Contralateral renal change in a unilateral ureteral obstruction rat model using intravoxel incoherent motion diffusion-weighted imaging.

OBJECTIVES: Most functional magnetic resonance research has primarily examined alterations in the affected kidney, often neglecting the contralateral kidney. Our study aims to investigate whether imaging parameters accurately depict changes in both the renal cortex and medulla in a unilateral ureteral obstruction rat model, thereby showcasing the utility of intravoxel incoherent motion (IVIM) in evaluating contralateral renal changes. METHODS: Six rats underwent MR scans and were subsequently sacrificed for baseline histological examination. Following the induction of left ureteral obstruction, 48 rats were scanned, and the histopathological examinations were conducted on days 3, 7, 10, 14, 21, 28, 35, and 42. The apparent diffusion coefficient (ADC), pure molecular diffusion (D), pseudodiffusion (D*), and perfusion fraction (f) values were measured using IVIM. RESULTS: On the 10th day of obstruction, both cortical and medullary ADC values differed significantly between the UUO10 group and the sham group (p < 0.01). The cortical D values showed statistically significant differences between UUO3 group and sham group (p < 0.01) but not among UUO groups at other time point. Additionally, the cortical and medullary f values were statistically significant between the UUO21 group and the sham group (p < 0.01). Especially, the cortical f values exhibited significant differences between the UUO21 group and the UUO groups with shorter obstruction time (at time point of 3, 7, 10, 14 day) (p < 0.01). CONCLUSIONS: Significant hemodynamic alterations were observed in the contralateral kidney following renal obstruction. IVIM accurately captures changes in the unobstructed kidney. Particularly, the cortical f value exhibits the highest potential for assessing contralateral renal modifications.

Doppler Ultrasound and Resistive Indices in the Diagnosis of Ureteropelvic Junction Obstruction in the Pediatric Population.

OBJECTIVES: Mercapto acetyl tri-glycine renogram (MAG3) scan has been the gold standard assessment of pediatric ureteropelvic junction obstruction (UPJO) but requires intravenous access and radiation exposure. While Doppler ultrasound measurements of resistive indices (RI) of the arcuate arteries have been proposed as an alternative assessment of obstruction, they have not been widely adopted in the pediatric population. We hypothesized that RI of the main renal artery (RA) is more strongly correlated with MAG3 findings than arcuate RI. METHODS: Pediatric patients with unilateral Society for Fetal Urology grade 3-4 hydronephrosis undergoing concomitant RUS and MAG3 were recruited. Doppler ultrasound peak systolic velocity (PSV); RI of bilateral RA at the origin, middle, and hilum; and RI of the superior, middle, and lower pole arcuate arteries were obtained. MAG3 differential renal function (DRF) and T½ were recorded. Differences in RI measurements (DRI) between the affected and normal kidney were calculated and compared with DRF and T½. RESULTS: 31 patients (median 4.6-month-old) were enrolled. Only RA RI at the origin differed between affected and normal kidneys (p < .001). DRI RA at the origin showed weak evidence for an association with MAG3 DRF < 40% (p .07). DRI was not associated with T½ > 20 minutes. CONCLUSION: There was weak evidence for an association between RA DRI at the origin and DRF but not with T½. These findings suggest that RA DRI may provide additional data in the evaluation of patients with UPJO to tailor the use of MAG3 and associated risk of radiation exposure to those patients most at risk for concomitant renal function impairment.

Kidney computed tomography perfusion in patients with ureteral obstruction.

