Navigating the Complexities of Symptomatic Hydronephrosis in Pregnancy.

The management of symptomatic hydronephrosis presents substantial challenges due to the absence of consensus within clinical guidelines concerning pain management, diagnostic approaches, therapeutic interventions, and follow-up protocols. This literature review focuses on complexities involving diagnostic challenges that arise from the difficulty in distinguishing physiological from pathological obstruction and treatment complexities that involve deciding on the most appropriate pain management medications and safe interventions while minimizing risks to both the mother and foetus. To address these challenges, a comprehensive search of electronic databases, including PubMed, Embase, and Google Scholar, was conducted for the terms "hydronephrosis", "hydronephrosis in pregnancy", "ionising radiation in pregnancy", and "safe analgesia in pregnancy". Moreover, Mendeley software was used to collect and organize the references. Diagnostic complexities involve selecting the appropriate imaging modality that balances accurate diagnosis with minimal radiation to the foetus. Ultrasound remains the first-line option. However, it has limitations in delineating the underlying aetiology. MRI avoids ionizing radiation but has restricted utility due to foetal movement artifacts. CT provides the highest diagnostic accuracy but raises foetal radiation exposure concerns, though ultra-low dose protocols (<1 mGy) are deemed acceptable by most guidelines. Management includes either a conservative approach, which is a safe option in the majority of cases, or intervention with a percutaneous nephrostomy or ureteric stent insertion, both with comparable symptom control. However, there is no consensus on the optimal frequency for drain changes to prevent rapid encrustation. Definitive procedures like ureteroscopy and percutaneous nephrolithotomies remain controversial. Most guidelines suggest limiting these interventions to specialist centres during the second trimester if required.

Cost-effectiveness of Resonance® metallic ureteral stent compared with standard polyurethane ureteral stents in malignant ureteric obstruction: A cost-utility analysis.

Background: Malignant ureteral obstruction (MUO) is a frequent challenge for urologists. Patients have poor prognoses, treatment aims to improve quality-of-life while optimising renal function. Standard practice in the United Kingdom is to use polyurethane stents, which require frequent surgical replacements for blockages and encrustation. More durable metallic stents are available, although these incur an increased initial purchase price. Aims: We aim to assess whether the use of polyurethane double-J (JJ) or metallic stent, Resonance® is more cost-effective for managing MUO in the UK healthcare setting. Methods: A Markov model was parameterised to 5 years with costs and health-related quality-of-life consequences for treating MUO with Resonance metallic stent (Cook Medical), versus standard JJ stents, from the UK care system perspective, with 3.5% discounting. Deterministic and probabilistic sensitivity analyses were undertaken to assess the effect of uncertainty. Results: Over 5 years, approximately four fewer repeat surgical interventions were estimated in the metallic stent arm compared with the JJ stent, driving a 23.4% reduction in costs. The mean estimates of costs and benefits indicate that treatment of MUO with Resonance for 5 years is dominant over JJ stents. Over 5 years a cost-saving of £2164.74 and a health gain of +0.046 quality-adjusted life years (QALYs) per patient is estimated. With a maximum willingness to pay of £20 k per QALY, a net monetary benefit (NMB) of £3077.83 is estimated. Probabilistic sensitivity analysis at a willingness to pay threshold of £20 000 indicates an 89.3% probability of Resonance being cost-effective over JJ stents. Within 1-year savings of £726.53 are estimated driven by a reduction of two fewer repeat surgical interventions when using the metallic stent. Conclusions: Resonance metallic stents for the treatment of MUO reduce the number of repeat procedures and could be a cost-effective option for the treatment, potentially offering efficiencies to the healthcare system.

Hydronephrosis Due to Intraureteral Migration of Missed Intrauterine Device.

