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Congestive heart failure (CHF) is often associated with impaired kidney function. Over- activation of the renin–angiotensin–aldosterone system (RAAS) contributes to avid salt/water retention and cardiac hypertrophy in CHF. While the deleterious effects of angiotensin II (Ang II) in CHF are well established, the biological actions of angiotensin 1-7 (Ang 1-7) are not fully characterized. In this study, we assessed the acute effects of Ang 1-7 (0.3, 3, 30 and 300 ng/kg/min, IV) on urinary flow (UF), urinary Na+ excretion (UNaV), glomerular filtration rate (GFR) and renal plasma flow)RPF) in rats with CHF induced by the placement of aortocaval fistula. Additionally, the chronic effects of Ang 1-7 (24 µg/kg/h, via intra-peritoneally implanted osmotic minipumps) on kidney function, cardiac hypertrophy and neurohormonal status were studied. Acute infusion of either Ang 1-7 or its agonist, AVE 0991, into sham controls, but not CHF rats, increased UF, UNaV, GFR, RPF and urinary cGMP. In the chronic protocols, untreated CHF rats displayed lower cumulative UF and UNaV than their sham controls. Chronic administration of Ang 1-7 and AVE 0991 exerted significant diuretic, natriuretic and kaliuretic effects in CHF rats, but not in sham controls. Serum creatinine and aldosterone levels were significantly higher in vehicle-treated CHF rats as compared with controls. Treatment with Ang 1-7 and AVE 0991 reduced these parameters to comparable levels observed in sham controls. Notably, chronic administration of Ang 1-7 to CHF rats reduced cardiac hypertrophy. In conclusion, Ang 1-7 exerts beneficial renal and cardiac effects in rats with CHF. Thus, we postulate that ACE2/Ang 1-7 axis represents a compensatory response to over-activity of ACE/AngII/AT1R system characterizing CHF and suggest that Ang 1-7 may be a potential therapeutic agent in this disease state. [ABSTRACT FROM AUTHOR]

Bladder augmentation (BA) maybe required before renal transplantation in children with end stage renal disease (ESRD). Herein we report a case of a 7-year-old boy with ESRD, contracted bladder and severe bilateral reflux secondary to posterior urethral valve (PUV), successfully managed by simultaneous bilateral nephrectomy, bilateral ureterocystoplasty and renal transplantation. [ABSTRACT FROM AUTHOR]

• With 3D Navigo™ system the targeted approach outperforms the systematic one. • The systematic biopsy detects high risk disease and should not be omitted. • Biopsy may be omitted when no visible lesion is demonstrated on mpMRI. The introduction of multi parameter magnetic resonance imaging (mpMRI) of the prostate in combination with MRI/TRUS fusion and systematic biopsy resulted in improved detection of prostate cancer. The aim of the current study was to document the performance of MRI/TRUS fusion biopsy of the prostate using the Navigo™ software in a contemporary cohort of patients from nonreferral centers. We performed a two centers prospective data collection (2014–2020) for men with clinically suspected Pca and patients on active surveillance for low-risk Pca that were referred for TRUS biopsy after performing mpMRI of the prostate with a visible lesion. The primary outcome was detection of clinically significant cancer (csPca) defined as ISUP grade group ≥2. Patients were stratified according to biopsy technique and PI-RADS category. The study group included 236 patients of whom 129 (54.9%) were diagnosed with Pca and 82 (34.7%) with csPca (GG ≥ 2) on combined biopsy. The overall detection of csPca was 31% for targeted vs. 25.4% for systematic biopsy with an absolute difference of 5.6% in favor of the fusion technique. No significant difference between the two techniques was observed for detection of benign prostate or GG1 disease. The improved performance of the targeted approach was noted only in patients with PI-RADS 4 and 5 lesions. Of the patients with csPca 10 (12%) were diagnosed only by the systematic biopsy while 20 (24%) were detected only in the fusion biopsy. Systematic biopsy of prostate lobe without MRI lesion detected only 2 cases (∼1%) with high grade disease. Detection of csPca by mpMRI/TRUS fusion biopsy using the 3D Navigo™ system is feasible. The targeted approach outperforms the systematic one, however the later technique also detects high risk disease and should be included in the biopsy procedure. The overall detection rate (34.9%) of clinically significant prostate cancer by both targeted and systematic sampling is relatively low. [ABSTRACT FROM AUTHOR]

