Routine intraoperative ureteric stenting for kidney transplant recipients.

BACKGROUND: Major urological complications (MUCs) after kidney transplantation contribute to patient morbidity and compromise graft function. The majority arise from vesicoureteric anastomosis and present early after transplantation. Ureteric stents have been successfully used to treat such complications. A number of centres have adopted a policy of universal prophylactic stenting at the time of graft implantation to reduce the incidence of urine leaks and ureteric stenosis. Stents are associated with specific complications, and some centres advocate a policy of only stenting selected anastomoses. This is an update of our review, first published in 2005 and last updated in 2013. OBJECTIVES: To examine the benefits and harms of routine ureteric stenting to prevent MUCs in kidney transplant recipients. SEARCH METHODS: We contacted the Information Specialist and searched the Cochrane Kidney and Transplant's Specialised Register (up to 19 June 2024) using search terms relevant to this review. Studies in the Register are identified through searches of CENTRAL, MEDLINE, and EMBASE, conference proceedings, the International Clinical Trials Registry Platform (ICTRP) Search Portal, and ClinicalTrials.gov. SELECTION CRITERIA: Our meta-analysis included all randomised controlled trials (RCTs) and quasi-RCTs designed to examine the impact of using stents for kidney transplant recipients. We aimed to include studies regardless of the type of graft, the technique of ureteric implantation, or the patient group. DATA COLLECTION AND ANALYSIS: Summary estimates of effect were obtained using a random-effects model, and results were expressed as risk ratios (RR) and their 95% confidence intervals (CI). Confidence in the evidence was assessed using the Grading of Recommendations Assessment, Development and Evaluation (GRADE) approach. MAIN RESULTS: Twelve studies (1960 patients) were identified. One study was deemed to be at low risk of bias across all domains. The remaining 11 studies were of low or medium quality, with a high or unclear risk of bias in at least one domain. Universal prophylactic ureteric stenting versus control probably reduces major urological complications (11 studies: 1834 participants: RR 0.30, 95% CI 0.16 to 0.55; P < 0.0001; I2 = 16%; moderate certainty evidence; number needed to treat (17)); this benefit was confirmed in the only study deemed to be at low risk of bias across all domains. This benefit was also seen for the individual components of urine leak and ureteric obstruction. Universal prophylactic ureteric stent insertion reduces the risk of MUC in the subgroup of studies with short duration (≤ 14 days) of stenting (2 studies, 480 participants: RR 0.39, 95% CI CI 0.21 to 0.72; P = 0.003; I2 = 0%) and where stenting was continued for > 14 days (8 studies, 124 participants: RR 0.22, 95% CI 0.08 to 0.61; P = 0.004; I2 = 29%). It is uncertain whether stenting has an impact on the development of urinary tract infection (UTI) (10 studies, 1726 participants: RR 1.32, 95% CI 0.97 to 1.80; P = 0.07; I² = 60%; very low certainty evidence due to risk of bias, heterogeneity and imprecision). Subgroup analysis showed that the risk of UTI did not increase if short-duration stenting was used (9 days) and that there was no impact on UTI risk when the prophylactic antibiotic regime co-trimoxazole 480 mg/day was used. Stents appear generally well tolerated, although studies using longer stents (≥ 20 cm) for longer periods (> 6 weeks) had more problems with encrustation and migration. There was no evidence that the presence of a stent resulted in recurrent or severe haematuria (8 studies, 1546 participants: RR 1.09, 95% CI 0.59 to 2.00; P = 0.79; I2 = 33%). The impact of stents on graft and patient survival and other stent-related complications remains unclear as these outcomes were either poorly reported or not reported at all. AUTHORS' CONCLUSIONS: Routine prophylactic stenting probably reduces the incidence of MUCs, even when the duration of stenting is short (≤ 14 days). Further high-quality studies are required to assess optimal stent duration. Studies comparing selective stenting and universal prophylactic stenting, whilst difficult to design and analyse, would address the unresolved quality of life and economic issues.

Anti-fibrotic effects of synthetic TGF-ß1 and Smad oligodeoxynucleotide on kidney fibrosis in vivo and in vitro through inhibition of both epithelial dedifferentiation and endothelial-mesenchymal transitions.

