scholarly journals May be Urinary Excretion of α2-macroglobulin (MW 720 kDa) a Proteinuric Marker of Podocytopathy? Insight from Analysis of 204 Patients with Glomerulonephritis (GN) and Nephrotic Syndrome, 177 with Functional Outcome

2021 ◽  
Vol 8 (3) ◽  
pp. 01-06
Author(s):  
Claudio Bazzi

Background: In IgAN with cellular crescents (CIgAN) urinary excretion of α2-macroglobulin (α2m/C, MW 720 kDa) may be a marker of podocytes damage induced by crescents. The purpose of the study was the evaluation of the clinical significance of α2m/C excretion in 177 patients with glomerulonephritis (GN), nephrotic syndrome (NS) and functional outcome. Methods: In all 177 patients α2m/C excretion was measured; the patients were divided in 2 groups: α2mC=0 (n. 72) and α2m/C >0 (n. 105); for each group were assessed the outcomes considered in combination: Remission & persistent nephrotic syndrome (PNS) with long lasting NRF designed “Remission & NRF”; ESRD & eGFR < 50% & PNS with CRF designed “Progression and progression risk”. Results: In 72 patients with α2m/C=0 “Remission & NRF” was 78% and “Progression & progression risk” was 22%; in 105 patients with α2m/C>0 “remission & NRF” was 52% and “Progression & progression risk” was 48%. “Remission & NRF” in each GN type with α2m/C=0 was: 100% in MCD and LN; 82%, 79%, 67% in FSGS, IMN, MPGN; in α2m/C>0 “Progression and progression risk” was 0%, 38%, 46%, 54%, 56%, 85% in MCD, LN, IMN, MPGN, FSGS, CIgAN with cellular crescents, respectively. Conclusion: Urinary excretion of α2m is a very simple marker available in all clinical practice laboratories, marker of damage of podocytes at least in CIgAN and LN with crescents and marker of GFB damage in different GN types and useful to predict outcome and treatment responsiveness.

1981 ◽  
Vol 46 (03) ◽  
pp. 623-625 ◽  
Author(s):  
B Boneu ◽  
F Bouissou ◽  
M Abbal ◽  
P Sie ◽  
C Caranobe ◽  
...  

SummaryIn order to compare the plasmatic progressive antithrombin activity to the concentration of three thrombin inhibitors, antithrombin III (AT III), α2 macroglobulin (α2, M), α1 anti-trypsin (α1 AT) in nephrotic syndrome, a prospective study was carried out on a group of 28 children affected with the disease. A dramatic reduction of the level of AT III and of α1 AT, two inhibitors of molecular weight close to that of albumin, was observed. The decreased level of AT III was counterbalanced by an increase in α2 M. This phenomenon accounts for the increased progressive antithrombin activity observed in all the affected children. It is suggested that the above compensatory mechanism explains the absence of thrombotic accidents in this series and that the benefit of heparin therapy is doubtful in these conditions.


Stroke ◽  
2014 ◽  
Vol 45 (suppl_1) ◽  
Author(s):  
Katherine O Brag ◽  
Erica Jones ◽  
Dominique Monlezun ◽  
Alex George ◽  
Michael Halstead ◽  
...  

