bluuebunny/crossref_metadata_2025 huggingface dataset:
MO176: Study of Urinary Monocyte Chemoattractant Protein-1(MCP-1) Level in Morbidly Obese Patients before and After Bariatric Surgeries and its Relation to Renal Function
Authors: Sabry Alaa , Eldeep Ahmed
Published: May 2022

BACKGROUND AND AIMS

To assess the level of renal inflammatory marker monocyte chemoattractant protein -1(MCP-1), measure the urinary MCP to urinary creatinine concentration ratio in morbidly obese patients before and after bariatric surgeries. To study if there any possible relation between the MCP1 levels and renal function before and after surgery.

METHOD

This prospective study of 40 morbidly obese patients undergoing bariatric surgery was recruited in the study in the interval between October 2018 and July 2019. Evaluate the level of MCP-1, urinary creatinine, urinary albumin, glomerular filtration rate, body weight, body mass index, CRP, serum albumin, blood pressure and lipid profile before and after 3 months of bariatric surgeries.

RESULTS

The mean urinary level of MCP1 preoperative was 105.19 ± 15.25 pg/mL (range between 75.41 and 131.67) and this level was decreased postoperatively to 74.20 ± 22.77 (range between 30.5 and 114.4) with high statistically significant difference (P < .001). While urinary MCP1/creatinine ratio, bariatric surgery significantly reduced the mean of urinary MCP1/creatinine ratios from 2.08 ± 1.43 to 0.86 ± 0.51 (P < 0.001). Significant improvement of blood pressure, CRP, lipid profile and body mass index after bariatric surgeries.

CONCLUSION

We reported that urinary MCP-1 levels following bariatric surgery can be used as potential marker to the ongoing renal inflammatory process.
MO182: Safety Analysis of Anticoagulant Therapy in Stage 4 CKD in Combination with AF
Authors: Igamberdieva Ranokhon , Abdullaev Sherzod
Published: May 2022

BACKGROUND AND AIMS

A renocardial comorbid condition with a combination of chronic kidney disease (CKD) and atrial fibrillation (AF) increases the risk of thromboembolic complications (TEC) and hemorrhagic events. As kidney function worsens, this risk only increases. Anticoagulant therapy is the standard for prevention of acute cerebrovascular accident (ACVA) in AF. Clinical data on the use of new oral anticoagulants (NOACs) in patients with advanced CKD and AF are very limited, which indicates the relevance of research. Analysis of safety and efficacy indicators of rivaroxaban in patients with stage 4 CKD in combination with AF.

METHOD

The study included 106 patients with a glomerular filtration rate (GFR) of 15–29 mL/min/1.73 m2 and AF. A total of 73 patients took rivaroxaban at a dose of 15 mg/day and 33 patients took warfarin, the dose of which was individually adjusted according to INR values. The average follow-up period was 18 months. Thromboembolic complications were the primary endpoint. The secondary endpoint is the development of haemorrhagic events (major and minor bleeding).

RESULTS

In the rivaroxaban group, the mean CHA2DS2 VASc score was 4.9, the HAS BLED score was 3.2, and in the warfarin group, 4.5 and 3.1, respectively. The incidence of stroke in the rivaroxaban group was observed in one patient (1.37%), and in the warfarin group in two patients (6.06%). The results of the study on the primary endpoint indicate that the indicators in both groups did not differ significantly (P = .24). The incidence of haemorrhagic events such as minor bleeding in the rivaroxaban group on the BARC scale was n = 31 (42.5%), and n = 24 (72.7%) in the warfarin group (P < .01). This indicator on the ISTH scale is n = 27 (36.9%) and n = 21 (63.6%), respectively. Major bleeding was observed in the rivaroxaban group n = 2 (2.74%), and in the warfarin group n = 2 (6.06%) on the BARC and ISTH scales (P = .31). Heamorrhagic events were significantly more frequent in the warfarin group compared with the rivaroxaban group.

CONCLUSION

The data obtained from this study indicate a favourable safety profile of NOAC (rivaroxaban) compared with a vitamin K antagonist in patients with stage 4 CKD in combination with AF.
MO185: Post-Translational Carbamylation of Sortilin is Associated with Cardiovascular Calcification in Chronic Kidney Disease
Authors: Jankowski Vera , Saritas Turgay , Kjobly Mads , Speer Thimoteus , Thirup Soren , Kramann Rafael , Jankowski Joachim , Floege Jürgen , Marx Nikolaus , Göttsch Claudia
Published: May 2022

BACKGROUND AND AIMS

Sortilin, an intracellular sorting receptor, has been identified as a cardiovascular (CV) risk factor in the general population. Patients with chronic kidney disease (CKD) are highly susceptible to developing CV complications such as CV calcification. However, specific CKD-induced post-translational protein modifications of sortilin and their link to CV calcification remain unknown.

METHODS

Circulating sortilin isolated from two independent CKD cohorts was analysed by matrix-assisted laser desorption/ionization time of flight mass spectrometry (MALDI-TOF/TOF mass spectrometry). The binding partner affinity was analysed by surface plasmon resonance spectroscopy. The effect of carbamylated sortilin on vascular calcification was analysed in vitro using human coronary artery smooth muscle cells.

RESULTS

In CKD patients, targeted mass spectrometric analyses of circulating sortilin revealed an increase in carbamylated lysine residues with kidney function decline. Carbamylation did not affect dimer formation of sortilin assessed by mass spectrometry. We observed an increased affinity of interleukin 6 to in vitro carbamylated sortilin. Carbamylated sortilin increased SMC calcification in vitro that was accelerated by interleukin 6, while carbamylated albumin and collagen type I did not affect SMC calcification. Mass-spectrometry imaging of human calcified arteries revealed in situ carbamylated sortilin. In CKD patients, sortilin carbamylation was associated with coronary artery calcification volume, independent of age, kidney function and other risk factors. Moreover, patients with carbamylated sortilin displayed significantly faster coronary artery calcification progression than patients without sortilin carbamylation.

