Urinary Extracellular Vesicles and Their miRNA Cargo in Patients with Fabry Nephropathy

Current biomarkers of Fabry nephropathy lack sensitivity in detecting early kidney damage and do not predict progression of nephropathy. Urinary extracellular vesicles (uEVs) and their molecular cargo could reflect early changes in renal impairment as they are secreted by the cells lining the urinary tract. We aimed to conduct a proof-of-concept study to investigate whether analysis of uEV characteristics and expression of uEV-derived microRNAs (miRNAs) could be applicable in studies to predict the development and progression of nephropathy in Fabry disease. A total of 20 Fabry patients were divided into two groups, depending on the presence of nephropathy. Chronological urine samples collected during 10-year follow-up were used for uEVs isolation with size exclusion chromatography. Nanoparticle tracking analysis was used to determine concentration and size of uEVs. We evaluated the expression of five uEV-derived miRNAs by qPCR (miR-23a-3p, miR-29a-3p, miR-30b-5p, miR-34a-5p, miR-200a-3p). There was no difference in the concentration and size of uEVs between patients with and without nephropathy at last follow-up or longitudinally. However, we found increased expression of miR-29a-3p and miR-200a-3p in uEVs isolated from chronological samples of patients with Fabry nephropathy. This may indicate an attempt by the organism to prevent the progression of renal damage leading to end-stage renal disease as previously reported in type 1 diabetes. In addition, we found an increased expression of miR-30b-5p in the 10-year period in uEVs of patients without renal dysfunction. miR-30b-5 was reported to have a protective role in podocyte injury and may possibly be important in Fabry nephropathy. These findings indicate that uEVs and their molecular cargo could be a promising target of studies focusing on elucidation of Fabry nephropathy. Nevertheless, total concentration and size of uEVs were neither indicative of the presence nor progression of Fabry nephropathy, while the role of the analyzed miRNAs in Fabry nephropathy progression was merely indicated and needs further in-depth studies.

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Endovascular mechanical thrombectomy and stenting in a case of central vein thrombosis

BMJ Case Reports ◽

10.1136/bcr-2020-236508 ◽

2021 ◽

Vol 14 (2) ◽

pp. e236508

Author(s):

Rajesh Vijayvergiya ◽

Navjyot Kaur ◽

Saroj K Sahoo ◽

Ashish Sharma

Keyword(s):

Mechanical Thrombectomy ◽

Transluminal Angioplasty ◽

Brachiocephalic Vein ◽

Central Vein ◽

Vein Thrombosis ◽

Catheter Directed Thrombolysis ◽

Stage Renal Disease ◽

End Stage ◽

Vein Stenosis

Central vein stenosis and thrombosis are frequent in patients on haemodialysis for end-stage renal disease. Its management includes anticoagulation, systemic or catheter-directed thrombolysis, mechanical thrombectomy and percutaneous transluminal angioplasty (PTA). Use of mechanical thrombectomy in central vein thrombosis has been scarcely reported. We hereby report a case of right brachiocephalic vein thrombosis with underlying stenosis, which was successfully treated by mechanical thrombectomy followed by PTA and stenting. The patient had a favourable 10 months of follow-up.

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Living Kidney Donation: Practical Considerations on Setting Up a Program

Transplantology ◽

10.3390/transplantology2010008 ◽

2021 ◽

Vol 2 (1) ◽

pp. 75-86

Author(s):

Maria Irene Bellini ◽

Vito Cantisani ◽

Augusto Lauro ◽

Vito D’Andrea

Keyword(s):

Good Practice ◽

Kidney Donation ◽

Living Kidney Donation ◽

Exchange Programs ◽

Paired Exchange ◽

Stage Renal Disease ◽

End Stage ◽

Additional Value ◽

Work Up

Living kidney donation represents the best treatment for end stage renal disease patients, with the potentiality to pre-emptively address kidney failure and significantly expand the organ pool. Unfortunately, there is still limited knowledge about this underutilized resource. The present review aims to describe the general principles for the establishment, organization, and oversight of a successful living kidney transplantation program, highlighting recommendation for good practice and the work up of donor selection, in view of potential short- and long-terms risks, as well as the additional value of kidney paired exchange programs. The need for donor registries is also discussed, as well as the importance of lifelong follow up.

