Stress urinary incontinence (SUI) is an age health‐related issue that generates interest due to its considerable public health burden and the controversies surrounding treatment. It is highly prevalent affecting 30–40% of all women during their lifetime. Midurethral slings are the standard of gold standard treatment for female patients with SUI. They have excellent short‐term cure rates; however, their efficacy tends to decrease over time and patients often report urinary incontinence recurrence. This paper addresses the applicability of regenerative medicine and tissue engineering for the treatment of SUI in female patients. Cell‐based treatment with periurethral injection of autologous adipose or muscle‐derived stem cells have been used for SUI; however, the cure rates and SUI recurrence at 1 year were 40% and 70%, respectively. Novel minimally invasive approaches, such as low‐intensity extracorporeal shock wave therapies have shown promising results in SUI animal models. In addition, local injection of growth factors, chemokines, and specific antibodies have shown histological evidence of neoangiogenesis, nerve, and sphincter regeneration in rodents and nonhuman primates with SUI. The use of bioactive factors and proteins secreted by cells, which is called secretomes, have been recognized as key regulators of various mechanisms, such as immunomodulation, angiogenesis, inflammation, apoptosis, and tissue repair. Emerging therapies aiming to replace or restore tissues and organ functionality may improve the long‐term efficacy and in the near future may represent the standard of care for the treatment of SUI.
Background: Chronic tubulointerstitial fibrosis is a common final pathway leading to end stage kidney disease in cats and has no effective treatment. The use of cell-based molecules to treat kidney fibrosis may be a promising approach. The objectives were to test the effects of intra-renal chemokine CXCL12 injection in a pre-clinical cat model of unilateral ischemia/reperfusion (I/R)-induced kidney fibrosis and then, within a clinical pilot study, test the safety/feasibility of CXCL12 injection in cats that might have early chronic kidney disease (CKD).Methods:Pre-clinical: Thirty cats received intra-renal injection of 100, 200, or 400 ng of recombinant human CXCL12, or sterile saline, into the I/R kidney 70 days post-injury, or were non-injured, non-injected controls (n = 6/group). Kidney collagen content was quantified 4 months post-treatment using Masson's Trichrome and Picrosirius Red (PSR) stained tissues. In a separate study (n = 2) exploring short-term effects of CXCL12, 200 ng CXCL12 was injected into I/R kidneys and then harvested either 30 min (n = 1) or 1 month (n = 1) post-injection. Kidney concentrations of CXCL12, matrix metalloproteinase 1 (MMP-1), and lysyl oxidase-like enzyme 2 (LOXL-2) were quantified via ELISA. Clinical Pilot: 14 client-owned cats with potential early kidney disease received a single-treatment, bilateral intra-renal injection of 200 ng CXCL12 (n = 7), or received no injection (n = 7). Blood/urine samples were collected monthly for 9 months to assess renal function and CKD staging.Results:Pre-clinical: I/R increased the affected kidney collagen content, which both mid and high doses of CXCL12 restored to normal (ps < 0.05 vs. untreated). I/R increased collagen fiber width, which both mid and high doses of CXCL12 restored to normal (p < 0.001 vs. untreated). Early changes in kidney MMP-1, associated with collagen breakdown, and subsequent decreases in LOXL-2, associated with collagen cross-linking, in response to CXCL12 treatment may contribute to these findings. Clinical Pilot: Bilateral intra-renal injection of CXCL12 using ultrasound guidance in cats with CKD was feasible and safe in a general practice clinical setting with no obvious side effects noted during the 9-month follow-up period.Conclusions: Intra-renal injection of CXCL12 may prove to be an effective treatment for kidney fibrosis in cats with CKD. Additional mechanistic and clinical evaluations are needed.
risk of recurrence of RCC of native kidneys and death in patients with end-stage renal disease (ESRD), according to their dialysis or transplantation status.METHODS: We performed a retrospective analysis of all patients with ESRD diagnosed with RCC between 2010 and 2019 in our center, and stratified them according to their dialysis (D) or kidney transplantation (KT) status.Patients' characteristics were compared by using Chi-square (or Fischer) and t-tests. Survival was assessed by Kaplan-Meier and Cox proportional hazards model. RESULTS: 40 patients were followed for a median of 41 months [IQR 22-71], 22 KT and 18 D. KT had a lower ASA score (p<0.001) and lower grade of tumor (p[0.014). All other clinical and pathological characteristics were similar between groups. The risk of RCC recurrence was similar between them (HR[0.402; p[0.458). 5-year recurrence-free survival was 96% in KT and 89% in D (p[0.443). All recurrences were on the contralateral kidney, without impact on patient or graft survival. In multivariable Cox regression analysis, no predictor was significantly associated with the risk of recurrence, including presence of KT. No cancer-related deaths were seen during follow-up, with the majority of deaths being related to cardiovascular disease (100% in KT and 60% in D). 5-year overall survival was 91% and 72% for KT and D, respectively (p[0.181). KT did not have a lower survival compared to D patients (HR[0.343; p[0.202). In multivariable analysis the presence of a renal transplant had no effect on survival (HR[0.002; p[0.167). Time on dialysis was the only independent predictor of overall survival (HR[1.058; p[0.049).CONCLUSIONS: Most RCCs in renal transplant recipients are low-grade and exhibit many favorable pathological characteristics. Immunosuppression doesn't seem to have an impact on outcomes, but an increased time on dialysis seems to be associated with worse survival. As so, waiting time for low stage/low grade RCC could be reduced.
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