Objective: This study examined the reliability of the various parameters obtained in diagnostic ureteroscopy for upper-tract urothelial carcinoma (UTUC) in predicting the degree of differentiation in the final pathological report after radical nephroureterectomy (RNU). Methods: We conducted a retrospective review of patients undergoing RNU at a single tertiary hospital between 2000 and 2020. Only patients who underwent preoperative diagnostic ureteroscopy (URS) were included. The results of urine selective cytology, endoscopic appearance of the tumor, and biopsy taken during ureteroscopy were compared to the final pathological report. Results: In total, 111 patients underwent RNU. A preliminary URS was performed in 54. According to endoscopic appearance, 40% of the "solid"-looking tumors were high grade (HG), while 52% of those with a papillary appearance were low grade (LG). Positive cytology predicted HG tumors in 86% of cases. However, 42% of patients with negative cytology had HG disease. The biopsies acquired during URS showed that HG disease findings matched the final pathology in 75% of cases. However, 25% of patients noted as being HG, based on URS biopsies, were noted to have LG disease based on nephroureterectomy biopsies. Full analyses revealed that 40% of the cases diagnosed as LG based on the URS biopsies actually had HG disease. Conclusions: Direct tumor observation of papillary lesions, negative cytology, and biopsies indicating LG disease are of low predictive value for classifying the actual degree of tumor differentiation. No single test can accurately rule out HG disease. In light of the rising use of neo-adjuvant chemotherapy in UTUC, a reliable predictive model should be developed that accurately discriminates between HG and LG disease. [ABSTRACT FROM AUTHOR]

Introduction: The aim of our study was to examine the influence of tumor complexity and operative variables on the degree and rate of post-nephron sparing surgery (NSS) acute kidney injury (AKI). Methods: We retrospectively reviewed the records of 477 patients who underwent NSS for enhancing renal masses in our institution. AKI was determined using the latest definition by AKIN and RIFLE criteria. Serum creatinine was assessed daily starting from day 1 post-surgery and until discharge (usually on postoperative day 3). Estimated glomerular filtration was determined using the Modification of Diet in Renal Disease equation. Results: Overall, 191 patients (40%) developed postoperative AKI, and most of them (88%) were grade 1. Multivariate analysis revealed that the most significant and independent variables associated with AKI were operation time (p = 0.02), ischemia time (p = 0.02), and the use of tissue adhesive for tumor bed closure (p = 0.02). Other important factors (by univariate analysis) were the need for blood transfusion (p = 0.003) and estimated blood loss (p = 0.007). Conclusions: Operative time, ischemia, and tumor bed closure method are independent predictors of post-NSS AKI. Efforts should be made to limit prolonged ischemia and to reduce viable parenchymal loss. Further studies concerning the functional impact of AKI in these patients will be required. [ABSTRACT FROM AUTHOR]

Acute kidney injury (AKI) is a common clinical problem that still lacks effective treatment. Phosphodiesterase- 5 (PDE5) inhibitors possess anti-apoptotic and antioxidant properties, making it a promising therapy for ischemiareperfusion (I/R) injury of various organs. The present study evaluated the early nephroprotective effects of Tadalafil, a PDE5 inhibitor, in an experimental model of renal I/R. Sprague-Dawley rats were divided into two groups: vehicle-treated I/R (n = 10), and Tadalafil (10 mg/kg po)-treated I/R group (n = 11). After removal of the right kidney and collection of two baseline urine samples, the left renal artery was clamped for 45 min followed by reperfusion for 60, 120, 180, and 240 min. Functional and histological parameters of the kidneys from the various groups were determined. In the vehicle-treated I/R group, glomerular filtration rate was significantly reduced compared with that in normal kidneys. In addition, the ischemic kidney showed remarkable cast formation, necrosis, and congestion, a consistent pattern of acute tubular necrosis. Furthermore, urinary excretion of NGAL and KIM-1, two novel biomarkers of kidney injury, substantially increased following I/R insult. In contrast, Tadalafil treatment resulted in a significant improvement in kidney function and amelioration of the adverse histological alterations of the ischemic kidney. Noteworthy, the urinary excretion of NGAL and KIM-1 markedly decreased in the Tadalafil-treated I/R group. These findings demonstrate that Tadalafil possesses early nephroprotective effects in rat kidneys subjected to I/R insult. This approach may suggest a prophylactic therapy for patients with ischemic AKI. [ABSTRACT FROM AUTHOR]

