scholarly journals Clinical and Histological Outcome Predictors in Renal Limited Pauci-Immune Crescentic Glomerulonephritis: A Single Centre Experience

2012 ◽  
Vol 25 (1) ◽  
pp. 287-292 ◽  
Author(s):  
A. Gigante ◽  
C. Salviani ◽  
K. Giannakakis ◽  
E. Rosato ◽  
B. Barbano ◽  
...  
Keyword(s):  
Serum Creatinine ◽  
Crescentic Glomerulonephritis ◽  
Alternative Pathway ◽  
Rapidly Progressive Glomerulonephritis ◽  
Renal Outcome ◽  
Fibrinoid Necrosis ◽  
Histological Features ◽  
Systemic Involvement ◽  
University Of Rome

Renal-limited vasculitis is a pauci-immune crescentic glomerulonephritis with no signs of systemic involvement, representing one of the most common causes of rapidly progressive glomerulonephritis. The study aims to examine clinical and histological features in twenty-four patients with RLV diagnosed by the Nephrology Department of Sapienza University of Rome, Italy, evaluating the role of these parameters in predicting renal survival. Patients details, clinical and histological features and outcomes were recorded at the time of renal biopsy and over a mean follow-up period of 36±6 months. In our study, serum creatinine at presentation was significantly higher in patients who had a poor outcome than in those who survived with independent renal function (6.3±2.47 mg/dl vs 2.84±2.01 mg/dl, P= 0.002). The presence of C3c was found in the area of glomerular fibrinoid necrosis and in small arteries and arterioles with fibrinoid necrosis in 17 patients (P= 0.018). In conclusion, serum creatinine at presentation and focal C3c depositions in areas of glomerular and arteriolar fibrinoid necrosis were the best determinants of poor renal outcome, maybe underlining the pathogenic role of alternative pathway activation of complement system but also demonstrating the focal distribution of necrotizing lesions.

scholarly journals P0276SERUM C3 LEVELS AND THE PROGNOSIS OF ANCA-ASSOCIATED VASCULITIS: A SINGLE-CENTER RETROSPECTIVE STUDY

2020 ◽  
Vol 35 (Supplement_3) ◽  
Author(s):  
Annalisa Carta ◽  
Elisa Russo ◽  
Leda Cipriani ◽  
Daniela Picciotto ◽  
Michela Saio ◽  
...  
Keyword(s):  
Renal Damage ◽  
Alternative Pathway ◽  
Rapidly Progressive Glomerulonephritis ◽  
Renal Outcome ◽  
Secondary Outcome ◽  
Rank Test ◽  
P Value ◽  
Risk Of Death ◽  
Anca Associated Vasculitis

