bluuebunny/crossref_metadata_2025 huggingface dataset:
#2808 REMDESIVIR FOR MODERATE-TO-SEVERE COVID-19 PNEUMONIA IN MAINTENANCE DIALYSIS PATIENTS: A RETROSPECTIVE COHORT STUDY
Authors: Gutierrez Stephanie
Published: June 2023

Background and Aims

Remdesivir has shown better patient outcomes and shorter time to recovery among hospitalized patients with moderate to severe COVID-19 pneumonia. However, data on its safety and efficacy in dialysis patients is lacking.

Method

Dialysis patients with moderate to severe COVID-19 pneumonia who were given remdesivir were matched 1:2 to those who received standard-of-care (SOC) based on age, sex, COVID-19 severity and CKD etiology.

Results

The final cohort comprised 201 patients and 67 were given remdesivir. Median age was 52 years, majority were male (51.7%), 94% were on hemodialysis (94%) and 48% had diabetic nephropathy. The 28-day probability of survival among moderate COVID-19 cases was 100% for both remdesivir and SOC group. In severe cases, the survival probability for remdesivir recipients was lower compared to SOC (67.63% vs 87.72%), but this was not statistically significant. Overall, median length of stay (LOS) was significantly shorter by 17 days (QR: 11-24) in the remdesivir group, compared to 21 days [IQR: 16-24] in the SOC group (p = 0.0485). Median LOS in the remdesivir group was only significantly shorter in those with moderate COVID-19 pneumonia but not in severe cases. Early administration of remdesivir resulted in a significantly shorter LOS with a median of 10 days [IQR: 7-15] compared to18 days [IQR: 13-25] in the SOC group (p = 0.0240). When stratified by severity, there was no significant difference whether remdesivir was given early or late.

Conclusion

Remdesivir administration within 48 hours of admission in maintenance dialysis patients with moderate COVID-19 pneumonia resulted in a significantly shorter LOS. However, there was no significant difference in 28-day mortality in early or late administration of remdesivir in both moderate and severe COVID-19 pneumonia among HD patients. Thus, survival was similar to SOC. Our study showed that it is safe to use in dialysis patients.
#2813 INCREASED RISK OF CARDIOVASCULAR DISEASE PRECEDING DIAGNOSIS OF INCIDENT ANCA-ASSOCIATED VASCULITIS: A DANISH NATIONWIDE STUDY
Authors: Pedersen Louis Nygaard , Polcwiartek Christoffer , Nelveg-Kristensen Karl-Emil , Carlson Nicholas , Kristensen Salome , Torp Christian , Gregersen Jon Waarst
Published: June 2023

Background and Aims

ANCA-associated vasculitis (AAV) is associated with an increased risk of cardiovascular disease (CVD). The risk of CVD seems to be increased shortly after initial diagnosis as well as in the long-term setting. However, no studies have addressed the risk of CVD in the period preceding an AAV diagnosis. Since the diagnosis of AAV often is associated with a substantial diagnostic delay, we hypothesize that patients with AAV consistently are at an increased risk of developing CVD already before they even are diagnosed with AAV.

Method

Using a nested case-control framework, patients with AAV were identified through the Danish Nationwide Registries from 1996-2021 and matched 1:3 with age- and sex-matched controls without AAV. Each control was assigned the same index date (date of AAV-diagnosis) as their corresponding case. Conditional logistic regression was used to compute age, sex and comorbidity adjusted Hazard Ratios (HRs) for major adverse cardiovascular events (MACE), ischemic heart disease, heart failure, venous thromboembolism, atrial fibrillation, ischemic stroke, pericarditis, and ventricular arrhythmias/ICD-implantation/cardiac arrest (VA/ICD/CA) within 12 months, 6 months, 3 months, 2 months and 1 month before the index date.

Results

A total of 2371 patients with AAV (median age: 63 yrs, 53.7% male) were matched with 7113 controls. In patients with AAV, 10.33% had a cardiovascular outcome within 12 months preceding diagnosis as compared to 3.84% of controls (HR 3.05 [95% CI, 2.48-3.75]). The associated risk of cardiovascular outcomes was similarly increased in the temporal proximity of the diagnosis, with the highest HR at 1 month prior to index date (HR 10.73 [95% CI, 7.05-16.32], Fig. 1). In individual analysis, a significantly higher HR was observed for all outcomes (excluding VA/ICD/CA), Fig. 2.

Conclusion

AAV disease is associated with an increased risk of CVD in the months preceding diagnosis, which underlines the importance of early clinical vigilance toward CVD starting in the diagnostic phase of AAV.
#2868 PREDICTION OF MAJOR GASTROINTESTINAL BLEEDING EVENTS IN HEMODIALYSIS
Authors: Larkin John , Lama Suman , Chaudhuri Sheetal , Willetts Joanna , Winter Anke , Jiao Yue , Stauss-Grabo Manuela , Usvayt Len , Hymes Jeffrey , Maddux Franklin , Wheeler David C , Stenvinkel Peter , Floege Jürgen
Published: June 2023

Background and Aims

INitiativeS on advancing Patients’ outcomes In REnal disease (INSPIRE) is an academia and industry collaboration set forth to identify critical investigations needed to advance the practice of medicine in nephrology. At the inaugural INSPIRE meeting, the group came to a consensus that major bleeding events represent potentially preventable complications that occur more frequently in people with kidney disease versus the general population [1]. Given the most common class of bleeding event is gastrointestinal bleeding (GIB) [2], the INSPIRE group assessed if a machine learning model could be developed to assist with determining a hemodialysis (HD) patient's 180-day GIB hospitalization risk.

Method

Model was developed using adult HD patient data from United States (2017-2020). Patient data was randomly split (50% training, 30% validation, and 20% testing). HD treatments ≤180 days before GIB hospitalization were classified as positive observations, and others were negative observations. Datasets were randomly sampled to build an XGBoost model that considered 386 exposures initially and was refined to the top 50 exposures. Unseen testing dataset was used to determine final model performance.

