Management Of Acute Kidney Injury Research Articles

Yerba Mate Attenuates Oxidative Stress Induced Renal Cell Damage

IntroductionIn this study, the protective effects of yerba mate aqueous extract, which is widely used in traditional medicine, against hydrogen peroxide (H2O2)-induced toxicity were evaluated in human embryonic kidney (HEK) 293T cells. MethodsHydrogen peroxide was used to induce oxidative stress in HEK 293T cells and create an in vitro model of acute kidney injury. The MTT assay was used to evaluate cell viability, and HPLC methods were used to determine the phenolic components of yerba mate extract. For mechanistic insight, the levels of malondialdehyde, superoxide dismutase, and catalase, which are the basic parameters of oxidative stress, were investigated in H2O2-treated HEK 293T cells. ResultsThe aqueous extract of yerba mate at a concentration of 62.5 µg/ml prevented H2O2-induced oxidative damage to HEK 293T cells by 70%. Morphological studies have also shown that yerba mate can inhibit cellular damage caused by H2O2. The HPLC analysis of phenolic compounds in yerba mate extract revealed the presence of chlorogenic acid, caffeic acid, rutin, and quercetin. Further, it was observed that yerba mate can significantly increase catalase and superoxide dismutase levels and decrease malondialdehyde levels. ConclusionsOur study demonstrated the ability of an aqueous extract of yerba mate to counteract H2O2-induced cell damage in HEK 293T cells. These data present yerba mate as a potent antioxidant with potential benefits for the management of acute kidney injury.

Analysis of prescription pattern and evaluation of possible drug related problems in acute kidney injury patients

Introduction: Drug-induced acute kidney injury (AKI) is a significant cause of morbidity and mortality, accounting for 8% to 60% of in-hospital AKI cases. Impaired renal function leads to the accumulation of drugs and their metabolites in the body, increasing the nephrotoxic burden and the risk of AKI. Objective: The study aims to assess the necessity of appropriate dosage adjustment in patients with acute kidney injury (AKI) and the utilization of previously nephrotoxic drugs. Method: A prospective observational study was conducted among Acute Kidney Injury patients for a period of about 6 months. The collected data were analyzed using SPSS v.20. Pearson’s chi-square tests, correlation, and linear regression analysis were employed to examine the collected data. Results: A study of 207 patients revealed that 97% were prescribed antibiotics, with penicillin being the most common (46.9%). Cephalosporin and piperacillin/tazobactam were prescribed to 38.80% and 37.81% of patients, respectively. Concerningly, only 24% of prescriptions for acute kidney injury (AKI) patients were appropriate, while 86.9% and 58.4% exhibited overdosing and contraindications. More than half of the AKI patients (114 out of the total) had previously used nephrotoxic medications, potentially contributing to their kidney injury. Improved dosage adjustment practices in AKI treatment and monitoring of nephrotoxic drug use are crucial to prevent renal complications. Conclusion: The study’s findings emphasize AKI development, drug patterns, antibiotics and nephrotoxic drugs highlighting the importance of awareness and effective management of AKI.

Heterogeneity in Acute Kidney Injury Management in Critically Ill Patients: National Survey

We conducted a descriptive survey study with 365 multidisciplinary critical care providers to examine the heterogeneity in using tools for diagnosing acute kidney injury (AKI) in critical care settings. Results indicated that 52% of respondents used point-of-care ultrasound, followed by 15% using novel biomarkers and 8% using formal kidney ultrasound imaging for diagnostic testing. Cystatin C was the most commonly used novel biomarker (72% of respondents). Only 6% used prediction models and an integrated clinical decision support system to identify patients at high-risk for developing AKI. We confirmed that significant variation exists in the diagnosis of critically ill patients with AKI.