INTRODUCTION: Kidney perfusion on CT is an encouraging surrogate for renal scintigraphy in assessing renal function. However, data on dynamic volumetric CT in patients with kidney obstruction is lacking. Thus, the aim of this study is to determine the feasibility of CT-based renal perfusion using a dynamic volume to assess renal hemodynamics at different degrees and durations of obstruction. MATERIALS AND METHODS: We included patients with unilateral kidney obstruction in our single-center, prospective study. The patients were divided into three groups. Patients without dilatation of the pelvicalyceal system (PCS) and normal parenchyma thickness were included into Group 1; patients with PCS dilatation and parenchyma thickness 1.8-2.4 cm-into Group 2; and patients with ureteropyelocalicoectasia and parenchyma thickness less than 1.8 cm-into Group 3. RESULTS: Total of 56 patients were enrolled. In Group 1 mean values of cortical and medullar arterial blood flow, blood volume, and extraction fraction were within the normal range. Changes in contralateral kidney were not determined. Patients from Group 2 showed significant differences in blood flow parameters in the cortical and medulla of the obstructed kidney. No changes in perfusion values in the contralateral kidney was observed. In patients from Group 3 there was a marked decrease in perfusion on the side of obstruction compared to Group 2, indicating that the degree of expansion of the PCS directly correlates with the change in blood flow. However, in the contralateral kidney, these indicators exceeded the normal values of perfusion. CONCLUSION: CT perfusion allows to objectively assess changes in blood flow in the setting of renal obstruction. The degree of obstruction directly affects the measured rate of blood flow.

Poliuria post-obstructiva. Análisis fisiopatológico de un caso / Post-obstructive polyuria. Pathophysiological analysis of a case

The relief of the impediment to urinary flow is the treatment of acute kidney failure due to urinary tract obstruction. However, there is a risk of inducing massive polyuria, which can be self-limited or produce severe contraction of the intravascular volume with pre-renal acute kidney failure and alterations in the internal environment. Polyuria, urine output > 3 L/d or > 200 mL/min for more than 2 hours, can have multiple causes, and can be classified as osmotic, aqueous or mixed. Post-obstructive polyuria obeys different pathogenic mechanisms, which overlap and vary during a patient's evolution. Initially, there is a decrease in vasoconstrictor factors and an increase in renal blood flow, which, added to the excess of urea accumulated, will cause intense osmotic diuresis (osmotic polyuria due to urea). Added to these factors are the positive sodium and water balance during acute renal failure, plus the contributions of crystalloid solutions to replace diuresis (ionic osmotic polyuria). Finally, there may be tubular dysfunction and decreased solutes in the renal medullary interstitium, adding resistance to the action of vasopressin. The latter causes a loss of free water (mixed polyuria). We present the case of a patient with post-obstructive polyuria where, by analyzing the clinical symptoms and laboratory alterations, it was possible to interpret the mechanisms of polyuria and administer appropriate treatment for the pathogenic mechanism.

[Post-obstructive polyuria. Pathophysiological analysis of a case]. / Poliuria post-obstructiva. Análisis fisiopatológico de un caso.

The relief of the impediment to urinary flow is the treatment of acute kidney failure due to urinary tract obstruction. However, there is a risk of inducing massive polyuria, which can be self-limited or produce severe contraction of the intravascular volume with pre-renal acute kidney failure and alterations in the internal environment. Polyuria, urine output > 3 L/d or > 200 mL/min for more than 2 hours, can have multiple causes, and can be classified as osmotic, aqueous or mixed. Post-obstructive polyuria obeys different pathogenic mechanisms, which overlap and vary during a patient's evolution. Initially, there is a decrease in vasoconstrictor factors and an increase in renal blood flow, which, added to the excess of urea accumulated, will cause intense osmotic diuresis (osmotic polyuria due to urea). Added to these factors are the positive sodium and water balance during acute renal failure, plus the contributions of crystalloid solutions to replace diuresis (ionic osmotic polyuria). Finally, there may be tubular dysfunction and decreased solutes in the renal medullary interstitium, adding resistance to the action of vasopressin. The latter causes a loss of free water (mixed polyuria). We present the case of a patient with post-obstructive polyuria where, by analyzing the clinical symptoms and laboratory alterations, it was possible to interpret the mechanisms of polyuria and administer appropriate treatment for the pathogenic mechanism.

Metal stent for the ureteral stricture after surgery and/or radiation treatment for malignancy.

