DOCSLIB.ORG

Organ Manifestations and Long-Term Outcome of Fabry Disease in Patients with the GLA Haplotype D313Y

Total Page：16

File Type：pdf, Size：1020Kb

Download full-text PDF Read full-text
Organ Manifestations and Long-Term Outcome of Fabry Disease in Patients with the GLA Haplotype D313Y Open Access Research BMJ Open: first published as 10.1136/bmjopen-2015-010422 on 8 April 2016. Downloaded from Organ manifestations and long-term outcome of Fabry disease in patients with the GLA haplotype D313Y Daniel Oder,1,2 Nurcan Üçeyler,2,3 Dan Liu,1 Kai Hu,1 Bernhard Petritsch,4 Claudia Sommer,2,3 Georg Ertl,1 Christoph Wanner,1,2 Peter Nordbeck1,2 To cite: Oder D, Üçeyler N, ABSTRACT et al Strengths and limitations of this study Liu D, . Organ Objectives: The severity of Fabry disease is manifestations and long-term dependent on the type of mutation in the α- ▪ outcome of Fabry disease in This is the first non-case report study investigat- galactosidase A (AgalA) encoding gene (GLA). This patients with the GLA ing the clinical impact of the GLA genotype haplotype D313Y. BMJ Open study focused on the impact of the GLA haplotype D313Y in a group of respective participants. 2016;6:e010422. D313Y on long-term organ involvement and function. ▪ On the basis of the results, this mutation should doi:10.1136/bmjopen-2015- Setting and participants: In this monocentric study, be considered a non-pathological haplotype, 010422 all participants presenting with the D313Y haplotype which has important implications for therapy between 2001 and 2015 were comprehensively clinically planning and prognosis in affected individuals. ▸ Prepublication history for investigated at baseline and during a 4-year follow-up if ▪ The main limitation is the small number of indivi- this paper is available online. available. Five females and one male were included. duals investigated during follow-up and the lack To view these files please Primary and secondary outcome measures: of clinical data in participants exceeding the visit the journal online Cardiac, nephrological, neurological, laboratory and seventh decade in life, even though in affected (http://dx.doi.org/10.1136/ quality of life data. patients Fabry disease usually manifests much bmjopen-2015-010422). Results: AgalA enzyme activity in leucocytes (0.3 earlier. Furthermore, only one male participant is included. Received 2 November 2015 ±0.9 nmol/min/mg protein (mean±SD)) and serum Revised 2 March 2016 lyso-Gb3 (0.6±0.3 ng/mL at baseline) were in normal Accepted 3 March 2016 range in all patients. Cardiac morphology and function were normal (left-ventricular (LV) ejection fraction 66 life-threatening accumulation of globotriao- ±8%; interventricular septum 7.7±1.4 mm; LV posterior sylceramides (Gb3) in lysosome-carrying http://bmjopen.bmj.com/ 1–5 wall 7.5±1.4 mm; normalised LV mass in MRI 52±9 g/ tissues. In addition to gender, clinical man- m2; LV global longitudinal strain −21.6±1.9%) and ifestations and disease severity are largely there were no signs of myocardial fibrosis in cardiac dependent on the underlying GLA muta- MRI. Cardiospecific biomarkers were also in normal tion.3467Initially described as a multisyste- range. Renal function was not impaired (estimated mic disorder mainly involving the three organ glomerular filtration rate MDRD 103±15 mL/min; systems of the heart, kidneys and nervous serum-creatinine 0.75±0.07 mg/dL; cystatin-c 0.71 system, newer studies suggest that besides ±0.12 mg/L). One female patient (also carrying a Factor ‘ ’ on September 25, 2021 by guest. Protected copyright. 1 these classical FD mutations involving a com- Department of Internal V Leiden mutation) had a transitory ischaemic attack. 