bluuebunny/crossref_metadata_2025_split huggingface dataset:
#785 The novel fibrosis biomarker LG1M is prognostic for long-term readmission after AKI
Authors: Sparding Nadja , Genovese Federica , Karsdal Morten Asser , Selby Nicholas 
Published: May 2024

Abstract

Background and Aims
People who survive Acute Kidney Injury (AKI) experience increased risk of long-term adverse outcomes, including a significantly elevated rate of readmission to hospital. This may be related to the pathophysiological consequences of AKI, including extracellular matrix (ECM) remodeling in the kidneys and other organs. Tools to monitor the long-term health risk of patients after AKI are needed to improve patient outcome. Here, we investigated the potential of the novel ECM remodeling biomarker LG1M, reflecting laminin degradation mediated by MMP-9, as a prognostic marker for readmission after AKI.

Method
We measured LG1M in plasma samples collected 1 year after the episode of AKI using the nordicLG1MTM ELISA assay in plasma samples from 791 patients from the AKI Risk in Derby (ARID) study, who were then followed prospectively until year 3. 390 of the patients had been hospitalized for an episode of AKI and 401 patients who did not sustain AKI were included as controls (non-AKI). Correlation of LG1M levels with age, serum creatinine, eGFR, PCR, ACR, and CRP was tested with Spearman rank correlation (all variables measured at year 1). Uni- and multivariate Cox regression analysis was used to analyze the association of LG1M with the risk of readmission.

Results
LG1M levels were significantly higher in the AKI group (median [IQR] = 31.9 [25.7-42.8] ng/mL) compared to the control group (median [IQR] = 30.3 [24.9-37.2] ng/mL, P &lt; 0.01). In the AKI group, LG1M correlated with age (r = 0.16, P &lt; 0.01), serum creatinine (r = 0.33, P &lt; 0.0001), eGFR (r = −0.35, P &lt; 0.0001), and ACR (r = 0.23, P &lt; 0.0001). In the control group, LG1M only correlated with serum creatinine (r = 0.22, P &lt; 0.0001) and eGFR (r = −0.22, P &lt; 0.0001). By year 3, 265 out of 390 patients in the AKI group and 258 out of 401 patients in the control group were readmitted (Chi-squared test, P = 0.28). In a univariate Cox model with readmission as outcome, LG1M was significant associated with readmission in the AKI group (HR [95% CI] = 1.007 [1.001-1.013], P &lt; 0.05) but not in the control group (HR [95% CI] = 1.005 [0.997-1.013], P = 0.23). When adjusting for age, sex, ACR, and eGFR measured at year 1 as well as baseline CKD and diabetes status, LG1M lost it significance in the AKI group (HR [95% CI] = 1.004 [0.998-1.011], P = 0.22) and was still non-significant in the control group (HR [95% CI] = 1.002 [0.994-1.011], P = 0.57).

Conclusion
In this study, we showed that the novel biomarker LG1M is prognostic for readmission in patients after AKI. Our findings may indicate that this biomarker, reflecting laminin degradation, can be used as a novel post-AKI biomarker that can help assess patients’ long-term health risks.
#2071 The metabolic syndrome impact in the onco-nephrological scenario of renal cancer: when comorbidities beat surgery
Authors: Trevisani Francesco , Scilipoti Pietro , Rosiello Giuseppe , Bettiga Arianna , Musso Giacomo , Re Chiara , Alfano Massimo , Bertini Roberto , Montorsi Francesco , Salonia Andrea , Larcher Alessandro , Capitanio Umberto 
Published: May 2024

Abstract

Background and Aims
Metabolic syndrome (MS) represents a pathological state in which many risk factors for CKD including obesity, hyperglycemia, hypertension and dyslipidemia co-occur within individuals. In the past decade different lines of evidence underlined the relationship between MS and CKD, two increasing worldwide serious threat to life. With the rise of onco-nephrology, there is a strong need to define the role of MS in the nephrological management of oncological patients.
Our study aimed to assess the impact of metabolic syndrome on renal function in patients undergoing partial nephrectomy (PN) for renal cancer (RC).