Migration of intrauterine devices (IUDs) to the ureter causing ureteral obstruction is an extremely rare event. A 45-year-old female patient was admitted to our hospital with a complaint of pain in the right flank and inferior right quadrant of the abdomen. On genitourinary system ultrasonography, grade 3 hydronephrosis was found in the right kidney. On the abdominopelvic radiography, there was an appearance consistent with two IUDs, one in the region consistent with the course of the right distal ureter and the other in the usual localisation. The first IUD was thought to have spontaneously detached from the uterus, so a second IUD was implanted. A right-sided extravesical ureteroneocystostomy (Lich-Gregoir) operation was performed. The operation was terminated with the placement of a 4.8 French, 26 cm double-J stent in the ureter. The patient was followed up in our hospital for 26 months and she was asymptomatic during follow-up, hydronephrosis was resolved completely, and no complications were encountered during follow-up clinical and ultrasonography examinations.

The STING in the tale of Teflon®: Delayed ureteric obstruction after subureteric transurethral injection with polytetrafluoroethylene paste for vesicoureteral reflux.

INTRODUCTION: "Subureteric Teflon INGection" (STING) of polytetrafluoroethylene (PTFE/polytef) paste to treat vesicoureteral reflux (VUR) in children was popularised in 1984. It was later abandoned as an implantation material because of the possibility of migration from the injection site. Giant-cell foreign-body granuloma to Polytef in the bladder is a rare cause of ureteric obstruction. Only a handful of cases have been reported in the literature. METHODS: We performed a prospective analysis of a series of 6 adult patients who had childhood STING and presented with foreign-body granuloma to Polytef in the bladder. We report their clinical presentation, findings and treatment. RESULTS: 1 male and 5 females with a history of STING procedure in childhood for VUR presented in later life with foreign-body granuloma to Polytef. The median age at first STING procedure and at presentation to the Urology Department was 3 and 34 years respectively. The most common clinical presentations were flank pain and urinary tract infection (UTI) and all patients had radiological findings of calcified lesions at the vesicoureteric junction(s). 4 patients had histological findings of giant-cell foreign-body granuloma. 4 patients required definitive ureteric reimplantation. CONCLUSION: Polytef granuloma causing distal ureteric obstruction may give rise to significant morbidity and renal damage. Due to the likelihood of progression of the granuloma, excision and ureteric reimplantation is considered the standard approach in the management of patients with viable kidneys. LEVEL OF EVIDENCE: Level 5.

The implications when offering percutaneous nephrostomy for the management of malignant obstructive uropathy secondary to urological malignancy: can we be more selective?

Background & Objectives: Percutaneous nephrostomy (PN) for malignant ureteric obstruction (MUO) is increasingly accessible with high success rates. However, it is not without associated risks and morbidity, impacting quality of life, while not improving overall survival. In two UK hospitals, we investigated the outcomes of undergoing PN for MUO, to inform future patient counselling and selection for this intervention. Methods: A retrospective audit of electronic records identified patients that received PN for bladder, and prostate cancer (PCa) between January 2015 and December 2018. Hospital 1 had a 24-h nephrostomy service, while Hospital 2 had a limited service; Group A: recurrent or treatment-resistant PCa, Group B: primary PCa, Group C: Bladder cancer. Results: A total of 261 patients (Hospital 1 = 186, Hospital 2 = 75), had PN insertion. Seventy-eight had prostate or bladder cancer. Group A n = 30, Group B n = 12, Group C n = 36. Median age = 79 [interquartile range (IQR) = 72-86]. Following PN insertion, 12-month mortality was significantly greater in Hospital 1 at 82%, versus 52% in Hospital 2 (p = 0.015). Median survival: Group A: 177 days (IQR = 80-266), Group B: 209 days (IQR = 77-352), Group C: 145 days (IQR = 97-362). There was no significant difference in same-admission mortality, although group A had the greatest same-admission mortality at 17%. A total of 69% of all patients received bilateral nephrostomies. Patients with bilateral versus unilateral PN had no difference in mortality or nadir creatinine. Conclusion: Most patients with malignant obstruction secondary to prostate or bladder cancer lived less than 12 months after PN insertion. When offering PN, careful consideration of disease prognosis should be made, and frank discussion of the implications of a life-long nephrostomy with patients and relatives.