89 Medicine I and One patient showed white matter lesions in brain MRI, bination of pain, cryptogenic stroke at 910 fi 11 12 Comprehensive Heart Failure but none had Fabry-associated pain attacks, pain young age, myocardial brosis and 13 14 Center (CHFC), University crises, evoked pain or permanent pain. Health-related pathological renal function, there might Hospital Würzburg, quality of life analysis revealed a reduction in individual additionally exist mild, so-called ‘late onset’ Würzburg, Germany well-being. At long-term follow-up after 4 years, no and/or mono-phenotypical GLA mutation 2Fabry Center for significant change was seen in any parameter. variants, which are in need of further clinical Interdisciplinary Therapy 3–5 (FAZIT), University Hospital Conclusions: The results of the current study suggest characterisation. Among the currently Würzburg, Würzburg, that the D313Y genotype does not lead to severe organ known over 600 pathogenic GLA muta- Germany manifestations as seen in genotypes known to be tions,15 16 the D313Y (Exon 6, c.937G.T) 3 Department of Neurology, causal for classical FD. mutational variant has been reported to University Hospital Würzburg, Würzburg, Germany cause only mild clinical symptoms in observa- 4Department of Diagnostic tional case reports, suggesting a good progno- 17–20 and Interventional Radiology, sis and no need of specific therapy. University Hospital Würzburg, INTRODUCTION However, owing to the currently only anec- Würzburg, Germany Anderson-Fabry disease (FD) is an inherited dotal data available, the long-term impact of Correspondence to X linked lysosomal storage disorder, caused the D313Y mutation on organ function still Dr Peter Nordbeck; by enzyme deficiency of α-galactosidase remains poorly understood, which hinders [email protected] A (AgalA), which leads to potentially concluding therapeutic recommendations. Oder D, et al. BMJ Open 2016;6:e010422. doi:10.1136/bmjopen-2015-010422 1 Open Access BMJ Open: first published as 10.1136/bmjopen-2015-010422 on 8 April 2016. Downloaded from The aim of this study was to improve the pathophysio- (LVPWed) thicknesses. The LV ejection fraction (LVEF) logical understanding of the D313Y genotype by observ- was calculated based on the 2-chamber and 4-chamber ing the long-term changes in organ function in mutation views by using the Simpson’s formula. The transmitral carriers. Clinical, biomarker, health-related quality of life flow was determined by placing the Doppler window (HRQoL) and imaging data were analysed at baseline between the tips of the mitral valve leaflets, consecutively (BL) and during long-term follow-up (FUP) in all measuring the peak flow velocities in early (E wave) and respective patients who were examined at the Fabry late (A wave) systole. Blood-pooled pulsed Doppler Center for Interdisciplinary Therapy (FAZIT) of the imaging of the mitral valve inflow was used to quantify University Hospital Würzburg, Germany. the ratio of early-to-late (E/A) diastolic flow velocity and to gain the deceleration time. The standard apical views of the LV were acquired for offline quantification of METHODS myocardial deformation values by 2D speckle tracking Study population using ECHO-Pac Software (GE Vingmed Ultrasound AS) The investigations were approved by the local ethics com- as described before.23 24 After manual selection of the mittee of the University and University Hospital region of interest (ROI) was sufficiently performed, the Würzburg, Bavaria, Germany, and all patients gave speckles were at first automatically assumed and then written informed consent in accordance with the fi fi fi modi ed and con rmed by the user. 2D grey scale Declaration of Helsinki. Patients were identi ed during images were recorded with a frame rate of 60–80 frames their stay at FAZIT for clinical evaluation and treatment. per second and particular care was taken in ensuring Genetic testing revealed the GLA mutation D313Y (Exon that the entire ventricular wall was clearly visible in all 6, c.937G.T) in six patients from five different families (5 – frames. The system automatically tracked the tissue female; age 33±15 years, range 18 51 years at BL). No within the