BACKGROUND: To assess the efficacy and safety of self-expanding metal ureteral stent for the stricture following surgery and/or radiation for malignancy. METHODS: We performed 36 metal ureteral stent insertion procedures (32 patients) between May 2019 and June 2020. The main inclusion criterion was the patients with ureteral stricture due to surgery and/or radiation treatment for malignancy. The diagnosis of stricture was ascertained by history and radiographic imaging. The etiologies underlying the strictures were: surgery and/or radiation therapy for cervical and rectal cancer, surgery for ovarian cancer. The primary outcome was the stent patency rate, and the secondary outcomes were the postoperative complications and glomerular filtration rate (GFR). Stent patency was defined as stent in situ without evident migration, unanticipated stent exchange or recurrent ureteral obstruction. Cost analysis was calculated from stent cost, anesthesia cost and operating room fee. RESULTS: The pre-metallic stent GFR was 22.53 ± 6.55 mL/min/1.73 m2. Eight patients were on double-J stents before insertion of metallic stents. The total annual cost of per patient in our study was $10,600.2 US dollars (range $9394.4-$33,527.4 US dollars). During a median follow-up time of 16 months (range 8-21 months), 27 cases (31 sides, 84%) remained stent patency. Twelve patients died from their primary malignancy carrying a patency stent. Stent migration was observed in 4 patients within 10 months after insertion. Ectopic stents were endoscopically removed and replaced successfully. Three stents were occluded, and no encrustation was seen in our study. Three and four patients had postoperative fever and gross hematuria, respectively. Infection was observed in 2 cases, mandating antibiotics therapy. In addition, postoperative volume of hydronephrosis postoperatively was significantly reduced compared with preoperation (54.18 ± 15.42 vs 23.92 ± 8.3, P = 0.019). However, no statistically significant differences regarding GFR, creatinine levels, blood urea nitrogen and hemoglobin existed between preoperation and last follow-up. CONCLUSIONS: The current study demonstrated that metal ureteral stent is effective and safe in the treatment of stricture following surgery and/or radiation therapy for malignant cancer. Patients hydronephrosis could be improved by the stent placement.

Quantitative evaluation of upper urinary tract pump function in pigs with acute unilateral lower ureteral obstruction by 640-slice dynamic volume CT.

BACKGROUND: It is a challenging problem to differentiate obstructive hydronephrosis from noninvasive evaluation of renal pelvis and ureteral motility in patients. The purpose of this study was to explore the value of 640-slice dynamic volume CT (DVCT) in the quantitative measurement of upper urinary tract (UUT) pump function after acute unilateral lower ureteral obstruction in pigs. METHODS: In this study, a perfusion pig model was constructed by constant pressure perfusion testing of the renal pelvis and left nephrostomy. The perfusion and pressure measuring devices were connected to create a state of no obstruction and acute obstruction of the lower part of the left ureter. After successful modelling, continuous dynamic volume scanning of the bilateral renal excretion phase was performed with 640-slice DVCT, and pump functions of the renal pelvis and part of the upper ureter were calculated and analysed. No obstruction or acute obstruction of the lower part of the left ureter was observed. Pump functions of the renal pelvis and part of the upper ureter were determined. RESULTS: The results showed that after LUUT fistulostomy, the time difference between the average UUT volume and positive volume value increased gradually, and the calculated flow velocity decreased, which was significantly different from that of the RUUT. The volume difference of the LUUT increased significantly in mild obstruction. In the bilateral control, the volume change rate of the LUUT increased with mild obstruction and decreased with severe obstruction, and there was a significant difference between the left and right sides. CONCLUSION: The continuous dynamic volume scan and measurement of 640-slice DVCT can obtain five pump function datasets of UUT in pigs with acute lower ureteral obstruction.

Pyeloplasty in Adults With Ureteropelvic Junction Obstruction in Poorly Functioning Kidneys: A Systematic Review.

