Assessment Of Renal Function Research Articles

A multitasking renal function assessment Janus biosensor based on photonic spin Hall effect at epsilon-near-zero threshold frequency of YaBa2Cu3O7 ceramic material

A multitasking renal function assessment Janus biosensor based on photonic spin Hall effect at epsilon-near-zero threshold frequency of YaBa2Cu3O7 ceramic material

Unveiling the prognostic journey: renal function trajectories in 'de novo' heart failure with reduced ejection fraction - insights from a cohort study and their impact on patient outcomes

Abstract Background HFrEF poses significant clinical challenges globally. Renal dysfunction frequently coexists with HF, exacerbating prognosis. However, the dynamic trajectory of renal function in 'de novo' HFrEF patients and its prognostic implications remain understudied. Methods We conducted a prospective cohort study involving 370 'de novo' HFrEF patients. Renal function was initially assessed upon admission and re-evaluated at the end of the titration period. The CKD-EPI formula was used for renal function assessment. Patients were followed up for a median of 15 months. Statistical analyses were performed to evaluate predictors of adverse outcomes. Results Baseline renal function significantly influenced outcomes, with eGFR < 45 ml/min associated with higher mortality and heart failure readmissions. Among patients with available renal function data at discharge (n=354), 87 (24.6%) had eGFR < 45 ml/min, while 267 (72.2%) ≥ 45 ml/min. Patients with eGFR < 45 ml/min exhibited older age, higher prevalence of comorbidities, lower haemoglobin levels, and higher creatinine and NT-proBNP levels, both at admission and discharge. Furthermore, they were less likely to receive certain heart failure medications at discharge. During follow-up, 46 deaths (13.0%) and 105 events of combined all-cause death and readmission due to heart failure (29.6%) occurred. Patients with eGFR ≥ 45 ml/min exhibited a lower overall mortality (HR: 0.29, p < 0.001) and all-cause death and heart failure readmissions (HR: 0.32, p < 0.001) both in univariate and multivariate analysis (HR: 0.63, p = 0.028 for mortality; HR: 0.53, p = 0.038 for combined endpoint). See Figure 1. Among patients with available renal function data at follow-up (n=304), 240 (78.9%) had eGFR ≥ 45 ml/min (stabilization or improvement), and 64 (21.1%) had eGFR < 45 ml/min (deterioration or previously < 45 ml/min). Patients with eGFR < 45 ml/min at follow-up exhibited older age, lower BMI, higher prevalence of comorbidities, lower haemoglobin levels, and higher NTproBNP levels at admission and discharge. They were also less likely to receive certain crucial heart failure medications at discharge and follow-up (Table 1). During follow-up, 31 deaths (10.1%) and 87 events of combined death and readmission due to heart failure (38.6%) occurred. In univariate analysis, patients with eGFR ≥ 45 ml/min exhibited a lower overall mortality (HR: 0.27, p < 0.001) and admissions (HR: 0.30, p < 0.001), which remained significant in multivariate analysis (HR: 0.43, p = 0.048 for mortality; HR: 46, p = 0.014 for admissions). See Figure 1. Conclusion Our findings underscore the importance of integrated heart-kidney care in 'de novo' HFrEF patients. Continuous monitoring of renal function and interventions to prevent deterioration are crucial for optimizing outcomes. Further research is needed to validate these findings and explore targeted therapeutic strategies for renal protection in HFrEF.

Iodine Assessment of Carbon Dioxide Angiography in Iliac Branched Repair.

The objective of this study was to investigate whether the use of carbon dioxide (CO2) angiography decreases the intraoperative use of iodine contrast medium (ICM), thereby decreasing the risk of developing postoperative renal damage in patients undergoing iliac branch device (IBD) implantation. Patients undergoing IBD implantation at a single tertiary center between May 2013 and August 2019 were screened for inclusion in the study. A cohort of patients in whom an intraoperative imaging protocol using predominantly CO2 was compared with a control group in whom ICM was used (CO2 and ICM groups). Fusion imaging was used in both groups. Retrospective review of the medical charts and all imaging was performed. Variables were expressed as median with interquartile range (IQR) or absolute number and percentage. Wilcoxon-Mann-Whitney and χ2 tests were used to compare continuous and categorical variables, respectively. P values of <0 .05 were considered statistically significant. Twenty-three patients were included in the CO2 group and 21 in the ICM group without significant differences in patient characteristics between the groups. Intraoperative iodine exposure was lower in the CO2 group than in the ICM group (8.2 g [IQR, 7.1-10.9 g) vs 15.8 g (IQR 7.6-21 g); P = 0.015, respectively). There were no differences in technical success, clinical success, fluoroscopy time, and dose-area product in the 2 groups. There were no adverse events that could be related to the intraoperative use of CO2. There was no difference in postoperative survival nor renal function assessment between the groups despite the higher number of accessory renal arteries embolized in the CO2 group (P = 0.221). Reduction of intraoperative ICM exposure during IBD implantation is feasible through the predominant use of CO2 automated angiography. This can be done safely without affecting the technical success or radiation exposure. The immediate postoperative renal damage was low when a modern intraoperative imaging protocol with ICM was used and was not significantly reduced by the use of CO2. Further and larger studies are needed to investigate the long-term effects. This study aimed to investigate how to minimize intraoperative risk during iliac branched repair exploring the intraoperative use of automated carbon dioxide angiography in order to decrease the use of contrast media protecting renal function and thereby potentially impacting long-term survival.

