bluuebunny/crossref_metadata_2025_split huggingface dataset:
MO050MUTATION TYPES AND ENZYME LEVELS IN FABRY DISEASE IN A MULTICENTER STUDY
Authors: Sodre Luciana , Huaira Rosalia , Braga Luciane , Contreras Carlos , Colugnati Fernando , Coutinho Marcelo , Fernandes Natalia Maria Da Silva 
Published: May 2021

Abstract

Background and Aims
Fabry disease is a chronic, progressive and multi-systemic hereditary condition, related to a Xq22 mutation in X chromosome, which results in deficiency of acid alpha-galactosidase, hence reduced capacity of globotriaosylceramide (Gb3) degradation. Gb3 accumulates in lysosomes throughout virtually every organ, thus causing considerable morbidity and mortality. Objectives: To evaluate the types of Fabry disease mutations and enzyme levels of Alpha Galactosidase and Lyso Gb3 in a multicenter study; the RIM FABRY BRASIL PROJECT.

Method
We conducted a transversal study that consists of data analysis secondary to the multicenter project: Clinical and Epidemiological Analysis of Fabry's Disease in Dialysis Centers in Brazil, “PROJETO RIM FABRY BRASIL”. Included 854 dialysis centers throughout Brazil and 75059 individuals screened using a questionnaire and signing an Informed Consent Form. The data were entered into a computer program (algorithm) that filters the possible carriers of Fabry's disease. The program / algorithm discarded those who probably did not have Fabry's disease and sent blood suspects to filter enzyme dosage and genetic testing of those suspected of the disease.

Results
75059 individuals from the RIM FABRY BRASIL project were screened, where 58.37% were men and 41.54% women. 408 individuals with mutations for Fabry disease were identified, including patients with kidney and Family history of the disease, 34.6% men and 65.4% women with a mean age of 42.7 years. 47 different mutations were identified, with a higher prevalence of c.352C&gt; T p.Arg118Cys (24.8%), followed by c.376A&gt; G p.Ser126Gly (13.1%), c.1102G&gt; A p.Ala368Thr ( 7.8%), c.937G&gt; T p.Asp313Tyr (7.8%), c.870G&gt; C p.Met290Ile (7.3%). Alfa GalA dosage was performed in 120 men, with 90% of them showing decreased enzyme and Lyso Gb3 dosage of 320 individuals, (36.2% men and 63.8% women) 72.5% normal and 27.5% increased.

Conclusion
The most frequent mutations were: c.352C&gt; T p.Arg118Cys, followed by c.376A&gt; G p.Ser126Gly, c.1102G&gt; A p.Ala368Thr, c.937G&gt; T p.Asp313Tyr, c.870G&gt; C p.Met290Ile. 90% of men showed a decrease in the enzyme Alpha GalA and 27.5% of individuals had increased Lyso Gb3.
MO052COL4A3/COL4A4 AS A CAUSE OF MULTICYSTIC KIDNEY DISEASE
Authors: Bada Bosch Teresa , Sevillano Angel , Afonso Sara , Gutierrez Eduardo , Cavero Escribano Teresa , Gutiérrez Elena , Garcia Florencio , Morales Enrique , Caro Espada Paula Jara , Praga Manuel 
Published: May 2021

Abstract

Background and Aims
Thin basement membrane nephropathy (TBMN), the most common cause of persistent microhaematuria (mH), is due to mutations in genes codifying alfa-3 and alfa-4 collagen IV chains (COL4A4/COL4A3). Initially considered as a benign condition, subsequent studies have shown that an important number of patients develop proteinuria and CKD. We reported in a previous small study the presence of multicystic kidney disease (MCD) in some TBMD patients. In this study we aimed to evaluate the presence of MCD in a larger cohort of TBMD patients and analyze its association with renal outcomes.

Method
We collected 50 patients with a diagnosis of TBMD based on the presence of persistent mH (&gt;5 erythocytes per high power field in more than 90% of urinary sediments and radiological examinations to exclude other causes of mH) and at least one first-degree relative with persistent mH. TBMD diagnosis was confirmed by renal biopsy (glomerular basement membrane thickness less than 150nm) in 18 patients and by genetic test (pathogenic mutations in COL4A3/COL4A4) in 6 patients. MCD was diagnosed by the presence of uncountable cysts on renal ultrasonography.