Uretero-neocystostomy: a retrospective comparison of open, laparoscopic and robotic techniques.

BACKGROUND: Uretero-neocystostomy (UNC) is the gold-standard for distal-ureter repair. Whether the surgery should be conducted minimally invasive (laparoscopic (LAP), robotic RAL)) or open remains unanswered by the literature. METHODS: Retrospective analysis of surgical outcome of patients treated with UNC for distal ureteral stenosis (January 2012 - October 2021). Patient demographics, estimated blood loss (EBL), surgical technique, operative time, complications and length of hospital stay (LOS) were recorded. During the follow-up period, patient underwent renal ultrasound and kidney function tests. Success was defined as relieve of symptoms or no findings of obstruction needing urine drainage. RESULTS: 60 patients were included (9 RAL, 25 LAP, 26 open). The different cohorts were similar of age, gender, American Society of Anesthesiologists (ASA) score, body-mass index and history of prior treatment of the ureter. No intraoperative complications were detected in all groups. There was no conversion to open surgery in the RAL group, whereas one was found in the LAP arm. Six patients had a recurrent stricture, but with no significant difference between the cohorts. EBL was not different between the groups. LOS was significantly lower in the RAL + LAP group compared to open (7 vs. 13 days, p = 0.005) despite significantly longer operating times (186 vs. 125.5 min, p = 0.005). CONCLUSION: Minimal invasive UNC, especially RAL, is a feasible and safe surgical method and provides similar results in terms of success rates in comparison to open approach. A shorter LOS could be detected. Further prospective studies need to be done.

Intrinsic unilateral ureteral endometriosis: A rare case report.

INTRODUCTION AND IMPORTANCE: Ureteral endometriosis is a rare disease and it has variable and subtle clinical presentation and often it lead to delayed diagnosis and worse outcome. CASE PRESENTATION: Here we present a 44-year-old married lady who presented with dull aching right iliac fossa pain. CT urography right moderate hydro-uretero nephrosis with a suspicion of a mass in the lower right ureter. Diagnostic rigid ureteroscopy showed completely intraluminal polypoidal pedunculated right lower ureteral mass with near total occlusion of the lumen, which was excised completely by Ho: Yag laser. Histopathology confirmed pure endometriosis tissue with no ureteral tissue. Follow up showed no recurrence of the mass, however eventually the patient developed deterioration in kidney function due to the long-standing undiscovered obstruction. CLINICAL DISCUSSION: Ureteral endometriosis can cause silent obstruction for a long time. Surgical intervention has different modalities according to the type of U.E, and it is the appropriate treatment method for U.E causing complete obstruction to preserve kidney function. CONCLUSION: Ureteral endometriosis is a rare but should be included in the differential diagnosis of premenopausal women with ureteral obstruction of unknown cause. Early intervention is critical for better outcomes.

Use of metallic ureteric stents for chronic ureteric obstruction and its association with value-based care.

Introduction: We aimed to compare the real-world data and our clinical experience with metallic stents (MSs) and conventional polymeric stents (PSs) in the management of both malignant and benign chronic ureteric obstruction (CUO), in terms of clinical outcomes and costs. Methods: Clinical data from our institution, including outcomes for all ureteric stents inserted for long-term management of CUO from all causes from 2014 to 2017, were retrospectively reviewed and compared between the MS and PS episodes. Results: A total of 247 stents were placed in 63 patients with CUO over the 4-year study period. Of these, 45 stents were MSs. There was no significant difference in all baseline characteristics between the MS and PS groups, except for the aetiology of obstructive cause. Mean indwelling stent duration was significantly greater for MS than for PS (228.6 ± 147.0 vs. 146.1 ± 66.0 days, P < 0.001), thereby leading to lower average number of stent changes per year in the MS group compared to the PS group (1.4 vs. 6.3 times, respectively). Despite the higher unit cost of MS compared to PS, there was no significant mean cost difference overall (cost per dwelling day SGD 7.82 ± SGD 10.44 vs. SGD 8.23 ± SGD 20.50, P = 0.888). Conclusion: Resonance MS is a better option than PS to manage CUO from malignant and benign causes because its significantly longer indwelling time mitigates the higher unit cost of the stent. It potentially reduces the number of procedures and operations in patients. Thus, it should be considered for all patients with CUO requiring long-term ureteric drainage.

