bluuebunny/crossref_metadata_2025 huggingface dataset:
#5147 PREDICTING NON-DIABETIC KIDNEY DISEASE IN PATIENTS WITH TYPE 2 DIABETES MELLITUS: EXTERNAL VALIDATION OF FOUR PREDICTIVE MODELS
Authors: Roldán Deborah Soledad , Rey Angela , Gruss Enrique , Shabaka Amir
Published: June 2023

Background and Aims

Several prediction models have been published for estimating the probability of non-diabetic kidney disease in kidney biopsies performed in patients with diabetes mellitus. External validation and comparison of these models is essential prior to their clinical application. The aim of this study was to validate and compare the predictive capacity of four previously described clinical models as a tool to predict non-diabetic kidney disease (NDKD) in diabetic patients.

Method

We retrospectively reviewed kidney biopsies performed in patients with type 2 diabetes mellitus between January 1999 and December 2022 in our centre. The probability of presence of NDKD was calculated by using the clinical and laboratory parameters at the time of the decision to perform a biopsy, according to 4 models; Surinrat's model, Liu's model, Li's model and Garcia-Martin's model (see Table 1). Overall model fit was assessed, calibration curves were plotted and discrimination for each model was assessed by using the receiver operating characteristic (ROC) curve in line with the transparent reporting of a multivariable prediction model for individual prognosis or diagnosis (TRIPOD) guidelines.

Results

The study included 280 patients, 68.9% were males and the mean age was 65.4 ± 11.9 years. 172 patients (61.4%) had a diagnosis of non-diabetic kidney disease. On calculating the risk of NDKD, Surinrat's, Li's and Garcia-Martin's models predicted 33.6%, 64.8% and 53.4% of NDKD when using the “probable NDKD” threshold, and 60.7%, 81% and 90.7% respectively when including the “grey zones”. Fleiss’ Kappa test showed a fair agreement between the four models when using the “probable NDKD” threshold (k = 0.23, 95% CI 0.13-0.33, p<0.001) and when including the “grey zones” (k = 0.39, 95% CI 0.29-0.49, p<0.001). On using the “probable NDKD” threshold, the overall accuracy for Surinrat's, Liu's, Li's and Garcia-Martin's models was 50.7%, 62.7%, 63.6% and 65.3% respectively, while on including the “grey zones” the accuracy slightly increased in the first to models to 54.3% and 66.4% respectively while decreasing in Garcia-Martin's model to 64.2%. Area under the ROC curve (AUC) was higher in Garcia-Martin's model (AUC 0.66, 95% CI 0.58-0.74, p<0.001) compared to Lin's model (AUC 0.59, 95% CI 0.50-0.67, p = 0.044), while Surinrat's and Liu's models did not discriminate (AUC 0.55, 95% CI 0.47-0.64, p = 0.214 and AUC 0.58, 95% CI 0.49-0.63, p = 0.084).

Conclusion

There is a fair agreement between the four models for predicting non-diabetic kidney disease in type 2 diabetic patients. Of the models studied, Garcia-Martin's model most accurately predicted non-diabetic kidney disease in type 2 diabetes patients, although discrimination remained poor. These models may not be suitable for guiding clinicians on indicating a kidney biopsy in diabetic patients in our population.
#5163 RATIONAL USE OF ECULIZUMAB IN SECONDARY ATYPICAL HAEMOLYTIC UREMIC SYNDROME
Authors: García-Galán Lucía Cordero , Escribano Teresa Cavero , Gutiérrez Eduardo , Pérez Justo César Sandino , Cuellar Hernando Trujillo , Auñón Pilar , Martínez Marta Rivero , González Celia , Hernández Paúl , Morales Enrique
Published: June 2023

Background and Aims

Secondary atypical hemolytic uremic syndrome (secondary aHUS) is a heterogeneous group of thrombotic microangiopathies (TMA) associated with various underlying conditions. Unlike primary aHUS, there is still no hard evidence on the efficacy of complement blockade in treating secondary aHUS since the two main series in the literature that investigate this subject show discrepant results. Our work aims to reassess Eculizumab's efficacy in treating secondary aHUS.

Method

Observational, retrospective, single-center study, in which we analyzed the hematological and renal evolution of 24 patients diagnosed with secondary aHUS who received treatment with Eculizumab compared with a control cohort of 14 patients who did not receive Eculizumab. Complete renal response was defined as the recovery of renal function before the event, partial renal response as a recovery of 50% of lost glomerular filtration rate, and hematological response as normalization of hemoglobin and platelets.

Results

We found no statistically significant differences in baseline characteristics or disease severity between both groups. After a median of 5 doses of Eculizumab, the group of patients who received complement blockade presented a significant difference in renal response (complete in 47.8% of patients and partial in 17.4%) compared to the control cohort (complete response 14.3% and partial of 14.3%). Rates of hematological remission were similar in both groups (87% in the eculizumab cohort and 85.7% in the control cohort).

Conclusion

Rational and early use of Eculizumab in patients with secondary aHUS could be an effective and safe therapeutic option, guaranteeing better renal recovery compared to patients who do not receive complement blockade.
#5195 MORTALITY OF PATIENTS ON CHRONIC HEMODIALISYS: CAUSED OR RELATED TO SARS-COV-2 INFECTION?
Authors: Ambrogio Martina , Rosati Erica , Spasiano Andrea , De Luca Gianmarco , Urciuolo Federica , Michieli Giulia , Cingolani Antonella , Cutuli Salvatore Lucio , De Pascale Gennaro , Grandaliano Giuseppe , Panocchia Nicola
Published: June 2023

Background and Aims

Patients on chronic hemodialysis (HD) treatment had a higher mortality rate than the general population with SARS-CoV-2 infection. The ERA registry showed a 20% mortality at 28 days for these patients. The aim of the study was to evaluate the causes and risk factors of mortality for patients on chronic HD hospitalized with SARS-CoV-2 infection; particularly if the cause of death is directly attributable to the COVID-19 infection or to another pathology.