Results

The incidence of 180-day GIB hospitalization was 1.18% in the HD population (n = 451,579), and 1.16% among patients in the testing dataset (n = 27,991). The model showed an area under the curve = 0.69, sensitivity = 57.9%, specificity = 68.9%, accuracy = 68.8% and balanced accuracy = 63.4%. Exposures with largest effect size observed via Shapley values were older age (group mean GIB event = 68.2 years vs no GIB event = 63.4 years), shorter days since last all-cause hospital admission (group mean GIB event = 203.2 days vs no GIB event = 253.2 days), and higher serum 25-hydroxy (OH) vitamin D levels from most recent lab (group mean GIB event = 33.4 ng/mL vs no GIB event = 30.5 ng/mL). Other important predictors included lower hemoglobin and iron indices, longer dialysis vintage, and proton pump inhibitor use (Fig. 1).

Conclusion

The machine learning model appears suitable for early detection of GIB event risk in HD, yet prospective testing is needed. The association between higher 25OH vitamin D and GIB events was unexpected and warrants investigation. A consistent signal has been observed in warfarin users without kidney disease among which 25OH vitamin D levels of 30–100 ng/mL were shown to associate with the highest GIB risk [3].
#2892 CRITICAL ROLE OF SERUM RESPONSE FACTOR IN PODOCYTE EPITHELIAL–MESENCHYMAL TRANSITION OF DIABETIC NEPHROPATHY
Authors: Zhao Long , Xu Yan
Published: June 2023

Background and Aims

To investigate the expression and function of serum response factor (SRF) in podocyte epithelial–mesenchymal transition (EMT) of diabetic nephropathy (DN).

Method

Expression of SRF, pSRF, synaptopodin, P-cadherin, ZO-1, α-SMA, FSP-1, fibronectin and collagen-1 were examined in podocytes or renal cortex following high glucose. SRF was upregulated by SRF plasmids and downregulated by CCG-1423 to investigate how SRF influence podocyte EMT in DN. Streptozocin was used to generate DM in rats.

Results

① High glucose induced EMT and SRF upregulation in podocytes (Figure 1). High glucose suppressed synaptopodin and ZO-1 expression, and induced SRF, pSRF collagen-1, FSP-1 and α-SMA expression. SRF transferred from cytoplasm to nuclei obviously and the level of SRF was also increased in podocytes after high glucose treatment. ② SRF overexpression mediated EMT, migration and barrier dysfunction of podocytes (Figure 2). Overexpression of exogenous SRF reduced epithelial synaptopodin expression, and increased collagen-1, FSP-1, α-SMA and Snail expression in podocytes. Transwell chamber migration assay showed that overexpression of SRF significantly upregulated the migration of podocytes across the pores of transwell filters. Albumin filtration assay showed that albumin easily diffused across the monolayer of podocytes transfected with SRF cDNA. ③ Inhibition of SRF preserved phenotypes of podocytes in vitro (Figure 3). CCG-1423 selectively suppressed the expression of pSRF and SRF in podocytes after high glucose stimulation. Besides, simultaneous treatment of podocytes with CCG-1423 also significantly abolished the reduction of synaptopodin expression and the induction of collagen-1, FSP-1, α-SMA and Snail expression. CCG-1423 also reduced the transfer of SRF from cytoplasm to nucleus in podocytes treated with high glucose. ④ The effect of CCG-1423 in diabetic rats (Figure 4–-5). CCG-1423 significantly abrogated the reduction of synaptopodin expression and the induction of SRF, collagen-1, α-SMA and FSP-1 expression in renal cortex tissues. Masson and PAS staining demonstrated that renal glomerular fibrosis was present in DM group, and after 8 weeks treatment with CCG-1423, renal glomerular fibrosis was dramatically ameliorated. In addition, CCG-1423 significantly preserved P-cadherin expression and suppressed α-SMA and FN expression in DN rats. More importantly, CCG-1423 dramatically decreased 24-h urine protein excretion by about 50%, and increased serum albumin, compared with DM group.

Conclusion

Together, increased SRF activity provokes podocytes EMT and dysfunction in DN. Targeting SRF by small molecule inhibitor may be an attractive therapeutic strategy for DN.
#2912 HYDRATION STATUS IN PATIENTS ON STANDARD HEMODIALYSIS OR ONLINE HEMODIAFILTRATION: ITS RELATIONSHIP WITH PARAMETERS MEASURED OR ESTIMATED BY BIVA
Authors: Vega Nicanor , Alman Francisco Alonso , López Yanet Parodis , Ortega Sebastian Hillebrand , Anton-Perez Gloria
Published: June 2023

Background and Aims

Altered fluid status and inadequate fluid management, independently and concurrently with depletion of lean mass adversely affect patients’ quality of life, outcomes and prognosis of hemodialysis (HD) patients, both standard (HD) and Hemodiafiltration on-line (HDFOL).

Method

We conducted a population-based on 470 patients, retrospective longitudinal cohort study, to determine the physical characteristics of bioimpedance measurements and indexes obtained by BIVA on maintenance HD and HDFOL patients, and to analyze the hydration status of the extra and intracellular compartments. The Propensity Score Matching (PSM) procedure, matches case records with similar control records. It first runs a logistic regression with the case/control group variable as the dependent variable. Then it selects a match for each case from the control group based on the PSM from the logistic regression. Euhydrated and Overhydrated groups were macheted separately.

Results

see Table 1, Figure 1 and 2.

