bluuebunny/crossref_metadata_2025 huggingface dataset:
#5876 ISLET TRANSPLANTATION VERSUS INSULIN ALONE IN TYPE 1 DIABETIC KIDNEY TRANSPLANT RECIPIENTS: A FRENCH NATIONWIDE STUDY ON BEHALF OF THE TREPID GROUP
Authors: Maanaoui Mehdi , Lenain Rémi , Foucher Yohann , Chetboun Mikael , Kerr-Conte Julie , Blancho Gilles , Buron Fanny , Lablanche Sandrine , Caillard Sophie , Kessler Laurence , Berney Thierry , Vantyghem Marie-Christine , Hazzan Marc , Pattou François
Published: June 2023

Background and Aims

Islet transplantation is associated with a benefit on glycaemic control compared to optimized insulin therapy in recent clinical trials. However, there is a lack of evidence concerning the long-term impact of islet transplantation on type 1 diabetic kidney transplant recipients’ prognosis.

Method

Every type 1 diabetic recipient transplanted with a kidney in France between 2000 and 2017 was included. Patients transplanted with pancreatic islets were compared to controls treated with insulin alone according to a matching method based on time-dependent propensity scores (using the following variables : yera of transplantation, donor age, and recipient age, serum creatinine, HBA1c, BMI, cardiovascular background) which allow to ensure patients comparability at the time of islet transplantation. The primary outcome was graft failure, defined by death or return to dialysis.

Results

Among 2393 type 1 diabetic patients transplanted with a kidney during the study period, 381 were eligible to islet transplantation, including 47 that were actually transplanted with islets. Median time for islet transplantation was 34.8 months [21.8-48.4]. Probabilities of insulino-independence and islet graft survival at 1, 5 and 10 years were respectively 63.8% [51.5-79.2], 46.3% [33.9-63.2], 38.7% [25.9-57.8] and 89.4% [81.0-98.6], 87.2% [78.2-97.3], 78.2% [66.2-92.4]. After matching, we observed a significant benefit of islet transplantation compared to insulin alone on graft failure, with a HR of 0.48 [0.20-0.94], mainly explained by a protective effect on the risk of death (HR = 0.38 [0.11-0.95]). We finally estimated the life-expectancy for a 10-year follow-up and found 9.61 years [9.02-10.00] in the islet transplantation group versus 8.85 years [7.97-9.56], with a difference of 8.88 months [-2.16-20.44]

Conclusion

We observe a significant benefit of islet transplantation on the risk of graft failure and death in type 1 diabetic kidney transplant recipients. These results provide incentives to promote islet transplantation in this population.
#5878 PROTECTIVE EFFECTS OF VITAMIN D ON HYPERANDROGENEMIA-INDUCED-ACUTE KIDNEY INJURY THROUGH THE INTERACTION WITH THE RAS/INOS PATHWAY
Authors: Masjedi Fatemeh , Karimi Zeinab , Roozbeh Jamshid
Published: June 2023

Background and Aims

The onset and development of metabolic abnormalities are closely related to polycystic ovary syndrome (PCOS). It has not yet been determined whether PCOS contributes to kidney injury, and the mechanism underlying the condition is not fully understood. Treatment with vitamin D has been shown to have beneficial effects on women with PCOS and renal disease. This study investigated the hypothesis that vitamin D supplementation exerts renoprotective effects via regulating the renin-angiotensin system (RAS)/inducible nitric oxide synthase (iNOS) pathway

Method

Female Sprague-Dawley rats were randomly divided into five groups (n = 10): (a) control, (b) sham, (c) dehydroepiandrosterone (DHEA, 6 mg/100 g day-1 S.Q.), (d) DHEA + vitamin D (1000 IU/Kg; 3 days/week), and (e) vitamin D. Plasma, ovary, and kidney levels of angiotensin-converting enzyme (ACE) activity was determined using FAPGG-based colorimetric method. The amount of NO was measured by determining the concentrations of nitrite and nitrate end products in the plasma and tissue samples using the Griess method. Histopathological changes in the ovary and kidney were also evaluated.

Results

Plasma testosterone increased in DHEA-treated rats compared with controls, indicating a hyperandrogenic state. Further, hyperandrogenemia-induced-acute kidney injury increased the plasma, renal, and ovarian angiotensin-converting enzyme (ACE) activities in association with elevations in the plasma and urine nitrite and nitrate levels; these changes were reversed by vitamin D treatment.

Conclusion

Hyperandrogenemia causes systemic abnormalities through RAS imbalance and NO metabolism disturbances, followed by apparent destruction of renal and ovarian tissues. Vitamin D supplementation attenuated these hyperandrogenemia-associated acute kidney injuries, likely via interaction with the RAS/iNOS pathway.
#5884 HLA COMPATIBILITY DOES NOT INFLUENCE KIDNEY GRAFT SURVIVAL AND DOES NOT IMPACT THE DEVELOPMENT OF POST-TRANSPLANT NEOPLASIA
Authors: Bartoli Giulia , Strologo Andrea Dello , Simone Simona , Arena Maria , Salerno Maria Paola , Silvestri Patrizia , Ditonno Pasquale , Romagnoli Jacopo , Gesualdo Loreto , Grandaliano Giuseppe
Published: June 2023

Background and Aims

HLA compatibility is a key issue in deceased and living kidney allocation, although the continuous improvement of immunosuppressive protocols might have reduced its relevance. However, an increased immunosuppression is associated with several adverse events, including the development of post-transplant neoplasia. Indeed, several reports demonstrated that the improvement in immunosuppressive drug efficiency corresponded to an increase incidence of malignancies after kidney transplantation. Thus, the aim of our study was to investigate the effect of HLA compatibility on kidney graft survival and incidence of post-transplant neoplasia.