OBJECTIVES: To systematically summarize the available evidence concerning the impact of pyeloplasty on symptoms and differential renal function (DRF) in adults with unilateral UPJO in poorly functioning kidneys (PFK), and to identify potential predictors of kidney function recovery that could help clinicians select candidates for pyeloplasty. METHODS: A literature search (MEDLINE, Embase, Google Scholar, Scopus, ClinicalTrials.gov, and the WHO Clinical Trials Registry) and systematic review were performed up to September 2020 according to the PRISMA guidelines. PFK were defined as a baseline DRF ≤30% on renal scintigraphy. The primary endpoints were symptom relief and postoperative scintigraphic DRF. Predictors of kidney function recovery were evaluated and compared among studies. RESULTS: Nine studies comprising 731 patients met the inclusion criteria and were included for evidence synthesis. A DRF increase >5% occurred in 13.3%-53.8% of 160 patients with a pre- and postoperative renal scan. Symptoms improved in 73.3%-93.3% of 141 adults after pyeloplasty. Neither patient's age, baseline DFR, comorbidities, degree of hydronephrosis, kidney parenchymal thickness, nor kidney biopsy findings consistently predicted a significant DRF increase among 375 patients undergoing pyeloplasty. CONCLUSION: Based on a low level of evidence, pyeloplasty may relieve symptoms and stabilize kidney function in adults with UPJO in PFK. A significant number of patients showed a DRF increase >5%, yet no consistent predictor of kidney function recovery was identified. Until more evidence becomes available, pyeloplasty could be considered for selected cases after accounting for the risks of a failure requiring a future nephrectomy.

Gastrin, via activation of PPARα, protects the kidney against hypertensive injury.

Hypertensive nephropathy (HN) is a common cause of end-stage renal disease with renal fibrosis; chronic kidney disease is associated with elevated serum gastrin. However, the relationship between gastrin and renal fibrosis in HN is still unknown. We, now, report that mice with angiotensin II (Ang II)-induced HN had increased renal cholecystokinin receptor B (CCKBR) expression. Knockout of CCKBR in mice aggravated, while long-term subcutaneous infusion of gastrin ameliorated the renal injury and interstitial fibrosis in HN and unilateral ureteral obstruction (UUO). The protective effects of gastrin on renal fibrosis can be independent of its regulation of blood pressure, because in UUO, gastrin decreased renal fibrosis without affecting blood pressure. Gastrin treatment decreased Ang II-induced renal tubule cell apoptosis, reversed Ang II-mediated inhibition of macrophage efferocytosis, and reduced renal inflammation. A screening of the regulatory factors of efferocytosis showed involvement of peroxisome proliferator-activated receptor α (PPAR-α). Knockdown of PPAR-α by shRNA blocked the anti-fibrotic effect of gastrin in vitro in mouse renal proximal tubule cells and macrophages. Immunofluorescence microscopy, Western blotting, luciferase reporter, and Cut&tag-qPCR analyses showed that CCKBR may be a transcription factor of PPAR-α, because gastrin treatment induced CCKBR translocation from cytosol to nucleus, binding to the PPAR-α promoter region, and increasing PPAR-α gene transcription. In conclusion, gastrin protects against HN by normalizing blood pressure, decreasing renal tubule cell apoptosis, and increasing macrophage efferocytosis. Gastrin-mediated CCKBR nuclear translocation may make it act as a transcription factor of PPAR-α, which is a novel signaling pathway. Gastrin may be a new potential drug for HN therapy.

Interferon-γ enhances the therapeutic effect of mesenchymal stem cells on experimental renal fibrosis.

Mesenchymal stem cells (MSCs) administered for therapeutic purposes can be activated by interferon-γ (IFN-γ) secreted from natural killer cells in injured tissues and exert anti-inflammatory effects. These processes require a substantial period of time, leading to a delayed onset of MSCs' therapeutic effects. In this study, we investigated whether pretreatment with IFN-γ could potentiate the anti-fibrotic ability of MSCs in rats with ischemia-reperfusion injury (IRI) and unilateral ureter obstruction. Administration of MSCs treated with IFN-γ strongly reduced infiltration of inflammatory cells and ameliorated interstitial fibrosis compared with control MSCs without IFN-γ treatment. In addition, conditioned medium obtained from IFN-γ-treated MSCs decreased fibrotic changes in cultured cells induced by transforming growth factor-ß1 more efficiently than that from control MSCs. Most notably, secretion of prostaglandin E2 from MSCs was significantly increased by treatment with IFN-γ. Increased prostaglandin E2 in conditioned medium obtained from IFN-γ-treated MSCs induced polarization of immunosuppressive CD163 and CD206-positive macrophages. In addition, knockdown of prostaglandin E synthase weakened the anti-fibrotic effects of MSCs treated with IFN-γ in IRI rats, suggesting the involvement of prostaglandin E2 in the beneficial effects of IFN-γ. Administration of MSCs treated with IFN-γ might represent a promising therapy to prevent the progression of renal fibrosis.