Conclusion

1) Compared to standard HD, the HDFOL technique maintains a better water balance between the intracellular and extracellular spaces, especially when the patient is euhydrated. In overhydrated patients, although the ECW/ICW ratio is high, it is lower in patients on HDFOL. 2) The stability of cell membranes in HDFOL is better than in HD. 3) For an adequate assessment of any of the parameters measured directly or derived from the BIA, it must be a “sine qua non” condition that the patient is in a state of euhydration. 4) In hemodialysis patients, the phase angle, must first be considered as a marker of hydration status, and then as a marker of nutritional status.
#2920 MAGNESIUM DEFICIENCY ABROGATES THE RENOPROTECTIVE EFFECT OF DPP-4 INHIBITOR ON CISPLATIN-INDUCED KIDNEY INJURY
Authors: Iwakura Takamasa , Ema Chiemi , Fujikura Tomoyuki , Fukasawa Hirotaka , Yasuda Hideo
Published: June 2023

Background and Aims

Cisplatin is an effective chemotherapeutic agent, but often induces acute kidney injury (AKI). Magnesium (Mg) deficiency is often found in cancer patients, and the nephrotoxicity of cisplatin is exacerbated under Mg deficiency [1]. We previously reported the potential of Dipeptidyl peptidase-4 (DPP-4) inhibitor to attenuate cisplatin nephrotoxicity in rats and diabetic cancer patients [2, 3]. However, it remains to be investigated whether DPP-4 inhibitor can preserve its renoprotective effect under Mg deficiency. The purpose of this study was to examine whether DPP-4 inhibitor can prevent cisplatin-induced AKI even under Mg deficiency.

Method

Sprague Dawley rats received Mg-deficient diet for 7days to induce Mg deficiency. AKI was induced in rats by injecting cisplatin intravenously. Oral administration of a DPP-4 inhibitor, once a day, was started 1day before injecting cisplatin. Mg sulfate was once injected intraperitoneally just before injecting cisplatin to correct Mg deficiency (Fig. 1A). By using our previous cohort data [3], we divided diabetic cancer patients treated with high-dose cisplatin (>50 mg/m2)-containing regimens into 4 groups according to the use/unused of Mg sulfate or DPP-4 inhibitor. The change of estimated glomerular filtration rate (eGFR) within 2 weeks after cisplatin treatment was compared between the groups.

Results

At the peak of AKI (day 5), Mg sulfate supplementation significantly attenuated the increase of blood urea nitrogen (BUN), and combination of Mg sulfate and DPP-4 inhibitor further suppressed the increase of BUN as compared to rats received only cisplatin. However, DPP-4 inhibitor alone did not attenuate the increase of BUN under Mg deficiency (Fig. 1B). The result of serum creatinine (sCr) was consistent with that of BUN (Fig. 1C). This effect was associated with a reduced renal cell death as evaluated with the terminal uridine nick-end labeling (TUNEL)+ cells (Fig. 1D).The change of eGFR was significantly less in the patients treated with both of DPP-4 inhibitors/Mg supplementation, compared to those without DPP-4 inhibitors/Mg supplementation. The effect was not found in patients with either DPP-4 inhibitor alone or Mg supplementation alone as compared to those without DPP-4 inhibitor/Mg supplementation (Fig. 2).

Conclusion

Our results suggested that Mg deficiency must be corrected to exert the renoprotective effect of DPP-4 inhibitor on cisplatin nephrotoxicity. The molecular mechanisms underlying this phenomenon remain to be defined.
#2934 SGLT-2 INHIBITORS DELAY KIDNEY FAILURE PROGRESSION AND REDUCE NEED OF DIALYSIS IN CHRONIC KIDNEY DISEASE PATIENTS: A META-ANALYSIS
Authors: Mahendra Aditya Indra , Samsu Nur , Gunawan Atma , Rifai Achmad
Published: June 2023

Background and Aims

chronic kidney disease (CKD) is the main complication of type 2 diabetes mellitus (type 2 DM) with up to 7 million cases requiring dialysis therapy. The newest type 2 DM therapy, sodium-glucose co-transporter-2 inhibitor (SGLT-2 inhibitor), has developed into an attractive option for patients with comorbid CKD because of its effect on blood pressure and albuminuria, in addition to its effect on lowering blood sugar. Therefore, we conducted a systematic review and meta-analysis aimed at assessing the effect of SGLT-2 inhibitors in preventing the progression of renal failure and the need for dialysis in CKD patients with and without type 2 DM.

Method

We performed an analysis of randomized controlled trials of SGLT-2 inhibitors reporting renal outcomes in patients with and without type 2 DM. We searched the PUBMED, MEDLINE, and CENTRAL databases from baseline to August 2022 to identify suitable studies. The major outcome evaluated was the combination of a persistent increase in serum creatinine two times from baseline and the need for dialysis.

Results

Of the 2890 identified articles, ten studies were included in the inclusion criteria assessing the effect of using SGLT-2 inhibitors. Out of 76,312 participants, 1716 participants experienced a 2-fold increase in serum creatinine, and 647 participants required dialysis. The use of SGLT-2 inhibitors significantly reduced progressive renal failure and the need for dialysis in both patients with type 2 DM (RR: 0.65, 95% CI 0.60–0.71, p = 0.000) and patients without type 2 DM (RR: 0.59, 95% CI 0.46–0.77, p = 0.000). Subgroup analysis also showed that SGLT-2 inhibitors showed a significant effect in the group with eGFR > 60 ml/min (RR: 0.53, 95% CI 0.45-0.62, p = 0.000) and the group with eGFR 30- 60 ml/min (RR:0.66, 95% CI, 0.57-0.75, p = 0.000).

Conclusion

SGLT-2 inhibitors can significantly inhibit the progression of CKD and reduce the risk of needing dialysis in patients with and without type 2 DM. These effects were shown consistently across groups with varying baseline eGFR values.
#2938 DE NOVO DSA IS ASSOCIATED WITH HUMAN PERIPHERAL BLOOD CXCR5+PD-1+CD8+ T CELLS AND PD-1 PD-L1 MRNA EXPRESSION IN KIDNEY TRANSPLANT PATIENTS
Authors: Ekinci Nurten Sayin , Kocak Huseyin , Ucar Fahri , Yilmaz Vural Taner , Darbas Sule , Kisaoglu Abdullah , Kilinc Yahya , Aydinli Bulent , Uzuner Sezin Yakut
Published: June 2023

Background and Aims

Donor-specific antibody (DSA) development is mainly responsible for chronic antibody-mediated rejection. The immunological events that cause the development of DSA is not fully elucidated. The relationship between the Follicular Cytotoxic T cell subgroup and the development of DSA is unknown. In this study we aimed to examine CD8+CXCR5+PD-1+ follicular cytotoxic T cell levels and expression levels of PD1/PD-L1 genes in peripheral blood lymphocytes in recipients who de-novo DSA positive or negative after kidney transplantation (KTX).