Clinicopathological Characteristics and Prognosis of Lupus Nephritis Patients with Acute Kidney Injury

Introduction: Acute kidney injury (AKI) is common in lupus nephritis (LN) and a risk factor for chronic kidney failure. Here, we aimed to assess the characteristics and prognosis of LN patients with AKI. Methods: AKI and AKI severity stages in LN patients were defined by the Kidney Disease Improving Global Outcomes (KDIGO) classification. Long-term renal outcomes and patient mortality between different stages of AKI were compared by Cox regression analysis. Results: Of 1272 LN patients, 225 (17.69%) had AKI and 72 (5.66%) were AKI stage 3. Compared with the non-AKI group, the proportion of male patients was significantly higher in the AKI group (p = 0.002). In addition, there were markedly higher proportions of hematologic system damage, more severe renal manifestations, and higher Systemic Lupus Erythematosus Disease Activity Index (SLEDAI) scores in the AKI group than in the non-AKI group. The active and chronic lesions in renal biopsy were significantly higher in LN patients with AKI than those without AKI. During a median follow-up of 53 months, Kaplan-Meier curve showed that LN patients with AKI stage 3 had significantly poorer long-term renal outcomes (p = 0.002) and patient survival (p < 0.001) than those without AKI. Furthermore, AKI stage 3, but not stage 1 or 2 was significantly associated with adverse renal outcomes (hazard ratio [HR] = 2.52, 95% confidence interval [CI] 1.01–6.28, p = 0.048) and all-cause mortality (HR = 2.80, 95% CI: 1.18–6.61, p = 0.019) in LN patients. In patients with AKI, increased baseline serum creatinine and severe glomerular sclerosis were independent risk factors for worse renal outcomes, while higher blood pressure, increased baseline serum creatinine, and anti-Sjogren’s syndrome A positivity could indicate poor survival. Discussion: LN patients with AKI stage 3, but not stages 1 and 2, have poorer long-term renal outcomes and patient survival. Our study demonstrates the importance of early identification and management of AKI in LN patients.

A proposed framework for advancing acute kidney injury risk stratification and diagnosis in children: a report from the 26th Acute Disease Quality Initiative (ADQI) conference

Acute kidney injury (AKI) in children is associated with increased morbidity, reduced health-related quality of life, greater resource utilization, and higher mortality. Improvements in the timeliness and precision of AKI diagnosis in children are needed. In this report, we highlight existing, novel, and on-the-horizon diagnostic and risk-stratification tools for pediatric AKI, and outline opportunities for integration into clinical practice. We also summarize pediatric-specific high-risk diagnoses and exposures for AKI, as well as the potential role of real-time risk stratification and clinical decision support to improve outcomes. Lastly, the key characteristics of important pediatric AKI phenotypes will be outlined. Throughout, we identify key knowledge gaps, which represent prioritized areas of focus for future research that will facilitate a comprehensive, timely and personalized approach to pediatric AKI diagnosis and management.

