bluuebunny/crossref_metadata_2025 huggingface dataset:
#4973 PATHOGENIC ROLE OF D313Y MUTATION IN FABRY DISEASE
Authors: Greco Rosita , Vilio Rosalba DI , Mollica Agata , Papalia Teresa
Published: June 2023

Background and Aims

Fabry disease (FD) is a multisystem lysosomal storage disorder caused by mutations in the GLA gene. The significance of the mutation p.D313Y in the GLA gene is under debate. Our aim is to evaluated the pathogenic role of the D313Y.

Method

For clinical FD phenotype a 60-year-old woman (index case) with cadaveric donor renal transplantation and unknown cause of renal disease was undergoing genetic investigation. She reported D313Y as single variant in the GLA gene. A prospective analysis of clinical manifestation, genetic and biochemical (lyso-GB3 and enzyme activity) data was performed in all her brothers, sisters and sons. Data were assessed as part of routine follow-up visits.

Results

Genotype information of our index case was: nucleotide change c.937G>T, exon 6 involved, amino acid change p.Asp313Tyr, HGMD accession CM930335, mutation type missense. In our cohort comprising n.9 family members: n°5 (55%, n°3 females, n°3 males age range 45-60) had the p.D313Y mutation. In nobody the biomarker lyso-Gb3 was elevated. Two brothers (age range of 40-50 y) died for acute cardiovascular attack before genetic investivagation was performed. The 5 family members showed the following clinical features: 2 hypertension and cardiac hypertrophy (2M, 44/61y); our index case renal failure, LVH and bruning pains; 2F with burning pains (49/46y). Enzyme replacement therapy (ERT) was started in our index case. Annual routine visits are performed in the others.

Conclusion

D313Y mutation seems to correlate with clinically rilevant symptoms (mainly cardiovascular and renal) compatible with FD, also without lyso-Gb3 elevation. ERT might be considered as therapeutic option not only in patients with already organ involvement, but also in paucisymptomatic to prevent disease progression.
#5018 EFFECTS OF CANDESARTAN COMPARED TO LOSARTAN ON INHIBITING MESANGIAL EXPANSION IN DIABETIC MODEL RATS RECEIVING ROSMARINIC ACID
Authors: Sakti Pandu Tridana , Samsu Nur , Rifai Achmad
Published: June 2023

Background and Aims

Oxidative stress and activation of the renin-angiotensin system (RAS) due to chronic hyperglycemia are the pathogenesis of diabetic nephropathy (DN). Until now, therapy for DN has not shown satisfactory results. Rosmarinic acid (RA) which has antioxidant, anti-inflammatory, anti-fibrosis effects, and ARB which can inhibit RAS activation may have a synergistic effect to prevent DN progression. This study aims to determine the effect of inhibiting mesangial expansion in diabetic rat models after being given a combination of RA and ARB (candesartan or losartan).

Method

True experimental laboratory trial with randomized post-test only control group method on Rattus norvegicus strain Wistar rats. Diabetic rats were prepared by giving a high-fat diet (60% fat calories) and a single injection of 40 mg/kg streptozotocin. Mice were divided into 4 groups, each consisting of 4 rats: negative control (healthy rats); positive control (placebo diabetic rats); diabetic rats that received RA and candesartan; diabetic rats that received RA and losartan. The rat glomerulus was evaluated to assess mesangial expansion using ImageJ 1.48 software after 8 weeks of treatment by a pathologist blindly. Data analysis with One-way ANOVA and Tukey's post hoc tests.

Results

The results of the percentage of the mesangial matrix in the positive control group (81.49% ± 1.45) were higher than the negative control group (58.82% ± 0.99). The results of the percentage of the mesangial matrix in the RA + candesartan treatment group (61.56% ± 0.35) and the RA + losartan treatment group (62.28% ± 0.77) showed lower results than the positive control group, with the One-way ANOVA test results showing significant differences (p: 0.000). Tukey's post hoc tests showed the positive control group that received a high-fat diet and induced diabetes with STZ significantly increased mesangial expansion compared to negative control (MD: [22.66]; 95% CI: [20.62], [24.72]; p: 0.000). The RA + candesartan treatment group significantly inhibited mesangial expansion compared to the positive control (MD: [-19.92]; 95% CI: [-21.97], [-17.87]; p: 0.000), as well as the RA + losartan treatment group (MD: [-19.21]; 95%CI: [-21.26], [-17.16]; p: 0.000). The RA + candesartan treatment group showed a better effect in inhibiting mesangial expansion compared to the RA + losartan treatment group, but not significantly (p: 0.735).

Conclusion

The combination of rosmarinic acid with candesartan or losartan has the effect of inhibiting mesangial expansion in diabetic rats.
#5035 CRESCENTIC GLOMERULONEPHRITIS IN A PAEDIATRIC POPULATION: A SINGLE-CENTRE EXPERIENCE FROM SOUTH ASIA
Authors: Sajjan Basavaraj , Bhadauria Dharmandr , Prasad Narayan , Kaul Anupma , Jain Manoj
Published: June 2023

Background and Aims

Crescentic glomerulonephritis (CrGN) is defined clinically by Rapidly progressive renal failure due to crescent formation in ≥ 50% of glomeruli. Most of these patients have a relatively poor prognosis. Therefore, early diagnose and treatment of these patients may help to prevent renal complications. There is a scarce data on pediatric CrGN. We aim to study the etiopathogenesis and outcome of CrGN in children and adolescents.

