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Kidney Int. 2020 Apr;97(4):793-804. doi: 10.1016/j.kint.2019.11.022. Epub 2019 Dec 13.

In a Phase 1a escalating clinical trial, autologous mesenchymal stem cell infusion for renovascular disease increases blood flow and the glomerular filtration rate while reducing inflammatory biomarkers and blood pressure.

Author information

1
Division of Nephrology and Hypertension, Mayo Clinic, Rochester, Minnesota, USA.
2
Division of Nephrology and Hypertension, Mayo Clinic, Rochester, Minnesota, USA; Department of Family Medicine, Creighton University, Omaha, Nebraska, USA.
3
Department of Radiology, Mayo Clinic, Rochester, Minnesota, USA.
4
Transfusion Medicine, Mayo Clinic, Rochester, Minnesota, USA.
5
Division of Nephrology and Hypertension, Mayo Clinic, Rochester, Minnesota, USA. Electronic address: stextor@mayo.edu.

Abstract

Atherosclerotic renovascular disease (ARVD) reduces tissue perfusion and eventually leads to loss of kidney function with limited therapeutic options. Here we describe results of Phase 1a escalating dose clinical trial of autologous mesenchymal stem cell infusion for ARVD. Thirty-nine patients with ARVD were studied on two occasions separated by three months. Autologous adipose-derived mesenchymal stem cells were infused through the renal artery in 21 patients at three different dose levels (1, 2.5 and 5.0 × 105 cells/kg) in seven patients each. We measured renal blood flow, glomerular filtration rate (GFR) (iothalamate and estimated GFR), renal vein cytokine levels, blood pressure, and tissue oxygenation before and three months after stem cell delivery. These indices were compared to those of 18 patients with ARVD matched for age, kidney function and blood pressure receiving medical therapy alone that underwent an identical study protocol. Cultured mesenchymal stem cells were also studied in vitro. For the entire stem cell treated-cohort, mean renal blood flow in the treated stenotic kidney significantly increased after stem cell infusion from (164 to 190 ml/min). Hypoxia, renal vein inflammatory cytokines, and angiogenic biomarkers significantly decreased following stem cell infusion. Mean systolic blood pressure significantly fell (144 to 136 mmHg) and the mean two-kidney GFR (Iothalamate) modestly but significantly increased from (53 to 56 ml/min). Changes in GFR and blood pressure were largest in the high dose stem cell treated individuals. No such changes were observed in the cohort receiving medical treatment alone. Thus, our data demonstrate the potential for autologous mesenchymal stem cell to increase blood flow, GFR and attenuate inflammatory injury in post-stenotic kidneys. The observation that some effects are dose-dependent and related to in-vitro properties of mesenchymal stem cell may direct efforts to maximize potential therapeutic efficacy.

KEYWORDS:

blood flow; blood pressure; clinical trial; kidney oxygenation; renal artery stenosis; stem cells

PMID:
32093917
DOI:
10.1016/j.kint.2019.11.022

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