bluuebunny/crossref_metadata_2025 huggingface dataset:
#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

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>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 < 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

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

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 (<30 mg/g), 379 had moderately increased albuminuria (30-300 mg/g) and 74 had severely increased albuminuria (>300 mg/g). All patients had eGFR >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

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 < 0.001) Urea (mg/dL) 116.1 ± 31.7 (compliant) 174.2 ± 42.2 (no compliant) p < 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 <0.01), DBP (mmHg) 75 ± 3.1 vs 79.4 ± 1 <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 >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

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

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 < 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

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.
#3004 Serum miRNAs as novel biomarkers and modulators of rapidly progressing chronic kidney disease in patients with diabetes
Authors: Mcdowall Callum , Shalamanova Liliana , Wilkinson Fiona , Pritchett James , White Stephen , Kalra Philip A
Published: May 2024

Background and Aims

Chronic kidney disease (CKD) is very common in diabetes, occurring in around 40% of patients. Without treatment, CKD can lead to end stage renal disease (ESRD), which requires costly dialysis and transplantation. Current treatments aim to prevent CKD or slow down its progression to ESRD. The speed of CKD progression is patient-specific, and at present there are no biomarkers which can predict which patient with diabetes will develop CKD; level of albuminuria is an important but variably reliable biomarker of speed of CKD progression.

The current methods for rapid identification of patients prone to accelerated CKD progression are limited, as they are based on measuring estimated glomerular filtration rate (eGFR) over prolonged periods of time, as well as albuminuria. Therefore, there is a clinical need for novel biomarkers that can predict early potential rapid CKD progression in patients.

The aim of this project is to determine whether serum microRNAs (miRs) can be used as biomarkers to predict the speed of CKD progression in diabetes patients, and to identify potential treatment targets associated with such dysregulated miRs.

Method

miRs were isolated from sera of 34 patients with type 2 diabetes classed with either slow or fast progressing CKD by their eGFR (n = 17; obtained from the Salford Kidney Study sample collection). Several miRs were found to be significantly dysregulated in fast progressing patients by using Next Generation Sequencing (NGS) of miRs in individual serum samples. An additional 49 diabetic CKD patient serum samples (slow (n = 29) or fast progressors (n = 20)) were used to validate the potential miR biomarker panel by qPCR.

Results

The NGS miR analysis of the initial 34 CKD patient sera produced a panel of 16 miRs that were either significantly upregulated or downregulated in the fast-progressing patients compared to slow progressors. The qPCR validation of this initial panel in 49 additional CKD patient serum samples demonstrated that 6 miRs were significantly upregulated in the fast-progressing patients. The levels of these miRs correlated with demographic and clinical parameters. ROC curve analysis revealed that the individual predictive power of each of those 6 miRs to define either a slow or fast progressing CKD patient was between 63-75%. Determination of a miR combination the strongest predictive power is ongoing.

Conclusion

A potential biomarker panel of 6 miRs has been identified and validated by qPCR, with each miR having a predictive power of between 63-75% for fast progression of CKD. A panel of miRs that could accurately predict progression speed of CKD patients could lead to faster and earlier diagnosis of patients to enable better treatment.

Work is ongoing to explore the predictive power of this miR biomarker panel, and potential novel therapeutic targets to prevent CKD or delay its progression to ESRD.
#2929 Plasma levels of brain injury markers NfL and GFAP are independently predicted by glomerular filtration rate in patients with chronic kidney disease
Authors: Axelsson Torunn , Zetterberg Henrik , Axelsson Markus , Svensson Maria K , Saeed Aso , Guron Gregor
Published: May 2024

Background and Aims

Patients with chronic kidney disease (CKD) have a high prevalence of cerebrovascular disease and cognitive impairment. The aim of the present study was to measure brain injury biomarkers in plasma in a cohort of patients with CKD stages 3 and 4, without a diagnosis of cerebrovascular disease, and to determine factors that independently predicted plasma levels of these biomarkers.