region and divided the myocardium into additional GLA mutations or genetic polymorphisms standard segments. The tracking was visually checked were found in these individuals. Comprehensive clinical and, if necessary, adjusted. The trace analysis was auto- data and blood parameters were acquired at BL and matically displayed after validating the tracking. LV during FUP after 4 years if available as described below. global and segmental longitudinal peak systolic strain rate and strain values were extracted from basal, mid Family analysis and apical segments of the septal and lateral walls. Detailed family pedigrees were compiled in each patient. Family history was recorded including potential Cardiac MRI FD-related signs and symptoms, history of heart or Cardiac MRI (cMRI) was performed on a 1.5 T full-body kidney disease, cerebrovascular events, death at young MRI scanner (Magnetom Symphony Quantum/Avanto, http://bmjopen.bmj.com/ age and respective causes of death. Siemens Medical Systems, Erlangen, Germany) in breath- hold technique with ECG triggering. After morphological Clinical assessment cine imaging using steady state free precession techni- All study participants underwent physical examination ques, patients received gadopentetate dimeglumine with particular focus on cardiac, renal and neurological (Bayer Health Care, Leverkusen, Germany) in the stand- signs and symptoms. Blood pressure, heart rate and the ard dose of 0.2 mmol/kg body weight per intravenous body mass index were determined. injection. Late contrast agent enhanced images were acquired using T1-weighted inversion recovery imaging on September 25, 2021 by guest. Protected copyright. Electrocardiogram sequences (field of view 240×320 mm2, matrix size Standardised 12-channel ECGs were performed in all 165×256, slice thickness 8 mm, echo time 3.4 ms, repeti- patients at rest and during cardiac stress test. tion time 7.5 ms). Consecutive short-axis slices covering Additionally,
Load more

Recommended publications
  • (UPCR) Levels in Diabetic Nephropathy Patients
    Journal of Personalized Medicine Article Gender Differences in Genetic Associations of RAB38 with Urinary Protein-to-Creatinine Ratio (UPCR) Levels in Diabetic Nephropathy Patients 1, 2,3,4, 1 1 Zhi-Lei Yu y, Chung-Shun Wong y , Yi Ting Lai , Wan-Hsuan Chou , Imaniar Noor Faridah 1,5, Chih-Chin Kao 6,7 , Yuh-Feng Lin 2,7,8,* and Wei-Chiao Chang 1,9,10,11,* 1 Department of Clinical Pharmacy, School of Pharmacy, Taipei Medical University, Taipei 110301, Taiwan; [email protected] (Z.-L.Y.); [email protected] (Y.T.L.); [email protected] (W.-H.C.); [email protected] (I.N.F.) 2 Graduate Institute of Clinical Medicine, College of Medicine, Taipei Medical University, Taipei 110301, Taiwan; [email protected] 3 Department of Emergency Medicine, Taipei Medical University-Shuang Ho Hospital, New Taipei City 235041, Taiwan 4 Department of Emergency Medicine, School of Medicine, College of Medicine, Taipei Medical University, Taipei 11031, Taiwan 5 Faculty of Pharmacy, Ahmad Dahlan University, Yogyakarta 55164, Indonesia 6 Division of Nephrology, Department of Internal Medicine, Taipei Medical University Hospital, Taipei 110301, Taiwan; [email protected] 7 Division of Nephrology, Department of Internal Medicine, School of Medicine, College of Medicine, Taipei Medical University, Taipei 110301, Taiwan 8 Division of Nephrology, Department of Internal Medicine, Shuang Ho Hospital, Taipei Medical University, New Taipei City 235041, Taiwan 9 Master Program for Clinical Pharmacogenomics and Pharmacoproteomics, School of Pharmacy, Taipei Medical University, Taipei 110301, Taiwan 10 Integrative Research Center for Critical Care, Wan Fang Hospital, Taipei Medical University, Taipei 110301, Taiwan 11 Department of Medical Research, Shuang Ho Hospital, Taipei Medical University, New Taipei City 235041, Taiwan * Correspondence: [email protected] (Y.-F.L.); [email protected] (W.-C.C.) Z.-L.Y.
