bluuebunny/crossref_metadata_2025_split huggingface dataset:
#2003 Genetic association in patients with chronic kidney disease of unknown etiology: an observational study
Authors: Tiwari Vaibhav , Shikarwar Tarun , Bhalla A K 
Published: May 2024

Abstract

Background and Aims
Chronic kidney disease (CKD), impacting over 850 million people worldwide, is a diverse group of inherited and acquired nephropathies. While only about 10% of adult CKD is hereditary, predominantly due to mutations in genes like PKD1, PKD2, and PKHD1, the etiology often remains unidentified, leading to challenges in management, especially in transplantation and genetic counseling contexts. This study used whole exome sequencing to investigate CKD of unknown origin, aiming to improve diagnostic yields and establish genetic associations. Our objective was to find the diagnostic yield of Whole exome sequencing in patients with CKD of unknown etiology and to establish genetic association for same.

Method
The study was conducted in the Department of Nephrology and the Institute of Genetics and Genomics at Sir Ganga Ram Hospital, New Delhi. It was an observational cross-sectional analysis.
All patients, both male and female of all age groups with Chronic Kidney Disease of unknown etiology who were willing to participate.
All patients, both male and female of all age groups with Chronic Kidney Disease of known etiology were excluded as following:

Results
In the investigation of 56 chronic kidney disease samples with unknown etiology, genetic testing yielded 45 mutated gene variants in 37 subjects. The variants comprised 32 missense mutations, 8 deletions, 3 nonsense mutations, and 1 splice site mutation. Variant zygosity was as follows: 34 heterozygous, 6 homozygous, and 2 hemizygous. Pathogenic variants were detected in 9 patients (20%), likely pathogenic in 6 (13.33%), and variants of uncertain significance in 29 (64.44%). Eighteen subjects (32.14%) demonstrated no genetic mutations.
A genetic diagnosis was established in 15 patients, representing a diagnostic yield of 26.78%. Stratified by disorder, the yield was 40% for glomerular, 100% for tubular, 50% for renal calculi, and 18.42% for undetermined CKD. Genetic testing facilitated a novel diagnosis or an alteration of the existing diagnosis in 6 patients (10.71%).

Conclusion
The results affirm the efficacy of genetic testing in elucidating the etiologies of chronic kidney disease where traditional diagnostic methods do not yield definitive causation. Genetic alterations were identified in a significant proportion of the patient population, indicating the presence of underlying genetic contributors to the disease. The identification of pathogenic and likely pathogenic variants highlights the potential of genetic testing to impact clinical decision-making and patient care.
#646 SGLT2 inhibitor alleviates hypomagnesemia in patients with chronic kidney disease: a retrospective observational study
Authors: Osawa Kosuke , Ohya Masaki , Yamamoto Shuto , Nakashima Yuri , Tanaka Yusuke , Yamano Yukiko , Takatsuka Taisuke , Araki Shin-Ichi 
Published: May 2024

Abstract

Background and Aims
Magnesium (Mg2+) is a critical component in numerous biological processes. Hypomagnesemia is associated with an increased risk of cardiovascular events and vascular calcification in individuals with and without chronic kidney disease (CKD). Sodium-glucose cotransporter-2 (SGLT2) inhibitors have been proposed for treating CKD, based on their reported benefits to the kidney and cardiovascular system and in increasing serum Mg2+ levels in patients with type 2 diabetes mellitus. However, the underlying mechanisms remain unclear. In this retrospective observational study, we aimed to investigate the changes in serum Mg2+ levels after administering SGLT2 inhibitors and to identify factors contributing to these changes.

Method
We retrospectively examined 57 patients with CKD who received treatment at Wakayama Medical University between January 1, 2017, and December 31, 2022. We assessed changes in serum Mg2+ levels at baseline and 1, 3, and 6 months post-treatment. Patients were stratified into tertiles based on baseline Mg2+ levels. Multivariate regression analyses were conducted to identify factors associated with changes in Mg2+ levels.

Results
SGLT2 inhibitor treatment was associated with a significant increase in serum Mg2+ levels in the low and intermediate tertiles but not in the high tertile. Multivariate analysis revealed that gender, baseline serum Mg2+, and sodium-chloride difference were independent predictors of the increase in serum Mg2+ levels.

