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JCI Insight Apr 2022Kidney fibrosis is the final common pathway of progressive kidney diseases, the underlying mechanisms of which are not fully understood. The purpose of the current study...
Kidney fibrosis is the final common pathway of progressive kidney diseases, the underlying mechanisms of which are not fully understood. The purpose of the current study is to investigate a role of Piezo1, a mechanosensitive nonselective cation channel, in kidney fibrosis. In human fibrotic kidneys, Piezo1 protein expression was markedly upregulated. The abundance of Piezo1 protein in kidneys of mice with unilateral ureter obstruction (UUO) or with folic acid treatment was significantly increased. Inhibition of Piezo1 with nonspecific inhibitor GsMTx4 markedly ameliorated UUO- or folic acid-induced kidney fibrosis. Mechanical stretch, compression, or stiffness induced Piezo1 activation and profibrotic responses in human HK2 cells and primary cultured mouse proximal tubular cells (mPTCs), which were greatly prevented by inhibition or silence of Piezo1. TGF-β1 induced increased Piezo1 expression and profibrotic phenotypic alterations in HK2 cells and mPTCs, which were again markedly prevented by inhibition of Piezo1. Activation of Piezo1 by Yoda1, a Piezo1 agonist, caused calcium influx and profibrotic responses in HK2 cells and induced calcium-dependent protease calpain2 activation, followed by adhesion complex protein talin1 cleavage and upregulation of integrin β1. Also, Yoda1 promoted the link between ECM and integrin β1. In conclusion, Piezo1 is involved in the progression of kidney fibrosis and profibrotic alterations in renal proximal tubular cells, likely through activating calcium/calpain2/integrin β1 pathway.
Topics: Animals; Calcium; Fibrosis; Folic Acid; Integrin beta1; Ion Channels; Kidney Diseases; Mice; Ureteral Obstruction
PubMed: 35230979
DOI: 10.1172/jci.insight.152330 -
Nature Communications Oct 2023palmitoylation, a reversible post-translational modification, is initiated by the DHHC family of palmitoyltransferases and reversed by several acyl protein...
palmitoylation, a reversible post-translational modification, is initiated by the DHHC family of palmitoyltransferases and reversed by several acyl protein thioesterases. However, the role and mechanisms for protein palmitoylation in renal fibrosis have not been elucidated. Here we show protein palmitoylation and DHHC9 were downregulated in the fibrotic kidneys of mouse models and chronic kidney disease (CKD) patients. Ablating DHHC9 in tubular cells aggravated, while inducing DHHC9 overexpression with adeno-DHHC9 transfection or iproniazid treatment protected against kidney fibrosis in male mouse models. Mechanistically, DHHC9 palmitoylated β-catenin, thereby promoted its ubiquitination and degradation. Additionally, acyl protein thioesterase 1 (APT1) was induced in the fibrotic kidneys, which depalmitoylated β-catenin, increased its abundance and nuclear translocation. Ablating tubular APT1 or inhibiting APT1 with ML348 markedly protected against unilateral ureter obstruction (UUO) or ischemia/reperfusion injury (IRI)-induced kidney fibrosis in male mice. This study reveals the regulatory mechanism of protein palmitoylation in kidney fibrosis.
Topics: Humans; Male; Mice; Animals; beta Catenin; Lipoylation; Renal Insufficiency, Chronic; Ureteral Obstruction; Fibrosis; Kidney
PubMed: 37865665
DOI: 10.1038/s41467-023-42476-z -
Advances in Clinical and Experimental... Aug 2017Ureteropelvic junction obstruction (UPJO) causes a reduction in the urine flow from the renal pelvis into the ureter. Untreated UPJO may cause hydronephrosis, chronic... (Review)
Review
Ureteropelvic junction obstruction (UPJO) causes a reduction in the urine flow from the renal pelvis into the ureter. Untreated UPJO may cause hydronephrosis, chronic infection or urolithiasis and will often result in progressive deterioration of renal function. Most cases of UPJO are congenital; however, the disease can be clinically silent until adulthood. Other causes, both intrinsic and extrinsic, are acquired and include urolithiasis, post-operative/inflammatory/ischemic stricture, fibroepithelial polyps, adhesions and malignancy. In the past, the most frequent symptom of UPJO in neonates and infants was a palpable flank mass. Nowadays, thanks to the widespread use of maternal and prenatal ultrasound examinations, asymptomatic hydronephrosis is diagnosed very early. In adults and older children symptoms may include intermittent abdominal or flank pain, nausea, vomiting and hematuria. In addition to high specificity and sensitivity in detecting UPJO, modern technologically advanced equipment such as ultrasound, magnetic resonance imaging and computed tomography provides a lot of information about the function of the affected kidney and the anatomy of the surrounding tissues. Treatment options for UPJO include a wide spectrum of approaches, from active surveillance or minimally invasive endourologic techniques to open, laparoscopic or robotic pyeloplasty. The main goal of therapy is to relieve symptoms and maintain or improve renal function, but it is difficult to define treatment success after UPJO therapy.
