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1.
BMC Nephrol ; 25(1): 158, 2024 May 08.
Article in English | MEDLINE | ID: mdl-38720274

ABSTRACT

BACKGROUND: Ureteropelvic junction obstruction (UPJO) is the most common cause of pediatric congenital hydronephrosis, and continuous kidney function monitoring plays a role in guiding the treatment of UPJO. In this study, we aimed to explore the differentially expressed proteins (DEPs) in the urinary extracellular vesicles(uEVs) of children with UPJO and determine potential biomarkers of uEVs proteins that reflect kidney function changes. METHODS: Preoperative urine samples from 6 unilateral UPJO patients were collected and divided into two groups: differential renal function (DRF) ≥ 40% and DRF < 40%.We subsequently used data-independent acquisition (DIA) to identify and quantify uEVs proteins in urine, screened for DEPs between the two groups, and analyzed biofunctional enrichment information. The proteomic data were evaluated by Western blotting and enzyme-linked immunosorbent assay (ELISA) in a new UPJO testing cohort. RESULTS: After one-way ANOVA, a P adj value < 0.05 (P-value corrected by Benjamin-Hochberg) was taken, and the absolute value of the difference multiple was more than 1.5 as the screening basis for obtaining 334 DEPs. After analyzing the enrichment of the DEPs according to Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment combined with the protein-protein interaction (PPI) network results, we selected nicotinamide adenine dinucleotide-ubiquinone oxidoreductase core subunit S1 (NDUFS1) for further detection. The expression of NDUFS1 in uEVs was significantly lower in patients with DRF < 40% (1.182 ± 0.437 vs. 1.818 ± 0.489, P < 0.05), and the expression level of NDUFS1 was correlated with the DRF in the affected kidney (r = 0.78, P < 0.05). However, the NDUFS1 concentration in intravesical urine was not necessarily related to the change in DRF (r = 0.28, P = 0.24). CONCLUSIONS: Reduced expression of NDUFS1 in uEVs might indicate the decline of DRF in children with UPJO.


Subject(s)
Biomarkers , Extracellular Vesicles , Ureteral Obstruction , Child, Preschool , Female , Humans , Male , Biomarkers/urine , Extracellular Vesicles/metabolism , Hydronephrosis/urine , Hydronephrosis/congenital , Kidney/metabolism , Kidney Pelvis , Proteomics/methods , Ureteral Obstruction/urine , Ureteral Obstruction/congenital
2.
J Urol ; 207(2): 432-440, 2022 02.
Article in English | MEDLINE | ID: mdl-34551596

ABSTRACT

PURPOSE: Robot-assisted laparoscopic pyeloplasty (RALP) use in children has increased, though many centers still favor open pyeloplasty (OP) in infants. This study aims to compare safety and efficacy of RALP and OP in infants. MATERIALS AND METHODS: A single-institution, retrospective cohort study of infants <1 year of age who underwent primary RALP or OP between January 2009 and June 2020 was performed. Primary outcomes were intraoperative and 30-day complications, postoperative radiographic improvement at last clinic visit, and operative failure leading to redo pyeloplasty. Multivariable logistic regression was performed for 30-day complications to adjust for demographic variation between groups. Survival analysis was performed to compare time to diagnosis of operative failure leading to redo pyeloplasty. RESULTS: Among 204 patients, 121 underwent OP and 83 underwent RALP (74.5% male). RALP patients were older (median 7.2 vs 2.9 months, p <0.001) and larger (median 8.2 vs 5.9 kg, p <0.001) than OP patients. Radiographic improvement was seen in 91.1% of RALP patients and 88.8% of OP patients at last visit. Median (interquartile range) followup in months was 24.4 (10.8-50.3) for the full cohort. In adjusted analysis, the odds of a 30-day complication (OR 0.40, 95% CI 0.08-2.00) was lower for RALP compared to OP, though not statistically significant. In survival analysis, there was no difference in time to diagnosis of operative failure and redo pyeloplasty between groups (p=0.65). CONCLUSIONS: RALP is a safe and effective alternative to OP for infants, with comparable intraoperative and 30-day complications, radiographic improvement at last followup, and risk of pyeloplasty failure.


