Expression of uPAR in Urinary Podocytes of Patients with Fabry Disease

Background. Despite enzyme replacement therapy, Fabry nephropathy still progresses. Podocyturia is an irreversible event that antedates proteinuria and leads to chronic renal failure. We evaluated a potential mechanism of podocyte detachment via the expression of the urokinase-type Plasminogen Activator Receptor (uPAR) in urinary podocytes of Fabry patients.Methods. This is a cross-sectional study that included controls (n=20) and Fabry patients (n=44) either untreated (n=23) or treated with agalsidase-β(n=21).Variables. Variables are estimated glomerular filtration rate (eGFR), urinary protein : creatinine ratio, and urinary uPAR+ podocyte : creatinine ratio. uPAR mRNA expression in response to lyso-Gb3, a bioactive glycolipid accumulated in Fabry disease, was studied in cultured human podocytes.Results. Controls and Fabry patients had similar age, gender, and renal function. Urinary uPAR+ podocytes were higher in patients than in controls. Untreated patients were significantly younger; had more females, and presented lower urinary protein : creatinine ratios and significantly higher urinary uPAR+ podocytes than treated subjects. In treated patients, urinary uPAR+ podocytes correlated with urinary protein : creatinine ratio (ρ=0.5;p=0.02). Lyso-Gb3 at concentrations found in the circulation of Fabry patients increased uPAR expression in cultured podocytes.Conclusions. Urinary podocytes expressing uPAR are increased in Fabry patients, especially in untreated patients. The potential contribution of uPAR expression to podocyte detachment merits further studies.

Download Full-text

Correlation of 24-hour urinary protein excretion and spot urine protein-creatinine ratio in women with preeclampsia: A cross sectional study

MedPulse International Journal of Gynecology ◽

10.26611/10121736 ◽

2021 ◽

Vol 17 (3) ◽

pp. 62-66

Author(s):

K Hima Bindu ◽

Keyword(s):

Cross Sectional Study ◽

Urinary Protein Excretion ◽

Urinary Protein ◽

Creatinine Ratio ◽

Sectional Study ◽

Urine Protein ◽

Cross Sectional ◽

Spot Urine ◽

Protein Excretion

Download Full-text

Association between obesity and urinary albumin-creatinine ratio in the middle-aged and elderly population of Southern and Northern China: a cross-sectional study

BMJ Open ◽

10.1136/bmjopen-2020-040214 ◽

2021 ◽

Vol 11 (1) ◽

pp. e040214

Author(s):

Shan Qin ◽

Anping Wang ◽

Shi Gu ◽

Weiqing Wang ◽

Zhengnan Gao ◽

...

Keyword(s):

Kidney Diseases ◽

Northern China ◽

Cross Sectional Study ◽

Urinary Albumin ◽

Creatinine Ratio ◽

Sectional Study ◽

The South ◽

Northern Population ◽

Cross Sectional ◽

Albumin Creatinine Ratio

ObjectiveThe relationship between obesity and albuminuria has not been clarified. This study aimed to investigate the correlation between obesity and the urinary albumin-creatinine ratio (UACR) in Southern and Northern China.DesignA descriptive, cross-sectional study.SettingEight regional centres in REACTION (China’s Risk Evaluation of cAncers in Chinese diabeTic Individuals, a lONgitudinal study), including Dalian, Lanzhou, Zhengzhou, Guangzhou, Guangxi, Luzhou, Shanghai and Wuhan.ParticipantsA total of 41 085 patients who were not diagnosed with chronic kidney disease (CKD) and had good compliance were selected according to the inclusion criteria. Patients who were diagnosed with CKD, who had other kidney diseases that could lead to increased urinary protein excretion, who were using angiotensin-converting-enzyme inhibitors or angiotensin II receptor blockers and whose important data were missing were excluded.ResultsParticipants with both, central and peripheral obesity, had a higher risk of elevated UACR, even after adjusting for multiple factors (OR: 1.14, 95% CI: 1.07 to 1.12, p<0.001), and the risk of high UACR in the South was more prominent than that in the North (OR South: 1.22, 95% CI: 1.11 to 1.34; OR North: 1.13, 95% CI: 1.04 to 1.22, p<0.001). The risk was also elevated in the male population, hypertensive individuals, glycosylated haemoglobin (HbA1c)≥6.5% and age ≥60 years in the South. Besides the above groups, diabetes was also a risk factor for the Northern population.ConclusionsIn China, people with both central and peripheral obesity are prone to a high UACR, and the southern population has a higher risk than northern population. Factors such as male sex, hypertension, HbA1c≥6.5% and an age ≥60 years are also risk factors for CKD.