Figure: Background and Aims Despite improved survival, patients affected by ANCA-associated vasculitis (AAV) presenting with rapidly progressive glomerulonephritis (RPGN) still remain at a higher risk of death relative to the general population. Recent findings suggest a role for the activation of the complement alternative pathway in the pathogenesis of the disease. We aimed to retrospectively evaluate the presentation and outcome of a cohort of patients with AAV and RPGN according to ANCA specificity, investigating the role of complement pathways. Method We retrospectively examined 1,547 biopsies performed between 1996 and 2019 in our center, which included 124 patients presenting with paucimmune RPGN. Patients without ANCA serology and/or with missing data (n=44), ANCA negative RPGN (n=15) and anti-GBM disease (n=2) were excluded from our analysis. Seventy-eight patients with AAV and RPGN (63 biopsy proven) were analysed and compared according to ANCA serotype (n=30 MPO, n=21 PR3). Furthermore, data were analysed on the basis of median levels of serum C3 (1.05 g/l). Statistical analysis Data are mean ± SD or median and interquartile range for variables not normally distributed. Groups were compared using ANOVA after logarithmic transformation of skewed variables. Primary endpoint was renal survival defined as need for renal replacement therapy (NRRT); secondary outcome was patient survival. Cumulative and renal survivals were calculated using Kaplan-Meier method and differences between groups were analysed with the log-rank test. Multivariate Cox proportional hazard analysis for time to NRRT was performed to determine the significance of different risk factors in renal outcome. A p value of < 0.05 was considered statistically significant. Results Patients had a mean age of 64± yrs and eGFR ±15 ml/min at diagnosis. Patients with MPO-AAV were older (69±11 vs. 61±14 yrs, p=0.02) and showed lower levels of C3 (1.0±0.22 vs 1.25±0.2 g/l, p=0.009) as compared to PR3 patients. Moreover, those presenting with C3 levels lower than median value had more advanced renal damage at diagnosis (eGFR 7± ml/min vs 15.5± ml/min, p= 0.04). Serum C3, but not C4 levels, significantly correlated with eGFR, proteinuria and serum uric acid at diagnosis. Twenty-seven (39.7%) reached ESRD requiring RRT. The 1-, 5- and 10- yrs patients renal survivals were 81%, 62.9 % and 52.4%. Renal outcome was neither influenced by ANCA serotype nor gender but patients with C3 levels below median value exhibited a worse renal prognosis (Log rank p=0.02) and a 5 times higher risk of NRRT (HR 5.1, 95% CI 1.4-18.7, p=0.01) independently by potential confounding factors. Conclusion Referral to the nephrologist was late, at an advanced stage of disease, indicating the need to improve the awareness of AAV and RPGN in order to favour early treatment. In this cohort, low C3 indicated a more severe renal damage and predicted poorer renal outcome thus suggesting a role of complement activation in the pathogenesis and progression of these nephritides.

scholarly journals Role of CD8+ T cells in crescentic glomerulonephritis

2019 ◽  
Vol 35 (4) ◽  
pp. 564-572 ◽  
Author(s):  
Anqun Chen ◽  
Kyung Lee ◽  
Tianjun Guan ◽  
John Cijiang He ◽  
Detlef Schlondorff
Keyword(s):  
T Cells ◽  
Immune Complex ◽  
T Cell Activation ◽  
Cd8 T Cells ◽  
Cell Activation ◽  
Crescentic Glomerulonephritis ◽  
Rapidly Progressive Glomerulonephritis ◽  
Inflammatory Cells ◽  
Gain Access

Abstract Crescentic glomerulonephritis (cGN) comprises three main types according to the pathogenesis and immunofluorescence patterns: anti-glomerular basement membrane antibody cGN, vasculitis-associated cGN and post-infectious immune complex cGN. In this brief review of the immune-pathogenesis of cGN, the focus is mainly on the role of CD8+ T cells in the progression of cGN. Under control conditions, Bowman’s capsule (BC) provides a protected immunological niche by preventing access of cytotoxic CD8+ T cells to Bowman’s space and thereby podocytes. Even in experimental nephrotoxic nephritis, leukocytes accumulate around the glomeruli, but remain outside of BC, as long as the latter remains intact. However, when and where breaches in BC occur, the inflammatory cells can gain access to and destroy podocytes, thus converting cGN into rapidly progressive glomerulonephritis (RPGN). These conclusions also apply to human cGN, where biopsies show that loss of BC integrity is associated with RPGN and progression to end-stage kidney disease. We propose a two-hit hypothesis for the role of cytotoxic CD8+ T cells in the progression of cGN. The initial insult occurs in response to the immune complex formation or deposition, resulting in local capillary and podocyte injury (first hit). The injured podocytes release neo-epitopes, eventually causing T-cell activation and migration to the glomerulus. Upon generation of breaches in BC, macrophages and CD8+ T cells can now gain access to the glomerular space and destroy neo-epitope expressing podocytes (second hit), resulting in RPGN. While further investigation will be required to test this hypothesis, future therapeutic trials should consider targeting of CD8+ T cells in the therapy of progressive cGN.

scholarly journals Glomerulonephritis with Crescents in Children: Etiology and Predictors of Renal Outcome