Method

In this study, the expression levels of PD-1, PD-L1 genes were determined using the Real-Time Quantitative PCR method from peripheral blood samples of 22 KTX patients with de-novo DSA positive, 20 KTX patients with DSA negative and 21 healthy control (Table 1). Our patient groups were PRA negative before transplantation. Expression (%) levels of target cells were evaluated by flow cytometry method. IBM SPSS Statistics for Windows Version 22 and R.3.3.2 software were used to evaluate the data.

Results

PD-1 expression level was higher in the KTX patients with de-novo DSA positive compared to the KTX patients with DSA negative group (p:0.006 CT: 0,84±0,23). According to the results of flow cytometry, CD8+CXCR5+PD-1+ cell expression (%) levels were found to be significantly higher in patients (3,06±1,98) compared to the transplant control group (0,52±0,40) (p: 0.001) (Figure 1).

Conclusion

It shows that there may be a direct correlation between DSA and PD-1 / PDL-1 mRNA level and CXCR5+PD1+CD8+ follicular cytotoxic T cell in transplant patients after kidney transplantation.
#2948 β-2-MICROGLOBULIN AND β-TRACE-PROTEIN DO NOT IMPROVE ESTIMATION OF GFR IN KIDNEY TRANSPLANT RECIPIENTS COMPARED TO CREATININE AND CYSTATIN C
Authors: Kure Nathalie , Krogstrup Nicoline , Oltean Mihai , Jespersen Bente , Birn Henrik , Nielsen Marie Bodilsen
Published: June 2023

Background and Aims

Precise estimates of glomerular filtration rate (eGFR) are important in kidney transplant recipients (KTRs). Current eGFR formulas based on plasma creatinine and/or cystatin C are associated with significant bias. We investigated whether race free formulas based on plasma values of β-trace-protein and β-2-microglobulin performed better than formulas based on creatinine and cystatin C in a Scandinavian cohort of KTRs.

Method

We included samples and data from the randomised, controlled trial CONTEXT. GFR was measured by plasma clearance of 51Cr-EDTA or iodothalamate. eGFR was calculated using the new race-free CKD-EPI eGFR-creatinine and/or cystatin C(2021) formulas as well as the CKD-EPI eGFR-β-trace-protein and/or eGFR-β-2-microglobulin formulas. GFR estimates were evaluated at 3 (n = 82) and 12 (n = 64) months post-transplant using mean bias, precision, and accuracy. Also, formulas were analysed for their ability to correctly classify changes in measured GFR from 3 to 12 months.

Results

At 12 months eGFR-creatinine-cystatin C performed best according to mean bias (−4.54 ml/min/1.73 m2), precision (SD = 8.18 ml/min/1.73 m2) and accuracy (P10 = 47%) among creatinine and cystatin C based formulas (Table 1). Among the β-trace-protein and β-2-microglobulin based formulas, eGFR-β-trace-protein-β-2-microglobulin performed best according to precision (SD = 7.64 ml/min/1.73 m2) and accuracy (P10 = 36%) (Table 1). eGFR-β-trace-protein-β-2-microglobulin and eGFR-creatinine-cystatin C performed similar when comparing residuals (p = 0.481). eGFR-β-trace-protein, eGFR-β-trace-protein-β-2-microglobulin and eGFR-creatinine-cystatin C performed best in correctly classifying changes in mGFR from 3 to 12 months.

Conclusion

β-trace-protein and β-2-microglobulin do not improve the measurement of GFR compared to creatinine and cystatin C based formulas in KTRs.
#2964 THE ROLE OF RENAL DYSFUNCTION DURING ANTICOAGULANT USE IN COPD PATIENTS WITH ATRIAL FIBRILLATION
Authors: Karimdjanova Guzal
Published: June 2023

Background and Aims

Renal dysfunction is known to be the most important predictor of outcome in patients with atrial fibrillation (AF). Purpose of the study was to evaluate the prognostic role of kidney dysfunction in terms of possible cardiovascular events and bleeding in patients with COPD and AF treated with oral anticoagulants.

Method

We examined 56 COPD patients with CHF and AF who received oral anticoagulants. Renal function (creatinine level and estimated glomerular filtration rate - eGFR) was assessed at baseline and at follow-up. The functional state of the kidneys was calculated using the CKD-EPI-2011 formula. Initially, the risk of bleeding was assessed using the HAS-BLED score. The deterioration of the functional state of the kidneys was noted with an increase in the level of creatinine or a decrease in eGFR by at least 20%.

Results

In addition to the standard treatment for COPD in the presence of AF, patients received oral anticoagulants during a six-month follow-up. The deterioration of the functional state of the kidneys was observed in 18.3% of patients. In patients with kidney dysfunction, the frequency of episodes of CHF decompensation and non-massive bleeding (MB) was significantly higher. When reduced glomerular filtration rate did not affect the frequency of bleeding and stroke. The oral anticoagulants used did not significantly affect the observed renal dysfunction and did not affect the occurrence of new cardiovascular events in patients with COPD. It turned out that the predictors of renal dysfunction in patients with COPD are age, female gender, and lower hemoglobin levels. In multivariate analysis, renal dysfunction was identified as an independent predictor of non-massive bleeding (OR 2.04, 95%, p<0.05).

Conclusion

In patients with COPD and atrial fibrillation, the presence of kidney dysfunction was an additional aggravating factor associated with adverse cardiovascular prognosis in the medium term and the risk of bleeding. However, oral anticoagulants did not affect the degree of deterioration in renal function or the incidence of cardiovascular events.
#2965 DYNAMICS OF THE FUNCTIONAL STATE OF THE KIDNEYS IN PATIENTS WITH DIABETES MELLITUS AND A HIGH RISK OF CI-AKI AND THE USE OF PREVENTIVE MEASURES
Authors: Nigmonov Baxodir , Muminov Shavkat , Saipova Durdona
Published: June 2023

Background and Aims

Analysis of the pathogenetic mechanisms of the development of contrast nephropathy in patients with coronary artery disease on the background of type 2 diabetes mellitus and the effectiveness of the proposed preventive measures.