Method

This was a cross-sectional cohort study including 110 patients with CKD stages 3 and 4, and 55 healthy, matched, controls, recruited from the outpatient clinic at Sahlgrenska university hospital, Gothenburg, Sweden. None of the included study subjects had a diagnosis of cerebrovascular disease, cognitive impairment, or any other neurological disease. Plasma concentrations of neurofilament light (NfL), glial fibrillary acidic protein (GFAP) and phosphorylated Tau (p-Tau231) were analyzed with ultrasensitive single molecule array (SIMOA). Measured GFR (mGFR) was determined by plasma clearance of ⁵¹Cr-EDTA. Values are medians [interquartile range]. For linear regression analyses standardised beta coefficients (β) are presented.

Results

Characteristics of CKD patients and healthy controls are presented in Table 1. Plasma concentrations of NfL (37.5 [22.1-47.5] vs. 13.4 [10.5-16.7] ng/L, p < 0.001), p-Tau231 (25.7 [19.1-38.7] vs. 13.9 [10.5-16.3] ng/L, p < 0.001) and GFAP (190 [140-281] vs. 153 [116-211] ng/L, p = 0.001) were significantly elevated in patients with CKD vs. controls. In CKD patients, mGFR showed statistically significant inverse correlations to plasma concentrations of NfL, p-Tau231, and GFAP (Table 2). In multiple regression analyses, mGFR was associated with plasma levels of NfL (β = −0.457, p < 0.001) and GFAP (β = −0.322, p < 0.001) independently of diabetes, age, troponin-T, b-hemoglobin, and aortic pulse-wave velocity. However, mGFR was not significantly associated with plasma levels of p-Tau231 in a multiple regression analysis.

Conclusion

Plasma levels of brain injury markers NfL, p-Tau231 and GFAP were elevated in patients with CKD stages 3 and 4, without a history of cerebrovascular disease, compared to healthy controls. Furthermore, mGFR independently predicted plasma concentrations of NfL and GFAP in multiple regression models. These results raise the possibility that reduced GFR per se may be associated with subclinical brain injury.
#1164 Smoking cessation and atherosclerotic cardiovascular events and mortality in chronic kidney disease
Authors: Han Seung Hyeok , Joo Young Su , Koh Hee Byung , Park Jung Tak , Yoo Tae-Hyun , Oh Kook-Hwan , Kang Shin-Wook
Published: May 2024

Background and Aims

Smoking cessation is recommended to reduce excess atherosclerotic cardiovascular disease (ASCVD) and mortality in patients with chronic kidney disease (CKD). However, this recommendation is largely based on observational studies on the general population, involving participants with preserved kidney function. Therefore, we aimed to evaluate the association of smoking dose and smoking cessation duration with ASCVD and mortality in patients with CKD.

Method

We compiled a comprehensive pooled dataset comprising 66,245 participants with CKD from the KNOW-CKD and the UK Biobank cohort. Participants were categorized according to smoking dose and duration of smoking cessation base on a questionnaire. The primary outcome encompassed a composite of ASCVD or all-cause mortality. An ASCVD event was defined according to the ICD-10 codes in the claim and death register records.

Results

Over a median follow-up period of 13.2 years, 14,671 (22.1%) participants reached the primary outcome. Compared to never smokers, former and current smokers exhibited a 1.30- and 2.14-fold higher risk of the primary outcome, respectively. Among former smokers, the hazard ratios (HRs) (95% confidence intervals [CIs]) for smoking loads <20 and ≥20 pack-years were 1.05 (1.00–1.10) and 2.14 (2.05–2.25), respectively. The increased risk of the primary outcome was attenuated by longer smoking cessation. The HRs (95% CIs) for smoking cessation of <10 years, 10–20 years, and >20 years were 1.75 (1.65–1.86), 1.43 (1.34–1.52), and 1.11 (1.06-1.16), respectively, compared with never smokers.

