Renal replacement therapies in neonates: issues and ethics

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Abstract

Chronic irreversible kidney disease requiring dialysis is rare in the neonate. Many such neonates are diagnosed following antenatal ultrasound with congenital abnormalities of the kidneys and urinary tract. There is an increased incidence of prematurity and infants that are small for gestational age. Given the natural improvement in renal function that occurs in the neonatal period, some with extremely poor renal function may, with careful management of fluid and electrolytes, be kept off dialysis until the creatinine reaches a nadir when a definitive plan can be made. There is a very high incidence of comorbidity and this affects survival, which for those on dialysis is about 80% at five years. The multiple and complex ethical issues surrounding the management of these very young children are discussed.

Introduction

The numbers of neonates requiring dialysis for chronic, irreversible kidney disease (CKD) are extremely low. Most registries present data for infants aged <2 years rather than neonates, for which numbers vary from seven to 12 per million age-related population. For example, that would be 20–30 at any time in the UK, with a population of 64 million, and 100–150 in the USA, with a population of 325 million. The European Society for Pediatric Nephrology and European Renal Association‒European Dialysis and Transplant Association (ESPN/ERA-EDTA), the International Pediatric Peritoneal Dialysis Network (IPPN), and Australia and New Zealand (ANZDATA) registries have looked to specifically identify neonates within the infant group. A total of 264 neonates started chronic dialysis in 32 countries between 2000 and 2011. They represented around 18% of infants aged <2 years on dialysis in both eastern and western Europe but only 6.8% in Australia and New Zealand. In Japan, neonates were 8.6% of dialysed children aged <5 years [1]. These variations are likely to be related to local attitudes to termination of pregnancy following detection of a life-threatening renal abnormality, to attitudes to acceptance of such infants on to renal replacement therapy (RRT) programmes, and to resources available. Commencement of dialysis is also dependent on local experience and policies.

Section snippets

The neonatal kidney

Kidney development commences at five weeks of gestation. By weeks 6–9 the first glomeruli are formed and by week 36 nephrogenesis ceases, by which time there are the definitive numbers of around one million glomeruli in each kidney. Therefore the premature infant's kidneys are especially vulnerable to insult during the period of ongoing nephrogenesis. A bladder is detectable by week 9, and thereafter fetal urine contributes to >90% of amniotic fluid volume.

Ninety percent of infants pass urine

Factors predisposing the neonate with chronic kidney disease to acute kidney injury

The proportion of babies requiring RRT that is premature or small for gestational age (SGA) is higher than that in babies of the equivalent gestation without CKD. Up to one-quarter is born prematurely and one-fifth is SGA [3], [4], [5] compared to around 8% in otherwise normal pregnancies [6]. These infants are therefore subject to all the complications associated with low birth weight, including chronic lung disease and developmental abnormalities, as well as the potential for insult to the

Frequent diagnoses in neonates requiring long-term renal replacement therapy

The majority of children in whom a need for RRT presents in the neonatal period have congenital abnormalities of the kidneys and urinary tract (CAKUT). Some children may have autosomal recessive polycystic kidney disease (ARPKD), with very large kidneys. Renal tubular dysgenesis is a rare cause. About 50% of these infants are diagnosed antenatally. This offers the benefits of antenatal counseling of families about the potential outcome of the pregnancy, and immediate optimization of medical

When to start dialysis

A clear-cut need to start dialysis is unusual, unless there is renal or tubular agenesis or anuria. Many infants, especially those with CAKUT, have ongoing urine production and, with attention to fluid and electrolyte balance and nutrition, may be kept without dialysis until they have recovered from respiratory complications or show improvement in kidney function, which would be expected in all neonates during the first few weeks of life. Some babies may show a surprising improvement in renal

Prognostic indicators

In addition to birth weight, gestation, and pulmonary hypoplasia, there are other factors that impact on outcome and therefore influence the decision of the physician whether or not to recommend dialysis (Box 1). The most important of these is comorbidity. Estimates suggest that this is present in as many as 73% of neonates requiring RRT [1], [9] and covers a complete spectrum of disabilities. Studies have linked comorbidity to poor outcome, with a five-fold higher mortality risk over five

