Malcolm Lewis

Unilateral multicystic dysplastic kidney: the case for nephrectomy

Management of unilateral multicystic dysplastic kidneys (MCDK) presents physicians and surgeons with a significant dilemma. Recent studies have indicated that the incidence of short term complications of MCDK is low and many authors have recommended conservative non-operative treatment. Surgery has been proposed by some because of the potential complications of hypertension, infection, and malignant change. Three children with hypertension secondary to MCDK seen at this institution in the past four years, one of whom had been discharged from follow up as a result of ‘disappearance’ of the cystic kidney on ultrasound examination, are reported. We believe that the risks of hypertension secondary to MCDK have been understated, and that based on the conclusions of these studies, many children may be receiving suboptimal follow up. We currently favour elective nephrectomy as the treatment of choice for this lesion.

Demographics of blood pressure and hypertension in children on renal replacement therapy in Europe

Hypertension is a well-known complication in children on renal replacement therapy and an important risk factor for cardiovascular disease in later life. In order to define the prevalence of and risk factors for hypertension among children, we enrolled 3337 pediatric patients from 15 countries in the ESPN/ERA-EDTA Registry of whom 464 were on hemodialysis, 851 on peritoneal dialysis, and 2023 had received a renal allograft. Hypertension was defined as either systolic or diastolic blood pressures in the 95th percentile or greater for age, height, and gender or use of antihypertensive medication. Analyses were adjusted for age, gender, duration, and modality of renal replacement therapy. In 10 countries in which information on the use of antihypertensive medication was available, hypertension was present in over two-thirds of hemodialysis, peritoneal dialysis, or transplant patients. Blood pressure values above the 95th percentile were significantly more prevalent in very young patients (under 3 years) compared to 13- to 17-year olds (odds ratio 2.47), during the first year compared to over 5 years of renal replacement therapy (odds ratio 1.80), and in patients on hemodialysis compared to transplant recipients or those on peritoneal dialysis (odds ratios of 2.48 and 1.59, respectively). Over time, mean blood pressures decreased in both hemodialysis and transplant patients, but not in peritoneal dialysis patients. Hence, our findings highlight the extent of the problem of hypertension in children with end-stage renal disease in Europe.

Immunisation against varicella in end stage and pre-end stage renal failure

OBJECTIVES To investigate the seroconversion rate and duration of persistence of protective antibody titres after varicella immunisation in children with renal failure. DESIGN 32 children (25 end stage and 7 pre-end stage renal failure) were immunised using 2 × 2000 plaque forming unit doses of varicella vaccine 3 months apart. Varicella antibody titres were measured by enzyme linked immunosorbent assay. RESULTS All children initially seroconverted after immunisation. At a mean follow up of 20.3 months, 23 of 28 had protective antibody titres, 4 children having died of unrelated causes. Two children required a third booster dose. 11 children underwent renal transplantation; 10 had protective titres at the time of transplantation and, at a mean of 23.4 months after immunisation, 6 currently have protective titres. Minor side effects occurred after 11 vaccine doses in 9 children. No child developed varicella, despite 10 clear episodes of exposure to the wild-type virus. CONCLUSIONS Varicella immunisation in children with end stage and pre-end stage renal failure results in a high rate of seroconversion and persistence of protective antibody titres. More widespread use of the vaccine before renal transplantation is recommended.

Improvement in the Renal Prognosis in Nephropathic Cystinosis

BACKGROUND AND OBJECTIVES Nephropathic cystinosis (NC) is an autosomal recessive disorder occurring in one to two per 100,000 newborns. Because of the rarity of NC, long-term outcome data are scarce. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS 245 NC patients from 18 countries provided data to the ESPN/ERA-EDTA registry. We matched NC patients on renal replacement therapy (RRT) to non-NC children on RRT. RESULTS Between 1979 and 2008, mean age at the start of RRT among NC children increased by 0.15 year per calendar year (95% confidence interval, 0.10 to 0.21) from 8.8 to 12.7 years, whereas we did not observe this in non-NC children. Five-year survival after the start of RRT improved in NC patients from 86.1% (before 1990) to 100% (since 2000) as compared with the control population (89.6% and 94.0%). NC patients received a renal allograft more often (relative risk, 1.09; 95% confidence interval, 1.00 to 1.17) as compared with matched RRT children, and 5-year graft survival was better (94.0% versus 84.0%). NC dialysis patients were less often hypertensive than non-NC children matched for age, country, and dialysis modality (42.7% versus 51.7%) and had lower parathyroid hormone levels (median, 56 versus 140 pg/ml). Although height at start of RRT slightly improved during the past decade, children with NC remained significantly shorter than non-NC children at the start of RRT. CONCLUSIONS We demonstrated improved survival of the renal function as well as better patient and graft survival after the start of RRT in a large European cohort of NC patients over the last two decades.

Long-term outcome of meningococcal sepsis-associated acute renal failure.

Setting: Twenty-one of 209 children admitted to the intensive care unit with meningococcal septicemia developed oliguric acute renal failure necessitating renal replacement therapy. Patients: Twelve survivors underwent renal assessment at a median of 4.2 yrs postpresentation. Result: Two had abnormal glomerular filtration rate, proteinuria, and hypertension; one had isolated proteinuria; and one had an isolated renal parenchymal defect on DMSA scan. Conclusion: Long-term follow-up of this population is recommended.

Childhood steroid-sensitive nephrotic syndrome: Does the histology matter?

