bluuebunny/crossref_metadata_2025 huggingface dataset:
#2949 Diverse effect of STAT3 inhibition on murine primary tubular epithelial cells
Authors: Manzéger Anna , Szakal Zsofia , Kokeny Gabor
Published: May 2024

Background and Aims

The incidence of chronic kidney diseases increases worldwide, and kidney fibrosis is the final common pathway regardless of the etiology. TGF-β plays a crucial role in the pathogenesis, affecting pro-fibrotic genes and transcription factors. STAT3 (signal transducer and activator of transcription 3) acts via the JAK/STAT signaling. Inhibition of STAT3 in animal studies was shown to attenuate the progression of kidney fibrosis. Yet, the effect of STAT3 inhibition on renal tubular epithelial cells has not been elucidated. We aimed to investigate in vitro the impact of pharmacological STAT3 inhibition with NSC74859 (NSC) and STATTIC on the expression of fibrosis associated genes of primary tubular epithelial cells.

Method

Primary tubular epithelial cells from kidneys of C57Bl6/J mice were isolated and used in our studies. Cells (P10-P15) were seeded on gelatin-coated 6-well culture plates (100000 cells/well) and subjected to treatment with 10 ng/ml TGF-β, 100 µM NSC, 10 µM STATTIC or vehicle (n = 3/group) as follows: Control; NSC; STATTIC; TGF-β; TGF-β+NSC; TGF-β+STATTIC. After 24 h treatment, mRNA and protein expressions were analyzed. Statistical evaluation was performed using Kruskal-Wallis test.

Results

In cells not treated with TGF-β, neither NSC nor STATTIC treatment affected the expression of Tgfb1 (TGF-β) and Acta2 (SMA) genes compared to controls (100%), but reduced Col1a1 expression to 58% and 54%, respectively (p < 0.05). NSC reduced to 54%, while STATTIC tended to increase (169%) the gene expression of Egr2 transcription factor. TGF-β treatment induced STAT3 phosphorylation by 45% accompanied by a fibrotic response and epithelial-to-mesenchymal transition (EMT) as indicated by significantly increased Tgfb1, Acta2, Egr2 and Col1a1 (p < 0.05). NSC treatment did not inhibit the TGF-β-induced Tgfb1 upregulation (178%), but markedly, although not significantly, reduced the expression of Acta2 (100%), Egr2 (98%) and Col1a1 (114%) in the TGF-β+NSC group. Interestingly, although STATTIC treatment dramatically inhibited STAT3 expression (38%, p < 0.05) it significantly enhanced the TGF-β-induced overexpression of Tgfb1 (210%, p < 0.01) and Egr2 (307%, p < 0.05), while markedly reduced Acta2 (64%, p < 0.001) and Col1a1 (81%, p < 0.01) in the TGF-β+STATTIC group.

Conclusion

Our results indicate that in vitro inhibition of STAT3 using two inhibitors with same mode of action lead to diverse responses in primary murine tubular epithelial cells, partially suppressing EMT markers but inducing pro-fibrotic EGR2. Further studies are needed to clarify the underlying mechanisms.
#1894 Disappearance of proteinuria is not a surrogate marker of improvement in IgA nephropathy
Authors: Cho Byoung-Soo , Yun Hyaejin , Jung Sungmin , Cho Won Hee , Lee Hyun-Soon
Published: May 2024

Background and Aims

IgA nephropathy is one of the most common chronic glomerulonephritis and 30-45% falls into chronic kidney disease over a period of 20 to 25 years. Lots of treatment regimens are tried such as RAAS blocker, corticosteroids, complement inhibitors, Nefecon, Atrasentan, SGLT2 inhibitor etc., however disappearance of proteinuria has been regarded as surrogate marker of improvement. We performed follow up renal biopsy to confirm the efficacy of disappearance of proteinuria.

Method

During last 10 years, our clinic performed 1,867 cases of renal biopsies at OPD level. Of which 585 cases (31.3%) were IgA nephropathy.

We performed follow up renal biopsies in 149 cases, who showed improved proteinuria after methylprednisolone pulse therapy.

Follow renal biopsy findings were divided into 3 groups:

One cycle of methylprednisolone pulse therapy consists of methylprednisolone (20-30 mg/kg, max 1 gm/day) for 3 consecutive days. Depends on the pathological grade, we performed 3 to 17 cycles every 2 weeks.

Results

Male to female ratio was 0.96(73:76), Mean age was 38.4 years old. Of the 149 follow up biopsies, 75 cases (50%) showed improved pathology (Group A), 60 cases (40%) showed no pathological changes (Group B) and 14 cases (10%) showed aggravated pathology (Group C).

Conclusion

Normalized proteinuria could not be a surrogate marker of renal improvement, because only 50% showed pathological improvement. Follow up renal biopsy might be a mandatory procedure to define the efficacy of treatment in IgA nephropathy.
#1153 Short course of steroids as a treatment for immune checkpoint inhibitors-associated acute kidney injury
Authors: Escribano Teresa Cavero , Lopes Vanessa , Ordoñez Katherine Peña , Soto Mara Serrano , Pérez Mariana Rivera , Valdivia Verónica Ruth Mercado , Moliz Candela , Macia Manuel , Gutiérrez Eduardo , Auñón Pilar
Published: May 2024

Background and Aims

Immune checkpoint inhibitors (ICPi) have been a revolution in oncology. Due to their mechanism of action they can produce inflammatory adverse events, called “immune related adverse events” (IrAEs). Immune-mediated renal toxicity appears to be infrequent (2.2-5%), with acute tubulointerstitial nephritis being the most common form, clinically manifested as acute kidney injury (AKI). Corticosteroids are a highly effective treatment. However, the most suitable regimen has not been established.

Method

Retrospective multicenter study to evaluate the efficacy and safety of a short course of steroids (Group A) versus a long course (Group B) in patients with a clinical or histologic diagnosis of ICPi-associated acute kidney injury (ICPi-AKI). Short-duration regimen was considered to be that with a duration ≤3 months. Renal response was assessed 3 months after initiation of steroid therapy. Partial and complete renal response rates were compared in both groups, as well as relapses of ICPi-AKI with the lowering or suspension of steroid treatment. The development of adverse effects attributable to corticosteroids and the evolution of the oncologic disease were also evaluated.