Conclusion

Among former smokers with CKD, the risk of ASCVD or mortality was substantially attenuated with less smoking load and a longer duration of smoking cessation. Our findings support the preexisting recommendations for smoking cessation to improve clinical outcomes in patients with CKD.
#1434 A study of the factors related to the change in eGFR after arteriovenous fistula creation in CKD patients and its impact on kidney prognosis
Authors: Hara Masatoshi , Nakai Kentaro , Tokumoto Masanori , Nakano Toshiaki
Published: May 2024

Background and Aims

Occasionally, we observe cases of transiently increased estimated glomerular filtration rate (eGFR) after arteriovenous fistula (AVF) creation in patients with chronic kidney disease (CKD). However, there is limited research on the factors influencing the change in eGFR after AVF creation and its impact on kidney prognosis.

Method

In this single-center retrospective cohort study conducted from April 1, 2021, to July 31, 2023, 141 patients with CKD were enrolled. The participants were categorized into two groups: the increased eGFR group and the non-increased eGFR group after AVF creation. Factors contributing to increased eGFR after AVF creation were identified using through univariate and multivariate logistic regression analysis.

Predictive variables included demographic and clinical variables such as sex, age, presence of diabetes mellitus (DM), history of cardiovascular diseases, urinary protein level, systolic blood pressure (SBP) on admission, the use of RAAS inhibitors and diuretics, and smoking history. Additionally, the period from AVF creation to dialysis induction was compared between both groups by the Mann-Whitney U test.

Results

Mean age was 69.3 ± 12.4. 75.9% were male, and 48.2% had DM. Among the 141 patients, 44 (31.2%) experienced an increase in eGFR after AVF creation.

There was no significant difference in eGFR at the time of AVF creation between the increased eGFR group and the non-increased eGFR group (6.4 ± 1.5 vs. 6.2 ± 1.7 ml/min/1.73 m2, P = 0.56). Multivariate adjustment revealed that DM (Odds ratio [OR] 2.55, 95% confidence interval [95% CI] 1.01-6.45), hypertension (OR 0.97, 95% CI 0.95-0.99), and smoking history (OR 0.40, 95% CI 0.16–0.98) were associated with the eGFR increase after AVF creation. The time from AVF creation to dialysis induction was significantly longer in the increased eGFR group than in the non-increased eGFR group (median, 76.5 days vs. 42.0 days, P = 0.02).

Conclusion

Factors associated with accelerated atherosclerosis, such as hypertension and smoking, were significantly negatively correlated with increased eGFR. Conversely, DM was significantly associated with increased eGFR after AVF creation. Increased eGFR after AVF creation significantly prolonged the time to dialysis induction compared to the non-increased eGFR group.
#1466 Age- and kidney function-dependent life expectancy of patients after COVID-19
Authors: Siwy Justyna , Wendt Ralph , Peters Björn , Dudoignon Emmanuel , Banasik Miroslaw , Hecking Manfred , Spasovski Goce , Mischak Harald , Beige Joachim
Published: May 2024

Background and Aims

The life expectancy among survivors of SARS-CoV-2 infection may be influenced by age, pre-existing health conditions, and the severity of the initial infection. This study aimed to investigate the life expectancy in patients that survived the acute phase of COVID-19 and the association with kidney function.

Method

Survival data of 649 unvaccinated patients from our previous study “Prospective Validation of a Proteomic Urine Test for Early and Accurate Prognosis of Critical Course Complications in Patients with SARS-CoV-2 Infection” (CRIT-COV-U) [1] was collected until December 2023 in six different countries. These patients had been recruited within the first and second wave in 2020-2021 (mostly infected with wild-type virus) and had survived the acute phase of COVID-19 (CritCov-U study period 21 days after infection). The age dependent death rate in this cohort was compared to age- and sex-matched data of non-SARS-CoV-2 infected patients (n = 5192) extracted from human urinary database. The association of chronic kidney disease biomarker CKD273 with mortality was investigated in both cohorts using Kaplan-Meier analysis. Cox-regression analysis was used to assess variables associated with mortality in the COVID-19 population.