Method

This is an observational, retrospective, multicenter center study including 1506 patients receiving a single kidney transplant at the Gemelli and Policlinico “Consorziale” kidney transplant centers from 1/1/2000 to 1/2/2022. The primary outcomes were death-censored graft survival and the development of post-transplant neoplasia. HLA compatibility was measured as the number of HLA mismatches (MM) at the three main class I (A and B) and class II (DR) loci. To this purpose, both donor and recipients were genotyped for HLA A, B and DR. We included in the analysis all deceased and living kidney donor transplants and excluded recipients from AB0 incompatible living kidney donors and with pre-transplant donor specific antibodies.

Results

Based on HLA compatibility, we divided our patients’ population in three groups (0-2 MM, 369 patients 3-4 MM, 856 patients and 5-6 MM, 281 patients). At univariate analysis (Kaplan-Meyer) number of MM were not associate with death-censored graft survival (Logrank p = 0.6) whereas we observed a significant association with the development of post-transplant neoplasia (Logrank p = 0.01). However, multivariate analysis (Cox model including recipient age, induction and maintenance immunosuppressive therapy) demonstrated that patients with 3-4 (HR 1.033, 95% CI 0.676-1.580, p = 0.9) and 5-6 MM (HR 1.342, 95% CI 0.853-2.111, p = 0.2) did not have any statistically significant increase in the risk to develop a post-transplant malignancy.

Conclusion

In this observational retrospective multicenter analysis, we demonstrated that HLA incompatibility, as indicated by the number of HLA A, B and DR MM, does not predict death-censored graft survival and does not impact the development of post-transplant neoplasia. Our observation would suggest that the missing effect of HLA compatibility on graft outcome is not associated with an increased long-term over-immunosuppression.
#5885 HYPOXIA INDUCES COMPLEMENT ACTIVATION ON HUMAN KIDNEY EPITHELIAL CELLS
Authors: Moldakhmetova Saltanat , Ali Simi , Sheerin Neil
Published: June 2023

Background and Aims

Ischemia-reperfusion injury is an inevitable event associated with kidney transplantation (Tx) and has a major impact on short- and long-term graft survival. Proximal tubular epithelial cells are both a source of complement during Tx and a target of complement activation. The normal kidney has a capacity to protect itself from complement activation through cellular expression of complement regulatory proteins. In this study we investigated whether hypoxia and reoxygenation increase C3 deposition and alter complement regulatory protein expression (CD46, CD59 and CD55).

Method

In vitro, HKC-8 renal proximal tubular epithelial cells were subjected to 24h of hypoxia (1% O2) and then reoxygenated for 4h (O2 = 21%) in the presence of 40% normal human serum. qRT-PCR was used to estimate the level of VEGF-A (as a positive control), C3, CD46, CD59 and CD55 expression. Similar analysis was performed in untreated, normoxic cells. Immunofluorescence staining was used to determine C3 deposition on the cell surface and intensity quantified by ImageJ. Experiments were repeated three times.

Results

qRT-PCR analysis of HKC-8 cells in hypoxia revealed significant increases in the expression of VEGF-A after 24h (p = 0.0113). C3 expression following hypoxia and reoxygenation increased insignificantly. Increased expression of CD59 with the presence of serum was observed in epithelial cells (p = 0.026). However, no significant change was seen in the expression of CD55 and CD46. Reoxygenation in human serum led to significantly greater deposition of C3 on hypoxic cells compared with normoxic HKC-8 cells (Figure 1, 2).

Conclusion

Our preliminary data suggests that hypoxia and reoxygenation significantly increases C3 deposition on the proximal tubular cell surface. CD59, as one of the regulators of complement activation is upregulated at mRNA level after hypoxia followed by 4h reperfusion in the presence of serum. These data demonstrate that hypoxia and reoxygenation activate complement system with upregulation of CD59 as a cell defence. However, expression of CD46 and CD55 do not change. Further study is needed to identify the impact of hypoxia on complement regulation in primary epithelial cells and kidney tissues.
#5891 REPEAT RENAL BIOPSIES IN ADULT LUPUS NEPHRITIS PATIENTS
Authors: Majid Zakia , Afifi Rania , Mikdam Najoua , Chkaari Nawfal Mtioui , Khayat Salma El , Zamd Mohamed Ali , Medkouri Ghislaine , Benghanem M
Published: June 2023

Background and Aims

The role of repeat renal biopsy in lupus nephritis (LN) to guide treatment or predict prognosis has been controversial.The objective of this work is to evaluate the indications requiring the use of a second renal biopsy, as well as to describe the histological results and the therapeutic management according to the results.

Method

This is a descriptive retrospective study, covering 450 renal biopsy performed between January 1, 2020 and December 31, 2022 at the nephrology department of the Casablanca University Hospital. The patients were selected from the kidney biopsy register.

Results

Thirty patients followed for lupus nephritis had benefited from a 2nd renal biopsy. The average age of our patients was 36.4 years with a sex ratio of 0.8. The average time from first to second biopsy was 2, 1 years. The indications for a second renal biopsy was included a suspected flare (76.6%), of which had worsening proteinuria with or without rising serum creatinine (90%), or lack of treatment response (23.4%). 22 patients (73,3%) had proliferative class on their first renal biopsy. When comparing first and second renal biopsy, 26 patients (86.6%) switched histological classes .When categorized as proliferative versus non-proliferative, 21 (95.4%) patients with proliferative class on the first biopsy remained similar on the second biopsy. The mean chronicity index (CI) was significantly different for 10 consecutive biopsies with worsening CI noted with increased number of renal flares. 11 patients (36,6%) required intensification in immunosuppressive therapy after the second renal biopsy whereas 3 patients (10%) experienced a reduction in immunosuppression. 16 patients (53,3%) did not experience any change in immunosuppression.

