Abstract: TH-PO316

The Impact of Uninephrectomy on Subsequent AKI Outcomes

Session Information

Category: Acute Kidney Injury

  • 001 AKI: Basic


  • Kim, Myung-gyu, NIH/NIDDK, Bethesda, Maryland, United States
  • Kojima, Hiroshi, NIH/NIDDK, Bethesda, Maryland, United States
  • Street, Jonathan, NIH/NIDDK, Bethesda, Maryland, United States
  • Koritzinsky, Erik H., NIH/NIDDK, Bethesda, Maryland, United States
  • Hu, Xuzhen, NIH/NIDDK, Bethesda, Maryland, United States
  • Yuen, Peter S.T., NIH/NIDDK, Bethesda, Maryland, United States
  • Star, Robert A., NIH/NIDDK, Bethesda, Maryland, United States

The long-term risk of kidney donation (uninephrectomy) is controversial, but appears modest (hypertension; ESRD very rarely). However, the short-term risks including acute kidney injury (AKI) are not well studied. Although uninephrectomy (uni-Nx) alone causes a clinically silent hyperfiltration, the impact of hyperfiltration on AKI outcomes is still unknown. Here, we examine whether uni-Nx alone could be a risk factor for AKI development and recovery.


In C57BL/6 mice, uni-Nx or sham operation was performed and then renal and tubular function was assessed by transcutaneous measurement of glomerular filtration rate (GFR) using FITC-sinistrin and furosemide simulation test (FST), respectively. At 2 wks after uni-Nx or sham, animals were subjected to 28 min ischemia reperfusion injury (IRI) then followed for 4 wks.


Uni-Nx induced renal hypertrophy and increased expression of tubular transporter in the remaining kidney. These structural changes were accompanied by functional compensation. GFR recovered to more than 70% of normal after 1 wk. Interestingly, urinary output in response to furosemide remained unchanged during 2 wks after uni-Nx, suggesting that hyperfiltration also increased tubular secretion and action of furosemide. Two weeks after uni-Nx, animals were subjected to IRI. The GFR one day post-IRI was lower and BUN was higher in uni-Nx than sham mice. Uni-Nx also significantly delayed recovery of renal function over the next 4 wks. Interestingly, a higher urine production in response to furosemide, but not GFR, just before IRI was strongly correlated with more ischemic renal damage in uni-Nx mice. This suggests that the changes in tubular function, rather than changes in GFR, after uni-Nx could be risk/protective factors for subsequent AKI development.


Mice with a single kidney 1) have the expected compensatory changes in GFR and tubular function; 2) an unexpectedly severe functional deterioration to IRI 2 wks after uni-Nx; and 3) an unexpectedly delayed recovery over the next 4 wks. In addition, the baseline tubular function (and not baseline GFR) can better predict the risk of subsequent AKI. These results may provide important clues in developing new risk stratification and management strategies in patients with a single kidney.


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