Results

Mortality was age dependent in both cohorts and markedly higher in patients who had survived the acute phase of COVID-19 in comparison to non-infected individuals (Fig. A-E). Within the first year after infection, mortality was up to 16.5 times higher in patients younger than 50 years in comparison to non-infected controls. Kidney status estimated by the CKD273 score was associated with a poor outcome in both COVID-19 patients and age- and sex-matched controls, respectively (Fig. F-G). The hazard ratio (HR) for mortality during the first year of follow-up for patients with the highest CKD273 score was 12.7, a huge increase in comparison to HR = 6.6 in the matched control group. In the Cox-regression model, CKD273 significantly contributed to death prediction, next to age and COVID-19 severity score at baseline.

Conclusion

SARS-CoV-2 infection during the first and second wave increased the risk of mortality in the follow-up period beyond the acute phase of the first 21 days. Kidney function appears to be a key element in the underlying molecular pathology of this process, indicating the importance of kidney-protective measures. Of note, among those who survived the acute phase of COVID-19, increase in mortality within the first year after infection compared to a non-infected control group was highest in the younger individuals.
#2282 Outcomes of renal amyloidosis: 8 years experience of tertiary center
Authors: Peres Nadiesda , Da Costa José Oliveira , Marchão Natália , Gameiro Joana , Rodrigues Natacha , Pereira Marta Sofia Henriques , Nogueira Estela , Jorge Sofia , Lopes José António , Godinho Iolanda
Published: May 2024

Background and Aims

Amyloidosis is a disease caused by the extracellular deposition of amyloid material that leads to organ dysfunction. Renal involvement is frequent and is characterized by amyloid fibrils pathologic deposition in glomeruli, vessels and interstitium. The most common presentation is nephrotic-range proteinuria or nephrotic syndrome and can progress to end stage kidney disease (ESKD). Prognosis is usually poor, especially with cardiac and severe renal involvement that requires renal replacement therapy. The goal of this study was to analyse the outcomes of patients with amyloidosis followed at the nephrology clinic in our centre.

Method

Descriptive analysis of all confirmed amyloid patients, followed by the Nephrology department from January 2015 to June 2023.

Results

We identified 49 patients with a mean age of 64 ± 16 years [18-88], mainly Caucasian (n = 47, 82%) and male (n = 28, 57%). The majority of patients were diagnosed through renal biopsy (26, 53%). The most common amyloid type was AL (n = 18, 38%), followed by ATTR (n = 16, 33%) and AA (n = 12, 25%). In 3 patients the amyloid type couldn't be characterized. Renal presentation was mostly as CKD 28/49 (57%), 15/49 (30.6%) as nephrotic syndrome and 6/49 (12%) patients as AKI. At presentation, almost half of the patients (24/49, 49%) had nephrotic-range proteinuria, with a mean proteinuria of 6.72 ± 6.12 g/d [0.103-19.8] and mean sCr was 2.6 ± 3.1 mg/dl [0.5-18.9].

AL amyloidosis had an almost equal distribution between lambda (9/18, 50%) and kappa chain (8/18, 44%, one unknown). Extrarenal involvement was frequent, mainly cardiac (12/18, 67%). Also 12/18 (67%) patients needed dialysis after a mean of 9 ± 15 months post-diagnosis, 16/18 (89%) received treatment and mortality was 61%, in mean 16 ± 17 months post-diagnosis, mainly due to disease progression.

AA amyloidosis was secondary to chronic infection in 7/12 (58%), 3/12 (25%) autoimmune diseases and in 2/12 (17%) unknown. Extrarenal involvement was less frequent, also mainly cardiac (3/12, 25%). 7/12 (58%) patients needed dialysis after a mean of 97 ± 117 months post-diagnosis and mortality was 58%, in mean 46 ± 66 months post-diagnosis, mainly due to acute infection. Two patients were diagnosed already on dialysis.

