Low-Intensity Extracorporeal Shockwave Therapy (LI-ESWT) in Renal Diseases: A Review of Animal and Human Studies.

Background: Low-intensity extracorporeal shockwave therapy (LI-ESWT) has been suggested as a treatment for vascular diseases such as ischemic heart disease, diabetic foot ulcers, and erectile dysfunction. Primarily, LI-ESWT is known for its ability to stimulate angiogenesis and activation of stem cells in target tissues. Application of LI-ESWT in chronic progressive renal diseases is a novel area. The aim of the present review was to summarize available data on the effects of LI-ESWT used in the setting of renal diseases. Methods: We systematically searched PubMed, Medline, and Embase databases for relevant studies. Our review included the results from preclinical animal experiments and clinical research. Results: Eleven animal studies and one clinical study were included in the review. In the animal studies, LI-ESWT was used for the treatment of hypertensive nephropathy (n=1), diabetic nephropathy (n=1), or various types of ischemic renal injury (ie, artery occlusion, reperfusion injury) (n=9). The clinical study was conducted in a single-arm cohort as a Phase 1 study with patients having diabetic nephropathy. In animal studies, the application of LI-ESWT was associated with several effects: LI-ESWT led to increased VEGF and endothelial cell proliferation and improved vascularity and perfusion of the kidney tissue. LI-ESWT reduced renal inflammation and fibrosis. LI-ESWT caused only mild side effects in the clinical study, and, similarly, there were no signs of kidney injury after LI-ESWT in the animal studies. Conclusion: LI-ESWT, as a non-invasive treatment, reduces the pathological manifestations (inflammation, capillary rarefaction, fibrosis, decreased perfusion) associated with certain types of renal disease. The efficacy of renal LI-ESWT needs to be confirmed in randomized clinical trials.

Escherichia coli type-1 fimbriae are critical to overcome initial bottlenecks of infection upon low-dose inoculation in a porcine model of cystitis.

Most uropathogenic Escherichia coli (UPEC) express type-1 fimbriae (T1F), a key virulence factor for urinary tract infection (UTI) in mice. Evidence that conclusively associates this pilus with uropathogenesis in humans has, however, been difficult to obtain. We used an experimental porcine model of cystitis to assess the role of T1F in larger mammals more closely related to humans. Thirty-one pigs were infected with UPEC strain UTI89 or its T1F deficient mutant, UTI89ΔfimH, at inoculum titres of 102 to 108 colony forming units per millilitre. Urine and blood samples were collected and analysed 7 and 14 days post-inoculation, and whole bladders were removed at day 14 and analysed for uroepithelium-associated UPEC. All animals were consistently infected and reached high urine titres independent of inoculum titre. UTI89ΔfimH successfully colonized the bladders of 1/6 pigs compared to 6/6 for the wild-type strain. Intracellular UPEC were detectable in low numbers in whole bladder explants. In conclusion, low doses of UPEC are able to establish robust infections in pigs, similar to what is presumed in humans. T1F are critical for UPEC to surpass initial bottlenecks during infection but may be dispensable once infection is established. While supporting the conclusions from mice studies regarding a general importance of T1F in successfully infecting the host, the porcine UTI models' natural high, more human-like, susceptibility to infection, allowed us to demonstrate a pivotal role of T1F in initial establishment of infection upon a realistic low-inoculum introduction of UPEC in the bladder.

A Porcine Model for Urinary Tract Infection.

Urinary tract infection (UTI) is the most common bacterial infectious disease with a high frequency of recurrence and the leading cause of septicemia. In vivo experimentation has contributed significantly to the present-day knowledge on UTI pathogenesis. This research has traditionally been based on murine models of UTI. Occasional conflicting results between UTI in mice and humans and increasing skepticism toward small rodent models in general warrant the need of novel large-animal infection models that better resemble the anatomy and physiology of humans, and thus better mimic the course of infection in humans. Here, we report, to our knowledge, the first large-animal model of cystitis. The model is based on pigs, and the protocol supports the establishment of persistent, non-ascending infection in this animal and is established without invasive surgical procedures, pain, and discomfort for the animal. The course of infection is monitored by cystoscopy, microscopy of bladder biopsies, and biochemical analysis of urine and blood samples. At termination, harvested whole bladders from infected pigs are analyzed for microbiological colonization using microscopy, histology, and viable bacterial counts. The model is a useful tool in future studies of UTI pathogenesis and opens up novel possibilities to bridge the current knowledge obtained from small-animal UTI models to UTI pathogenesis in humans.