bluuebunny/crossref_metadata_2025 huggingface dataset:
#3163 SARS-COV-2 OMICRON INFECTIONS AMONG VACCINATED MAINTENANCE HEMODIALYSIS PATIENTS: OUTCOMES AND COMPARISON TO DELTA VARIANT
Authors: Hagai Keren Cohen , Wand Ori , Drori Idan , Einbinder Yael , Nacasch Naomi , Benchetrit Sydney
Published: June 2023

Background and Aims

Infections with the B.1.1.529 Omicron variant of SARS-CoV-2 became predominant worldwide in late 2021, replacing the previously dominant B.1.617.2 Delta variant. While these variants are highly transmissible and can evade vaccine protection, population studies suggested that outcomes after infection with Omicron variant were better than with Delta. Data regarding prognosis of maintenance hemodialysis (MHD) patients infected with Omicron vs. Delta variants are limited.

Method

This retrospective, cohort study included all patients with end-stage kidney disease treated with MHD at Meir Medical Center, Kfar Saba, Israel, who were diagnosed with SARS-CoV-2 infection between June 2021 and May 2022.

Results

Twenty-six MHD patients were diagnosed with the Delta variant and 71 with Omicron. SARS-CoV-2 infection severity was significantly worse among those infected with the Delta variant: 50% developed severe or critical COVID-19 vs. 5% in the Omicron group (p<0.001). Among MHD infected with Omicron, 57% were asymptomatic during their illness. For the entire cohort, 30-day mortality was 5.2%. It was higher among MHD in the Delta group (5/26, 19.2%) than in the Omicron group (0/71; p<0.001), as was 90-day mortality (5/26, 19.2% vs. 3/71, 4.2%, respectively; p = 0.02). Mean age was comparable between groups. Patients infected with Omicron variant received a higher mean number of vaccine doses before infection, as compared to Delta group (p<0.001).

Conclusion

Infection with the SARS-CoV-2 Delta variant was associated with worse outcomes compared with Omicron, among patients on MHD. However, despite mild disease among vaccinated MHD patients, infection with Omicron variant was still associated with significant 90-day mortality rate.
#3185 INFLUENCE OF COMBINED CYP 3A4/5 AND POR*28 GENETIC POLYMORPHISMS ON TACROLIMUS AND CCLOSPORINE DOSE REQUIREMENTS IN INCIDENT RENAL TRANSPLANT PATIENTS
Authors: Elsharkawy Magdy , Ismail Dina , Ebid Abdel-Hameed , Lotfy Neama , Mahmoud Mohamed
Published: June 2023

Background and Aims

Calcineurin inhibitors, cyclosporine and tacrolimus have a narrow therapeutic index and have wide intra- and inter individual pharmacokinetic variability. They are metabolized mainly by CYP3A4 and CYP3A5. The P450 oxidoreductase POR*28 variant allele has been associated with changes in cytochrome P450 enzymatic activity that can affect the therapeutic level of both medications. The aim of this study is to investigate the allelic frequency of the POR*28 in Egyptian renal transplant patients and to evaluate the effect of the presence of CYP3A5*1, CYP3A4*22, and POR*28 genetic polymorphism on calcineurins inhibitos dose requirements and adjustments.

Method

A prospective clinical trial that included 130 renal transplant patients placed on either tacrolimus or cyclosporine. Patients were genotyped for POR*28, CYP3A4*22, and CYP3A5*1. The relation between the present genetic polymorphisms and tacrolimus and cyclosporine doses and dose adjustments were studied at days 14, 30, and 90 post-transplantation.

Results

The POR*28 allele frequency in the studied population was 29.61%. The tacrolimus dose-adjusted trough concentration ratio (C0/D) was highly statistically significant in the fast metabolizers group (CYP3A5*1/POR*28T carriers) than in the slow metabolizers group (CYP3A5*3/*3/CYP3A4*22 carriers) throughout the study (14, 30, and 90 days) (p value 0.001, <0.001, and 0.003, respectively). There was no significant effect for this gene combination on cyclosporine (C0/D).

Conclusion

Combining the CYP3A5*1, POR*28, and CYP3A4*22 genotypes can be of significant value in early tacrolimus dose requirements and adjustments. However, it does not have any influence on cyclosporine dose requirements.
#3230 CHARACTERISTICS OF PROTEIN LOSS WITH MEDIUM CUT-OFF MEMBRANES COMPARED TO HIGH FLUX MEMBRANES
Authors: Wang Xiaoling , Grobe Nadja , Fisher Colleen , Colvin Kylie , Ho Chih-Hu , Kotanko Peter
Published: June 2023

Background and Aims

Medium cut-off membranes (MCO) have been introduced with the claim that larger pores enhance the removal of middle-sized uremic toxins. To date, no adequately powered randomized controlled trial has demonstrated that this membrane characteristic translates into improved mortality. A well-described consequence of larger pore sizes is a higher dialytic albumin loss [1]. In addition, other proteins could also be lost with MCO, including ones that are beneficial or even essential, e.g., to patients’ nutritional status. To better understand the spectrum of proteins cleared with MCO, we set up an ex vivo HD simulation system and compared protein loss characteristics between MCO and high-flux (HF) dialyzers.

Method

Over the course of an hour, a single reservoir of 2.5 liters EDTA human plasma was ultrafiltered using two Fresenius 2008T machines. One machine served the MCO dialyzer (Theranova 400), the other the HF dialyzer (Fresenius Optiflux F180NR). Ultrafiltrate (UF) was returned to the plasma reservoir (Figure 1A). Blood flow was 400ml/min, dialysate flow was zero, ultrafiltration rate was 13ml/min. UF samples were taken at ∼10 min intervals. Upon experiment completion, residual filtrate was collected from the dialysate compartment. Samples were stored at −80°C until analysis with Bradford protein assay, silver-stained SDS-Page, and Olink Proteomics (Watertown, MA). Selected samples underwent 3K MWCO protein concentration.

