scholarly journals Emerging Urinary Markers of Renal Injury in Obstructive Nephropathy

2014 ◽  
Vol 2014 ◽  
pp. 1-7 ◽  
Author(s):  
Giuseppe Lucarelli ◽  
Vito Mancini ◽  
Vanessa Galleggiante ◽  
Monica Rutigliano ◽  
Antonio Vavallo ◽  
...  
Keyword(s):  
Renal Function ◽  
Renal Injury ◽  
Renal Damage ◽  
Interstitial Fibrosis ◽  
Renal Outcome ◽  
Obstructive Nephropathy ◽  
Tubulointerstitial Injury ◽  
Tubular Atrophy ◽  
Renal Function Deterioration

The effects of obstruction on renal function are the consequence of many factors that profoundly alter all components of glomerular function. Besides the acute effects on glomerular filtration rate and tubule function, a chronic obstruction induces tubular and interstitial injury that results from the activation of different pathways. The progression of tubulointerstitial injury leads to chronic renal damage characterized by tubular atrophy, inflammatory cell infiltration, and interstitial fibrosis. Obstructive nephropathy is an evolving disease in which the renal damage continues even after relief of the obstruction. In particular, it has been demonstrated that the time of relief is the most important factor in predicting long-term renal function deterioration. In this setting, the EGF/MCP-1 ratio, urinary NGAL, and urinary KIM-1 are useful early biomarkers of progressive renal damage and could have a potential role in predicting the long-term renal outcome. This minireview summarizes the role of these emerging urinary biomarkers of obstructive nephropathy based on the current understanding of the pathophysiology of renal injury.

scholarly journals Biomarkers of Chronic Renal Tubulointerstitial Injury

2019 ◽  
Vol 67 (9) ◽  
pp. 633-641 ◽  
Author(s):  
Serena M. Bagnasco ◽  
Avi Z. Rosenberg
Keyword(s):  
Interstitial Fibrosis ◽  
Renal Tissue ◽  
Experimental Models ◽  
Renal Outcome ◽  
Tubulointerstitial Injury ◽  
Tubular Atrophy ◽  
Non Invasive ◽  
Diagnosis And Prognosis

Progression of renal parenchyma injury is characterized by increasing interstitial fibrosis and tubular atrophy, irrespective of the cause. Histopathologic assessment of renal tissue obtained by biopsy remains the gold standard for determining the presence and extent of tubulointerstitial scarring. Discovery of robust non-invasive means for capturing a snapshot and for longitudinal monitoring of parenchymal deterioration has been the focus of intense multimodal effort by investigators within the renal community and beyond. Research in this field has included the use of in vitro and in vivo experimental models and has fostered the development and evaluation of tissue and biofluid assays for novel analytes with potential translation to the diagnosis and prognosis of kidney disease. Here, we examine recent advances in the search of “biomarkers” for detection of renal tubulointerstitial scarring and prediction of renal outcome in human renal disease.

scholarly journals Urothelial-based reconstructive surgery for upper- and mid-ureteral defects: Long-term results

2016 ◽  
Vol 10 (9-10) ◽  
pp. 290
Author(s):  
Barak Rosenzweig ◽  
Yoram Mor ◽  
Tomer Erlich ◽  
Menachem Laufer ◽  
Harry Winkler ◽  
...  
Keyword(s):  
Renal Function ◽  
Reconstructive Surgery ◽  
Long Term Results ◽  
Obstructive Nephropathy ◽  
Complication Rates ◽  
Long Term Outcomes ◽  
Renal Function Deterioration ◽  
The Mean ◽  
Long Term Preservation

<p><strong>Introduction:</strong> Ureteral strictures can result in obstructive nephropathy and renal function deterioration. Surgical management of ureteral defects, especially in the proximal- and mid-ureter, is particularly challenging. Our purpose was to analyze the long-term outcomes of urothelial-based reconstructive surgery for upper- and mid-ureteral defects.</p><p><strong>Methods:</strong> We conducted a retrospective analysis of a single tertiary centre’s database, including 149 patients treated for ureteral defects between 2001 and 2011. Thirty-one patients (21%) underwent complex urothelial-based surgical repairs for upper- and mid-ureter defects. Patients’ median age was 61 years. The mean length of the ureteral strictures was 2.5 cm, located in upper-, mid-ureter, or in between in 19 (61%), 10 (32%), and two (6%) patients, respectively. All patients were treated with a primary urothelial-based repair. Median followup time was 26 months. The primary outcome of the study was the long-term preservation of renal function and lack of clinical obstruction. The secondary endpoint of the study was the assessment of the intra- and postoperative complication rates.</p><p><strong>Results:</strong> Most of the lesions were benign (22, 71%), while nine strictures (29%) were malignant. Seven patients (23%) suffered from postoperative complications, five of which were infectious. The median pre- and postoperative calculated glomerular filtration rates were 66 ml/min/1.72m2 and 64ml/min/1.72m2, respectively. Success rate was 84%, defined as lack of need for re-operation or kidney drainage at the last followup.</p><p><strong>Conclusions:</strong> Upper- and mid-ureteral defects present a complex pathology necessitating experienced reconstructive surgical skills. Our data suggest good long-term results for primary urothelialbased reconstructions for these pathologies.</p>