A Rare and Late Complication of Subureteric Teflon Injection With Non-Animal Stabilized Hyaluronic Acid/Dextranomer Gel.

Primary non-syndromic vesicoureteral reflux (VUR) is the commonest paediatric anomaly of the urinary tract. Complications of high-grade VUR include recurrent urinary tract infections, pyelonephritis, reflux nephropathy, and irreversible renal failure. The primary aim of its management centres on minimizing the number of urinary tract infections and renal scarring via surgical correction or continuous antibiotic prophylaxis. A rare complication of surgical treatment by subureteric Teflon injection with non-animal stabilized hyaluronic acid/dextranomer gel (NASHA/Dx) is ureteric obstruction. We report the case of a 38-year-old female who was diagnosed with ureteric obstruction secondary to subureteric injection with Deflux injection 30 years after endoscopic correction of VUR. She was successfully treated with ureteric reimplantation. Although considered efficient and safe, subureteric injection of bulking agent Deflux can be associated with delayed ureteric obstruction. This case highlights the need for long-term follow-up to allow timely detection and management of delayed ureteric obstruction. The possibility of late complication must also be addressed when obtaining pre-operative informed consent.

Acute kidney injury from presumptive intramural ureteral hemorrhage secondary to diphacinone rodenticide exposure in a dog.

OBJECTIVE: To describe the clinical features and outcome of a dog with anticoagulant rodenticide (diphacinone) exposure, which was subsequently diagnosed with a coagulopathy characterized by hemoperitoneum, and presumptive ureteral wall hemorrhage contributing to acute kidney injury (AKI). CASE SUMMARY: A 4-year-old, female neutered Australian Cattle Dog was evaluated for an acute onset of lethargy, decreased appetite, and a mild right thoracic limb lameness. Radiographs and point of care ultrasound demonstrated retroperitoneal and peritoneal effusion. Diagnostic abdominocentesis confirmed hemorrhagic effusion. Complete blood count, biochemistry, and coagulation profile showed a regenerative anemia (PCV 32%), thrombocytopenia (platelets 96 × 109 /L [96 × 103 /µl]), azotemia (BUN 38.9 mmol/L [109 mg/dl], creatinine 512.8 µmol/L [5.8 mg/dl]), and coagulopathy (prothrombin time >100 s, activated partial thromboplastin time >42.3 s). The client reported access to anticoagulant rodenticide up to 72 hours prior to presentation. Ultrasonographic examination revealed bilateral pyelectasia and hydroureter with thickened distal ureteral walls at the level of the ureteral-vesicular junctions. The ultrasonographic conclusion was presumptive intramural ureteral hemorrhage resulting in ureteral obstruction. The patient was diagnosed with AKI with likely prerenal, renal, and postrenal components. Treatment included vitamin K and frozen plasma transfusion. The patient recovered fully and was discharged 3 days after presentation. Two days after discharge, the patient had improvement in azotemia (BUN 10.7 mmol/L [30 mg/dl], creatinine 176.6 µmol/L [2.0 mg/dl]). Gas chromatography-mass spectrometry confirmed presence of diphacinone in the blood. Repeat ultrasound and biochemistry 60 and 210 days, respectively, after discharge showed resolution of ureteral wall thickening, hydroureter, pyelectasia, and recovery of kidney parameters. NEW OR UNIQUE INFORMATION: Although nephropathies secondary to anticoagulant therapy have been described in people, the authors believe this is the first report of diphacinone anticoagulant rodenticide exposure contributing to an AKI secondary to obstruction from ureteral wall hemorrhage in the veterinary literature.

