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Tubulointerstitial injury and the progression of chronic kidney disease

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Abstract

In chronic kidney disease (CKD), once injury from any number of disease processes reaches a threshold, there follows an apparently irreversible course toward decline in kidney function. The tubulointerstitium may play a key role in this common progression pathway. Direct injury, high metabolic demands, or stimuli from various other forms of renal dysfunction activate tubular cells. These, in turn, interact with interstitial tissue elements and inflammatory cells, causing further pathologic changes in the renal parenchyma. The tissue response to these changes thus generates a feed-forward loop of kidney injury and progressive loss of function. This article reviews the mechanisms of this negative cycle mediating CKD.

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Acknowledgments

Supported in part by grants R01 DK049362 and R01 DK075663 from the National Institute of Diabetes, Digestive and Kidney Diseases.

Author information

Authors and Affiliations

  1. Division of Kidney Diseases, Department of Pediatrics, Northwestern University Feinberg School of Medicine and Children’s Memorial Hospital, Chicago, IL, USA

    Kavita S. Hodgkins & H. William Schnaper

  2. Children’s Memorial Hospital Box #37, 2300 Children’s Plaza, Chicago, 60614, IL, USA

    Kavita S. Hodgkins

Authors
  1. Kavita S. Hodgkins
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  2. H. William Schnaper
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Corresponding author

Correspondence to Kavita S. Hodgkins.

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Answers

1. (B)

2. (C)

3. (B)

4. (D)

5. (A)

Questions (Answers provided following the reference list)

Questions (Answers provided following the reference list)

  1. 1.

    Histologic changes shown to correspond to worsening GFR in CKD include all of the following EXCEPT:

    1. A.

      Decreased number of peritubular capillaries

    2. B.

      Severity of glomerular injury

    3. C.

      Intensity of interstitial inflammation

    4. D.

      Increased interstitial volume and fibrosis

  2. 2.

    Proteinuria and the presence of other molecules in the filtrate affect tubulointerstitial cells by which of the following mechanisms:

    1. A.

      Proteinuria inhibits activity of the membrane attack complex, or C5b-9

    2. B.

      Albumin, acting through its receptor, megalin, down-regulates NF-κB

    3. C.

      Free fatty acids activate PPAR leading to tubular cell apoptosis

    4. D.

      Generation of ROS is decreased by exposure to iron in the filtrate

  3. 3.

    Cells hypothesized to be the source of myofibroblasts responsible for unbalanced production of ECM include all of the following EXCEPT:

    1. A.

      Tubular epithelial cells

    2. B.

      Podocytes

    3. C.

      Bone marrow precursor cells

    4. D.

      Vascular pericytes

  4. 4.

    Tissue responses to tubulointerstitial injury include which of the following:

    1. A.

      Renal parenchymal blood flow is increased to maintain unchanged oxygen tension

    2. B.

      Inflammatory cells recruited to the tubulointerstitial milieu are inactivated by high urea concentrations

    3. C.

      Renin is inactivated, resulting in hypoxia and oxidative stress

    4. D.

      EMT is induced in part by the actions of TGF-β, CTGF, and PAI-1

  5. 5.

    Tubular injury affects progression of chronic kidney disease by which of the following pathways:

    1. A.

      Hypoxia is worsened by capillary injury and limitation of oxygen diffusion

    2. B.

      Tubular dropout causes a decrease in single-nephron blood flow of remaining glomeruli

    3. C.

      Autoregulation of glomerular blood flow is preserved

    4. D.

      Atrophy of tubules results in increased filtrate delivery to the macula densa, increasing GFR through tubuloglomerular feedback

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Hodgkins, K.S., Schnaper, H.W. Tubulointerstitial injury and the progression of chronic kidney disease. Pediatr Nephrol 27, 901–909 (2012). https://doi.org/10.1007/s00467-011-1992-9

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  • DOI: https://doi.org/10.1007/s00467-011-1992-9

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