Method

Retrospective observational study of pediatric patients of age ≤ 18years with biopsy-proven CrGN from January 2010 to December 2021. Clinical and laboratory data with validated renal biopsy report were obtained from the hospital information system. CrGN was defined as crescents in ≥50% glomeruli. Rapidly Progressive Glomerulonephritis (RPGN) is the clinical presentation of CrGN, which is classified based on immunofluorescence findings and serology. Risk factors predicting poor renal outcome were determined.

Results

Of 47 (13.8% of total biopsy proven CrGN) patients, 30 were male patients (M:F ratio 1.7:1) and median age of 14 (range 7–18) years. 32 (68%) patients had immune complex GN and 14 (30%) had pauci-immune crescentic GN and 1 (2%) had anti-GBM Disease. Among Immune complex GN, the following aetiologies were found: IgA nephropathy (n=13, 27.6%), lupus nephritis (n=7, 15%), postinfectious GN (n=5, 11%), Henoch Schoenlein purpura (n=1, (2%), membranoproliferative GN type II (n=2, 4%) and others (n=5, 5%). 4 out of 14 patients with pauci-immune GN showed antineutrophil cytoplasmic antibodies (ANCA). 9 (19%) patients were dialysis dependent at the time of discharge. Patients with complete or partial remission were 23 (46.8%) at the time of discharge. Risk factors predicting poor renal outcome were oliguria, hypertension, interstitial fibrosis and tubular atrophy (IFTA), and serum creatinine at presentation.

Conclusion

Immune complex GN is the most common etiology, that constitutes 68% of patients with crescentic GN. Majority of pauci-immune GN were ANCA negative (71%). Poor renal outcome is related to severity of initial presentation and extent of IFTA.
#5111 HEMODIALYSIS TUNNELED CATHETERS LOCK WITH TAUROLOCK™ VERSUS A COMBINATION OF GENTAMYCINE AND HEPARINE
Authors: Borisov Biser , Vasileva Vanya
Published: June 2023

Background and Aims

Catheter-associated infections (CAIs) and thrombosis (CAT) are the most common complications, associated with the use of tunneled catheters for hemodialysis. The incidence of infections is about 1.8-6.5/1000 catheter-days, and thromboses are the main cause of catheter dysfunction and loss of vascular access in 30-40% of patients. The aim of our study was to determine the incidence of these complications in patients in whom we used prophylactic “locking” of their tunneled catheters.

Method

The patients included in the study signed an Informed Consent (№29.06.2021) approved by the Research Ethics Committee at MU-Pleven. The study was conducted in the period 01.10.2021 - 31.03.2022, a total of six months. The study included 23 men and 22 women with an average age of 60.82 (+/-13,629) years, and the age difference between the three groups can be considered insignificant (P = .046). All patients had tunneled catheters placed >3 months ago (mean duration was 714 +/- 247 catheter-days) as the only vascular access for hemodialysis treatment. After a clinical examination and a negative result of two blood cultures, the patients were randomly divided into three groups of 15 (fifteen) people each, a total of 45 (forty-five) participants: group A – locking the catheter only with TauroLock™ (Tauropharm, Waldbüttelbrunn, Germany), group B – locking with gentamicin (10 mg/ml) and heparin (1250 IU/ml) and group C – locking with TauroLock™ for three months, then – with heparin and gentamicin for the next three months of the study. Patients were monitored for the major complications of catheter-related infection (CRI) and catheter-related thrombosis (CRT). All data was statistically processed with Statgraphics 19.

Results

The median duration for tunneled catheters was 8,105 catheter-days (CD). One complication was reported in each of the three groups: group A – one case of CRI, groups B and C – one case of CRT each. No cases of catheter-associated bloodstream infection, requiring prolonged treatment and catheter thrombosis, requiring replacement of the tunneled catheter were reported. Reported costs for patients treated with TauroLock™ were calculated at 3 EUR/each dialysis session, and for patients treated with gentamicin and heparin – 0.88 EUR/dialysis session.

Conclusion

The data from our study unequivocally support the thesis that locking the catheter with a solution containing TauroLock™ is comparable to the effect of locking the catheter with a solution containing an antibiotic and anticoagulant. In the short term, the difference in the price of medicines is significant, but it does not exceed the potential losses of public funds in the medium and long term. We recommend the use of a similar prophylactic regimen in all patients with tunneled catheters as the only possible vascular access for hemodialysis or with an expected duration of use greater than ninety days.
#5157 ESTIMATION OF RENAL KT/V FROM 24-HOUR URINE VOLUME AND UREA DISTRIBUTION VOLUME IN PERITONEAL DIALYSIS
Authors: Zeiler Matthias , Fioravanti Gilda , Federico Antonio , Ramazzzotti Valentina , Silvestri Simona , Fioravanti Giuseppe , Santarelli Stefano
Published: June 2023

Background and Aims

Residual renal function is an important factor in peritoneal dialysis (PD) regarding technical survival and implementation of incremental therapy schemes. The aim of the retrospective study was to develop an estimation formula of renal Kt/Vurea in PD based on urine output and anthropometric data.

Method

In 235 adult PD patients (151 males, 84 females, median age 66 years, median BMI 26.0, diuresis >100 ml/day) urine output was registered together with anthropometric and lab data during the first peritoneal equilibration test. The dose of furosemide therapy was noted. Urea distribution volume calculated using the formula of DuBois. Measurement of urea in blood and urine was performed by a standard kinetic test with urease.

