MO444MACROPHAGE DENSITIES CORRELATE WITH LONG-TERM FUNCTION IN PAUCI-IMMUNE AND MEMBRANOUS GLOMERULONEPHRITIS AS WELL AS IN HYPERTENSIVE NEPHROPATHY

2021 ◽  
Vol 36 (Supplement_1) ◽  
Author(s):  
Maren Bettina Pfenning ◽  
Jessica Schmitz ◽  
Kevin Schulte ◽  
Carsten Hafer ◽  
Abedalrazag Ahmad Khalifa ◽  
...  
Keyword(s):  
Kidney Diseases ◽  
Laboratory Data ◽  
Kidney Injury ◽  
Membranous Glomerulonephritis ◽  
Renal Outcome ◽  
Renal Diseases ◽  
Hypertensive Nephropathy ◽  
And Control ◽  
Control Samples

Abstract Background and Aims Macrophages and monocytes are main players in innate immunity. In renal diseases, their role is poorly understood. Our multicentric cross-sectional study aimed to study the prevalence of macrophages and monocytes in various human native kidney diseases. For this, we used precise pixel-based digital quantification of their densities in renal biopsies and correlated our findings with clinical data. Method We included 324 patients, who underwent a diagnostic renal biopsy. Additional normal kidney samples from 16 tumour nephrectomies were used as controls. According to the diagnosed diseases, we established 17 patient groups. Biopsies were stained for CD68+-macrophages using automated immunohistochemistry (Ventana Ultra) and selected groups were further subtyped for CD14+-monocytes and CD163+-M2-macrophages (67 cases, pauci-immune glomerulonephritis (PIGN), IgA-nephropathy (IgAN) and control samples). Digitized sections (Leica) were analysed using the open-source software QuPath to quantify cell densities (positively stained areas displayed as percentages of ROI) in renal cortex, medulla and extrarenal tissue, respectively. Detailed clinical and laboratory data at timepoint of biopsy were available for all patients. Additional data for follow-up were achievable in 158 cases. Results Renal disease samples presented higher mean macrophage densities compared to control cases (CD68: cortex 1.2 vs. 0.2%, p<0.001, medulla 0.8 vs. 0.04%, p<0.001; CD163: cortex 3.2 vs. 0.5%, p<0.001, medulla 2.3 vs. 0.6%, p<0.05), but CD14+-density did not differ between patients and control samples. The highest cortical CD68+-density occurred in PIGN (1.98%) and in medulla in ascending infections (1.86%). The lowest cortical CD68+-densities were measured in thin basal membrane syndrome / Alport-syndrome (0.56%) and in medulla in immunotactoid and fibrillary glomerulopathy (0.26%). Chronic kidney disease displayed lower percentages of CD68+-densities (cortex: 1.15%; medulla: 0.49%) compared to acute kidney injury (cortex: 1.84%, p<0.001; medulla: 1.08%, p<0.001) and acute on chronic kidney injury (cortex: 1.81%, p<0.001; medulla: 1.43%, p<0.001). We detected a correlation of CD68+- and CD163+-infiltration with kidney function (eGFR) in cortex and medulla at the time of biopsy (CD68: r=-0.51 for cortex, r=-0.60 for medulla; CD163: r=-0.71 for cortex, r=-0.73 for medulla; p<0.001) and follow up (CD68: r=-0.41 for cortex, r=-0.34 for medulla, p<0.001; CD163: r=-0.46 for cortex, r=-0.50 for medulla, p<0.05). Older patients (>64 years) showed a higher medullary M2-infiltration (1.81% vs. 4.34%, p<0.005). The eGFR at the time of biopsy inversely correlated (p<0.05) with cortical CD68+-density in IgAN (r=-0.39), PIGN (r=-0.53), membranous glomerulonephritis (MGN; r=-0.70), focal segmental glomerulonephritis (r=-0.63), and hypertensive nephropathy (HNP; r=-0.44). At follow-up, this correlation (p<0.05) was still present in PIGN (r=-0.43), MGN (r=-0.58), and HNP (r=-0.77). In PIGN, cortical CD163+-density and eGFR were associated (p<0.001) at timepoint of biopsy (r=-0.51) and follow-up (r=-0.51). Particularly, cANCA-vasculitis showed a strong correlation between eGFR and cortical CD68+- as well as CD163+-densities at time of biopsy (CD68: r=-0.78; CD163: r=-0.75, p<0.001) and also for follow-up (CD68: r=-0.48; CD163: r=-0.68, p<0.05). Conclusion Macrophages may promote progression of human renal diseases, whereas monocytes do not correlate with eGFR-decline. Especially, in cANCA- vasculitis CD163+- infiltration is associated with renal outcome. Additional studies are needed to investigate, whether macrophages can serve as predictive markers or therapeutical targets in native renal diseases.