CONCLUSION

Carbamylated sortilin is a risk factor for CV calcification and may contribute to elevated CV complications in patients with CKD.
MO193: Capillary Point-Of-Care Creatinine Testing in Kidney Disease Patients
Authors: Rosset-Zufferey Sarah , Emanuel Uehlinger Dominik , Sidler Daniel
Published: May 2022

BACKGROUND AND AIMS

Creatinine measurement is part of daily nephrological practice to estimate the glomerular filtration rate (eGFR). Creatinine is usually measured in plasma or in serum by the Jaffe method or enzymatic reactions [1]. New point-of-care testing (POCT) devices have been developed to allow rapid creatinine quantification from venous, arterial or capillary samples [2, 3]. Importantly, capillary sampling and quantification could enable autonomous patient-performed creatinine measurements at home. This method has so far not been extensively tested in chronic kidney disease (CKD), kidney transplanted (TPL) and haemodialysis [HD]-dependent patients. The 2-fold aim of this study was to assess the adequacy and patient acceptance of capillary creatinine POCT in the aforementioned different kidney disease patients’ groups.

METHOD

Consecutive eligible patients followed at the nephrology outpatient unit of the Bern University Hospital were included. In each patient, creatinine was both measured by Nova Max® Creatinine in three different capillary measurements (index test) and from venous sampling by the central hospital laboratory (enzymatic reference test). In HD patients, analyses were performed before and after a HD session. Intra-essay variation and correlation between the index and the reference test were calculated. In order to explore patients’ acceptance and perception of autonomous capillary creatinine measurement at home, subjects were asked to fill a standardized survey.

RESULTS

A total of 128 patients were included: 33 CKD, 68 TPM and 27 HD. Capillary POCT creatinine ranged from 55–604 umol/L, 50–458 umol/L and 133–872 umol/L for CKD, TPL and HD patients, respectively. Intra-assay variation was 23 umol/L (IQR: 10.5–47.5 umol/L), corresponding to 12% (IQR: 7–21%) variation. Correlation between capillary and plasma creatinine was high at r2 = 0.89, 0.76 and 0.72 for CKD, TPL and HD patients, respectively. Within the latter group, correlation was considerably higher after dialysis (r2 = 0.83) compared to before dialysis (r2 = 0.55). Overall, 54 patients (42%) filled the questionnaire; 97% considered POCT creatinine an easy test to perform and 94% considered it an implementable test at home. Over three quarters of the sample (77%) associated such intervention with improvement for patient care. Patients were particularly sensitive to the potential time saving and capacity to monitor their creatinine levels swiftly.

CONCLUSION

Autonomous capillary POCT creatinine measurement is an adequate, relevant and implementable test in specific subgroups of kidney disease patients. Correlation with plasma creatinine is high for CKD and TPL patients, while there are important inter-assay variations in HD patients. This test has economical, ecological and logistic implications that warrant further evaluation. The next step in evaluating this test would require an investigation of its reproducibility and clinical impact over time.
MO196: Moderate-To-Severe CKD-Associated Pruritus (CKD-AP) is Independently Associated with Worse Health-Related Quality of Life (HRQOL) Among Dialysis Patients
Authors: Ion Titapiccolo Jasmine , Bellocchio Francesco , Goethel-Paal Berit , Eva Baró Salvador Maria , Schofield Michaela , Rincon Bello Abraham , Chrisholm Chis , Basnayake Kolitha , Trkulja Marjelka , Stuard Stefano , Neri Luca
Published: May 2022

BACKGROUND AND AIMS

Chronic kidney disease–associated pruritus (CKD-aP) is common, yet underrecognized condition among end-stage kidney disease patients. We sought to evaluate the prevalence of CKD-aP and its impact on health-related quality of life (HRQOL) among dialysis patients across five European countries.

METHOD

This is a retrospective, observational analysis of data abstracted from the EuCliD® database (European Clinical database), the clinical information system adopted in Fresenius Medical Care (FMC) outpatient dialysis facilities in several European countries. Patient-Reported Outcomes Measures (PROM) were collected as part of a continuous quality improvement program launched for the first time in all centres belonging to the Nephrocare network in France, Italy, Spain, United Kingdom and Ireland. The presence and severity of CKD-aP were documented based on information captured by both the Kidney Disease Quality of Life (KDQOL™-36) and the 5-D Itch questionnaires. HRQOL was assessed with KDQOL™-36. Clinical and demographic data have been extracted from EuCliD®. The relationship between CKD-aP and HRQOL was evaluated with generalized linear models.

RESULTS

The ePROM campaign attained a large participation rate with very low attrition. Among 9974 who were actively treated in the clinics and were able to fill in a self-reported questionnaire, 8157 responded to the survey and only 1033 (11.2%) refused to participate. We enrolled 6221 patients in the present secondary analysis. The study flowchart is reported in Figure 1. Slightly more than half of patients (52%) reported no CKD-aP, 25% mild, whereas roughly 23% reported moderate-to-severe CKD-aP. Patients reporting more severe CKD-aP had shorter dialysis vintage, higher phosphate and parathormone, and more frequently diabetes. Average KDQOL-36 scores are reported in Figure 2a. We observed a strong, graded relationship between CKD-aP severity and KDQOL-36 scores (Figure 2b). The association was robust to adjustment for potential confounders. The quality of life penalty associated with more severe pruritus was clinically significant based on distribution based minimal clinically important difference threshold for the KDQOL-36 scales.

