Need For Renal Replacement Therapy Research Articles

Multicentre, retrospective cohort study protocol to identify racial and ethnic differences in acute kidney injuries in children and adolescents with diabetic ketoacidosis

IntroductionApproximately 40% of children with diabetic ketoacidosis (DKA) develop acute kidney injury (AKI), which increases the risk of chronic kidney damage. At present, there is limited knowledge of racial or...

Impact of extracorporeal haemoadsorption during prolonged cardiopulmonary bypass on the incidence of acute kidney injury.

The usage of cardiopulmonary bypass (CPB) in cardiothoracic surgery contributes to the activation of the inflammatory response. In certain cases, the systemic inflammatory response may be immoderate, leading to organ dysfunction, such as acute renal failure or multiorgan dysfunction. This study aimed to examine the effect of haemoadsorption (HA) therapy on inflammatory markers and renal damage indices during cardiopulmonary bypass and in the early postoperative period. We conducted a retrospective analysis of prospectively collected data in a single tertiary care center on patients operated between January 2021 and May 2022. The levels of inflammatory markers and renal parameters in blood samples (Interleukin (IL) 6, C-reactive protein (CRP), white blood cells, lactate, procalcitonin (PCT), and NT-proBNP, urea, creatinine, glomerular filtration rate (GFR), mechanical ventilation days and intensive care unit (ICU) days) were compared between the three groups. Data from the Jafron HA 330 (n=20) and CytoSorb300 (n=20) groups were compared with those from the control group (n=20). All patients underwent cardiopulmonary bypass for more than 120min. Baseline patient characteristics were similar in all three groups. Acute kidney injury (AKI) was diagnosed in 17 patients (28.3%); seven patients were in the Jafron HA 330, two in the CytoSorb300, and eight in the control group. We found that IL1α, IL 6, IL8, Lactate dehydrogenase, PCT, NT-proBNP, CRP, Leukocyte, and TNFα had no significant or clinical difference between the CytoSorb 300 and Jafron HA 330 adsorber groups. Our results indicate that haemoadsorption therapy does not significantly reduce the risk of AKI after prolonged CPB, but decreases the need for renal replacement therapy.

Outcomes of Adult Patients With COVID-19 Transitioning From Venovenous to Venoarterial or Hybrid Extracorporeal Membrane Oxygenation in the Extracorporeal Life Support Organization Registry.

This retrospective analysis of the Extracorporeal Life Support Organization (ELSO) registry evaluates the outcomes and identifies risk factors associated with conversion from initial venovenous extracorporeal membrane oxygenation (ECMO) support to venoarterial or hybrid ECMO in patients with coronavirus disease 2019 (COVID-19). We collected deidentified data on all adult patients (≥18 years old) diagnosed with COVID who received venovenous extracorporeal membrane oxygenation between March 2020 and November 2022. Patients initially placed on an ECMO configuration other than venovenous (VV) ECMO were excluded from the analysis. Our analysis included data from 12,850 patients, of which 393 (3.1%) transitioned from VV ECMO to an alternative mode. The primary outcome measure was in-hospital mortality, and the conversion group exhibited a higher in-hospital mortality rate. We also examined baseline variables, including demographic information, biochemical labs, and inotrope requirements. Univariate analysis revealed that pre-ECMO arrest, the need for renal replacement therapy, and the use of inotropic agents, particularly milrinone, were strongly associated with the risk of conversion. Notably, even after implementing a 3:1 propensity score matching, the impact of conversion on both mortality and complications remained substantial. Our study underscores an elevated risk of mortality for COVID-19 patients initially treated with VV ECMO who subsequently require conversion to VA-ECMO or hybrid ECMO.

#2424 Higher 24-hour urine sodium-to-potassium ratio is associated with worse renal outome

Abstract Background and Aims Low sodium and high potassium intake are advised to control blood pressure and may improve long term cardiorenal outcomes. The optimal potassium intake for patients with chronic kidney disease remains to be defined. We investigated whether the 24-hour urine sodium-to-potassium ratio (Na/K-ratio), which incorporates estimates of both sodium and potassium intake, could predict long-term renal outcome. Method We selected adult outpatients of a Dutch tertiary hospital who collected at least one 24-hour urine collection with available sodium and potassium measurements between 1998-2023. Patients with a history of dialysis or kidney transplantation were excluded. We examined the need for persistent renal replacement therapy (RRT), defined as dialysis or kidney transplantation, using Cox regression. The association between the 24-hour urine Na/K-ratio and the estimated glomerular filtration rate (eGFR) slope was assessed using linear regression in patients who had ≥3 eGFR measurements available in ≥3 years. The linear regression analysis was adjusted for age, sex, baseline eGFR, diabetes mellitus and hypertension. In the Cox regression analysis, we additionally adjusted for the interaction between the 24-hour urine Na/K-ratio and baseline eGFR. Hypertension was defined as a clinical diagnosis or an office blood pressure ≥140/90 mmHg. Results We included 720 patients aged 50 ± 15 years, of whom 52% were male, 58% had hypertension and 31% diabetes mellitus. The baseline eGFR was 64 ± 34 ml/min/1.73 m2. The 24-hour urine Na/K ratio was 2.5 ± 1.2 in a median number of 1 (IQR = 1-2) urine collection. During a median follow-up of 11.2 (14.0) years, 29% of patients needed RRT. In 575 patients with sufficient eGFR measurements (mean 12 ± 8 measurements per subject) the median annual eGFR decline was 1.51 (IQR = 0.49-3.98) ml/min/1.73 m2. Every unit increase in the 24-hour urine Na/K-ratio was associated with a 19% higher risk for persistent RRT need (HR 1.19, 95% CI 1.03-1.39; p = 0.02) and an additional 0.44 ml/min/1.73 m2 (95% CI −0.83, −0.04; p = 0.03) decline in eGFR. Conclusion This study suggests that higher 24-hour urine Na/K-ratio is associated with faster kidney function decline and the need for RRT, independent of hypertension, in a selected group of outpatients.

