with mildly active disease.

Iron requirements based upon iron absorption tests are poorly predicted by haematological indices in patients with inactive inflammatory bowel disease.

Fe deficiency and Fe-deficiency anaemia are common in patients with inflammatory bowel disease (IBD). Traditional clinical markers of Fe status can be skewed in the presence of inflammation, meaning that a patient's Fe status can be misinterpreted. Additionally, Fe absorption is known to be down-regulated in patients with active IBD. However, whether this is the case for quiescent or mildly active disease has not been formally assessed. The present study aimed to investigate the relationship between Fe absorption, Fe requirements and standard haematological indices in IBD patients without active disease. A group of twenty-nine patients with quiescent or mildly active IBD and twenty-eight control subjects undertook an Fe absorption test that measured sequential rises in serum Fe over 4 h following ingestion of 200 mg ferrous sulphate. At baseline, serum Fe, transferrin saturation, non-transferrin-bound Fe (NTBI), ferritin and soluble transferrin receptor were all measured. Thereafter (30-240 min), only serum Fe and NTBI were measured. Fe absorption did not differ between the two groups (P = 0·9; repeated-measures ANOVA). In control subjects, baseline haematological parameters predicted Fe absorption (i.e. Fe requirements), but this was not the case for patients with IBD. Fe absorption is normal in quiescent or mildly active IBD patients but standard haematological parameters do not accurately predict Fe requirements.

Post-prandial iron absorption in humans: comparison between HFE genotypes and iron deficiency anaemia.

BACKGROUND & AIMS: Measurement of serum iron increase after ingestion of a meal could be an efficient method of comparing post-prandial iron absorption between groups of individuals. We determined whether the rise in post-prandial serum iron is increased in fully treated patients with hereditary haemochromatosis (HFE C282Y+/+; HH) compared to iron deficiency anaemia (IDA), iron-replete heterozygous subjects (HFE C282Y+/-) and iron-replete controls (HFE C282Y-/-). METHODS: Serum iron increase was measured over 4h after a meal containing 13.1 mg non-haem iron. RESULTS: Post-prandial increase in serum iron was similar in treated HH versus IDA (P=0.54), but greater than control subjects (P<0.0001). In five HH patients, using (58)Fe as a tracer, the rate of iron absorption was increased (P<0.05) and serum non-transferrin bound iron showed a tendency to increase (P=0.06). Serum iron curves did not differ for heterozygous subjects and controls (P=0.65). CONCLUSIONS: Using the serum iron method we found a comparable increase in post-prandial iron absorption in treated HH and IDA compared with controls. While post-prandial iron absorption in the group heterozygous for the C282Y mutation was modestly increased relative to controls, this difference was not statistically significant.

Proton pump inhibitors suppress absorption of dietary non-haem iron in hereditary haemochromatosis.

BACKGROUND AND AIMS: During the long-term treatment of patients with hereditary haemochromatosis (HH) the authors observed that proton pump inhibitors (PPI) reduced the requirement for maintenance phlebotomy. Gastric acid plays a crucial role in non-haem iron absorption and the authors performed a case review and intervention study to investigate if PPI-induced suppression of gastric acid would reduce dietary iron absorption in C282Y homozygous patients. METHODS: Phlebotomy requirements to keep serum ferritin approximately 50 microg/l before (mean 6.1 (SE 0.6) years) and during (3.8 (0.9) years) administration of a PPI were evaluated in seven patients and a post-prandial study was performed to determine whether PPIs reduce absorption of non-haem iron (14.5 mg) from a test meal in a further 14 phlebotomised patients with normal iron stores. RESULTS: There was a significant reduction (p<0.001) in the volume of blood removed annually before (2.5 (0.25) l) and while taking (0.5 (0.25) l) a PPI. Administration of a PPI for 7d suppressed absorption of non-haem iron from the meal as shown by a significant reduction (all p<0.01) in: area under the serum curve (2145 (374) versus 1059 (219)), % recovery of administered iron at peak serum iron (20.5 (3.2) versus 11.0 (2.0)%) and peak serum iron (13.6 (2.4) vs 6.1 (1.2) micromol/l) (all values are before vs during PPI). CONCLUSIONS: Administration of a PPI to patients with HH can inhibit the absorption of non-haem iron from a test meal and the habitual diet.

