bluuebunny/crossref_metadata_2025_split huggingface dataset:
#2555 C4d—a novel predictor of the disease progression and treatment failure in primary focal segmental glomerulosclerosis?
Authors: Zagorec Nikola , Horvatic Ivica , Kasumović Dino , Šenjug Petar , Sovic Slavica , Ljubanović Danica Galešić , Galesic Kresimir 
Published: May 2024

Abstract

Background and Aims
Complement system seems to play a role in the pathogenesis of primary focal segmental glomerulosclerosis (pFSGS) where, due to unpredictable clinical course and outcome, novel prognostic factors are sought. The split product of C4 and tissue marker of complement activation, C4d, is a potential candidate whose prognostic significance was determined in this study.

Method
Patients &gt;18 years with features consistent with pFSGS (full blown nephrotic syndrome, diffuse podocyte foot processes effacement and exclusion of known causes of FSGS), were recruited from our Hospital registry of kidney biopsies, from 2003 to 2021. Patients with end-stage renal disease (ESRD) defined as eGFR &lt;15 ml/min/1.73 m2 were not included. Every renal biopsy specimen was analyzed by light, immunofluorescence and electron microscopy with additional immunochemistry for C4d performed on paraffin-embedded tissue using monoclonal rabbit antibody (detection system Ventana BenchMark Ultra). Samples with at least one non-globally sclerosed glomerulus (GSG) were examined by two renal pathologists who classified every non-GSG into C4d positive and negative. Based on ratio of C4d+ non-GGS/total N of non-GSG and C4d+ nonsclerotic glomeruli (NSG)/total N of NSG, patients were stratified into two groups: &lt;50% and ≥50%. Primary outcome was defined as composite of ESRD and initial eGFR declining &gt;50%. Failure to meet criteria for at least partial remission at the last follow-up visit according to KDIGO 2021 Guidelines was defined as treatment failure. Numeric variables are shown as median with interquartile range (IQR) and P value &lt;0.05 was considered as significant.

Results
Relevant data of 58 included patients with renal outcomes are shown in Table. Median follow up was 90.7 (IQR 48-167) months. Patients with ≥50% of C4d+ non-GSG had higher proportion of treatment failure (Table) and worse renal survival (log-rank test, p = 0.006). In multivariate Cox regression analysis, after inclusion of age, sex, initial eGFR and 24-h proteinuria, IFTA, serum albumin and C4d category, only C4d ≥50% (HR = 4.077, 95% CI 1.101-15.09, p = 0.035) and IFTA (HR = 1.052, 95% CI 1.019-1.085, p = 0.002) remained independent predictors of progression to defined endpoint. Likewise, patients with ≥50% of C4d+ NSG/total N of NSG had higher proportion of treatment failure (chi-square, p = 0.03) and worse renal survival (log-rank, p = 0.037).

Conclusion
C4d deposition is an independent predictor of disease progression, treatment failure and renal survival in pFSGS. Significant influence of NSG-C4d deposition on disease progression may indicate pathophysiological role of the complement system activation in pFSGS independently of the presence of glomerular sclerosis.
#1386 Hypertension is associated with deterioration of kidney function among patients with systemic lupus erythematosus, with or without lupus nephritis
Authors: Benchetrit Sydney , Bar-Ziv Dorin , Kabaha Mohamad , Kenis Irina , Tayer-Shifman Oshrat E , Cohen-Hagai Keren 
Published: May 2024

Abstract

Background and Aims
Systemic lupus erythematosus (SLE) frequently involves the kidneys, contributing to morbidity and mortality among this population. While hypertension often coexists with kidney involvement, it is not represented in the Systemic Lupus International Collaborating Clinics (SLICC)/American College of Rheumatology (ACR) Damage Index. Its effect on the morbidity and mortality of the SLE population in the Middle East should be evaluated. Our aims is to characterize the role of hypertension in Israeli SLE patients and identify variables associated with decreased eGFR over time.

Method
This retrospective study, conducted between 2014–2023 included adult patients with a diagnosis of SLE for at least 12 months. Kidney involvement was assessed based on a diagnosis of lupus nephritis (LN) on kidney biopsy. Hypertension was diagnosed based on documented diagnosis. Systolic and diastolic blood pressures were collected as continuous variables at multiple time-points. Associated variables, including socio-demographics, disease-related characteristics, kidney-related factors, comorbidities and all-cause mortality were assessed.