Subject(s)
Kidney Pelvis/surgery , Laparoscopy/adverse effects , Plastic Surgery Procedures/adverse effects , Postoperative Complications/epidemiology , Robotic Surgical Procedures/adverse effects , Ureteral Obstruction/surgery , Female , Follow-Up Studies , Humans , Infant , Infant, Newborn , Kidney Pelvis/diagnostic imaging , Laparoscopy/statistics & numerical data , Length of Stay/statistics & numerical data , Male , Operative Time , Postoperative Complications/etiology , Plastic Surgery Procedures/methods , Plastic Surgery Procedures/statistics & numerical data , Retrospective Studies , Robotic Surgical Procedures/statistics & numerical data , Survival Analysis , Treatment Outcome , Ureter/diagnostic imaging , Ureter/surgery , Ureteral Obstruction/congenital , Ureteral Obstruction/mortality
3.
Urol Int ; 105(11-12): 1046-1051, 2021.
Article in English | MEDLINE | ID: mdl-34218231

ABSTRACT

INTRODUCTION: In this study, we aimed to investigate the correlation between Cajal cell density and preoperative and postoperative radiological and scintigraphic parameters in ureteropelvic junction obstruction (UPJO). METHODS: The study group consisted of 41 renal units (38 consecutive patients; 13 female and 25 male) surgically treated for UPJO. UPJ specimens from patients were immuno-stained with CD117 (c-kit) antibody for interstitial Cajal cells (ICCs). The relation between Cajal cell density and preoperative and postoperative radiological and scintigraphic parameters was evaluated. RESULTS: The mean age of the patients was 8.52 ± 8.86 (0-35) years. The density of Cajal cells was defined in 2 groups for convenient analysis as 0-5 cells (low) in 19 (46.3%) patients and >5 cells (moderate-high) in 22 (53.6%). There was significant difference between the preoperative and postoperative anteroposterior diameters of the related kidneys in both Cajal groups (p = 0.001-low, p = 0.000-moderate-high) independent of Cajal cell density. Regression in hydronephrosis postoperatively was determined in both Cajal groups (77.8%-low, 64.7%-moderate-high); however, there was no difference between them (p = 0.39). Preoperative T1/2 was significantly longer in the low Cajal group (p = 0.02). Postoperative T1/2 decreased in both low (p = 0.000) and moderate-high (p = 0.001) Cajal groups, but no difference was found between them (p = 0.24). There was significant improvement in the kidney differential function after surgery in the low Cajal density group (p = 0.015) while there was no correlation between the scintigraphic success or improvement and Cajal cell density (p = 0.51). DISCUSSION/CONCLUSION: ICC deficiency/density could not be shown as a predictive factor for the determination of success rate of pyeloplasty. Despite the lack of any evidence for the degree of deficiency as an indicator for the severity of obstruction and prediction of surgical success, further studies are needed for confirmation.


Subject(s)
Hydronephrosis/diagnostic imaging , Interstitial Cells of Cajal/pathology , Kidney Pelvis/diagnostic imaging , Ureter/diagnostic imaging , Ureteral Obstruction/diagnostic imaging , Adolescent , Adult , Child , Child, Preschool , Female , Humans , Hydronephrosis/pathology , Hydronephrosis/surgery , Infant , Infant, Newborn , Kidney Pelvis/abnormalities , Kidney Pelvis/surgery , Male , Treatment Outcome , Ureter/abnormalities , Ureter/surgery , Ureteral Obstruction/congenital , Ureteral Obstruction/pathology , Ureteral Obstruction/surgery , Urologic Surgical Procedures , Young Adult
4.
J Laparoendosc Adv Surg Tech A ; 31(7): 843-848, 2021 Jul.
Article in English | MEDLINE | ID: mdl-34042526

ABSTRACT

Introduction: Success rate of laparoscopic pyeloplasty for ureteropelvic junction obstruction (UPJO) in children is comparable with open pyeloplasty. Prolonged ileus and injury to adjacent viscera more often occurred in transperitoneal approach; however, longer operation time is noted in retroperitoneal approach. Purpose: This study presented a hybrid retroperitoneoscopic pyeloplasty (HRP), for congenital UPJO in infants weighing <10 kg. Materials and Methods: From February 2017 to June 2020, 10 HRP procedures were performed in 9 patients by 1 surgeon. Retroperitoneal dissection of the renal pelvis and the upper third ureter was first performed, followed by extracorporeal suturing for pyeloureterostomy. Results: Mean operative age and body weight were 4.23 ± 3.69 months and 6.18 ± 1.57 kg. Operative, CO2 inflation, and extracorporeal suture time were 147.9 ± 39.5, 40.6 ± 11.2, and 62.9 ± 26.1 minutes, respectively. Surgical outcome was confirmed by renal ultrasound and diuretic renogram. Postoperative follow-up duration was 15.2 ± 7.7 months. Three patients had postoperative febrile urinary tract infection and recovered after antibiotic treatment. Conclusion: In infants or smaller children with UPJO, the HRP procedure may be considered as an effective and minimally invasive alternative with shorter learning curve for inexperienced surgeons.


