bluuebunny/crossref_metadata_2025 huggingface dataset:
#968 Impact of the presence of acute kidney injury at the time of renal biopsy on long-term prognosis of IgA nephropathy
Authors: Kim Hyun-Jung , Jeon Hyejin , Lee Seunghye , Kim Jin Hyun , Jung Sehyun , Jang Hani , Chang Se-Ho
Published: May 2024

Background and Aims

IgA nephropathy is the most common primary glomerular disease and an important cause of end-stage renal disease. Factors such as decreased renal function, persistent proteinuria, hypertension, and older age predict a poor prognosis in IgA nephropathy. Current international prediction tools for IgA nephropathy determine prognosis based on renal function using estimated glomerular filtration rate (eGFR) at the time of kidney biopsy. However, we observed differences in prognosis between patients with and without concurrent acute kidney injury (AKI) at the time of kidney biopsy. Therefore, we aimed to investigate whether renal function at the time of renal biopsy is a suitable indicator for assessing the long-term prognosis of patients with IgA nephropathy with AKI.

Method

We retrospectively analyzed a total of 185 patients who were diagnosed with IgA nephropathy between 2009 and 2016 at the Gyeongsang National University Hospital. Clinical data, including pathological, demographic, and laboratory findings of patients, were used. We divided the patients into two groups based on the progression rate of kidney function per year, ‘Progression’ or ‘Non-progression group’. AKI was defined according to the KDIGO Clinical Practice Guidelines.

Results

Among a total of 185 patients, 113 showed a sustained decline in eGFR of more than 1 ml/min/1.73 m2 per year. The mean eGFR level of the non-progression group was significantly lower than that of the progression group (p = 0.027). The percentage of patients with AKI in the non-progression group was 25%, which was higher than that in the progression group (p < 0.001). The two groups had no significant differences in comorbid disease, medications at kidney biopsy, and treatment. In sub-analysis, the mean eGFR at kidney biopsy was significantly lower than that in the non-AKI group (p < 0.001). The mean estimated risk, calculated by the international prediction tool, was significantly lower in the AKI group. On the other hand, the mean rate of actual GFR decline per year was higher in the non-AKI group (p < 0.001).

Conclusion

We confirmed a discrepancy between the predicted prognosis and the actual decline in GFR, particularly in the AKI group. We found that AKI at the time of renal biopsy was a good long-term prognostic factor. There is a need to conduct further research to confirm whether this is due to early detection of AKI and early active treatment.
#3108 Rituximab in adult-onset IgA vasculitis
Authors: Trivioli Giorgio , Fenoglio Roberta , Pillebout Evangeline , Hocevar Alojzija , Bruchfeld Annette , Lundberg Sigrid , Mohammad Aladdin , Maritati Federica , Jayne David R W , Mcadoo Stephen , Roccatello Dario , Vaglio Augusto
Published: May 2024

Background and Aims

Adult-onset IgA Vasculitis (IgAV) is poorly responsive to glucocorticoids (GC) and conventional immunosuppressive therapies, such as cyclophosphamide. Rituximab has been successfully used in a few cases and may represent a safer and potentially more effective option [1]. Crescentic IgA Nephropathy (cIgAN), a rare entity that shares features of renal vasculitis with IgAV, is also frequently refractory to cyclophosphamide, while response to rituximab is unknown. We investigated outcomes after rituximab in a multicentre European cohort of adult-onset IgAV and cIgAN.

Method

We screened clinical records of patients followed at 18 European consorted centres who were ≥18 years old at the onset of IgAV and received ≥1 rituximab dose. Furthermore, we identified patients with cIgAN (≥25% crescentic glomeruli and rapidly progressive glomerulonephritis), who were treated with rituximab. Remission was defined as Birmingham Vasculitis Activity Score (BVAS) <3 at month 6 after rituximab and renal response as stable or improved eGFR and ≥50% proteinuria reduction. Relapse was defined as an increase in BVAS requiring a change in immunosuppressive therapy. Outcomes of IgAV with severe nephritis (eGFR <60 mL/min) were compared with those of cIgAN.

Results

We included 61 patients with IgAV and 15 with cIgAN (Table). Rituximab was administered as initial therapy in 23/61 (38%) patients with IgAV and 13/15 with cIgAN (87%), while the remainder had refractory or relapsing disease. Active skin involvement was present in 49 patients (80%) and nephritis in 55 patients (90%) with IgAV at the time of starting rituximab. This was given alone in 13/61 (21%) or combined with GC in 48 (79%) patients with IgAV and in all those with cIgAN. Furthermore, cyclophosphamide was used in 15% of patients with IgAV and 40% of those with cIgAN. Remission at 6 months was achieved by 52 (85%) patients with IgAV and 12/13 (92%) of those treated with rituximab alone. A renal response was observed among 49/55 (89%) of those with nephritis. Patients with IgAV and severe nephritis had similar eGFR to those with cIgAN at the time of starting rituximab, but the latter had lower rate of remission and a higher frequency of kidney failure. A relapse occurred in 15/52 patients (29%) who achieved remission a median of 13 months (10-15) after rituximab. Eight patients resumed rituximab and achieved again remission.

