Single Center Research Articles

Retrospective study revealed integration of CNV-seq and karyotype analysis is an effective strategy for prenatal diagnosis of chromosomal abnormalities

Fetal chromosomal abnormalities are the main cause of adverse pregnancy outcomes and are the focus of invasive prenatal diagnosis. Recent studies have demonstrated that various techniques have distinct advantages. Achieving high-resolution and effective prenatal chromosomal abnormality diagnosis requires a multi-technology integration strategy. Based on retrospective samples from a single center, we propose that integrating CNV-seq and karyotype analysis is an effective strategy for prenatal diagnosis of chromosomal abnormalities. In this study, 13.80% of the pregnant women (347/2514) were found to have likely pathogenic or pathogenic fetal chromosomal abnormalities using this integrated approach. Among these cases, 53.89% (187/347) had consistent chromosomal abnormalities detected by both CNV-seq and karyotyping analysis, while 19.02% (66/347) and 27.09% (94/347) of cases were diagnosed solely by CNV-seq or karyotyping, respectively. Fetal chromosomal abnormalities were identified in 18.39% of samples with abnormal ultrasound, which was significantly higher than the percentage found in samples with normal ultrasound (p < 0.001). Samples with multiple ultrasound abnormalities and single-indicator ultrasound abnormalities such as nasal bone dysplasia, renal dysplasia, or echogenic fetal bowel also had higher rates of chromosomal abnormalities (p < 0.05) compared to normal samples. Analyzing samples with Trio family data (N = 521) revealed that about 94% of variants of uncertain significance were inherited from parents and were non-pathogenic. Overall, integrating CNV-seq and karyotype analysis is an effective strategy for prenatal diagnosis of chromosomal abnormalities. This study provides valuable insights for correlating prenatal screening indicators with chromosomal abnormalities.

#1174 Prevalence and factors contributing to erythropoietin hyporesponsiveness in CKD patients on hemodialysis: a single center, cross sectional study

Abstract Background and Aims Anemia, one of the most frequent early complications of CKD is associated with a reduced QOL, cardiovascular morbidity, accelerated CKD progression, and it is an independent predictor of mortality. The successful management of anemia is a vital part of patient care, that improves clinical outcomes. According to the literature, 90% of renal anemia patients responded in a dose-dependent manner to rHu EPO, whereas the remaining 5–10% of patients had either a blunted or absent response to this agent, despite high-dose therapy. Erythropoietin hyporesponsiveness is a strong, independent predictor of mortality risk. Various factors have been associated with ESA hypo responsiveness in different studies. Both the inability to achieve a target hemoglobin and administration of high dose epoetin -alpha are associated with increased risk of CVD complications. AIMS AND OBJECTIVES Method STUDY PERIOD: December 2021 to DECEMBER 2022 STUDY DESIGN: Observational cross sectional study. SAMPLE SIZE: N = 144: Patients older than 18 years old undergoing hemodialysis for at least 3 months before the study were enrolled. History of inpatient treatment, infection, bleeding or transfusion within the last month, hematologic disorders sickle cell disease, MDS and active malignancies were excluded. Required parameters were recorded on every month follow up;Demographic data, Cause of ESRD, Dialysis vintage, ESAs dose (Unit/week), type, Medications history; Dose (mg/week) of iron preparation & use of medication like ACEi, ARBs, dialysis adequacy(Kt/V), haemogram, Liver function test, Kidney function test Iron profile, Serum parathyroid hormone, Serum calcium & phosphorus, CRP, Anti EPO antibodies(if required). We used the European Best Practice Guideline (EBPG) II definition to define ESA hyporesponsiveness for our study purpose(Increase in erythropoietin dose ≥25% to maintain the same Hgb level or < 1 mg/dL gain in Hgb after 4 weeks. EHRI was calculated by dividing weekly ESA dose per kilogram of body weight (IU/Kg/W) by hemoglobin level (g/dL). Based on EHRI, patients were assigned or divided into 2 groups. Group I (EHRI<16) and Group II (EHRI ≥ 16). Patients in the Group II were labeled as erythropoietin hyporesponsive patients and they were compared with others in order to identify the impact of different factors on ESA. Results Among 144 patients, 80 were male and 64 females and 28.4% were diabetic. Mean EHRI were calculated for all patients and based on EHRI pts were divided into two study groups, Gr-I (EHRI<16) & Gr-II(EHRI ≥16). EHRI ≥16 group was considered as ESA hyporesponsive groups. The study parameters were compared between the groups and its statistical significance measured. The overall prevalence of ESA hyporesponsive in our study was 26.3%. Conclusion The overall prevalence of ESA hyporesponsive in our study was 26.3%. Iron deficiency anemia, inadequate dialysis, chronic inflammation, malnutrition, secondary hyperparathyroidism and increased dialysis vintage were the factors associated with ESA hyporesponsiveness.

