bluuebunny/crossref_metadata_2025 huggingface dataset:
#2390 Does incompatible kidney transplantation provide a reliable alternative? An updated meta-analysis
Authors: Abdelshafi Abdelrahman , Hamdallah Aboalmagd , Ismail Rahma Abdelaziz , Mohammed Yasmine Adel , Hassan Ghada Mahmoud Ibrahim , Elgebaly Mohamed , Aboali Amira A , Shaltout Mariam A , Nada Sarah A , Kedwany Ahmed M , Barakat Ahmed
Published: May 2024

Background and Aims

The ABO system often poses one of the challenges to kidney transplantation, but due to the scarcity of organs, ABO incompatible kidney transplantation (ABOi-kTx) has gained the clinical attention. So, we aim in this study to evaluate the impact of ABO incompatible kidney transplantation on patients' clinical outcomes in comparison with ABO compatible kidney transplantation (ABOc-kTx).

Method

We searched six electronic databases: PubMed, Scopus, WOS, Cochrane, Embase, and Medline to identify relevant studies published until October 8th 2023, with no filters applied during the research process. After screening of 8562 studies, we included observational studies that compared any clinical outcomes of ABO incompatible kidney transplantation with ABO compatible kidney transplantation across various age groups. Synthesized odds ratios (ORs) with 95% confidence intervals (CIs) are used to present the differences between the two groups based on random-effects models.

Results

Our comprehensive search according to the eligible criteria of this study resulted in 102 studies including 254 496 patients in both groups. Due to the clinical heterogeneity, we used random effects models for quantitative synthesis of the eligible studies. Our meta-analysis showed that there was a statistically significant higher mortality ratio after one year, 3 years and 5 years (odds ratio [OR] 2.21 [95% CI 1.56–3.14], P < .00001; I² = 53%), (OR 1.86 [1.35–2.75], P = .0001; I² = 61%), (OR 1.69 [1.20–2.40], P = .003; I² = 75%), respectively. While there was no statistically significant difference at 8-years after transplantation (OR 1.05 [0.76–1.46], P = .77; I² = 58%). Pooled data of graft failure from our studies revealed higher incidence in ABOi-kTx group after one year (OR 2.44 [1.81–3.28], P < .00001; I² = 64%), 3 years (OR 1.57 [1.24–1.98], P < .00001; I² = 54%) and after 5 years (OR 1.57 [1.23–2.01], P =  .0003; I² = 76%), There was not any statistically significant difference between both groups after 8 years. Acute anti-body mediated rejections were noticed to be statistically higher in ABOi-kTx group (OR 2.51 [2.12–2.97], (P < .00001); I² = 20%). Also, there was a significantly higher incidence of CMV infection in ABOi-kTx group (OR 1.27 [1.08–1.48], (P  =  .003); I² = 58%).

Conclusion

Although that ABOi-kTx is inferior to ABOc-kTx in the first 5 years after the transplantation in patient and graft mortality. Both groups are similar in both outcomes after 8 years post transplantation. Considering the higher incidence of acute rejection in the ABOi-kTx group and increased infection rate, desensitization techniques should be furtherly developed for better survival and complication outcomes.
#2825 BK virus in transplant patients: an enemy to fear or a challenge to accept? The 17-year experience of our transplant center
Authors: Iafisco Alma , Tacente Chiara , Petrosino Anna , Galeandro Egidio , Colonnelli Roberto , Bartoli Benedetta , Carriero Concetta , Iaria Giuseppe , De Paolis Paolo
Published: May 2024

Background and Aims

Reactivation of the BK virus in immunosuppressed patients is a risk factor for the development of BKV nephropathy. Ten percent of transplant patients are affected by BKV nephropathy, and 50% of them experience graft loss. The purpose of this study is to assess the medium to long-term effects of an early immunosuppression reduction strategy in the presence of urinary and/or serum BKV replication in a large population of kidney transplant recipients from our center.

Method

A retrospective observational study was conducted on 681 patients from immediate post-transplant with at least 6 months of observation. 91.5% of them were on the same immunosuppressive therapy (MMF, Steroid, tacrolimus). A total of 16200 samples were collected from blood and urine simultaneously for PCR quantification of BKV over a post-transplant period of 54.4 ± 34.2 months. Immunosuppression reduction began after two repeated biweekly detections of viruria >105 copies/ml and/or viremia >103 copies/ml.

Results

35% of cases tested positive for viruria, with 19% also positive for viremia. Onset and peak viruria and viremia were observed at 4.1 ± 3.3 months and 4.2 ± 3.5 months, and 5.3 ± 4.6 and 5.4 ± 4.1 months, respectively. Viruria negativization occurred in 79.4% of patients after 13.2 ± 9.7 months, while viremia disappeared in 94.6% after 9.2 ± 7.5 months. In 5 patients with persistent viruria and viremia, therapy with Cidofovir or Leflunomide was initiated following biopsy. 14.3% of patients with persistent viruria maintained low replication and stable renal function. No episodes of acute rejection occurred. Only one case of irreversible BKV nephropathy was observed.

Conclusion

Timely reduction of immunosuppression allows excellent control of BKV replication, stability of renal function in the medium to long term, and makes the occurrence of irreversible chronic BKV nephropathy rare.
#2052 Reciprocal interplay between miR-155-5p and SOCS1 in the development of renal and vascular damage in experimental diabetes
Authors: Arjona María Kavanagh , Herrero del Real Isabel , Prieto Ignacio , Jiménez-Castilla Luna , Lazaro Iolanda , Lopez-Franco Óscar , Egido Jesus , Gomez-Guerrero Carmen
Published: May 2024

Background and Aims

Chronic kidney disease and atherosclerosis are common vascular complication of diabetes and a global health issue. Hyperglycemia, dyslipidemia, and cytokines activate Janus kinase/signal transducers and activators of transcription (JAK/STAT) signaling pathway to induce mediators of inflammation and oxidative stress, which are critical events in the progression of renal and vascular damage in diabetic patients. MicroRNAs are small, non-coding molecules and key regulators of gene expression. There is evidence of microRNA-155 (miR-155) involvement in diabetes complications, but the underlying mechanisms are unclear. In this study, gain- and loss-of-function experiments were applied to investigate the interplay between miR-155-5p and suppressor of cytokine signaling 1 (SOCS1) in the regulation of JAK/STAT pathway during renal and vascular injury in diabetes.