scholarly journals P0695ANALYSIS OF HOSPITALIZATION EVENTS IN NON-DIALYSIS CKD PATIENTS

2020 ◽  
Vol 35 (Supplement_3) ◽  
Author(s):  
Marcora Mandreoli ◽  
Dino Gibertoni ◽  
Antonio Santoro
Keyword(s):  
Hospital Admissions ◽  
Laboratory Data ◽  
Kidney Injury ◽  
Vascular Diseases ◽  
Hospitalization Rate ◽  
Renal Diseases ◽  
Ckd Stage ◽  
Emilia Romagna Region ◽  
Specific Care

Abstract Background and Aims Data are limited about rates and causes of hospitalization in patients with Chronic Kidney Disease (CKD) during maintenance period. In the present study, we investigate the amount, characteristics and trends of hospital admissions in a large cohort of pre-dialysis CKD patients followed within the Emilia-Romagna Region (Italy) PIRP project. Method Patients who were enrolled in the PIRP project in the period 1.4.2004-31.12.2018 constitute the study population. The PIRP database contains clinical and laboratory data collected at each follow-up visit. Hospitalization data regarding admissions occurred during patients’ follow-up in PIRP were obtained from the regional hospital discharges database through unique individual linkage. Day-hospital admissions and hospitalizations aimed at arteriovenous fistula creation and peritoneal catheter placement were excluded. Results In almost 15 years of observation, 27,886 patients were enrolled in PIRP, mostly males (65,3%) with baseline median age of 75 years and baseline median eGFR=32.3 mL/min/1.73m2. Among them, 19,288 (69.2%) generated 72,432 hospitalizations during their follow-up in the project. The number of hospitalizations per person/year was 1.06 overall, increasing from 0.38 for stage CKD 1 to 1.93 for stage CKD 5 (Fig.1). The median length of stay was 9 days. Overall, cardio-vascular diseases were the main cause of hospitalization (30.0% of admissions), with renal diseases, tumors and respiratory diseases each accounting for over 10% of admissions, although the distribution of causes of hospitalization varies according to CKD stage (Fig.2). About one fifth of patients had one or more hospitalizations for acute kidney injury. The trend analysis revealed a steadily decreasing hospitalization rate for patients that were on CKD stage 4 and 5 at baseline, a constant hospitalization trend over time for patients who began their follow-up in stages 1 to 3a, while hospitalization rate of patients in CKD 3b stage declined after 9 years (Fig 3). Conclusion The study broadens our knowledge on the hospitalizations “consumption” by the population with CKD in the non-dialysis phase. It confirms that patients with CKD represent a vulnerable population, needing about 1 hospitalization / year / patient. The trend towards a reduction in hospitalizations during the follow-up period could be traced back to the specific care model, which encourages a more frequent management of patients in the Nephrology clinics.

scholarly journals CD73 Overexpression in Podocytes: A Novel Marker of Podocyte Injury in Human Kidney Disease

2021 ◽  
Vol 22 (14) ◽  
pp. 7642
Author(s):  
Zoran V. Popovic ◽  
Felix Bestvater ◽  
Damir Krunic ◽  
Bernhard K. Krämer ◽  
Raoul Bergner ◽  
...  
Keyword(s):  
Kidney Disease ◽  
Kidney Diseases ◽  
Kidney Injury ◽  
Membranous Glomerulonephritis ◽  
Human Kidney ◽  
Protective Role ◽  
Control Group ◽  
Podocyte Injury ◽  
Ccr2 Expression ◽  
Cd73 Expression