CONCLUSION

CKD-aP was common in a large, representative sample of the dialysis population in five European countries. We observed a large, clinically important, quality of life penalty associated with CKD-aP even after adjusting for potential confounders.
MO201: Effects of Aspirin in Primary Prevention of Cardiovascular (CV) Disease in People with Chronic Kidney Disease (CKD): Results of the TIPS3 Trial
Authors: Mann Johannes F E , Joseph Philip , Gao Peggy , Pais Prem , Xavier Denis , Dans Tony , Lopez Jaramillo Patricio , Gamra Habib , Tyrwhitt Jessica , Yusuf Salim
Published: May 2022

BACKGROUND AND AIMS

Subjects with CKD carry a high (CV) risk. Whether this risk is blunted by aspirin is controversial. We examined CV outcomes of CKD participants of the TIPS3 trial.

METHOD

The International Polycap Study3 (TIPS3) randomized people (N = 5713) with and without CKD, but without previous CV disease, to aspirin, aspirin plus polypill, polypill or respective placebo in a factorial design. In 983 participants that were randomized to aspirin or placebo, eGFR was below 60 mL/min/1.73 m2 at baseline (CKD). The primary outcome for this comparison was non-fatal myocardial infarction (MI), non-fatal stroke or CV death. The mean follow-up was 4.6 years.

RESULTS

In all participants, there were 250 primary MACE outcomes, 116 on aspirin and 134 on placebo (HR 0.86; 95% CI 0.67–1.10). In those with CKD, there were 65 primary MACE outcomes, 26 in the 502 participants on aspirin, 39 in the 481 participants on placebo, HR 0.57 (95% CI 0.34–0.94). Directionally similar results were found for aspirin versus placebo for the secondary outcome all-cause death with 312 events in all participants (HR 0.87; 0.70–1.07) and 82 events in CKD patients (HR 0.64; 0.41–0.99). There was no significant interaction of eGFR <60 mL/min with the treatment effects of aspirin versus placebo. Major and minor bleedings were rare and not different between groups.

When aspirin was combined with a polypill (containing atenolol, ramipril, hydrochlorothiazide and simvastatin) and compared to double placebo, in all participants the HR for the MACE outcome was 0.69, 0.50–0.97 and for all-cause death 0.80, 0.59–1.08; in CKD patients the HR was 0.37, 0.18–0.75 for MACE and HR 0.49, 0.29–0.97 for death.

CONCLUSION

Results suggest that the CV risk in people with CKD may be substantially alleviated with aspirin alone and in combination with a polypill.
MO210: Anti-Receptor Type M Antibodies of Phospholipase A2 in the Diagnosis of Primary Membrane Nephropathy
Authors: Daniel Diaz Garcia Juan
Published: May 2022

BACKGROUND AND AIMS

Idiopathic membranous nephropathy (IMN) is one of the main causes of nephrotic syndrome in the adult population. Approximately between 20% and 40% of patients who suffer from it require replacement therapy in a period of 10–15 years. Recently, it has been reported that antibodies against the Type M phospholipase A2 receptor (APLA2R) are responsible for between 69% and 82% of cases with IMN in different parts of the world. Until now, the diagnosis and clinical follow-up of IMN requires the performance of a renal biopsy and proteinuria measurements.

METHOD

Diagnostic test study in a cohort of 106 patients who continued to be followed up in the nephrology outpatient clinic (EC), in the period from 1 January 2009 to 31 January 2017. Serum samples were taken and analyzed of patients with histological diagnosis of IMN with proteinuria > and <1 g in 24 h and other glomerular diseases other than IMN such as lupus nephritis, diabetic nephropathy, primary glomerular diseases and kidney donors (healthy subjects) with measurement of APLA2R by ELISA (EUROIMMUN ) concomitant with measurement of 24-h urine proteinuria.

RESULTS

In 22 of 106 patients, an APLA2R concentration >9 RU/mL was found and all these cases had IMN (21 active IMN, Proteinuria >1 g in 24 h and 1 inactive IMN, Proteinuria < 1 g in 24 h). The prevalence of seropositivity in cases with active IMN was 78% (21/27). APLA2R concentrations were positively correlated with 24-h urine proteinuria (r = .68) and serum cholesterol (r = .42) and negative with serum albumin (r = −0.34). All these correlations were statistically significant with a P < .001. The area under the ROC curve (AB-ROC) of APLA2R was 0.87 (95% CI 78–0.96). When comparing subjects with active IMN versus other subjects with glomerular diseases, with a cut-off point of 9 RU/mL, the sensitivity was 78% and the specificity 99%.

CONCLUSION

The APLA2Rs have an adequate diagnostic utility to diagnose IMN in the selected population; especially in subjects with proteinuria greater than 1 g/day, with a sensitivity of 78% with a specificity of 99%. The APLA2Rs are useful for the diagnosis of idiopathic membranous nephropathy, especially when there is proteinuria greater than 1 g in 24 h. The APLA2Rs measured by ELISA with titers greater than 9 RU/mL exclude other glomerular diseases and are highly specific for the diagnosis of IMN, which could prevent the performance of a renal biopsy.
MO213: Sars-COV-2 Vaccination DID Not Affect the Clinical Course of IGA Nephropathy in Latvian Adult Cohort
Authors: Rācenis Kārlis , Jana Saulīte Anna , Popova Anna , Saulīte Mikus , Kroiča Juta , Petersons Aivars , Cernevskis Harijs , Lejnieks Aivars , Oļeiņika Kristīne , Šlisere Baiba , Seilis Janis , Kuzema Viktorija
Published: May 2022

BACKGROUND AND AIMS

The current strategy to fight against the COVID-19 pandemic involves active patient vaccination. Patients with renal and autoimmune diseases are in high risk for severe COVID-19 infection [1]. Therefore they should be prioritized for vaccination. Immunoglobulin A nephropathy (IgAN) is one of the most common primary glomerulonephritis triggered by mucous membrane alteration; however, there is a discussion about vaccination-caused IgA flare [2]. The immunological nature of IgAN and misleading information in public sources leaves patients skeptical about whether to get vaccinated [3]. The study aimed to investigate the impact of SARS-CoV-2 vaccination on the clinical course of IgA nephropathy.

