bluuebunny/crossref_metadata_2025 huggingface dataset:
#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

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

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 >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

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.
#777 Renal recovery for patients with ANCA-associated vasculitis and low eGFR in a Spanish cohort
Authors: Maldonado Maria , León-Machado Lina María , Ortega Esther , Shabaka Amir , Rivas Begoña , Vega Cristina , León Mariana , Sã¡nchez Cã¡mara Luis Alberto , Caravaca-Fontán Fernando , Juarez Gema Maria Fernandez
Published: May 2024

Background and Aims

Renal failure secondary to ANCA-associated vasculitis (AAV) represents a clinical and therapeutic challenge [1]. Fifteen percent to 38% of the patients develop end-stage kidney disease within 5 years, and once patients need dialysis, 29% to 82% die or remain on dialysis 3 to 6 months after its initiation [2]. Therefore, effectively managing renal vasculitis and preventing patients from reaching dialysis have important consequences [2].

A post hoc analysis of ADVOCATE trial examined outcomes in a patient subgroup with severe renal insufficiency (i.e., estimated glomerular filtration rate (eGFR) ≤20 ml/min per 1.73 m2) at enrollment into the trial, and observed an average eGFR increase of 16.1 and 7.7 ml/min per 1.73 m2 in the avacopan and prednisone groups, respectively (P = 0,003) [2].

This study aimed to compare the average eGFR increase in our cohort of AAV with severely reduced GFR (<20 ml/min) treated with different induction treatment schemes.

Method

We performed a retrospective study which included 19 patients with the diagnosis of AAV and severe renal insufficiency at onset with eGFR between 15 to 20 ml/min per 1.73 m2.

We analyzed the eGFR increase after 12 months of follow-up, according to the induction treatment scheme: cyclophosphamide, rituximab, a combination of cyclophosphamide and rituximab and other (prednisone alone, prednisone with plasma exchange or prednisone with mycophenolic acid). We compared our results to those obtained in the avacopan and prednisone groups in the ADVOCATE trial.

Results

In the subgroup of eGFR between 15 to 30 ml/min per 1.73 m2, patients had at enrollment a mean eGFR of 21 ± 5 ml/min per 1.73 m2 and after 12 months of follow-up the mean eGFR was 41 ± 23 ml/min per 1.73 m2 with an increase of 20 ± 23 ml/min per 1.73 m2.

In the subgroup of eGFR between 15 to 20 ml/min per 1.73 m2, patients had at enrollment a mean eGFR of 17 ± 2 ml/min per 1.73 m2 and after 12 months of follow-up, the mean eGFR was 35 ± 20 ml/min per 1.73 m2 with an increase of 18 ± 21 ml/min per 1.73 m2. After 12 months of follow-up, the mean increase of eGFR was 18, 17, 10 and 23 ml/min per 1.73 m2 in the cyclophosphamide, rituximab, a combination of cyclophosphamide and rituximab and other groups, respectively. We compared our results with the post hoc analysis of the ADVOCATE trial in Table 1 and our results are similar to the avacopan group and better than the prednisone group (p < 0.05).

Conclusion

In our cohort of eGFR between 15 to 20 ml/min per 1.73 m2 at enrollment, the mean increase in eGFR after 12 months of follow-up was similar to the avacopan group and greater than the prednisone group in the ADVOCATE trial.
#2344 Empagliflozin attenuates renal fibrosis through the DsbA-L-CAS-STING pathway in unilateral ureteral obstruction model
Authors: Kwon Soon Hyo , Park Ku Tae
Published: May 2024

Background and Aims

Chronic kidney disease (CKD) is associated with an increase in morbidity and mortality. Renal fibrosis is a common pathway leading to the progression of CKD. Recent studies have reported an improvement of CKD with use of sodium glucose cotransport 2 inhibitors (SGLT2i) in both patients with DM and those without it. However, the mechanism of SGLT2is effect upon CKD has not been elucidated. In current study, we examined the effect of SGLT2i on renal fibrosis in rats caused by unilateral ureteral obstruction (UUO).

Methods

Male Sprague Dawley rats (9-10 weeks, weighing 320-360 g) were randomly assigned to two groups (n=8 each). One group received empagliflozin after UUO induction while the other group was left untreated. Kidneys were harvested two weeks after UUO. We evaluated the mitochondrial damage pathway presumed to contribute to the inflammation.

Results

UUO has resulted in marked renal fibrosis and triggered the activation of the cGAS-STING pathway. Kidneys in the empagliflozin treated group exhibited reduced size compare to the untreated group. Creatinine levels were lower in the empagliflozin group. Empagliflozin has been shown to attenuate renal fibrosis in histopathology. Western blot analysis revealed increased expression of disulfide-bond A oxidoreductase-like proteins (DsbA-L) was decreased cGAS-STING-NFκB in the empagliflozin group compared to the non-empagliflozin treated group (Fig. 1).

