bluuebunny/crossref_metadata_2025 huggingface dataset:
MO049FUNCTIONAL IMPORTANCE OF MAPKBP1 PROTEIN DOMAINS IN NEPHRONOPHTHISIS
Authors: Hartig Christin , Schönauer Ria , Sewerin Sebastian , Ertel Anastasia , Jin Wenjun , Hantmann Elena , Saunier Sophie , Benmerah Alexandre , Halbritter Jan
Published: May 2021

Background and Aims

Nephronophthisis is an autosomal-recessive kidney disease that accounts for a significant proportion of end-stage renal disease (ESRD) in childhood, adolescence and early adulthood. Biallelic pathogenic variants in MAPKBP1, encoding the c-Jun N-terminale kinase (JNK)-binding protein 1, are associated with development of Nephronophthisis and subsequent chronic kidney disease (CKD) (Macia et al, AJHG, 2017). We recently characterized MAPKBP1 as microtubule-associated protein that is able to localize to centrioles and the base of primary cilia depending on dimerization via its C-terminal coiled-coil domain (Schönauer et al, Kidney Int, 2020). However, the physiological function of its N-terminal WD40 and intermediate JNK-binding domain is still poorly understood. By in vitro comparison of artificial domain deletions with known and novel patient variants, we aim at pinpointing functional consequences of pathogenic MAPKBP1 in cilia and cell cycle control.

Method

N-terminally GFP-tagged MAPKBP1 constructs with either full-domain deletions or patient-derived variants were expressed in non-ciliated HeLa and ciliated H69 cells for fluorescence microscopy studies. Furthermore, RNA-seq analysis using primary patient cells was conducted to investigate differentially regulated molecular pathways compared to healthy control individuals.

Results

Immunofluorescence microscopy revealed inappropriate intracellular localization upon single or combined deletion of any MAPKBP1 protein domain. Compared to wild type, all deletion variants showed reduced intensity at the centrosome and ciliary base. Despite preserved dimerization ability, loss of the intermediate JNK-binding domain (JBD) most effectively abolished centrosomal or ciliary targeting, whereas loss of the N-terminal WD40-domain induced strongest mitotic aberrations. Unlike wild type, both, artificial and patient-derived truncating variants were able to enter the nucleus. RNA-seq analysis using primary patient fibroblasts with varying C-terminal truncations will allow important insights into common gene expression profiles unveiling consequences of aberrant intracellular trafficking.

Conclusion

In the present work, we demonstrate that all protein domains are indispensable for appropriate MAPKBP1 intracellular localization and function. Most of clinically reported patient variants exhibiting C-terminal truncation of varying lengths resulted in comparable intracellular behavior in presence of an intact N-terminal WD40 domain. Surprisingly, deletion of the JNK-binding domain alone aggravated functional disturbances hinting at a prominent regulatory role of this protein part interdepending with dimerization. Further insights into domain-specific functions will explain molecular disease mechanisms of MAPKBP1.
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

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> T p.Arg118Cys (24.8%), followed by c.376A> G p.Ser126Gly (13.1%), c.1102G> A p.Ala368Thr ( 7.8%), c.937G> T p.Asp313Tyr (7.8%), c.870G> 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> T p.Arg118Cys, followed by c.376A> G p.Ser126Gly, c.1102G> A p.Ala368Thr, c.937G> T p.Asp313Tyr, c.870G> 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

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 (>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 <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

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

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 <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<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

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

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<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<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

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

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 ∼ <60 ml/min/1.73m2, and 20.3 (9.95-41.3) for eGFR <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

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 >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.
MO365URINARY BIOMARKERS AND POOR OUTCOMES IN PATIENTS WITH COVID-19 ADMITTED TO A REFERENCE HOSPITAL IN NORTHEAST BRAZIL
Authors: Cavalcante Meneses Gdayllon , Freire Bezerra Gabriela , Andrade Lucena Lima Lana , Justino Bandeira Izabel Cristina , Coelho Lopes Nicole , Pinheiro Dantas Márcia Maria , Brasileiro Mota Sandra Maria , Lemos Moura Moreira Albuquerque Polianna , Costa Martins Alice Maria , De Francesco Daher Elizabeth , Bezerra da Silva Junior Geraldo
Published: May 2021

Background and Aims

Kidney biomarkers improve early and specific AKI detection and also poor outcomes in different clinical contexts. Kidney disease is an important risk factor for poor outcomes in COVID-19. The aim of this study was to evaluate association of early levels of kidney biomarkers with poor outcomes in hospitalized patients with COVID-19.