2011 ◽  
Vol 2011 ◽  
pp. 1-5 ◽  
Author(s):  
K. Alsaad ◽  
N. Oudah ◽  
A. Al Ameer ◽  
K. Fakeeh ◽  
A. Al Jomaih ◽  
...  
Keyword(s):  
Renal Function ◽  
Crescentic Glomerulonephritis ◽  
Clinicopathological Features ◽  
Renal Outcome ◽  
Histological Features ◽  
Younger Age ◽  
Renal Prognosis ◽  
The Mean ◽  
Nephrotic Range Proteinuria ◽  
Observation Period

Objective. To investigate the clinicopathological features and outcome of glomerulonephritis with crescents among Saudi children. Method. This is a retrospective study of cases of crescentic glomerulonephritis (CrGN) seen over a 9-year period. Histological features and renal function were recorded. Results. Thirty-seven cases were enrolled. The mean percent of glomeruli with crescents was 39% (±19). Lupus nephritis (LN) was the commonest etiology (54.1%). At presentation, the serum creatinine (SCr) was 218.2 (±174.3) umol/l, and 57.1% of the cases had nephrotic range proteinuria. By the end of the observation period, SCr dropped to 81.0 (±67.7) umol/l (P=0.001). Worsening renal function was associated with younger age (P=0.002), non-LN etiology (P=0.01), more crescents (P=0.019), and ATN (P=0.05). At the end of the followup, more patients in the LN group were dialysis-free (P=0.017) and had improved renal function (0.01) than in the non-LN group. Using multivariate analysis, the only independent factor found to predict need for dialysis or change in SCr level was percent of globally sclerosed glomeruli (P=0.034). Conclusion. LN is the main cause of CrGN in our cohort of children. The LN group had less globally sclerorsed glomeruli and better renal prognosis than the non-LN group.

scholarly journals Glomerular Immune Deposition in MPO-ANCA Associated Glomerulonephritis Is Associated With Poor Renal Survival

2021 ◽  
Vol 12 ◽  
Author(s):  
Wei Lin ◽  
Chanjuan Shen ◽  
Yong Zhong ◽  
Joshua D. Ooi ◽  
Peter Eggenhuizen ◽  
...  
Keyword(s):  
Platelet Count ◽  
Serum Creatinine ◽  
Immune Complex ◽  
Rapidly Progressive Glomerulonephritis ◽  
Vascular Lesions ◽  
Response To Treatment ◽  
Complement C3 ◽  
Renal Outcome ◽  
Histological Lesion ◽  
Immune Deposits

BackgroundRapidly progressive glomerulonephritis caused by antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV) is typically characterized as pauci-immune glomerulonephritis. However, immune complex (IC) deposition in the glomerulus has been reported in a growing number of studies. Here, we assess the presence of glomerular immune deposits alongside renal outcome in myeloperoxidase (MPO)-ANCA associated glomerulonephritis (MPO-ANCA GN).MethodsClinical and histopathologic characteristics of 97 patients with MPO-ANCA GN classified by renal biopsy from January 2008 to December 2019 were extracted retrospectively from electronic medical records. The extent of immune deposits in the kidney (C3, C4, C1q, IgA, IgG, IgM) at diagnosis were analyzed by immunofluorescence (IF). Patients were followed up for a median period of 15 months. The response to treatment and outcomes of renal and histological lesion changes were also assessed.ResultsIn our study, 41% (40/97) of patients showed positive IF (≥2+) for at least one of the six immunoglobulin or complement components tested. Patients with IC deposits showed higher levels of serum creatinine (p=0.025), lower platelet counts (p=0.009), lower serum complement C3 (sC3) (≤790 ml/L) (p=0.013) and serum IgG (p=0.018) than patients with pauci-immune (PI) deposition at diagnosis. End-stage renal disease was negatively associated with eGFR (HR 0.885, 95% CI 0.837 to 0.935, p<0.0001), platelet count (HR 0.996, 95% CI 0.992 to 1.000, p=0.046) and serum globulin (HR 0.905, 95% CI 0.854 to 0.959, p=0.001). Patients with lower sC3 levels showed a worse renal outcome than the patients with normal sC3 at diagnosis (p=0.003). Analysis of the components of the renal deposits found that patients with IgG deposits exhibited a poorer renal outcome compared to patients that were IgG negative (p=0.028). Moreover, Bowman’s capsule rupture occurred less frequently in patients with IgM deposition compared with IgM negative counterparts (p=0.028). Vascular lesions and granuloma-like lesions had been seen more frequently in cases with IgA deposition than those without IgA deposition (p=0.03 and 0.015, respectively).ConclusionIn conclusion, patients with immune complex deposits in the kidney showed less platelet count, lower sC3 and sIgG levels, and higher serum creatinine levels. Patients with low sC3 at initial and with continued low sC3 during the treatment displayed a trend toward poorer kidney survival. Moreover, the IC group showed a worse renal outcome than the PI group, further enforcing the present strategy of introducing complement targeted therapies in AAV.