Conclusion

Rituximab alone or in combination with GC and immunosuppressants appeared to achieve a high rate of remission in this cohort of adult-onset IgAV. Renal response among those with severe nephritis was also good, while this was worse among patients with cIgAN, suggesting substantial differences among these conditions despite similar histological appearances.
#1917 SGLT2-Inhibition in patients with Alport syndrome – an international, retrospective and in parts prospective observational large cohort study
Authors: Boeckhaus Jan , Gross Oliver
Published: May 2024

Background and Aims

Large-scale trials showed positive outcomes of SGLT2-inhibitors (SGLT2i) in elderly patients with CKD. Patients with Alport syndrome, a type IV collagen disease, develop CKD early in life. Whether the use of SGLT2i is safe and effective in patients with the type IV collagen disease Alport syndrome (and thus a different pathogenesis) has not yet been investigated specifically besides case reports.

Method

For the first time, this observational, multicenter, international study (NCT02378805) assessed 112 patients with AS from nine countries and 21 trial sites after start of SGLT2i at early stages of their chronic kidney disease (CKD). The study's primary endpoint was change of albuminuria in albumin/g creatinine after start of therapy with SGLT2i.

Results

Compared to the large randomized trials investigating the effect of SGLT2i in CKD, the adult patients in this trial were much younger (38 ± 14 years; n = 101), had a better eGFR (63 ± 35 ml/min/1.73m2; n = 98) and had a higher albuminuria (1699 ± 1472 mg/g creatinine; n = 51). At a mean time on SGLT2i-therapy of 6 ± 1 months, albuminuria decreased significantly (1727 ± 1564 vs. 1203 ± 1165 mg/g creatinine; n = 33; p = 0.01). Compared to baseline, at the first three follow-up visits after initiation of SGLT2i-therapy, a significant reduction of albuminuria >30% was observed. Mean loss of eGFR was 9 ± 12 ml/min/1.73 m² almost one year after initiation of SGLT2i-therapy (n = 35). At a mean follow up of 12 ± 2 month after initiation of SGLT2i-therapy, serum-albumin increased significantly from 3.7 ± 0.7 to 4.0 ± 0.4 g/dL (n = 18; p = 0.019). At a total of 68 patient-years at risk, adverse events occurred in 11/85 patients (13%). Two very serious adverse events (acute necrotizing pancreatitis and Fournier's gangrene) occurred.

Conclusion

This study demonstrated that SGLT2i, when added to RASi, have the potential to reduce the rate of albuminuria in adult patients with Alport Syndrome. The study will be continued to provide valuable data on the long-term course of CKD under SGLT2i-therapy in AS to investigate if the promising reduction of albuminuria results in a clinical relevant delay in renal failure. This observational study successfully formed the scientific basis for the current randomized controlled trial with SGLT2i in children and young adults with AS Double Protect Alport.
#1392 MEST-C score correlation with proteinuria reduction after SGLT2i treatment in patients with IgA nephropathy
Authors: Xydakis Dimitris , Antonaki Ergini , Tzali Eleni , Papapanagiotou Michalis , Petra Christina , Kostakis Kostantinos , Vardaki Eleftheria
Published: May 2024

Background and Aims

Sodium-glucose cotransporter 2 inhibitors (SGLT2i) are associated with better cardiovascular outcomes and with nephroprotection independent of diabetes status. Recent data suggest that SGLT2i significantly reduce proteinuria in patients with IgA nephropathy (IgAN). Data available for the use of the MEST-C score to determine if treatment would benefit IgAN patients is scarce. The aim of our study was to assess the degree of proteinuria reduction after SGLT2i treatment in IgAN and its possible association with the MEST-C score.

Method

63 adult patients with biopsy-proven IgA nephropathy, eGFR ≥ 30 mL/min/1.73 m2 (CKD-epi), and total urine protein of >0.5 grams/day at screening were included. Patients with secondary IgAN and crescents were excluded. All receiving maximally tolerated RASi for at least 12 weeks. All patients started dapagliflozin 10 mg once per day after baseline data were registered. The total follow-up was 12 months. The main outcome was the decline in eGFR and the reduction in 24-hour proteinuria from SGLT2i initiation to 1,3, 6, 9, 12 months, end-stage renal disease, or kidney or cardiovascular death. Three repeated measurements of proteinuria (mg/24H) were performed, 90 days before SGLT2i treatment initiation, and only patients with stable proteinuria were enrolled in the study.

Results

49 patients (35/14 M/F), with mean age of 41,9 ± 19,6 years, completed follow up. 8 patients discontinued treatment due to adverse events attributed to dapagliflozin. At baseline eGFR was 68.21±18,1 ml/min/1.73 m2 and Upr: 2196±1091 mg/24H. The MEST-C scores were correlated with the serum creatinine level, proteinuria, and hematuria. The mean serum creatinine level was higher in M1, E1, S1, and T1 compared with score “0”. It was statistically significant (p = 0.03) only in the T-score. The mean proteinuria level was again higher in M1, S1, and T1 but reached statistical significance (p = 0.037) in only the T1-score. E1 has higher hematuria.

The Upr/24H difference for dapagliflozin was −24.7% (95% CI −27.5, −23.2; p < 0.001) at the end of follow-up (month 12). Proteinuria reduction was similar across all eGFRs, age, and baseline proteinuria.

Among MEST-C score parameters, T1 had a negative impact on the antiproteinuric effect of dapagliflozin (p = 0.01)

No hypoglycemic events were reported and no deaths occurred.

