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Original articles
The demographic characteristics of children with chronic kidney disease stages 3–5 in South East England over a 5-year period
  1. Jon Jin Kim,
  2. Caroline J Booth,
  3. Simon Waller,
  4. Pernille Rasmussen,
  5. Christopher J D Reid,
  6. Manish D Sinha
  1. Department of Paediatric Nephrology, Evelina Children's Hospital, Guys & St Thomas’ NHS Foundation Trust, London, UK
  1. Correspondence to Dr Manish D Sinha, Department of Paediatric Nephrology, Room 64, SKY LEVEL, Evelina Children's Hospital, Guys & St Thomas’ NHS Foundation Trust, Westminster Bridge Road, London SE1 7EH, UK; manish.sinha{at}nhs.net

Abstract

Objective To analyse the demographics of children with moderate to severe chronic kidney disease (CKD) stages 3–5 over a 5-year period for the population of South East England.

Methods Retrospective study of all children <18 years of age with estimated glomerular filtration rate (eGFR) <60 ml/min/1.73 m2 managed at Evelina Children's Hospital, London from 2005 to 2009. eGFR was estimated using the Schwartz formula, and stages of CKD were defined using Kidney Disease Outcome Quality Initiative criteria. We excluded all patients with a functioning kidney transplant.

Results There were 293 children (58% male) with a median (IQR) age of 6.7 (2.3, 12.1) years; 288 were aged <16 years and five 16–18 years at first presentation. The mean incidence and prevalence of children <16 years with CKD stage 3–5 during the 5-year study period was 17.5 and 90.0 per million age-related population (pmarp), respectively. There was a marked increase in incidence and prevalence over the 5 years (incidence 8.4 to 25.2 pmarp; prevalence 79.5 to 104.7 pmarp). There was an initial peak in children presenting under 2 years of age (48/141, 34%) due to congenital renal disease, and a second peak in the 12–15.9-year age group (32/141, 23%) due to glomerulonephritides. Forty-five children (15%) were transplanted, and 22 (8%) transitioned to adult care. There were seven deaths giving a death rate of 0.84 per 100 patient-years.

Conclusions We observed a steady increase in the incidence and prevalence of children with CKD stage 3–5. As a result of improved management, the majority of children with CKD will proceed to kidney transplantation, transition to adult nephrology services, and continue to require lifelong medical care.

  • chronic kidney disease
  • dialysis
  • incidence
  • prevalence
  • renal dysplasia

http://dx.doi.org/10.1136/archdischild-2012-302400

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    What is already known on this topic

    • Chronic kidney disease (CKD) is one of the most common chronic illnesses of childhood, which leads to lifelong health needs including future need for organ transplantation.

    • Worldwide registries have shown an increase in the prevalence of children in established renal failure and requiring dialysis or transplantation.

    • Incidence of CKD in children, however, has remained static.

    What this study adds

    • On the basis of internationally defined criteria, the incidence and prevalence of children with predialysis CKD in South East England increased from 2005 to 2009.

    • The mean incidence and prevalence of children <16 years with CKD during the 5-year study period was 17.5 and 90.0 pmarp, respectively.

    • Our findings have major implications for provision of healthcare services for children with CKD in the UK.

    Introduction

    Chronic kidney disease (CKD) is a major public health issue affecting an estimated 6–16% of surveyed adult populations in the developed world.1–4 Both predialysis CKD and established renal failure (ERF) requiring dialysis and transplantation have rapidly increased in adults over the last two decades.2–5 Although children with ERF account for a fraction of the total ERF patient population, it is a devastating illness during childhood, with a profound impact on the child and their family.6 CKD is one of the most common chronic illnesses of childhood, which leads to lifelong health needs including future need for organ transplantation.7

    CKD is now categorised on the basis of increasing severity of renal dysfunction in adults and children.8 ,9 In the UK, the incidence and prevalence of children with ERF has remained stable in the last decade at, respectively, 8.0 and 47.4 per million children <15 years of age.10 ERF only represents the ‘tip of the iceberg’ of children with CKD, and more inclusive data describing the epidemiology of both predialysis and dialysis-dependent CKD in children are needed. Population-based studies in children including both predialysis and dialysis-dependent stages of CKD report an incidence of 7–12 and prevalence of 29–74 cases per year per million in children <18 years of age.6 ,11–13 There are few data regarding this for the UK. Furthermore, other aspects, such as differences in screening methods, limitations of GFR estimation equations and difficulties in capturing the whole patient population, make data interpretation and comparison difficult.14 ,15

    In this report, we describe the demographic characteristics of children with moderate to severe CKD at our unit, which is the sole tertiary paediatric nephrology service for a defined area of the South East of England. We included all children with both predialysis CKD stages 3–5 and dialysis-dependent ERF over a recent 5-year period.