Method

Clinical data of chronic HD patients admitted for COVID-19 infection at Fondazione Policlinico Gemelli from March 15th 2020 to February 28th 2022 were analysed. Univariate and multivariate regression analysis for mortality risk factors was performed. Causes of mortality were obtained by hospital discharge forms. COVID-19 related cause of death was defined through intra-hospital codes as COVID-19 pneumonia, COVID-19 ARDS and COVID-19 respiratory failure.

Results

One hundred and fifty-two chronic HD patients were hospitalized for COVID-19 infection. Table 1 shows the general characteristics of the patients. The 28-day all-cause mortality was 21.9%, wich 11.9% was COVID-19 related. Table 2 shows the cause of mortality. Multivariate Cox regression demonstrated that an increased risk of death from COVID-19 at 28 days was significantly and independently associated with age >73 years (HR 1.05, 95% CI 1.0-1.09; p<0.05), Charlson Comorbidity Index (CCI) > 5 at entry (HR 1.28, 95% CI 1.02-1.60; p<0.01), Continuous Renal Replacement Therapies (CRRT) (HR 2.89, 95% CI 1.03-8.11; p = 0.04) and the presence of peripheral vasculopathy (HR 3.48, 95% CI 1.31-9.27; p = 0.01). Plasma albumin >25 g/L at entry (HR 0.87, 95% CI 0.80-0.96; p<0.01) and pre-admission SARS-CoV-2 vaccination (HR 0.25, 95% CI 0.09-0.72; p = 0.01) significantly reduced the risk of mortality.

Conclusion

Our study shows that on the total of deaths with a positive COVID-19 test, 59% were caused by the infection while the remaining 41% occurred from other causes. Age, CCI, the presence of peripheral vascular disease and the need for CRRT are independent risk factors for mortality. Vaccination was confirmed as a protective factor.
#5207 CENTRAL NERVOUS SYSTEM INVOLVEMENT IN EOSINOPHILIC GRANULOMATOSIS WITH POLYANGIITIS: A DIAGNOSTIC DILEMMA
Authors: Nicolau Carla , Barata Rui , Vieira Miguel Bigotte , Pereira Tiago Assis , Góis Mário , Viana Helena , Sousa João , Ribeiro Francisco , Nolasco Fernando
Published: June 2023

Background

Central nervous system involvement is extremely rare in eosinophilic granulomatosis with polyangiitis, and associated with very poor prognosis. A high index of suspicion is needed to diagnose this entity and initiate prompt treatment for this life-threatening condition.

Case presentation

A 71-year-old man was admitted to our hospital with lower limb weakness, loss of vision in the left eye and diplopia for four weeks. Four months prior to admission he reported unintentional weight loss and wheezing. Laboratory studies revealed anemia, eosinophilia and high antineutrophil cytoplasmic antibodies (ANCA) anti myeloperoxidase (MPO) levels. Brain computerized tomography (CT) was normal. Although corticosteroids were started, addition of other immunosupressants was delayed due to ongoing infection. During the next three days, the patient presented with worsening kidney function and was disoriented, agitated and combative. Lumbar puncture and brain CT scan showed no acute abnormalities. Therefore, plasmapheresis was started. During the third session of plasmapheresis, the patient became drowsy and non-responsive. Brain CT scan revealed subdural hematoma with uncal herniation. Trepanation and initiation of hemodialysis were required. Kidney biopsy revealed focal proliferative glomerulonephritis with fibrocellular crescents. Magnetic resonance imaging and ophthalmological evaluation showed abnormalities compatible with vasculitic disease. Cyclophosphamide was added to prednisolone, with renal and extra renal manifestations improvement. One year later, the patient is autonomous, with right hand paresis, stable kidney function (serum creatinine 2.5 mg/dL) and negative ANCA MPO serology.

Conclusion

Neurological involvement in GEPA is heterogeneous and requires differential diagnosis with central nervous system infections, adverse effects of corticosteroids and complication of plasmapheresis. The diagnosis is challenging and demands a high level of suspicion. Otherwise, it may lead to delayed, erroneous diagnosis and worse survival.
#5227 KIDNEY FAILURE RISK EQUATION (KFRE) VS GRAMS SCORE, WHICH ONE PREDICTS BETTER THE INITIATION OF RENAL REPLACEMENT THERAPY?
Authors: Collado Alba Temprado , Blandino Marisa Vidal , Cosano Gema Montilla , Gómez Cristina Andrades , Lopez-Mendoza Manuel , Prieto Francisco Javier Toro
Published: June 2023

Background and Aims

In patients with Advanced Chronic Kidney Disease (ACKD) stage G4 it is necessary to use prognostic tools to predict the need for Kidney Replacement Therapy (KRT), especially in elderly patients, the most used is the Kidney Failure Risk Equation (KFRE). The Grams Score (GS) predicts the risk of KRT, cardiovascular events and mortality, providing better prediction for the choice of KRT modality but requires more parameters in its equation. Ours objective was compare both KFRE and GS prognostic equations to validate which one better predicts the onset of KRT.

Method

Descriptive, retrospective study of a cohort of patients older than 65 years with G4 CKD attending for the first time in 2016–2017. Follow-up for 5 years or first clinical event defined as need for KRT (including Conservative Renal Treatment with GFR = <8 ml/min/1.72m2) or death. Variables needed to calculate KFRE and GS were collected, as well as events occurred.