Subject(s)
Hydronephrosis/congenital , Kidney Pelvis/surgery , Multicystic Dysplastic Kidney/surgery , Nephrotomy/methods , Plastic Surgery Procedures/methods , Retroperitoneal Space/surgery , Ureteral Obstruction/surgery , Body Weight , Female , Humans , Hydronephrosis/surgery , Ileus/congenital , Ileus/surgery , Infant , Kidney/diagnostic imaging , Kidney/surgery , Kidney Pelvis/diagnostic imaging , Learning Curve , Male , Operative Time , Postoperative Complications/etiology , Sutures , Treatment Outcome , Ultrasonography , Ureteral Obstruction/congenital , Urologic Surgical Procedures/methods
6.
Exp Cell Res ; 393(1): 112086, 2020 08 01.
Article in English | MEDLINE | ID: mdl-32416091

ABSTRACT

OBJECTIVE: Ureteropelvic junction obstruction (UPJO) is a common renal obstructive disorder, but its pathogenic mechanisms remain largely unclear. We aimed to investigate the potential involvement of the renin-angiotensin system in congenital UPJO pathogenesis. METHODS: Differentially expressed proteins in exosomes isolated from amniotic fluid of patients with congenital UPJO were characterized using iTRAQ (isobaric tags for relative and absolute quantification)-based proteomics. The expressions of angiotensin-converting enzyme (ACE) and aminopeptidase N (AP-N) in HK2 cells were inhibited by quinapril and siRNA, respectively. Cell proliferation and reactive oxygen species were measured by EdU staining and flow cytometry, respectively. Gene expression was detected by Western blot or qRT-PCR. The inflammatory factors were measured through ELISA. Mice that underwent unilateral ureteral obstruction were used as the animal model. RESULTS: The identity of exosomes from amniotic fluids was confirmed by the expression of CD9 and CD26. In total, 633 differentially expressed proteins were identified in the amniotic fluid-derived exosomes from patients with UPJO, including 376 up- and 257 down-regulated proteins associated with multiple biological processes. Of them, ACE and AP-N were significantly decreased in the amniotic fluid exosomes. Inhibition of ACE and AP-N resulted in suppressed cell proliferation; repressed IARP, AT1R, and MAS1 expression; elevated ROS production; and increased IL-1ß, TNF-α, and IL-6 levels in HK2 cells. Decreased ACE expression and elevated IL-1ß levels were also observed in the mouse model. CONCLUSION: Suppression of ACE and AP-N expression mediates congenital UPJO pathogenesis by repressing renal tubular epithelial proliferation, promoting ROS production, and enhancing inflammatory factor expression.


Subject(s)
CD13 Antigens/metabolism , Peptidyl-Dipeptidase A/metabolism , Proteomics , Ureteral Obstruction/pathology , Animals , CD13 Antigens/genetics , Humans , Kidney Diseases/metabolism , Kidney Pelvis/metabolism , Kidney Pelvis/pathology , Mice, Inbred C57BL , Peptidyl-Dipeptidase A/genetics , Proto-Oncogene Mas , Renin-Angiotensin System/physiology , Ureteral Obstruction/complications , Ureteral Obstruction/congenital
7.
Ultrasound Q ; 36(1): 20-23, 2020 Mar.
Article in English | MEDLINE | ID: mdl-32118861

ABSTRACT

OBJECTIVE: The aims of the study were to measure renal hemodynamic indexes and to evaluate postsurgical recovery in children diagnosed with obstructive hydronephrosis using color Doppler ultrasound. METHODS: This study enrolled 36 patients with ureteropelvic junction obstruction who underwent Anderson-Hynes pyeloplasty. The peak systolic velocity (PSV) and the resistive index (RI) of the main renal arteries (MRAs) and interlobar renal arteries (IRAs) were measured using color Doppler ultrasound. Renal hemodynamic indexes were measured before surgery and 2, 4, 6, 8, 10, 12, 14, and 16 weeks after surgery. RESULTS: Split renal function and renal parenchymal thickness were positively correlated with PSV and negatively correlated with RI. Anterior-posterior diameter had no significant correlation with PSV or RI. The PSV in MRAs and IRAs were lower than those of the contralateral kidneys but increased after surgery. Anderson-Hynes pyeloplasty was successfully performed in all patients, including one patient whose kidney was removed 16 weeks after surgery. The RI in the MRAs and IRAs were higher than those of the contralateral kidneys but decreased within 2 weeks after surgery. Peak systolic velocity and RI were still atypical 16 weeks after surgery. The hemodynamic index of the nonfunctional kidney did not show improvement after surgery. CONCLUSIONS: Peak systolic velocity and RI were correlated with renal function and renal parenchymal thickness but were not correlated with dilatation of the renal pelvis. Peak systolic velocity increased whereas RI decreased after surgery and were stable at 8 weeks, but remained abnormal 16 weeks after surgery. Hemodynamic measurements may be a useful and convenient method to evaluate surgical outcomes after Anderson-Hynes pyeloplasty.


