bluuebunny/crossref_metadata_2025 huggingface dataset:
#770 Urinary PTM3 Fetuin-A in CKD patients with and without diabetic kidney disease
Authors: Musolino Michela , D'agostino Mario , Tripodi Loredana , Zicarelli Mariateresa , Cianfrone Paola , Andreucci Michele , Coppolino Giuseppe , Bolignano Davide
Published: May 2024

Background and Aims

Fetuin-A is a member of the cystatins superfamily, primarily synthesized in the liver, which is involved in multiple physiological processes including calcium homeostasis, cell signaling, calcification inhibition and the regulation of insulin sensitivity. Diabetes mellitus may impact upon Fetuin-A regulation and kidney tubular cells produce Fetuin-A as part of stress and inflammatory response and release it in urine in case of kidney damage.

A novel post-translational modification (PTM) fragment derived from the cleavage of Fetuin-A (PTM3) has recently emerged as a very sensitive biomarker for early kidney damage, but its usefulness in the context of CKD has not been assessed yet. In this study, we aimed at evaluating the clinical significance of urinary PTM3 fetuin A in a pilot cohort of CKD patients with or without diabetic kidney disease (DKD).

Method

We enrolled 47 adult patients with CKD (mean CKD-Epi 40.10 ± 16.5 mL/min/1.73 m2) due to DKD (n = 34) or other causes (n = 13). PTM3 levels were measured in the urine (uPTM3) using a commercially available ELISA kit. 15 healthy individuals served as controls. Clinical, anthropometric and laboratory parameters were also recorded.

Results

Collectively, all CKD patients displayed higher levels of uPTM3 than the ones of control group (0.84 [0.10-1.15] vs 29.68 [2.50-55.16] ng/mL p = 0.0005).

Moreover, uPTM3 values were higher in DKD patients than in non-DKD CKD patients (39.4 [4.20-28.2] vs. 4.15 [0.29-1.38] p < 0.01).

uPTM3 had a remarkable diagnostic capacity at ROC analysis to discriminate CKD patients from controls (AUC 0.776; p < 0.001; Fig. 1) and, within CKD patients, to discriminate between DKD and non-DKD patients (AUC 0.673; p = 0.02; Fig. 2). At multivariate correlation analyses, only proteinuria (β = 0.442; p = 0.02) and BMI (β = 0.334; p = 0.04) values remained significantly associated with uPTM3 Fetuin-A in the whole cohort, thus indicating that renal damage following metabolic syndrome may play a significant impact on the overall balance of this protein.

Conclusion

uPTM3 could be a novel sensitive biomarker reflecting renal damage in CKD patients and could also represent an additional tool for assessing the renal involvement in diabetic patients.

Further studies are needed to evaluate whether uPTM3 measurement may predict different disease evolution in these patients.
#2169 Transplant renal artery stenosis in recipients with resistant arterial hypertension
Authors: Smaliakova Maria , Kalachyk Aleh , Komissarov Kirill , Kozak Oleg , Liovina Darya , Plaksa Dzmitry
Published: May 2024

Background and Aims

Transplant Renal Artery Stenosis (TRAS) is a vascular complication after kidney transplantation. It worsens the prognosis of the graft and the patient's life.

The aim was to study the incidence of TRAS as a cause of resistant arterial hypertension in kidney transplant recipients in the Republic of Belarus and the efficiency of its endovascular treatment.

Method

The study included 187 kidney transplant recipients. Blood pressure of 72 (38.5%) patients was less than 130/80 mmHg without taking antihypertensive drugs. Arterial hypertension was diagnosed in 115 (61.5%) recipients. The study included clinical, laboratory and instrumental methods (24-hour blood pressure monitoring, Doppler ultrasound, graft scintigraphy with captopril).

Results

31 (16.6%) recipients needed to take one antihypertensive drug, 43 (23.0%)—2 drugs, 41 (21.9%)—3 or more.

17 (9.1%) recipients did not have target blood pressure correction while taking more than 4 antihypertensive drugs. There was decreased blood flow in the graft artery with a peak systolic velocity > 200 cm/s in 14 (7.5%) cases. These patients were submitted to the graft nephroscintigraphy with caplopril where 8 grafts (4.3%) were diagnosed signs of TRAS. These recipients were submitted to the renal angiography with the injection of 150 (100; 200) ml of contrast agent.

5 (2.7%) recipients were diagnosed with hemodynamically significant TRAS of more than 70 (65; 75) % and received percutaneous transluminal angioplasty and stenting. All these patients had a decrease of glomerular filtration rate and resistant arterial hypertension before operation. The average age of the patients with TRAS was 57.4 ± 11.0 years, the period after transplantation was 11 ± 3 months. Their blood tests did not show dyslipidemia, but 4 out of 5 cases had diabetes mellitus. Their postoperative period had no complications. The patient was placed on dual antiplatelet therapy with aspirin and clopidogrel. There was an increase in glomerular filtration rate by 27 ± 7 ml/min/1.73 m2 and a decrease in systolic blood pressure by 40 (40; 45) mm Hg in the early postoperative period. Graft artery stenting allowed reducing the number of antihypertensive drugs to one tablet in 4 out of 5 patients.

Conclusion

Transplant Renal Artery Stenosis is a rare but significant complication of the late postoperative period that may cause resistant hypertension in kidney transplant recipients. Timely identification and stenting of the graft artery improves the graft functioning and reduces blood pressure.
#554 Baseline neutrophil gelatinase-associated lipocalin (NGAL) levels for early prediction and ruling out future contrast nephropathy
Authors: Shacham Yacov , Banai Shmuel , Frydman Shir
Published: May 2024

Background and aims

Neutrophil gelatinase-associated lipocalin (NGAL), is an early marker of acute kidney injury (AKI). There is only limited data, however, on the optimal timing for assessment, the cut-off values and its utilization for ruling out AKI We aimed to investigate the diagnostic utility of sequential NGAL measurements for both prediction and ruling out of AKI among patients with ST segment elevation (STEMI) undergoing primary coronary intervention (PCI).

