scholarly journals Membrane attack complex (MAC) deposition in renal tubules is associated with interstitial fibrosis and tubular atrophy: a pilot study

2022 ◽  
Vol 9 (1) ◽  
pp. e000576
Author(s):  
Shudan Wang ◽  
Ming Wu ◽  
Luis Chiriboga ◽  
Briana Zeck ◽  
Beatrice Goilav ◽  
...  
Keyword(s):  
Interstitial Fibrosis ◽  
Membrane Attack Complex ◽  
Staining Intensity ◽  
Cross Sectional Study ◽  
Renal Tubules ◽  
Tubulointerstitial Injury ◽  
Tubular Atrophy ◽  
Cross Sectional ◽  
Stage Renal Disease ◽  
Complement C9

IntroductionTreatment failures for lupus nephritis (LN) are high with 10%–30% of patients progressing to end-stage renal disease (ESRD) within 10 years. Interstitial fibrosis/tubular atrophy (IFTA) is a predictor of progression to ESRD. Prior studies suggest that tubulointerstitial injury secondary to proteinuria in LN is mediated by complement activation in the tubules, specifically through the membrane attack complex (MAC). This study aimed to investigate the associations between tubular MAC deposition with IFTA and proteinuria.MethodsIn this cross-sectional study, LN kidney biopsies were assessed for MAC deposition by staining for Complement C9, a component of the MAC. Chromogenic immunohistochemistry was performed on paraffin-embedded human renal biopsy sections using unconjugated, murine anti-human Complement C9 (Hycult Biotech, clone X197). Tubular C9 staining intensity was analysed as present versus absent. IFTA was defined as minimal (<10%), mild (10%–24%), moderate (25%–50%) and severe (>50%).ResultsRenal biopsies from 30 patients with LN were studied. There were 24 (80%) female sex, mean age (SD) was 33 (12) years old and 23 (77%) had pure/mixed proliferative LN. Tubular C9 staining was present in 7 (23%) biopsies. 27 patients had minimal-to-mild IFTA and 3 patients had moderate IFTA. Among the C9 + patients, 3 (43%) had moderate IFTA as compared with none in the C9- group, p=0.009. C9 + patients had higher median (IQR) proteinuria as compared with C9- patients: 6.2 g (3.3–13.1) vs 2.4 g (1.3–4.6), p=0.001 at the time of biopsy. There was no difference in estimated glomerular filtration rate (eGFR) between the C9 + and C9- groups.ConclusionThis study demonstrated that tubular MAC deposition is associated with higher degree of IFTA and proteinuria, which are predictors of progression to ESRD. These results suggest that tubular MAC deposition may be useful in classification of LN. Understanding the role of complement in tubulointerstitial injury will also identify new avenues for LN treatment.

Relationship between renal tubulointerstitial fibrosis and serum prolidase enzyme activity

2020 ◽  
Vol 45 (5) ◽  
pp. 567-573
Author(s):  
Baris Eser ◽  
Ibrahim Dogan ◽  
Erdal Komut ◽  
Sumeyra Koyuncu ◽  
Nihal Aydemir ◽  
...  
Keyword(s):  
Enzyme Activity ◽  
Renal Biopsy ◽  
Interstitial Fibrosis ◽  
Cross Sectional Study ◽  
Collagen Turnover ◽  
Tubular Atrophy ◽  
Cross Sectional ◽  
Renal Tubulointerstitial Fibrosis ◽  
Key Enzyme