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Vasculitis ANCA: Alternativas de tratamiento y las expectativas en los pacientes

Karger Kompass Neumología ◽

10.1159/000513798 ◽

2021 ◽

pp. 1-2

Author(s):

Carolina Aguilar-Martínez

Keyword(s):

Systematic Review ◽

Cox Regression ◽

Meta Analysis ◽

Significant Risk ◽

Limiting Factor ◽

Significant Survival ◽

Stage Renal Disease ◽

End Stage ◽

Immunosuppression Therapy

Background: The benefits of treating anti-neutrophil cytoplasmic autoantibody-associated vasculitis (AAV) in advancing age remains unclear with most published studies defining elderly as ≥65 years. This study aims to determine outcomes of induction immunosuppression in patients aged ≥75 years. Methods: A cohort of patients aged ≥75 years with a diagnosis of AAV between 2006 and 2018 was constructed from 2 centres. Follow-up was to 2 years or death. Analysis included multivariable Cox regression to compare mortality and end-stage renal disease (ESRD) based on receipt of induction immunosuppression therapy with either cyclophosphamide or rituximab. A systematic review of outcome studies was subsequently undertaken amongst this patient group through Pubmed, Cochrane and Embase databases from inception until October 16, 2019. Results: Sixty-seven patients were identified. Mean age was 79 ± 2.9 years and 82% (n = 55) received induction immunosuppression. Following systematic review, 4 studies were eligible for inclusion, yielding a combined total of 290 patients inclusive of our cohort. The aggregated 1-year mortality irrespective of treatment was 31% (95% CI 25–36%). Within our cohort, induction immunosuppression therapy was associated with a significantly lower 2-year mortality risk (hazard ratio [HR] 0.29 [95% CI 0.09–0.93]). The pooled HR by meta-analysis confirmed this with a significant risk reduction for death (HR 0.31 [95% CI 0.16–0.57], I2 = 0%). Treated patients had a lower pooled rate of ESRD, but was not statistically significant (HR 0.71 [95% CI 0.15–3.35]). Conclusion: This meta-analysis suggests that patients ≥75 years with AAV do benefit from induction immunosuppression with a significant survival benefit. Age alone should not be a limiting factor when considering treatment.

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Kinetics and Topology of DNA Associated with Circulating Extracellular Vesicles Released during Exercise

Genes ◽

10.3390/genes12040522 ◽

2021 ◽

Vol 12 (4) ◽

pp. 522

Author(s):

Elmo W. I. Neuberger ◽

Barlo Hillen ◽

Katharina Mayr ◽

Perikles Simon ◽

Eva-Maria Krämer-Albers ◽

...

Keyword(s):

Extracellular Vesicles ◽

Size Exclusion ◽

Affinity Capture ◽

Healthy Humans ◽

Dnase Digestion ◽

And Topology ◽

Single Bout ◽

Exclusion Chromatography ◽

Free Circulating Dna ◽

Line Elements

Although it is widely accepted that cancer-derived extracellular vesicles (EVs) carry DNA cargo, the association of cell-free circulating DNA (cfDNA) and EVs in plasma of healthy humans remains elusive. Using a physiological exercise model, where EVs and cfDNA are synchronously released, we aimed to characterize the kinetics and localization of DNA associated with EVs. EVs were separated from human plasma using size exclusion chromatography or immuno-affinity capture for CD9+, CD63+, and CD81+ EVs. DNA was quantified with an ultra-sensitive qPCR assay targeting repetitive LINE elements, with or without DNase digestion. This model shows that a minute part of circulating cell-free DNA is associated with EVs. During rest and following exercise, only 0.12% of the total cfDNA occurs in association with CD9+/CD63+/CD81+EVs. DNase digestion experiments indicate that the largest part of EV associated DNA is sensitive to DNase digestion and only ~20% are protected within the lumen of the separated EVs. A single bout of running or cycling exercise increases the levels of EVs, cfDNA, and EV-associated DNA. While EV surface DNA is increasing, DNAse-resistant DNA remains at resting levels, indicating that EVs released during exercise (ExerVs) do not contain DNA. Consequently, DNA is largely associated with the outer surface of circulating EVs. ExerVs recruit cfDNA to their corona, but do not carry DNA in their lumen.