Methods

We included 133 patients with STEMI treated with PCI. Blood samples for plasma NGAL were drawn immediately before PCI (NGAL 0) and 24 hours after PCI (NGAL 24). Optimal threshold for the development of AKI were determined using receiver operating characteristic curves (ROC). Patients were also assessed for the dynamics between NGAL 0 and NGAL 24 levels.

Results

Mean age was 62 ± 13 years and 78% were men, and a total of 20 (15%) developed AKI. Patients with AKI demonstrated higher plasma NGAL 0 levels (164 ± 42 vs. 95 ± 30 ng/mL; p < 0.001) as well as NGAL 24 levels (142 ± 41 vs. 93 ± 36 ng/mL; p < 0.001). There were no significant changes between NGAL 0 & 24 hours within the 2 groups (Fig. 1). According to the ROC curve analysis NGAL 0 performed better than NGAL 24 for AKI prediction (Fig. 2). The optimal NGAL 0 level for AKI prediction was >125 ng/mL (AUC 0.841, 95% CI 0.801–0.961, p < 0.001), with a sensitivity of and specificity of 70% and 84% respectively, while the negative predictive value of NGAL 0<125 ng/mL was 94%.

Conclusions

Among STEMI patients, NGAL levels before primary PCI may be utilized both for ruling out and for the prediction of AKI.
#1771 ANXA13 protects against acute kidney injury by inhibiting TGF-β/Smad3 pathway
Authors: Jiaxiao Li , Chen Junzhe , Tang Ying , Huang Xiaoru , Lan Hui Yao
Published: May 2024

Background and Aims

Acute kidney injury (AKI) is a common clinical syndrome characterized by rapid loss of kidney function but with limited diagnostic and treatment options. Annexins (ANXA) are a superfamily of calcium-dependent and lipid-binding proteins involved in multiple intracellular and extracellular functions. As a founding member of ANXA, ANXA13 is considered the prototype of a conserved evolutionary property of the annexin superfamily and is restricted to kidney and intestinal epithelial cells. However, it is currently unclear whether ANXA13 is a key regulator of AKI. Therefore, we aimed to investigate the role of ANXA13 in AKI.

Method

Kidney biopsy tissues from AKI patients were collected for immunohistochemical examination and ELISA method was used to detect the concentration of ANXA13 in serum and urine. A mouse model of AKI induced by ischemia-reperfusion injury (IRI) was established to verify the role of ANXA13 in AKI. RNA sequencing was also used to explore the mechanism of ANXA13 in AKI, and this result was further confirmed using Smad3 wild-type (WT) and knockout (KO) mice.

Results

AKI patients had reduced serum ANXA13 levels and increased urinary ANXA13 levels compared with healthy controls. The levels of ANXA13 in both serum and urine are related to serum creatinine (Scr). In kidney tissue, ANXA13 was significantly reduced in both AKI patients and IRI-AKI mice. By overexpressing ANXA13 by specifically transferring ANXA13-expressing plasmid into IRI-AKI mice via ultrasound microbubble-mediated kidney, we found that ANXA13 reduced Scr and blood urea nitrogen (BUN) levels and renal function in IRI-AKI mice. damage. In contrast, knockdown of ANXA13 by shANXA13 plasmid significantly exacerbated renal injury. Mechanistically, we found that the protective mechanism of ANXA13 was related to the inhibition of the TGF-β/Smad3-p21 cell cycle arrest pathway, and the aggravating effect of shANXA13 was reversed in Smad3 knockout mice. In turn, activation of Smad3 also suppresses ANXA13 mRNA and protein levels in vivo and in vitro.

Conclusion

ANXA13 can intervene in AKI by inhibiting the TGF-β/Smad3-p21 cell cycle blocking pathway. In turn, activation of Smad3 inhibits ANXA13 expression. Therefore, ANXA13 may be a new therapeutic target for AKI.
#2512 Behaviour of Human Proenkephalin A 119-159 (penKid) in an in vitro model of hemoadsorption
Authors: Perin Natascha , Lorenzin Anna , de Cal Massimo , Morisi Niccolò , Brendolan Alessandra , Lentini Paolo Luca Maria , Zanella Monica , Ronco Claudio
Published: May 2024

Background and Aims

Proenkephalin A 119-159 (penKid) is a stable surrogate marker for enkephalins (endogenous opioids regulating kidney function).

Different clinical studies have shown severity-dependent increased penKid levels in patients with sepsis-associated acute kidney injury (AKI), indicating that penKid can be used for prediction and diagnosis of AKI and need of renal replacement therapy (RRT) and even subclinical forms of AKI. In the absence of targeted therapies, organ support in terms of RRT is the ultimate treatment in severe AKI cases. Hemoadsorption is utilized as an adjunctive therapy in septic patients.

The aim of this study is to define the penKid removal ratio in conditions of in vitro hemoadsorption (HA) using a synthetic microporous hemo-compatible resin.

Method

The lyophilized peptide was solved in 20 mM Dipotassium phosphate, 6 mM Disodium EDTA [pH 8], avoiding concentrations higher than 1 mg/mL.

The compound was diluted in 50 mL of plasma to ensure homogeneous distribution.

A batch of blood of 1000 mL with adjusted hematocrit at 30% and albumin concentration of 3 g% was utilized.

