Increase In Serum Creatinine Research Articles

The impact of MELD exception points for hydrothorax on posttransplant mortality: a propensity score-matched analysis.

Hepatic hydrothorax is a challenging complication of end-stage liver disease, and.patients with this complication can receive model for end-stage liver disease (MELD) exception points if they meet specific criteria as defined by United Network for Organ Sharing (UNOS). This research aimed to analyze the effect of receiving MELD exception points for hepatic hydrothorax on posttransplant mortality, using a national transplant database. Patients >18 years in the UNOS database awaiting liver transplant between 2012 and 2023 were identified based on their petition for MELD exception points. Using a 1: 1 propensity score-matched analysis, 302 patients who received MELD exception points for hepatic hydrothorax were compared with 302 patients who did not receive MELD exception points.Demographic, clinical and laboratory values were compared. The primary outcome was posttransplant mortality. Multivariate logistic regression controlled for potential confounders. No significant difference was observed in mean age (58.20 vs 57.62 years), mean initial MELD score (16.93 vs 16.54), or mean Child-Pugh score (9.77 vs 9.74) in patients with hepatic hydrothorax receiving MELD exception points versus their matched cohort who did not recieve exception points. The proportion of males was slightly higher among patients who received MELD exception points (57.6% males vs 53.6% males). A majority of patients in both groups had Child-Pugh grade C (>56%). Patients receiving MELD exception points for hepatic hydrothorax had a statistically significant 44% decrease in the odds of posttransplant death compared to those who did not (OR 0.56; 95% CI 0.37-0.88; P = 0.01). Among the combined cohort, each year increase in age resulted in a 3.9% increase in mortality (OR 1.04; 95% CI 1.01-1.07; P = 0.005), and every one-unit increase in serum creatinine resulted in a 40% increase in mortality (OR 1.40; 95% CI 1.03-1.92; P = 0.03). Receiving MELD exception points for hepatic hydrothorax is associated with a significant reduction in the odds of posttransplant mortality. These findings underscore the importance of MELD exception points for hepatic hydrothorax among patients with decompensated cirrhosis, potentially improving patient prioritization for liver transplantation and influencing clinical decision-making.

#645 Inferring trends in renal function based on a single serum creatinine with a spot urine creatinine-to-osmolality ratio in outpatient settings

Abstract 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.

#1382 Kidney outcomes after bariatric surgery: a population-based cohort study

Abstract Background and Aims Obesity is associated with nephrolithiasis, chronic kidney disease (CKD), and kidney failure. Bariatric surgeries, including Roux en-Y gastric bypass (RYGB) and sleeve gastrectomy (SG), are effective treatments of severe obesity and may mitigate obesity-related kidney diseases such as CKD and kidney failure, but could on the other hand induce hyperoxaluria and nephrolithiasis, posing a potential risk to the kidneys. We examined the risk of nephrolithiasis, acute kidney injury (AKI), CKD, and kidney failure after bariatric surgery. Method We included individuals undergoing bariatric surgery (RYGB or SG) in Denmark between 2006 and 2018 using population-based registries. These individuals were age- and sex-matched 1:5 to a background general population cohort and a cohort with hospital-diagnosed obesity. Nephrolithiasis was identified by diagnosis codes within the Danish National Patient Registry (DNPR). AKI was defined as an increase in serum creatinine (sCr) of ≥26.5 µmol/L within 48 hours or a relative increase of ≥1.5 times within seven days or from a median outpatient baseline value. CKD was defined as the presence of two outpatient eGFR samples below 60 ml/min/1.73 m2, with a minimum interval of three months between each measurement. Kidney failure was defined by recordings of kidney transplantation or chronic dialysis in DNPR. One- and ten-year cumulative incidences (risks) were computed for each cohort accounting for the competing risk of death. Rates of incident nephrolithiasis, AKI, incident CKD, and incident kidney failure in post-bariatric-surgery patients were compared with the background population cohort and obesity cohort using multivariable Cox regression adjusting for age, sex, and Charlson Comorbidity Index (CCI)-score. Results We included 18,827 individuals with bariatric surgery (17,200 with RYGB and 1,627 with SG). Median follow-up was 8.1 years (5.2-9.2), 8.0 years (4.6-9.1), and 7.9 years (4.2-9.1) for the overall bariatric cohort, the background population cohort, and the obesity cohort, respectively. Within the bariatric cohort, the ten-year risk of nephrolithiasis was 2.8%, the one-year risk of AKI was 2.7%, while the ten-year risks of CKD, and kidney failure were 0.2% and 0.1%, respectively. When comparing the post-bariatric-surgery cohort with the general population cohort, the adjusted hazard ratio (HR) was 2.92 (95% CI; 2.61, 3.27) for nephrolithiasis, 2.60 (95% CI; 2.06, 3.28) for AKI, 0.36 (95% CI; 0.18, 0.73) for CKD, and 0.81 (95% CI; 0.49, 1.32) for kidney failure. Compared with the obesity cohort, the adjusted HRs for adverse events were at 1.73 (95% CI: 1.56, 1.91) for nephrolithiasis, 1.63 (95% CI; 1.38, 1.92) for AKI, 0.41 (95% CI; 0.26, 0.66) for CKD, and 0.65 (95% CI; 0.42, 0.98) for kidney failure. Conclusion Individuals with bariatric surgery had a higher ten-year rate of nephrolithiasis and a higher one-year rate of AKI, but reduced rates of CKD and kidney failure within ten years after surgery compared with both the background cohort and the obesity cohort.