Method

The study included 56 patients with type 2 diabetes, the average age of the patients was 58 years, the CG consisted of 20 healthy persons. In most patients, the reason for which the endovascular radiopaque procedure (EVRCP) was performed was associated with atherosclerotic lesions: coronary artery disease, chronic lower limb ischemia (CLLI), atherosclerosis of the brachiocephalic arteries (BCA). EVRCP was performed on the vessels of the coronary basin, BCA, abdominal aorta and its branches, lower extremities. A retrospective analysis included a comparative analysis of two groups of patients with type 2 diabetes who underwent (EVRCP): 29 patients who developed CI-AKI (CI-AKI+ group) and 27 patients in whom the post-procedure period was uneventful. CI-AKI was defined as an increase in venous creatinine concentration of more than 25% by the end of 48 hours after EVRCP. During this phase of the study, the patient's medical history was analyzed - their anamnestic data, glycemic status, general urinalysis, kidneys, estimated glomerular filtration rate (eGFR) initially, 2,4,6,8 and 10 days after the procedure.

Results

The CI-AKI+ and CI-AKI- groups were compared in terms of clinical and anamnestic, hematological, urological data and the results of echocardiography and renal ultrasound with each other and with representatives of the CG. The CI-AKI+ and CI-AKI- groups did not differ in nosological distribution (Fig. 1): in both groups, half of the patients with EVRCP were performed due to the presence of coronary pathology (51.72% and 48.15%, respectively), the rest in patients it was comparable for CCI and CVD (27.59% and 20.69% in the CI-AKI+ group and 25.93% each in the CI-AKI- group).

Conclusion

Taking into account the OR of CI-AKI in patients with DM in the presence of identified predictors, a risk scale was developed. A risk score of 28 points or more demonstrates a predictive sensitivity in terms of the development of CI-AKI of 96.55% (p<0.001).
#2971 LONG-TERM EFFECTS OF THE NEW NORDIC RENAL DIET ON PHOSPHOROUS HOMEOSTASIS IN PATIENTS WITH CHRONIC KIDNEY DISEASE STAGE 3 AND 4
Authors: Hansen Nikita Misella , Kamper Anne Lise , Rix Marianne , Feldt-Rasmussen Bo , Pareek Manan , Sørensen Mads Vaarby , Berg Peder , Leipziger Jens , Astrup Arne , Salomo Louise
Published: June 2023

Background and Aims

Chronic kidney disease (CKD) causes severe disturbances in phosphate metabolism. The New Nordic Renal Diet (NNRD) is a whole food approach designed by our group, with low dietary phosphorus content (850 mg/day). In a 1-week study, NNRD had positive effects on phosphorus homeostasis in patients with CKD stage 3-4 [1]. The aim of the present study was to examine the long-term health effects of a dietary intervention with NNRD in patients with CKD stage 3-4 [2].

Method

A 26-week randomized, controlled, non-blinded trial comparing the effect of NNRD vs. non-restricted habitual diet. Patients in the NNRD group received weekly home delivery of fresh food items (free of charge) and recipes for five days of the week, and on the remaining two days they were instructed to prepare meals according to the NNRD food principles. The study was designed with seven follow-up visits in the outpatient clinic where fasting blood samples and 24-hour urine collection were delivered. Linear mixed-effects models were used to assess the effects of the intervention, time, and the potential interaction between intervention and time. The primary endpoint was the difference in 24-hour urine phosphorus excretion between the two study groups. Secondary endpoints included fractional phosphorus excretion and plasma fibroblast growth factor 23 (p-FGF23).

Results

Sixty patients (mean age 54 years, 31 women) with mean eGFR of 34 ml/min/1.73 m2 were included. Two patients were withdrawn due to dialysis initiation. In the NNRD-group (n = 29), mean 24-hour urine phosphorus excretion during the intervention period was 651 mg (SD, 35 mg) vs. 930 mg (SD, 84 mg) in the control group (n = 29), between-group difference 279 (95% CI; -372, -91; P < 0.001) (Figure 1). Mean fractional phosphorus excretion was 11% (SD, 5%) in the NNRD-group and 14% (SD, 7%) in the control group, between-group difference 3% (95% CI; -6.4, -0.8; P = 0.01). Mean p-FGF23 was 162 pg/ml (SD, 130 pg/ml) in the NNRD-group and 215 pg/ml (SD, 230 pg/ml) in the control group, between-group difference 52 pg/ml (95% CI; -100, 73; P = 0.03). P-urea was 3.4 mmol/L lower in the NNRD group (95% CI; -5.3, -0.2, P = 0.03). P-albumin was 1.1 g/L higher in the NNRD group (95% CI; 0.02, 2.4; P = 0.04) and 24-h urine bicarbonate excretion was 4.1 mmol higher in the NNRD group (95% CI; 0.7, 7.5, P = 0.01). There was no difference between study groups in p-phosphorous, p-creatinine, p-potassium, p-calcium, p-lipids, or proteinuria.

Conclusion

NNRD intervention in the context of fresh food delivery and recipes was feasible and had a major beneficial effect on phosphorous parameters in patients with CKD 3-4.
#3023 KARYOMEGALIC INTERSTITIAL NEPHRITIS SECONDARY TO FAN1 VARIANTS: CHARACTERIZATIONS AND OUTCOMES. RESULTS OF THE FAN1 STUDY GROUP
Authors: Michelle Clince , Elhassan Elhussein , Bleyer Anthony , Mcanallen Susan , Kidd Kendrah , Conlon Peter
Published: June 2023

Background and Aims

Karyomegalic Interstitial Nephritis (KIN) is a rare monogenic disorder caused by biallelic variants in Fanconi Anaemia-associated Nuclease 1 (FAN1), a gene involved in DNA repair. Less than 50 cases have been reported in the literature. Affected individuals suffer from kidney and pulmonary disease and increased susceptibility to cancer. In this international study, we report comprehensive clinical and genetic data on 32 individuals with FAN1-defined KIN.