Results

271 patients who met the inclusion criteria were analyzed. The clinical characteristics are shown in Table 1. The Grams model showed good discrimination for initiating KRT at 2 and 4 years, AUC 0.84 [95%CI 0.77-0.91] and AUC 0.81 [95%CI 0.75-0.87], respectively. The ROC curves presented by both equations showed good discrimination, AUC 0.82 [95%CI 0.74-0.91] and AUC 0.80 [95%CI 0.74-0.87].When comparing the need for 2-year KRT with both equations, we observed both ROC curves were similar (p = 0.356). Table 2 shows results from logistic regression analysis. For the 2-year KRT event by Grams, patients with a score > = 17.85% were 11.53 [95%CI 5.16-27.78] times more likely to initiate KRT. However, compared to KFRE with a score > = 20.77%, they had 17.53 [95%CI 7.59-40.47] times higher probability of KRT (both p<0.001). When we compared both equations in multivariate analysis only the KFRE was significant (ODR 0.217 (95%CI 0.87-0.54).

Conclusion

In our population, both prognostic equations showed good discrimination to program initiation of KRT. However, the GS could underestimate this need while the KFRE seems to discriminate it better.
#5285 SERUM IRON AND NUTRITIONAL STATUS ARE ASSOCIATED IN PATIENTS WITH CHRONIC KIDNEY DISEASE
Authors: Lin Ting-Yun , Hung Szu-Chun
Published: June 2023

Background and Aims

Both anemia and malnutrition are highly prevalent in patients with chronic kidney disease (CKD). Iron deficiency plays a significant role in anemia of CKD. However, whether iron deficiency contributes to malnutrition in CKD is unclear.

Method

We examined the association of iron status with nutritional status among patients with CKD stages 3–5 not yet on dialysis. The iron indices for assessing iron status included serum iron, serum ferritin, and transferrin saturation. Nutritional status was determined using body composition assessed by anthropometric measures and multi-frequency bioelectrical impedance, serum albumin, handgrip strength, Malnutrition Inflammation Score (MIS), and dietary protein and energy intake. We performed linear regression analyses to explore the cross-sectional association between iron status and different nutritional assessment tools.

Results

A total of 157 patients (age 64 ± 12 years; 93 men and 64 women; diabetes 39%) with CKD [estimated glomerular filtration rate (eGFR) 24.4 ± 13.4 ml/min/1.73 m2] were included. Patients were stratified as low (<70 μg/dL) or high (≥70 μg/dL) serum iron. Compared with patients with high serum iron (n = 104), patients with low serum iron (n = 53) were more likely to be female and had a significantly lower eGFR, hemoglobin, lean tissue index, serum albumin, handgrip strength, and dietary protein intake but a significantly higher MIS. In adjusted linear regression analyses, there was a significant association of serum iron with serum albumin, handgrip strength, and MIS (all adjusted P < 0.05). Serum ferritin was not associated with nutritional status, while the association between transferrin saturation and handgrip strength was only marginal (adjusted P = 0.044).

Conclusion

Higher serum iron is associated with better nutritional status in patients with CKD. Serum iron may be considered a complementary tool to assess nutritional status in CKD.
#5330 CYCLIN D1 AMELIORATES ISCHEMIA/REPERFUSION-INDUCED ACUTE KIDNEY INJURY
Authors: Huang Yuliang , Chen Junzhe , Shao Xiaofei , LI Jinxiang , Tang Ying
Published: June 2023

Background and Aims

Acute kidney injury (AKI) is a life-threatening condition. The absence of oxygen during the acute ischemic phase would disturb energy metabolism and cause kidney tubular epithelial cell damage. Fatty Acid Oxidation (FAO) is the main source of energy production of renal proximal tubular epithelial cells. Timely promoting FAO, increasing supplies of energy, and promoting cell proliferation are essential to improve kidney injury, but there is no clinically recognized effective treatment for this. Cyclin D1(CCND1), a member of the cell cycle family, plays a vital role in cell proliferation. Our previous study found that CCND1 improved AKI accompanied with increased fatty acid oxidation. Therefore, we investigated the role and molecular basis for CCND1 involvement in fatty acid oxidation of AKI.

Method

CCND1 was evaluated in AKI in human kidney proximal tubular epithelial cells (HK-2 cells) and male C57BL/6J mice (wild type). The protective role of CCND1 in AKI was investigated in a mouse model of ischemia-reperfusion AKI treated by ultrasound-microbubble-mediated kidney-specifically transferring CCND1-expressing plasmids in male C57BL/6J mice (wild type). Eight-week-old male C57BL/6J mice (wild type) were subjected to bilateral renal artery occlusion for 30min followed by 24h of reperfusion. We evaluated FAO, proliferation, and autophagy in vitro and in vivo. In addition, we evaluated the concentrations of blood urea nitrogen and creatinine, evaluated kidney ultrastructure and so on.

Results

In vivo studies had shown that activation of CCND1 can prevent AKI-induced lipid accumulation, kidney tubule injury and kidney function declined after ischemia-reperfusion injury. Compared to test control, the treatment significantly (p<0.05) lowered the concentrations of blood urea nitrogen and creatinine. Kidney specific overexpression of CCND1 promoted FAO, promoted proliferation and reduced apoptosis. Mechanistically, CCND1 activated the AMPK pathway, which increased the expression of phosphorylation AMP activated protein kinase (p-AMPK) and upregulated FAO. On the contrary, inhibiting the expression of CCND1 exacerbated impairment of FAO and disturbed energy metabolism.

Conclusion

Thus, CCND1 improved FAO and reduced lipid accumulation via active AMPK pathway in kidney proximal tubular epithelial cells (PTECs). Hence, reconstruction of the expression of CCND1 may be a novel therapeutic strategy for treating AKI.
#5353 THE IDIOPATIC HYPOCRYOGLOBULINEMIA AS AN EMERGING MEMBRANOPROLIPHERATIVE GLOMERULONEPHRITIS
Authors: Longo Roberta , Ceruti Cecilia , Marchisio Martina , Morrone Marco , Caruso Nunziante , Guarino Annalisa , Fenoglio Roberta , Sciascia Savino , Roccatello Dario
Published: June 2023

Background and Aims

A considerable number of patients with high clinical suspicion for cryoglobulinaemic vasculitis either show negative results for the detection of cryoglobulins or show only trace amounts which cannot be characterized for composition. We aimed at establishing whether the failure to detect or the detection of trace amounts of cryoglobulin with conventional methods either identifies a peculiar subset of low level cryoglobulinaemia (from now on hypocryoglobulinaemia) or represents a separate entity.

