Serum uromodulin-a marker of kidney function and renal parenchymal integrity

Nephrol Dial Transplant. 2018 Feb 1;33(2):284-295. doi: 10.1093/ndt/gfw422.


Background: An ELISA to analyse uromodulin in human serum (sUmod) was developed, validated and tested for clinical applications.

Methods: We assessed sUmod, a very stable antigen, in controls, patients with chronic kidney disease (CKD) stages 1-5, persons with autoimmune kidney diseases and recipients of a renal allograft by ELISA.

Results: Median sUmod in 190 blood donors was 207 ng/mL (women: men, median 230 versus 188 ng/mL, P = 0.006). sUmod levels in 443 children were 193 ng/mL (median). sUmod was correlated with cystatin C (rs = -0.862), creatinine (rs = -0.802), blood urea nitrogen (BUN) (rs = -0.645) and estimated glomerular filtration rate (eGFR)-cystatin C (rs = 0.862). sUmod was lower in systemic lupus erythematosus-nephritis (median 101 ng/mL), phospholipase-A2 receptor- positive glomerulonephritis (median 83 ng/mL) and anti-glomerular basement membrane positive pulmorenal syndromes (median 37 ng/mL). Declining sUmod concentrations paralleled the loss of kidney function in 165 patients with CKD stages 1-5 with prominent changes in sUmod within the 'creatinine blind range' (71-106 µmol/L). Receiver-operating characteristic analysis between non-CKD and CKD-1 was superior for sUmod (AUC 0.90) compared with eGFR (AUC 0.39), cystatin C (AUC 0.39) and creatinine (AUC 0.27). sUmod rapidly recovered from 0 to 62 ng/mL (median) after renal transplantation in cases with immediate graft function and remained low in delayed graft function (21 ng/mL, median; day 5-9: relative risk 1.5-2.9, odds ratio 1.5-6.4). Immunogold labelling disclosed that Umod is transferred within cytoplasmic vesicles to both the apical and basolateral plasma membrane. Umod revealed a disturbed intracellular location in kidney injury.

Conclusions: We conclude that sUmod is a novel sensitive kidney-specific biomarker linked to the structural integrity of the distal nephron and to renal function.

Keywords: kidney failure; renal biomarker; serum assay; thick ascending limb; uromodulin.

MeSH terms

  • Adolescent
  • Adult
  • Biomarkers / blood*
  • Case-Control Studies
  • Child
  • Child, Preschool
  • Cohort Studies
  • Creatinine / blood
  • Cystatin C / blood
  • Female
  • Glomerular Filtration Rate
  • Glomerulonephritis / blood
  • Glomerulonephritis / pathology*
  • Hemorrhage / blood
  • Hemorrhage / pathology*
  • Humans
  • Infant
  • Lung Diseases / blood
  • Lung Diseases / pathology*
  • Lupus Erythematosus, Systemic / blood
  • Lupus Erythematosus, Systemic / pathology*
  • Lupus Nephritis / blood
  • Lupus Nephritis / pathology*
  • Male
  • Middle Aged
  • ROC Curve
  • Renal Insufficiency, Chronic / blood
  • Renal Insufficiency, Chronic / pathology*
  • Uromodulin / blood*
  • Young Adult


  • Biomarkers
  • Cystatin C
  • UMOD protein, human
  • Uromodulin
  • Creatinine

Supplementary concepts

  • Rapidly progressive glomerulonephritis with pulmonary hemorrhage