Conclusion

In the present study, the use of SGLT2i was associated with a significant reduction of proteinuria in patients with IgA nephropathy and maximally tolerated RASi. We analyzed renal outcomes in association with pathologic features. We established that the presence of the T1 score has a negative impact on proteinuria reduction after SGLT2i treatment. Further studies are needed to investigate the impact of the use of the Oxford Classification score for developing individual treatment therapies.
#751 Noninvasive evaluation of histopathology in immunoglobulin A nephropathy by contrast-enhanced ultrasonography
Authors: Zheng Ke , Wang Gangan , Li Xuemei
Published: May 2024

Background and Aims

IgA nephropathy is a common primary glomerulonephritis. Renal pathology provides a visual reflection of renal lesions, but percutaneous renal biopsy carries risks This study explores a non-invasive method for evaluating the renal pathological changes in IgA nephropathy patients. We attempt to correlate contrast-enhanced ultrasonography parameters with IgA nephropathy pathological changes, discussing the potential value of this approach in assisting the assessment of IgA nephropathy renal pathology.

Method

This prospective study included 26 IgAN cases eventually confirmed through renal pathology. Prior to renal biopsy, patients underwent contrast-enhanced ultrasound examination and conventional renal ultrasound. Ultrasound contrast parameters, including time-intensity curve (TIC) peak intensity, time to peak, rise time, and mean transit time, were recorded. Correlation analyses were conducted between conventional ultrasound, contrast-enhanced ultrasound parameters, clinical data, and pathology scores.

Results

Significant differences in peak intensity were observed between different Oxford C scores, with significant statistical differences between C0 and C1, as well as C0 and C2 (P < 0.05). Quantitative analysis revealed correlations between peak intensity, time to peak, and C scores (r = −0.571, P < 0.05; r = 0.498, P < 0.05). Time to peak correlated with T scores (r = −0.445, P < 0.05). No correlations were found between other contrast-enhanced ultrasound parameters and Lee's grading, Oxford MEST-C M, E, or S scores.

Conclusion

Contrast-enhanced ultrasonography parameters, specifically time-intensity curve peak intensity and time to peak, correlate with renal pathology C scores. Contrast-enhanced ultrasound holds clinical significance in the non-invasive assessment of renal pathological changes in IgA nephropathy patients.
#2423 Molecular classification of lupus nephritis based on immune pathway profiling—correlations with histological class and clinical manifestations
Authors: Zhang Danting , Xie Ruiyan , Yap Desmond
Published: May 2024

Background and Aims

The ISN/RPS 2003 classification is the current gold standard histopathological classification for lupus nephritis (LN), and has important roles in guiding treatment and predicting prognosis. The classification system, largely based on light microscopy features, does not inform the underlying immunological aberrations. A classification based on molecular typing of immune-related pathways may better stratify LN patients and help select treatments that target specific immune cascades.

Method

The normalized expression matrix and clinical data were extracted from Gene Expression Omnibus database, Human Cell Atlas (Hacohen-Human-CELseq2) and Nephroseq. Four chip datasets (GSE127797, 32591, 69438 and 37463) and one single cell dataset were analyzed. Sample gene set enrichment analysis (ssGSEA) method was used to derive immune phenotype with gene expression data. The hierarchical clustering with ssGSEA scores of selected gene sets was used to classify LN tissues. Functional characterization and protein-protein interactions of the differential expression genes (DEGs) of three groups were compared with healthy donors using Metascape (absolute log FC > 1 and adjusted P-value < .05). Kruskal-Walli test and chi-square test were performed to compare the clinical parameters of the different groups.

Results

We analyzed 96 immune-related gene sets in the glomerular and tubulointerstitial regions of LN kidney biopsy samples. The immune-related genes were categorized into three clusters (Immune-Mild, Immune-Moderate and Immune-Severe) based on the degree of immune pathway activation. Interferon-stimulated genes are a hallmark of LN, with high signals in all three clusters. When compared to other groups, the Immune-Mild cluster from the glomerular region showed no T-cell activation or T cell receptor pathway. Also, the Immune-Mild (tubulointerstitial) group also showed minimal lymphocyte activation or migration. Protein-protein interactions networks with MOCDE components further suggested that STAT1 and ISG15 the hub genes in different clusters. The gene expressions of hub genes were then compared among epithelial cells and 21 immune cells from LN and heath controls. Immune clusters are correlated with clinical phenotypes, in which Immune-Mild Group (Glomerular) showed high prevalence of Class II and V LN, and Immune-Mild (Tubulointerstitial) showed more Class V LN. Immune-Severe group also showed higher degree of proteinuria and blood pressure but lower eGFR compared to Immune-Moderate and Immune-Mild groups.

Conclusion

A new molecular classification of LN based on the degree of immune pathway activation shows correlation with clinical manifestations and may potentially guide personalized therapy in LN patients.
#1895 Elucidating Asprosin's role as an intracellular metabolism regulator in diabetes and obesity-induced renal damage
Authors: Park Cheol Whee , Lim Ji Hee , Kim Yaeni , Kim Tae Woo , Kim Eun Nim
Published: May 2024

Background and Aims

Asprosin, an adipokine with a multifaceted function that encompasses inducing insulin resistance, promoting inflammation, and stimulating appetite, is the focus of our investigation. We seek to establish its pivotal role as a mediator in regulating cellular energy metabolism, particularly in the context of renal damage induced by diabetes and obesity.

