UK Renal Registry 13th Annual Report (December 2010): Chapter 5: demography of the UK paediatric renal replacement therapy population in 2009.

AIMS: To describe the demographics of the paediatric RRT population under the age of 16 years in the UK and to analyse changes in demography with time. METHODS: Extraction and analysis of data from the UK Renal Registry (UKRR). RESULTS: There were 751 children <16 years old with established renal failure (ERF) in the UK in December 2009. The reported prevalence under the age of 16 years was 65 per million age related population (pmarp) and the reported incidence 9.3 pmarp. The incidence and prevalence for South Asian patients was much higher than that of the White and Black populations. Of the patients for whom a primary renal diagnosis had been reported, renal dysplasia ± reflux was the most common cause of ERF accounting for 34.0% of prevalent cases. There has been growth in treatment numbers in all paediatric renal centres between 1995 and 2010. Whilst the rate of transplantation within 90 days of commencing RRT has remained at around 25-30% of patients, the use of HD has increased by 4% at the expense of PD. CONCLUSIONS: The paediatric ERF population continued to expand with a slow increase in both incidence and prevalence rates. The high incidence in patients from ethnic minority groups will lead to a greater proportion of the population being from these groups in time. To maintain the high proportion of engrafted patients it will be necessary to encourage living donation in the ethnic minority population.

UK Renal Registry 12th Annual Report (December 2009): chapter 14: demography of the UK paediatric renal replacement therapy population in 2008.

AIMS: To describe the demographics of the paediatric RRT population in the UK and analyse changes in demographics with time. METHODS: Extraction and analysis of data from the UK Paediatric Renal Registry and the UK Renal Registry (UKRR). RESULTS: The UK paediatric established renal failure (ERF) population in December 2008 was 905 patients. The prevalence under the age of 16 years was 56 per million age related population (pmarp) and the incidence 7.4 pmarp. The incidence and prevalence for South Asian patients was much higher than that of the White and Black populations. Renal dysplasia was the most common cause of ERF accounting for 33% of prevalent cases. Diseases with autosomal recessive inheritance were a common cause of ERF in all ethnic groups, 23.5% of prevalent and 18% of incident cases. Whilst the incidence and prevalence of diseases with autosomal recessive inheritance in the South Asian population was 3 times that of the white population, this was not the sole reason for the increased proportion of South Asian patients with ERF, as diseases with no defined inheritance were twice as common in this ethnic group than in White patients. Prevalent mortality stood at 9.4%. Most deaths were in patients presenting with ERF early in life and mortality varied markedly according to the aetiology of ERF. The proportion with new grafts from living donors has steadily risen to 54%. Children from ethnic minority groups were less likely to have an allograft and living donation was less frequent in this population. For those on dialysis, 56% were receiving peritoneal dialysis. This was the main treatment modality for patients under 4 years of age. CONCLUSIONS: The paediatric ERF population continued to expand slowly. Incidence and prevalence rates were stable and similar to other developed nations. The high incidence in patients from ethnic minority groups will lead to a greater proportion of the population being from these groups in time. To maintain the high proportion of engrafted patients it will be necessary to encourage living donation in the ethnic minority population. Case note analysis of the factors involved in mortality would be valuable.

Production of fumonisins by Fusarium verticillioides strains on solid and in a defined liquid medium--effects of L-methionine and inoculum.

In order to evaluate the toxicological and carcinogenic effects of fumonisins, large amounts of fumonisins need to be purified, which requires optimal conditions for production in culture. Five strains of F. verticillioides were compared for their ability to produce fumonisins in solid and liquid media with and without the addition of methionine, a fumonisin precursor. Inoculations were made either with lyophilized cultures or a concentrated inoculum. Growth in liquid medium, measured by biomass, was directly correlated to total fumonisin production when a lyophilized inoculum was used. Fumonisin production was stimulated by the addition of 0.2% L-methionine to solid media for most strains. Levels ranged from 1500-3900 mg/kg in rice, and 2900-12500 mg/kg in maize cultures inoculated with lyophilized cultures; 200-4800 mg/kg in rice, and 1500-4200 mg/kg in maize cultures inoculated with concentrated inoculum. Strains that produced relatively high levels of fumonisins in solid media did not necessarily do so in liquid medium and vice versa. Total fumonisin levels in liquid medium ranged from 40-590 mg/l inoculated with lyophilized cultures and < 1-110 mg/l inoculated with concentrated inoculum, without adding the precursor. F. verticillioides strains therefore varied in their ability to produce fumonisins, and conditions for production need to be optimized individually for each strain.

Fumonisin B1-induced hepatocellular and cholangiocellular tumors in male Fischer 344 rats: potentiating effects of 2-acetylaminofluorene on oval cell proliferation and neoplastic development in a discontinued feeding study.

Fumonisin B1 (FB1) is a naturally occurring mycotoxin produced by Fusarium verticillioides. Dietary exposure to FB1 has been linked to human cancer in certain parts of the world, and treatment with FB1 causes oval cell proliferation and liver tumors in rats. To study the potential role of oval (liver progenitor) cells in the cellular pathogenesis of FB1-induced liver tumors, we gave male F344 rats prolonged treatment with FB1 for 25 weeks, followed by return to control diet until 50 weeks ('stop study'). The time course of FB1-induced liver lesions was followed by examination of serial liver biopsies at set time intervals and post-mortem liver tissue at the end of the study. The effects of different FB1 treatment regimens (5 versus 25 weeks), as well as the modulating effect of 2-acetylaminofluorene (2-AAF), on the kinetics of oval cell proliferation and development of liver tumors were compared. Prolonged treatment with FB1 in normal diet caused persistent oval cell proliferation and generation of both hepatic adenomas and cholangiofibromas (CFs). These liver lesions occurred in the setting of chronic toxic hepatitis and liver fibrosis/cirrhosis, similar to that seen in human hepatocarcinogenesis. Some adenomas and CFs were dysplastic, and one post-mortem liver contained a hepatocellular carcinoma. OV-6+ oval cells were noted in close relation to proliferative neoplastic liver lesions, and some of these lesions expressed OV-6, suggesting that all these cell types were derived from a common progenitor cell. 2-AAF enhanced the size of FB1-induced glutathione S-transferase pi+ hepatocellular lesions and the incidence of CFs in post-mortem liver specimens, but this was not statistically significant. In conclusion, this study supports the involvement of dietary FB1 in liver carcinogenesis in male F344 rats. Oval cells may be the source of both the hepatocellular and cholangiocellular tumors induced by prolonged treatment with FB1. 2-AAF appears to have an enhancing effect on FB1-induced liver tumors, presumably due to its potent inhibitory effects on hepatocyte regeneration.