Results
Mean age at diagnosis was 43.7 years, 34% were males and 18% had hypertension. At baseline, serum creatinine (SCr) was 0.9 mg/dL, proteinuria 0.48 gr/24h and 9 patients (18%) had CKD (estimated glomerular filtration rate -eGFR- lower than &lt;60 mL/min/1.73m2). 7 patients (14%) had CKD G3 and 2 (4%) CKD G4. Kidney cysts were found in 34 patients (68%) and 19 (38%) met MCD criteria. After a mean follow-up of 14.7±11.5 years, 23 patients (46%) had CKD. Among them, 17 patients (34%) had CKD G3, 2 (4%) CKD G4, and 4 (8%) CKD G5. Hypertension was more frequent among CKD patients as compared with no-CKD patients (39 vs 0%, p 0.00), proteinuria was higher (0.58±0.68 vs 0.39±0.58 g/24h, p 0.05) and MCD more frequent (65.2% vs 14.8%, p 0.00). Patients with MCD had higher SCr (2.1 vs 1.1 mg/dL, p 0.004) and lower eGFR (41.7 vs 77.2 mL/min/1.73m2, p 0.00) at the end of follow-up, and MCD was the only risk factor for the occurrence of CKD (OR 6.49, 95% CI 1.3-31.6) by multivariable analysis that included age, hypertension and proteinuria.

Conclusion
MCD is frequently observed in TBMD patients and is a risk factor for the progression of CKD.
MO055THE IMPACT OF THE COVID-19 PANDEMIC ON MOOD STATUS AND TREATMENT ADHERENCE IN PATIENTS WITH FABRY DISEASE
Authors: Dincer Mevlut Tamer , Karaca Cebrail , Sarac Betul , Ahmadzada Saffa , Bakir Alev , Alagoz Selma , Kiykim Ertugrul , Trabulus Sinan , Seyahi Nurhan 
Published: May 2021

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.
MO058PREDICTORS OF MORTALITY IN PATIENTS WITH NEPHROBLASTOMA: A SYSTEMATIC REVIEW AND META-ANALYSIS
Authors: Makrufardi Firdian , Safika Erri Larene 
Published: May 2021

Abstract

Background and Aims
Nephroblastoma constitutes 90-95% of the 5 types of kidney tumors that are most common in children. Studies for clinical management of patients with nephroblastoma are continuing today and several factors are thought to influence the mortality. This study is aimed to evaluate the outcome of patients with nephroblastoma and its associated factors.

Method
The dataset was defined by searching PubMed, EMBASE, Google Scholar that had been published until December 2020. No language or date restriction was performed during literature searching. The meta-analysis was conducted using Review Manager Software version 5.4. Factors investigated included gender, age, and site of tumor with p &lt;0.05 considered significant.

Results
The final analysis was conducted on 5 studies, and 2 were multi-institutional. Overall, 17279 patients with nephroblastoma were included in this study. The pooled data demonstrate there was significant difference in the mortality incidence of nephroblastoma patients with gender, (OR=1.25 [1.02, 1.52], p=0.03). Significant difference result was also seen in the incidence of mortality with age (OR=2.05 [1.86, 2.26], p&lt;0.00001). There was no association in the mortality of nephroblastoma patients with site of tumor (OR=1.28 [0.79, 2.09], p=0.31). No publication bias was found in our study.

Conclusion
The incidence of mortality in nephroblastoma patients still has to be a concern in patient management. Gender and age are factors that associate with incidence of mortality in nephroblastoma patients.
MO059COLEC10 AND 3MC SYNDROME: EXPANDING THE GENOTYPIC AND PHENOTYPIC SPECTRUM OF A VERY RARE DISEASE
Authors: Migliorero Martina , Kalantari Silvia , Bracciamà Valeria , Sorbini Monica , Arruga Francesca , Peruzzi Licia , Biamino Elisa , Amoroso Antonio , Vaisitti Tiziana , Deaglio Silvia 
Published: May 2021