Results

Sixty-three patients were included, 30 (48%) of whom received a short course of corticosteroids. Type of malignancy and oncologic treatment were similar in both groups. Baseline serum creatinine (1.1 mg/dL Group A and 0.9 mg/dL Group B; p = 0.53) and at ICPi-AKI diagnosis (3.0 mg/dL in Group A and 2.8 mg/dL in Group B; p = 0.43) were comparable. As shown in the table below, cumulative prednisone dose was lower in Group A than in Group B (1654 mg vs 4030 mg; p = 0.001). The overall renal response was 92% (87% Group A and 97% Group B; p = 0.2). There were no differences in complete response (40% Group A and 40% Group B; p = 1) or partial response (47% Group A and 57% Group B; p = 0.4). There were no recurrences of AKI after rechallenge of ICPi treatment. Adverse events related to corticosteroids were similar. There was a trend towards greater progression of oncologic disease in group B (64% versus 40%; p = 0.08).

Conclusion

A short course of steroids (< 3 months) is equally effective as a treatment for ICPi-AKI as longer courses, both in terms of renal response and relapse rate of ICPi-AKI. Adverse events related to steroid treatment were comparable in both groups. There appeared to be greater oncologic progression in the prolonged steroid treatment group.
#1472 Prevalence of Mendelian and non-Mendelian forms of genetic disease in a Swiss cohort of adult kidney stone formers
Authors: Anderegg Manuel , Olinger Eric , Bargagli Matteo , Geraghty Rob , Pohlmeier Lea , Nater Alexander , Sayer John , Vogt Bruno , Halbritter Jan , Schaller André , Fuster Daniel
Published: May 2024

Background and Aims

Molecular mechanisms of kidney stone formation remain unknown in most patients. Previous studies showed high heritability of nephrolithiasis, but analysis of Mendelian disease in selected cohorts and genome-wide analysis were yet unable to entirely explain heritability. While prevalence of Mendelian disease in selected nephrolithiasis cohorts has already been studied, data on prevalence and characteristics of genetic disease in unselected adults with nephrolithiasis are lacking. This study was conducted to fill this important knowledge gap.

Method

We performed whole exome sequencing in 787 participants of the Bern Kidney Stone Registry, an unselected cohort of adults with ≥1 past kidney stone episode (KSF), and 114 non-stone-forming individuals (NKSF). An exome-based panel of 34 established nephrolithiasis genes was analyzed and variants assessed according to ACMG criteria. Pathogenic (P) or likely pathogenic (LP) variants were considered diagnostic.

Results

Mean age of KSF was 47 ± 15 years, and 18% were first time KSF. A Mendelian kidney stone disease was present in 2.9% (23 of 787) of KSF. The most common genetic diagnoses were cystinuria (SLC3A1, SLC7A9; n = 13), Vitamin D-24 hydroxylase deficiency (CYP24A1; n = 5) and primary hyperoxaluria (AGXT, GRHPR, HOGA1; n = 3). 8.1% (64 of 787) of KSF were monoallelic for LP/P variants predisposing to nephrolithiasis, most frequently in SLC34A1/A3 or SLC9A3R1 (n = 37), CLDN16 (n = 8) and CYP24A1 (n = 8). KSF with Mendelian disease had a lower age at the first stone event (30 ± 14 years vs. 36 ± 14 years, p = 0.003), were more likely to have cystine stones (23.4% vs. 1.4%) and less likely to have calcium oxalate monohydrates stones (31.9% vs. 52.5%) compared to KSF without genetic diagnosis. The phenotype of KSF with variants predisposing to nephrolithiasis was subtle and showed significant overlap with KSF without diagnostic variants. In NKSF, no Mendelian disease was detected, and LP/P variants were significantly less prevalent compared to KSF (1.8% vs. 8.1%).

Conclusion

Mendelian disease is uncommon in unselected adult KSF, yet variants predisposing to nephrolithiasis are significantly enriched in adult KSF. While the identified variants predisposing to nephrolithiasis may explain some of the unresolved heritability, likely additional intermediate effect size variants in known and yet unknown kidney stone genes remain to be discovered for us to fully understand the genetic factors leading to the high heritability of nephrolithiasis.
#1028 Experience with ravulizumab in atypical hemolytic uremic syndrome
Authors: Saiz Víctor Joaquín Escudero , Chillarón Marta Martínez , Morantes Laura , Grau Julia Ollé , Guillen-Olmos Elena , Xipell Marc , Molina-Andujar Alicia , Piñeiro Gaston , Poch Esteban , Bastida Carla , Porras Luis Fernando Quintana , Pelicano Miquel Blasco
Published: May 2024

Background and Aims

The arrival of eculizumab revolutionized the treatment of Atypical Hemolytic Uremic Syndrome (aHUS). Ravulizumab also offers C5 inhibition, but with 3-4 times longer half- life. We describe the experience with ravulizumab in patients with aHUS in two scenarios: 1. Switching from another C5 inhibitor in stable patients; 2. Direct initiation of therapy with ravulizumab (naïve).

Method

We present 9 patients with an average age of 42 ± 13 years and weight of 81 ± 12.4 kg. The switch to ravulizumab was initiated 2 weeks after the last dose of eculizumab in switch patients, while in naïve patients it was initiated after excluding other causes of aHUS. The initial dose was 2700 mg, followed by a second dose of 3300 mg after 2 weeks, and subsequently every 2 months. Analytical variables of renal function, hematological parameters, and complement were collected.

Results

Switch : 6 patients (50% females), 4/6 were transplant recipients (3 on prophylactic treatment). Regarding renal function, 5/6 patients had a complete response with eculizumab (creatinine 1.33 ± 0.32 mg/dL, eGFR 59.5 ± 34.3 mL/min/1.73 m2, proteinuria 115 ± 91.5 mg/g), and all of them had a complete hematological response. After the switch, all patients maintained a complete hematological response, stability of renal function, and serum complement levels.