Download Full-text

4091Mechanical dispersion by speckle tracking echocardiography in fabry disease

European Heart Journal ◽

10.1093/eurheartj/ehz745.0103 ◽

2019 ◽

Vol 40 (Supplement_1) ◽

Author(s):

T F Cianciulli ◽

M C Saccheri ◽

A M Risolo ◽

J A Lax ◽

R J Mendez ◽

...

Keyword(s):

Fabry Disease ◽

Speckle Tracking ◽

Heart Diseases ◽

Systolic Dysfunction ◽

Cross Sectional Study ◽

Left Ventricular ◽

Peak Strain ◽

Cross Sectional ◽

Mechanical Dispersion ◽

Group I

Abstract Background Fabry disease is a rare X-linked storage disorder caused by a deficiency of the lysosomal enzyme α-galactosidase A and generally causes multi-organ dysfunction. Heart disease is the main cause of death, due to severe left ventricular (LV) systolic dysfunction and sudden death. In several heart diseases, the LV systolic dysfunction and ventricular arrhythmias are associated with mechanical dispersion (MD). The presence of MD in patients with FD has not been studied yet. In this cross-sectional study, we investigated the prevalence of MD in patients with FD. Methods Complete echocardiographic and speckle tracking echocardiographic (STE) data were collected. MD is an index of inter-segmental discoordination of contraction which has been used to quantify LV dyssynchrony and was defined as the standard deviation (SD) of time to peak negative strain in 17 left ventricular segments. Patients were divided into two groups according to whether or not they had left ventricular hypertrophy (LVH). MD was defined as an SD >49 msec. Results We studied 108 patients with FD, 24 patients (22%) were excluded due to inadequate imaging quality or presence of comorbidities, so the final study population consisted of 84 patients (mean age 33.3±14.6 years, 60.7% women). LVH in FD appears at older ages than in patients without LVH (48±12.5 y/o vs 27.8±11.1 y/o, p<0.0001). Patients with FD without LVH (Group I) showed normal global longitudinal peak strain (GLPS) (21.2±2.5%) and no MD (32.7±8.8 msec). In Group II (n=23) patients with FD with LVH, 17 (73.9%) had MD >49 msec prolonged mechanical dispersion (73.3±20.7 msec) and reduced GLPS (13.6±4.0%). MD was more pronounced in Fabry patients with LVH than in patients without LVH (63.4±24.7 msec vs. 32.7±8.8 msec, p<0.0001). GLPS was lower in Fabry patients with LVH than in patients without LVH (15.3±4.7% vs 21.2±2.5%, p<0.0001). Figure 1 Conclusions To our knowledge, this is the first study to demonstrate the prevalence of mechanical dispersion in patients with FD. Mechanical dispersion was seen in 73.9% of patients with FD with LVH. This dyssynchrony should be taken into account in patients who develop heart failure or life-threatening ventricular tachyarrhythmias.

Download Full-text

MO055THE IMPACT OF THE COVID-19 PANDEMIC ON MOOD STATUS AND TREATMENT ADHERENCE IN PATIENTS WITH FABRY DISEASE

Nephrology Dialysis Transplantation ◽

10.1093/ndt/gfab080.0027 ◽

2021 ◽

Vol 36 (Supplement_1) ◽

Author(s):

Mevlut Tamer Dincer ◽

Cebrail Karaca ◽

Betul Sarac ◽

Saffa Ahmadzada ◽

Alev Bakir ◽

...