Method

We conducted experiments using type 2 diabetic db/db mice and obesity-induced high-fat diet mice. These animal models were categorized into two groups: one received Asprosin neutralizing antibodies (250 μg/mouse/21 days), targeting the 28-amino acid peptide located proximal to Asprosin's C-terminus (KKKELNQLEDRYDKDYLSGELGDNLKMK), while the other received an AMPK activator (Metformin) associated with the regulation of Asprosin receptors (OLFR734/G proteins-cAMP-PKA). Additionally, we cultured renal constituent cells (mesangial cells, glomerular endothelial cells) in high glucose and palmitic acid conditions and silencing Asprosin expression using siRNA. We assessed the levels of Asprosin, AMPK, and their respective downstream signaling pathways.

Results

Asprosin was found to be overexpressed in the serum and kidney tissues of both db/db mice and high-fat diet mice, as well as in renal constituent cells cultured under high glucose and palmitic acid conditions. Interfering with Asprosin led to reduced body and liver weight in mice, improved glucose tolerance, and mitigated renal injury in vivo. Asprosin knockdown ameliorated lipid accumulation and inflammatory infiltration, both in vitro and in vivo. Moreover, Asprosin absence activated the AMPK/Sirts/mTOR signaling pathway, while the AMPK activator Metformin reversed the effects of Asprosin on lipid accumulation and inflammatory response, confirming Asprosin's direct role in intracellular lipid metabolism.

Conclusion

The mechanism of intracellular energy metabolism regulation mediated by Asprosin presents promising potential for targeted organ therapy in the development and prevention of diabetic kidney disease. Inhibiting Asprosin suppressed lipid accumulation and inflammation in diabetic kidney disease through the activation of AMPK-associated signaling pathway.
#539 The active ingredient in the Nuphar lutea plant DTBN, ameliorates kidney damage and inflammation in a mouse model of chronic kidney disease (CKD)
Authors: Landau Daniel , Khalilia Jannat , Arazi Eden , Tobar Ana , Gopas Jacob , Segev Yael
Published: May 2024

Background and Aims

Complications associated with Chronic Kidney Disease (CKD), such as disease progression and anemia, are closely linked to heightened inflammation mediated by the innate immune response. This inflammation can be mitigated through the use of anti-inflammatory agents. 6,6′-dihydroxythiobinupharidine (DTBN), an active compound derived from the aquatic plant Nuphar lutea, demonstrates notable anti-inflammatory properties, primarily by inhibiting NF-κB and LPS-induced cytokine activation. DTBN has shown efficacy in priming neutrophils, enhancing phagocytosis, regulating reactive oxygen species (ROS) production, and modulating NET formation. This study aimed to assess the impact of DTBN on CKD in mice.

Method

Male C57BL/6J mice, aged 8 weeks, were subjected to an adenine diet known to induce CKD through crystal deposition and tubulointerstitial inflammation. Both control and CKD-induced mice received intraperitoneal injections of DTBN (25 μg QOD) or saline and were euthanized after 8 weeks for evaluation.

Results

CKD mice treated with DTBN exhibited a significant decrease in serum urea and creatinine levels compared to untreated CKD mice (reduction by 1.4-fold and 1.3-fold, respectively). Histological analysis of kidney tissues revealed a notable reduction in F4/80 positive macrophage infiltration (3.4-fold decrease) and damaged renal areas (three-fold decrease), along with diminished kidney TGF-β levels in DTBN-treated CKD mice. Moreover, the p65 subunit of NF-κB showed a three-fold reduction in CKD mice treated with DTBN compared to untreated CKD mice. Indices of kidney inflammation (IL-1β, IL-6, and P-STAT3) were notably decreased in CKD mice treated with DTBN (reduction by 1.4-fold, 1.6-fold, and 2.9-fold, respectively) compared to untreated CKD mice. Notably, DTBN treatment in control mice did not induce apparent tissue damage; however, it led to reduced weight gain and mild hypoalbuminemia without proteinuria.

Conclusion

DTBN demonstrated significant improvements in renal function and inflammation indices in CKD mice. Hence, DTBN and substances similar to DTBN could be considered as supplementary treatments for CKD patients.
#181 Dysbiosis of gut microbiota in patients with chronic kidney disease
Authors: Yasuno Tetsuhiko , Ito Kenji
Published: May 2024

Background and Aims

The human intestinal tract contains 100 trillion microorganisms, and 500–1000 microbial strains exist in each individual, classified into two main phyla: Firmicutes and Bacteroidetes.

The gut bacterial microbiota is altered in patients with chronic kidney disease (CKD). However, the bacterial composition at each stage of CKD is unclear in these patients, including those receiving renal replacement therapy. In this report, we present the changes in the gut microbiota among patients with CKD.

Method

A total of 93 individuals were recruited for the study. Seventy-three patients had stage 3–5 CKD, including those receiving renal replacement therapy (CKD group), and 20 were age- and sex-matched controls (CKD stage 1–2). Gut microbiome composition was analyzed using a 16S ribosomal RNA gene-based sequencing protocol.

Results

The beta diversity of the samples was evaluated via principal coordinates analysis (PCoA).