Conclusion

SGLT2i mitigated the progression of renal damage and fibrosis. This reno-protective effect is associated with increased DsbA-L and decreased of cGAS and STING pathway. These findings suggest that SGLT2i may alleviate mitochondrial damage in the UUO model. In addition, SGLT2i could be a promising medication to treat various forms of CKD.
#998 Amide proton transfer-weighted magnetic resonance imaging for application in renal fibrosis: a radiological-pathological based analysis
Authors: Zhang Yingying , Zhao Dan , Wang Wei , Niu Yangyang , Shen Aijun , Xiang Yongsheng , Xie Hongyan , Wu Lehao , Yu Chen
Published: May 2024

Background and Aims

Renal fibrosis (RF) being the most important pathological change in the progression of CKD, is currently assessed by the evaluation of a biopsy. This present study aimed to apply a novel functional MRI (fMRI) protocol named amide proton transfer weighting (APTw) to evaluate RF non-invasively.

Method

Male Sprague-Dawley (SD) rats were initially subjected to bilateral kidney ischemia/reperfusion injury (IRI), unilateral ureteral obstruction (UUO) and Sham operation, respectively. All rats underwent APT mapping on the 7th and the 14th day after operation. Besides, 26 patients undergoing renal biopsy at the Nephrology Department of Shanghai Tongji Hospital between July 2022 and May 2023. Patients underwent APT and apparent diffusion coefficient (ADC) mappings within 1 week before biopsy. MRI results of both patients and rats were calculated by comparing with gold standard histology for fibrosis assessment.

Results

In animal models, the cortical APT (cAPT) and medullary APT (mAPT) values were positively correlated with the degree of renal fibrosis. Compared to the sham group, IRI group showed significantly increased cAPT and mAPT values on the 7th and 14th day after surgery, but no group differences were found in ADC values. Similar results were found in human patients. Cortical/medullary APT values were significantly increased in patients with moderate-to-severe fibrosis than patients with mild fibrosis. ROC curve analysis indicated that APT value displayed a better diagnostic value for RF. Furthermore, combination of cADC and cAPT improved fibrosis detection by imaging variables alone (p < 0.1).

Conclusion

APT values had better diagnostic capability at early stage of RF compared to ADC values, and the addition of APT imaging to conventional ADC will significantly improve the diagnostic performance for predicting kidney fibrosis.
#1215 Association between dietary magnesium intake and incident chronic kidney disease
Authors: Koh Hee Byung , Park Jung Tak , Kim Hyo Jeong , Joo Young Su
Published: May 2024

Background and Aims

Recent studies suggest a close association between low serum magnesium levels and kidney injury. However, whether dietary magnesium intake relates with kidney function is not well known. In this study, the relationship of dietary magnesium intake with the development of chronic kidney disease (CKD) was evaluated.

Method

This observational prospective study screened 210,965 European adults aged 40-70 who underwent dietary questionnaire from April 2009 to June 2012 in UK Biobank cohort. Participants with underlying CKD (baseline eGFR  <  60 mL/min/1.73 m² or urine albumin-to-creatinine ratio >30 mg/g/Cr) or implausible energy intake (reported energy intake  <  1.1 × basal metabolic rate [BMR] or 2.5 × BMR) were excluded. Dietary magnesium intake was assessed through online 24-hour recall dietary questionnaire and adjusted for energy intake using residual method. The participants were categorized into quartile according to energy-adjusted dietary magnesium intake. Primary outcome was incident CKD diagnosed through ICD-10 and OPCS-4 codes. Incident CKD defined as eGFR  < 60 mL/min/1.73 m² was also assessed as an additional primary outcome in the sub-cohort with primary care creatinine follow-up data.

Results

A total of 114,916 participants was included in the final analysis. The median age was 57.0 (IQR, 50.0-63.0) years and 56.8% were female. Median magnesium intake amount per person was 345.6 (IQR, 296.8-402.5) mg/day. During a 1,095,128.6 person-year follow-up, CKD outcome occurred in 3,337 patients. Incidence of CKD was progressively lower in patients with higher magnesium intake (3.2%, 2.9%, 2.8%, and 2.7% in Q1-4, respectively). Cox regression analysis revealed that the hazard ratios (HRs) for incident CKD decreased in a stepwise manner towards higher magnesium intake quartiles (2Q: HR, 0.89; 95% CI, 0.81-0.98; 3Q: HR, 0.87; 95% CI, 0.0.79-0.95; 4Q: HR, 0.84; 95% CI, 0.76-0.92) relative to 1Q (P for trend  < 0.001). This association was maintained even after adjustments were made for confounding factors. Similar results were observed with eGFR-defined CKD outcome (2Q: adjusted HR [AHR], 0.75; 95% CI, 0.64-0.89; 3Q: AHR, 0.73; 95% CI, 0.61-0.87; 4Q: AHR, 0.70; 95% CI, 0.58-0.85) relative to 1Q (P for trend  < 0.001).