#1505 Late-onset lupus nephritis: clinical-epidemiological, histological, prognostic and therapeutical implications: a single center experience

Abstract Background and Aims Systemic lupus erythematosus (SLE), a chronic autoimmune disease, and lupus nephritis (LN), are typically diagnosed in women in fertile age. Late-onset SLE is defined as a disease onset over 50 years. Our main objective was to analyze the clinical, histological, prognostic and therapeutical features related to LN in our late-onset SLE population. Method A single center and retrospective study was performed comparing clinical-demographic, histological, prognostic and therapeutical data of 45 LN biopsied patients from 1994 to 2023. We divided the study population according to the age of onset of LN into classic-onset (< 45 years) and late-onset (> 45 years). Results Late-onset LN patients showed a higher association with Sjögren's and antiphospholipid syndrome, more cardiovascular comorbidities at presentation, poorer renal function at diagnosis and higher SDI score. On histology they showed more non-proliferative LN classes (II followed by V). Late-onset LN responders needed more time to achieve response but had fewer relapses. Non responsive patients had more incidence of acute kidney injury (AKI) and more glomerulosclerosis and interstitial fibrosis-tubular atrophy (IFTA) at presentation, as well as more need for renal replacement therapy (RRT) at diagnosis and at follow-up. The principal independent variables associated with relapse were the younger age at SLE diagnosis and an initial partial renal response (PRR). Patients of both groups who experienced relapse received higher doses of intravenous cyclophosphamide and less mycophenolic acid (MFA) analogues. Patients who received induction with MFA analogues were more likely to achieve complete renal response (CRR) or non-renal response (NRR). Conclusion late-onset LN is often accompanied by poor renal function at presentation. It seems imperative to establish a tailored approach in this fragile population in order to avoid unnecessary immunosuppression.

#1716 IgA nephropathy: our center's experience

Abstract Background and Aims IgA Nephropathy (IgAN) is the most common primary glomerulopathy worldwide. In the last years, significant advances have been made in understanding its pathophysiology and developing newer promising treatments. The accuracy of the International Risk-Prediction Tool in IgAN (IRP-IgAN) was already validated. Herein, we retrospectively analysed the relation of this risk score and the kidney outcomes. Method We performed a single center retrospective observational cross-sectional study of patients with histological diagnosis of IgAN between 2015 and 2023 in Centro Hospitalar de Setúbal, aiming to describe the demography, clinical presentation, histological characteristics, treatment and follow up of our cohort. The International Risk-Prediction Tool in IgAN was applied for patient stratification. Results Twenty-eight patients were diagnosed with IgAN in this eight-year period. Mean age was 46 years-old (SD ±12.2) and 71.4% were male. The majority were Caucasian (n = 26) with only two patients of Asian e African descent, respectively. The mean calculated Charlson Comorbidity Index was 1.43 (SD ±1.5). Eighteen patients (64.3%) had known arterial hypertension, diabetes was seen only in 2 patients, obesity in 4 patients, and hepatitis B in 2 patients. No cardiovascular disease or cancer was documented. On presentation, 71.4% (n = 20) had hypertension, 14.3% (n = 4) presented with rapidly progressive renal insufficiency, and 14.3% (n = 4) presented with nephrotic syndrome. Two patients (7.1%) required dialysis on presentation. Also, the mean glomerular filtration rate (GFR) was 55.3 ml/min (SD ±31.9) and mean proteinuria level (protein-to-creatinine ratio) was 2.42g/g (SD ±2.41). Most patients had hematuria (82.1%), C3 consumption was seen in only one patient while 10 patients had isolated higher levels of IgA. Mean time between the first symptoms or documented clinical features and dedicated Nephrology consultation was 2.9 years (SD ±3.78). Regarding the histological data and considering de MEST-C score, 71.4% had mesangial hypercellularity in more than 50% of the glomerulus (M1), 25% had endocapillary hypercellularity (E1), 17% had segmental glomerulosclerosis of at least one glomerulus (S1), 7% had interstitial fibrosis or cortical atrophy in 25-50% of the cortical area (T1) and 11% in more than 50% (T2), 17.9% had crescents in less than 25% of the glomerulus (C1) and 2.6% in more than 25% (C2). Fibrinoid necrosis was noticed in 7.1% of the patients. The presence of IgA in the mesangium on IF was universal and 18 patients (64.3%) had C3 co-stain. Approximately half of the patients (46.4%) were already on angiotensin converting enzyme inhibitor (ACEI) or angiotensin receptor blockers (ARB) by the time of clinical presentation and nearly all (92.9%) by the time the diagnosis was established. SGTL-2 inhibitors were started in 42.9% of the patients. Eight patients (28.6%) started immunosuppression therapy, within a mean time from histological diagnosis of 0.7 years (SD ±1.03). Of those, all of them were on corticosteroids, one patient was additionally under oral cyclophosphamide and another one under mofetil mycophenolate. According to the IRP-IgAN, patients were stratified in low (35.7%), intermediate (10%) and high risk (8%) of kidney disease progression (GFR decline >50%) or ESKD. In a mean time of 0.53 (SD ±0.34) years of follow-up after diagnosis, 8 patients (28.6%) required renal replacement therapy, with 7 choosing hemodialysis and 1 peritoneal dialysis. Six patients lost follow-up. Three patients died a mean time of 1.2 years after diagnosis, one from immunosuppression-related adverse events. We also found an association between higher risk group and progression to ESKD (p < 0.001). Conclusion The IRP-IgAN tool is a useful tool for prediction of kidney disease progression and the need for renal replacement therapy. The supportive care in IgAN even with antiproteinuric approach could be insufficient for patients with high and intermediate risk. The risk progression to ESKD is indeed heterogeneous, and close follow-up of these patients should be guaranteed.