Method

Using a modified precipitation technique in hypo-ionic medium, we prospectively identified between 2008 and 2021 237 patients (median age 60.8 years [22-97], 137 females) having <0.5% cryocrit and clinical suspicion of autoimmune disorder

Results

54 out of 237 patients (22.7%) had a history of HCV infection. 169 out of 237 patients (71%) had an established underlying disease, while 68 patients (28.6%) (median age 62.9 years [29-93], 35 females) did not show either laboratory markers or clinical symptoms consonant with an underlying aetiology. These 68 cases with only trace amounts of cryoglobulins were defined as having a putatively idiopathic hypocryoglobulinaemia. Nineteen of these 68 patients (27.9%) had a history of HCV infection. Twenty-four patients out of 68 (35.3%) were positive for rheumatoid factor (RF), while 25 (36.7%) patients had signs of complement consumption, and 36 (52.9%) had increased inflammatory indexes. Seven patients only had arthralgia and constitutional symptoms while 61 out of 68 (89.7%) presented with at least one of the three cardinal signs of cryoglobulinaemic vasculitis including skin lesions, peripheral nerve involvement, and glomerulonephritis. Seventy-five percent of the subjects had type III hypocryoglobulins. In patients with hypocryoglobulinaemia the histologic features of glomerulonephritis (also examined by electron microscopy) resembled those of mixed cryoglobulinaemia-associated glomerulonephritis

Conclusion

In conclusion, hypocryoglobulins are often polyclonal and are mainly unrelated to HCV infection. Patients who present high clinical suspicion for vasculitis, especially glomerulonephritis and yet test negative for cryoglobulinaemia detected by standard techniques, could require deeper investigation even in the absence of HCV infection, RF activity or signs of complement consumption.
#5367 CLINICAL SIGNIFICANCE OF NORMO-HYDRATION STATE IN PERITONEAL DIALYSIS PATIENTS
Authors: Hashmi Amna , Szabo Reka P , Varga Istvan , Kardos Laszlo , Balla Jozsef
Published: June 2023

Background and Aims

The assessment of fluid status in dialysis patients is of paramount importance. Managing persistent volume overload and instability during dialysis is a significant challenge, with concomitant symptomatic and asymptomatic intradialytic hypotension (IDH) that results in dialysis-induced myocardial ischemia (cardiac stunning) and long patient recovery times.Our aim was to estimate the status of hydration in our peritoneal dialysis population by body composition monitoring (BCM) device to modify our pharmacological and dialysis policy and to evaluate echocardiographic parameters of the RV functions in patients with end-stage renal disease (ESRD) undergoing PD.

Method

We used a Fresenius Body Composition Monitor (BCM), a whole-body bioimpedance spectroscopy (50 frequencies, 5–1,000 kHz), to assess the body composition of 35 patients on peritoneal dialysis in our centre..We measured body weight, 24 h diuresis and performed a BCM session. Analysed results of echocardiography focused on RV (tricuspid annular plane systolic excursion (TAPSE). As per statistics, comparisons between 2 groups done by students t test, Mann Whitney U test or Wilcoxon test. Correlation between data was done by Pearson or spearman correlation. And lastly categorical variables were assessed by fisher's exact, and Chi squared test.

Results

Average age was 47 years old (SD 9,45 t-test p = 0,1154:). Gender distribution was 54,3% of our patients were female. 8,6% of our patients were anuric, 91,4% had residual urine (more than 1 litre). TAPSE value were average 23,17 mm (±4,5).We measured over-hydration in 8 cases by BCM that followed dialysis policy modification. In 8 PD patients we measured more than 2 L volume overload (VO) with BCM followed by dialysis policy modification (fluid intake restriction, diuretic dose increasing, frequent solution exchange).

Conclusion

Our data raised the importance of regular echocardiography to identify it. More attention should be focused on improving BP and volume control and identifying treatment strategies that effectively lower further deterioration in PD patients. One way of doing this is monitoring with BCM. With this clinician can manage persistent overload in CAPD patients, to better modify the dialysis regime, restrict fluid intake and use diuretics, to all in all preserve LV and RV function, and to prevent deterioration of the peritoneal membrane, and most importantly improve their survival.
#5386 ONCO-NEPHROLOGY: THE ROLE OF KIDNEY BIOPSY IN THE MANAGEMENT OF SIDE EFFECTS OF TARGETED THERAPIES
Authors: Caruso Nunziante , Lalloni Stefania , Marchisio Martina , Morrone Marco , Rabajoli Gianluca , Careddu Andrea , Geraci Giovanni , Fenoglio Roberta , Sciascia Savino , Roccatello Dario
Published: June 2023

Background and Aims

The introduction of innovative therapies, resulting from revisiting cancer as a disease of the immune system, has changed the scenario of complications. These new classes of drugs, such as targeted therapies and immune checkpoint inhibitors, assure substantial advantages in cancer therapy, despite some side affecting various organs, including the kidney. Histological evaluations of kidney disorders induced by targeted/immunotherapy are limited.

Method

In this study we examined the histological features of patients treated with new cancer agents who underwent kidney biopsy for new onset kidney failure and/or urinary abnormalities.