Method

Mesangial, tubuloepithelial, and vascular smooth muscle cells were transfected with miR-155-5p mimic or inhibitor, SOCS1 expression plasmid or siRNA, before stimulation with cytokines or high-glucose. Apolipoprotein E deficient mice with streptozotocin-induced diabetes were treated with either SOCS1-encoding adenovirus or miR-155-5p inhibitor. Samples were analyzed for the expression of miR-155-5p, SOCS1, and mediators of renal and vascular damage.

Results

In diabetic mice, the expression of miR-155-5p correlated inversely with SOCS1 levels and positively with markers of renal dysfunction, atherosclerosis, inflammation and oxidative stress. In renal cells, transfection with miR-155-5p mimic downregulated SOCS1, activated STAT1 and cytokine expression, and stimulated cell proliferation and migration. Mimic transfection also promoted the transition from contractile to synthetic phenotype in vascular smooth muscle cells. Conversely, both miR-155-5p antagonism and SOCS1 overexpression protected cells from inflammatory damage. In vivo SOCS1 gene delivery in diabetic mice decreased miR-155-5p and prevented kidney and vascular injury. Finally, therapeutic inhibition of miR-155-5p alleviates albuminuria, renal inflammation and fibrosis in diabetic mice, and also reduced atherosclerosis burden and improved plaque stability.

Conclusion

The modulation of miR-155/SOCS1 axis protects against diabetic renal and vascular damage in mice, thus highlighting its potential as therapeutic target for chronic complications of diabetes.
#2852 Iron status and incident diabetes in kidney transplant recipients
Authors: Rawee Pien , Kremer Daan , van der Vaart Amarens , Touw Daan J , van Dijk Peter R , de Borst Martin H , Bakker Stephan J L , Eisenga Michele F
Published: May 2024

Background and Aims

Kidney transplant recipients (KTR) are prone to develop post-transplant diabetes (PTD). Iron plays a role in glucose homeostasis and patients with iron overload have a high prevalence of diabetes. Since iron overload can also occur in KTR, we investigated whether levels of ferritin are associated with incident PTD in KTR.

Method

This is a prospective observational cohort study of adult KTR ≥1 year after transplantation of the Transplantlines Insulin Resistance and Inflammation Biobank and Cohort study. Cox regression analyses were applied to study the association of serum ferritin with incident PTD (fasting plasma glucose ≥126 mg/dL, or nonfasting plasma glucose ≥200 mg/dL combined with diabetes symptoms, or use of glucose-lowering medication). Models were adjusted for age, sex, body mass index, C-reactive protein (CRP), diabetes risk factors, transplantation factors, and immunosuppressive drugs. To explore potential clinical cut-offs of ferritin levels from which the risk of PTD might increase, categories of ferritin (<100, 100-300, 300-500, and >500 µg/L) were used in subsequent analysis.

Results

We included 399 KTR (age 51 [IQR, 41-59 years], 54% males, and at a median of 6.1 [3.0-12.1] years after transplantation) without diabetes at baseline. During a median follow-up of 9.7 [7.6-10.3] years, 45 KTR (11%) developed PTD. In multivariable Cox regression analyses, serum ferritin levels were significantly associated with incident PTD independent of adjustment for potential confounders (Table 1, hazard ratio (HR) per 50 µg/L, 1.12; 95% CI 1.05-1.18; P = 0.0002). Furthermore, in analysis with ferritin categories, we identified that KTR with ferritin >500 µg/L (n = 38) had a significantly higher chance of PTD compared to KTR with ferritin between 100-300 µg /L (Fig. 1, HR, 3.66; 95% CI 1.37-9.77; P = 0.01). KTR with ferritin levels <100 and between 300-500 µg/L had a similar risk of PTD compared to KTR with ferritin levels between 100-300 µg/L.

Conclusion

Ferritin levels are associated with PTD in KTR, independent of other known diabetes risk factors, including inflammation. KTR with ferritin levels above 500 µg/L appear particularly prone to develop PTD. Further investigation should determine the underlying mechanisms and consequences of these findings with respect to target goals of ferritin levels after kidney transplantation.
#100 Hospital readmissions for fluid overload among individuals with diabetes mellitus
Authors: Cai Jiashen , Huang Dorothy , Kadir Hanis Abdul , Huang Zhihua , Ng Li Choo , Ang Andrew , Tan Ngiap Chuan , Bee Yong Mong , Tay Wei Yi , Tan Chieh Suai , Lim Cynthia
Published: May 2024

Background and Aims

Hospital readmissions due to recurrent fluid overload in diabetes can be avoided with evidence-based interventions. To identify at-risk individuals, we evaluated the incidence and risk factors associated with fluid overload-related hospital readmissions and developed risk prediction models for readmissions for fluid overload in people with diabetes.