#236 Immediate or delayed initiation of renal replacement therapy in patients with leptospirosis and acute kidney injury: a target trial emulation

Abstract Background and Aims Leptospirosis is a widespread zoonosis responsible for 60,000 deaths annually worldwide [1]. Acute kidney injury (AKI) stands out as a hallmark of the disease. Leptospirosis-induced AKI (AKI-L) has been entertained as a potential cause of chronic kidney injury of unknown etiology, which is a significant burden in tropical rural settings [2]. Anecdotal evidence suggests that early renal replacement therapy (RRT) may improve mortality associated with AKI-L [3]. Conversely, several randomized controlled trials (RCTs) conducted in intensive care units have refuted the positive impact of early RRT on mortality in patients with other causes of AKI and sepsis [4]. Given these contradicting results, the optimal timing for initiating RRT in patients with leptospirosis and severe AKI remains uncertain. In this emulated RCT, we aimed to evaluate the impact of the timing of RRT on mortality and worsening renal failure (WRF) in patients hospitalized with leptospirosis, stage 3 AKI on admission, and no immediate need for RRT. Method We conducted a retrospective cohort study in two academic centers in Réunion island between 2010 and 2020. During this period, we included adult patients with documented leptospirosis and stage 2 or 3 AKI. Then we selected patients with stage 3 AKI to perform a target trial emulation, adapted from the AKIKI trial's design. Patients were categorized according to the allocated treatment strategy. Patients assigned to the “early” group received RRT within 48 hours following hospital admission while patients in the “delayed” group did not. A propensity score was derived for each imputed dataset using multivariate logistic regression. The propensity score estimates the probability of treatment allocation as a function of covariates assessed upon hospital entry. These covariates included those used in the SAPSII score and patients' baseline renal function. The primary outcome was a composite outcome assessed at one year: death or WRF. Results The cohort included 380 patients. We selected 295 patients with stage 3 AKI to perform the emulated RCT. Eight two (28%) patients were started on RRT within 48 hours of admission and were assigned to the early group. The delayed group included the remaining 213 patients, with 25% undergoing subsequent RRT and 75% not requiring such intervention. The median time to RRT initiation was 2 (1-3) days. Fifty-nine patients (20%) met the primary outcome: 14 patients (4.7%) died during their hospital stay or within 1 year after discharge, and 45 (15.3%) developed WRF. In the main analysis, the adjusted odds ratio (OR) for primary outcome occurrence was of 2.12 (95% confidence interval: 1.03 to 4.37, p = 0.04; reference group: “delayed” strategy). In secondary analyses, there was a significantly higher probability of WRF at one year in patients assigned to the “early strategy” (OR = 2.79 [1.28-6.11], p = 0.010). Mortality at one year according to RRT timing strategy did not differ (p = 0.6). Conclusion Early initiation of RRT was not found to improve the combined outcome of death and development of WRF in patients with leptospirosis and stage 3 AKI. A strategy based on a delayed initiation of RRT should be formally recommended for patients with severe AKI-L as in the general population of critically ill patients.

#635 Effect of multi-biomarker panels based on urinary N-terminal osteopontin on prediction of diabetic kidney disease in patients with diabetes mellitus