Pattern Of Renal Analytes Following Renal Function Assessment Of Infants In A Tertiary Health Facility In Southern Nigeria

Background/Objectives Electrolyte imbalance is a common finding in infants, and the story is so in the tropical countries, where most patients are usually victims of fluid losses from various etiologies. This study is aimed at assessing the profile and pattern of electrolytes imbalance and other parameters of renal function assessmentamong infants (0-12 months) in our environment. Methods/Subjects This cross-sectional study was carried out over a 6-month period on infants who wereadmitted into University of Calabar Teaching Hospital (UCTH) and investigated forelectrolyte, urea and creatine, after a hospitalstay of ≥24 hours. Blood samples were taken from such patients, analyzed and values obtained were compared with the reference intervals to ascertain the level of deviation from the expected normal for age. Results The total number of children that participated on the study was 200, made up of 106(53.0%)males and 94(47.0%) females. The children were classified based on their different ages from 0 to 12 months. Children aged 0-1month made up the bulk of the study population (57.0%). Low level of bicarbonate occurred in 65.5% of all the children. Hyponatremia (37.7%) and Hyperkalemia (28.9%), occurred in 0 -1month age group. These derangements have been known to contribute negatively to the outcome of the admitted infant if not corrected. Most of the infants had normal values of the individual electrolytes. Conclusion In view of the fact that infants are more vulnerable to electrolyte imbalance, prevention of electrolyte imbalances is preferable to treatment.

The role of nuclear medicine techniques; Tc-99m-labeled dimercaptosuccinic acid, diethylenetriaminepentaacetic acid, and mercaptoacetyltriglycine scintigraphies in pediatric surgery

The purpose of this review is to highlight the pivotal role of nuclear medicine in pediatric surgery, specifically in the diagnosis and management of nephro-urological conditions. This review focuses on the applications and advantages of three key nuclear medicine techniques: Tc-99m dimercaptosuccinic acid (DMSA), Tc-99m diethylenetriaminepentaacetic acid (DTPA), and Tc-99m mercaptoacetyltriglycine (MAG3) scintigraphies. These imaging modalities are crucial for providing detailed anatomical and functional information with minimal invasiveness, essential for evaluating congenital anomalies, urinary tract infections, and obstructive uropathies in children. DMSA Scintigraphy is established as the gold standard for detecting renal cortical scarring and assessing functional renal parenchymal damage. It offers superior sensitivity and specificity compared to other imaging techniques, making it indispensable for identifying renal scars from recurrent urinary tract infections or pyelonephritis. DTPA Scintigraphy is critical for measuring glomerular filtration rate (GFR) and analyzing renogram curves, providing quantitative assessments of renal function. It effectively evaluates renal perfusion and identifies perfusion defects and renal ischemia, essential for managing conditions like renal artery stenosis and unilateral kidney disease. MAG3 Scintigraphy excels in dynamic renal scintigraphy, particularly in patients with impaired renal function. It provides high-quality images and superior diagnostic capability, making it invaluable for assessing ureteropelvic junction obstruction and other obstructive uropathies in pediatric patients. The review concludes by emphasizing the integration of these scintigraphy techniques with SPECT/CT, enhancing diagnostic accuracy and providing comprehensive anatomical and functional insights. Despite concerns regarding radiation exposure, measures such as dose optimization and advanced imaging techniques ensure safety and efficacy in pediatric applications.