    [Show full text]
  • Diagnostic Accuracy of Spot Urine Protein-To-Creatinine Ratio For
    O RIGINAL ARTICLE Diagnostic accuracy of spot urine protein-to- creatinine ratio for proteinuria and its association with adverse pregnancy outcomes in Chinese pregnant patients with pre-eclampsia HC Cheung *, KY Leung, CH Choi ABSTRACT diagnosing proteinuria in Chinese pregnant patients (33 mg/mmol) was similar to that stated in the International guidelines have Introduction: international literature (30 mg/mmol). A cut-off of endorsed spot urine protein-to-creatinine ratio of 20 mg/mmol provided a 100% sensitivity, and 52 >30 mg protein/mmol creatinine as an alternative mg/mmol provided a 100% specificity. There was to a 24-hour urine sample to represent significant no significant difference in spot urine protein-to- proteinuria. This study aimed to determine the creatinine ratio between cases with and without accuracy of spot urine protein-to-creatinine ratio adverse pregnancy outcome. in predicting significant proteinuria and adverse pregnancy outcome. Conclusions: Spot urine protein-to-creatinine ratio had a positive and significant correlation with 24-hour This case series was conducted in a Methods: urine results in Chinese pre-eclamptic women when regional obstetric unit in Hong Kong. A total of the ratio was <200 mg/mmol. Nonetheless, this ratio 120 Chinese pregnant patients with pre-eclampsia was not predictive of adverse pregnancy outcome. delivered at Queen Elizabeth Hospital from January 2011 to December 2013 were included. Relationship of spot urine protein-to-creatinine ratio and 24-hour Hong Kong Med J 2016;22:249–55 proteinuria; accuracy of the ratio against 24-hour DOI: 10.12809/hkmj154659 urine protein at different cut-offs; and relationship 1 HC Cheung *, MB, BS, MRCOG of such ratio and adverse pregnancy outcome were 1 KY Leung, FRCOG, FHKAM (Obstetrics and Gynaecology) studied.
    [Show full text]
  • An Unusual Case of Acute Kidney Injury with Edematous Kidneys and Venous Micro Thrombi: a Case Report
    Hijazi F, et al., J Nephrol Renal Ther 2019, 5: 023 DOI: 10.24966/NRT-7313/100023 HSOA Journal of Nephrology & Renal Therapy Case Report countries, AKI is a disease of the young [8] and children [9], in whom An Unusual Case of Acute volume-responsive “prerenal” mechanisms are common [10]. We present a case of a young adult presenting with unexplained AKI. Kidney Injury with Edematous Case History Kidneys and Venous Micro A 20-year-old man with non-significant past medical history who presented to the emergency room with a 2 day-history of low back Thrombi: A Case Report and bilateral flank pain. He also had mild nausea and feverishness. Fadi Hijazi, Nizar Attallah, Rakesh Madhyastha* The patient also reported thirst and polyuria. He did not have edema, rashes, or arthralgia. No respiratory symptoms were reported. He took Department of Nephrology, Medical Subspecialties Institute, Cleveland Clinic Abu Dhabi, Abu Dhabi, UAE 10 tablets of acetaminophen and 2 tablets of ibuprofen over those 2 days. He did not have any alcohol or illicit drugs use. Abstract Vital signs were normal. Physical examination was positive for mild costovertebral angle tenderness on both sides. Otherwise, the This case report describes a young patient with Acute Kidney rest of the physical exam was unremarkable. He had no skin rash. Injury (AKI) stage 3, low grade micro-hematuria (3-5 dysmorphic red blood cells in each high power field [RBC/HPF]), low grade pro- Initial laboratory testing revealed a serum creatinine of 341 umol/L teinuria (Urine Protein To Creatinine (UPCR) of around 1 gm/gm), (3.8 mg/dl), and urinalysis showed proteinuria (2+), and 0-3 and 3-5 edematous kidneys on ultrasound, and unusual histologic finding on kidney biopsy.