Renal damage progresses despite improvement of renal function after relief of unilateral ureteral obstruction in adult rats

2004 ◽  
Vol 287 (6) ◽  
pp. F1283-F1293 ◽  
Author(s):  
Keiichi Ito ◽  
Jie Chen ◽  
Maher El Chaar ◽  
Joshua M. Stern ◽  
Surya V. Seshan ◽  
...  
Keyword(s):  
Renal Function ◽  
Ureteral Obstruction ◽  
Renal Damage ◽  
Interstitial Fibrosis ◽  
Unilateral Ureteral Obstruction ◽  
Pharmacological Intervention ◽  
Adult Rats ◽  
Group 5 ◽  
Group 1

Progression of renal damage after relief of unilateral ureteral obstruction (UUO) has been demonstrated, especially in neonatal rats. We evaluated renal function and renal damage after relief of 3-day UUO in five groups of adult rats: group 1, no treatment; group 2, 3-day UUO; groups 3- 5, 3-day UUO followed by relief; group 3, 7-day relief; group 4, 14-day relief; and group 5, 28-day relief. Glomerular filtration rate (GFR), renal blood flow (RBF), tissue transforming growth factor-β (TGF-β), interstitial fibrosis and fibroblast expression, tubular apoptosis, macrophage infiltration, expression of nitric oxide synthases (NOS), and urinary nitrate/nitrite (NO2/NO3) were evaluated. RBF and GFR were decreased to <10% of baseline by 3 days of UUO. GFR and RBF in a previously obstructed kidney (POK) returned to baseline by 14 days after relief. Both tissue TGF-β1 and interstitial fibrosis were significantly higher in POK of groups 3- 5 compared with groups 1 and 2 . In group 5, the numbers of infiltrating macrophages, fibroblasts, and apoptotic tubular cells were higher in POK compared with group 1. Urinary NO2/NO3 was significantly higher than baseline from 3 to 27 days after relief of UUO. Expression of NOS isoforms was increased in tubules. As interstitial fibrosis contributes to decreased renal function, these results suggest that the acute recovery in function may be compromised in the long term by the progressive renal fibrosis which was found. Furthermore, pharmacological intervention at the time of relief of UUO, targeted to fibrotic processes, may contribute to long-term recovery of renal function.

scholarly journals Extracapillary proliferation scoring correlates with renal outcome and contributes to stratification in adult patients with immunoglobulin A nephropathy

2019 ◽  
Author(s):  
Jhonny L Moreno ◽  
Lida M Rodas ◽  
Juliana Draibe ◽  
Xavier Fulladosa ◽  
Montserrat Gomá ◽  
...  
Keyword(s):  
Renal Function ◽  
Interstitial Fibrosis ◽  
Severe Disease ◽  
Immunoglobulin A ◽  
Renal Outcome ◽  
Immunoglobulin A Nephropathy ◽  
Renal Survival ◽  
Oxford Classification ◽  
Tubular Atrophy ◽  
Renal Biopsies

Abstract Background The revised Oxford classification of diagnostic renal biopsies has been proposed to aid in the prediction of renal outcome. We aimed to validate the histological crescents and interstitial fibrosis and tubular atrophy (IFTA) subgrouping, and to investigate the additional value of the proportion of crescents (CatPE) in the prediction of renal outcome. Methods Data were retrospectively collected over 10 years, from the time of diagnosis, by systematic review of medical records from 90 patients with renal biopsies recruited to cohorts from two hospitals in Spain. Patients were classified into three groups for the analysis: CatPE >25% (C2), CatPE <25% (C1) and without this type of lesion (C0). The end point was renal survival defined by either >50% reduction in glomerular filtrate rate or end-stage renal disease. Results Renal survival at 5 years was 90% in group C0, 81% in group C1 and 31% in group C2 (P = 0.013). The presence of >25% crescents in the sample was associated with more severe disease when compared with <25%, as demonstrated by more interstitial fibrotic change and by lower estimated glomerular filtration rate at diagnosis, as well as worse renal function at 2 and 5 years. At the time of diagnosis and at 24 months, the group with IFTA >50% had poorer renal function compared with the other groups. Conclusions We have confirmed the predictive value for renal survival of the revised Oxford classification in a two-centre study. We found worse renal outcome in patients with severe tubulointerstitial fibrosis and atrophy. Patients with extracapillary lesions >25% and IFTA >50% had a worse renal prognosis due to more severe kidney injury. These results contribute to patient stratification in immunoglobulin A nephropathy for therapeutic, epidemiological and basic research.