Results

The cohort included 30 adult patients. The most frequently administered therapies were immunotherapy (30%), targeted therapy (26.7%), immunotherapy plus targeted therapy (13.3%), immunotherapy plus chemotherapy (13.3%), targeted therapy plus chemotherapy (16.7%). The most common histological finding was tubular interstitial nephritis (30%) that was associated with acute tubular necrosis in 4 cases, and thrombotic microangiopathy (23.3%). After kidney biopsy, 16 of the 30 patients were treated according to the histological diagnosis. Fourteen patients were treated with steroids. One patient with membranous nephropathy was treated with a single dose of rituximab. A patient with severe thrombotic microangiopathy requiring dialysis received a treatment with eculizumab for 3 months. Overall some renal response was obtained in all patients treated with glucocorticoids, while complete kidney response was achieved in the patient treated with rituximab. Cancer treatment was resumed without change in 21 out of 30 patients.

Conclusion

Kidney biopsy is critical for the management of kidney toxicities and should be strongly encouraged for patients showing adverse kidney effects of novel cancer agents.
#5394 PHYSICAL ACTIVITY AND THE RISK OF DEMENTIA IN END-STAGE RENAL DISEASE PATIENTS WITH HEMODIALYSIS: A NATIONWIDE POPULATION-BASED STUDY
Authors: Choi Hong Sang , Kim Minah , Oh Tae Ryon , Suh Sang Heon , Kim Chang Seong , Bae Eun Hui , MA Seong Kwon , Kim Soo Wan
Published: June 2023

Background and Aims

Several studies have reported that dementia has a high prevalence in patients with end-stage renal disease (ESRD) patients. However, the relationship between physical activity and the risk of developing dementia has not been elucidated in ESRD patients with hemodialysis.

Method

A total 19,877 hemodialysis patients aged ≥ 40 years who underwent health check-ups were identified from the Korean National Health Insurance Service database and were analysed in this study. Individuals with physical activities were defined as meeting following criteria: (i) three or more days/week of vigorous activity of at least 20 min per day or (ii) five or more days/week of moderate-intensity activity of at least 30 min per day. The occurrence of dementia was monitored through the end of 2018 by the ICD-10 codes.

Results

During the 4.6-year follow-up, 1,755 patients with hemodialysis developed dementia. Physical activity was associated with the lower risk of any dementia (hazard ratio [HR], 0.779, 95% confidence interval (CI), 0.7-0.867) even after adjusting for several confounding factors. Risk of developing dementia was still lower in hemodialysis patients with physical activity when we analyse the risk of Alzheimer's dementia and vascular dementia separately (HR 0.817 and 0.685, respectively). In subgroup analyses, the risk of dementia tended to lower in hemodialysis patients with physical activity than without physical activity in all subgroups.

Conclusion

Physical activity is associated the lower risk of developing dementia in ESRD patients with hemodialysis.
#5441 EVIDENCE THAT CHAPERONE 4-PBA TREATMENT ALLEVIATES THE RENAL PHENOTYPE IN ALPORT SYNDROME MOUSE MODELS
Authors: Ioannou Pavlos , Odiatis Christoforos , Antoniadou Kyriaki , Pieri Myrtani , Papagregoriou Gregory , Malatras Apostolos , Samiotaki Martina , Horaček Matija , Ljubanovic Danica Galesic , Stylianou Kostas , Deltas Constantinos
Published: June 2023

Background and Aims

Alport Syndrome (AS) is a severe inherited glomerulopathy caused by mutations in the genes encoding the α-chains of type IV collagen, the most abundant component of the glomerular basement membrane (GBM). Alport patients lack effective therapies beyond blockade of the renin-angiotensin system). This work describes the repurposing of two FDA-approved chemical chaperones (4-PBA and TUDCA) to rescue two AS mouse models: a knock-in and a compound heterozygous model bearing the Col4a3-p.Gly1332Glu mutation, recapitulating the most common mutation found in Cypriot patients.

Method

In either a short-term or long-term treatment, AS and wild type (WT) mice received chaperones or vehicle daily. To examine the biochemical and histological effects of chaperones on treated mice, kidney, blood, and urine samples were collected after therapy.

Results

Electron microscopy studies showed that the GBM of the 4-PBA treated AS mice after the long-term treatment has a considerable improvement in morphology, compared with vehicle-treated or TUDCA-treated AS mice. Importantly, EM measurements displayed a significant (p-value<0.0001) reduction of lesions and a decline of the lesions-severity in the GBM of 4-PBA treated AS mice. No adverse effects were noted in the GBM of the chaperone-treated wild-type mice. Also, the interstitial fibrosis, global and segmental glomerulosclerosis were ameliorated in the 4-PBA treated AS mice. Additionally, the treatment with 4-PBA maintained proteinuria and hematuria at low levels in AS mice. Importantly the de novo 35 kDa Col4a3 fragment which was previously detected in non-treated AS mice, was reduced after treatment with 4-PBA.

Conclusion

Together, these results suggest a therapeutic potential for the 4-PBA agent in combating renal dysfunction in AS.
#5443 ASSOCIATION OF SERUM CALCIUM-TO-MAGNESIUM RATIO WITH CARDIOVASCULAR AND CEREBRAL VASCULAR DISEASES IN DIALYSIS PATIENTS
Authors: Lee Sua , Lee Soyoung , Kim Kyeong Min , Hong Yu Ah , Park Hoon Suk , Shin Jong Ho , Choi Bum Soon , Kim Byung Soo , Ban Tae Hyun
Published: June 2023

Background and Aims

Cardiovascular disease (CVD) and cerebral vascular accident (CVA) are the important complications and the leading causes of death in dialysis patients. High serum calcium (Ca) level promotes the clotting cascades and vascular calcification, which leads to CVD and CVA. Magnesium (Mg) is a well-known Ca blocker, inhibiting the formation of thrombin. An imbalance between serum Ca and Mg levels has been reported as an associated factor with CVD and mortality. This study investigated the associations of serum Ca-Mg ratio with CVD and CVA in dialysis patients.