Continuous kidney replacement therapy outcomes in infants and newborns

Background Continuous kidney replacement therapy (CKRT) is utilized in the management of acute kidney injury (AKI). For infants and newborns, it is a challenging procedure. This study aimed to determine the outcomes of CKRT among infants and newborns, given the limited literature available. Methods A retrospective study reviewed charts and the Virtual Performance System in pediatric intensive care unit (PICU) in a tertiary care center in Saudi Arabia. This study included 40 patients (aged 0–1 year) who underwent CKRT from September 2009 to December 2019. Exclusion comprised individuals with a CKRT duration of &lt;24 hours and patients whose primary diagnosis was cardiac in origin. Demographics, nature of diseases, presence of multiorgan failure, modality, and prescriptions of the CKRT were reported. Statistical analysis identified the correlation between the outcome and the mentioned data. Results The median age at intensive care unit (ICU) admission (0–12) was 5 months, and the median weight (2.20–9.70) was 5.45 kg. The most common category was bone marrow transplantation (42.5%), followed by metabolic conditions (20%). The most common modality was continuous venovenous hemodialysis (n = 21; 56.8%). The median blood flow rate (20–100) was 50 mL/min, and the median dialysate flow rate (100–800) was 400 mL/h. The median duration of PICU stay (0.80–139.01) was 16.97 days. Twelve patients (30%) survived, while the majority, 28 (70%), did not survive. The median duration of CKRT was 38.95 h. Most of the patients, 37 out of 40 (92.5%), developed complications during CKRT, with hypothermia (62.5%). The nonsurvived group had a higher weight (6 vs. 4.3 kg, P &lt; 0.01) and was older at ICU admission (6 vs. 3.33 months, P = 0.02). The primary diagnostic category, reason to initiate CKRT, and the presence of multiorgan failure were found to be significantly correlated with the outcome (P &lt; 0.01). Additionally, a significant correlation was found between serum creatinine levels after 3 months of CKRT and age at ICU admission (correlation coefficient 0.47, P = 0.05). Fifty percent of the patients had an overall survival time, from initiating CKRT until the PICU patients’ physical discharge, of 13 days (95% confidence interval: 9–26). Conclusion The overall mortality rate for all causes of CKRT initiation was 70%. However, newborns and infants who underwent CKRT for metabolic causes exhibited an 88% survival rate. Additionally, weight, age at ICU admission, coagulopathies, and the presence of multiorgan failure showed a significant a correlation with the outcome.

Contrast Agent Administration as a Source of Liability: A Legal Database Analysis.

Background Radiology ranks high in terms of specialties implicated in medical malpractice claims. While most radiologists understand the risks of liability for missed findings or lapses of communication, liability for the use of contrast agents in imaging procedures may be underappreciated. Purpose To review the clinical context and outcomes of lawsuits alleging medical malpractice for contrast-related imaging procedures. Materials and Methods Two large U.S. legal databases were queried using the terms "Contrast" and "Radiology OR Radiologist" from database inception to October 31, 2022, to identify cases with published decisions or settlements related to medical malpractice in patients who underwent contrast-related imaging procedures. The search results were screened to include only those cases involving the practice area of health care law where there was at least one claim of medical negligence against a health care institution or provider. Data on the medical complications alleged by patients after contrast agent administration and on the trial were extracted and reported using descriptive statistics. Results A total of 151 published case summaries were included in the analysis. Anaphylactic reaction following contrast agent administration was the most common medical complication observed (30% [45 of 151 cases]), of which failure to diagnose developing anaphylaxis or failure to treat the anaphylactic reaction made up the majority of allegations (93% [42 of 45]). Inappropriate management of contrast media extravasation (27% [41 of 151]) and alleged contrast agent-induced acute kidney injury (13% [19 of 151]) were the next most frequent causes of lawsuits. Of the 11 cases of alleged kidney injury that went to trial, all resulted in a judgment in favor of the defense. Conclusion This study highlights the key reasons for medical malpractice lawsuits associated with use of contrast media and outcomes from these lawsuits. © RSNA, 2023 Supplemental material is available for this article. See also the editorial by Trop in this issue.

Recent Advances of Proteomics in Management of Acute Kidney Injury.

Acute Kidney Injury (AKI) is currently recognized as a life-threatening disease, leading to an exponential increase in morbidity and mortality worldwide. At present, AKI is characterized by a significant increase in serum creatinine (SCr) levels, typically followed by a sudden drop in glomerulus filtration rate (GFR). Changes in urine output are usually associated with the renal inability to excrete urea and other nitrogenous waste products, causing extracellular volume and electrolyte imbalances. Several molecular mechanisms were proposed to be affiliated with AKI development and progression, ultimately involving renal epithelium tubular cell-cycle arrest, inflammation, mitochondrial dysfunction, the inability to recover and regenerate proximal tubules, and impaired endothelial function. Diagnosis and prognosis using state-of-the-art clinical markers are often late and provide poor outcomes at disease onset. Inappropriate clinical assessment is a strong disease contributor, actively driving progression towards end stage renal disease (ESRD). Proteins, as the main functional and structural unit of the cell, provide the opportunity to monitor the disease on a molecular level. Changes in the proteomic profiles are pivotal for the expression of molecular pathways and disease pathogenesis. Introduction of highly-sensitive and innovative technology enabled the discovery of novel biomarkers for improved risk stratification, better and more cost-effective medical care for the ill patients and advanced personalized medicine. In line with those strategies, this review provides and discusses the latest findings of proteomic-based biomarkers and their prospective clinical application for AKI management.