#259 Predictive capacity and comparison of new biomarkers for AKI in patients undergoing non-cardiac surgery

Abstract Background and Aims The diagnosis of AKI, according to the KDIGO guidelines, is still based on a tangible increase in serum creatinine which, however, cannot be detected until 24-48 hours after renal damage. Unfortunately, it has not been possible to identify among the various new biomarkers the one that is potentially able to detect AKI early, to intervene promptly to preserve renal function. The aim of this study was to analyze, in a population of patients undergoing major non-cardiac surgery, the most recent urinary biomarkers to evaluate their predictive potential for AKI and compare them with creatinine levels. Method 22 patients (18 males, 4 females) with an average age of 76 (67-85) years were enrolled for the study. 22 urine samples were analyzed by: Results Carrying out a correlation between the new biomarkers for AKI (Nephrocheck, NGALds and SEPP1) with creatinine levels at different times (pre-operative, post-operative and 24 h post-operative) shows a significant correlation only with NGALds (respectively p = 0.017, p = 0.035 and p = 0.012) (Table). Subdividing patients based on the increase in creatinine levels from pre-operation to 24 hours post-operation, the only biomarker that showed an increase in values ​​was NGALds, while the others showed levels discordant with creatinine. Conclusion By analyzing the new biomarkers and comparing them with the creatinine data, it emerged that NGALds alone significantly correlated with the latter at different times. The other urinary biomarkers (Nephrocheck and SEPP1) showed no correlation with creatinine levels. Based on this outcome, it could be assumed that NGALds is the biomarker which, due to its characteristics already stated in numerous studies and its correlation with creatinine, could be used and replace the latter as an early biomarker of AKI.

#1614 Fenofibrates and chronic kidney disease – Is there anything to worry about?

Abstract Background and Aims Chronic Kidney Disease (CKD) patients have increased risk of cardiovascular disease and dyslipidemia is a frequent comorbidity. Many patients are medicated with anti-lipidemic agents to reduce atherosclerotic disease and coronary vascular events. Fenofibrates are lipid-lowering agents used to treat mixed dyslipidemia and hypertriglyceridemia and are widely used by primary care physicians. Many studies described reversible increase in serum creatinine (SCr) associated with fenofibrates use, but the underlying mechanism is poorly understood. Whether hypercreatinemia is secondary to alterations in creatinine metabolism, tubular handling, or reflects a true impairment in kidney function remains unknown. This phenomenon is also fairly unknown to many primary care providers and, as a result, patients with a SCr rise while on fenofibrates are often referred to nephrology consultation. In this study, we have analyzed the effect of fenofibrate withdrawal on SCr, eGFR and hemoglobin (Hb) in patients referred to nephrology consultation for CKD or decrease of eGFR. Our aim was to understand the impact of fenofibrates withdrawal on kidney function and to look for factors that might influence the risk of fenofibrate nephrotoxicity. Methods We conducted a retrospective observational study, reviewed electronic medical records and collected data of all adult patients discontinued on fenofibrates at first nephrology consultation, between January 2022 and October 2023. Ninety patients were included, of which four were excluded due to simultaneous suspension of antihypertensive drugs. Patients were subsequently evaluated for clinical reasons from 2 to 6 months after the first appointment, with new laboratory data collected, including Hb, SCr and lipid profile. eGFR was calculated using MDRD 4 formula. Continuous variables were compared by t-test and categorical variables were compared by chi-square test. A p value of < 0.05 was considered statistically significant. All data was analyzed using Stata software. Results A total of eighty-six patients were included in this study, 65% (n=56) were male, mean age of 71.2 ± 11.4 years old; all patients were medicated with fenofibrates due to dyslipidemia and 77% (n=66) were also on statins; 94% (n=81) had hypertension, 60% (n=52) had type 2 diabetes mellitus, and 20% (n=17) had ischemic cardiopathy. Ninety-two percent (n=79) were taking renin-angiotensin system inhibitors (RASi). Nearly half the patients (49% n = 42) had stage 4 CKD and 45% (n = 39) had stage 3 CKD; Main causes of CKD were presumed diabetic kidney disease (34% n = 29) and ischemic nephropathy (15% n = 13), 30% (n = 26) of patients had undetermined etiology. Upon fibrate discontinuation, mean SCr was 2.1 ± 0.6 mg/dL and mean eGFR was 31.3 ± 10.9 mL/min/1.73 m2. Mean Hb was 12.5 ± 2.0 g/dL. After fenofibrate discontinuation, eGFR significantly improved in mean 15.2 mL/min/1.73 m2 (31.3 vs 46.5 mL/min/1.73 m2, p < 0.0001) with a mean reduction of SCr of 0.6 mg/dL (2.1 vs 1.5 mg/dL, p < 0.0001). Mean Hb increased 0.4 g/dL (12.4 vs 12.7 g/dL, p = 0.112). Mean total cholesterol was 168.4 ± 56.4 mg/dL and mean triglycerides was 234.8 ± 285.3 mg/dL. Only one patient was restarted on fenofibrate due to severe hypertriglyceridemia. Fenofibrate discontinuation effect on eGFR improvement remained statistically significant when adjusted for diabetes, hypertension, CKD etiology and RASi use. Conclusion Our study reports a consistent increase in eGFR and SCr decrease following discontinuation of fenofibrate, as other reports before. A true effect on eGFR could be supported by the Hb rise, though it did not reach statistical significance. The exact mechanism by which fenofibrates increase SCr remains to be clarified. Cardiovascular disease is the main cause of death amongst CKD population and the potential benefits of fenofibrates should not be disregarded. Our results suggest that patients started on fenofibrates should be carefully selected, specially if CKD is present, and kidney function monitoring should be considered. A drop in eGFR should prompt physicians to weigh on the strict indications for fenofibrates use.