Results

Figure 1B shows the UF protein concentration at several time points. Total protein loss (in mg) during the one-hour simulation was 18 (HF) and 239 (MCO) in the UF, and 10 and 359 in the residual filtrate, respectively. SDS-PAGE protein gel revealed that HF filtrate contained less amount of protein than MCO filtrate when equal filtrate volumes were loaded (Figure 1C, lane 3 vs 2, lane 6 vs 5). Smaller proteins were more abundant in HF vs MCO filtrate when equal amounts of protein were loaded (lane 4 vs 2, lane 7 vs 5). UF from both membranes contained less proteins >100 kD than plasma (lane 1).

Finally, UF (collected at 20 and 60 min) and residual filtrate were concentrated to ∼1mg/ml and analyzed using targeted biomarker analysis with Olink® Target 96 Organ Damage panel. Ten of the 92 panel proteins were above the limit of detection (LOD; Table 1). The MCO-to-HF protein concentration ratio in equal filtrate volumes ranged from 1.7 to 13.1.

Conclusion

Our results show a higher amount of protein loss with MCO compared to HF. The HF filtrate protein distribution is skewed towards lower molecular weights compared to MCO filtrate. All 10 proteins identified were more abundant in MCO filtrate compared to HF filtrate. Further identification and quantification of protein loss during hemodialysis will improve our understanding of the clinical impact of different dialysis membranes.
#3252 PRESEPSIN AS A POTENTIAL BIOMARKER FOR RENAL INVOLVEMENT IN PATIENTS WITH SYSTEMIC LUPUS ERYTHEMATOSUS
Authors: Iaremenko Oleg , Koliadenko Daria , Stepanova Natalia , Iaremenko Kateryna
Published: June 2023

Background and Aims

Presepsin is a soluble CD14 subtype known as a sepsis biomarker. Recently, it has been reported to correlate with kidney function decline in elderly patients with chronic kidney disease and to predict acute kidney injury in patients with sepsis. However, the potential role of presepsin in systemic lupus erythematosus (SLE) with kidney involvement is still unclear. This study aimed to evaluate the relationship between serum presepsin level and SLE disease activity and laboratory parameters and to validate presepsin as a biomarker for lupus nephritis (LN).

Method

This cross-sectional study included 78 SLE patients aged 38.9±12.8 years. Among them, there were 68 (87.2%) women, 36 (46.2%) patients with LN, and 42 (53.8%) patients without LN. LN was diagnosed by renal biopsy and/or according to the renal SLE disease activity index (SLEDAI) criteria. Patients with infections were not included in the study. Serum presepsin level was determined by ELISA. The diagnostic value of presepsin level for the detection of LN was assessed by receiver-operating characteristic curves (ROC), the area under the curve (AUC), and 95% confidence intervals (CI). Spearman and Pearson correlation tests were performed to evaluate the relationships between presepsin level and SLEDAI score, serum complement concentrations, anti-double-stranded DNA antibodies (anti-dsDNA), inflammatory markers, urinary protein, and estimated glomerular filtration rate (eGFR) with CKD-EPI.

Results

The median serum presepsin level was significantly higher in patients with LN than in those without kidney damage [145 (110-197) pg/ml vs 102 (82-146) pg/ml, p = 0.011]. The ROC analysis found that the most appropriate cut-off point for presepsin concentration as a biomarker for LN in LSE patients was 106 pg/ml with a sensitivity of 81.8% (95% CI 64.5-93.0), and specificity of 54.3% (95% CI 36.6-71.2). The AUC was 0.714 (95% CI 0.592-0.837) with a positive predictive value of 62.8% (95% CI 46.7-77.0), and a negative predictive value of 76.0% (95% CI 54.9-90.6) (Fig. 1). The mean value of eGFR was 83.8±27.0 ml/min/1.73 m2 in the LN group and 94.1±18.0 ml/min/1.73 m2 in the non-LN group (p = 0.112). A significant negative correlation was observed between presepsin levels and eGFR in LN patients (Fig. 2). Moreover, presepsin levels in the LN group significantly correlated with SLEDAI score (r = 0.372, p = 0.036), anti-dsDNA titer (r = 0.363, p = 0.04) and severity of proteinuria (r = 0.630, p<0.01). No such associations were found in SLE patients without kidney involvement. Presepsin concentration did not correlate with C3, C4, C-reactive protein, erythrocyte sedimentation rate, and procalcitonin levels in both groups.

Conclusion

Serum presepsin may be considered a potential biomarker for the detection of kidney damage in patients with SLE. Further studies focusing on the clinical and pathological associations of presepsin in LN would be of interest.
#3253 STUDY OF THE EFFECT OF TWO BARIATRIC SURGERY TYPES ON RENAL FUNCTION AND MCP 1 LEVELS
Authors: Sabry Alaa , Bahy Ahmed
Published: June 2023

Background and Aims

Bariatric surgery has been the most effective and permanent treatment for severe obesity and has resulted in significant improvement or reduction of comorbidities due to obesity. To evaluate and compare the outcome of two types of bariatric surgery (LMGB and LSG) on renal functions and urinary MPC-1 level in morbidly obese patients after three months of surgery.

Method

Forty morbidly obese patients underwent bariatric surgery between October 2018 and July 2019. Two types of bariatric surgery were done; laparoscopic mini gastric bypass (LMGB) and laparoscopic sleeve gastrectomy (LSG). Group A include 26 patients underwent LSG and group B include 14 patients.

Results

There were no statistically significant difference in the postoperative mean weight, BMI, neck circumference, WC, Hip circumference, WHR, SBP and DBP in the cases between the 2 types of surgeries (LSG and LMGB) also, there were no statistically significant difference in the mean post urinary MCP1 (73.53±21.25&75.43±26.17,P>0.5), post microalbuminuria (8.83± 6.26 &10.02± 8.6,P>0.05),post urinary creatinine (109.21± 43.22&99.19±48.65,P>0.05), post MCP1/Cr ratio (0.78±0.36&1.01±0.70,P>0.05), post CRP(5.73± 3.04&5.77±3.17, P>0.05), post serum creatinine (0.74±0.05&0.75± 0.07,P>0.05), eGFR (100.32±9.54&104.39±9.54,P>0.05), s.cholesterol, s.HDL and s.TGs in the cases who had either LSG operation (group A) or LMGB operation (group B).