Effect of a novel phosphodiesterase type 5 inhibitor,CPD1,on unilateral renal interstitial fibrosis caused by ureteric obstruction in mice / 中国药理学通报

Aim To investigate the effects of CPD1,a novel phosphodiesterase 5 inhibitor,on renal pathological phenotype and fibrotic protein expression in renal fibrosis model mice. Methods Male C57BL/6 J mice were divided into three groups randomly(sham group,UUO group and UUO+CPD1 group). Unilateral ureteric obstruction model was constructed by surgery,and CPD1(5 mg·kg-1·d-1)was administered by intragastric administration two hours after the modeling for seven days. HE and Sirius Red staining were used to observe the distribution of tissue structural lesions and fibrosis. Immunohistochemical staining and Western blot were used to detect the expression of fibronectin(FN),α-SMA,collagen-I and kidney injury molecule-1(Kim-1). Results Compared with sham operation group,the renal tubules of mice were dilated and accompanied by a large amount of inflammatory infiltration. Moreover,the expressions of FN,α-SMA,collagen-I and Kim-1 proteins increased significantly(P<0.05)in UUO group. CPD1 treatment improved the kidney structure and decreased the expression of collagen fibers. Furthermore,CPD1 inhibited the expression of FN,α-SMA,collagen-I and Kim-1 markedly(P<0.05). Conclusions Phosphodiesterase 5 inhibitor CPD1 alleviates the progression of renal fibrosis induced by unilateral ureteral obstruction through down-regulating ECM deposition in the extracellular matrix and expression of Kim-1. The specific mechanism remains to be further studied.

Ureteral Endometriosis Presenting As Left Ureteral Obstruction: A Case Report.

Ureteral endometriosis is a very rare but serious form of infiltrating endometriosis since the risk of urinary tract obstruction and secondary loss of renal function exists. Although not always possible, the clinical and radiologic assessment may help in obtaining a preoperative diagnosis. We report the case of a 42-year-old woman with left ureteral endometriosis, revealed by left flank pain. Imaging revealed left obstructive uropathy with an endometriotic cyst of the left ovary and a spiculated lesion of the left parametrium. She underwent laparotomy, resection of the diseased ureter with primary re-anastomosis, resection of a left parametrial lesion and an endometriotic left ovarian cystectomy. The pathological assessment confirmed the diagnosis of ureteral endometriosis. Follow-up of the patient showed complete resolution with a stable, normal kidney function. In conclusion, ureteral endometriosis involvement is infrequent but should be included in the differential diagnosis in a premenopausal woman with ureteral obstruction of unknown cause. An early diagnosis and obstruction relief are critical to a successful outcome.

Spontaneous Rupture of the Renal Pelvis Due to Extrinsic Obstruction by Metastatic Retroperitoneal Lymphadenopathy.

Spontaneous rupture of the renal pelvis due to metastatic disease is a rare complication. Renal pelvis rupture often goes undiagnosed in cases of non-traumatic origin due to its vague abdominal and flank symptoms. We present a case of an 81-year-old male with primary non-small cell lung cancer who had renal pelvis rupture due to extrinsic compression of the ureter by retroperitoneal lymphadenopathy secondary to metastatic disease.

Comparison of the effects of extrinsic compression on the drainage performance of three ureteric stents.

OBJECTIVES: To share our centre's experience dealing with ureteric obstruction, in particular malignant obstructions, by investigating the deformation and flow velocity of three commonly used, readily accessible ureteric stents under at different compression levels and surface change at three time points (new, 1 month and 3 months after implantation). SUBJECTS AND METHODS: Scanning electron microscope (SEM) analysis was conducted on ureteric JJ stents, including the Cook Universa Soft, the Kang Yi Bo (KYB) antireflux and the Urovision Visiostar ESWL JJ stents. Deformation caused by compression was measured using a digital force gauge. Intraluminal flow velocity was tested with the stents subject to different compression levels. RESULTS: The Urovision Visiostar JJ stent demonstrated significantly better anti-compression capability. The Cook Universa Soft and KYB antireflux JJ stents showed favourable draining velocity without compression, but the velocity dropped substantially on compression. The velocity of the KYB antireflux JJ stent reduced substantially after 3 months of implantation, while the Urovision Visiostar achieved the best draining effect when under compression at all three time points. CONCLUSION: The Urovision Visiostar JJ stent demonstrated significantly greater resistance to compression than the other two JJ stents, as well as better drainage under compression. Patients with benign or malignant ureteric compression might benefit from use of the Urovision Visiostar stent. Large prospective clinical trials are needed to confirm these findings.