Regarding ATTR amyloidosis, all patients had a positive genetic test, extrarenal involvement was very frequent (13/16, 81%), mostly cardiac and peripheric nervous system. No patients required dialysis during follow-up, and one patient died of unknown cause.

Conclusion

In our cohort, renal AL and AA amyloidosis had poor prognosis, with a high progression to ESKD and very significant mortality, irrespective of treatment. Conversely, ATTR amyloidosis patients had lower progression to dialysis and death, probably as a consequence of disease-modifying therapies instituted in recent years.
#606 Impact of real-world off-label dose of apixaban on long-term clinical outcomes in patients with atrial fibrillation and chronic kidney disease
Authors: Shin Ho Sik , Kil Song Yi , Park Byung Hwa , Kim Ye Na , Jung Yeonsoon , Rim Hark
Published: May 2024

Background and Aims

Apixaban represent one of the cornerstone treatments to prevent cardioembolic events in patients with nonvalvular atrial fibrillation (NVAF). However, the choices of Apixaban dose guided by the decision-making process of the physician, which considers specific according to kidney functions are inconsistent in the real-world practice. The objective of the present study is to evaluate the effects of real-world Off-label dose of Apixaban on long-term clinical outcomes in NVAF patients with chronic kidney disease (CKD).

Method

Our database of AF patients diagnosed with CKD from 2018 to 2023 was used to obtain laboratory, echocardiography, electrocardiogram (ECG), and clinical outcomes data. Inclusion criteria were all AF patients with CKD using Apixaban. And we compared bleeding, systemic thrombotic events including stroke/systemic embolism and death according to off-label real -world dose of Apixaban.

Results

Among 635 patients with AF and CKD (76.9 ± 10.4 years), 335 (52.8%) patients took off-label underdosed Apixaban. Difference in the baseline characteristics was not observed among patients including CHA2DS2 VASc score and HASBLED score. During the median 18-month follow-up, a lower incidence of bleeding events (P = 0.001) was observed in the off-label underdosed Apixaban group compared to those with standard dose or off-label overdosed Apixaban. However, there was no significant difference of systemic thrombotic events including stroke/systemic embolism and death according to off-label real-world dose of Apixaban (off-label underdose vs. standard dose, P = 1.000; off-label overdose vs. standard dose, P = 1.000; off-label underdose vs. off-label overdose, P = 0.609). In multivariate analysis, HASBLED score was independent risk factors for bleeding events (OR 9.650; CI 1.998-46.622; P = 0.005).

Conclusion

Compared with standard or off-label overdose of Apixaban, off-label underdose of Apixaban was associated with a lower risk of bleeding in patients with AF and CKD, with no difference in the risk of stroke/systemic embolism or death, supporting the apixaban dosing tailored to specific clinical features and drug pharmacokinetics of the Asian patients.
#990 Association between frailty and chronic kidney disease: findings from CHARLS
Authors: Liu Fang , Jiamin Yuan
Published: May 2024

Background and Aims

Frailty is a complex age-related clinical condition characterized by a decline in physiological capacity of several organ systems, with a resultant increased susceptibility to stressors. Little is known about the association between frailty and chronic kidney disease (CKD) among Chinese adults. The present study sought to investigate the relationship between frailty and CKD based on a large, nationally representative survey.

Method

The participants were 4231 adults aged ≥50 years from the China Health and Retirement Longitudinal Study (CHARLS). Based on the FRAIL scale, frailty and prefrailty were defined. CKD was defined as eGFR less than 60 mL/min/1.73 m2, calculated according to the CKD Epidemiology Collaboration (CKD-EPI) equation, or self-reported CKD. Logistic regression models were conducted to analyze the cross-sectional relationship between frailty and CKD. Cox proportional hazards regression models were used to examine the effect of frail status and frail components on CKD.