Method

We performed a comprehensive literature review and an online survey to compile updated data of new and published cases via the FAN1 Study Group. Data collected included genotype, age at diagnosis, initial cause of presentation, kidney progression, transplantation status, and occurrence of cancer and pulmonary disease.

Results

Clinical and genetic data were obtained on 32 individuals, 20 previously unpublished. A total of 27 disease-causing variants in FAN1 were identified, predominantly protein-truncating alleles (see table 1). The median age of initial presentation was 39 years (range 1–69), and 26 (81%) were males. Kidney biopsy was performed in 15 individuals, where characteristic tubular karyomegaly was observed in all biopsies. Extrarenal manifestations were observed in 13/32 (40%) individuals and included liver dysfunction (9%), respiratory disease (22%) and malignancy (9%). At last assessment, 15 (46%) individuals progressed to end-stage kidney disease at an average age of 37.2 years (range 27 to 48 years). Eight (25%) individuals received a kidney transplant at a mean age of 45.1 years (range 34 to 62 years). 25% of individuals with a FAN1 variants developed a malignancy post-transplant. Overall mortality in this group was 12.5% (n = 4). 37.5% (n = 3) of transplant recipients died. One patient died from lung cancer 2.5 years post-transplant, another died from pulmonary aspergillosis 10 years post-transplant and a third died 10 years post-transplant due to interstitial lung disease. Post infectious respiratory failure was the cause of death for the remaining non-transplanted patient.

Conclusion

FAN1 variants result in a high burden of kidney failure and extrarenal comorbidities in this young population group. Incidence of malignancy was almost double that which has been reported in the general transplant population. This result may suggest that careful consideration and counselling should be provided to patients with FAN1 prior to transplantation given their potential for increased risk of malignancy and respiratory failure. In this study, international collaboration has provided new clinical and genetic data for 20 cases of FAN1 not previously published adding to our understanding of the natural history of a very rare disease. Please contact michelleclince@gmail.com if you have a case that you could contribute to our survey.
#3047 A NEW ADJUNCTIVE THERAPY WITH AVACOPAN FOR ANCA-ASSOCIATED VASCULITIS
Authors: Yoshii Ryuichi , Kajiwara Kengo , Matsushita Koki , Nakamura Tomohumi , Tomita Masao , Mukoyama Masashi
Published: June 2023

Background and Aims

Glucocorticoids have been the standard treatment for anti-neutrophil cytoplasm autoantibody-associated vasculitis (AAV). Avacopan, a complement C5a receptor inhibitor, has been approved for the treatment of AAV in Japan, the USA, Germany, and Austria. The use of avacopan is supported by evidence from trials demonstrating disease remission with limited use of glucocorticoids [1–3]. Avacopan is a new, promising adjunctive agent for standard induction therapy for AAV and may potentially reduce steroid use.

Method

We assessed treatment responses of patients with AAV who did not require dialysis between 2018 and 2023. Group 1 consisted of six adult patients who were treated with avacopan (30 mg, twice daily) plus reduced-dose prednisone, and Group 2 consisted of 14 patients who received high-dose prednisone. We compared the mean dose of prednisone, Birmingham Vasculitis Activity Score (BVAS), creatinine, urine protein/creatinine ratio (UPCR), and C-reactive protein (CRP) at weeks 0 and 12 between the two groups.

Results

The mean total prednisone dose of oral glucocorticoids at both weeks 0 and 12 was much lower in Group 1 than in Group 2 (p<0.05). Mean BVAS, creatinine, UPCR, and CRP in Group 1 was comparable to Group 2. Steroid-related toxicity occurred in three of six (50%) patients in Group 1, and 5 of 14 (36%) patients in Group 2. Liver damage related to avacopan occurred in two of six (33%) patients in Group 1.

Conclusion

Herein, we describe practice observations on the use of avacopan in patients with AAV. While further studies are needed to confirm the efficacy of avacopan because the number of cases treated with avacopan is still lacking, our findings suggest that avacopan was beneficial in AAV patients because of the absence of steroid dependence.
#3062 ROLE OF ONLINE HEMODIAFILTRATION (OL-HDF) IN THE CONTINUOUS MEASUREMENT OF THE DIALYSIS DOSE
Authors: Alman Francisco Alonso , López Yanet Parodis , Ortega Sebastian Hillebrand , Vega Nicanor , Anton-Perez Gloria
Published: June 2023

Background and Aims

OL-HDF provides multiple advantages and benefits to patients compared to conventional high-flow hemodialysis (HFHD). Current monitors have a wide variety of biosensors and devices that provide continuous information on the patient's biological parameter and the efficiency of the dialysis session. Monofrequency bioimpedance (BIVA) provides information regarding the state of hydration (HE) and nutrition (EN) of our patients.

Method

Observational study in 493 patients, distributed in 8 dialysis centers and with a three different model of dialysis monitor. Demographic data, dialysis techniques and regimens, mean values for one month of ultrafiltration rate readings and KT are analyzed. The continuous measurement of DD is estimated by the ion dialysance biosensor. The OL-HDF technique is post-dilutional. The BIVA measurement is performed between 10 and 30 minutes after the end of the session. The Kt/V is estimated from the total TBW (V) by BIVA, using the Watson and Hume-Wiers formulas. Statistical analysis: descriptive, t-Student for statistics of groups and independent samples, Chi square for the association in cross tables.

Results

See Table 1.

Conclusion

Obtaining lower dialysis dose values in OL-HDF than in HFHD in some monitor models, despite longer dialysis times and greater dialyzer surface area, is probably due to dilution due to post- re-infusion and/or to the positioning of the dialysance sensors within the hydraulic circuit. This makes us think about the advisability of maintaining urea Kt/V measurements, by laboratory, to ensure adequate dialysis quality.
#3069 CIRCULATING SCLEROSTIN AFFECTS URINARY CALCIUM EXCRETION AMONG STONE FORMERS
Authors: Rodrigues Fernanda Guedes , Ormanji Milene Subtil , Pietrobom Igor , Matos Ana Cristina , de Borst Martin , Heilberg Ita Pfeferman
Published: June 2023

Background and Aims

Sclerostin plays an important role in bone metabolism and adipose tissue. Experimental studies suggest that sclerostin also influences urinary calcium excretion (Uca), but this relationship has not been addressed in humans. We aimed to study the association of UCa levels with serum sclerostin, bone mineral density (BMD) and body composition among stone-formers (SF).