Naïve : 3 cases (2 males); 2/3 required hemodialysis (HD) at presentation. The renal response was complete in two patients and partial in the third (who discontinued HD after 90 days and currently remains stable with stage G3b chronic kidney disease). All three patients had a complete hematological response.

Only 3 adverse effects were documented (arthralgia, headache, and rhinitis), with no cases of infection.

Conclusion

The use of ravulizumab is effective both in maintaining a complete response after switching from eculizumab and as a first-line therapy. The safety profile is comparable, with the main difference being the dosing regimen, as ravulizumab requires fewer administrations and leads to a reduction in direct and indirect costs.
#2167 Polyclonal immunoglobulin free light chains: an evidence of cardiac remodeling in patients with glomerular diseases
Authors: Churko Anna , Rumyantsev Aleksander
Published: May 2024

Background and Aims

It was previously shown, that polyclonal immunoglobulin free light chains (FLC) are the independent predictor of mortality in patients with decompensated heart failure, chronic kidney disease (CKD) and also in general population. Mechanisms of this phenomenon are still unknown. The aim of our study is to reveal the possible relationships between FLC and cardiac remodeling in patients with glomerular diseases.

Method

We included 97 patients with biopsy-proven diagnosis of different immune-mediated glomerular diseases, 53% were men, mean age was 48 ± 14.6 years. Serum Freelite FLC levels were measured as well as standard clinical and laboratory investigation. At the time of biopsy transthoracic echocardiography was also performed. Glomerular filtration rate (eGFR) was estimated by “2021 CKD-EPI Creatinine” equation.

Results

Median of eGFR was 46.8 ml/min/1.73 m² (28.7-80.0), FLC-kappa level was 27.4 mg/l (16.8- 48.4), FLC-lambda level was 28.2 mg/l (20.8-43.3). FLC-kappa levels were above reference range in 65%, FLC-lambda levels – in 54%. LV diastolic dysfunction (DD) was present in 68%. Comparison in groups showed that the elevation of FLC-kappa more than 19.4 mg/l was associated with bigger LV mass index (LVMI) – 138.3 ± 30.2 g/m² vs 99.9 ± 31.2 g/m² р = 0.022, the parallel correlation was found between LVMI and levels of FLC-lambda higher than 26.3 mg/l (136.2 ± 64.8 g/m² vs 104.0 ± 36.6 g/m², р = 0.023). Spearman analysis has shown statistically significant correlations between FLC levels and E/e’- Rs = 0.501 p = 0.0001 for FLC-kappa, Rs = 0.343 p = 0.012 for FLC-lambda. Combined FLC level higher than 52.9 mg/l was a significant predictor of DD with area under the ROC curve (AUC) 0.703 (sensitivity 76.5%, specificity 62.5%).

Conclusion

Elevation of serum pFLC level could be a promising marker of cardiac remodeling, especially, of DD in patients with glomerular diseases. Possible pathogenic role of FLC in cardiorenal relationships may be revealed in further studies.
#2111 Prediction of ESRD in IgA nephropathy using IgA: C3 ratio at diagnosis. 10 year cohort
Authors: Ker Robert , Rankin Alistair , Doyle Arthur
Published: May 2024

Background and Aims

IgA Nephropathy is the commonest glomerular pathology with a wide range of outcomes depending on the severity of the circulating serological pathophysiology and on the resulting inflammatory response in the kidney. Prediction of kidney loss, which results in renal failure in 20-40% of cases -versus very benign disease, has largely used traditional clinical parameters such as proteinuria, hypertension and already established renal decline at the point of diagnosis. There has been variable utility from biopsy severity scoring. Pathogenicity of IgA immune complexes may result from activation of complement via the alternative pathway and assessment of serum IgA and complement C3 has been suggested as a marker of pathogenicity. We examined the utility of IgA to C3 ratio in predicting outcomes in a cohort over 10 years

Method

We examined all the electronic records of biopsy proven IgA cases from 2010 onwards when serum electrophoresis and serum complement became been widely tested at all new renal presentations. These cases were followed to end stage kidney disease or death. A subset of diagnosed patients also had MEST-C score.

Results

Of 319 biopsy proven IgA cases between 2010 and 2023, 216 had serum IgA and complement studies at diagnosis, with median PCR 309 and median serum creatinine 177. 56 patients had IgA:C3 >4. Outcome of “death or renal replacement therapy” rather than the surrogate “RRT or doubling serum creatinine” was possible due to the length of follow up. Median follow up was 4.5 years, during which 101 (46%) died or reached ESRD. Among those with IgA:C3 > 4, 35 (61%) median survival 5 years, versus 67(42%) of those < 4 (median survival 10 years). Hazard ratio for IgA:C3 >4 was 1.9 (1.2-3.2) Cox Proportional Hazard show this to be independent from presenting creatinine, proteinuria, but not independent of age.

A cohort of 107 biopsy proven IgA cases between 2010 and 2015 had data on CMEST score. 62 of this cohort also had IgA and complement measured. There was no correlation with CMEST score, or occurrence of crescents present on biopsy

There were no differences in the treatments used following diagnosis of IgA Nephropathy. Similar proportions receiving steroid, calcineurin or mycophenolate.

Conclusion

IgA to C3 ratio is readily available result which powerfully predicts IgA outcome independently from pathology score and traditional clinical severity estimates. It may well become a useful indicator to target novel immune/complement therapies.
#2684 Free light chains levels in ANCA associated vasculitis: a new potential inflammatory biomarker
Authors: Kronbichler Andreas , Barnini Cecilia , Matyjek Anna
Published: May 2024

Background and Aims

Anti-neutrophil cytoplasmic antibody (ANCA)-associated vasculitis is a systemic disease characterized by an immune-mediated process where inflammation plays a central role. The widely available serum biomarkers of inflammation are not always able to detect ongoing disease activity in ANCA-associated vasculitis (AAV) patients. Free light chains (FLCs) expression levels have been proposed as new promising biomarker in some immune-mediated and inflammatory diseases. The aim of this study is to evaluate the expression levels of FLCs in patients affected by AAV and investigate the potential effect of rituximab treatment on FLCs levels.