Conclusion

There were no statistically significant difference as regard renal function, urinary MCP-1 level and weight loss between LSG and LMGB.
#3355 GERIATRIC NUTRITIONAL RISK INDEX AND EARLY MORTALITY IN INCIDENT HEMODIALYSIS PATIENTS
Authors: Cho Ajin , Park Ji Hyeon , Kim Do Hyoung , Kim Hyun Kyung
Published: June 2023

Background and Aims

The nutrition status at initiation of hemodialysis (HD) might be associated with early mortality in patients undergoing HD. The Geriatric Nutritional Risk Index (GNRI) is a simple and useful nutritional screening method, and this study aimed to investigate the association between the initial GNRI and mortality in incident patients in the first year after initiation of HD.

Method

A nationwide retrospective cohort study was conducted based on the Korean Renal Data System database. Patients who underwent HD from January 2016 to December 2019 and were eligible for GNRI screening were included. They were followed up until the end of 2020 or study departure. Patients were compared by GNRI quartiles. The primary outcome was all-cause mortality, and a Cox proportional hazard model was used to analyze the association between GNRI and mortality. Accuracy comparison of the models including GNRI or body mass index (BMI) were analyzed by Receiver-operating characteristic curves, and the differences were tested by the DeLong test.

Results

A total of 10,545 patients were included, and the mean age was 63.9 ± 3.7 years. Patients with GNRI < 91.4 at the initiation of HD were older, were more often female, and a lower proportion of them had arteriovenous fistula for vascular access. A high GNRI value at the initiation of HD was associated with low all-cause mortality (hazard ratio (HR) 0.93; 95% confidence interval (95%CI) 0.92–0.94; p <0.001). The group with GNRI < 91.4 (Quartile 1) showed the lowest survival in the first year after HD initiation (p < 0.001). Quartile 1 and Quartile 2 (91.4 – 96.8) showed a significantly increased all-cause mortality (HR 3.64; 95%CI 2.60 – 5.10; p < 0.001 for Quartile 1 and HR 1.55; 95% CI 1.09 – 2.22; p = 0.015 for Quartile 2) in comparison with Quartile 4 (101.4 – 129.6). Risk of cardiovascular mortality was high in the Quartile 1 (vs. Quartile 4; HR 3.16; 95%CI 1.94 – 5.13; p < 0.001). In addition, Area Under the ROC Curve (AUC) values for all-cause mortality were 79.1 (95%CI 77.1–81.2) and 75.9 (95%CI 73.8–78.1) for GNRI and BMI, respectively, and the differences of AUCs were significant (p < 0.001).

Conclusion

This study demonstrates that low GNRI levels are associated with all-cause and cardiovascular mortality in HD patients during the early ESRD period. These findings suggest that GNRI is a significant predictor of mortality in these patients.
#3356 COVID-19 PANDEMIC EFFECT ON HOSPITALIZATION OF HEMODIALYSIS PATIENTS
Authors: Croft Kaitlyn , Zhang Yan , Neri Luca , Carioni Paola , Arkossy Otto , Stauss-Grabo Manuela , Usvyat Len A , Stuard Stefano , Winter Anke
Published: June 2023

Background and Aims

During the COVID-19 pandemic many facets of our lives were affected, including the healthcare systems worldwide. We aimed to assess the hospitalization rates of hemodialysis (HD) patients with confirmed COVID-19 infection (COVID-19+) versus other patients (i.e., patients with no documented COVID-19 infection in the European Clinical Database (EuCliD®)) in 2020 and their relation to HD patients from the pre-pandemic era in 2019.

Method

We included 63,216 HD patients treated in 2019-2020 in NephroCare centers from 23 countries from EuCliD® in the Europe, Middle East, and Africa (EMEA) region. Monthly hospitalization rates (hospital admission per 10,000 patients) were estimated separately for COVID-19+ and other HD patients in 2020, and HD patients treated in 2019, with COVID-19+ status as a time-varying variable. The number of COVID-19 cases and deaths were extracted from data released by the European Commission Joint Research Centre (ECJRC)[1]. The correlation between the monthly hospitalization rates and numbers of COVID-19 cases and deaths in general population (GP) were evaluated.

Results

Characteristics of the approximately 42,000-43,000 monthly treated HD patients were comparable between 2019 and 2020 (Table 1). The hospitalization rates were much higher for COVID-19+ HD patients throughout 2020 compared to other HD patients in 2020 and HD patients in 2019. The hospitalization rates were highest in the spring of 2020 for COVID-19+ HD patients. However, in 2020 other HD patients’ hospitalization rates were lower than the 2019 HD patients’ hospitalization rates. Interestingly the hospitalization rates of other HD patients in 2020 dipped even more below hospitalizations for HD patients in 2019 following the GP pandemic waves (Figure 1). Hospital admission for both COVID-19+ and other HD patients were inversely correlation with the pandemic conditions in GP (Figure 2; spearman correlation coefficients [ρ] with COVID-19 cases/deaths in GP, -0.77/-0.22 and -0.29/-0.64, respectively, for COVID-19+ and other HD patients).

Conclusion

Our study indicated the COVID-19 pandemic had an impact on hospitalization rates of both HD patients with a COVID-19 diagnosis and those patients without a documented COVID-19 infection. Potential reasons of decreased hospitalization rates in patients without a documented COVID-19 diagnosis could be healthcare resource constraints or regarding patient concerns about exposure to COVID-19 in hospital settings [2].
#3386 PROTON-PUMP INHIBITORS AND SERUM CONCENTRATIONS OF UREMIC TOXINS IN PATIENTS WITH CHRONIC KIDNEY DISEASE
Authors: Chamieh Carolla El , Larabi Islam Amine , Laville Solene , Jacquelinet Christian , Combe Christian , Fouque Denis , Laville Maurice , Frimat Luc , Pecoits-Filho Roberto , Lange Céline , Stengel Benedicte , de Pinho Natalia Alencar , Alvarez Jean-Claude , Massy Ziad , Liabeuf Sophie
Published: June 2023

Background and Aims

Use of proton-pump inhibitors (PPIs) is common in patients with chronic kidney disease (CKD). PPIs and many uremic toxins (UTs) are eliminated by a kidney tubular organic anion transporter system. In a cross-sectional study, we sought to evaluate the association between PPI prescription and serum concentrations of various UTs.