scholarly journals Experimentally induced anti-myeloperoxidase vasculitis is not attenuated in factor B or VISTA deficient mice

2021 ◽  
Author(s):  
Fernanda Flórez-Barrós ◽  
Simon J. Freeley ◽  
El Li Tham ◽  
Michael G. Robson
Keyword(s):  
Serum Creatinine ◽  
Biochemical Parameters ◽  
Alternative Pathway ◽  
Proteinase 3 ◽  
Wild Type ◽  
Factor B ◽  
Pathway Activation ◽  
Nephrotoxic Nephritis ◽  
Deficient Mice

Background: Anti-neutrophil cytoplasmic antibody vasculitis is characterised by antibodies to myeloperoxidase or proteinase 3. Previous work in murine anti-myeloperoxidase vasculitis has shown a role for the alternative pathway complement component factor B and the anaphylotoxin C5a. However, mice deficient in properdin, which stabilizes the alternative pathway convertase, were not protected. VISTA-deficient mice were protected in the nephrotoxic nephritis model but the role of VISTA in anti-myeloperoxidase vasculitis is unknown. Objectives: This study had two aims. Firstly, we attempted to reproduce previous findings on the role of factor B in anti-myeloperoxidase vasculitis. Secondly, we examined the role of VISTA in this model, in order to see if the protection in the nephrotoxic nephritis model extended to anti-myeloperoxidase vasculitis. Methods: Anti-myeloperoxidase vasculitis was induced in wildtype, factor B, or VISTA deficient mice. Disease was assessed by quanitfying glomerular crescents and macrophages, in addition to albuminuria and serum creatinine. Results: When wild type and factor B deficient mice were compared, there were no differences in any of the histological or biochemical parameters of disease assessed. Similarly, when wild type or VISTA defiicent mice were compared, there were no differences. Conclusions: Factor B deficient mice were not protected which is in contrast to previous studies. Therefore alternative pathway activation is not essential in this model, under the conditions used in this study. VISTA deficient mice were not protected, suggesting that therapies targetting VISTA may not be effective in vasculitis.

Juvenile xanthogranuloma of the subdural spaces mimicking chronic hematoma with positive FDG uptake on PET: case report

2020 ◽  
Vol 26 (4) ◽  
pp. 449-453
Author(s):  
Jacob A. Kahn ◽  
Jeffrey T. Waltz ◽  
Ramin M. Eskandari ◽  
Cynthia T. Welsh ◽  
Michael U. Antonucci
Keyword(s):  
Potential Role ◽  
Response To Treatment ◽  
Juvenile Xanthogranuloma ◽  
Imaging Features ◽  
Limited Information ◽  
Advanced Imaging ◽  
Systemic Involvement ◽  
The Central Nervous System ◽  
Infancy And Early Childhood

The authors report an unusual presentation of juvenile xanthogranuloma (JXG), a non–Langerhans cell histiocytosis of infancy and early childhood. This entity typically presents as a cutaneous head or neck nodule but can manifest with more systemic involvement including in the central nervous system. However, currently there is limited information regarding specific imaging features differentiating JXG from other neuropathological entities, with diagnosis typically made only after tissue sampling. The authors reviewed the initial images of a young patient with shunt-treated hydrocephalus and enlarging, chronic, extraaxial processes presumed to reflect subdural collections from overshunting, and they examine the operative discovery of a mass lesion that was pathologically proven to be JXG. Their results incorporate the important associated histological and advanced imaging features, including previously unreported metabolic activity on FDG PET. Ultimately, the case underscores the need to consider JXG in differential diagnoses of pediatric intracranial masses and highlights the potential role of PET in the initial diagnosis and response to treatment.