Conclusion
SGLT2 inhibitor treatment in CKD patients is associated with an increase in serum Mg2+ levels, particularly in those with lower baseline levels. The serum Mg2+-improving effect of SGLT2 inhibitors is influenced by baseline serum Mg2+ levels, sodium-chloride difference, and gender. These findings suggest the potential utility of SGLT2 inhibitors for treating hypomagnesemia in CKD.
#2725 Chronic kidney disease is a risk factor for hyperchloremic metabolic acidosis after plasma exchange
Authors: Simon Sanédy , van Sandwijk Marit , Engberink Rik Olde 
Published: May 2024

Abstract

Background and Aims
Observational studies have demonstrated that metabolic acidosis due to hyperchloremia is an often encountered metabolic disorder following plasma exchange (PE) with an albumin-saline solution. Because of the reduced capacity for acid and chloride excretion, we hypothesized that patients with chronic kidney disease have the highest risk for hyperchloremic metabolic acidosis, in particular when multiple PE sessions are performed in a limited period.

Method
We prospectively collected data from all patients who received PE at Amsterdam UMC, between February 2023, and January 2024. We collected data on demographics, exchanged plasma volume, replacement fluids, and collected blood for analysis of sodium, chloride and bicarbonate before and after plasma exchange. We selected patients who received ≥5 plasma exchanges in an intensive cycle (≥4.2 sessions/week). We excluded patients who received Omniplasma, intravenous sodium bicarbonate or dialysis during the PE period. We assessed the effect of PE and kidney function on plasma bicarbonate and chloride concentration throughout the PE period with repeated measures mixed ANOVA, corrected for baseline plasma bicarbonate concentration, volume of exchanged plasma and PE intensity.

Results
Data from 26 patients, corresponding to 130 plasma exchanges, were included in the analysis. The mean age was 56 ± 14 years and 46% was female. Mean eGFR was 45 ± 14 ml/min/1.73 m2. Patients with an eGFR ≤59 ml/min/1.73 m2 (n = 17) had a significantly lower baseline plasma bicarbonate concentration (19.0 ± 2.8 versus 24.0 ± 1.9 mmol/L; p &lt; 0.001) and used oral bicarbonate supplements (29% versus 0%; p = 0.02) more often than patients with an eGFR ≥60 ml/min/1.73 m2 (n = 9). Despite the lower baseline plasma bicarbonate and more frequent use of oral bicarbonate supplements, the plasma bicarbonate levels decreased the most in subjects with an eGFR ≤59 ml/min/1.73 m2 (mean difference −4.2; 95% CI −7.1 to −1.3; p = 0.006; Fig. 1A) during a cycle of 5 PE sessions. Baseline plasma chloride concentration was similar in both groups (103 ± 7 vs 103 ± 4 mmol/L) and increased the most in patients with an eGFR ≤59 ml/min/1.73 m2 (mean difference −1.4; 95% CI −2.2 to 5.0; p = 0.426; Fig. 1B).

Conclusion
Repeated plasma exchange with albumin-saline as a replacement fluid is associated with a significant decrease in plasma bicarbonate concentration in patients with impaired kidney function. Future studies should determine whether this hyperchloremic metabolic acidosis has impact on the patients’ symptoms or long-term outcome.
#212 The clinical significance of circulating piRNAs in extracellular vesicles in patients with idiopathic membranous nephropathy
Authors: Sun In O , Cho A Young , Kwon Soon Hyo 
Published: May 2024

Abstract

Background and Aims
Of various small RNAs, many miRNAs have been studied as potential biomarkers for various renal diseases. However, there are few literatures about P-element-induced wimpy testis-interacting RNAs (piRNAs), which are the most recently discovered class of small RNAs. Therefore, we investigated the clinical significance of piRNAs in idiopathic membranous (IMN) patients.

Method
We prospectively enrolled 60 participants, including those with IMN (n = 19) and idiopathic nephrotic syndrome (INS; n = 21) and healthy volunteers (HVs; n = 20) in this study. Using RNA sequencing, we assessed the serum extracellular vesicle (EV)-piRNA profiles of all participants. We investigated whether the piRNAs could be helpful to discriminate IMN from INS and predict the treatment response of patients with IMN. Based on achievement of clinical remission, IMN patients were divided in to two groups: a well-responding (IMN-W) and refractory (IMN-R) group [IMN-W (n = 9) vs IMN-R (n = 10)].