Exaggerated renal fibrosis in lncRNA Gas5-deficient mice after unilateral ureteric obstruction.

AIMS: Abnormal expression of long non-coding RNAs (lncRNAs) occurs in several diseases including renal fibrosis. Notably, growth arrest-specific 5 (Gas5) is a lncRNA, which functions as an essential modulator of cell proliferation and growth. However, the role and expression of lncRNA Gas5 associated with renal fibrosis remains controversial. Herein, we investigate the effect of lncRNA Gas5 deficiency in renal fibrosis induced by the operation of unilateral ureteric obstruction (UUO) in mice. MAIN METHODS: Sera and urine of mice were used to detect markers of renal function. Further, Masson and immunohistochemical staining, western blotting as well as qRT-PCR were performed to observe the distribution and expression of fibrosis marker in the kidney tissue of the mice. KEY FINDINGS: Unlike the wild type mice, the obstructed kidney in Gas5+/- mice showed more severe renal fibrosis and collagen deposition. In the UUO-Gas5+/- group, the serum levels of uric acid, serum creatinine, and the urine levels of albumin-to-creatinine ratio were higher. Moreover, the expression of mRNA and protein of α-smooth muscle actin (α-SMA), vimentin, collagen IV, fibronectin, and matrix metalloproteinase 9 (MMP9) were higher, whereas that of phosphatase and tensin homolog (PTEN) were lower with the difference being statistically significant (p < 0.05). SIGNIFICANCE: lncRNA Gas5 was up-regulated in renal fibrosis tissues, and its deficiency exacerbated renal fibrosis in the UUO mice model.

Laparoscopic pyeloplasty as an alternative to nephrectomy in adults with poorly functioning kidneys due to ureteropelvic junction obstruction.

OBJECTIVES: To evaluate outcomes of laparoscopic pyeloplasty (LP) in adults with poorly functioning kidney due to ureteropelvic junction obstruction (UPJO). METHODS: A retrospective comparative analysis was performed between adult patients who underwent LP due to UPJO with differential renal function (DRF) ≤ 15% and DRF > 15%. LP success rate and complications were assessed. LP success was defined as symptoms improvement and DRF improvement or stabilization. DRF and estimated glomerular filtration rate (eGFR) were analyzed before and 12 months after surgery to evaluate renal function recovery. DRF was estimated using Tc-99 m DMSA renal scintigraphy. RESULTS: Among 121 LP performed in the study period at our institution, 15 and 42 were included in the DRF ≤ 15% and DRF > 15% groups, respectively. At a median follow-up of 17.8 months, all patients with DRF ≤ 15% reported symptoms improvement. LP success rate was 86.7% and 90.5% (p = 0.65) for patients with DRF ≤ 15% and DRF > 15%, respectively. There were no complications in the DRF ≤ 15% group, while there were three complications recorded in the DRF > 15% group (Clavien 2 and 3b). In the DRF ≤ 15% group, mean pre-operative and post-operative DRF was 9.5% ± 3.6 and 10.5% ± 7.8 (p = 0.49), respectively. Median pre-operative and post-operative eGFR was 68.5 ml/min and 79.8 ml/min (p = 0.93), respectively. Two patients had DRF improvement after LP. CONCLUSIONS: LP in adult patients with UPJO and poor function kidneys is an effective and safe procedure. DRF recovery is seen in a minority of the patients; however, LP is an alternative to nephrectomy.

Refining the unilateral ureteral obstruction mouse model: No sham, no shame.

Fibrosis, as a common final pathway in many renal diseases, contributes significantly to the decline of organ function and to progression to end-stage renal disease. To establish therapeutic interventions that target fibrosis, animal models are essential. The most widely used model of renal fibrosis is the unilateral ureteral obstruction (UUO) model. Typically, the control for this model is a sham-operated animal. Sham surgery causes pain and distress to these control animals, and here we aim to show that there is no difference in the main read-outs of this model between sham-operated animals and non-operated C57BL/6J mice. In five experiments, quantification of Picro Sirius Red stained collagen in the renal cortex did not show any difference between 15 sham and 25 non-operated individuals. A comparison of the regulation of genes involved with fibrosis did not show any difference between sham and non-operated groups at 21 days post surgery either. We conclude that there are no significant differences between non-operated controls and sham animals with respect to collagen deposition and fibrosis pathways in the UUO mouse model.