Method

This is a prospective study conducted at the Instituto Dr. Jose Frota Hospital, an important public reference hospital for COVID-19 in northeast Brazil. Medical records with clinical, epidemiologic, laboratory and outcomes were collected. The urinary NGAL, KIM-1, MCP-1 and nephrin were the kidney biomarkers quantified at hospital admission. ELISA assays were used for analysis and biomarkers urinary concentrations were adjusted for urinary creatinine. Data were expressed as mean± standard deviation or median.

Results

A total of 69 patients collected urine and were included in this study. Male gender was predominant (65%) and mean age was 56±19 years. Regarding outcomes, the group had 62% of death, 92% of ICU admission and 65% of invasive respiratory support in ICU. Urinary NGAL and MCP-1 were significantly elevated in patients that needed invasive respiratory support in comparison with non-invasive support: uNGAL (median=104 [IQR=74-153] vs 71 [31-79] ng/mg-Cr, p=0.013), and uMCP-1 (3055 [1127-5008] vs 1315 [574-2127] pg/mg-Cr, p=0.027). Urinary nephrin and KIM-1 was also elevated, however with no statistical significance. Moreover, all urinary biomarkers were higher in ICU admission group and death group, but with p>0.05. In ROC curve analysis for prediction of invasive respiratory support, uNGAL had AUC=0.696 (0.565-0.827),p=0.012 and cut-off=78 ng/mg-Cr; uMCP-1 had AUC=0.676 (0.539-0.813), p=0.023 and cut-off=1354 pg/mg-Cr. In survival analysis, patients with uNGAL >78 ng/mg-Cr had worse prognosis and died more quickly (19 vs 48 days, log-rank test; p=0.01). In patients with uMCP-1 >1354 pg/mg-Cr, they also died more quickly, but with no significance (25 vs 48 days, log-rank test; p=0.08).

Conclusion

Urinary biomarkers NGAL and MCP-1 quantified at hospital admission were associated with poor outcomes, mostly with needed of invasive respiratory support in ICU. Prediction cut-off values for invasive respiratory support was useful to determine the survival prognosis.
MO371TIME AND THE ETIOLOGY OF ACUTE KIDNEY INJURY DEFINE PROGNOSIS IN THE COURSE OF COVID-19
Authors: Murt Ahmet , Dincer Mevlut Tamer , Karaca Cebrail , Trabulus Sinan , Seyahi Nurhan , Altiparmak Mehmet Riza
Published: May 2021

Background and Aims

Kidneys are among the affected organs in COVID-19 and there may be different etiologies resulting in acute kidney injury (AKI) in different stages of the disease. There have been previous studies focusing on incidence and mortality of AKI in COVID-19 but none has made in depth analysis in relation to the background pathophysiology. Based on previous observations, we hypothesized that all AKIs seen in COVID-19 are not uniform and we aimed to analyze the etiologies and prognosis of AKI among hospitalized COVID-19 patients in relation to the time of AKI during different phases of the disease.

Method

A total of 1056 patients were admitted to the designated COVID-19 clinics from March to July in 2020. 77 Patients who were younger than 18 years old and 7 kidney transplant patients were excluded from the study. 427 of the remaining patients were confirmed by real time polymerase chain reaction (RT-PCR) test.). As eGFR below 60 mL/min/1,73 m2 was already shown to be related to mortality, these patients (44) were also excluded. As immunologic response is generally accepted to start with the second week of COVID-19 course, patients were classified into three groups, those who had AKI on admission, those who developed AKI in the first week and those who developed AKI starting from 7th day. Initial lymphocyte counts, creatinine levels, electrolytes, acid-base status and changes in the inflammatory markers were compared between the groups. A comparison between patients who survived and who died was also performed.

Results

89 of the 383 included COVID-19 patients developed AKI. 24% of those who developed AKI died. Patients who developed AKI later had higher peak CRP and D-dimer levels with lower nadir lymphocyte counts (p=0,000, 0,004 and 0,003 respectively). Additionally, patients who died had higher initial inflammatory marker levels and lower lymphocyte counts than those who survived. Mortality of patients who had AKI on hospital admission (13%) was similar to the overall COVID-19 mortality for inpatients, however it was as high as 44% for those who developed AKI after 7th day. Early AKI was related to pre-renal causes and had a milder course. However, later AKIs were more related to immunologic response and had significantly higher mortality. Patients who died had significantly higher ferritin and d-dimer levels upon their hospital admissions (p=0,000). Electrolyte disturbances, metabolic acidosis and mortality were also higher in patients who developed AKI later. Hypernatremia (OR: 6,5, 95% CI: 3 – 13,9) and phosphorus disturbances (both hyperphosphatemia (OR: 3,3; 95%CI: 1,6 – 6,9) and hypophosphatemia (OR: 3,9; 95% CI: 2,0-7,9)) were related to mortality.