Kidney fibrosis is a common process of various kidney diseases leading to end-stage renal failure irrespective of etiology. Myofibroblasts are crucial mediators in kidney fibrosis through production of extracellular matrix (ECM), but their origin has not been clearly identified. Many study proposed that epithelial and endothelial cells become myofibroblasts by epithelial dedifferentiation and endothelial-mesenchymal transition (EndoMT). TGF-ß1/Smad signaling plays a crucial role in partly epithelial-mensencymal transition (EMT) and EndoMT. Thus, we designed the TGF-ß1/Smad oligodeoxynucleotide (ODN), a synthetic short DNA containing complementary sequence for Smad transcription factor and TGF-ß1 mRNA. Therefore, this study investigated the anti-fibrotic effect of synthetic TGF-ß1/Smad ODN on UUO-induced kidney fibrosis in vivo model and TGF-ß1-induced in vitro model. To examine the effect of TGF-ß1/Smad ODN, we performed various experiments to evaluate kidney fibrosis. The results showed that UUO induced inflammation, ECM accumulation, epithelial dedifferentiation and EndoMT processes, and tubular atrophy. However, synthetic TGF-ß1/Smad ODN significantly suppressed UUO-induced fibrosis. Furthermore, synthetic ODN attenuated TGF-ß1-induced epithelial dedifferentiation and EndoMT program via blocking TGF-ß1/Smad signaling. In conclusion, this study demonstrated that administration of synthetic TGF-ß1/Smad ODN attenuates kidney fibrosis, epithelial dedifferentiation, and EndoMT processes. The findings propose the possibility of synthetic ODN as a new effective therapeutic tool for kidney fibrosis.

MiR-9-5p protects from kidney fibrosis by metabolic reprogramming.

MicroRNAs (miRNAs) regulate gene expression posttranscriptionally and control biological processes (BPs), including fibrogenesis. Kidney fibrosis remains a clinical challenge and miRNAs may represent a valid therapeutic avenue. We show that miR-9-5p protected from renal fibrosis in the mouse model of unilateral ureteral obstruction (UUO). This was reflected in reduced expression of pro-fibrotic markers, decreased number of infiltrating monocytes/macrophages, and diminished tubular epithelial cell injury and transforming growth factor-beta 1 (TGF-ß1)-dependent de-differentiation in human kidney proximal tubular (HKC-8) cells. RNA-sequencing (RNA-Seq) studies in the UUO model revealed that treatment with miR-9-5p prevented the downregulation of genes related to key metabolic pathways, including mitochondrial function, oxidative phosphorylation (OXPHOS), fatty acid oxidation (FAO), and glycolysis. Studies in human tubular epithelial cells demonstrated that miR-9-5p impeded TGF-ß1-induced bioenergetics derangement. The expression of the FAO-related axis peroxisome proliferator-activated receptor gamma coactivator 1 alpha (PGC-1α)-peroxisome proliferator-activated receptor alpha (PPARα) was reduced by UUO, although preserved by the administration of miR-9-5p. We found that in mice null for the mitochondrial master regulator PGC-1α, miR-9-5p was unable to promote a protective effect in the UUO model. We propose that miR-9-5p elicits a protective response to chronic kidney injury and renal fibrosis by inducing reprogramming of the metabolic derangement and mitochondrial dysfunction affecting tubular epithelial cells.

Blocking the histone lysine 79 methyltransferase DOT1L alleviates renal fibrosis through inhibition of renal fibroblast activation and epithelial-mesenchymal transition.

Disruptor of telomeric silencing-1 like (DOT1L) protein specifically catalyzes the methylation of histone H3 on Lys79 (H3K79) and is implicated in tumors. But its role in tissue fibrosis remains unclear. Here we demonstrated that injury to the kidney increased DOT1L expression and H3K79 dimethylation in renal tubular epithelial cells and myofibroblasts in a murine model of unilateral ureteral obstruction. Administration of EPZ5676, a highly selective inhibitor of DOT1L, attenuated renal fibrosis. Treatment with EPZ5676 or DOT1L small interfering RNA also inhibited TGF-ß1 and serum-induced activation of renal interstitial fibroblasts and epithelial-mesenchymal transition (EMT) in vitro. Moreover, blocking DOT1L abrogated injury-induced epithelial G2/M arrest; reduced expression of Snail, Twist, and Notch1; and inactivated several profibrotic signaling molecules in the injured kidney, including Smad3, epidermal growth factor receptor, platelet-derived growth factor receptor, signal transducer and activator of transcription 3, protein kinase B, and NF-κB. Conversely, DOT1L inhibition increased expression of phosphatase and tensin homolog, a protein associated with dephosphorylation of tyrosine kinase receptors, and prevented decline in levels of Klotho and Smad7, 2 renoprotective factors. Thus, our data indicate that targeting DOT1L attenuates renal fibrosis through inhibition of renal fibroblasts and EMT by suppressing activation of multiple profibrotic signaling pathways while retaining expression of renoprotective factors.-Liu, L., Zou, J., Guan, Y., Zhang, Y., Zhang, W., Zhou, X., Xiong, C., Tolbert, E., Zhao, T. C., Bayliss, G., Zhuang, S. Blocking the histone lysine 79 methyltransferase DOT1L alleviates renal fibrosis through inhibition of renal fibroblast activation and epithelial-mesenchymal transition.