#2027 Activation of histone deacetylase-1 in fibroblasts and pericytes induces renal interstitial fibrosis after ischemia-reperfusion injury

Abstract Background and Aims Following an acute kidney ischemic event the chromatin remodelling enzyme, histone deacetylase-1 (HDAC1), is activated in many cell types of the kidney including fibroblasts and pericytes. During kidney injury, the fibroblasts/pericytes differentiate into the myofibroblasts and produce extracellular matrix that can lead to a permanent decline in kidney function. Pharmacological inhibition of HDACs can attenuate ischemia-reperfusion-injury (IRI) mediated interstitial fibrosis. The hypothesis of this study was that fibroblast/pericyte HDAC1 activation promotes myofibroblast differentiation and interstitial fibrosis. Method Tamoxifen inducible, fibroblast/pericyte HDAC1 knockout (KO) mice (HDAC1Fl/Fl; Col1a2-CreEr) and littermate controls (HDAC1Fl/Fl) were used. Male and female mice were given tamoxifen by ip at 8-10 weeks of age and IRI or sham surgery completed after a 2-week tamoxifen washout period. A mild, 18 min, bilateral, warm IRI model was used, and samples collected over 4 weeks. Glomerular filtration rate (GFR) was assessed using transdermal FITC-Sinistrin clearance. In vitro experiments with kidney fibroblast cells (NRK49F) overexpressing empty vector or HDAC1 were used for RNA-sequencing to determine the HDAC1-dependent myofibroblast transcriptome. Results We confirmed that HDAC1 was knockdown in myofibroblast cells from KO mice with co-localization of HDAC1 and PDGFRβ or α-smooth muscle actin in the kidneys of IRI mice. Twenty-four hours post-surgery, all IRI mice exhibited 2-3 times increase in serum creatinine and a ∼50% reduction in GFR compared to sham mice (control IRI = 513 ± 129 μl /min/100 g body mass, control sham = 1010 ± 218, n = 4-5, p = 0.02; KO IRI = 529 ± 116, KO sham = 1187 ± 59 μl/min/100 g body mass, n = 4-5, p = 0.004). Subsequent GFR measurements over the next 4 weeks showed a gradual recovery of renal function of IRI mice starting at week 2 and fully restored to sham values by week 4. However, the male control IRI mice had significant focal interstitial fibrosis 2- and 4-weeks post injury (4-week data: sham = 0.3 ± 0.09 % of cortical area, IRI = 1.2 ± 0.2%, n = 6/group, p = 0.0011) but this was attenuated in the KO male IRI mice (sham = 0.4 ± 0.07% n = 4, IRI = 0.5 ± 0.1%, n = 7, p = 0.93). The female mice, regardless of genotype, had very little kidney damage or interstitial fibrosis at 4 weeks. Transcriptomes of NRK49F cells overexpressing HDAC1 had an upregulation of 55 genes related to pro-inflammatory cytokines and tumour necrosis factor signalling and downregulation of 367 genes related to cell junctions, cytoskeleton proteins, and cell adhesion compared to the empty vector control cells. Fibroblast proliferation rates were not statistically different among the groups, suggesting HDAC1 does not affect myofibroblast proliferation but rather pro-inflammatory gene expression. Conclusion In male mice, fibroblast/pericyte activation of HDAC1 leads to the production of pro-inflammatory cytokines that we predict will lead to immune cell infiltration and crosstalk that leads to the excessive production of interstitial fibrosis following IRI.

#1375 Association of NT-proBNP and kidney function progression in chronic kidney disease patients without heart failure

Abstract Background and Aims Elevated N-terminal pro-B-type natriuretic peptide (NT-proBNP) is reported to be associated with higher risk of decline in kidney function. However, little evidence exists about the relationship between NT-proBNP and kidney function progression stratified by estimated glomerular filtration rate (eGFR) in chronic kidney disease (CKD) patients without heart failure. Therefore, we aim to investigate the association of NT-proBNP and CKD progression in different CKD stages for CKD patients without heart failure. Method A multicentric retrospective cohort study recruited 23860 patients diagnosed with CKD from China Renal Data System (CRDS) database. Eligible participants were classified into five groups according to eGFR. CKD progression was defined as a composite of an increase in serum creatinine ≥50% or a decrease in eGFR ≥40% from baseline or a need for kidney replacement therapy. A linear regression model evaluated the relationship between eGFR and NT-proBNP. Cox regression analysis assessed the association between NT-proBNP and CKD progression. We also performed restricted cubic spline (RCS) and threshold effect analysis to investigate non-linear relationships between NT-proBNP and CKD progression. Results In a linear regression model, NT-proBNP was negatively correlated with eGFR in CKD patients. Each decrease of 15 ml/min/1.73 m2 in eGFR was associated with 1.06-fold, 1.50-fold, 1.52-fold, 1.94-fold, 3.37-fold higher levels of log (NT-proBNP) in CKD patients with stage 1-2, 3a, 3b, 4 and 5 respectively. In the multivariable Cox hazard model, elevated NT-proBNP was associated with a greater risk of kidney function progression, particularly among CKD stage 3 patients (stage 3a: HR, 1.42, 95% CI, 1.32-1.53; stage 3b: HR, 1.43, 95% CI, 1.32-1.54), with P-interaction≤0.001. However, the correlation of NT-proBNP and CKD progression had no statistical significance among CKD patients with stages 4-5 after sensitivity analyses. RCS and two-segment Cox regression model showed reversed L-shaped non-linear relationships between NT-proBNP and CKD progression in CKD patients with stages 1-4, with the inflection point at 250 pg/mL, 750 pg/mL, 653 pg/mL, 526 pg/mL, but not in stage 5 (Figure). Conclusion NT-proBNP may be a reliable biomarker to predict CKD progression in stages 1-3 CKD (mainly for stage 3) without heart failure. This helps clinicians predict a decline in kidney function early and set the threshold for therapy. However, the predictive role of NT-proBNP in in advanced CKD patients is insignificant.