Conclusion

Higher intake of dietary magnesium may relate with lower risk of incident CKD in adults with normal kidney function.
#1323 Kidney health in children with X-linked hypophosphatemia: lessons from the prospective multicenter study in Germany and Switzerland
Authors: Böckmann Ineke , Leifheit-Nestler Maren , John Ulrike , Metzing Oliver , Rehberg Mirko , Schlingmann Karl Peter , Weitz Marcus , Wühl Elke , Sparta Giuseppina , Schnabel Dirk , Hoppe Bernd , Haffner Dieter
Published: May 2024

Background and Aims

X-linked hypophosphatemia (XLH) is the most common genetic cause of hypophosphatemia. Mutations in the PHEX gene cause elevated circulating levels of fibroblast growth factor 23 (FGF23), phosphaturia, rickets and osteomalacia. Conventional treatment with phosphate salts and active vitamin D is associated with nephrocalcinosis and preclinical studies in mice have shown that a chronic high phosphate load causes proximal tubular injury and fibrosis. There is no detailed analysis on kidney health in XLH patients yet.

Method

We conduct a prospective observational multicenter study in Germany and Switzerland to evaluate kidney health in pediatric XLH patients. Patients receive conventional therapy or burosumab, a fully humanized anti-FGF23 antibody. Clinical and biochemical data, blood and urine samples are collected annually.

Results

To date, 137 patients (80 girls, mean age 10.5 years) from 40 centers are included. 22% of patients have been treated conventionally for 7.5 years, 78% of patients have received burosumab for 2.3 years with 3.7 years of conventional therapy beforehand. Children with XLH show increased systolic blood pressure and body mass index (BMI), and overweight (BMI >90th percentile) and hypertension (systolic blood pressure >95th percentile) were each found in 20% of patients. A reduced eGFR (<90 ml/min/1.73 m2) and/or nephrocalcinosis was noted in 7% and 28% of patients, respectively. Microalbuminuria is twice as prevalent in children with XLH as in healthy children (14% vs 7%). Urinary lithogenic substances (calcium, oxalate, glycolate) are increased in 1.8-22.8%, and citrate is decreased in 12.3% of XLH patients. Tubular injury markers neutrophil gelatinase-associated lipocalin (NGAL) and Dickkopf-3 (DKK3) are elevated in urine of children with XLH, Chitinase 3-like 1 (CHl3L1) is comparable to children with chronic kidney disease, while kidney injury molecule-1 (Kim-1), indicating proximal tubule cell injury, is within a normal range. The renal inflammation marker monocyte chemoattractant protein-1 (MCP-1) is elevated in children with XLH, and epidermal growth factor (EGF), a marker of tubular cell repair, is decreased compared to healthy adults.

Conclusion

Pediatric XLH patients on conventional or burosumab therapy show enhanced systolic blood pressure slightly associated with elevated BMI, and significant renal comorbidity, i.e. reduced eGFR, nephrocalcinosis, increased urinary lithogenic substances, elevated urinary markers of glomerular and tubular injury and inflammation. The impact of conventional versus burosumab treatment are still being investigated.
#1543 Risk factors of obstructive sleep apnea-hypopnea syndrome in patients with chronic kidney disease
Authors: Xue Qin , Liu Hui
Published: May 2024

Background and Aims

Both obstructive sleep apnea-hypopnea syndrome (OSAHS) and chronic kidney disease (CKD) are common disease. Patients with OSAHS were evidenced to have oxidative stress, increased albuminuria and renal injury. Previous reports show high prevalence of OSAHS among CKD patients, while its risk factors are hardly investigated. The objective of this study is to assess the risk factors of OSAHS in patients with CKD.

Method

We selected 181 patients with CKD who were hospitalized in department of Nephrology, Shanghai Jiao Tong University Affiliated Sixth People's Hospital from September 2020 to February 2023. All participants underwent full-night standard nocturnal polysomnography (PSG) monitoring in the sleep center using Alice 4, 5 or 6 devices. An apnea hypopnea index (AHI)>5 events/h was consistent with the diagnosis of OSA. The 181 Patients are divided into three groups based on the level of AHI to studied the differences of clinical and biochemical characteristics. According to Kidney Disease Improving Global Outcomes (KDIGO) risk categories, all patients are divided into non very high risk and very high risk group, logistic regression is used for analyzing risk factors of OSAHS in patients with CKD.

Results

The prevalence of OSAHS was 86.7% (157 of 181), with 29.8% mild, 30.9% moderate and 25.9% severe respectively. The urea nitrogen (P=0.039) and cystatin C (P = 0.030) levels in patients of severe OSAHS group were significantly higher than those within non or mild OSAHS group. The eGFR in non or mild OSAHS group was significantly higher than moderate OSAHS group (P = 0.036). Pearson correlation analysis showed a significant negative correlation between AHI (p = 0.022), ODI (p = 0.033), and hypopnea index (p = 0.004) of sleep parameters and eGFR, while a significant positive correlation was found between LaSO2 (p = 0.005), MaSO2 (p = 0.030), and eGFR. Stepwise linear regression analysis showed that the hypopnea index was an independent risk factor for eGFR (p = 0.033, R2: 0.215), and CT90 was an independent risk factor for UACR (p  <  0.001, R2: 0.105). Logistic regression analysis revealed that hypopnea index (OR = 1.058) was significantly correlated with very high risk in KDIGO risk categories (p  <  0.05).