Results

24-hour urine volume ranged from 100 to 3800 ml (median 1150 ml), similar in both sexes. Renal Kturea showed a significant linear correlation to daily urine volume (r=0.78, p<0.01) independent from sex and diuretic dose: renal Kturea = 5.116 + 0.0221 x 24-hour urine volume (renal Kturea in liters/week, 24-hour urine volume in ml). Urea distribution volume varied between 24 and 60 liters (median 36.4 liters), and calculated renal Kt/V ranged from 0.05 to 2.57 (median 0.84). Estimated renal Kt/V, based on the before mentioned equation divided by urea distribution volume, correlated significantly to calculated renal Kt/V (r=0.75, p<0.01). The goodness of fit analysis showed a mean absolute error of 0.24. The Bland-Altman Plot confirmed a tendency of over-estimation for renal Kt/V < 1.0 and under-estimation for higher renal Kt/V. A restriction of the analysis to 24-hour urine volume up to 1500 ml (n=142 patients, median age 69 years, BMI 25) resulted in an improvement of renal Kt/V estimation (goodness of fit analysis: mean absolute error 0.20).

Conclusion

The estimation of renal Kt/V in PD patients seems to be feasible utilizing 24-hour urine volume and anthropometric data.
#5304 ACCURACY OF PLATELET INDICES AS PREDICTOR OF IN-HOSPITAL MORTALITY IN PATIENTS WITH ACUTE KIDNEY INJURY REQUIRING RENAL REPLACEMENT THERAPY
Authors: Balasa Melvy June
Published: June 2023

Background and Aims

Acute kidney injury (AKI) is a major medical complication associated with a markedly increased risk of death, particularly in patients admitted to the ICU where in-hospital mortality exceeds 50%1. This study aimed to determine the accuracy of MPV, platelet count, and PDW as predictors of adverse outcomes in patients with AKI who received initiation renal replacement therapy (RRT).

Method

A retrospective cohort single-center study was done in a local private tertiary hospital in Cebu. Four hundred ninety-one patients with AKI who underwent RRT between January 2018 and December 2021 were enrolled. A retrieval of data on demographic and clinical parameters during the initiation of RRT was done. The impact of mortality-related factors were identified using univariate and multivariate logistic regression analysis. Determination of optimal cut-off values of platelet indices for in-hospital mortality was done.

Results

This study showed that the in-hospital mortality of patients was 58.45%, with a mean age of 68.6 ± 16.28 years among non-survivors. Among the platelet indices, platelet count and PDW were good predictors of in-hospital mortality in patients who received initiation renal replacement therapy. The optimal cut-off value of platelet count was 173 x 103/uL (sensitivity 56.45%, specificity 62.25%, PPV 67.78%, NPV 50.40%, AUC 0.604). The optimal cut-off value of PDW was 16.45% (sensitivity 50.87%, specificity 71.57%, PPV 71.57%, NPV 50.87%, AUC 0.611).

Conclusion

Platelet indices are feasible parameters that can be used as prognostic markers for mortality in patients with AKI requiring RRT. The in-hospital mortality of patients with AKI requiring initiation RRT is high (58.45%). Low platelet counts, high MPV values, and high PDW values are associated with poorer outcomes and higher mortality risk as compared to patients with normal indices.
#5337 PHENOTYPIC CHANGES OF LYMPHOCYTES FOLLOWING RENAL TRANSPLANTATION
Authors: Vagiotas Xaralampos , Lioulios Georgios , Moysidou Eleni , Xochelli Aliki , Kasimatis Efstratios , Tsoulfas Georgios , Papagianni Aikaterini , Fylaktou Asimina , Stangou Maria
Published: June 2023

Background and Aims

Phenotypic changes in lymphocytes have been described following renal transplantation (RT), including both CD4 and CD8 subpopulations. The present work aims to prospectively assess of T lymphocyte phenotypic alterations, after RT and compare differences between deceased (DR) and living (LR) donor recipients.

Method

One hundred six RTRs were included in the study, 78/106 (74%) DR, age 52.5(15)yrs and 28/106 (26%) LD, 35(21)yrs. Lymphocytes, CD4, CD8, CD4CD28null, CD8CD28null, CD16+CD56+ (NK) and CD4+CD25+FoXP3+ (Tregs) were evaluated at peripheral blood, by flow cytometry, at certain time points: RT and 3, 6, 12 months (T0, T3, T6, T12, respectively).

Results

During follow up, at T3, T6, T12, eGFR was 61(23.6), 62.2(31.1), 63.5(23.9)ml/min/1.73 m2, p=NS and 59.1(24.8), 61(25.3), 62(22.7), p=NS, in DR and LR group, respectively. eGFR showed no significant difference between DR and LR at any time point. At any time point, T0, T3, T6, 12, lymphocytes were significantly increased in DR compared to LR groups, P = .001, p<0.0001, P = .002, p<0.0001, similarly CD4, P = .001, p<0.0001, P = .001, p<0.0001, and CD8 cells, P = .002, p<0.0001, P = .005, P = .006, respectively. Tregs were increased at T0, T3, T6, not at T12, p<0.0001, p<0.0001, P = .001, P = .1, respectively. At this point, Tregs were increased in RTRs with eGFR>50ml/min/1.73 m2, 20.3(9.3) vs. 27.2(18.6), P = .03. CD4CD28null, CD8CD28null cells did not change during follow up, and there was no difference between two groups at any time point.

