Uromodulin: old friend with new roles in health and disease

Abstract

The most abundant urinary protein, TammHorsfall protein, later renamed uromodulin, is expressed exclusively by the thick ascending limb cells of the kidney and released into urine from the apical cell membrane.

How Kidney Cell Death Induces Renal Necroinflammation

“…Uromodulin is selectively produced by the cells of the thick ascending limb and secreted into the distal tubule. 115 Uromodulin is a sticky glycoprotein generating large aggregates that embed everything that is present in distal tubules such as cytokines, blood cells, or necrotic tubular cell debris bacteria. 115 In this manner, uromodulin promotes clearance from the distal tubule, which is an important anti-inflammatory mechanism.…”

“…115 Uromodulin is a sticky glycoprotein generating large aggregates that embed everything that is present in distal tubules such as cytokines, blood cells, or necrotic tubular cell debris bacteria. 115 In this manner, uromodulin promotes clearance from the distal tubule, which is an important anti-inflammatory mechanism. However, any injury of the thick ascending limb epithelium allows uromodulin to leak from its native compartment into the interstitial space.…”

Cystic Kidney Disease: A Primer

“…Blood pressure is usually normal or borderline low because of salt wasting. 33 Hyperuricemia and gout may be present. MCKD presents later than NPHP, with most patients reaching ESRD between the third and sixth decade of life.…”

“…Diagnosis is suspected in individuals with a positive family history of kidney disease, bland urinary sediment, and characteristic sonographic findings. 33 Kidneys are often echogenic and normal to small in size on US, and medullary cysts are typically not observed. The presence of gout in MCKD2 patients distinguishes this disorder from MCKD1.…”

“…25 MCKD is now more appropriately characterized as an autosomal dominant tubulointerstitial kidney disease, which is defined as a group of disorders characterized by autosomal dominant inheritance, bland urinary sediment with minimal blood and protein, pathologic changes of tubular and interstitial fibrosis, and slowly progressive chronic kidney disease. 33 Patients present with CKD and bland urine with decreased urinary concentrating ability. As in NPHP, there may be a history of polydipsia and polyuria.…”