Low-intensity shockwave therapy in the treatment of diabetic nephropathy: a prospective Phase 1 study.

BACKGROUND: Low-intensity shockwave therapy (LI-SWT) is suggested as a therapy for promoting tissue regeneration. In pigs, it was recently found that LI-SWT improved renal function after ischaemic injury. Our objectives were to study glomerular filtration rate (GFR) and albuminuria in diabetic nephropathy (DN) after treatment with LI-SWT. The present pilot study reports on the clinical safety of LI-SWT in DN. METHODS: A total of 14 patients with diabetes mellitus and Stage 3 chronic kidney disease were recruited for this prospective, one-arm Phase 1 study. The patients were treated with six sessions of LI-SWT during a 3-week period. At each session, 3000 shockwaves were applied to each kidney with 0.265 mJ/mm2, extended focal size and 4 Hz. Follow-up visits were performed at 1, 3 and 6 months. RESULTS: In general, the treatment was well tolerated. Transient macroscopic haematuria was observed in three patients immediately after LI-SWT. The majority of patients experienced lower back tenderness lasting up to 2 days after treatment. There was no need for analgesic treatment. LI-SWT showed no negative effect on GFR and albuminuria. At baseline, median (interquartile range) GFR was 33.5 mL/min/1.73 m2 (27.8-43.8) compared with 36.0 mL/min/1.73 m2 (27.5-52.0) at 6 months follow-up. In parallel, median albuminuria was 256 mg/24 h (79-619) at baseline and tended to decrease to 137 mg/24 h (41-404) 6 months after LI-SWT. There was no statistical difference between baseline and follow-up results. CONCLUSIONS: LI-SWT is a safe treatment for DN. Inclusion of more patients is needed to determine whether LI-SWT can improve renal functional outcomes.

Clinical, fiscal and environmental benefits of a specialist-led virtual ureteric colic clinic: a prospective study.

OBJECTIVES: To evaluate the clinical, fiscal and environmental impact of a specialist-led acute ureteric colic virtual clinic (VC) pathway. PATIENTS AND METHODS: All patients with uncomplicated acute ureteric colic, referred to a single tertiary centre, were prospectively entered into the study over a 4-year period (January 2015-December 2018). Inclusion criteria were: low-dose non-contrast computed tomography of kidneys, ureters and bladder; white blood cell count <16 × 109/L; pain controlled; normal renal function; and no clinical concern. Primary outcomes were: time (days) from referral to VC outcome; VC outcome (discharge, further VC, face-to-face [FTF] clinic, extracorporeal shockwave lithotripsy [ESWL], ureterorenoscopy [URS], percutaneous nephrolithotomy [PCNL]); and adverse events (sepsis or obstruction). Secondary outcomes were patient and stone demographics, cost and environmental analysis. The minimum follow-up was 3 months. RESULTS: A total of 1008 patients entered the study, of whom 91.5% (n = 922) were of working age. The median (interquartile range) time from presentation to VC outcome was 2 (4) days. VC outcomes were as follows: 16.3% of patients (n = 164) were discharged; 18.2% (n = 183) were discharged after further VC; 17.2% (n = 173) underwent an intervention; and 48.4% (n = 488) were referred to an FTF clinic. Interventions comprised: PCNL 0.5% (n = 5); ESWL 7.7% (n = 78); and URS 8.9% (n = 90). Stone demographics were as follows: 570 patients (56.5%) had lower, 157 (15.6%) had upper, 96 (9.5%) had mid-ureteric and 163 (16.2%) had renal calculi, and in 22 patients (2.2%) the stones had recently passed. The mean (sd) stone size was 3.5  (2.3) mm. Two adverse events (0.2%) were reported. Introducing a VC saved £145,152 for Clinical Commissioning Groups, the equivalent NHS tariff payment of performing 106 URS procedures or 211 ureteric stent insertions. Overall, 15,085 patient journey kilometres were avoided, equal to 0.70-2.93 metric tonnes of carbon dioxide equivalent production and the need to plant 14.7 trees to achieve carbon balance. CONCLUSION: A specialist-led acute ureteric colic VC reduced time to treatment decision to a median of 2 days. This creates additional clinic capacity and reduces the fiscal burden of traditional clinics and their associated carbon footprint.

Placebo-Controlled Study of Effects of Low-Energy Shockwave Therapy (LE-ESWT) on Erectile Tissue in a Diabetic Animal Model.

