Uromodulin ELISA

(Tamm-Horsfall-Glycoprotein)
EQ 6821-9601
 Protein characteristics

• Synthesised only in renal epithelial cells forming

the thick ascending limb of the loop of Henle and
the early distal convoluted tubule

• Molecular weight: 105 kDa

• 30 % of protein mass are carbohydrates

• Highest concentrated protein in urine (50 mg/d)

• But also lower secretion rate into the blood

(conc.: 200 ng/mL)
 Normal range
Males +
Males females children
females
n 190 89 101 443
Mean 222 199 241 204
SD 95 79 104 89
75th percentile 275 251 308 254
Median 207 188 230 193
25 percentile 149 144 165 143
 Sample stability
U ro m o d u lin [n g /m L ]

- Umod is very stable, even after 4 weeks of storage at increased temperatures

450
400
350
300
250 -20
°C
200 4 °C
150 37 °C
100
50
0
5011 5015 29 43 50 61 65 66
Sample ID#
And only 5µl serum is needed! (1:100 Dilution)
 Autoantibody positive patients
(with probable kidney involvement)

Anti-
Healthy Anti-PLA2R Anti-GBM
dsDNA
controls positive positive
positive
n 190 20 20 10
Mean [ng/ml] 222 87 110 41
SD [ng/ml] 95 54 76 22
75th percentile [ng/ml] 275 110 135 52
Median [ng/ml] 207 82 107 37
25 percentile [ng/ml] 149 48 39,0 22

500
p<0.001

p<0.001
400
p<0.001
-- -- Mean
----- Median

300

200
Urom odulin [ng/m l]

100

0
Healthy blood anti-dsDNA anti-PLA2-R anti-GBM
donors n=190 n=20 n=20 n=10
 Uromodulin in SLE patients
(with and without kidney involvment)

52 sera from clinically characterized SLE patients (48f, 4m; age 15-82) were tested for sUmod by
ELISA (EUROIMMUN, Germany). 32 of these patients had an active or inactive kidney involvement,
while 20 patients did not show any kidney damage according to the clinical reports.
 Uromodulin levels in different stages
of chronic kidney disease

Stages defined by doctor:

eGFR Cystatin C according to Hoek
eGFR and other comorbidities (Diabetis,
(values >90 unreliable)
high blood pressure…)
 Uromodulin can identify
beginning of kidney disease

ROC analysing the ability of different parameters to differentiate between patients without
chronic kidney disease (CKD stage 0) and CKD stage 1; BUN = blood-urea-nitrogen;
eGFR = estimated glomerular filtration rate; AUC = area-under-the-curve.

*Data from Scherberich at al. publication in preparation

Uromodulin levels in different stages
of chronic kidney disease
 Uromodulin can identify
beginning of kidney disease
 Comparison to established
renal markers

*Data from Scherberich at al. publication in preparation

UMOD – after kidney transplantation
n=44
 Advantages of Uromodulin

- Direct marker for kidney vitality

- No estimations/calculations necessary
• eGFR is estimated based on creatinine/cystatin C levels (serum) or
creatinine clearance (urine)
• Different equations for estimating eGFR available
- Synthesized only in the kidney (in contrast to creatinine and cystatin C)
- Independent of muscle mass and protein intake (in contrast to creatinine)
- No 24h urine collection (as for creatinine clearance)
- Early diagnostic marker (early loss of renal function can be identified in the
„creatinine-blind“ range)
 Indications

Indication: Nephropathies

 Marker for kidney function and vitality

 Decreasing levels of uromodulin with decreasing kidney function:

direct correlation to estimated glomerular filtration rate (eGFR)
 Only marker that can distinguish between controls and stage 1
CKD cases
 Risk factor for chronic kidney disease (CKD)

 Marker for monitoring therapy of CKD (hypertension, diabetes,

tumors)
 Predictive marker after kidney transplantation
Thank you!