Dynamic changes in the real-time glomerular filtration rate and kidney injury markers in different acute kidney injury models

In this study, we dynamically monitored the glomerular filtration rate and other assessment of renal function and markers of injury in various mice models of acute kidney injury. Male C57BL/6 mice were utilized to establish acute kidney injury models of sepsis, ischemia reperfusion, cisplatin, folic acid, aristolochic acid and antibiotic. In addition to the real time glomerular filtration rate, renal LCN-2 and HAVCR-1 mRNA expression levels, and serum creatinine, urea nitrogen and cystatin c levels were also used to evaluate renal function. In addition, the protein levels of LCN-2 and HAVCR-1 in renal, serum and urine were measured. Our results demonstrated that the changes in biomarkers always lagged the real time glomerular filtration rate during the progression and recovery of renal injury. Cystatin-c can reflect renal injury earlier than other markers, but it remains higher in the recovery stage. Perhaps the glomerular filtration rate does not reflect the greater injury caused by vancomycin plus piperacillin.

Association of urinary albumin excretion with all-cause and cardiovascular mortality among patients with rheumatoid arthritis: a national prospective study.

Rheumatoid arthritis (RA) patients suffering from chronic renal insufficiency tend to exhibit subtle manifestations at the beginning. Urine albumin to creatinine ratio (ACR) is a sensitive indicator for early assessment of renal function. However, it is unclear whether it serves as an independent risk factor influencing the prognosis of RA patients. National Health and Nutrition Examination Survey (NHANES) data from 2009-2018 were included. Kaplan-Meier (K-M) curves were plotted to compare the cumulative survival probability of RA patients with different urinary albumin excretion. The association of ACR with mortality among RA patients was investigated with Cox regression model, restricted cubic spline (RCS) and stratified analyses. The prognostic efficacy of ACR and estimated glomerular filtration rate (eGFR) was evaluated by receiver operating characteristic (ROC) curves. The Cox regression model adjusted with covariates showed a 53% (HR 1.53, 95% CI 1.06-2.21) increase in all-cause mortality and a statistically non-significant increase in cardiovascular disease (CVD) mortality in RA patients with microalbuminuria (30mg/g ≤ACR<300mg/g). ACR≥300mg/g was associated with an increase in all-cause mortality (HR 2.62, 95% CI 1.55-4.45) and CVD mortality (HR 5.67, 95% CI 1.96-16.39). RCS demonstrated a nonlinear correlation between ACR and all-cause mortality in RA patients with microalbuminuria. Subgroup analysis showed that CVD mortality was higher in RA patients with microalbuminuria characterized by the following features: female, other ethnicity, eGFR≥60 ml/min/1.73 m2, hypertension or hyperlipidemia. Compared with eGFR, ACR provided better prognostic efficacy than eGFR with higher values of the area under the curve (AUC) for all-cause mortality (AUC=0.683, 95% CI 0.613-0.754) and CVD mortality (AUC=0.681, 95% CI 0.541-0.820). ACR is an independent risk factor affecting the prognosis of RA patients. The all-cause mortality was increased in RA patients with albuminuria. There was an upward trend in the CVD mortality of those with macroalbuminuria when ACR increased.

Predictors of outcomes in conservative management of high-grade renal trauma

BackgroundManagement of high-grade renal trauma is debatable, with the recent evidence embracing a conservative approach in the management of even grade 5 renal injuries. The study aimed to analyze the clinical profile of patients with high-grade renal trauma, assessing their management strategies, outcomes, complications, and need for ancillary procedures.MethodsA retrospective analysis of prospectively maintained data was performed involving blunt abdominal trauma patients with high-grade renal injuries (Grade 4 and 5) presenting to our hospital from January 2018 to December 2022. Patient data analyzed included demographics, clinical presentation, injury characteristics, complications, ancillary procedures, and mortality rates. All patients underwent renal functional assessment using an isotope renogram scan at the 3-month follow-up. Data collected were entered into a database and subjected to descriptive analysis using Jamovi version 2.3.28.ResultsThe study included 45 patients with a mean age of 29 years and a male-to-female ratio of 41:4. Most patients (n = 42) were managed conservatively. Thirty-eight patients had grade 4 injuries, and seven had grade 5 injuries. Twenty-six patients suffered renal parenchymal injuries alone, three patients had renal vascular injuries alone, and 16 patients had both parenchymal and vascular injuries. Grade 5 renal injury (p < 0.001), vascular high-grade injury (p < 0.001), angioembolization (p < 0.001), and blood transfusions (p = 0.021) were significantly associated with the incidence of poorly functioning kidney in high-grade renal trauma patients managed conservatively. Multinomial logistic regression analysis revealed angioembolization (p < 0.001), poorly functioning kidney post-trauma (p < 0.001), and blood transfusions (p < 0.001) were significantly associated with high-grade renal vascular injuries compared to high-grade renal parenchymal injuries.ConclusionConservative management is advisable for high-grade renal trauma in hemodynamically stable patients. High-grade vascular injuries are more severe than parenchymal injuries and correlate with poorer renal functional outcomes. Grade 5 renal injury, predominantly vascular high-grade injury, and the requirement for angioembolization and blood transfusions serve as significant predictors of poorly functioning kidneys post-trauma. Urologists should consider these predictors when counseling patients regarding potential outcomes following conservative management of high-grade renal trauma.