Method

We conducted a retrospective multicenter study enrolling AAV patients in complete remission of AAV (defined as BVAS/GPA = 0); those with clinical suspicion of underlying hematologic malignancy were excluded. We analyzed κ and λ FLCs serum concentrations and evaluated their correlation with biomarkers of immune system activation, such as erythrocyte sedimentation rate (ESR), C-reactive protein (CRP), serum immunoglobulin (Ig) levels, serum C3 and C4 complement and albumin levels (which has a negative correlation with acute inflammatory phase). We assessed impact of rituximab (RTX) therapy within the last 6 months on the same laboratory parameters.

Results

A total of 137 patients with AAV were recruited, who were gender balanced, had an average age of 68 years and an estimated glomerular filtration rate of 68 (43-89) mL/min/1.73 m2. Fifty-one patients received rituximab treatment (RTX group), while 86 patients were on other immunosuppressive maintenance therapies (non-RTX group). In comparison to non-RTX group, patients treated with RTX experienced higher complement C3 levels, lower ESR levels and lower FLCs κ (p = 0.063) and λ (p = 0.013) levels. The differences between RTX and non-RTX groups in terms of FLCs were even more prominent after correction to total Ig concentration (p = 0.004 for κ /Ig and p = 0.003 for λ /Ig, respectively). Both, serum free κ and λ levels were found to correlate significantly with ESR (R = 0.55 and p < 0.001 for κ; R = 0.53 and p < 0.001 for λ) and albumin (R = ‒0.38 and p < 0.001 for κ; R = ‒0.33 and p < 0.001 for λ). Additionally, serum free κ levels showed an inverse association with C3 (R = ‒0.18 and p = 0.041).

Conclusion

In subjects with AAV, FLC levels were found to be associated with markers of inflammation and complement activation; hence FLCs levels may represent a promising biomarker for detection of subclinical inflammation in AAV patients on maintenance therapy. Rituximab therapy showed a potential to reduce the levels of markers of subclinical inflammation, including FLCs.
#1532 Correlation between TNF-alpha, IL-4 and IL-6 levels and vitamin D in patients with SLE lupus nephritis
Authors: Khusankhodjaeva Feruza , Sharapov Olimkhon , Daminova Kamola
Published: May 2024

Background and Aims

Systemic lupus erythematosus (SLE) is an autoimmune connective tissue disease characterized by multisystem organ damage and high titers of autoantibodies to a number of nuclear and cytoplasmic antigens. Numerous abnormalities of the cytokine network have been observed in patients suffering from SLE. However, the relationship between cytokines and vitamin D in damage to the kidneys and various organs has not been studied enough.

Aim

To determine whether interleukin-6.4 (IL-6.4) and tumor necrosis factor (TNF-alpha) levels correlate with vitamin D deficiency in patients with SLE/FN.

Method

We determined the levels of TNF-alpha, IL-6, IL-4 and vitamin D in the blood of patients with SLE/FN in 108 people.

Results

Levels of TNF-alpha, IL-4 and IL-6 were higher in SLE/FN patients with vitamin D deficiency. Further analysis showed that this association was dependent on an inverse correlation (P = 0.017, r = ‒0, 49) for IL-6, (P = 0.023, r = ‒0.42) for IL-4, and (P = 0.76, r = ‒0.243) for TNF-alpha. The average level of TNF-alpha was (3.2+/-6.92 pg/ml), IL-4 and IL-6 showed results (2.13+/-8.72 pg/ml) and 5.02+ /-7.22 pg/ml) respectively for patients with vitamin D deficiency, while it was for IL-6, for IL-4 (3.5+/-6.43 pg/ml) and TNF- alpha (4.33+/-8.61 pg/ml) for patients with normal concentrations of vitamin D in the blood and IL-6, (1.02+/-5.1 pg/ml), IL-4 (2.13+/- 6.4 pg/ml), TNF-alpha (1.45+/-5.28 pg/ml), for the healthy control group, respectively. The difference was statistically significant (P = 0.002). We found a significant positive correlation between TNF-alpha, IL-4 and IL-6 and low vitamin D levels, respectively, and with the SLE Disease Activity Index (SLEDAI). (r = +0.743 and +0.772, respectively).

Conclusion

Increased levels of IL-4, IL-6 and TNF-alpha may influence the development and progression of nephritis in patients with SLE, in addition, the production of large amounts of IL-4, IL-6 and TNF-alpha correlates with low levels of vitamin D in the blood.
#1422 Exploring BAFF, APRIL, and clinical characteristics in IgA nephropathy: a decade-long study in the Bulgarian population
Authors: Kostadinova Iva , Bogov Boris , Lyubomirova Mila , Kyurkchiev Dobroslav , Todorov Todor
Published: May 2024

Background and Aims

IgA nephropathy (IgAN) represents a significant global health concern, contributing substantially to chronic kidney disease and renal failure. Despite its widespread impact, the Bulgarian population lacks comprehensive epidemiological data and specific biomarkers for IgAN. This decade-long retrospective study, conducted at a tertiary Nephrology Clinic in Bulgaria, aims to explore the clinical characteristics and serum levels of BAFF and APRIL in biopsy-confirmed IgAN patients and healthy controls.

Method

The study includes 125 biopsy-confirmed IgAN patients and 30 healthy controls. Notably, 70.4% of IgAN patients were male, with an average age of 35.94 ± 11.91 years. Baseline characteristics reveal advanced disease stages at diagnosis, possibly linked to delayed biopsy (24.22 ± 32.9 months from initial symptoms) and the absence of a screening program. Analyses of serum biomarkers (C3, BAFF, and APRIL) are conducted to identify any significant variations between IgAN patients and healthy volunteers.