Conclusion

OSAHS is high prevalence in patients with CKD. Regression analysis shows that hypopnea index is not only an independent risk factor for eGFR but also a significant predictor associated with very high risk according to KDIGO risk category.
#2902 How does IGF-1 levels relate to different stages of chronic kidney disease
Authors: Chowdhury Kowser Hossain , Iqbal M Masud , Rahman Israt Z , Saha Debasish , Saha Sourav , Hossain M Sahadat , Morshed Raquib , Hassan Mz , Chaudhury Sr , Chowdhury Maa
Published: May 2024

Background and Aims

Insulin like growth factor-1 (IGF-I) influences glomerular filtration rate (GFR).Chronic kidney disease (CKD) influences the IGF/GH axis also. Serum IGF-I level is proposed to be a risk factor for renal and cardiovascular complications which is accentuated in CKD.

This study is undertaken to observe the level of serum IGF-1 in different stages of chronic kidney disease and its association with cardio-metabolic risk factors

Method

This cross-sectional pilot study included consecutive 102 CKD patients of advanced renal failure (CKD3-5). Also 52 healthy subjects (free from any known disease) served as healthy referent for IGF-1 level. Stable CKD subjects ( <  15% deviation of eGFR in 3 months) from OPD of study center were included as cases. Information on socio-demographic and clinical characteristics with medical histories was collected from all in a predesigned data collection sheet Urine spot samples and fasting blood samples were collected and stored at −80°C for future analyses. The four-variable Modification of Diet in Renal Disease (MDRD) study equation was used for calculation of the eGFR using enzymatic creatinine. IGF-I was determined by ELISA method.

Results

Mean age was of CKD subjects was 50.45 ± 10.45 years with male-49% female-51%. Most common primary disease responsible for CKD was GN (53%) followed by DM (21%), HTN (13.0%) and rest others. The IGf-1 level was 297 ± 107 (range 79-588) in CKD patients and in healthy it was 246 ± 82 (114-529) ng/ml, (p < 0.004). The IGF-1 value at 25th percentile of healthy was only present in 12.7% of CKD and above 75th it was present in 42% of CKDs (p < 0.11).

Study subjects in CKD 3 was 36%, in 4- 44% and in 5- 24%. The serum IGF-1 levels at CKD 3, 4 and 5 was 246 ± 82, 278 ± 95 and 328 ± 101 ng/ml, (p  <  0.014); Hb% 11.1 ± 1.4, 11.3 ± 1.5 and 10.6 ± 1.5 g% (p  <  0.001); calcium 9.5 ± 1.4, 9.6 ± 1.4 and 8.9 ± 1.0 mg% (P  <  0.014); phosphate 3.6 ± 1.1, 3.6 ± 0.4 and 4.2 ± 1.0 mg%(p  <  0.02); iPTH 24 ± 27, 22 ± 16 and 61 ± 82 pg/ml (p  <  0.01) and albumin 4.5 ± 1.1, 4.56 ± 1.4 and 8.9 ± 1.0 mg%, (p  <  0.04) respectively in 3 stages. The correlation study showed only a negative association of IGF-1 with eGFR (p  <  0.01).The logistic regression analysis showed (taking in consideration of cardio-metabolic risk factors) only a significant association of eGFR with IGF-1.

Conclusion

The Serum IGF-1 level had an increasing value along with alterations in other biochemical parameters at advancing stage of CKD. This increase in IGF-1 value seems to be a reflection of progressing CKD rather than a causal relation to other cardio-metabolic risk markers.
#1551 The presence of proteinuria is associated with impaired cerebral oxygenation during exercise in chronic kidney disease
Authors: Theodorakopoulou Marieta P , Dipla Konstantina , Zafeiridis Andreas , Faitatzidou Danai , Koutlas Aggelos , Devrikis Nikolaos , Georgiou Areti , Karkamani Eleni , Doumas Michael , Papagianni Aikaterini , Sarafidis Pantelis
Published: May 2024

Background and Aims

Cognitive impairment and reduced exercise tolerance are common in patients with chronic kidney disease (CKD), in part due to reduced brain function. Cerebral perfusion and oxygenation are significant determinants of brain activation and have been shown to be significantly impaired in CKD. This analysis aims to examine the impact of proteinuria on cerebral oxygenation during a mild physical stress in patients with pre-dialysis CKD.

Method

66 patients with CKD stage 2-4 were included in this post-hoc analysis; 24-h urine samples were used for evaluation of proteinuria. All participants underwent a 3-min intermittent handgrip exercise (HG) at 35% of their maximal voluntary contraction. Changes in cerebral oxygenation (oxyhemoglobin-O2Hb) and deoxyhemoglobin-HHb) and regional blood volume (total hemoglobin-tHb) were continuously recorded during HG-exercise by near-infrared spectroscopy (NIRS).