Conclusion

Immune profile, was improved in both groups, DR or LR, however a significantly better effect managed in LR, although elimination of CD28 molecule could not be restored. Interestingly, Tregs were associated only by renal function one year following RT.
#5436 CHARACTERIZATION OF KIDNEY FUNCTIONAL DAMAGE ASSOCIATED TO CO-TREATMENT WITH IMMUNE CHECKPOINT INHIBITORS AND CISPLATIN
Authors: Tascón Javier , Casanova Alfredo G , Vicente-Vicente Laura , Pescador Moisés , Prieto Marta , Martín Ana Isabel Morales
Published: June 2023

Background and Aims

Advances in the knowledge of the immune response against tumors and the evasion mechanisms of these have led to develop new cancer therapies focused on improving the immune response and thus increasing patient survival. This is the case of immunotherapeutic treatment based on immune checkpoint inhibitors (ICI). However, treatment based on these antibodies is associated with autoimmune side effects, in most of the body organs, that limit their use. Although nephrotoxicity is rare, renal effects have been shown to worsen the prognosis of cancer patients. Recently, therapies based on the combination of immuno and chemotherapy have been approved. They have improved efficacy but have increased the risk of suffering nephrotoxic adverse effects. Our hypothesis is that kidney damage associated with ICIs could be subclinical and not evidenced by the parameters used in clinical practice (mainly plasma creatinine). The aim of this work was to characterize functional kidney damage associated with ICI (anti-CTLA-4) in combination with chemotherapy (cisplatin) in a murine model.

Method

C57BL/6 mice were treated with combined therapy of cisplatin (10 mg/kg, single dose) and anti-CTLA-4 (10 or 15 mg/kg/day, for 6 days) administrated by intraperitoneal injection. In addition, groups treated with drug monotherapies and a control group were included. Urine and blood samples were collected at baseline, on day 3 and on day 6 (sacrifice). Biomarkers of subclinical kidney damage were determined by ELISA in urine samples. There were albumin, neutrophil gelatinase-associated lipocalin (NGAL) and kidney injury molecule 1 (KIM-1). Blood samples were centrifuged to obtain plasma, in which creatinine and urea were measured using colorimetric techniques. Data were analyzed with the statistical software SPSS®.

Results

Plasma creatinine and urea were elevated in the combined therapy groups with respect to the monotherapies. However, these parameters were similar to the normal range, so they do not reflect obvious kidney injury. It was evidenced a statistically significant elevation of biomarkers of subclinical kidney damage in the combined therapy groups with respect to monotherapies and control group.

Conclusion

This study suggests that the combination of anti-CTLA-4 with cisplatin could cause a potenciation effect on subclinical kidney damage compared to monotherapies. This experimental model would make possible to study the nephrotoxicity mechanisms of ICI. Moreover, it could have a potential diagnostic utility through the identification of biomarkers of subclinical kidney damage, that would avoid biopsy.
#5462 METABOLIC PROFILING IN CHILDREN WITH END STAGE RENAL DISEASE ON PERITONEAL DIALYSIS: PRELIMINARY RESULTS OF AN ONGOING PRESPECTIVE STUDY
Authors: Kondou Antonia , Dotis John , Karava Vasiliki , Begou Olga , Taparkou Anna , Panteris Eleftherios , Gika Helen , Theodoridis George , Printza Nikoleta
Published: June 2023

Background and Aims

Peritoneal dialysis (PD) is the main renal replacement treatment for children and adolescents with end stage kidney disease (ESRD). Peritoneal fibrosis is a major complication in long-term PD patients. Aim of the present study is to record the metabolic "fingerprint" of children on PD and to investigate its correlation with PD history and dialysis adequacy as well as the emergence of potential biomarkers that could detect early or predict peritoneal dysfunction.

Method

Serum samples from 15 patients undergoing peritoneal dialysis were analyzed. Two targeted LC-MS methodologies were used for the determination of 107 metabolites in total. The obtained results were compared based on demographic and clinical parameters, both before and after the dialysis procedure. Serum samples were further divided into subgroups, based on PD duration, creatine clearance, sex, anuria. Reragding metabolic techologies used, all samples were analyzed by a hydrophilic interaction liquid chromatography coupled to mass spectrometry (HILIC-MS / MS) method previously developed and validated in our laboratory for the simultaneous determination of amino acids and their derivatives in biological fluids. Αlso, high flow analysis was carried out (LC-qTOF analysis – HPLC /MS).

Results

8-OH-2-deoxyguanosine (8-hydroxy-2' -deoxyguanosine (8-OHdG) was the only metabolite found to differentiate between serum samples collected before and after PD (p<0.05). Grouping the samples by age groups (child, teen and late teen-young adult) we found out that succinate like lactate, N-acetyl-β-d-glucosaminidase (NAG), are potential markers for the quality of PD. Grouping the patients by number of peritonitis episodes (3 groups: no episodes, 1-2 episodes and >3 episodes) cytosine, riboflavin, glutamic acid, methylxantine and malate found to differentiate between the three groups (p <0.05). Regrading the creatinine cleranace, xylose, dCDP, HIAA, pyroglutamic, A CoA and methylxantine seems to be significan biomarkers. Grouping the patients based on the presence or absence of diuresis,HIAA, kynurenic,glucuronic and pantothenic acid found to differentiate between the two groups (p<0.05)

Conclusion

Based on the literatute the majority of the metabolites showed a statistically significant difference are involved in the inflammation process. Our results are the preliminary results of an ongoing prospective study. Limitation of the study, is the small sample of patients, which does not allow safe clinical interpretation. In any case, metabolomics seems to be a useful tool for the study and identification of biomarkers in patients with ESRD on PD.
#5471 THE URINARY BIOMARKERS IGFBP7 AND IGFBP7 X TIMP2 PRE-EMPTIVELY IDENTIFY PATIENTS AT RISK OF CONTRAST NEPHROTOXICITY
Authors: Quintero Patricia García , Casanova Alfredo G , Tascón Javier , Prieto Marta , Pescador Moisés , Lopez-Hernandez Francisco J , Martín Ana Isabel Morales , Vicente-Vicente Laura
Published: June 2023