AbstractObjectivesThe severity of interstitial fibrosis/tubular atrophy (IFTA) is the most important determinant of the irreversible progression of chronic kidney disease (CKD). Prolidase is the key enzyme in collagen turnover and is associated with an extracellular matrix increase. We aimed to evaluate the relationship between the presence and degree of IFTA and serum prolidase enzyme activity (SPEA) in patients undergoing a renal biopsy.MethodsThis cross-sectional study included 56 patients who underwent a renal biopsy (30 males; mean age 45.3 ± 16.8 years) and also 54 healthy volunteers (21 males; mean age 42.7 ± 8.2 years). IFTA scoring was performed on the basis of percentage of IFTA presence in renal biopsy tissues (1=<10%; 2=10–24%; 3=25–50%; 4=>50%). SPEA was measured by spectrophotometric method.ResultsThe proteinuria and SPEA levels of the patients were significantly higher than the controls (p<0.001 and p<0.001, respectively). SPEA decreased significantly when the IFTA score increased (p<0.002). In the correlation analysis, the IFTA score was negatively correlated with SPEA (rs=−0.461, p<0.001), and positively correlated with proteinuria (rs=0.274, p=0.041).ConclusionThese findings suggest that increased collagen turnover decreases over time concerning the progression of renal fibrosis. Monitoring of SPEA level may useful as a biomarker for early determination of CKD progression and severity.

scholarly journals Prevalence of Microalbuminuria and Overt Proteinuria in Hypertension and Their Relations with Renal Function in a Rural Population of Bangladesh

2014 ◽  
Vol 24 (2) ◽  
pp. 59-64 ◽  
Author(s):  
ANME Karim ◽  
D Das ◽  
M Salahuddin ◽  
GA Marjan ◽  
MN Islam ◽  
...  
Keyword(s):  
Adult Population ◽  
Negative Relationship ◽  
Cross Sectional Study ◽  
Dipstick Test ◽  
Significant Deterioration ◽  
Cross Sectional ◽  
Spot Urine ◽  
Urine Dipstick Test ◽  
Overt Proteinuria ◽  
Stage Renal Disease

Hypertension is the third leading cause of chronic kidney disease (CKD) in Bangladesh. Microalbuminuria and overt proteinuria are the markers of the CKD. So detection of microalbuminuria and overt proteinuria in hypertensive subjects will help to identify the patient at risk of developing progressive renal impairment. This cross sectional study was carried out in a rural area of Bangladesh.1134 adult population (age between 18 and 65 years) were screened. A total of 217 (19.1%) were detected hypertensive; spot urine dipstick test was done among them. Those who where dipstick negative further studied for presence of microalbumin [ mg/L ]. Blood glucose level, serum creatinine, and estimated glomerular filtration rate (eGFR) were evaluated. A group of normotensive people (n=245) taken as comparison group. Microalbuminuria and overt proteinuria were present in 26.4% and 9.7% of the hypertensive subjects, respectively. Correlation between microalbuminuria and eGFR showed that two variables exhibited a tendency for negative relationship, although correlation was not statistically significant (P=0.186, r=-0.064). Overt proteinuric subjects showed no statistically significant deterioration of eGFR (81.6±21.1). Microalbuminuria and overt proteinuria are prevalent among the hypertensive rural Bangladeshi people. So early detection of microalbuminuria and overt proteinuria will help to prevent or delay the development of end stage renal disease. DOI: http://dx.doi.org/10.3329/bjmed.v24i2.18700 Bangladesh J Medicine 2013; 24 : 59-64

scholarly journals Electrocardiogram changes in patients with end stage renal disease on chronic haemodialysis

2019 ◽  
Vol 7 (11) ◽  
pp. 4020
Author(s):  
Kareem Mohsin Yousif ◽  
Hamid Obaid Khadhim Al Jaaed
Keyword(s):  
Renal Disease ◽  
Social History ◽  
End Stage Renal Disease ◽  
Cross Sectional Study ◽  
Premature Ventricular Complex ◽  
Chronic Haemodialysis ◽  
Ecg Changes ◽  
Cross Sectional ◽  
Stage Renal Disease ◽  
End Stage