Pomegranate juice recuperates N’-Nitrosodiethylamine-induced kidney injury: evidence from biochemical and histological approaches

BackgroundPomegranate is considered as one of the oldest elixirs having various properties. Renal fibrosis is a preliminary sign of pathological degradation in most ailments related to kidney. Several efforts have been made for the discovery of cost-effective and safe therapeutics for the alleviation of renal diseases. There is a major dearth of studies on the action of pomegranate juice (PGJ) against NDEA-instigated kidney injury. This study investigates the protective and antifibrotic action of PGJ in restricting the occurrence of experimental renal fibrosis in Wistar rats. Renal injury was generated by a single intraperitoneal dose of 10 ml kg−1 b.wt. (1% NDEA stock), while fresh PGJ (i.p.) in doses of 2 ml kg−1 b.wt was administered thrice a week on alternate days for two weeks to observe amelioration. The renal function indices (blood urea, creatinine, and uric acid), SOD, CAT, LPO levels and renal anatomy (H&E, MT, Picrosirius and SEM) were investigated.ResultsThe assessment of renal function demonstrates augmented levels of blood urea, creatinine and uric acid in NDEA-administered groups in comparison with controls. SOD, CAT declined significantly in NDEA Day-7- and Day-14-treated animals, while the MDA levels raised by ~ 70.5% and ~ 76.3% in these groups, respectively. However, supplementation of PGJ provided recuperation from these elevated levels in injured groups. H&E staining of the controls exhibited normal renal structure with intact glomerulus and Bowman’s capsule, while NDEA generated congestion of glomerular tuft, convoluted tubules with cloudy swelling and multiple subsidence of the renal tissue. Noticeable presence of collagen fibers in the interstitium of cortex region of kidney was observed by MT staining along with gross ultrastructural deterioration in NDEA-administered animals by electron microscopy. PGJ supplementation exhibited restoration of renal anatomy and physiology.ConclusionsPomegranate may be considered as a potent nutraceutical to prevent NDEA-induced renal damage and may be included as a daily dietary supplement.

Two cases of Dent disease type 1 with Bartter-like phenotype and literature review

The clinical presentation, treatment, and follow-up of two boys with type 1 Dent disease who exhibited a Bartter-like phenotype were retropectively analysed. The related literature of pediatric patients with type 1 Dent disease who had hypokalemia and metabolic alkalosis was screened through databases such as PubMed, CNKI, and Wanfang until February 1, 2024, and common features among these patients were summarized through literature review. A total of 7 literatures were included, and 9 children were included in the analysis. All patients were male, presenting with significant low molecular weight proteinuria and hypercalciuria. Other prominent characteristic phenotypes included short stature (7/8), hypophosphatemia (8/9), and rickets (6/8). Seven previously reported patients had missense or nonsense mutations, while 2 patients in this study carried possible pathogenic mutations in the CLCN5 gene, c.315+2T>A (p.?) and c.584dupT (p.I196Yfs*6), respectively. Five patients were able to maintain blood potassium levels around 3 mmol/L with oral potassium chloride solution combined with non-steroidal anti-inflammatory drugs (ibuprofen or indomethacin). The follow-up showed that 2 patients developed chronic kidney disease stage 4 and stage 3 at the age of 13 and 21 years, respectively. The phenotypic overlap between Dent disease and Batter syndrome is considerable,with the distinguishing feature being the presence of significant low molecular weight proteinuria. Patients with type 1 Dent disease presenting with the Bartter-like phenotype have a high prevalence of short stature, hypophosphatemia, and rickets. Non-steroidal anti-inflammatory drugs can be used to correct hypokalemia in patients under periodic renal function assessment.

Estimated glomerular filtration rate in clinical practice: Consensus positioning of the Brazilian Society of Nephrology (SBN) and Brazilian Society of Clinical Pathology and Laboratory Medicine (SBPC/ML).