Background and Aims

Drug nephrotoxicity is a serious medical and economic concern. In fact, 25% of the 100 most used drugs in intensive care units are toxic to the kidney, which limits their use and, therefore, the correct therapy for the patient. The administration of contrast media (CM) during diagnostic tests or surgical interventions carries the risk of contrast-induced nephropathy (CIN), which is a clinical condition defined as an increase in plasma creatinine of 25% or 0.5 mg/dL above baseline within 3-5 days after administration. Because once installed CIN has no treatment, identification of new biomarkers predicting patients at risk of CIN before receiving CM may be crucial to prevent future kidney complications. Clinical studies conducted in other medical areas have identified new urinary biomarkers, such as insulin like growth factor binding protein 7 (IGFBP7) and tissue inhibitor of metalloproteinases 2 (TIMP2), that anticipate the risk of developing kidney damage after the administration of different potentially nephrotoxic compounds. The objective of this work was to evaluate the usefulness of these biomarkers to predict CIN in cardiac patients.

Method

A clinical study was carried out with 154 patients from the University Hospital of Salamanca Cardiology Department who subsequently received a CM. Prior to contrast administration, urine samples were collected. In addition, their plasma creatinine level was registered for the following 5 days to evaluate the development of CIN. Patients were divided into Controls (who did not develop CIN) and Cases (who developed CIN). IGFBP7 and TIMP2 biomarkers were quantified in urine samples by ELISA. Subsequently, the differences between both groups were evaluated using the Mann-Whitney U test and the diagnostic capacity of each biomarker was analyzed through the generation of its receiver operating characteristic (ROC) curve.

Results

Of the total number of patients, 123 were assigned to the Controls group and 31 to the Cases group. In both groups the distribution of sex and risk factors was similar, except for the case of age and body mass index, which was slightly lower and higher, respectively, in the Controls group. IGFBP7 was significantly higher in Cases (p < 0.01) compared to the Controls, and the IGFBP7 x TIMP2 product further improved this significance (p < 0.001). Specifically, the area under the ROC curve for IGFBP7 was 0.67 (95% confidence interval of 0.56-0.78); while that for IGFBP7 x TIMP2 increased to 0.73 (with a 95% confidence interval of 0.63-0.84). In contrast, TIMP2 alone showed no differences between both groups of patients.

Conclusion

The biomarkers IGFBP7 and IGFBP7 x TIMP2 could therefore be used for the prophylactic identification and management of patients at risk of developing CIN.
#5527 ALDOSTERONE, CORTISOL AND URINE VOLUME CAN EXPLAIN DISCREPANCIES BETWEEN DIETARY AND URINARY NA/K RATIO
Authors: van Vliet Anne Myrthe , Zwager Charlotte , Rauh Manfred , Titze Jens , Engberink Rik Olde
Published: June 2023

Background and Aims

Increased urinary sodium-to-potassium (Na/K) ratio has been associated with chronic kidney disease. However, we demonstrated that urinary Na/K ratio does not accurately reflect dietary Na/K ratio. Rhythmic patterns of sodium storage and release from the skin interstitium are associated with aldosterone and cortisol levels and previous studies linked tissue sodium accumulation to water conservation. Therefore, we investigated whether the discrepancy between urinary and dietary Na/K ratio could be explained by these factors.

Method

For this post-hoc analysis, we used data from the long-term sodium balance studies Mars105 and Mars520. These studies collected 24-hour urine samples and controlled dietary salt intake for 105 (4 men) and 205 days (6 men) at levels of 6, 9 and 12 grams per day. We calculated the difference between urinary and dietary Na/K ratio. We tested whether this difference varied across salt intake levels in a linear mixed-effects model. Furthermore, we fitted two linear mixed-effect models to explain discrepancies between urinary and dietary Na/K ratio. In the first model, sodium intake, potassium intake, urinary aldosterone and urinary cortisol were fixed effects and for each factor random slopes per participant were allowed. In the second model, sodium intake, potassium intake and urine volume were fixed effects and for each factor random slopes per participant were allowed. Each salt intake level was assessed separately.

Results

The median difference between 24-hour urinary and dietary Na/K ratio was −0.21 (IQR −0.47 to 0.09). At higher salt intake levels the underestimation was significantly larger (mean difference −0.11, −0.22 and −0.36 for 6, 9 and 12 grams salt intake, respectively; P<0.001). At each salt intake level, higher urinary aldosterone was associated with underestimation of the dietary Na/K ratio (Figure 1A). In contrast, higher urinary cortisol and higher urine volume were associated with relative overestimation of the dietary Na/K ratio (Figure 1B and C, respectively).

Conclusion

The discrepancy between dietary and urinary Na/K ratio can be explained by sodium intake, aldosterone, cortisol and urine volume. This suggests that tissue sodium accumulation contributes to the inaccuracy of a single 24-hour urine collection for estimation of dietary sodium and potassium intake.
#5547 SERUM PERIOSTIN IN KIDNEY TRANSPLANT RECIPIENTS AS A NOVEL BIOMARKER PREDICTING RENAL FUNCTION LOSS
Authors: Kurnik Anna , Batko Krzysztof , Krzanowska Katarzyna , Malyszko Jolanta , Żorawska Ewa Koc- , Zorawski Marcin , Banaszkiewicz Małgorzata , Woziwodzka Karolina , Małyszko Jacek , Krzanowski Marcin
Published: June 2023

Background and Aims

Experimental studies have shown periostin is expressed throughout organogenesis, particularly within the kidney interstitium. Periostin is enhanced in different tissues of patients with nephropathy and has been considered as a candidate biomarker of kidney injury.