#2171 The impact of preoperative hypertension and blood pressure control on kidney outcomes after surgery for localized kidney cancer: a prospective study

Abstract Background and Aims Kidney surgery represents the treatment of choice for localized renal cell carcinomas (RCC). Postoperative acute kidney injury (AKI) is reported in 40% of the patients undergoing partial nephrectomy [1]. A nephron-sparing approach is not always feasible for anatomical as well as oncological reasons and total nephrectomy is associated with an even higher risk of both acute and chronic impairment of renal function. Recently, interest has risen in the development of prediction models able to preoperatively identify patients at higher risk of AKI and chronic kidney disease (CKD) development after kidney surgery, but the role of hypertension in this field is yet underexplored. The aim of the present study was therefore to assess the impact of hypertension and blood pressure control on kidney outcomes after surgery for RCC. Method We prospectively enrolled 45 patients with an estimated glomerular-filtration-rate (eGFR) > 45 ml/min per 1.73 m2 who underwent kidney surgery for RCC at our institution between May 1, 2022, and September 30, 2023. Clinical characteristics of the study cohort are reported in Table 1. In-hospital AKI was defined as an increase of serum creatinine > 0.3 mg/dl from baseline and CKD development (defined as eGFR <60 ml/min/1.73 m2) was evaluated at 3 months. Ambulatory blood pressure monitoring (24h-ABPM) was assessed at baseline. Comparisons between groups were made by analysis of variance. Comparisons of proportions among groups were made using the χ2 test. Multivariate logistic regression analysis was used to describe the relationship between clinical variables and the presence of in-hospital AKI. Results Among the 45 patients enrolled, 42% (n = 19) developed postoperative AKI, of whom 32% (n = 6) had a complete kidney function recovery, whereas 68% (n = 13) developed CKD. Of the 39 patients with a basal ABPM evaluation, 87% (n = 34) had a diagnosis of hypertension. For 35% (n = 12) of these patients a first diagnosis of hypertension was made. AKI patients had higher median SBP (143 ± 9 vs 133 ± 12 mmHg, p = 0.008) and SBP variability (24 ± 4 vs 20 ± 5 mmHg, p = 0.01) compared with non-AKI patients. Preoperative 24h-SBP >130 mmHg was independently associated with in-hospital AKI (p = 0.05), regardless of age, gender, hypertension, diabetes and antihypertensive treatment. Considering the 3-month eGFR, we observed that compared with non-AKI patients, baseline 24h-SBP was higher, as a trend, in AKI patients who did not develop CKD or in those developing CKD on previous normal kidney function (de novo CKD), while no difference in 24h-SBP was observed between AKI and non-AKI patients in the subgroup of patients with preoperative CKD (CKD on CKD) (Fig. 1). Conclusion Preoperative hypertension, a potentially modifiable risk factor, is associated with an increased risk of AKI after kidney surgery. Moreover, an early identification of hypertension is of utmost importance taking into account that a strict blood pressure control, regardless of renal function at baseline, may be crucial to counteract the development or the progression of CKD.

#1103 Delayed initiation or reduced initial dose of calcineurin-inhibitors for kidney transplant recipients: a systematic review and meta-analysis

Abstract Background and Aims Delayed graft function (DGF) is more common in donors after cardiac death, especially expanded criteria donors and those with longer cold ischaemia time, older or with an increased serum creatinine. There is no agreement on the optimal immunosuppressive approach in patients at increased risk of DGF, with strategies including a delayed introduction of calcineurin inhibitors (CNI) or initial low dose CNI. Our aim was to evaluate the benefits and harms of delayed initiation of CNI or reduced CNI dose as initial immunosuppression therapy for kidney transplant (KT) recipients at high risk of DGF. Method We searched the Cochrane Kidney and Transplant Register of Studies up to 07 March 2023 through contact with the Information Specialist using search terms relevant to this review. Studies in the Register are identified through searches of CENTRAL, MEDLINE, and EMBASE, conference proceedings, the International Clinical Trials Register (ICTRP) Search Portal, and ClinicalTrials.gov. We included all randomized controlled trials (RCTs) and quasi-RCTs evaluating early vs delayed initiation of CNI or reduced vs standard initial dose of CNI in kidney transplant (KT) recipients at high risk of DGF. Three authors independently assessed study eligibility, and two assessed the risk of bias, certainty of evidence, extracted the data, and performed the analysis. Results were reported as risk ratios with 95% confidence intervals for dichotomous outcomes and as mean difference with 95% CI for continuous outcomes. Statistical analysis was performed using the random-effects model. Risk of bias was assessed with RoB2 and the certainty of the evidence according to GRADE methods. Results Thirteen studies were included (2386 randomized participants). Incidence of DGF (RR 1.09, 95% CI 0.89 to 1.32; I2 = 18%) and acute rejection (RR 0.98, 95% CI 0.72 to 1.33; I2 = 54%) were similar between early and delayed introduction of CNI, as well as between low vs standard dose of CNI (DGF: RR 1.16, 95% CI 0.90 to 1.50; I2 = 9%; acute rejection: RR 0.70, 95% CI 0.43 to 1.14; I2 = 58%). There were also no differences in secondary outcomes such as graft function, graft loss, risk of death, or infection. Conclusion In patients at high risk of DGF, the strategy of delaying CNI introduction or starting at a lower dose does not reduce the risk of DGF.

