Significant Decline In Renal Function Research Articles

#2743 Impact of fatty acid-binding protein 4 on SUMOylation balance and renal tubular epithelial cell senescence in acute kidney injury

Abstract Background and Aims Dysregulated lipid metabolism and cellular senescence intricately interact in the context of acute kidney injury (AKI). Fatty acid-binding protein 4 (FABP4), a critical enzyme regulating lipid metabolism, potentially induces cell senescence through lipotoxicity in AKI. However, the specific mechanisms remain unclear. Method We established an ischemia-reperfusion-induced AKI (IRI-AKI) model in C57 mice and quantified and localized FABP4 expression in renal tissues using Western blotting (WB), qPCR, and immunofluorescence (IF). Oil Red O staining and beta-galactosidase staining were employed to assess lipid deposition and cellular senescence in tubular cells. The same measurements were repeated in IRI-AKI by knocking out Fabp4. Additionally, bulk mRNA sequencing and single-cell sequencing were conducted on renal tissues to analyze key molecules and related mechanisms. Results In vivo, we observed a significant decline in renal function, severe tubular epithelial damage, and abundant inflammation in the IRI-AKI group, which was noticeably alleviated in the Fabp4 knockout group (Fig. 1). Furthermore, we detected upregulation of FABP4 expression in the kidneys of IRI-AKI, primarily localized in the tubular epithelial cells. Fabp4 knockout effectively reduced tubular lipid accumulation and cellular senescence (Fig. 3). Through integrating mRNA and single-cell sequencing data, UBC9, an E2 enzyme involved in protein SUMOylation, emerged as a potential key regulator of cell senescence and AKI. WB and qPCR both confirmed the upregulation of UBC9 expression in IRI-AKI and its downregulation after Fabp4 knockout. Conversely, we observed that downregulated SUMOylation in IRI-AKI was upregulated in the Fabp4 knockout group (Fig. 4). Conclusion In conclusion, FABP4 modulates the expression of UBC9 and SUMOylation, thereby mediating cellular senescence and causing renal tubular cell damage in IRI-AKI. The mechanisms underlying FABP4’s regulation of UBC9 and the opposing trend between UBC9 and SUMOylation require further elucidation.

Ketorolac Dosing and Outcomes in Neonates Following Congenital Heart Surgery: A Retrospective Analysis.

Pain management is essential for postoperative surgery. Given the association of opioids with adverse outcomes, interest in the use of nonopioid analgesics, such as ketorolac, has increased. Published data on use in neonates are limited. To describe ketorolac dosing and safety and efficacy outcomes in the first 48 hours postcardiac surgery in neonates. We performed a single-center retrospective cohort study of neonates (ages < 28 d) who received ketorolac following cardiac surgery from November 2020 to July 2023 (inclusive). The primary safety outcome was a clinically significant decline in renal function, as defined by the composite of an increase in serum creatinine by greater than or equal to 0.3 mg/dL from baseline within 96 hours of ketorolac initiation and urine output less than or equal to 0.5 mL/kg/hr for 6 hours. The secondary safety outcome was clinically significant bleeding, defined as the composite of major bleeding by the International Society on Thrombosis and Hemostasis pediatric criteria and severe/fatal bleeding by the criteria of Nellis et al (2019). Efficacy was measured by opioid utilization based on a standardized pain score-driven analgesia protocol. Ketorolac was administered at 0.5 mg/kg every 6 hours as per an institutional clinical management algorithm. Thirty-nine patients met the eligibility criteria. The median ketorolac dose was 0.5 mg/kg/dose, and median (interquartile range [IQR]) duration of therapy was 48 hours (6-48 hr). No patients experienced a significant decline in renal function, and there were no clinically significant bleeding events. The median (IQR) IV morphine milligram equivalents (MMEs)/kg/d of opioid administration was 0.2 MME/kg/d (0.1-0.25 MME/kg/d) at the time of ketorolac initiation and 0.1 MME/kg/d (0.1-0.2 MME/kg/d) at 48 hours post-ketorolac initiation. If validated prospectively, these findings suggest that a ketorolac regimen of 0.5 mg/kg/dose every 6 hours in neonates postcardiac surgery may be safe with regard to renal function and bleeding risk. Additional randomized studies would be needed to determine efficacy with regard to opioid-sparing capacity.