Method

We conducted a cross-sectional analysis using baseline data from a multicenter prospective cohort for dialysis patients in South Korea. A total of 860 patients were divided into tertile groups according to serum Ca-Mg ratio levels. Patients with serum Ca-Mg ratio less than 3.28 were classified as the low group, and patients with serum Ca-Mg ratio more than 3.87 were classified as the high group, and the rest were classified as the middle group. Serum Ca level was calculated and applied as corrected Ca level considering serum albumin level. The associations of serum Ca-Mg ratio with prevalence of acute coronary syndrome (ACS), congestive heart failure, aortic artery calcification, and CVA were assessed.

Results

The average age of all patients was 59.1±12.1 years, and the average duration of dialysis was 7.9±5.9 years, and the duration of the low group was shorter than those of other groups. The high group had higher prevalence of peripheral vascular disease (P = 0.004). Serum albumin, phosphorus and Mg levels in the high group were lower than other groups (P<0.001). The prevalence of ACS showed higher in the high group than in other groups (P = 0.017). The prevalence of cerebral infarction showed higher in the high group than the low group (P = 0.016). In multivariable logistic regression analysis, higher Ca-Mg ratio was independently associated with the prevalence of ACS (Odds ratio 1.321, 95% confidential interval 1.009-1.728, P = 0.043) and cerebral infarction (Odds ratio 1.392, 95% confidential interval 1.002-1.896, P = 0.036).

Conclusion

A high Ca-Mg ratio was associated with the development of ACS and cerebral infarction. If the optimal cut-off of Ca-Mg ratio is determined, it can be used as a predictive marker for ACS and cerebral infarction.
#5448 INCIDENCE OF ACUTE PULMONARY EDEMA AFTER THE SYSTEMATIC USE OF ULTRASOUND B-LINES
Authors: Urso Alessandra , Mallamaci Francesca , Tripepi Rocco , Panuccio Vincenzo Antonio
Published: June 2023

Background and Aims

Acute pulmonary edema (APE) due to fluid overload is considered the most feared complication in hemodialysis patients. Various diagnostic tests have been proposed to assess fluid status in patients with end stage kidney failure (ESKF) and among these lung ultrasound (by measuring the number of B-Lines) is emerging as a promising tool to identify pulmonary congestion in this patient-population.

Method

In the setting of a retrospective study, we pragmatically compared the incidence rate of APE in our center before and after the implementation of lung ultrasound as a routine practice in our unit. Two periods were considered. A pre-implementation period [from 01/01/2007 to 31/12/2008, total person-time: 1913 months/patient, n = 98 patients (Group 1), 85 prevalent and 13 incident patients] and a post-implementation period [from 01/01/2017 to 31/12/2018, total person-time: 2061 months/patient, n = 108 patients (Group 2), 81 prevalent and 27 incident patients]. By accurately reviewing the electronic medical records, all episodes of APE were counted, i.e. all episodes characterized by sudden or worsening dyspnea associated with signs of salt and water overload, confirmed by chest auscultation or chest X-Ray, which required an additional dialysis session and excluding events due to infectious or irritating problems.

Results

The two groups (Group 1 vs Group 2) were quite similar between them as for age (64±15 vs 67±14 years, p = 0.06), proportion of males (65% vs 62%, p = 0.37) and median dialysis vintage [40 months (interquartile Range, IQR: 16–93 months) vs 46 months (IQR: 12–92), p = 0.76]. The two groups did not differ as for diabetes (21% vs 25%, P = 0.33), hypertension (75% vs 71%, p = 0.36), and smoking habit (29% vs 28%, p = 0.51). Of note, the proportion of patients with background cardiovascular comorbidities was significantly higher in patients of Group 2 (enrolled in the post-implementation period) than in those of Group 1 (31% vs 19%, p = 0.04]. A total of 37 APE episodes in 18 patients (from 1 to 4 episodes per patient) were identified in patients of Group 1 vs 7 APE episodes in 5 patients (from 1 to 2 episodes per patient) in those of Group 2. The incidence rate of APE was 82% lower in patients during the post-implementation period (4 episodes per 100 patients/year, 95% CI: 1–8) than in those during the post implementation period (23 episodes per 100 patient/year, 95% CI: 17–32) (incidence rate ratio: 0.18, 95% CI: 0.10-0.29, p<0.001).

Conclusion

The systematic use of lung ultrasound (simple, easy to learn, rapid and non-invasive method, easily performed at the patient's bed) in every day clinical practice drastically reduced (-82%) the episodes of APE in hemodialysis patients. Further observational and interventional studies are needed to confirm these results.
#5478 REAL-WORLD SIGNS AND SYMPTOMS AT DIAGNOSIS IN PATIENTS WITH C3 GLOMERULOPATHY - INTERIM RESULTS FROM A MULTI-COUNTRY STUDY
Authors: Proudfoot Clare , Pannagl Katharina , Nguyen Jennifer , King Andrea , Murphy Kathleen , Decourcy Jonathan , Lafayette Richard
Published: June 2023

Background and Aims

C3 glomerulopathy (C3G) is a rare form of glomerulonephritis, with an estimated incidence of 1 – 2 per million per year. C3G is associated with a high risk of disease progression with approximately 50% of patients reaching kidney failure within 10 years of diagnosis. Common signs and symptoms include proteinuria, hematuria, edema and hypertension. The aim of this analysis was to better understand the clinical characteristics of C3G patients from the US, Europe and Asia, at the time of diagnosis.

Method

An analysis was conducted using interim data from the Adelphi C3G Disease Specific Programme (DSP), a cross-sectional survey of C3G-treating nephrologists in US, EU5 (France, Germany, Italy, Spain, UK), China and Japan (study ongoing since August 2022; interim analysis based on data until November). Nephrologists completed structured forms administered via online links for consecutive patients presenting with C3G. The forms included demographic and clinical information including signs, symptoms, and lab values amongst others.