METHOD

Adult patients treated in Pauls Stradins Clinical University Hospital with morphologically proven IgAN were included in the study. Patients with secondary IgAN were excluded. Evaluation of clinical and laboratory markers was performed on inclusion visit and on the second visit 6 months later. SARS-CoV-2 vaccination type and status were noted on both visits. Estimated GFR was calculated with CKD-EPI creatinine–cystatin equation. IBM SPSS Statistics version 27 and Microsoft Excel 10 were used for data analysis.

RESULTS

The study involved 54 patients, 36 were unvaccinated and 18 were fully vaccinated. A significant difference between the two groups was observed by baseline proteinuria. Other differences were not observed. Fourteen patients were vaccinated with mRNA vaccine, 13 with Comirnaty and 1 with Spikevax, and four patients were vaccinated with Vaxzevria vector vaccine. The differences between the two groups are shown in Table 1. During study period, two patients had COVID-19 infection; a patient in the vaccinated group had COVID-19 prior to vaccination.

CONCLUSION

SARS-CoV-2 vaccination did not affect the clinical course of IgA nephropathy. Our study results indicate that SARS-CoV-2 vaccination in IgA nephropathy patients was safe regarding renal function and disease activity markers.
MO229: Is Nodular Glomerulosclerosis Always Associated with Diabetic Nephropathy?
Authors: Nabil Hamouche , Chettati Mariam , Fadili Wafaa , Laouad Inass
Published: May 2022

BACKGROUND AND AIMS

Nodular glomerulosclerosis (NGS) is a histological diagnosis that can be found in several etiologies. It corresponds to a particular form of expansion of the extracellular matrix within the mesangium.

Glomerulosclerosis is not very specific, its nodular form is on the other hand more interesting from an etiological point of view since only a few pathologies can take this aspect, the most frequent are diabetes (mainly), membranoproliferative glomerulonephritis (MPGN) and renal expression of gammopathies monoclonal.

In the absence of an identified etiology, NGS is said to be idiopathic. This entity, described 30 years ago, is very rare and therefore largely unrecognized. Some pathophysiological hypotheses have emerged in recent years, particularly involving smoking, high blood pressure or insulin resistance.

The aims of our study were as follows:

METHOD

Monocentric retrospective study of patients with NGS in renal biopsy, collected between January 2016 and December 2021 at Mohammed VI University hospital of Marrakech.

The epidemiological, clinical and etiological characteristics were studied.

RESULTS

We have collected 108 NGS. Of our patients, 47.22% presented with NGS of diabetic origin and 52.95% with non-diabetic NGS. For patients with NGS of diabetic origin, the indication for PBR was glomerular syndrome (19 patients), nephrotic syndrome (7 patients), rapidly progressive renal failure or severe renal failure (11 patients), recent diabetes (7 patients), absence of diabetic retinopathy (3 patients), presence of extra-renal signs (2 patients) and monoclonal peak (2 patients).

The diagnosis of idiopathic NGS was made after eliminating all the etiologies of NGS (normal complement dosage, no diabetes, no monoclonal peak, negative IFD, history of smoking and hypertension and dyslipidemia) and immunohistochemistry. Two patients were tested for deposits of the kappa and lambda chains, thus eliminating the myeloma.

Among the risk factors for idiopathic SNB detected in our work, we cite:

CONCLUSION

The most common etiology of NGS remains diabetes, but this lesion can be seen in other conditions such as MPGN, Randall disease, amyloidosis, monotypic immunoglobulin deposition, non-immunoglobulin and idiopathic glomerulopathies.

Idiopathic nodular glomerulosclerosis is a rare entity, frequent in most series in humans, which contrasts with the data of our study. On the other hand, a causal link between this histological entity and smoking, hypertension and Metabolic syndrome has been well established in several studies, which is consistent with the data from our work.
MO239: Clinical Evaluation of Immunological and Clinical Recurrence of Immune-Mediated Nephropathies after SARS-COV-2 Vaccine
Authors: Musetti Claudio , Fornara Laura , Cantaluppi Vincenzo
Published: May 2022

BACKGROUND AND AIMS

The mass vaccination for COVID-19 has raised new concerns for patients with immune-mediated nephropathies: there is a small but growing literature of case-reports linking SARS-CoV-2 vaccines with heightened off-target immune responses leading to de novo or relapsing glomerular diseases [1, 2].

Aim of this study was to evaluate how many and how severe were the relapses of immune-mediated nephropathies after the SARS-CoV-2 vaccine in a single center.

METHOD

This is a retrospective study held in Italy from the start of the vaccination campaign (late December 2020) to December 31st 2021. We included all patients with an immune-mediated nephropathy (either on or off immunosuppressive therapy—IS), excluding patients with an end-stage renal disease or kidney transplant.

In Italy we used mRNA (Comirnaty by Pfizer-BioNTech or Spikevax by Moderna) or adenoviral vector vaccines (Vaxzevria by AstraZeneca or Janssen), without any preference for patients with kidney disease, but those on active IS were given preferentially an mRNA vaccine.

There was no active surveillance of lab tests after vaccination and post-vaccine tests were either concomitant to programmed visits or suggested on a patient by patient basis.