Results

No significant differences between the 2 groups were detected in age (proteinuric vs nonproteinuric: 68.4 ± 10.6 vs 67.2 ± 10.8; p = 0.676), eGFR (41.3 ± 18.9 vs 46.3 ± 14.8; p = 0.248) and BMI (28.4 ± 4.9 vs 28.1 ± 4.8; p = 0.803). The MMSE score (proteinuric vs nonproteinuric: 28.0 ± 1.6 vs 28.0 ± 1.7; p = 0.938) and MVC (22.3 ± 7.0 vs 23.9 ± 7.5; p = 0.416) were not significantly different between groups. The average response in cerebral oxygenation during exercise was lower in patients with proteinuric CKD (O2Hb: 1.02 ± 0.87 vs 1.61 ± 0.95; p = 0.018 and diffO2Hb 1.53 ± .97 vs 2.07 ± 1.25; p = 0.065). The average tHb response (index of regional-blood-volume) was also lower in patients with proteinuria (0.51 ± 1.08 vs 1.16 ± 0.92 p = 0.013); however, no differences in HHb (-0.50 ± 0.55 vs -0.45 ± 0.54; p = 0.717) –an index of oxygen extraction capacity- among groups were detected. In univariate linear analysis the level of proteinuria did not show significant correlations with NIRS parameters.

Conclusion

The presence and not the level of proteinuria is associated with impaired brain activation during a mild physical task in patients with predialysis CKD. Future studies evaluating the role of proteinuria in the decline of cerebral function and cognitive impairment are needed.
#3043 Epidemiology of infective endocarditis in long term hemodialysis patients in France, from 2014 to 2019
Authors: Clemmer Edouard , Moranne Olivier , Messikh Ziyad , Boudemaghe Thierry
Published: May 2024

Background and Aims

Infective endocarditis (IE) is a frequent pathology among patients treated with long-term hemodialysis (HD). Its epidemiology and risk factors are scarcely reported in this specific population in France. This study aims to describe the frequency and characteristics of IE in long-term hemodialysis patients in mainland France.

Method

From the national Programme de médicalisation des systèmes d'information (PMSI) data, we selected patients initiating a renal replacement therapy by long-term hemodialysis from 2014 to 2017, with a follow up from 2017 to 2019. Within this population, we defined hospitalizations due to IE by using the CIM-10 coding system. We analyzed various comorbidities such as sociodemographic factors, cardiovascular diseases, cancer, diabetes and vascular access, identified within the PMSI during a minimum duration of 4 years, looking for IE risk factors. As the IE incidence has a low frequency for this follow up length, it was analyzed with a Poisson distribution model.

Results

We studied 38 569 patients, with a 36 month follow up. Fig. 1 shows IE incidence during the follow up, in which we identified 2492 cases of EI. The incidence rate was 6.69, or 7 out of 100 000 at first month and 1.97 out of 100 000 at twelve months. In multivariate analysis we found the following risk factors associated with EI: having a central vascular catheter (CVC) as initial vascular access while starting renal replacement therapy, compared to an arteriovenous fistula, OR 2.49 [2.29-2.71], diabetes OR 1.25 [1.14-1.35], cardiovascular conditions OR 1.35 [1.23-1.48] and increasing age was associated with a reduction of an IE diagnosis odds.

Conclusion

Our study highlights a high IE frequency among long-term hemodialysis patients. Its incidence is particularly high during the first year and decreases afterwards. The main risk factors were: CVC, preexisting cardiovascular conditions and diabetes.
#553 Renal tubular damage is an independent risk factor for all-cause and cardiovascular mortality in a community-based population: the Takahata Study
Authors: Suzuki Takaya , Ichikawa Kazunobu , Watanabe Masafumi , Konta Tsuneo
Published: May 2024

Background and Aims

Renal tubulointerstitial damage is a risk for renal failure. However, the association between renal tubulointerstitial damage and all-cause and cardiovascular mortality in the general population remains unclear. In this prospective cohort study, we examined this point using urinary β2-microglobulin/creatinine ratio (UBCR) as a marker of renal tubulointerstitial damage in the general Japanese population.

Methods

We examined the association between UBCR values at entry and all-cause and cardiovascular mortality during the follow-up period (median 9.2 years) in 3 427 residents (mean age 62.5 years, 45.1% male, mean eGFR 81.6 ml/min/1.73 m², ≥1+ protein 4.4%) of Takahata Town in Japan.

Results

Study participants were divided into two groups (low < 300 μg/gCre, high ≥300 μg/gCre) based on UBCR at entry. Kaplan-Meier analysis showed a significantly higher incidence of all-cause and cardiovascular mortality in the high UBCR group (Log-rank P < 0.01). A multivariate Cox proportional hazards analysis adjusted for age, sex, eGFR, urinary protein level, comorbidities, smoking status, and other background factors showed a hazard ratio of 1.47 (95% CI 1.09-2.00, P = 0.01) for all-cause mortality and a hazard ratio of 1.82 (95% CI 1.06-3.12, P = 0.03) for cardiovascular death in the high-UBCR group. The addition of high UBCR to conventional risk factors, including eGFR and urinary protein level, significantly improved the net reclassification improvement (NRI) for all-cause and cardiovascular mortality (P < 0.01).