#1851 Pregnancy outcomes in women with glomerular disease: Mansoura experience

Abstract Background and Aims Pregnancy is a “stress test” for the kidney, and may initiate, aggravate, or unmask a kidney disease. Pregnancy in women with glomerular disease remains challenging. Glomerular disease increases the risks of adverse pregnancy outcomes especially in case of reduced eGFR, proteinuria or uncontrolled hypertension. The heterogeneity of the diseases, severity and settings does not allow making precise outcome predictions. Few data are available from African countries. Aim of this study is to review the outcomes of 43 pregnant women with biopsy-proven glomerulonephritis followed-up in 2020-2022, in a new unit for obstetric nephrology set up in Mansoura, Egypt. Method We reviewed archived paper and electronic records for history, clinical data, and laboratory investigations as well as immunologic profile of all women with glomerular diseases followed up since the start of our activity. Outcomes included timing and mode of delivery, maternal and foetal mortality, neonatal ICU admission, low birth weight (<2.5 kg), and presence of congenital anomalies. In the postpartum period, data on maternal renal function was also analysed. Renal function impairment was defined as ≥150% increase in postpartum serum creatinine compared to antenatal baseline values. Results 43 patients were included. Lupus nephritis accounted for 52.4%, minimal change disease 16.7%, focal segmental glomerulosclerosis 14.3%, membranous nephropathy 7.1%, thrombotic microangiopathy, membranoproliferative, crescentic, and focal proliferative GN accounted for 2.4% (one case) each. Patients were referred in the 22 (4-37) weeks of pregnancy from regional urban and rural obstetric services. At referral 27 (62.8%) patients were in stage 1, 8 (18.6%) in stage 2, 7 (16.3%) in stage 3 and 1 (2.3%) in stages 4-5 CKD. Proteinuria at referral was 1000 (16-34.500 mg/d). Twenty-two (51.2%) women were hypertensive at referral. Obstetric outcomes were assessed in 36 pregnancies, which resulted in 30 live birth (78.9%); with one postnatal mortality, no miscarriage (<24 gestational weeks), in 4 (10.5%) intrauterine deaths and in 4 (10.5%) induced abortion. Of the living born babies, 2 (6.7%) were extremely preterm (<28 weeks), 8 (26.7%) early preterm (28-34 weeks) and 8 (26.7%) late preterm (34-37 weeks). Renal progression was assessed in 33 cases, occurring in 0% in patients with MCD, MN and membranoproliferative, 3 (17.6%) in LN, 2 (50%) FSGS, 100% of patients with focal proliferative, TMA and crescentic GN (one case for each). Out of 3 mothers who were in CKD stages 3b-5 at referral, one started dialysis. Conclusion Glomerulonephritis in pregnancy is probably referred late in our setting, and lupus nephropathy was the most frequent diagnosis. Preterm delivery and low birth weight are frequent in this population and the risk of maternal kidney function impairment is confirmed as higher in lupus nephropathy and when baseline kidney function impairment, proteinuria and hypertension are present.

#2672 Cryoglobulin-Induced membranoproliferative glomerulonephritis in a HEV-infected kidney transplant recipient: outcomes post ribavirin failure

Abstract Background and Aims Hepatitis E is a zoonosis caused by hepatitis E virus (HEV), which was first discovered 40 years ago. It is the most prevalent hepatitis virus worldwide. Most hepatitis E cases are self-limiting acute hepatitis, but the virus has been recognized to cause chronic hepatitis. Following the first case report of chronic hepatitis E (CHE) in a transplant recipient, CHE has recently been identified as associated with chronic liver damage induced in immunocompromised patients such as transplant recipients. CHE can induce extra-hepatic manifestations, such as immune-mediated thrombocytopenia, neurological symptoms, and kidney injuries. Few cases of glomerulonephritis (GN) and cryoglobulinemia in transplant patients have been related with CHE, with a good progression thanks to viral control with ribavirin introduction. There have been no reported cases in the literature of good progress in renal function in renal transplant patients despite failure of treatment with Ribavirin. Method We report here what is to our knowledge, the first documented case of HEV-induced de novo cryoglobulinemic membranoproliferative glomerulonephritis in a renal transplant patient with a ten-year history of CHE infection unsuccessfully treated with ribavirin. Results A 69-year-old man underwent a kidney transplant for diabetes type 1. 7 years after transplantation, he was diagnosed with a chronic genotype 3.1H-HEV infection. He was treated by Ribavirin, but it did not allow to eradicate HEV but a biochemical response. At 18 years post transplant, he presented with asthenia, abdominal pains and increased liver enzyme levels: liver tests were disrupted with cytolysis and cholestasis. He presented also a nephritic syndrome with high blood pressure, oedemas, increased serum creatinine level, proteinuria with hypoalbuminemia and de novo microscopic hematuria. Biological analysis revealed presence of type 2 cryoglobulinemia with monoclonal IgM Kappa (2285 mg/L), and polyclonal immunoglobulins association. Rheumatoid factor was increased (573 UI/ml) and C4 level was reduced (0.04 g/L). The concentration of HEV RNA in the serum was 750 000 UI/mL. Viral serologies were performed for HBV, HCV, HAV, HIV, EBV, CMV. Hematologic diseases were ruled out by analyzing a bone marrow biopsy specimen. Histologic analysis of a kidney biopsy specimen revealed diffuse endocapillary proliferation, diffuse mesangial proliferation and focal glomerular basal membrane duplication. One arteriolar section showed a focal lesion of vasculitis (Fig. 1). There was no argument for allograft rejection. Immunofluorescence microscopy revealed mesangial and capillary wall deposits of IgM, IgG, C3 and C1q, polytypic for k and l light chains. We suspected cryoglobulinemic membranoproliferative glomerulonephritis induced by VHE. The initial treatment plan involved 10 sessions of plasmapheresis and steroid pulses (500 mg/d for 3 days), alongside a course of rituximab (1 g/week for 4 weeks). However, the patient experienced intolerance to rituximab, prompting a switch to Obinutuzumab. Subsequently, the anti-HEV therapy was modified, and the patient was placed on a course of Sofosbuvir. Consequently, three months after treatment kidney function kidney improved with return to baseline and cryoglobulinemia became undetectable. However, proteinuria remained impaired and VHE RNA was still present. Conclusion Cryoglobulinemia is rarely associated with glomerular disease in HEV infection, and cases currently reported in the literature showed a favorable outcome with ribavirin. This case is the first to display a chronic HEV infection with cryoglobulin-induced glomerulonephritis with global improvement despite unsuccessful treatment with ribavirin. Although the difficulty of managing immunity in the treatment of cryoglobulinemia by immunodepleting treatment, with the risk of increased viral replication in the absence of an effective antiviral, it seems interesting to offer a first-line treatment of cryoglobulinemia that appears to improve renal function despite continued viral replication. These results need to be confirmed in further studies.