Discovery of indol-6-yl-pyrrolo[2,3-c]pyridin-7-one derivatives as bromodomain-containing protein 4 (BRD4) inhibitors for the treatment of kidney fibrosis.

Uncovering new therapeutics for kidney fibrosis hold promise for chronic kidney disease (CKD). Considerable studies confirmed that BRD4 inhibition ameliorated kidney injury and fibrosis. In the study, we synthesized a series of indol-6-yl-pyrrolo[2,3-c]pyridin-7-one derivatives and biologically evaluated against BRD4 for structure-activity relationship (SAR). Notably, compound 3r (ZLD2218) exhibited the most potent inhibitory activity against BRD4, with the IC50 value of 107 nM, which was comparative to 92 nM of positive control JQ-1. Importantly, at the dose of 15 and 30 mg/kg/d for consecutive 8 days, ZLD2218 alleviated kidney injury and fibrosis in unilateral ureteral obstruction (UUO) mice, with the 30 mg/kg/d being competitive to 100 mg/kd/d of JQ1. Mechanically, ZLD2218 inhibited BRD4 expression and further suppressed fibrotic signaling in the kidneys of UUO mice and TGF-ß1-stimulated TCMK-1 cells. Furthermore, ZLD2218 at the dose of 30 mg/kg/d for 8 days to C57BL/6J mice did not affect liver, kidney function and organ pathological changes. Collectively, compound 3r (ZLD2218) might be a promising lead compound of BRD4 inhibitor for the treatment of kidney fibrosis.

Evaluation of Galdakao-modified Valdivia position in endoscopic management of malignant ureteric obstruction.

BACKGROUND: Malignant ureteric obstruction (MUO) due to pelvic malignancies is challenging for endourological management and carries high failure rates for retrograde cystoscopic ureteric stenting. METHODS: We adopted Galdakao-modified Valdivia (GMV) position in the management of MUO in an operating room equipped with a C-arm fluoroscopy unit and an ultrasound device. We prospectively studied the added value of this approach in 50 cases who failed retrograde ureteric stenting. RESULTS: Thirty-seven (74%) cases were done under a high level of spinal anesthesia. Mean operative time was 62 min. Antegrade ureteric stenting succeeded in 45/50 (90%) patients who failed retrograde ureteric stenting. GMV position facilitated simultaneous retrograde and antegrade management of MUO. Eight patients (16%) underwent auxiliary cystoscopic procedures to reduce the mass over the ureteric orifice (UO) guided by antegrade methylene blue or over a probing antegrade guidewire. Nephrostomy tube was inserted in the same setting in 16/50 (32%) cases. Antegrade flow of contrast to the bladder (P < 0.001) and ureteric kinks rather than tight stenosis or infiltration of UO (P = 0.014) were significantly associated with the success of antegrade ureteric stenting. No major complications were encountered. CONCLUSION: GMV position is an ideal choice for management of MUO as it allows simultaneous access to the lower and the upper urinary systems to accomplish ureteric stenting either in a retrograde or an antegrade fashion as well as the ability to insert a nephrostomy tube in the same setting, thus shortening the inpatient care and this should be the standard of care in cases with MUO.

Jackstones in the renal pelvis: A rare calculus.