scholarly journals Glomerular function in relation to fine airborne particulate matter in a representative population sample

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Ying-Mei Feng ◽  
Lutgarde Thijs ◽  
Zhen-Yu Zhang ◽  
Esmée M. Bijnens ◽  
Wen-Yi Yang ◽  
...  
Keyword(s):  
Serum Creatinine ◽  
Population Sample ◽  
Airborne Particulate Matter ◽  
Blood Stream ◽  
Renal Outcome ◽  
Cross Sectional ◽  
Cholesterol Ratio ◽  
Median Serum ◽  
Renal Responses

AbstractFrom 1990 until 2017, global air-pollution related mortality increased by 40%. Few studies addressed the renal responses to ultrafine particulate [≤ 2.5 µm (PM2.5)], including black carbon (BC), which penetrate into the blood stream. In a Flemish population study, glomerular filtration estimated from serum creatinine (eGFR) and the urinary albumin-to-creatinine ratio were measured in 2005–2009 in 820 participants (women, 50.7%; age, 51.1 years) with follow-up of 523 after 4.7 years (median). Serum creatinine, eGFR, chronic kidney disease (eGFR < 60 mL/min/1.73 m2) and microalbuminuria (> 3.5/> 2.5 mg per mmol creatinine in women/men) were correlated in individual participants via their residential address with PM2.5 [median 13.1 (range 0.3–2.9) μg/m3] and BC [1.1 (0.3–18) μg/m3], using mixed models accounting for address clusters. Cross-sectional and longitudinally, no renal outcome was associated with PM2.5 or BC in models adjusted for sex and baseline or time varying covariables, including age, blood pressure, heart rate, body mass index, plasma glucose, the total-to-HDL serum cholesterol ratio, alcohol intake, smoking, physical activity, socioeconomic class, and antihypertensive treatment. The subject-level geocorrelations of eGFR change with to BC and PM2.5 were 0.13 and 0.02, respectively (P ≥ 0.68). In conclusion, in a population with moderate exposure, renal function was unrelated to ultrafine particulate.

P0590ADVERSE RENAL OUTCOME FOLLOWING ADMINISTRATION OF INTRAVITREAL ANTI-VASCULAR ENDOTHELIAL GROWTH FACTOR INHIBITORS IN A SINGLE TERTIARY CENTRE IN MALAYSIA

2020 ◽  
Vol 35 (Supplement_3) ◽  
Author(s):  
Maisarah Jalalonmuhali ◽  
Tengku Ain Fathlun Tengku Kamalden ◽  
Nurul 'Ain Sham Ismail ◽  
See Yen Yong ◽  
Wei Ting Teo ◽  
...  
Keyword(s):  
Blood Pressure ◽  
Vascular Endothelial Growth Factor ◽  
Growth Factor ◽  
Serum Creatinine ◽  
Post Treatment ◽  
Angiogenic Factor ◽  
Renal Outcome ◽  
Vascular Endothelial ◽  
Anti Vegf ◽  
Endothelial Growth Factor