Abstract Background and Aims Diabetic kidney disease (DKD), occurs in 20–40% of patients with diabetes mellitus (DM), is the leading cause of end-stage renal disease (ESRD). DKD is a clinical diagnosis mainly based on the persistent albuminuria and reduced estimated glomerular filtration rate (eGFR) [1]. However, increased UACR and reduced eGFR are the final consequences due to DKD, novel biomarkers are critical for predicting DKD development. Osteopontin (OPN) is a profibrotic adhesion phosphoprotein that participates in cell chemotaxis, adhesion, migration, and proliferation, as well as extracellular matrix (ECM) hyperplasia. Hyperglycemia could enhance OPN gene expression through the activation of the renin-angiotensin system (RAS), mTOR pathway, NF-κB, and TGF-β pathway and then cause podocyte injury and ECM hyperplasia. Therefore, OPN upregulation is not only the result of various pathophysiological processes in DKD, but also results in kidney injury. Osteopontin (OPN) could predict incident DKD in DM patients [2], N-terminal OPN (ntOPN) has a stronger profibrotic adhesion effect than full-length OPN. This study aims to reveal the clinical benefit of ntOPN as a potential marker to identify DM patients at high risk of DKD, and establish ntOPN-based diagnostic and forecast models for renal outcomes in DM patients. Method We performed a cross-sectional study of 316 adults with Type 1 DM≥ 5 years or Type 2 DM, then followed by a prospective observational cohort study of 143 adult DM patients without renal involvement at baseline and follow-up for at least one year. During the follow-up period, the primary endpoint was “DKD occurrence”, defined as the presence of one of the following conditions in DM patients [3]: (1) repeat UACR ≥30 mg/g at least 2 of 3 measurements within 3 to 6 months; (2) eGFR <60 mL/min/1.73 m2 for more than three months; (3) renal pathological findings were consistent with DKD. The secondary endpoint was “DKD progression”, which included: (1) eGFR sustained decreased by at least 25%; (2) development of ESRD, and/or need for renal replacement therapy; (3) death from the renal cause. Logistic regression analysis was performed to analyze the relationship between parameters and the events of DKD occurrence and progression. Receiver operator characteristic (ROC) analysis was used to assess the predictive ability of established models for clinical endpoints. Results The median value of urinary ntOPN (UntOPN) was 44.15 ng/ml in the cross-sectional cohort, DKD prevalence was significantly higher in the high UntOPN group than in the low UntOPN group. The ROC curves of UntOPN, urinary neutrophil gelatinase-associated lipocalin (UNGAL), and their combination indicated that both combination and ntOPN alone perform better than UNGAL for DKD diagnosis (Fig. 1A). In the prospective cohort, UntOPN was an independent risk factor and further improved the predictive ability for DKD occurrence and DKD progression than UNGAL (Figs. 1B and 1C). Based on the parameters detected as risk factors for DKD occurrence and progression, we set up a series of multi-biomarker panels for DKD prediction using UntOPN, UNGAL, serum cystatin C, serum creatinine (Scr), UACR, and TCH/HDL-C ratio. Compared with the model of Scr + UACR, the area under ROC curve (AUC) of the six-biomarker model was higher, and also ranked the highest among the six ROC curves in predicting 1-year risk of DKD occurrence and DKD progression (Figs. 1B and 1C). Conclusion Our results showed that urinary ntOPN is associated with DKD development, and elevated urinary ntOPN is an independent predictor for DKD occurrence and progression. Compared with the traditional biomarkers of Scr + UACR, our multi-biomarker models based on urinary ntOPN performed better in predicting DKD development, which could provide more accurate tools for DKD risk prediction, thereby improving the renal prognosis in DM patients.

#198 Different patterns of renal thrombotic microangiopathy

Abstract Background and Aims Thrombotic microangiopathy (TMA) is a renal lesion often associated with microangiopathic hemolysis. However, there are cases of TMA that present without hemolysis, hematuria or even proteinuria, sometimes being an incidental histopathological finding. In these situations, little is known about the long-term effects on renal function. The aim of our study is to describe the clinical and histopathological presentation of patients with renal TMA biopsied in our center, focusing on those without hemolysis and with low clinical suspicion of TMA. Method We conducted a retrospective observational unicentric study. Clinical and histological parameters were collected from patients biopsied between 2015 and 2023, whose renal biopsy (RB) showed TMA, with a minimum follow-up of 6 months. We excluded renal transplant recipients. Results Data were collected from 41 patients (17 men, 24 women), with a mean age at the time of RB of 54 ± 16 years and a mean eGFR of 80 ± 23 ml/min/1.72 m2. 12 of them (29%) had chronic kidney disease (CKD). Twenty-seven patients (66%) did not have hemolysis at diagnosis. Compared to patients with hemolysis, they were of older age (58 vs 47 years, p = 0.030) and had higher prevalence of CKD (41% vs 7%, p = 0.028). They had a milder clinical presentation, with lower creatinine (168 vs 419 μmol/L, p = 0.029), lower need for renal replacement therapy (RRT) (4% vs 50%, p = 0.001), less hematuria (33% vs 79%, p = 0.008) and proteinuria (67% vs 100%, p = 0.035). Histologically, patients without hemolysis had less fibrosis (56% vs 86%, p = 0.084) and fewer chronic TMA lesions (double contours, wrinkling of the basement membrane) (52% vs 93%, p = 0.009), despite delayed renal biopsy compared to patients with hemolysis (99 ± 118 vs 28 ± 30 days since clinical presentation, p = 0.036). The causes of TMA that were most commonly associated with the absence of hemolysis were drugs (89% without hemolysis) and glomerulopathies such as IgA nephropathy, minimal change disease and fibrillary glomerulonephritis (100% without hemolysis). Within this group of patients without hemolysis, 13 (32%) had a low clinical suspicion of TMA, defined as the absence of hemolysis, hypertension and predisposing factors, in some cases being an incidental finding in the RB. As expected, they also had a mild presentation and did not require RRT. In some cases, they even presented without proteinuria (7 patients, 64%). When comparing the severity of the lesions in renal tissue with patients with high clinical suspicion of TMA, patients with low clinical suspicion presented a similar prevalence of mesangiolysis, vascular damage and a similar proportion of affected glomeruli. Chronic TMA lesions were present in both groups (Table 1). When analysing the evolution of renal function, there are several confounding factors to consider (higher prevalence of CKD in patients without hemolysis, targeted treatment in patients with hemolysis, different time of follow-up between groups...). In our results, there were no statistically significant differences in the evolution of creatinine and proteinuria between groups, even when TMA was an incidental finding. In our sample, these findings were not attributable to a larger number of other histopathological lesions in patients with low suspicion of TMA, as there were no differences between groups (see Table 1). Conclusion Renal TMA should be suspected even in the absence of hemolysis, hypertension or proteinuria, as in our sample one third of diagnoses were incidental and their mild presentation may have delayed renal biopsy. The severity of histological lesions and the evolution of renal function in these cases are comparable to those of patients with a high clinical suspicion. Therefore, its prompt identification, etiological study and treatment are equally important. Currently, we have insufficient data to provide the different clinical scenarios in which TMA should be suspected. However, based on our findings, in the presence of drugs TMA should be considered in the differential diagnosis along with Acute Interstitial Nephritis, even in the absence of urinary abnormalities.