Resources

The costs of RRT are substantial, and are particularly high in the infant, both in the short term because of the need for frequent reviews of the dialysis regimen, feeds and medications; and in the long-term because of the requirement for a lifetime of therapy. Such costs inevitably affect a country's ability to treat these infants, depending on available resources. Table 1 shows IPPN data on the number of children taken on to RRT programs according to the gross national income per capita of

Survival of neonates on renal replacement therapy

Survival of very young children on dialysis is good and similar to that in older children when the effects of comorbidity are removed [9]. Fig. 2 shows the survival to age 5 years for the recent combined registries neonatal data between the years 2000 and 2011 [1], of US neonates and infants aged 1 month to 2 years in the era 1992–2005 [12], and a further analysis over three years in the USA for the era 2000–2012 [13]. The first thing to notice is that the survival of the neonates is similar to

Heath-related quality of life

The outcome for the future quality of life for the newborn is another important question that families want answered. In a follow-up study of 41 young adults who had CKD stage 4/5 from infancy, 13% were on dialysis and 87% had a transplant at the time of the analysis; 54% had comorbidities. Lower health-related quality of life (HRQoL) scores were associated with comorbidities, being on dialysis, more than one treatment modality change, and being of short stature. Compared to a healthy,

Ethical aspects of renal replacement therapy in infants

The decision as to whether to start RRT in the neonate can be fraught with complex ethical issues, especially in the child with comorbidities that also affect their survival and quality of life, and in parts of the world with limited resources. The European Paediatric Dialysis Working Group Guidelines, drawn up in 2014, state that when deciding whether to start RRT in the infant, comorbidities, predicted quality of life for the child and family, availability of resources (both medical and those

Views of pediatric nephrologists and the multidisciplinary team on starting renal replacement therapy in neonates and infants

Even in well-resourced countries there differences of opinion among pediatric nephrologists as to whether RRT is justified in all newborns who require it, and especially so in those with comorbidity [16]. In a survey of pediatric nephrology teams in Canada, Germany, Japan, the UK, and the USA in 2010, only 30% of pediatric nephrologists said that they would offer RRT to all neonates and 50% to all infants aged 1–12 months. The most influential factor in rejecting RRT for infants was

The role of ethics in decision-making

So, can ethics help us when faced with these circumstances? Ethics are a set of principles that distinguish between right and wrong. However, rarely is there one single ‘right’ way to do something. Ethics therefore provide a means of evaluating and choosing between different, often competing, options and are about analyzing values rather than facts.

The UK Royal College of Paediatrics and Child Health has produced guidelines on withholding and withdrawing life-saving treatment. The guidelines

Sources of ethical conflict

As well as withholding or withdrawing life-sustaining therapies, there are additional situations when ethical conflicts may arise. Among these are: when application of clinical facts alone cannot determine what should be done; when there is disagreement about the right course of action; and when application of moral principles leads to conflict. Below are some examples of such ethical conflicts.

Is withholding or withdrawing life-sustaining treatments ever acceptable?

The French Neonatal Society Recommendations state that “Withholding or withdrawing life-sustaining treatment may be acceptable, and unreasonable therapeutic obstinacy is condemned. To withhold or withdraw a life-sustaining treatment can be justified when the intention is to cease opposing, in an unreasonable manner, the natural course of a disease” [19]. A particularly difficult concept for affluent areas is the role of resources in the decision making process. Clearly there are countries that

Conflicts in decision-making responsibilities

There is no international concordance about who should be responsible for decision-making in ethical disputes, and opinions vary between countries. The US Presidential Commission for the Study of Bioethical Issues is an advisory panel of the nation's leaders in medicine, science, ethics, religion, law, and engineering. The Bioethics Commission seeks to identify and promote policies and practices that ensure scientific research, health care delivery, and technological innovation are conducted in

Are neonates treated differently from infants, older children or adults?

In 1995 it was written that “Clinicians frequently give young patients more chances to revive from and survive their illnesses than they offer to older, particularly elderly, patients. Clinicians also seem more willing to impose greater burdens on children with fewer chances of success than adults” [23]. Conversely, a more recent review stated that “Dialysis is not a therapy that doctors feel to be morally obligatory in most cases. Whereas many doctors recommend dialysis for most infants with

Conclusion

The number of neonates requiring RRT is small. However, their outcome is good, and equal to that of infants, providing that they do not suffer from comorbidities. Ethical issues are complex and every chosen pathway must be in the child's best interests.

Conflict of interest statement

None declared.

Funding sources

None.

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