Results

The average baseline estimated glomerular filtration rate (eGFR) was 61.78 ± 27.72 ml/min/1.73 m², with a mean serum creatinine of 126 ± 67.83 μmol/l at the time of kidney biopsy. Among the patients, 51.2% had an eGFR below 60 ml/min, indicating CKD stage 3 or worse according to the KDIGO classification Binary logistic regression analysis identifies anemia as a significant contributor to disease progression, with a risk influence approximately 3.3 times higher for GFR decline over time. Anemia emerges as a crucial predictor for serum creatinine doubling, carrying a higher risk than hyperuricemia. Analyses of C3 (p = 0.658), BAFF (p = 0.432), and APRIL (p = 0.227), demonstrated no significant differences in their serum levels between IgAN patients and healthy volunteers.

Conclusion

This study provides comprehensive insights into IgAN in the Bulgarian population, addressing the dearth of epidemiological data and biomarkers. Anemia emerges as a significant predictor for disease progression, emphasizing its potential clinical relevance. However, C3, BAFF, and APRIL exhibit no notable variations, underscoring the need for additional biomarker exploration to enhance understanding of IgAN dynamics in this population.
#2284 Clinical characteristics and renal survival of patients with monoclonal gammopathy of renal significance (MGRS)
Authors: Tsiakas Stathis , Panagakis Anastasios , Skalioti Chrysanthi , Kapsia Eleni , Stergiou Ioanna E , Voulgarelis Michael , Boletis Ioannis , Marinaki Smaragdi
Published: May 2024

Background and Aims

Monoclonal gammopathy of renal significance (MGRS) comprises a diverse group of renal disorders related to a nephrotoxic monoclonal immunoglobulin. Due to the rarity of the disease and the recent definition of MGRS-associated kidney lesions, data about long-term clinical outcomes remain limited.

Method

A single-center, retrospective cohort study was conducted including data of all patients with biopsy-proven MGRS who were followed at our center between 2005 and 2023. We examined the clinicopathologic characteristics and renal survival of the patients. Disease progression was defined as an eGFR decline >30% or end-stage kidney disease (ESKD). Univariate Cox regression analysis was used to assess the relationship between clinical features and disease progression.

Results

A total of 23 adults (males 43.5%) with a median age of 65 years (IQR 55-70) were included in our study. At presentation, median eGFR was 51 ml/min/1.73 m2 (IQR 40-80) and proteinuria 3.94 g/24 h (IQR 2.00-6.26). Serum or urine monoclonal protein was not detected in 4 patients (18.2%). MGRS-associated renal lesions included Ig-related amyloidosis (n = 8), monoclonal immunoglobulin deposition disease (n = 7), cryoglobulinemic glomerulonephritis (n = 2), C3 glomerulopathy (n = 2), proliferative glomerulonephritis with monoclonal IgG deposits (n = 1), immunotactoid glomerulopathy (n = 1) and miscellaneous (n = 2). Most patients were treated with a plasma cell-directed regimen (77.3%) and the rest with B-cell-directed (13.6%) or conservative therapy (9.1%). Median follow-up for the cohort was 45 months (IQR 27-67). Thirteen patients responded to treatment (52.1%), achieving a reduction in proteinuria (0.44 vs 3.94 g/24 h, p:001) and maintenance of eGFR (60 vs 56 ml/min, p:0.363) at the last follow-up visit. All responders had received clone-directed therapy. Disease progression occurred in 8 patients (34.8%), three of whom reached ESKD (13.0%). Renal survival, defined as survival without ESKD, was 84.6% at 48 months (CI 73.3-101.7). Factors that were associated with disease progression were Ig-related amyloidosis (HR: 6.94, CI: 1.30-36.84, p:0.023) and eGFR < 45 ml/min at diagnosis (HR: 14.73, CI: 1.62-132.95, p:0.017).

Conclusion

MGRS is a heterogeneous clinical entity manifesting with varying degrees of proteinuria and kidney injury. Impaired kidney function at diagnosis and Ig-related amyloidosis correlated with worse renal prognosis in our cohort. Early identification and clone-directed treatment of MGRS may improve long-term renal survival.
#514 Efficacy of continues low dose rituximab in PLA2R-associated primary membranous nephropathy
Authors: Cui Zhuan , Wang Song , Wanf Yue , Zheng Danxia
Published: May 2024

Background and Aims

We reported that rituximab 100 mg monthly showed an effective regimen for low anti-phospholipase A2 receptor (anti-PLA2R) primary membranous nephropathy (PMN), especially for those elderly and susceptible PMN. Here we attempted to compare effect of the rituximab (RTX) 100 mg monthly vs traditional corticosteroid-cyclophosphamide (GC-Cy) for the treatment of PLA2R-associated PMN in our hospital.

Method

All the included PMN patients were treated in our hospital between June 2017 and June 2022 and were retrospectively analyzed. The inclusion criteria:(1) age >18 years old, (2) biopsy-proven PMN, (3) anti-PLA2R titers >20 RU/ml, (4) nephrotic syndrome (NS, both proteinuria >3.5 g/24 and serum albumin <30 g/L), (5) eGFR >30 ml/ min. 1.73 m2, (6) followed up at least 12 months. Patients were stratified into the RTX and GC-Cy groups according to their received treatment. In the RTX group, patients received RTX 100 mg monthly until the NS was remission or at least serum anti-PLA2R less than 2 RU/ml. In the GC-Cy group, patients received prednisolone (0.5-1.0 mg/kg/day) or methylprednisolone (similar dose) orally for 1-2 months, then dosage was reduced gradually, and the total duration about one year; meanwhile received intravenous cyclophosphamide (0.6-1.0 g every month), total doses 6-12 g.