Functional and molecular evaluation of using aliskiren during acute and chronic partial ureteral obstruction in rat solitary kidney.

AIMS: To study the effect of direct renin inhibitor (aliskiren) on the renal function during acute and chronic partial ureteral obstruction (PUO) in rat solitary kidney. MAIN METHODS: Sixty male Sprague-Dawley rats were randomly allocated into three groups (20 rats each); sham, PUO and aliskiren groups. Right nephrectomy was performed in all groups. Rats in PUO and aliskiren groups were subjected to left PUO and received no treatment and aliskiren (10 mg/kg, orally, once per day till sacrification), respectively. Blood samples were then collected for biochemical measurements. Ten rats from each group were sacrificed after two weeks, while the remaining rats were sacrificed after four weeks. Left kidneys were harvested for histopathological examination, BCL-2, interleukin (IL)-6, transforming growth factor (TGF)-ß1, collagen I and fibronectin relative gene expression and assessment of glutathione (GSH), superoxide dismutase (SOD), malondialdehyde (MDA) and nitric oxide (NO) activity. KEY FINDINGS: After two and four weeks of PUO, aliskiren significantly recompensed the rise of serum creatinine (Scr) and blood urea nitrogen (BUN). Aliskiren also revealed significantly better histopathological results regarding cortical and medullary necrosis, regeneration and inflammatory cell infiltration. Aliskiren group showed statistically significant up-regulation of BCL-2 and down-regulation of IL-6, TGF-ß1, collagen I and fibronectin relative gene expression. Aliskiren significantly increased GSH and SOD activity and reduced MDA and NO activity. Moreover, aliskiren administration for four weeks after PUO significantly yielded more renoprotective effect compared to its administration for two weeks. SIGNIFICANCE: Aliskiren ameliorates the deterioration of the renal function during acute and chronic PUO in a solitary kidney.

MiR-155-5p promotes renal interstitial fibrosis in obstructive nephropathy via inhibiting SIRT1 signaling pathway.

Protection against renal fibrosis is important for the management of obstructive nephropathy. We researched the roles and possible mechanism of miR-155-5p in renal interstitial fibrosis, which may provide a potential endogenous target for renal interstitial fibrosis in obstructive nephropathy. Herein, NRK-49F cells were transfected with miR-155-5p mimic, miR-155-5p inhibitor, SIRT1 plasmid and/or SIRT1 siRNA. The unilateral ureteral obstruction (UUO) model was built with male C57 black mice and administrated with SRT1720 by tail vein injection. Levels of miR-155-5p, SIRT1 and relative proteins (TGF-ß1, α-SMA, Collage I and fibronectin) in NRK-49F cells or mice kidney tissues were measured with quantitative reverse transcription polymerase chain reaction or Western blot. The target gene of miR-155-5p was analyzed through TargetScan and dual-luciferase reporter assay. Mice kidney tissue was stained with Masson trichrome. It was found that miR-155-5p overexpression promoted the expressions of fibroblast related proteins expression and inhibited the SIRT1 expression in NRK-49F cells, while miR-155-5p silencing had an opposite effect. SIRT1 can bind with miR-155-5p. MiR-155-5p inhibited the level of SIRT1. Fibroblast related proteins were up-regulated by miR-155-5p and down-regulated by SIRT1 in NRK-49F cells, while the up-regulatory effect of miR-155-5p was reversed by SIRT1. MiR-155-5p expression was up-regulated and SIRT1 expression was down-regulated in the kidney tissue of UUO mice. SRT1720 attenuated the fiber deposition, up-regulated SIRT1 level and down-regulated the levels of fibroblast related proteins in UUO model mice. To conclude, miR-155-5p promotes renal interstitial fibrosis in obstructive nephropathy via inhibiting SIRT1 signaling pathway.

Non-invasive evaluation of obstruction after ureteroscopic stone removal: Role of renal resistive index assessment.