Conclusion

A 2nd renal biopsy was justified in most cases, making it possible to establish a precise diagnosis, to identify the evolution of the histological lesions, and to guide the therapeutic management.
#5902 KIDNEY INVOLVEMENT IN HAEMATOLOGICAL MALIGNANCIES: THE IMPORTANCE OF EARLY NEPHROLOGICAL REFERRAL
Authors: Maso Vittorio DI , Perencin Brigitta , Zacchi Alberto , Yazbek Ahmad , Toffoli Federico , Zanconati Fabrizio , Bianco Francesco
Published: June 2023

Background and Aims

Kidney is often injured in the setting of hematological malignancies. Although, kidney involvement negatively influences the prognosis of these patients, often the referral to clinical nephrology is late. The aims of this study were to investigate the long-term outcomes of haematological diseases with renal involvement demonstrated by kidney biopsy and the association between nephrological referral earliness and survival.

Method

Monocentric retrospective study evaluating overall survival (OS) (time to death) and renal free survival (RFS) (time to renal replacement therapy) in patients affected by hematologic malignancies with renal involvement demonstrated by kidney biopsy. Data have been collected by January 1st 2009 to December 30th 2021. Results reported as median (min-max) and percentage (%).

Results

46 patients; M/F = 1.3; age: 70 years (39.5-91.2). Follow-up: 17,8 months (0.13-125.4). Data at kidney biopsy: creatinine was 3.13 mg/dL (0.6-14), eGFR was 20 ml/min/1.73 m2 (3-110), proteinuria was 5.1 g/24h (0.15-38.6), Bence-Jones proteinuria detected in 74% of patients. Clinical presentations: AKI (63.1%), Nephrotic syndrome (36.9%). Patient referral by Nephrologist (28.2%), Hematologist (26.1%), General Practitioner (21.7%); Emergency Department (17.4%), Others (6.6%). The most frequent histological diagnosis was amyloidosis (32.7%), followed by cast nephropathy (19.2%). Renal Replacement Therapy was required in 41.3% patients. Treatment: 38 patients underwent chemotherapy (56.4% complete/very good hematologic response; 12.8% partial and 30.6% without response). Overall Survival at 24 months was 63.8% and it was reduced in patients with AKI at presentation (Fig. 1) and in patients without treatment response (Fig. 2). RFS was shorter in patients who presented with AKI and affected by Myeloma Cast. Early Nephrological referral was associated with a better RFS (Fig. 3).

Conclusion

Haematological malignancies with renal involvement causing AKI have the worst prognosis. Kidney biopsy has a prognostic significance and early nephrological referral associated with haematological treatment response correlate with a better renal outcome. These data point to the central role of a multidisciplinary team aimed to the detection and treatment of renal damage due to hematologic malignancies.
#5903 CLINICAL OUTCOME CORRELATION AMONG NEWLY DIAGNOSED LUPUS NEPHRITIS IN RELATION TO PERIPHERAL BLOOD LYMPHOCYTE SUBSET: A PROSPECTIVE STUDY
Authors: Balasubramaniam Karthik , Rangaswamy Dharshan
Published: June 2023

Background and Aims

Given the heterogeneity in presentation, treatment practices and the outcome of lupus nephritis, there is a need for new protocols to predict outcome and rationalize treatment.

Aim

To prospectively study the correlation between peripheral blood lymphocyte subset, inflammatory markers and clinical outcomes among newly diagnosed lupus nephritis patients.

Method

Lymphocyte subset typing by flow cytometry method done at diagnosis and end of 6 months. SLEDAI -2k score. Intensive phase of Immunosuppression individualized by treating physician. Urine protein excretion was used to assess the final treatment outcome. Statistical analyses done using SPSS software. Two-sided P value of < 0.05 was considered significant. Pearson correlation coefficient formula used for correlations. Logistic regression done to identify factors responsible for clinical remission achieved at six months. Inclusion: All newly diagnosed renal biopsy proven Class 3, class 4, Class 5 or a combination class of lupus nephritis patients seen at Kasturba Hospital and Medical College, Manipal. Exclusion: Patients with active/recent infection, active malignancy, those with prior explosion to immunosuppression. Outcome measures, 1. To detect correlation if any, between peripheral blood lymphocyte subset, serum inflammatory markers and disease activity score at presentation. 2. To determine correlation if any, between peripheral blood lymphocyte subset and clinical remission achieved following immunosuppressive regimens at the end of six months of initial intensive treatment phase.

Results

22 patients were taken for study. Relationship between SLEDAI score, lymphocyte subset characters, and clinical outcome given in Table 1 and 2. There was good correlation between lymphocyte subset characters, inflammatory markers and SLEDAI score, indicating ability of lymphocyte subset characters to characterize the severity of lupus nephritis. We found significant difference in lymphocyte subset characters between baseline and at the end of 6 months treatment. But there was no significant correlation for remission attainment with lymphocyte subset characters and SLEDAI score.

Conclusion

1. Correlation found between peripheral blood lymphocyte subset, serum inflammatory markers and disease activity score at presentation and 6 months of treatment of lupus nephritis. 2. Peripheral blood Lymphocyte subset analysis was not found useful in predicting clinical outcome in lupus nephritis at the end of 6 months of intensive treatment.
#5999 GRADES II-III INTRA-ABDOMINAL HYPERTENSION INCREASE THE RISK OF GRAFT LOSS OR DEATH AFTER KIDNEY TRANSPLANTATION
Authors: Ardura Paula , Manrique María Martínez , Acosta-Ochoa Isabel , Gordillo Raquel , Sanz-Ballesteros Sandra , Peláez Ana Lucía Valencia , Lorenzo Arturo , Fidalgo Veronica , Mendiluce Alicia , Coca Armando
Published: June 2023

Background and Aims

Intra-abdominal hypertension (IAH) is common among post-surgical, critically ill and kidney transplant patients, and is associated with acute kidney injury and increased morbidity and mortality. We aimed to describe the medium-term effect of IAH on graft and patient survival after deceased-donor kidney transplantation.