Results
A total of 182 patients were followed for a mean duration of 16.2 ± 13.8 years. Fifty-nine patients (32.4%) had chronic hypertension. Hypertension was more prevalent among SLE patients with LN [odds ratio (OR) 1.5, 95% CI 0.8-2.9, p = 0.23] as well as patients with chronic kidney disease (OR 7.2, 95% CI 1.9-27.7, p = 0.001). Patients with chronic hypertension had significantly relatively high rate of proteinuria at last follow-up (54.7%). On univariate analysis, patients with hypertension had higher rates of end-stage kidney disease (ESKD) (11.9% vs 1.6%, p = 0.003), heart failure (20.3% vs. 0.8%, p &lt; 0.001), and all-cause mortality (16.9% vs. 0%, p &lt; 0.001). All deaths (n = 10) occurred among hypertensive patients. LN and age were the most important predictors of hypertension on multivariate analysis (OR 6.2, 95% CI 2.4-16, p &lt; 0.001; OR 1.1, 95% CI 1.1-1.2 p &lt; 0.001, respectively). Repeated measures analysis showed that hypertension was significantly associated with decreased eGFR among SLE patients with or without LN (Fig. 1). Systolic and diastolic blood pressure were significantly correlated with age and inversely correlated with eGFR at last follow-up (Spearman's correlation coefficient 0.4, p &lt; 0.01; 0.1, p = 0.07; −0.4, p &lt; 0.01; −0.2, p = 0.04, respectively).

Conclusion
Hypertension is prevalent among Israeli patients with SLE, constituting a substantial comorbidity associated with ESKD, heart failure and mortality, irrespective of LN presence. Routine assessment and vigorous treatment of hypertension should be part of the management of patients with SLE.
#1093 Remission rates and long-term outcomes of relapsed idiopathic nephrotic syndrome children treated with cyclophosphamide vs. cyclosporin A
Authors: Vachvanichsanong Prayong , Sophark Praewa , Limratchapong Chompoonut , Dissaneewate Pornsak 
Published: May 2024

Abstract

Background and Aims
Approximately seventy percent of nephrotic syndrome (NS) children experience relapse episodes which are classified as frequently-relapsing nephrotic syndrome (FRNS), steroid-dependent nephrotic syndrome (SDNS), or steroid-resistant nephrotic syndrome (SRNS). In such cases, immunosuppressive drugs are combined to reduce the steroid side effects and prolong the remission period. However, the benefit of immunosuppressants and their side effects should be balanced.

Objectives
This study aimed to determine the remission rates and long-term outcomes of FRNS, SDNS, and SRNS children treated with cyclophosphamide vs. cyclosporin A (Cy A).

Methods
A retrospective review of medical records of children (aged &lt; 15 years) with relapsed idiopathic nephrotic syndrome at Prince of Songkla University Hospital, southern Thailand during 2010-2021 was conducted. Demographic data, treatment responses, and adverse events were recorded. The remission rates, incidences of infection and acute kidney injury (AKI) in FRNS/SDNS and SRNS were compared between oral cyclophosphamide and Cy A treatments.

Results
There were 148 relapsed NS children, 102 (68.9%) boys, with a median age of 4.6 (IQR 2.5-8.4) years. FRNS, SDNS, and SRNS accounted for 37 (25.0%), 50 (33.8%), and 61 (41.2%) children, respectively.
The cyclophosphamide treatment group (N = 135) had significantly higher remission rates in FRNS/SDNS than SRNS (63/85 (74.1%) vs. 11/50 (22.0%), P &lt; 0.001), while the difference in remission rates in the Cy A treatment group (N = 53) was not statistically significant between FRNS/SDNS and SRNS (14/20 (70.0%) vs. 18/33 (54.5%), P = 0.265).
Patients who had the Cy A treatment had significantly higher proportions of infections and AKI than children in the cyclophosphamide treatment group (20/53 (37.7%) vs 10/95 (10.5%), P &lt; 0.001 and 21/53 (39.6%) vs 9/95 (9.5%), P &lt; 0.001, respectively).
Of the 148 children, at a median follow-up time of 8.7 (IQR 5.2–12.2) years, 21 (14.2%) and 9 (6.1%) children had developed chronic kidney disease (CKD) stage III or end-stage kidney disease (ESKD), respectively. The mean duration from CKD stage III to ESKD was 5.0+5.5 months.