#57 Tubular biomarkers in proteinuric kidney diseases

Abstract Background and Aims Proteinuria is not only a biomarker of chronic kidney disease (CKD) and a risk predictor of adverse outcomes but also a driver of kidney disease progression. The excessive filtration of plasma proteins through the glomerular filtration barrier exerts a toxic effect on tubular cells which ultimately leads to fibrosis and end-stage kidney disease (ESKD. The aim of this study was to assess the levels of various tubular biomarkers in both serum and urine in patients with biopsied glomerular and proteinuric kidney diseases, and correlate them with renal histology and kidney outcomes. Method A retrospective study and observational study was conducted at a single center from January 2016 to December 2021. Serum and urine samples were collected on the same day of renal biopsy and were correlated with histological data from a cohort of 156 patients with proteinuric kidney diseases. Kidney outcomes were registered during a median follow-up period of 26 months and defined as a decrease in eGFR ≥ 40% from baseline or the development of end-stage kidney disease. The following urinary markers, adjusted to urine creatinine, were analyzed: β2-mcg (beta 2 microglobulin), α1-mcg (alpha 1 microglobulin), NGAL (Neutrophil Gelatinase-Associated Lipocalin), uKIM-1 (Kidney Injury Molecule-1), MCP-1 (Monocyte Chemoattractant Protein-1), uDKK-3 (urinary Dickkopf-3), and uUMOD (uromodulin). Serum markers sKIM-1 and uUMOD were also collected. Results Regarding the etiology of proteinuric kidney disease, the majority corresponded to glomerular disease (68.6%) followed by diabetic kidney disease (12.8%). Higher levels of proteinuria were associated with increased values of β2-mcg and α1-mcg levels and low levels of uUMOD and sUMOD. A significant correlation between the extent of interstitial fibrosis and specific biomarkers was observed: uDKK3 (rho = 0.804, p < 0.001), sKIM-1 (rho = 0.472, p < 0.001), sUMOD (rho = −0.370, p < 0.001), uUMOD (rho = −0.317, p < 0.001), MCP-1 (rho = 0.374, p < 0.001), uKIM-1 (rho = 0.368, p < 0.001), and β2-mcg (rho = 0.392, p < 0.001). Multivariate regression analysis identified uDKK3 as an independent predictor of interstitial fibrosis (Beta 0.728, p < 0.001) adjusted for age, serum creatinine and proteinuria. Elevated levels of MCP-1 and uKIM-1 were associated with a higher risk of significant cortical interstitial inflammation >10% in the logistic regression analysis adjusted for eGFR, proteinuria, and microhematuria: MCP-1 OR = 5.14, 95% CI (2.27−11.62), p < 0.001 and uKIM-1 OR = 1.64, 95% CI (1.05−2.58), p = 0.031. Patients with higher tertiles of β2mcg, MCP1, uDKK3, and KIM1s, and lower tertiles of uUMOD and sUMOD experienced a significantly reduced renal event-free survival in the analysis of Kaplan-Meier model (Fig.). Moreover, of all the evaluated markers, uDKK3 was identified as the best predictor of renal events [HR = 1.03, 95% CI (1.01−1.06), p = 0.008], independently of age, baseline eGFR, proteinuria, and the extent of interstitial fibrosis at the time of renal biopsy. Conclusion Tubular biomarkers may offer prognostic value in proteinuric kidney diseases, particularly uDKK3, exhibiting a notable correlation with interstitial fibrosis and serving as a potential predictor of CKD progression.

Variation in care for inpatients with avoidant restrictive food intake disorder leads to development of a novel inpatient clinical pathway to standardize care

IntroductionThere is limited evidence to guide management of patients with avoidant restrictive food intake disorder (ARFID) admitted for medical stabilization. We describe variations in inpatient care which led to the development of a multidisciplinary inpatient clinical pathway (ICP) to provide standardized management and examine differences after the ICP was implemented.MethodsA retrospective review of patients with ARFID admitted to Adolescent Medicine, Gastroenterology, and General Pediatrics at a single academic center was conducted. We compare hospital utilization and use of consulting services during the pre-ICP (2015–2017) and post-ICP (2018–2020) periods.Results110 patients were admitted with ARFID (n = 57 pre- vs. n = 53 post-ICP). Most presented with moderate/severe malnutrition (63% pre vs. 81% post; p = 0.11) and co-morbid anxiety and/or depression (74% pre vs. 92% post; p = 0.01). There was some variation in use of enteral tube feeding by service in both periods (p = 0.76 and p = 0.38, respectively), although overall use was consistent between periods (46% pre vs. 58% post; p = 0.18). Pre-ICP, use of the restrictive eating disorder protocol differed across services (p < 0.001), with only AM using it. Overall, utilization of the restrictive eating disorder protocol decreased from 16% pre-ICP to 2% post-ICP (p = 0.02). There was variation by service in psychiatry/psychology (range 82–100% by service; p = 0.09) and social work consultations (range 17–71% by service; p = 0.001) during the pre-ICP period, though variation was reduced in the post-ICP period (p = 0.99 and p = 0.05, respectively). Implementation of the ICP led to improvements in these consultative services, with all patients in the post-ICP period receiving psychiatry/psychology consultation (p = 0.05) and an increase in social work consults from 44 to 64% (p = 0.03). Nutrition consults were consistently utilized in both periods (98% pre vs. 100% post; p = 0.33).ConclusionThe ICP was developed to standardize inpatient medical stabilization for patients with ARFID. In this single center study, implementation of the ICP increased standardized care for inpatients with ARFID with variation in care reduced: there were improvements in the use of consulting services and a reduction in the use of the restrictive eating disorder protocol. The ICP demonstrates the potential to further standardize and improve care over time.

#1049 Genetic characteristics of autosomal dominant polycystic kidney disease in a Greek population

Abstract Background and Aims Autosomal dominant polycystic kidney disease (ADPKD) is the predominant monogenic renal genetic disorder, and the fourth leading cause of end stage kidney disease. Confirmatory genetic testing defines the disease, provides prognostic information and may support therapeutic management. This study aims to investigate the genetic characteristics of a substantial cohort of ADPKD patients from a single Greek center. Method Ninety-three patients (46 females, 47 males with a mean age of 34 ± 15 years) were enrolled from 59 distinct families attending the outpatient ADPKD clinic at the Nephrology Department of the General Hospital of Athens “G. Gennimatas.” Genetic analysis included targeted next-generation sequencing (tNGS) of over 600 clinically relevant genes, Sanger sequencing, and Multiplex ligation-dependent probe amplification (MLPA). Whole exome and whole genome sequencing (WES and WGS) studies were conducted in 3 patients with negative results. Magnetic Resonance Imaging (MRI) was performed in 74 out of 93 patients, revealing more than 10 renal cysts in all but one patient. Children with a positive family history (FH) displayed at least one cyst in echography, while two without FH had multiple renal cysts. Results Genetic diagnosis was established in 88 of 93 patients (94.5%). Seventy patients (75%), demonstrated single nucleotide variants (SNVs) and large deletions (4 patients) in the PKD1 gene, whereas SNVs and large deletions (5 patients) in the PKD2 gene were identified in 15 (16%) patients. Additionally, mutations in genes other than PKD1 and PKD2 were identified in 3 patients (3.5%). Two cases, involving a father and son, revealed the presence of a SEC61B variant; the father exhibited more than 10 renal cysts and liver cysts in the MRI, while the son displayed only liver cysts. Additionally, a third patient, a woman with nephrolithiasis and over 10 renal cysts in the MRI, exhibited a SLC3A1 variant. Notably, 5 patients (5.5%) with ADPKD phenotype had negative genetic analyses, despite the application of both WES and WGS in three of these patients. Truncating mutations in PKD1 were observed in 43 of 70 cases, (61%), while the rest (39%) had non-truncating mutations. Detected variants were classified as Pathogenic (45.5%), Likely Pathogenic (36%), and Variants of Uncertain Significance (VUS-13.5%, 12 cases), according to the guidelines of the American College of Medical Genetics and Genomics. Reclassification to Likely Pathogenic could be proposed for 6 out of 12 cases with VUS variants for which family segregation was noted. Finally, 52% and 82% of the detected variants have not been previously reported in ClinVar and gnomAD databases, respectively. Conclusion In this ethnically homogenous population, truncating mutations in the PKD1 gene were the predominant genetic cause of ADPKD, followed by PKD1 non-truncating mutations, PKD2 gene variants and other rare or undefined genetic etiologies.