Results

We found that prevalence of frailty in CKD individuals was 13.9% while in patients without CKD was 8.4%. The prevalence of CKD in robust group was 6.0%, in prefrail group was 10.1% and in frail group was 14.0%. In frail status, after adjusted, the incidence of CKD was 1.713 (95% CI 1.109-2.646) in the frail group compared with robust group (P = 0.015). While there was no statistical difference in the incidence of CKD among the prefrail group and robust group. In frail components, after adjusted, weight loss was associated with higher risk of CKD [HR (95% CI): 1.617 (1.170-2.235)].

Conclusion

We found that the prevalence of frailty was relatively high in the population. In frail status, both prefrail and frail were associated with a higher risk of CKD. In frail components, weight loss was associated with an increase incidence of CKD. Frailty is reversible, so early identification of frailty may reduce the incidence of CKD and improve the adverse consequences associated with CKD.
#1880 Disease outcomes associated with decreased estimated glomerular filtration rate: a Phenome-wide association study
Authors: Li Chunyang , Yang Wanyi , Zeng Xiaoxi
Published: May 2024

Background and Aims

This study aimed to identify associations between decreased creatinine-based estimated glomerular filtration rate (eGFR) and a broad range of related outcomes.

Method

Polygenic risk score (PRS) was calculated using PLINK1.9 software according to the tutorial with summing of risk alleles weighted by the effect sizes of 347308 white participants in UK Biobank. Genome-wide association study (GWAS) summary statistical data of creatinine-based eGFR from CKDGen consortium was utilized as base data. The phenome codes of disease outcomes were derived from the primary and secondary diagnoses of ICD-10 and ICD-9 codes in the HSE records in the U.K. Biobank. Then, the association between genetically predicted eGFR and following disease outcomes were evaluated using logistic regression adjusting for age (continuous variables), sex (male/female), assessment cancer (category variables), and the first 10 genetic principal components (PCs) (continuous variables). PRS of eGFR was scaled to a unit reflecting one SD (equals to 1) decrease of PRS. We applied the Bonferroni correction (P threshold = 0.05/665 phe codes = 7.52 × 10−5) to correct for multiple testing.

Results

Totally, 19857 SNPs (pruned by r2 < 0.1 within the 250 kb region, P < 0.01) from base data were retained for PRS calculation. Our Phe was identified that one standard deviation (SD) decrease in the PRS of eGFR significantly associated with chronic renal failure (OR = 1.27, 95% CI: 1.25-1.30, P = 1.66 × 10−158), intestinal malabsorption (OR = 1.18, 95% CI: 1.13-1.22, P = 1.76 × 10−16), other hypothyroidism (OR = 1.06, 95% CI: 1.04-1.07, P = 4.98 × 10−13), calculus of kidney and ureter (OR = 0.92, 95% CI: 0.89-0.94, P = 4.91 × 10−11), gout (OR = 1.07, 95% CI: 1.05-1.10, P = 2.34 × 10−8), chronic nephritic syndrome (OR = 1.21, 95% CI: 1.12-1.30, P = 3.20 × 10−7), Hypertensive renal disease (OR = 1.15, 95% CI: 1.09-1.21, P = 4.72 × 10−7), acute renal failure (OR = 1.04, 95% CI: 1.02-1.06, P = 4.58 × 10−6), glaucoma (OR = 0.95, 95% CI: 0.93-0.98, P = 2.16 × 10−5) and unspecified renal failure (OR = 1.10, 95% CI: 1.05-1.16, P = 2.70 × 10−5).

Conclusion

Genetically predicted deceased eGFR associated with a series of disease outcomes, providing evidence for prevention of following diseases in patients with kidney function impairment.
#1961 Cardiovascular-kidney-metabolic syndrome components and cardio-vascular disease mortality based on half-a-million Asian adults
Authors: Wu Mei-Yi , Tsai Min Kuang , Chien Kuo-Liong , Wen Chi Pang
Published: May 2024

Background and Aims

The American Heart Association (AHA) has recently issued guidelines addressing the “Cardiovascular-Kidney-Metabolic (CKM) Syndrome” to mitigate cardiovascular diseases. In parallel, European healthcare entities have established the CaReMe (CArdioRenal and MEtabolic) Partnership, emphasizing interdisciplinary health concepts. This study aims to evaluate CKM prevalence and its associated components in a substantial Asian cohort, along with the risk of cardiovascular mortality.