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Vascular access types in patients starting hemodialysis after failed kidney transplant: does close nephrology follow-up matter?

The Journal of Vascular Access ◽

10.5301/jva.5000631 ◽

2016 ◽

Vol 18 (1) ◽

pp. 22-25 ◽

Cited By ~ 3

Author(s):

Naveed Ul Haq ◽

Mohamed Said Abdelsalam ◽

Mohammed Mahdi Althaf ◽

Abdulrahman Ali Khormi ◽

Hassan Al Harbi ◽

...

Keyword(s):

Vascular Access ◽

Clinic Visit ◽

Study Data ◽

Renal Transplant Recipients ◽

Transplant Recipients ◽

Early Referral ◽

Period Data ◽

Stage Renal Disease ◽

End Stage

Background Native arteriovenous fistulae (AVFs) are preferred while central venous catheters (CVCs) are least suitable vascular access (VA) in patients requiring hemodialysis (HD). Unfortunately, around 80% of patients start HD with CVCs. Late referral to nephrologist is thought to be a factor responsible for this. We retrospectively analyzed the types of VA at HD initiation in renal transplant recipients followed by nephrologists with failed transplant. If early referral to nephrologist improves AVF use, these patients should have higher prevalence of AVF at HD initiation. Methods All patients who failed their kidney transplants from January 2002 to April 2013 were included in the study. Data regarding planning of VA by nephrologist, documented discussion about renal replacement therapy (RRT), estimated glomerular filtration rate (eGFR) at 6 months and last clinic visit before HD initiation, time of VA referral, and subsequent VA at dialysis initiation were gathered and analyzed. Results Eighty-three patients failed their transplants during study period. Data were inaccessible in six patients. Eleven patients started peritoneal dialysis (PD) while 66 started HD. Thirty-two had previous functioning VA while 34 needed VA. There were 11/34 patients (32%) with eGFR <15 mL/min at six months while 21/34 (61%) had eGFR <15 mL/min at last clinic visit before HD initiation. Only 11/34 (32%) had documented RRT discussion, 8/34 (24%) had VA referral, and 7/34 (21%) had vein mapping. A total of 30/34 (88.3%) started HD with CVC while 4/34 (11.3%) started HD with AVF (p<0.0001). Conclusions Early referral to nephrologist by itself may not improve VA care amongst patient with end-stage renal disease.

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MO282EARLY RENAL RECOVERY AFTER A FIRST FLARE OF PAUCI IMMUNE GLOMERULONEPHRITIS

Nephrology Dialysis Transplantation ◽

10.1093/ndt/gfab104.0040 ◽

2021 ◽

Vol 36 (Supplement_1) ◽

Author(s):

Jeremy Zaworski ◽

Cyrille Vandenbussche ◽

Pierre Bataille ◽

Eric Hachulla ◽

Francois Glowacki ◽

...