Recurrence was defined as relapse of nephrotic or nephritic syndrome, doubling of urinary proteins with a max value > 1 g/24h, acute kidney injury with an active urinary sediment, or positivization or 5-fold increase of serological markers of disease activity (i.e.: ANCA in AAV).

RESULTS

A total of 38 patients (M: F 28:10, age at vaccine 45.9 ± 19.1 years) completed the vaccination protocol: among them, the most common nephropathy was membranous nephropathy (n = 12, 31.6%), followed by IgA nephropathy (n = 7, 18.4%), minimal change disease (n = 6, 15.8%) and ANCA-associated vasculitis (n = 6, 15.8%); 26 patients (68.4%) had at least one other comorbidity. We observed six relapses (4 MN, 1 IgA, 1 AAV), of which only one (MN) developed a mild oedema. The mean time from the first vaccine dose to the relapse was 101 ± 71 days (5–199 days) and only two episodes occurred within 4 weeks from a vaccine dose. We could not find an association between recurrences and maintenance IS at the time of vaccine or any other variable. The overall post-vaccine incidence rate of relapses was 35.8/100 patient-years, as compared with 14.0/100 patient-years historically observed in the same cohort [IRR 2.55, 95% confidence interval (CI) 0.89–5.97].

CONCLUSION

Relapses of immune-mediated nephropathies are not common after SARS-CoV-2 vaccine and we did not observe any clinically relevant relapse. However the overall rate of relapse seems to be a little higher than prior vaccination [3], but only 2/6 patients recurred soon after a vaccine dose. As these relapses seem to be self-limiting, a post-vaccine monitoring could be useful in patients at high risk of severe disease.
MO252: Complement 3 Deposits on Renal Tubule and Glomeruli in Phospholipase A2 Receptor-Related Idiopathic Membranous Nephropathy
Authors: Cui Haoyuan , LI Chao , LI Hang , Wen Yu-Bing , Chen Limeng
Published: May 2022

BACKGROUND AND AIMS

Evidence shows galactose-deficient IgG4 is able to act complement system via lectin pathway in phospholipase A2 receptor (PLA2R) related idiopathic membranous nephropathy (IMN). However, the severity of PLA2R-related IMN runs parallel with neither the electron microscope stage nor the complement density in situ. We find positive complement factor 3 (C3) deposition on renal proximal tubule in some IMN patients and manage to analysis the relationship between it and the severity of the disease.

METHOD

We retrospectively involved 113 PLA2R related IMN patients from March 2017 to October 2019. The inclusion criteria were diagnosed by kidney biopsy with complete clinical and pathological data. The exclusion criteria were with any secondary causes such as lupus nephritis type V, Sjogren's syndrome, hepatitis B associated glomerulonephritis and atypical membranous nephropathy. We divided total patients into four subgroups according to the C3 deposition site. We defined no C3 deposition subgroup (40,35%) as C3 appeared in neither glomeruli nor tubule, C3 glomeruli deposition subgroup (32, 28%) as C3 deposited on glomeruli only, C3 tubule deposition subgroup (12, 11%) as C3 deposited on tubule only, C3 extensive deposition subgroup (29, 26%) as C3 deposited on both glomeruli and tubule.

RESULTS

Clinical data of four groups were as follows: Male/female ratio were 22/18, 23/9, 5/7, 16/13, P = .252; The median of age were 50 (33, 57), 51 (42, 57), 57 (49, 61), 51 (33, 57), P = .412; The median of were 24-h urine protein were 4.4 (2.0, 6.9), 5.0 (2.7, 8.3), 4.9 (2.5, 11.2), 5.5 (2.4, 10.2) g/L, P = .427. The average serum albumin were 28.6 ± 6.8, 27.2 ± 6.7, 24.6 ± 2.7, 25.5 ± 6.0 g/L, P = .046. The median of serum creatinine were 70 (57, 82), 77 (65, 92), 68 (57, 89), 69 (58, 80) μmol/L, P = .255. The median of serum C3 were 1.14 (1.0, 1.33), 1.17 (1.04, 1.36), 1.22 (1.0, 1.34), 1.11 (0.99, 1.23) g/L, P = .291. The median of anti-PLA2R antibody were 0 (0, 55), 29 (25, 33), 12 (0, 136), 35 (19, 131) RU/mL, P = .049.

CONCLUSION

There were differences in serum anti-PLA2R antibody and Alb in patients with different C3 deposition. Patients with extensive C3 deposition showed higher PLA2R antibody.
MO254: Baseline Characteristics of Patients Enrolled in the Ongoing Phase 3 Randomized, Double-Blind, Active-Control Trial of Sparsentan for the Treatment of Focal Segmental Glomerulosclerosis (DUPLEX)
Authors: Trachtman Howard , Radhakrishnan Jai , Komers Radko , Mercer Alex , Rosenberg Noah
Published: May 2022

BACKGROUND AND AIMS

Uncontrolled focal segmental glomerulosclerosis (FSGS) often follows a progressive course to end-stage kidney disease and has a profound negative impact on patient quality of life and long-term survival. Treatments that reduce proteinuria and risk of kidney disease progression are urgently needed. Sparsentan is a novel dual endothelin angiotensin receptor antagonist (DEARA) being investigated for FSGS. The Phase 3 DUPLEX study is examining the potential long-term antiproteinuric and nephroprotective potential and safety of sparsentan compared with an active control, angiotensin receptor blocker (ARB) irbesartan in adults and pediatric patients with FSGS. Here we report the baseline characteristics for all patients enrolled in the DUPLEX trial.