Blood was spiked with lyophilized synthetic penKid to achieve the target concentration of 600 pmol/L. Blood was adjusted for a volume of 1000 mL, maintained at 37° and continuously stirred during the experiment.

HA was performed with QB = 150 mL/min in a closed-loop configuration. A sorbent minimodule of HA380 (Jafron, Zhuhai, People Republic of China) was utilized. Samples were taken at 5, 15, 30, 60 and 120 minutes from the initiation of the circulation. Total removal and reduction ratios were calculated to assess the adsorption.

This procedure was repeated three times.

Results

Initial penKid concentrations in blood corresponded to the desired target.

In the three experiments penKid concentrations displayed a consistent decrease that approached 75% removal ratio at 120 minutes (Figs 1 and  2). Minimal variability was observed confirming a consistent behavior of the interaction between the sorbent and the molecule.

Conclusion

The results suggest that penKid is effectively removed during hemoadsorption and its levels should be evaluated in light of these results when in vivo hemoadsorption is carried out in critically ill patients.
#3018 Aciclovir or valaciclovir neurotoxicity in renal patients: increasing number of neurotoxicity cases are diagnosed in Sweden by a blood test
Authors: Helldén Anders
Published: May 2024

Background and Aims

Kidney transplant patients are at high risk for developing zoster infections, as well as patients with impaired renal function. Aciclovir (ACV) and its prodrug valaciclovir are effective medications to treat these herpes infections. The medications typically have mild side effects such as nausea and vomiting, headache, and skin rash. More uncommon but serious side effects include elevated creatinine, acute kidney failure, and aciclovir-induced neuropsychiatric symptoms (AINS). The latter is difficult to distinguish from the viral infection treated, thus prolonged treatment with ACV may cause further deterioration and increase the chance for coma and need for intensive care treatment. ACV is excreted by glomerular filtration and tubular secretion and should be doses according to renal function. A small part is metabolized by alcohol dehydrogenase and aldehyde dehydrogenase to its main metabolite 9-carboxymethoxymethylguanine (CMMG), but as renal function decreases more CMMG is found in the urine, serum, and CSF. We have earlier shown that a serum CMMG cut-off level of 10.8 µmol/L is predictive of AINS. Hemodialysis alleviates the symptoms dramatically, but AINS need to be diagnosed first. The knowledge about our method has increased in Sweden, but has more AINS cases been diagnosed in Sweden now than for 10 years ago?

Method

Data from our therapeutic drug monitoring (TDM) database of ACV and CMMG levels were studied during the period 2013 to 2023. Serum samples with a CMMG concentration above 10.8 µmol/L were collated and compared to the total number of samples per year. Some patients were monitored with more than one blood sample during the treatment period and the number of single patients was also included.

Results

The database consisted of 4521 serum ACV and CMMG samples during the study period with 727 samples with a CMMG concentration above 10.8 µmol/L. The number of CMMG serum samples increased from 278 in 2013 to 601 in 2023. A total of 363 patients had at least one sample above 10.8 µmol/L. A median of 33 (range 17 to 59) single patients were diagnosed with AINS per year.

Conclusion

Measurement of both ACV and CMMG has increased the number of AINS cases in Sweden and are requested to a higher extent now than 10 years ago. Two more laboratories in Sweden measure or will start to measure ACV and CMMG, one laboratory in Bristol have had the method since 2007, but there are too few laboratories performing the analysis in other countries, causing severe suffering for patients and high costs for healthcare.
#1954 Effects of lanosterol synthase (LSS) gene on the development of acute kidney injury after cardiac surgery
Authors: Simonini Marco , Cocchini Lorenzo , Lanzani Chiara Livia , Raimondo Davide , D'urbano Luca , Citterio Lorena , Zagato Laura , Vezzoli Giuseppe , Manunta Paolo
Published: May 2024

Background and Aims

Acute kidney injury (AKI) is a common post-cardiac surgery complication, significantly affecting morbidity and mortality. Recent studies reported that high plasma levels of endogenous ouabain (EO), a stress hormone secreted by the adrenal glands, are associated to worse kidney outcomes after cardiac surgery. Our group demonstrated that EO activity is affected by a missense variant (rs2254524, C -> A, Val642Leu) in Lanosterol Synthase (LSS) gene, an enzyme implicated in EO synthesis. The aim of this work is to analyze the relationship between this LSS polymorphism and the development of AKI after cardiac surgery.

Method

1237 patients undergoing elective cardiac surgery were enrolled in the study. Preoperative biological samples were collected (Table 1). LSS genotypes were determined for each patient. The primary outcome was AKI development, according to KDIGO 2012 guidelines.

Results

21.4% of patients developed AKI. Different preoperative clinical variables were analyzed, identifying five independent risk factors significantly correlated to AKI development in multivariate logistic regression analysis: age (p < 0.001), FE (p = 0.005), NYHA class (p < 0.001), reoperation (p = 0.002) and complex surgical intervention (p < 0.001), Table 2. No significant differences were observed between preoperative EO plasma levels and allelic variants of LSS gene and patients with the less common A allele were not associated to a more severe preoperative clinical presentation, expressed as EuroScore II value (AA 2.54 ± 3.86 vs AC 2.15 ± 2.52 vs CC 2.04 ± 2.73; p = ns). LSS minor variants turned out significantly associated with the incidence of AKI (AA = 29.3%; AC = 25.3%; CC = 17.2%; X2 p < 0.001—Fig. 1). This evidence remains significant after correction for covariates associated to AKI previously reported (Log regression p = 0.002; RR for AA variant: 2.09 (IC95% 1.15-3.78))