Results
We found 11 piRNAs that were upregulated and 6 that were downregulated in patients with IMN when compared to HVs. There were 22 miRNAs that were upregulated and 23 that were downregulated in patients with IMN when compared to the INS. Among these miRNAs, we found 5 piRNAs, whose levels were significantly up- or downregulated in patients with IMN compared to HVs and patients with INS. There were 50 upregulated and 11 downregulated piRNAs in patients with IMN-R when compared to patients with IMN-W. Of these piRNAs, the expression level of piRNA-42775 and piRNA-36743 were found to be inversely correlated with proteinuria on kidney biopsy. Meanwhile, a positive correlation was observed between renal function and expression of piRNA-43108.

Conclusion
Patients with IMN have a distinct EV-piRNA expression profile compared with INS and HVs. In addition, circulating EV-piRNAs could be useful to predict the treatment response of IMN patients.
#1307 Glomerular galactose-deficient IgA1 (KM55) positive may be associated with poor prognosis in DKD patients
Authors: Xu Xiaoyi , Guo Weiyi , Cheng Hong , Sun Lijun , Wang Guoqin , Cheng Wenrong , Dong Hongrui 
Published: May 2024

Abstract

Background and Aims
Diabetic kidney disease (DKD) and IgA nephropathy (IgAN) are prevalent renal diseases with a high incidence rate, and the prognosis is notably poorer when these two diseases coexist. However, it remains uncertain whether the pathological changes associated with DKD combined with IgA deposition (DKD-IgA deposition) are linked to a worsened prognosis.

Method
To address this question, we conducted an analysis comparing the clinicopathological characteristics and prognosis of DKD-IgA deposition patients to DKD patients as controls (Fig. 1).

Results
The results revealed that DKD-IgA patients exhibited higher cholesterol levels compared to DKD patients (6.2 ± 2.0 vs. 5.4 ± 1.9 mmol/L, p = 0.042). The group with DKD-IgA deposition had a significantly shorter follow-up duration (10.9 ± 10.6 months) compared to the control group (20.4 ± 18.7 months, p = 0.029). However, they exhibited higher levels of serum creatinine at the end of the follow-up period (343.8 ± 328.0 μ mol/L vs. 182.1 ± 124.6 μmol/L, p = 0.031). Kaplan-Meier analysis showed a higher cumulative incidence of poor events in the DKD-IgA deposition group (p = 0.036) (Fig. 2). In addition, we also detected galactose deficient IgA1 (KM55) in the kidneys and serum of patients with DKD-IgA deposition. Of the 24 patients with DKD-IgA deposition, 54.5% (24/44) showed positive glomerular KM55 results. Immunofluorescence analysis revealed that KM55 and IgA were predominantly colocalized in the mesangial and capillary regions (Fig. 3). Furthermore, the subgroup with KM55 positivity had a shorter disease duration compared to the KM55 negative subgroup (66.0 vs. 120.0 months, p = 0.048). The serum levels of galactose-deficient IgA1 (Gd-IgA1) (6296.4 ± 1535.4 vs. 4057.4 ± 1082.0 ng/mL, p = 0.010) and C4 (0.4 ± 0.1 vs. 0.3 ± 0.1 g/L, p = 0.020) were significantly higher in the KM55 positive subgroup than in the KM55 negative subgroup. Furthermore, it was observed that the KM55 positive subgroup exhibited a considerably higher incidence of reaching the renal endpoint compared to the control group (64.3% vs. 20.0%, p = 0.047).

Conclusion
These study results suggest that individuals with DKD who display glomerular IgA deposition alongside KM55 positivity may experience a more unfavorable prognosis.
#2389 Enhancing immunoglobulin A nephropathy management: insights from the IGAN-MIC project
Authors: Jiang Gengru , Chen Qinkai , Zhang Qinghong , MA Tean , Chen Chaosheng , Bi Guangyu , Xing Changying 
Published: May 2024

Abstract

Background and Aims
Immunoglobulin A nephropathy (IgAN) comprises a substantial proportion of primary glomerulonephritis cases in China, yet comprehensive nationwide data regarding its diagnosis and treatment are lacking. The Immunoglobulin A Nephropathy Management Quality Improvement Initiative Project in China (IGAN-MIC) seeks to establish an IgAN cohort collaboration network to comprehend real-world IgAN management practices in China.

Method
The IGAN-MIC project convened 15 Chinese experts from 14 regions to form an expert committee to develop a registry of IgAN patients to evaluate regional differences in IgAN management from 2015 to 2024. The registry will involve comprehensive data collection from electronic medical records, encompassing key aspects including demographic and clinical characteristics, renal biopsies, diagnoses, comorbidities, laboratory findings, and treatment modalities, facilitating a detailed analysis of disease progression and changes in treatment strategies from initial diagnosis through subsequent follow-up periods.