    Methods

    This was a retrospective study including all children and young adults aged <18 years old who had been receiving their CKD care at the Evelina Children's Hospital, London over a 5-year period between 1 January 2005 and 31 December 2009 inclusive.

    The Evelina Children's Hospital London, UK is the sole tertiary paediatric nephrology centre for a defined population from the South of London and the South East of England. On the basis of our established geographical referral pattern, we estimated the number of children and young adults aged <18 years served by our unit to be 1.73 million as per the 2001 UK census report.16 Analysis of referral rates to our unit as part of manpower and provision of resource assessment has shown an increase of 39% in new patients seen by our paediatric nephro-urology services during the 5-year study period (unpublished data, see figure S1 in the online supplementary appendix).

    Patients were identified after review of electronic hospital records of all attendances to nephrology and urology clinics during the study period. Estimated GFR (eGFR) was determined for all children who attended outpatient clinic appointments and had their plasma creatinine measured during the study period. Children with eGFR <60 ml/min/1.73 m2 had further review of their case records. Patients on dialysis were identified from a separate electronic database. Inclusion criteria were (1) age <18 years during the study period and (2) eGFR <60 ml/min/1.73 m2 on two occasions at least 1 year apart. Children who presented during the first year of life were included in this analysis if they continued to have renal dysfunction with eGFR <60 ml/min/1.73 m2 12 months after the initial presentation. Children with functioning kidney transplants were excluded.

    Renal function was determined by estimating the GFR using the Schwartz formula17 with our previously described correction factor.18 ,19 Stages of CKD were defined according to published definitions8 ,9 using Kidney Disease Outcome Quality Initiative (KDOQI) criteria: stage 3a, 45–60 ml/min/1.73 m2; stage 3b, 30–44.9 ml/min/1.73 m2; stage 4, 15–29.9 ml/min/1.73 m2; stage 5, <15 ml/min/1.73 m2; stage 5d, dialysis dependent.9

    In all patients, plasma creatinine was measured using the ‘enzymatic method’ (enzymatic creatinine). In a subset of subjects (n=71), plasma creatinine was also measured using a validated and National Institute of Standards and Technology-traceable stable isotope dilution electrospray liquid chromatography mass spectrometry (LC-MSMS) method using an AB/Sciex API5000 instrument (Applied Biosystems, Warrington, UK) (MSMS creatinine).20 ,21 The median (IQR) eGFR using MSMS creatinine was 29.6 (19.9, 41.4) ml/min/1.73 m2. There was significant correlation between eGFR calculated using enzymatic creatinine and MSMS creatinine (r=0.99, p<0.0001) (figure 1).

    Figure 1
    Figure 1

    Correlation between estimated glomerular filtration rate (eGFR) calculated using isotope dilution electrospray liquid chromatography mass spectrometry (LC-MSMS) to measure serum creatinine and eGFR calculated using the enzymatic method to measure serum creatinine. In both instances, eGFR was calculated using the Schwartz formula (n=71).

    Baseline characteristics collected included age, gender, ethnicity (as stated by patient/family) and primary aetiology. Primary aetiology for CKD and distribution of subjects by age was categorised as per the recently published UK Paediatric Renal Registry report.22 Patients aged 16–18 years are shown as a separate group to allow comparison with other studies.6 ,11–13 For all included subjects, data on their height and creatinine were collected once a year from a clinic visit on or closest to their birthday anniversary month.

    We calculated (i) the annual incidence and prevalence of CKD per million age-related population (pmarp) on 31 December and (ii) the ‘mean’ incidence and prevalence during the 5-year study period. ‘Incident’ subjects were defined as ‘new patients’ who presented with an eGFR <60 ml/min/1.73 m2 to our centre during the study period, and ‘prevalent’ subjects those with eGFR <60 ml/min/1.73 m2 and ongoing follow-up at our centre during the study period.