Method

192 consecutive patients who received a cadaveric renal allograft transplant at our hospital were included in this study. IAP was measured every 8h for at least the first 72h after surgery using the urinary bladder technique, and an average value was obtained. Patients were followed up for 24 months or until a composite outcome (defined as graft loss or recipient death) occurred. Clinical, anthropometric, and analytical data was extracted from our hospital's database. Statistical analysis was performed using IBM SPSS Statistics 22. The study was approved by the local ethics committee.

Results

192 patients were included. Relevant clinical and anthropometric data are summarized in Table 1. Patients with grades II or III IAH were more frequently male, had longer dialysis vintage, received more frequently hemodialysis as renal replacement therapy and suffered delayed graft function, graft loss or death more repeatedly. In Kaplan-Meier analysis, grade II IAH or higher were associated with lower composite-outcome free survival (Log-Rank: 8.053; p = 0.018) (Figure 1).

Conclusion

Grade II-III IAH appear to be a risk factor for graft loss or recipient death in our sample of deceased donor kidney transplant recipients. Monitoring of intra-abdominal hypertension could provide useful information to identify patients at higher risk of post-transplant complications.
#6004 THE EFFECT OF COVID-19 WITH OR WITHOUT ACUTE KIDNEY INJURY ON INPATIENT MORTALITY IN ENGLAND
Authors: Kolhe Nitin , Fluck Richard , Taal Maarten
Published: June 2023

Background and Aims

COVID-19 and acute kidney injury (AKI) are each associated with increased mortality but the interaction between these two conditions has not been adequately investigated with appropriate control groups. The aim of this national study was to assess patient characteristics and mortality and well as associations with higher mortality in patients with or without COVID and with or without AKI.

Method

We extracted 3,324,748 finished consultant episodes (FCE) of all adult patients admitted patients between March 20 and March 21 from England's national database of all hospitals. We excluded patients on chronic dialysis, acute dialysis in CKD, acute dialysis with no AKI codes or not residing in England. We also excluded multiple FCEs within same spell and duplicate FCEs. We extracted all diagnoses and procedure codes for the cohort. We divided the study period in two phases of SARS CoV-2 strains. “Other” strain of SAR CoV-2 was dominant between 1st March 2020 and 21st December 2020 and “Alfa” strain was dominant between 22nd December 2020 to 17th May 2021. The end date of each phase was based on more than 50% decline in each variant. We further categorised phases based on publication of the RECOVERY trial.

Results

There were 663,628 patients with 2,385,337 admissions out which 856,544 had AKI as identified by N17 codes while 1,528,793 had no AKI. There were 1,008,774 admissions in 133,988 patients who did not have AKI or COVID (group 1) and 520,019 admissions in 256,037 patients who had COVID (group 2). Amongst admission with AKI, there were 630,342 admissions in 218,270 patients who did not have COVID-19 (group 3) and 226,202 admissions with COVID in 55,333 patients (group 4). Patients in group 4 were older (75.4 ± 13.8 years) and had greater length of stay (17.1 ± 17 days) than all other groups. Acute dialysis was performed in 1.4% of patients in group 3 and 3.6% of patients in group 4. Crude in-hospital mortality was highest in group 4 at 28.7% and lowest in group 1 (1.1%). Critical care requirement was lowest in group 1 (1.2%) compared to group 4 (10.9%) as was ITU mortality (4.8% versus 47.8%). In multivariable analysis, when compared with group 1, patients in group 4 had highest odds of death (OR 22.28, 95%CI 21.79, 22.78) followed by patients with group 2 (OR 9.67, 95%CI 9.46, 9.88) (Figure 1). Patients in group 3 had OR of 6.44, 95%CI 6.30, 6.58. Odds of death were lower during post-RECOVERY phase with “Other” (OR 0.80, 95%CI 0.79, 0.81) and "Alfa" (OR 0.86, 95%CI 0.85, 0.87) SARS CoV-2 strains (Figure 2).

Conclusion

This national study shows that the COVID pandemic had great impact on mortality in England and the odds of death increased substantially when complicated by AKI. Moreover, AKI associated with COVID was associated with a substantially higher odds of death than AKI due to other causes. The change in practice after publication of the RECOVERY trial was associated with a lower odds of death.
#6011 VIRAL INFECTION AND DE NOVO PRODUCTION OF DONOR SPECIFIC ANTIBODIES IN KIDNEY TRANSPLANTATION: DCD VS DBD
Authors: Gianassi Iacopo , Lomi Jacopo , Bartiromo Marilù , Maria Lorenzo DI , Caroti Leonardo , Larti Aida , Cutruzzulà Roberta , Antognoli Giulia , Odone Ludovica , Sossai Giulia , Moscato Marco , Palazzini Giulia , Allinovi Marco , Cirami Calogero
Published: June 2023

Background and Aims

Viruses are among the most common causes of opportunistic infection after transplantation and an accurate screening and follow-up is needed in order to prevent related complication as systemic damages and worsening of kidney function. On the other hand, in the first years after transplantation, antibody-mediated rejection (ABMR) is one of the first cause of graft lost and de novo production of donor specific antibody (dnDSAs) is the main source. In this monocentric study we analysed data of 255 patient transplanted from January 2016 to February 2022. We studied the incidence of viral infection and dnDSAs in the first one year after transplantation in different sub-groups of patients.