Introduction: Hematoma expansion (HE) is an established predictor of mortality and poor functional outcome after intracerebral hemorrhage (ICH). The computed tomography angiography (CTA) “spot” sign predicts HE and deterioration. The “dot” sign on delayed post-contrast CT (PCCT) has undetermined clinical significance but is thought to represent a slower rate of bleeding than the “spot” sign. We aimed to compare the sensitivity of a “dot” sign with the “spot” sign and establish the clinical significance of the “dot” sign. Methods: Patients with ICH presenting to our center July 2008-May 2013 were identified from our stroke registry. Only patients with baseline CT, CTA and PCCT and follow-up CT 6-36 hours later were included. Patients with clot evacuation between baseline and follow-up CT were excluded. HE was defined as 1) any ≥ 1cc increase and 2) significant ≥ 12.5cc increase or >33% increase in volume. Differences in cohort characteristics were assessed using appropriate statistical tests and sensitivity was calculated from 2x2 tables. Unadjusted logistic regression models were used to investigate the relation of “spot” and “dot” signs with HE and poor functional outcome (discharge mRS 4-6). Results: Of the 210 ICH patients included in the analyses (median age 61, 44.7% female, 66.2% black), 39 (18.5%) patients had a PCCT “dot” sign and 19 (9%) had a CTA “spot” sign. Significant HE occurred in 15% with “dot” sign and 8% with “spot” sign. The PCCT “dot” sign had a sensitivity of 0.52 in predicting significant HE and a sensitivity of 0.69 in predicting discharge mRS 4-6 (compared with 0.24 and 0.30 for “spot” sign, respectively). Patients with a “dot” sign, but without a “spot” sign, had significantly increased odds of any HE (OR 5.7, 95% CI 1.9-17.8, p=0.003), mRS 4-6 (OR 8.1, 95% CI 1.03-64.6, p=0.048), and death (OR 8.1, 95% CI 1.4-48.4, p=0.02), but not significant HE (OR 2.2, 95% CI 0.7-6.7, p=0.15). Conclusions: The PCCT “dot” sign was more sensitive in predicting hematoma expansion than the CTA “spot” sign and predicted hematoma expansion and poor functional outcome even in the absence of the “spot sign.” The utility of PCCT imaging in acute evaluation of ICH patients requires validation, but our study supports clinical relevance of the “dot” sign.


Stroke ◽  
2013 ◽  
Vol 44 (suppl_1) ◽  
Author(s):  
Carolyn A Cronin ◽  
Patricia Langenberg ◽  
Tara M Dutta ◽  
Steven J Kittner

Introduction: ECASS III showed benefit of IV tPA for acute ischemic stroke (AIS) 3-4.5 hr from onset in a select group of patients from Europe, with this extended treatment subsequently recommended by the AHA/ASA. We prospectively enrolled AIS patients treated with IV tPA as this recommendation was being applied in clinical practice, to determine safety and efficacy in a representative cohort from the USA. Methods: Consecutive AIS patients treated with IV tPA at 18 primary stroke centers throughout Maryland were approached and informed consent obtained during hospitalization. Sites ranged from small community hospitals to large academic medical centers. In-hospital and demographic data were obtained from each site’s GWTG database or directly from the medical record. Study personnel blinded to the treatment time window obtained 90 day modified Rankin Scale (mRS) by structured phone interview. Patients were grouped by time to treatment (≤ 3hr vs. 3-4.5hr) and compared for presence of additional exclusion criteria from ECASS III that are not standard practice in the USA for ≤ 3hr (age >80, history of stroke and diabetes, oral anticoagulant treatment, and NIHSS>25). Good functional outcome (mRS 0-1 and 0-2), mortality, and symptomatic intracerebral hemorrhage (sICH) were analyzed. Results: Patients treated 3-4.5hr were somewhat younger (mean age 62.6 vs. 66.6, p=0.06), and had smaller infarcts (median NIHSS 5 vs. 8, p=0.04). There was only partial adherence to the additional ECASS exclusions (Table 1). There were no significant differences by time to treatment in sICH, mortality, or 90 day functional outcome (Table 2). Conclusion: For US patients treated with IV tPA 3-4.5 hr from onset in every day practice, there is no evidence for increased risk or worse outcomes compared to standard treatment up to 3 hr.


PEDIATRICS ◽  
1953 ◽  
Vol 12 (3) ◽  
pp. 233-252
Author(s):  
ENRIQUE GALÁN ◽  
MANUEL PÉREZ-STABLE ◽  
ORLANDO GARCÍA FAEZ ◽  
EMILIO UNANUE ◽  
OTTO GARCÍA ◽  
...  