#59 Fibroblast Growth factor 23 for prediction of outcome in community-acquired acute kidney injury: a prospective observational study

Abstract Background and Aims Serum FGF23 level has been found to be elevated in AKI through multiple previous studies. Moreover, higher FGF23 level was associated with mortality and adverse outcomes in critically ill patients and patients undergoing cardiac surgery who developed AKI suggesting that FGF23 can have a prognostic value in AKI. The current study aims to investigate the association of serum FGF23 levels with morbidity and mortality in patients with community-acquired AKI. Method A longitudinal prospective study was carried out that included 64 patients who presented with community-acquired AKI to Mansoura Nephrology and Dialysis Unit (MNDU) at Mansoura University Hospital. Serum intact FGF23 level was measured after admission. patients were followed up during hospital stay and then at 90-day after admission. The primary outcomes were hospital and 90-day mortality and renal recovery. Results In this study, nine of the studied 64 AKI patients (14.1%) died during hospital admission and 18 out of 62 AKI patients (29%) died during the 90-day follow up period including those who died during hospital admission. Hospital mortality was significantly higher in patients with shock, sepsis, hypoalbuminemia, or high FGF23 in univariate analysis (p < 0.05). However, when binary logistic regression was carried out, shock was the only significant independent predictor for mortality [p value = 0.015; adjusted odds ratio = 12.465], while serum FGF23 did not independently predict in-hospital [p value = 0.589; adjusted odds ratio = 1.001] or 90-day mortality [p value = 0.055; adjusted odds ratio = 1.003] when entered in the regression equation together with the other confounders. Serum FGF23 in this study was not also associated with renal recovery, need for renal replacement, or the duration from peak serum creatinine to renal recovery (p > 0.05). Conclusion This research showed that serum iFGF23 could not predict mortality, renal recovery, or need for renal replacement therapy in patients with community-acquired AKI.

#1517 Glomerular immune complex deposits on electron microscopy in ANCA associated vasculitis: clinical and outcomes features

Abstract Background and Aims Glomerulonephritis related to antineutrophil cytoplasmic autoantibodies (ANCA) is typically referred to as “pauci-immune”, however, it is not unusual for kidney biopsies to exhibit some immune complex deposition within glomeruli on electron microscopic study. Such deposits in ANCA-glomerulonephritis have not been widely studied, and their potential pathologic and clinical significance is not clear, although a possible synergistic effect between immune complexes and ANCA in producing more severe glomerulonephritis is suggested in the literature. Method An observational retrospective study was conducted using a dataset comprising all patients with ANCA associated vasculitis diagnosis from a Portuguese Center between march 2011 and march 2023. Demographic and clinical data were collected from medical records. Electron microscopy reports from kidney biopsies were examined for the presence of electron-dense deposits. Descriptive statistics were used to describe all reports. The objective of this study was to explore associations between the presence or absence of such deposits and clinical data, including serum creatinine, urine protein-creatinine ratio levels (PCR) at the time of biopsy as well as overall survival and renal outcomes at follow-up. Non-parametric Mann-Whitney U test and the Chi-squared test were used for continuous and categorical variables respectively. Kaplan-Meier curves were used for assessing time to event data. All analyses were two-tailed and a p value ≤ 0.05 was considered significant. Results From a total of 39 patients with ANCA associated vasculitis diagnosis, 33 underwent at least one kidney biopsy, and among them, 17 were analysed by electron microscopy. 8 (47%) of biopsies showed glomerular immune complex deposits by electron microscopy; Table 1 describes demographic data of both groups (immune complex deposits—D; no-immune complex deposits—ND). The median numbers of glomeruli examined by electron microscopy were identical between the two groups. In group D there was less patients with positive titers for ANCA (p = 0.034) and serum creatinine levels were higher at admission (mean 7.1 mg/dL IQR: 5.6-8.1 versus 4.2 IQR 3.2-7.1), despite the lack of definitive statistical significance (p = 0.123). Urine protein-to-creatinine ratio did not differ between groups. The need for renal replacement therapy at admission was greater for patients with dense deposits on kidney biopsy (p = 0.008). At the end of follow-up (median 48, IQR 24-48 months), death and progression to end stage kidney disease occurred in 25.0% and 37.5% of group D patients versus 11.1% and 22.2% of ND patients, respectively (Fig. 1). Conclusion Immune complex deposits were found on electron microscopy in nearly half of kidney biopsies. Our data suggest that these immune complex deposits are common and might play a role in clinical presentation, overall survival and renal prognosis. The small sample size of our cohort is a limitation, as well as the retrospective nature of the study. Larger cohorts and more comprehensive electron microscopic studies are warranted to better characterize this population.