Exploration of Risk Factors of the Onset of Antibiotics-induced Acute Kidney Injury and Its Transfer to Chronic Kidney Disease Using the Medical Information Database

Drug-induced acute kidney injury (AKI) is a serious adverse drug reaction, which results in a significant decline in renal function and is known to progress to chronic kidney disease (CKD). Therefore, appropriate drug therapy is important to avoid the risk of drug-induced AKI and CKD, which are serious concerns in clinical practice. In this study, using the medical information database of Hamamatsu University Hospital, we investigated the risk factors that accelerate the onset of drug-induced AKI or its progression to CKD in patients who received aminoglycoside antibiotics (AGs) or glycopeptide antibiotics (GPs), which are strongly associated with drug-induced AKI and CKD. We performed logistic regression analysis using patients' background, laboratory test results, and concomitant drug use, among other such factors as explanatory variables and drug-induced AKI or CKD onset as objective variables to explore the risk factors for drug-induced AKI and CKD. Our results showed that co-administration of amphotericin B, piperacillin-tazobactam and other AGs and GPs, increased serum creatinine (Scr) and chloride concentrations, serum lactate dehydrogenase activity, and decreased serum albumin concentration were risk factors for drug-induced AKI onset. Moreover, a reduced blood urea nitrogen:Scr ratio at drug-induced AKI onset served as a risk factor for CKD. These results suggest that careful monitoring of the aforementioned factors is important to ensure appropriate usage of these drugs in patients treated with AGs and GPs.

Festivity: The Effects of Traditional Holidays on the Graft Function Among Stable Kidney Recipients

PurposeWe observed transient elevations in creatinine levels among kidney recipients after three traditional holidays in Taiwan. This retrospective cohort study aimed to compare the changes in eGFR levels after Chinese New Year, Dragon Boat Festival, and Mid-Autumn Festival, all of which are associated with high-calorie and high-fat diets. Materials and MethodsWe conducted a retrospective analysis of 364 kidney recipients with stable graft function who were following at Chang Gung Memorial Hospital Linkou from 2018 to 2020. The graft function before and after the festival was determined by calculating the eGFR level using the serum creatinine measured during clinic visits prior to and following the festival. The patients were then categorized into subgroups based on their sex, BMI, and co-morbidities. The eGFR levels before and after the festival were evaluated and compared within these subgroups. ResultsA total of 301 kidney recipients have been finally included in this retrospective cohort study. The analysis showed a significant decrease in overall eGFR levels after Chinese New Year (from 56.92 ± 29.70 to 55.14 ± 24.79, P = .006), Mid-Autumn Festival (from 54.03 ± 24.61 to 53.35 ± 24.33, P = .008), and Dragon Boat Festival only in 2020 (from 50.98 ± 24.35 to 49.99 ± 23.45, P = .018). The analysis of subgroups suggested a tendency of renal function decline after all 3 traditional holidays in patient groups with DM or hypertension or nonoverweight status. ConclusionIn this study, we observed a significant decline in renal function among kidney recipients following traditional holidays in Taiwan, particularly among recipients with hypertension or diabetes mellitus or those who were not overweight.

Expression of Rejection-Associated Transcripts in Early Protocol Renal Transplant Biopsies Is Associated with Tacrolimus Exposure and Graft Outcome.

Subclinical inflammation in protocol biopsies relates to tacrolimus exposure and human leukocyte antigen (HLA) matching. We aimed to characterize transcripts associated with rejection and tacrolimus exposure and the latter's association with transplant outcomes. We tested whether gene expression is associated with rejection using strictly normal protocol biopsies (n = 17) and biopsies with T cell-mediated rejection (TCMR) or antibody-mediated rejection (ABMR) according to Banff criteria (n = 12). Subsequently, we analyzed these transcripts in a set of 4-month protocol biopsies (n = 137) to assess their association with donor and recipient characteristics, the intensity of immunosuppression, and the graft outcome. Differential expression (false discovery rate (FDR) < 0.01, fold (change (FC) > 3) between normal and rejection biopsies yielded a set of 111 genes. In the protocol biopsy cohort (n = 137), 19 out of these 111 genes correlated with tacrolimus trough levels at the time of biopsy (TAC-C0), and unsupervised analysis split this cohort into two clusters. The two clusters differed in donor age and tacrolimus trough levels. Subclinical rejection, including borderline lesions, tended to occur in the same cluster. Logistic regression analysis indicated that TAC-C0 at the time of biopsy (OR: 0.83, 95%CI:0.72-0.06, p = 0.0117) was associated with cluster 2. In a follow-up averaging 70 ± 30 months, this patient group displayed a significant decline in renal function (p = 0.0135). The expression of rejection-associated transcripts in early protocol biopsies is associated with tacrolimus exposure and a faster decline in renal function.

Ketorolac in neonates and infants following congenital heart surgery: a retrospective review.