Method

Single-centre retrospective cohort study of 1531 adults with diabetes and hospitalized in Singapore General Hospital for fluid overload, congestive heart failure, pulmonary edema and generalized edema between 2015 and 2017. Patients were included if they had diabetes mellitus identified by the SingHealth Diabetes Registry according to diagnosis codes, laboratory results and/or the use of glucose-lowering medication and had follow up visits, but excluded if their estimated glomerular filtration rate (eGFR) <15 ml/min/1.73 m2. Baseline data on demographics, comorbidities, biochemistry and medication use during admission were retrieved from electronic medical records up till 30 December 2018. The outcomes were fluid overload- related readmissions within 30 days and 90 days of discharge of the index hospitalization. Multivariable Cox proportional-hazards regression analysis was performed with inclusion of covariates with p≤0.10 on univariate analysis. Multivariable regression models developed were compared with the LACE index with net reclassification index (NRI).

Results

Among 1531 patients, median age was 73 (IQR 64, 81) and readmissions for fluid overload within 30 days and 90 days occurred in 131 (8.6%) and 264 (17.2%) patients, respectively.

Individuals with 30- or 90-day readmissions were more likely to have prior hospitalization for fluid overload and more frequent ED visits within 6 months before the index hospitalization, cardiovascular disease, hypertension, and required high-dose intravenous furosemide during the index hospitalization, or current smoker.

Clinical and clinico-psychosocial models for 30- and 90-day readmissions for fluid overload were developed (Table 1). The clinical and clinico-psychosocial models showed better discrimination and calibration than LACE index for predicting 30- and 90-day readmissions for fluid overload. The NRIs for clinical models were i. 30-day readmissions: +22.1%, ii. 90-day readmissions: +27.9% respectively, while the NRIs for clinico-psychosocial models were i. 30-day readmissions: +22.4%, ii. 90-day readmissions: +28.9% respectively (Fig. 1).

Conclusion

Patients with diabetes who are at-risk of readmission for fluid overload can be identified for targeted interventions to reduce preventable hospitalizations.
#1488 Dialysate sodium and short-term blood pressure variability in patients with intradialytic hypertension: a randomized crossover study
Authors: Iatridi Fotini , Ekart Robert , Efstathios Xagas , Karpetas Antonios , Theodorakopoulou Marieta P , Karkamani Eleni , Chalkioti Ioanna , Revela Ioanna , Giamalis Panagiotis , Sarafidis Pantelis
Published: May 2024

Background and Aims

Increased blood pressure (BP) variability (BPV) is associated with high cardiovascular risk in hemodialysis. Patients with intradialytic hypertension (IDH) also exhibited an increased cardiovascular risk than hemodialysis patients without this condition. The impact of non-pharmacological BP-lowering interventions on BPV in this population remains unknown. This analysis evaluated the effect of low (137 mEq/L) compared to standard (140 mEq/L) dialysate sodium concentration on short-term BPV in patients with IDH.

Method

In a randomized cross-over manner, 29 patients with IDH underwent 4 hemodialysis sessions with low (137 mEq/L) followed by 4 sessions with standard (140 mEq/L) dialysate sodium or vice versa according to randomization arm. 48-h ABPM was performed from the start of the 4th session on each dialysate sodium. BPV indices during the 48-h, 24-h, day-time and night-time periods were calculated with validated formulas.

Results

Mean 48-h BP was lower by 5.3/2.6 mmHg with low compared to standard dialysate sodium concentration, (p = 0.005/p = 0.007) respectively). All 48-h systolic BPV indices examined showed non-significant differences between low and standard dialysate sodium (SBP-SD: 16.99 ± 5.39 vs. 16.98 ± 4.33 mmHg; p = 0.982; SBP-wSD: 15.93 ± 5.02 vs. 16.12 ± 4.16 mmHg, p = 0.769; SBP-ARV: 11.99 ± 3.67 vs. 11.45 ± 3.35 mmHg, p = 0.392 and SBP-CV: 12.36 ± 3.65 vs. 11.92 ± 3.18%, p = 0.302, with low vs. standard dialysate sodium, respectively). Diastolic BPV indices were numerically, but not statistically, lower with low dialysate sodium. Overall, significant differences were observed in some further comparisons relevant to a trend for lower BPV during daytime 2 and higher BVP during nighttime 2 during treatment with low dialysate sodium.

Conclusion

Low dialysate sodium concentration does not affect BPV levels in patients with IDH. Future research should further explore alternative interventions to reduce BP and BPV in this high-risk population.
#1556 An unusually high prevalence of TMEM67 c.1843T>C (p.Cys615Arg) variant in Russia
Authors: Yanus Grigoriy , Suspitsin Evgeny , Tumakova Anastasia , Zvereva Alyona , Durasova Tatiana , Voiskovaya Kseniya , Shavkin Aleksey , Imyanitov Evgeny
Published: May 2024

Background and Aims

A hypomorphic TMEM67 variant c.1843T>C (p.Cys615Arg) (rs201893408) is associated with an autosomal-recessive condition characterized by a combination of nephronophthisis and liver fibrosis, and, in some cases, neurologic manifestations. According to the gnomAD database, it reaches the highest prevalence in Swedish population (MAF=17/26128, 0.00065). In two large European studies of nephronophthisis and related conditions, the contribution of this pathogenic allele to TMEM67-associated disorders reached 15%-27%. The report presents the first evidence for the major contribution of this recurrent variant to nephronophthisis in Russia.

Method

Blood DNA samples of 29 pediatric patients, undergoing chronic renal replacement therapy in a dialysis department of a large pediatric medical center, were evaluated by targeted (“clinical exome”) sequencing. KAPA HyperCap Heredity Panel (Roche) was used for target enrichment. Sequencing was performed on Illumina Nextseq2000 device. The alignment on GRCh37 reference genome sequence was made using BWA 0.7.12; HaplotypeCaller (GATK 3.3.0) was used for variant calling. Causative variants were verified by Sanger sequencing.