Hyaline fibromatosis syndrome: a rare, yet recognizable syndrome.

Hyaline fibromatosis syndrome is a rare autosomal recessive disorder caused by ANTXR2 pathogenic variants. The disorder is characterized by the deposition of amorphous hyaline material in connective tissues. The hallmarks of the disease are joint contractures, generalized skin stiffness, hyperpigmented papules over extensor surfaces of joints, fleshy perianal masses, severe diarrhea, and gingival hypertrophy. The severity of the disease varies and prognosis is poor. No specific treatment is yet available. Most patients with the severe form of the condition pass away before the second year of age. In this study, we describe the clinical and molecular findings of a cohort of seven hyaline fibromatosis syndrome patients who were diagnosed and followed up at a single tertiary reference center in Turkey. Genomic DNA was extracted by standard salting out method from peripheric blood samples of three patients. In one patient DNA extraction was performed on pathology slides since peripheric blood DNA was not available. All coding exons of the ANTXR2 were amplified and sequenced on ABI Prism 3500 Genetic Analyser. Sanger sequencing was performed in 3 patients and homozygous c.945T>G p.(Cys315Trp), c.1073dup p.(Ala359CysfsTer13), and c.1074del p.(Ala359HisfsTer50) variants were identified in ANTXR2. All patients passed away before the age of five years. HFS is a rare, progressive disorder with a broad phenotypic spectrum. HFS can be recognized easily with distinctive clinical features. Nevertheless, it has poor prognosis with increased mortality due to severe clinical decompensation.

#2343 Fabry disease screening in patients with chronic kidney disease and dialysis at a single medical center in Taiwan

Abstract Background and Aims Chronic Kidney Disease (CKD) poses a significant global health challenge, with diverse contributing factors impacting its progression. Among these, Fabry Disease, a rare lysosomal storage disorder, has emerged as a potential complicating factor. Despite its relevance, the prevalence of Fabry Disease among CKD patients, particularly in Taiwan, remains insufficiently explored. Recognizing and understanding the occurrence of Fabry Disease in CKD populations are crucial for comprehensive patient care and may have implications for treatment strategies. Additionally, investigating the relationship between kidney function and Plasma α-Gal A activity is essential. α-Gal A, the enzyme deficient in Fabry Disease, may experience altered activity levels in the presence of compromised kidney function. Clarifying this connection is pivotal for gaining insights into the intricate interplay between Fabry Disease and CKD. This study aims to achieve three key objectives (1) Determine Fabry Disease Prevalence among CKD Patients in Taiwan.(2) Investigate the Impact of Kidney Function on Plasma α-Gal A Activity.(3) Characterize Gene Mutation Patterns and Demographic Data of Fabry Patients in CKD Population in Taiwan: Method Fabry Disease assessment involved a two-stage process, tailored to the patient's gender. Males underwent a dry blood test measuring α-galactosidase activity; samples below 15% of the adult average were deemed positive. Females were screened based on lyso-Gb3 levels in whole blood; a result exceeding 0.8 ng/ml was considered positive. Positive screenings prompted genomic DNA extraction, and the GLA gene's seven exons and intron 4 segment ([GRCh38/Hg38] chrX:101,399,610-101,399,874) were PCR-amplified. Sanger sequencing identified pathogenic variants. This gender-specific, multi-step approach ensures precision. Defined thresholds and advanced genomic techniques enhance diagnostic accuracy. The method provides a robust means of identifying Fabry Disease, supporting early intervention and personalized treatment. Results Study Recruitment: Initially, 2000 subjects enrolled, but 155 withdrew, yielding a final cohort of 1845 patients for analysis. Screening and Referral: Among 1602 subjects, 26 males (1.6%) were referred for DBS LysoGB3 check-up due to low serum α-Gal A activity. In a cohort of 243 females, 6 individuals (2.4%) underwent GLA genetic sequencing due to elevated lyso-GB3 levels. Clinical Presentation - Male Case: A male with acute stroke symptoms and CKD stage 3b (eGFR 34.5 mL/min/1.73 m²) showed significantly low DBS α-Gal A activity (0.48 μmol/hr) and elevated Plasma LysoGB3 (28.08 ng/ml).GLA genetic sequencing revealed a specific deletion (c.1072-1074delGAG, p. (Glu358 del)) in exon 7, leading to a Fabry disease diagnosis, classifying it as a specific type. The family pedigrees of this male patient are visually represented in Fig. 1, illustrating the genetic relationships within the family. Clinical Presentation - Female Case: A female on hemodialysis for four years, cause unknown, exhibited a DBS LysoGB3 level of 0.5 ng/ml. GLA genetic sequencing identified a nucleotide variation (c.640-801G&amp;gt;A) in intron 4, establishing a diagnosis of Fabry disease with the cardiac variant (301500). Fig. 2 demonstrates the relationship between serum DBS GLA activity and different stages of CKD. Our analysis reveals that in CKD stages 1, 2, 3 (3a and 3b), and 4, the serum GLA activity is significantly higher compared to stage 5. Conclusion The prevalence of Fabry Disease in our cohort was 0.1% (2 out of 1845 individuals), featuring one female with the cardiac variant and one male with the class type. Our investigation unveiled a significant rise in serum GLA activity in CKD stages 1–4 compared to stage 5, suggesting potential implications for early CKD detection. Moreover, serum α-Gal A activity displayed a notable correlation with age, BUN, and eGFR across CKD stages 1–5, questioning its status as a biomarker for advanced CKD and aging in CKD patients. This prompts consideration for a large-scale study to validate this hypothesis.