The CD73 pathway is an important anti-inflammatory mechanism in various disease settings. Observations in mouse models suggested that CD73 might have a protective role in kidney damage; however, no direct evidence of its role in human kidney disease has been described to date. Here, we hypothesized that podocyte injury in human kidney diseases alters CD73 expression that may facilitate the diagnosis of podocytopathies. We assessed the expression of CD73 and one of its functionally important targets, the C-C chemokine receptor type 2 (CCR2), in podocytes from kidney biopsies of 39 patients with podocytopathy (including focal segmental glomerulosclerosis (FSGS), minimal change disease (MCD), membranous glomerulonephritis (MGN) and amyloidosis) and a control group. Podocyte CD73 expression in each of the disease groups was significantly increased in comparison to controls (p < 0.001–p < 0.0001). Moreover, there was a marked negative correlation between CD73 and CCR2 expression, as confirmed by immunohistochemistry and immunofluorescence (Pearson r = −0.5068, p = 0.0031; Pearson r = −0.4705, p = 0.0313, respectively), thus suggesting a protective role of CD73 in kidney injury. Finally, we identify CD73 as a novel potential diagnostic marker of human podocytopathies, particularly of MCD that has been notorious for the lack of pathological features recognizable by light microscopy and immunohistochemistry.

scholarly journals Significance of Crescentic Glomeruli in Acute Kidney Injury with Rheumatoid Arthritis

2019 ◽  
Vol 9 (1) ◽  
pp. 42-48
Author(s):  
Ali Ayaash ◽  
Dipesh Maan ◽  
Anastasios Kapetanos ◽  
Mark Bunker ◽  
Mary Chester Wasko ◽  
...  
Keyword(s):  
Rheumatoid Arthritis ◽  
Acute Kidney Injury ◽  
Kidney Injury ◽  
Renal Outcome ◽  
Primary Role ◽  
Tubular Necrosis ◽  
Immune Mediated ◽  
Autoimmune Conditions ◽  
Spontaneous Improvement

Crescentic glomerulonephritis (GN) without immune reactants or deposits (referred to as pauci-immune) is typically characterized by the presence of anti-neutrophilic cytoplasmic antibodies (ANCA). While ANCA-negative patients might be expected to have a more benign course, they often have poor renal outcomes, especially without treatment with steroids and immune-modulating therapy. Pauci-immune crescentic GN can also co-exist with other autoimmune conditions, including rheumatoid arthritis (RA). Here, we describe an ANCA-negative patient with RA who developed dialysis-requiring acute kidney injury (AKI) with findings consistent with focal pauci-immune crescentic GN (i.e., no IgG or immune complex on kidney biopsy). Coexistent conditions included Klebsiella sepsis attributed to pneumonia, rhabdomyolysis, leukocytoclastic immune-mediated skin vasculitis, and positive ANA. He had spontaneous improvement in renal function without immunosuppressive therapy. This crescentic GN was not associated with poor renal outcome as AKI resolved with supportive care and treatment of his infection. The AKI was likely multifactorial with co-existing acute tubular necrosis in the setting of Kebsiella sepsis and rhabdomyolysis, and the crescentic GN was felt more likely to be related to the infection rather than having a primary role. This case highlights the importance of viewing crescentic GN in the context of the clinical picture, as it may not always lead to the need of aggressive immune suppression and is not a universally poor prognostic kidney finding. However, these cases do warrant close follow-up as our patient had recurrent RA disease manifestations over the next 2 years that eventually led to his death from severe pulmonary hypertension.

scholarly journals Circular RNAs as Novel Diagnostic Biomarkers and Therapeutic Targets in Kidney Disease

2021 ◽  
Vol 8 ◽  
Author(s):  
Jianwen Yu ◽  
Danli Xie ◽  
Naya Huang ◽  
Qin Zhou
Keyword(s):  
Kidney Disease ◽  
Kidney Diseases ◽  
Expression Patterns ◽  
Therapeutic Targets ◽  
Kidney Injury ◽  
Renal Diseases ◽  
Circular Rnas ◽  
Specific Expression ◽  
Glomerular Diseases ◽  
Diagnosis And Prognosis