Objective: Low-energy extracorporeal shockwave therapy (LE-ESWT) has been shown to induce organ repair and neo-vascularization. The ability of LE-ESWT to improve erectile function in rodents as measured by improvements in intracavernosal pressure is well-established in various pathological situations. The underlying molecular mechanism are unclear and likely vary between different disorders, making rational drug design for synergetic effects with LE-ESWT difficult, without further research. In this placebo-controlled study, we aim to establish whether LE-ESWT can activate neovascularization biomarkers in diabetic tissues. Material and Methods: Forty Wistar rats, aged 8 weeks, were randomly divided into 4 groups: 8 untreated controls, 12 controls that underwent LE-ESWT treatment, 8 controls with induced diabetes mellitus (DM) and 12 with DM underwent LE-ESWT treatment. DM was induced by streptozotocin. LE-ESWT treatment was performed with a Duolith SD1 machine (Storz), with a total amount of energy of 6.4 J per treatment. The rats received a total of three LE-ESWT treatments with 2-week intervals between treatments. Results: Diabetic rats had significantly elevated blood glucose concentrations compared to control rats (P < 0.001) and experienced significant weight loss compared to controls (P < 0.001). Diabetic rats had elevated creatinine and urea and lower albumin (P < 0.001). Histologic analysis of penile tissue showed significant levels of vascular endothelial growth factor (VEGF) and fibroblast growth factor (FGF) expression in the LE-ESWT groups compared to controls (P< 0.01). Conclusion: LE-ESWT induces neo-angiogenesis as expressed by VEGF and FGF in erectile tissue in normal and diabetic rats.

Low-Intensity Shockwave Therapy (LI-ESWT) in Diabetic Kidney Disease: Results from an Open-Label Interventional Clinical Trial.

PURPOSE: Treatment with low-intensity shockwave therapy (LI-ESWT) is associated with angiogenesis and is suggested as a treatment for different types of vascular diseases. It was hypothesized that LI-ESWT improves the renal filtration barrier and halts the progression of GFR decline in diabetic kidney disease (DKD) potentially through VEGF and NO formation. We present the first data on LI-ESWT in human DKD. METHODS: The study was designed as an interventional, prospective, one-arm, Phase 1 study. We investigated change in GFR and albuminuria in 28 patients with DKD treated with six sessions of LI-ESWT over three weeks. The patients were followed for six months. Urine excretion of kidney injury markers, vascular endothelial growth factor (VEGF) and nitric oxide metabolites (NOx) was studied after LI-ESWT. RESULTS: There were no significant changes in GFR and albuminuria up to six months after LI-ESWT compared to baseline. Urine VEGF was transiently reduced one month after LI-ESWT, but there were no other significant changes in urine VEGF or NOx after LI-ESWT. Secondary analysis showed that NOx increased after LI-ESWT in patients who had low levels of NOx at baseline. Kidney injury marker trefoil factor 3 (TFF3) increased acutely after the first session of LI-ESWT indicating transient endothelial repair. Other markers of kidney injury were stable in relation to LI-ESWT. CONCLUSION: LI-ESWT treatment did not significantly improve kidney function and albumin excretion. It is concluded that LI-ESWT is not harmful. A randomized blinded study should be performed to clarify whether adjunctive treatment with LI-ESWT is superior to standard treatment of DKD.

Single-Center Experience with Three Metallic Ureteral Stents (Allium® URS, Memokath™-051, and Resonance®) for Chronic Ureteral Obstruction.