METHOD

DUPLEX is an ongoing, global, Phase 3, multicenter, randomized, double-blind, active-controlled study designed to evaluate the efficacy and safety of sparsentan versus irbesartan in adult and pediatric patients (≥8–75 years old) with FSGS. The study duration is 268 weeks: a 112-week double-blind period followed by an open-label extension period of up to 156 weeks. The primary efficacy endpoint is the slope of eGFR over approximately 2 years of randomized treatment. Key inclusion and exclusion criteria are shown in Table 1. Patients receiving renin–angiotensin–aldosterone system (RAAS) inhibitors underwent a 2-week washout prior to randomization. Patients were randomized 1:1 to sparsentan or irbesartan (target dose 800 and 300 mg/day, respectively), stratified by screening eGFR and urine protein/creatinine ratio (UP/C). The blinded and aggregated baseline characteristics of all patients enrolled in the DUPLEX trial are summarized descriptively.

RESULTS

The DUPLEX study is fully enrolled with 371 patients (336 adult and 35 pediatric) across 179 study sites in 22 countries. Selected demographic and clinical characteristics in the total population are reported in Table 2.

CONCLUSION

DUPLEX is the largest randomized controlled trial to date in FSGS. Patients with FSGS enrolled in the DUPLEX trial display demographic and clinical characteristics consistent with the profile previously reported in the broader population of patients globally with FSGS not in remission.
MO267: Traditional and Disease-Related Cardiovascular Risk Factors in Anca-Associated Vasculitis: A Prospective, Two-Centre, Observational Cohort Study
Authors: Vegting Yosta , Lars Penne Erik , Hilhorst Marc , Pagnoux Christian , Houben Eline
Published: May 2022

BACKGROUND AND AIMS

ANCA-associated vasculitis (AAV) has been associated with increased risk of cardiovascular (CV) events. The purpose of the present study was to asses cardiovascular risk determinants and outcomes in a two-centre prospective cohort of AAV patients.

METHOD

Prevalent patients diagnosed with AAV ≥ 3 months were recruited over a period of 8 months from the Northwest Clinics in the Netherlands and 3 months from the Mount Sinai Hospital in Canada, and followed for 3–5 years. A comprehensive CV risk assessment was performed at inclusion. Subjects were followed up yearly until the first cardiovascular event, death or end of follow-up, whichever came first. Cardiovascular events were assessed by an independent outcome panel. Cox proportional hazards analyses were performed to relate baseline characteristics to the first CV event.

RESULTS

A total of 144 patients were included (median age 64.6 years, male sex 56%, median BVAS score 0, median Framingham risk score 14.3%). After a median follow-up of 2.91 years, 28 non-fatal and 4 fatal CV events were registered in 16 patients. Twelve patients died of non-cardiovascular causes. The incidence of fatal and non-fatal CV events was 5.5 per 100 patient-years. In a univariable analysis an association was found between traditional risk factors and risk of CV events [hazard ratio (HR) (95% confidence interval)], including age [HR 1.08 (95% CI 1.03–1.14)], HbA1c [HR 1.59 (95% CI 1.15–2.22)], systolic blood pressure [HR 1.04, 1.01–1.06), history of CV event [HR 3.47 (95% CI 1.29–9.32)] and Framingham risk score [HR 1.05 (95% CI 1.03–1.08)]. After adjusting for age and sex, HbA1c [HR 1.70 (95% CI 1.17–2.48)] and previous CV event [HR 2.90 (95% CI 1.02–8.21)] remained significantly associated with CV events. In a multivariable cox regression analysis (adjusted for Framingham risk score), a longer disease duration was associated with CV events [HR 1.08 (95% CI 1.01–1.16)].

CONCLUSION

The present study is the largest prospective study on CV risk in patients with AAV and showed that CV risk was driven by both traditional and disease-related risk factors. Disease duration is associated with increased risk of CVE, but which precise disease-related factors accounts for this finding, and whether it can be acted upon remain to be determined.
MO276: Renal Tubular CD24 Upregulation Aggravates Folic Acid-Induced Acute Kidney Injury Through Inhibition of Regulatory T Cells in Mice
Authors: Schwartz Doron , Grupper Ayelet , Zubkov Asia , Chernichovski Tamara , Arber Nadir , Shashar Moshe , Schwartz Edith
Published: May 2022

BACKGROUND AND AIMS

Acute kidney injury (AKI) is characterized by cell death and inflammation. CD24 is a sialoglycoprotein which is induced during tissue damage and is not expressed in matured renal tissue. We explored the role of CD24 in the pathogenesis of folic acid-induced AKI (FA-AKI) in mice.

METHOD

A single i.p. injection of folic acid induced AKI in WT and CD24-/- mice. Renal function tests, histological analysis, immunohistochemistry, Western blot analysis and ELISA were performed to assess the severity of renal damage and the intensity of the inflammatory response.

RESULTS

FA-AKI induced the expression of CD24 in the distal tubular epithelial cells. Compared to WT mice, FA-AKI CD24-/- mice exhibited an attenuated reduction in renal function and histological injury, lower serum IL-10 and interferon γ, and decreased expression of renal TNFα. Renal and systemic IL-33 were upregulated in both groups. However, it was more pronounced in FA-AKI CD24-/- animals. FA-AKI CD24-animals exhibited increased splenic margination and renal infiltration of regulatory T cells (Tregs). At day 7, FA-AKI CD24-/- mice demonstrated increased expression of tubular pro-apoptotic (activated caspase 3) and decreased anti-apoptotic (Bcl-xL) proteins compared with WT animals. Administration of anti CD24 antibody to FA-AKI mice attenuated the decrease in renal function and ameliorated the histological injury in comparison with untreated animals.

Renal biopsies from patients with ATN stained strongly for CD24 in the distal tubules.