Conclusion

Findings of this study suggest that AKI in COVID-19 is not of one kind. When developed, AKI should be evaluated in conjunction with the disease stage and possible etiologies
MO372IN-HOSPITAL MORTALITY IN ACUTE CARDIAC DISEASES IS ASSOСIATED WITH CERTAIN PHENOTYPES OF ACUTE KIDNEY INJURY
Authors: Efremovtseva Marina , Avdoshina Svetlana , Kobalava Zhanna
Published: May 2021

Background and Aims

Impaired renal function is a common finding in patients with cardiac diseases and confers an adverse prognosis in this population. To evaluate the incidence, phenotypes and prognostic value of cardiorenal interrelations in patients with acute decompensated heart failure (ADHF) and non-ST-elevation acute coronary syndrome (NSTE-ACS).

Method

we examined 278 patients with ADHF (85.3% had anamnesis of symptomatic HF with frequent hospitalizations, 20.1% had ejection fraction <35%) and 288 with NSTE-ACS (64.9% developed myocardial infarction (MI)). In ADHF group in comparison with NSTE-ACS the patients were younger (69.7±10.2 vs 72±12.1 years, p<0.01), there were more males (55.4 vs 36.5%, p<0.001), smokers and alcohol abusers (47.8 and 30.6% vs 8 and 5.6%, p<0.001). The comorbidities were more typical for ADHF group: atrial fibrillation 46 vs 24% (p<0.001), obesity 55.8 vs 30.9% (p<0.001), anemia 40.6 vs 25.3% (p<0.001), diabetes mellitus 33.1 vs 23.3% (p<0.01).

Chronic kidney disease (CKD) and acute kidney injury (AKI) were diagnosed according to KDIGO 2012 Guidelines. AKI phenotypes were identified depending on time of development (community- or hospital-acquired), persistency (transient or persistent), history of CKD (AKI de novo or AKI on CKD).

Results

Incidence of CKD in patients with ADHF and NSTE-ACS was 45 and 46.5%, CKD was first diagnosed on admission in 57.6 and 64.2% of patients respectively. In 7.6% cases of ADHF and 14.2% of NSTE-ACS groups the duration of impaired kidney function was unknown. No associations of existing CKD and in-hospital mortality were detected.

Incidence of AKI in ADHF and NSTE-ACS groups was 43.5 and 37.2%. The hospital-acquired AKI, AKI on CKD and persistent AKI were found in 52.9, 47.9 and 46.3% of ADHF patients, and in 57.9, 58.9 and 50.5% in NSTE-ACS group respectively. In-hospital mortality was higher in patients with AKI in ADHF and NSTE-ACS groups (12.4 vs 5%, p<0.01 and 17.8 vs 3.3%, p<0.001). Mortality in patients with ADHF and hospital-acquired persistent AKI de novo and community-acquired persistent AKI on CKD was 41 and 29%, and in community-acquired transient AKI on CKD in the NSTE-ACS group – 29%.

Conclusion

Different cardiorenal interrelations were revealed in 75.2% of patients with ADHF and in 61.8% with NSTE-ACS. In patients with acute cardiac diseases high in-hospital mortality is tightly associated with phenotypes of hospital-acquired persistent AKI de novo and community-acquired persistent AKI on CKD in ADHF, and in community-acquired transient AKI on CKD in the NSTE-ACS.
MO373EXPERIENCE OF EXTRACORPOREAL BLOOD PURIFICATION METHODS APPLICATION TO PATIENTS WITH SEVERE COVID - 19
Authors: Jabayeva Nilufar , Kuanyshbek Aidyn , Kapyshev Timur , Lesbekov Timur , Bekishev Bolat , Li Tatyana
Published: May 2021

Background and Aims

In the rapidly changing conditions of life due to the COVID - 19 pandemic, the medical society around the world have faced with the question of treatment previously unknown, multi-faceted and insidious infection. The coronavirus infection has forced doctors to reconsider the tactics of intensive care patients in critical condition. To date, overall mortality rate from COVID – 19 varied from 8.11 to 120.85 per 100.000 population (Johns Hopkins University mortality analyses). Mortality rate in extremely severe cases exceeds 60% - 78% (Yang et al., Lancet Respiratory Medicine, 2020. Zhou et al., Lancet, 2020).