Chronic kidney disease (CKD) represents one of today's main public health problems. Serum creatinine measurement and estimation of the glomerular filtration rate (GFR) are the main tools for evaluating renal function. There are several equations to estimate GFR, and CKD-EPI equation (Chronic Kidney Disease - Epidemiology) is the most recommended one. There are still some controversies regarding serum creatinine measurement and GFR estimation, since several factors can interfere in this process. An important recent change was the removal of the correction for race from the equations for estimating GFR, which overestimated kidney function, and consequently delayed the implementation of treatments such as dialysis and kidney transplantation. In this consensus document from the Brazilian Societies of Nephrology and Clinical Pathology and Laboratory Medicine, the main concepts related to the assessment of renal function are reviewed, as well as possible existing controversies and recommendations for estimating GFR in clinical practice.

99mTc-DMSA and 99mTc-DTPA identified renal dysfunction due to microplastic polyethylene in murine model

In the previous study (Im et al., 2022), we revealed microplastic (MP) was accumulated and cleared through the kidneys via PET imaging. Here, we aimed to identify the renal dysfunction due to polyethylene (PE) MP in the kidney tissue. Mice were exposed to 100 ppm (∼equivalent to 0.1 mg/mL)/100 μL of PE for 12 weeks (n = 10). PE uptake in the kidney tissues was confirmed using confocal microscopy. QuantSeq analysis was performed to determine gene expression. Renal function assessment was performed using 99mTc-Diethylene triamine penta acetic acid or 99mTc-Dimercaptosuccinic acid. Measurement of creatinine, BUN, and albumin levels in serum and urine samples was also estimated. [18F]-FDG was also acquired. PE increased expression of Myc, CD44, Programmed Death-Ligand 1 (PD-L1), and Hypoxia-Inducible Factor (HIF)-1α, which indicates a potential link to an increased risk of early-onset cancer. An increase in glucose metabolism of [18F]-FDG were observed. We assessed renal failure using 99mTc-Diethylene triamine penta acetic acid and 99mTc-Dimercaptosuccinic acid scintigraphy to determine the renal function. Renal failure was confirmed using serum and urine creatinine, serum blood urea nitrogen levels, serum albumin levels, and urine albumin levels in PE exposed mice, relative to the control. In sum, PE exposure induced renal dysfunction in a murine model.

A New Era for PET/CT: Applications in Non-Tumorous Renal Pathologies.

Non-tumorous kidney diseases include a variety of conditions affecting both the structure and function of the kidneys, thereby causing a range of health-related problems. Positron emission tomography/computed tomography (PET/CT) has emerged as a potential diagnostic tool, offering a multifaceted approach to evaluating non-tumorous kidney diseases. Its clinical significance extends beyond its conventional role in cancer imaging, enabling a comprehensive assessment of renal structure and function. This review explores the diverse applications of PET/CT imaging in the evaluation of non-cancerous kidney diseases. It examines PET/CT's role in assessing acute kidney injuries, including acute pyelonephritis and other forms of nephritis, as well as chronic conditions such as immune complex-mediated glomerulonephritis and chronic kidney disease. Additionally, the review delves into PET/CT's utility in evaluating complications in renal transplant recipients, identifying renal histiocytosis and detecting renal amyloidosis. The current review aims to promote further research and technological advancements to popularize PET/CT's clinical utility in diagnosing and treating non-tumorous kidney diseases.

Acrylamide-targeting renal miR-21a-5p/Fibrotic and miR122-5p/ inflammatory signaling pathways and the role of a green approach for nano-zinc detected via in silico and in vivo approaches.