Pain management is essential in the immediate post-surgical period. We sought to describe the ketorolac dose regimen in neonates and infants following cardiac surgery. Secondary outcomes included renal dysfunction, bleeding, and pain management. We performed a single-centre retrospective cohort study of neonates and infants (aged < 12 months) who received ketorolac following cardiac surgery, from November 2020 through November 2021 (inclusive). Ketorolac was administered at 0.5 mg/kg every 6 hours. Safety was defined by absence of a clinically significant decline in renal function (i.e., increase in serum creatinine [SCr] by ≥ 0.3 mg/dL from baseline within 48 hours and/or urine output ≤ 0.5 mL/kg/hour for 6 hours) and absence of clinically significant bleeding defined as major by International Society on Thrombosis and Hemostasis paediatric criteria or Severe/Fatal Bleeding Events by Nellis et al. Efficacy measures included pain scores and opioid utilisation. Fifty-five patients met eligibility criteria. The median (range) dose and duration of ketorolac administration was 0.5 mg/kg/dose for 48 (6-90) hours. Among all patients, there was not a statistically significant difference observed in median SCr within 48 hours of baseline (p > .9). There were no major or severe bleeding events. The median (range) opioid requirements (morphine intravenous equivalents per kg per day) at 48 hours post-ketorolac initiation was 0.1 (0-0.8) mg/kg/day. If validated prospectively, these findings suggest that a ketorolac regimen 0.5 mg/kg/dose every 6 hours in neonates and infants post-cardiac surgery may be safe with regard to renal function and bleeding risk, and effective regarding opioid-sparing capacity.

Adenine model of chronic renal failure in rats to determine whether MCC950, an NLRP3 inflammasome inhibitor, is a renopreventive

BackgroundChronic renal failure (CRF) is defined by a significant decline in renal function that results in decreased salt filtration and inhibition of tubular reabsorption, which ultimately causes volume enlargement. This study evaluated the potential renopreventive effects of the NLRP3 inflammasome inhibitor MCC950 in adenine-induced CRF in rats due to conflicting evidence on the effects of MCC950 on the kidney.MethodsSince the majority of the kidney tubular abnormalities identified in people with chronic renal disease are comparable to those caused by adding 0.75 percent of adenine powder to a rat's diet each day for four weeks, this method has received broad approval as a model for evaluating kidney damage. Throughout the test, blood pressure was checked weekly and at the beginning. Additionally, oxidative stress factors, urine sample examination, histological modifications, and immunohistochemical adjustments of caspase-3 and interleukin-1 beta (IL-1) levels in renal tissues were carried out.ResultsResults revealed that MCC950, an inhibitor of the NLRP3 inflammasome, had a renopreventive effect, which was demonstrated by a reduction in blood pressure readings and an improvement in urine, serum, and renal tissue indicators that indicate organ damage. This was also demonstrated by the decrease in neutrophil gelatinase-associated lipocalin tubular expression (NGAL).The NLRP3 inflammasome inhibitor MCC950 was found to significantly alleviate the worsening renal cellular alterations evidenced by increased expression of caspase-3 and IL-1, according to immunohistochemical tests.ConclusionThe NLRP3 inflammasome inhibitor MCC950 demonstrated renopreventive effects in the CRF rat model, suggesting that it might be used as a treatment strategy to stop the progression of CRF.

Incidence and predictors of clinically significant renal function decline among non-valvular atrial fibrillation patients on non-vitamin K oral anticoagulant: A multicenter study

Incidence and predictors of clinically significant renal function decline among non-valvular atrial fibrillation patients on non-vitamin K oral anticoagulant: A multicenter study

Incidence and predictors of clinically significant renal function decline among non-valvular atrial fibrillation patients on Warfarin: A multicenter study

Incidence and predictors of clinically significant renal function decline among non-valvular atrial fibrillation patients on Warfarin: A multicenter study

A combination of 5/6-nephrectomy and unilateral ureteral obstruction model accelerates progression of remote organ fibrosis in chronic kidney disease.

Chronic kidney disease (CKD) involves progressive renal fibrosis, which gradually reduces kidney function and often causes various complications in extrarenal tissues. Therefore, we investigated fibrogenesis in extrarenal tissues (heart, liver, and lungs) in different experimental CKD models, such as the 5/6-nephrectomy (5/6 Nx), unilateral ureteral obstruction (UUO), and a combination (2/3 Nx + UUO). We evaluated the degree of fibrogenesis in kidneys and extrarenal tissues by histological analysis and quantification of fibrosis-related gene and protein expression. To elucidate the fibrosis mechanisms observed in 2/3 Nx + UUO mice, we evaluated the effect of indoxyl sulfate (IS), a typical uremic toxin accumulated in CKD, and transforming growth factor-β (TGF-β), a fibrosis-related factor, on fibrosis using human hepatoma (HepG2) and RAW264.7 cells. A significant decline in renal function was observed in the 5/6 Nx and 2/3 Nx + UUO models, whereas a significant increase in renal fibrosis was observed only in the obstructed kidneys. Notable amount of fibrosis was induced in the liver and heart in the 2/3 Nx + UUO model, with the induction of macrophage infiltration and increased tissue IS and TGF-β levels. In agreement with the results of in vivo experiments, co-stimulation with IS, TGF-β, and macrophage-conditioned medium increased the expression of fibrogenic genes in HepG2 cells. We demonstrated that the 2/3 Nx + UUO model induced both loss of renal function and renal fibrosis in the earlier stages, providing a novel CKD model that induces remote organ fibrosis in a shorter time.