#1561 A tool for the “screening” of the dialysis facilities environmental impact

Abstract Background and Aims The great number of resources needed for hemodialysis treatment can be a limiting factor in the perspective of access to care, especially in developing Countries, and may have a negative impact on the environment. The aim of the study was to develop a questionnaire that is easy and informative of the ecologic impact (energy costs and waste production) of a single dialysis center. The questionnaire's goal is to highlight potentially modifiable factors that are responsible of the ecologic footprint of dialysis. Method A team of 8 people, 3 nephrologists, 3 representatives of dialytic equipment companies and 2 of water treatment systems, developed the questionnaire. The items have been decided after two meetings in person. The completed questionnaire included 49 items divided into three sections, exploring the organization techniques of the dialysis center, its consumption and its water treatment system's characteristics. The questionnaire was then submitted to 11 dialysis centers and made available from 30 September 2022 to 1 February 2023, and included data collected in May 2022. An investigator assisted within filling in the form and collecting feedback on the comprehension of the questions and on any problems that may have surfaced during the compilation of the questionnaire. Results The questionnaires were completed by the center's managers who, unanimously, thought that the form was easily understandable and without significant problems during the compilation. The data collected evidenced that there is almost no real knowledge of the center's consumptions and that also many data about power and water consumption and of waste production are ignored and are therefore missing. No center is fueled by renewable energies. Data refers to a total of 10337 dialysis treatments, with an average 940 treatments per center. Electrical consumption and waste production are in line with the literature, with an average of 13 KwH and 1,9 kg consumption per treatment, respectively. The average water consumption in our sample (550 L per treatment) seems to be higher than expected. Standard dialysate flow was greater than or equal to 500 ml/min in both HD and HDF, except in two centers. Five centers had a water treatment system which is more than eight years old. Average values of each center are reported in the Table 1. Conclusion Our questionnaire appears to be an easily fillable option to carry out consumption “screenings” of each dialysis center. The form could also prove itself useful for a large-scale investigation, to collect an adequate amount of data and to conduct a thorough research to highlight critical issues that could affect the center's consumption. A wider spread of this questionnaire could improve the awareness of nephrologists about their dialysis structure's consumption, taking part in the cultural revolution which is needed to develop a “greener” nephrology.

Continuous Glucose Monitoring for Management of Type 2 Diabetes and Perinatal Outcomes.

To evaluate the association between continuous glucose monitoring in pregnant people with type 2 diabetes and perinatal outcomes. This was a retrospective cohort study of pregnant people with type 2 diabetes who received prenatal care and delivered singleton, nonanomalous neonates at a single academic tertiary care center from November 1, 2019, to February 28, 2023. The primary outcome was a composite of neonatal morbidity, including hypoglycemia, hyperbilirubinemia, shoulder dystocia, large for gestational age at birth, preterm birth, neonatal intensive care unit (NICU) admission, or perinatal death. Demographics and outcomes were compared by type of monitoring (continuous glucose monitoring vs intermittent self-monitoring of blood glucose), and multivariable logistic regression estimated the association between continuous glucose monitoring use and perinatal outcomes. Of 360 pregnant people who met the inclusion criteria, 82 (22.7%) used continuous glucose monitoring. The mean gestational age at continuous glucose monitoring initiation was 21.3±6.4 weeks. The use of continuous glucose monitoring was associated with lower odds of the primary composite neonatal morbidity (65.9% continuous glucose monitoring vs 77.0% self-monitoring of blood glucose, adjusted odds ratio [aOR] 0.48, 95% CI, 0.24-0.94). Continuous glucose monitoring use was also associated with lower odds of preterm birth (13.4% vs 25.2%, aOR 0.48, 95% CI, 0.25-0.93) and NICU admission (33.8% vs 47.6%, aOR 0.36, 95% CI, 0.16-0.81). In pregnant people with type 2 diabetes, continuous glucose monitoring use was associated with less neonatal morbidity, fewer preterm births, and fewer NICU admissions.

#2426 Diabetes treatment in CKD patients—do we treat according to the guidelines?

Abstract Background and Aims T2DM is a global pandemic, frequently complicated by DKD, that may result in ESRD and cardiovascular complications. Despite advancements in diabetes and cardiovascular risk management, the prevalence of DKD continues to grow. During the last years SGLT2i and GLP1RAs have demonstrated effectiveness in cardiorenal protection. The 2020 KDIGO guidelines recommend these treatments for cardiorenal protection in DKD patients. No data was published on the rate of implementing these guidelines. Identifying a gap between the guidelines and the actual treatment given to patients allows active intervention to enhance adherence to the guidelines and may improve health outcomes of patients. The aim of the study was to assess KDIGO guidelines implementation by nephrologists in a nephrology clinic, compared to a multidisciplinary diabetes-CKD clinic. This team includes a nephrologist, diabetologist, diabetes nurse and dietitian. The focus is on lifestyle modification education and advanced treatments for DKD. Method This study is a retrospective, descriptive, and quantitative convenience sample at a single medical centre. Study population included adult patients over 18 years, with T2DM and CKD, who were treated at the nephrology and diabetes-CKD clinics between May 2021 and May 2022. Type 1 diabetic patients and patients requiring dialysis were excluded. Demographic, diabetes and CKD related data were collected. Utilization of KDIGO recommended medications was analysed and compared between the two clinics. Results 587 and 100 patients from nephrology and diabetes-CKD clinics, respectively, were included. Baseline characteristics are described in Table 1. Recommended anti diabetic and other CKD treatments utilization is described in Table 2. Implementation of recommended medications, including SGLT2i and GLP1RAs, was significantly higher in the diabetes-CKD clinic, demonstrating a significant disparity in guideline adherence between the two clinics. Conclusion DKD is a common complication of T2DM that may progress to ESRD, and associated with increased cardiovascular risk. The evolving landscape of treatment is reflected in updated guidelines from various professional organizations, including KDIGO. These guidelines position SGLT2i and GLP1RAs as 1st and 2nd line treatments for patients with T2DM and CKD. Patients treated at the diabetes-CKD clinic were younger, had higher incidence of dyslipidemia and IHD and their diabetes was less controlled compared to the nephrology clinic patients. Despite the guidelines, underuse of recommended antidiabetic medications and other treatments persists in nephrology clinics. However, the multidisciplinary approach of the diabetes-CKD clinic, showed improved adherence to guidelines. In conclusion, the study provides insights into the challenges of implementing KDIGO guidelines in real world nephrology clinical settings. Further research is warranted to understand factors contributing to the low adherence. The findings suggest that a multidisciplinary approach may enhance guideline compliance and subsequently improve outcomes in managing DKD in T2DM.