Method

The investigation focused on a cohort of 565 940 participants aged 20 years and above enrolled in a health screening program in Taiwan spanning from 1994 to 2017. The study assessed cardiovascular disease (CVD) and cause-specific mortality related to CKM stages and its components—hypertension, diabetes, chronic kidney disease, metabolic syndrome, and hyperlipidemia. Multivariable Cox proportional hazards models were employed to calculate hazard ratios (HRs).

Results

In this cohort with more than half-a-million Asian adults, approximately 74.3% exhibit CKM syndrome, distributed as 28.1% in Stage 1, 38.9% in Stage 2, 4.9% in Stage 3, and 2.4% in Stage 4. Among individuals aged 50 and above, almost 90% had CKM. The CKM components—hypertension (20.5%), chronic kidney disease (CKD) (11.1%), hyperlipidemia (28.4%), metabolic syndrome (13.1%), and diabetes (5.5%)—display diverse prevalence rates. We identified 13,449 participants who had CVD mortality, and the median follow-up was 15 years. CKM predicts CVD mortality with a dose-response relationship: Hazard Ratios (HRs) for Stage 2 is 2.34 (95% confidence interval (CI): 2.06, 2.65); HR for Stage 3 is 2.69 (95% CI: 2.36, 3.07), and HR for Stage 4 is 4.70 (95% CI: 4.11, 5.39). Within CKM, 43.3% have two or more components, 20.4% have three or more, and 7.3% have four or more. In those aged 65 and above, 66.6% have two or more components, 37.9% have three or more, and 17.8% have four or more. Participants with two or more components exhibit a higher CVD mortality risk than those with a single CKM component.

Conclusion

The prevalence rates of CKM and its components vary, contributing to distinct risks of cardiovascular disease mortality. A clustering phenomenon exists among different components, where an increased number of clustered factors corresponds to a higher risk of cardiovascular disease mortality.
#2756 Metabolomic prediction of end stage renal disease in large national biobanks
Authors: Barrett Jeffrey
Published: May 2024

Background and Aims

Identifying at-risk individuals likely to progress to end-stage renal disease as early as possible is important to effectively concentrate preventative interventions. Existing predictive tools, like the kidney failure risk score, are effective for individuals who already have moderate to severe kidney disease. Here we examine whether comprehensive metabolomics can improve performance in individuals with mildly impaired kidney function.

Method

Using an NMR metabolomics platform we measured >200 biomarkers including creatinine, albumin, lipids, fatty acids, amino acids, glycolysis metabolites and inflammation markers in blood samples from all 500,000 participants of the UK Biobank, who have >10 years of linked prospective follow-up data. We used machine learning to develop a score to predict kidney disease progression based on biomarkers, age and sex. We compared its performance to eGFR in a held out set of individuals in UK Biobank, and replicated in 200,000 participants of the Estonian Biobank.

Results

Among individuals with prevalent diabetes, hypertension or eGFR < 90 the biomarker score performs as well as or better than eGFR for all individuals. In particular it outperforms among individuals with only moderate (eGFR 60-75) or mild (eGFR 75-90) impairment of kidney function with an AUC increase from 0.63 to 0.72 and 0.48 to 0.70, respectively (Figure). This improvement is driven by contributions from numerous biomarkers, including lipids and inflammation markers. Furthermore, because these biomarkers capture diverse metabolic risk, the biomarker score also strongly predicts major adverse cardiovascular outcomes.

Conclusion

This large dataset allows detailed investigation of the value of metabolomics in identifying future risk of severe kidney disease early. In particular these biomarkers can highlight individuals who do not already have very low eGFR.