Success for renal tubule cell assist device in phase II trial for acute kidney injury

We have characterized the expression and secretion of the acute kidney injury (AKI) biomarkers insulin-like growth factor binding protein 7 (IGFBP7) and tissue inhibitor of metalloproteinases-2 (TIMP-2) in human kidney epithelial cells in primary cell culture and tissue. We established cell culture model systems of primary kidney cells of proximal and distal tubule origin and observed that both proteins are indeed expressed and secreted in both tubule cell types in vitro. However, TIMP-2 is both expressed and secreted preferentially by cells of distal tubule origin, while IGFBP7 is equally expressed across tubule cell types yet preferentially secreted by cells of proximal tubule origin. In human kidney tissue, strong staining of IGFBP7 was seen in the luminal brush-border region of a subset of proximal tubule cells, and TIMP-2 stained intracellularly in distal tubules. Additionally, while some tubular colocalization of both biomarkers was identified with the injury markers kidney injury molecule-1 and neutrophil gelatinase-associated lipocalin, both biomarkers could also be seen alone, suggesting the possibility for differential mechanistic and/or temporal profiles of regulation of these early AKI biomarkers from known markers of injury. Last, an in vitro model of ischemia-reperfusion demonstrated enhancement of secretion of both markers early after reperfusion. This work provides a rationale for further investigation of these markers for their potential role in the pathogenesis of acute kidney injury.

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Effect of basement membrane and colloid osmotic pressure on renal tubule cell volume

AJP Renal Physiology ◽

10.1152/ajprenal.1977.233.4.f325 ◽

1977 ◽

Vol 233 (4) ◽

pp. F325-F332

Author(s):

M. A. Linshaw ◽

F. B. Stapleton ◽

F. E. Cuppage ◽

J. J. Grantham

Keyword(s):

Basement Membrane ◽

Osmotic Pressure ◽

Cell Volume ◽

Cell Size ◽

Renal Tubule ◽

Colloid Osmotic Pressure ◽

Outer Diameter ◽

Tubule Cell ◽

Cation Pump ◽

Renal Tubule Cell

Renal tubule cell volume is thought to be kept constant by a cation pump. When active transport is blocked, intracellular impermeant solutes cause cells to swell. Cell size is then determined by transmembrane hydrostatic and colloid osmotic forces. We studied the importance of passive transmembrane forces in determining cell size in isolated rabbit proximal straight tubules (PST). We blocked active solute transport with ouabain and evaluated subsequent changes in cell size by measuring outer diameter of nonperfused tubules. Tubules in a ouabain and 6 g/100 ml protein bath swelled only 40% above control. However, removal of the tubule basement membrane with collagenase dissipated a transmembrane hydrostatic pressure and caused more swelling. Final cell volume was determined largely by bath protein concentration. Tubules in ouabain and collagenase swelled enormously in hyponcotic protein, moderately in isoncotic protein, and could be shrunk below control in hyperoncotic protein. Intracellular colloid osmotic pressure was estimated to exceed 38 cmH20. We conclude that hydrostatic and colloid osmotic forces are major determinants of cell size in isolated PST treated with ouabain.

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Urinary Cell Cycle Arrest Biomarkers as Early Predictors of Acute Kidney Injury Following Ventricular Assist Device Implant or Cardiac Transplantation

Journal of Cardiothoracic and Vascular Anesthesia ◽

10.1053/j.jvca.2021.10.013 ◽

2021 ◽

Author(s):

Amit Alam ◽

Aayla K. Jamil ◽

Johanna S. Van Zyl ◽

Horacio Medel-Martinez ◽

Teodoro Bottiglieri ◽

...

Keyword(s):

Cell Cycle ◽

Acute Kidney Injury ◽

Cell Cycle Arrest ◽

Ventricular Assist Device ◽

Cardiac Transplantation ◽

Kidney Injury ◽

Assist Device ◽

Ventricular Assist ◽

Cycle Arrest ◽

Early Predictors

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Outcomes after left ventricular assist device implantation in patients with acute kidney injury

Journal of Thoracic and Cardiovascular Surgery ◽

10.1016/j.jtcvs.2019.03.064 ◽

2020 ◽

Vol 159 (2) ◽

pp. 477-486.e3 ◽

Cited By ~ 2

Author(s):

Samuel A. Silver ◽

Jin Long ◽

Yuanchao Zheng ◽

Andrew B. Goldstone ◽

Doug Franz ◽

...

Keyword(s):

Acute Kidney Injury ◽

Left Ventricular Assist Device ◽

Ventricular Assist Device ◽

Kidney Injury ◽

Left Ventricular ◽

Assist Device ◽

Ventricular Assist ◽

Device Implantation ◽

Left Ventricular Assist

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Readmissions after Acute Kidney Injury during Left Ventricular Assist Device Implantation Hospitalization

American Journal of Nephrology ◽

10.1159/000505772 ◽

2020 ◽

Vol 51 (3) ◽

pp. 172-181 ◽

Cited By ~ 1

Author(s):

Carl P. Walther ◽

Wolfgang C. Winkelmayer ◽

Anita Deswal ◽

Jingbo Niu ◽

Sankar D. Navaneethan

Keyword(s):

Acute Kidney Injury ◽

Left Ventricular Assist Device ◽

Kidney Injury ◽

Left Ventricular ◽

Assist Device ◽

Ventricular Assist ◽

Left Ventricular Assist ◽

Relationship Of ◽

The Relationship ◽

Readmission Risk

Background: Acute kidney injury (AKI) frequently complicates hospitalizations for left ventricular assist device (LVAD) implantation. Little is known about the relationship of AKI with subsequent readmissions, and we investigated the relationship of AKI during LVAD implantation hospitalization with all-cause and cause-specific 30-day readmissions. Methods: We used a United States (US) nationwide all-payer administrative database, identifying patients who underwent implantable LVAD placement 2010–2015. Patients were classified into 3 mutually exclusive groups based on presence and severity of AKI during the LVAD placement hospitalization: no AKI, AKI, and AKI requiring dialysis (AKI-D). Outcomes were all-cause and cause-specific 30-day readmissions. Results: Within 30 days after discharge 25.4% of patients were readmitted. Of those without AKI, 23.9% were readmitted, compared to 25.5% of those with AKI and 42.2% of those with AKI-D. Compared to no AKI (adjusted for demographics, index hospitalization and chronic comorbidity factors, and year), odds of 30-day readmission were 2.18 (95% CI 1.37–3.49) times higher for those with AKI-D, whereas those with AKI not requiring dialysis had similar 30-day readmission risk (OR 1.03 [95% CI 0.89–1.20]). Those with AKI-D had higher risk of 30-day readmission for infection (OR 2.02 [95% CI 1.13–3.61]), gastrointestinal (GI) bleed (2.32 [95% CI 1.24–4.34]), and kidney disease (13.9 [95% CI 4.0–48]). There was no increased risk for stroke readmission with AKI or AKI-D. Conclusion: AKI-D was associated with highest 30-day readmission risk, possibly related to negatively synergistic effects of LVAD, kidney dysfunction, and dialysis related factors on infection and GI bleeding risks. AKI alone was not associated with increased readmission risk.

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