Abstract

Background and Aims
3MC syndrome is an autosomal recessive disorder encompassing a variable spectrum of abnormalities, among which facial dysmorphisms are characteristic. Mutations in genes which encode proteins involved in the lectin complement pathway MASP1, COLEC11 and recently COLEC10 have been identified in patients with 3MC syndrome, supporting their key role during human development. We present a 5 years old patient with typical 3MC phenotypic characteristics, including blepharophimosis, telecanthus, high arched eyebrows, fifth finger clinodactyly, horseshoe kidneys, diastasis recti, umbilical depression and sacral dimple. The diagnosis was confirmed by sequencing of COLEC10 gene and the putative pathogenic variant was functionally validated through in vitro assays.

Method
COLEC10 gene was analyzed through Sanger sequencing. The secreted protein CL-L1 was investigated in the plasma of the patient and her parents by Western blot. The variant was introduced by a site-specific mutagenesis approach into a plasmid encoding wild-type human CL-L1. HeLa cells were then transfected with the mutated or wild-type plasmid and culture supernatant evaluated in a migration assay.

Results
A homozygous frameshift variant c.807_810delCTGT p.(Cys270Serfs*33) was identified in the patient. Segregation studies confirmed the parents’ carrier status for the variant. Functionally, the variant affects the chemo-attractive feature of CL-L1, as HeLa cells are less sensitive to the mutant protein compared to the WT one, resulting in a reduced migratory response.

Conclusion
We report a patient affected by 3MC syndrome who, besides typical phenotypic signs, presents a patent ductus arteriosus, never described in association to COLEC10 before. The variant causative role was functionally confirmed in an in vitro assay, where the mutated protein failed to act as a chemo-attractant. We thus provide further evidence for CL-L1 role during embryonic development
MO032URINARY EXCRETION DISORDER IN 125 PATIENTS WITH GITELMAN SYNDROME
Authors: Zhao Bingbin , Zhang Lei , Shi Xiaoxiao , Ji Peili , Xu Lubin , Chen Limeng 
Published: May 2021

Abstract

Background and Aims
Long-term oral prescription of thiazide diuretics, which can block the sodium chloride co-transporter (NCC) of the distal tubule, has been recognized to affect the function of the proximal tubule. But the underlying mechanism is largely unknown. Gitelman syndrome (GS) is a recessively inherited salt-losing tubulopathy due to the loss-of-function mutation of NCC, which can be used as a good model to understand the pathophysiological mechanism of thiazide-related disorders. In this study, we summarized the clinical characteristics of proximal tubular function in the cohort of patients with GS, and explore the possible mechanisms of proximal tubular dysfunction secondary to distal tubular disorder.

Method
Patients who were diagnosed with GS (confirmed by gene sequencing) in our hospital from August 1, 2005 to December 31, 2019 were enrolled, as well as the selected gender- and age-matched healthy controls. For patients whose SLC12A3 gene was sequenced as a single heterozygous mutation, further whole exome sequencing was performed to clarify the gene mutation. Clinical data including demographic information, symptoms, and hematuria tests were collected. The hydrochlorothiazide test was performed to assess the function of NCC. Characteristics of calcium and phosphate metabolism and uric acid of patients were analyzed.

Results
A total of 125 patients with genetic diagnosed GS were enrolled, and 33 patients (26.4%) were with only a single heterozygous mutation. Twenty-five patients completed whole exome sequencing, and 9 patients (36%) were finally diagnosed with compound heterozygous mutations. Seven mutation sites were newly detected by whole exome sequencing, including 3 missense mutations, 1 splice-site point mutation and 3 intron mutations. Serum uric acid in GS patients was significantly higher than that in healthy controls (347.5±91.7 vs 309.9±85.3μmol/L; P&lt;0.001). The proportions of men and women with hyperuricemia were 19.4% and 34.5%, respectively. Urinary fraction excretion of uric acid in the hyperuricemia group was significantly lower than that of patients with normal serum uric acid. Compared with healthy controls, GS patients had higher blood calcium level (2.41±0.17 vs 2.32±0.09mmol/L; P&lt;0.001). However, urinary calcium, parathyroid hormone (26.79±14.21 vs 33.18±11.58μmol/L; P=0.005), and 25-hydroxyvitamin D (15.88±6.46 vs 19.56±6.06 nmol/L; P=0.001) were lower in GS patients. Lower blood magnesium level was associated with lower parathyroid hormone level.