Conclusions
Seventy percent of FRNS/SDNS children achieved remission with either Cy A or cyclophosphamide, but the SRNS children achieved remission proportionately better with Cy A than cyclophosphamide. However, the Cy A-treated children had higher proportions of infections and AKI than the cyclophosphamide treatment group. Overall, one-fifth of the relapsed childhood NS children developed CKD.
#1442 Retrospective evaluation of etiology, clinical and laboratory findings in patients diagnosed with secondary and genetic FSGS
Authors: Yilmaz Aysenur , Suleymanova Vafa , Dirim Ahmet Burak , Kalayci Tugba , Artan Ayse Serra , Oto Ozgur Akin , Ozturk Sukru , Palanduz Sukru , Ozturk Savas , Turkmen Aydin , Yazici Halil 
Published: May 2024

Abstract

Background and Aims
Focal segmental glomerulosclerosis (FSGS) is a glomerulonephritis characterized by segmental sclerosis in at least one of the glomeruli and may develop due to primary, secondary, genetic etiology. We compared clinical, histopathological, and laboratory findings, treatment options, and response to treatment in patients with secondary and genetic FSGS.

Method
This study analyzed 172 patients with secondary and genetic FSGS at our Glomerular Diseases Clinic (1987-2022). Criteria included at least 16 weeks of follow-up, absence of other primary glomerular diseases, and age over 18. Retrospective data were collected on demographics, diagnosis, renal biopsies, genetic tests, imaging, treatments, treatment responses, end-stage renal disease (ESRD) development, and transplantation. The focus was on predicting genetic FSGS and ESRD.

Results
103 of our patients were female (59.8%), and the mean age at diagnosis was 38.46 ± 13.75 years. Of these patients, 29 were diagnosed with genetic FSGS and 141 with non-genetic secondary FSGS. Forty-one patients with non-genetic secondary FSGS were obese, and 21 had a single kidney. The patients had a median follow-up of 78 (38-134) months. 28 patients developed ESRD during follow-up, 16 of whom underwent renal transplantation. Familial renal disease (p &lt; 0.001), familial ESRD (p &lt; 0.001), and hematuria at diagnosis (p = 0.005) were more common in patients with genetic FSGS. Comparison of genetic FSGS and non-genetic secondary FSGS patients shown in Figure 1. The number of glomeruli with global sclerosis (p = 0.006) and C3 accumulation (p = 0.048) on renal biopsy was more frequent in patients with ESRD. Comparison of ESRD and non-ESRD patients are shown in Figure 2.

Conclusion
Differentiating genetic and non-genetic secondary FSGS is vital in clinical practice. For those with a family history of renal disease, hematuria, or unresponsive to immunosuppressive therapy, consider genetic FSGS and request genetic testing. Patients with secondary FSGS, diagnosed with high creatinine, a substantial presence of sclerosing glomeruli on biopsy, and C3 accumulation, should be closely monitored for ESRD.
#1782 Clinicopathological study of renal limited pauci-immune vasculitis and its short-term outcome: a single centre observational study
Authors: Sangma Benjamin , Sharma Manjuri , Doley Prodip 
Published: May 2024

Abstract

Background and Aims
Pauci immune crescentic glomerulonephritis, is a leading cause of RPGN. The majority of patients with PICGN have glomerular diseases as a part of a systemic small vessel vasculitis, a minority may present as renal-limited vasculitis. In north-east India, there are still no major studies in this group of patients. Therefore, our study involving north-east Indian population constitutes an effort to prospectively study the clinico-pathological feature of patients with PICGN and assess the short-term outcome.

Method
This single-centre, prospective, observational, study was conducted over 12 months at the Department of Nephrology, Gauhati Medical College. All renal biopsy-proven patients with pauci-immune renal vasculitis were included, excluding those with secondary vasculitis. Baseline characteristics and laboratory data were recorded, and disease activity was assessed using the Birmingham Vasculitis Activity Score. The ANCA tests were performed using a standardised essay for both indirect immunofluorescence assay and antigen-specific ELISA. The renal biopsy specimen obtained was evaluated by light microscopy and direct immunofluorescence. The sample size was calculated based on the prevalence of pauci-immune glomerulonephritis, and data were analysed using SPSS.