Method

Data was obtained from our monocentric registry, from January 2016 to February 2022. Starting from 299 kidney transplantation we obtained 255 patients with a complete annual follow-up for viral infection and DSA monitoring. We compared the incidence of viral infection and dnDSAs in different sub-group: transplanted from donation after brain-death treated with Basiliximab as induction therapy (DBDb), transplanted from donation after brain-death treated with rabbit anti-human thymocyte immunoglobulin (rATG) as induction therapy (DBDt), transplanted from donation after circulatory death treated with rATG as induction therapy (DCD) and transplanted treated with rATG as induction (DBDt+DCD).

Results

Global incidence of viral infection was 73% and dnDSAs formation was present in 12,5% of all patients. DBDs showed an incidence of 69% of viral infection and 10% of dnDSAs while in DBDt these values were 77,4% and 25%, respectively. In DCD data of viral infection was higher (96,7%) whereas dnDSAs was 14%. rATG (DBDt+DCD) displayed 87,1% of viral infection and 19% of dnDSAs.

Conclusion

Viral infection and dsDNAs are two paramount aspects in kidney transplantation and demonstrate different incidences depending on donation profile and immunosuppressive induction therapy. Specifically rATG seems to be associated to an higher rate of viral infection and DCD is the more relevant sub-group. Furthermore, rATG was associated with higher dsDNAs rate, especially in DBD treated with rATG. On the best of our knowledge, this data was never observed before. These data, due to the low number of cases, need to be confirmed from larger cohorts. Moreover our study underlines how significant is to develop a personalized approach in order to reduce complications associated to immunosuppressive therapies.
#6018 SODIUM-GLUCOSE CO-TRANSPORTER-2 INHIBITOR USE IN THE MANAGEMENT OF PATIENTS WITH CHRONIC KIDNEY DISEASE AND TYPE 2 DIABETES MELLITUS
Authors: Alzetani Sarah , Suresh Vijayan
Published: June 2023

Background and Aims

Sodium-glucose co-transporter-2 (SGLT-2) inhibitors were initially developed for the management of type 2 diabetes mellitus (T2DM). Results from large placebo-controlled clinical outcome trials have now highlighted efficacy of SGLT-2 inhibitors in reducing the risk of CKD progression [1,2]. NICE CKD guidelines now recommend use of SGLT-2 inhibitors alongside standard of care in those patients with T2DM [3]. This has subsequently extended SGLT-2 inhibitor licensing highlighting the importance of wider multi-disciplinary team practise awareness. The aim of this audit was to assess the level of implementation of updated NICE guidelines in patients under a specialist CKD clinic in Birmingham.

Method

A database of renal diabetics under a specialist CKD clinic in May 2022 was generated via the trust electronic patient record system. Patients with a recorded diagnosis of T2DM and estimated glomerular filtration rate (eGFR) >25ml/min (current UK regulatory licensing for SGLT-2 inhibitor use) were included. Parameters of renal function (urine albumin: creatinine ratio (uACR) and eGFR) as well as medication histories were retrospectively collected for 158 patients and analysed using descriptive statistics.

Results

Results demonstrated 19% (n = 43) of 143 patients with an accessible drug history were prescribed an SGLT-2 inhibitor. Less than half (44%) of those prescribed standard of care (ACEI/ARB) with a uACR >30 mg/mmol (n = 34) were prescribed an SGLT-2 inhibitor as per NICE recommendations. The prescribing of SGLT-2 inhibitors in patients at different stages of CKD was noted except in those with eGFR <30 ml/min.

Conclusion

Results suggest a number of patients with T2DM are not prescribed an SGLT-2 inhibitor as per NICE recommendations for CKD management. Whilst considering sample size limitation as well as possible contraindications relevant to SGLT-2 inhibitor treatment, these findings may reflect the recent update to NICE guidelines and delayed dissemination of information between multi-disciplinary teams around extended SGLT-2 inhibitor licensing. Glycaemic control is less effective in later stages of CKD however, trials have demonstrated the independent role of SGLT-2 inhibitors in reducing the risk of CKD progression irrespective of their attenuated ability to lower glucose in reduced kidney function [1,2]. It is imperative patients not currently prescribed an SGLT-2 inhibitor are reviewed for treatment eligibility and any contraindications. Results of this study were fed back to the local renal and diabetes team with the recommendation for development of clear guidelines for use of SGLT-2 inhibitors in all eligible patients in order to achieve maximum healthcare benefits. In addition, there are ongoing discussions with primary care regarding review of their use of SGLT-2 inhibitors.
#6041 THE IMMUNE EFFECTS OF SARS-COV-2 INFECTION AND BNT162B2 VACCINATION IN CKD PATIENTS AND TRANSPLANT RECIPIENTS
Authors: Nazaruk Paulina , Tkaczyk Ignacy , Jędrzejczak Anna , Krata Natalia , Paczek Leszek , Foroncewicz Bartosz , Mucha Krzysztof
Published: June 2023

Background and Aims

The use of vaccination against severe acute respiratory syndrome coronavirus (SARS-CoV-2) significantly limited the spread of the coronavirus disease 2019 (COVID-19) pandemic. However, it was reported that after 6 months of vaccination (including the BNT162b2 vaccine) immunity decreases in general population. The results for chronic kidney disease (CKD) patients and solid-organ transplant (SOT) recipients appeared similar. Therefore, it was proposed to use an immune booster with the next, third or fourth vaccination dose to prolong immunity. We aimed to find the most effective immunization schedules in CKD patients in comparison to kidney (KTRs) and liver transplant recipients (LTRs).

Method

We retrospectively analyzed the data of randomly selected 40 patients with IgA nephropathy (IgAN) as representatives of the CKD group and 78 SOT recipients (37 KTRs and 41 LTRs). They received two or three 30 μg doses of BNT162b2 vaccine. The follow up was performed in five time points (TP1-5): 4-6 weeks after the 1st dose (TP1), 4-8 weeks after 2nd dose (TP2), 9-20 weeks after 2nd dose (TP3), 21-32 weeks after 2nd dose and 1-12 weeks after 3rd dose (TP4), 33-48 weeks after 2nd dose, at the same time 4-20 weeks after 3rd dose (TP5). We assessed the anti-SARS-CoV-2 spike 1 protein IgG antibody (anti-S1 Ab) titer as well as graft function, COVID-19 history and patients’ clinical condition.