#2432 DNA damage analysis with oxidative stress index in patients developing contrast nephropathy after coronary angiography

Abstract Background and Aims Contrast Nephropathy (KN) is acute kidney injury that occurs after exposure to contrast material. Advanced age, chronic kidney disease, heart failure, anemia, hypertension, diabetes mellitus, and hyperuricemia have been reported in the literature to increase the risk of KN development. In addition, oxygen radicals have an important place in the pathogenesis of contrast nephropathy development. Specific biomarkers are used in clinics to determine oxidative stress and antioxidant status. In particular, measurement of total antioxidant status (TAS) and total oxidant status (TOS) can provide useful information about an individual's overall serum antioxidative status. The ratio of TOS to TAS level gives the oxidative stress index (OSI). One of the most investigated metabolites for DNA damage is 8-hydroxy-2-deoxyguanosine (8-OhdG), which is accepted as a biomarker of oxidative damage to DNA. In our study, we planned to investigate DNA damage and important predisposing factors for contrast nephropathy using oxidative stress markers. Method Between February 2021 and April 2022, blood was taken from 191 patients who underwent coronary angiography (CAG) by the Cardiology Department at ESOGU before CAG and at 72 hours after CAG. Patients who met the criteria for contrast nephropathy development (those with a serum creatinine increase of 25% or more compared to baseline or an increase of 0.5 mg/dl or more) were included as the case group in our study. Our study is a prospective study consisting of 85 cases and 106 controls, totaling 191 participants. TAS, TOS, OSI, and 8-OhDG levels were compared between both groups and before-after procedure. This study was supported by ESOGU BAP project number 1621. Results The mean age of the developing group was calculated as 68.13 ± 10.37, while it was calculated as 61.03 ± 9.97 in the control group (p = 0.00). In the case group, there were 30 (35.3%) without heart failure, while there were 75 (70.8%) without heart failure in the control group (p = 0.00). In univariate analyzes, we found that advanced age and heart failure were the most important indicators for KMN. When we compared those with and without KMN, we saw that TOS values decreased less in the group with post-angiography nephropathy than in those without it. We found a positive correlation between uric acid and TAS. In the KMN group, it was found that there was a statistically significant increase in TAS value after CAG, while there was a decrease in OSI value, and no statistically significant difference was found for TOS and 8-OhDG. In patients who underwent percutaneous intervention, it was found that there was a statistically significant increase in TAS value after CAG, while TOS and OSI decreased, and no significant difference was found for 8-OhDG. Conclusion Although previous studies have shown that oxidative stress plays an important role in contrast nephropathy pathogenesis, a strong relationship between KMN development and oxidative stress could not be found in our study. Our study is the first study to examine DNA damage with 8-OhDG in KMN, and it has been shown that there is no increase in DNA damage with KMN development. It is thought that one of the reasons leading to this result may be that contrast agents used today are selected as less toxic substances used in less volumes during processing, which may prevent DNA damage from occurring. Another result reached in our study is that TAS level increased in patients undergoing percutaneous intervention, while TOS and OSI decreased; that is, revascularization can reduce TOS and ultimately oxidative status.”

The impact of the stress hyperglycemia ratio on the risk of contrast-associated acute kidney injury in patients undergoing coronary angiography: a large real-world cohort study

BackgroundContrast-associated acute kidney injury (CA-AKI) is an important complication in the perioperative period of coronary angiography (CAG). Dysglycemia is closely associated with the occurrence of CA-AKI. However, the association between stress hyperglycemia and CA-AKI in patients undergoing CAG remains unclear. The study aims to investigate the association of the stress hyperglycemia ratio (SHR) and CA-AKI under CAG in a large real-world cohort.MethodsThis was a retrospective observational study, and patients undergoing CAG were enrolled. SHR is calculated by dividing the random blood glucose with the estimated average glucose derived from the glycosylated hemoglobin (HbA1c), and subjects were divided into five groups according to SHR. The outcome was CA-AKI defined as an increase in serum creatinine of ≥ 0.3 mg/dL (26.5 μmol/L) or 1.5-fold higher than normal levels in 48 h. The association was assessed with logistic regression and restricted cubic spline analysis.ResultsIn 19,965 participants (men: 73.3%, mean age: 63.1 ± 10.8 years) undergoing CAG, a total of 1,621 CA-AKI cases occurred. There were reverse J-shaped associations between the SHR and CA-AKI after adjustment for other confounding factors. Moreover, SHR improved the predictive effectiveness of the traditional Mehran score (AUC 0.65 vs 0.63, P < 0.001), a predictive model of CA-AKI in patients undergoing percutaneous coronary intervention.ConclusionsThere were reverse J-shaped associations of SHR with CA-AKI risk among patients undergoing CAG, and the assessment of SHR before CAG may assist clinicians in identifying patients at higher risk of CA-AKI.

Time-Dependent Molecular Changes Following MDMA-Induced Nephrotoxicity

: The increasing recreational use of ecstasy (MDMA) poses significant risks to human health, including reports of fatal renal failure due to its adverse renal effects. While MDMA-induced renal toxicity might result from systemic effects, there is also substantial evidence of direct harm to renal tissues by MDMA or its metabolites. The precise mechanisms underlying renal toxicity remain unclear. This study explored the impact of a single intraperitoneal dose of MDMA (20 mg/kg) on rat kidneys. Serum BUN and creatinine levels were evaluated to assess renal function, while TNF-α and TGF-β protein concentrations were measured using ELISA. mRNA levels of Bax, Bcl-xl, and Bcl-2 were quantified using quantitative RT-PCR. Additionally, apoptosis and histopathological changes in renal tissue were examined. Results showed a transient increase in serum BUN and creatinine in MDMA-treated rats. There were decreases in TNF-α and TGF-β levels in the renal tissue. Both pro-apoptotic Bax and anti-apoptotic Bcl-xl gene expressions were significantly reduced, whereas Bcl-2 expression and apoptosis did not show significant changes. No structural alterations were observed in the renal tissues. Overall, this study suggests that the renal adverse effects of MDMA may be mediated through the disruption of cytokine pathways, with notable reductions in TGF-β possibly linked to decreased TNF-α levels.

Inhibitory effect of flavonoids on multidrug and toxin extrusion protein 1 function: Implications for food/herb-drug interaction and drug-induced kidney injury.