Method
We retrospectively analyzed data from 1,112 patients undergoing PN at a tertiary referral center between 2000 and 2023. Patients with metastatic disease, hereditary cancer or a solitary kidney were excluded. Renal function was evaluated with eGFR values using CKD-EPI 2021 formula. AKI and CKD onset were defined using K-DIGO 2012 criteria.
MS was defined as at least 3 of the following conditions: obesity, insulin resistance, dyslipidemia and hypertension. Multivariable analyses (MA) were used to determine the impact of MS on preoperative eGFR impairment and post-operative AKI. Covariates were intraoperative blood loss, surgical experience, pT stage, type of surgery (open vs minimally invasive), pre-existing CKD, age, and comorbidities (defined as Charlson Comorbidity Index&gt;3).

Results
Overall, the rate of MS was 9% (n = 100). The median follow-up was 60 months (IQR 28-68). Patients with MS had lower preoperative eGFR (78 ml/min vs. 87 ml/min), higher estimated blood loss (500 ml vs. 300 ml) and higher rate of complications (38% vs. 29%) relative to non-MS counterparts (all p &lt; 0.001). Additionally, the rate of AKI was 25% (n = 25) vs 18% (n = 182) for metabolic vs non-MS patients (p = 0.01), respectively. At MVA, MS was an independent predictor for both lower preoperative eGFR (OR 1.07, 95% CI 1.01-1.14, p = 0.01) and higher risk of AKI (OR 2.1, 95% CI 1.3-4.1, p = 0.01). MS patients had a worse kidney function at baseline, had higher risk of AKI immediately after surgery and a higher risk of CKD onset over time, with a steep reduction of eGFR even at long term follow-up (Fig. 1).

Conclusion
Renal cancer patients diagnosed with MS harbored an increased risk of both AKI and CKD even with a partial nephrectomy. Therefore, the role of onco-nephrologists and nutritionists remains a cornerstone in the management of such cohort of patients, before and after surgery.
#2884 Dose-dependent EGR1 expression in the rat renal medulla after chronic NSAID treatment
Authors: Kokeny Gabor , Haghighi Samaneh , Haghighi Arezoo , Zadori Zoltan 
Published: May 2024

Abstract

Background and Aims
Nonsteroidal anti-inflammatory drugs (NSAIDs) are widely used in clinical medicine. Chronic use of NSAIDs is associated with reduced renal medullary blood flow, potentially causing severe and irreversible damage including papilla necrosis. We have previously demonstrated that chronic hyperosmolar injury in the renal medulla induces the expression of pro-fibrotic TGF-beta1 and EGR1. However, the impact of chronic NSAID treatment on EGR1 and pro-fibrotic factors in renal cortex and medulla remains unexplored. Thus, we aimed to analyze the effects of chronic NSAID treatment in the rat renal medulla.

Method
Male Wistar rats (250-260 grams) were orally treated twice daily for two weeks with various NSAIDs: indomethacin (IND, 2 mg/kg), naproxen (NAP, 10 or 20 mg/kg), celecoxib (CEL, 10 and 30 mg/kg), or vehicle (1% hydroxyethylcellulose). Left kidney was removed for histology and immunohistochemistry, the right kidney medulla was separated for mRNA analysis. Kruskal-Wallis test was performed for statistical analysis.

Results
NSAIDs caused significant tubular dilatation in all treated groups except IND. CEL (10, 30 mg/kg) and NAP (10 mg/kg) markedly increased epithelial atrophy. NAP 10 and 30 mg/kg induced a dose-dependent, 2-fold and 3.2-fold TIMP1 mRNA over-expression, respectively. Only NAP 20 mg/kg induced significant, 2.5-fold EGR1 mRNA expression. Both IND and CEL increased a 2-fold EGR1 protein expression in the medulla, but NAP induced a dose-dependent 5- and 10-fold increase of EGR1 protein.

Conclusion
Our study show that EGR1 and TIMP1 might play an important role in the development of NSAID induced tissue injury in the rat renal medulla. Further studies are needed to shed light on the molecular pathogenesis.
#900 Endotrophin is associated with long-term risk of kidney function decline in normoalbuminuric persons with type 2 diabetes in the Joslin Kidney Study
Authors: Genovese Federica , Kobayashi Hiroki , Sparding Nadja , Møller Alexandra Louise , Karsdal Morten Asser , Krolewski Andrzej 
Published: May 2024

Abstract

Background and Aims
Endotrophin is a pro-fibrotic and pro-inflammatory molecule derived from the post-translational processing of type VI collagen. Evidence for an association of increased circulating levels of endotrophin with increased risk of kidney and cardiovascular-related outcome and all-cause mortality in persons with type 2 diabetes have recently emerged. Here we want to investigate endotrophin as an early marker of kidney-related outcome risk in persons with type 2 diabetes with normal levels of albuminuria.