Conclusions

UBCR, a marker of tubulointerstitial damage, was identified as a risk factor for all-cause and cardiovascular mortality in the general population independent of eGFR and urinary protein levels.
#939 Association between alcohol consumption and the risk of incident chronic kidney disease in community-dwelling older adults
Authors: Sun In O , Bae Eunjin , Hyun Young Youl , Chung Sungjin , Kwon Soon Hyo , Yoo Kyung Don , Yu Byung Chul , Ko Gang-Jee , Yang Jae Won , Hwang Won Min , Shin Sung Joon , Hong Yu Ah
Published: May 2024

Background and Aims

The relationship between alcohol consumption and kidney function decline is not well established, especially in older adults. This study aimed to investigate the effects of alcohol consumption on the risk of incident chronic kidney disease (CKD) in community-dwelling older adults.

Method

Adults aged ≥ 65 years with an estimated glomerular filtration rate (eGFR) ≥60 mL/min/1.73 m2 and without proteinuria between 2009 and 2010 were recruited and followed through December 2018 from a Korean national population-based cohort. Alcohol consumption was categorised into non-, mild, moderate, and heavy drinking groups based on self-administered questionnaires. New-onset CKD was defined as an eGFR <60 mL/min/1.73 m2.

Results

Of the total 122,319 subjects, the non-, mild, moderate, and heavy drinking groups were 99,091 (81.0%), 14,842 (12.1%), 4,257 (3.5%), and 4,139 (3.4%), respectively. During follow-up, 19,796 (20.0%), 4,636 (31.2%), 1,696 (39.8%), and 1,695 (41.0%) developed CKD in the non-, mild, moderate, and heavy drinking groups. Univariate Cox regression analyses showed a significantly increased risk of incident CKD in older adults in all drinking groups compared to non-drinkers (all P < 0.001). However, hazard ratios (HR) for developing CKD were 0.90 (95% confidence interval [CI] 0.87–0.94, P < 0.001) for mild, 0.89 (95% CI 0.84–0.95, P < 0.001) for moderate, and 0.93 (95% CI 0.88–0.99, P = 0.027) for heavy drinkers after fully adjusting for confounding variables. This inverse relationship between alcohol consumption and CKD risk was observed in males in all drinking groups, whereas in females it was found only in mild drinkers.

Conclusion

In the subgroup analysis, the beneficial effect of alcohol consumption on incident CKD was prominent among moderate drinkers aged 65–75 years, male mild drinkers aged ≥ 75 years, and female mild drinkers aged < 85 years. This study shows that alcohol consumption is inversely associated with the risk of incident CKD in older adults. Further studies are required to elucidate the effects of alcohol on kidney damage in older adults.
#284 Risk of dose-dependent methotrexate therapy on renal functions in patients with rheumatoid arthritis
Authors: Elsharabasy Reem , Gamal Dalia , Khedr Lamis , Farid Sara , Mohsen Ghada
Published: May 2024

Background and Aims

Methotrexate is often used as first-line therapy for RA because of its proven efficacy, good safety profile, and low cost. The importance of MTX also comes from the fact that in combinatory treatments, the efficacy of bDMARDs or tsDMARDs is always higher when these drugs are combined to MTX, suggesting making MTX at the base of any conventional treatment of RA. Although renal impairment is a major concern in patients taking high-dose MTX for the treatment of malignancy, it has not been fully examined in RA patients treated with low-dose MTX, so we aimed at studying the dose- dependent effects of MTX on renal function and creatinine clearance.

Method

Three hundred and sixty adult RA patients, regularly attending rheumatology OPC for regular follow up participated in this retrospective cohort study. Young children, patients with any degree of renal impairment and other rhematic diseases were excluded. Serum creatinine and creatinine clearance were followed up at 1 year and 3 years of different doses of MTX therapy, and results were compared to baseline levels.

Results

Patients’ ages had a mean of 44.60 years, with most being females (80.6%). Range of disease duration was 2-34 years with the mean of 9.93 years. Most of the patients had significant disease activity, where 36.4% had moderate activity and 26.1% of them had high disease activity according to DAS 28 score. We noticed a significant decline of the creatinine clearance at 1 & 3 years follow up regardless the MTX dose used (P-value: ≤0.001 for both).

Conclusion

We may conclude that MTX therapy has a potential nephrotoxic effect regardless the dose or the duration of therapy, mandating a close monitoring of renal functions for patients maintained on the drug.
#1948 Transcriptome analysis of the effect of roxadustat on osteoclasts
Authors: Li Afang , Zuo Li
Published: May 2024

Background and Aims

In recent years, hypoxia-inducing factor prolyl hydroxylase inhibitors (HIF-PHIs) have been widely used in the treatment of renal anemia, bringing a revolutionary breakthrough in the treatment of anemia in CKD patients. However, HIF-PHIs acts on a variety of cells and regulates the expression of multiple target genes. Some studies have reported that HIF-PHIs plays an important role in regulating bone metabolism and promoting the differentiation and calcification of osteoblasts, but its influence on osteoclasts remains controversial. This study intends to explore the effect of roxadustat, a representative drug of HIF-PHIs, on osteoclasts.