Keyword(s):

Renal Disease ◽

End Stage Renal Disease ◽

Interstitial Fibrosis ◽

Univariate Analysis ◽

Renal Recovery ◽

Neurological Involvement ◽

Factors Associated ◽

Stage Renal Disease ◽

End Stage

Abstract Background and Aims Renal involvement is a severe manifestation of ANCA-associated vasculitis. Patients often progress to end-stage renal disease. The potential for renal recovery after a first flare has seldom been studied. Our objectives were to describe the evolution of the estimated glomerular filtration rate (eGFR) and identify factors associated with the change in eGFR between diagnosis and follow-up at 3 months (ΔeGFRM0–M3) in a cohort of patients with a first flare of pauci-immune glomerulonephritis. Methods This was a retrospective study over the period 2003–2018 of incident patients in the Nord-Pas-de-Calais (France). Patients were recruited if they had a first histologically-proven flare of pauci immune glomerulonephritis with at least 1 year of follow up. Kidney function was estimated with MDRD-equation and analysed at diagnosis, 3rd, 6th and 12th months. The primary outcome was ΔeGFRM0–M3. Factors evaluated were histological (Berden classification, interstitial fibrosis, percentage of crescents), clinical (extra-renal manifestations, sex, age) or biological (severity of acute kidney injury, dialysis, ANCA subtype). Results One hundred and seventy-seven patients were included. The eGFR at 3 months was significantly higher than at diagnosis (mean ± standard deviation, 40 ± 24 vs 28 ± 26 ml/min/1.73 m2, p < 0.001), with a ΔeGFRM0–M3 of 12 ± 19 ml/min/1.73 m2. The eGFR at 12 months was higher than at 3 months (44 ± 13 vs 40 ± 24 ml/min/1.73m2, p = 0.003). The factors significantly associated with ΔeGFRM0–M3 in univariate analysis were: sclerotic class according to Berden classification, percentage of interstitial fibrosis, percentage of cellular crescents, acute tubular necrosis, neurological involvement. The factors associated with ΔeGFRM0–M3 in multivariate analysis were the percentage of cellular crescents and neurological involvement. The mean increase in eGFR was 2.90 ± 0.06 ml/min/1.73m2 for every 10-point gain in the percentage of cellular crescents. ΔeGFRM0–M3 was not associated with the risks of end-stage renal disease or death in long-term follow-up. Conclusions Early renal recovery after a first flare of pauci-immune glomerulonephritis occurred mainly in the first three months of treatment. The percentage of cellular crescents was the main independent predictor of early renal recovery.

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MO302ACUTE POST-INFECTIOUS GLOMERULONEPHRITIS IN ADULTS: A TUNISIAN SINGLE CENTER EXPERIENCE

Nephrology Dialysis Transplantation ◽

10.1093/ndt/gfab104.0060 ◽

2021 ◽

Vol 36 (Supplement_1) ◽

Author(s):

Imen El Meknassi ◽

Mrabet Sanda ◽

Guedri Yosra ◽

Zellema Dorsaf ◽

Azzabi Awatef ◽

...

Keyword(s):

Acute Kidney Injury ◽

Kidney Injury ◽

Acute Glomerulonephritis ◽

Industrialized Countries ◽

Single Center Experience ◽

Nephritic Syndrome ◽

Stage Renal Disease ◽

End Stage ◽

Post Infectious

Abstract Background and Aims Acute post-infectious glomerulonephritis (APIGN) is a reactive immunological disease. Its prevalence in industrialized countries is declining contrasting with developed ones. It is uncommon in adults but the prognosis may be reserved. The aim of our study was to evaluate the epidemiological, clinical and histological features of APIGN as well as its prognosis. Method A retrospective and descriptive study was conducted in our department. Were included all cases of histologically proven APIGN between December 2006 and December 2017. Results We had collected 38 cases. The mean age was 37.7 ± 17.8 years. The sex ratio was 1.92. Twelve (31.6%) patients were diabetic and four of them had already a chronic kidney disease (CKD). APIGN was preceded by an infection in 27 cases with an average interval of 10 ± 5 days. The most common site of infection was the respiratory tract (15 cases). At presentation, 27 patients had nephritic syndrome and 13 had nephrotic-range proteinuria. Hematuria was observed in 97.4%, peripheral edema in 84.2% and hypertension in 73.7% of cases. Most patients (78.9%) had acute kidney injury and 10 (26.3%) patients required dialysis. Renal biopsy had shown benign acute glomerulonephritis in 31 cases and malignant form in 7 cases. An underlying nephropathy was found in 12 cases with mostly a diabetic nephropathy. Corticosteroids were used in 3 cases of benign APIGN and 5 cases of malignant form. During the follow-up, CKD was noted in 14(36.8%) patients including 7(18.4%) patients who progressed to end-stage renal disease. Poor prognostic factors were diabetes, the presence of an underlying nephropathy in the biopsy, acute kidney injury and the need for dialysis. Conclusion The APIGN is uncommon in adults, yet its prognosis may be reserved with progression to CKD.