Results

We found Ab titer in IgAN group higher than in SOT patients (p = 0.05). LTRs achieved higher values than KTRs. 55 patients received 3 doses of vaccination. The protective level after the 3rd dose was not observed only in 8.4% at TP4 and 5% at TP5. We demonstrated the advantage in Ab levels of a 2 doses vaccination scheme with and without COVID-19 history over a 3 doses in a group of patients with no COVID-19 history in TP 1-4 (p = <0,001 - 0,005, respectively, Table1). Subjects in 2 doses schedule had a longer time to infection from the last dose compared to the 3 doses schedule (31.5-39 vs. 9 weeks, MD). No deterioration of renal or graft function was noted and no rejection episodes were diagnosed.

Conclusion

Immunocompromised patients are non-homogeneous with respect to the vaccine response immunity. Therefore, the approach to the vaccination schedule should be individualized based on measurements of vaccination response and medical history including COVID-19 history. Combined post-infectious and post-vaccination immunization appears to be the most effective in producing anti-SARS-CoV-2 responses.
#6044 HEART RATE VARIABILITY AT REST AND IN RESPONSE TO PHYSICAL AND MENTAL STRESS: A COMPARATIVE STUDY BETWEEN HEMODIALYSIS AND PERITONEAL DIALYSIS PATIENTS
Authors: Faitatzidou Danai , Dipla Konstantina , Theodorakopoulou Marieta , Koutlas Aggelos , Sampani Erasmia , Tsitouridis Alexandros , Dimitriadis Chrysostomos , Pateinakis Panagiotis , Zafeiridis Andreas , Papagianni Aikaterini , Sarafidis Pantelis
Published: June 2023

Background and Aims

Cardiac arrhythmias and sudden death are the leading causes of cardiovascular mortality in end-stage-kidney-disease (ESKD). Autonomic dysfunction contributes to the arrhythmogenic background of ESKD patients. This is the first study to compare linear and non-linear heart-rate-variability (HRV) indices between hemodialysis (HD) and peritoneal (PD) patients, both at rest and in response to mental- and physical-stimulation maneuvers.

Method

Thirty-four HD and 34 PD patients matched for age, sex, and dialysis-vintage, as well as 17 age- and sex-matched controls were studied. Autonomic function was examined by linear and non-linear-HRV indices. Heart-rate was recorded continuously with Finometer-PRO at rest and during orthostatic, mental-arithmetic, sit-to-stand, and handgrip-exercise tests.

Results

No significant between-group differences were observed in resting HRV indices (RMSSD: HD:57.1±81.1 vsPD:69.6±113.4ms; p = 0.792) except for DFA-a1 index (HD:0.87±0.40 vs PD:0.70±0.20, p = 0.047). All HRV indices during the mental arithmetic test (RMSSD HD:128.2±346.0 vs PD:87.5±150.0ms; p = 0.893) and the physical stress tests were similar between HD and PD patients. Both dialysis groups presented similar patterns of HRV responses to orthostatic and handgrip exercise tests; however, after the sit-to-stand test RMSSD, SD1,SD2 and DFA-a2 indices were higher compared to rest only in HD patients (RMSSD: 57.1±81.1 vs126.7±185.7ms, p = 0.028), suggesting a greater difficulty of HD patients in recovering normal ANS function following a physical stress-test.

Conclusion

HRV indices at rest and after mental and physical stimulation did not differ between HD and PD patients, however the ANS response following the sit-to-stand test was more impaired in HD. These findings suggest that ANS dysfunction is not largely affected by dialysis modality but small differences in normal ANS recovery may exist.
#6060 A NOVEL CT-BASED RADIOMICS APPROACH FOR KIDNEY FUNCTION EVALUATION IN ADPKD
Authors: Calvaruso Luca , Fulignati Pierluigi , Larosa Luigi , Tran Huong Elena , Votta Claudio , D’ambrosio Viola , Condello Giulia , Ferraro Pietro Manuel , Boldrini Luca , Grandaliano Giuseppe
Published: June 2023

Background and Aims

Clinical management of autosomal dominant polycystic kidney disease (ADPKD) might take advantage of the use of new tools to predict risk of progression towards end stage kidney disease (ESKD). The aim of this study is to develop and validate a model based on radiomic features to predict kidney function among patients with ADPKD obtained from CT scans performed for the determination of total kidney volume (TKV).

Method

We retrospectively selected a cohort of 58 patients with ADPKD who underwent CT scan from February 2020 to March 2021, including 30 patients with eGFR ≥ 60 mL/min/1.73 m2 and 28 with eGFR < 60 mL/min/1.73 m2 at baseline. An expert radiologist generated a region of interest (ROI) segmentation for cystic kidney compounds, obtaining 58 ROIs from which we extracted 217 radiomic features using a dedicated software. We built three different logistic regression models to predict kidney function based on different predictors: height-adjusted TKV (ht-TKV), a selected radiomic feature (F_cm_merged.clust.tend), and both. Area under the curve (AUC) of the receiver operating characteristic (ROC) and accuracy were employed to evaluate models’ performance in discriminating between the two eGFR groups. Internal 3-fold cross-validation (CV) was performed.