Safety and Efficacy of Retrograde Pyeloperfusion for Ureteral Protection during Renal Tumor Cryoablation.

PURPOSE: To determine safety and efficacy of retrograde pyeloperfusion for ureteral protection during cryoablation of adjacent renal tumors. MATERIALS AND METHODS: Retrospective review of 155 patients treated with renal cryoablation, including adjunctive retrograde pyeloperfusion, from 2005 to 2019 was performed. Ice contacted the ureter in 67 of the 155 patients who represented the study cohort. Median patient age was 68 years old (interquartile range [61, 74]), 52 patients (78%) were male, and 37 tumors (55%) were clear cell histology. Mean tumor size was 3.4 ± 1.3 cm, and 42 tumors (63%) were located at the lower pole. Treatment-related complication and oncologic outcomes were recorded based on a review of post-procedural images and chart review. RESULTS: Technical success of cryoablation was attained in 67 cases (100%), and technical success of pyeloperfusion was attained in 66 cases (99%). A total of 13 patients (19.4%) experienced SIR major C or D complications related to the procedure, including hemorrhage (n = 4), urine leak (n = 3), transient urinary obstruction (n = 2), pulmonary embolism (n = 1), hypertensive urgency (n = 1), acute respiratory failure (n = 1), and ureteropelvic junction (UPJ) stricture (n = 1). No complications were attributable to pyeloperfusion. Three of 45 patients with biopsy-proven renal cell carcinoma experienced local recurrence resulting in local recurrence-free survival of 92% (95% confidence interval, 81.5%-100%) 3 years after ablation. CONCLUSIONS: Retrograde pyeloperfusion of the renal collecting system is a relatively safe and efficacious option for ureteral protection during renal tumor cryoablation. This adjunctive procedure should be considered for patients in whom cryoablation of a renal mass could potentially involve the ureter.

Preservation of the mesureter to reduce urinary complications: analysis of data from the observational Leipzig School MMR study.

OBJECTIVE: To evaluate the feasibility and effect of mesureteral preservation on urinary complications in the context of total mesometrial resection (TMMR), a surgical treatment for cervical cancer. DESIGN: Retrospective cohort study with historic control. SETTING: Single tertiary academic centre. POPULATION: Women older than 18 with primary cervical cancer staged FIGO IB1-IIB enrolled in the prospective Leipzig School MMR study and underwent total mesometrial resection (TMMR) without adjuvant radiation. METHOD: We retrospectively analysed 100 consecutive TMMR procedures which were performed for cancer of the uterine cervix and in which the mesureter was preserved (intervention group, 01/2014-06/2017). We compared this group with the previous 100 consecutive TMMRs, which were performed before the introduction of mesureteral preservation (control group, 09/2010-01/2014). MAIN OUTCOME MEASURES: The occurrence of urological and specifically ureteral complications. RESULTS: Mesureteral preservation was feasible and was associated with a significant decrease in ureteral complications (11% without mesureteral preservation versus 3% with mesureteral preservation, P = 0.049). Furthermore, we found a significant decrease in the number of postoperative percutaneous nephrostomies and re-operations (7% versus none, P = 0.014). There was also a trend towards a decrease in other urinary complications such as postoperative bladder atony and uretero-vaginal fistulas. CONCLUSION: The mesureter constitutes a convenient dissection plane enabling the preservation of lateral ureteral blood supply during TMMR. In our study, maintenance of mesureteral integrity was associated with a significant reduction in ureteral complications. Mesureteral preservation might also be useful in other types of pelvic surgeries that carry a high risk of ureteral damage. TWEETABLE ABSTRACT: Surgical preservation of the mesureter in cervical cancer patients was associated with a reduction in urinary complications.

Use of indocyanine green to minimise uretero-enteric strictures after robotic radical cystectomy.