Method

We studied a randomly selected subgroup of participants in the CKD-REIN prospective cohort (adult patients with a confirmed diagnosis of CKD and estimated glomerular filtration rate (eGFR) <60ml/min/1.73m²) with available frozen samples collected at baseline. PPI prescription was recorded at baseline. Serum concentrations of 10 UTs were measured using a validated liquid chromatography tandem mass spectrometry technique. Multiple linear regression was performed, with the log UT concentration as the dependent variable.

Results

Of the 680 included patients [median age: 68 years; median eGFR: 32 ml/min/1.73 m2], 31% had PPI prescriptions at baseline. Patients using PPIs had higher levels of certain UTs in comparison to other patients, including total and free indoxyl sulfate (IS), total and free p-cresylsulfate, total and free p-cresylglucuronide (PCG), phenylacetylglutamine (PAG), free kynurenine, and free hippuric acid. After adjustment for baseline comorbidities, number of co-prescribed drugs and laboratory data including eGFR, associations between PPI prescription and elevated serum concentrations of free and total IS, free and total PCG, and PAG remained significant.

Conclusion

Our results indicate that PPI prescription is independently associated with serum UT retention. These findings indicate a potential mechanism for side effect of PPIs in CKD patients that will need to be confirmed by longitudinal studies.
#3404 UTILITY OF RENAL BIOPSY IN THE ETIOLOGY, MANAGEMENT AND OUTCOME OF POSTPARTUM ACUTE KIDNEY INJURY
Authors: Jain Manoj , Bhadauria Dharmandr , Prasad Narayan , Kaul Anupma
Published: June 2023

Background and Aims

Acute kidney injury (AKI) is a serious complication during pregnancy and postpartum period resulting in significant maternal morbidity, mortality and fetal loss. Pregnancy related acute kidney injury is still more prevalent in developing countries. This study aims to evaluate renal biopsies in postpartum period AKI (PPAKI) with etiology and its management and outcome.

Method

Retrospective analysis of 83 native renal biopsies received in the department of pathology, SGPGIMS, Lucknow, a tertiary care center in India with PPAKI from January 2007 to December 2021 were analyzed. Clinical and laboratory data were retrieved and renal biopsy histology slides were reviewed.

Results

Eighty-three patients with mean age 27.5±4.6 years had biopsy proven PPAKI. Cesarian section, vaginal delivery, hysterectomy and abortion were performed in 51, 19, 2 and 11 patients respectively. The cause of AKI was sepsis (38.6%), postpartum hemorrhage (26.5%), thrombotic microangiopathy (TMA) (11%), pre-eclampsia (3.7%) and other (20%). Duration of onset of AKI after delivery/abortion ranged from 0 to 30 days (mean 4.5±6.3 days). Fetal loss was seen in 31.7% patients. Biopsy showed partial/complete renal cortical necrosis (56.6%), TMA (24.1%), acute tubular injury (ATI) (4.8%), Lupus nephritis flare in 3.6% and other glomerular diseases (8.4%) and Tubulointerstitial nephritis in (1.2%) patient. All received multiple sessions of haemodialysis and 10 patients also had plasmapheresis. During hospital stay one died due to sepsis and shock, remainder were discharged in a stable condition with complete recovery in (5), partially recovery in (7); and 61 (71%) patients required continued renal replacement therapy. Two patients died and two had subsequent live related renal transplantation on available follow-up.

Conclusion

AKI is a serious complication in postpartum period and require early and prompt attention to reduce fetal and maternal morbidity. Sepsis is the commonest cause of postpartum AKI
#3412 THE THROMBOTIC EVENTS IN PATIENTS WITH ANCA-ASSOCIATED VASCULITIS: A RETROSPECTIVE COHORT STUDY AND MENDELIAN RANDOMIZATION ANALYSIS
Authors: Chen Xin , Zhang Shuo , You Ruilian , Xia Peng , Shi Xiaoxiao , Ting Wuhai , Wen Yu-Bing , Qin Yan , Chen Limeng
Published: June 2023

Background and Aims

Thrombotic event in ANCA-associated vasculitis (AAV) was prevalent but not clarified in the causal relationship between AAV and thrombotic events. We tried to identify the clinical characteristics and risk factors of thrombotic events in a large sample-size retrospective cohort and investigate the causal relationship by Mendelian randomization (MR) analysis.

Method

In this retrospective, observational study, all hospitalized AAV patients were included in a single-center tertiary hospital in China from Jan 2013 to April 2022. Clinical data were collected for multivariate regression analysis to determine the risk factors of thrombotic events. As for MR analysis, we selected single nucleotide polymorphisms (SNPs) related to AAV from published genome-wide association studies. The outcome data containing deep vein thrombosis (DVT) and pulmonary embolism (PE) were extracted from the UK biobank. The inverse variance weighted (IVW) method and weighted median (WM) were performed in MR analysis.

Results

A total of 1203 primary AAV patients were enrolled, with 11.3% developing thrombotic events, with the average age of 49 (ranging from 43.75 to 59.75), and males occupied 56.3%. AAV patients with thrombosis were older (>65 years, 44.9% vs. 29.9%, P<0.001) and with more commodities like chronic kidney disease (CKD, 22.8%)or artery disease(CAD, 11.8%). The thrombotic incidences were more common in eosinophilic granulomatosis with polyangiitis (EGPA, 19.5%), with prolonged hospitalization without significant difference in hospital mortality. Multivariate regression suggested that age over 65 years (OR = 1.574, P = 0.029), EGPA (OR = 3.686, P = 0.029), elevated D-dimer (>2 mg/L, OR = 7.119, P<0.001), and end-stage renal disease (ESRD) status were associated with thrombosis events in patients with AAV. In addition, MR analysis showed that EGPA could increase the risk of developing DVT and PE (OR = 1.0038, 95%CI = 1.0035-1.0041, P = 0.009).