Early measurement of interstitial fibrosis predicts long-term renal function and graft survival in renal transplantation

1996 ◽  
Vol 83 (8) ◽  
pp. 1082-1085 ◽  
Author(s):  
M. L. Nicholson ◽  
T. A. McCulloch ◽  
S. J. Harper ◽  
T. J. Wheatley ◽  
C. M. Edwards ◽  
...  
Keyword(s):  
Renal Function ◽  
Renal Transplantation ◽  
Graft Survival ◽  
Interstitial Fibrosis ◽  
Early Measurement

scholarly journals Clinicopathologic Features of Infection-Related Glomerulonephritis with IgA Deposits: a French Nationwide Study

2020 ◽  
Author(s):  
Elodie Miquelestorena-Standley ◽  
Charlotte Jaulerry ◽  
Marie-Christine Machet ◽  
Nolwenn Rabot ◽  
Christelle Barbet ◽  
...  
Keyword(s):  
Interstitial Fibrosis ◽  
Outcome Data ◽  
Renal Outcome ◽  
Tubular Atrophy ◽  
Short Delay ◽  
Adult Men ◽  
Staphylococcus Infections ◽  
Endocapillary Proliferative Glomerulonephritis ◽  
Stage Renal Disease ◽  
End Stage

Abstract Background: Infection-related glomerulonephritis with IgA deposits (IRGN-IgA) is a rare disease but it is increasingly reported in the literature. Data regarding epidemiology and outcome are lacking, especially in Europe. We aimed to assess the clinical, pathologic and outcome data of IRGN-IgA. Methods: Clinical and outcome data from patients from 11 French centers over the 2007-2017 period were collected retrospectively. We reviewed pathologic patterns and immunofluorescence of renal biopsies and evaluated C4d expression in IRGN-IgA. We analyzed the correlation between histological presentation and outcome. Results: Twenty-seven patients (23 men, mean age: 62±15 years) were included. Twenty-one (78%) had Staphylococcus aureus infection and twelve (44%) were diabetic. At the time of biopsy, 95.2% had haematuria, 48.1% had a serum creatinine level of >4 mg/dL, and 16% had hypocomplementemia. The most common pathologic presentation included mesangial (88.9%) and endocapillary proliferative glomerulonephritis (88.9%) with interstitial fibrosis and tubular atrophy (IF/TA) (85.1%). Diffuse and global glomerular C4d expression was found in 17.8%, mostly in biopsies with acute or subacute patterns, and was associated with a short delay between infection and renal biopsy compared to segmental and focal staining. After median follow-up of 13.2 months, 23.1% died, 46.2% had persistent renal dysfunction and 15.4% reached end-stage renal disease. Renal outcome was correlated to IF/TA severity. Conclusions: Infection-related glomerulonephritis with IgA deposits is usually associated with Staphylococcus infections and mainly affects adult men. This entity has a poor prognosis which is correlated to interstitial fibrosis and tubular atrophy severity.

scholarly journals Coagulation parameters are associated with the prognosis of immunoglobulin A nephropathy: a retrospective study

2020 ◽  
Author(s):  
Ming Xia ◽  
Di Liu ◽  
Liang Peng ◽  
Yan Li ◽  
Haiyang Liu ◽  
...  
Keyword(s):  
Retrospective Study ◽  
Interstitial Fibrosis ◽  
Immunoglobulin A ◽  
Coagulation System ◽  
Renal Outcome ◽  
Immunoglobulin A Nephropathy ◽  
Tubular Atrophy ◽  
Coagulation Parameters ◽  
T Score ◽  
Stage Renal Disease