#624 The impact of hemoadsorption in patients with borderline chronic kidney disease undergoing coronary artery bypass grafting

Abstract Background and Aims With an annual incidence of up to 30%, cardiac surgery–associated acute kidney injury (CSA-AKI) may be one of the most underappreciated yet frequent complications and renal protective adjustments are crucial. We evaluated the impact of hemoadsorption as adjunctive therapy on clinical outcome in Kidney Disease Improving Global Outcomes (KDIGO) G2/A2) patients undergoing coronary artery bypass grafting (CABG). Method During a three-year period, 40 patients undergoing CABG with borderline chronic kidney disease (KDIGO-G2/A2) were treated with adjunctive hemoadsorption therapy and were compared by propensity score-matched 40 patients (KDIGO G2/A2) (Control). Primary endpoints were the need for renal replacement therapy (RRT)/dialysis and/or worsening of KDIGO stage in the perioperative period. Secondary endpoints were the change in inflammatory biomarkers, vasopressor requirement and ICU/hospital stay. In the study group, a 300 mL hemoadsorber (Cytosorbents Inc, NJ) was used for the entire duration of cardiopulmonary bypass (CPB). All patients were prepared via enhanced recovery after surgery (ERAS) protocol and surgical procedures were performed under moderate hypothermia with pulsatile flow and ultrafiltration. Patients with septic shock, limited life expectancy and refused to give consent were excluded. Results After institutional ethics committee approval was obtained, written informed consent was received from each patient. No significant difference was noted between groups in demographic, operative data and preoperative baseline laboratory. At the end of CPB; s-Creatinine (mg/dL) (1.85 ± 0.6 vs 2.751 ± 0.6; p = 0.035), NT-proBNP (pg/L) (130 ± 30 vs 180 ± 40; p = 0.04), IL-6 (pg/mL) (8.2 ± 4 vs 22.2 ± 4; p = 0.012) and myoglobulin (pg/L) (210 ± 75 vs 310 ± 80; p = 0.04) levels were significantly lower in the study group versus control. Clinical outcome is summarized in Figure. Conclusion This pioneering study demonstrated the additional protective effects of hemoadsorption in patients with borderline chronic kidney disease (KDIGO-G2/A2) undergoing CABG. Elimination of inflammatory parameters might be a complementary mechanism resulting in lesser worsening of kidney function/need of RRT and ICU stay. These findings require validation in large, multicenter trials.

#2564 Terlipressin given by continuous infusion versus boluses in the treatment of hepatorenal syndrome: a systematic review and meta-analysis

Abstract Background and Aims Hepatorenal syndrome (HRS) is one of the complications among patients with cirrhosis. Available guidelines recommended terlipressin with albumin as part of HRS management. To date there is no consensus on whether terlipressin should be given via bolus or continuous intravenous infusion. This study aims to compare the effectiveness and safety of continuous intravenous infusion versus intravenous boluses of terlipressin in the treatment of patients with HRS and cirrhosis. Method A comprehensive search for databases of randomized controlled trials (RCTs) comparing continuous intravenous infusion versus intravenous boluses of terlipressin among adult patients with hepatorenal syndrome was done. PubMed, EMBASE, the Cochrane Library, and ClinicalTrials.gov were searched using relevant terms including hepatorenal syndrome, acute kidney injury, cirrhosis, terlipressin, bolus, and continuous infusion until December 2023. Response to therapy defined as decrease in serum creatinine or regression of acute kidney injury was the primary outcome of interest, while safety in terms of drug-related events, mortality, and transplant-free survival were the secondary outcomes. Data extraction was performed using a standardized data form. The reviewers independently screened the studies and assessed the methodological quality using the Cochrane Risk of Bias tool and any discrepancies were resolved by consensus among the authors. Random-effects meta-analysis was done using Review Manager 5.4. Results A total of three studies, one high quality and two moderate quality RCTs, were included in the review, involving a total of 240 patients. Pooled analysis showed that continuous infusion was as effective or better than bolus infusion in achieving the primary outcome (RR 1.12, 95% CI 0.95-1.32, I2 = 0%). In one study, 28- and 90-day mortality were not significantly different, while 90-day transplant-free survival was not significantly different between continuous and bolus groups from another trial (53% vs 69% p = 0.26). Higher incidence of adverse events were also reported in the bolus group, RR 0.37, 95% CI 0.13-1.04 (p = 0.06). Conclusion There is limited evidence to suggest that continuous infusion of terlipressin may demonstrate resolution of acute kidney injury more frequently than bolus infusion, and that continuous infusion is associated with decreased adverse events. Larger randomized controlled trials with higher quality are needed to ascertain the effects on mortality, need for renal replacement therapy, and transplant-free survival.

#2512 Behaviour of Human Proenkephalin A 119-159 (penKid) in an in vitro model of hemoadsorption

Abstract 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.

#2724 Renal amyloidosis cohort registry in our health area

Abstract Background and Aims Renal amyloidosis is the pathological phenomenon of amyloid deposition in the kidney with marked differences in renal function impairment, proteinuria, need for renal replacement therapy (RRT) and exitus, depending on the protein involved. Light chain amyloidosis (AL) and serum protein A (AA) amyloidosis are the most common. Typical symptoms are severe proteinuria, nephrotic syndrome, and end-stage chronic kidney disease (ESRD). Method Retrospective study of a cohort of patients with renal amyloidosis. Data extracted from the biopsy registry of the HUVM Nephrology Service (2013-2022). We collected demographic, clinical, analytical, histological and clinical outcome variables (RTT, Exitus). Results are analyzed using Mayo Clinic staging criteria. Results 19 patients with a mean age of 63.4a; 57.9% male. Mean laboratory values at diagnosis: creatinine (Cr) 1.56 mg/dl and proteinuria 3.9 g/24 h. Abdominal fat biopsy in 13 cases; 3 (23%) tested positive. Comparative analysis of AL vs non-AL forms, Cr values (1.14 vs 2.27 mg/dl respectively) (p=0.57) differed. Proteinuria according to the histological location of the amyloid: 4.6 g/24 h in glomerular involvement vs. 0.3 g/24 h in those who did not present it (p<0.05). 31.6% required RTT with a mean onset time of 250.6 d from biopsy. Exitus of 21.1%: average time of 426.5 d. (See analysis in attached table). Conclusion We did not observe significant deterioration of renal function, which is greater in non-AL forms of amyloidosis. Fat biopsy was less cost-effective than reported in the literature. Significantly lower levels of proteinuria were found in the amyloidosis group without glomerular involvement. In our series, the prognostic capacity associated with the MAYO staging was confirmed.