Subject(s)
Hemodynamics , Hydronephrosis/diagnostic imaging , Hydronephrosis/surgery , Ultrasonography, Doppler, Color , Ureteral Obstruction/diagnostic imaging , Ureteral Obstruction/surgery , Female , Humans , Hydronephrosis/congenital , Infant , Kidney/abnormalities , Kidney/blood supply , Kidney/diagnostic imaging , Male , Ureteral Obstruction/congenital
8.
Urologe A ; 59(3): 261-265, 2020 Mar.
Article in German | MEDLINE | ID: mdl-32030434

ABSTRACT

A primary, congenital megaureter means a dilatation of the ureter with a ureteric diameter ≥7 mm due to a structural or functional obstruction of the ureterovesical junction and represents the second most likely cause of neonatal hydronephrosis. Conservative management is the primary treatment option for many patients due to a high spontaneous remission rate of up to 85%. Concerning diagnostic management, meticulous and repeat postnatal evaluation by ultrasound is mandatory to identify patients who are at risk of renal deterioration. Routine voiding cystourethrography or contrast-enhanced voiding urosonography is currently recommended for all patients to detect vesicoureterorenal reflux and other concomitant pathologies. The relevance of the additional information provided by this examination must be critically questioned considering the lack of clinical consequences. Moreover, the question arises as to whether these examinations should be prolonged until clinical symptoms occur. Nevertheless, a subvesical obstruction should still be ruled out for male patients with a bilateral megaureter. The same critical discussion is necessary for the routine use of diuretic renography in patients with primary megaureter. In principal, this examination is used to determine the global as well as the split renal function and in addition is considered to offer an evaluation of the extent of obstruction. Similarly, the question arises of whether this examination should be mandatory for every child with a primary megaureter or whether the decision should be based on the extent of the upper urinary tract dilatation. The trend of diagnostic management should go towards individualized and risk-adapted diagnostic measures.


Subject(s)
Hydronephrosis/diagnostic imaging , Ureter/abnormalities , Ureteral Diseases/diagnostic imaging , Ureteral Obstruction/congenital , Child , Humans , Hydronephrosis/therapy , Male , Radionuclide Imaging , Ultrasonography, Prenatal , Ureter/diagnostic imaging , Ureteral Diseases/therapy , Ureteral Obstruction/diagnostic imaging , Ureteral Obstruction/therapy , Urination , Urography/methods
11.
Pediatr Nephrol ; 35(12): 2231-2239, 2020 12.
Article in English | MEDLINE | ID: mdl-31811536

ABSTRACT

Antenatal hydronephrosis (AHN) is the most frequently detected abnormality by prenatal ultrasonography. Differential diagnosis of AHN includes a wide variety of congenital abnormalities of the kidney and urinary tract ranging from mild abnormalities such as transient or isolated AHN to more important ones as high-grade congenital vesicoureteral reflux or ureteropelvic junction obstruction. It is well known that the outcome depends on the underlying etiology. Various grading systems have been proposed for the classification of AHN on prenatal and postnatal ultrasonography. Mild isolated AHN represents up to 80% of cases, is considered to be benign, and majority of them resolve, stabilize, or improve during follow-up. Controversies exist regarding the diagnosis and management of some important and severe causes of AHN such as high-grade vesicoureteral reflux and ureteropelvic junction obstruction. Current approach is becoming increasingly conservative during diagnosis and follow-up of these patients with less imaging and close follow-up. However, there is still no consensus regarding the clinical significance, postnatal evaluation, and management of infants with AHN. The aim of this review is to discuss the controversies and provide an overview on the management of AHN.


Subject(s)
Fetal Diseases/diagnosis , Hydronephrosis/diagnosis , Fetal Diseases/pathology , Humans , Hydronephrosis/pathology , Hydronephrosis/therapy , Infant, Newborn , Ultrasonography, Prenatal , Ureteral Obstruction/congenital , Ureteral Obstruction/diagnostic imaging , Urinary Tract/abnormalities
12.
J Neonatal Perinatal Med ; 13(1): 91-96, 2020.
Article in English | MEDLINE | ID: mdl-31609706

ABSTRACT

BACKGROUND: Renal pelvic dilatation (RPD) is a frequent finding in fetal ultrasound. The aim of the study is to correlate the prenatally detected moderate and severe pyelectasis with the postnatal outcome. METHODS: A retrospective analysis involving 90 cases of prenatally detected moderate and severe RPD referred to our prenatal diagnosis centre with 18 months of urological follow-up. Prenatal ultrasound was correlated with postnatal renal function, assessed by plasmatic creatinine and/or renal scintigraphy performed before surgery. RESULTS: Cases were divided between two groups according to postnatal management: group A including 35 newborns (38.9%) that needed surgical treatment and group B with 55 patients (61.1%) who were managed conservatively. The group A presented higher median RPD (18 mm, IQR 12-25 mm) compared to the group B (11 mm, IQR 10-14 mm). The most common anomaly detected within group A was pelvi-ureteric junction (PUI) obstruction (43%). Within group B 32 cases (58%) showed spontaneous resolution of hydronephrosis during postnatal follow up. In case of moderate pyelectasis the risk of postnatal surgery was 25% and raised to 60% for severe RPD. In our study, 29 newborns showed pathologic scintigraphies: 25 required surgery while 4 did not find indication for surgery due to ipsilateral renal function irreversible damage. 6 patients had high creatinine level (>0.6 mg/dl). 35 cases out of 90 (39%) developed monolateral irreversible renal function impairment. CONCLUSION: Moderate and severe RPD are often correlated with postnatal renal damage, therefore a close multidisciplinary follow-up is required. Prenatal scanning is highly predictive of postnatal outcome and can address properly the prenatal counseling.


