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NDT Advance Access published online on October 7, 2008
Nephrology Dialysis Transplantation, doi:10.1093/ndt/gfn542
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© The Author [2008]. Published by Oxford University Press on behalf of ERA-EDTA. All rights reserved. For Permissions, please e-mail: journals.permissions@oxfordjournals.org


Characteristics and survival of young adults who started renal replacement therapy during childhood

Anneke Kramer1, Vianda S. Stel1, Jane Tizard2, Enrico Verrina3, Kai Rönnholm4, Runólfur Pálsson5, Heather Maxwell6 and Kitty J. Jager1

1 ERA–EDTA Registry, Department of Medical Informatics, Academic Medical Center, University of Amsterdam, Amsterdam, The Netherlands 2 Renal Unit, Bristol Royal Hospital for Children, Bristol, UK 3 Department of Pediatric Nephrology, Instituto Gaslini, University of Genoa, Genoa, Italy 4 Department of Paediatric Nephrology and Transplantation, Hospital for Children and Adolescents, University of Helsinki, Helsinki, Finland 5 Division of Nephrology, Department of Medicine, Landspitali University Hospital, Reykjavik, Iceland 6 Renal Unit, Royal Hospital for Sick Children, Yorkhill, Glasgow, UK

Correspondence and offprint requests to: Anneke Kramer, ERA-EDTA Registry, Department of Medical Informatics, Academic Medical Center, PO Box 22700, Amsterdam 1100 DE, The Netherlands. Tel: +31-205669006; Fax: +31-206919840; E-mail: a.kramer{at}amc.uva.nl



   Abstract
Top
 Abstract
Introduction
 Subjects and methods
 Results
 Discussion
 Conclusions
 Appendix
 References
 
Background. Little is known about the group of children on renal replacement therapy (RRT) who reach the age of 18 years and are transferred from paediatric to adult nephrology services. The aim of this study was to describe patient demographics, primary renal diseases, treatment history and determine the risk factors for mortality of these young adults who started RRT in childhood.

Methods. We included 1777 young adults who had started RRT during childhood and turned 18 between 1985 and 2004 from nine European renal registries submitting data to the ERA-EDTA Registry. The chi-square test was used to test differences between patient groups and Cox regression analysis to examine patient survival.

Results. Young adults who began RRT during childhood increased the total number of adult patients starting RRT by 1.5% per annum. The annual number of children on RRT turning 18, per million persons (Pmarp) reaching the age of 18 years, increased between 1985 and 2004 from 71 to 116. Over time, there was an increase in the percentage of young adults who started RRT at a very young age, a greater number of children with hypoplasia/dysplasia and cystic kidneys and more young adults who started RRT with peritoneal dialysis or pre-emptive transplantation. The unadjusted 5-year patient survival from the 18th birthday was 95.1% (95% CI 93.9–96.0). The average life expectancy was 63 years for young adults with a functioning graft and 38 years for those remaining on dialysis.

Conclusions. The number Pmarp of young adults on RRT has increased over time. Their characteristics and treatment history changed. Their survival prospects are good; however, transplant recipients have an expected remaining lifetime that is at least twice as high as for young adults on dialysis.

Keywords: childhood; Europe; registry; renal replacement therapy; survival



   Introduction
Top
 Abstract
 Introduction
Subjects and methods
 Results
 Discussion
 Conclusions
 Appendix
 References
 
Substantial improvements in dialysis management and kidney transplantation in the last four decades have led to an increased acceptance to renal replacement therapy (RRT) and an increased survival of children with end-stage renal disease (ESRD) [1–7]. As a result, young adults with a history of paediatric RRT have been entering into adult RRT programmes since the 1970s. Whereas most papers in this area of paediatric nephrology have focused on the incidence, prevalence and patient survival of children starting RRT [5–11], this group of young adults who started RRT during childhood has received little attention.