OBJECTIVES: The aim of this study is to evaluate prediction of postoperative ureteral obstruction needing ureteral stent insertion by evaluating the resistive index (RI) values and the grade of hydronephrosis. MATERIAL AND METHODS: A total of 66 adult patients undergoing stentless endoscopic ureteral stone treatment (URS) between January 2018 and January 2019 were included in this prospective study. Preoperative patient and stone characteristics were noted. All patients were evaluated with renal Doppler ultrasonography study to assess degree of hydronephrosis and RI values. A renal Doppler ultrasonography was repeated at postoperative 1st, 3rd and 7th days. Changes in both RI and hydronephrosis levels before and after the procedures were noted. On the postoperative 7th day, patients were divided into two groups including obstructive and non-obstructive cases according to RI values assessed where a RI value of 0.7 was accepted as the cut-off for obstruction. The preoperative and perioperative characteristics of both groups were evaluated in a comparative manner. RESULTS: The mean patient age was 43.6 ± 1.72 years. Significant improvements were noted in RI and grade of hydronephrosis after the operation. The grade of hydronephrosis and RI values were found to improve more significantly on postoperative 3rd day when compared to the postoperative 7th day (p < 0.01 and p < 0.01). A significant correlation was detected between the grade of hydronephrosis (>grade 2) and obstructive RI values (> 0.7) in each postoperative visits (p: 0.001). RI values (> 0.7) at postoperative seventh days were correlated with larger mean stone size, increased ureteral wall thickness, increased diameter of the ureter proximal to the stone, and longer duration of the operation. Preoperative high-grade hydronephrosis indicated obstructive RI values at postoperative seventh day (p = 0.001) Conclusion: Changes in RI values on Doppler sonography and the grade of hydronephrosis may be a guiding parameter in assessing postoperative ureteral obstruction.

Functional outcomes after pyeloplasty in solitary kidneys: structured analysis with the implication of Acute Kidney Injury Network (AKIN) staging criteria to predict long-term renal function recoverability.

OBJECTIVES: To assess the long-term functional outcomes after pyeloplasty in solitary kidney (SK) models and to define factors affecting postoperative renal function recoverability in adults. PATIENTS AND METHODS: We retrospectively evaluated all adult patients who underwent pyeloplasty for pelvi-ureteric junction obstruction (PUJO) in SK. Long-term renal function was assessed by diuretic scintigraphy and morphological changes were also determined, e.g. renal parenchymal volume (RPV) and parenchymal thickness (PT). We considered a >20% increase in glomerular filtration rate (GFR) as improvement, >20% decrease as deterioration, and changes within 20% as stationary renal function. Univariate and multivariate analysis for factors affecting renal function recoverability, including the Acute Kidney Injury Network (AKIN) Staging System postoperatively, were performed. RESULTS: The study included 62 patients with a mean (SD) age of 29 (10.5) years. At a median of 48 months, the mean (SD) GFR increased from 41.3 (17) to 48.5 (20.1) mL/min (P < 0.001), with a significant increase in RPV and PT (P = 0.02 and P = 0.001, respectively). Follow-up renal function was static, improved and decreased in 39 (63.4%), 17 (27%) and six (9.6%) patients, respectively. Functional success was achieved in 90.4%. Patient's age ≥39 years, PT ≤0.75 cm and higher early postoperative AKIN staging were predictors associated with a 4.8-, 3.2- and 2.7-fold deterioration in renal function. CONCLUSION: Pyeloplasty in SK preserved renal function in 90.4% of the present patients. Pyeloplasty in SK when associated with older age, decreased PT preoperatively, and early higher AKIN staging postoperatively was associated with poor renal function recoverability.

Urinary kidney injury molecule-1: a novel biomarker to monitor renal function in patients with unilateral ureteral obstruction.

