The Promise of Tubule Biomarkers in Kidney Disease: A Review

Am J Kidney Dis. 2021 Nov;78(5):719-727. doi: 10.1053/j.ajkd.2021.03.026. Epub 2021 May 27.


For over 70 years, serum creatinine has remained the primary index for detection and monitoring of kidney disease. Tubulointerstitial damage and fibrosis are highly prognostic for subsequent kidney failure in biopsy studies, yet this pathology is invisible to the clinician in the absence of a biopsy. Recent discovery of biomarkers that reflect distinct aspects of kidney tubule disease have led to investigations of whether these markers can provide additional information on risk of chronic kidney disease (CKD) progression and associated adverse clinical end points, above and beyond estimated glomerular filtration rate and albuminuria. These biomarkers can be loosely grouped into those that mark tubule cell injury (eg, kidney injury molecule 1, monocyte chemoattractant protein 1) and those that mark tubule cell dysfunction (eg, α1-microglobulin, uromodulin). These kidney tubule biomarkers provide new opportunities to monitor response to therapeutics used to treat CKD patients. In this review, we describe results from some unique contributions in this area and discuss the current challenges and requirements in the field to bring these markers to clinical practice. We advocate for a broader assessment of kidney health that moves beyond a focus on the glomerulus, and we highlight how such tools can improve diagnostic accuracy and earlier assessment of therapeutic efficacy or harm in CKD patients.

Keywords: Acute interstitial nephritis (AIN); acute tubule necrosis (ATN); biomarker; epidermal growth factor (EGF); interleukin 18 (IL-18); kidney damage; kidney function; kidney injury marker 1 (KIM-1); monocyte chemoattractant protein 1 (MCP-1); renal tubule; review; tubular atrophy; tubular disease; tubule dysfunction; tubule injury; tubulointerstitial fibrosis; uromodulin (UMOD); α1-microglobulin (A1M).

Publication types

  • Research Support, N.I.H., Extramural
  • Review

MeSH terms

  • Albuminuria
  • Biomarkers
  • Glomerular Filtration Rate
  • Humans
  • Kidney Tubules
  • Renal Insufficiency, Chronic* / diagnosis


  • Biomarkers