#1214 Post-kidney transplant cancer: incidence, risk factors and future perspectives. Real-world analysis of a single Italian center

Abstract Background Our retrospective observational study aims to describe the epidemiology of cancer after KTx and to investigate its risk factors and the impact on therapeutic management and survival, in a big monocentric cohort of kidney transplant patients (KT-ps). The association between a specific modification of immunosuppressive therapy after cancer diagnosis and survival outcomes will be analyzed. Methods Retrospective collection of data in KTx-ps transplanted between January 2004 and December 2021, subjected to outpatient follow-up with a median follow-up of 7 [1-19] years. Results We included 930 KTx-ps with mean age at KTx of 49 years. 91% had received pre-TR dialysis, for an average of 52 months. The majority had received KTx from a deceased donor (84%). 74% had undergone induction therapy with Basiliximab and 26% ATG. Maintenance therapy included in most cases the use of steroids (87%), calcineurin inhibitors (tacrolimus 92%, ciclosporin 8%), and mycophenolate (94.6%). Patients with at least one cancer (CAN+) were 177 (19%). The mean time from TR to oncological diagnosis was 83 months. Non-melanoma skin cancers (NMSC) were the most common tumors (55%), while solid tumors were observed in 38.6% of cases. Deceased donor was more represented in CAN+. CAN+ were older and with higher BMI. They had greater presence of vasculitis as basic nephropathy. In the period between 2016 and 2021, induction therapy with ATG was significantly associated with CAN+. In multivariable analysis, ATG emerged as an independent risk factor for CAN+ (p=0.014) and, in survival analyses, ATG was strongly and significantly related to the earlier development of CAN+ (p=0.010). During follow up, cancer-related causes were the second cause of mortality (23%); the average time from cancer diagnosis to death was 23 months. The median survival from TR was 148 (CAN+) and 82 months (CAN−). After oncological diagnosis, significant evidence on tumor survival was derived from the shift to mTOR inhibitors compared to the group with definitive drug suspension (p=0.004). Conclusion The data reported by our study confirm the relevance of cancer as a complication in KTx. ATG represent an independent risk factor for cancer; in this context, a personalized choice of immunosuppressive therapy to be proposed at the time of TR represents a crucial point in the prevention of neoplastic risk. In the KTx-ps, therapeutic strategies with antineoplastic agents and management of immunosuppression therapy after malignancy remain important research perspectives in the near future.

#826 Protein-energy wasting and sarcopenia in assessing the outcomes and quality of dialysis

Abstract Background and Aims Sarcopenia is one of the serious complications of long-term hemodialysis (HD) therapy and is one of the independent predictors of morbidity and mortality in this population. Sarcopenia is associated with low physical activity, depression and low social adaptation. There are few estimates of the sarcopenia prevalence in HD patients, and they fit into the range of 15-30% in the general group and 45-60% among patients over 60 yo. The aim: in a prospective study, to clarify the prevalence, outcomes and risk factors of sarcopenia in comparison with protein and energy wasting (PEW) severity data. The results of the first year follow-up of the first cohort in the ongoing study are presented below. Method In the group of 99 prevalent patients of single HD center (vintage 26.4; 21.8-93.3 months; age 55±17 years, HD/HDF for 4-4.5 hours three-time weekly; Kt/V 1.57±0.31), the prevalence of sarcopenia was estimated (muscle mass was assessed anthropometrically and by bioimpedance (BIA), BodyStat 5000). The presence of sarcopenia was assessed by EWGSOP2 criteria, muscle strength - by wrist expander. The reference values for men and women were &amp;gt;27 kg and &amp;gt;16 kg. The PEW degree was assessed by 24-point scale (BMI, arm circumference, skin-fat fold above the triceps, arm muscle circumference, total protein, albumin, transferrin, absolute lymphocytosis; max 3 point for each). Obesity was established at BMI &amp;gt;30 kg/m² or according to the fat mass index &amp;gt;9 kg/m² in men and &amp;gt;13 kg/m² in women. The quality of life was assessed by KDQOL-SF™ after exclusion of patients with significant depression by the Beck scale. Results The muscle mass indices calculated anthropometrically (IMMA) and by bioimpedance (IMMB) were well correlated: IMMA=0.15+1.06×IMMB, R²=76%; diagnostic efficacy (in detecting sarcopenia) IMMA to IMMB was 86%. The prevalence of PEW by stage: absent (scores of all assessed scales - 3) – 59%, grade 1 (average score ≥2 and &amp;lt;3) – 32%, grade 2 (average score ≥1 and &amp;lt;2); in one patient, PEW was classified as severe (average score of scales &amp;lt;1). In the univariate and in the multiple adjusted analysis (for age, gender, provided dialysis dose and average ultrafiltration, hemoglobin and phosphate levels), the degree of PEW or the presence of PEW was not associated with the risk of death. At the same time, the phase angle (PA) of bioimpedance had such a link: the PA increase in by 1° was associated with a 24.4% reduction in the risk of death (95%CI 3.9-40.4%; p=0.022), and the inclusion of the same set of variables in the regression analysis model as for the PEW only weakened, but did not eliminated the link (OR decrease by 26.9%; 0.3-46.4%; p=0.048). The risk of death was not associated with obesity. Sarcopenia was detected in 52% of patients. It was not associated with the presence (severity) of PEW in women, but in men it was 1.48 times more common in the presence of PEW (p=0.049); in the entire group, the higher prevalence of sarcopenia in the presence of PEW (by 34%) did not reach significance (p=0.3). In multiple regression analysis, the presence of sarcopenia was associated with a 1.95-fold higher risk of death (95% CI 1.001-3.809; p=0.050). In the presence of sarcopenia, the quality of life scores were significantly lower for the scales of Physical functioning, Energy, and Physical Composite Score. The higher prevalence of sarcopenia among men than in women remains unexplained. It is possible that uniform thresholds for muscle mass and muscle strength are not suitable for all populations and require clarification. Conclusion Sarcopenia is the feature of more than half of HD patients and is significantly associated with an increased risk of death. PEW and sarcopenia, including partially similar indicators in their estimates, turned out to be poorly related in HD patients, and sarcopenia is more closely associated with hard outcomes than PEW. A separate assessment of these conditions and a search for contributing factors for its development/progression are required in prospective studies. One of the key objectifying indicators of the PEW and sarcopenia assessment could be the phase angle of bioimpedance associated with both clinical predictors and outcomes.