Purpose The primary toxic effects of methotrexate (MTX) are myelosuppression and/or intestinal mucositis. The objective of the present study is to investigate the effect of MTX on germ cell apoptosis and spermatogenesis in a rat. Methods Male Sprague–Dawley rats were divided into three experimental groups: control rats treated with vehicle; MTX-2 rats treated with one dose (20 µg/kg) of MTX given IP and killed on the second day; and MTX rats treated with IP MTX (20 µg/kg) and killed on day 4. Johnsen’s criteria and the number of germinal cell layers in the testes were used to categorize the spermatogenesis. TUNEL assay was used to determine germ cell apoptosis. Western blotting was used to determine Bax and Bcl-2 protein levels. Statistical analysis was performed using the non-parametric Kruskal–Wallis ANOVA test, with p less than 0.05 considered statistically significant. Results On day 2, MTX-treated animals demonstrated minimal changes in the histological parameters of spermatogenesis, but germ cell apoptosis increased significantly (threefold increase, p = 0.002) compared to control rats. On day 4, MTX-treated rats demonstrated a trend toward a decrease in germ cell apoptosis, compared to day 2, and showed histological signs of impaired spermatogenesis (decreased number of germ cell layers and Johnsen’s criteria). A significant increase in cell apoptosis in MTX-treated rats was correlated with higher Bax/Bcl-2 protein levels. Conclusions MTX induced germ cell apoptosis and impaired spermatogenesis in rat testes. [ABSTRACT FROM AUTHOR]

Introduction and Objectives: We report our experience with pediatric shock wave lithotripsy (SWL) using two types of lithotripters: Dornier HM3 (HM3) and Dornier Lithotripter SII (DLS). Study Design: We retrospectively reviewed the charts of children who underwent SWL between 2002 and 2016. Patients were divided into two groups based on the type of the lithotripter: during 2002–2009, we used the electrohydraulic HM3 lithotripter which was replaced in 2009 with the DLS electromagnetic lithotripter. Clinical and perioperative parameters were compared. Results: Our cohort included 107 children who underwent SWL. Average age was 11.5 ± 5.1 years. Average stone size was 10.6 ± 4.9 mm. HM3 was used in 38% of children and DLS2 in 62% (n = 41 and 66, respectively). There were no significant differences in age, gender, stone size, or location between the groups. The total SFR did not differ statistically between HM3 and DLS (83% vs. 74%, p = 0.35). SFR after one SWL was higher with the HM3 (78% vs. 62%, p = 0.093). Re-treatment rate was 22% and 17% (HM3 vs. DLS, p = 0.61). Complication rates were low, with renal colic being the most common (HM3 10%, DLS 20%, NS). Conclusions: SWL in the pediatric population using the DLS showed good results with low complication rates that are equivalent to the gold standard HM3. [ABSTRACT FROM AUTHOR]

Purpose: to evaluate a unique subpopulation of radical prostatectomy (RP) candidates with "negative" prostate 68Ga-labeled prostate-specific membrane antigen (PSMA) positron emission tomography (PET) computed tomography (CT) imaging scans and to characterize the clinical implications of misleading findings. Materials and Methods: This case-control retrospective study compared the final histological outcomes of patients with "negative" pre-RP PSMA PET/CT prostate scans (with a prostate maximal standardized uptake value [SUVmax] below the physiologic uptake) to those with an "intense" prostatic tracer uptake (with a SUVmax above the physiologic uptake). The patients underwent an RP between March 2015 and July 2019 in five academic centers. Data on the demographics, comorbidities, prostate-specific antigen (PSA) and rectal exam findings, prior biopsies, imaging results, biopsies, and RP histology results were collected. Results: Ninety-seven of the 392 patients who underwent an RP had PSMA PET/CT imaging preoperatively. Fifty-two (54%) had a "negative" uptake (in the study group), and 45 (46%) had a "positive" uptake (in the control group). Only the lesion size and SUVmax values on the PSMA PET/CT differed between the groups preoperatively. On the histological analysis, only the ISUP score, seminal vesicles invasion, T stage, and positive margin rates differed between the groups (p < 0.05), while 50 (96%) study group patients harbored clinically significant disease (ISUP ≥ 2), with an extra-prostatic disease in 24 (46%), perineural invasion in 35 (67%), and positive lymph nodes in 4 (8%). Conclusions: Disease aggressiveness generally correlated with an intense PSMA uptake on the preoperative PSMA PET/CT, but a subpopulation of patients with clinically significant cancer and aggressive characteristics showed a deceptively weak PSMA uptake. These data raise a concern about the unqualified application of PSMA PET/CT for staging RP candidates. [ABSTRACT FROM AUTHOR]