#4343 COMPARISONS OF CLINICAL OUTCOMES BETWEEN HYPERTENSIVE AND NORMOTENSIVE LIVING KIDNEY DONORS: A NATIONWIDE PROSPECTIVE COHORT STUDY

Abstract Background and Aims Living kidney donors with hypertension is potential candidates to solve the imbalance between supply and demand for renal transplantation. However, the safety of hypertensive donor is not sufficiently ensured after donor nephrectomy and there are limited studies, which compare the clinical outcomes between hypertensive and normotensive donors. Method All data from this study were obtained from the Korean Organ Transplantation Registry (KOTRY). A total 672 hypertensive donors and 5,134 normotensive living kidney donors were included from May 2014 to December 2020. Primary outcome was the occurrence of proteinuria and the development of lower renal function, defined as an estimated glomerular filtration rate (eGFR) less than 60 or 45 ml/min/1.73 m2. Results Compared to normotensive donors, hypertensive donors had lower eGFR before nephrectomy and remained lower after kidney transplantation. However, the risk of eGFR below 60 ml/min/1.73 m2 (adjusted HR, 0.87; 95% CI 0.70-1.09; P = 0.226) or below 45 ml/min/1.73 m2 (adjusted HR, 1.49; 95% CI 0.77-2.86; P = 0.234) was not significantly increased in hypertensive donors after multiple adjustment. When comparing the rate of eGFR decline between the hypertensive and normotensive donors, there was no significant difference (adjusted unstandardized β, −0.19; −1.15 – 0.76, P = 0.691). The incidence of proteinuria occurrence in hypertensive donor was increased, and it tended to increase even after 4-5 years. Hypertensive donors were found to have significantly more proteinuria than normotensive donors (adjusted HR, 1.83; 95% CI 1.13-2.96; P = 0.014). Conclusion Our study indicated that the risk of proteinuria after donation was increased in hypertensive donor, while it was not translated into significant decline in renal function. The continuous and careful monitoring for proteinuria should be required in hypertensive donor after nephrectomy.

#6578 ACUTE KIDNEY INJURY IN PATIENTS WITH VENTRICULAR SEPTAL RUPTURE: A SINGLE CENTER STUDY

Abstract Background and Aims Ventricular septal rupture (VSR) is an infrequent but dreaded complication of acute myocardial infarction(AMI). Acute kidney injury(AKI) is one of the major determinants of morbidity and mortality in these patients. Renal replacement therapy (RRT) is, in this set of patients of high-risk nature and can be prolonged. Focused data on the management of AKI in patients with VSR from developing countries is scarce. We present a large cohort of patients presenting with VSR from a tertiary care Centre in South India, evaluating the incidence of AKI, RRT, and short-term outcomes in this cohort. Method Observational study of all adult patients diagnosed with VSR following AMI over 5 years in a single centre in Chennai, India. Demographic characteristics, co-morbidities,clinical and laboratory,Serial renal function tests and urine output was noted. eGFR was calculated using the CKD-EPI formula.AKI definition and staging -KDIGO clinical Practice Guidelines. Data analysis was done using the IBM SPSS version 24. P-value less than 0.05 is used to indicate statistical significance. Results During the study period, 3024 patients presented to our hospital with acute coronary syndrome (ACS) and seventy patients presented with VSR (2.3%). Of these, forty-seven (67.1%) developed AKI. A nephrology consult was obtained for thirty-three (70%) patients. Older age, higher total count and lower systolic blood pressure were significantly associated with the occurrence of AKI. The mortality in the AKI group was significantly higher (63.8%). VSR closure was done in 12.7% and 21.7% of the AKI and non-AKI groups respectively. Surgical VSR repair was done in 61.7% and 60.8% of the patients with and without AKI respectively. Most of the patients (26, 55.3%) presented with KDIGO stage 3 AKI and all were oliguric. 10 and 11 patients were staged into KDIGO stages 1 and 2 respectively. 26 patients with Stage 3 AKI, only 14 (29.7%%) of them received nephrology consult.. RRT was initiated in fifteen patients (31.9%). The indications for RRT were oliguria, pulmonary oedema, metabolic acidosis, and worsening electrolyte disturbance.Acute peritoneal dialysis was initiated in 11 patients (73.3%) using a 43cm swan neck double cuffed tunnelled Tenckhoff peritoneal dialysis catheter placed at the bedside. Percutaneous peritoneal dialysis catheter insertion by a nephrologist was done in and the rest was inserted by open laparotomy technique by a trained general surgeon. All 11 were initiated on urgent low volume supine exchanges. Of these ten patients had manual exchanges done by a trained peritoneal dialysis nurse and one patient was put on automated peritoneal dialysis. The average volume per dwell was 500 ml±250 ml which was gradually increased if there was no leak. The total average peritoneal dialysis volume per day was 10L±2 L. The strength of bags (1.36%, 2.25%, 3.86%) dextrose was determined based on volume status and patients’ hemodynamics. No patient had a leak or peritoneal dialysis-related peritonitis. All patients’ peritoneal dialysis catheter was immobilized with a tight abdominal dressing. One patient continued continuous ambulatory peritoneal dialysis at home as there was no recovery of renal function and was lost to follow up. Sustained low-efficiency dialysis was performed on four patients. Duration of Sustained low-efficiency dialysis ranged from 6-8 hours with average blood flows of 150 ml/min and average fluid removal between 1.5-3L. Unfractionated heparin was used in three patients, and one was heparin free saline dialysis. Discharge eGFR in the AKI group was significantly lower as compared to the non-AKI group. (38 vs 104ml/min/1.73m2, p&amp;lt;0.001). Follow up was done on 14 at 3 months, The mean eGFR was 57.8ml/min/1.73 m2 when compared to 81.8 ml/min/1.73 m2. Conclusion The incidence of AKI is high and is associated with a high rate of mortality in patients with VSR. Peritoneal dialysis is a safe and effective option for those patients requiring RRT. Follow up of AKI patients at three months did not show a significant decline in renal function