    [Show full text]
  • Proteinuria and Hematuria
    Proteinuria and Hematuria Proteinuria (including Albuminuria) Qualitative Testing (dye-impregnated paper strip- “dipstick”)- 1-4+ Quantitative Testing > Urine protein to creatinine ratio (UPCR) (gm/gm) in a “spot” urine sample or a timed collection > Urine albumin to creatinine ratio (UACR) (mg/mg) in a “spot” urine or a timed collection > Urine albumin concentration (mg/dL) (UAC) > Urine albumin excretion rate (mg/d or μg/min (UAER) in timed urinary collection > Urine protein excretion rate (UPER) in a timed urinary collection-usually 24 hours (UACR or UAC preferred) Proteinuria and the Nephrotic Syndrome: Definitions Proteinuria: >Overt- Urinary excretion of >300mg total protein/d or a UPCR of >200mg/gm > Covert- (microalbuminuria) UAER of 30- 300mg albumin/d (20-200μg/min or a UACR of 17-250mg/gm (M) or 25-355mg/gm (F) Nephrotic Syndrome: > Urinary excretion of >3.5gm total protein/d or a UPCR of >3.0gm/gm (Adult) + Hypoalbuminemia (Edema and Hyperlipidemia are variable) Proteinuria: Evaluation Spot morning second voided urine samples are best– UAC or UACR or UPCR Dipstick testing is only semi-quantitative and is influenced by urine concentration (Specific Gravity or Osmolality) Dipstick tests are relatively insensitive for globulins and light-chains False positive Dipsticks with alkaline urine and after contrast agent or cephalosporins Myoglobin and Hemoglobin can give a + test Proteinuria: Evaluation Dipsticks: Negative- <10mg/dL Trace - 10mg/dL 1+- 30mg/dL 2+- 100mg/dL 3+- 300mg/dL 4+- >1000mg/dL Proteinuria: Evaluation
    [Show full text]
  • Seventh Congress of the International Bioiron Society (IBIS)
    Seventh Congress of the International BioIron Society (IBIS) Biennial World Meeting (BioIron 2017) May 7 – 11, 2017 UCLA Meyer & Renee Luskin Conference Center | Los Angeles, USA Featuring Special Events: Introductory Course – May 7, 2017 “Essentials of BioIron for Clinicians and Scientists” “Meet the Expert” Sessions for Trainees May 10 – 11, 2017 INTERNATIONAL BIOIRON SOCIETY PROGRAM BOOK Acknowledgments IBIS This conference has received support from the NIH NCATS UCLA CTSI Grant Number UL1TR0001881. This conference has received support from the NIH/NIDDK R-13 Grant. This conference has received support from the NIXHNHLBI-R-13 Grant. Seventh Congress of the International BioIron Society Page 2 Table of Contents IBIS Seventh Congress of the Internationl BioIron Society (IBIS) Biennial World Meeting (BioIron 2017) May 7 - 11, 2017 UCLA Meyer & Renee Luskin Conference Center | Los Angeles, USA Welcome Message ..............................................................................................................................Page 4 Board of Directors ................................................................................................................................Page 5 General Meeting Information ...............................................................................................................Page 6 Special Events .....................................................................................................................................Page 8 Local Activities .....................................................................................................................................Page
    [Show full text]
  • Clinical Pharmacy and Clinical Trials Eur J Hosp Pharm: First Published As 10.1136/Ejhpharm-2013-000276.585 on 12 March 2013
    Clinical pharmacy and clinical trials Eur J Hosp Pharm: first published as 10.1136/ejhpharm-2013-000276.585 on 12 March 2013. Downloaded from Conclusions CPC-128 START SMART THEN FOCUS – a Survey oF ANTIMICROBIAL STEWARDSHIP GUIDELINES ●● It showed better clinical outcomes in the gemcitabine plus nab-paclitaxel group in PFS. IMPLEMENTATION IN ENGLAND ●● The nab-paclitaxel can be an effective second-line chemo- doi:10.1136/ejhpharm-2013-000276.585 therapy in gemcitabine resistant patients. 1P Howard, 2J Cooke, 3C Fry, 4C McNulty, 5H Khoda, 3S Wellstead, 6J Stockley, No conflict of interest. 7H Loveday, 5L Brown. 1Leeds Teaching Hospitals NHS Trust, Pharmacy, Leeds, UK; 2University of Manchester, Pharmacy, Manchester, UK; 3Department of Health, Infectious CPC-127 SEVERAL TYPES OF PROTEINURIA AND ASSOCIATED Diseases and Blood Policy, London, UK; 4Health Protection Agency, Primary Care Unit, FACTORS AMONG HIV-INFECTED ADULTS IN THE Gloucester, UK; 5Health Protection Agency, HCAI and AMR Programme Team, London, HAART ERA UK; 6Worcester Acute Hospitals NHS Trust, Microbiology, Worcester, UK; 7University of West London, College of Nursing Midwifery and Healthcare, London, UK doi:10.1136/ejhpharm-2013-000276.584 1E Guiller, 2C Psomas, 3M Chaton, 4A Cournil, 2J Reynes. 1University Hospital of Background Start Smart then Focus Antimicrobial Stewardship Montpellier, Pharmacy, Montpellier Cedex 5, France; 2University Hospital of Montpellier, (AMS) guidance for England was launched in November 2011 on Department of Infectious Diseases, Montpellier Cedex 5, France; 3University Hospital European Antimicrobial Awareness Day. of Montpellier, Biochemistry, Montpellier Cedex 5, France; 4University Hospital of Purpose To identify the extent of guideline implementation, Montpellier, IRD Inst Res Devt, Montpellier Cedex 5, France whether the guidelines had improved AMS, and to collect examples of good practise.