OBJECTIVE: To evaluate the impact of indocyanine green (ICG) for assessing ureteric vascularity on the rate of uretero-enteric stricture formation after robot-assisted radical cystectomy (RARC) with intracorporeal urinary diversion (ICUD). PATIENTS AND METHODS: We identified 179 patients undergoing RARC and ICUD between January 2014 and May 2017, and divided the patients into two groups based on the utilisation of ICG for the assessment of ureteric vascularity (non-ICG group and ICG group). We retrospectively reviewed the medical records to identify the length of ureter excised. Demographic, perioperative outcomes (including 90-day complications and readmissions), and the rate of uretero-enteric stricture were compared between the two groups. The two groups were compared using the t-test for continuous variables and the chi-squared test for categorical variables. A P < 0.05 was considered statistically significant. RESULTS: A total of 132 and 47 patients were in the non-ICG group and the ICG group, respectively. There were no differences in baseline characteristics and perioperative outcomes including operating time, estimated blood loss, and length of stay. The ICG group was associated with a greater length of ureter being excised during the uretero-enteric anastomosis and a greater proportion of patients having long segment (>5 cm) ureteric resection. The median follow-up was 14 and 12 months in the non-ICG and ICG groups, respectively. The ICG group was associated with no uretero-enteric strictures compared to a per-patient stricture rate of 10.6% and a per-ureter stricture rate of 6.6% in the non-ICG group (P = 0.020 and P = 0.013, respectively). CONCLUSION: The use of ICG fluorescence to assess distal ureteric vascularity during RARC and ICUD may reduce the risk of ischaemic uretero-enteric strictures. The technique is simple, safe, and reproducible. Larger studies with longer follow-up are needed to confirm our findings.

Nrf2 signaling attenuates epithelial-to-mesenchymal transition and renal interstitial fibrosis via PI3K/Akt signaling pathways.

BACKGROUND: Nrf2 constitutes a therapeutic reference point for renal fibrosis and chronic kidney diseases. Nrf2-related signaling pathways are recognized to temper endothelial-to-mesenchymal transition (EMT) in fibrotic tissue. Nevertheless, the mechanism by which Nrf2 mitigates renal interstitial fibrosis is imprecise. METHODS: The relationship between Nrf2 and renal interstitial fibrosis was investigated using the unilateral ureteral obstruction (UUO) model of Nrf2-/- mice. The mice were separated into four groups, based on the treatment and intervention: Nrf2-/- + UUO, Nrf2-/- + Sham, WT + UUO and WT + Sham. Histological examination of renal tissue following the hematoxylin-eosin and Masson staining was carried out, as well as immunohistochemical staining. Additionally, to confirm the in vivo discoveries, in vitro experiments with HK-2 cells were also performed. RESULTS: The Nrf2-/- + UUO group showed more severe renal interstitial fibrosis compared to the WT + UUO, Nrf2-/- + Sham and WT + Sham groups. Furthermore, the manifestations of α-SMA and Fibronectin significantly increased, and the manifestation of E-cadherin considerably decreased in kidney tissues from the group of Nrf2-/- + UUO, compared to the WT + UUO group. The Nrf2 protein level significantly decreased in HK-2 cells, in reaction to the TGF-ß1 concentration. In addition, the overexpression of Nrf2 presented contradictory results. What is more, the PI3K/Akt signaling pathway was discovered to be activated in the proteins extracted from cultured cells, and treated with Nrf2 siRNA and kidney tissues from the Nrf2-/- + UUO group. CONCLUSIONS: The results we obtained demonstrate that Nrf2 signaling pathway may perhaps offset the development of EMT, prompted by TGF-ß1 and renal interstitial fibrosis. Likewise, the anti-fibrotic effect of Nrf2 was imparted by the inactivation of PI3K/Akt signaling. From our discoveries, we deliver new insight related to the prevention and treatment of kidney fibrosis.

Ureteral stent versus no ureteral stent for ureteroscopy in the management of renal and ureteral calculi.