The unweighted and weighted UniFrac distances revealed a tendency toward separation of microbiota in the samples according to the CKD stage 1–2 and CKD stage 3–5, 5D groups. At the genus level, the butyrate-producing bacteria Lachnospira, Blautia, Coprococcus, Anaerostipes, and Roseburia were more abundant in the control group (Linear Discriminant Analysis score of >3) than in the CKD group. Lachnospira was more abundant in the control group than in patients with CKD stage 3a. Compared to the control group, multiplex butyrate-producing bacteria were deficient in patients with CKD stage 3b–5D, including in patients receiving renal replacement therapy.

Conclusion

Our findings highlight that the gut bacterial composition, including butyrate-producing bacteria, deteriorates from CKD stage 3b. Even after renal replacement therapy, the bacterial composition did not change.
#2494 Pharmacological enhancement of circadian clock ameliorated fibrosis in adenine induced chronic kidney disease
Authors: Park Sang Hoon , Jo Sang Kyung , Kim Myung-Gyu
Published: May 2024

Background and Aims

Circadian clock regulates diverse biological processes. Recent studies demonstrating the important role of dysregulated molecular clock system in several metabolic diseases as well as in chronic kidney disease (CKD) suggest that modulation of clock machinery might be an attractive therapeutic target.

Method

We optimized a substance (compound X) that enhances the circadian molecular rhythm and validated its effect in HK-2 cells as well as in mouse model of adenine induced CKD.

Results

By using transcriptome analysis of whole kidneys, we identified that 19% of CKD associated genes showed rhythmic expressions in circadian manner. Gene enrichment analysis revealed that the rhythmic genes involved in extracellular matrix/collagen/myofibroblasts showed upregulation while those involved in transport/brush border/proximal tubule showed downregulation in CKD. Treatment with compound X in HK-2 cells resulted in marked attenuation of epithelial mesenchymal transition upon transforming growth factor-b (TGF- b) stimulation. Along with these in vitro data, we also observed the preserved kidney function and less interstitial fibrosis in compound X treated CKD mice. The protective effect was associated with suppression of inflammation, cell cycle arrest/cellular senescence as well as restoration of several transporters in proximal tubular cells.

Conclusion

This is the first study that showed that circadian rhythm might be a novel target for CKD progression by suppressing inflammation/fibrosis and enhancing tubular functions. Unlike other strategies targeting single pathway, targeting circadian rhythm seems to be more promising due to its multi-target effects. A better understanding of the complex role of circadian clock in kidney diseases may provide new perspectives for the prevention and treatment of CKD.
#177 Assessment and comparison of physician gaps related to clinical knowledge of IgA nephropathy
Authors: Larkin Amy
Published: May 2024

Background and Aims

Understanding physician gaps related to IgA nephropathy (IgAN) can inform development of tools to improve physician knowledge and competence related to both diagnosis and treatment. Additionally, comparisons among specialists (nephrologists) and generalists (primary care physicians, PCPs) can segment educational needs for combined or customized education to close identified gaps.

Method

A survey instrument of 25 multiple choice, knowledge- and case-based questions allowed participants to assess their clinical knowledge related to IgAN. The survey was available online to physicians without monetary compensation or charge. Respondent confidentiality was maintained and responses were de-identified and aggregated prior to analyses. Initial data collection occurred from March 16, 2023 to May 19, 2023.

Results

In total, 98 nephrologists and 57 PCPs completed the full assessment within the data collection period.

Conclusion

This assessment of physicians’ clinical knowledge yielded important insights into gaps related to IgAN. Both nephrologists and PCPs need education on pathophysiology of IgAN and emerging treatment pathways, role of proteinuria and risk correlations to ESRD with IgAN, clinical use of the International IgAN Prediction Tool, and KDIGO recommendations for managing IgAN. PCPs need additional education on basic IgAN prevalence as well as clinical strategies for diagnosis. Further studies are planned to assess the effect of medical education on decreasing these clinical practice gaps.
#2836 Prevalence and risk factors associated with chronic kidney disease among type-2 diabetes mellitus patients – a single centre experience
Authors: Suvvari Tarun Kumar
Published: May 2024

Background and Aims

Globally, diabetes mellitus is one of the major causes of increased morbidity. One of the key complications of T2D is chronic kidney disease (CKD). Current evidence demonstrates that people with type 2 diabetes (T2D) are at a higher risk of developing chronic kidney disease (CKD) with greater morbidity and mortality. So, we aimed to find out the prevalence of CKD among T2DM patients and to evaluate the correlation between age, duration of diabetes, HbA1c, and UACR with eGFR among T2DM patients.

Method

An observational cross-sectional study was conducted at department of medicine, tertiary care hospital for 2 months. Along with demographic and anthropometric data The following clinical data were collected: estimated glomerular filtration rate (eGFR), serum creatinine, urinary albumin creatinine ratio (UACR), and HbA1c levels. Spearman rank correlation was used to determine the correlation between eGFR and various parameters.

Results

A total of 96 patients were included in the study. 65% of the study participants were sedentary and 35% were physically active. 41 (42.7%) were obese and 21 (21.9%) were overweight. The mean Duration of diabetes is 5.62 ± 4.68 years. The mean estimated glomerular filtration rate (eGFR) is 74.33 ± 31.01 mL/min/1.73 m2. The Prevalence of CKD is 35.4%. 21.8% belongs to G3a category and 8.3% belongs to G3b category. Spearman's correlation coefficient test revealed negative correlation between eGFR and duration of diabetes, HbA1c and UACR (Spearman's correlation coefficient values are −0.577, −0.595 and −0.709 respectively).