Method

Bone marrow mononuclear cells (BMMCs) from 6-8 weeks old male C57BL/6 wild mice were extracted and induced to differentiate into osteoclasts using macrophage colony-stimulating factor (M-CSF) and receptor activator of nuclear factor-κB ligand (RANKL). Meanwhile, lipopolysaccharide (LPS) was used to simulate the inflammatory environment in CKD patients. According to the experimental group, different concentrations of roxadustat (0 μM, 2.5 μM, 5 μM, 10μM) were added simultaneously. When osteoclast induction reached day 6, mRNA was extracted for transcriptome sequencing and bioinformatics analysis.

Results

As shown in Table 1, different concentrations of roxadustat were given to primary bone marrow monocytes under both conditions, and there were 3 biological replicates for each sample. The reproducibility scatter plot showed that the data in each group had good repeatability (Fig. 1), and the heat map for basic difference analysis of each sample was shown in Fig. 2. The trend analysis results of the two groups were shown in Fig. 3. BMMCs group and LPS stimulated group showed two upward trends, respectively. KEGG enrichment analysis of these two upward trends showed that HIF-1, MAPK, PI3K-Akt, NF-κB and osteoclast differentiation pathways were significantly enriched in both groups. It is suggested that roxadustat can promote osteoclast differentiation and increase inflammatory response with the increase of roxadustat concentration. The enrichment analysis of the two groups showed that there was no significant enrichment pathway.

Conclusion

We explored the differentiation of osteoclasts under normal conditions and osteoclast differentiation under simulated inflammation in CKD patients respectively. Transcriptomic analysis results showed that HIF-1, MAPK, PI3K-Akt, NF-κB and osteoclast differentiation pathways were significantly enriched with the increase of roxadustat concentration. It is suggested that the use of roxadustat may promote bone destruction and increase the risk of inflammatory response.
#1815 The neutrophil/lymphocyte, neutrophil/HDL-cholesterol, and monocyte/HDL-cholesterol ratios as simple markers of low-grade inflammation in CKD patients
Authors: Lajdová Ingrid , Spustová Viera , Wsolová Ladislava , Okša Adrián
Published: May 2024

Background and Aims

Chronic kidney disease (CKD) has been associated with inflammation and oxidative stress, as well as with high cardiovascular (CV) morbidity and mortality. The neutrophil/lymphocyte (NLR), neutrophil/HDL-cholesterol (NHR), and monocyte/HDL-cholesterol (MHR) ratios have been linked both to inflammation and increased CV risk in a variety of diseases. The aim of this study was to investigate changes in these ratios in CKD patients of stage 2-5 without any clinical and laboratory signs of inflammation, and to compare these indicators with those in healthy volunteers.

Method

A retrospective cross-sectional study was conducted in 88 healthy volunteers and 187 CKD patients (50 of stage 2, 44 of stage 3a, 45 of stage 3b and 48 of stage 4-5). Patients with acute renal impairment, nephrotic proteinuria, infections, systemic inflammation, malignancies and hematologic diseases were excluded, as were those receiving hypolipidemic, corticosteroid, immunosuppressive or immunostimulant drugs. The whole blood samples were collected and the absolute numbers of neutrophils, lymphocytes, and monocytes were used for calculation of NLR, NHR and MHR, respectively. Serum creatinine, HDL-cholesterol, C-reactive protein (CRP) and albumin were measured and eGFR calculated according to the CKD EPI equation. Statistical analysis was performed with the Mann-Whitney, Shapiro–Wilk, Kruskal-Wallis, and Spearman's correlation tests using the SPSS software.

Results

The NLR, NHR and MHR were higher in CKD patients when compared to healthy volunteers (P < 0,001), but only NLR and NHR increased significantly across CKD stages (P < 0,01). The ratio differences between CKD stages were more evident for NHR which was also in best correlation with eGFR (ρ = −0,406, P < 0,001). The CRP values increased across CKD stages as well (P < 0,01) although remaining within the reference range. The NLR, NHR and MHR were significantly related to CRP with NHR providing the best correlation (ρ = 0,289, P < 0,001).

Conclusion

This study showed that NLR and NHR increased across CKD stages 2-5 and could be used to identify low-grade inflammation in this population even within normal CRP values.
#331 Vascular and lipid profile interplays in pediatric CKD patients
Authors: Sallam Dina E
Published: May 2024

Background and Aims

Chronic kidney disease (CKD) is characterized by irreversible kidney damage and/or progressive loss of function. Children with CKD often have additional CVD risk factors, including hypertension and dyslipidemia. They may have myocardial abnormalities and early atherosclerosis evidence, such as coronary artery calcification, abnormal flow-mediated dilation, increased carotid intima-medial thickness (CIMT), and increased aortic stiffness. These abnormalities seem to be, in part, related to the degree of uremia.