Keyword(s):

Fabry Disease ◽

Access To Health Care ◽

Patient Adherence ◽

Depression Scale ◽

Control Measures ◽

Infusion Therapy ◽

Control Group ◽

Cross Sectional ◽

Enzyme Replacement ◽

Home Based

Abstract Background and Aims Fabry disease is a rare metabolic disorder, lifelong enzyme replacement therapy with recombinant human alpha-galactosidase A (agalsidase) constituted the cornerstone of disease-specific therapy. COVID-19 pandemic and epidemic control measures including lockdowns impaired access to health care services. We examined the effect of COVID-19 pandemic and lockdown measures on mood status and management of Fabry disease patients. Method We conducted a cross-sectional study between October 2020 and December 2020. We used the Hospital Anxiety and Depression Scale (HADS) to evaluate the mood statuses of FD patients and the Morisky Medication Adherence Scale (MMAS-4) to assess patient adherence. We also examined age and sex-matched control group to compare mood status. Results A total of 68 (Male 48.5 %, mean age 37.0) FD patients were under regular follow-up in our institution, 59 of those patients were taking ERT every other week. Two of our patients had reported having a COVID-19 infection, and both of them recovered. 25 patients reported to miss an ERT for a median of one dose, 16 of these 25 patients have reported that they did not come to the hospital because of infection fear. Half of the patients had adopted home-based infusion; they arranged a nurse for home-based infusion therapy by their own means. According to MMAS-4 FD patients had good adherence to their therapy (Median score 0, range 0-2). Mood status of FD patients and controls are shown in Table 1. Both HADS depression and anxiety scores were higher in the control group compared to FD patients. Additionally, abnormal scores were more prevalent for HADS depression scores in controls (Figure 1). Conclusion We found that the mood status of FD patients was better than the control group. Traumatic growth may be an important factor to explain this finding. Their adherence to therapy was good. Home-based therapy was the preferred method by the patients. Government-supported home therapy programs might be beneficial for FD patients to increase adherence to the therapy.

Download Full-text

Kidney Transplant in Fabry Disease: A Revision of the Literature

Medicina ◽

10.3390/medicina56060284 ◽

2020 ◽

Vol 56 (6) ◽

pp. 284 ◽

Cited By ~ 2

Author(s):

Irene Capelli ◽

Valeria Aiello ◽

Lorenzo Gasperoni ◽

Giorgia Comai ◽

Valeria Corradetti ◽

...

Keyword(s):

Renal Function ◽

Kidney Transplantation ◽

Fabry Disease ◽

Therapeutic Option ◽

Gene Mutations ◽

Disease Recurrence ◽

Long Term Effects ◽

Enzyme Replacement ◽

Fabry Nephropathy

Fabry disease is classified as a rare X-linked disease caused by a complete or partial defect of enzyme alpha-galactosidase, due to GLA gene mutations. This disorder leads to intracellular globotriaosylceramide (Gb3) deposition associated with increased Gb3 plasma levels. Most of the symptoms of the disease, involving kidneys, heart and nervous system, result from this progressive Gb3 deposition. The incidence is estimated in 1/50,000 to 1/117,000 in males. Fabry nephropathy begins with microalbuminuria and/or proteinuria, which, in the classic form, appear from childhood. Thus, a progressive decline of renal function can start at a young age, and evolve to kidney failure, requiring dialysis or renal transplantation. Enzyme replacement therapy (ERT), available since 2001 for Fabry disease, has been increasingly introduced into the clinical practice, with overall positive short-term and long-term effects in terms of ventricular hypertrophy and renal function. Kidney transplantation represents a relevant therapeutic option for Fabry nephropathy management, for patients reaching end-stage renal disease, but little is known about long-term outcomes, overall patient survival or the possible role of ERT after transplant. The purpose of this review is to analyze the literature on every aspect related to kidney transplantation in patients with Fabry nephropathy: from the analysis of transplant outcomes, to the likelihood of disease recurrence, up to the effects of ERT and its possible interference with immunosuppression.

Download Full-text