    Statistical analysis

    The mean, median, SD and IQRs were calculated for all relevant variables. The Kruskall–Wallis test was used to test differences in eGFR at presentation of incident subjects per year, with p<0.05 considered significant. All statistical analyses were performed with GraphPad Prism 5.0.

    Results

    Demographics and aetiology

    Over the 5-year time period, 293 children (58% male) received medical management for their CKD; median (IQR) age of all the patients at first presentation to paediatric nephrology services was 6.7 (2.3, 12.1) years, with 288 aged <16 years and five aged 16–18 years.

    All results below relate to the 288 children who were aged <16 years at first presentation unless specified. We discuss the results relating to the five incident children presenting aged 16–18 years in a later subsection. The proportion of children with CKD stage 3a, 3b, 4, 5 and 5d was 21%, 29%, 26%, 12% and 11%, respectively. Children of Caucasian ethnicity were most prevalent (202 (70%)) with those of Asian origin next most common (42 (15%)) (figure 2).

    Figure 2
    Figure 2

    Ethnic origin of 288 children <16 years of age with stage 3–5 chronic kidney disease during the 5-year study period 2005–2009 in the South East of England, UK.

    Table 1 displays the primary renal diseases for all patients <16 years of age with CKD included in the study. Structural renal abnormalities including hypodysplasia, reflux nephropathy and bladder obstruction were the predominant cause in 170 children (59%) followed by glomerular disease in 50 (17%).

    View this table:
    Table 1

    Primary renal diseases in 288 children <16 years of age with stage 3–5 chronic kidney disease included in the study

    Incidence and prevalence

    The mean incidence and prevalence of children <16 years with CKD during the 5-year study period was 17.5 and 90.0 pmarp, respectively. The annual incidence and prevalence of children with CKD during the study period are shown in figure 3.

    Figure 3
    Figure 3

    Annual incidence (diamonds) and prevalence (squares) of children <16 years with stages 3–5 of chronic kidney disease (excluding patients receiving dialysis) during the 5-year study period 2005–2009 in the South East of England, UK. pmarp, per million age-related population.

    The prevalence of children aged <16 years with stage 3–5 CKD increased from 79.5 pmarp in 2005 to 104.7 pmarp in 2009. During this period, the incidence also increased, from 8.4 pmarp in 2005 to 25.2 pmarp in 2009. The mean (SD) eGFR at presentation of incident patients during the 5-year study period was 29.4 (17.7) ml/min/1.73 m2. There was no significant change in eGFR at presentation of incident patients over the study period (p=0.78) (see figure S2 in the online supplementary appendix). Figure 4 displays the prevalent CKD population at each annual time point by CKD stage. There was no significant change in the proportion of children in the various stages of CKD, although the number of children with CKD had increased during the study.

    Figure 4
    Figure 4

    Prevalent population of children <16 years with stages 3–5 of chronic kidney disease (CKD) (excluding patients receiving dialysis) at each year time point by stage of CKD during the 5-year study period 2005–2009 in the South East of England, UK. The numbers in the figure denote the number of children in each CKD category.

    Incident patients with stages 3–5 of CKD during the study period

    There were 141 (83 male) incident patients during the 5-year study period. Their median (IQR) age was 5.6 (0.3, 12.0) years with eGFR of 30.5 (12.9, 45.5) ml/min/1.73 m2. The distribution of their primary renal disease was similar to that for prevalent patients (data not shown). Figure 5 displays this incident patient cohort by stage of CKD and age group.

    Figure 5
    Figure 5

    Incident patient cohort over the 5-year study period (n=141) by stage of chronic kidney disease and clinically relevant age group. The numbers on the ‘y-axis’ denote ‘number of children with CKD’.

    There was an initial peak in children aged <2 years representing early presentation of congenital renal disease (48/141, 34%), with a second peak in the 12–15.9-year age group (32/141, 23%). Young children (aged <2 years) had, as expected, the lowest eGFR at presentation (compared with other age groups). With increasing age, an increasing proportion of patients presented with higher eGFR (data not shown). Overall, 20/141 (14%) patients presented with ERF requiring dialysis soon after presentation. Six of these patients were >12 years of age, with five having glomerular disease as the cause of CKD. Figure 6 shows the primary renal disease by age group.