Introduction: Any disruption in renal function can have cascading effects on overall health. Understanding how a heat-born toxicant like acrylamide (ACR) affects kidney tissue is vital for realizing its broader implications for systemic health. Methods: This study investigated the ACR-induced renal damage mechanisms, particularly focusing on the regulating role of miR-21a-5p/fibrotic and miR-122-5p/inflammatory signaling pathways via targeting Timp-3 and TP53 proteins in an In silico preliminary study. Besides, renal function assessment, oxidative status, protein profile, and the expression of renal biomarkers (Timp-1, Keap-1, Kim-1, P53, TNF-α, Bax, and Caspase3) were assessed in a 60-day experiment. The examination was additionally extended to explore the potential protective effects of green-synthesized zinc oxide nanoparticles (ZNO-MONPs). A four-group experiment including control, ZNO-MONPs (10mg/kg b.wt.), ACR (20mg/kg b.wt.), and ZNO-MONPs + ACR was established encompassing biochemical, histological, and molecular levels. The study further investigated the protein-binding ability of ZNO and MONPs to inactivate caspase-3, Keap-1, Kim-1, and TNFRS-1A. Results: ZNO-MONPs significantly reduced ACR-induced renal tissue damage as evidenced by increased serum creatinine, uric acid, albumin, and oxidative stress markers. ACR-induced oxidative stress, apoptosis, and inflammationare revealed by biochemical tests, gene expression, and the presence of apoptotic nuclei microscopically. Also, molecular docking revealed binding affinity between ACR-BCL-2 and glutathione-synthetase, elucidating the potential mechanisms through which ACR induces renal damage. Notably, ZNO-MONPs revealed a protective potential against ACR-induced damage. Zn levels in the renal tissues of ACR-exposed rats were significantly restored in those treated with ACR + ZNO-MONPs. In conclusion, this study establishes the efficacy of ZNO-MONPs in mitigating ACR-induced disturbances in renal tissue functions, oxidative stress, inflammation, and apoptosis. The findings shed light on the potential renoprotective activity of green-synthesized nanomaterials, offering insights into novel therapeutic approaches for countering ACR-induced renal damage.

Electrolyte disruption in drug-resistant tuberculosis: Managing risks for improved treatment outcomes

This editorial sheds light on the critical issue of electrolyte imbalance in drug-resistant tuberculosis (TB), a significant challenge exacerbated by the prolonged and intensive treatment regimens required for multidrug-resistant (MDR) and extensively drug-resistant (XDR) TB strains. The use of second-line drugs, such as fluoroquinolones and aminoglycosides, necessary in these cases, often disrupts electrolyte homeostasis, leading to complications like hypokalemia and hypomagnesaemia. These disturbances can pose serious risks to patients, including cardiac arrhythmias and renal dysfunction. Beyond medication effects, TB itself induces systemic inflammation and metabolic alterations, further complicating electrolyte balance. Effective management necessitates vigilant monitoring of electrolyte levels throughout treatment, coupled with renal function assessments and nutritional support.

Early and late assessment of renal allograft dysfunction using intravoxel incoherent motion (IVIM) and diffusion-weighted imaging (DWI): a prospective study.

To evaluate the ability of the Intravoxel Incoherent Motion (IVIM) and monoexponentially ADC in renal allograft function in the early and late phases of transplantation, and to predict their effectiveness in discrimination of the graft pathology. This is a prospective study included participants scanned with quantitative diffusion and perfusion sequences on a 3-T MR scanner (Philips, Ingenia); the ADC and IVIM parameters; were calculated. Correlations and regression analysis with the eGFR, transplantation periods, and pathology were assessed. This study included 105 renal allograft recipients (85 males, and 20 females with mean age = 32.4 ± 11.9years and age range = 22-61years). There was a significant positive correlation between the whole parameters of the ADC and IVIM with eGFR however, the cortical parameters showed higher significant correlation coefficients (p < 0.001). Regression analysis revealed the most significant model can predict eGFR groups included cortical pseudo diffusion (D*) and cortical ADC (p < 0.001). In graft dysfunction eGFR was 61.5ml/min and normal graft was 64ml/min. This model demonstrates a high performance of an AUC 96% [0.93-0.97]. In the late transplantation, there is a higher correlation with D* compared to ADC, p-values = 0.001. IVIM and ADC Values are significant biomarkers for renal allograft function assessment, cortical ADC, and D* had the highest performance even in situations with mild impairment that is not affect the eGFR yet as cases of proteinuria with normal eGFR. Furthermore, D* is superior to ADC in the late assessment of the renal transplant.

Impairment of Renal Function in Perinatal Asphyxia with Hypoxic Ischemic Encephalopathy in Term Neonates