Background: End stage renal disease (ESRD) is irreversible loss of renal function which is physiologically defined by a GFR of less than 15 ml / minute. ESRD is associated with a higher incidence of coronary artery disease and serious arrhythmia especially ventricular arrhythmia. The goal of study is to determine whether ESRD and haemodialysis (HD)are associated with occurrence of significant electrocardiogram (ECG) changes or not.Methods: This is a cross-sectional study design which involved 22 patients with ESRD on regular HD in Al Sadre teaching hospital / Al Najaf. Both sexes was included in this study. All patients underwent full medical history and examination which included the following aspects: Age, Sex, Occupation, BP, HR, RBS, B.urea, S.creatinine , Serum electrolyte (Na+, K+, Cl-, Ca++), Lipid profile (Cholesterol , Triglyceride, HDL, LDL), Duration of CRF, Duration of dialysis, Social history including (smoking, alcohol) and Drug used by the patient. Resting EGC and Hotler ECG.Results: Eighteen patients exhibited emergence of simple ectopic activity premature atrial complex (PAC) and premature ventricular complex (PVC) events and four patients exhibited (ST,T changes). Potentially lethal arrhythmias and other serious ECG changes are not detected in our patient’s sample.Conclusion: In this study, neither ESRD nor haemodialysis were associated with development of serious ECG changes or emergence of significant arrhythmia.

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 Acute Intradialytic Complications in End Stage Renal Disease on Maintenance Hemodialysis

2012 ◽  
Vol 52 (187) ◽  
Author(s):  
R K Agrawal ◽  
S Khakurel ◽  
R Hada ◽  
D Shrestha ◽  
A Baral
Keyword(s):  
Renal Failure ◽  
Renal Disease ◽  
End Stage Renal Disease ◽  
Tertiary Care ◽  
Cross Sectional Study ◽  
Maintenance Hemodialysis ◽  
Care Hospital ◽  
Cross Sectional ◽  
Stage Renal Disease ◽  
End Stage

Introduction: Hemodialysis is the preferred method of treatment for Nepalese patients with End Stage Renal Disease. Despite the technological advances and better understanding of physiology associated with hemodialysis, a number of complications are known to be associated with hemodialysis. This study was undertaken to study the frequency of acute intradialytic complications in patients undergoing hemodialysis. Methods: A cross-sectional study was conducted at Nephrology unit of a tertiary care hospital from 15 June, 2007 to 15 December, 2007. A total of 28 patients were included in the study. Patients with acute renal failure and acute on chronic renal failure were excluded from the study. Results: Total sessions of hemodialysis during the period were 1455. Hypotensive episode were 66 (4.5%) and was the commonest complication and followed by hypertensive episodes were 58 (3.8%). Other problems encountered were transfusion reactions were 23 episodes (1.5%), rigors not related to transfusions were 13 episodes (0.8%), nausea/vomiting were 20 episodes (1.4%), muscle cramps were 12 episodes (0.8%), hypoglycemia were 6 episodes 5(0.4%). Conclusions: The frequency of intradialytic complications is low and many of them are not life threatening. Keywords: complications; end stage renal disease; hemodialysis; hypertension; hypotension.

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.

Effect of hyperparathyroidism on vascular stiffness in hemodialysis patients

QJM ◽  
2021 ◽  
Vol 114 (Supplement_1) ◽  
Author(s):  
Magdy Mohamed Saeed El-Sharkawy ◽  
Ahmed Hassan Mohamed El Thakaby ◽  
Ahmed Abdelmoniem Emara ◽  
Ahmed Mohamed Abdelkhalek
Keyword(s):  
Arterial Stiffness ◽  
Pulse Wave ◽  
Cross Sectional Study ◽  
Hemodialysis Patients ◽  
Mean Value ◽  
University Hospitals ◽  
Cross Sectional ◽  
Risk Of Death ◽  
Group B ◽  
Stage Renal Disease