Conclusion

Patients with at least one mutated allele of LSS variant have a higher probability of developing AKI after cardiac surgery. We think these results could be of interest to further understand cellular mechanisms underlying AKI development, especially in the cardiac surgery field.
#2886 Machine learning-based assessment of serum creatinine and NT-proBNP levels for predicting mortality in patients with heart failure and kidney injury
Authors: Đurović Vladimir , Petrović Milovan , Ilić Aleksandra , Milosavljević Anastazija Stojšić , Milovančev Aleksandra , Velicki Lazar , Maksimović Snežana Čemerlić , Popović Milica , Majstorović Gordana Stražmešter , Golubović Sonja , Knežević Violeta , Petrović Lada
Published: May 2024

Background and Aims

In a population hospitalized for acute heart failure, about 20% are affected by acute kidney injury, a significant independent factor linked to increased mortality both during hospitalization and within one year. While existing research offers insights, crafting a precise model to predict mortality in heart failure cases remains a complex task, primarily due to the difficulties in pinpointing critical determinants and achieving high accuracy. The aim of our research was to assess the efficacy of serum creatinine and NT-proBNP levels as predictors for mortality in heart failure patients, using machine learning.

Method

In our retrospective cross-sectional study, we examined the records of 1,042 patients hospitalized due to acute heart failure at the Institute of Cardiovascular Diseases of Vojvodina, spanning the period from January 1, 2021, to December 31, 2022. The data was initially cleaned, after which we employed a Random Forest model for our analysis. The dataset was partitioned into a training subset, constituting 70% of the data, and a testing subset, comprising the remaining 30%. To achieve optimal precision, we ran the model 100 times. Key performance metrics, including mean sensitivity, specificity, accuracy, F1 score, Matthew's correlation coefficient (MCC), and the area under the Receiver Operating Characteristic (ROC) curve (AUC), were derived from the model to assess its efficacy.

Results

Following data cleansing, the dataset encompassed a total of 389 patients, of which 58% were male. The median age in this cohort was 71 years, with an interquartile range (IQR) of 63 to 79 years. Key laboratory findings included a median serum creatinine level of 111 µmol/L (IQR: 85-167 µmol/L) and a median NT-proBNP level of 6,589 pg/mL (IQR: 2,822-15,608 pg/mL). After the partition, the median number of patients in the training set was 272 and the testing set comprised 117 patients. The performance of the Random Forest model was characterized by a sensitivity of 0.530, specificity of 0.916, an overall accuracy of 0.856, and an F1 score of 0.516. The MCC stood at 0.439 with the AUC under the ROC curve being 0.713.

Conclusion

While the relatively low sensitivity observed in our model could be attributed to the generally lower levels of serum creatinine upon admission and the retrospective nature of the study, which may have influenced the model's ability to identify all true positive cases effectively, serum creatinine and NT-proBNP levels hold promise as effective predictors for mortality in heart failure patients.
#645 Inferring trends in renal function based on a single serum creatinine with a spot urine creatinine-to-osmolality ratio in outpatient settings
Authors: Hsu Shih-Ping
Published: May 2024

Background and Aims

Assessing trends in renal function can be challenging when paired serum creatinine (SCr) levels are not available, especially at the initial visit for evaluating renal function. The aim of this study was to validate the use of a spot urine creatinine-to-osmolality ratio (sUCr/Osm) as a surrogate indicator of urinary creatinine excretion rate for inferring renal function trends.1 The objective is to create a flowchart that assists in determining appropriate outpatient management based on a single SCr value with sUCr/Osm.

Method

The current study conducted a secondary analysis using the primary datasets provided by The Assessment, Serial Evaluation, and Subsequent Sequelae of Acute Kidney Injury (ASSESS-AKI) Study.2 The term “stable renal function” refers to the absence of an interval increase in SCr of greater than or equal to 26.5 μmol/L (0.3 mg/dL) from a visit three months earlier to the index visit. The definition of “unstable renal function” is the presence of an interval increase in SCr of 26.5 μmol/L (0.3 mg/dL) or more within the same duration. The cut-off value for sUCr/Osm was set at 7.07 when Cr is measured in μmol/L (0.08 when Cr is measured in mg/dL), which represents the 95% lower reference limit.1 A positive designation was given if the value of sUCr/Osm was not less than the 95% lower reference limit, and negative otherwise. The comparative test employed a tubular injury biomarker, urinary neutrophil gelatinase-associated lipocalin (UNGAL). The cut-off value for UNGAL was established at 100 ng/mL based on the maximum Youden's Index value. A positive result was defined as a UNGAL level less than or equal to 100 ng/mL, while a negative result was defined as a UNGAL level greater than 100 ng/mL.

Results

Of all the participants (N = 1, 570), 596 (38.0%) were female sex. The age (mean ± standard deviation) was 64.6 ± 13.0 years, the body mass index (BMI) was 30.1 ± 7.7 kg/m2, and the SCr level was 102.5 ± 51.4 μmol/L (1.16 ± 0.58 mg/dL). The sensitivity of sUCr/Osm in identifying “stable renal function” for all individuals was 0.926 (95% confidence interval: 0.912-0.939), with a positive predictive value of 0.906 (0.891-0.921) and an accuracy of 0.845 (0.827-0.863). These values of sUCr/Osm were either better or comparable to those of UNGAL- 0.867 (0.849-0.884), 0.917 (0.902-0.932), and 0.808 (0.788-0.827), respectively. In individuals (N = 521) with an estimated glomerular filtration rate (eGFR) of less than 60 cc/min/1.73m², sUCr/Osm also performed better or similarly to UNGAL. Table 1 provides direct comparisons between sUCr/Osm and UNGAL in identifying “stable renal function”.