Circular RNAs (circRNAs) are a novel type of non-coding RNAs that have aroused growing attention in this decade. They are widely expressed in eukaryotes and generally have high stability owing to their special closed-loop structure. Many circRNAs are abundant, evolutionarily conserved, and exhibit cell-type-specific and tissue-specific expression patterns. Mounting evidence suggests that circRNAs have regulatory potency for gene expression by acting as microRNA sponges, interacting with proteins, regulating transcription, or directly undergoing translation. Dysregulated expression of circRNAs were found in many pathological conditions and contribute to the pathogenesis and progression of various disorders, including renal diseases. Recent studies have revealed that circRNAs may serve as novel reliable biomarkers for the diagnosis and prognosis prediction of multiple kidney diseases, such as renal cell carcinoma (RCC), acute kidney injury (AKI), diabetic kidney disease (DKD), and other glomerular diseases. Furthermore, circRNAs expressed by intrinsic kidney cells are shown to play a substantial role in kidney injury, mostly reported in DKD and RCC. Herein, we review the biogenesis and biological functions of circRNAs, and summarize their roles as promising biomarkers and therapeutic targets in common kidney diseases.

Renal pathology

2017 ◽  
Author(s):  
James Carton
Keyword(s):  
Kidney Disease ◽  
Basement Membrane ◽  
Reflux Nephropathy ◽  
Kidney Injury ◽  
Renal Pathology ◽  
Renal Diseases ◽  
Obstructive Nephropathy ◽  
Hypertensive Nephropathy ◽  
Membranous Glomerulopathy ◽  
Post Infectious

This chapter discusses renal pathology, including acute kidney injury (AKI), chronic kidney disease (CKD), nephrotic syndrome, hereditary renal diseases, Alport’s syndrome and thin basement membrane lesion, hypertensive nephropathy, diabetic nephropathy, minimal change disease (MCD), focal segmental glomerulosclerosis (FSGS), membranous glomerulopathy, glomerulonephritis, IgA nephropathy, post-infectious glomerulonephritis, C3 glomerulopathy, anti-glomerular basement membrane disease, monoclonal gammopathy-associated kidney disease, acute tubular injury, acute tubulointerstitial nephritis, reflux nephropathy, and obstructive nephropathy.

scholarly journals iTRAQ-based comparative proteomics analysis reveals specific urinary biomarkers for various kidney diseases

2019 ◽  
Author(s):  
Juan Jin ◽  
Jianguang Gong ◽  
Li Zhao ◽  
Yiwen Li ◽  
Qiang He
Keyword(s):  
Biomarker Discovery ◽  
Bioinformatics Analysis ◽  
Kidney Diseases ◽  
Kidney Injury ◽  
Renal Diseases ◽  
Urinary Proteins ◽  
Proteomics Analysis ◽  
Kegg Pathway Analysis ◽  
Go Enrichment ◽  
Differentially Abundant Proteins

Abstract Background Urinary proteomics has been extensively applied to investigate renal diseases including acute kidney injury (AKI), chronic kidney disease (CKD), IgA nephropathy (IgAN) and diabetic CKD. However, differential urinary proteome studies have not been reported for multiple diseases. The present study was aimed to explore early clinical diagnosis biomarkers for patients with AKI, AKI+CKD, diabetic CKD, non-diabetic CKD with IgAN and non-diabetic CKD without IgAN. Methods Differentially expressed proteins (DEPs) were screened by iTRAQ labeling and 2-D LC-MS/MS. Bioinformatics analysis was performed by subsequent GO enrichment and KEGG pathway analysis. DEPs were authenticated by ELISA assay. Results 156, 156, 286, 187 and 184 differentially abundant proteins were identified in patients with AKI, AKI+CKD, diabetic CKD, and non-diabetic CKD with or without IgAN. Comparative analysis indicated that 34, 35 and 17 unique DEPs were found in AKI, AKI+CKD and CKD samples, respectively. 91 and 14 specific DEPs were screened out in diabetic CKD and non-diabetic CKD. In comparison with Non-diabetic CKD with IgAN (38 DEPs), 47 unique urinary proteins were found in Non-diabetic CKD without IgAN. Among these DEPs, urinary SAA1 and HGFAC were only unregulated in AKI and Non-diabetic CKD without IgAN implying that they might be employed as the potential indicators of the two diseases. C5, APOC1 and Reg3A upregulation was not exclusively expressed in each disease which suggested that they could not be used for biomarker to distinguish one disease from the other. Conclusion Collectively, this research contributes to the urinary biomarker discovery from multiple renal diseases.