Subject(s)
Conservative Treatment , Hydronephrosis/therapy , Pyelectasis/therapy , Ureteral Obstruction/surgery , Urologic Surgical Procedures , Vesico-Ureteral Reflux/therapy , Creatinine/metabolism , Female , Humans , Hydronephrosis/complications , Hydronephrosis/congenital , Hydronephrosis/diagnostic imaging , Infant, Newborn , Kidney Pelvis/surgery , Male , Pregnancy , Pyelectasis/diagnostic imaging , Pyelectasis/metabolism , Radionuclide Imaging , Remission, Spontaneous , Renal Insufficiency/congenital , Renal Insufficiency/etiology , Renal Insufficiency/metabolism , Retrospective Studies , Severity of Illness Index , Solitary Kidney , Ultrasonography, Prenatal , Ureter/surgery , Ureteral Obstruction/congenital , Ureteral Obstruction/diagnostic imaging , Urethral Stricture/diagnostic imaging , Urethral Stricture/metabolism , Urethral Stricture/therapy , Urogenital Abnormalities/diagnostic imaging , Urogenital Abnormalities/metabolism , Urogenital Abnormalities/therapy , Vesico-Ureteral Reflux/diagnostic imaging , Vesico-Ureteral Reflux/metabolism
13.
J Pediatr Urol ; 16(1): 107.e1-107.e5, 2020 Feb.
Article in English | MEDLINE | ID: mdl-31818677

ABSTRACT

BACKGROUND: Pregnancy is associated with reactivation and transmission of latent polyomavirus to fetus. Polyomavirus is also known to cause ureteral stenosis and hydronephrosis. OBJECTIVE: The aim of this study was to investigate whether the urinary polyomavirus could be used as a potential biomarker in newborns with ureteropelvic junction obstruction (UPJO). STUDY DESIGN: Urinary polyomavirus virus was measured by PCR in 42 newborn infants with fetal hydronephrosis history. Random urine samples were obtained from newborns immediately after birth and from their mothers at the time of delivery. Results were compared with 25 healthy infants matched for gestational and postnatal ages. The diagnosis of UPJO was established by diuretic renal scintigraphy. UPJO was graded according to the Society for Fetal Urology (SFU) classification. RESULTS: The urine samples of healthy infants showed no detectable polyomavirus. No statistically significant difference was found in the median urinary polyomavirus level between grade 1 (1000 copies/mL) and grade 2 (1500 copies/mL) UPJO infants. When the median urinary BKV values were compared for each grade of UPJO, patients with grade 3 and 4 had significantly higher urinary polyomavirus levels than those with grades 1 or 2 (P < 0.001). There was a strong correlation between the median polyomavirus in the urine of pregnant women and the urine of newborns with UPJO (P < 0.001). DISCUSSION: Data suggest that routine screening of urinary polyomavirus may help to identify infants with severe obstruction in whom early surgical intervention could reduce the risk of developing progressive kidney disease. To the best of our knowledge this is the first prospective study to present the role of urinary polyomavirus in newborn infants with UPJO to distinguish between patients who would benefit from early surgical intervention. CONCLUSION: Urinary polyomavirus is a potential biomarker of UPJO in newborns with fetal hydronephrosis.


Subject(s)
Hydronephrosis/congenital , Kidney Pelvis , Polyomavirus/isolation & purification , Ureteral Obstruction/congenital , Urine/virology , Female , Humans , Hydronephrosis/urine , Infant, Newborn , Male , Prospective Studies , Ureteral Obstruction/urine
14.
BMJ Case Rep ; 12(11)2019 Nov 24.
Article in English | MEDLINE | ID: mdl-31767607

ABSTRACT

Presented here is the case of a 21-year-old man, with a family history of unilateral renal agenesis, who presented with obstruction of his solitary functioning right kidney. Initially thought to be secondary to an obturator fossa hernia on endoscopic and retrograde pyelography assessment, diagnosis of obstruction secondary to an aberrant middle rectal artery was determined at laparotomy and division of this vessel relieved the patient's obstruction without any short-term or long-term complications. To the best of the authors' knowledge, this is the first reported case in the literature of hydroureteronephrosis secondary to an aberrant middle rectal artery.