Conclusion

In conclusion, nearly 1/3rd of study participants reported CKD. Our study provides consistent and recent clinical data showing an inverse association of eGFR with age and duration of diabetes. This study highlights that age and duration of diabetes are key parameters associated with declining renal functions in people with T2DM.
#1082 Early-stage chronic kidney disease as a risk factor for suicide: a nationwide observational cohort study
Authors: Joo Kwon Wook , Park Sehoon , Kim Jung-Hyun
Published: May 2024

Background and Aims

Chronic kidney disease (CKD) is associated with poor psychological well-being. Whether early-stage CKD is a risk factor for suicide warrants further research.

Method

This nationwide, retrospective, cohort study aimed to evaluate the risk of suicide in patients with early-stage CKD and identify the associated risk factors. A total of 3 945 198 individuals aged ≥19 years who underwent the 2009 national health screening were enrolled. Among them, 202 291 patients had early-stage CKD (estimated glomerular filtration rate (eGFR) ≥30 and <60 mL/min per 1.73 m2 and/or dipstick albuminuria ≥1+). The study outcome was suicide as confirmed by the nationwide death register based on death certificates.

Results

The study population had a mean age of 59 ± 15 years, and 47% were male. We identified 930 suicides (incidence rate, 0.45 per 1 000 person-years) in the CKD group and 11 332 suicides (incidence rate, 0.27 per 1 000 person-years) in the non-CKD group. Early-stage CKD was significantly associated with an increased risk of suicide in multivariable analysis adjusted for demographic characteristics; lifestyle habits; comorbidities, including diabetes and hypertension; economic status; and depression (hazard ratio, 1.16; 95% confidence interval, 1.09‒1.25). Suicide risk was higher in individuals with proteinuria but preserved kidney function (eGFR >60 mL/min per 1.73 m2 and dipstick albuminuria >1+) than in those without CKD. In the CKD group, older males and current smokers had a higher risk of suicide.

Conclusion

CKD even in the early stages is associated with significantly higher risk of death from suicide. Hence, healthcare providers may need to examine the mental health of patients with early-stage CKD and other risk factors to prevent suicide.
#501 Evaluation of the accuracy of serum creatinine-based GFR calculations across the different levels of renal function among Filipinos
Authors: Pangan Ghiyll Evannie , Villanueva Anthony Russell
Published: May 2024

Background and Aims

Chronic kidney disease (CKD) is a worldwide health concern which continues to increase in prevalence. Early studies have evaluated kidney function by measuring serum creatinine (sCr) and/or the estimated glomerular filtration rate (eGFR). To date, there are limited studies that correlate nuclear GFR scans and eGFR by equations that include the Cockroft-Gault (CG), Modification of Diet in Renal Disease (MDRD), and Chronic Kidney Disease Epidemiology Collaboration equation (CKD-EPI) 2021 in Asians, specifically in a Filipino population. This study aims to compare the accuracy of GFR scan results and GFR estimated from the formulas across different levels of kidney functions, age groups, gender, and co-morbidities among a Filipino subset.

Method

A cross-sectional study was done among 2986 patients who underwent Nuclear GFR scan in a single kidney center. Results obtained were compared to estimated GFR results. Weighted Kappa and Bland-Altman Analyses were used to test for agreement between the measured and estimated GFR results.

Results

Absolute GFR values derived from the three equations demonstrated moderate reliability with results from nuclear scan when intraclass correlation coefficients were calculated with CKD-EPI 2021 being the highest. When further categorized into GFR levels, there was substantial level of agreement between each equation and GFR scan, with all weighted kappa coefficients being at least 0.700 with CG having the highest result (Table 1). Furthermore, when subgroup analysis was done according to age group, gender, and comorbidities, CG was found to be the most accurate per category (Table 2).

Conclusion

CKD-EPI 2021 was the most accurate in the actual GFR values however we cannot fully eliminate the utility of CG due to its categorical accuracy and in monitoring the deterioration of renal function.
#1575 Cardio-renal syndrome in patients with Fabry disease on enzyme replacement therapy
Authors: Parshina Ekaterina , Prokopenko Elena , Zulkarnaev Aleksei , Popov Mikhail , Kotalevskaya Yulia , Shumakov Dmitry , Gubina Daria
Published: May 2024

Background and Aims

Fabry disease (FD) is a rare X-linked lysosomal storage disorder in which mutations of the GLA gene cause a decreased or absent activity of the alpha-galactosidase A (α-Gal A) and intracellular accumulation of globotriaosylceramide and other sphingolipids [1]. FD causes a variety of symptoms, including heart and kidneys damage - cardiorenal syndrome (CRS) type 5. In patients with FD, CRS is known to increase the risk of cardiovascular events and death [2].

The aim of our study was to assess renal function and outcomes in patients with FD and CRS receiving enzyme replacement therapy (ERT).