Abstract Background: Interstitial fibrosis/tubular atrophy (T) score is a known determinant of the progression of immunoglobulin A nephropathy (IgAN). Strong evidence indicates that the components of the coagulation system closely linked with fibrotic events have been highlighted in the kidney. However, whether the coagulation system can affect the renal outcome of IgAN remains unclear. Herein, we investigated the association of coagulation parameters and pathological phenotype of IgAN and their combined effects on the deterioration of renal function. Methods: This retrospective study included N=291 patients with biopsy-proven IgAN from May 2009 to April 2013 in the Second Xiangya Hospital. Clinical data, pathological features were collected, and the associations of coagulation parameters at biopsy, T score, and renal outcome were evaluated. T score indicated the degree of tubular atrophy or interstitial fibrosis. The renal outcome was defined as an end-stage renal disease (ESRD) or an irreversible 50% estimated glomerular filtration rate (eGFR) reduction. Results: Shorter prothrombin time (PT) and the activated partial thromboplastin time (APTT) were significantly associated with T (both p<0.001). PT (<11.15s) or APTT (<29.65s) had worse cumulative survival rate (p=0.008, p=0.027 respectively) and were significantly but not independently associated with a higher risk of renal outcome (p=0.012, p=0.032 respectively). In the combined analyses of PT, APTT, and T lesions, the odd ratios for the outcome were significantly higher in the presence of T with PT (<11.15s) or APTT (<29.65s). Conclusion: Shorter PT and APTT are associated with an increased incidence of the T lesion and are additional factors that portend a poorer prognosis in IgAN. Monitoring coagulation function might be important when assessing the risk of progression. Additional studies exploring the molecular mechanism between coagulation and IgAN pathology are needed.

scholarly journals Dicer deficiency in proximal tubules exacerbates renal injury and tubulointerstitial fibrosis and upregulates Smad2/3

2018 ◽  
Vol 315 (6) ◽  
pp. F1822-F1832 ◽  
Author(s):  
Zhengwei Ma ◽  
Qingqing Wei ◽  
Ming Zhang ◽  
Jian-Kang Chen ◽  
Zheng Dong
Keyword(s):  
Kidney Disease ◽  
Renal Injury ◽  
Renal Fibrosis ◽  
Interstitial Fibrosis ◽  
Proximal Tubules ◽  
Tubulointerstitial Fibrosis ◽  
Obstructive Nephropathy ◽  
Pathological Feature ◽  
Tubular Injury

Renal fibrosis is a common pathological feature in chronic kidney disease (CKD), including diabetic kidney disease (DKD) and obstructive nephropathy. Multiple microRNAs have been implicated in the pathogenesis of both DKD and obstructive nephropathy, although the overall role of microRNAs in tubular injury and renal fibrosis in CKD is unclear. Dicer (a key RNase III enzyme for microRNA biogenesis) was specifically ablated from kidney proximal tubules in mice via the Cre-lox system to deplete micoRNAs. Proximal tubular Dicer knockout (PT- Dicer KO) mice and wild-type (WT) littermates were subjected to streptozotocin (STZ) treatment to induce DKD or unilateral ureteral obstruction (UUO) to induce obstructive nephropathy. Renal hypertrophy, renal tubular apoptosis, kidney inflammation, and tubulointerstitial fibrosis were examined. Compared with WT mice, PT- Dicer KO mice showed more severe tubular injury and renal inflammation following STZ treatment. These mice also developed higher levels of tubolointerstitial fibrosis. Meanwhile, PT- Dicer KO mice had a significantly higher Smad2/3 expression in kidneys than WT mice (at 6 mo of age) in both control and STZ-treated mice. Similarly, UUO induced more severe renal injury, inflammation, and interstitial fibrosis in PT- Dicer KO mice than WT. Although we did not detect obvious Smad2/3 expression in sham-operated mice (2–3 mo old), significantly more Smad2/3 was induced in obstructed PT- Dicer KO kidneys. These results supported a protective role of Dicer-dependent microRNA synthesis in renal injury and fibrosis development in CKD, specifically in DKD and obstructive nephropathy. Depletion of Dicer and microRNAs may upregulate Smad2/3-related signaling pathway to enhance the progression of CKD.

The Relevance of Periglomerular Fibrosis in the Evaluation of Routine Needle Core Renal Biopsies

2011 ◽  
Vol 135 (1) ◽  
pp. 117-122
Author(s):  
Joseph Jenkins ◽  
Sergey V. Brodsky ◽  
Anjali A. Satoskar ◽  
Gyongyi Nadasdy ◽  
Tibor Nadasdy
Keyword(s):  
Renal Function ◽  
Renal Biopsy ◽  
Renal Injury ◽  
Interstitial Fibrosis ◽  
Renal Diseases ◽  
Glomerular Sclerosis ◽  
Poor Renal Function ◽  
Renal Biopsies ◽  
Biopsy Report ◽  
Relationship Of