Method
Endotrophin was measured using the nordicPRO-C6TM assay (Nordic Bioscience, Herlev, Denmark) in serum of 1088 individuals with type 2 diabetes from the Joslin Diabetes Study. 635 individuals had normal to mildly increased albuminuria (&lt;30 mg/g), 379 had moderately increased albuminuria (30-300 mg/g) and 74 had severely increased albuminuria (&gt;300 mg/g). All patients had eGFR &gt;60 and where hence classified as CKD stage 1 and 2. Risk of kidney disease progression was defined as a 40% decline in eGFR within 10 years.

Results
In the cohort (n = 1088), a total of 128 patients progressed to 40% eGFR decline. High levels of circulating endotrophin were associated with an increased risk of kidney disease progression in unadjusted logistic regression analysis (OR for T3 vs T1+T2 (PRO-C6): 2.1 [95% CI: 1.4-3.0], p = 0.0001) and after adjustment for eGFR, HbA1c, age and sex (OR for T3 vs T1+T2 (PRO-C6): 1.8 [95% CI: 1.1-2.6], p = 0.005). When looking at patients classified in albuminuria stages, endotrophin was significantly associated with kidney disease progression in the individuals with normal to mildly increased albuminuria (39 events) (OR for T3 vs T1+T2 (PRO-C6): 2.6 [95% CI: 1.3-4.9], p = 0.005 in unadjusted analysis and 2.3 [95% CI: 1.1-4.5], p = 0.02 after adjustment for eGFR, HbA1c, age and sex, but it was not significantly associated to kidney progression in the groups with moderately (49 events) and severely (40 events) increased albuminuria.

Conclusion
This study sheds further light on the potential of endotrophin as an early marker of long-term adverse kidney outcome in persons with type 2 diabetes. The association of circulating endotrophin with increased risk of kidney disease progression had already been reported both in CKD and DKD patients (for shorter-term outcome), and this study further expands on the applicability of endotrophin as a biomarker in persons with type 2 diabetes without an overt kidney disease, who will nevertheless progress to develop CKD in a 10-year time horizon.
#2094 Very low protein integrated diet (sVLPD), without keto analogues, in patients with advanced chronic renal failure: clinical and economic benefits
Authors: Cecchi Sofia 
Published: May 2024

Abstract

Background and Aims
The integrated very low protein diet (sVLPD) has proven effective in slowing the progression of stage 5 chronic renal failure and in postponing the start of dialysis treatment (1)SVLPD with keto analogues is difficult to implement due to the high number of tablets to be taken(2), therefore, to increase compliance we decided to prescribe, in compliance with the guidelines of normal clinical practice, SVLPD (0.3 g/prot/day) integrated with only essential amino acid drugs without the use of keto analogues, in stage 5 patients and we have verified its effectiveness, safety and clinical and economic effects(3).

Method
129 patients were started on dietary therapy (middle age 75.2 ± 13.7, 60.5%male, all with hypertension, 40.3% with diabetes and 24.8% with heart disease) who were tested at the beginning of the observation, every 3 months and for 24 months, characterizing blood chemistry tests and body composition (with impedance analysis).

Results
During the 24-month observation period 91 patients (70.5%) were compliant with dietary therapy. Chronic kidney disease progression is slowed with average eGFR 11.6 ± 3.3 (compliant) vs. 9.3 ± 2.7 (no compliant) mL/min/1.73 m2, p &lt; 0.001) Urea (mg/dL) 116.1 ± 31.7 (compliant) 174.2 ± 42.2 (no compliant) p &lt; 0.002; and initiation of dialysis treatment (adjusted HR = 0.361, CI 0.200–0.650, p = 0.001) was delayed without evidence of malnutrition, in compliant versus noncompliant patients. Metabolic acidosis was well compensated in both groups with an improving trend in bicarbonate levels in compliant patients. Hemoglobin, uricemia, serum albumin, glycemia (downward trend NS), potassium, sodium, chlorium, calcium, magnesium, pH, lipids remained within normal values. Better blood pressure control was observed in compliant patients compared to non-compliant patients (SBP (mmHg) 136.9 ± 11.8 vs 150.1 ± 7 &lt;0.01), DBP (mmHg) 75 ± 3.1 vs 79.4 ± 1 &lt;0.001) During the observation, there were 24 deaths (13 patients older than 85 years), 20 peritoneal dialysis hospitalizations, 36 hemodialysis hospitalizations, 4 preventive living transplants and 15 renal functional recoveries with eGFR consistently &gt;15 mL/min/ 1.73 m2. The months of dialysis avoided generated gross savings in terms of healthcare expenditure equal to EUR 3,076,470; the expenditure sustained by the Marche region for protein-free products (EUR 90 per patient per month) was EUR 158,358. As a result, the total net savings were EUR 2,918,112.