When children on RRT reach adulthood, they are transferred from a paediatric to an adult nephrology service with different staff and organizational structure where they are expected to take more responsibility for their own care than before. It is of interest for both paediatric and adult nephrologists to gain information on the characteristics of this group. In the case of paediatric nephrologists, these patients reflect the outcome of their efforts over the many years when these children attended their units. For adult nephrologists it is important to know more about the background of these patients who newly enter their practice and to learn about their prognosis.

The aim of this study is to describe the patient demographics, primary renal diseases and treatment history, and to determine the risk factors for mortality in young adults who started RRT during childhood.



   Subjects and methods
Top
 Abstract
 Introduction
 Subjects and methods
Results
 Discussion
 Conclusions
 Appendix
 References
 
Data collection
The ERA-EDTA Registry collects data annually on RRT patients from a large number of national and regional renal registries in Europe. These data include a patient identifier, date of birth, gender, primary renal disease, date of start of RRT, history of RRT treatment modalities and date and cause of death. Methods used for data collection and data processing have been previously reported [12].

Population
For this study, we used data on young adults on RRT, whom we defined as patients who had started RRT during childhood and who reached the age of 18 years. European national and regional registries that sent us individual patient data on such patients for the period from 1 January 1985 to 31 December 2004 participated in this study, including Andalusia (Spain), Austria, Catalonia (Spain), Finland, Greece, Iceland, Norway, Scotland (United Kingdom) and The Netherlands.

Data analysis
To describe the characteristics of young adults on RRT and their prognosis after their 18th birthday, we used data from 1777 RRT patients who turned 18 between 1985 and 2004.

Patient characteristics and treatment history of young adults on RRT who reached their 18th birthday were studied from two perspectives: (1) the age at the start of RRT and (2) the time period when they turned 18. Numbers per million age-related population (Pmarp) were calculated by dividing the number of young adults on RRT reaching the age of 18 years by an estimate of the number of all young adults in the general population turning 18. This estimate was calculated by taking one-fifth of the general population aged 15–19 years. To determine how many young adults on RRT contributed to the total number of adult patients starting RRT, we used additional data from the ERA-EDTA Registry database. Renal diseases and causes of death were defined according to the ERA-EDTA coding systems and were subsequently classified into groups (see the Appendix). A change in dialysis modality was defined as a transfer to another dialysis modality for a period longer than 60 days. The chi-square test was used to test differences in the characteristics of young adults on RRT between age groups and between time periods.

Cox regression analysis was used to examine patient survival of young adults on RRT after reaching their 18th birthday and to assess the relative risks of patient and treatment characteristics in relation to survival. The starting point was the 18th birthday, whereas recovery of renal function, loss to follow-up and reaching the end of the study period were censored observations. In addition, we calculated the expected remaining lifetime and the average life expectancy for young adults on dialysis and young adults living with a functioning graft. Although the average cannot be known until all patients in the cohort have died, the expected remaining lifetime can be projected by assuming that these young adults will die at the same rates as those observed among groups of recently prevalent (2003–04) ESRD patients [4].

Statistical tests were two-tailed and differences were considered to be statistically significant when the P-value was <0.05. Ninety-five percent confidence intervals were provided where relevant. For all data analyses SAS 9.1 was used.



   Results
Top
 Abstract
 Introduction
 Subjects and methods
 Results
Discussion
 Conclusions
 Appendix
 References
 
Between 1985 and 2004, 1777 children on RRT reached the age of 18 years. During this period, young adults on RRT added a further 1.5% of the number of incident adult patients entering adult RRT services; this percentage decreased from 2.1% in 1985–89 to 1.2% in 2000–04.

Characteristics and treatment history of young adults who started RRT during childhood
Age at first RRT.
Figure 1 shows that the number Pmarp (i.e. per million persons reaching the age of 18 years) of young adults on RRT reaching their 18th birthday increased from 71 Pmarp in 1985 to 116 Pmarp in 2004. In addition, there was a change in the age distribution at the start of RRT. The number of young adults who had started RRT below the age of 5 years increased between 1985 and 2004 from 1 to 24 Pmarp, and the number of those who had started RRT between 5 and 10 years of age increased from 4 to 22 Pmarp. The number of young adults who had started RRT after the age of 10 years remained constant at around 80 Pmarp during the study period.