Method

Retrospective analysis of electronic medical record of one hundred and five kidney transplant recipients (KTRs) was performed. Only patients under sequential ambulatory care, with a history of at least 2 years post-transplant were included. Median (IQR) follow-up and time post-transplant was 4.42 (2.65, 4.58) and 4.29 (3.04, 8.07) years, respectively. Additionally, thirty-two health volunteers (HV) were enrolled. Biochemical testing was performed using commercially-available immunoassays.

Results

Median [IQR] serum periostin was significantly lower in KTRs as compared with HV (959 [732, 1204] vs. 1176 [997, 1408]; P<0.01). Higher serum periostin was observed in male patients (7.01 [6.84, 7.22] vs. 6.79 [6.64, 7.07], P<0.05) and a significant relationship was noted for interleukin 6 (IL6; r=0.24, P=0.01) and baseline estimated glomerular filtration (eGFR) (r=0.20, P=0.04). Patient age (P=0.60), body-mass index P=0.08), cardiovascular disease (P=0.31), diabetes (P=0.45), current smoker status (P=0.27), nor anemia (P=0.23) were not associated with serum periostin. In a generalized additive model adjusted for baseline renal function and IL-6, serum periostin showed a signficant nonlinear association (P=0.04) with eGFR change over follow-up.

Conclusion

Previous studies reported an association between periostin expression and the severity of histological injury within the kidney in both inflammatory and non-inflammatory conditions. Serum periostin may be a potential marker aiding in prediction of renal function in KTRs.
#5555 TAKAYASU ARTERITIS IN THE TIME OF SARS-COV-2
Authors: Finocchiaro Pietro , Caridi Graziella , Catalano Francesco , Postorino Adele , Tripepi Rocco , Mallamaci Francesca , Panuccio Vincenzo Antonio
Published: June 2023

Background and Aims

SARS CoV 2 infection is characterized by pulmonary, cardiovascular, neurological and other complications. New onset hypertension after SARS Cov 2 infection was observed in various studies with an unclear mechanism. Vessel inflammation is a common finding in these patients.

Case

A young woman (24 years old) referred to our Unit for high blood pressure levels appeared few days after SARS COVID 2 infection. She had a positive familiar history of hypertension. A 24 hours blood pressure monitoring confirmed hypertension and the patient was treated with a beta-blocker and referred to the nephrologist. Physical examination was negative and peripheral pulses were palpable. Blood pressure was 150/90 mmHg without significative discrepancy (<10 mmHg) between right and left arm and between upper and lower limbs. Carotid-femoral and carotid-radial pulse wave velocity was in the upper limit of the normal range (9.8 and 8.0 m/sec respectively), renal function was preserved (serum creatinine 0.6 mg/dl, eGFR 154 ml/min) and proteinuria was 450 mg/die. C-reactive protein was 13 mg/L. Complement components C3 and C4 as well as IgG and anti-neutrophil cytoplasmic antibody (ANCA) levels were in the normal range. IgA and IgM were slightly elevated and anti-nuclear antibody (ANA) levels were 1:160. TSH was in the normal range. Patient was switched to calcium channel blockers and a screening to exclude secondary hypertension was performed. Hormonal profile showed hypersecretion of cortex and medullary adrenal gland (high renin and aldosterone, plasma and urinary cortisol, and epinephrine levels). Patient was treated with ACE inhibitor and showed an optimal blood pressure profile. Abdominal-Chest CT angiography detected no increase in adrenal gland dimension. Conversely, a left renal artery stenosis and a mild enlargement of the para-aortic tissue, suggestive of a retroperitoneal fibrosis, was described (Figure 1). A Doppler ultrasound examination confirmed a high systolic peak velocity in left renal artery and a low resistive index in the left kidney. According to the diagnosis of renal fibrosis, patient was treated with oral prednisone at a dosage of 1 mg/Kg/BW. Three months later, Doppler ultrasound and CT were materially unchanged. After a case revision and a negative evidence of inflammation at PET-FDG examination, the Takayasu Arteritis diagnosis was formulated and the patient underwent left renal artery angioplasty. Oral prednisone was tapered and methotrexate was started. One month later blood pressure and Doppler ultrasound velocimetric parameters were normalized.

Conclusion

This case report suggests that Takayasu arteritis may occur after SARS COVID 2 infection.
#5633 USE OF HEPARIN GRAFTED DIALYZER (EVODIAL) FOR HEMODIALYSIS IN PATIENTS WITH HIGH RISK OF BLEEDING: A SINGLE CENTER EXPERIENCE
Authors: Pushevski Vladimir , Markovska Zhaklina Shterjova- , Usprcov Julijana , Gjorgjievski Nikola , Trajcheska Lada , Milenkova Mimoza , Bushljetik Irena Rambabova-
Published: June 2023

Background and Aims

During hemodialysis exposure of the blood to the dialysis membrane and the tubing system can activate blood cells and promote clotting activation. So usually, some form of anticoagulation, most frequently heparin, is used to prevent blood coagulation. However, there are patients with increased risk for bleeding (patients with active bleeding, major surgery in past 72 hours, severe trombocytopenia) where use of heparin free regime is mandatory. Evodial dialyzer (Gambro-Hospal, France) [1] contains a heparin-grafted membrane aiming to provide a system with a low thrombogenicity that can be used without or with low dose heparin in order to reduce the patients' bleeding risk. As high-quality evidence of the optimal choice of anticoagulation in these patients is limited we wanted to show our experience with the use of Evodial dialyzer.