Jackstones are a rare subtype of calculi, characterised by radiating spicules. We describe a case of multiple jackstones in the urinary upper tract. A 53-year-old man was referred for evaluation of left flank pain. Imaging revealed a left pelvic-ureteric junction obstruction and several left renal calculi. A left supine percutaneous nephrolithotomy was performed and two jackstone calculi were extracted. The presence of multiple jackstones in the renal pelvis should prompt for evaluation for obstruction and complete stone clearance should be achieved to avoid recurrence.

Safety of neoadjuvant chemotherapy in patients with muscle-invasive bladder cancer and malignant ureteric obstruction.

OBJECTIVES: To determine whether patients with carcinoma invading bladder muscle (MIBC) and ureteric obstruction can safely receive cisplatin-based neoadjuvant chemotherapy (C-NAC), and to determine whether such patients require relief of obstruction with a ureteric stent or percutaneous nephrostomy prior to beginning C-NAC. PATIENTS AND METHODS: We performed a single-institution retrospective analysis of MIBC patients receiving C-NAC and falling into three groups: no ureteric obstruction (NO); relieved ureteric obstruction (RO); and unrelieved ureteric obstruction (URO). To address whether patients with obstruction can safely receive C-NAC, we compared patients with NO to those with RO, with the primary outcome of premature chemotherapy discontinuation. To investigate whether patients with obstruction should have the obstruction relieved prior to NAC, we compared RO to URO patients using a primary composite outcome of grade ≥ 3 adverse events, premature chemotherapy discontinuation, dose reduction, or dose interruption. The primary outcomes were compared using multivariable logistic regression. Sensitivity analyses were performed for the RO vs URO comparison, in which patients with only mild degrees of obstruction were excluded from the URO group. RESULTS: A total of 193 patients with NO, 49 with RO, and 35 with URO were analysed. There were no statistically significant differences between those with NO and those with RO in chemotherapy discontinuation (15% vs 22%; P = 0.3) or any secondary outcome. There was no statistically significant difference between those with RO and URO in the primary composite outcome (51% vs 53%; P = 1) or any secondary outcome. CONCLUSION: Patients with ureteric obstruction can safely receive C-NAC. Relief of obstruction was not associated with increased safety of C-NAC delivery.

In vivo evidence for therapeutic applications of beclin 1 to promote recovery and inhibit fibrosis after acute kidney injury.

Autophagy regulator beclin 1 activity determines the severity of kidney damage induced by ischemia reperfusion injury, but its role in kidney recovery and fibrosis are unknown and its therapeutic potentials have not been tested. Here, we explored beclin 1 effects on kidney fibrosis in three models of acute kidney injury (AKI)-ischemia reperfusion injury, cisplatin kidney toxicity, and unilateral ureteric obstruction in mouse strains with three levels of beclin 1 function: normal (wild type), low (heterozygous global deletion of beclin 1, Becn1+/-), and high beclin 1 activity (knockin gain-of-function mutant Becn1, Becn1FA). Fourteen days after AKI induction, heterozygous mice had more, but knockin mice had less kidney fibrosis than wild-type mice did. One day after ischemia reperfusion injury, heterozygous pan-kidney tubular Becn1 null mice had more severe kidney damage than homozygous distal tubular Becn1 null mice did, which was similar to the wild-type mice, implying that proximal tubular beclin 1 protects the kidney against ischemia reperfusion injury. By 14 days, both pan-kidney heterozygous Becn1 null and distal tubular homozygous Becn1 null mice had poorer kidney recovery than wild-type mice did. Injection of beclin 1 peptides increased cell proliferation in kidney tubules in normal mice. Beclin 1 peptides injection either before or after (2-5 days) ischemia reperfusion injury protected the kidney from injury and suppressed kidney fibrosis. Thus, both endogenous beclin 1 protein expression in kidney tubules and exogenous beclin 1 peptides are kidney protective via attenuation of acute kidney damage, promotion of cell proliferation, and inhibition of kidney fibrosis, consequently improving kidney recovery post-AKI. Hence, exogenous beclin 1 peptide may be a potential new therapy for AKI.