#1348 Acute kidney injury: evaluation of factors to predict the need of dialysis therapy

Abstract Background and Aims Acute kidney injury (AKI) is a clinical syndrome with heterogeneous pathophysiological mechanisms, associated with higher morbidity and mortality risk. The existing evidence shows that an episode of AKI increases the risk of chronic kidney disease and end-stage kidney disease, with considerable effects on long term outcomes. Current risk prediction scores were mostly calculated in the setting of contrast induced nephropathy and cardiac surgery reporting the patient's risk of AKI immediately before and after the invasive procedure. To date, no scoring models are available to assess the risk of progression and necessity of renal replacement therapy (RRT) for patients in the course of AKI. Method A prospective observational cohort study was conducted enrolling patients with AKI treated within the Nephrology, Dialysis and Kidney Transplant Unit of IRCCS Azienda Ospedaliero-Universitaria di Bologna from January 2022 to July 2023. The inclusion criteria were: 1) age >18 years, 2) stage 3 AKI according to the current KDIGO guidelines or presence of urgent RRT indication (severe hyperkalemia, metabolic acidosis or fluid overload refractory to medical treatment). The indication for RRT was given based on clinical judgement. Type of RRT, dialyzer and ultrafiltration rate were applied according to the clinical features of the patient. The primary endpoint was the association between AKI features and RRT. Secondary endpoints were evaluation of patients treated with RRT for factors associated with renal recovery. Results We studied 56 patients. The mean age ± SD was 69.8 ± 15.3 years (range, 18-94) and 37 (66.1%) were males. 18 patients (32.1%) were treated with conservative therapy and 38 (67.9%) with RRT. The factors correlated with the necessity of RRT were previous cardiovascular disease (p = 0.002), diabetes mellitus (p = 0.017), Charlson score >5 (p = 0.035), volume overload (p = 0.002), urine output level (p = 0.033) and C reactive protein (CRP; p = 0.020). Multivariate analysis found significant association of cardiovascular disease (OR, 5.94; 95% CI, 1.45 to 24.34; p = 0.013) and elevated CRP (OR, 1.08; 95% CI, 1.00 to 1.16; p = 0.049) during AKI episode with the RRT need in the study cohort. Higher ultrafiltration rate during RRT was correlated with non recovery of kidney function (OR, 1.86; 95% CI, 1.09 to 3.14; p = 0.021). Conclusion Cardiovascular disease and higher CRP were associated with necessity of RRT. More intensive fluid removal during RRT resulted as negative predictor of kidney function recovery. Further studies with larger study samples and randomized design are necessary to confirm these findings.

Association between hydroxyethyl starch 130/0.4 administration during noncardiac surgery and postoperative acute kidney injury: A propensity score-matched analysis of a large cohort in China

Study objectiveThe use of hydroxyethyl starch 130/0.4 has been linked to renal injury in critically ill patients, but its impact on surgical patients remains uncertain. DesignA retrospective cohort study. SettingThis study was conducted at one tertiary care hospital in China. PatientsWe evaluated the records of 51,926 Chinese adults who underwent noncardiac surgery from 2013 to 2022. Patients given a combination of hydroxyethyl starch 130/0.4 and crystalloids were propensity-matched at a 1: 1 ratio of baseline characteristics to patients given only crystalloids (11,725 pairs). InterventionsEligible patients were divided into those given a combination of hydroxyethyl starch 130/0.4 and crystalloid during surgery and a reference crystalloid group consisting of patients who were not given any colloid. MeasurementsThe primary outcome was the incidence of acute kidney injury. Secondarily, acute kidney injury stage, need for renal replacement therapy, intensive care unit transfer rate, and duration of postoperative hospitalization were considered. Main resultsAfter matching, hydroxyethyl starch use [8.5 (IQR: 7.5–10.0) mL/kg] did not increase the incidence of acute kidney injury compared with that in the crystalloid group [2.0 vs. 2.2%, OR: 0.90 (0.74–1.08), P = 0.25]. Nor did hydroxyethyl starch use worsen acute kidney injury stage [OR 0.90 (0.75–1.08), P = 0.26]. No significant differences between the fluid groups were observed in renal replacement therapy [OR 0.60 (0.41–0.90), P = 0.02)] or intensive care unit transfers [OR 1.02 (0.95–1.09), P = 0.53] after Bonferroni correction. Even in a subset of patients at high risk of renal injury, hydroxyethyl starch use was not associated with worse outcomes. ConclusionsHydroxyethyl starch 130/0.4 use was not significantly associated with a greater incidence of postoperative acute kidney injury compared to receiving crystalloid solutions only.

Hepcidin, in contrast to heparin binding protein, does not portend acute kidney injury in patients with community acquired septic shock.