Method

During 12 months 106 dialysis sessions in 59 patients were performed. Reasons for using Evodial : active bleeding, hematological conditions, complications of vascular access. Changes in the dialyzer or the blood lines, or any aditional interventions were examined.

Results

Low dose unfractionated heparin (1250 IE total) was used in 10 (9,4%) sessions, and it was added in 15 (14%) more sessions because of problems with the coagulation. In 4 (2,8%) sessions we had to terminate dialysis because of clotting.

Conclusion

Heparin grafted dialyzers can be safely used in patients with high risk for bleeding. Although results are worse than the ones reported in literature [2] where regional citrate anticoagulation (RCA) is used, it can be reasonable alternative when RCA is unavailable.
#5718 ASSOCIATION OF MULTIPLE PLASMA BIOMARKER LEVELS WITH KIDNEY DISEASE ACTIVITY IN FABRY DISEASE
Authors: Özcan Şeyda Gül , Atli Zeynep , Eren Necmi , Dincer Mevlut Tamer , Turkmen Kultigin , Ozer Hakan , Trabulus Sinan , Seyahi Nurhan
Published: June 2023

Background and Aims

Fabry disease is a rare, systemic, genetic, and metabolic lysosomal storage disease. Phenotypic heterogeneity prevents accurate predictions for the disease progression. We aimed to evaluate the association of multiple plasma biomarkers with disease severity in Fabry disease.

Method

In a cross-sectional study, we examined 76 Fabry, 46 CKD patients and 41 healthy controls. We studied KIM-1, MCP-1, YKL-40, TNFR-1, TNFR-2, cystatin-C with enzyme linked immunoassay. Fabry patients on renal replacement therapy were excluded from the analysis.

Results

Demographic, clinical and laboratory data of the study participants are shown in Table 1. eGFR was calculated with creatinine and creatinine-cystatin C using CKD-EPI formula. While there was no difference between Fabry patients and healthy controls regarding eGFR(cr); eGFR(cr-cys) was significantly lower in Fabry patients. Biomarker levels in three groups were shown in Table 2. After performing age, sex and BMI adjusted analysis, MCP-1 was significantly lower in Fabry patients compared to CKD group (p:0.01). MCP-1 was significantly higher in Fabry patients with cardiac involvement than in those without cardiac involvement (p:0.039). KIM-1 was significantly higher in Fabry patients comparing to healthy controls (p:0.01). There was no significant difference regarding biomarker levels between Fabry patients with and without kidney involvement. YKL-40 was significantly lower in Fabry patients without kidney involvement compared to both control groups (p:0.025), probably reflecting the effect of ERT.

Conclusion

MCP-1, KIM-1, YKL-40 and Cystatin C seems to be useful markers for the management of Fabry patients. Each biomarker is associated with different aspect of the disease. MCP-1 might be a useful regarding Fabry disease activity especially in patients with cardiac involvement. KIM-1 might be an early sign in Fabry disease. Cystatin-C should be used for better management of patients since it shows renal involvement better than creatinine.
#5730 PERLECAN AS A POTENTIAL BIOMARKER OF CARDIOVASCULAR RISK: ROLE OF ENDOTHELIAL GLYCOCALYX IN CHRONIC KIDNEY DISEASE
Authors: Arévalo Gemma Valera , Rubio Andrea Figuer , Espada Paula Jara Caro , Yuste Claudia , Morales Enrique , Costoso Noemi Ceprian , Bodega Guillermo , Ramirez Rafael , Alique Matilde , Carracedo Julia
Published: June 2023

Background and Aims

Chronic kidney disease (CKD) is associated with cardiovascular disease (CVD). CVD is in turn related to endothelial dysfunction, endothelial dysfunction, and degradation of the endothelial glycocalyx (EG), releasing its components into the bloodstream. The EG consists of glycosaminoglycans and proteoglycans, such as Perlecan. The aim of the study is to analyse the levels of perlecan in plasma in different stages of CKD, and to relate them to age and inflammatory monocytes, as well as their adhesion capacity (CD54/ICAM-1).

Method

An observational cross-sectional study was carried out. 56 patients were included: advanced chronic kidney disease (ACKD) (n=13), haemodialysis (HD) (n=13), peritoneal dialysis (PD) (n=15) and transplant recipients (TX) (n=15). Thirteen healthy subjects (CT) were analysed. Plasma perlecan levels were quantified using ELISA and phenotyping of monocyte subpopulations (classical (CD14++CD16-), intermediate (CD14+CD16+) and non-classical (CD14+CD16++)), as well as CD54 (ICAM-1) expression by flow cytometry. Statistical analysis: ANOVA and Spearman correlation.

Results

Patients with CKD had higher plasma levels of perlecan than healthy participants (p-value = 0.044 vs ACKD, 0.028 vs HD and 0.002 vs PD) (Fig. 1). These levels were associated with higher percentage of classical monocytes (p=0,011) intermediate monocytes (p=0,009) and non-classical monocytes (p=0,003) expressing ICAM-1 but not with a higher expression of ICAM-1 per monocyte. Perlecan levels correlate negatively with age (p=0,03) (Table 1).

Conclusion

Patients with ACKD, HD and PD have elevated plasma perlecan levels compared to CT and TX. Elevated perlecan concentrations are associated with increased ICAM-1 expression on monocytes, which is important for its possible role in the development of atherosclerosis. Perlecan may be postulated as a molecule of interest to assess endothelial and cardiovascular damage in CKD patients.
#5868 PREVALENCE AND MANAGEMENT OF CHRONIC COMPLICATIONS IN PATIENTS WITH DIABETES AND ADVANCED CHRONIC KIDNEY DISEASE: A RETROSPECTIVE AUDIT
Authors: D'souza Cimona , Kakkar Acrisa , Suresh Vijayan , Bellary Srikanth
Published: June 2023

Background and Aims

Current guidelines recommend that all patients with Chronic Kidney Disease (CKD) stage 3b or higher should be monitored and treated for anaemia, mineral bone disorder (BMD) and metabolic acidosis. We audited the prevalence and management of these complications in a cohort of patients with diabetes and advanced CKD.