The role of tubular reabsorption in the pathogenesis of nephrotic edema led the authors to study the participation of antidiuretic hormone and adrenal steroids in regard to changes in renal hemodynamics and tubular function during different clinical events that may induce an increase or a decrease of urinary flow in nephrotic children. Formaldehydogenic steroids in urine, plasma and ascitic fluid and serum antidiuretic substance were simultaneously studied with clearance tests, electrolyte excretion and plasma constituents through 10 different periods of observations. From previous and present studies on renal function it was found that changes in renal hemodynamics and tubular transport mechanisms are responsible for variations in urinary flow leading to accumulation or disappearance of edema in the nephrotic syndrome. An increase in urinary flow was seen to occur with no change in the GFR but with a marked decrease in the U/P inulin and potassium ratio. Serum antidiuretic substance appeared to correlate closely with antidiuresis. Injection of nephrotic sera into peritoneal cavity of rats was followed by an antidiuretic effect similar to that produced by pitressin and posterior pituitary hormone. Antidiuretic factor seemed to be present in the globulin fraction of plasma proteins. No such effect was seen with intraperitoneal injections of plasma albumin, protein-free filtrate and ascitic fluid. An increase in titer of antidiuretic substance was observed during initial doses of ACTH and the reverse at the onset of diuretic response. Urinary excretion of formaldehydogenic steroids depended partly on diuresis in nephrotic children; this was not so in control cases. The influence of tubular function was suggested by the relationship found between urinary excretion of steroids and the V/Cin and V/Cth ratio and between clearance of steroids and diuresis. The influence of renal functional disturbance prevented a correct evaluation of adrenal activity by estimation of urinary steroids in nephrotic children. During the edematous-oliguric stage of nephrosis and in the absence of any stimulating or depressing effect upon the elaboration of adrenal steroids their urinary excretion was not significantly different from that seen in control cases. Formaldehydogenic steroids did not seem to have a direct role in producing variations of urine flow in nephrotic children. Increase and decrease in diuresis occurred simultaneously with an increase and a decrease in urinary and plasma steroids and vice versa. Formaldehydogenic material was found in variable amounts in the ascitic fluid suggesting an appreciable retention in the increased extracellular fluid during the oliguricedematous stage of the nephrotic syndrome. This material appears to be mostly true adrenal steroids. Potassium excretion was related to urinary steroids in nephrotic children but not in control cases. Potassium clearance was related to glomerular filtration in both control and nephrotic children. At the present time it remains a matter of some speculation of the role that steroids present in extracellular fluids may play in the physiologic and morphologic changes known to occur in the course of the nephrotic syndrome and experimentally reproduced by injection of DOCA to animals.


Stroke ◽  
2019 ◽  
Vol 50 (9) ◽  
pp. 2500-2506 ◽  
Author(s):  
Frank A. Wollenweber ◽  
Steffen Tiedt ◽  
Anna Alegiani ◽  
Burkhard Alber ◽  
Christopher Bangard ◽  
...  

Nephron ◽  
1990 ◽  
Vol 56 (1) ◽  
pp. 24-29 ◽  
Author(s):  
Eleazar Shafrir ◽  
Emile Levy ◽  
Richard Deckelbaum

2016 ◽  
Vol 72 (3) ◽  
Author(s):  
Annabella Braschi ◽  
Vincenzo Cristian Francavilla ◽  
Maurizio Giuseppe Abrignani ◽  
Renzo Lombardo ◽  
Furio Colivicchi ◽  
...  

The measurement of QT dispersion in the surface electrocardiogram has been proposed as a non invasive method for assessing inhomogeneity of myocardial repolarization and has been linked to an increased risk of arrhythmic cardiac death. Several studies have evaluated the use of QTd in a wide variety of cardiac diseases and have reached conflicting conclusions regarding its clinical significance.


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