BACKGROUND: Ureteroscopy combined with laser stone fragmentation and basketing is a common approach for managing renal and ureteral stones. This procedure is associated with some degree of ureteral trauma. Ureteral trauma may lead to swelling, ureteral obstruction, and flank pain and may require subsequent interventions such as hospital admission or secondary ureteral stent placement. To prevent such issues, urologists often place temporary ureteral stents prophylactically, but the value of doing so remains unclear. OBJECTIVES: To assess the effects of postoperative ureteral stent placement after uncomplicated ureteroscopy. SEARCH METHODS: We performed a comprehensive search using multiple databases (the Cochrane Library, MEDLINE, Embase, Scopus, Google Scholar, and Web of Science), trials registries, other sources of grey literature, and conference proceedings, up to 01 February 2019. We applied no restrictions on publication language or status. SELECTION CRITERIA: We included trials in which researchers randomised participants undergoing uncomplicated ureteroscopy to placement of a ureteral stent versus no ureteral stent. DATA COLLECTION AND ANALYSIS: Two review authors independently classified studies and abstracted data from the included studies. We performed statistical analyses using a random-effects model. We rated the certainty of evidence (CoE) according to the GRADE approach. MAIN RESULTS: Primary outcomesStenting may slightly reduce the number of unplanned return visits (16 trials with 1970 participants; very low CoE), but we are very uncertain of this finding.Pain on the day of surgery as measured on a visual analogue scale (scale 0 to 10; higher values reflect more pain) is probably similar (mean difference (MD) 0.32 higher, 95% confidence interval (CI) 0.13 lower to 0.78 higher; 4 trials with 346 participants; moderate CoE). Pain on postoperative days 1 to 3 may show little to no difference (standardised mean difference (SMD) 0.25 higher, 95% CI 0.32 lower to 0.82 higher; 8 trials with 683 participants; low CoE). On postoperative days 4 to 30, stented participants may experience more pain (8 trials with 903 participants; very low CoE), but we are very uncertain of this finding.Stenting may result in little to no difference in the need for secondary interventions (risk ratio (RR) 1.15, 95% CI 0.39 to 3.33; 10 studies with 1435 participants; low CoE); this corresponds to three more interventions per 1000 participants (95% CI 13 fewer to 48 more).Secondary outcomesStenting may reduce the need for narcotics (7 trials with 830 participants; very low CoE), but we are very uncertain of this finding.Rates of urinary tract infection (UTI) up to 90 days are probably not substantially different (RR 0.94, 95% CI 0.59 to 1.51; 10 trials with 1207 participants; moderate CoE); this corresponds to three fewer infections per 1000 participants (95% CI 23 fewer to 29 more).Ureteral stricture rates up to 90 days may be slightly reduced (14 trials with 1625 participants; very low CoE), but we are very uncertain of this finding.Rates of hospital admission may be slightly reduced (RR 0.70, 95% CI 0.32 to 1.55; 13 studies with 1647 participants; low CoE). This corresponds to 15 fewer admissions per 1000 participants (95% CI 33 fewer to 27 more). AUTHORS' CONCLUSIONS: Findings of this review illustrate the trade-offs of risks and benefits faced by urologists and their patients when it comes to decision-making about stent placement after uncomplicated ureteroscopy for stone disease. We noted that both desirable and undesirable effects were small in absolute terms, with findings based mostly on low and very low CoE. The main issues reducing our confidence in research findings were study limitations (mostly risk of performance and detection bias) and imprecision. We were unable to conduct any of the preplanned subgroup analyses, in particular those based on stone size, stone location, and use of ureteral dilation, which may be important effect modifiers. Given the importance of this question, higher-quality and sufficiently large trials are needed to better inform decision-making.

Rhein alleviates renal interstitial fibrosis by inhibiting tubular cell apoptosis in rats.

BACKGROUND: Ureteral obstruction causes injury of the renal tissues and can irreversibly progress to renal fibrosis, with atrophy and apoptosis of tubular cells. The goal of the current study was to examine the effects of rhein on the apoptosis o renal tubular cells as well as renal fibrosis using a rodent model of unilateral ureteral obstruction (UUO). METHODS: UUO was induced through ureteral ligation, then animals received treatments with rhein or vehicle. The control rats only received sham operation. The renal tissue was harvested 1 week after surgery for assessment of kidney fibrosis. RESULTS: The expressions of collagen I and α-smooth muscle actin (α-SMA), as well as the severity of renal tubular apoptosis and fibrosis were time-dependently increased following UUO. Treatments with rhein partially inhibited such responses. Renal interstitial fibrosis was associated with STAT3 (signal transducer and activator of transcription 3) phosphorylation as well as altered expressions of Bax and Bcl2, both apoptosis-related proteins. Treatment with rhein also partly blocked these responses. CONCLUSION: These findings demonstrated that rhein mitigated apoptosis of renal tubular cell as well as renal fibrosis in a UUO rodent model. This curative effect is likely mediated via suppression of STAT3 phosphorylation.

How to stent the ureter after kidney transplantation in children?-A comparison of two methods of urinary drainage.