Results

In this interim analysis, 88 nephrologists had completed records for 277 patients in this survey, including 95 in US, 120 in EU5, 39 in China and 23 in Japan. Median patient age at diagnosis was 40.9, and 60% were male. 80% had C3 glomerulonephritis (C3GN) and 19% had dense deposit disease (DDD). Median proteinuria at diagnosis was 2.9 g/day, and was ≥1 g/day in 82% of patients. Median eGFR at diagnosis was 50 ml/min/1.73m2 (Table 1). In addition to proteinuria, the main clinical signs and symptoms at diagnosis were hematuria, edema, hypertension and fatigue. Pain, appetite loss and sleep problems were also reported. Physicians described disease severity at diagnosis as moderate in 53% and severe in 31% of patients.

Conclusion

This study allows evaluation of a rare disease across geographies. C3G patients experience substantial symptomatic and clinical burden at diagnosis. This symptom burden, high proteinuria, and relatively low eGFR is consistent with physician assessment that the disease is moderate or severe by the time of diagnosis. Facilitating early diagnosis of C3G and rapid initiation of treatment could be beneficial for patients in slowing disease progression.
#5479 EXPLORING CANADIAN PATIENT EXPERIENCES OF LIVING WITH LUPUS NEPHRITIS
Authors: Cardwell Francesca , George Sydney , Boucher Adrian , Barber Megan , Cheema Kim , Elliott Susan , Clarke Ann
Published: June 2023

Background and Aims

Lupus nephritis (LN) is one of the most severe manifestations of SLE; however, the Canadian patient experience remains understudied. This research investigated patient experiences and perspectives of 1) LN diagnosis; 2) living with LN; and 3) LN healthcare and treatment.

Method

Patients aged ≥18 years with biopsy-proven pure or mixed ISN/RPS Class III, IV, or V LN and fulfilling the ACR 1997 or SLICC 2012 Classification Criteria for SLE were purposefully recruited from a Canadian lupus cohort to participate in semi-structured in-depth interviews. These were conducted virtually and transcribed verbatim for subsequent thematic analysis using NVivo Qualitative Data Analysis Software.

Results

Thirty patients with LN were interviewed; 86.7% were female, mean (SD) age was 42.1 (16.4) years, mean (SD) age at SLE diagnosis was 29.8 (15.3) years (Table 1). Patients reported challenges seeking, receiving and adjusting to the LN diagnosis, and all described emotional impacts associated with diagnosis. Most patients had limited knowledge of LN prior to diagnosis, and this lack of understanding made it difficult to contextualise their illness (Figure 1). Patients reported both emotional wellbeing and physical health impacts associated with living with LN. While most have continued in paid employment, patients identified altered career aspirations, role changes, and the need for accommodations in the workplace. Patients also described modified leisure and social activities (Figure 1). While many identified supportive friends and family, a lack of nuanced understanding of their experiences by others was reported. LN was described as a factor in family planning considerations amongst those of childbearing age. Specifically, fear of changing LN medications and their reproductive side effects, fear of experiencing a flare while pregnant/when parenting, and concerns about passing on LN/other autoimmune conditions to their children emerged (Figure 1). Numerous aspects of LN management present challenges for patients, including visiting a range of healthcare providers, taking medication, monitoring diet, stress management and ensuring adequate rest. While many reported successful LN management with medication, others expressed concern with cost and side effects. The challenges associated with a lack of LN-specific information and resources were identified (Figure 1).

Conclusion

A lack of individual and public understanding of LN coupled with the uncertainties of diagnosis/living with LN create a substantial psychosocial burden as patients negotiate acceptable risk in the face of uncertainty (e.g., in family planning, treatment, paid employment, leisure). Results emphasize the need for wider LN awareness and will inform the development of LN-specific patient resources to increase understanding of LN and better support decision-making.
#5482 CIRCULATING BIOMARKERS OF COLLAGEN REMODELING AS MARKERS FOR DEVELOPMENT OF MICROALBUMINURIA IN TYPE 2 DIABETES: THE PRIORITY TRIAL
Authors: Møller Alexandra Louise , Curovic Viktor Rotbain , Rasmussen Daniel G K , Genovese Federica , Karsdal Morten A , Hansen Tine , Rossing Peter
Published: June 2023

Background and Aims

Kidney disease progression is characterized by extensive deposition of extracellular matrix components such as collagen. Therefore, we assessed the effect of spironolactone on collagen remodeling biomarkers and investigated the association between the markers and development of microalbuminuria in serum of persons with type 2 diabetes and normoalbuminuria.

Method

We measured collagen type III (PRO-C3), VI (PRO-C6; endotrophin), VII (PRO-C7), and XXVIII (PRO-C28) formation, and a fragment of degraded crosslinked collagen type III (CTX-III) in serum of persons with high-risk (stratified by a urinary proteomics classifier, CKD273) for development of microalbuminuria, randomized to either spironolactone 25 mg or placebo. Crude and adjusted Cox models were applied to investigate the association between baseline biomarker levels and development of the primary outcome, persistent microalbuminuria, and development of microalbuminuria in at least one morning void sample, used as a secondary outcome.

Results

In the PRIORITY trial, spironolactone treatment did not prevent progression to microalbuminuria compared to placebo. All biomarkers were measured in 154 participants at baseline and 117 at end-of-study (week 208). Treatment with spironolactone did not affect serum levels of any of the investigated collagen remodeling biomarkers compared to placebo, and there were no differences in delta-biomarker levels between baseline and end-of-study (p ranging 0.277-0.875). In crude analyses, serum endotrophin was associated with both the primary (n = 44) and secondary outcome (n = 74) (HR per two-fold higher level: 1.58, 95% CI: 1.03-2.44, p = 0.037 and 1.62, 1.12-2.35, p = 0.010), whereas serum PRO-C3 was only associated with the secondary outcome (1.89, 1.19-2.99, p = 0.007). After adjustment for sex, baseline age, systolic blood pressure, estimated glomerular filtration rate, urinary albumin-creatinine ratio, and HbA1c, serum endotrophin and PRO-C3 remained significantly associated with the secondary outcome (1.52, 1.03-2.24, p = 0.036 and 1.73, 1.08-2.78, p = 0.022). Levels of PRO-C7, PRO-C28, and CTX-III were not associated with the specified outcomes. Neither baseline levels of serum endotrophin nor PRO-C3 correlated with baseline CKD273 levels (R: 0.00-0.06, p>0.47).