Background: Perinatal asphyxia is a major cause of neonatal morbidity and mortality worldwide including in Bangladesh. It causes damage to almost every tissue and organ of the body. In kidneys, renal insufficiency may occur promptly even within 24 hours of asphyxia. So, renal function assessment is essential for accurate management of metabolic derangement in neonates as prolonged hypoxic ischemic episode can lead to irreversible cortical necrosis with onset of acute renal failure.Objectives: To find out renal impairment and to measure serum creatinine, serum electrolyte and eGFR, Also to compare biochemical parameters level and determine the frequency of AKI among the asphyxiated neonates with HIE.Materials and Methods: This cross-sectional study was conducted in the neonatal care unit of Sir Salimullah Medical College Mitford Hospital, Dhaka. A total of 70 term neonates suffered from perinatal asphyxia with different stages of Hypoxic ischaemic encephalopathy. A ‘p’ value &lt;0.05 was considered as statistically significant.Results: Among 70 term neonates having HIE, it was observed that 62.9% neonates had moderate birth asphyxia followed by mild (28.6%) and severe (8.6%). Newborns with SGA (71.4%) had more renal impairment than AGA. Among biochemical variables Blood urea and serum creatinine were high and eGFR was low in stage Π. Among electrolytes, hyponatremia was present in 24.3% of cases and more in stage Π, and hyperkalemia was present in 21.4% of cases and more in stage Ш. AKI was found in 18.6% of cases, Risk (stage 1) was 77%, Injury (stage Π) was 15.3% and Failure (stage 3) was 7.7 %.Conclusion: Renal impairment was found in 18.5% of term asphyxiated neonates with HIE according to pRIFLE and AKIN criteria and Biochemical parameters showed no significant changes between different stages of HIE. KYAMC Journal Volume: 14, No: 04, January 2024: 198-205.

Associations between renal function, hippocampal volume, and cognitive impairment in 544 outpatients.

Cognitive impairment and brain atrophy are common in chronic kidney disease patients. It remains unclear whether differences in renal function, even within normal levels, influence hippocampal volume (HCV) and cognition. We aimed to investigate the association between estimated glomerular filtration rate (eGFR), HCV and cognition in outpatients. This single-center retrospective study enrolled 544 nonrenal outpatients from our hospital. All participants underwent renal function assessment and 3.0 T magnetic resonance imaging (MRI) in the same year. HCV was also measured, and cognitive assessments were obtained. The correlations between eGFR, HCV, and cognitive function were analyzed. Logistic regression analysis was performed to identify the risk factors for hippocampal atrophy and cognitive impairment. Receiver-operator curves (ROCs) were performed to find the cut-off value of HCV that predicts cognitive impairment. The mean age of all participants was 66.5 ± 10.9 years. The mean eGFR of all participants was 88.5 ± 15.1 mL/min/1.73 m2. eGFR was positively correlated with HCV and with Mini-Mental State Examination (MMSE) and Montreal Cognitive Assessment (MoCA) scores. Univariate and multivariate logistic regression analysis showed Age ≥ 65 years, eGFR < 75 mL/min/1.73 m2, Glucose ≥6.1 mmol/L and combined cerebral microvascular diseases were independent risk factors for hippocampal atrophy and Age ≥ 65 years, left hippocampal volume (LHCV) <2,654 mm3 were independent risk factors for cognitive impairment in outpatients. Although initial unadjusted logistic regression analysis indicated that a lower eGFR (eGFR < 75 mL/min/1.73 m2) was associated with poorer cognitive function, this association was lost after adjusting for confounding variables. ROC curve analysis demonstrated that LHCV <2,654 mm3 had the highest AUROC [(0.842, 95% CI: 0.808-0.871)], indicating that LHCV had a credible prognostic value with a high sensitivity and specificity for predicting cognitive impairment compared with age in outpatients. Higher eGFR was associated with higher HCV and better cognitive function. eGFR < 75 mL/min/1.73 m2 was an independent risk factor for hippocampal atrophy after adjusting for age. It is suggested that even eGFR < 75 mL/min/1.73 m2, lower eGFR may still be associated with hippocampal atrophy, which is further associated with cognitive impairment. LHCV was a favorable prognostic marker for predicting cognitive impairment rather than age.

Heterogeneity in methods for estimating renal function in anticancer drug development.

e23002 Background: Accurate assessment of renal function is critical in oncology clinical trials. Many anti-cancer agents are renally excreted or cleared, and impaired kidney function can significantly impact drug safety and efficacy. In an effort to modernize renal eligibility criteria the American Society of Clinical Oncology–Friends of Cancer Research Organ Dysfunction Working Group recommended that if renal toxicity and clearance are not of direct treatment-related concern, then patients with impaired renal function should be included in trials (Lichtman, JCO, 2017). However, a diversity of approaches are available to determine renal function. Methods: We systematically searched the clinicaltrials.gov database to review renal eligibility criteria for phase III clinical trials. These trials evaluated systemic anti-cancer therapies in adult patients between October 28th 2013, and October 28th 2023. Studies were excluded if they did not include eligibility criteria related to renal function. The demographics of the trials and methods used for estimating renal function were recorded. Results: 436 trials met criteria for review and 231 trials, enrolling 111,424 patients, met our inclusion criteria. Systemic therapies explored included: immunotherapy (98 trials, 42%), targeted therapy (110 trials, 48%), chemotherapy (17 trials, 7%) or other regimens (6 trials, 3%). Renal function exclusion criteria are shown in the Table. Among studies that estimated renal function with a formula, 140 (61%) studies used Cockcroft-Gault, 3 (1%) used Modification of Diet in Renal Disease, 9 (4%) used an institutional standard, 10 (4%) used a heterogenous combination of estimation equations, and 69 (30%) trials did not specify the estimation approach. Conclusions: In phase III clinical trials involving adult cancer patients, there is substantial heterogeneity in methodologies utilized for determining renal function as related to trial eligibility. Harmonization of approaches to estimate renal function in oncology trials may improve trial accessibility, generalizability, and comparability. [Table: see text]