Figure 1
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  		Fig. 1 Number Pmarp (per million persons reaching the age of 18 years) of young adults who started RRT during childhood reaching the age of 18 years (between 1985 and 2005), by age group at the start of RRT.

 
Primary renal disease.
As shown in Table 1, the most common primary renal diseases were pyelonephritis, glomerulonephritis and hypoplasia/dysplasia. Hypoplasia and dysplasia were most common in the group who had started RRT at a very young age (P < 0.0001). Pyelonephritis (P < 0.001) and glomerulonephritis (P < 0.0001) became progressively more common with increasing age at the start of RRT. Table 2 shows that the number as well as the percentage of young adults with glomerulonephritis decreased with time (P < 0.0001), especially in those patients who were older than 10 years of age at the start of RRT (data not shown). The numbers, percentages and numbers Pmarp of young adults on RRT with hypoplasia/dysplasia and with cystic kidneys increased with time (P < 0.0001 and P < 0.05, respectively).


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  		Table 1 Patient characteristics of young adults who started RRT during childhood, according to the age at the start of RRT

 

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  		Table 2 Characteristics of young adults who started RRT during childhood, according to the period in which they turned 18

 
Treatment modality at start of RRT.
The majority of the young adults on RRT had received haemodialysis as the first treatment modality, followed by peritoneal dialysis as the second most common modality (Table 1). The number and percentage of patients who had started with haemodialysis increased with age (P < 0.0001), whereas the percentage of those who started with peritoneal dialysis decreased with age (P < 0.0001). In addition, subgroup analysis showed that the percentage of young adults on RRT who had received haemodialysis as the first treatment modality declined over the study period (P < 0.0001), due to a decrease in the relative number of patients in the older age categories, whereas the numbers, percentages as well as the numbers Pmarp of those receiving peritoneal dialysis at the onset of RRT and those with a pre-emptive transplant increased (both P < 0.0001) across all age categories. Most young adults on RRT continued to receive the initial treatment modality (34.6%) or changed treatment modality once before reaching the age of 18 years (42.4%). The most frequent modality changes were from dialysis to transplant and from transplant to haemodialysis. The transition from one dialysis modality to the other was very rare, except in the youngest age group, in which a quarter of children changed from peritoneal dialysis to haemodialysis. Patients who received their first transplant following a period on dialysis spent an average of 15.3 months on dialysis. This period decreased with age, from 25.4 months in the 0–4 age group to 10.2 months in the oldest age group.

Treatment modality at the age of 18 years.
Table 1 shows that by the time children reached the age of 18 years, 60.4% of them had a functioning graft (32.6% with a kidney from a deceased donor, 19.8% with a living donor kidney and 8.0% with a kidney from an unknown source). Almost 75% of the young adults who started RRT before the age of 15 years had a functioning graft at their 18th birthday. This percentage decreased with age (P < 0.0001) due to the lower percentage of young adults with a transplant from a deceased donor (P < 0.0001) in the older age groups, which can at least partly be explained by the shorter time spent on RRT before reaching the age of 18 years. In spite of that, the percentage of children with a transplant from a living donor remained more or less constant at ~20% across all age groups. As shown in Table 2, the percentage of young adults with a functioning graft at their 18th birthday increased from 52.6% in the period 1985–89 to 70.1% in 2000–04. Subgroup analysis (data not shown) demonstrated that this increase was partly due to an increase in the number of pre-emptive transplants across all age categories and partly due to a rise in the number of transplants performed after a period of dialysis in young adults who had started RRT before the age of 10 years. Overall, 71.2% of the young adults on RRT received a kidney allograft during childhood, of whom 59.6% received a graft once, 10.0% twice, 1.3% three times and 0.2% four times.