We would like to share our clinical experience of extracorporeal blood purification methods application to patients in ICU with various clinical manifestations, as well as the presence of comorbid pathology.

Method

We conducted a retrospective analysis of 239 medical records of patients hospitalized in the ICU of JSC NRCSC Nur-Sultan, Kazakhstan because of severe course of COVID 19. Period of hospitalization from 16.06.2020 to 29.09.2020, the total number of beds - 97, in the ICU - 25.

Results

The total number of patients with COVID -19 - 239 patients. In ICU -67 patients. Patients required in renal replacement therapy (RRT) – 31 patients.

Among patients on RRT males-28 (90.3%) - female-3 (9.67%).

Mean age-60 years.

Distribution of the comorbid pathology.

Indications for RRT: acute respiratory failure in the absence of heart failure or fluid overload; presence of diffuse alveolar damage (DAD) (detected by high-resolution CT); PaO2 / FiO2 ≤ 300 mm Hg Duration:> 6-24 hours per column with a blood flow rate of 80-120 ml/min. In addition, indications for the urgent start of extracorporeal treatment are:

The duration of hospitalization in the ICU – 12.54 days.

Combinations and duration of the procedures.

Laboratory data - Leukocyte, CRP, Interleukine, procalcitonin, Creatinin, presepsin in dynamics.

General Mortality – 37 from 239 (15.5%)

Mortality in ICU – 37 from 67 (55.2%)

According to literature review, the mortality rate of patients with severe COVID - 19 in the ICU (Fawad Rahim et al, Cureus . 2020 Oct 12;12(10):e10906. doi: 10.7759/cureus.10906.) without the use of CRRT exceeds 70-77%.)

Conclusion

Our analysis had showed a positive effect of early use (1 day of hospitalization) of extracorporeal methods of blood purification, on a decreasing of inflammation indicators, as well as positive survival rate of patients with severe COVID-19 course in ICU conditions.
MO375EPIDEMIOLOGY AND PREDICTORS OF CARDIAC BYPASS ASSOCIATED AKI IN A MIDDLE-INCOME CARIBBEAN COUNTRY
Authors: Fisher Lori-Ann , Stephenson Sunil , Tulloch-Reid Marshall , Anderson Simon
Published: May 2021

Background and Aims

AKI is a common and resource intensive complication of cardiopulmonary bypass surgery (CPB) in high income-countries occurring in up to one third of surgeries performed. However, little is known of its incidence and impact in the small island developing states of the Caribbean. We describe the incidence, risk factors and outcomes of AKI following CPB at a referral cardiac centre in Jamaica.

Method

A review of the Medical Records of adult patients (aged ≥ 18 years) with no prior ESRD or dialysis requirement undergoing CPB at the University Hospital of the West Indies, Mona between January 1, 2016 to June 30, 2019 inclusive was undertaken. Demographics, pre-operative status, intraoperative and post-operative data were abstracted. The primary outcome was all-cause 30-day mortality. AKI was defined as meeting the KDIGO criteria based on the peak serum creatinine measurement obtained within 72 hours post-operatively. Multivariable logistic regression was used to examine the risk factors for and impact of AKI on all-cause mortality.

Results

Of the 259 persons who underwent CPB in the study period, 211 (58% men, mean age 58.1±12.9 years, median± IQR Euro-score II of 1.4 ± 1.4) met inclusion criteria. AKI occurred in 37.3 % (80) of patients with 43.8% (35) KDIGO I, 32.5% (26) KDIGO II and (19) 23.7% KDIGO III. Renal replacement therapy was required in 3.2% (7) of patients.

In a multivariable logistic regression model, baseline CKD (eGFR<60mL/min/1.732m2; odds ratio, 95%CI: 5.32,1.72-15.90), Prolonged bypass time (1.73,1.21-2.48; per hour), intraoperative PRBC transfusion (2.33,1.08-5.03) and elevated 24-hour post-operative Neutrophil/Lymphocyte ratio>18 (3.00, 1.07-8.35) were associated with an increased risk of AKI.