Abstract Background Cardiovascular disease (CVD) is present in &gt; 50% of patients undergoing dialysis and the relative risk of death due to CVD events in HD patients is reported to be 20 times higher than in the general population. In fact, in patients on renal replacement therapy (RRT) the prevalence of coronary heart disease and ventricular hypertrophy has been described to be 40% and 70% respectively, other CVD events include hypertention, arrhythmias, valvular calcification and arterial stiffness. Objective To detect the prevalence of arterial stiffness among end stage renal disease patients on prevalent hemodialysis with hyperparathyroidism. Patients and Methods This observational cross sectional study was conducted on 60 prevalent hemodialysis patients attending at hemodialysis unit of Ain Shams University hospitals, with convenient sampling method. The included patients are clinically stable on thrice weekly hemodialysis sessions for 4 hours per session. Results The Dual Pulse Wave Doppler (DPWD) method we proposed in this study may be considered as a useful and convenient option for clinical local Pulse Wave Velocity (PWV) measurement, this clinical practical and reproducible method had the capability to detect an increased local PWV of LCCA (which reflect arterial stiffness) in the patients with PTH &gt; 300 more than the patients with PTH &lt; 300 as it showed that in Group B (PTH&gt;300), the measured carotid artery local PWV values ranged from 6.22 m/s to 8.84 m/s and the mean value was 7.81 ± 0.72 m/s, which was higher than 6.72 ± 1.06 m/s (ranging from 4.48 m/s to 8.44 m/s) of Group A (PTH&lt;300). Conclusion Our study showed that there is a high prevalence of arterial stiffness in prevalent hemodialysis patients.

scholarly journals Fenofibrate Improved Interstitial Fibrosis of Renal Allograft through Inhibited Epithelial-Mesenchymal Transition Induced by Oxidative Stress

2019 ◽  
Vol 2019 ◽  
pp. 1-12 ◽  
Author(s):  
Yishu Wang ◽  
Lei Pang ◽  
Yanghe Zhang ◽  
Jiahui Lin ◽  
Honglan Zhou
Keyword(s):  
Oxidative Stress ◽  
Rat Model ◽  
Renal Allograft ◽  
Epithelial Mesenchymal Transition ◽  
Interstitial Fibrosis ◽  
Peroxisome Proliferator ◽  
Tubular Atrophy ◽  
Peroxisome Proliferator Activated Receptor ◽  
Mesenchymal Transition ◽  
Stage Renal Disease

The best treatment for end-stage renal disease is renal transplantation. However, it is often difficult to maintain a renal allograft healthy for a long time following transplantation. Interstitial fibrosis and tubular atrophy (IF/TA) are significant histopathologic characteristics of a compromised renal allograft. There is no effective therapy to improve renal allograft function once IF/TA sets in. Although there are many underlying factors that can induce IF/TA, the pathogenesis of IF/TA has not been fully elucidated. It has been found that epithelial-mesenchymal transition (EMT) significantly contributes to the development of IF/TA. Oxidative stress is one of the main causes that induce EMT in renal allografts. In this study, we have used H2O2 to induce oxidative stress in renal tubular epithelial cells (NRK-52e) of rats. We also pretreated NRK-52e cells with an antioxidant (N-acetyl L-cysteine (NAC)) 1 h prior to the treatment with H2O2. Furthermore, we used fenofibrate (a peroxisome proliferator-activated receptor α agonist) to treat NRK-52e cells and a renal transplant rat model. Our results reveal that oxidative stress induces EMT in NRK-52e cells, and pretreatment with NAC can suppress EMT in these cells. Moreover, fenofibrate suppresses fibrosis by ameliorating oxidative stress-induced EMT in a rat model. Thus, fenofibrate may effectively prevent the development of fibrosis in renal allograft and improve the outcome.

scholarly journals Peritoneal Microbiome in End-Stage Renal Disease Patients and the Impact of Peritoneal Dialysis Therapy

2020 ◽  
Vol 8 (2) ◽  
pp. 173
Author(s):  
Liliana Simões-Silva ◽  
Ricardo Araujo ◽  
Manuel Pestana ◽  
Isabel Soares-Silva ◽  
Benedita Sampaio-Maia
Keyword(s):  
Peritoneal Dialysis ◽  
Human Microbiome ◽  
Cross Sectional Study ◽  
Cross Sectional ◽  
Peritoneal Tissue ◽  
Stage Renal Disease ◽  
End Stage ◽  
The Impact