Results

The ht-TKV, radiomic and combined models presented respectively an AUC (95% confidence interval) of 0.79 (0.67, 0.91), 0.83 (0.72, 0.93), 0.84 (0.74, 0.94), confirmed by the CV. Mean (standard deviation) values of the accuracy over CV iterations were 0.67 (0.10), 0.77 (0.09), 0.77 (0.09) for the three models. A model combining ht-TKV with a radiomic feature based on CT images from polycystic kidneys resulted effective in the prediction of baseline kidney function in our cohort. Furthermore, a logistic regression model based on a different radiomic feature (F_cm.2.5Dmerged.info.corr.2) selected among a subcohort of 29 ADPKD patients with a clinical follow-up, predicted rapid progression with a AUC of 0.81, a sensitivity of 100% and a specificity of 53%.

Conclusion

This is among the first studies which aimed to investigate, in a clinical setting, radiomics potential ability in discriminating eGFR at baseline and to explore as well whether a reliable radiomic feature could be taken into account in predicting faster rapid kidney function impairment over time. Further studies should implement a model extension to predict kidney function slope in order to confirm the role of radiomics in ADPKD management.
#6124 INTERACTIONS BETWEEN FIBROBLAST GROWTH FACTOR 23 AND SYSTEMIC INFLAMMATION IN PATIENTS WITH CHRONIC KIDNEY DISEASE
Authors: Abinti Matteo , Vettoretti Simone , Mattinzoli Deborah , Caldiroli Lara , Molinari Paolo , Ikehata Masami , Alfieri Carlo Maria , Castellano Giuseppe , Messa Piergiorgio
Published: June 2023

Background and Aims

In patients with Chronic Kidney Disease (CKD), serum concentration of Fibroblast Growth Factor 23 (FGF23) is inversely correlated with Glomerular Filtration Rate (eGFR), as an adaptive mechanism to counterbalance the alterations of mineral metabolism. Transcription, secretion and cleavage from the intact form (iFGF23) to the c-terminal fraction (cFGF23) are regulated by several mechanisms among which inflammatory mediators seem to play a significant role. We investigated whether there was any correlation between FGF23 and several inflammatory mediators.

Method

In the present study we evaluated cross sectionally the correlation between FGF23 (iFGF23 and c-FGF23) and some pro-inflammatory (IL-6, TNFα, MCP-1)) and anti-inflammatory (IL-10) cytokines in a cohort of 111 prevalent CKD patients stages III-V not yet on dialysis. We excluded patients with infections or chronic inflammatory diseases in the last 3 months, neoplasia or under immunosuppressive therapy. FGF23 and cytokines were dosed by ELISA.

Results

Descriptive characteristics of the cohort are reported in Table 1. We found an increase in inflammation as eGFR declines: IL6 (r = -0,315, p<0,001), TNFa (r = -0,202, p = 0,033) and MCP1 (r = -0,278, p = 0,003). Furthermore, the ratio between C-terminal FGF23 to intact FGF23 (c/iFGF23) was directly related to eGFR, even if it did not reach statistical significance (r = 0,127, p = 0,113). The correlations between FGF23 and markers of osteo-mineral metabolism and inflammation are reported in Table 2. We found positive correlations of iFGF23 with: IL-6 (r = 0,465, p<0,001), TNFα (r = 0,241, p = 0,009) and IL-10 (r = 0,198, p = 0,044) Conversely, cFGF23 only correlated with MCP-1 (r = 0,264, p = 0,005). c/iFGF23 resulted inversely correlated with IL-6 (-0,326, p<0,001) and positively with MCP-1 (r = 0,178, p = 0,061). After the adjustment for eGFR, iFGF23 maintained his correlations only with IL-6 (r = 0,370, p < 0,001) and TNFα (r = 0,163, p = 0,044) while c/iFGF23 was negatively correlated with IL-6 (r -0,251, p = 0,008) and positively with MCP-1 (r = 0,204, p = 0,032).

Conclusion

Our data confirm that in CKD patients, as the renal function declines, there is an important increase of inflammatory cytokines and a tendency to an impaired cleavage of FGF23 from the intact to the c-terminal form. Furthermore, we observed strong correlations of iFGF23 with several inflammatory cytokines (IL-6, TNFα, IL-10) that seem to be independent of eGFR. On the contrary we did not find any correlation of cFGF23 with inflammatory mediators, except for MCP-1. Therefore, we believe that overall our results suggest that inflammatory markers are differently associated with cFGF23 and iFGF23, as if inflammation may independently influence FGF23 turnover (i.e, c/iFGF23 ratio).
#6129 INTRADIALYTIC PARENTERAL NUTRITION IMPROVES PROTEIN STORES IN CHRONIC HEMODIALYSIS PATIENTS
Authors: Molina Pablo , Quilis Aina , Ureña Paula Gandía , Saura Laura Porcar , Llopis Pilar , Parra Manuel , Antón Alejandro Valero , Barrilero Elena Galván , Castillo Belén Vizcaino , Moya Mercedes González , Pérez-Boix Gabriela , Rodrigo María , Climente Mónica , Calabuig Maria Asuncion Sancho
Published: June 2023

Background and Aims

Intradialytic parenteral nutrition (IDPN) is a form of supplemental nutrition used to treat patients with malnutrition who receive hemodialysis (HD) and in which the oral feeding is not enough to cover basic caloric needs. Although this technique could improve biochemical markers of nutrition, information regarding its effect on body deposits is lacking. We evaluated the effect of IDPN on body composition parameters and nutritional status in prevalent HD patients.

Method

Retrospective observational study that included all prevalent hemodialysis patients who received NPID for more than 3 months at our Center from January 2018 to December 2022. All the patients received a concentrated 3-in-1 parenteral nutrition formula consisting of glucose solution, a lipid emulsion and an amino acid solution without electrolytes (OLIMEL N9®, Baxter). IDPN was infused at a constant rate not exceeding 300 ml/hour, via the venous drip chamber of HD monitor using infusion pump. Changes in lean tissue mass (LTM), intracellular water (ICW), and body cell mass (BCM) assessed by multifrequency bioimpedance spectroscopy (BIS) at baseline and at 3, 6, 9 and 12 months (primary outcomes) and other biochemical and anthropometric parameters (secondary outcomes) were used to assess the effect of NPID.

