Klomjit N. et al., 2020: It Comes As a Shock: Kidney Repair Using Shockwave Therapy

Monday, 15 March 2021

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Klomjit N, Lerman A, Lerman LO.
From the Division of Nephrology and Hypertension (N.K., L.O.L.), Mayo Clinic, Rochester, MN.
Department of Cardiovascular Disease (A.L.), Mayo Clinic, Rochester, MN.

Abstract

Chronic kidney disease is a global health care burden, yet clinically-proven treatments are limited. Low-intensity shockwave, which utilizes ≈10% of the energy levels used in clinically indicated shockwave lithotripsy, is a promising technique to ameliorate ischemia and regenerate tissues. It has been demonstrated to improve healing in tissues such as bone, muscle, myocardium, and kidney via several mechanisms, particularly through promoting neovascularization. Low-intensity shockwave stimulates mechanoreceptors located primarily in endothelial and proximal tubular cells and subsequently upregulates vascular endothelial growth factors. This, in turn, promotes angiogenesis and ameliorates renal hypoxia, inflammation, and fibrosis, and ultimately preserves renal function. Furthermore, low-intensity shockwave can stimulate release of homing factors to attract endothelial progenitor or stem cells into injured kidneys for tissue repair. These effects may be beneficial in several kidney disease models, including renal artery stenosis, diabetic kidney disease, and various chronic kidney diseases, although most studies reported to date have been performed in animal models. Because of its low energy intensity, the procedure is relatively tolerable and safe, yet, more clinical studies are needed to establish its efficacy beyond currently existing strategies. Therefore, low-intensity shockwave therapy emerges as an alternative therapeutic approach that may offer a promising noninvasive intervention for treating renal diseases. Registration- URL: https://www.clinicaltrials.gov; Unique identifier: NCT02515461; NCT03602807; and NCT03445247.
Hypertension. 2020 Dec;76(6):1696-1703. doi: 10.1161/HYPERTENSIONAHA.120.14595. Epub 2020 Nov 2. PMID: 33131308

Comments 1

Hans-Göran Tiselius on Monday, 15 March 2021 09:30

This article is a review of experience with low intensity shock wave treatment (LiSW) with the aim of improving renal function in patients with chronic kidney disease. Given the extensive information on tissue injuries caused by SWL, it is not immediately obvious that shockwave energy, although administered at lower energy levels than those used for stone disintegration, can improve renal function!!
The vascular and tissue injuries associated with SWL have been extensively studied and in most patients such damage is transient. It is correct, as the authors state, that SWL in many patients have been replaced by endourological procedures. The reason for that is, however, not because of fear for kidney injury, but rather the generally higher rate of stone-free rates obtained with low-invasive endoscopy. Nevertheless, despite this therapeutic shift SWL is still a major method for stone removal world-wide.
Interestingly, LiSW with energy densities of approximately 10% of that used for lithotripsy seems to be a promising method for treating patients with chronic kidney disease. Based on experiments in animals the effect of LiSW is explained by stimulated neo-vascularisation and counteraction of the inflammatory process. The series of biochemical events caused by LiSW are briefly summarised below. It is shown that several factors are increased and others decreased; some of them are shown below:
beta-integrin is increased
Focal adhesive kinase is increased
Piezo-1 is increased
Flk-1 receptors are upregulated
Vascular endothelial growth factor is increased
Angio poietin-1 is increased
Endothelial nitric oxide synthetase is increased
Macrophages were decreased
Tumour necrosis factor-alpha (TNF) is decreased
Transformation growth factor beta is decreased
Nuclear factor is decreased
Stromal-derived factor 1 is increased
Stem cell factor is increased
NOX-1 and NOX-2 are decreased
Podocytes were preserved
In summary renal oxidative stress was decreased and renal hypoxia reduced. Renal function improved and S-Creatinine and U-Protein decreased
The authors refer to several observations from animal experiments. One human study on diabetic kidney disease treated with Modulith SLX2 at energy levels 0.136-0.265 mJ/mm2 is mentioned. Those treatments were carried out with 3000 sw/patient at 4Hz and with large focus. LiSW was given twice a week for 3 weeks. In this specific experiment albuminuria was reduced.
This application of LiSW is indeed very interesting and it will be exciting to see what further research in this field can give.