#2645 Clinical features and outcomes of steroid resistant focal sclerosing glomerulosclerosis (FSGS) in a single tertiary nephrology centre in Malaysia

Abstract Background and Aims Steroid resistant FSGS is defined as persistence of proteinuria with &amp;lt;50% reduction from baseline despite prednisolone 1 mg/kg/d for at least 16 weeks. We aim to study the clinical presentations, treatment, treatment response and kidney survival among steroid resistant FSGS patients. Method This retrospective study included all patients who had undergone renal biopsy in HSIS and had documented diagnosis of steroid resistant FSGS from January 2007 until December 2022. Data was collected and analysed using SPSS version 17. Results are expressed in mean ± standard deviation (SD) unless stated otherwise. Results A total of 74 patients had primary FSGS out of which 15 were identified as steroid resistant. Median age was 33 years old with 53% being female. Median weight at diagnosis was 73.7kg with BMI of 28kg/m2. One third had no co-morbid disease while 4 patients had underlying diagnosis of minimal change disease. Proteinuria on presentation was 7.6g with albumin levels of 16 g/L. No difference was seen between steroid resistant and steroid sensitive cohort with regards to age, proteinuria, GFR and laboratory parameters. Median duration of steroid was 38.8 months with duration of high dose steroids were 5 months and complications often set in by 2 months of therapy. Steroid toxicity occurred in 13 patients with most common complication seen was Cushingoid features (8/13) followed by acne (2/13) and diabetes mellitus (2/13). There were more steroid complications in steroid resistant cohort compared to the steroid sensitive. Second line was initiated in all patients but one with cyclosporin A being the most common choice (11/14) followed by Azathioprine (2/14) and cyclophosphamide (3/14). The median duration of second line agent was 22 months with CNI specifically being for 18 months. 3 patients developed CNI toxicity and was given cyclophosphamide while one patient developed CNI resistance and was given IV Rituximab. 4 (%) patients went on to achieve complete remission, 8 had partial remission while the rest did not achieve remission. 9 patients had normal renal function, while 3 developed chronic kidney disease. One patient went on to become end stage renal disease while 2 patients died. There was no difference in terms of renal or patient outcome between steroid resistant and steroid sensitive FSGS. Conclusion Steroid resistant FSGS is a challenging entity of FSGS that warrants close monitoring for complications and management. The outcomes were not different between steroid sensitive and steroid resistant FSGS however, the steroid complications were more common in steroid resistant FSGS.

#516 Cancer after kidney transplantation in the single transplant center

Abstract Background and Aims A retrospective analysis of peculiarities of development of malignant neoplasms in patients after kidney transplantation receiving long-term immunosuppression. Method In this study we evaluated incidence of malignancies observed among 718 renal transplant recipient with at least 6 months of follow-up. A total of 561 men and 257 women, mean age at transplantation 36.3 ± 8.3 years were included. Results Thirty-three out of 718 recipients (4.6%) developed malignant neoplasia: 45.5% of these were Kaposi's sarcomas, 12.1%—cancers of the uterine cervix, 12.1% cancer of the stomach, 12.1% - basal cell carcinomas, 6.06% - post transplant lymphoproliferative disorder. There was no significant effect of either cyclosporine A, tacrolimus doses or OKT3/ATG on the incidence of the tumors. The median time from onset of end-stage renal failure (dialysis start) and from the transplantation to the diagnosis of the tumor make up 32 (16-161) and 23 (5-158) mouths, respectively. One renal transplant recipient suffered from multiple myeloma with aggressive course. Three patients diagnosed with renal cell carcinoma of the transplant: clear cell carcinoma, papillary carcinoma, mucinous adenocarcinoma via 264, 24 and 4 months respectively. Conclusion The importance of strict adherence to intensive monitoring transplant patients, which can detect tumors at an early stage. Strict adherence to intensive follow-up of transplant patients is important, which makes it possible to identify neoplasms at an early stage, when organ-preserving treatment is feasible and effective. In addition, modification of immunosuppressive therapy in such patients involves reducing the dose or, if possible, completely eliminating calcineurin inhibitors and starting taking mTOR inhibitors (sirolimus or everolimus), taking into account the antitumor effect of this group of immunosuppressants.