Acute Kidney Injury and Sepsis after Cardiac Surgery: The Roles of Tissue Inhibitor Metalloproteinase-2, Insulin-like Growth Factor Binding Protein-7, and Mid-Regional Pro-Adrenomedullin.

Identifying a panel of markers detecting kidney injury before the glomerular filtration rate reduction is a challenge to improving the diagnosis and management of acute kidney injury (AKI) in septic patients. This study evaluated the roles of tissue inhibitor metal proteinase-2, insulin growth factor binding protein-7 (TIMP2*IGFBP7), and mid-regional pro-adrenomedullin (MR-proADM) in patients with AKI. This study was prospectively conducted in an intensive care unit (ICU) enrolling 230 patients who underwent cardiac surgery. Biomarkers were evaluated before and after 4 h of the cardiac surgery. Whereas urine and creatinine alterations appeared at 23.2 (12.7-36.5) hours after cardiac surgery, urinary TIMP2*IGBP7 levels were higher at 4 h in AKI patients (1.1 ± 0.4 mg/L vs. 0.08 ± 0.02 mg/L; p < 0.001). Its concentration > 2 mg/L increases AKI risk within the following 24 h, clearly identifying the population at high risk of renal replacement therapy (RRT). In patients with sepsis, MR-proADM levels were 2.3 nmol/L (0.7-7.8 nmol/L), with the highest values observed in septic shock patients (5.6 nmol/L (3.2-18 nmol/L)) and a better diagnostic profile than procalcitonin and C-reactive protein to identify septic patients. MR-proADM values > 5.1 nmol/L and urine TIMP2*IGBP7 levels > 2 mg/L showed a significantly faster progression to RRT, with a mean follow-up time of 1.1 days. TIMP2*IGBP7 and MR-proADM precociously diagnose AKI in septic patients after cardiac surgery, giving prognostic information for RRT requirement.

Precision management of acute kidney injury in the intensive care unit: current state of the art.

Acute kidney injury (AKI) is a prototypical example of a common syndrome in critical illness defined by consensus. The consensus definition for AKI, traditionally defined using only serum creatinine and urine output, was needed to standardize the description for epidemiology and to harmonize eligibility for clinical trials. However, AKI is not a simple disease, but rather a complex and multi-factorial syndrome characterized by a wide spectrum of pathobiology. AKI is now recognized to be comprised of numerous sub-phenotypes that can be discriminated through shared features such as etiology, prognosis, or common pathobiological mechanisms of injury and damage. The characterization of sub-phenotypes can serve to enable prognostic enrichment (i.e., identify subsets of patients more likely to share an outcome of interest) and predictive enrichment (identify subsets of patients more likely to respond favorably to a given therapy). Existing and emerging biomarkers will aid in discriminating sub-phenotypes of AKI, facilitate expansion of diagnostic criteria, and be leveraged to realize personalized approaches to management, particularly for recognizing treatment-responsive mechanisms (i.e., endotypes) and targets for intervention (i.e., treatable traits). Specific biomarkers (e.g., serum renin; olfactomedin 4 (OLFM4); interleukin (IL)-9) may further enable identification of pathobiological mechanisms to serve as treatment targets. However, even non-specific biomarkers of kidney injury (e.g., neutrophil gelatinase-associated lipocalin, NGAL; [tissue inhibitor of metalloproteinases 2, TIMP2]·[insulin like growth factor binding protein 7, IGFBP7]; kidney injury molecule 1, KIM-1) can direct greater precision management for specific sub-phenotypes of AKI. This review will summarize these evolving concepts and recent innovations in precision medicine approaches to the syndrome of AKI in critical illness, along with providing examples of how they can be leveraged to guide patient care.