Results

Among other findings, we have identified two unrelated Russian patients, homozygous for TMEM67 p.Cys615Arg mutation; none of them have previously been diagnosed with nephronophthisis. Patient D, a 11-year-old girl, presented with unexplained chronic kidney disease with unremarkable ultrasound findings. Patient B was an 8-year-old girl with chronic kidney disease linked to bilateral ureterohydronephrosis. In both patients, cholestatic hepatitis of unknown etiology was diagnosed. No neurological involvement was reported. The parents of both girls denied consanguinity. One more Russian patient homozygous for p.Cys615Arg variant had been previously described [Andreeva and Savenkova, 2022; in Russian]: the 2-year-old child born from non-consanguineous parents had prenatally identified multiple renal cysts, nephrogenic arterial hypertension, and laboratory signs of cholestasis. The analysis of Ruseq database (ruseq.ru) confirmed high prevalence of TMEM67 c.1843T>C (p.Cys615Arg) variant in Russian population (MAF=14/10860, 0.0013).

Conclusion

TMEM67 c.1843T>C (p.Cys615Arg) allele is particularly common in Russian pediatric patients with chronic kidney disease and liver involvement, and, therefore, deserves to be analyzed in other countries with predominantly Slavic population.
#1368 Podocytopathy associated with IgA nephropathy: is it really a prognostic factor?
Authors: Vázquez Belèn Gallegos , Hurtado Angela María Cordoba , Ortiz Rafael Valdez , Navarro Lucia Monserrat Perez , Abraham Virgilia Soto
Published: May 2024

Background and Aims

Since 2017, the clinical value of podocyte injury in IgA nephropathy (IgAN) has been studied, the presence of podocyte hypertrophy and tip- lesions are markers of podocyte damage. It has been observed that these histological findings tend to be treated with immunosuppression, so they have a better kidney prognosis, but those who do not receive immunosuppression have a worse prognosis. In Latin America there are no cohorts that evaluate the clinical course of these lesions.

Method

Cases and control.

Results

A total of 37 patients with a diagnosis of IgAN were evaluated, of these 27% presented podocytopathy (IgAN-P) and 72.9% presented IgAN without histological data in the optical microscopy of podocytopathy (IgAN-NP), with an average follow-up of 41 ± 32 months. Clinically, the proteinuria in IgAN-P patients was higher with a mean of 3.9 ± 3.0 gr/gr vs 1.6 ± 1.5 gr/gr in the group with IgAN-NP, without being statistically significant p = 0.54. Kidney function in the group with podocytopathy was slightly lower with an average eGFR of 65.9 ± 45 ml/min/1.73 m2 vs 80.2 ± 36.4 ml/min/1.73 m2 p = 0.23, associated with a greater presence of granular casts in podocytopathy (92% vs 80% p = 0.02) describing probable associated acute tubular injury. Histologically, patients with podocytopathy presented 80% of podocyte hypertrophy and 2% of tip-type FSGS. The findings in the MEST-C score had no differences between the groups, except for mesangial proliferation that was present in 96.3% of subjects with podocytopathy compared to 70% of subjects without podocytopathy, p = 0.02. The prognosis based on the international score was not statistically significant between the groups p = 0.59. Patients with podocytopathy tended to be treated with immunosuppression prior to the biopsy in 50% vs 37% in the group without podocytopathy p = 0.01, however once the histological diagnosis was obtained it was more common to decide to continue with immunosuppressants in subjects with podocytopathy with 90% vs 63% (p = 0.11). Finally, long-term results reported no differences in the requirement for kidney replacement therapy. When evaluating MAKE outcomes, there were no differences between groups with respect to ESKD; 40% decrease in eGFR and need for kidney replacement therapy.

Conclusion

In previous reports the presence of podocytopathy reported as podocyte hypertrophy and tip-lesions were 16%. In our population this finding was more frequent (27%), with podocyte hypertrophy being more prevalent. Greater proteinuria and worse kidney function were observed compared to IgAN-NP, justifying a greater frequency of immunosuppressive therapy, impacting the kidney outcome being the same as that reported in patients without podocytopathy. Similar result to that observed in previous cohorts.
#271 The nexus between TMA/TTP, MIS-C, and SLE
Authors: Sallam Dina E
Published: May 2024

Background and Aims

The long-term complications of COVID-19 infection & Multisystem inflammatory syndrome in children (MIS-C) on immune system are still unknown, however there're reports on development of autoimmune disease, highlighting their immune-related nature.

MIS-C can induce Thrombotic Microangiopathy (TMA), by inducing endothelial dysfunction, platelet activation, & microthrombi formation, whereas SLE induces TMA/Thrombotic thrombocytopenic purpura (TTP), with ADAMTS13 activity < 10%, or 2ry TMA with ADAMTS13 activity ≥ 10%, where SLE/TTP carries a bad prognosis.

Method

Our case is one of its kind, where a 12-year- old girl, who was previously infected with SARS-CoV-2, presented with new-onset SLE, associated MIS-C & 2ry TMA/TTP. She presented with convulsions, oliguria, heart failure, impaired kidney function, microangiopathic hemolytic anemia, pancytopenia, highly elevated LDH, & was diagnosed as TMA.

Results

COVID serology was +ve for IgG, & -ve for IgM, & -ve SARS-CoV-2 PCR, a diagnosis of MIS-C was postulated. Further investigations revealed low C3, C4, +ve ANA, anti-ds DNA & anti-phospholipid Antibodies. Brain imaging showed left cerebellar calcification. Echocardiography showed biventricular dysfunction with EF 30%, where the diagnosis of SLE according to Euler/ACR criteria was confirmed, with 2ry TMA.

Emergency hemodialysis, PRBCs transfusion, pulse steroid with total plasma exchange (TPE), were initiated without marked improvement. Rituximab was started on 4th day, but she had generalized convulsion, arrythmia & sudden death occurred.

Results of ADAMTS13 activity was < 1%, with +ve autoantibodies, so diagnosis of TMA/TTP was confirmed.