Conclusion

To assess renal function, sUCr/Osm may be effectively used to infer the trend. Fig. 1 presents a flowchart for the corresponding management based on a single SCr-based eGFR and sUCr/Osm.
#3066 Long-term outcomes after AKI in hospitalized patients with COVID-19
Authors: Da Silva Bernardo Marques , Gameiro Joana , Teixeira Joana , Costa Cláudia S , Branco Carolina , Oliveira João , Bernardo João , Marques Filipe Cordeiro , Fonseca José Agapito , Lopes José António
Published: May 2024

Background and Aims

Acute kidney injury (AKI) is frequent in hospitalized patients and contributes to adverse short- and long-term outcomes. We aimed to evaluate the association of AKI and long-term adverse renal events and mortality in a cohort of patients hospitalized with COVID-19.

Method

Single-center and retrospective study of hospitalized patients admitted to a Dedicated Unit for COVID-19 at Centro Hospitalar Universitário Lisboa Norte, Portugal, between March 2020 and October 2020. AKI was defined and classified according to the Kidney Disease: Improving Global Outcomes (KDIGO) classification, using SCr criteria. The analyzed outcomes were development of major adverse kidney events (MAKE), major adverse renal cardiovascular events (MARCE), and mortality over a two-year follow-up period.

Results

From the included 409 patients, AKI occurred in 60.4% (n = 247). Within two years after discharge, 31.8% (n = 130) of patients had an eGFR <60 mL/min/1.73 m2 and/or a 25% decrease on eGFR and 1.7% (n = 7) of patients required RRT, 6.1% (n = 25) of patients had CV events and 27.9% (n = 114) of patients died. The incidence of MAKE was 61.4% (n = 251), and MARCE was 67.5% (n = 276). On a multivariate analysis, older age (adjusted HR 1.02 (95% CI: 1.01-1.04), p = 0.008), cardiovascular disease (adjusted HR 2.22 (95% CI: 1.24-3.95), p = 0.007), chronic kidney disease (adjusted HR 5.15 (95% CI: 2.22-11.93), p < 0.001), and AKI (adjusted HR 1.76 (95% CI: 1.12-2.78), p = 0.015) were independent predictors of MAKE. Older age (adjusted HR 1.06 (95% CI: 1.04-1.08), p < 0.001) and neoplasia (adjusted HR 4.88 (95% CI: 2.37-10.04), p < 0.001) were independent predictors of mortality.

Conclusion

In this cohort of hospitalized patients with COVID-19, AKI was independently associated with the risk of long-term need for dialysis and/or renal function decline and/or mortality after hospital discharge.
#1187 Acute kidney injury and tubulointerstitial nephritis following prescription of anticancer drugs: VigiBase analysis
Authors: Jeong Kyunghwan , Yoon Soo-Young , Kim Jin Sug , Lee Jeong-Yeun , Kim Hyun Kyu , Kim Dae Kyu , Hwang Hyeon Seok , Yon Dong Keon
Published: May 2024

Background and Aims

Anticancer drugs can have varying effects on the kidneys, depending on their characteristics. Various anticancer drugs may be nephrotoxic and can potentially cause renal impairment. We aimed to analyze the risk of renal adverse reactions according to different types of anticancer drugs using a global reporting system.

Method

We conducted an analysis on VigiBase, the World Health Organization pharmacovigilance database from Dec 1967 to Jul 2023 via disproportionate Bayesian reporting method. We further categorized the anticancer drugs into four groups: cytotoxic therapy, hormone therapy, immunotherapy, and targeted therapy. Reporting odds ratio (ROR) compares observed and expected values to find the associations of each category of anticancer drugs with acute kidney injury (AKI) and tubulointerstitial nephritis (TIN).

Results

We observed 32,722 AKI and 2,056 TIN reports which were reported as anticancer drug-related renal adverse reactions. Noteworthy trends emerged in AKI reports following anticancer drugs: cytotoxic therapies consistently dominated with 13,925 cases, while AKI cases related to targeted therapies and immunotherapies surged to 14,236 and 3,816 cases over three decades, respectively. Notably, TIN exhibited a significant increase, particularly after the popular usage of immunotherapy between 2015 and 2020, surpassing other categories of anticancer drugs. The highest disproportionality signal for AKI was associated with immunotherapies (ROR, 8.92; confidence interval [CI], 8.63–9.21, followed by cytotoxic therapies (ROR, 7.14; 95% CI, 7.01–7.26), targeted therapies (ROR, 5.83; 95% CI, 5.73–5.93), and hormone therapies (ROR, 2.59; 95% CI, 2.41–2.79). In the case of TIN, a significantly higher disproportionality signal was found for immunotherapies (ROR, 21.74; 95% CI, 20.39–23.18), followed by cytotoxic therapies (ROR, 2.60; 95% CI, 2.40–2.82), and targeted therapies (ROR, 1.54; 95% CI, 1.40–1.69). Hormone therapies did not exhibit a significant disproportionality signal. Separate analyses were also conducted for the ROR of AKI and TIN for each individual anticancer drug.

Conclusion

AKI and TIN were substantially observed following the administration of anticancer drugs. Noticeably, renal adverse reactions following immunotherapy, which have been experiencing an increase in utilization, were more prominent than other types of anticancer drugs. Clinicians should consider the increased risk of renal adverse reactions after specific anticancer drugs.
#2657 Evaluation of the impact of a nephrologist led acute kidney Injury clinic in a large district general hospital
Authors: Khandaker Mustakim , Rahman Saeed
Published: May 2024

Background and Aims

Acute kidney injury (AKI) has a significant impact on inpatient hospital admissions costing the NHS in the UK an estimated £1bn. Hospitalisation complicated by AKI results in increased length of stay and mortality and up to a fifth of discharged patients are readmitted to hospital within 30 days. Traditionally district general hospitals in the UK have limited nephrology cover. In our large district general hospital, a new nephrologist led AKI clinic was established to review patients whose inpatient admissions were complicated by a stage 2 or 3 AKI. Over a 7-month period the aim was to evaluate this new clinic and its impact for local patients and the hospital trust.