Conclusion

Thrombotic events were not rare in Chinese patients with AAV with independent risk factors such as highly elevated D-dimer and EGPA, which served as a causal risk factor for DVT and PE.
#3420 CLINICAL CHARACTERISTICS AND PRIMARY OUTCOMES OF PATIENTS WITH ANCA-ASSOCIATED VASCULITIS AND CENTRAL DIABETES INSIPIDUS
Authors: Chen Xin , Zhang Shuo , Xia Peng , Shi Xiaoxiao , Ting Wuhai , Wen Yu-Bing , Qin Yan , Tian Xinping , Zhu Huijuan , Chen Limeng
Published: June 2023

Background and Aims

Anti-neutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV) is characterized by systemic small-vessel vasculitis and may rarely present as central diabetes insipidus (CDI). AAV-associated CDI should be recognized to avoid unnecessary biopsies of the pituitary gland and minimize the risk of irreversible loss of pituitary function. In this study, we aimed to determine the clinical characteristics and prognosis of patients with AAV-associated CDI.

Method

This was a nested case-control study where AAV patients with CDI at the Peking Union Medical College Hospital were followed from January 2012 to April 2022. Case-control matching with AAV patients without CDI was performed (1:2), and participants were matched by age, sex, and AAV classification. We collected clinical data every 3–6 months and conducted a literature review using PubMed to identify relevant articles published from 1983–2022.

Results

Among 1203 hospitalized AAV patients, 16 patients with CDI were included (1.3%). The average age was 49 years, and men accounted for 56.3%. Granulomatosis with polyangiitis (GPA) accounted for 87.5% of patients. AAV patients with CDI had more ear, nose, and throat (ENT) (81.3%) involvement and less renal impairment than those in the control group (P<0.05). After a mean follow-up of four years, 50% of patients were in remission, 37.5% relapsed, and 12.5% died. Our literature review suggested that patients in Asian countries tend to be older men and have higher MPO-ANCA positivity than those in European countries. Furthermore, PR3-ANCA positivity may predict disease recurrence.

Conclusion

AAV patients with CDI had more ENT involvement and a higher eGFR. MPO-ANCA positivity is more commonly observed in Asian countries than in European countries, and PR3-ANCA positivity may predict recurrence.
#3423 DIAGNOSTIC SIGNIFICANCE MAGNETIC RESONANCE IMAGING IN CHRONIC HEART FAILURE OF VARIOUS GENESIS
Authors: Egamberdieva Dano , Ruzmetova Iroda , Khodjibekova Yu M , Karimova Yu A
Published: June 2023

Background and Aims

Based on a comparative assessment of radiological, ultrasound, clinical and laboratory studies, to determine the diagnostic significance of cardio-MRI.

Method

We analyzed echocardiographic and magnetic resonance imaging of the heart in 40 patients who were examined and treated in the cardiology departments of the Republican Medical Specialized Scientific and Practical Center for Therapy and Medical Rehabilitation. The information content of the use of instrumental research methods in patients with chronic heart failure was evaluated. Information on demographic characteristics, including age, gender, education, occupation, was collected from doctors visits using a standard questionnaire.

Results

The average age of patients was 57 years. 40% of the surveyed were made up of men. When studying risk factors for the disease, 49% of all patients had arterial hypertension, 18% had type 2 diabetes mellitus, 21% of patients were active smokers, and 11% had a family history of risk of cardiovascular disease. 36% of patients had a history of myocardial infarction, percutaneous coronary interventions. The mean LV EF was 42% and the mean right ventricular EF (RVEF) was 48%. In patients with CHF of ischemic origin, in the vast majority of cases, the results of echocardiographic and MRI examinations of the heart were comparable. The conducted MRI of the heart had an additional informative value in case of doubtful ECG and EchoCG data, as well as in differential diagnosis. The results of MRI were more accurate in determining the etiology of myocardial hypertrophy, in particular hypertrophic cardiomyopathy.

Conclusion

The diagnostic value of cardio-MRI showed great diagnostic value in the diagnosis of ischemic damage and non-coronary diseases of the myocardium.
#3428 DEPLETED HDAC3 ATTENUATES HYPERURICEMIA-INDUCED RENAL INTERSTITIAL FIBROSIS VIA MIR-19B-3P/SF3B3 AXIS
Authors: Wei Jiali , Wang Minhui
Published: June 2023

Background and Aims

Hyperuricemia (HN) is a threat for the occurrence of renal interstitial fibrosis (RIF). Dysfunctional histone deacetylase 3 (HDAC3) elicit renal fibrosis and damage. This study aimed to explore the role of HDAC3 in HN-induced RIF from microRNA-19b-3p/splicing factor 3b subunit 3 (miR-19b-3p/SF3B3) axis.

Method

1. The HN model was established on rats to induce RIF by oral administration of adenine and potassium oxalate; 2. HN rats were injected with related vectors (sh-HDAC3, mimic-miR-19b-3p, sh-HDAC3+miR-19b-3p inhibitor) to suppress and/or promote HDAC3 and/or miR-19b-3p; The detection indicators are listed as follows: (1) Blood samples and urine samples were collected for UA, BUN, Scr and 24 h urine protein measurement; (2) Renal pathological damages, RIF index and renal cell apoptosis were measured by HE, Masson and TUNEL staining; (3) α-SMA, TGF-β1 and FN contents in renal tissues were detected by IHC staining; (4) mRNA and protein levels of HDAC3, miR-19b-3p and SF3B3 in renal tissues were detected by RT-qPCR and/or WB. (5) Interaction of HDAC3 and miR-19b-3p was detected by ChIP and dual luciferase reporter gene assay; (6) Interaction of miR-19b-3p and SF3B3 was predicted/detected by bioinformatics website/dual luciferase reporter gene assay.