Topics: Humans; Hydronephrosis; Kidney Pelvis; Prognosis; Risk Factors; Ureteral Obstruction; Urinary Bladder; Urodynamics
PubMed: 29068584
DOI: 10.17219/acem/59509 -
Best Practice & Research. Clinical... Aug 2012Retroperitoneal fibrosis is a rare syndrome hallmarked by a fibrosclerotic tissue in the retroperitoneum, often leading to encasement of the ureters. About two-thirds of... (Review)
Review
Retroperitoneal fibrosis is a rare syndrome hallmarked by a fibrosclerotic tissue in the retroperitoneum, often leading to encasement of the ureters. About two-thirds of cases of retroperitoneal fibrosis are idiopathic, while the remaining cases are secondary to a variety of different causes, including drugs, tumors and infections. Idiopathic retroperitoneal fibrosis may be associated with abdominal aorta aneurysms, with vasculitis of the thoracic aorta and of epi-aortic vessels, or both. Most patients present with abdominal and/or low back pain. Serum markers of inflammation are usually, but not invariably, elevated. The diagnosis is secured by computed tomography or magnetic resonance imaging, which typically show an enhancing retroperitoneal mass medially dislodging the ureters. Positron emission tomography can be useful to document the extent and metabolic activity of the inflammatory process. Treatment rests on glucocorticoids with a tapering scheme variably combined with immunosuppressive agents. In cases of ureter obstruction, relief of obstruction by stenting or ureterolysis is required.
Topics: Biomarkers; Flank Pain; Glucocorticoids; Humans; Immunosuppressive Agents; Low Back Pain; Magnetic Resonance Imaging; Positron-Emission Tomography; Rare Diseases; Retroperitoneal Fibrosis; Tomography, X-Ray Computed; Ureteral Obstruction
PubMed: 23040359
DOI: 10.1016/j.berh.2012.07.004 -
International Braz J Urol : Official... 2023Ureterocalicostomy is a technique that was first described by Neuwirt in 1948 (1) The laparoscopic access was initiated in 2003 by Cherullo et al. (2), following the...
PURPOSE
Ureterocalicostomy is a technique that was first described by Neuwirt in 1948 (1) The laparoscopic access was initiated in 2003 by Cherullo et al. (2), following the established principles of open surgery. In 2004, Gill et al. had two patients with UPJO treated with laparoscopic ureterocalicostomy, with success (3). In 2014, Arap et. al. presented a case series with good results in adults and children in our service (4). There are factors that prepare the surgeon for an ureterocalicostomy, such as the renal cortex thickness, although the decision is mainly taken during the procedure (5).
MATERIAL AND METHODS
A 24 years-old female patient with right lumbar pain was referred to our institution. She already had a right open pyeloplasty two years ago. The CT scan presented a right hydronephrotic kidney, DMSA scan with 30% of relative function and a DTPA scan with an obstructive pattern.
RESULTS
A laparoscopic ureterocalicostomy was performed due to the intra-operative findings (inferior kidney pole thickness and challenging access to the uretero-pelvic junction). The overall time was 130 minutes with no complications. The patient was discharged in two days and the double J was withdrawn in four weeks. The CT scan within one year demonstrates a reduction of the hydronephrosis. She had no more lumbar pain.
CONCLUSION
In complex cases, the laparoscopic ureterocalicostomy proves to be a safe and efficient procedure, with a free tension-free anastomosis and the advantages of the laparoscopic access.