Results
The study involved 24 patients, predominantly females (70.83%), aged 14-65 years, presenting predominantly with pedal oedema and oliguria. Laboratory findings showed varying levels of haemoglobin, total count, platelet count, creatinine, and 24-hour urine protein. 50% of the patients were (MPO) positive, 33.3% were (PR3) positive while 16% were ANCA negative. Renal biopsy analysis showed a majority with mixed class according to the Berden classification. Treatment involved induction with Methylprednisolone and Cyclophosphamide, with dialysis administered to 58.3% of patients. At six months, 36.3% had a stable GFR, and 50% were on maintenance hemodialysis. Factors predicting renal loss included oliguria, dialysis at presentation, and fibrous/fibrocellular crescents. The best predictor of renal outcome was serum creatinine at presentation.

Conclusion
Pauci-immune CrGN is a severe disease affecting a wide age range. Early diagnosis and treatment initiation are crucial for better outcomes, including lower ESRD risk and relapse rates. Prognostic factors include baseline serum creatinine levels and fibrous crescents. Optimising treatment regimens may improves outcomes.
#1165 Targeted-release budesonide can preserve the glomerular filtration rate in patients diagnosed with IgA nephropathy after 3 months of administration.
Authors: Keskinis Christodoulos , Moysidou Eleni , Pateinakis Panagiotis , Christodoulou Michalis , Stai Stamatia , Zoidakis Jerome , Stangou Maria 
Published: May 2024

Abstract

Background and Aims
The four-hit hypothesis constitutes the main immunological sequence of the IgA nephropathy (IgAN) pathogenesis. However, the activation of intestinal-renal axis is considered the initial step during IgA nephropathy (IgAN) pathogenesis. Aim of this prospective pilot study is to evaluate parameters which influence early response to targeted release budesonide.

Method
Adult IgAN patients, diagnosed the last 10 years, maintaining eGFR &gt;30 ml/min/1.73m2 and Uprotein &gt;750 mg/24 hr, despite standard supportive treatment, commenced on budesonide 16 mg/d, and followed for 3 months. Renal biopsies were re-evaluated and scored according to Oxford classification, parameters of renal function recorded at time of diagnosis (T-d),at the beginning of treatment (T0), and 3 months later (T3).

Results
Fifteen IgAN patients, M/F:12/3, Mean age: 52 (34-74) years from two different departments fulfilled the criteria and they have already started on budesonide treatment, 51.6 ± 45 months following diagnosis. eGFR had declined from T-d to T0, 57.43 ± 10.58 to 49.23 ± 13.63 ml/min/1.73 m2, p = 0.03, and Uprot was stable 3.33 ± 1.16 to Uprot = 2.98 ± 1.19 gr/24 hrs, p = NS. During the 3 first months of budesonide (T3), eGFR showed slight improvement, eGFR = 54.38 ± 13.67 while Uprot remained stable 3.17 ± 1,04 gr/24 hrs. Improvement in renal function was not associated with any of histologic findings, but was remarkably more evident within patients with &lt;4 years of diagnosis, eGFR from 62 ± 5.2 to 73 ± 2.4, compared to change in the eGFR from 23 ± 5.6 ml/min/1.73 m2 to 25 ± 3.6 ml/min/1.73 m2.

Conclusion
Our preliminary findings suggest that, independent of renal histology, budesonide treatment showed a trend in improving renal function, mainly in patients with relatively short time from diagnosis. So, budesonide can
#1347 Development and validation of a nomogram for predicting complete kidney function recovery after drug-induced acute interstitial nephritis
Authors: Caravaca-Fontán Fernando , Praga Manuel , Fernández-Juárez Gema 
Published: May 2024

Abstract

Background and Aims
Drug-induced acute interstitial nephritis (DI-AIN) represents a common cause of acute kidney injury. Early withdrawal of the culprit drug along with corticosteroid therapy (CS) remains the mainstay of treatment. Despite this, up to 50% of patients may not fully recover kidney function after DI-AIN.
The aims of this study were to develop and externally validate a predictive nomogram to assess the probability of complete recovery (CR) of kidney function at 6 months after treatment.

Method
Multicenter, retrospective, observational study in 13 nephrology departments belonging to the GLOSEN group. Patients with biopsy proven DI-AIN treated with CS between 1996-2023 were included. Other potential causes of AIN such as infections or systemic diseases were carefully ruled out. Dataset was randomly divided into training group (n = 164) and validation group (n = 60). The least absolute shrinkage and selection operator (LASSO) regression was used to screen the main predictors of CR (serum creatinine value &lt;25% of the last value before DI-AIN), and used to build the nomogram. Accuracy of the nomogram was assessed by discrimination and risk calibration, in the training and validation sets.