Conclusion

TMA are a diverse group of disorders that causes microvasculature thrombosis, which is inherited, or acquired 2ry to SLE or COVID-19 infection, where high index of suspicions should be raised for early diagnosis and prompt management, meanwhile COVID-19 infection can induce the development of autoimmune diseases. Herein we raise the question of cause of TMA/TTP, was it 2ry only SLE, or to the previous COVID-19 infection & MIS-C, and if this SLE itself was 2ry also to the previous COVID infection, or all it was by chance?
#2511 Usefulness of cystatin C in measuring renal function in patients with liver cirrhosis
Authors: Lim Seong Kyeol , Kim So M I , Lee Eun Kyoung , Jeon Ji Hyun , Cho Jong Tae
Published: May 2024

Background and Aims

Liver cirrhosis (LC) is often accompanied by acute kidney injury, and renal function is known to be a significant factor in mortality of patients with LC. However, LC is a representative protein-energy-wasting disease, and there are limitations in measuring renal function using muscle based creatinine (Cr). Therefore, this study tried to investigate the discrepancy in the estimated glomerular filtration rate (eGFR) using conventional serum Cr and cystatin C in patients with LC

Method

In total, 121 patients were enrolled, and eGFR was calculated using the Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) equation based on both serum Cr and cystatin C levels. Each eGFR was classified into three categories with GFR < 10 mL/min/1.73 m2 (group A), 10-50 mL/min/1.73 m2 (group B), and > 50 mL/min/1.73 m2 (group C) mL/min/1.73 m2, distribution was evaluated according to Child-Pugh classification.

Results

Of the 121 patients, 69 were Child-Pugh A, 32 were Child-Pugh B, and 20 were Child-Pugh C. The mean eGFR using serum Cr was 85.35 mL/min/1.73 m2, which was higher than the eGFR using cystatin C of 69.52 mL/min/1.73 m2 (p < 0.05) After converting eGFRcr to eGFRcystatinC, the number of patient with group change was 11 (15.9%) in the Child-pugh A, 8 (18%) in Child-Pugh B and 5(25%) in Child-Pugh C (Child-Pugh A: 9 in A↔B, 2 in B→C, Child-Pugh B: 5 in A↔B, 3 in B→C, Child-Pagh C: 4 in A→B, 1 in B→C). Except for 2 patients, eGFR decreased when converting eGFRcr to eGFRcystatinC (p < 0.05).

Conclusion

In patients with LC, the eGFRcystatinC is significantly lower than that of eGFRcr. And this was significant in cirrhotic patient with a high Child-Pugh class.
#2936 Chronic kidney disease in systemic sclerosis
Authors: Safont Amparo Roda , Aznar Carmen Pilar Simeon , Del Castillo Alfredo Guillen , Pérez Jose Manuel Porcel , Pla Vicent Fonollosa , Medrano Alfons Segarra
Published: May 2024

Background and Aims

Systemic sclerosis is a heterogeneous autoimmune disease with multiorgan involvement. To assess the clinical and epidemiological manifestations of patients with SSc who present CKD, and its implication in the prognosis and its importance in early detection.

Method

Selected 102 Caucasian patients (12 men and 90 women) diagnosed with SSc who were seen consecutively in the Scleroderma Unit at Vall d'Hebron Hospital since 1980. The following demographic variables were collected: sex, age, common cardiovascular risk factors (diabetes mellitus, hypertension, dyslipidemia), age at clinical onset, age at diagnosis, skin subtype of SSc according to the LeRoy and Medsger classification, visceral conditions, osteoarticular conditions, capillaroscopic pattern, biochemical parameters of renal function and immunological alterations, renal morphological alterations by ultrasound, and treatments.

Results

Overall, 102 SSc patients were included, of whom 24 (23.5%) had renal failure. The mean plasma creatinine value was 0.92 mg/dl and the mean GFR by CKD-EPI was 74.80 ml/min. The 76.5% had GFRe ≥60 ml/min (SScCKD-), with mean serum creatinine 0.85 ± 0.17 mg/dl and mean GFRe 82.13 ml/min (SD 20.53 ml/min); 23.5% had GFRe <60 ml/min (SScCKD+), in them mean serum creatinine was 1.09 ± 0.15 mg/dl and mean GFRe was 51.29 ml/min (SD 6.68 ml/min). By stage: 18 patients had G1 stage, 60 patients had G2 stage, 18 patients had GFR 3a and 6 patients GFR G3b. No proteinuria or hematuria was detected in any of the patients.

In univariate analysis, limited cutaneous subtype was significantly more frequent in the SScCKD+ group (20, 83.3% vs. 44, 56.4%, p = 0.017) and the diffuse cutaneous subtype was more frequent in the SScCKD- group (0, 0% vs. 23, 29.4%, p < 0.001). In the study of associated antibodies, ACAs (20, 83.3% vs. 36, 46.1%, p = 0.001) were statistically significantly more frequent in the SScCKD+ group. No ATA were detected in SScCKD+ patients while in the SScCKD- group 25.6% had ATA (p = 0.003). Pulmonary involvement in the form of PAH was significantly more frequent in the SScCKD+ group (13, 54.1% vs. 19, 24.3%, p< 0.05). In pulmonary involvement in the form of ILD no differences were found (9, 37.5% vs. 37, 47.4% in SScCKD+ and SScCKD- patients, respectively). Regarding PFR results, there were no differences in the percentage of patients with FVC below 70% or 50% of the expected value (6, 25% vs. 15, 19.2% and 1, 4.1% vs. 4, 5.1%, respectively). Significant differences were found in mortality in the two groups (12, 50% vs. 16, 20.5%, in the SScCKD+ and SScCKD- group, respectively, p < 0.05), but not in the causes of death.