Topics: Child; Adult; Humans; Female; Young Adult; Ureteral Obstruction; Ureter; Kidney; Kidney Pelvis; Hydronephrosis; Laparoscopy; Pain; Urologic Surgical Procedures
PubMed: 37267617
DOI: 10.1590/S1677-5538.IBJU.2022.0521 -
Urology Journal Jul 2014The Whitaker test was conceived and developed by Roger H. Whitaker (May 25, 1939) while he was a resident at Cambridge University in the late 1960s and early 1970s. The...
PURPOSE
The Whitaker test was conceived and developed by Roger H. Whitaker (May 25, 1939) while he was a resident at Cambridge University in the late 1960s and early 1970s. The test combines a urodynamic study with antegrade pyelography to measure the pressure differential between the renal pelvis and the bladder. The test can differentiate between patients with residual or recurrent obstruction and those with dilatation secondary to permanent changes in the musculature.
MATERIALS AND METHODS
We present the history of the Whitaker test and its place in modern practice.
RESULTS
It is useful in evaluating patients with questionable ureteropelvic or ureterovesical junction obstruction and primary defects in the ureteral musculature. It can also be used to determine when percutaneous nephrostomy tubes can be safely discontinued in postoperative patients.
CONCLUSION
The merit of the Whitaker test in comparison to other less invasive tests, specifically diuretic renography, is the subject of much debate. However, such debate erroneously presupposes that the tests are directly comparable, which they are not. The correct use for the Whitaker test is to assesses potential upper tract obstruction in equivocal cases and should only be utilized when equivocal results are obtained by other less invasive tests, obstruction is suspected in a poorly functioning kidney, a negative renogram with colic, intermittent obstruction, and percutaneous access already exists and the cause of dilatation needs investigating.
Topics: Diagnostic Techniques, Urological; Dilatation, Pathologic; History, 20th Century; Humans; Kidney Pelvis; Pressure; Recurrence; Ureteral Obstruction; Urinary Bladder; Urodynamics; Urography
PubMed: 25015627
DOI: No ID Found -
Acta Physiologica (Oxford, England) Aug 2022Cyclooxygenase-2 (COX-2) activity protects against oxidative stress and apoptosis early in experimental kidney injury. The present study was designed to test the...
AIM
Cyclooxygenase-2 (COX-2) activity protects against oxidative stress and apoptosis early in experimental kidney injury. The present study was designed to test the hypothesis that COX-2 activity attenuates fibrosis and preserves microvasculature in injured kidney. The murine unilateral ureteral-obstruction (UUO) model of kidney fibrosis was employed and compared with human nephrectomy tissue with and without chronic hydronephrosis.
METHODS
Fibrosis and angiogenic markers were quantified in kidney tissue from wild-type and COX-2 mice subjected to UUO for 7 days and in human kidney tissue. COX-enzymes, prostaglandin (PG) synthases, PG receptors, PGE , and thromboxane were determined in human tissue.
RESULTS
COX-2 immunosignal was observed in interstitial fibroblasts at baseline and after UUO. Fibronectin, collagen I, III, alpha-smooth muscle actin, and fibroblast specific protein-1 mRNAs increased significantly more after UUO in COX-2 vs wild-type mice. In vitro, fibroblasts from COX-2 kidneys showed higher matrix synthesis. Compared to control, human hydronephrotic kidneys showed (i) fibrosis, (ii) no significant changes in COX-2, COX-1, PGE -, and prostacyclin synthases, and prostacyclin and thromboxane receptor mRNAs, (iii) increased mRNA and protein of PGE -EP receptor level but unchanged PGE tissue concentration, and (iv) two- to threefold increased thromboxane synthase mRNA and protein levels, and increased thromboxane B tissue concentration in cortex and outer medulla.
CONCLUSION
COX-2 protects in the early phase against obstruction-induced fibrosis and maintains angiogenic factors. Increased PGE -EP receptor in obstructed human and murine kidneys could contribute to protection.
Topics: Animals; Cyclooxygenase 2; Dinoprostone; Fibrosis; Humans; Kidney; Mice; Prostaglandins E; Prostaglandins I; RNA, Messenger; Receptors, Prostaglandin E, EP2 Subtype; Thromboxanes; Up-Regulation; Ureter; Ureteral Obstruction
PubMed: 35543087
DOI: 10.1111/apha.13828 -
NMR in Biomedicine Aug 2021We evaluated the use of quantitative MRI relaxometry, including the dispersion of spin-lock relaxation with different locking fields, for detecting and assessing tubular...