Outcomes of the Ankura Stent Graft for Endovascular Repair of Infrarenal Abdominal Aortic Aneurysm.

The purpose of this retrospective cohort study is to report outcomes of endovascular aortic repair (EVAR) with the novel endograft, Ankura (Lifetech Scientific, Shenzen, China). We identified all patients who underwent elective EVAR with Ankura stent graft in a tertiary unit from January 2015 to November 2021. Patients with ruptured infrarenal and juxtarenal aortic aneurysms were excluded from the study. All patients were anatomically suitable according to the instructions for use (IFU). Follow-up (FU) included computed tomography angiography (CTA) at 1 month, 12 months, and yearly thereafter if endoleak (EL) was not present. Primary outcomes included technical success (primary and secondary) and 30-day overall mortality and morbidity. Secondary outcomes included late overall and aneurysm-related mortality as well as influence of suprarenal fixation of the endograft on renal function at 12 months using eGFR (CKI-EPI formula). The Ankura endograft was successfully implanted in 116 patients (mean age=71.1 years, 96.5% male). Mean aneurysm diameter was 62.3 mm. Median FU was 34 months (2-72 months). Primary and secondary technical success were 95.7% and 100%, respectively. Overall type I EL was 5% (2 proximal, 3 distal) and type II EL was 13%. Thirty days mortality and morbidity were 0% and 5.2%, respectively. All-cause mortality during FU was 13.9% (n=16); aneurysm-related mortality was 2.6% (n=3). Limb endograft patency was 100%. Freedom from reintervention was 98.2% at 2 years, and 97.4% at 4 and 6 years respectively. There was a statistically significant difference between preoperative (73.69 mL/min/1.73 m2) and postoperative (66.66 mL/min/1.73 m2) eGFR at 12 months (p<0.001). Ankura endograft has demonstrated an efficacious durability with low aneurysm-related mortality and high iliac limb patency rate. Elective EVAR is associated with significant decline in renal function at 12 months in our study. Larger series studies are necessary to evaluate long-term safety and efficacy of Ankura endograft. Ankura stent graft is a novel PTFE endograft with suprarenal fixation for infrarenal aneurysm repair. This retrospective cohort study of 116 patients provide a first "picture" of Ankura safety and efficacy in a European tertiary vascular center. High technical success rate, low aneurysm related mortality and high limb patency rate are the main findings of the study with a negative impact of suprarenal fixation on kidney function during follow up.

Aldehyde Dehydrogenase 2 Ameliorates LPS-Induced Acute Kidney Injury through Detoxification of 4-HNE and Suppression of the MAPK Pathway.

Lipopolysaccharide (LPS)-induced septic acute kidney injury (AKI) is determined as a devastating organ dysfunction elicited by an inappropriate response to infection with high morbidity and mortality rates. Previous evidence has illustrated an indispensable role of mitochondrial aldehyde dehydrogenase 2 (ALDH2) in the pathogenesis of sepsis-induced multiorgan abnormalities. Specifically, this study investigated the potential role of ALDH2 in sepsis-induced AKI. After LPS administration, we observed a significant decline in renal function, increased inflammatory cytokines, oxidative stress, 4-hydroxy-2-nonenal (4-HNE) accumulation, and apoptosis via MAPK activation in ALDH2-/- mice; in contrast, pretreatment with Alda-1 (an ALDH2 activator) alleviated the LPS-induced dysfunctions in mice. Moreover, in vitro analysis revealed that ALDH2 overexpression in mouse tubular epithelial cells (mTECs) improved the inflammatory response, oxidative stress, 4-HNE accumulation, and apoptosis via MAPK inhibition, whereas ALDH2 knockdown in mTECs aggravated these parameters via MAPK activation. Therefore, ALDH2 may protect against LPS-induced septic AKI by suppressing 4-HNE/MAPK pathway.