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.

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.

Dietary sources of inorganic microparticles and their intake in healthy subjects and patients with Crohn's disease.

Dietary microparticles are non-biological, bacterial-sized particles. Endogenous sources are derived from intestinal Ca and phosphate secretion. Exogenous sources are mainly titanium dioxide (TiO2) and mixed silicates (Psil); they are resistant to degradation and accumulate in human Peyer's patch macrophages and there is some evidence that they exacerbate inflammation in Crohn's disease (CD). However, whether their intake differs between those with and without CD has not been studied. We aimed to identify dietary microparticle sources and intakes in subjects with and without CD. Patients with inactive CD and matched general practice-based controls (ninety-one per group) completed 7 d food diaries. Intake data for dietary fibre and sucrose were compared as positive controls. All foods, pharmaceuticals and toothpastes were examined for microparticle content, and intakes of Ca and exogenous microparticles were compared between the two groups. Dietary intakes were significantly different between cases and controls for dietary fibre (12 (SD 5) v. 14 (SD 5) g/d; P=0.001) and sucrose (52 (SD 27) v. 45 (SD 18) g/d; P=0.04) but not for Ca. Estimated median TiO2 and Psil intakes (2.5 and 35 mg/individual per d respectively, totalling 10(12)-10(13) microparticles/individual per d) were broadly similar to per capita estimates and while there was wide variation in intakes between individuals there was no significant difference between subjects with CD and controls. Hence, if exposure to microparticles is associated with the inflammation of CD, then the present study rules out excess intake as the problem. Nonetheless, microparticle-containing foods have now been identified which allows a low-microparticle diet to be further assessed in CD.

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.

Intake of dietary iron is low in patients with Crohn's disease: a case-control study.

Patients with Crohn's disease (CD) often experience Fe deficiency (ID) and frequently alter their diet to relieve abdominal symptoms. The present study set out to assess whether patients with CD have dietary habits that lead to low Fe intakes and/or reduced bioavailable Fe compared with control subjects. Patients with asymptomatic CD were matched to controls (n 91/group). Dietary intakes of Fe and contributions from different food groups were compared using a 7 d food diary. Promoters and inhibitors of non-haem Fe absorption were investigated and a recently published algorithm was applied to assess bioavailable Fe. Fewer patients than controls met the reference nutrient intake for Fe (32% CD patients v. 42% controls). Overall, patients had significantly lower mean Fe intakes (by 2.3 mg/d) and Fe density (by 0.26 mg/MJ (1.1 mg/1000 kcal)) compared with controls (both P<0.001). Differences were mainly due to a preference among CD patients for low-fibre non-Fe fortified cereals, particularly breakfast cereals. In particular, control subjects had higher Fe intakes than matched CD subjects for men (P<0.001) and women less than 50 years (P=0.03). Intakes of both ascorbic acid (P<0.001) and phytic acid (P<0.01), but not animal tissue (P=1.0), were lower in patients with CD, but these had no overall effect on the predicted percentage of bioavailable Fe. Thus total bioavailable Fe was reduced in patients with CD due to lower intakes (P<0.01). Dietary Fe intakes are low in CD patients, which may contribute to an increased risk of ID and anaemia. Changing dietary advice may compromise perceived symptoms of the disease so the need for Fe supplementation should be carefully considered.

Longitudinal evaluation of the pharmacokinetics of cyclosporin microemulsion (Neoral) in pediatric renal transplant recipients and assessment of C2 level as a marker for absorption.