CONCLUSION

During AKI, upregulation of CD24 promotes renal inflammation through inhibition of Tregs infiltration and diversion of cell death towards necrosis rather than apoptosis. Neutralization of CD24 may prove as a target for future therapies in AKI.
MO279: Vitamin D Supplementation Attenuates Hyperandrogenemia-Associated Acute Kidney Injury in Female Sprague-Dawley Rats
Authors: Masjedi Fatemeh , Roozbeh Jamshid , Karimi Zeinab
Published: May 2022

BACKGROUND AND AIMS

Polycystic ovary syndrome (PCOS) is closely related to the onset and development of metabolic abnormalities. However, the correlation between PCOS and kidney injury has not been clarified, and the underlying mechanism remains unknown. Vitamin D therapy has beneficial effects in women with PCOS and renal injuries. Therefore, this study was designed to explain the mechanisms responsible for kidney damages in a model of hyperandrogenic rats and the healing effects of vitamin D.

METHOD

Female Sprague-Dawley rats were randomly divided into five groups (n = 10): (i) control, (ii) sham, (iii) dehydroepiandrosterone (DHEA, 6 mg/100 g day-1 S.Q.), (iv) DHEA + vitamin D (1000 IU/Kg; 3 days/week), and (v) vitamin D. Plasma total testosterone, plasma creatinine (Cr), blood urea nitrogen (BUN), plasma and tissue levels of total oxidant status (TOS), total antioxidant capacity (TAC) and oxidative stress index (OSI), and histopathological changes of ovary and kidney were determined.

RESULTS

Plasma testosterone increased 9-fold in DHEA-treated rats compared with controls. They also had increased Cr, BUN, and severe renal tubular injury. Plasma and tissue TAC levels showed significant decreases, whereas TOS and OSI showed significant increases in the DHEA group. A significant injury in the glomerular and tubular parts of the kidney and ovarian follicular structure was observed in DHEA-administered rats. Vitamin D treatment attenuated TOS levels and significantly improved TAC levels. Kidneys and ovaries histopathological changes were significantly improved by vitamin D treatment.

CONCLUSION

Hyperandrogenemia causes systemic abnormalities through oxidative stress-related mechanisms, followed by obvious destruction to renal and ovarian tissues. Vitamin D supplementation attenuated these hyperandrogenemia-associated acute kidney injuries.
MO282: Sigma-1 Receptor Agonists are Protective in Renal Ischemia/Reperfusion Injury
Authors: Roland Toth Akos , Lakat Tamas , Hodrea Judit , Balogh Dora B , Vannay Adam , Wagner Laszlo , Szabo Attila , Fekete Andrea , Hosszu Adam
Published: May 2022

BACKGROUND AND AIMS

Renal ischemia/reperfusion injury (IRI)-induced acute kidney injury is associated with high mortality and morbidity and effective therapies are lacking. We previously showed that Sigma-1 receptor (S1R) agonist fluvoxamine treatment is protective against renal IRI (Hosszu et al, 2017). Here in a rat model, we studied the renoprotective effect of specific, high affinity S1R agonists focusing on the S1R-Akt-eNOS signaling pathway and renal vasoregulation.

METHOD

8-week old male Wistar rats (n = 8/group) were subjected to 50 min unilateral ischemia with contralateral nephrectomy, kidney tissue was harvested 24 h after reperfusion. 30 min prior to the ischemic insult rats were treated i.p. as follows: (i) isotonic saline as vehicle; (ii) highly specific, high affinity S1R agonist SA-4503; or (iii) SA-4503 + S1R antagonist NE100. Sham-operated rats were used as controls. Renal functional parameters (BUN, serum creatinine, serum aspartate aminotransferase, kidney injury molecule 1 (Kim1), neutrophil gelatinase-associated lipocalin (Ngal) were evaluated. Structural damage was assessed on PAS-stained kidney sections. Renal S1R, phospho-Akt and phospho-eNOS, Hif-1α protein levels and serum nitric oxide (NO) concentration were measured. In vitro experiments were performed on HK2 human proximal tubular epithelial cells treated with a 10 µM dose of S1R agonist SA-4503 or PRE-084.

RESULTS

Impaired kidney function and structural damage after I/R were ameliorated by SA-4503. Expressions of early and sensitive tubular injury markers Kim1 and Ngal were markedly less elevated in SA-4503-treated rats. This recovery was blocked with the addition of the S1R antagonist NE100. S1R, phospho-Akt and phospho-eNOS protein levels were significantly elevated in the kidneys of SA-4503 treated rats. Vasodilator nitric oxide concentration was reduced in the kidney after IRI, but returned to control levels in SA-4503-treated rats. Treatment with S1R agonists SA-4503 and PRE-084 increased the NO production of HK-2 cells.

CONCLUSION

The specific and high affinity S1R agonist SA-4503 acts directly on proximal tubular cells by activating the S1R-NOS system. Thereby SA-4503 is renoprotective by increasing vasodilative NO production and thus improving post-ischemic renal perfusion. Based on our data activation of S1R and downstream signaling pathways could provide a novel therapeutic option in renal IRI.

Founding

OTKA PD-131 637; FK-124 491; 2020–4.1.1.-TKP2020-6 183 069 269; 2020–4.1.1.-TKP2020-6 183 169 273; KDP-2020/1 019 145
MO303: Impact of Dexamethasone and Inhaled Nitric Oxide on Severe Acute Kidney Injury in Critically ill Patients With COVID-19
Authors: Bobot Mickaël , Tonon David , Peres Noémie , Guervilly Christophe , Lefèvre Flora , Carvelli Julien , Papazian Laurent , Max Howard , Leone Marc , Lopez Alexandre , Bommel Youri , Volff Maxime , Velly Lionel , Bruder Nicolas , Hraiech Sami , Simeone Pierre , Bourenne Jérémy , Forel Jean-Marie
Published: May 2022

BACKGROUND AND AIMS

Kidney failure is the second most frequent condition after acute respiratory distress syndrome (ARDS) in critically ill patients with severe COVID-19 and is strongly associated with mortality. The aim of this multicentric study was to assess the impact of the specific treatments of COVID-19 and ARDS on the risk of severe acute kidney injury (AKI) in critically ill COVID patients.