Results
The IGAN-MIC project has garnered applications from 78 healthcare institutions, with 7 of them already incorporated into the initiative and initiated data collection. As of January 1, 2024, the project has enrolled 543 pathologically confirmed IgAN patients diagnosed between 2015 and 2023 from these 7 centers. At the time of diagnosis, the median (IQR) of age was 38.00 (30.00, 48.00) years; 54.51% were females; the median (IQR) of eGFR was 75.41 (51.93, 104.09) mL/min/1.73 m2 and the median (IQR) 24-hour urinary protein was 1263.50 (645.30, 2362.64) mg/day. For these patients, the utilization rates of RAS inhibitors (RASi), SGLT2 inhibitors (SGLT2i) and glucocorticoids at initial treatment were 53.41%, 3.51%, and 42.73% respectively. The utilization rate of SGLT2i from 2022 to 2023 was 9.90%, as the first indication for SGLT2i in CKD was approved in China in September 2022. A detailed outline of patient baseline characteristics is presented in Table 1 below.

Conclusion
These initial findings in the registry showed that the Chinese IgAN patients were young, had mildly reduced renal function, and with massive proteinuria at the time of initial diagnosis. For initial treatment, only half of the patients received RASi, and only one tenth received SGLT2i. More education needs to be focused on promoting guideline-directed medical therapies in the future. Given that nationwide data on Chinese IgAN patients are limited, the IGAN-MIC project is anticipated to broaden its registry to include more healthcare institutions and Chinese IgAN patients in the future, with the aim of providing a more in-depth understanding of the changing clinical presentations and ongoing follow-up scenarios among IgAN patients, contributing crucial insights to the clinical management of IgAN.
#2991 Two cases of chronic lymphocytic leukemia associated immunotactoid glomerulopathy: variable clinical presentation, close hematological collaboration
Authors: Markóth Csilla , Szász Róbert , Bidiga László , Prohászka Zoltán , Balla József , Mátyus János 
Published: May 2024

Abstract

Background and Aims
Immunotactoid glomerulopathy (ITG) is a very rare disease, observable in less than 0.1% of native kidney biopsy samples. It is most often associated with hematological diseases. We confirmed ITG in two cases among our 850 kidney biopsy patients in the past 9 years. In both patients, chronic lymphocytic leukemia (CLL) was the underlying cause.

Method
Case 1, a 56-year-old man was admitted due to severely increased proteinuria (2 g/day) with preserved renal function, while case 2, a 57-year-old-man was referred with rapidly decreasing eGFR (20 ml/min/1.73m2) with nephrotic syndrome (serum albumin level was 24 g/l). In case 1, no previous history of hematological disease was known, in case 2, CLL - that did not require treatment - was diagnosed half a year before admission. He still had no kidney involvement even 3 months after the CLL diagnosis. We performed kidney biopsy.
Light microscopy revealed mesangial proliferative-atypical membranous pattern in case 1, and membranoproliferative pattern in case 2. Immunofluorescence microscopy showed IgG1-lambda deposition, electron microscopy confirmed the organised deposits, microtubular structures with a diameter of 44 nanometers in both cases. Neither monoclonal gammopathy nor systemic immune disease was confirmed. In case 2, low titer ANA positivity, low C3 and high anti-C1q antibody titer was detected, lupus nephritis was ruled out. Previously, lymphocyte count was slightly increased in case 1, CLL was confirmed after kidney biopsy. The immunoglobulin heavy chain variable region gene somatic hypermutation status was borderline in case 1, while in the other case it was unmutated. Fluorescein in situ hybridisation revealed trisomy 12 in both cases. In case 1, chemotherapy was not used due to Rai stage 0, and with appropriate antihypertensive treatment, we could preserve kidney function, and proteinuria was persistently low (below 1 g/day). In case 2, due to Rai stage 1, and progressive renal and lymph node involvement, immunochemotherapy was started (obinutuzumab-venetoclax). Three months later eGFR stabilized at 27 ml/min/1.73 m2, proteinuria decreased below 1 g/day, the C3 level normalized.