    Figure 6
    Figure 6

    Incident patient cohort over the 5-year study period (n=141) by primary renal disease category and clinically relevant age group. The numbers on the ‘y-axis’ denote ‘number of children with CKD’.

    The main cause of CKD in children aged <2 years was congenital abnormalities of the kidney and urinary tract (CAKUT) (81%), in contrast with glomerular disease in 36% of the children older than 12 years.

    Subjects aged 16–18 years

    Five children (two male) were >16 years when they first presented to the study. Aetiology varied: reflux nephropathy, haemolytic uraemic syndrome, focal segmental glomerular sclerosis, nephronophthisis and hyperuricaemia. In addition, there was an average of 13 prevalent patients each year and a total of eight patients receiving dialysis in the 5-year study period.

    Patients leaving the study

    During the 5-year study period, 79/293 (27%) patients left the study. Forty-five children received kidney-only transplantation, 22 were transitioned to adult nephrology services, four moved to other paediatric nephrology units in the UK, and one child was lost to follow-up. There were seven deaths during the study period (four in stage 5d and three in stage 5). Three deaths were due to sepsis, one following haemorrhage from a ruptured vessel while central access was being obtained, and one secondary to pulmonary oedema and fluid overload. Two children were managed palliatively, as active management of their CKD with dialysis and transplantation was not felt to be in their best interests. The overall death rate was 0.84 per 100 patient-years.

    Discussion

    In this study, we describe the demographics of children with CKD in the South East England region over a 5-year period from 2005–2009. We report an expanding service with increasing incidence and prevalence of children with stage 3–5 CKD. There was a preponderance of young children aged <2 years and the main aetiology was CAKUT.

    Our study has observed an increase in both the incidence and prevalence of patients with CKD. This is in keeping with the increasing prevalence of children with ERF in the UK.22 A similar increase has also been observed in the incidence of children receiving renal replacement therapy, from 8.1 pmarp in the period 1995–1999 to 9.6 pmarp in the most recent period, 2005–2009.22 Our study has observed an increase in prevalence over a relatively short period of 5 years. The most likely cause for this observation is improved patient survival as a result of improved nutrition and dialysis delivery techniques, in addition to better general management of children with CKD—and this is similar to that previously observed in similar populations. The most likely reason for the rapid increase in incidence in our study is secondary to increasing referrals to our clinical services, and this in keeping with the data shown in figure S1 of the online supplementary appendix. It would be interesting to know if the increase in incidence observed in our cohort is a result of improved case ascertainment at primary/secondary levels of care or, in fact, represents a true increase in CKD in the population, and, if the latter is true, what the reasons are. We wondered if the higher prevalence at our centre reflect a more gradual decline in renal function in our patients, perhaps relating to control of proteinuria and blood pressure (not described in this report). We accept that, given the relatively short follow-up periods reported here, this is less likely to be the underlying cause, and that these issues merit detailed analysis in a prospective study in the future.

    The incidence and prevalence in our study are higher than in other epidemiological studies published previously. The reported incidence and prevalence (pmarp) were, respectively, 12.1 and 74.1 in Italy, 11.9 and 56.0 in Belgium, 8.7 and 71.7 in Spain, 7.7 and 59 in Sweden, and 10.5 and 66 in France.9–13 However, direct comparisons cannot be made, as different inclusion criteria, study design and data collection methods were used. Most other studies included milder stages of CKD and used prospective registry or survey data collection methods.2 The increasing incidence and prevalence of children with more significant levels of renal dysfunction in our study further highlight the importance of these data.

    The characteristics of patients with CKD in the South East of England were similar to the population of children having renal replacement therapy in the UK.10 However, the proportion of subjects from ethnic minorities in this report differs from those of the UK as a whole, in keeping with the high immigrant population in central London.16 Thus, although the majority of patients were of white ethnicity, the proportion of patients of Asian and African descent were over-represented compared with the underlying population demographics.16

    The aetiology of CKD in patients in this study is comparable to that reported the literature.15 Almost 60% of prevalent cases were due to CAKUT, which explains the higher proportion of boys. In contrast with other published reports, there were no cases due to cancer and fewer subjects with ‘unknown’ aetiology as the cause of CKD. We categorised cause of CKD according to the UK Renal Registry reports, which are based on physician diagnosis. Although dysplasia and reflux nephropathy were listed separately, there is significant overlap between the two diagnoses. Further, as our understanding of the underlying genetics and pathogenesis improves, it is likely that the diagnostic categories will change and become more defined in the future.