Contemporary Acute Kidney Injury Management

ACUTE kidney injury (AKI) was discussed in a session chaired by Jolanta Malyszko, Medical University of Warsaw, Poland, and Danilo Fliser, Saarland University Medical Centre, Homburg, Germany, at the 60th European Renal Association (ERA) Congress, which took place in Milan, Italy, between 15th–18th June 2023. The moderators started by announcing that ERA has created a new working group on AKI.

Bicarbonate-Based Solution for the Management of Established Acute Kidney Injury: A Pilot Open-Label Observation Study.

Background Administration of intravenous (IV) solutions constitutes a key component of acute kidney injury (AKI) management. However, the optimal IV fluid solution in the setting of AKI remains uncertain. In this study, we assessed whether the use of bicarbonate-containing solution in patients with established AKI is associated with early renal recovery as compared to bicarbonate-free solutions. Methods We performed an open-label observational pilot study in 59 patients with established AKI. IV fluid solutions that were used include bicarbonate-based solution with low chloride content (80 mEq/L of 8% sodium bicarbonate in a solution that contains 77 mEq/L of sodium, 77 mEq/L of chloride and 25 g/L of glucose) or solutions without bicarbonate with high chloride content (0.9% normal saline, 0.45% half-saline, normal ringer, or 4% succinylated gelatine). We evaluated the association of IV fluids type with renal recovery. Results The median age of study participants was 66 years (inter-quartile range (IQR) 37-85), and 59% (n=35) were men. The prevalence of diabetes and chronic kidney disease (CKD) stages 1-3 were 34% (n=20) and 39% (n=23), respectively. Patients who received bicarbonate-based IV solutions had a greater reduction of serum creatinine (sCr) per day (delta sCr) as compared with patients who received bicarbonate-free solutions (-0.29±0.47 vs. 0.07±0.42; p=0.007). The renal recovery was faster in patients who received bicarbonate-based solutions as compared to the bicarbonate-free group (days from peak sCr to baseline sCr: 5.6±2.1 vs. 7.6±2.8; p < 0.001, respectively). Conclusions We observed faster renal recovery in patients with established AKI who received the bicarbonate-based solution with low chloride content. Our study findings require confirmation in larger cohorts.

Acute Kidney Injury in Liver Cirrhosis.

Acute kidney injury (AKI) is common in cirrhotic patients affecting almost 20% of these patients. While multiple etiologies can lead to AKI, pre-renal azotemia seems to be the most common cause of AKI. Irrespective of the cause, AKI is associated with worse survival with the poorest outcomes observed in those with hepatorenal syndrome (HRS) and acute tubular necrosis (ATN). In recent years, new definitions, and classifications of AKI in cirrhosis have emerged. More knowledge has also become available regarding the benefits and drawbacks of albumin and terlipressin use in these patients. Diagnostic tools such as urinary biomarkers and point-of-care ultrasound (POCUS) became available and they will be used in the near future to differentiate between different causes of AKI and direct management of AKI in these patients. In this update, we will review these new classifications, treatment recommendations, and diagnostic tools for AKI in cirrhotic patients.

Extracorporeal blood purification therapies for sepsis-associated acute kidney injury in critically ill patients: expert opinion from the SIAARTI-SIN joint commission

