Kidney Week

Abstract: PO0641

Microvascular Loss and Remodeling in Human Kidneys Distal to Severe Atherosclerotic Renovascular Disease

Session Information

• CKD Mechanisms - 2
  October 22, 2020 | Location: On-Demand
  Abstract Time: 10:00 AM - 12:00 PM

Category: CKD (Non-Dialysis)

• 2103 CKD (Non-Dialysis): Mechanisms

Authors

• Klomjit, Nattawat, Division of Nephrology and Hypertension, Department of Medicine, Mayo Clinic, Rochester, Minnesota, United States

Nattawat Klomjit,

• Eirin, Alfonso, Division of Nephrology and Hypertension, Department of Medicine, Mayo Clinic, Rochester, Minnesota, United States

Alfonso Eirin,

• Zhu, Xiang yang, Division of Nephrology and Hypertension, Department of Medicine, Mayo Clinic, Rochester, Minnesota, United States

Xiang yang Zhu,

• Pawar, Aditya S., Division of Nephrology and Hypertension, Department of Medicine, Mayo Clinic, Rochester, Minnesota, United States

Aditya S. Pawar,

• Puranik, Amrutesh S., Langone Health, New York University, New York, New York, United States

Amrutesh S. Puranik,

• Ferguson, Christopher M., Division of Nephrology and Hypertension, Department of Medicine, Mayo Clinic, Rochester, Minnesota, United States

Christopher M. Ferguson,

• Kim, Seo Rin, Division of Nephrology and Hypertension, Department of Medicine, Mayo Clinic, Rochester, Minnesota, United States

Seo Rin Kim,

• Jordan, Kyra L., Division of Nephrology and Hypertension, Department of Medicine, Mayo Clinic, Rochester, Minnesota, United States

Kyra L. Jordan,

• Tang, Hui, Division of Nephrology and Hypertension, Department of Medicine, Mayo Clinic, Rochester, Minnesota, United States

Hui Tang,

• Lerman, Amir, Department of Cardiovascular Disease, Mayo Clinic, Rochester, Minnesota, United States

Amir Lerman,

• Textor, Stephen C., Division of Nephrology and Hypertension, Department of Medicine, Mayo Clinic, Rochester, Minnesota, United States

Stephen C. Textor,

• Lerman, Lilach O., Division of Nephrology and Hypertension, Department of Medicine, Mayo Clinic, Rochester, Minnesota, United States

Lilach O. Lerman,

Background

Renovascular disease (RVD) may induce hypertension and kidney injury, but its effect on the microcirculation of the post-stenotic human kidney remains unclear.

Methods

Kidneys were collected from patients with RVD undergoing unilateral nephrectomy due to refractory hypertension (n=5) and deceased donor kidneys (DK) discarded due to incompatibility (n=7). Renal microvasculature (MV) was studied in vitro using micro CT after infusing contrast agent into the renal artery. Kidneys were also compared for angiogenic gene and protein expression.

Results

Age and sex were comparable between RVD and DK. RVD had reduced density of medium-sized (0.2-0.3mm) MV vs. donor kidneys (Fig. A-B, p=0.04), whereas density of small (0.02-0.2mm) and large (0.3-0.5 mm) MV was similar. Vascular tortuosity ratio was higher in RVD vs DK (Fig. C, p=0.05). The number/tubule of peritubular capillaries (PTC) was significantly lower in RVD, as was CD31+ area, whereas numbers of new angiogenic vessels (β3 integrin+, Fig. D) and pericytes were higher. Renal fibrosis and MV remodeling (media/lumen) were greater in RVD, as were oxidative stress and angiopoietin-1 expression, whereas VEGF (p=0.9) and FLK-1 (p=0.2) protein or gene expression were unchanged.

Conclusion

Human RVD kidneys develop marked MV remodeling and loss, particularly of PTC and medium-size MV. Angiopoietin-1 upregulation may promote new PTC formation, but fails to offset overwhelming MV loss distal to severe RVD. These findings underscore the major component of microvascular injury in the development of ischemic kidney disease.

Funding

• NIDDK Support