Method

We performed a retrospective analysis of the medical records of 10 patients (pts) from 7 unrelated families with established diagnosis of FD and cardiac and renal involvement. Pts #1 and #3 are siblings, pt # 10 is their mother; pt #9 is mother of pt #8 (Table 1). The diagnosis was confirmed by DNA diagnostics in all plus levels of α-Gal A enzymatic activity, globotriaosylsphingosine concentrations in some patients. All the patients underwent ERT. Seven out of 10 patients received blockers of the renin-angiotensin-aldosterone system, 3 - did not receive due to contraindications.

Results

All 10 patients, including 3 women, had left ventricular hypertrophy - left ventricular wall thickness (LVWT) ≥ 1.2 cm. (Table 1). Average LVWT was 1.850 ± 0.097 cm. Two patients had atrial fibrillation. None of the patients had proteinuria 1 g/24 h or higher. In all еGFR was below 60 ml/min/1,73 m2: 4 patients had CKD-G3a, 4 – G3b, 1 – G4 and 1 – G5. Average еGFR was 41,111 ± 8.069 ml/min/1,73 m2 excluding hemodialysis (HD) patient.

There were 4 unfavorable outcomes in our group: death occurred in 3 patients from cardiac pathology (congestive heart failure), one patient reached CKD-G5 at 25 years of age and started HD treatment. Patient on HD, brother of deceased pt #1, began receiving ERT after the start of renal replacement therapy. The death of pt #1, who had a very high Lyso-Gb3 level - 118.36 ng/ml (normal 0.05-3.0 ng/ml), appears to be related to the late diagnosis and delayed start of ERT.

Conclusion

Patients with FD and CRS are likely to have a high risk of cardiovascular complications, loss of kidney function and death, especially with a late start of enzyme replacement and cardio-renoprotective therapy. Early diagnosis of FD and timely initiation of treatment are important in preventing the serious complications and death.
#742 High TSH and low FT3 levels are associated with chronic kidney disease in three population-based studies from Germany
Authors: Stracke Sylvia , von Rheinbaben Sabrina Freiin , Voelzke Henry , Gollasch Maik , Koenig Maximilian , Steinhagen-Thiessen Elisabeth , Ittermann Till
Published: May 2024

Background and Aims

High serum thyroid-stimulating hormone (TSH) levels have previously been associated with a low estimated glomerular filtration rate (eGFR), but studies associating thyroid hormone levels with albuminuria revealed inconsistent results. The aim of our study was to investigate associations of serum levels of TSH, fT3 and fT4 with eGFR and albuminuria in population-based cohorts.

Method

We used cross-sectional data from 7,933 individuals aged 20 to 93 years of the Berlin Aging Study II (BASE II) and the Study of Health in Pomerania (SHIP-START; SHIP-TREND) to associate serum TSH, fT3, and fT4 levels with eGFR and albuminuria. To calculate eGFR, CKD-EPI and FAS equations were used. Albuminuria was defined as an urinary albumin-to-creatinine ratio (UACR) ≥ 30 mg/g.

Results

In multivariable analyses adjusted for confounding, we found inverse non-linear associations of serum TSH levels with eGFR, while serum fT3 levels showed a positive association with eGFR. High as well as low serum fT4 levels were associated with a lower eGFR. Age but not sex modified the association between thyroid hormone levels and eGFR. The inverse associations between serum TSH levels with eGFR were strongest in the youngest age groups, while the positive associations between serum fT3 levels and eGFR were strongest in older individuals. No significant associations between thyroid hormone levels and albuminuria were found.

Conclusion

In conclusion, we showed that high TSH, low fT3 as well as low and high fT4 levels were independently associated with a reduced kidney function in a non-linear fashion. Our results indicate that high TSH / hypothyroidism might be associated with a reduced kidney function. Thyroid function might be more tightly related to the eGFR than to albuminuria in the general population.
#1668 The 60:40 conundrum: are women with CKD discriminated against after referral to a nephrology clinic?
Authors: Vautcranne Adèle , Bianco Lavinia , Mazé Béatrice , Fois Antioco , Chatrenet Antoine , Moio Maria Rita , Torreggiani Massimo , Piccoli Giorgina
Published: May 2024

Background and Aims

The representation of women in kidney medicine clinical trials has diffused the belief that women are discriminated although epidemiological data suggest that chronic kidney disease (CKD) is more prevalent among females than males. We aimed to test whether sex distribution varies at nephrology referral, inclusion in a clinical study or at the starting of dialysis.

Method

This was a retrospective, monocentric study conducted in a large non-university hospital in central France. We exploited data from patients included in the PRO-RE-RE-PRO study on the effect of diet on the progression of CKD. We evaluated patients’ characteristics and gender at the time of the first consultation in the Unit for the Care of Advanced CKD (UIRAV), at the inclusion in the PRO-RE-RE-PRO study and at the beginning of the kidney replacement therapy.

Results

866 patients were included in this study as they were referred to the UIRAV, 59% males and 41% females. Female patients were older but less comorbid and were referred at the same eGFR than males. The same proportion of males/females was observed in patients included in the PRO-RE-RE-PRO study. No sex differences were observed at dialysis start. Survival was significantly higher in females. Overall, distribution across sex remained stable over time.