Hans-Göran Tiselius

This article is a review of experience with low intensity shock wave treatment (LiSW) with the aim of improving renal function in patients with chronic kidney disease. Given the extensive information on tissue injuries caused by SWL, it is not immediately obvious that shockwave energy, although administered at lower energy levels than those used for stone disintegration, can improve renal function!!
The vascular and tissue injuries associated with SWL have been extensively studied and in most patients such damage is transient. It is correct, as the authors state, that SWL in many patients have been replaced by endourological procedures. The reason for that is, however, not because of fear for kidney injury, but rather the generally higher rate of stone-free rates obtained with low-invasive endoscopy. Nevertheless, despite this therapeutic shift SWL is still a major method for stone removal world-wide. 
Interestingly, LiSW with energy densities of approximately 10% of that used for lithotripsy seems to be a promising method for treating patients with chronic kidney disease. Based on experiments in animals the effect of LiSW is explained by stimulated neo-vascularisation and counteraction of the inflammatory process. The series of biochemical events caused by LiSW are briefly summarised below. It is shown that several factors are increased and others decreased; some of them are shown below:
beta-integrin is increased
Focal adhesive kinase is increased
Piezo-1 is increased
Flk-1 receptors are upregulated
Vascular endothelial growth factor is increased
Angio poietin-1 is increased
Endothelial nitric oxide synthetase is increased
Macrophages were decreased
Tumour necrosis factor-alpha (TNF) is decreased
Transformation growth factor beta is decreased
Nuclear factor is decreased
Stromal-derived factor 1 is increased
Stem cell factor is increased
NOX-1 and NOX-2 are decreased
Podocytes were preserved
In summary renal oxidative stress was decreased and renal hypoxia reduced.  Renal function improved and S-Creatinine and U-Protein decreased
The authors refer to several observations from animal experiments. One human study on diabetic kidney disease treated with Modulith SLX2 at energy levels 0.136-0.265 mJ/mm2 is mentioned. Those treatments were carried out with 3000 sw/patient at 4Hz and with large focus. LiSW was given twice a week for 3 weeks. In this specific experiment albuminuria was reduced.
This application of LiSW is indeed very interesting and it will be exciting to see what further research in this field can give.

Hans-Göran Tiselius

This article is a review of experience with low intensity shock wave treatment (LiSW) with the aim of improving renal function in patients with chronic kidney disease. Given the extensive information on tissue injuries caused by SWL, it is not immediately obvious that shockwave energy, although administered at lower energy levels than those used for stone disintegration, can improve renal function!! The vascular and tissue injuries associated with SWL have been extensively studied and in most patients such damage is transient. It is correct, as the authors state, that SWL in many patients have been replaced by endourological procedures. The reason for that is, however, not because of fear for kidney injury, but rather the generally higher rate of stone-free rates obtained with low-invasive endoscopy. Nevertheless, despite this therapeutic shift SWL is still a major method for stone removal world-wide. Interestingly, LiSW with energy densities of approximately 10% of that used for lithotripsy seems to be a promising method for treating patients with chronic kidney disease. Based on experiments in animals the effect of LiSW is explained by stimulated neo-vascularisation and counteraction of the inflammatory process. The series of biochemical events caused by LiSW are briefly summarised below. It is shown that several factors are increased and others decreased; some of them are shown below: beta-integrin is increased Focal adhesive kinase is increased Piezo-1 is increased Flk-1 receptors are upregulated Vascular endothelial growth factor is increased Angio poietin-1 is increased Endothelial nitric oxide synthetase is increased Macrophages were decreased Tumour necrosis factor-alpha (TNF) is decreased Transformation growth factor beta is decreased Nuclear factor is decreased Stromal-derived factor 1 is increased Stem cell factor is increased NOX-1 and NOX-2 are decreased Podocytes were preserved In summary renal oxidative stress was decreased and renal hypoxia reduced. Renal function improved and S-Creatinine and U-Protein decreased The authors refer to several observations from animal experiments. One human study on diabetic kidney disease treated with Modulith SLX2 at energy levels 0.136-0.265 mJ/mm2 is mentioned. Those treatments were carried out with 3000 sw/patient at 4Hz and with large focus. LiSW was given twice a week for 3 weeks. In this specific experiment albuminuria was reduced. This application of LiSW is indeed very interesting and it will be exciting to see what further research in this field can give. Hans-Göran Tiselius

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