Renal biopsy specimens from 51 children with steroid-sensitive nephrotic syndrome who were following a frequently relapsing or steroid-dependent course were reviewed by two histopathologists. In all cases the biopsy was performed prior to the commencement of an 8-week course of cyclophosphamide. The clinical courses of these patients both prebiopsy and for a minimum of 2 years after completion of cyclophosphamide therapy were analyzed using retrospective case note analyses. The distribution of histologic diagnoses differed significantly from that reported by the International Study of Kidney Disease in Children in their study of children who underwent biopsy at the time of presentation, there being an excess of focal segmental glomerulosclerosis and mild mesangial hypercellularity in this series. The prebiopsy clinical course did not predict for histologic diagnosis, and there was no correlation between prebiopsy course or histology and postcyclophosphamide course. The findings of this study support the clinical impression that steroid sensitivity rather than histology is the major determinant of prognosis in childhood nephrotic syndrome and that frequency of relapse alone is not an indication for biopsy.

Determinants of eGFR at start of renal replacement therapy in paediatric patients

BACKGROUND Few studies have investigated the determinants of glomerular filtration rate (GFR) in paediatric patients starting on dialysis or with a transplant. METHODS Data were collected as part of the European Society of Paediatric Nephrology/European Renal Association-European Dialysis and Transplant Association registry from 14 European countries and referred to incident paediatric patients starting on renal replacement therapy (RRT) between 2002 and 2007 under the age of 18 years. Estimated glomerular filtration rate (eGFR) was calculated using the Schwartz formula. Data were adjusted for age, gender, treatment modality at start, primary cause of renal failure (PRD) and regions in Europe (eGFR(adj)). RESULTS Median eGFR in the 938 patients starting RRT was 10.4 mL/min/1.73 m(2) (5th and 95th percentile: 4.0-26.9). Twenty-six patients (2.8%), mainly infants with Finnish-type nephropathy, started with eGFR levels >50 mL/min/1.73 m(2). Younger age, female gender, starting on dialysis and having a short time between the first visit to a paediatric nephrologist (PN) and start of RRT were associated with lower eGFR at start of RRT. Gender differences were only present during adolescent age and disappeared when using the same K value for both genders. The various PRDs showed large differences in the rate of decline in eGFR between the first visit to a PN and start of RRT; however, this did not result in differences in eGFR(adj) at start of RRT. CONCLUSIONS The main determinants of eGFR at start of RRT were age, gender, treatment modality at start, and the time between the first visit to a PN and start of RRT. Research is needed to determine the consequences of these differences.

UK Renal Registry 15th annual report: Chapter 4 demography of the UK paediatric renal replacement therapy population in 2011.

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: Data were collected from all 13 paediatric renal centres within the UK. A series of cross-sectional and longitudinal analyses were performed to describe the demographics of paediatric RRT patients. Results: A total of 856 children and young people under 18 with ERF were receiving treatment at paediatric nephrology centres in 2011. At the census date, 80.1% had a functioning transplant, 10.5% were receiving peritoneal dialysis (PD) and 9.4% were receiving haemodialysis (HD). In patients aged <16 years the prevalence of ERF was 56.8 pmarp and the incidence 8.3 pmarp. Analysis of trends over the last 15 years shows that both incidence and prevalence are increasing. A third of the prevalent patients had one or more reported comorbidities. At transfer to adult services, 86% of patients had a functioning renal transplant. Pre-emptive transplantation was seen to occur in 31% of children starting RRT under 16 years, with lower rates seen in girls and ethnic minorities. Survival in childhood amongst children starting RRT was the lowest in those aged less than 2 years. Conclusions: The data provided in this report show increasing trends over 15 years in the incidence and prevalence of established renal failure. This is important for the planning of the provision of care for children needing renal replacement therapy. Further research is required to understand the gender and ethnic differences in pre-emptive transplantation rates and the reduced survival amongst children aged less than 2 years.

UK Renal Registry 11th Annual Report (December 2008): Chapter 13 Demography of the UK paediatric renal replacement therapy population.

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. Results: The UK paediatric established renal failure (ERF) population in April 2008 was 875 patients. The prevalence under the age of 16 years was 55 per million age related population (pmp) and the incidence 7.92 pmp. The incidence and prevalence for South Asian and Other ethnic groups were 3 times 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 more common in patients from ethnic minority groups. The spectrum of diseases seen has changed over a generation. Overall 5 year survival for children with ERF was 91.8%. Five year survival of infants starting dialysis was just 62%. Transplanted patients accounted for 74% of the current population. The proportion with grafts from living donors has steadily risen to 34%. 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, 57% 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. The spectrum of diseases seen has already changed over a generation with the treatment of young children with diseases such as congenital nephrosis. The incidence of cystinosis causing ERF was reduced, probably reflecting better early treatment.

Seizures following renal transplantation in childhood

Abstract Few studies have investigated the incidence of seizures following renal transplantation in childhood. The aim of this study was to determine this incidence and to identify risk factors. Retrospective casenote analysis was carried out on 119 transplants performed in 109 children over 10 years. Twenty-one transplants (in 20 children) were complicated by seizures, the majority of which occurred in the first 55 days after transplantation. Seizures were more common in the 5- to 10-year-old age group (P=0.03), but were no more common in those with a prior history of seizure (P=0.69). Their aetiology was predominantly multifactorial; hypertension (n=15), fever/infection (n=4) and acute allograft rejection (n=6) were commonly identified risk factors; 2 were secondary to intracerebral pathology. Most seizures were short lived, required minimal therapy and had a good long-term neurological outcome. In conclusion, seizures are relatively common following paediatric renal transplantation. Parents are now routinely counselled of this risk.