An Empirical Biomarker-Based Calculator for Cystic Index in a Model of Autosomal Recessive Polycystic Kidney Disease-The Nieto-Narayan Formula

PLoS One. 2016 Oct 3;11(10):e0163063. doi: 10.1371/journal.pone.0163063. eCollection 2016.


Autosomal recessive polycystic kidney disease (ARPKD) is associated with progressive enlargement of the kidneys fuelled by the formation and expansion of fluid-filled cysts. The disease is congenital and children that do not succumb to it during the neonatal period will, by age 10 years, more often than not, require nephrectomy+renal replacement therapy for management of both pain and renal insufficiency. Since increasing cystic index (CI; percent of kidney occupied by cysts) drives both renal expansion and organ dysfunction, management of these patients, including decisions such as elective nephrectomy and prioritization on the transplant waitlist, could clearly benefit from serial determination of CI. So also, clinical trials in ARPKD evaluating the efficacy of novel drug candidates could benefit from serial determination of CI. Although ultrasound is currently the imaging modality of choice for diagnosis of ARPKD, its utilization for assessing disease progression is highly limited. Magnetic resonance imaging or computed tomography, although more reliable for determination of CI, are expensive, time-consuming and somewhat impractical in the pediatric population. Using a well-established mammalian model of ARPKD, we undertook a big data-like analysis of minimally- or non-invasive blood and urine biomarkers of renal injury/dysfunction to derive a family of equations for estimating CI. We then applied a signal averaging protocol to distill these equations to a single empirical formula for calculation of CI. Such a formula will eventually find use in identifying and monitoring patients at high risk for progressing to end-stage renal disease and aid in the conduct of clinical trials.

Publication types

  • Meta-Analysis

MeSH terms

  • Animals
  • Biomarkers* / blood
  • Biomarkers* / urine
  • Blood Urea Nitrogen
  • Child
  • Creatinine / blood
  • Cystatin C / blood
  • Cysts / pathology
  • Hepatitis A Virus Cellular Receptor 1 / blood
  • Humans
  • Interleukin-18 / blood
  • Kidney / diagnostic imaging
  • Kidney / metabolism
  • Kidney / physiopathology
  • Kidney Transplantation
  • Lipocalin-2 / blood
  • Magnetic Resonance Imaging
  • Mice
  • Polycystic Kidney, Autosomal Recessive / blood*
  • Polycystic Kidney, Autosomal Recessive / diagnostic imaging
  • Polycystic Kidney, Autosomal Recessive / pathology
  • Polycystic Kidney, Autosomal Recessive / urine*
  • Rats
  • Renal Insufficiency / blood*
  • Renal Insufficiency / pathology
  • Renal Insufficiency / urine*
  • Severity of Illness Index
  • Ultrasonography


  • Biomarkers
  • Cystatin C
  • HAVCR1 protein, human
  • Hepatitis A Virus Cellular Receptor 1
  • Interleukin-18
  • Lipocalin-2
  • Creatinine

Grant support

The author(s) received no specific funding for this work.