How has the management of paediatric kidney disease developed over the years?

Professor Lesley Rees, Consultant Paediatric Nephrologist, Great Ormond Street Hospital for Children, London, UK

Paediatric Nephrology

Paediatric Nephrology is a relatively young specialty: it was in the 1970s that renal replacement therapy (RRT) (dialysis and transplantation) for children began.

At first such treatment was only offered to older children; acceptance of infants began in the 1980s. Indeed RRT is still not available everywhere in the world: 80% of children who receive RRT live in Europe, North America or Japan. Even within Europe there are differences that are principally related to economic factors, prejudicing against younger children who are more costly to treat.

The incidence of CKD increases with age: in the UK 3% of children on RRT are under two years of age, 28% are aged two to eight, 28% are 8 to 12, and 40% are 12 to 16 years. The prevalence of RRT ranges from 18 to 100 per million age-related population. Prevalence has increased over the years due to a combination of inclusion of younger children and those with comorbidities, and improved survival.

Advances in paediatric nephrology management

As well as advances in surgical techniques and technology for RRT, our therapeutic toolkit continues to expand and we take for granted many treatments that are now in routine use. A large number of important developments took place in the 1980s.

Despite these advances, three major complications of CKD remain and continue to adversely affect the outcome of our patients: poor growth, bone disease and cardiovascular disease (CVD).

To name but a few: ACE inhibitors revolutionised the treatment of hypertension alongside our understanding of their role in the attenuation of the progression of CKD; ciclosporine improved outcomes for patients post-transplant, for whom immunosuppression had before been just steroids and azathioprine; and prevention of anaemia with erythropoietin rather than blood transfusion has improved the health, wellbeing and future chances of transplantation for thousands of patients.

Despite these advances, three major complications of CKD remain and continue to adversely affect the outcome of our patients: poor growth, bone disease and cardiovascular disease (CVD).

Growth

Height prognosis has improved considerably during the last decades. There are two studies from the US of the growth of children with CKD: in 2006, one third of children were below the third centile for height; whereas between 2005 and 2013, this figure was only 12%.

This improvement applies to children on RRT as well. Between 1985 and 1988 the European Dialysis and Transplant Association (EDTA) Registry reported that the mean height standard deviation score (HtSDS) was −3.0. In Germany between 1998 and 2009, mean HtSDS improved to −1.8. Puberty had been a time when growth was particularly badly affected: EDTA data showed that the pubertal growth spurt was delayed by as much as two years and the overall height gain was significantly reduced.

In Europe between 1990 and 2011, 55% of patients attained an adult height within the normal range, whereas this figure has risen to 62% for 2006–11.

It is during the peripubertal years that the improvement in growth in children on RRT seems to be the greatest, with age at onset of puberty and the pubertal growth spurt being unaffected in the German data. Notably, final height is improving: In Europe between 1990 and 2011, 55% of patients attained an adult height within the normal range, whereas this figure has risen to 62% for 2006–11.

These developments are likely to be due to better understanding and management of the complications of CKD such as nutrition (particularly in infants), anaemia, acidosis, bone disease, derangements of the GH IGF-1 axis, and of dialysis machines and programmes, and parallels an improvement in the survival of our patients. Reduction of steroid use post-transplant has also contributed, and the use of rhGH.

Chronic kidney disease mineral and bone disorder (CKD-MBD)

The role played by abnormal calcium, phosphate and parathyroid hormone (PTH) metabolism in bone disease and vascular calcification in CKD (CKD-MBD) continues to be unravelled, and new phosphate binders and vitamin D analogues are being developed.

Complications of CKD-MBD continue (although the child with severe bone deformities is no longer seen in the developed world) and CVD continues to be the main cause of death for patients on RRT.

However, there continues to be controversy over best management of hyperparathyroidism, which is reflected in the diverse spread of PTH values seen across the international community. Complications of CKD-MBD continue (although the child with severe bone deformities is no longer seen in the developed world) and CVD continues to be the main cause of death for patients on RRT.

Survival

Survival is improving, particularly in younger children, by 12% and 20% in those more than and less than 5 years of age respectively for each 5 year period between 1990 and 2010. The expected remaining lifetime for those up to 14 years of age depends on treatment modality, being around 20 years for those on dialysis but around 60 years for transplanted patients

The future

Despite these advances, we must aspire to continue to improve the outcome for children with CKD, and, most importantly, that one day all children in the world will be able to receive the treatment they need.

References:

Rees L, Schaefer F, Schmitt C, Shroff R, Warady B (2017) Chronic dialysis in children and adolescents: challenges and outcomes. Lancet Child Adolesc Health 1: 68–77

Rees, L (2016) Growth hormone therapy in children with CKD after more than two decades of practice. Pediatr Nephrol 31:1421-35.