The prognosis of young adults who started RRT during childhood
After reaching the age of 18 years, the unadjusted overall 1-, 2- and 5-year patient survival was 99.2% (95% CI 98.6–99.6), 98.0% (95% CI 97.2–98.5) and 95.1% (95% CI 93.9–96.0), respectively. Table 3 shows the survival rates and hazard ratios in different subgroups adjusted for age, gender, primary renal disease and treatment modality of young adults on RRT beyond the age of 18 years. The age at the start of RRT, gender and primary renal disease (with exception of category ‘other’) did not affect the prognosis of young adults after their 18th birthday. Patients in the primary renal disease category ‘other’, including multisystem disorders and very rare diseases, had a significantly higher risk of death than those with glomerulonephritis, pyelonephritis or hypoplasia/dysplasia (P < 0.05). Furthermore, the risk of death would be about five times higher if young adults were on dialysis on their 18th birthday compared to those with a functioning graft (HR 5.32; 95% CI 2.63–10.79).


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  		Table 3 One-, two- and five-year survival rates and hazard ratios since the age of 18 years (for young adults on RRT) after adjustment for age at the start of RRT, gender, primary renal disease and treatment modality

 
In the period 2003–04, the average life expectancy for young adults on RRT was 63.2 years (expected remaining lifetime 45.2 years) for those with a functioning graft (62.8 and 64.2 years for males and females, respectively) and 38.2 years (expected remaining lifetime 20.2 years) for those remaining on dialysis (38.1 and 38.4 years for males and females, respectively).



   Discussion
Top
 Abstract
 Introduction
 Subjects and methods
 Results
 Discussion
Conclusions
 Appendix
 References
 
This is the first study that has examined the patient demographics, primary renal diseases, treatment history and the outcome in adult life of young adults turning 18 whilst on RRT. The results showed that the number Pmarp (i.e. per million persons reaching the age of 18 years) of young adults receiving RRT increased between 1985 and 2004. Since 1985, the patient characteristics of young adults who had their care transferred to adult nephrology services have changed in that there was an increase in the percentage of patients who started RRT at a young age. Simultaneously, the pattern of primary renal diseases has changed as has the pattern of first treatment modality. The prognosis of young adults on RRT following their 18th birthday was good. Their survival prospects were independent of age at the start of RRT, but highly dependent on having, or not having, a functioning transplant at their 18th birthday.

Characteristics and treatment history of young adults who started RRT during childhood
In view of the small numbers, in daily practice it would be rare for a nephrologist who cares for adult patients to take over the care of a young adult who started RRT during childhood. As shown, young adults who started RRT during childhood and reached the age of 18 years increased the total number of adult patients starting RRT by only 1.5%.

The characteristics of the group of young adults on RRT have changed over time. The changes in age distribution, at the onset of RRT, over the study period were probably largely due to a more liberal acceptance policy, and possibly improved survival prior to the commencement of RRT, of young children with hypoplasia/dysplasia or cystic kidneys. Furthermore, a more proactive policy towards pre-emptive transplantation in children with ESRD may be responsible in part for the relative decline in the average age at the start of RRT. In addition, the increase in the number Pmarp of young adults on RRT was due to the improved patient survival on RRT in the young-age categories [5].

Advances in dialysis techniques have made it possible to dialyse children successfully, keeping the rate of dialysis technique failure low and allowing children to survive and grow sufficiently to undergo kidney transplantation. In addition, the increase in the number Pmarp of young children, as well as technical advances [11,13,14] and a more frequent use of PD in children in general [10,11,15], has led to a higher frequency of PD as the first treatment modality in young adults at the start of RRT. Similarly, the increasing number Pmarp of children receiving a (pre-emptive) transplant and the improved survival of transplanted patients over the study period [7,11,16,17] contributed to a greater number Pmarp of young adults who had a functioning graft at their 18th birthday.

