Lerman, Lilach O.

Key Points Renovascular disease impairs the capacity of human adipose tissue–derived mesenchymal stem/stromal cells to repair ischemic murine kidneys. miR-378h modulated the capacity of renovascular disease adipose tissue–derived mesenchymal stem/stromal cells to repair ischemic kidneys in vivo . Background Renovascular disease leads to renal ischemia, hypertension, and eventual kidney failure. Autologous transplantation of adipose tissue–derived mesenchymal stem/stromal cells (MSCs) improves perfusion and oxygenation in stenotic human kidneys, but associated atherosclerosis and hypertension might blunt their effectiveness. We hypothesized that renovascular disease alters the human MSC transcriptome and impairs their reparative potency. Methods MSCs were harvested from subcutaneous abdominal fat of patients with renovascular disease and healthy volunteers ( n =3 each), characterized and subsequently injected (5×10 5 /200 μ l) into mice 2 weeks after renal artery stenosis or sham surgery ( n =6/group). Two weeks later, mice underwent imaging and tissue studies. MSCs from healthy volunteers and in those with renovascular disease were also characterized by mRNA/microRNA (miRNA) sequencing. Based on these, MSC proliferation and mitochondrial damage were assessed in vitro before and after miRNA modulation and in vivo in additional renal artery stenosis mice administered with MSCs from renovascular disease pretreated with miR-378h mimic ( n =5) or inhibitor ( n =4). Results MSCs engrafted in stenotic mouse kidneys. Healthy volunteer MSCs (but not renovascular disease MSCs) decreased BP, improved serum creatinine levels and stenotic-kidney cortical perfusion and oxygenation, and attenuated peritubular capillary loss, tubular injury, and fibrosis. Genes upregulated in renovascular disease MSCs versus healthy volunteer MSCs were mostly implicated in transcription and cell proliferation, whereas those downregulated encoded mainly mitochondrial proteins. Upregulated miRNAs, including miR-378h, primarily target nuclear-encoded mitochondrial genes, whereas downregulated miRNAs mainly target genes implicated in transcription and cell proliferation. MSC proliferation was similar, but their mitochondrial structure and reparative function both in vivo and in vitro improved after miR-378h inhibition. Conclusions Renovascular disease impaired the reparative capacity of human MSCs, possibly by dysregulating miR-378h that targets mitochondrial genes. Podcast This article contains a podcast at https://dts.podtrac.com/redirect.mp3/www.asn-online.org/media/podcast/JASN/2024_08_21_ASN0000000000000440.mp3

Objective: Arterial hypertension (HTN) coexisting with chronic kidney disease (CKD) presents a significant global healthcare challenge, with limited effective clinical interventions. Electro-Hydraulic Acoustic Therapy (eHAT), a lower-energy modality vs. lithotripsy, emerges as a promising technique for relieving ischemia and promoting tissue regeneration. We hypothesized that eHAT would reduce blood pressure (BP) and preserve renal function in patients with hypertension and CKD. Design and method: Twenty medically treated patients with HTN and Stage IIIa/b CKD enrolled in this prospective, single-arm study were treated over 3-weeks with six eHAT sessions (2400 shockwaves/kidney; 0.09 mJ/mm2 at 2.66Hz; NephrospecTM, Curespec, Yehud, Israel). Follow-up (FU) visits at 1, 3, 6, and 12 months involved measurements of attended and unattended office BP, ambulatory BP and estimated glomerular filtration rate (eGFR). Results: The treatment was well tolerated. All BP measurements strongly tended to decline over 12 months and showed a similar pattern.(Table 1, Figs. 1-3), whereas eGFR was well preserved (Table 1, Fig. 4). Conclusions: Conclusion. eHAT is a tolerable and safe procedure and, moreover, a 3-week regimen tends to reduce BP and preserve eGFR in patients with HTN and CKD. Therefore, eHAT may constitute a novel, safe, and non-invasive alternative therapeutic approach in the management of HTN in the context of CKD.