Conclusion

The presence of CKD in SSc conferred a clinical profile and prognosis.
#2945 Albuminuria – a neglected cause of referral to Nephrology
Authors: Silva Bárbara , Oliveira Ana Isabel , Farinha Ana , Azevedo Ana
Published: May 2024

Background and Aims

Albuminuria has been a recognized marker of cardiovascular risk for several years. Since 2012, the KDIGO guidelines have included this marker in the definition of chronic kidney disease (CKD), regardless of the Glomerular Filtration Rate (GFR). Despite this, a decade after, albuminuria is rarely researched as a marker of kidney disease, especially in Primary Health Care.

We aim to assess the percentage of patients referred from the Health Centre to the Nephrology consultation of a district hospital, with an indication of the albuminuria value and also which percentage considered it the main cause of referral.

Method

Retrospective observational study of all patients referred from the Health Centre to the Nephrology consultation, from January 2022 to May 2023. A statistical analysis was carried out using Microsoft Excel 2016 (Microsoft ™).

Results

A total of 248 patients were referred and accepted for the nephrology consultation, 52.4% female, average age 74.8 years, with almost 80% (n = 198) of patients aged 65 or over and 41.5% (n = 103) aged over 80.

The reasons for referral were: 53.6% due to an increase in creatinine levels; 21% due to imaging alterations; 19% due to a reduction in GFR and only 6.4% (16 patients) due to a urinary alteration, which included the presence of albuminuria.

Only 26.2% (n = 65) of the patients referred had mentioned the value of albuminuria, and of these, around 73% (n = 49) already had an albuminuria value greater than or equal to 30 mg/dL; however, in only 14 of these patients (5.6% of all the patients referred) was albuminuria the main reason for the referral.

Of the 49 patients with albuminuria: 44 patients (89.8%) had cardiovascular disease (around 98% with hypertension and around 28% with HF) and 34 patients (69.4%) had diabetes; 32 patients (65.3%) were medicated with ACE inhibitors/ARBs and only 13 patients (26.5%) were medicated with iSGLT2.

The percentages of use of ACEIs/ARAs and iSGLT2 remain the same when analyzing the 14 patients who were referred for albuminuria.

Conclusion

Albuminuria remains an overlooked marker of CKD despite being an early marker and for which there are several interventions that seem to prevent the worsening and progression of CKD. It is imperative to train doctors, especially family doctors, in the early diagnosis of CKD, particularly in the presence of albuminuria and to implement measures to control it.
#1853 Comparative analysis of atherosclerotic risk factors in dialysis patients
Authors: Rroji (Molla) Merita , Spahia (Zeneli) Nereida , Cafi Erind , Kasa Marsida , Seferi Saimir
Published: May 2024

Background and Aims

Prevailing studies indicate a correlation between elevated serum phosphate levels and an augmented incidence of cardiovascular events. In patients undergoing dialysis, hyperphosphatemia contributes to vascular and valvular calcifications. This study analyzes the interrelation of phosphate levels, inflammatory markers, and additional risk determinants in the development of carotid artery atherosclerosis in individuals receiving peritoneal dialysis (PD) versus hemodialysis (HD).

Method

A cohort of 39 PD and 53 HD patients were recruited, all undergoing stable renal replacement therapy (RRT) for three to thirty-six months. B-mode ultrasonography assessed the carotid artery intima-media thickness (CIMT) and detected plaque and calcification occurrences. Patients were specified as having atherosclerosis when CIMT was greater than 1 cm, and the presence of plaque was identified. Logistic regression analysis was employed to discern the connection between potential risk factors and the incidence of atherosclerosis.

Results

The study encompassed 92 participants, 61% undergoing HD and an average age of 53.4 years (standard deviation ± 14.5 years). The tubulo-interstitial disease was the predominant initial pathology, followed by chronic glomerulonephritis and nephroangiosclerosis. Diabetic nephropathy was identified as the etiology of end-stage renal disease (ESRD) in 23.1% of PD and 11.4% of HD subjects (p = 0.047). Notably, PD patients showed better residual renal function (RRF) (p < 0.001), urine volume over 24 hours (p < 0.001), and C-reactive protein (CRP) (p = 0.047), alongside diminished phosphate (p = 0.01), parathyroid hormone (PTH) (p < 0.05), alkaline phosphatase (p < 0.05), and albumin levels (p < 0.001) relative to their HD counterparts. Atherosclerosis prevalence was 66.3%, inclusive of the entire diabetic cohort. The incidence of atherosclerosis did not significantly diverge between PD and HD groups [56.4% vs 73.6% in HD, respectively]. Atherosclerotic patients were older (p < 0.001) and exhibited heightened phosphate levels (p = 0.012), pulse pressure (p = 0.01), and calcium index (Ci) (p = 0.034). Multiple regression analysis elucidated age, phosphate, RRF, PTH, pulse pressure, diabetes, and HD modality as autonomous factors linked to atherosclerosis.

Conclusion

Beyond conventional risk factors like age and diabetes, metabolic disorders arising from renal insufficiency were identified as contributing to atherosclerotic development. Multivariate analysis identified phosphate, RRF, and pulse pressure (PP) as independent atherosclerotic risk factors. The HD modality carried an elevated atherosclerotic risk compared to PD. It was thought that preserving RRF in PD patients would improve phosphate regulation and maybe even improve endothelial function, explaining the differences found.
#850 The association between proteinuria and stroke: results from the non-communicable diseases screening programme of Chiang Mai Region, Northern Thailand
Authors: Hall Charlie
Published: May 2024

Background and Aims

Stroke is a significant global health issue, representing the second leading cause of death and a major contributor to disability. It can be classified into two main types: ischemic stroke, caused by blockage of a brain blood vessel, and haemorrhagic stroke, resulting from blood vessel rupture. Chronic kidney disease (CKD) is another prevalent health concern, affecting approximately 10% of all populations worldwide. CKD impairs kidney function and has been associated with an increased risk of cerebrovascular events, including stroke. Within the Northern Thai population, the prevalence of CKD is higher than the global average, underscoring the importance of investigating the relationship between CKD and stroke in this region.