Incorporating low haemoglobin into a risk prediction model for conversion in minimally invasive gynaecologic oncology surgeries

Background A well-known complication of laparoscopic management of gynaecologic masses and cancers is the need to perform an intraoperative conversion to laparotomy. The purpose of this study was to identify novel patient risk factors for conversion from minimally invasive to open surgeries for gynaecologic oncology operations. Methods This was a retrospective cohort study of 1356 patients ≥18 years of age who underwent surgeries for gynaecologic masses or malignancies between February 2015 and May 2020 at a single academic medical centre. Multivariable logistic regression was used to study the effects of older age, higher body mass index (BMI), higher American Society of Anaesthesiologist (ASA) physical status, and lower preoperative haemoglobin (Hb) on odds of converting from minimally invasive to open surgery. Receiver operating characteristic (ROC) curve analysis assessed the discriminatory ability of a risk prediction model for conversion. Results A total of 704 planned minimally invasive surgeries were included with an overall conversion rate of 6.1% (43/704). Preoperative Hb was lowest for conversion cases, compared to minimally invasive and open cases (11.6 ± 1.9 vs 12.8 ± 1.5 vs 11.8 ± 1.9 g/dL, p<.001). Patients with preoperative Hb <10 g/dL had an adjusted odds ratio (OR) of 3.94 (CI: 1.65–9.41, p=.002) for conversion while patients with BMI ≥30 kg/m2 had an adjusted OR of 2.86 (CI: 1.50–5.46, p=.001) for conversion. ROC curve analysis using predictive variables of age >50 years, BMI ≥30 kg/m2, ASA physical status >2, and preoperative haemoglobin <10 g/dL resulted in an area under the ROC curve of 0.71. Patients with 2 or more risk factors were at highest risk of requiring an intraoperative conversion (12.0%). Conclusions Lower preoperative haemoglobin is a novel risk factor for conversion from minimally invasive to open gynaecologic oncology surgeries and stratifying patients based on conversion risk may be helpful for preoperative planning.

#501 Evaluation of the accuracy of serum creatinine-based GFR calculations across the different levels of renal function among Filipinos

Abstract Background and Aims Chronic kidney disease (CKD) is a worldwide health concern which continues to increase in prevalence. Early studies have evaluated kidney function by measuring serum creatinine (sCr) and/or the estimated glomerular filtration rate (eGFR). To date, there are limited studies that correlate nuclear GFR scans and eGFR by equations that include the Cockroft-Gault (CG), Modification of Diet in Renal Disease (MDRD), and Chronic Kidney Disease Epidemiology Collaboration equation (CKD-EPI) 2021 in Asians, specifically in a Filipino population. This study aims to compare the accuracy of GFR scan results and GFR estimated from the formulas across different levels of kidney functions, age groups, gender, and co-morbidities among a Filipino subset. Method A cross-sectional study was done among 2986 patients who underwent Nuclear GFR scan in a single kidney center. Results obtained were compared to estimated GFR results. Weighted Kappa and Bland-Altman Analyses were used to test for agreement between the measured and estimated GFR results. Results Absolute GFR values derived from the three equations demonstrated moderate reliability with results from nuclear scan when intraclass correlation coefficients were calculated with CKD-EPI 2021 being the highest. When further categorized into GFR levels, there was substantial level of agreement between each equation and GFR scan, with all weighted kappa coefficients being at least 0.700 with CG having the highest result (Table 1). Furthermore, when subgroup analysis was done according to age group, gender, and comorbidities, CG was found to be the most accurate per category (Table 2). Conclusion CKD-EPI 2021 was the most accurate in the actual GFR values however we cannot fully eliminate the utility of CG due to its categorical accuracy and in monitoring the deterioration of renal function.

#3009 The impact of living donor hypertension on later function of kidney graft in kidney transplantation

Abstract Background and Aims Living donor (LD) selection is a crucial step in kidney transplantation (KTX). The impact of hypertension (HT) of LD on later kidney graft function remains insufficiently understood. Method We retrospectively reviewed recipients of LD KTX at a single tertiary center (Geneva University Hospitals, Geneva, Switzerland) from January 2003 to December 2021 with a follow-up until December 2022. LD blood pressure (BP) values obtained with office measurement and 24 h ambulatory BP monitoring (ABPM) were the main predictors, while recipients estimated glomerular filtration rate (eGFR) and proportion of kidney fibrosis on biopsies were the outcomes. Multivariate analyses were adjusted for the following pre-KTX donor characteristics: Age, gender, ethnicity, body mass index and eGFR. Results In total, 212 LD KTX recipients were included with LD mean age 51 ± 11 and 133 women (62.7%). According to European guidelines definition, 73 (34.4%) LD were hypertensive based on office BP. On a sub-group of 112 LD with ABPM, 64 (57.1%) were hypertensive. Systolic office BP was negatively associated with eGFR at 6 months, 1 year, 5 year and 10 year follow-up (p &amp;lt; 0.05 for all). Systolic office BP was positively associated with kidney fibrosis at 1 year follow-up (p &amp;lt; 0.05). Those associations were not significant after multivariate adjustment. Age at donation remained significantly associated eGFR and kidney fibrosis after multivariate adjustment (p &amp;lt; 0.05 in both models). Conclusion Based on our experience, a significant proportion of LD are hypertensive at kidney donation. While an adverse impact of HT on later kidney function and fibrosis could be measured, this effect seemed negligible after accounting for other more relevant clinical characteristics, with age at donation being decisive.

#2682 Evaluation of clinical, pathological findings and treatment outcomes of patients diagnosed with lupus nephritis: a single center experience