Acute kidney injury (AKI) is a common and severe complication in patients treated at an Intensive Care Unit (ICU). The pathogenesis of AKI has been reported to involve hypoperfusion, diminished oxygenation, systemic inflammation, and damage by increased intracellular iron concentration. Hepcidin, a regulator of iron metabolism, has been shown to be associated with sepsis and septic shock, conditions that can result in AKI. Heparin binding protein (HBP) has been reported to be associated with sepsis and AKI. The aim of the present study was to compare serum hepcidin and heparin binding protein (HBP) levels in relation to AKI in patients admitted to the ICU. One hundred and forty patients with community acquired illness admitted to the ICU within 24 hours after first arrival to the hospital were included in the study. Eighty five of these patients were diagnosed with sepsis and 55 with other severe non-septic conditions. Logistic and linear regression models were created to evaluate possible correlations between circulating hepcidin and heparin-binding protein (HBP), stage 2-3 AKI, peak serum creatinine levels, and the need for renal replacement therapy (RRT). During the 7-day study period, 52% of the 85 sepsis and 33% of the 55 non-sepsis patients had been diagnosed with AKI stage 2-3 already at inclusion. The need for RRT was 20% and 15%, respectively, in the groups. Hepcidin levels at admission were significantly higher in the sepsis group compared to the non-sepsis group but these levels did not significantly correlate to the development of stage 2-3 AKI in the sepsis group (p = 0.189) nor in the non-sepsis group (p = 0.910). No significant correlation between hepcidin and peak creatinine levels, nor with the need for RRT was observed. Stage 2-3 AKI correlated, as expected, significantly with HBP levels at admission in both groups (Odds Ratio 1.008 (CI 1.003-1.014, p = 0.005), the need for RRT, as well as with peak creatinine in septic patients. Initial serum hepcidin, and HBP levels in patients admitted to the ICU are biomarkers for septic shock but in contrast to HBP, hepcidin does not portend progression of disease into AKI or a later need for RRT. Since hepcidin is a key regulator of iron metabolism our present data do not support a decisive role of initial iron levels in the progression of septic shock into AKI.

Patterns of Multiple Organ Dysfunction and Renal Recovery in Critically Ill Children and Young Adults Receiving Continuous Renal Replacement Therapy.

Acute kidney injury requiring dialysis (AKI-D) commonly occurs in the setting of multiple organ dysfunction syndrome (MODS). Continuous renal replacement therapy (CRRT) is the modality of choice for AKI-D. Mid-term outcomes of pediatric AKI-D supported with CRRT are unknown. We aimed to describe the pattern and impact of organ dysfunction on renal outcomes in critically ill children and young adults with AKI-D. Retrospective cohort. Two large quarternary care pediatric hospitals. Patients 26 y old or younger who received CRRT from 2014 to 2020, excluding patients with chronic kidney disease. None. Organ dysfunction was assessed using the Pediatric Logistic Organ Dysfunction-2 (PELOD-2) score. MODS was defined as greater than or equal to two organ dysfunctions. The primary outcome was major adverse kidney events at 30 days (MAKE30) (decrease in estimated glomerular filtration rate greater than or equal to 25% from baseline, need for renal replacement therapy, and death). Three hundred seventy-three patients, 50% female, with a median age of 84 mo (interquartile range [IQR] 16-172) were analyzed. PELOD-2 increased from 6 (IQR 3-9) to 9 (IQR 7-12) between ICU admission and CRRT initiation. Ninety-seven percent of patients developed MODS at CRRT start and 266 patients (71%) had MAKE30. Acute kidney injury (adjusted odds ratio [aOR] 3.55 [IQR 2.13-5.90]), neurologic (aOR 2.07 [IQR 1.15-3.74]), hematologic/oncologic dysfunction (aOR 2.27 [IQR 1.32-3.91]) at CRRT start, and progressive MODS (aOR 1.11 [IQR 1.03-1.19]) were independently associated with MAKE30. Ninety percent of critically ill children and young adults with AKI-D develop MODS by the start of CRRT. Lack of renal recovery is associated with specific extrarenal organ dysfunction and progressive multiple organ dysfunction. Currently available extrarenal organ support strategies, such as therapeutic plasma exchange lung-protective ventilation, and other modifiable risk factors, should be incorporated into clinical trial design when investigating renal recovery.

Predicting chronic kidney disease progression with artificial intelligence

BackgroundThe use of tools that allow estimation of the probability of progression of chronic kidney disease (CKD) to advanced stages has not yet achieved significant practical importance in clinical setting. This study aimed to develop and validate a machine learning-based model for predicting the need for renal replacement therapy (RRT) and disease progression for patients with stage 3–5 CKD.MethodsThis was a retrospective, closed cohort, observational study. Patients with CKD affiliated with a private insurer with five-year follow-up data were selected. Demographic, clinical, and laboratory variables were included, and the models were developed based on machine learning methods. The outcomes were CKD progression, a significant decrease in the estimated glomerular filtration rate (eGFR), and the need for RRT.ResultsThree prediction models were developed—Model 1 (risk at 4.5 years, n = 1446) with a F1 of 0.82, 0.53, and 0.55 for RRT, stage progression, and reduction in the eGFR, respectively,— Model 2 (time- to-event, n = 2143) with a C-index of 0.89, 0.67, and 0.67 for RRT, stage progression, reduction in the eGFR, respectively, and Model 3 (reduced Model 2) with C-index = 0.68, 0.68 and 0.88, for RRT, stage progression, reduction in the eGFR, respectively.ConclusionThe time-to-event model performed well in predicting the three outcomes of CKD progression at five years. This model can be useful for predicting the onset and time of occurrence of the outcomes of interest in the population with established CKD.