    [Show full text]
  • Storm in a Pee Cup: Hematuria and Proteinuria
    Storm in a Pee Cup: Hematuria and Proteinuria Sudha Garimella MD Pediatric Nephrology, Children's Hospital-Upstate Greenville SC Conflict of Interest • I have no financial conflict of interest to disclose concerning this presentation. Objectives • Interpret the current guidelines for screening urinalysis, and when to obtain a urinalysis in the pediatric office. • Interpret the evaluation of asymptomatic/isolated proteinuria and definitions of abnormal ranges. • Explain the evaluation and differential diagnosis of microscopic hematuria. • Explain the evaluation and differential diagnosis of gross hematuria. • Explain and discuss appropriate referral patterns for hematuria. • Racial disparities in nephrology care 1. APOL-1 gene preponderance in African Americans and risk of proteinuria /progression(FSGS) 2. Race based GFR calculations which have caused harm 3. ACEI/ARB usage in AA populations: myths and reality Nephrology Problems in the Office • Hypertension • Proteinuria • Microscopic Hematuria • Abnormal Renal function The Screening Urinalysis • Choosing Wisely: • Don’t order routine screening urine analyses (UA) in healthy, asymptomatic pediatric patients as part of routine well child care. • One study showed that the calculated false positive/transient abnormality rate approaches 84%. • Population that deserves screening UA: • patients who are at high risk for chronic kidney disease (CKD), including but not necessarily limited to patients with a personal history of CKD, acute kidney injury (AKI), congenital anomalies of the urinary tract, acute nephritis, hypertension (HTN), active systemic disease, prematurity, intrauterine growth retardation, or a family history of genetic renal disease. • https://www.choosingwisely.org/societies/american-academy-of-pediatrics-section-on- nephrology-and-the-american-society-of-pediatric-nephrology/ Screening Urinalysis: Components A positive test for leukocyte esterase may be seen in genitourinary inflammation, irritation from instrumentation or catheterization, glomerulonephritis, UTIs and sexually transmitted infections.
    [Show full text]
  • Urinalysis Vs Urine Protein–Creatinine Ratio to Predict Significant
    Journal of Perinatology (2008) 28, 461–467 r 2008 Nature Publishing Group All rights reserved. 0743-8346/08 $30 www.nature.com/jp ORIGINAL ARTICLE Urinalysis vs urine protein–creatinine ratio to predict significant proteinuria in pregnancy BK Dwyer1, M Gorman2, IR Carroll3 and M Druzin1 1Division of Maternal Fetal Medicine, Department of Gynecology and Obstetrics, Stanford University, Stanford, CA, USA; 2Department of Family and Community Medicine, University of California, Davis, CA, USA and 3Division of Pain Medicine, Department of Anesthesiology, Stanford University, Stanford, CA, USA evaluation. A rapid screening test to predict 24-h proteinuria, in Objective: To compare the urine protein–creatinine ratio with urinalysis combination with other presenting signs and symptoms, can help a to predict significant proteinuria (X300 mg per day). clinician determine the appropriate amount of surveillance and Study Design: A total of 116 paired spot urine samples and 24-h urine guide care during the initial 24-h period. Traditionally, the dipstick 2 collections were obtained prospectively from women at risk for urinalysis has been used as this screening test. preeclampsia. Urine protein–creatinine ratio and urinalysis were The dipstick urinalysis measures the concentration of protein in compared to the 24-h urine collection. the urine and is susceptible to fluctuations in the water content of the urine. Dilute urine may underestimate the amount of protein Result: The urine protein–creatinine ratio had better discriminatory that would be collected in a 24-h urine collection, whereas power than urinalysis: the receiver operating characteristic curve had a concentrated urine may overestimate it. Prior studies have reported greater area under the curve, 0.89 (95% confidence interval (CI) 0.83 to that dipstick urinalysis has varying degrees of accuracy, with 0.95) vs 0.71 (95% CI 0.64 to 0.77, P<0.001).
