The regenerative capacities of mesenchymal stromal cells (MSC) make them suitable for renal regenerative therapy. The most common delivery route of MSC is via intravenous infusion, which is associated with off-target distribution. Renal intra-arterial delivery offers a targeted therapy but limited knowledge is available regarding the fate of MSC delivered via this route. Therefore, we studied the efficiency and tissue distribution of MSC after renal intra-arterial delivery to a porcine renal ischemia reperfusion model. MSC were isolated from adipose tissue of healthy male pigs, fluorescently labelled and infused into the renal artery of female pigs. Flow cytometry allowed MSC detection and quantification in tissue and blood. In addition, qPCR was used to trace MSC by their Y-chromosome. During infusion, a minor number of MSC left the kidney via the renal vein and no MSC were identified in arterial blood. Ischemic and healthy renal tissue were analyzed 30 minutes and 8 hours after infusion and 1-4 x 104 MSC per gram of tissue were detected, predominantly, in the renal cortex, with a viability greater than 70%. Confocal microscopy demonstrated mainly glomerular localization of MSC, but they were also observed in the capillary network around tubuli. The infusion of heat inactivated (HI)-MSC, which are metabolically inactive, through the renal artery showed that HI-MSC were distributed in the kidney in a similar manner as regular MSC, suggesting a passive retention mechanism. Long term MSC survival was analyzed by Y-chromosome tracing and demonstrated that a low percentage of the infused MSC were present in the kidney 14 days after administration, while HI-MSC were completely undetectable. In conclusion, renal intra-arterial MSC infusion limited off-target engraftment, leading to efficient MSC delivery to the kidney, most of them being cleared within 14 days. MSC retention was independent of the metabolic state of MSC, indicating a passive mechanism.

Normothermic machine perfusion (NMP) is increasingly considered for pre-transplant kidney quality assessment. However, fundamental questions about differences between in vivo and ex vivo renal function, as well as the impact of ischemic injury on ex vivo physiology, remain unanswered. This study utilized magnetic resonance imaging (MRI), alongside conventional parameters to explore differences between in vivo and ex vivo renal function and the impact of warm ischemia on a kidney's behavior ex vivo. Renal MRI scans and samples were obtained from living pigs (n=30) in vivo. Next, kidney pairs were procured and exposed to minimal, or 75 min of warm ischemia, followed by 6 hours of hypothermic machine perfusion. Both kidneys simultaneously underwent 6-hour ex vivo perfusion in MRI-compatible NMP circuits to obtain multiparametric MRI data. Ischemically injured ex vivo kidneys showed a significantly altered regional blood flow distribution compared to in vivo and to minimally damaged organs. Both ex vivo groups showed diffusion restriction relative to in vivo. Our findings underscore the differences between in vivo and ex vivo MRI-based renal characteristics. Therefore, when assessing organ viability during NMP, it should be considered to incorporate parameters beyond the conventional functional markers that are common in vivo.

Objective: Cytology is recommended as part of the follow-up of high-grade non-muscle-invasive bladder cancer (NMIBC). However, currently there are no solid guideline recommendations regarding the use of voided urine versus bladder washing for cytology as part of the diagnosis or follow-up of NMIBC. The aim of this study was to investigate whether the cytological outcome was equal regarding the two techniques. Materials and methods: The authors reviewed all outpatient flexible cystoscopies carried out in their department in 2013. Patient records in the registry of pathology were examined and those with simultaneous urine and bladder washing cytology were included. Previous urothelial disease and positive histology within 3 months after the cystoscopy were registered. Results: A total of 1458 patients had both voided urine and bladder washing cytology and were included in the study, of whom 643 (44%) had a history of urothelial disease. An equal outcome of urine and bladder washing cytology was found in 1447 patients (99.2%). For the remaining 11 patients, only four patients underwent further examinations based on cytology findings in addition to what had already been planned after cystoscopy. Of the included patients, 100 (6.9%) had a positive histological outcome within 3 months. Conclusions: In most patients, no relevant difference between voided urine and bladder washing cytology was observed. Therefore, if cytology is indicated, it is recommended to use the test that is most readily available locally. The additional gain in using both urine and bladder wash is minimal, and can therefore be discarded.

The immunomodulatory and regenerative properties of mesenchymal stromal cells (MSCs) make MSC therapy a promising therapeutic strategy in kidney disease. A targeted MSC administration via the renal artery offers an efficient delivery method with limited spillover to other organs. Although local administration alleviates safety issues with MSCs in systemic circulation, it introduces new safety concerns in the kidneys. In a porcine model, we employed intra-renal arterial infusion of ten million allogenic adipose tissue-derived MSCs. In order to trigger any potential adverse events, a higher dose (hundred million MSCs) was also included. The kidney function was studied by magnetic resonance imaging after the MSC infusion and again at two weeks post-treatment. The kidneys were assessed by single kidney glomerular filtration rate (skGFR) measurements, histology and inflammation, and fibrosis-related gene expression. None of the measured parameters were affected immediately after the administration of ten million MSCs, but the administration of one hundred million MSCs induced severe adverse events. Renal perfusion was reduced immediately after MSC administration which coincided with the presence of microthrombi in the glomeruli and signs of an instant blood-mediated inflammatory reaction. At two weeks post-treatment, the kidneys that were treated with one hundred million MSCs showed reduced skGFR, signs of tissue inflammation, and glomerular and tubular damage. In conclusions, the intra-renal administration of ten million MSCs is well-tolerated by the porcine kidney. However, higher concentrations (one hundred million MSCs) caused severe kidney damage, implying that very high doses of intra-renally administered MSCs should be undertaken with caution.

Gold standard treatment of symptomatic hydrocele or spermatocele is surgery. Despite a minor procedure, complications such as bleeding and infections leading to reoperations may be devastating for ...

Purpose: We sought to determine the reproducibility of magnetic resonance imaging renography using 3 different mathematical models and 2 different approaches to convert the relative signal intensity into quantitative indices. Furthermore, we wanted to examine the influence of fluid intake on the obtained renal parameters. Materials and Methods: A total of 10 healthy volunteers 13 to 16 years old were subjected to magnetic resonance imaging 3 times within 10 weeks, including an examination where fluid intake was increased. At each examination 0.1 mmol/kg gadolinium diethylenetriamine pentaacetic acid was administrated intravenously as a rapid bolus during a fast magnetic resonance renography sequence. Images were acquired in the coronal plan, and 1,200 images were recorded during approximately 7 minutes. Cortical data were analyzed to estimate absolute and differential function of renal parameters by converting signal intensities into quantitative units. Results: Using the simple approach that a change in magnetic resonance imaging signal is linearly related to the change in gadolinium diethylenetriamine pentaacetic acid concentration, we found reproducibility in the range of 1% to 5% of all estimations of the differential renal function. The relative glomerular ultrafiltration (ml per minute per cm³ kidney cortex) was calculated and a reproducibility of 7% was observed for relative glomerular ultrafiltration (using the model based on deconvolution). Increased hydration caused a significant change in most parameters. Conclusions: Contrast enhanced magnetic resonance renography is reproducible in the normal human kidney but excessive water intake has a significant influence on these parameters. Further studies are required to elucidate whether similar measurements can be applied to a kidney with impaired function.