Results
The study group comprised 224 patients with DI-AIN, of whom: 51 (31%) in the training group and 19 (32%) in the validation set, achieved CR at 6 months after treatment with CS. Median age was 70 (IQR 57–76), and 115 (51%) were males. The clinical characteristics were well balanced between the training and validation data sets. The selected variables by LASSO were age (under/above 65 years), gender, degree of interstitial fibrosis and time to CS initiation (under/above 7 days). Based on multivariable logistic regression model, a nomogram was developed for assessing the probability of CR (Fig. 1). The area under the curve (AUC) of the nomogram was 0.809 (95% CI 0.721–0.880) indicating a good discriminative power. Bootstrap self- sampling was performed 1000 times for validation of the nomogram model. The AUC was 0.837 (95 % CI: 0.705–0.931), indicating good predictive stability. Calibration plot revealed that the predicted outcomes aligned well with the observations. Decision curve analysis (DCA), and clinical impact curve analysis (CICA) suggested that the model had clinical benefit.

Conclusion
We constructed and validated a practical nomogram with good discrimination and calibration, to predict the probability of CR of kidney function at 6 months in DI-AIN treated with corticosteroids. This clinical tool can provide clinicians with an estimate of kidney prognosis and can potentially assist them in titrating the intensity and duration of corticosteroid therapy.
#1495 5 and 10 year kidney outcomes in acute interstitial nephritis: a retrospective single-centre cohort study
Authors: Sebastian Kuruvilla , Cowhig Cliona , Coughlan Conor , Mayer Nick , Burke Louise , Gleeson James , Eustace Joseph , Moran Sarah , Clarkson Michael 
Published: May 2024

Abstract

Background and Aims
Acute interstitial nephritis (AIN) is a common cause of acute kidney injury (AKI), histologically characterized by an interstitial inflammatory cell infiltrate. Data regarding long term kidney outcomes is lacking. We performed a retrospective cohort study to evaluate the long-term kidney and mortality outcomes in patients with biopsy-proven AIN between 2011-2018.

Method
We serve as a tertiary referral centre and sole nephrology provider for a population of over 650,000 people. We identified biopsy-proven AIN cases from the years 2011-2018 from our pathology database. Demographic data, creatinine, eGFR (calculated using CKD-EPI 2021 formula), dialysis and mortality data were collected from our electronic medical record. Ethical approval was obtained.

Results
Between 2011 – 2018, 576 native kidney biopsies were performed in our centre. 66 (11.5%) cases had pathologically confirmed AIN as the primary kidney diagnosis. Long-term outcome data was available for 90.9% (60).
The median age at time of biopsy was 52.5 years (IQR 41.5 - 68.3). 68% of patients were male. The aetiology of AIN was medication in 42%, autoimmune in 15% and infection-associated in 3%. Of the cases of drug-induced AIN the predominant culprits agents were non-steroidal anti-inflammatories 28%, proton pump inhibitors in 24%, antibiotics 20%, with other medications in 8%.
The median eGFR at the time of biopsy was 13.6 (IQR 7.9 -25.4) mls/min/1.73 m2. The median eGFR at year 1 was 47.8 (IQR 30.7 - 72.7) mls/min/1.73 m2, 54.4 (IQR 31.2 -79.6) mls/min/1.73 m2 at year 5 and 69.4 (IQR 19.9 - 86.1) mls/min/1.73 m2 at year 10. See Table 1 for results.
At one year 64.3% of cases had eGFR &lt; 60 mls/min/1.73 m2 (CKD III or higher). Interestingly the rate of CKD was lower at years 5 and 10 (54.7% and 50% respectively). GFR &lt;30 mls/min (CKD IV or higher) were present in 25% at year 1, 26% at year 5 and 37% at year 10.
23% (14/60) people had dialysis-requiring AKI at the time of biopsy. Of these 21.4% (3) remained dialysis dependent at one year. In this group, no additional cases of ESKD were seen between years 1 through 5, one additional case of ESKD occurred by year 10.
A composite outcome of kidney failure (GFR &lt;15, dialysis or kidney transplantation) occurred in 48.2% at year 1, 54.7% at year 5 and 56.2% at year 10.
Mortality data was available on 58 patients. 18.9% (11) people had died at 10 years follow-up. 8 out of the 11 deaths were within 5 years, 2 of which were within 1 year of diagnosis.

Conclusion
In this single centre study, kidney failure occurred in 48% of people at 10 years of follow up. 78% of dialysis-requiring cases recover independent renal function.