Systematic review on outcomes used in clinical research on autosomal recessive polycystic kidney disease—are patient-centered outcomes our blind spot?

Abstract

Background Autosomal recessive polycystic kidney disease (ARPKD) is a rare severe hepatorenal disease. Survivors of pulmonary hypoplasia and patients with milder presentations often achieve long-term survival but frequently require kidney and/or liver transplantation. Objective To examine the use of clinical, surrogate and patient-centered outcomes in studies on ARPKD with special attention to core outcomes of the Standardized Outcomes in NephroloGy project for children with chronic kidney disease (SONG-Kids). Data sources and study eligibility criteria A systematic MEDLINE literature search identified 367 ARPKD studies published since 1990; however, of these 134 were excluded because they did not report any clinical outcomes (e.g. only histopathological, genetic, protein structure or radiological markers), 19 studies because they only included prenatal patients and 138 because they were case reports with ≤ 3 patients. Study appraisal Seventy-six eligible studies were examined for study type, size, intervention, and reported outcomes by organ system and type, including all SONG-kids tier 1–3 outcomes. Participants There were 3231 patient-reports of children and adults with ARPKD. Results The overwhelming majority of studies reported clinical and surrogate outcomes (75/76 (98%) and 73/76 (96%)), but only 11/76 (14%) examined patient-centered outcomes and only 2/76 (3%) used validated instruments to capture them. Of the SONG-Kids core outcomes, kidney function was reported almost universally (70/76 (92%), infection and survival in three quarters (57/76 (75%), 55/76 (72%)) and measures of life participation (including neurological impairment) only rarely and inconsistently (16/76 (21%)). Limitations Thirty studies (39%) were of low quality as they were either narrative case reports (n = 14, 18%) and/or patients with ARPKD were an indistinguishable subgroup (n = 18, 24%). Only 28 trials compared interventions, but none were randomized. Conclusions and implications Studies that reported clinical outcomes in ARPKD usually covered the core outcome domains of kidney function, infections, and survival, but measures of life participation and patient-centered outcomes are distinctly lacking and require more attention in future trials. Graphical abstract

Kidney concentrating capacity in children with autosomal recessive polycystic kidney disease is linked to glomerular filtration and hypertension

“…Autosomal recessive polycystic kidney disease is a very rare (1:20,000 live births) but severe multisystemic, typically early-onset disease. It can lead to perinatal mortality in 20-30% of newborns and neonatal survivors throughout childhood, with chronic kidney failure prevalence in approximately 50% of them [1,2]. The most common clinical complication besides chronic kidney disease and congenital hepatic fibrosis is arterial hypertension; this affects about 90% of patients with…”

“…Autosomal recessive polycystic kidney disease (ARPKD) is a rare but severe disease with a high mortality rate and increased morbidity leading to childhood chronic kidney failure in approximately 50% of children [1,2]. It is primarily a tubular disorder, and it affects mainly children, but late manifestations in adulthood also exist [3,4].…”

Polycystic Kidney Disease Drug Development: A Conference Report

“…16 Hypertension occurs with increased frequency in children with ADPKD, with an overall prevalence of 20%-40%. 42 Children with ADPKD who have hypertension have larger kidneys and a faster kidney growth rate than those with normal blood pressure. 43 , 44 These data may open the field for early-onset hypertension as an important marker in clinical trials.…”

“…Most previous studies focused on the description of clinical endpoints such as patient or organ survival. 42 Patient- and family-centered outcome measures could, in the future, be of major importance for this early onset severe disorder that can impose a major psychosocial burden on patients and their families and caregivers. Clearly, much more work is needed in this field.…”

Drug Development for Cystic Kidney Diseases

“…ADPKD is the most common monogenic disorder that can lead to kidney failure, with a prevalence of 600,000 people in the United States (1). ARPKD is associated with significant kidney- and liver-related morbidity and mortality in children, with >50% of affected individuals progressing to kidney failure within the first decade of life (2).…”