Method

Inpatients with stage 2 and 3 AKI were identified by a specialist AKI nurse and nephrologist as suitable for the clinic. A discharge summary was generated with the stage and cause of AKI. Patients were seen within 6 weeks of discharge by either a nephrologist or a specialist AKI nurse. Data was retrospectively collected, and this included diagnosis, causes of AKI, highest stage of AKI, progression of chronic kidney disease (CKD) and referral to tertiary chronic kidney disease services. Using the hospital's own AKI dashboard, we looked at 30-day readmission rates of all AKIs and overall hospital length of stay over this period.

Results

Retrospective data was collected for 245 patients who attended the clinic over 7 months. 43.9% had a stage 3 AKI, 41.4% had a stage 2 AKI, the remainder of patients were CKD patients with progression or had an underlying glomerular pathology. The most common cause for AKI was hypovolaemia (41.8%) followed by infection/sepsis (37.7%). Most AKIs fully resolved (58.1%), 7% of patients had not resolved and 27% partially resolved. 12.3% of patients were referred onto nephrology tertiary services.

Over the course of the 7 months, the trend of 30-day readmission rates dropped from 18.2% to 10.1% (Fig. 1). There was no significant change in hospital length of stay.

Conclusion

The nephrology led AKI clinic has had a meaningful impact in our post discharge patient care. We have been able to review patients in a timely manner providing them with a holistic approach. A significant number of patients were identified and referred early for specialist tertiary CKD management. Over the 7-month period there was a reduction in 30-day readmission rates however it has not yet affected overall length of stay. This study supports a nephrologist led AKI clinic in a district general hospital.
#768 Renal-limited thrombotic microangiopathies and hemolytic uremic syndromes, on behalf of the MATRIX consortium group
Authors: Maisons Valentin , Mesnard Laurent , Duval Anna , Frimat Marie , Fakhouri Fadi , Grange Steven , Servais Aude , Cartery Claire , Chauvet Sophie , Ohlmann Sophie , Vuiblet Vincent , Halimi Jean Michel
Published: May 2024

Background and Aims

Thrombotic microangiopathies (TMA) are usually associated with hematological features (RH-TMA). The epidemiology of TMA limited to kidneys (RL-TMA) is unclear.

Method

Patients with TMA and native kidney biopsies were identified during the 2009-2022 period in 20 French hospitals.

Results

RL-TMA was present in 341/757 (45%) patients and associated with lower creatinine levels (184 [115-297] vs 346 [206-626] µmol/L) than RH-TMA. RL-TMA resulted from virtually all KDIGO causes (more frequently from anti-VEGF treatment and hematological malignancy, less frequently from shiga toxin-associated hemolytic uremic syndrome (HUS), systemic sclerosis, gemcitabine and bacterial infection) but less frequently combined (≥3 causes/triggers: RL-TMA: 5%; RH-TMA: 12%). RL-TMA were associated with significantly lower major cardiovascular events (10% vs 20%), kidney replacement therapy (23% vs 43%) and death (12% vs 20%) than RH-TMA during follow-up (median: 28 (interquartile range: 7-72) months.

Atypical HUS (aHUS) was found in 326 patients (RL-TMA: 43%, RH-TMA: 46%). Among the 69 patients with complement-mediated aHUS, 17 (25%) had RL-TMA and eculizumab was used in 43 (62%) (RL-TMA: 35%; RH-TMA: 71%). Among the 257 other aHUS patients, including 51% with RL-TMA, complete complement evaluation was performed in 85 (33%) (RL-TMA: 33%, RH-TMA: 33%) and eculizumab was used in 29 (11%). The effects of eculizumab were unclear.

Conclusion

RL-TMA represent a very high proportion of TMA patients, result from virtually all causes, including the 25% of patients with complement-mediated aHUS, and have a poor prognosis. Anti-C5 therapy is rarely used in RL-TMA, even in proven complement-mediated aHUS, and thus its effects remain to be assessed.
#1748 The burden of cardiorenal syndrome: epidemiological data and treatment: a one-center experience
Authors: Stathopoulou Elpiniki , Giannou Panagiota , Alexakou Zoi , Bora Margarita , Aggelis George , Stambolliu Emelina , Kourniotis Dimitrios , Papras Athanasios , Chalkia Aglaia , Kapota Athanasia , Petras Dimitrios
Published: May 2024

Background and Aims

Cardiorenal syndrome (CRS) is an entity combining cardiac and renal dysfunction in a bi-directional way. Six subtypes of CRS have been described, all of which are associated with high morbidity and mortality rates. CRS treatment—no matter the subtype—is until nowadays a field of investigation, aiming to the reduction of fluid overload and venous congestion. The primary endpoint of this study was to estimate the frequency of cardiorenal induced AKI compared to other AKI etiologies in hospitalized patients. We furthermore aimed to determine the burden of the therapeutic regimen in hospitalization duration and renal deterioration.

Method

This is a retrospective, quantitative analysis of hospitalized adult patients in General Hospital of Athens Hippokration suffering from AKI of various etiologies. No age or sex limitations were used for the purposes of this study.