This study aimed at assessing the interrelationship between vascular status and lipid profile abnormalities in different stages of CKD in pediatric patients.

Method

This cross-sectional study was done on 99 patients: 33 with stage 5 CKD on regular hemodialysis & 33 pre-dialysis CKD stage 2-4 on conservative management & 33 age and sex matched controls. Anthropometric measures, blood pressure readings, and a lipid profile were done to all groups. Intima media thickness was measured using B-mode ultrasound doppler in both the common and internal carotid arteries (CCA, ICA).

Which is a non-invasive way to measure the artery walls and track the early impacts of the atherosclerotic process.

Results

There was an obvious increase in blood pressure the percentiles in all CKD patients in relation to controls. The waist-to-hip ratio in CKD 2-4 patients was significantly higher than in CKD 5 patients, and both were higher than the controls, with means (±SD) of 1.01 (0.19), 0.88 (0.10), and 0.86 (0.05), respectively. Except for high-density lipoproteins (HDL), the lipid profile, including triglycerides, cholesterol, and low-density lipoproteins (LDL), were all significantly increased when comparing CKD 2-4 to CKD 5, and both higher than the controls: 170.45 (42.04), 166.00 (45.57), and 100.88 (26.19) for triglycerides (p 0.001). The right and left ICA and CCA showed a significant increase in the intimal thickness being higher in the CKD 5 group than the CKD 2-4 and both higher than the controls. On studying the correlation between the duration of CKD in years and other variables, we found a positive correlation with triglycerides (r = 0.409 & p = 0.001) and right CCA IMT (r = 0.271 & p = 0.028); however, the HDL (r = −0.326 & p = 0.007) revealed a negative correlation in all CKD patients. The HDL level showed an inverse correlation with right CCA and ICA.

Conclusion

Patients with CKD have an increased waist-to-hip ratio, dyslipidemia, and increased carotid IMT, which are factors that lead to the early development of atherosclerosis. Special care should be directed to CKD patients, especially those in stages 2-4, to control their lipid profile and postpone the development of atherosclerosis as much as possible.
#1740 Survival of native arteriovenous fistulas in elderly patients
Authors: León-Póo Mariana , Abreu Ángel Méndez , Baz Miguel Gutiérrez , Gómez Beatriz Patiño , Cordon Alfredo , Corona Clara Cases , Jiménez Sandra Vicente , Fernández Elia Pérez , Gruss Enrique
Published: May 2024

Background and Aims

Current guidelines recommend native arteriovenous fistulas (nAVF) as the first-choice vascular access for hemodialysis. However, the patient's age may make its indication doubtful. The aim of our study was to know the association between primary survival (PS), defined as the time to the first reparation, and secondary survival (SS), defined as the end of the working life of a nAVF, with the patient's age.

Method

We conducted a prospective observational study based on a historical database including 795 nAVF from incident patients, both treated in an in-hospital dialysis unit (HDU) and an out-of-hospital dialysis center (DC), made between 1998 and 2022 and followed-up until June 2023. We performed Kaplan Meier survival curves to estimate PS and SS of the nAVF for each age group (≤ 50, 50-70 and ≥ 70 years) and a multivariate logistic regression analysis of PS and SS adjusted by comorbidity (Charlson's Comorbidity Index without age (CCI)), sex, nAVF indication at end stage kidney disease (ESKD) clinics, location of the nAVF, in-hospital dialysis unit or out-of-hospital dialysis center treated patient and initial laboratory parameters (albumin, hemoglobin and phosphorus).

Results

The medium age of the patients included was 63.4 years; 68% were males, 34% had diabetes and 63.3% had a CCI ≥ 3 at the time de nAVF was made. 53.5% of all the nAVF were indicated at the ESKD clinics; 57.9% of them were radiocephalics, 33.4% brachiocephalics and 8.8% brachiobasilics. Almost 40% of the fistulas had an in-hospital use. In the survival study we didn't find statistically significant differences for age or sex, but both PS and SS were lower for patients with a CCI ≥ 3, and SS was significantly better for the first nAVF of the patient and for radio-cephalic nAVF, as shown in Fig. 1. These results were concordant to the univariant analysis, in which we didn't find differences for age group or sex, but both PS and SS were worse in patients with a CCI ≥ 3 (HR 1.32, p 0.037). Patients with lower albumin levels at the time the nAVF was made had a lower PS (HR 0.62, p < 0.001); and SS also had a statistically significant association with being treated at an out-of-hospital dialysis center (HR 0.69, p 0.024) and the indication of the nAVF at the ESKD clinics (HR 0.71, p 0.036). Nevertheless, in the multivariate logistic regression analysis we only found significant differences, both for PS and SS, regarding the albumin levels at the time the nAVF was made (HR 0.62, p 0.001).

Conclusion

The survival of a native arteriovenous fistula, both primary and secondary, does not correlate to the patient's age, sex, comorbidity, indication at the ESKD clinics or the location of the fistula.