MP23-09 ACUTE KIDNEY INJURY AND ITS DURATION IN PATIENTS TREATED WITH RADICAL CYSTECTOMY IN THE ENHANCED RECOVERY AFTER SURGERY ERA: OPTIMIZING THE SELECTION OF PATIENTS FOR RESTRICTIVE FLUID THERAPY

You have accessJournal of UrologyCME1 May 2022MP23-09 ACUTE KIDNEY INJURY AND ITS DURATION IN PATIENTS TREATED WITH RADICAL CYSTECTOMY IN THE ENHANCED RECOVERY AFTER SURGERY ERA: OPTIMIZING THE SELECTION OF PATIENTS FOR RESTRICTIVE FLUID THERAPY Alberto Martini, Riccardo Leni, Francesco Pellegrino, Giuseppe Basile, Simone Scuderi, Mario De Angelis, Luigi Nocera, Giuseppe Rosiello, Giorgio Gandaglia, Andrea Gallina, Francesco Montorsi, Alberto Briganti, and Marco Moschini Alberto MartiniAlberto Martini More articles by this author , Riccardo LeniRiccardo Leni More articles by this author , Francesco PellegrinoFrancesco Pellegrino More articles by this author , Giuseppe BasileGiuseppe Basile More articles by this author , Simone ScuderiSimone Scuderi More articles by this author , Mario De AngelisMario De Angelis More articles by this author , Luigi NoceraLuigi Nocera More articles by this author , Giuseppe RosielloGiuseppe Rosiello More articles by this author , Giorgio GandagliaGiorgio Gandaglia More articles by this author , Andrea GallinaAndrea Gallina More articles by this author , Francesco MontorsiFrancesco Montorsi More articles by this author , Alberto BrigantiAlberto Briganti More articles by this author , and Marco MoschiniMarco Moschini More articles by this author View All Author Informationhttps://doi.org/10.1097/JU.0000000000002562.09AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookLinked InTwitterEmail Abstract INTRODUCTION AND OBJECTIVE: Acute kidney injury (AKI) is not an uncommon occurrence after Radical cystectomy (RC). An integral part of the enhanced recovery after surgery (ERAS) protocol is restrictive fluid therapy in the postoperative period. Yet, this might enhance the occurrence of postoperative AKI and not all patients might benefit from it. We aimed to investigate whether AKI and its duration is associated with worse renal functional outcomes to identify individuals that should not be treated with restrictive fluid therapy following RC. METHODS: Patients who underwent RC at a single high-volume institution between 2015-2020 whose postoperative course followed the ERAS protocol were evaluated. The LOWESS and Cox regression were used to assess the impact of AKI (according to the RIFLE criteria: i.e., more than 25% reduction in preoperative baseline eGFR or more than 1.5-fold increase in preoperative creatinine) and its duration (0-3 vs more than 3 days) on significant renal impairment (eGFR reduction of greater or equal to 25%) at 12 months. Finally, we evaluated predictors of AKI duration ≥4 days as this was associated with worse outcomes in terms of renal function. RESULTS: Among 501 patients, 46% developed postoperative AKI. Patients who developed AKI were older (71 vs 69 years-old, p=0.024), and had higher Charlson Comorbidity Index (CCI >2 in 54 vs 38%, p=0.002). Baseline eGFR, type of surgical approach (open vs robot), use of neoadjuvant treatment were balanced between groups (all p >0.05). Overall, 24% had a significant decline in renal function at 12-month. Figure 1 displays the correlation between the probability of eGFR reduction at 12-month with the duration of AKI and the relative frequency of AKI across the postoperative days. A prolonged duration of postoperative AKI (≥4 days) was predictor of 12-month decline (HR 7.25, 95%CI 3.93,13.4, p <0.001). A high comorbidity burden (CCI≥3) was associated with prolonged postoperative AKI (OR 1.71, 95%CI 1.16,2.95, p=0.04). CONCLUSIONS: Prolonged AKI (≥4 days) is associated with worse renal functional outcome after RC. The sole predictor of prolonged AKI was CCI≥3. Patients with a high comorbidity burden should not be treated with restrictive fluid therapy as part of the ERAS protocol following RC. Source of Funding: no © 2022 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 207Issue Supplement 5May 2022Page: e384 Advertisement Copyright & Permissions© 2022 by American Urological Association Education and Research, Inc.MetricsAuthor Information Alberto Martini More articles by this author Riccardo Leni More articles by this author Francesco Pellegrino More articles by this author Giuseppe Basile More articles by this author Simone Scuderi More articles by this author Mario De Angelis More articles by this author Luigi Nocera More articles by this author Giuseppe Rosiello More articles by this author Giorgio Gandaglia More articles by this author Andrea Gallina More articles by this author Francesco Montorsi More articles by this author Alberto Briganti More articles by this author Marco Moschini More articles by this author Expand All Advertisement PDF DownloadLoading ...