Method

All patients for which accurate proteinuria measurement was obtained as part of the NCD screening program in Chiang Mai, Northern Thailand were included in the study.

Multilinear cox regression analysis was used to estimate the hazards ratio for the association between proteinuria on stroke. The model was adjusted for other significant confounders of the association including age, sex, CKD, diabetes, hypertension and hypercholesterolaemia

Results

In a cohort of 3967 patients for which accurate proteinuria measurements were obtained and for whom had complete data for covariates, there was no evidence for an association between proteinuria and stroke. Hazards ratio for stroke in patients with trace proteinuria (adjusted for covariates) was 1.08 (95% CI 0.80-1.45) and positive proteinuria 0.06 (0.78-1.44) compared to a baseline of no proteinuria.

Conclusion

This study provides important insights into stroke risk factors in the Northern Thai population. The lack of substantial association between proteinuria and stroke suggests that proteinuria may not independently contribute to stroke risk in this cohort. Generalizability, however, is limited due to overrepresentation of diabetes and hypercholesterolaemia in the cohort, which is a strong independent risk factor for stroke. Increasing age is identified as the most critical risk factor for stroke. Understanding these associations can guide targeted interventions and public health strategies for stroke prevention in this population. The study limitations highlight the importance of analysis of a cohort that is more representative of a wider population in terms of chronic disease, such as diabetes and hypercholesterolaemia, and highlights the importance of longer follow up to fully elucidate whether proteinuria has an association with stroke. Furthermore the study raises questions as to whether measurement of proteinuria via urine dipstick analysis may limit conclusions that can be drawn compared to more robust methods such as urine albumin:creatinine or urine protein:creatinine ratios. Finally this study may be underpowered to detect subtle changes of a hazards ratio of less than 1.2, so is at risk of a type 2 statistical error.
#443 LEVIL evaluates the impact of HDx on HR-QoL and symptoms, including durability-of-effect and variability
Authors: Penny Jarrin , Mcintyre Christopher
Published: May 2024

Background and Aims

Current hemodialysis (HD), utilizing conventional high-flux dialyzers, is handicapped by clearance limitations (larger-sized uremic toxins), which contribute to poor health-related quality-of-life (HR-QoL) and symptom-burden. Recent international consensus and guideline-setting efforts have explicitly prioritized identification and management of symptoms and subjective experience, whilst also acknowledging the lack of tools available to fully appreciate and continuously monitor these challenges. This study aimed to utilize dynamic patient-reported-outcome-measurement tool (PROM), London Evaluation of Illness (LEVIL-developed in-house), to iteratively interrogate patient-experience and to confirm previously reported HR-QoL benefits of the use of expanded hemodialysis (HDx) using medium cut-off dialyzer (extending the spectrum of uremic toxins being addressed). Furthermore, this study aimed to extend appreciation of effects on patient subjective experience to include durability-of-effects, variability of symptom-measures and impact of HDx withdrawal.

Methods

We conducted a multi-centre interventional study in 47 patients established on conventional thrice weekly centre-based HD in Ontario, Canada. Study protocol was 15-months in length with five phases 1) one-month observation (high-flux-HD), 2) three-months HDx 3) two-month wash-out (high-flux-HD), 4) six-months HDx, 5) three-month wash-out (high-flux-HD). HR-QoL and symptom-burden were evaluated using LEVIL throughout study.

Results

HDx-therapy improved HR-QoL [p 0.0006 (19% from baseline)] and a variety of symptoms including general wellbeing [p 0.005 (23%)], energy [p 0.004 (33%)], sleep-quality [p 0.001 (33%)], pruritus [0.003 (30%)], pain [p 0.01 (19%)], restless leg syndrome [p 0.0006 (15%)], mood [p 0.02 (12%)], appetite [ p 0.03 (9%)], breathlessness [p 0.001 (9%)], and HD-recovery [p 0.004 (26%)]. Response was more pronounced in those with poorer HR-QoL and higher symptom-burden. Improvements were durable over time with continued use with less symptom-variability (range 10-35% improvement). Improvements diminished gradually with return to high-flux-HD. The drivers of poor HR-QoL were largely general-wellbeing, energy, sleep-quality, pruritus, and bodily pain.

Conclusion

Use of a dynamic PROM effectively allowed appreciation of HR-QoL burden in HD-patients. Use of HDx-therapy results in improved patient subjective outcomes that are durable and associated with significantly lower variation in important symptom-domains than patients experience with receiving conventional high-flux-HD.
#2589 Predictive value of serum lactate in ICU dialysis-dependent AKI patients
Authors: Jerman Alexander , Šturm Hana , Suligoj Brina , Persic Vanja
Published: May 2024

Background and Aims

Hyperlactatemia is frequently observed in critically ill patients. It is often associated with unfavorable outcomes and serves as a strong predictor of mortality. Renal replacement therapy aims to mitigate lactate accumulation in this particular subgroup of patients, but the effectiveness of this therapy in reducing morbidity and mortality in acute kidney injury (AKI) associated lactic acidosis remains inconclusive. The aim of this retrospective study was to evaluate the predictive role of serum lactate in dialysis-dependent AKI patients stratified on three different underlying etiologies (septic shock, concomitant liver failure and metformin-associated lactic acidosis).

Method

A retrospective, single-center cohort analysis was conducted to examine patients with AKI who underwent hemodialysis in our ICU between 2022 and 2023 and had a serum lactate > 4 mmol/L. Patients were stratified according to underlying etiology: isolated septic shock with AKI, shock with concomitant AKI and fulminant liver failure (serum ammonia > 100 µmol/L), and AKI with metformin-associated lactic acidosis (MALA). We compared patients according to age and 3-day, 30-day, and 90-day mortality. Finally, we performed receiver-operating-curve (ROC) analysis to potential predictive power of serum lactate for 30-day mortality.