PURPOSE: This study aimed to investigate the clinical significance of urinary kidney injury molecule-1 (KIM-1) to monitor renal function in patients with obstructive unilateral ureteral calculi. METHODS: Kidneys of 12 male C57BL/6J mice, as well as their urine and plasma specimens, were extracted to detect KIM-1 expressions 24 h after unilateral ureteral obstruction (UUO) construction or sham surgery. Meanwhile, a cohort of 89 patients with unilateral ureteral calculi was retrospectively reviewed. 46 of which received double-J ureteral stent indwelling (group 1) and the remaining 43 were treated conservatively (group 2). Urinary KIM-1 levels in the baseline, 2 h and 1 day after treatments were analyzed. RESULTS: KIM-1 expressions were dramatically higher in mice underwent UUO surgery when compared with the sham group. Clinical data showed urinary KIM-1 levels decreased as time went by for patients in group 1 (1.787 ± 1.081 ng/mL for baseline, 1.668 ± 1.162 ng/mL for 2 h and 0.935 ± 0.526 ng/mL for 1 day after operation; p = 0.0001). Nevertheless, for those in group 2, a mild increase (1.659 ± 0.997 ng/mL, 1.691 ± 0.872 ng/mL and 1.675 ± 0.911 ng/mL, correspondingly; p = 0.9869) was observed. Additionally, a urinary KIM-1 value of 1.04 ng/mL had a sensitivity of 83.1% and specificity of 62.5% to predict the presence of hydronephrosis (95% CI: 0.641-0.873, AUC: 0.757, p < 0.001). CONCLUSIONS: Urinary KIM-1 is a sensitive biomarker of post-renal acute kidney injury (AKI) and might predict the presence of hydronephrosis. It can be used as an effective surrogate to monitor renal function.

A negative feedback loop between JNK-associated leucine zipper protein and TGF-ß1 regulates kidney fibrosis.

Renal fibrosis is controlled by profibrotic and antifibrotic forces. Exploring anti-fibrosis factors and mechanisms is an attractive strategy to prevent organ failure. Here we identified the JNK-associated leucine zipper protein (JLP) as a potential endogenous antifibrotic factor. JLP, predominantly expressed in renal tubular epithelial cells (TECs) in normal human or mouse kidneys, was downregulated in fibrotic kidneys. Jlp deficiency resulted in more severe renal fibrosis in unilateral ureteral obstruction (UUO) mice, while renal fibrosis resistance was observed in TECs-specific transgenic Jlp mice. JLP executes its protective role in renal fibrosis via negatively regulating TGF-ß1 expression and autophagy, and the profibrotic effects of ECM production, epithelial-to-mesenchymal transition (EMT), apoptosis and cell cycle arrest in TECs. We further found that TGF-ß1 and FGF-2 could negatively regulate the expression of JLP. Our study suggests that JLP plays a central role in renal fibrosis via its negative crosstalk with the profibrotic factor, TGF-ß1.

Comparative Proteome Analyses of Ureteropelvic Junction Obstruction and Surrounding Ureteral Tissue.

Ureteropelvic junction (UPJ) obstruction is a common problem in children, but its etiology remains unclear. In this study, the proteome profiles of the obstructed segment and its surrounding distal and proximal parts were comparatively evaluated. Twelve children younger than 2 years of age with unilateral intrinsic UPJ obstruction were included. The excised operational tissue was divided into three parts immediately after resection: the obstructed part (Obst), the distal normal ureteral part (Dist), and the proximal part of the obstructed segment (Prox). Proteins extracted from the tissue samples were subjected to two-dimensional gel electrophoresis analysis to identify differentially regulated proteins. Spot analysis revealed that four proteins, namely tropomyosin beta and alpha-1 chains, actin and desmin, were upregulated in Obst in comparison to Dist. A similar analysis between Obst and Prox showed that heat shock protein beta-1 and carbonic anhydrase-1 were upregulated in Obst, while tropomyosin alpha 3 chain and ATP synthase beta were upregulated in Prox. The last comparative analysis between Dist and Prox revealed upregulation of annexin-A5 and annexin-A1 in Dist and vimentin, mitochondrial ATP synthase subunit-beta, peroxiredoxin-2, and apolipoprotein-A1 in Prox. Bioinformatics analysis using the STRING server indicated that the differentially regulated proteins, altogether, point to the changes occurring in muscle filament sliding pathway. When regulations occurring in each group were mutually compared, a change in lipase inhibition activity was detected by STRING. This is the first study scrutinizing changes occurring in protein profiles in UPJ.