Subject(s)
Anorectal Malformations/complications , Arteriovenous Malformations/complications , Hydronephrosis/congenital , Rectum/blood supply , Solitary Kidney/complications , Ureteral Obstruction/congenital , Humans , Male , Young Adult
15.
Top Companion Anim Med ; 36: 22-24, 2019 Sep.
Article in English | MEDLINE | ID: mdl-31472725

ABSTRACT

A 4-month-old, intact male, domestic longhair cat was admitted with a 2-month history of abdominal distention. Physical examination revealed a mild inspiratory distress and a large palpable intraabdominal mass, in an otherwise bright and alert cat. Abdominal ultrasonography revealed a large hypoechoic cystic structure compatible with hydronephrosis or a renal cyst. On exploratory celiotomy, hydronephrosis of the right kidney was documented and ureteronephrectomy was performed. Histopathology of the excised tissues revealed severe stenosis in the proximal ureteral lumen without evidence of obstructive material, a normal ureteral epithelium and severe atrophy of the renal cortex and medulla, supporting the diagnosis of congenital unilateral ureteral stenosis. The cat recovered uneventfully and 8 months later was in excellent clinical condition. Congenital ureteral stenosis with secondary hydronephrosis may occur rarely in cats and should be included in the differential diagnosis of progressive abdominal distention in young cats.


Subject(s)
Cat Diseases/congenital , Hydronephrosis/veterinary , Ureteral Obstruction/veterinary , Animals , Cat Diseases/diagnosis , Cat Diseases/surgery , Cats , Hydronephrosis/congenital , Hydronephrosis/diagnosis , Male , Treatment Outcome , Ultrasonography/veterinary , Ureteral Obstruction/congenital , Ureteral Obstruction/diagnosis , Ureteral Obstruction/surgery
16.
J Pediatr Urol ; 15(3): 242.e1-242.e9, 2019 May.
Article in English | MEDLINE | ID: mdl-30979613

ABSTRACT

INTRODUCTION: The diagnosis of renal function impairment and deterioration in congenital urinary tract obstruction (UTO) continues to be extremely challenging. The use of new renal biomarkers in this setting may favor early renal injury detection, allowing for a reliable choice of optimal therapeutic options and the prevention or minimization of definitive renal damage. OBJECTIVE: The aim of the study was to investigate a selection of promising biomarkers of renal injury with the intention of evaluating and comparing their profile with clinically based decisions for surgical intervention of infants with congenital obstructive uropathies. STUDY DESIGN: The first-year profile of renal biomarkers, serum creatinine (sCr), serum and urine cystatin C (CyC), neutrophil gelatinase-associated lipocalin (NGAL), kidney injury molecule-1 (KIM-1), transforming growth factor beta-1 (TGF-ß1), retinol-binding protein (RBP), and microalbuminuria (µALB), was analyzed in a cohort of 37 infants with congenital UTO, divided into three subgroups, 14 cases with grade III unilateral hydro(uretero)nephrosis, 13 cases with grade III bilateral hydro(uretero)nephrosis, and 10 cases with low urinary tract obstruction (LUTO), compared with 24 healthy infants matched by gestational age and birth weight. Serum and urine samples were stored at -70 °C and thereafter analyzed by quantitative enzymatic immunoassay. RESULTS: Compared with the control group (Figure), all renal biomarker values were significantly increased in patients (P ≤ 0.02). In the unilateral hydronephrosis and LUTO group, RBP (P ≤ 0.043), NGAL (P ≤ 0.043), KIM-1 (P ≤ 0.03), and TGF-ß1 (P ≤ 0.034) values dropped significantly after surgery. Neutrophil gelatinase-associated lipocalin alone and in combination with urine and serum CyC demonstrated the best performance in determining the need for surgery (area under the curve, 0.801 and 0.881, respectively). Biomarker profile analysis was suggestive of surgical intervention in 55.4% (7/13) of non-operated cases, and most of the biomarker values were above the cutoff levels within at least 3 months before the clinically based surgical decision in 58% (14/24) of all operated patients. DISCUSSION: To the best of the authors' knowledge, this is the first study to present the clinical use of selected group of serum and urinary biomarkers in the setting of UTO to distinguish between patients who would benefit from surgery intervention. The most promising results were obtained using NGAL, RBP, TGF-ß1, and KIM-1, especially in the unilateral hydro(uretero)nephrosis and LUTO subgroups when compared with the control group. CONCLUSIONS: Urine biomarkers, alone and in combination, demonstrated high potential as a non-invasive diagnostic tool for identifying infants who may benefit from earlier surgical intervention.


