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

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.

Aim

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).

Contributors

Charlotte Gimpel, Max Christoph Liebau & Franz Schaefer

Publication

Journal: Pediatric Nephrology volume
Volume: 36
Issue: 12
Pages: 3841 - 3851
Year: 2021
DOI: 10.1007/s00467-021-05192-8

Further Study Information

Current Stage: Completed
Date:
Funding source(s): Open Access funding enabled and organized by Projekt DEAL. C.G. is supported by the German Federal Ministry of Research and Education (BMBF grant 01GM1903I). M.C.L. is supported by the German Federal Ministry of Research and Education (BMBF grant 01GM1903B) and the German Research Council (DFG, LI 2397/5-1). This study has been supported by ERKNet. ERKNet is cofounded by the European Union within the framework of the Third Health Programme “ERN-2016-Framework Partnership Agreement 2017-2021.”


Health Area

Disease Category: Kidney disease

Disease Name: Polycystic kidney disease

Target Population

Age Range: Unknown

Sex:

Nature of Intervention:

Stakeholders Involved

Study Type

- Systematic review of outcomes measured in trials

Method(s)

- Systematic review

Relevant publications were searched for in MEDLINE using the search term ((ARPKD) OR "autosomal recessive polycystic kidney disease" OR "congenital hepatic fibrosis" OR "hepatorenal cystic syndrome") AND (child* OR young adult OR adolescent* OR pediatric). The last search update was performed on 09 April 2021 yielding 897 studies. A flow diagram listing the number of excluded papers by reason is given in Fig. 1. Studies published prior to 1990 were excluded because there was significant heterogeneity regarding the definition of ARPKD