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Background and Purpose: Endothelin‐1 (ET‐1) receptor A (ETA) antagonists reduce proteinuria and prevent renal outcomes in chronic kidney disease (CKD) patients, but their utility has been limited because of associated fluid retention, resulting in increased heart failure risk. Understanding the mechanisms responsible for fluid retention could result in solutions that preserve renoprotective effects while mitigating fluid retention, but the complexity of the endothelin system has made identification of the underlying mechanisms challenging. Approach: We utilized a previously developed mathematical model of ET‐1 kinetics, ETA receptor antagonism, kidney function, haemodynamics, and sodium and water homeostasis to evaluate hypotheses for mechanisms of fluid retention with ETA antagonism. To do this, we simulated the RADAR clinical trial of atrasentan in patients with type 2 diabetes and CKD and evaluated the ability of the model to predict the observed decreases in haematocrit, urine albumin creatinine ratio (UACR), mean arterial pressure (MAP), and estimated glomerular filtration rate (eGFR). Background and Key Results: An effect of ETA antagonism on venodilation and increased venous capacitance was found to be the critical mechanism necessary to reproduce the simultaneous decrease in both MAP and haematocrit observed in RADAR. Conclusions and Impact: These findings indicate that fluid retention with ETA antagonism may not be caused by a direct antidiuretic effect within the kidney but is instead be an adaptive response to venodilation and increased venous capacity, which acutely tends to reduce cardiac filling pressure and cardiac output, and that fluid retention occurs in an attempt to maintain cardiac filling and cardiac output. [ABSTRACT FROM AUTHOR]

Aim: Rutin is a flavonoid glycoside obtained from the plant Ruta graveolens. It was known to have immunosuppressant activities. This study was focused on effect of rutin against immunoglobulin A (IgA) nephropathy. Methods: IgA nephropathy was induced in Sprague–Dawley rats with various inducing agents described in text. During the later part of the induction phase, rutin was administered. Control group rats did not receive any treatment or inducing agent, induced group rats received only the inducing agents, whereas treatment group received the inducing agents as well as rutin. Results: During the study, various biochemical parameters pertaining to kidney function were evaluated and also, the expression of proteins and cytokines responsible for inflammation and fibrosis were assessed. The effect of rutin in IgA nephropathy was promising as treatment with rutin reduced the deposition of IgA in the glomeruli of rats. Along with this we also tried to establish the probable mechanism of action of rutin and based on the summary of the results it was concluded that rutin reduced the inflammation and fibrosis related to IgA nephropathy by inhibiting the TGF‐β/SMAD pathways and ultimately reducing the expression of α‐smooth muscle actin (α‐SMA). Conclusion: Comprehending all the above consideration, it may be safely said that that rutin alleviated inflammation and also fibrosis mediated by IgA, by suppressing the transforming growth factor‐β (TGF‐β) activities through suppressor of mothers against decapentaplegic pathways and reduced the epithelial‐to‐mesenchymal transition by downregulating the α‐SMA which is a marker for fibrosis. [ABSTRACT FROM AUTHOR]

Aim: IgA nephropathy (IgAN) is the most common primary glomerular disease worldwide. Pregnant IgAN patients are more susceptible to adverse pregnancy outcomes (APO). However, the risk factor for APO and its effects on the long‐term renal outcome of pregnant IgAN patients remained unclear. Methods: We performed a retrospective observational study covering 2003–2019 that included 44 female IgAN patients with pregnancy history to investigate the risk factor for APO and its impact on clinical outcome in IgAN. Renal function outcome and proteinuria remission were evaluated in pregnant IgAN women with and without APO. Results: In this retrospective and observational study, we found that patients with APO exhibited higher levels of serum creatinine and IgM, and lower haemoglobin levels while other clinical characteristics, pathological characteristics and therapy protocol had no significant difference. We found that anaemia and a higher level of serum IgM were independent risk factors for APO. IgAN pregnant women without APO experienced a higher proportion of proteinuria remission than those with APO, but there is no difference in the renal function outcome. Conclusion: Pregnant IgAN patients with higher risks, including lower haemoglobin levels and higher IgM levels deserve intensive monitoring, and aggressive therapy to reduce proteinuria should be carried out in pregnant IgAN patients with APO. [ABSTRACT FROM AUTHOR]