Results

1. HN induced renal dysfunction, renal pathological damages, RIF and renal cell apoptosis of rats; HN rats showed elevated HDAC3, SF3B3 and reduced miR-19b-3p in renal tissues. 2. Suppressed HDAC3 or promoted miR-19b-3p relieved HN-induced renal dysfunction, renal pathological damages, RIF and renal cell apoptosis; HDAC3 bound to the promoter of miR-19b-3p; miR-19b-3p negatively regulated SF3B3; miR-19b-3p depletion abrogated down-regulated HDAC3-induced effects on HN-induced RIF.

Conclusion

HDAC3 bound to the promoter of miR-19b-3p to regulate SF3B3. Depressed HDAC3 relived HN-induced RIF by restoring miR-19b-3p and knocking down SF3B3. Targeting HDAC3 and miR-19b-3p/SF3B3 axis may be a promising therapeutic strategy for preventing HN-induced RIF.
#3434 A FREE OPEN-SOURCE FRAMEWORK TO INFER PATIENT-LEVEL EGFR SLOPES FOR ASSOCIATION WITH MOLECULAR DATA
Authors: Boys Charlotte , Saez-Rodriguez Julio
Published: June 2023

Background and Aims

Unfolding over years or decades, patient kidney disease trajectories can be characterised using routinely collected longitudinal data. One frequently measured marker of kidney function is serum creatinine, used in clinical settings to estimate the glomerular filtration rate (eGFR). Change in eGFR over time has been put forward as a proxy endpoint for clinical trials, and most work on inferring eGFR slopes has been done in this context. However, 'omics-based studies of the molecular mechanisms of kidney disease have so far largely neglected to make use of longitudinal data linked to tissue samples. Here, we build on existing approaches [1, 2] and provide an open-source, R framework to infer eGFR slopes from routinely available clinical data linked to biobank samples.

Method

In our framework, we calculate eGFR from serum creatinine measurements using the CKD-EPI 2021 formula. To aid data adjudication, we implement criteria outlined by Hapca et al. [1] for automatic flagging of acute kidney injury (AKI) events, and extend the criteria to detect potential in-patient stays. Since the biopsy procedure may arise as a result of loss of kidney function and/or coincide with a change in treatment regime, we use a two-spline linear mixed effects model similar to that proposed by Vonesh et al. [2] to differentiate between immediate-post-biopsy (acute) and chronic eGFR slopes. Additionally, to account for non-random dropout due to the onset of dialysis or occurrence of kidney transplant, we jointly model the longitudinal and dropout processes. Our framework is made available as free, open-source software in R.

Results

From routinely collected longitudinal clinical data, we generate patient-specific values characterising the post-biopsy disease trajectory. These values can then be incorporated into the analysis of 'omics data to find molecular patterns associated with treatment response or prognosis.

Conclusion

We have developed an open-source R framework for inferring patient-level eGFR slopes from serum creatinine measurements linked to biobank samples. Leveraging this data could improve 'omics studies of the molecular mechanisms of kidney disease, allowing us to incorporate information about disease trajectory and treatment response and thus ask questions of the molecular data which have real clinical relevance.
#3437 THE ASSOCIATION OF INTERLEUKIN-6 TO ALBUMIN RATIO WITH MORTALITY IN PATIENTS WITH KIDNEY FAILURE
Authors: LI Xiejia , Qureshi Abdul Rashid Tony , Suliman Mohamed , Heimbürger Olof , Barany Franz Peter , Stenvinkel Peter , Lindholm Bengt
Published: June 2023

Background and Aims

Systemic inflammation - characterized by high interleukin-6 (IL-6) and low albumin circulating concentrations - associates with worse outcomes in patients with kidney failure (KF). We examined the value of IL-6 to albumin ratio (IAR) to stratify risk of death in KF patients.

Method

In 435 incident dialysis patients (median age 56 years, 61.8% male, 31% diabetes mellitus (DM), 38.4% cardiovascular (CV) disease (CVD)), plasma IL-6 and albumin were measured at baseline to calculate IAR. We performed receiver operating characteristic curve (ROC) to compare the discriminatory performance of albumin, IL-6 and IAR for predicting all-cause and CV mortality. We divided patients into IAR tertiles and analysed: 1) cumulative incidence of all-cause mortality and CV mortality censored for renal transplantation during follow up of up to 60 months; 2) the association of IAR and all-cause and CV mortality risk according to Fine-Gray analysis taking renal transplantation as competing risk; and 3) the restricted mean survival time (RMST) and differences of RMST (∆RMST) between IAR tertiles to describe quantitative differences of survival time.

Results

Among 435 patients, 146 patients (33.6%) died, and 175 (40.2%) patients underwent renal transplantation during median 24.9 months of follow-up; 83 (56.8%) of the 146 deaths were due to CVD. The area under the ROC curve (AUC) of IAR (0.696 for all-cause mortality; 0.657 for CV mortality) was higher than that of both albumin and IL-6. As shown in Fig. 1 A and B: 1) the cumulative incidence of all-cause and CV mortality of patients in middle and high IAR tertiles was significantly higher than in low IAR tertile; 2) higher IAR associated with higher risk of all-cause (sub-hazard ratio (sHR) 1.93, 95% confidence interval (CI) 1.22-3.06 for high IAR tertile) and CV mortality (sHR 1.99, 95% CI 1.03-3.87 for middle IAR tertile) risk after adjusting for age, sex, DM, CVD, and smoking; and 3) ∆RMST at 59 months showed shorter survival time in middle and high IAR tertiles compared with low IAR tertile for all-cause (∆RMST -6.21 months for middle vs low tertile; ∆RMST -11.4 months for high vs low tertile) and CV mortality (∆RMST -4.73 months for middle vs low tertile; ∆RMST -7.49 months for high vs low tertile).

Conclusion

Higher IAR was independently associated with significantly higher all-cause and CV mortality risk in KF patients. These results suggest that IAR may provide useful prognostic information in patients with KF.
#3447 ENVIRONMENTAL MELAMINE EXPOSURE AND ADVERSE KIDNEY OUTCOMES IN PATIENTS WITH TYPE 2 DIABETES MELLITUS
Authors: Tsai Yi-Chun , Wu Ming-Tsang
Published: June 2023

Background and Aims

The impact of environmental melamine exposure on kidney outcomes in type 2 diabetes (T2D) remains unclear. The aim of this study is to evaluate the relationship between melamine and adverse kidney progression in T2D population.