Purpose: Patients with chronic ureteral obstruction (CUO) are traditionally managed with polymer stents/nephrostomy. However, these are prone to failure and require regular exchange. This study evaluates the efficacy of Allium® URS, Memokath™-051, and Resonance® metallic ureteral stents in managing patients with CUO. Methods: Following institutional approval (Imperial College Healthcare NHS Trust, UK, Registration Number SPS_045), operating theater records were reviewed to identify patients with CUO managed with Allium® URS, Memokath™-051, or Resonance® metallic ureteral stents (September 2015/July 2020). Baseline patient variables (age, gender, underlying etiology, and American Society of Anesthesiologists score) and stricture characteristics (length, level, and continuity) were extracted. Intraoperative and postoperative clinical and radiologic assessments at 6 weeks, 3 months, and then every 6 months, as well as any emergency attendances, were reviewed. The primary outcome was duration of functional stent survival. Secondary outcomes included intraoperative placement success and, as an estimate of renal function, mean serum creatinine over time. Results: One hundred twenty-nine stent insertion episodes (SIEs) (Allium® URS: 23; Memokath™-051: 48; Resonance®: 58) occurred in 76 patients (Allium® URS: 16; Memokath™-051: 31; Resonance®: 29). Kaplan-Meier estimates demonstrated that Resonance® provided superior functional stent survival. Overall median actual functional stent follow-up was 11.4 months for Allium® URS, 5.5 months for Memokath™-051, and 11.7 months for Resonance®. 47.8% of Allium® URS (11/23), 64.6% of Memokath™-051 (31/48), and 19% of Resonance® SIEs (11/58) failed. No Resonance® SIEs for benign indication ended in failure. Intraoperative placement success was high (Allium® URS: 95.7%; Memokath™-051 and Resonance®: both 100%). In the first year following SIE, creatinine ranged from +21.3% to +46.7% for Allium® URS, -7.8% to +8.9% for Memokath™-051, and -9.4% to +27.3% for Resonance®. Conclusions: Allium® URS, Memokath™-051, and Resonance® metallic ureteral stents are all viable management options of CUO. In this cohort, Resonance® provided superior functional stent survival. Prospective large-scale comparisons with long-term follow-up are needed to help inform stent choice dependent on individual patient and stricture characteristics.

Managing Small Ureteral Stones: A Retrospective Study on Follow-Up, Clinical Outcomes and Cost-Effectiveness of Conservative Management vs. Early Surgery.

INTRODUCTION: The management of ureteral calculi has evolved over the past decades with the advent of new surgical and medical treatments. The current guidelines support conservative management as a possible approach for ureteral stones sized = 10 mm. OBJECTIVES: We purport to follow the natural history of ureteral stones managed conservatively in this retrospective study, and attempt to ascribe an estimated health-care and cost-effectiveness, from presentation to time of being stone-free. MATERIALS AND METHODS: 192 male and female patients with a single ureteral stone sized = 10 mm were included in this study. The clinical and cost-related outcome was analyzed for different stone sizes (0-4, 4-6 and 6-10 mm). The effectiveness of selected follow-up (FU) scans was also analyzed. RESULTS: Stone size was found to be related to the degree of hydronephrosis and to the likelihood of need for a surgical management. Conservative management was found to be clinically effective, as 88% of the patients did not require surgery for their stone. 96.1% of the patients with a stone 0-4mm managed to expel their ureteral stone. Bigger ureteral stones were found to be more costly. The cost-effectiveness of the single FU scans was found to be related to their efficiency, while the global cost-effectiveness of conservative management vs. early surgery was higher for smaller stones (26.8 vs. 17.32% for stones 0-4 vs. 6-10 mm). CONCLUSION: Conservative management is clinically effective with a significant cost-benefit, particularly for the subgroup of stones sized 0-4 mm, where a need for FU scans is in dispute.

Can low-intensity extracorporeal shockwave therapy improve erectile dysfunction? A prospective, randomized, double-blind, placebo-controlled study.

OBJECTIVE: The aim of this study was to investigate whether low-intensity extracorporeal shockwave therapy (LI-ESWT) can be used as a treatment for men with erectile dysfunction of organic origin. MATERIALS AND METHODS: This prospective, randomized, blinded, placebo-controlled study included 112 men unable to have intercourse either with or without medication. Erectile dysfunction was assessed at screening and 5, 12 and 24 weeks after treatment. Assessment was performed by interview and using the Erection Hardness Scale (EHS) and the International Index of Erectile Function (IIEF-15) questionnaire. The men were randomly assigned either to LI-ESWT (n = 51, active group) or placebo (n = 54, placebo group). They received five treatments over 5 weeks. Both the participants and the doctors were blinded to the treatment. After 10 weeks, the placebo group received active treatment (active placebo group). RESULTS: Twenty-nine men (57%, active group) were able to obtain an erection after treatment and to have sexual intercourse without the use of medication. In the placebo group, only five men (9%) showed similar results (p = 0.0001). The EHS after 5 weeks showed that men in the active group experienced a significant improvement in their erectile dysfunction, but no significant result was found with the use of the IIEF - Erectile Function domain. CONCLUSIONS: This placebo-controlled study over 5 weeks shows that 57% of the men who suffered from erectile dysfunction had an effect from LI-ESWT. After 24 weeks, seven (19%, active group) and nine (23%, active placebo group) men were still able to have intercourse without medication. This study shows a possible cure in some patients, but more research, longer follow-up in the placebo group and an international multicentre randomized study are needed.