Multidrug and toxin extrusion protein 1 (MATE1), an efflux transporter mainly expressed in renal proximal tubules, mediates the renal secretion of organic cationic drugs. The inhibition of MATE1 will impair the excretion of drugs into the tubular lumen, leading to the accumulation of nephrotoxic drugs in the kidney and consequently potentiating nephrotoxicity. Screening and identifying potent MATE1 inhibitors can predict or minimize the risk of drug-induced kidney injury. Flavonoids, a group of polyphenols commonly found in foodstuffs and herbal products, have been reported to cause transporter-mediated food/herb-drug interactions. Our objective was to investigate the inhibitory effects of flavonoids on MATE1 in vitro and in vivo and to assess the effects of flavonoids on cisplatin-induced kidney injury. Thirteen flavonoids exhibited significant transport activity inhibition (>50%) on MATE1 in MATE1-MDCK cells. Among them, the six strongest flavonoid inhibitors, including irisflorentin, silymarin, isosilybin, sinensetin, tangeretin, and nobiletin, markedly increased cisplatin cytotoxicity in these cells. In cisplatin-induced in vivo renal injury models, irisflorentin, isosilybin, and sinensetin also increased serum creatinine and blood urea nitrogen levels to different degrees, especially irisflorentin, which exhibited the most potent nephrotoxicity with cisplatin. The pharmacophore model indicated that the hydrogen bond acceptors at the 3, 5, and 7 positions may play a critical role in the inhibitory effect of flavonoids on MATE1. Our findings provide helpful information for predicting the potential risks of flavonoid-containing food/herb-drug interactions and avoiding the exacerbation of drug-induced kidney injury via MATE1 mediation.

Real-Time Use of SGLT2i Verified in Pre-dialysis: The RSVP Cross-sectional Study.

The use of sodium-glucose cotransporter 2 inhibitors (SGLT2i) in nephrology practice is increasingly becoming standard of care in patients with diabetes or those with proteinuria. The primary outcome was to identify the proportion of pre-dialysis patients with chronic kidney disease (CKD) G3a, G3b, or G4 prescribed an SGLT2i and describe their characteristics. This was a retrospective, multicentric, cross-sectional study of patients with CKD followed at 4 pre-dialysis clinics in the province of Quebec, Canada. We collected data of multiple covariates associated with prescribing SGLT2i in patients over 18 years of age with CKD G3a, G3b, or G4. We then performed a multivariate logistic regression to assess their associations. Of the 874 patients included, 22.7% were prescribed an SGLT2i. Factors most strongly associated included male sex (odds ratio [OR] = 4.88, 95% CI = 2.38-10.03), being prescribed metformin (OR = 4.30, 95% CI = 2.23-8.31), having type 2 diabetes (OR = 4.00, 95% CI = 1.86-8.62), or having an albumin-to-creatinine ratio greater than 300 mg/g (OR = 1.84, 95% CI = 1.08-3.14). The majority of patients (60.4%) had their SGLT2i initiated by the pre-dialysis clinic and the most frequent adverse event was an initial increase in serum creatinine 1 week after starting treatment (33.9%). An increasing number of patients with CKD are being prescribed SGLT2i. Nonetheless, significant disparities in sex, severity of disease, and comorbidities remain. We suggest that specific strategies be put in place to promote prescribing of SGLT2i in women and other at-risk populations, in particular among nephrology teams, to improve patient care.

Abemaciclib for the Treatment of HR+HER2- Metastatic Breast Cancer: An Institutional Experience.

(1) Background: Abemaciclib combined with endocrine therapy is a standard first- or later-line of treatment for HR+/HER2- metastatic breast cancer (MBC). The aim of this retrospective cohort study was to describe the outcomes of patients treated in a real-world setting, with particular focus on elderly patients. (2) Patients and methods: Patients treated with abemaciclib between November 2019 and February 2022 were included in the study. Data were collected from electronic medical records. The primary objective was to determine real-world progression-free survival (rwPFS), and secondary objectives included median overall survival (mOS) and safety. (3) Results: Analysis included 134 patients, with a median follow-up of 42 months. Median age was 62 years, with 29.9% aged 70+ years. A total of 51.5% of patients received abemaciclib in first-line, predominantly with aromatase inhibitor (68.1%). Median rwPFS was 21 in first-line and 20 months in the second-line, with no significant difference between treatment lines (HR 0.96; p = 0.88). Patients treated in the third- or later-line had a significantly shorter rwPFS, at 7 months (HR 1.48, p = 0.003). mOS was not reached in the first-line setting. For second- and third- or later-lines, mOS was 29 and 19 months, respectively. There was no significant difference in mOS between first- or second-line (HR 1.37, p = 0.36). In the 70+ group, median rwPFS was 15 months and mOS was 25 months with no significant difference compared to younger patients (rwPFS HR 1.1; p = 0.65; OS HR 1.4; p = 0.21). Most common adverse events (AEs) were diarrhoea (68.7%), anaemia (64.9%), and increased serum creatinine (63.4%). Grade 3/4 AEs were reported in 21.6% of patients. Dose reductions occurred in 30.6% of patients and were more frequent in patients 70+ (40%) compared to younger patients (28%); the difference was not significant (p = 0.22). At study cut-off, 64.9% of patients discontinued abemaciclib, primarily due to disease progression (73.5%). (4) Conclusions: Our study provides valuable insights into the effectiveness and safety of abemaciclib for the treatment of MBC. We observed comparable outcomes in terms of rwPFS and OS between the first two lines, suggesting consistent effectiveness across treatment lines. In addition, our findings suggest that older age (70+) does not significantly impact the effectiveness and tolerability of abemaciclib, although the careful monitoring and management of AEs are warranted.

Perioperative Acute Renal Injury: Revisiting Pathophysiology.