Method

We retrieved data from patient records, including clinical characteristics, nutritional, biochemistry and hormonal data as well as BMD and body composition determined by dual energy X-ray absorptiometry. Serum sclerostin levels were measured using ELISA kits. Determinants of UCa were studied using multivariate linear regression.

Results

A total of 107 SF (35.8 ± 9.3 years, 54% male) with eGFR of 99.8 ± 14.5 mL/min/1.73 were included. The subjects were divided by sex and clustered into tertiles according to UCa as shown in Table 1. Men in the highest UCa tertile had higher body mass index (BMI) and serum sclerostin levels, were more likely to have hypertension and metabolic syndrome, had lower lean mass, a trend towards higher fat mass (p = 0.06), and no statistical differences in BMD. Women in the highest UCa tertile had higher BMI and a trend towards higher serum sclerostin levels (p = 0.06), were more likely to have hypertension and metabolic syndrome, with no differences in BMD. Sclerostin was positively correlated with fat mass (r = 0.38, p = 0.004) and inversely correlated with lean mass (r = -0.32, p = 0.01) among men, but not among women. To further adjust for the influence of weight load on BMD for both sexes, the latter was also expressed as a ratio per BMI (BMD/BMI). Although lumbar spine BMD/BMI was inversely associated with UCa (β -0.26, p = 0.01) in univariate analysis, it lost significance in the multivariate model (Table 2). Hypertension, metabolic syndrome and serum sclerostin were independent determinants of UCa (Table 2).

Conclusion

Present findings disclosed that serum sclerostin, hypertension and metabolic syndrome were independent determinants of urinary calcium in stone formers. These data suggest that in addition to the hormones traditionally thought to alter calcium reabsorption in the kidney, sclerostin may play a significant additional role, warranting further intervention studies in order to test potential medication strategies to reduce calciuria in this population.
#3091 A STUDY FOR HOSPITALIZED PATIENTS WITH COVID-19 WITH/WITHOUT IMMUNOSUPPRESSION AND RENAL FAILURE: DOES THE SURVIVAL RATE CHANGE?
Authors: Vakiani Styliani , Triantafyllidou Maria , Katsanos Dimitris , Lakoniti Klaoudia , Vakianis Panteleimon
Published: June 2023

Background and Aims

Introduction The purpose of our research topic was to study the survival of immunocompromised or non-immunosuppressed patients as well as patients with Chronic Kidney Disease who were hospitalized due to covid-19 infection during a two-year period (2020-2022).

Method

Material and Methods A total of 1270 patients (of whom 570 were women) with a mean age of 63 years (+/- 24 years) were studied. From these, 1000 patients were without immunosuppression and 270 were theoretically and practically immunosuppressed, including 30 patients with Chronic Kidney Disease and of these 10 were with end-stage Chronic Kidney Disease. It is important to mention that 87 patients had to be hospitalized in the ICU, of which 74 died. The rest were hospitalized in the Biocontainment Unit, where 92 deaths were observed. 100 patients without immunosuppression died and 66 with immunosuppression. From the patients with End-Stage Chronic Kidney Disease, 3 died, theoretically falling into the immunocompromised category. The treatment protocol included all the therapeutic measures recommended by CCD.

Results

There was no statistically significant difference betweem the rate of death in immunocompromised patients and those who belonged in non immunocompromised group. However, there was a simple difference in deaths (66 out of 270 immunosuppresed patients) and 100 in non-immunocompromised patients, while there was also a difference in their need for hospitalization in the ICU and the Unit for Special Infections, but not statistically significant.

Conclusion

In conclusion, it appears that the immunocompromised are more prone to severe diseases having poor outcome. Furthermore, it was observed that patients with End Stage Chronic Kidney Disease had a fairly low mortality rate even though they are considered immunocompromised.
#3103 OMENTIN-1 AND SUBCLINICAL ATHEROSCLEROSIS IN ESKD PATIENTS UNDERGOING HEMODIALYSIS AND IN KIDNEY TRANSPLANT RECIPIENTS
Authors: Zicarelli Mariateresa , Greco Marta , Arcidiacono Valentina , Presta Pierangela , Caglioti Alfredo , Andreucci Michele , Dragone Francesco , Foti Daniela , Coppolino Giuseppe , Bolignano Davide
Published: June 2023

Background and Aims

In end-stage kidney disease (ESKD) patients, atherosclerosis is a key-player for cardiovascular risk, being influenced by endothelial dysfunction, inflammation and mineral dysmetabolism. Omentin-1 is an adipokine involved in various pathological conditions (diabetes, metabolic syndrome, obesity), and has recently been studied as a prognostic factor for atherosclerosis progression and mortality in the general population. In this study, we evaluated the possible relationships between Omentin-1 and incipient carotid atherosclerosis in the clinical setting of ESKD.

Method

Circulating blood Omentin-1 levels were measured in a cohort of 77 asymptomatic ESKD patients (40 kidney transplant recipients, Ktx and 37 chronic hemodialysis patients, HD) and in 30 healthy controls. Carotid intima-media thickness (cIMT) was measured before a single HD session or before a Ktx outpatient visit. Pathological cIMT was defined for mean values > 0.9 mm and/or an unilateral cIMT above the 75th percentile.

Results

Omentin-1 levels were higher in the entire ESKD cohort than in healthy controls (324 [90.3-770] vs. 110 [35.4-240.9] pg/ml; p = 0.03). Ktx patients had lower levels than HD patients (p = 0.01) while higher Omentin-1 levels were found in HD patients (474.9 [197.2-1432.1] ng/ml) compared to both healthy subjects (p = 0.009) and Ktx (p = 0.01). Mean cIMT in all ESKD was 0.78 ± 0.32 mm. 36 patients (46.7%) with pathological cIMT values displayed lower Omentin-1 levels as compared with others (168.7 [51.1-457.8] vs 474.9 [197.2-1432.1] and p = 0.004). Multivariate correlations analyses indicated Omentin-1 as the stronger independent predictor of carotid atherosclerosis (β-0.687; p = 0.03) in the whole cohort, even more than age, total cholesterol and diastolic BP.