Conclusion
ITG can develop in the early stages of CLL, but it can also indicate CLL progression. The light microscopy histological pattern and, in parallel, the clinical appearance can be of varying severity. Immunochemotherapy resulting reduction of CLL tumor burden and cessation of complement damage, both play a role of improving renal status. Our cases also draw attention to the need for close collaboration with hematologists.
#2959 Correlation of urinary MCP-1 with different histopathological classes of lupus nephritis
Authors: Khedr Lamis , EL-Shinnawy Howayda , Mahmoud Osama , El Mohsen Waleed Abd , Ahmed Amr 
Published: May 2024

Abstract

Background and Aims
Lupus nephritis (LN) affects almost two-thirds of Systemic lupus erythematosus (SLE) patients. Renal biopsy is the gold standard for the classification of LN. Minimally invasive techniques, as urinary biomarkers, are promising tools for the diagnosis and monitoring of SLE. This study aimed to determine urinary MCP-1 level association with different LN histopathological classes.

Method
This study included 40 patients with active lupus nephritis proteinuria &gt;0.5 gm and/or active urinary sediment and/or decline in kidney function indicated for renal biopsy by the nephrology team. Morning urine samples were collected to measure MCP-1 level by enzyme-linked immunosorbent assay (ELISA). Full blood cell count, serum creatinine level, blood urea nitrogen (BUN) was collected. Biopsies were classified according to ISN /RPS, and biopsy results were correlated with MCP-1 level. We excluded patients with overlap syndrome, active infection, and malignancy. All the patients were diagnosed according to the American College of Rheumatology (ACR) diagnostic criteria.

Results
Mean age 28.75 ± 6.37 years. Female patients were 33 (82.5%) and 7 (17.5%) male patients. Mean creatinine was 2.71 ± 0.55 mg/dl in the active cases and 0.84 ± 0.10 mg/dl in the control group. The mean albumin was 3.1 ± 0.61 mg/dl in the active cases, and 4.05 ± 0.42 mg/dl in the control group. The mean eGFR was 56.14 ± 20.40 ml/min/1.73 m in the active cases, and 99.63 ± 6.90 40 ml/min/1.73 m in the control group. Our study showed a significant correlation between disease activity and urinary MCP-1 level. The Median MCP-1 level was 618.4 ng/l in patients with active LN and 120.05 ± 87.53 ng/l in patients with inactive LN with a sensitivity of 97.5% and specificity 95%. Level of urinary MCP-1 was highest in class IV with median of 998 followed by class III 567 then class V with median 357 ng/ml

Conclusion
Urinary MCP-1 level provided an auxiliary noninvasive tool to distinguish between different histopathological classes of active LN.
#509 Idiopathic nephrotic syndrome in children in Chad
Authors: Abdelkerim Charfadine Senoussi , Guillaume Mahamat Abderrramane , Djidita Hagre Youssouf 
Published: May 2024

Abstract

Background and Aims
The objective of our study was to describe the characteristics and outcomes of Nephrotic Syndrome (SN) in children from three major hospitals in one of the world's poorest countries, Chad.

Method
This observational, cross-sectional, descriptive, and multicenter study took place over a period of 36 months (1 January 2019–31 December 2021) and was carried out in three hospitals in N'Djamena, Chad. Children aged 1–15 years presenting with NS were included in the study.

Results
Out of 16,776 children hospitalized or followed up with in outpatient clinics, 24 cases of NS were identified, yielding a prevalence of 0.14%. The median age at presentation was 6.16 years (1–10). Nineteen children were male (sex ratio 3.8). Eight cases were classified as impure NS (33.3%). Edema was present in all patients, while oliguria was present in 29.16% (n = 7), and arterial hypertension was present in 20.83% (n = 5) of cases. Mean proteinuria, albuminemia, and total proteins were 2.86 g/L, 19.13 g/L and 30.41 g/L, respectively. The median serum creatinine was 87.3 µmol/L (75–1375 µmol/L). Three patients experienced acute renal failure upon admission. Four patients had secondary NS. All idiopathic NS patients (n = 20) who had received corticosteroid therapy had a 90% response rate to steroids. Non-responsive or relapsed patients underwent kidney biopsy (n = 7), revealing focal segmental glomerulosclerosis (FSGS; n = 4) as the most common histological lesion, followed by minimal change disease (n = 2) and membranoproliferative glomerulonephritis (n = 1). The median length of hospitalization stay was 10.67 (5–27) days. None of the patients with idiopathic NS died. At the last follow-up, sixteen patients (80%) achieved long-term complete remission with normal renal function; however, four of those had subsequent relapses. One patient with secondary NS died.

Conclusion
In Chad, childhood idiopathic nephrotic syndrome predominantly affects young males; steroid sensitivity is as high as 95%, and in the long-term, 80% of patients achieve remission with normal renal function.