scholarly journals Eculizumab in Gemcitabine-Induced Thrombotic Microangiopathy: Experience of the French Thrombotic Microangiopathies Reference Centre

2021 ◽  
Author(s):  
Maximilien Grall ◽  
Florence Daviet ◽  
Noémie Jourde Chiche ◽  
François Provot ◽  
Claire Presne ◽  
...  
Keyword(s):  
Renal Function ◽  
Thrombotic Microangiopathy ◽  
Kidney Injury ◽  
Renal Outcome ◽  
Control Group ◽  
Packed Red Blood Cells ◽  
Reference Centre ◽  
Renal Function Recovery ◽  
Function Recovery

Abstract Background Gemcitabine is a broadly prescribed chemotherapy, the use of which can be limited by renal adverse events, including thrombotic microangiopathy (TMA). Methods This study evaluated the efficacy of eculizumab, a monoclonal antibody targeting the terminal complement pathway, in patients with gemcitabine-induced TMA (G-TMA). We conducted an observational, retrospective, multicenter study in 5 French centres, between 2011 and 2016. Results Twelve patients with a G-TMA treated by eculizumab were included. The main characteristics were acute renal failure (100%), including stage 3 acute kidney injury (AKI, 58%) and renal replacement therapy (17%), hypertension (92%) and diffuse oedema (83%). Eculizumab was started after a median of 15 days (range 4–44) following TMA diagnosis. A median of 4 injections of eculizumab was performed (range 2–22). Complete hematological remission was achieved in 10 patients (83%) and blood transfusion significantly decreased after only one injection of eculizumab (median of 3 packed red blood cells (range 0–10) before treatment vs 0 (range 0–1) after one injection, P < 0.001). Two patients recovered completely renal function (17%), and 8 achieved a partial remission (67%). Compared to a control group of G-TMA without use of eculizumab, renal outcome was more favourable. At the end of the follow up, median eGFR was 45 vs 33 ml/min/1.73m2 respectively in the eculizumab group and in the control group. Conclusions These results suggest that eculizumab is efficient on haemolysis and reduces transfusion requirement in G-TMA. Moreover, eculizumab may improve renal function recovery.

scholarly journals MO377HOW THE ITALIAN COVID-19 LOCKDOWN AFFECTED NEFROLOGICAL ACTIVITY IN A LOMBARD CENTER

2021 ◽  
Vol 36 (Supplement_1) ◽  
Author(s):  
Paolo Albrizio ◽  
Silvano Costa ◽  
Annalisa Foschi ◽  
Ivo Angelo Antonio Milani ◽  
Stefano Rindi ◽  
...  
Keyword(s):  
Acute Kidney Injury ◽  
Kidney Injury ◽  
First Aid ◽  
The Other ◽  
Renal Diseases ◽  
Significant Difference