AKI after CPB resulted in greater hospital (23.6 versus 14.6 days, p<0.001) and ICU stay (8.1 versus 3.3 days, p<0.001) and a 6-fold increase in 30-day mortality after adjusting for age and sex (HR, 95 CI: 6.40, 2.38-17.25). (see Figure 1 Kaplan Meier survival estimates for AKI)

Conclusion

The occurrence of AKI following CPB is comparable to that reported in the literature and is associated with poor short-term outcomes. Larger multicentre prospective studies to predict risk, identify interventions to reduce mortality and assess long term complications of AKI following CPB in Caribbean countries are needed.
MO378WHAT LIES BENEATH ANTICOAGULATION-RELATED ACUTE KIDNEY INJURY
Authors: Trujillo Hernando , Sandino Pérez Justo , Cavero Escribano Teresa , Gutierrez Eduardo , Sevillano Angel , Praga Manuel
Published: May 2021

Background and Aims

Acute kidney injury (AKI) secondary to glomerular hemorrhage in the context of overanticoagulation, commonly known as anticoagulant-related nephropathy (ARN), is a relatively novel recognized entity. Preexisting or underlying kidney disease seems to be a predisposing factor; however, few studies have described histologic findings in patients with ARN. We aimed to examine underlying kidney pathology in patients on oral anticoagulation who presented an episode of AKI with hematuria in whom a kidney biopsy was performed.

Method

Spanish retrospective observational multicenter case study in patients treated with oral anticoagulants who developed macroscopic or intense hematuria followed by AKI. Only patients with available kidney biopsy specimens were included. Histologic findings and clinical data throughout follow-up were analyzed. The main outcome was to describe pathologic findings in kidney biopsy specimens of patients with clinical suspicion of ARN. The secondary outcome was to assess kidney outcomes during follow-up.

Results

Twenty-four patients were included with a median age of 76 years (interquartile range [IQR] 64-81) and a follow-up period of 10.1 (IQR 1.3-41.1) months. 79% were male, 22 (91%) had hypertension and 9 (37%) were diabetic. Most cases (91%) were on anticoagulation with vitamin K antagonists. At admission, 87% of cases presented gross hematuria with a median serum creatinine (SCr) of 4.2 mg/dl and a median INR of 2.3. During follow-up, median highest (peak) SCr was 6.3 mg/dl and 11 (45%) patients required acute dialysis. Kidney biopsy showed that all patients except one had an underlying nephropathy (confirmed IgA nephropathy in 16 [66.7%], probable IgA nephropathy in 2, diabetic nephropathy in 3, nephrosclerosis in 1, and idiopathic nodular glomerulosclerosis in 1). Tubules filled with red cells and red cell casts were observed in 66.7% of the cases and acute tubular necrosis in 70.8%. Management included anticoagulation withdrawal in 14 cases (58.3%) and immunosuppressive treatment with corticosteroids (n = 17 [70.8%]) and mycophenolic acid (n = 5 [20.8%]). At 12 weeks after discharge, 11 patients had >50% decrease in SCr (with respect to peak SCr), 6 had <50% decrease and 5 were on chronic dialysis.

Conclusion

IgA nephropathy was the most common underlying kidney disease in our biopsy-proven series of ARN, in which a significant percentage of patients did not achieve kidney function recovery.
MO381RISK FACTORS FOR AKI DURING COVID-19 AMONG NON-DIALYSIS CKD PATIENTS
Authors: Coca Armando , Burballa Carla , Centellas Pérez Francisco Javier , Acosta-Ochoa Isabel , Pérez Martínez Juan , Rodriguez Eva , Fidalgo Veronica , Ortega Cerrato Agustin , Crespo Marta
Published: May 2021

Background and Aims

AKI is a strong risk factor for adverse outcomes during Coronavirus disease (COVID-19) in the general population. CKD has been correlated with increased risk of AKI both in the outpatient and inpatient settings. We aimed to define potential risk factors for AKI among patients with non-dialysis CKD admitted due to COVID-19.

Method

Multicenter, observational cohort study including 136 adult patients with CKDand 136 age- and sex-matched controls who required admission for COVID-19 in three academic hospitals. Viral infection was confirmed by real-time RT-qPCR and/or serologic testing in all cases. Disease severity on admission was classified according to the WHO—China Joint Mission Report on COVID-19; briefly subjects with COVID-19 were divided into mild (laboratory confirmed, without pneumonia), moderate (laboratory confirmed with pneumonia), severe (dyspnea and/or lung infiltrates >50% of the lung field within 24–48 h) and critical (respiratory failure requiring mechanical ventilation, shock, or other organ failure that requires intensive care). AKI was defined using the 2012 KDIGO classification. CKD was defined as sustained eGFR <60 and >15 ml/min/1.73m2 within the 6 months prior to COVID-19 hospitalization. Baseline eGFR was calculated using the CKD-EPI equation. Demographic and clinical data were gathered from medical records. Outcomes were recorded during the following 28 days after admission. We applied logistic regression analysis to describe potential predictors for AKI.