Effect of Vupanorsen on Non-High-Density Lipoprotein Cholesterol Levels in Statin-Treated Patients With Elevated Cholesterol: TRANSLATE-TIMI 70.

Background:Genetic loss-of-function variants in ANGPTL3 are associated with lower levels of plasma lipids. Vupanorsen is a hepatically targeted antisense oligonucleotide that inhibits Angiopoietin-like 3 (ANGPTL3) protein synthesis.Methods:Adults with non–high-density lipoprotein cholesterol (non-HDL-C) ≥100 mg/dL and triglycerides 150 to 500 mg/dL on statin therapy were randomized in a double-blind fashion to placebo or 1 of 7 vupanorsen dose regimens (80, 120, or 160 mg SC every 4 weeks, or 60, 80, 120, or 160 mg SC every 2 weeks). The primary end point was placebo-adjusted percentage change from baseline in non–HDL-C at 24 weeks. Secondary end points included placebo-adjusted percentage changes from baseline in triglycerides, low-density lipoprotein cholesterol (LDL-C), apolipoprotein B (ApoB), and ANGPTL3.Results:Two hundred eighty-six subjects were randomized: 44 to placebo and 242 to vupanorsen. The median age was 64 (interquartile range, 58–69) years, 44% were female, the median non–HDL-C was 132.4 (interquartile range, 118.0–154.1) mg/dL, and the median triglycerides were 216.2 (interquartile range, 181.4–270.4) mg/dL. Vupanorsen resulted in significant decreases from baseline over placebo in non–HDL-C ranging from 22.0% in the 60 mg every 2 weeks arm to 27.7% in the 80 mg every 2 weeks arm (all P<0.001 for all doses). There were dose-dependent reductions in triglycerides that ranged from 41.3% to 56.8% (all P<0.001). The effects on LDL-C and ApoB were more modest (7.9%–16.0% and 6.0%–15.1%, respectively) and without a clear dose-response relationship‚ and only the higher reductions achieved statistical significance. ANGPTL3 levels were decreased in a dose-dependent manner by 69.9% to 95.2% (all P<0.001). There were no confirmed instances of significant decline in renal function or platelet count with vupanorsen. Injection site reactions and >3× elevations of alanine aminotransferase or aspartate aminotransferase were more common at higher total monthly doses (up to 33.3% and 44.4%, respectively), and there was a dose-dependent increase in hepatic fat fraction (up to 76%).Conclusions:Vupanorsen administered at monthly equivalent doses from 80 to 320 mg significantly reduced non–HDL-C and additional lipid parameters. Injection site reactions and liver enzyme elevations were more frequent at higher doses, and there was a dose-dependent increase in hepatic fat fraction.Registration:URL: https://clinicaltrials.gov; Unique identifier: NCT04516291.

Prediction of significant renal function decline after open, laparoscopic, and robotic partial nephrectomy: External validation of the Martini's nomogram on the RECORD2 project cohort.

Martini etal. developed a nomogram to predict significant (>25%) renal function loss after robot-assisted partial nephrectomy and identified four risk categories. We aimed to externally validate Martini's nomogram on a large, national, multi-institutional data set including open, laparoscopic, and robot-assisted partial nephrectomy. Data of 2584 patients treated with partial nephrectomy for renal masses at 26 urological Italian centers (RECORD2 project) were collected. Renal function was assessed at baseline, on third postoperative day, and then at 6, 12, 24, and 48 months postoperatively. Multivariable models accounting for variables included in the Martini's nomogram were applied to each approach predicting renal function loss at all the specific timeframes. Multivariable models showed high area under the curve for robot-assisted partial nephrectomy at 6- and 12-month (87.3% and 83.6%) and for laparoscopic partial nephrectomy (83.2% and 75.4%), whereas area under the curves were lower in open partial nephrectomy (78.4% and 75.2%). The predictive ability of the model decreased in all the surgical approaches at 48 months from surgery. Each Martini risk group showed an increasing percentage of patients developing a significant renal function reduction in the open, laparoscopic and robot-assisted partial nephrectomy group, as well as an increased probability to develop a significant estimated glomerular filtration rate reduction in the considered time cutoffs, although the predictive ability of the classes was <70% at 48 months of follow-up. Martini's nomogram is a valid tool for predicting the decline in renal function at 6 and 12 months after robot-assisted partial nephrectomy and laparoscopic partial nephrectomy, whereas it showed a lower performance at longer follow-up and in patients treated with open approach at all these time cutoffs.

Associations of Carbonaceous Compounds and Water-Soluble Inorganic Ions in Ambient PM2.5 with Renal Function in Older Individuals: The China BAPE Study.