The prognosis of young adults who started RRT during childhood
Despite having been on RRT, sometimes for a prolonged period, the prognosis of young adults on RRT after their 18th birthday was good. This study revealed that patient survival after the age of 18 years did not depend on the history of RRT modalities, but was primarily determined by the type of RRT that was being employed at their 18th birthday; young adults with a functioning kidney transplant had much higher survival probability compared to those on dialysis. This was also reflected in their expected remaining lifetime, which was at least twice as high for transplant recipients compared with dialysis patients.

For the daily practice of nephrologists who provide care to young adults on RRT, it is important to note that the prognosis of these patients is at least as good as or maybe even better than that of prevalent patients aged 20–24 or 25–29 years, a considerable proportion of whom started RRT only in their twenties; patients aged 20–24 years have an expected remaining lifetime of 18.6 years if on dialysis and 40.3 years with a functioning graft, while patients aged 25–29 years have an expected remaining lifetime of 16.4 years and 35.6, respectively [18]. However, a potential survival advantage of being a young adult who started RRT as a child may be the result of survivor bias, since these adults have already survived a period on RRT.



   Conclusions
Top
 Abstract
 Introduction
 Subjects and methods
 Results
 Discussion
 Conclusions
Appendix
 References
 
This study demonstrates that only a small percentage of patients on RRT entering the adult nephrology services comprise young adults who started RRT during childhood. Over the past two decades the number of these patients per million age-related population has been increasing. In addition, the patient characteristics and treatment history of this group have changed over time. This study also shows that the prognosis of these young adults does not depend on their medical history, but is primarily determined by treatment modality. As young adults with a functioning graft have a life expectancy that is twice as long as that of those who remain on dialysis, our results, again, underline the importance of renal transplantation.



   Appendix
Top
 Abstract
 Introduction
 Subjects and methods
 Results
 Discussion
 Conclusions
 Appendix
References
 
ERA-EDTA codes for primary renal disease (PRD) in children (I: glomerulonephritis, II: focal segmental glomerulosclerosis, III: pyelonephritis, IV: cystic kidneys, V: hypoplasia/dysplasia, VI: haemolytic uraemic syndrome, VII: hereditary nephropathy, VIII: miscellaneous and IX: unknown)Go