• CellDetect is a novel histochemical staining for detection of UC. • CellDetect shows high sensitivity and negative predictive value. • Further validation is warranted, particularly in patients with high grade tumors. • Compared to U-FISH and cytology, CellDetect had better detection rates. To compare the performance of CellDetect, a new biomarker with urine cytology and UroVysiontechnology for bladder cancer detection. We performed an IRB approved prospective, blinded single center study in patients on routine surveillance for nonmuscle invasive bladder cancer and those scheduled for transurethral resection of bladder tumor or radical cystectomy. Patients with bladder catheters, neobladder, ileal conduit, urinary stones, or those with upper tract carcinoma were excluded from the study. Voided urine sample was collected from the participants and each sample was divided into three equal aliquots (CellDetect, Urine cytology and Urovysion). Pathology of the operative specimen was considered the gold standard to which the three markers were compared. The study group included 93 patients with median age was 68 years (range: 34–92 years) with male to female ratio of 12:1. Pathologic evaluation revealed malignancy in 43 cases (46%) of whom 81% had previous history of urothelial bladder cancer. Among all studied markers CellDetect exhibited the best performance followed by urine cytology and U-FISH with diagnostic odds ratio of 4.33, 3.85, and 2.5 respectively. The overall sensitivity, specificity, negative predictive value, and positive predictive value for this test were 84%, 80%, 88%, and 74% respectively. The advantage of this new biomarker was observed both in high grade and low-grade cases. This study demonstrates the advantage of CellDetect as a urine-based assay to detect urothelial bladder cancer over urine cytology and U-FISH test. The high performance was maintained across all cancer grades and stages without compromising the assay specificity. Additional studies are required to test if it can be a noninvasive alternative to cystoscopy. [ABSTRACT FROM AUTHOR]

Very Low Prostate PET/CT PSMA Uptake May Be Misleading in Staging Radical Prostatectomy Candidates. Very Low Prostate PET/CT PSMA Uptake May Be Misleading in Staging Radical Prostatectomy Candidates. Finding very low/"negative" PET/CT PSMA reads amongst patients encompassing higher-risk disease supports this hypothesis. [Extracted from the article]

Background: Ischemia/reperfusion (I/R) is an important cause of acute renal failure and delayed graft function, and it may induce chronic renal damage by activating epithelial to mesenchymal transition (EMT) of renal tubular cells. Heparanase (HPSE), an endoglycosidase that regulates FGF-2 and TGFβ-induced EMT, may have an important role. Therefore, aim of this study was to evaluate its role in the I/R-induced renal pro-fibrotic machinery by employing in vitro and in vivo models. Methods: Wild type (WT) and HPSE-silenced renal tubular cells were subjected to hypoxia and reoxygenation in the presence or absence of SST0001, an inhibitor of HPSE. In vivo, I/R injury was induced by bilateral clamping of renal arteries for 30 min in transgenic mice over-expressing HPSE (HPA-tg) and in their WT littermates. Mice were sacrificed 48 and 72 h after I/R. Gene and protein EMT markers (α-SMA, VIM and FN) were evaluated by bio-molecular and histological methodologies. Results: In vitro: hypoxia/reoxygenation (H/R) significantly increased the expression of EMT-markers in WT, but not in HPSE-silenced tubular cells. Notably, EMT was prevented in WT cells by SST0001 treatment. In vivo: I/R induced a remarkable up-regulation of EMT markers in HPA-tg mice after 48–72 h. Noteworthy, these effects were absent in WT animals. Conclusions: In conclusion, our results add new insights towards understanding the renal biological mechanisms activated by I/R and they demonstrate, for the first time, that HPSE is a pivotal factor involved in the onset and development of I/R-induced EMT. It is plausible that in future the inhibition of this endoglycosidase may represent a new therapeutic approach to minimize/prevent fibrosis and slow down chronic renal disease progression in native and transplanted kidneys. [ABSTRACT FROM AUTHOR]

Purpose: Interruption of renal blood flow is often necessary during nephron sparing surgery (NSS) and can induce renal injury. This study examines whether tadalafil, a phosphodiesterase-5 (PDE-5) inhibitor and well-known vasodilator, exerts nephroprotective effects in patients undergoing NSS. Methods: This non-randomized study included 49 patients with enhancing solid renal mass. All patients were subjected to open NSS during which clamping the renal artery was performed. Twenty-two patients were pretreated with tadalafil 1 day prior NSS and 2 days following surgery. The other 27 patients underwent the same surgical procedure but did not receive tadalafil (controls). Urine samples were collected before surgery and following renal pedicle clamp removal. Urine levels of NGAL and KIM-1, two novel biomarkers for acute kidney injury (AKI), were determined. Results: Clamping the renal artery induced kidney dysfunction as reflected by increases in urinary NGAL and KIM-1 in all participants. These increases in urinary NGAL and KIM-1 excretion were evident 1 h after renal ischemia and lasted for 72 and 24 h, respectively. Pretreatment with tadalafil reduced the absolute urinary excretion of KIM-1, but not of NGAL. Although the incidence of AKI was comparable between tadalafil-treated and untreated NSS subjects, the elevation in serum creatinine (SCr) was significantly attenuated in tadalafil-treated group as compared with NSS controls. Conclusions: Tadalafil exerts nephroprotective effects in AKI following NSS, as was evident by reduced urinary excretion of KIM-1 and attenuation of SCr elevation. Carefully controlled large clinical studies are needed before defining the role of PDE-5 inhibition therapy in these patients. [ABSTRACT FROM AUTHOR]