Method

A retrospective audit was undertaken using KDIGO guidelines as standard and necessary approvals were secured from the governance team at University Hospitals Birmingham. We included patients with (a) diabetes (b) eGFR 30 and 15 ml/min/1.73 m2) and (c) attending diabetes clinics as of 30/09/2022. Using electronic patient records, we collected: demographics, co-morbidities, complications, treatments, body weight, BMI, blood pressure and serial biochemistry (creatinine, Hba1c, cholesterol, UAlb/Creat ratio, bicarbonate, haemoglobin, vitamin D, parathyroid hormone (PTH). Following definitions were applied: anaemia as Hb <13 g/dl for men and <12 g/dl for women, BMD as vitamin D <40 nmol/l plus raised PTH, acidosis as bicarbonate <22 meq/l. Data was analysed using SPSS 26. Descriptive statistics (frequencies and cross tabulations) were used to estimate prevalence. Independent means test was used for continuous variables. Comparison between groups was undertaken using the Chi Square test and one way ANOVA test.

Results

Data for 192 subjects (110 European (EUR), 40 South Asian (SA), 42 African-Caribbean (AFC) /other) was analysed. Mean age (SD) was 73 (+/-11) years. There were no significant differences in general characteristics between the ethnic groups except for albuminuria which was greater in SA and AFC compared to EUR (193 v 133 v 95.5mg/mmol; p=.038). 47% of the cohort had at least one diabetes related complication. 63/192 (32.8%) had cardiovascular disease, 49/192 (25.5%) had retinopathy and 19/192 (9.9%) had neuropathy. Insulin was the most common prescribed glucose lowering agent 105/192 (55%) with proportionately more SA treated with insulin (65%). Anaemia was present in 171/183 (93.4%) of the patients. 82/101 (81.2%) had BMD, and 135/168 (82.8%) of patients had metabolic acidosis. 65/192 (33.9%) of patients had all 3 complications. Only 38/133 (22%) of those with anaemia were receiving treatment out of which only 36.8% were treated adequately with a Hb of >10g/l. Corresponding figures for BMD and metabolic acidosis were: BMD: 39/82 (47.6%) treated and 42% optimally corrected, metabolic acidosis: 54/135 (40%) treated and 53% optimally corrected. There were no significant differences between ethnic groups in prevalence or treatment of these complications.

Conclusion

The prevalence of CKD related complications is high. The management of these complications however, is suboptimal. Increased emphasis on the management of these complications is required to improve outcomes in patients with advanced CKD.
#5983 PULMONARY INVOLVEMENT IN AUTOSOMAL DOMINANT POLYCYSTIC KIDNEY DISEASE
Authors: De Rosa Liliana , Vespa Marta , Catania Martina , Bucci Romina , Joli Giancarlo , Carrera Paola , Mancassola Giulia , Bianca Pierpaolo , Paolisi Michele , Manunta Paolo , Vezzoli Giuseppe , Alibrandi Maria Teresa Sciarrone
Published: June 2023

Background and Aims

Autosomal dominant policystic kidney disease (ADPKD) is the most common genetic kidney disease. It is caused by mutations in PKD1 and PKD2 genes, which encode for polycystin-1 (PC-1) and polycystin-2 (PC-2), two proteins localized in the primary cilia which regulate calcium permeability and cellular signaling pathways. The major phenotype of the disease is the formation of multiple cysts in the kidneys but in many cases it also involves other organs like heart, brain and lungs. The latters are not yet well studied; some papers report a higher prevalence of bronchiectasis in ADPKD patients compared to the general population; morover, one work describes the absence of PC-1 in motile cilia of ADPKD pts compared to controls, who actually do express the protein. Based on available literature, we hypothesized that the PC-1 and PC-2 could have a role also in motile cilia. Exaled nasal nitric oxide (nNO) is an indirect marker of cilia dysfunction, standardized for the screening of primary ciliary dyskinesia, a motile ciliopathy, in which very low levels of nNO are found because of the entrapment of NO in the abundant stagnant mucus.

Method

We recruited 27 patients with ADPKD and 25 randomly selected controls. We compared nNO measurements between the two groups, stratifying for truncated mutations and eGFR. After stratification according to ADPKD genetic mutation, we analyzed separately each of the two subgroups with the control group.

Results

nNO levels were no different in ADPKD patients compared with healthy controls (mean ± standard deviation: 850±240 vs 923±290; P = .3). However in sub-group analysis, lower nNO measurements were found in patients with truncated mutation (769±164) compared to the control group (924±290, P = .05). No association was observed between renal functions expressed as eGFR and nNO levels.

Discussion

Overall nNO levels did not differ in ADPKD individuals compared to controls, although lower nNO measurements were observed in ADPKD patients exhibiting a truncated mutation.

Conclusion

Even at the edge of the statistical significance (P = .05), given it's confirmed in a wider population, this finding could signify that pts who carry a more aggressive genotype (PKD-1 truncated mutation) may not express polycystins in motile cilia; this aspect is in line with the verified knowledge that this kind of mutation ends up in the total absence of the protein. On the other hand, pts with a missense mutation may still express the protein in motile cilia, therefore without any functional impairment.