Results

The baseline parameters (included age, gender, anti-PLA2R antibody, urinary protein, serum albumin, and eGFR) did not differ significantly between the two groups (see Table 1). Total RTX dosed were 819 ± 240 (400-1200 mg) in the RTX group. After different treatment, anti-PLA2R antibody was significantly higher in rituximab group than in the GC-Cy group at 3 months (P < 0.05), but were not significantly different between the two groups at 6, 9, and 12 months (P > 0.05, see Fig. 1A); urinary proteins were significantly higher in RTX group than in the GC-Cy group at 3, 6, and 9 months (P < 0.001), but were not significantly different between the two groups at 12 months (P > 0.05, see Fig. 1B); serum albumin were significantly lower in RTX group than in the GC-Cy group at 3, 6, 9 and 12 months (P < 0.01, see Fig. 1C). The total remission rate was not significantly different between the two groups at 12 months (P > 0.05, see Fig. 1D).

Conclusion

Compared to traditional GC-Cy treatment, RTX 100 mg monthly appeared as a weak but lasting effective regimen for anti-PLA2R-associated PMN.
#2653 Long term renal outcome of patients with idiopathic membranous nephropathy – Croatian single center cohort
Authors: Brinar Ivana Vukovic , Prlic Margareta Fistrek , Ivandic Ema , Ćorić Marijana , Bulimbasic Stela , Kurtov Karlo , Kovačić Ines Bosnić , Kos Jelena , Dika Zivka , Jelakovic Ana , Jelaković Bojan
Published: May 2024

Background and Aims

Membranous nephropathy (MN) is the most prevalent cause of nephrotic syndrome in adult population. Our aim was to assess long term renal outcome of primary membranous nephropathy patients.

Method

In this retrospective study adult patients with biopsy proven membranous nephropathy from 2000 till 2015 with follow up of at least 5 years from UHC Zagreb were included. Extensive clinical workup was done to exclude patients with secondary MN. Except otherwise stated, data are shown as N (%) or median with interquartile range (IQR) and accompanied p levels.

Results

Between 2000 and 2015, 48 patients were diagnosed to have idiopathic/primary membranous nephropathy, out of which 33 (68%) MN patients had follow up of at least 5 years and where further analyzed. They were predominantly male 20 (60.6%) of average age of 52 years (min – max 19 - 76). High risk MN patient 25 (75%) were treated with immunosuppressive therapy, dominantly with cyclophosphamide and corticosteroids. During the median follow up of 10 (7 – 14) years, 19 (57%) accomplished complete remission and 11 (33%) partial remission. One (3%) patient did not achieve remission and 2 (6.1%) were in relapse of nephrotic syndrome at last follow up. Proteinuria significantly decreased (6.2 (3.3 – 10.9) vs. 0.2 (0.14 – 0,90); p < 0.001) and there was no significant change in creatinine level (87 (42.8 – 101.5) vs. 93 (68.5 – 140.5; p = 0.332)). In follow up there were 5 (15%) carcinomas detected; one of each origin (colon, pancreas, lung, prostate, lymph nodes) approximately 7,8 years after the diagnose of MN. Limitation of this study could be selection bias but there was no difference in renal function at presentation of all MN patients and those who had at least 5 years follow up.

Conclusion

Renal long-term outcome of patients with idiopathic MN in our cohort was excellent. Nevertheless, there is high prevalence of cancer and therefore regular screening for cancer disease should take place in this population of patients. Also, drugs with cancerogenic potential should be avoided, as well as bear in mind cumulative dose of drugs applied.
#3051 Light chain only variant of proliferative glomerulonephritis with monoclonal immunoglobulin deposits: a case report
Authors: Martins Ana Cristina , Laranjinha Ivo
Published: May 2024

Background and Aims

Proliferative glomerulonephritis with monoclonal immunoglobulin deposits (PGNMID) is an entity characterized by glomerular deposition of monoclonal immunoglobulins, typically IgG. Recently, a cohort of 17 patients presenting with light chain only variant of PGNMID was published. Strikingly, in this cohort, glomerular deposition of C3 was detected in all cases. We herein report a case of PGNMID with a rare presentation on the kidney biopsy.

Case presentation

We present the case of a 73-year-old female with a past medical history of rheumatoid arthritis and hypertension, under methotrexate 10 mg per week, prednisone 2.5 mg per day, amlodipine, nebivolol, azilsartan, and a recurrent naproxen intake. She presented with fatigue, anorexia, weight loss of about 12% of her body weight, epistaxis, oral bleeding ulcers, and lower extremities oedema. Pancytopenia, acute kidney injury (urea 150 mg/dL, creatinine 2.92 mg/dL), and nephrotic syndrome (serum albumin of 2.7 mg/dL and proteinuria of 12 g/day) were noted. Further evaluation showed an imbalance of the free light chains’ ratio with kappa light chain's level of 1250 mg/dL. Serum protein electrophoresis and immunofixation were normal. A CT scan showed numerous cervical, mediastinal, and iliac enlarged lymph nodes.

Kidney biopsy showed an increase in mesangial cells and matrix and capillary walls’ thickening without nodular lesions under a light microscope. Immunofluorescence microscopy showed granular deposits of kappa light chains and no deposition IgA, IgG, IgM, C1q, C3, fibrin and lambda. Considering the previous literature, C3 was reanalyzed, with a consistent negative staining. Based on the above findings, a diagnosis of Light chain only variant of PGNMID was made. Concomitantly, evaluation of the bone marrow sample showed Small lymphocytic lymphoma. The patient was started on Bortezomib, cyclophosphamide and dexamethasone. Three months after proteinuria was 0.47 g/g and creatinine 1.7 mg/dL.

Conclusion

This case highlights the rare occurrence of a PGNMID with light chains only deposition (without C3 co-deposition) as a complication of small lymphocytic lymphoma. This contributes to the growing body of evidence surrounding this entity, with the particularity being that C3 was not detected. The authors hypothesized some pathophysiologic mechanisms to justify the absence of C3 co-deposition.
#1522 Comparative analysis of clinical and pathological traits in IgA nephropathy with nephrotic range proteinuria based on serum albumin level
Authors: Eum Sang Hun , Hong Suyeon , Hong Yu Ah , Ban Tae Hyun , Koh Eun Sil , Kim Yong Kyun , Chung Byung Ha , Shin Seok Joon , Yoon Hye Eun
Published: May 2024

Background and Aims

Presently, the clinical outcomes associated with IgA nephropathy exhibiting heavy proteinuria and the potential correlation between decreasing serum albumin levels and adverse prognosis have not been conclusively established. The present study was designed to elucidate the clinical and pathological characteristics of IgA nephropathy patients who present with nephrotic-range proteinuria, particularly in relation to serum albumin levels.