Results

A total amount of 1163 patients were enrolled over the course of 18 months. 430 (36.9%) of these patients were hospitalized in the cardiologic department, suffering from either acute or chronic heart failure (66.5% of which were men) with a mean age of 74.4 ± 11.4 years. Mean creatinine level at hospital admission was 2.7 ± 2 mg/dl. Out of these patients, 33.9% were treated using diuretics alone, while 25.5% also needed hemodialysis. Mean number of days of hospitalization was 9.4 ± 5.8 days and 11 ± 8.8 days, while creatinine exit was 2.9 ± 1.5 mg/dl and 4.2 ± 3 mg/dl respectively.

Conclusion

Cardiorenal syndrome is a quite common cause of AKI in patients being hospitalized. In our study, patients that needed treatment with diuretics compared to those requiring a combination of diuretics and hemodialysis had less days of hospitalization and a better kidney function outcome.
#2707 Prediction of plasma sodium changes in hypernatremic patients: the role of tissue sodium content
Authors: Simon Sanédy , van Vliet Anne Myrthe , Lindner Gregor , Vogt Liffert , Oppelaar Marjet , Engberink Rik Olde
Published: May 2024

Background and Aims

Hypo- and hypernatremia are frequently encountered electrolyte disturbances in clinical practice. Rapid correction of these dysnatremias can result in severe neurological complications. Therefore, various formulas have been developed to predict changes in plasma sodium concentration ([Na+]) after treatment. However, these kidney-centered formulas have been shown to be inaccurate. A potential explanation for the discrepancy between predicted and measured plasma [Na+] is the accumulation of sodium in the skin, which is not explicitly taken into account in these formulas. The purpose of this post-hoc analysis is to evaluate the association between factors related to tissue sodium accumulation and the discrepancy between measured and predicted plasma [Na+].

Method

We used data from a hypernatremic intensive care unit (ICU) cohort with 66 patients and 1,034 ICU days with complete data on sodium, potassium and water balance. We excluded ICU days with incomplete balances, dialysis and severe diarrhea. The predicted plasma [Na+] was calculated using the Barsoum-Levine (BL) and the Nguyen-Kurtz (NK) formula. Then, we calculated the discrepancy between predicted and measured plasma [Na+] (∆[Na+]). We fitted a linear mixed-effect model to investigate the association between factors related to tissue sodium content and ∆[Na+]. Age, sex, blood pressure, eGFR, CRP, plasma albumin, total body water (TBW), baseline plasma [Na+] and changes in plasma [Na+] were incorporated as fixed effects in the model, while the subjects were introduced as a random effect. TBW was estimated as 60% of body weight for males and 50% of body weight for females, corrected for fluid balances on subsequent ICU days.

Results

A total of 613 ICU days of 66 patients were included in our analysis. The mean age was 58 ± 15 years and 38% was female. The mean plasma [Na+] at inclusion day was 145 ± 9 mmol/L and mean eGFR CKD-EPI was 52 ± 28 ml/min/1.73 m2. On average, the deviation between predicted and measured plasma [Na+] was 3.8 ± 3.3 mmol/L for the BL formula and 3.9 ± 3.4 mmol/L for the NK formula. For both formulas, TBW (p = 0.01), baseline plasma [Na+] (p < 0.001) and plasma [Na+] change (p < 0.001) were significantly associated with the discrepancy between predicted and measured plasma [Na+] (Table 1). Plasma albumin (p = 0.02) was also significantly associated with this discrepancy when the NK formula was used.

Conclusion

In a hypernatremic ICU cohort, baseline plasma [Na+], estimated TBW and plasma [Na+] changes are associated with the inaccurateness of plasma [Na+] prediction. As baseline plasma [Na+] and estimated TBW are available when initiating treatment, incorporation of these variables in the currently available formulas may improve the prediction of plasma [Na+].
#2956 Hemodynamic evaluation of different replacement fluids during therapeutic plasmapheresis with Crit-line™
Authors: Moranne Olivier , Elassas Hajar
Published: May 2024

Background and Aims

Therapeutic plasmapheresis (TP) is an extracorporeal technique used to remove pathogenic macromolecules from the plasma. Human serum Albumin (HSA) or fresh frozen plasma can be used as replacement fluid, alone or in combination, and with or without the addition of a crystalloid such as saline. There is wide practice variation in the type of replacement fluid and according the procedure of TP such as single plasma exchange (SPE) or double plasmafiltration (DFPP). Replacing plasma with crystalloid carries a risk of hypotension if the proportion of replacement with crystalloid exceeds 30%. CRIT-LINE™ monitor estimate RBV changes during HD based on measurements of hematocrit and could be used in hemodialysis to prevent hypotensive episodes.

Method

We conducted a retrospective case series study in a tertiary center to evaluate RBV changes during TP (SPE & DFPP) in three patients with PIDC treated with chronic TP using SPE or DFPP according to guidelines. For each patient and procedure (SPE or DFPP) we compare different substitution fluid infusion protocol between 2021 and 2023. We evaluated each patient's sessions with CRITLINE™ continuous RBV monitoring during either SPE or DFPP with comparison of different replacement fluid protocols. For DFPP with plasmafractionator EC30 (Asahi Kasei Medical Co., Japan) or medopen30 (Infomed, Switzerland), we compare protocols as follows (1) continuous infusion of 500 ml of HSA 4% throughout the session and (2) 500 ml HSA 4% at the last 20 min of the session. For SPE, we compare protocols as follows (1) 100% volume of HSA 4% supplementation (2) a combination of 70% HSA 4% and 30% of saline started at the last part of the session (3) a combination of 70% HSA 4% and 30% of saline started at the first part of the of the session.