Subject(s)
Clinical Decision-Making , Ureteral Obstruction/metabolism , Ureteral Obstruction/surgery , Urethral Obstruction/metabolism , Urethral Obstruction/surgery , Urinary Bladder Neck Obstruction/metabolism , Urinary Bladder Neck Obstruction/surgery , Biomarkers/blood , Female , Humans , Infant , Male , Predictive Value of Tests , Ureteral Obstruction/congenital , Urethral Obstruction/congenital , Urinary Bladder Neck Obstruction/congenital , Urologic Surgical Procedures
17.
Indian J Pediatr ; 86(4): 354-359, 2019 04.
Article in English | MEDLINE | ID: mdl-30796705

ABSTRACT

OBJECTIVES: To study the etiology and clinical profile of congenital obstructive uropathy in children, renal status and growth at diagnosis and at follow-up and to determine the predictors for development of chronic kidney disease (CKD). METHODS: An observational (retrospective-prospective) study was conducted at a tertiary care hospital in South India from September 2014 through September 2016. Sixty children diagnosed to have congenital obstructive uropathy with a minimum follow-up period of 5 y were included and followed up prospectively for 2 more years during the study period. The data of the children at admission and follow-up was obtained from the medical records and analyzed. RESULTS: Congenital uretero-pelvic junction obstruction followed by Posterior urethral valve were the most common etiologies identified. Male preponderance (88.3%) was observed with poor urinary stream being the most common presentation (36.6%). Forty percent of the population had elevated creatinine. Fifteen percent were hypertensive and 25% had growth failure at diagnosis. However, there was a reduction in the number of children with poor estimated glomerular filtration rate (eGFR), hypertension and growth faltering during follow-up. Among the risk factors, hypertension at diagnosis [O.R-12.8 (2.21-74.22) and p value <0.05] and frequent urinary tract infection (UTI) [O.R-14.06 (2.32-85.42) and p value <0.05] were the most important factors for CKD progression. Children with low eGFR (< 60 ml/min/1.73m2) had more height faltering and hypertension at follow-up (p value <0.05). CONCLUSIONS: Hypertension and frequent UTI were observed to be strongly associated with progression of CKD. Estimated GFR was found to be significantly associated with faltering of height and hypertension. Preserving the renal function prevents growth faltering and development of hypertension at follow-up thereby ensuring a better quality of life.


Subject(s)
Urogenital Abnormalities/pathology , Child, Preschool , Female , Humans , Infant , Male , Sex Factors , Ureteral Obstruction/congenital , Ureteral Obstruction/pathology , Urogenital Abnormalities/therapy
18.
J Pediatr Urol ; 15(1): 44.e1-44.e7, 2019 Feb.
Article in English | MEDLINE | ID: mdl-30420258

ABSTRACT

INTRODUCTION: In children with congenital ureteropelvic junction obstruction (UPJO), urinary biomarkers could assist in the diagnosis of renal damage or kidneys at risk for damage. Urinary levels of interleukin-6 (IL6), neutrophil gelatinase-associated lipocalin (LCN2), monocyte chemoattractant protein-1 (MCP1), and transforming growth factor-ß1 (TGFB1) proteins have been correlated with renal damage in several contexts. Whether they might be useful non-invasive biomarkers of obstructive nephropathy due to unilateral and bilateral congenital UPJO was tested. PATIENTS AND METHODS: A cohort study was performed at People's Hospital of Xinjiang Uygur Autonomous Region in China. Bladder urine samples from 17 patients with UPJO were obtained before surgical intervention and from 17 healthy age-matched controls. Levels of IL6, LCN2, MCP1, and TGFB1 were determined by enzyme-linked immunosorbent assay and normalized to urinary creatinine levels. RESULTS: Levels of urinary LCN2, MCP1, and IL6 were significantly elevated in the urine from individuals with UPJO compared with controls (P = 0.0003, P = 0.0003, and P = 0.0073, respectively). Children with bilateral UPJO (n = 5) showed significantly higher levels of IL6, LCN2, and MCP1 protein in their urine compared with controls or those with unilateral UPJO (n = 12; P = 0.007, P < 0.0001, and P = 0.0002, respectively). Combining LCN2 and MCP1 slightly improved biomarker performance. DISCUSSION: Urinary biomarkers could be used in obstructed patients to monitor for renal damage and might find particular utility on patients with bilateral UPJO. Monitoring urinary biomarkers and imaging features in untreated patients could provide insights into the natural history of renal damage due to obstruction and will be necessary to test their performance characteristics as biomarkers. CONCLUSIONS: Urinary levels of LCN2 and MCP1 protein are promising biomarkers monitoring children with UPJO, particularly in those with bilateral disease.