    [Show full text]
  • Correlation Between Urine ACR and 24-H Proteinuria in a Real-World Cohort of Systemic AL Amyloidosis Patients Alissa Visram1,2, Abdullah S
    Visram et al. Blood Cancer Journal (2020) 10:124 https://doi.org/10.1038/s41408-020-00391-2 Blood Cancer Journal ARTICLE Open Access Correlation between urine ACR and 24-h proteinuria in a real-world cohort of systemic AL amyloidosis patients Alissa Visram1,2, Abdullah S. Al Saleh1,3,HarshParmar4, Jennifer S. McDonald5,JohnC.Lieske 6, Iuliana Vaxman1,7,8, Eli Muchtar1, Miriam Hobbs1, Amie Fonder1,YiL.Hwa1, Francis K. Buadi1, David Dingli1,MarthaQ.Lacy1, Angela Dispenzieri 1,PrashantKapoor1, Suzanne R. Hayman1, Rahma Warsame1, Taxiarchis V. Kourelis1, Mustaqeem Siddiqui 1, Wilson I. Gonsalves1,JohnA.Lust1,RobertA.Kyle1,S.VincentRajkumar 1,MorieA.Gertz 1, Shaji K. Kumar 1 and Nelson Leung 9 Abstract A 24-h urine protein collection (24hUP), the gold standard for measuring albuminuria in systemic AL amyloidosis, is cumbersome and inaccurate. We retrospectively reviewed 575 patients with systemic AL amyloidosis to assess the correlation between a urine albumin to creatinine ratio (uACR) and the 24hUP. The uACR correlated strongly with 24hUP at diagnosis (Pearson’s r = 0.87, 95% CI 0.83–0.90) and during the disease course (Pearson’s r = 0.88, 95% CI 0.86–0.90). A uACR ≥300 mg/g estimated a 24hUP ≥ 500 mg with a sensitivity of 92% and specificity of 97% (area under the receiver operating curve = 0.938, 95% CI 0.919–0.957). A uACR cutoff of 3600 mg/g best predicted a 24hUP > 5000 g (sensitivity 93%, specificity 94%), and renal stage at diagnosis was strongly concordant using either 24hUP or uACR as the proteinuria measure (k = 0.823, 95% CI 0.728–0.919).
    [Show full text]
  • Change in Albuminuria and GFR As End Points for Clinical Trials In
    Special Report Change in Albuminuria and GFR as End Points for Clinical Trials in Early Stages of CKD: A Scientific Workshop Sponsored by the National Kidney Foundation in Collaboration With the US Food and Drug Administration and European Medicines Agency Andrew S. Levey, Ron T. Gansevoort, Josef Coresh, Lesley A. Inker, Hiddo L. Heerspink, Morgan E. Grams, Tom Greene, Hocine Tighiouart, Kunihiro Matsushita, Shoshana H. Ballew, Yingying Sang, Edward Vonesh, Jian Ying, Tom Manley, Dick de Zeeuw, Kai-Uwe Eckardt, Adeera Levin, Vlado Perkovic, Luxia Zhang, and Kerry Willis The US Food and Drug Administration (FDA) and European Medicines Agency (EMA) are currently Complete author and article willing to consider a 30% to 40% glomerular filtration rate (GFR) decline as a surrogate end point for information provided before kidney failure for clinical trials of kidney disease progression under appropriate conditions. However, references. these end points may not be practical for early stages of kidney disease. In March 2018, the National Am J Kidney Dis. 75(1): Kidney Foundation sponsored a scientific workshop in collaboration with the FDA and EMA to evaluate 84-104. Published online changes in albuminuria or GFR as candidate surrogate end points. Three parallel efforts were pre- August 28, 2019. sented: meta-analyses of observational studies (cohorts), meta-analyses of clinical trials, and simula- doi: 10.1053/ tions of trial design. In cohorts, after accounting for measurement error, relationships between change j.ajkd.2019.06.009 in urinary albumin-creatinine ratio (UACR) or estimated GFR (eGFR) slope and the clinical outcome of © 2019 by the National kidney disease progression were strong and consistent.
