In the human body, uromodulin is exclusively produced in the kidneys by the tubule cells of the thick ascending limb of Henle‘s loop and secreted both into the lumen of the tubule and the blood stream. In the distal tubule lumen, uromodulin is present polymerised to the epithelium, offering protection against kidney stone formation. Due to its polymer structure, the uromodulin which is secreted via the urine is only to a small extent suitable for measurement. Uromodulin in serum, on the other hand, is exclusively present as a monomer and therefore can be more reliably quantified.
Moreover, uromodulin concentrations in urine only have a weak association with the estimated glomerular filtration rate (eGFR). In contrast, the uromodulin in serum (sUmod) correlates strongly with the eGFR.
The sUmod concentration allows identification of early stages of chronic kidney insufficiency already in the symptom-free phase as opposed to established glomerular markers, such as creatinine and cystatin C. A decrease of sUmod concentration in progressing kidney insufficiency shows a loss in function and integrity of the kidney parenchyma.
Based on the sUmod level, also long-term complications can be deduced. Epidemiological studies show that low sUmod concentrations are associated with an increased overall mortality, cardiovascular morbidity, heart insufficiency and the progression of kidney insufficiency. With respect to transplantations, low sUmod concentrations are predicative for long-term function loss of the transplant.
Serum uromodulin presents a sensitive marker of tubular function with a large potential for the prediction and early recognition of descreasing kidney function. This applies especially to diseases in which mainly the kidney tubules are damaged.