We evaluated the use of quantitative MRI relaxometry, including the dispersion of spin-lock relaxation with different locking fields, for detecting and assessing tubular dilation and fibrosis in a mouse model of unilateral ureter obstruction (UUO). C57BL/6 J and BALB/c mice that exhibit different levels of tubular dilation and renal fibrosis after UUO were subjected to MR imaging at 7 T. Mice were imaged before UUO surgery, and at 5, 10 and 15 days after surgery. We acquired maps of relaxation rates and fit the dispersion of spin-lock relaxation rates R at different locking fields (frequencies) to a model of exchanging water pools, and assessed the sensitivity of the derived quantities for detecting tubular dilation and fibrosis in kidney. Histological scores for tubular dilation and fibrosis, based on luminal space and positive fibrotic areas in sections, were obtained for comparison. Histology detected extensive tubular dilation and mild to moderate fibrosis in the UUO kidneys, in which enlargement of luminal space, deposition of collagen, and reductions in capillary density were observed in the cortex and outer stripe of the outer medulla. Relaxation rates R , R and R clearly decreased in these regions of UUO kidneys longitudinally. While R showed the highest detectability to tubular dilation and overall changes in UUO kidneys, S , a parameter derived from R dispersion data, showed the highest correlation with renal fibrosis in UUO. While relaxation parameters are sensitive to tubular dilation in UUO kidneys, S depends primarily on the average exchange rate between water and other chemically shifted resonances such as hydroxyls and amides, and provides additional specific information for evaluating fibrosis in kidney disease.
Topics: Animals; Dilatation; Disease Progression; Fibrosis; Kidney Tubules; Magnetic Resonance Imaging; Male; Mice, Inbred BALB C; Mice, Inbred C57BL; Spin Labels; Ureteral Obstruction; Mice
PubMed: 33963778
DOI: 10.1002/nbm.4539 -
BMC Urology Jun 2022For patients with malignant ureteral obstruction or stricture who require long-term internal drainage, plastic double-J stents (DJ stents) represent the mainstay of...
BACKGROUND
For patients with malignant ureteral obstruction or stricture who require long-term internal drainage, plastic double-J stents (DJ stents) represent the mainstay of therapeutic strategies. DJ stents should be replaced at least once every 6 months to avoid infection or obstruction. Although DJ stents are generally replaced under cystoscopy, successful fluoroscopy-guided retrograde replacement of DJ stents in the interventional suite has been described in the literature.
METHODS
Between April 2004 and May 2020, we exchanged 143 DJ stents in 19 male and 22 female patients under fluoroscopic guidance using Nelaton catheters, snare catheters, and 8F DJ stents. All procedures were performed with patients under sedation and local anesthesia. There were 39 patients with malignant ureteral obstruction and two patients with benign ureteral strictures. This study was approved by the Institutional Review Board. Technical success, clinical success, complications, procedure time, and mean interval between two procedures were retrospectively reviewed, and the factors affecting the success rate of the procedure were analyzed.
RESULTS
Obstruction was detected at the abdominal ureter in 4 patients, pelvic ureter in 29 patients, and intravesical ureter in 8 patients. Twenty-six patients underwent two or more sessions of the procedures, whereas 15 patients underwent single-session procedures. Total 34 outpatient-based procedures and 109 inpatient-based procedures were performed. Technical success and clinical success were achieved in 94.4% (135/143) and 93.3% (126/135) procedures, respectively. Mean procedure time was 21.5 min (range 9-192 min). Mean procedure interval was 101.8 days (range 5-306 days). Technical success was negatively affected by male sex and obstruction at the pelvic ureter and was positively affected by previous successful exchange. Left-sided ureteral stent placement and old age negatively influenced clinical success. Septic shock occurred in one patient and was treated with antibiotics.
CONCLUSION
Fluoroscopy-guided trans-urethral exchange of DJ stents is an effective and less painful procedure.
Topics: Constriction, Pathologic; Female; Fluoroscopy; Humans; Male; Retrospective Studies; Stents; Ureter; Ureteral Obstruction
PubMed: 35706037
DOI: 10.1186/s12894-022-01034-3 -
Archivos Espanoles de Urologia Sep 2019
Topics: Stents; Ureter; Ureteral Obstruction
PubMed: 31475686
DOI: No ID Found