Acute renal dysfunction and subsequent acute renal failure after cardiac surgery are associated with high mortality and morbidity. Early therapeutic or preventive intervention is hampered by the lack of an early biomarker for acute renal injury. Recent studies showed that urinary neutrophil gelatinase-associated lipocalin (NGAL or lipocalin 2) is upregulated early (within 1 to 3 h) after murine renal injury and in pediatric acute renal dysfunction after cardiac surgery. The authors hypothesized that postoperative urinary NGAL concentrations are increased in adult patients developing acute renal dysfunction after cardiac surgery compared with patients without acute renal dysfunction. After institutional review board approval, 81 cardiac surgical patients were prospectively studied. Urine samples were collected immediately before incision and at various time intervals after surgery for NGAL analysis by quantitative immunoblotting. Acute renal dysfunction was defined as peak postoperative serum creatinine increase by 50% or greater compared with preoperative serum creatinine. Sixteen of 81 patients (20%) developed postoperative acute renal dysfunction, and the mean urinary NGAL concentrations in patients who developed acute renal dysfunction were significantly higher early after surgery (after 1 h, mean ± SD, 4,195±6,520 vs. 1,068±2,129ng/ml; P < 0.01) compared with patients who did not develop acute renal dysfunction. Mean urinary NGAL concentrations continued to increase and remained significantly higher at 3 and 18 h after cardiac surgery in patients with acute renal dysfunction. In contrast, urinary NGAL in patients without acute renal dysfunction decreased rapidly after cardiac surgery. Patients developing postoperative acute renal dysfunction had significantly higher urinary NGAL concentrations early after cardiac surgery. Urinary NGAL may therefore be a useful early biomarker of acute renal dysfunction after cardiac surgery. These findings may facilitate the early detection of acute renal injury and potentially prevent progression to acute renal failure.

Dexmedetomidine attenuates ferroptosis byKeap1-Nrf2/HO-1 pathway inLPS-induced acute kidney injury.

Previous research has demonstrated that Dexmedetomidine (DEX), an α2 adrenergic agonist commonly used for its sedative and analgesic properties, can attenuate lipopolysaccharide (LPS)-induced acute kidney injury (AKI). This study explores the possibility that DEX's protective effects in LPS-induced AKI are mediated through the inhibition of ferroptosis, a form of regulated cell death characterized by iron-dependent lipid peroxidation, and the activation of the antioxidant response through the Keap1/Nrf2/HO-1 signaling pathway. We induced AKI in 42 mice using LPS and divided them into six groups: saline control, LPS, LPS + DEX, LPS + Ferrostatin-1 (LPS + Fer-1; a ferroptosis inhibitor), LPS + DEX with α2-receptor antagonist Altipamizole (LPS + DEX + ATI), and LPS + DEX with Nrf2 inhibitor ML385 (LPS + DEX + ML385). After 24h, we analyzed blood and kidney tissues. LPS exposure resulted in AKI, with increased serum creatinine, BUN, and cystatin C, and tubular damage, which DEX and Fer-1 ameliorated. However, Altipamizole and ML385 negated these improvements. The LPS group exhibited elevated oxidative stress markers and mitochondrial damage, reduced by DEX and Fer-1, but not when α2-adrenergic or Nrf2 pathways were blocked. Nrf2 and HO-1 expression declined in the LPS group, rebounded with LPS + DEX and LPS + Fer-1, and fell again with inhibitors; inversely, Keap1 expression varied. Our results demonstrate that DEX may protect against LPS-induced AKI, at least partially by regulating ferroptosis and the α2-adrenergic receptor/Keap1/Nrf2/HO-1 pathway, suggesting a potential therapeutic role for DEX in AKI management by modulating cell death and antioxidant defenses.

Acute kidney injury in acute decompensated heart failure related cardiogenic shock: data from the Alt-Shock2 registry

Abstract Funding Acknowledgements None. Background Acute kidney injury (AKI) is one of the most common complications in patients with cardiogenic shock (CS), proving the strict relationship between heart and kidney (the so-called cardio-renal syndrome). AKI is a marker of shock severity, but also independently associated with worse outcomes. Purpose Many data are available on the prevalence of AKI in acute heart failure, but very few studies assessed the role of AKI in CS and they were mainly focused on acute myocardial infarction (AMI)-related CS. Aim of our study was to analyze the impact of AKI on acute decompensated heart failure (ADHF)-CS. Methods Between March 2020 and August 2022, we prospectively enrolled 375 CS patients from a Cardiac Intensive Care Units Network of 12 centers. Among these patients 121 (33.9% of the whole cohort) with ADHF-CS were included for the present analysis. AKI was defined according to KDIGO 2012 criteria as serum creatinine increase ≥ 0.3 mg/dl or 1.5 times compared to admission value, or urinary output &amp;lt; 0.5 ml/kg/h. Results Table 1 shows the baseline characteristics of the cohort. Patients with AKI were older (70 years old [55.5; 76] vs 61 [54; 69], p&amp;lt;0.05), had more comorbidities and a worse CS profile on admission. On multivariable analysis, SCAI stage D-E on admission was independently associated with a higher risk of AKI 24 hours after admission (OR 5.54 and p = 0.01). Treatment with mechanical circulatory support did not prevent AKI (OR 0.84 and p = 0.8). Notably, patients with a greater reduction in central venous pressure (CVP) 24 hours after admission had a lower risk of AKI (deltaCVP in AKI group 0 [-3;0] versus deltaCVP in no-AKI group -3 [-6;0], p = 0.025). Kaplan-Meier curves showed significantly worse survival in patients with AKI (Figure 1A). Cox regression analysis confirmed an association between AKI and increased risk of death (HR 2.14, CI 95% 1.16-3.96, p = 0.01). Notably, this association was even more pronounced in patients with SCAI stages A-B-C (HR 2.81, CI 95% 1.30-6.09, p = 0.01). Finally, in patients treated with renal replacement therapy (RRT) there was no association with lower survival at 180-days follow up (Figure 1B). Conclusions Our study confirms that AKI is a predictor of adverse outcomes in patients with ADHF-CS. Effective decongestion 24 hours after admission was associated with a lower risk of AKI. Considering that AKI had a negative impact even at lower SCAI stages, our findings underscore the importance of early identification of renal injury to promptly target decongestion with pharmacologic therapy and, ultimately, early use of RRT.