Method

This retrospective cohort study was conducted using data from biopsy-confirmed IgA nephropathy patients presenting with nephrotic-range proteinuria between 2017 and 2022 from eight university-affiliated hospitals in South Korea. Patients were stratified into two groups based on a serum albumin level of 3.0 g/dl. The study involved a comparative assessment of clinical and pathological characteristics across these two groups, as well as an evaluation of clinical prognosis with respect to the end-stage kidney disease (ESKD).

Results

The analysis included a total of 127 patients. Of these, 86 patients had a serum albumin level above 3.0 g/dl (designated as the preserved albumin group, or PA group), while 41 patients had levels below 3.0 g/dl (designated as the reduced albumin group, or RA group). The baseline characteristics of the two groups were found to be statistically similar. The mean age of the patients was 46.46 years, and 46.46% were male. In the laboratory findings, the RA group had significantly elevated erythrocyte sedimentation rate compared to the PA group. Additionally, total cholesterol and low-density lipoprotein-cholesterol levels were significantly higher in the RA group compared to the PA group. Proteinuria was observed to be significantly higher in the RA group. Pathological examinations demonstrated that in electron microscopy (EM) findings, the RA group exhibited a more pronounced diffuse foot process effacement. Over the course of one year, the trend in creatinine changes exhibited differences between the two groups over time (time x group interaction P = 0.002). Furthermore, it appeared that the reduction in the quantity of proteinuria was more substantial within the RA group (time x group interaction P = 0.001). During a median follow-up period of 25.22 months (ranging from 11.98 to 49.23 months), 14 patients (11.02%) in the PA group progressed to ESKD, compared with 10 patient (24.39 %) in the RA group. However, there was no statistically significant difference between the two groups in terms of progression to ESKD (P = 0.330).

Conclusion

In patients diagnosed with IgA nephropathy presenting with nephrotic-range proteinuria, a decline in serum albumin levels was associated with diffuse foot process effacement, and the decrease in serum albumin was not found to be associated with adverse prognosis.
#1834 Prevalence of nephrolithiasis in patients with idiopathic hypercalciuria after two decades of follow-up
Authors: Suarez German Perez , Nanwani Avinash Chandu , Herrera Aidana Maria Barrera , Yánez María Isabel Luis , Canton Cesar García , Garcia-Nieto Victor Manuel
Published: May 2024

Background and Aims

Idiopathic hypercalciuria (IH) is the main metabolic abnormality that causes kidney stones. It is linked to high intestinal calcium absorption and osteopenia. However, not all patients diagnosed with IH develop kidney stones. In this study, we examined a cohort of patients diagnosed of IH during childhood to determine the prevalence of lithiasis in adulthood.

Method

Longitudinal study that evaluated the prevalence of lithiasis in 35 patients (12 female, 23 male) diagnosed of IH during childhood (mean age of 7.7 ± 3 years). The patients were followed until adulthood (mean age 28.2 ± 3.1 years) with a median follow-up of 18.2 years (IQR: 12.2-19.3). IH diagnosis was made by urinary calcium excretion higher than 4 mg/Kg/day in two consecutive samples. In both periods, clinical and demographic data were collected, including urinalysis and urinary ratios (calcium/creatinine, calcium/citrate, oxalate/creatinine, and citrate/creatinine) in an isolated sample of the first morning urine, as well as the performance of renovesical ultrasound.

Results

In pediatric age, 8 patients (26%) presented nephrolithiasis on ultrasound, and 14 (43.8%) in adulthood, 6 of them experiencing episodes of nephritic colic. During the study, we observed a decrease in urinary calcium excretion, as expressed by the calcium/creatinine ratio (adult age 0.16 ± 0.9 mg/dl vs. childhood 0.28 ± 0.1 mg/dl, p = 0.000), and an hypocitraturia increase (citrate/creatinine ratio in childhood 887 ± 349 mg/dl and in adulthood 357.7 ± 363 mg/dl, p = 0.000). A decreased citrate/creatinine ratio in adulthood was associated with nephrolithiasis (p < 0.007). Only 4 patients (50%) had nephrolithiasis at both ages.

Conclusion

These results suggest that hypercalciuria tends to correct spontaneously in adulthood, and although the prevalence of nephrolithiasis increased, it is more related to hypocitraturia.
#1246 The impact of severe nephrotic syndrome on thyroid function
Authors: Matyjek Anna , Rozanska Maria , Niemczyk Stanisław , Kronbichler Andreas
Published: May 2024

Background and Aims

Nephrotic syndrome (NS) is a clinical condition characterized by massive urinary loss of proteins, mostly albumin, but also hormones and their carrier proteins among others. The most frequently reported hormonal complication is thyroid dysfunction. The study aimed to assess the frequency of thyroid dysfunction in NS and its association with carrier protein levels and indicators of disease severity.

Method

A case-control study was conducted involving patients with newly diagnosed or relapsed severe NS, defined as proteinuria > 3.5 g/day and serum albumin ≤ 2.5 g/dL (NS group), and patients without proteinuria (control group). The evaluation included thyroid hormone profiles, serum levels of carrier proteins (prealbumin – PAB, and thyroid-binding globulin – TBG), and markers reflecting the course of NS.

Results

Forty-two nephrotic and 40 matched non-proteinuric patients were enrolled. The NS group comprised 67% males with a mean age of 49 years and an average proteinuria of 8.9 g/day (Table 1). The leading cause of NS was minimal change disease (22 patients), followed by membranous nephropathy (11 patients). The other causes included: amyloidosis (3 patients: AL – 2 cases, A – 1 case), focal segmental glomerulosclerosis (2 patients) and lupus nephritis (1 case). In 5 cases, no histological diagnosis was made.