Abstract Context—Renal interstitial fibrosis and, to a lesser extent, sclerotic glomeruli correlate with poor renal function. However, not all nonfunctional glomeruli are sclerotic. Many or most glomeruli with periglomerular fibrosis, while retaining blood flow, probably do not filter; therefore, they may not contribute to renal function. Objective—To examine the relationship of periglomerular fibrosis and the sum of globally sclerotic glomeruli and glomeruli with periglomerular fibrosis (GSG+PF) with interstitial fibrosis and renal function. Design—Native kidney biopsies from 177 patients with chronic renal injury were assessed for interstitial fibrosis, glomerular sclerosis, and GSG+PF. Renal biopsies with active or acute lesions were not included. The percentage of globally sclerotic glomeruli and GSG+PF was correlated with the degree of interstitial fibrosis and serum creatinine levels. Results—The percentage of GSG+PF correlates better with the degree of interstitial fibrosis and renal function than does the percentage of globally sclerotic glomeruli alone. This appears particularly true in chronic renal diseases of patients without diabetes. The number of globally sclerotic glomeruli correlates better with interstitial fibrosis and renal function than does the sum of globally and segmentally sclerotic glomeruli. Conclusions—The percentage of GSG+PF in a renal biopsy specimen provides a better estimate of chronic renal injury than does the percentage of sclerotic glomeruli alone, probably because many or most glomeruli with periglomerular fibrosis are nonfunctional. Therefore, we recommend that the number of glomeruli with periglomerular fibrosis also be provided in the renal biopsy report.

scholarly journals Long-term renal function and continence status in patients with

2013 ◽  
Vol 1 (4) ◽  
pp. 371 ◽  
Author(s):  
Luis H.P. Braga ◽  
Armando J. Lorenzo ◽  
Sumit Dave ◽  
Maria H. Del-Valle ◽  
Antoine E. Khoury ◽  
...  
Keyword(s):  
Renal Function ◽  
Glomerular Filtration Rate ◽  
Glomerular Filtration ◽  
Filtration Rate ◽  
Urogenital Sinus ◽  
Renal Outcome ◽  
Urinary Continence ◽  
Renal Ultrasound ◽  
Common Channel

Introduction: Urinary continence after cloacal repair is difficult to achieveand renal outcome in patients with cloacal malformations has been scarcelyreported. As a result, we reviewed our experience with cloacal malformationsto determine the status of continence and the long-term renal function in thesechildren.Methods: A retrospective chart review from 1990 to 2003 identified 12 patientswith cloacal malformation (1 posterior, 4 complex and 7 classical) who underwentsurgical reconstruction. The confluence was defined as high (commonchannel ≥ 3 cm) and low (< 3 cm) by cystovaginoscopy. Renal ultrasound,voiding cystouretrogram, renal scan and sacral radiograph were performedin all children. Most patients underwent 1-stage abdominoperineal pull-through,applying the principle of total urogenital sinus mobilization. We collected dataregarding hydronephrosis, vesicoureteral reflux and split differential renal function.Renal outcome was evaluated based on glomerular filtration rate and ageadjustedserum creatinine values (μmol/L). Urinary continence was definedas a dry interval > 4 hours.Results: Patients’ mean age at surgery was 20 months (range 7–29 mo). Ofthe 12 children who underwent cloacal repair, 7 (58.3%) had a common channel≥ 3cm. Renal anomalies were identified in 3 of 12 (25%) girls: there were 2 solitary kidneys and 1 pelvic kidney. Lumbar–sacral radiography demonstrated bony abnormalities in 11 of the 12 (91.6%) cases: hemivertebra in 3 cases, sacral agenesis in 4 cases, hypoplastic sacrum in 3 cases and bifid sacrum in 1 case. Total urogenital sinus mobilization through an abdominoperineal approach in a single stage was performed in 8 girls. Follow-up ranged from 4 to 14 years (mean 8.5 yr). Eight (66.6%) children had dry intervals > 4 hours, 5 (62.5%) of them were on clean intermittent catheterization through aMitrofanoff channel and 1 (12.5%) was through the urethra. The remaining 2 (25%) patients were voiding spontaneously. Three (33.3%) patients were totally incontinent, and 1 (8.3%) patient was awaiting reconstruction. The mean measured glomerular filtration rate was 93.5 mL/min/1.73m2 (range 34–152 mL/min/1.73m2). Four (57.1%) of 7 patients who had a common channel ≥ 3 cm ended up needing augmentation cystoplasty, compared with none of the patients with a common channel < 3 cm (57.1% v. 0%, p = 0.038).Conclusion: Urinary continence can be achieved in most patients with cloacalmalformation at the expense of major reconstructive surgery and despite thepresence of associated urological abnormalities. However, these childrenharbour an important risk for renal impairment later in life and should be closelymonitored.

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