Exposure to fine particulate matter (PM2.5) is proven to be associated with a decline in renal function. However, few studies have explored the acute renal damage from carbonaceous compounds and water-soluble inorganic ions (WSIIs), which constitute the bulk of total PM2.5 mass. We examined the acute effect of these constituents of ambient PM2.5 on renal function in older Chinese individuals. Seventy-one healthy people aged 60-69 years from Jinan, China, were enrolled and visited monthly and asked to complete survey questionnaires, undergo physical exams, and provide blood samples. The hourly concentrations of organic carbon, elemental carbon (EC), and WSIIs in ambient PM2.5 were collected from a fixed-site monitoring station. The association between PM2.5 constituents and estimated glomerular filtration rate (eGFR) was evaluated using linear mixed-effects models after controlling for a series of covariates. We observed that ambient carbonaceous compounds and WSIIs were associated with a significant decline in renal function. The interquartile range increased in the 24 h moving average of carbonaceous compounds, and WSIIs in ambient PM2.5 were associated with -13.11% [95% confidence interval (95% CI): -19.49, -6.21%] to -0.81% (95% CI: -4.17, 2.67%) changes in eGFR. We found significant associations between EC, chlorine (Cl-), sodium (Na+), and magnesium (Mg2+) and eGFR in single-pollutant, constituent-PM2.5, and residual-constituent models with a lag period of 0-24 h. This study demonstrated that carbonaceous compounds and WSIIs in PM2.5 were inversely associated with renal function.

Predictors of Decline in Renal Function 5 Years after EVAR.

While there exists copious short-term data regarding renal function following infra-renal endovascular abdominal aortic aneurysm repair (EVAR), long-term analysis is sparse. This is a single institution retrospective review of predictors of renal function decline 5 years after elective EVAR. All EVAR between 2007 and 2015 were queried. Patients in whom renal function was documented 5 years postoperatively were included in analysis. Exclusion criteria were ruptured aneurysm, mortality before 56 months, lack of follow-up, ESRD status, and concomitant renal intervention. The primary outcome investigated was a 20% or greater drop in glomerular filtration rate (GFR) 5 years postoperatively. The following variables at the time of surgery were investigated as potential predictors: age, gender, hypertension, hyperlipidemia, diabetes, CAD or prior MI, COPD, prior stroke, baseline eGFR under 60mL/min/1.73m2, supra-renal fixation, infra-renal fixation, neck diameter, neck length, and number of contrast CT. 354 EVAR were identified of which 143 met inclusion criteria (211 excluded). Univariate analysis revealed female gender (OR 2.7), hypertension (OR 9.4), baseline renal insufficiency (OR 3.8), larger neck diameter, and supra-renal fixation (OR 2.32) all predictive (P < .05) of GFR drop at 5 years. Multivariate binary logistic regression analysis found female gender (multivariate OR 3.9, P = .023) and baseline renal insufficiency (multivariate OR 3.0, P = .029) as significant predictors of greater than 20% GFR drop at 5 years. Only 2 patients of the 143 progressed to dialysis requirement at 5 years. Females and patients with baseline renal insufficiency are more vulnerable to significant decline in renal function 5 years following EVAR. Consistent with analogous literature, supra-renal fixation appears moderately deleterious toward renal function with no clinical significance in those with baseline normal renal function. The potential benefit of avoidance of supra-renal fixation in female patients with baseline renal insufficiency is worth further investigation in a more robust multi-center study.

177Lu-dotatate use in chronic kidney disease patients: A single center experience

Background: Peptide receptor radionuclide therapy with 177Lu-dotatate is a novel therapy for metastatic neuroendocrine cancers. It undergoes reabsorption at the proximal tubule; after the breakdown of the peptide fragment, 177Lu is retained and continues its decay process exposing the nephron to continuous low dose radiation. Pivotal NETTER-1 trial did not include patients with eGFR &lt;50 and so its effects in CKD patients is not known. Methods: We performed a retrospective chart review of all consecutive adult patients that received 177Lu-dotatate over 1 year at Mayo Clinic, Rochester. We analyzed renal and hematological laboratory data obtained prior to each of four treatment cycles and at 3- and 6-month post completion of all treatment. We defined CKD as eGFR &lt;60 ml/min and AKI as creatinine increase of ⩾0.3 from baseline by AKIN criteria. Results: Overall 86 patients were included in the study with 39 (45%) with known CKD. About three patients had CKD, four with eGFR of 20–30 ml/min. About 4 (4.6%) patients had AKI and the predominant cause being hypotension. Among the CKD patients the average eGFR improved after the first cycle of PRRT therapy from baseline of 49 (13) to 53.5 (17) ml/min ( p = 0.01) with no significant decline of renal function noted at 3- and 6-months post treatment follow up. Rate of thrombocytopenia and leukopenia were significantly more in the CKD patients starting even after single treatment. No drug dose correlation was noted. Conclusion: Patients with CKD are at a higher risk of hematological toxicity especially with thrombocytopenia and require close monitoring and ongoing dose adjustment. Ongoing safety studies to assess the long-term impact of 177Lu-dotatate on the kidney are needed.