Thyroid dysfunction secondary to NS was observed in the majority of patients, occurring 18-times more frequently than in the control group (67% vs 10%, OR = 18, 95% CI: 5.3-60.7). Euthyroid sick syndrome was the most commonly seen in NS (15 cases, 36%), followed by overt (8 cases, 19%) and subclinical hypothyroidism (5 cases, 12%). According to the current guidelines, levothyroxine supplementation was required in 11 patients (26% of the NS group, 36% of those with thyroid dysfunction).

Serum TSH correlated inversely with PAB (R = −0.63, p < 0.001), and positively with TBG (R = 0.39, p = 0.010), while no relationships were found between carrier proteins and free hormones (fT3 or fT4). The only indicator of NS severity related to thyroid function was serum albumin. It correlated, however, only with TSH (R = −0.41, p = 0.007), not with free hormones. Additionally, neither histological type, nor clinical course of NS distinguished between euthyroidism, euthyroid sick syndrome, or hypothyroidism (Table 2).

Conclusion

Thyroid dysfunction is a common complication of severe NS. Although euthyroid sick syndrome predominates, the proportion of patients with hypothyroidism who may potentially require levothyroxine replacement therapy remains substantial.
#822 Effect of renal Doppler ultrasound on the detection of nutcracker syndrome in children presenting orthostatic proteinuria
Authors: Lee Keum Hwa , Hwang Eun Jae , Kim Ji Hong , Park Se Jin , Shin Jae Il
Published: May 2024

Background and Aims

To assess the Doppler sonographic findings of the left renal vein (LRV) in children with orthostatic proteinuria compared to normal urine children.

Method

Renal Doppler ultrasound examinations were routinely performed on 50 consecutive children with orthostatic proteinuria and 53 normal urine children who have visited to the pediatric nephrology clinic at Severance hospital. The peak velocity (PV) was measured at the hilar portion of the left renal vein (LRV) and at the LRV between the aorta and the superior mesenteric artery.

Results

Age and sex did not differ between the two groups. The peak velocity ratios between aortomesenteric and hilar portions were 7.79+/−2.65 in children with orthostatic proteinuria and 6.32+/−3.01 in healthy normal children (p=0.01). The protein/creatinine ratio in the first morning urine did not differ between the two groups (0.09+/−0.03 in children with orthostatic proteinuria and 0.08+/−0.02 in healthy normal children (p = 0.144). However, the protein/creatinine ratio in the afternoon urine in children with orthostatic proteinuria (0.49+/−0.46) was significantly higher than that in healthy normal children (0.10+/−0.04) (p < 0.001). The peak velocity ratios between aortomesenteric and hilar portions positively correlated with the protein/creatinine ratio between the afternoon urine and the first morning urine (R = 0.21, P = 0.034).

Conclusion

Nutcracker syndrome may be an important cause of orthostatic proteinuria in children. Renal Doppler ultrasound of the LRV may be a useful screening tool in patients with suspected orthostatic proteinuria to evaluate whether the cause is nutcracker syndrome.
#2740 Pregnancy outcomes in patients with IgA nephropathy and the impact of pregnancy on the renal disease
Authors: Tummala Snikitha , Menda Jaideep , Bagchi Soumita , Subbiah Arunkumar , Bhowmik Dipankar , Mahajan Sandeep
Published: May 2024

Background and Aims

IgA nephropathy (IgAN), the predominant primary glomerulonephritis in adults,, frequently affects women in childbearing age. There is a dearth of information about the impact of pregnancy on the outcome in IgAN especially in the Indian population where it is known to have an aggressive disease phenotype. This retrospective cohort study examines pregnancy outcomes in women with biopsy-proven IgAN and the impact on renal outcome.

Method

In a retrospective cohort study, we assessed the medical records of women in child bearing age (18-40 years) diagnosed with biopsy proven primary IgAN from 2012-2022. Patients with end stage kidney disease (ESKD) at the time of biopsy and/or at time of conception and those who had undergone kidney transplantation were excluded. Maternal (pre-eclampsia, relapse, renal disease progression, etc.) and fetal outcomes (neonatal death, preterm delivery, intra-uterine growth retardation-IUGR, etc.) were recorded. Relapse was defined as increase in proteinuria to ≥1 g/day during pregnancy and renal disease progression as >40% sustained decline in eGFR and/or ESKD.

Results

Of 75 women assessed, 25 were lost to follow up. 34 did not conceive after biopsy. 20 pregnancies were documented in 14 patients. Three (15%) were medically terminated, 7 (35%) resulted in spontaneous abortions, and 10 (50%) culminated in live births. There was one neonatal death. 6/20(30%) pregnancies occurred while the patient was on ACEi/ARBs of which 5 pregnancies resulted in live births. 7/10 (70%) births were premature, 5 being moderate preterm (34-37 weeks) and 2 late preterm (32-34 weeks). IUGR below the 5th percentile affected 7/10(70%) of births. The mode of delivery was evenly split between vaginal (5, 50%) and Caesarian (5, 50%). From a maternal perspective, preeclampsia affected 3/10 (30%) patients. 5/10(50%) patients who delivered had a relapse during pregnancy with 2 developing nephrotic range proteinuria. 4 of them receiving steroids during pregnancy. All relapsed patients had persistent proteinuria >1 g/day postpartum. In 2 (20%) pregnancies, relapse developed during immediate post-partum period. In 4 patients, eGFR decreased by > 40 percent compared to their baseline (at biopsy) following the pregnancy.

Conclusion

Pregnancy is associated with adverse maternal and fetal outcomes in women with IgA nephropathy.

eGFR, estimated glomerular filtration rate. IUGR, Intra-uterine growth restriction (based on birth weight percentile, adjusted for gender and gestational age).

*Serum creatine of one patient during pregnancy is not available, analysis is done using values of other 9 patients. **Urine Protein of one patient is not available at the latest follow-up, analysis is done using values of 9 other patients.