Ureteral stenting after pediatric renal transplantation serves to prevent obstruction and urinary leakage, but can also cause complications. This study compares the complication rates of both methods. Data were retrospectively collected at Erasmus MC, Rotterdam, the Netherlands (splint group, n = 61) and Hospital for Sick Children, Toronto, Canada (JJ catheter group, n = 50). Outcome measures included urological interventions and incidence of UTIs during the first 3 months post-transplantation. The splint was removed after a median of 9 (IQR 8-12), the JJ catheter after 42 (IQR 36-50) days. Seven (11.5%) children in the splint group needed at least one urological re-intervention versus two in the JJ catheter group (P-value .20). UTIs developed in 19 children (31.1%) in the splint group and in twenty-five (50.0%) children in the JJ catheter group (P-value .04), with a total number of 27 vs. 57 UTIs (P-value .02). Nine (33.3%) vs. 35 (61.4%) of these, respectively, occurred during the presence of the splint (P-value <.001). Children with a JJ catheter developed more UTIs than children with a splint; the latter, however, tended to require more re-interventions. Modification of either method is needed to find the best way to stent the ureter.

The Protective Effect of Melittin on Renal Fibrosis in an Animal Model of Unilateral Ureteral Obstruction.

Renal fibrosis is the principal pathological process underlying the progression of chronic kidney disease that leads to end-stage renal disease. Melittin is a major component of bee venom, and it has anti-bacterial, anti-viral, and anti-inflammatory properties in various cell types. Thus, this study examined the therapeutic effects of melittin on the progression of renal fibrosis using the unilateral ureteral obstruction (UUO) model. In addition, the effects of melittin on inflammation and fibrosis in renal fibroblast cells were explored using transforming growth factor-ß1 (TGF-ß1). Histological observation revealed that UUO induced a considerable increase in the number of infiltrated inflammatory cells. However, melittin treatment markedly reduced these reactions compared with untreated UUO mice. The expression levels of inflammatory cytokines and pro-fibrotic genes were significantly reduced in melittin-treated mice compared with UUO mice. Melittin also effectively inhibited fibrosis-related gene expression in renal fibroblasts NRK-49F cells. These findings suggest that melittin attenuates renal fibrosis and reduces inflammatory responses by the suppression of multiple growth factor-mediated pro-fibrotic genes. In conclusion, melittin may be a useful therapeutic agent for the prevention of fibrosis that characterizes the progression of chronic kidney disease.

Tet3-mediated hydroxymethylation of epigenetically silenced genes contributes to bone morphogenic protein 7-induced reversal of kidney fibrosis.

Methylation of CpG island promoters is an epigenetic event that can effectively silence transcription over multiple cell generations. Hypermethylation of the Rasal1 promoter contributes to activation of fibroblasts and progression of kidney fibrosis. Here, we explored whether such causative hypermethylation could be reversed through endogenous mechanisms and whether such reversal of hypermethylation is a constituent of the antifibrotic activity of bone morphogenic protein 7 (BMP7). We show that successful inhibition of experimental kidney fibrosis through administration of BMP7 associates with normalization of Rasal1 promoter hypermethylation. Furthermore, this reversal of pathologic hypermethylation was achieved specifically through Tet3-mediated hydroxymethylation. Collectively, our findings reveal a new mechanism that may be exploited to facilitate therapeutic DNA demethylation to reverse kidney fibrosis.

Protective effect of hydrogen sulfide on renal injury in the experimental unilateral ureteral obstruction.

INTRODUCTION/OBJECTIVE: Ureteral obstruction is a common pathology and causes kidney fibrosis and dysfunction at late period. In this present study, we investigated the antifibrotic and antiinflammatory effects of hydrogen sulfide on kidney damage after unilateral ureteral obstruction (UUO) in rats. MATERIALS AND METHODS: 24 rats were divided into four groups. Group 1 was control, group 2 was sham, group 3 included rats with UUO and group 4 rats with UUO which were given sodium hydrogen sulfide (NaHS)-exogenous donor of hydrogen sulfide (intraperitoneally 56 µmoL/kg/day). After 14 days, rats were killed and their kidneys were taken and blood analysis was performed. Tubular necrosis, mononuclear cell infiltration and interstitial fibrosis were determined histopathologically in a part of the kidneys; nitric oxide (NO), malondialdehyde (MDA) and reduced glutathione (GSH) levels were determined in the other part of the kidneys. Urea-creatinine levels were investigated by blood analysis. Statistical analyses were made by the Chi-square test and one-way analysis of variance (ANOVA). RESULTS: There was no significantly difference for urea-creatinine levels among groups. Pathologically, there was serious tubular necrosis and fibrosis in group 3 and there was significantly decreasing of tubular necrosis and fibrosis in group 4 (p<0.005). Also, there was significantly increase of NO and MDA levels and decrease of GSH levels in group 3 compared to other groups (p<0.005). CONCLUSIONS: hydrogen sulfide prevents kidney damage with antioxidant and antiinflammatory effect.

Should we routinely stent after ureteropyeloscopy?