    Although progression of renal dysfunction is invariable in subjects with moderate to severe stages of CKD, improved survival will continue to result in increasing prevalence of patients with CKD and those requiring renal replacement therapy. A significant number of children will transition to adult nephrology services before reaching ERF. This is important in terms of planning of future service provision and highlights the need for further longitudinal studies of CKD progression and treatment.

    Although formal GFR measurement is the gold standard, it is invasive and time consuming. Our study used the Schwartz formula with a ‘k value’, which has previously been internally validated.18 We also provided data showing strong correlation of plasma creatinine measured using the ‘enzymatic’ method with creatinine measurement using mass spectrometry. Therefore, the method of GFR estimation in this study is reliable and applicable within the GFR ranges of the study population.

    Strengths of this study include the inclusion of subjects with moderate to severe stages of CKD over at least 1 year, ensuring completeness of data acquisition despite its retrospective nature. Furthermore, all patients being treated in the nephrology unit, which is the sole tertiary referral centre, were included, ensuring an accurate representation of the study population. This study has the following limitations. (i) We used KDOQI criteria for classification of CKD stage.8 ,9 Strictly speaking, these criteria do not apply to children <2 years of age, but were applied in this study to allow comparison with older children. In addition, we defined ‘chronic’ kidney disease as renal impairment for ≥1 year as compared with ≥3 months in the KDOQI criteria. (ii) We included infants who presented early in the first few months of life. As GFR improves in the first year of life, infants whose eGFR improved above 60 ml/min/1.73 m2 after 1 year of age were excluded from the study, as one of the study criteria was to obtain a true representation of the CKD population. A prospective study would obtain a more accurate incidence rate, although this has the limitations of a longer study period and larger drop-out rate. Therefore, this study is informative as a thorough capture of the study population. (iii) Our clinic population may be missing patients who are undiagnosed and so not referred. (iv) The estimated population of children served by our centre may be different, as there may be differences in referral patterns from district general hospital's to tertiary services, changing population numbers or because some centres sometimes refer children to more than one centre for the same or different renal diseases. (v) Patients with CKD may also be managed in the local district general hospital and therefore not attend the Evelina Children's Hospital, particularly those with milder CKD. However, children with eGFR <45 ml/min/1.73 m2 are probably transferred to our unit either solely or on a shared-care basis to benefit from the expertise of the multidisciplinary team. (vi) Patients who were transplanted, transitioned to adult services or moved to other units or died within 12-months of initial presentation were excluded, although these numbers would be small. (vii) New patients aged 16–18 years may be referred to either paediatric or adult nephrology services, and because we could not be sure of the proportion of that age group referred to our service, these data were displayed separately in the analysis. Further efforts should be made specifically to study this selected group of young adults, as their needs and treatment are often unique.

    In conclusion, we present a detailed report of the demographics of stages 3–5 of CKD in children from the South East of England. Both incidence and prevalence increased over the 5-year study period. A significant proportion of patients present in infancy with congenital structural abnormalities. Owing to the low death rate, the majority of children with CKD will proceed to receive kidney transplantation as children or will be transitioned to adult nephrology services for lifelong medical care. These issues have important implications for future research and healthcare provision planning and funding.

    Acknowledgments

    The authors would like to acknowledge Mr David Taylor for all his help with bioinformatics.

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    Supplementary materials

    • Supplementary Data

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    Footnotes

    • Contributors All authors fulfil the criteria for authorship and have contributed to the collection of data, analysis of results and writing of this manuscript leading to the completion of this manuscript. No-one who fulfils the criteria for authorship has been excluded.

    • Funding MDS acknowledges financial support from the Department of Health via the National Institute for Health Research (NIHR) comprehensive Biomedical Research Centre award to Guy's & St Thomas' NHS Foundation Trust in partnership with King's College London and King's College Hospital NHS Foundation Trust.

    • Competing interests None.

    • Provenance and peer review Not commissioned; externally peer reviewed.

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      R Mark Beattie
      Archives of Disease in Childhood 2013; 98 i-i Published Online First: 14 Feb 2013. doi: 10.1136/archdischild-2013-303759