Abstract Background and Aim Renal involvement of systemic lupus erythematosus (SLE) is known as lupus nephritis (LN). The prognosis of lupus patients with LN is worse than those without kidney involvement. Renal survival can be improved in patients with lupus nephritis with appropriate and timely treatment. The aim of our study is to compare the clinical and pathological findings of patients diagnosed with LN in our clinic by renal biopsy, the results of the treatment applied in our center, and renal survival with the literature. Method The local ethical committee approved the study design (date: 04/10/2021; reference number: 121/07) and all procedures were conducted in accordance with the Declaration of Helsinki. Forty-four patients diagnosed with lupus nephritis between January 2012 and January 2021 in the Nephrology Department of Ankara Dıskapı Yıldırım Beyazıt Education and Research Hospital were enrolled in this study. Patient data were analyzed retrospectively. Exclusion criteria were as follows: 1) Patients under 18 years of age, 2) patients with follow-up of period less than 6 months and who did not attend regular follow-ups, 3) patients with connective tissue diseases other than SLE. Results The mean age of the study population was 36.0 ± 10.8, and the majority were female. All patients had proteinuria at diagnosis. Class IV LN was the most common (36.4%). Majority of the patients were in the proliferative LN group (65.9%). A significant difference was found between patients diagnosed with proliferative LN (n = 29) and non-proliferative LN (n = 15) in terms of high serum creatinine levels, low serum complement, presence of anti-dsDNA antibodies and active urinary sediment with proliferative LN (p = 0.021, p = 0.024, p = 0.008, p = 0.008). Treatment responses at 6 and 12 months are shown in Table 1. A significant difference was found between the patients who were in complete remission (n = 16) at 12 months and those who were not in remission (n = 27) in terms of low systolic blood pressure and the estimated glomerular filtration rate (eGFR) at the time of diagnosis (p = 0.008, p = 0.016). It was observed that most of the patients who were not in complete remission at 12 months were in the proliferative LN group (p = 0.024). There was no significant difference in the partial and complete remission rates at 6 and 12 months between the group receiving steroids + cyclophosphamide (n = 14) and the group receiving steroid + mycophenolate mofetil (MMF) (n = 15) in the initial treatment of proliferative LN (p&amp;gt;0.05). In the group taking MMF treatment (n = 15) had a shorter time to reach complete remission than the group taking cyclophosphamide treatment, and it was statistically significant (Table 2) (p = 0.048). It was found that end-stage renal disease (ESRD) developed in 9% of the patients and 2 patients died during followed up period. Recurrence was detected in 8 patients, and it was observed that more than half of the patients with relapse could not achieve complete remission at 12 months. Patients with relapse had higher systolic blood pressure and serum total cholesterol level at the time of diagnosis compared to patients without recurrence (p = 0.013, p = 0.045). In addition, patients with relapse were found to have a higher level of proteinuria at the time of diagnosis (p = 0.036). Conclusion Lupus nephritis remains an important source of morbidity and mortality for SLE patients. SLE patients should be regularly examined for renal involvement. About 10-20% of patients diagnosed with lupus nephritis develop ESRD. Early diagnosis of LN and initiating appropriate treatment when diagnosed without delay is important for renal and patient survival. Although there were some different results, most of the statistically significant data in our study were found to be compatible with the existing literature. However, these data need to be confirmed by studies with high patient participation.

#2836 Prevalence and risk factors associated with chronic kidney disease among type-2 diabetes mellitus patients – a single centre experience

Abstract Background and Aims Globally, diabetes mellitus is one of the major causes of increased morbidity. One of the key complications of T2D is chronic kidney disease (CKD). Current evidence demonstrates that people with type 2 diabetes (T2D) are at a higher risk of developing chronic kidney disease (CKD) with greater morbidity and mortality. So, we aimed to find out the prevalence of CKD among T2DM patients and to evaluate the correlation between age, duration of diabetes, HbA1c, and UACR with eGFR among T2DM patients. Method An observational cross-sectional study was conducted at department of medicine, tertiary care hospital for 2 months. Along with demographic and anthropometric data The following clinical data were collected: estimated glomerular filtration rate (eGFR), serum creatinine, urinary albumin creatinine ratio (UACR), and HbA1c levels. Spearman rank correlation was used to determine the correlation between eGFR and various parameters. Results A total of 96 patients were included in the study. 65% of the study participants were sedentary and 35% were physically active. 41 (42.7%) were obese and 21 (21.9%) were overweight. The mean Duration of diabetes is 5.62 ± 4.68 years. The mean estimated glomerular filtration rate (eGFR) is 74.33 ± 31.01 mL/min/1.73 m2. The Prevalence of CKD is 35.4%. 21.8% belongs to G3a category and 8.3% belongs to G3b category. Spearman's correlation coefficient test revealed negative correlation between eGFR and duration of diabetes, HbA1c and UACR (Spearman's correlation coefficient values are −0.577, −0.595 and −0.709 respectively). Conclusion In conclusion, nearly 1/3rd of study participants reported CKD. Our study provides consistent and recent clinical data showing an inverse association of eGFR with age and duration of diabetes. This study highlights that age and duration of diabetes are key parameters associated with declining renal functions in people with T2DM.

#1664 Assessing vascular access thrombectomy service adherence to GIRFT recommendations: single centre experience

Abstract Background and Aims Studies showed that early thrombectomy of dialysis vascular access (VA) is associated with better outcomes [1], especially for native VA [2]. Timely treatment of VA thrombosis within 24-48 hours is recommended by GIRFT to minimize access loss and requirement for dialysis line insertion [3]. Our centre has approximately 430 HD patients but has no on-site vascular surgery or vascular access interventional radiology (IR) service. Wait time for elective VA surgery or fistuloplasty is &amp;gt;8 weeks and VA surveillance is based on routine clinical monitoring. VA prevalence is 62% AV fistula (AVF), 2% AV graft (AVG), 36% central venous catheter (CVC). Fistula thrombectomy is provided at another centre, with increasing waiting times over recent years due to shortage of interventional radiologists. This study evaluates adherence to GIRFT recommendations for patients at our centre requiring thrombectomy and will identify potential local strategies to reduce fistula thrombosis and CVC use. Method In a 24-months’ retrospective cohort analysis of maintenance HD patients with permanent VA, we obtained data on: Results 44 patients with permanent VA developed VA thrombosis. The median waiting time for thrombectomy was 8 days (Fig. 1). Post-intervention primary patency rate was 71% at 3-months and 60% at 6-months (Fig. 2). 61% of patients required hospital admission with a 12-day median length of stay, with total inpatient admission days of 403 days over 2 years (2022-2023), and total cost of £246,065 (Figs. 3 and 4). The median CFD-extended was 356 days, i.e. 9 days/patient/year with VA-related complications (Fig. 5). Conclusion This study shows that our centre's VA thrombectomy service falls far outside the GIRFT recommendation of intervention within 24-48 hours. The high associated rates of CVC use, inpatient bed days and avoidable costs place a heavy burden on patient outcomes and NHS resources. The ideal solution of an on-site thrombectomy service is difficult to achieve due to lack of vascular IR support. In response to this study, we now aim to reduce thrombosis rates by training additional interventional nephrologists in elective fistuloplasty, implementing a robust VA surveillance to improve early detection of malfunctioning VA suitable for elective intervention and improving staff education on fistula care.