Conclusion
This non-interventional longitudinal observational study is part of standard clinical practice and suggests that VLPD supplemented with only essential amino acids is safe and effective and could be widely used to reduce the incidence of dialysis treatments, with a favorable economic impact on the National Health Service.
#506 Long-term exposure to air pollution and CKD-associated mortality: results from the pooled cohort of the European multicentre ELAPSE-study
Authors: Zitt Emanuel , Kadelbach Pauline , Chen Jie , Jaensch Andrea , de Hoogh Kees , Andersen Zorana J , Samoli Evangelia , Brunekreef Bert , Hoek Gerard , Nagel Gabriele , Weinmayr Gudrun 
Published: May 2024

Abstract

Background and Aims
Air pollution has been shown to be associated with cause-specific mortality. However, mortality due to chronic kidney disease (CKD) is understudied in this context, with no European data available so far. We investigated the relation between long-term exposure to air pollution and CKD-associated mortality in the Effects of Low-Level Air Pollution: A Study in Europe (ELAPSE).

Method
Data of five population-based cohorts from four European countries from the pooled ELAPSE cohort were linked to data from local mortality registries. CKD-associated mortality was defined using ICD10 codes N18-N19 or corresponding ICD9 codes. Mean annual exposure at home address was determined with Europe-wide hybrid land use regression models for nitrogen dioxide (NO2), black carbon (BC), ozone (O3), particulate matter ≤2.5 µm (PM2.5) and several elemental constituents of PM2.5 with a spatial resolution of 100 m x 100 m. Cox regression models were adjusted for age (time-axis), cohort and sex (both as strata), calendar year of recruitment, smoking status, marital status, employment status and neighborhood mean income.

Results
Over a mean follow-up time of 20.4 years, 313 of 289,564 persons died from CKD. Associations were observed for all pollutants, positive for PM2.5 (hazard ratio (HR) with 95% confidence interval (CI) of 1.31 (1.03-1.66) per 5 µg/m3 increase), BC (1.26 (1.03-1.53) per 0.5 × 10− 5/m), NO2 (1.13 (0.93-1.38) per 10 µg/m3) and negative for O3 (0.71 (0.54-0.93) per 10 µg/m3). Results were robust when additionally adjusting for smoking intensity and duration, BMI, education or residential greenness, but susceptible to cohort selection. Findings are mainly based on the large Austrian cohort, that contributed 226 cases. Among the elemental constituents, Cu, Fe, K, Ni, S and Zn, representing different PM2.5 sources including traffic, industry, biomass and oil burning and long-range transport, were associated with CKD-related mortality.

Conclusion
In conclusion, our results suggest a possible association between air pollution from different sources with CKD-related mortality. Our results indicate that measures to improve air quality and decrease air pollution might also be beneficial from a renal perspective.
#771 Estimating glomerular filtration rate: does the diabetic status influence the performances of current equations?
Authors: Delanaye Pierre , Bjork Jonas , Flamant Martin , Ebert Natalie , Schaeffner Elke , Grubb Anders , Christensson Anders , Åkesson Anna , Nyman Ulf , Stehlé Thomas , Pottel Hans 
Published: May 2024

Abstract

Background and Aims
Diabetes is the first cause of chronic kidney disease (CKD) worldwide. The estimation of glomerular filtration rate (GFR) is one main tool to detect CKD. The most used biomarker remains serum creatinine and the European Kidney Function Consortium (EKFCcrea) equations is the most validated in Europe. More recently, another renal biomarker, cystatin C, has been proposed. In the current analysis, we studied the performances of the EKFC equations in a large cohort of subjects according to their diabetic status.