Arguments 'for' and 'against' ureteric stenting after ureteropyeloscopy are discussed. An individualised approach balancing renal function preservation, irritative lower urinary tract symptoms and emergent return to theatre needs to be adopted while being mindful of healthcare spending.

[Pigtail suture stent: decisive progress towards double-pigtail stent tolerance and unexpected properties of the suture in the ureter]. / Sondes JFil et MiniJFil: progrès décisifs dans la tolérance des sondes urétérales et propriétés inattendues du fil urétéral.

OBJECTIVE: Double-pigtail stent intolerance reduces the quality of life of patients. By decreasing the amount of material within the bladder, it should be possible to attenuate the symptoms linked to the stent. We evaluated the tolerance of a new stent with a dedicated questionnaire. PATIENTS ET METHODS: The major innovation of the pigtail suture stent (PSS and MiniPSS) was in the replacement of the lower part of the double-pigtail stent with a 0.3 F suture. One hundred and eight patients agreed to be fitted with a PSS. The double-pigtail stents of 24 patients complaining strongly of symptoms were replaced with PSS (group 1) and sixty-eight other patients were fitted directly with the PSS after an endoscopic intervention on the ureter (groups 2 and 3). Sixteen patients with non-obstructive kidney stone received MiniPSS (group 4). RESULTS: Completed questionnaires were obtained from 94 patients. In group 1, the replacement of the double-pigtail stent with a PSS significantly decreased urinary symptom scores (34.4±9.0 vs 20.3±7.4, P<0.0000007), and pain scores (10.1±5.1 vs 4.8±3.2, P=0.0001). The scores of the two first groups fitted with a PSS were similar. Following PSS or MiniPSS implantation, a clear dilation of the ureteral meatus was probably induced by the sutures, facilitating the introduction of an ureteroscope or a flexible ureteroscope sheath (12 F). Following extracorporeal shockwave lithotripsy, the stone fragments gradually slid down the PSS sutures, without renal colic. CONCLUSION: The PSS seems to improve the tolerance of ureteral stent. Unexpectedly, following PSS implantation, we observe a clear dilation of the ureter. We believe that use of a double-pigtail stent should no longer be considered the only way to drain the ureter. Instead, the form of the stent should depend on the patient's disease. LEVEL OF EVIDENCE: 5.

CD44v3-v10 reduces the profibrotic effects of TGF-ß1 and attenuates tubular injury in the early stage of chronic obstructive nephropathy.

CD44 family members are cell surface glycoproteins, which are expressed on tubular epithelial cells (TEC) solely upon kidney injury and are involved in renal fibrosis development. Renal interstitial fibrosis is the final manifestation of chronic kidney diseases and is regulated by a complex network of cytokines, including the profibrotic factor transforming growth factor-ß1 (TGF-ß1) and the two antifibrotic cytokines bone morphogenic protein-7 (BMP-7) and hepatocyte growth factor (HGF). The present study investigates the potential role of CD44 standard (CD44s) and CD44v3-v10 (CD44v3) isoforms as modulators of the balance between TGF-ß1 and HGF/BMP-7. CD44s is the shortest and most common isoform. CD44v3-v10 (CD44v3) has heparan sulfate moieties, which enable the binding to HGF/BMP-7, and hence, might exert renoprotective effects. Using transgenic mice overexpressing either CD44s or CD44v3 specifically on proximal TEC, we found that in vitro the overexpression of CD44v3 on primary TEC renders cells less susceptible to TGF-ß1 profibrotic actions and more sensitive to BMP-7 and HGF compared with TEC overexpressing CD44s. One day after unilateral ureteric obstruction, obstructed kidneys from CD44v3 transgenic mice showed less tubular damage and myofibroblasts accumulation, which was associated with decreased TGF-ß1 signaling and increased BMP-7 synthesis and signaling compared with kidneys from wild-type and CD44s transgenic mice. These data suggest that CD44v3 plays a renoprotective role in early stage of chronic obstructive nephropathy.

How much is a kidney worth? Cost-effectiveness of routine imaging after ureteroscopy to prevent silent obstruction.