    [Show full text]
  • Eudract Number: 2018-000477-77 (Version: 2; Version Date: 31 Jul 2018)
    Eudract Number: 2018-000477-77 (Version: 2; Version Date: 31 Jul 2018) CLINICAL NO PROFIT PROTOCOL EUDRACT NUMBER: 2018-000477-77 TITLE: Metformin versus Tolvaptan in adults with Autosomal Dominant Polycystic Kidney Disease (ADPKD): a phase 3a, independent, multi- centre, 2 parallel arms randomized controlled trial STUDY NAME: METROPOLIS VERSION: 2 VERSION DATE: 31 July 2018 Page 1 of 111 Eudract Number: 2018-000477-77 (Version: 2; Version Date: 31 Jul 2018) SPONSOR Name: Università degli Studi di Bari Dipartimento dell’Emergenza e dei Trapianti di organi (D.E.T.O.) Address: Piazza G.Cesare n.11-Policlinico- 70124 Bari Phone: +39 0805478627- Ufficio protocollo + 39080 5478614 E mail : [email protected] Signature ( per lo sponsor ) Prof. Loreto Gesualdo CHAIRMAN/STUDY Name: Prof. Loreto Gesualdo -Direttore U.O. COORDINATOR Nefrologia Universitaria – Azienda Policlinico di Bari Address: Piazza G.Cesare n.11 70124 Bari Phone: + 39 080 5594041 Fax: + 39 080 5478675 Email: [email protected] Prof. Loreto Gesualdo PRINCIPAL/COORDINATING Name: Prof. Loreto Gesualdo - Direttore U.O. INVESTIGATOR Nefrologia Universitaria – Azienda Policlinico di Bari Address: Piazza G. Cesare n.11 70124 Bari Phone: + 39 080 5594041 Fax: 39 080 5478675 Email: [email protected] Prof. Loreto Gesualdo MEDICAL WRITING Name: Prof. Loreto Gesualdo; Name: Dr. Giovanni Piscopo Page 2 of 111 Eudract Number: 2018-000477-77 (Version: 2; Version Date: 31 Jul 2018) TABLE OF CONTENTS A. LIST OF ABBREVIATIONS ....................................................................................
    [Show full text]
  • Microalbuminuria As an Early Predictor of Preeclampsia in the Pre
    Pregnancy Hypertension 15 (2019) 182–188 Contents lists available at ScienceDirect Pregnancy Hypertension journal homepage: www.elsevier.com/locate/preghy Microalbuminuria as an early predictor of preeclampsia in the pre- gestational diabetic population: A prospective cohort study T ⁎ Monica Zena,d, , Suja Padmanabhanb,d, Ngai Wah Cheungb,d, Adrienne Kirbye, Shilpa Jesudasonf, Thushari I. Alahakoona,d, Vincent W. Leec,d a Westmead Institute for Maternal & Fetal Medicine, Westmead Hospital, Westmead, New South Wales, Australia b Department of Diabetes & Endocrinology, Westmead Hospital, Westmead, New South Wales, Australia c Department of Renal Medicine, Westmead Hospital, Westmead, New South Wales, Australia d The University of Sydney, Westmead Hospital, Westmead, New South Wales, Australia e NHMRC Clinical Trial Centre, University of Sydney, Australia f Central and Northern Adelaide Renal and Transplantation Service, Royal Adelaide Hospital, South Australia, Australia ARTICLE INFO ABSTRACT Keywords: Objectives: To determine if microalbuminuria can be used as a predictive marker of preeclampsia and adverse Microalbuminuria pregnancy and neonatal outcomes in women with pre-existing diabetes and to compare the prognostic utility of Preeclampsia urinary albumin to creatinine ratio (uACR) and urinary protein to creatinine ratio (uPCR). Pre-existing diabetes Study Design: Multicentre prospective cohort study. Antenatal Diabetes in Pregnancy clinics at three tertiary Proteinuria referral hospitals in Western Sydney, Australia. 158 women with pre-existing diabetes requiring insulin in pregnancy. A spot uPCR and uACR was performed in each trimester. Pregnancy and fetal outcomes were in- vestigated using linear models and receiver-operating characteristic (ROC) curves. Main outcome measures: The primary outcome was preeclampsia (PE). Secondary outcomes investigated were other adverse pregnancy and neonatal outcomes.
    [Show full text]