#1118 Direct delivery of novel gene therapy to podocytes enables pathway to clinical translation for the treatment of glomerular diseases

Abstract Background and Aims Adeno associated vector (AAV) gene therapy has the potential to treat a wide range of kidney diseases via the targeted delivery of genes to kidney cells to repair cellular and renal function. Despite the potential to impact many kidney conditions, kidney AAV gene therapy has proven challenging due to technical and physiological hurdles limiting the ability of AAV to be effectively delivered to podocytes. We have developed a novel AAV gene therapy, PS-001, and local method of administration, to effectively and safely deliver the podocin gene NPHS2 to podocytes. Biallelic NPHS2 mutations are the most common cause of monogenic childhood nephrotic syndrome. Curative efficacy and resolution of disease phenotype was demonstrated in transgenic murine models following PS-001 gene therapy treatment. The potential for translation of this approach to NPHS2 nephropathy patients in the clinic was also demonstrated in pre-clinical studies in Gottingen Minipigs. Method Transgenic murine models representative of NPHS2-driven nephropathy were treated with an AAV gene therapy encoding NPHS2, including a knock in mouse model (Nphs2R140Q/−) which introduces a R140Q mutation in the podocin gene. Mice were assessed for improvement in disease phenotype via analysis of proteinuria, serum albumin, renal histopathology and survival. Mice were treated with an analogue of PS-001, as the PS-001 capsid is not permissive in rodents. Gottingen minipigs were treated with PS-001 and followed for 4 weeks. Clinically relevant doses and a procedure for local administration specifically to the kidney were established. In-life safety assessments from blood and urine were monitored and at study end pig tissues were assessed for podocin biodistribution using multiple assays (qPCR, RT-qPCR, ELISA, RNAScope and IF) and for toxicological effects via histopathological analysis. Results Using our AAV gene therapy platform, which includes a capsid that is highly effective at transducing human podocytes and promoter that drives gene expression specifically in the podocyte, the gene therapy product PS-001 encoding NPHS2 was generated. Using a murine analogue of PS-001, in vivo proof of concept studies in a translationally relevant murine disease model (Nphs2R140Q/−) showed NPHS2 delivery and podocin expression in glomeruli and efficacy in terms of renal function rescue. This was demonstrated by resolution of severe proteinuria (mean ACR ug/mg 6049 ± 2803 vs 192 ± 51 in PS-001 treated animals, n = 11), improved serum albumin (g/L 27.50 ± 3.33 g/L vs 30.75 ± 2.46 in PS-001 treated animals, P = .021) and reduction in glomerulosclerosis (mean sclerosed glomeruli 81% ± 19 vs 18.75% ± 12 in PS-001 treated animals, P &amp;lt; .0001). The methods to translate the approach to the clinical setting using a local administration were established in pigs. Administration of PS-001 resulted in transgene mRNA expression across 89% ± 11% of kidney glomeruli as assessed by RNAScope (n = 3 pigs), and transgene derived podocin could be specifically detected in podocytes as assessed by IF analysis. Using qPCR, RT-PCR and ELISA it was shown that using local administration, podocin gene expression was restricted exclusively to the kidney glomerulus, with gene expression undetectable in off-target organs including the liver. Additional toxicological assessments of renal and other organ function from urine and blood, and post-study histopathological assessments revealed no pre-clinical treatment-related safety concerns. Conclusion We present data showing development of an AAV gene therapy and method of administration for the delivery of transgenes specifically to podocytes. We have shown transgenes can be efficiently targeted to podocytes to replace defective genes or to use the podocyte as a protein factory to modulate glomerular biology. This technology therefore provides an important novel modality for potentially treating a broad range of glomerular disease. PS-001 is being developed as a novel approach to treat steroid resistant nephrotic syndrome caused by mutated NPHS2, and may become the first podocyte targeted gene therapy to enter clinical development.