Method

This longitudinal study enrolled 561 T2D patients during October 2016 and June 2020 and followed until December 2021. Baseline urinary melamine levels were measured by LC-MS/MS, and average daily intake (ADI) of melamine was estimated. Primary kidney outcomes were defined as doubling of serum creatinine levels or end stage kidney disease (ESKD), and secondary kidney outcomes included rapid decline in kidney function as estimated glomerular filtration rate (eGFR) decline > 5 ml/min/1.73m2/year.

Results

Baseline median urinary corrected melamine levels and estimated DI of melamine were 0.8 μg/mmol and 0.3 µg/kg/day in 561 T2D patients. During 3.7 years of follow-up, urinary corrected melamine level was positively correlated with reaching composite outcomes of either doubling of serum creation levels or ESKD and rapid decline in kidney function. Those with the highest quartile of urinary corrected melamine had 2.96-fold risk of composite outcomes of either doubling of serum creation levels or ESKD and 2.47-fold risk of eGFR decline > 5 ml/min/1.73m2/year. Estimated ADI of melamine also had significant correlation with adverse kidney outcomes. Furthermore, the positive relationship between melamine exposure and rapid decline in kidney function was only found in T2D patients with male, baseline eGFR ≥ 60 ml/min/1.73m2 or glycated hemoglobin ≤ 7%.

Conclusion

Melamine exposure is significantly associated with kidney outcomes in T2D patients, especially in those with male, well sugar control or preserved baseline kidney function.
#3505 DIAGNOSING HYPERTENSION IN HEMODIALYSIS PATIENTS USING HOME VERSUS ROUTINE PERIDIALYTIC BP MEASUREMENTS
Authors: Leonidou Kalistheni , Georgianos Panagiotis , Kollias Anastasios , Kontogiorgos Ioannis , Vaios Vasilios , Karligkiotis Apostolos , Mavromatidis Konstantinos , Zebekakis Pantelis , Stergiou George , Liakopoulos Vassilios
Published: June 2023

Background and Aims

Although routine blood pressure (BP) measurements taken shortly before or after dialysis provide imprecise reflection of interdialytic ambulatory BP, this method continues to form the basis for the diagnosis of hypertension among patients on hemodialysis. Home BP monitoring (HBPM) is a guideline-recommended technique that may improve the diagnosis of hypertension in this population. Using 44-hour ambulatory BP monitoring (ABPM) as the reference-standard method, this study aimed to compare the diagnostic performance of home versus routine pre- and postdialysis BP recordings in hemodialysis patients.

Method

In 70 stable patients with end-stage kidney disease receiving thrice-weekly hemodialysis, BP was assessed with the following methods: (i) routine predialysis and postdialysis BP measurements averaged over 2 weeks; (ii) HBPM for 7 days (dublicate morning and evening measurements, Microlife WatchBP Home N); (iii) ABPM (20 min intervals over an entire interdialytic interval - 44 hours, Microlife WatchBPO3).

Results

The mean age of the patients was 65.3±13.3 years; 45 patients (64%) were males, and 62 (88.7%) had a known history of hypertension. The mean [95% confidence interval (CI)] of the difference between ambulatory systolic BP (SBP) and (i) predialysis SBP was 11.43 (8.24, 14.62) mmHg, (ii) postdialysis SBP was 3.9 (0.37, 7.56) mmHg, and (iii) home SBP was 8.61 (6.05, 11.17). The area under the receiver operating characteristic curve for the detection of an ambulatory daytime SBP ≥135 mmHg was significantly higher for home SBP measurements 0.934 (95% CI: 0.871-0.996) as compared to predialysis 0.778 (95% CI: 0.643-0.913) and postdialysis 0.766 (95% CI: 0.623-0.909) BP recordings (P = 0.02 for both comparisons). 1-week averaged home SBP at the cut-off point of 141.0 mmHg provided the best combination of high sensitivity (85.7%) and high specificity (92.9%) in diagnosing systolic ambulatory hypertension.

Conclusion

The present study shows that among patients on hemodialysis, HBPM for 1 week provides greater accuracy than 2-week averaged routine pre- and postdialysis BP recordings in the diagnosis of hypertension confirmed by the reference-standard method of interdialytic ABPM.
#3507 IV CYCLOPHOSPHAMIDE VERSUS MYCOPHENOLATE MOFETIL AS INDUCTION REGIMEN IN PROLIFERATIVE LUPUS NEPHRITIS: A STUDY FROM NORTH-EAST INDIA
Authors: Sharma Manjuri , Bora Farha , Pegu Gayatri , Doley Prodip Kumar
Published: June 2023

Background and Aims

SLE is a chronic autoimmune disorder that can affect all organ systems. Clinically evident renal disease known as Lupus Nephritis (LN) occurs in upto 50% patients of SLE and upto 10% of LN patients develop ESRD. LN carries a significant morbidity and mortality and requires an early aggressive management. Our Aim is to study the effect of IV Cyclophosphamide (CYC) vs Mycophenolate Mofetil (MMF) as Induction regimen in proliferative Lupus Nephritis patients of North- East India.

Method

This is a prospective observational study conducted in the department of Nephrology, Gauhati Medical College, over a period of 1 year. Haematological and biochemical assay including serum creatinine, blood urea, serum albumin, ANA, Anti ds DNA, C3 and C4,24h urinary protein, estimated glomerular filtration rate (eGFR) of all patients were taken into account. Renal biopsy was performed under ultrasonographic guidance. SLEDAI Score and Activity and Chronicity Indexes were calculated for all patients. Statistical analysis was done by SPSS Version 22 for windows. Two tailed p<0.05 was considered to be statistically significant. A total of 64 biopsy proven LN patients of Class III, Class IV and Class V (Plus Class III/ Class IV) were enrolled in the study. We randomly assigned 34 patients with Class III through V lupus nephritis to IV CYC (NIH protocol/monthly) and 30 patients to MMF (2 gm/day) for 24 weeks as Induction Regimen. Both the groups received prednisone, tapered from a maximum starting dosage of 60 mg/day. All the patients were followed up for 6 months. Complete Response (CR) was considered when proteinuria<0.5g/g and Partial Response (PR) when proteinuria< 3g/g or there is reduction in proteinuria by at least 50%. Baseline characteristics and CR and PR were compared between the two groups.