Results

The median age of our cohort of 63 patients was 67 (range 52 - 74) years, with a median lactate level of 12.9 (7.6 – 18.0) mmol/L. The 3-day, 30-day and 90-day mortality rate was 57%, 78%, and 83%, respectively. We observed that patients with concomitant liver failure were significantly younger (p = 0.004). Interestingly, while all groups have comparable 90-day mortality, patients with septic shock exhibit extremely high 3-day mortality (74%), compared to 35% and 25% for acute liver failure and metformin-associated shock. ROC curve analysis showed that serum lactate was highly predictive of 30-day mortality in group of AKI with concomitant fulminant liver dysfunction. On the contrary, in metformin-associated hyperlactatemia the level of serum lactate showed no such prediction.

Conclusion

Our retrospective analysis underscores the crucial importance of differentiating between various groups of patients (septic shock, concomitant liver failure and metformin-associated lactic acidosis) in patients with hyperlactatemia. In metformin-induced kidney failure, the level of lactate does not predict mortality, while in the cases of AKI with concurrent acute liver dysfunction our results are highly suggestive that dialysis may not be effective for severe lactacidosis. The findings contribute valuable insights for designing future prospective studies in this complex patient population.
#2799 Myoglobin removal by hemadsorption: ex-vivo adsorption kinetics
Authors: Marcello Matteo , Lorenzin Anna , de Cal Massimo , Ramirez-Guerrero Gonzalo , Zanella Monica , Ronco Claudio
Published: May 2024

Background and Aims

Myoglobin, due to its molecular weight of 17 kDa and a Einstein-Stoke radius greater than expected, is classed as a middle molecular weight uremic toxin and presents a two-compartment model of distribution in the body. Rhabdomyolysis is a condition in which muscle cell content including myoglobin, are released into blood circulation due to severe injury to the muscle. Circulating myoglobin induces renal injury with several mechanisms: reduced concentration of nitric oxide in medullary renal arterioles, production of free radicals with oxidative stress, tubular necrosis as a consequence of tubular obstruction by myoglobin and cellular debris. A possible therapeutic option is the use of High Cut-off membranes but with the risk of significant loss of albumin and other proteins. The use of adsorption can overcome these limitations. The aim of our study is to assess the adsorption of myoglobin with neutral microporous styrene-divinylbenzene copolymer sorbent (e.g., HA330/380, Jafron Biomedical CO, Lts, Zhuhai City, China).

Method

Using a downscaled module of HA380 Cartridge, we set up an ex-vivo circulation experiment in which 1 liter of plasma containing 0.1 mg of myoglobin was pumped through the cartridge. We collected samples (3 mL) at different timepoints to measure Myoglobin concentration. We calculated the removal ratio (RR) and mass adsorbed at a given timepoints.

Results

Initial myoglobin concentration was 99.3 ng/ml. Final myoglobin concentration after 4 hours of experiment was 30.6 ng/ml. Removal Ratio at 4 hour was 69 % and mass adsorption of 0.068 mg of myoglobin.

Conclusion

To our knowledge, this is the first experiment that assessed the adsorption capacity of polystyrene-divinylbenzene sorbent. Our study, demonstrated high adsorption capacity in the first 4 hours of treatment therefore, confirming the possibility to use adsorption as an effective treatment option in rhabdomyolysis and avoiding complications associated to current dialytic treatment.
#1328 Haemodynamic effects of low versus high dialysate bicarbonate concentration in haemodialysis patients
Authors: Jensen Jonas Schandorph Kaalund , Peters Christian Daugaard , Jørgensen Ina Ejsing Hunnerup , Jensen Jens Dam , Buus Niels Henrik
Published: May 2024

Background and Aims

Haemodialysis (HD) treatment using standard dialysate bicarbonate concentrations cause transient metabolic alkalosis possibly associated with haemodynamic instability. We performed a detailed comparison of blood pressure (BP), haemodynamic parameters, electrolytes and orthostatic BP response with low (LDB) versus high dialysate bicarbonate concentration (HDB).

Method

Fifteen HD patients were examined in a single-blind, randomised, controlled, crossover study. Participants underwent a 4-hour HD session with dialysate bicarbonate concentration of 30 mmol/l (LDB) or 38 mmol/l (HDB) with one week between interventions. During HD, cardiac output (CO), total peripheral resistance (TPR), stroke volume (SV) and central blood volume were measured with ultrasound dilution technique (Transonic). Throughout dialysis, blood samples were obtained from the arterial cannula. Orthostatic BP was measured pre and post HD.

Results

With similar ultrafiltration volume (2.6 litres), systolic BP tended to decrease more during HDB compared to LDB (Fig. 1 and Table 1); the mean (95% confidence interval) between treatment differences in systolic BP were: 8 (-4;20) mmHg (end of HD) and 7 (0;15) mmHg (post HD). SV decreased (Fig. 2) whereas TPR increased significantly more during HDB compared to LDB with mean between treatment differences: SV: 12 (1;23) ml; TPR: -2.9 (-5.3;-0.5) mmHg/(L/min). CO tended to decrease more with HDB compared to LDB with mean between treatment difference 0.7 (0.0;1.4) L/min. HDB caused alkalosis, hypocalcaemia and lower plasma potassium, whereas patients remained normocalcaemic with normal pH during LDB (Table 1). Orthostatic BP response after dialysis did not differ significantly.

Conclusion

HDB compared to LDB was associated with hypocalcaemia and alkalosis and a more pronounced hypokalaemia which may impair preservation of BP, SV and CO during HD.