Subject(s)
Chemokine CCL2/urine , Interleukin-6/urine , Kidney Pelvis , Lipocalin-2/urine , Transforming Growth Factor beta1/urine , Ureteral Obstruction/congenital , Ureteral Obstruction/urine , Adolescent , Biomarkers/urine , Child , Child, Preschool , Cohort Studies , Female , Humans , Infant , Male
19.
Acta Paediatr ; 108(1): 50-57, 2019 01.
Article in English | MEDLINE | ID: mdl-29959876

ABSTRACT

AIM: Congenital ureteral obstruction is a fairly common condition in infants, and its clinical management has been long debated during the last decade. The long-term physiological consequences of today's conservative non-surgical management in many asymptomatic hydronephrotic children are unclear. METHODS: Experimental studies in rats and mice, retrospective studies in children and adults, as well as prospective studies in children are included in this mini review. RESULTS: Experimental models of hydronephrosis in rats and mice have demonstrated that partial ureteropelvic junction obstruction (UPJO) is casually linked with development of hypertension and renal injuries in later life. The mechanisms are multifactorial and involve increased activity of the renin-angiotensin-aldosterone system and renal sympathetic nerve activity. Furthermore, oxidative stress and nitric oxide deficiency in the affected kidney appear to play important roles in the development and maintenance of hypertension. Clinical case reports in adults and recent prospective studies in children have associated hydronephrosis with elevated blood pressure, which could be reduced by surgical management of the obstruction. CONCLUSION: Based on current experimental and clinical knowledge regarding the link between partial UPJO and changes in blood pressure, it is proposed that today's non-operative management of hydronephrosis should be reconsidered to reduce the risk of developing elevated blood pressure or hypertension in later life.


Subject(s)
Hydronephrosis/complications , Hypertension/epidemiology , Hypertension/etiology , Ureteral Obstruction/complications , Adolescent , Adult , Age Distribution , Animals , Blood Pressure Determination/methods , Child , Cohort Studies , Disease Models, Animal , Humans , Hydronephrosis/diagnosis , Hypertension/physiopathology , Incidence , Infant , Mice , Prognosis , Rats , Retrospective Studies , Risk Assessment , Severity of Illness Index , Sex Distribution , Ureteral Obstruction/congenital , Ureteral Obstruction/diagnosis
20.
Pediatr Nephrol ; 34(3): 443-448, 2019 03.
Article in English | MEDLINE | ID: mdl-30317433

ABSTRACT

BACKGROUND: Obstructive uropathy (OU) is a common cause of end-stage renal disease (ESRD) in children. Children who escape the newborn period with mild-to-moderate chronic kidney disease (CKD) continue to be at increased risk. The predictive ability of clinically available markers throughout childhood is poorly defined. METHODS: Patients with OU were identified in the Chronic Kidney Disease in Children Study. The primary outcome of interest was renal replacement therapy (RRT) (cases). Controls were age matched and defined as patients within the OU cohort who did not require RRT during study follow-up. RESULTS: In total, 27 cases and 41 age-matched controls were identified. Median age at baseline and age at outcome measurement were 10 vs. 16 years, respectively. First available glomerular filtration rate (GFR) (36.9 vs. 53.5 mL/min per 1.73 m2), urine protein/creatinine (Cr) (0.40 vs. 0.22 mg/mg) and microalbumin/Cr (0.58 vs. 0.03 mg/mg), and serum CO2 (20 vs. 22 mmol/L) and hemoglobin (12.4 vs. 13.2 g/dL) differed significantly between cases and controls, respectively. GFR declined 3.07 mL/min per 1.73 m2/year faster in cases compared to that in controls (p < 0.0001). Urine protein/Cr and microalbumin/Cr increased by 0.16 and 0.11 per year more in cases compared to those in controls, respectively (p ≤ 0.001 for both). Serum phosphate increased by 0.11 mg/dL and serum albumin and hemoglobin decreased by 0.04 (g/dL) and 0.14 (g/dL) per year more for cases compared to those for controls, respectively (p < 0.05 for all). CONCLUSIONS: Age-specific baseline and longitudinal measures of readily available clinical measures predict progression to ESRD in children with mild-to-moderate CKD from OU.


Subject(s)
Kidney Failure, Chronic/diagnosis , Renal Replacement Therapy/statistics & numerical data , Ureteral Obstruction/complications , Vesico-Ureteral Reflux/complications , Adolescent , Biomarkers/blood , Biomarkers/urine , Case-Control Studies , Child , Disease Progression , Female , Glomerular Filtration Rate , Humans , Kidney Failure, Chronic/etiology , Kidney Failure, Chronic/therapy , Kidney Function Tests/methods , Longitudinal Studies , Male , Prospective Studies , United States/epidemiology , Ureteral Obstruction/blood , Ureteral Obstruction/congenital , Ureteral Obstruction/urine , Vesico-Ureteral Reflux/blood , Vesico-Ureteral Reflux/congenital , Vesico-Ureteral Reflux/urine
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