METHOD

Data from a prospectively collected database of consecutive patients hospitalized in six ICUs for COVID-19 was retrospectively analysed. The incidence and severity of AKI were monitored during the entire ICU stay. Patients older than 18 years hospitalized in for COVID-19-related ARDS requiring mechanical ventilation were included.

RESULTS

A total of 164 patients were included in the final analysis, 97 (59.1%) displayed AKI, of which 39 had severe stage 3 AKI and 21 (12.8%) requiring renal replacement therapy (RRT). In univariate analysis, severe AKI was associated with ACEI exposure (P = .016), high blood pressure (P = .029), APACHE-II score (P = .004) and mortality at D28 (P = .008), D60 (P <  .001) and D90 (P <  .001). In multivariate analysis, the factors associated with the onset of stage 3 AKI were: exposure to CEI [OR: 4.238 (1.307–13.736); P = .016], APACHE II score (without age) [OR: 1.138 (1.044–1.241); P = .003] and iNO [OR: 5.694 (1.953–16.606); P = .001], protective factors were prone positioning [OR: 0.234 (0.057–0.967); P = .045] and dexamethasone [OR: 0.194 (0.053–0.713); P = .014].

CONCLUSION

Dexamethasone seems to prevent the risk of severe AKI and RRT, and iNO seems associated with severe AKI and RRT in critically ill patients with COVID-19. iNO must be used with caution in COVID-19 related ARDS.
MO310: Clinical Characteristics and Outcomes of Acute Kidney Injury in Hospitalized Patients With COVID-19: Experience at a Major Tertiary Care Center in Pakistan
Authors: Yaqub Sonia , Hamid Amna , Saeed Marwah , Awan Safia
Published: May 2022

BACKGROUND AND AIMS

Limited data exists on acute kidney injury (AKI) in patients hospitalized with COVID-19, its risk factors and associated outcomes from low-middle income countries. We aimed to determine the epidemiology of AKI and its impact on outcomes at a tertiary-care center in Karachi, Pakistan.

METHOD

A retrospective observational study was conducted at Aga Khan University Hospital from October to December 2020. Data on demographics, presenting clinical symptoms, laboratory results and patient outcomes were collected from medical records. AKI was defined according to KDIGO criteria.

RESULTS

Of 301 patients admitted with COVID-19, AKI developed in 188 (62.5%). The peak stages of AKI were stage 1 in 57%, stage 2 in 14.9% and stage 3 in 27.7%. Of these, 15 (8%) required KRT. Patients requiring ICU admission (63.8% versus 34.5%), vasopressors (31.9% versus 5.3%) or mechanical ventilation (25% versus 2.7%) had a higher risk of AKI. Independent predictors of AKI were elevated blood urea nitrogen and creatinine at the time of presentation, need for mechanical ventilation and use of anticoagulants. AKI, presence of proteinuria, elevated SCr at presentation, use of vasopressors and need for KRT were all significantly associated with in-hospital death, and the likelihood of mortality increased with the advancing stage of AKI.

CONCLUSION

Compared with other countries, AKI occurred more frequently among hospitalized patients with COVID-19 in a Pakistani cohort and was associated with a 7.7-fold increase in odds of in-hospital death. Patients with severe AKI had a greater likelihood of fatal outcomes compared with earlier stages or non-AKI patient groups.
MO315: Risk Factors for CSA-AKI and Performance of Leicester Score in a Spanish Cohort
Authors: Molina Andujar Alicia , Joaquin Escudero Victor , Blasco Miquel , Piñeiro Gaston , Poch Esteban
Published: May 2022

BACKGROUND AND AIMS

The incidence of acute kidney injury following cardiac surgery (CSA-AKI) is up to 30% and it places patients at an increased risk of death. Leicester score (LS) is a new score designed by Birnie et al. [1] and validated in 2014 in a British Cohort. It predicts CSA-AKI at any stage with better discrimination compared with the Clevaland Clinic Score (CCS) and Euroscore II. The aim of this study was to identify risk factors for CSA-AKI and to assess the performance of LS in a Spanish cohort.

METHOD

A unicentric retrospective study of patients that required cardiac surgery with cardio-pulmonary bypass (CPB) during 2015 in the Hospital Clinic de Barcelona. The inclusion criteria were patients >18 years old who were operated on for cardiac surgery [valve substitution (VS), coronary artery bypass graft (CABG) or a combination of both procedures] with the need of CPB. CSA-AKI was defined by the Kidney Disease Improving Global Outcomes (KDIGO) criteria.

RESULTS

A total of 444 patients were included, of which 171 (38.5%) developed CSA-AKI. The most frequent form of AKI was mild AKI (AKI stage 1), which was present in 105 patients (61.4%). AKI stage 3 was developed in 26 patients, 15 of which required RRT. A total of 66.7% of AKI cases met criteria in the first 24 h and the median duration until total recovery was 3 days. In the multivariate analysis, hypertension (OR 1.883), EGFR < 60 mL/min (OR 2.365) and peripheral vascular disease (OR 4.66) were associated with CSA-AKI. Either discrimination or calibration were better with LS compared with CCS and Euroscore II, with an AUC of 0.721 versus 0.595 and 0.662, respectively (Fig. 1).

CONCLUSION

Preoperative hypertension in patients with CKD with or without peripheral vasculopathy can identify patients at risk of CSA-AKI. LS has proved to be a valid score that could be used to identify patients at risk who could benefit in intervention studies.