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Abstract: FR-PO076

Serum Uromodulin as a Marker for AKI and Chronic Nephron Loss

Session Information

Category: Acute Kidney Injury

  • 101 AKI: Epidemiology‚ Risk Factors‚ and Prevention

Authors

  • Vonbrunn, Eva, Friedrich-Alexander-Universitat Erlangen-Nurnberg, Erlangen, Bayern, Germany
  • Ebert, Nadja, Friedrich-Alexander-Universitat Erlangen-Nurnberg, Erlangen, Bayern, Germany
  • Amann, Kerstin U., Friedrich-Alexander-Universitat Erlangen-Nurnberg, Erlangen, Bayern, Germany
  • Daniel, Christoph, Friedrich-Alexander-Universitat Erlangen-Nurnberg, Erlangen, Bayern, Germany
Background

Uromodulin (Umod) is expressed exclusively in the kidney in the thick ascending limb of the loop of Henle. It is secreted in the urine, where it is the most abundant glycoprotein. To a minor degree, Umod is also released basolaterally from cells into the serum. Actually, serum Umod-levels are an established, sensitive and robust marker for chronic kidney disease (CKD). Here, we investigate serum Umod-levels, renal Umod protein and mRNA expression in acute kidney injury (AKI) and in rat models of nephron loss.

Methods

Umod was first assessed in AKI using an ischemia-reperfusion (I/R) rat model. Blood and kidney samples were collected 10 min, 6h, 24h, 3d, 5d and 8w post reperfusion. To investigate the effect of nephron number on Umod levels, sera and tissue from healthy rats, uni- and 5/6-nephrectomized (Snx) rats were studied. Renal function (serum creatinine), histological changes (acute tubular injury), and renal damage markers (KIM-1) were evaluated in both models. Serum Umod levels were measured by ELISA and renal Umod mRNA expression by multiplex gene expression analysis. The amount and distribution of Umod protein in the kidney was examined by antibody-based detection methods.

Results

In AKI, serum creatinine increased markedly 24h after I/R. Serum Umod was also transiently increased, peaking between 6-24h and correlating with injury. Simultaneously, the amount of Umod-positive kidney cells decreased from 12,4±7,7% in healthy rats to 1,8±1,7% in kidneys 24h after I/R. In healthy kidneys Umod was detected mainly in the inner and outer strips, while it was substantially reduced and homogeneously distributed in the medulla, inner strip, and outer strip 24h after I/R. Moreover, mRNA expression of Umod decreased continuously after I/R and was lowest on day 1-5. In the models of nephron loss serum Umod correlated positively with nephron number showing highest levels in healthy rats (2192,2±323,8 pg/ml), which were significantly reduced after uni-nephrectomy (1262,9±208,8 pg/ml) and further reduced after Snx (939,8±193,5 pg/ml).

Conclusion

Serum Umod appears to be a sensitive marker for AKI showing a transient increase in serum levels in parallel with loss of Umod-expressing cells. Umod serum level correlated positively with nephron number. Thus, serum Umod appears as promising marker to assess acute and chronic renal failure.

Funding

  • Other NIH Support