Results

Median age was 80 years (IQR: 70-86). 58.8% of patients were males. The most common symptom on admission was fever (68.8%), followed by cough (57.7%). The majority of subjects presented with severe COVID-19 on admission (75.7%). During 28-day follow-up, 87 patients (32%) developed Stage 1 AKI, 17 subjects (6.3%) developed Stage 2 AKI and 12 patients (4.4%) developed Stage 3 AKI.

AKI was more frequent (61 vs 24.3%) and more severe (Stage 2 AKI: 10.3 vs 2.2%; Stage 3 AKI: 6.6 vs 2.2%) among CKD patients. In adjusted logistic regression analysis, only disease severity and baseline eGFR were independent predictors for AKI in COVID-19 patients that required hospitalization.

Conclusion

CKD patients suffer AKI more frequently and of higher severity during COVID-19. Baseline eGFR, along with COVID-19 severity, are strong predictor factors of AKI in this setting.
MO389PREDICTORS OF COMMUNITY-ACQUIRED ACUTE KIDNEY INJURY IN PATIENTS WITH ACUTE CARDIAC DISEASES
Authors: Efremovtseva Marina , Avdoshina Svetlana , Markova Maria , Kobalava Zhanna
Published: May 2021

Background and Aims

Acute kidney injury (AKI) is a common and serious problem associated with poor prognosis. The aim of the study was to reveal the prevalence and predictors of community-acquired AKI in patients with acute cardiac diseases.

Method

566 patients (278 with acute decompensated heart failure (ADHF), 288 with non-ST-elevation acute coronary syndrome (NSTE-ACS), 46% male, 71±11 years (M±SD), smokers 26%, arterial hypertension 91%, previous myocardial infarction (MI) 45%, diabetes mellitus (DM) 28%, atrial fibrillation 35%, chronic kidney disease (CKD) 46%, previous hospitalization with ADHF 36%, ejection fraction (EF) <35% 15%, blood pressure (BP) 142±30/83±16 mmHg) were examined. AKI was diagnosed according 2012 KDIGO Guidelines. Community-acquired AKI was identified in patients with elevated serum creatinine levels on admission, which decreased during hospitalization.

Results:

Incidence of AKI in all patients, patients with ADHF and NSTE-ACS was 40, 43.5 and 37.2%. In-hospital mortality in patients with AKI was higher than in those with stable kidney function (14.9 vs 3.6%, p<0.001). Community-acquired AKI was present in 18% of patients (20.5 and 15.6% in ADHF and NSTE-ACS respectively), in-hospital mortality was 16.7% (10.5 and 24.4% respectively). The risk assessment scale for community-acquired AKI was developed based on independent predictors of AKI, using binary logistic regression and ROC analysis (AUC 0.860, 95% CI 0.821-0.898).

Independent variables included in the model, and the corresponding points (pts) are listed below: clinical and demographic characteristics (male gender - 6 pts, alcohol abuse - 7 pts, DM - 1 pt), present on admission (MI - 5 pts, AHF/ADHF - 9 pts, systolic BP <120 - 10 pts, <110 - 15 pts, <90 mmHg - 27 pts; state of kidney function on admission: serum creatinine >98 and >128 mkmol/L - 14 and 22 pts, GFRCKD-EPI <45 and <15 ml/min/1.73 m2 - 7 and 14 pts; glucose level >7 mmol/L - 4 pts), outpatient intake of ACE inhibitors - 4 pts, absence of spironolactone in outpatient therapy - 1 pt. Diagnostically significant risk score for predicting AKI was >30 pts, the risk prediction model showed sensitivity 89%, specificity 66%.

Conclusion

Community-acquired AKI is common in patients in acute cardiovascular events, is associated with high mortality, and often is underdiagnosed. Usage of risk assessment scale in clinical practice may help to detect patients with high-risk of AKI on admission. Baseline kidney function and blood pressure level are main predictors of AKI in patients admitted with acute cardiac diseases.