Results

BVM decreased by 15% ± 5% in DFPP session with 500 ml HSA 4% at the last 20 min of the session and by 12% ± 3 in DFPP session with continuous infusion of 500 ml of HSA 4% throughout the session . In SPE, BVM decreased by 18% ± 2 in session with a combination of 70% HSA 4% and 30% of saline and by 10% in session with 100% albumin substitution. Hypotensive episodes occurred in session with a combination of 70% albumin 4% and 30% of saline at the end of session.

Conclusion

CRITLINE IV continuous RBV monitoring is an interesting tool that can be used to evaluate the optimal substitution fluid in TP and for prevention of hypotension. Randomized control trial are needed to confirm the results.
#1502 Short-term effects of gadolinium and gadoteric acid on kidney — impact on inflammation
Authors: Coimbra Susana , Rocha Susana , Viana Sofia D , Rebelo Rute , Valente Maria João , Rocha-Pereira Petronila , Catarino Cristina , Bronze-Da-Rocha Elsa , Belo Luís , Reis Flávio , Santos-Silva Alice
Published: May 2024

Background and Aims

The nephrotoxicity of free gadolinium [Gd (III)] has been reported, raising concerns about the safety of gadolinium-based contrast agents (GBCA), widely used in magnetic resonance imaging. The GBCA with macrocyclic structure, such as gadoteric acid (Gd-DOTA), appear as more stable. Using human proximal tubular cells cultures, we found that free Gd (III) triggers death by apoptosis and necrosis, and increases the expression of modulators of inflammation, hypoxia and fibrosis, which are known as major risk factors for the development and worsening of kidney disease.

Our aim was, using animal models, to evaluate the short-term effects of Gd (III) and of gadoteric acid on inflammatory biomarkers, at blood and renal tissue levels.

Method

Wistar rats were exposed to a single dose of Gd (III) or Gd-DOTA (groups A and B, respectively); a control group was also included (C). After 48h, blood and kidney samples were collected. The plasma levels of interleukin (IL)6 and transforming growth factor (TGF) beta 1 were assessed by ELISA; the kidney gene expression of IL6 (il6), TGF beta 1 (tgbf1) and nuclear factor-kappa B (nfkb1) was determined through qPCR.

Results

Gd (III) group (A) presented higher circulating IL6 levels (P = 0.001) and increased kidney gene expression of il6 (P = 0.013), tgbf1 (P = 0.006) and nfkb1 (P = 0.011) than the control group (C); compared to Gd-DOTA group (B), the IL6 plasma concentration (P = 0.005) and tgbf1 mRNA levels were also higher (P = 0.004). The Gd-DOTA group (B) presented increased gene expression of il6 (P = 0.006) than the control group (C).

Conclusion

Short-term exposition to free Gd (III) induced an inflammatory response, shown by the increase in circulating IL6, and in kidney gene expression of il6, tgbf1 and nfkb1. The exposition to Gd-DOTA was associated with a lower inflammatory response, showing only increased kidney gene expression of il6. Despite the much safer profile for Gd-DOTA, further studies are warranted, evaluating other biomarkers, to clarify the short-term, and even the long-term effects, of these compounds.

Acknowledgements

This work was financed by FCT through the project 2022.08400.PTDC; FCT, in the scope of the project UIDP/04378/2020 and UIDB/04378/2020 of the Research Unit on Applied Molecular Biosciences—UCIBIO and the project LA/P/0140/2020 of the Associate Laboratory Institute for Health and Bioeconomy—i4HB.
#1521 EZH2 promotes cyst growth in autosomal dominant polycystic kidney disease
Authors: Mao Zhiguo , Xue Cheng
Published: May 2024

Background and Aims

Autosomal dominant polycystic kidney disease (ADPKD) is the leading hereditary kidney disease worldwide. Epigenetic modulations of genes and proteins play important roles in ADPKD pathogenesis. In this study, the role of enhancer of zeste homolog 2 (EZH2), a histone lysine methyltransferase, was investigated in ADPKD.

Method

To elucidate the role of EZH2 in ADPKD pathogenesis, we employed inducible knockout models, specifically targeting Pkd1 alone (Pkd1fl/fl) or both Pkd1 and EZH2 (Pkd1fl/fl: Ezh2fl/fl) in mouse models. Molecular analyses included assessing EZH2 expression levels and H3K27 trimethylation in Pkd1 knockout cells, kidney tissues from Pkd1 knockout mice, and samples from ADPKD patients. Functional investigations involved the use of EZH2-specific inhibitors, GSK126 and EPZ-6438, to inhibit EZH2 activity. Additionally, Ezh2 knockdown was employed to assess its impact on cystogenesis in MDCK cells. The embryonic kidney cyst model was utilized to evaluate the effects of GSK126 and EPZ-6438 on cyst growth.

Results

We found that EZH2 expression and the trimethylation of lysine 27 on histone H3 (H3K27) were upregulated in Pkd1 knockout cells and kidney tissues of Pkd1 knockout mice and ADPKD patients. Using EZH2-specific inhibitors GSK126/EPZ-6438 and knockdown of Ezh2 both suppressed cystogenesis in MDCK cells. GSK126 and EPZ-6438 delayed cyst growth in the embryonic kidney cyst model. Double knockout of Pkd1 and Ezh2 significantly decreased the kidney volume, cyst indexes, H3K27 methylation level, and the proliferation of renal cystic epithelial cells compared with Pkd1 knockout mice. Moreover, GSK126 delayed cyst growth and protected renal function in both early- and late-onset Pkd1 conditional knockout mice. EZH2 promoted the proliferation of renal cystic epithelial cells by activating STAT3 through H3K27 methylation.

Conclusion

Inhibiting EZH2 emerged as a promising strategy to impede cyst growth and attenuate disease progression across various PKD models. These findings establish a molecular foundation for the potential use of EZH2-specific inhibitors in delaying ADPKD cyst growth in the future.