Results

Seventeen patients were included (women: 9, 53%; mean age: 68±15 y). After IDPN initiation, a gradual improvement in LTM, ICW and BCM was observed, reaching statistical significance at Month 3, 6, 9 and 12. Changes in fat inversely mirrored those of LTM (Table 1). Albumin levels and the normalized protein appearance increased, with a significant reduction in high-sensitive C-reactive protein and extracellular/intracellular body water ratio at month 9 and 12.

Conclusion

IDPN for 1-year was associated to increased muscle mass, supporting the hypothesis that this supplement nutrition could benefit nutritional status and revert protein-energy wasting in HD patients.
#6143 FAMILIAL LECITHIN: CHOLESTEROL ACYLTRANSFERASE (LCAT) DEFICIENCY AS A CAUSE OF CHRONIC KIDNEY DISEASE – A CASE REPORT
Authors: Obeidat Motaz , Obeidat Marya , Al-Shboul Mohammad
Published: June 2023

Background and Aims

Genetic causes of chronic kidney disease are becoming more recognized. Familial lecithin: cholesterol acyltransferase (LCAT) deficiency (FLD) is a rare genetic disorder caused by loss of function mutations in LCAT gene. Patients present with abnormal lipid profile characterized with markedly reduced HDL-C, corneal opacification, anemia, and renal disease, which eventually progresses to kidney failure. Several studies reported genetic variants in LCAT gene that are associated with FLD, and others in certain apolipoprotein genes that act as risk factors for the disease. Incomplete form of FLD, caused by certain mutation, leads to fish-eye disease characterized by progressive corneal opacification. FLD was described in studies from Europe, Latin and North America, Australia and Japan. In Jordan, genetic and clinical studies in FLD patients are absent.

Method

We present a 36-year-old female who presented with nephrotic-range proteinuria, high serum creatinine, hypertension and corneal opacity. Further examination showed a severely reduced HDL level, an increased triglycerides level, anemia and mild thrombocytopenia. Patient's laboratory values at presentation are shown in Table 1. Her blood film showed normocytic and normochromic red blood cells, anisopoikilocytosis and target cells. Light and electron microscopy examination of the kidney biopsy revealed intramembranous, subendothelial and mesangial lipid deposition and vacuolization. In addition, the patient was found to have a family history of corneal opacity and chronic kidney disease. Therefore, FLD was suspected. Whole exome sequencing was employed to identify FLD variants.

Results

The patient was found to be homozygous at 154+5delG in LCAT gene, heterozygous at 388T>C in apolipoprotein E gene (APOE) and homozygous at 1114G>C in WW domain-containing oxidoreductase gene (WWOX). The patient's chronic kidney disease was managed supportively with low salt diet, moderate protein intake, statins, angiotensin receptor blockers and blood pressure control. After one year of follow up, her serum creatinine is 220 μmol/l and estimated proteinuria is 1.2 gm/24 hrs.

Conclusion

FLD should be suspected in patients who present with kidney disease associated with significantly low HDL cholesterol and corneal opacity. Family members should also be screened for kidney disease and genetic mutation in LCAT gene. To date, treatment is mainly supportive and enzyme replacement therapy is not yet widely available.
#6184 PULSE WAVE VELOCITY AND AMBULATORY BLOOD PRESSURE IN PATIENTS WITH RENAL HYPERFILTRATION
Authors: Kodal Nil , Kurultak Ilhan , Karagoz Ferdi , Üstündağ Sedat
Published: June 2023

Background and Aims

Recent studies have been implicated that abnormally increased glomerular filtration rate, defined as renal hyperfiltration, may be a risk factor for the development of renal damage and cardiovascular disease. Herein, we aimed to investigate the possible relationship between renal hyperfiltration(RHf) and pulse wave velocity, ambulatory blood pressure measurements and clinical parameters.

Method

All individuals included the study were between 18 and 65 years old. The eGFR (CKD-EPI) values of above 140 ml/min/1.73 m² were defined as RHf. Nineteen individuals in the renal hyperfiltration group and 20 in the control group were included. Blood and urine samples of the cases were examined. The individuals with diabetes, obesity, pregnancy, hypertension, cardiovascular disease, peripheral artery disease, cerebrovascular disease, chronic rheumatological disease, and thyroid dysfunction were excluded from the study. The parameters related arterial stiffness and ambulatory blood pressure measurements were obtained in all cases. The results were analyzed statistically.

Results

The two groups were similar in terms of gender, age, BMI and smoking. In RHf group, total cholesterol, 24-hour urine proteinuria and albuminuria, SBP, DBP, MAP and PP values ​​were found higher than control group. Interestingly, the differences of “night time” measurements of all these hemodynamic parameters were more pronounced in RHf group. The trend of “non-dipper” pattern was to be higher in the hyperfiltration group. In arterial stiffness parameters the augmentation pressure (AP), central systolic pressure (CSP), reflection magnitude (RM), central diastolic pressure (CBP), and pulse pressure amplification (PPA) were found significantly different. Pearson's corelation analysis revealed that AP, CSP, CBP was the positively; RM was negatively correlated with eGFR in hyperfiltration group (Table 1 and 2). Multivariate linear regression analysis revealed that AP, 24-hour proteinuria and mean arterial pressure were the independent parameters related to hyperfiltration. Logistic regression showed that only AP was an independent predictor of hyperfiltration (p = 0.001, OR = 0.84; 0.757-0.935, CI 95%).

Conclusion

We found that augmentation pressure is the most important independent parameter correlated with RHf among arterial stiffness measurements. The vascular risk may be increased in this population.