PRD Version 1994 Version 1995 PRD group
Glomerulonephritis, NOT examined histologically 10 10 I
Focal segmental glomerulosclerosis with nephrotic syndrome in children 11 11 II
IgA nephropathy (proven by immunofluorescence, not code 76 and not 85) 12 12 I
Dense deposit disease, membrano-proliferative glomerulonephritis, type II (proven by 13 13 I
 immunofluorescence and/or electron microscopy) 13 13 I
Membranous nephropathy 14 14 I
Membrano-proliferative glomerulonephritis, type I (proven by immunofluorescence 15 15 I
 and/or electron microscopy—not code 84 or 89) 15 15 I
Crescentic (extracapillary) glomerulonephritis (types I, II, III) 16 16 I
Focal segmental glomerulosclerosis with nephrotic syndrome in adults 17 17 II
Glomerulonephritis, examined histologically, not given above 19 19 I
Pyelonephritis—cause not specified 20 20 III
Pyelonephritis associated with neurogenic bladder 21 21 III
Pyelonephritis due to congenital obstructive uropathy with/without vesico-ureteric reflux 22 22 III
Pyelonephritis due to acquired obstructive uropathy 23 23 III
Pyelonephritis due to vesico-ureteric reflux without obstruction 24 24 III
Pyelonephritis due to urolithiasis 25 25 III
Pyelonephritis due to other cause 29 29 III
Interstitial nephritis (not pyelonephritis) due to other cause, or unspecified (not mentioned above) 30 30 VIII
Nephropathy (interstitial) due to analgesic drugs 31 31 VIII
Nephropathy (interstitial) due to cis-platinum 32 32 VIII
Nephropathy (interstitial) due to cyclosporin A 33 33 VIII
Lead-induced nephropathy (interstitial) 34 VIII
Drug-induced nephropathy (interstitial), not mentioned above 39 39 VIII
Cystic kidney disease—type unspecified 40 40 IV
Polycystic kidneys, adult type (dominant) 41 41 IV
Polycystic kidneys, infantile (recessive) 42 42 IV
Medullary cystic disease, including nephronophthisis 43 43 IV
Cystic kidney disease—other specified type 49 49 IV
Hereditary/familial nephropathy—type unspecified 50 50 VII
Hereditary nephritis with nerve deafness (Alport syndrome) 51 51 VII
Cystinosis 52 52 VII
Primary oxalosis 53 53 VII
Fabry disease 54 54 VIII
Hereditary nephropathy—other specified type 59 59 VII
Renal hypoplasia (congenital)—type unspecified 60 60 V
Oligomeganephronic hypoplasia 61 61 V
Congenital renal dysplasia with or without urinary tract malformation 63 63 V
Syndrome of agenesis of abdominal muscles (prune belly) 66 66 V
Renal vascular disease—type unspecified 70 70 VIII
Renal vascular disease due to malignant hypertension 71 71 VIII
Renal vascular disease due to hypertension 72 72 VIII
Renal vascular disease due to polyarteritis 73 73 VIII
Wegener granulomatosis 74 74 VIII
Glomerulonephritis related to liver cirrhosis 76 76 VIII
Cryoglobulinemic glomerulonephritis 78 VIII
Renal vascular disease—due to other cause (not given above and not code 84–88) 79 79 VIII
Diabetes glomerulosclerosis or diabetic nephropathy—type I 80 80 VIII
Diabetes glomerulosclerosis or diabetic nephropathy—type II 81 80 VIII
Myelomatosis/light chain deposit disease 82 82 VIII
Amyloid 83 83 VIII
Lupus erythematosus 84 84 VIII
Henoch-Schonlein purpura 85 85 VIII
Goodpasture syndrome 86 86 VIII
Systemic sclerosis (scleroderma) 87 87 VIII
Haemolytic uraemic syndrome (including Moschcowitz syndrome) 88 88 VI
Multisystem disease—other (not mentioned above) 89 89 VIII
Tubular necrosis (irreversible) or cortical necrosis (different from 88) 90 90 VIII
Tuberculosis 91 91 VIII
Gout 92 92 VIII
Nephrocalcinosis and hypercalcaemic nephropathy 93 93 VIII
Balkan nephropathy 94 94 VIII
Kidney tumor 95 95 VIII
Traumatic or surgical loss of kidney 96 96 VIII
Other identified renal disorders 99 99 VIII
Chronic renal failure, etiology uncertain 0 0 IX



   Acknowledgments
 
We would like to thank the patients and staff of all the dialysis and transplant units who have contributed data via their national and regional renal registries. We would also like to thank Dr P. Castro (Andalusian Renal Registry), Dr R. Kramar [Austrian Dialysis and Transplant Registry (OEDTR)], Dr R. Deulofeu, Dr J. Comas, Dr E. Arcos and Dr J. Twose [Catalan Transplant Organisation (OCATT)], Dr P. Finne and Dr C. Grönhagen-Riska (Finnish Registry for Kidney Diseases), Dr G.A. Ioannidis (Hellenic Renal Registry), Dr T. Leivestad (Norwegian Renal Registry), Dr K Simpson (Scottish Renal Registry) and Dr F.T. de Charro [Dutch End-Stage Renal Disease Registry (RENINE)] for providing data. In addition, we would like to thank Dr K. Verrier-Jones, Cardiff University, UK, for her advice in the analysis of the data and Dr T. Leivestad, Dr J. Nieto Rey and Dr T.M. Donate Cubells for critically reading an earlier version of the manuscript. The ERA-EDTA Registry is funded by the European Renal Association–European Dialysis and Transplant Association (ERA-EDTA).

Conflict of interest statement. None declared.



   References
Top
 Abstract
 Introduction
 Subjects and methods
 Results
 Discussion
 Conclusions
 Appendix
 References
 

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Received for publication: 1. 2.08
Accepted in revised form: 4. 9.08


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