Method
Four cohorts from the EKFC dataset were considered in which the diabetic status was available: Lund, Sweden (n = 2,780), Berlin, Germany (n = 654), Créteil, France (n = 466), and Paris, France (n = 2,258). Serum creatinine and cystatin C were measured with calibrated assays. GFR was measured by plasma clearances (mGFR) (iohexol in Lund, Berlin and Créteil and 51Cr-EDTA in Paris). The performance of the equations was assessed by calculating bias, precision (IQR) and P30 (percentage of eGFR-values within ±30% of mGFR). As the characteristics of diabetic patients were different, we matched diabetic and non-diabetic patients using the following matching criteria: age (±3 years), sex (equal), mGFR (±3 mL/min/1.73 m²), and BMI (±2.5 kg/m²).

Results
In the whole population (n = 6,158), median [IQR] age was 61 [47; 72] years, with 45.8% of women. Mean measured GFR (mGFR) was 60 [39; 82] mL/min/1.73 m². Compared to non-diabetic subjects (n = 5,124), diabetic patients (n = 1,034) were older, more frequently males, heavier, had lower mGFR (45 vs 64 mL/min/1.73 m²), and higher creatinine (1.44 vs 1.06 mg/dL; p &lt; 0.0001) and cystatin C (1.67 vs 1.20 mg/L) concentrations. The performance of the EKFCcys equation was similar to EKFCcrea, but the EKFCcrea+cys had better P30 than single-biomarker equations. Globally, P30 were substantially lower in diabetic patients than in non-diabetic patients (Table). We could match data for 289 females and 546 males. The results in the matched cohorts were quite similar between diabetics and non-diabetics subjects, and this is true for every equation.

Conclusion
In conclusion, in a large dataset of patients including diabetics and non-diabetics, we showed that the EKFC equations are accurate in diabetic and non-diabetic patients. Combining the creatinine and cystatin C-based equations presents an added value. If accuracy of all equations seems better in non-diabetic than in diabetic subjects, it is probably more due to differences in age and (still more) in GFR levels than to the diabetic status.
#2994 Nephrotoxicity post injection of iodized PDC in patients with renal failure in the emergency room
Authors: Othmani Safia , Jouini Sarra , Hedhli Hana , Jemai Mouna , Jendoubi Asma , Hosni Dhekra , Bouarada Ghada 
Published: May 2024

Abstract

Background and Aims
Nephropathy following injection of iodinated contrast media (PDC) is the leading cause of iatrogenic acute renal failure. Several associated factors have been identified, including renal function before the procedure.

Objective
To study the incidence of nephrotoxicity post venous-injection of iodinated PDC in patients with impaired renal function.

Method
This was a prospective, descriptive, single-center study over a six-month period. Patients aged over 14 years and having undergone an injection of iodinated contrast products for diagnostic or therapeutic purposes were included. We excluded patients with stage IV renal insufficiency (Cl ≤ 29 ml/min) with or without indication for extra-renal purification. Nephropathy in this context was defined by an elevation in baseline plasma creatinine of more than 25% in the 48 to 72 hours following injection.

Results
During the study period, 135 patients were collected with a mean age of 46 ± 18 years and range of 16 to 97 years. The gender ratio was 3.2 with a male predominance.
Thirty-two patients had impaired renal function on admission, of which seven patients (5.2%) were known to have chronic renal failure and twenty-five patients (18.5%) had impaired renal function discovered on admission. The mean renal clearance was 90.9 ± 36.3 ml/min with extremes ranging from 30 ml/min to 176 ml/min. More than half of the patients had normal renal function (Stage G1 according to the KDIGO 2022 classification) (n = 79, 58.5%). The incidence of nephropathy post venous-injection of iodized PDCs was 15.6%. 111 patients (82.8%) benefited from per-procedure hydration protocol.
In univariate analysis, chronic renal failure or discovered on admission was associated with the risk of worsening renal function with a statistically significant difference, p respectively at 0.007 and 0.009. Furthermore, the correlation between the worsening of renal function as a function of initial plasma creatinine showed that initial plasma creatinine was higher in patients who developed iodinated contrast nephropathy with a statistically significant difference, p = 0.005, a sensitivity of 57% and a specificity of 78%. ROC curve analysis showed an AUC of 0.691; 95% CI [0.567-0.815], with a discriminant Cut off of plasma creatinine at 90.5 µmol/l.

Conclusion
The incidence of post-iodized PDC injection nephropathy was high in emergency room. Among the independent associated factors identified, chronic renal insufficiency or discovered on admission which requires special precautions, especially through optimal hydration.