PURPOSE: The 2012 American Urological Association (AUA) Clinical Effectiveness Protocols for Imaging in the Management of Ureteral Calculous Disease recommends routine postoperative imaging after ureteroscopy. We evaluated the cost-effectiveness of routine postoperative imaging after ureteroscopy. MATERIALS AND METHODS: We searched the literature to determine the risk of complications after routine ureteroscopy for stones, including the incidence of postoperative pain, stricture and silent obstruction. Sequelae of renal loss due to undiagnosed silent obstruction may include chronic kidney disease, end stage renal disease and cardiovascular disease. Imaging and procedure costs were obtained from Medicare reimbursement rates and the literature. The costs and prevalence of lifetime complications associated with silent loss of 1 kidney were obtained from the renal donor transplant literature. A decision tree was constructed to calculate the cost of a strategy of routinely imaging all patients after ureteroscopy vs selective imaging based on postoperative pain. We performed 1-way and 2-way sensitivity analyses. RESULTS: The average cost per patient of a strategy of routine imaging after ureteroscopy in all patients was $5,326 vs $5,196 for a strategy of selective imaging based on postoperative pain. Assuming a 2% rate of silent obstruction, the cost per kidney saved would be $6,262. CONCLUSIONS: While routine postoperative imaging carries a $130 per patient incrementally higher cost over that of a strategy of selective imaging in patients with postoperative pain, preventing renal loss and its attendant morbidity justifies the additional modest cost.

Routine intraoperative ureteric stenting for kidney transplant recipients.

BACKGROUND: Major urological complications (MUCs) after kidney transplantation contribute to patient morbidity and compromise graft function. The majority arise from the vesicoureteric anastomosis and present early after transplantation. Ureteric stents have been successfully used to treat such complications. A number of centres have adopted a policy of universal prophylactic stenting, at the time of graft implantation, to reduce the incidence of urine leaks and ureteric stenosis. Stents are associated with specific complications and some centres advocate a policy of only stenting selected anastomoses. OBJECTIVES: To examine the benefits and harms of routine ureteric stenting to prevent urological complications in kidney transplant recipients. SEARCH METHODS: We searched the Cochrane Renal Group's Specialised Register (up to 8 January 2013) through contact with the Trials' Search Co-ordinator using search terms relevant to this review. SELECTION CRITERIA: All RCTs and quasi-RCTs were included in our meta-analysis. DATA COLLECTION AND ANALYSIS: Four reviewers assessed the studies for quality against four criteria (allocation concealment, blinding, intention-to-treat and completeness of follow-up). The primary outcome was the incidence of MUCs. Further outcomes of interest were graft and patient survival and the incidence of adverse events (urinary tract infection (UTI), haematuria, irritative symptoms, pain and stent migration). Statistical analyses were performed using the random effects model and the results expressed as relative risk (RR) with 95% confidence intervals (CI). MAIN RESULTS: Seven RCTs (1154 patients) of low or moderate quality were identified. The incidence of MUCs was significantly reduced (RR 0.24, 95% CI 0.07 to 0.77, P = 0.02, NNT 13) by universal prophylactic stenting. This was dependent on whether the same surgeon performed, or was in attendance, during the operations. Two patients lost their grafts to infective urinary tract complications in the stented group. UTIs, in general, were more common in stented patients (RR 1.49, 95% CI 1.04 to 2.15) unless the patients were prescribed cotrimoxazole 480 mg/d: in which case the incidence was equivalent (RR 0.97, 95% CI 0.71 to 1.33). Stents appeared generally well tolerated, although studies using longer stents (≥ 20 cm) for longer periods (> 6 weeks) had more problems with encrustation and migration. AUTHORS' CONCLUSIONS: Routine prophylactic stenting reduces the incidence of MUCs. Studies comparing selective stenting and universal prophylactic stenting, whilst difficult to design and analyse, would address the unresolved quality of life and economic issues.

A solution for medical and legal problems arising from forgotten ureteral stents: initial results from a reminder short message service (SMS).

The objective of this study was to describe and present the initial results of a computer-based system that tracks ureteral stents and automatically sends a reminder through a short message service (SMS) to both the patient's and the urologist's mobile phones Using an integrated stent register program (SRP) and a stent extraction reminder program (SERP) with an electronic patient record program (EPRP) located within our hospital's computer network. In this system, the demographic data of all of the patients are recorded into the password-protected EPRP. After a stent is inserted, the surgeon enters the details of the operation into the EPRP. The SRP automatically asks the user to define the "optimal stent life (OSL)". The SERP checks the recorded patients daily and sends an SMS reminder to staff and patient when the OSL is reached. The SERP continues to send reminders via the SMS until stent is removed. We analyzed the success of the SMS recall system. A total of 186 patients received stents over an 11-month period. The patients in group-2 (n = 108) were recalled by the SERP, and the remainder of the patients (n = 78, group-1) were not included in the project. The mean delay from the designated OSL to the time of stent removal was 307 ± 118.6 (72-1,344) and 14.6 ± 2.06 (5-36) h in groups 1 and 2, respectively (p < 0.0001). Our initial results showed that the SRP and SERP prevent stent removal from being forgotten, thus preventing related medical and legal problems.