Sepsis-Associated Acute Kidney Injury is a life-threatening condition leading to high morbidity and mortality in critically ill patients admitted to the intensive care unit. Over the past decades, several extracorporeal blood purification therapies have been developed for both sepsis and sepsis-associated acute kidney injury management. Despite the widespread use of extracorporeal blood purification therapies in clinical practice, it is still unclear when to start this kind of treatment and how to define its efficacy. Indeed, several questions on sepsis-associated acute kidney injury and extracorporeal blood purification therapy still remain unresolved, including the indications and timing of renal replacement therapy in patients with septic vs. non-septic acute kidney injury, the optimal dialysis dose for renal replacement therapy modalities in sepsis-associated acute kidney injury patients, and the rationale for using extracorporeal blood purification therapies in septic patients without acute kidney injury. Moreover, the development of novel extracorporeal blood purification therapies, including those based on the use of adsorption devices, raised the attention of the scientific community both on the clearance of specific mediators released by microorganisms and by injured cells and potentially involved in the pathogenic mechanisms of organ dysfunction including sepsis-associated acute kidney injury, and on antibiotic removal. Based on these considerations, the joint commission of the Italian Society of Anesthesiology and Critical Care (SIAARTI) and the Italian Society of Nephrology (SIN) herein addressed some of these issues, proposed some recommendations for clinical practice and developed a common framework for future clinical research in this field.Graphical abstract

Predicting in-hospital outcomes of patients with acute kidney injury

Acute kidney injury (AKI) is prevalent and a leading cause of in-hospital death worldwide. Early prediction of AKI-related clinical events and timely intervention for high-risk patients could improve outcomes. We develop a deep learning model based on a nationwide multicenter cooperative network across China that includes 7,084,339 hospitalized patients, to dynamically predict the risk of in-hospital death (primary outcome) and dialysis (secondary outcome) for patients who developed AKI during hospitalization. A total of 137,084 eligible patients with AKI constitute the analysis set. In the derivation cohort, the area under the receiver operator curve (AUROC) for 24-h, 48-h, 72-h, and 7-day death are 95·05%, 94·23%, 93·53%, and 93·09%, respectively. For dialysis outcome, the AUROC of each time span are 88·32%, 83·31%, 83·20%, and 77·99%, respectively. The predictive performance is consistent in both internal and external validation cohorts. The model can predict important outcomes of patients with AKI, which could be helpful for the early management of AKI.

Furosemide in the management of acute kidney injury in the pediatric intensive care unit—retrospective cohort study

ObjectiveTo evaluate the effects of furosemide administration in critically ill children on the progression of acute kidney injury (AKI) and its outcomes compared to those not receiving furosemide.MethodA retrospective cohort study involving children aged 1 month (corrected) to 13 years admitted to the pediatric intensive care unit (PICU) and who were diagnosed with AKI within 24 h was screened for enrollment. Those who received furosemide are classified as the furosemide group, and others as no-furosemide group. The primary outcome was the proportion of patients with AKI (risk or injury stage) progressing to a higher stage. The secondary outcomes were kidney replacement therapy (KRT), fluid balance (%FO), urine output, multi-organ dysfunction, kidney recovery, length of mechanical ventilation, hospital stay including PICU, and all-cause mortality (PICU and hospital).ResultsThree hundred sixty-two patients’ data [furosemide group, n = 182; no-furosemide group, n = 180] were enrolled. The median (IQR) pediatric risk of mortality–III score was similar between groups [10, 4–16 vs. 10, 4–16; p = 0.244]. The primary outcome occurred in 51 (28%) in the furosemide and 36 (20%) in the no-furosemide group. The difference was not statistically significant [RR = 1.40, 95% CI 0.96 to 2.04, p = 0.074]. Higher mean (SD) urine output (ml/kg/hr) was noted in the furosemide group [2.3 (0.9) vs. 1.4 (0.6); p = < 0.001). Significantly higher mean (SD) organ dysfunction score [10 (4) vs. 8.3 (4.4); p < 0.001) and increased median (IQR) length of stay in mechanical ventilation [4, 3–6 vs. 3, 2–6 days; p < 0.001] and hospital [8, 5–11 vs. 6, 5–8 days; p < 0.001] and lower kidney recovery at discharge was noted in the furosemide group [n = 86, 47.3% vs. n = 104, 57.8%; RR = 0.80, 95% CI 0.64 to 0.99; p = 0.044]. No difference was noted in all-cause mortality, fluid balance, and KRT requirement.ConclusionFurosemide infusion in AKI management did not reduce the progression to a higher stage of AKI. Nevertheless, it was associated with higher morbidities.