Conclusion

Treatment with spironolactone did not change serum levels of collagen remodeling biomarkers. Serum endotrophin, reflecting collagen type VI formation and the pro-fibrotic molecule endotrophin, and PRO-C3, a marker of collagen type III formation, were associated with development of microalbuminuria in at least one urine sample, suggesting that these biomarkers are relevant risk markers for kidney disease development in type 2 diabetes.
#5490 GENERATIVE ARTIFICIAL INTELLIGENCE FOR CREATION OF SYNTHETIC HYPERTENSION TRIAL DATA
Authors: Jain Chirag , Judge Conor
Published: June 2023

Background and Aims

Synthetic data can be an effective supplement or alternative to real data for the training of machine learning models. Synthetic data may also be used to evaluate new tools, develop educational curricula, or remove undesirable biases in datasets. We aim to evaluate four synthetic data generation methods applied to hypertension randomized clinical trial data.

Method

The Systolic Blood Pressure Intervention Trial (SPRINT) trial showed that intensive BP control to SBP <120 mm Hg results in significant cardiovascular benefits in high-risk patients with hypertension compared with routine BP control to <140 mm Hg. The Synthetic Data Vault (SDV) is a Synthetic Data Generation ecosystem of libraries that allows users to easily generate new Synthetic Data that has the same format and statistical properties as the original dataset. SDV supports multiple types of data, including date-times, discrete-ordinal, categorical, and numerical. SPRINT data was pre-processed to create a single table of 140,000 patient visits with baseline variables (age, sex, race, aspirin use, estimated Glomerular Filtration Rate (eGFR)) and visit level variables (systolic and diastolic blood pressure, heart rate and total number of antihypertensive medications at end of visit). Using the SDV library for python, we used four generative models to create synthetic SPRINT data, 1. Gaussian copula model, 2. Conditional Tabular Generative adversarial network (CTGAN), 3. CopulaGan model, and 4. Tabular Variational Auto-encode (TVAE). We evaluated the results using the SDMetrics library which includes the shapes of the columns (marginal distributions), the pairwise trends between the columns (correlations), reproduce mathematical properties from your original data and new row synthesis. Finally, an overall quality score which represents an amalgamation of the marginal distribution and correlations was computed, where 0 indicates the lowest quality and 1 indicates the highest.

Results

Two hundred thousand synthetic patient visits were created for each method. The overall quality scores in order were 90.67% for Gaussian copula, 86.77% for TVAE, 81.03% for CTGAN’, and 79.7% for CopulaGAN. The column shape score which represents the marginal distribution was highest for Gaussian Copula (94.54%), followed by TVAE (88.44%), CTGAN (82.35%), and Copula GAN (80.27%). The column pair trend which corresponds to correlations was highest for Gaussian Copula (86.8%), followed by TAVE (85.1%), CTGAN (79.72%), and Copula GAN (79.12%).

Conclusion

Gaussian copula created the highest scoring synthetic SPRINT data based on the marginal distribution, correlations, and overall score. The Synthetic Data Vault is a feasible collection of methods for generation of synthetic clinical trial data for training future machine learning and AI models.
#5503 PIOGLITAZONE REVERSES MIR-130A AND MIR-199 DYSREGULATION INDUCED BY TGF-BETA DURING KIDNEY FIBROSIS
Authors: Mozes Miklos , Gantsetseg Garmaa , Manzéger Anna , Kokeny Gabor
Published: June 2023

Background and Aims

The peroxisome proliferator-activated receptor-γ (PPARγ) agonists have been shown to dampen TGF-β signaling and suppress miR-130a in VSMCs and also profibrotic miR-21-5p in the kidney. We have recently demonstrated that pioglitazone ameliorates established renal fibrosis by suppressing STAT3 and EGR1 [1], but its effect on renal miR-130a has not been investigated. Thus, we aimed to study how chronic oral pioglitazone treatment would affect TGF-β–driven renal miRNA dysregulation in mice.

Method

Ten week old male C57Bl6 control (CTL, n = 6) and TGF-β transgenic mice (TGFb, n = 12, having elevated plasma TGF-β1 level) were used. CTL mice and half of TGFb mice received regular chow. The second half of transgenic mice received pioglitazone containing chow (dose: 20mg/kg/day) for 5 weeks (TGFb+Pio, n = 6), when the kidneys were evaluated.

Results

Untreated TGFb mice had a 4.7-fold and 2.8-fold type I and type III collagen mRNA overexpression as compared to controls, respectively. This was accompanied by 3.8-fold pro-fibrotic Egr2 mRNA, 2.9-fold miR-130a, 3.9-fold miR-199 and 3.3-fold miR-21 overexpression. Chronic treatment with the PPARγ agonist pioglitazone reduced the expression of both collagen mRNAs and miRNAs miR-199 and miR-21 to control levels, but miR-130a reached even lower values than in control kidneys. Interestingly, the expression of miR-200a (regulated by TGF-beta and known to ameliorate fibrosis) was similar in all CTL and TGFb groups, regardless of treatment.

Conclusion

Our data indicate that PPARγ agonist pioglitazone not only attenuates the TGF-β induced miR-21 overexpression, but also the renal dysregulation of miR-130a and miR-199, supporting its anti-fibrotic effects.