Abstract Background and Aims Intravenous (IV) anti-vascular endothelial growth factor(VEGF) is a potent anti-angiogenic factor for the treatment of solid tumours. While, intravitreal anti-VEGF injection is used in the treatment for macular and retinal diseases. The effects of IV anti-VEGF agents are well documented to cause hypertension, renal impairment and proteinuria. However only few reports showed the significance of intravitreal anti-VEGF injection causing minimal change disease (MCD) and acute kidney injury (AKI). Hence, this study is to determine the outcome of renal function following intravitreal anti-VEGF injection. Method This is a prospective, cross sectional study recruiting patients from ophthalmology day-care operation theatre that were scheduled for intravitreal anti-VEGF injection in University Malaya Medical Centre (UMMC). On the day of the injection of anti-VEGF, patients’ demographic data (age, gender, medical background, medications), blood pressure, height, weight and investigations for serum creatinine and urine protein creatinine ratio (PCR) were collected. Following these, they will receive the intravitreal anti-VEGF as per schedule. All these patients were given a follow-up within 72hours to reassess blood pressure, serum creatinine and urine PCR. Results A total of 90 patients were recruited. However, 15 patients were subsequently excluded as there was no repeated serum creatinine at 72-hours post treatment. Their mean age was 67.25 ± 10.41. Among all, 3 patients had significance increased in serum creatinine (4%) with significance changed of urine PCR post treatment. Table 1 showed baseline parameters prior to treatment and table 2 was post treatment parameters. Higher serum creatinine and proteinuria pre intravitreal anti-VEGF were identified to have higher OR of 1.018 (95% CI 1.001-1.035) (p=0.043) and OR 1.004 (1.000-1.007) (p=0.025) respectively among those who developed AKI. In assessing the association between higher pre-treatment creatinine and proteinuria (independent variable) and development of AKI (dependent variable) estimated by logistic regression with no AKI as a reference group we found that there were no significance. Conclusion Following intravitreal anti-VEGF administration, there were no significant changes in blood pressure. However, 4% from our cohort had AKI and worsening proteinuria at 72 hours post treatment. These patients had higher serum creatinine and proteinuria prior to treatment. However, our study is underpowered to establish the relationship between intravitreal anti-VEGF and development of AKI. Further study with larger sample size and longer-term outcome is needed.

scholarly journals A novel drug response score more accurately predicts renoprotective drug effects than existing renal risk scores

2021 ◽  
Vol 12 ◽  
pp. 204201882097419
Author(s):  
Nienke M. A. Idzerda ◽  
Sok Cin Tye ◽  
Dick de Zeeuw ◽  
Hiddo J. L. Heerspink
Keyword(s):  
Type 2 Diabetes ◽  
Kidney Disease ◽  
Serum Creatinine ◽  
Risk Score ◽  
Drug Response ◽  
Drug Effects ◽  
Risk Scores ◽  
Renal Outcome ◽  
Response Score

Background: Risk factor-based equations are used to predict risk of kidney disease progression in patients with type 2 diabetes order to guide treatment decisions. It is, however, unknown whether these models can also be used to predict the effects of drugs on clinical outcomes. Methods: The previously developed Parameter Response Efficacy (PRE) score, which integrates multiple short-term drug effects, was first compared with the existing risk scores, Kidney Failure Risk Equation (KFRE) and The Action in Diabetes and Vascular Disease: Preterax and Diamicron Modified Release Controlled Evaluation (ADVANCE) renal risk score, in its performance to predict end-stage renal disease (ESRD; KFRE) and doubling of serum creatinine or ESRD (ADVANCE). Second, changes in the risk scores were compared after 6 months’ treatment to predict the long-term effects of losartan on these renal outcomes in patients with type 2 diabetes and chronic kidney disease. Results: The KFRE, ADVANCE and PRE scores showed similarly good performance in predicting renal risk. However, for prediction of the effect of losartan, the KFRE risk score predicted a relative risk change in the occurrence of ESRD of 3.1% [95% confidence interval (CI) −5 to 12], whereas the observed risk change was −28.8% (95% CI −42.0 to −11.5). For the composite endpoint of doubling of serum creatinine or ESRD, the ADVANCE score predicted a risk change of −12.4% (95% CI −17 to −7), which underestimated the observed risk change −21.8% (95% CI −34 to −6). The PRE score predicted renal risk changes that were close to the observed risk changes with losartan treatment [−24.0% (95% CI −30 to −17) and −22.6% (95% CI −23 to −16) for ESRD and the composite renal outcome, respectively]. Conclusion: A drug response score such as the PRE score may assist in improving clinical decision making and implement precision medicine strategies.

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