STING deficiency protects against wasp venom-induced acute kidney injury.

Recent evidence suggests a key role of the inflammatory responses in wasp venom-induced acute kidney injury (AKI). However, the potential regulatory mechanisms underlying the inflammatory responses in wasp venom-induced AKI remain unclear. STING reportedly plays a critical role in other AKI types and is associated with inflammatory responses and diseases. We aimed to investigate the involvement of STING in inflammatory responses associated with wasp venom-induced AKI. The role of the STING signaling pathway in wasp venom-induced AKI was studied in vivo using a mouse model of wasp venom-induced AKI with STING knockout or pharmacological inhibition and in vitro using human HK2 cells with STING knockdown. STING deficiency or pharmacological inhibition markedly ameliorated renal dysfunction, inflammatory responses, necroptosis, and apoptosis in wasp venom-induced AKI in mice. Moreover, STING knockdown in cultured HK2 cells attenuated the inflammatory response, necroptosis, and apoptosis induced by myoglobin, the major pathogenic factor in wasp venom-induced AKI. Urinary mitochondrial DNA upregulation has also been observed in patients with wasp venom-induced AKI. STING activation mediates the inflammatory response in wasp venom-induced AKI. This may offer a potential therapeutic target for the management of wasp venom-induced AKI.

#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

PEGylated Gambogic Acid Nanoparticles Enable Efficient Renal-Targeted Treatment of Acute Kidney Injury.

Acute kidney injury (AKI) is a common clinical syndrome lacking effective pharmacotherapy. Gambogic acid (GA), as an active ingredient of herbal medicines, exhibits antioxidant and anti-inflammatory effects that benefit the treatment of AKI, but its poor aqueous solubility limits effective renal delivery. We, for the first time, developed GA-based nanoparticles (GA-NPs) with preferential renal uptake for AKI treatment. By PEGylating with NH2-PEG5000-NOTA, hydrophobic GA was self-assembled into ∼4.5 nm nanoparticles, which showed the enhanced renal accumulation in AKI models from PET images. Importantly, the in vitro cell assays and in vivo tests of the two AKI models have confirmed the obvious nephroprotective effects and biosafety of GA-NPs. Therefore, this work indicates that GA-NPs can be a promising therapeutic candidate for the management of AKI.

Lessons learned from regional training of paediatric nephrology fellows in Africa.

Access to care for children with kidney disease is limited in less well-resourced regions of the world and paediatric nephrology (PN) workforce development with good practical skills is critical. Retrospective review of a PN training program and trainee feedback from 1999 to 2021, based at Red Cross War Memorial Children's Hospital (RCWMCH), University of Cape Town. A regionally appropriate 1-2-year training program enrolled 38 fellows with an initial 100% return rate to their country of origin. Program funding included fellowships from the International Pediatric Nephrology Association (IPNA), International Society of Nephrology (ISN), International Society of Peritoneal Dialysis (ISPD), and the African Paediatric Fellowship Program (APFP). Fellows were trained on both in- and out-patient management of infants and children with kidney disorders. "Hands-on skills" training included examination, diagnosis and management skills, practical insertion of peritoneal dialysis catheters for management of acute kidney injury and kidney biopsies. Of 16 trainees who completed > 1year of training, 14 (88%) successfully completed subspecialty exams and 9 (56%) completed a master's degree with a research component. PN fellows reported that their training was appropriate and enabled them to make a difference in their respective communities. This training program has successfully equipped African physicians with the requisite knowledge and skills to provide PN services in resource-constrained areas for children with kidney disease. The provision of funding from multiple organizations committed to paediatric kidney disease has contributed to the success of the program, along with the fellows' commitment to build PN healthcare capacity in Africa. A higher resolution version of the Graphical abstract is available as Supplementary information.