Abstract Background and Aims Italy and Lombard hospitals particularly, were hard affected by Covid-19 pandemic, mostly during spring and autumn, seasons characterized by two lockdown periods which were however, partly different as rules. During first lockdown in fact, by hospital decision, all ambulatorial activity was closed, including nephrological one. This did not happen during second lockdown period. How the different choices about hospital activity affected nephrological patients is the aim of this study. Method we evaluated all nephrological advices requested by first aid units of our 3 hospitals, all located in Lombardy, to our Nephrology Unit, splitting out data in 3 periods (I lockdown, summer and II lockdown) and comparing with 2019. Data collected were: number of advices requested by day, age, sex, previous regular nephrological follow-up, Covid-19 diagnosis, nephrological diagnosis after nephrological advice and outcome. Results as shown in table 1, during I lockdown period, with hospital decision of suspending our nephrological ambulatorial activity, we suffered an incremented rate of patients approaching local first aid units compared to 2019 same period with an increased rate of acute kidney injury, mostly for dehydration, and with a higher rate of patients requiring hospitalization. All these differences resulted statistically significant vs 2019 same period (figure 1). On the other side, no statically significant difference was found during the other two examined periods, including the II lockdown, while all our ambulatories were fully operating. Conclusion Covid-19 pandemic affected also the nephrological population with an increased rate of first aid units’ accesses, acute kidney injury events and hospitalization comparing to 2019. However, these differences were detectable only during the I lockdown period characterized by the suspension of all ambulatorial activity, including our Unit. The absence of statistically significant differences during summer and primarily during II lockdown period demonstrates the importance of nephrological ambulatorial activity in management of renal diseases and in prevention of acute events.

scholarly journals IL-20 in Acute Kidney Injury: Role in Pathogenesis and Potential as a Therapeutic Target

2020 ◽  
Vol 21 (3) ◽  
pp. 1009
Author(s):  
Tian-Yu Lin ◽  
Yu-Hsiang Hsu
Keyword(s):  
Chronic Kidney Disease ◽  
Acute Kidney Injury ◽  
Risk Factor ◽  
Renal Fibrosis ◽  
Inflammatory Mediator ◽  
Kidney Diseases ◽  
Kidney Injury ◽  
Renal Diseases ◽  
Pro Inflammatory Cytokines

Acute kidney injury (AKI) causes over 1 million deaths worldwide every year. AKI is now recognized as a major risk factor in the development and progression of chronic kidney disease (CKD). Diabetes is the main cause of CKD as well. Renal fibrosis and inflammation are hallmarks in kidney diseases. Various cytokines contribute to the progression of renal diseases; thus, many drugs that specifically block cytokine function are designed for disease amelioration. Numerous studies showed IL-20 functions as a pro-inflammatory mediator to regulate cytokine expression in several inflammation-mediated diseases. In this review, we will outline the effects of pro-inflammatory cytokines in the pathogenesis of AKI and CKD. We also discuss the role of IL-20 in kidney diseases and provide a potential therapeutic approach of IL-20 blockade for treating renal diseases.

Ultrastructural application of the patsc-GMS staining in various kidney diseases

1993 ◽  
Vol 51 ◽  
pp. 308-309
Author(s):  
Shigeki Namimatsu ◽  
Shin-ichi Nakamura ◽  
Yoshizo Nakagami ◽  
Tatsuo Oguro ◽  
Goro Asano
Keyword(s):  
Kidney Diseases ◽  
Periodic Acid ◽  
Membranous Glomerulonephritis ◽  
Human Kidney ◽  
Renal Diseases ◽  
Ammonia Water ◽  
Transmission Electron ◽  
Ultrathin Sections ◽  
Methenamine Silver ◽  
Grid Mesh

We have previously reported a new staining method, PATSC-GMS, for transmission electron microscopy. In the present study, we evaluated the stainability and usefulness of the PATSC-GMS method in tissues from renal diseases.Fifty human kidney biopsies comprising normal (n=2), membranous glomerulonephritis (n=10), Alport's syndrome (n=l), IgA nephropathy (n=4), and other cases (n=33) were studied. Samples were pre-fixed in 2.5% glutaraldehyde, post-fixed in 1% osmium tetroxide, and embedded in Epok-812 after dehydration. Ultrathin sections were made and placed on nickel grid mesh. The sections of the tissues were Pre-incubated in ammonia water(25%) for 10minutes, oxidized in 1% periodic acid for 20 minutes, reacted in 0.1% thiosemicarbazid (TSC) for lminute, post-incubated in ammonia water(25%) for 5minutes and stained with gelatin methenamine silver(GMS) solution: (50ml of 3% methenamine, 5ml of 2% gelatin, 5ml of 5% silver nitrate, 40ml of distilled water, and 5-6ml of 5% sodium tetraborate) was performed for 50C 50minutes in the oven.

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