bluuebunny/crossref_metadata_2025_split huggingface dataset:
#1556 An unusually high prevalence of TMEM67 c.1843T&gt;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

Abstract

Background and Aims
A hypomorphic TMEM67 variant c.1843T&gt;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&gt;C (p.Cys615Arg) variant in Russian population (MAF=14/10860, 0.0013).

Conclusion
TMEM67 c.1843T&gt;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

Abstract

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

Abstract

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 &lt; 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 &lt; 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

Abstract

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 &lt; 10 mL/min/1.73 m2 (group A), 10-50 mL/min/1.73 m2 (group B), and &gt; 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 &lt; 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 &lt; 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

Abstract

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 &lt;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 &lt; 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&lt; 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 &lt; 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

Abstract

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

Abstract

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 &lt; 0.001), urine volume over 24 hours (p &lt; 0.001), and C-reactive protein (CRP) (p = 0.047), alongside diminished phosphate (p = 0.01), parathyroid hormone (PTH) (p &lt; 0.05), alkaline phosphatase (p &lt; 0.05), and albumin levels (p &lt; 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 &lt; 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

Abstract

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.