BACKGROUND: There are important differences in CsA pharmacokinetics between adult and pediatric patients, such that pharmacokinetic data can not necessarily be extrapolated from the adult to the pediatric setting. Research in adult renal transplant patients has shown that adequate cyclosporin exposure (AUC0-4) in the first week post-transplant is important for successful clinical outcome, and that cyclosporin concentration at 2 h post-dose (C2) provides the optimal single-time point marker for AUC0-4. Clinically, dose management based on C2 level results in a low incidence of acute rejection in the adult renal transplant population. The study reported here undertook pharmacokinetic profiling in de novo renal transplant patients over a period of 6 months and retrospectively assessed alternative monitoring strategies based on pharmacokinetic findings and clinical outcomes. METHODS: This open-label, observational, prospective study was carried out at four UK transplant centers over a period of 6 months in pediatric de novo renal transplant recipients receiving the microemulsion formulation of cyclosporin (Neoral) according to local protocol. Twelve-hour pharmacokinetic profiles (8-16 blood samples each) were performed on days 5 and 14 and at weeks 4, 13 and 26 post-transplant. RESULTS: Thirty-two patients were recruited (median age 10 yr, range 3-18 yr). At 6 months, patient survival was 100% and graft survival was 91%. The incidence of clinically determined acute rejection was 41% (13 of 32). Six patients discontinued Neoral before 6 months: three due to graft loss, one due to rejection, one due to renal toxicity and one due to hypertrichosis. At all time points studied, C2 correlated more closely with AUC0-4 and with AUC0-12 than did the pre-dose cyclosporin concentration (C0, or trough). Patients achieving C2 > 1.5 microg/mL by the fifth postoperative day experienced no acute rejection in the first 6 months, compared with a 50% rejection rate among patients with C2 < 1.5 microg/mL (P < 0.05). Binary logistic regression analysis showed that C2 level >1.7 microg/mL was associated with approximately 90% probability of freedom from acute rejection. Analysis of renal function across patients grouped according to cyclosporine exposure (AUC0-4, C2) showed no adverse effects of higher/increased exposure on creatinine or GFR. CONCLUSIONS: C2 level provides a more reliable marker for CsA exposure than C0 in pediatric renal transplant recipients, and is more closely predictive of acute rejection risk. A C2 target of 1.7 microg/mL appears appropriate in this population during the immediate post-transplant period in order to maximize clinical benefit.

Chronic hemodialysis in infants and children under 2 years of age.

Over the past 16 years, 18 children under 2 years of age received chronic hemodialysis (HD) at our center. Five children were anuric at the start of HD and 6 had significant co-morbidity. The most common underlying diagnosis was posterior urethral valves. The median age at the start of HD was 12.2 months. A total of 39 episodes (defined as a discrete time period during which HD was the principle form of renal replacement therapy) of HD were performed, with a median duration of 7 months and 91.3 dialysis sessions per episode. Problems with vascular access were very common, with a revision ratio of 40%. Twenty-two line revisions were required for 36 episodes of line infection, with a median rate of line infection of 2.7 infections/patient years. The most commonly encountered organism was coagulase-negative Staphylococcus (69%). Twenty-three lines needed revision due to poor line function, despite the routine use of heparin. The effectiveness of HD was assessed in 11 patients who received HD for a continuous period of 3 or more months. The median urea reduction rate was 72%, while the parathyroid hormone levels improved to within twice the upper limit of the reference range in 69%. While there was no significant change in the median weight and height standard deviation score (SDS), the median SDS for head circumference showed significant improvement ( P=0.04). Both growth and developmental outcomes were strongly influenced by existing co-morbidity. Sixteen (89%) children were transplanted. Four (22%) children died, 3 after successful transplants. None of the deaths occurred on HD or resulted from its complications. In conclusion, HD in infants and small children is an effective and safe form of renal replacement therapy, but problems with vascular access limit its long-term use.