Factors influencing the occurrence of peritoneal dialysis (PD)-related infections are still far from fully understood. Recent studies described the existence of specific microbiomes in body sites previously considered microbiome-free, unravelling new microbial pathways in the human body. In the present study, we analyzed the peritoneum of end-stage kidney disease (ESKD) patients to determine if they harbored a specific microbiome and if it is altered in patients on PD therapy. We conducted a cross-sectional study where the peritoneal microbiomes from ESKD patients with intact peritoneal cavities (ESKD non-PD, n = 11) and ESKD patients undergoing PD therapy (ESKD PD, n = 9) were analyzed with a 16S rRNA approach. Peritoneal tissue of ESKD patients contained characteristically low-abundance microbiomes dominated by Proteobacteria, Firmicutes, Actinobacteria, and Bacteroidetes. Patients undergoing PD therapy presented lower species richness, with dominance by the Pseudomonadaceae and Prevotelaceae families. This study provides the first characterization of the peritoneal microbiome in ESKD patients, bringing new insight to the human microbiome. Additionally, PD therapy may induce changes in this unique microbiome. The clinical relevance of these observations should be further explored to uncover the role of the peritoneal microbiome as a key element in the onset or aggravation of infection in ESKD patients, especially those undergoing PD.

P0417THE ABSENCE OF C3 DEPOSIT IN MEMBRANOUS NEPHROPATHY IS ASSOCIATED WITH SPONTANEOUS REMISSION

2020 ◽  
Vol 35 (Supplement_3) ◽  
Author(s):  
Cristina Rabasco ◽  
Ana Martínez ◽  
Rosa Ortega ◽  
Mario Espinosa
Keyword(s):  
Membranous Nephropathy ◽  
Interstitial Fibrosis ◽  
Immunosuppressive Treatment ◽  
Spontaneous Remission ◽  
Glomerular Sclerosis ◽  
Tubular Atrophy ◽  
Positive Group ◽  
Stage Renal Disease ◽  
End Stage

Abstract Background and Aims Membranous nephropathy (MN) is the most common cause of biopsied nephrotic syndrome in adults. Recently, it has been reported that the pathogenesis of MN may be associated with an activation of the complement system. The pathway of activation is not clearly established. The intensity of C3 deposition could be a good marker of this activation in MN as has been shown in other diseases (IgA nephropathy, crescentic GN). The aim of this study is to evaluate clinical-pathological data in a cohort of patients with MN and the significance of glomerular C3 staining as a possible predictor of renal outcomes. Method We analysed patients with idiopathic MN biopsied in our department between January 2000 and December 2019, excluding those who had no material for IF (n = 115). The patients were divided into positive (87 cases) and negative (28 cases) based on glomerular C3 deposition. We assessed the clinical and histological characteristics and the percentage of spontaneous remission (SR) and end-stage renal disease (ESRD). Results A total of 115 patients with MN were followed with a median follow-up of 65 (25-161) months. We found no differences in baseline characteristics between both groups, with the exception that patients with C3 deposit had less albumin at the time of biopsy that negative patients [2.4 (2-2.9) vs 2.8 (2.3-3.1) g/dl, P=0.011)]. Patients with C3-negative had a higher percentage of SR than patients with C3-positive (75 vs 24%, P = 0.000) and less need for immunosuppressive treatment (18 vs 56%, P =0.001). At the most recent follow-up, C3-positive group had higher creatinine [1.42 (0.8-1.7) vs 0.97 (0.71-1) mg/dl, P=0.045] and proteinuria [1.64 (0.08-3.2) vs. 0.62 (0.05-0.79) g / 24h, P = 0.039]. Regarding histology, we found no differences in glomerular sclerosis, tubular atrophy and interstitial fibrosis. The renal survival analysis showed no statistically significant differences between both groups (P = 0.091). We analysed a subgroup of patients (n = 23) with antibodies against the phospholipase receptor on blood at the time of the biopsy (13/23 were positive). 84% of this positive group presented C3-positive in the renal biopsy vs 25% of the C3-negative group (P =0.008). Conclusion Patients without C3 staining show a higher rate of SR and less need for immunosuppressive treatment than patients with C3-positive. These results would support the theory that complement activation in this entity can play an important role. It is possible that these patients with negative C3 deposit represent a MN with evolution to SR and in these patients and that these patients do not need immunosuppressive treatment.

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