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

Scherberich, Jürgen E.; Gruber, Rudolf; Nockher, Wolfgang Andreas; Christensen, Erik Ilso; Schmitt, Hans; Herbst, Victor; Block, Matthias; Kaden, Jürgen und Schlumberger, Wolfgang (2018): Serum uromodulin-a marker of kidney function and renal parenchymal integrity. In: Nephrology Dialysis Transplantation, Bd. 33, Nr. 2: S. 284-295

Abstract

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 (r(s) = -0.862), creatinine (r(s) = -0.802), blood urea nitrogen (BUN) (rs = -0.645) and estimated glomerular filtration rate (eGFR)-cystatin C (r(s) = 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 mmol/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.

• Dokumententyp: Zeitschriftenartikel
• Fakultät: Medizin
• Themengebiete: 600 Technik, Medizin, angewandte Wissenschaften > 610 Medizin und Gesundheit
• ISSN: 0931-0509
• Sprache: Englisch