Conclusion

The main result of this study is the stability of the approximately 35-40% female to 60-65% male ratio from start of follow-up in all subsets of cases: patients referred to the unit dedicated to advanced CKD, patients recruited in the observational study, patients not included, or who refused to participate, patients on follow-up at the completion of the database. Furthermore, the same distribution is observed in dialysis patients, from dialysis start to the most recent update. Our data suggest that if a gender-selection bias exists in nephrology, it should be sought before the first nephrology referral. However, further studies are needed to ensure health equity.
#2373 Malignant tumors of the urinary bladder and Balkan endemic nephropathy – a 45 year study
Authors: Apostolovic Branislav , Glogovac Stevan , Tasic Danijela , Sterkovic Srdjan , Petrovic Ana , Petrovic Milan , Dimitrijevic Zorica , Paunovic Karolina , Mladenovic Slavoljub , Prokopovic Miomir , Bašić Dragoslav , Mitic Branka
Published: May 2024

Background and Aims

Balkan endemic nephropathy (BEN) is a chronic interstitial kidney disease limited geographically to specific regions. The wider importance of BEN is reflected in its associations with malignant tumors of the urothelium. For researchers, malignant tumors of the urinary bladder (MTUB) have been less studied and perhaps considered less interesting compared to malignant tumors of the upper urothelium. Balkan endemic nephropathy (BEN) is a chronic interstitial kidney disease limited geographically to specific regions. The wider importance of BEN is reflected in its associations with malignant tumors of the urothelium. For researchers, malignant tumors of the urinary bladder (MTUB) have been less studied and perhaps considered less interesting compared to malignant tumors of the upper urothelium.

Method

Balkan endemic nephropathy (BEN) is a chronic interstitial kidney disease limited geographically to specific regions. The wider importance of BEN is reflected in its associations with malignant tumors of the urothelium. For researchers, malignant tumors of the urinary bladder (MTUB) have been less studied and perhaps considered less interesting compared to malignant tumors of the upper urothelium.

Results

During the observed period, there were a total of 1447 cases of MTUB - 1109 (76.64%) male patients and 338 (33.36%) female patients. The average annual incidence rate (AAIR) of MTUB in endemic settlements for the observed period (1978-2024) is 15.64; in hypoendemic areas is 13.89, and in non-endemic areas is 14.62. The AAIR of MTUB in endemic settlements is 1.13 times higher than the rate in hypoendemic areas and 1.07 times higher compared to non-endemic settlements.

It is noteworthy that in the first period of observation, the AAIR of MTUB in endemic areas is 2.24 times higher than the rate in hypoendemic areas and 4.09 times higher than the rate in non-endemic areas. However, in the second and third periods of the study, it is significantly lower compared to the rates in hypoendemic and non-endemic areas.

The linear trend of MTUB for the observed period in endemic settlements is negative without statistical significance (y = −0.012x + 701; r2 = 0.048), while in non-endemic areas, it is positive and statistically significant (y = 1.340x + 0.172; r2 = 0.647).

Conclusion

The higher frequency of MTUB in the Jablanica district over the 45-year study of the region with BEN is limited to the first part of the research and may indicate a common nephropathogenic and carcinogenic etiological factor, confirming a positive correlation between BEN and malignant urothelial tumors. At the same time, in the last 25 years of the observed period, there has been a drastic decline in the frequency of both BEN and MTUB, as well as malignant tumors of the upper urothelium.
#3001 MtDNA copy number correlates to coronary artery calcium score and biological age in kidney failure patients
Authors: Schwarz Angelina , Qureshi Abdul Rashid Tony , Filograna Roberta , Wennberg Lars , Wernerson Annika , Witasp Anna , Stenvinkel Peter
Published: May 2024

Background and Aims

Chronic kidney disease (CKD) and kidney failure are connected to increased oxidative stress and vascular calcification, which are indicators for development of comorbidities and mortality outcome. Mitochondrial (mt)DNA copy number has been reported as independent predictor for frailty and mortality outcome of various cardiovascular diseases (CVD) and cancer.

We aimed that mtDNA copy number in whole blood of kidney failure patients can be correlated to coronary artery media calcification score and coronary artery calcium (CAC) score and be used as an independent predictor for comorbidities and mortality outcome.

Method

Quantitative PCR (qPCR) with TaqMan® probes for three mtDNA genes (mtND1, mtND4 and mtCOX1) and two single locus genes on nuclear DNA (hemoglobin subunit beta and 18S), for normalization, is performed on DNA samples isolated from collected blood of 196 kidney transplant donors and 211 recipients at basal timepoint and 32 at 1-year-follow-up timepoint, included in the KaroKidney biobank. Resulting mtDNA copy number is investigated for correlation to CAC score, patient mortality outcome, biological age determined by skin autofluorescence and other clinical parameters.

Results

In our Swedish kidney transplant cohort we can see statistically significant difference in mtDNA copy number between kidney failure patients (recipients) and healthy controls (donors). No obvious difference between females and males was observed. mtDNA copy number correlates to biological age determined by skin autofluorescence, CAC score and Framingham CVD risk score. In the 32 1-year-follow-up samples we could see significant increase/recovery of mtDNA copy number for male patients compared to their baseline before receiving a transplant.

Conclusion

In this study we show that mtDNA copy number in kidney failure patients correlates to biological age and CAC score, affirming mtDNA copy number as an independent predictor of frailty in this Swedish cohort of CKD patients. Additionally, we can see that a kidney transplant can lead to a significant increase of mtDNA copy number in blood one year later, suggesting a general increase in health quality.