Conclusion
In GS patients, low urinary calcium, high serum calcium and high serum uric acid levels were related with the compensation of proximal tubular function.
MO028AUTOSOMAL DOMINANT POLYCYSTIC KIDNEY DISEASE: REGISTRY OF NORTHERN CYPRUS
Authors: Bardak Simge , Oygar Düriye Deren , Behlul Ahmet 
Published: May 2021

Abstract

Background and Aims
Autosomal dominant polycystic kidney disease (ADPCK) is the most prevelant inherited kidney disease in adults, and the fourth common cause for renal replacement therapy worldwide and preventive measures should be taken to slow the decline in renal functions. From previous studies we already know that hereditary kidney diseases such as medullary kidney disease and tubular kidney diseases are frequent in Cyprus. In this study, we aim to find out the situation for ADPKC in North Cyprus and declare the overall magnitude of the problem in our region.

Method
From January 2004 to January 2021, we collected data from all patients with ADPCK irrespective of whether they were on RRT or not and who were followed in nephrology departments within Northern Cyprus. Clinical and demographic data of all the patients aged above 18 were collected. The affected families and their route of inheritance were determined. Need for renal replacement therapy (RRT) and types of RRT were noted. RRT rate and death rate were calculated.

Results
We collected information from a total of 79 patients with the diagnosis of ADPCK; 3 patients were excluded due to lost to follow up. There was no family history in 11% of patients. Inheritence was maternal in 53% and paternal in 42% whereas both maternal and paternal inheritence route were identified in 5%. 68 patients with family history were grouped in 24 families (2.8 patients/ family). The demographic and clinical data can be seen on Table 1. At some point during follow up 31 patients started with RRT. Mean age for RRT was 55 years (23-81). 5 (16%) patients initiated RRT with peritoneal dialysis, wheras 23 (74%) with hemodialysis, and 3 (10%) had preemptive renal transplantation. At the end of follow up period we found out that 35% (11/31) of patients who had RRT had transplantation, 32% (10/31) experienced peritoneal dialysis whereas 77% (24/31) experienced hemodialysis. 18 out of 76 (24%) patients died during the follow up period. The mean age of death was 71 years (53-81).

Conclusion
The prevalance of the disease when living patients were considered was 1.3 cases/10000 inhabitants which is low when compared with other studies. Hence ADPCK was not a common diagnosis in North Cyprus as other hereditary kidney diseases. This may show that some patients are underdiagnosed in the population. The frequency of patients without family history was high and also the number of patients per family was low when compared with other studies; these findings may also indicate an underdiagnosed problem. The patients were diagnosed late at a mean age of 47 Hence we need to perform further studies on ADPCK in our population since identifiying ADPCK patients and their families may help to adress the needs adequately, to plan lifelong supportive measures and to decrease high mortality rate of these patients.
MO358ACUTE KIDNEY INJURY AND MORTALITY RISK IN OLDER ADULTS WITH AND WITHOUT COVID-19: DATA FROM GEROCOVID STUDY
Authors: Xu Hong , Garcia-Ptacek Sara , Annetorp Martin , Bruchfeld Annette , Cederholm Tommy , Johnson Peter , Kivipelto Miia , Metzner Carina , Religa Dorota , Eriksdotter Maria 
Published: May 2021

Abstract

Background and Aims
Research regarding COVID-19 and acute kidney injury (AKI) in older adults is scarce. We evaluated the risk factors and outcomes of AKI in hospitalized older adults with and without COVID-19.

Method
Observational study of patients admitted to two geriatric clinics in the Stockholm Region of Sweden during the first wave of the COVID-19 pandemic from March 1st to June 15th 2020. The difference in incidence, risk factors and adverse outcomes for AKI between patients with or without COVID-19 were examined. Odds ratios (ORs) for AKI were obtained from logistic regressions. The hazard ratios (HRs) for the risk of in-hospital death were calculated from Cox proportional hazard regression models.