Conclusion

In ESKD patients, Omentin-1 reflects the severity of carotid atherosclerosis independently from traditional confounders and may serve as an additive biomarker for risk prediction and risk stratification. Future studies are awaited to confirm these preliminary findings in larger cohorts.
#3108 ASSOCIATION BETWEEN INCIDENT DEPRESSION AND CLINICAL OUTCOMES IN PATIENTS WITH CHRONIC KIDNEY DISEASE
Authors: Zhu Nanbo , Virtanen Suvi , Xu Hong , Carrero Juan Jesus , Chang Zheng
Published: June 2023

Background and Aims

Depression is highly prevalent and related to increased morbidity and mortality in patients on dialysis, but less is known among patients with earlier stages of CKD. This study investigated the associations between depression and clinical outcomes in patients with CKD not receiving dialysis.

Method

We identified 157 398 adults with CKD stages 3–5 not previously diagnosed with depression from the Stockholm CREAtinine Measurements (SCREAM) project. The primary outcomes included hospitalization, CKD progression (>40% decline in eGFR, initiation of kidney replacement therapy, or death due to CKD), major adverse cardiovascular events (MACE; myocardial infarction, stroke, or cardiovascular death), and all-cause mortality. Survival analyses were used to estimate the associations between incident depression and adverse health outcomes, adjusting for socio-demographics, kidney disease severity, healthcare utilization, comorbidities, and concurrent use of medications.

Results

During a median follow-up of 5.1 (interquartile range: 2.3–8.5) years, 12 712 (8.1%) patients received an incident diagnosis of depression. A total of 634 471 hospitalizations (4,600 935 hospitalized days), 42 866 MACEs, and 66,635 deaths were recorded, and 9 795 individuals met the criteria for CKD progression. In the multivariable-adjusted analyses, incident depression was associated with an elevated rate of hospitalized days (rate ratio: 1.77, 95% confidence interval [CI]: 1.71–1.83), as well as an increased rate of CKD progression (hazard ratio [HR]: 1.38, 95% CI: 1.28–1.48), MACE (HR: 1.22, 95% CI: 1.18–1.27), and all-cause mortality (HR: 1.41 95% CI: 1.37–1.45). The association with CKD progression was more evident after one year of depression diagnosis (HR: 1.47, 95% CI: 1.36–1.59). Results were consistent across a range of sensitivity analyses.

Conclusion

Among patients with non-dialysis-dependent CKD stages 3–5, incident depression is associated with poor prognosis, including hospitalization, CKD progression, MACE, and all-cause mortality.
#3115 THE ASSOCIATION OF FIBROBLAST GROWTH FACTOR-23 AND CARDIORENAL SYNDROME IN PATIENTS WITH DIABETES MELLITUS
Authors: Vasilkova Volha , Pchelin Ivan , Mokhort Tatiana
Published: June 2023

Background and Aims

Previous studies suggest that interactions between the heart and the kidney can contribute to the progressive dysfunction of both organs. Recently, there has been an increase in the prevalence of cardiovascular disease (CVD) and chronic kidney disease (CKD) due to increasing diabetes mellitus rate. It is known that fibroblast growth factor-23 (FGF-23) has been found to be related to kidney metabolism especially as a biomarker and a key factor to be used in the kidney field. The aim of our study was to assess potential therapeutic approaches of the use of FGF-23 in clinical settings as a potential circulating biomarker for CVD and CKD.

Method

A total of 155 patients with DT2, aged 34 to 84 years (60 [60;72]), were examined. Control group included 94 healthy people the same age. All patients underwent standard clinical and laboratory examination, with an assessment of the levels of FGF-23 in baseline plasma samples. Renal function was assessed based on the levels of serum creatinine, cystatin C, eGFR, which was calculated according to the CKD-EPI formula, and albuminuria, which was assessed as albumin/creatinine ratio (A/C). An echocardiographic examination was conducted according to the standard protocol with the calculation of dimensional, volume and speed characteristics.

Results

The levels of FGF-23 were significantly higher in DT2 patients with CKD 5 in comparison with stages 1–4. There were positive strong significant association between FGF-23 and creatinine (r = 0.71, p<0.001). In both unadjusted and adjusted analyses, probability of decreased eGFR was associated strongly with FGF-23 (COR; 95% CI 1.890; 1.362-2.622, p<0,001). When evaluating the dependence of the probability of decreased eGFR on the FGF-23 using the ROC analysis, the cut-off value of FGF-23 was 0,9 pmol/l. The sensitivity and specificity of the method were 75.3% and 74.5%, respectively (AUC 0.832±0.035 with 95% CI: 0.764-0.901, p<0.001).

DT2 patients with left ventricular hypertrophy (LVH) were characterized by higher levels of FGF-23 (2,45 [0,65;7,43] vs 0,57 [0,19;2,19] pmol/l in control group). DT2 patients with LVH and natriuretic peptides levels ≥ 35 pg/ml for BNP and/or ≥125 ng/ml for NT-proBNP had significantly high concentrations of FGF-23 than patients with normal levels of natriuretic peptides (3,22 [1,09;9,55] vs. 0,52 [0,27;1,08] pmol/l, p<0,0001). In order to assess the diagnostic significance of the FGF-23 for predicting left ventricular mass index (LVMI) thickening and increasing the proBNP concentration, a ROC analysis was performed. Thus, at the level of FGF-23 (AUC-0.702) = 0.9 pmol/l, the sensitivity and specificity for LVMI thickening were 66.9% and 67.3%.

Conclusion

Our study identifies FGF-23 as a promising target of novel therapeutic interventions in cardiorenal syndrome, which should be investigated in future clinical studies.