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Baseline Soluble Anti-erythropoietin Antibody Level Is an Independent Associated Factor for Follow-Up Erythropoietin Demand in Maintenance Dialysis Patients With End-Stage Renal Disease: A Prospective Cohort Study

Frontiers in Medicine ◽

10.3389/fmed.2020.00109 ◽

2020 ◽

Vol 7 ◽

Author(s):

Ying Zhang ◽

Shi-Zhu Bian ◽

Kun Yang ◽

Yiqing Wang ◽

Sha Tang ◽

...

Keyword(s):

Cohort Study ◽

Renal Disease ◽

Prospective Cohort Study ◽

Antibody Level ◽

End Stage Renal Disease ◽

Prospective Cohort ◽

Dialysis Patients ◽

Stage Renal Disease ◽

End Stage

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Alterations of Left Ventricular Hypertrophy in and Survival of Patients Receiving Hemodialysis: Follow-up of an Interventional Study

Journal of the American Society of Nephrology ◽

10.1681/asn.v12122759 ◽

2001 ◽

Vol 12 (12) ◽

pp. 2759-2767 ◽

Cited By ~ 5

Author(s):

Gérard M. London ◽

Bruno Pannier ◽

Alain P. Guerin ◽

Jacques Blacher ◽

Sylvain J. Marchais ◽

...

Keyword(s):

Confidence Interval ◽

Left Ventricular ◽

Independent Effect ◽

Lv Mass ◽

History Of ◽

Cv Disease ◽

Stage Renal Disease ◽

End Stage

ABSTRACT. Left ventricular (LV) hypertrophy (LVH) is a risk factor for mortality in patients with end-stage renal disease (ESRD). Whether the attenuation of LVH has a positive effect on survival of patients with ESRD has not been documented. The aim of this study was to determine the effect of parallel treatment of hypertension and anemia on LV mass (LVM) and to determine the effect of LVM changes on survival. A cohort of 153 patients receiving hemodialysis was studied. The duration of follow-up was 54 ± 37 mo. All patients had echocardiographic determination of LV dimensions and LVM at baseline and regular intervals until the end of the follow-up period. During the study, BP decreased from (mean ± SD) 169.4 ± 29.7/90.2 ± 15.6 to 146.7 ± 29/78 ± 14.1 mmHg (P< 0.001), and hemoglobin increased from 8.65 ± 1.65 to 10.5 ± 1.45 g/dl (P< 0.001). The LV end-diastolic diameter and mean wall thickness decreased from 56.6 ± 6.5 to 54.8 ± 6.5 mm (P< 0.001), and from 10.4 ± 1.6 to 10.2 ± 1.6 mm (P< 0.05), respectively. The LVM decreased from 290 ± 80 to 264 ± 86 g (P< 0.01). Fifty-eight deaths occurred, 38 attributed to cardiovascular (CV) disease and 20 attributed to non-CV causes. According to Cox analyses after adjustment for age, gender, diabetes, history of CV disease, and all nonspecific CV risk factors, LVM regression positively affected the survival. The hazard risk ratio associated with a 10% LVM decrease was 0.78 (95% confidence interval, 0.63 to 0.92) for all-causes mortality and 0.72 (95% confidence interval, 0.51 to 0.90) for mortality due to CV disease. These results show that a partial LVH regression in patients with ESRD had a favorable and independent effect on patients’ all-cause and CV survival.

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