Results

Of the total 64 patients, 57 patients (89%) were female, and 7 patients were male (11%) with the mean age of 31± 9.45 years. 24% patients had Class III LN and 76% had class IV LN. Complete Response was achieved in 13 patients (43%) in the MMF group and in 15 patients (44%) in CYC group. Partial Response was achieved in 11 patients (36.67%) in the MMF group and in 12 patients (35%) in the CYC group. There was a non-significant statistical difference between the two groups (p value ≥0.05 for both CR and PR).

Conclusion

The Northeastern population of India consists of various ethnic groups and there are records of variation in response to the Regimens in different geographical areas. In our study from North-east India, IV Cyclophosphamide and Mycophenolate Mofetil showed similar efficacy as Induction Regimen in proliferative Lupus Nephritis. However, there were higher rates of infection in the Cyclophosphamide group.
#3520 THE RELATIONSHIPS OF BONE TURNOVER MARKERS AND CEREBRAL WHITE MATTER ALTERATIONS IN PATIENTS UNDERGOING HEMODIALYSIS
Authors: Kuo Mei-Chuan , Lin Yi-Ting , Lin Hsiu-Fen , Chen Kung-Chao , Wu Ping-Hsun
Published: June 2023

Background and Aims

Patients with end-stage kidney disease (ESKD) have a higher prevalence rate of cognitive impairment than the general population. ESKD patients also present a worsening brain white matter damage than healthy subjects. Some studies showed a lower bone marrow density was associated with cognitive impairment, but limited studies investigated the relationship between bone turnover biomarkers and brain white matter damage in ESKD patients.

Method

Hemodialysis participants were enrolled in two hemodialysis units from August 2016 to January 2017. Participants' baseline characteristics, bone-turnover proteins, and Fazekas scale of brain magnetic resonance imaging (MRI) white matter lesions were recorded. Fazekas scale of periventricular lesions was defined as cerebral white matter hyperintensities in MRI from grade 0 to grade 3. Multivariable ordinal regression and logistic regression models were analyzed to identify the independent association between bone turnover proteins and the Fazekas scale of periventricular lesions.

Results

In 59 hemodialysis patients, a higher Fazeaks scale of periventricular lesions was found in elderly patients and correlated to a lower Mini-Mental State Examination (MMSE). Among 8 bone turnover proteins, the serum level of sclerostin (SOST) showed a dose-response effect (P value for trend = 0.004), corresponding to a higher level of SOST correlated with a lower grade on the Fazekas scale. After full adjustment with potential confounders, a negative association between SOST and Fazekas scale of periventricular lesions remained in the ordinal regression model (Odds ratio [OR] 0.886; 95% confidence interval [CI] 0.828-0.947, P value <0.001) and in the logistic regression model (OR 0.828; 95% 0.712-0.963, P value = 0.014).

Conclusion

The circulating SOST level was negatively associated with brain white matter damage. Our study result provided a potential link between bone turnover markers and brain damage.
#3521 ASSOCIATION BETWEEN NEPROLITHIASIS AND KIDNEY DISEASE PROGRESSION IN AUTOSOMAL DOMINANT POLYCYSTIC KIDNEY DISEASE PATIENTS: A PROSPECTIVE COHORT STUDY
Authors: Moon Hongran , Ryu Hyunjin , Kim Yong Chul , Park Hayne Cho , Oh Kook-Hwan , Oh Yun Kyu
Published: June 2023

Background and Aims

Nephrolithiasis is a common complication in Autosomal dominant polycystic kidney disease (ADPKD) patients and is known to occur in up to 8% to 36% of the patients. A few in vitro and in vivo studies showed that kidney and ureter stone formation could accelerate renal disease progression in ADPKD. However, its association between nephrolithiasis and renal function deterioration remains unknown in ADPKD patients.

Methods

This is a study from single center prospective cohort called HOPE-PKD. A total of 410 study subjects with abdominal computed tomography (CT) scan within 1 year before the enrollment were analyzed. Study subjects were divided into two groups according to the CT results as follows: Patients with papillary calcification, calyceal stone, ureter stone, or renal stone were classified as a stone group (n = 80, 19.5%), and patients only with renal cyst calcification or without any stones in the kidney and ureter were classified as a no-stone group (n = 330, 80.5%). The primary outcome was defined as the initiation of renal replacement therapy due to end-stage renal disease. The secondary outcome was a composite outcome of a 50% decline in estimated glomerular filtration rate (eGFR), doubling serum creatinine from baseline, or the initiation of renal replacement therapy. The hazard ratios (HRs) and 95% confidence interval (95% CI) for the outcome were analyzed using multivariate Cox regression analysis.

Results

There was no difference in the baseline characteristics between the stone group and the no-stone group. During a median 5.18 [interquartile range 3.41 - 8.03] year of follow-up, the primary and secondary outcomes occurred in 51 (12.4%) and 96 (23.4%) patients, respectively. In the unadjusted Cox regression analysis, there was no significant difference in the survival analysis between the two groups. However, after adjusting possible confounding factors (age, sex, body mass index, eGFR, comorbidity of hypertension and diabetes, serum uric acid, phosphorous and calcium level, results of PKD1 and PKD2 gene analysis, and Mayo classification), the stone group showed an increased risk of the primary and secondary outcome of HR 2.84 (95% CI 1.26 - 6.38; p-value 0.012) and HR 1.83 (95% CI 1.03 - 3.27; p-value 0.041), respectively compared to the no-stone group (Figure 1).

Conclusion

This is the first prospective cohort study showing that nephrolithiasis is associated with poor renal outcomes in patients with APDKD. Further clinical studies of nephrolithiasis in ADPKD patients are warranted to improve renal outcomes.