Results
We analyzed 316 older patients hospitalized for COVID-19 and 876 patients for non-COVID-19 diagnoses. The mean age was 83±9 years, 57% were women, and mean baseline kidney function as depicted by estimated glomerular filtration rate (eGFR) was 62±23 ml/min/1.73m2. AKI occurred in 92 (29%) of patients with COVID-19 vs. 159 (18%) without COVID-19. The severity of AKI was significantly worse in patients with COVID-19 compared with non-COVID patients. The odds for developing AKI were higher in patients with COVID-19 (adjusted OR, 1.70; 95% CI, 1.04-2.76), low baseline kidney function [4.19 (2.48-7.05), for eGFR 30 ∼ &lt;60 ml/min/1.73m2, and 20.3 (9.95-41.3) for eGFR &lt;30ml/min/1.73m2], and higher C-reactive protein (CRP) level (OR 1.81(1.11-2.95)). The risk of in-hospital death was highest in patients with COVID-19 and AKI [adjusted HR 23.5, 95% CI (8.75-63.0)], followed by COVID-19 without AKI [9.10 (3.52-23.6)] and by patients without COVID-19 and with AKI [6.38 (2.28-17.9)] after adjusting for patient demographics, vital signs, baseline kidney function and medications and using non-COVID patients with no AKI as reference.

Conclusion
Geriatric patients hospitalized with COVID-19 had a higher incidence of AKI compared with patients hospitalized with other diagnoses. AKI and COVID-19 were associated with in-hospital death. Optimal management of AKI may improve the outcome of COVID-19 in geriatric patients.
MO363CHECKPOINT-INHIBITOR-ASSOCIATED ACUTE KIDNEY INJURY AND MORTALITY: AN OBSERVATIONAL STUDY
Authors: Koks Marije , Ocak Gurbey , Suelmann Britt , Hulsbergen-Veelken Cornelia , Haitjema Saskia , Vianen Marieke , Verhaar Marianne , Kaasjager Karin , Khairoun Meriem 
Published: May 2021

Abstract

Background and Aims
Immune checkpoint inhibitors, approved for the treatment of various types of cancer, are known to cause a unique spectrum of autoimmune-related side effects, including acute kidney injury (AKI). The aim of this study was to describe the incidence, risk factors, renal outcomes, and mortality of AKI in patients receiving checkpoint inhibitors.

Method
Patients receiving checkpoint inhibitors between January 2013 and May 2020 were identified using the Utrecht Patient Oriented Database. AKI was defined as an increase in creatinine of ≥1.5 times the baseline value. Cox proportional hazard regression analysis was used to assess risk factors for AKI and to evaluate the relationship between AKI and mortality. Persistent kidney injury was diagnosed in AKI patients with a final creatinine measurement of &gt;1.3 times the baseline value.

Results
Out of 676 patients receiving checkpoint inhibitors, AKI occurred in 96 (14.2%) patients. Chart review showed that AKI was checkpoint inhibitor-associated in 32 (4.7%) patients. Baseline variables associated with AKI were a primary gynecological malignancy (HR 3.91, 95% CI 1.55 to 9.85), treatment with checkpoint inhibitor ipilimumab (HR 2.31, 95% CI 1.03 to 5.20), and pre-existent use of a diuretic (HR 2.61, 95% CI 1.21 to 5.60), an angiotensin-converting enzyme inhibitor or angiotensin-receptor blocker (HR 2.49, 95% CI 1.10 to 5.60), and a proton pump inhibitor (HR 1.69, 95% CI 1.04 to 2.75). In 35.4% of the patients who had developed AKI, persistent kidney dysfunction was observed at the end of follow-up. Patients who developed AKI had a 2.13-fold (95% CI 1.58 to 2.87) increased mortality risk compared to patients who did not develop AKI. Mortality risk was not increased by checkpoint inhibitor-associated AKI (HR 1.11, 95% CI 0.64 to 1.92), but only by AKI related to other causes (HR 2.87, 95% CI 2.04 to 4.04).

Conclusion
Patients receiving checkpoint inhibitors frequently develop AKI, however, checkpoint inhibitor-associated AKI does not seem to increase mortality.