Background: The impact of continuous flow resulting from contemporary left ventricular assist devices (LVAD) on renal vascular physiology is unknown. Renal resistive index (RRI) reflects arterial compliance, as well as renal vascular resistance, contributed by afferent and efferent arteriolar tone, the renal interstitium as well as renal venous pressures. Methods: Prospective, single center study with renal Doppler evaluation at baseline (pre‐implant) and at 3‐months support. Outcomes assessed include need for post‐operative renal replacement therapy (RRT), worsening renal function (WRF) defined as persistent increase from pre‐implant KDIGO chronic kidney disease stage, right ventricular (RV) failure, and survival to transplantation. Results: Pre‐implant RRI did not predict cardiorenal outcomes including right heart failure, need for renal replacement therapy or worsening renal function. Post‐implant RRI was significantly lower than pre‐implant RRI, with a distinct Doppler waveform characteristic of continuous flow. Post‐implant renal end‐diastolic velocity, but not RRI, correlated strongly with LVAD flow (Spearman rho −0.99, p < 0.001), with trend toward correlation with mean arterial pressure (Spearman's rho 0.63, p = 0.129). There was a negative correlation between post‐implant RRI and mean pulmonary artery pressure (Spearman's rho −0.81, p = 0.049), likely driven by elevated pulmonary capillary wedge pressure (Spearman's rho −0.83, p = 0.058). Conclusion: The hemodynamic contributors to RRI in LVAD supported patients are complex. Higher mean pulmonary artery and pulmonary capillary wedge pressures seen in lower RRI may reflect a smaller difference in systolic and diastolic flow. Future simultaneous Doppler assessment of the LVAD outflow graft and RRI may help understand the hemodynamic interactions contributing to this index. [ABSTRACT FROM AUTHOR]

Former Extremely Low Birthweight (ELBW) neonates suffer from adverse renal and cardiovascular outcomes later in life. Less is known about additional perinatal risk factors for these adverse outcomes which we have investigated in this study. We compared renal outcome between ELBW children and controls, to find perinatal risk factors for poorer renal outcome and to unveil associations between kidney function and blood pressure. This study included 93 former ELBW children and 87 healthy controls with a mean age of 11 years at assessment. We measured cystatin C-based estimated glomerular filtration rate (eGFR) and blood pressure. Blood pressure and eGFR levels were compared between cases and controls. We subsequently investigated perinatal risk factors for adverse outcome amongst ELBW children. ELBW children have significantly higher blood pressure (mean SBP percentile 75thvs. 47th, p <0.001) and lower mean eGFR (94 vs. 107 ml/min/1.73 m2, p = 0.005) compared to the control group. Elevated blood pressure did not correlate with perinatal characteristics and none of them had microalbuminuria. ELBW children with eGFR <90 ml/min/1.73 m2 were ventilated longer (17 vs. 9 days, p = 0.006), more frequently male (OR = 3.33, p = 0.055) and tended to suffer more from intraventricular hemorrhage (40% vs. 15.8%, p = 0.056). There was no association between blood pressure and kidney dysfunction. Conclusions: Understanding risk profiles for unfavorable outcomes may help to identify children at increased risk for kidney dysfunction. Poorer eGFR was associated with longer ventilation, male sex, and intra-ventricular hemorrhage but not with blood pressure. This knowledge can lead to safer neonatal therapeutic regimens for ELBW infants, a more intensive follow-up and earlier treatment initiation for children at highest risk. What is Known: • Extremely Low Birthweight (ELBW) neonates suffer later in life from adverse renal and cardiovascular outcomes. • Perinatal risk factors that further predict the individual risk for adverse outcomes are not well known. What is New: • Poorer eGFR in adolescence was associated with male sex, longer ventilation and intra-ventricular hemorrhage at birth but not with blood pressure. • Former ELBW infants had higher blood pressures compared to controls, but no microalbuminuria. • This knowledge can lead to potential precision medicine, safer neonatal therapeutic regimens for ELBW infants, a more intensive follow-up and earlier treatment initiation for children at highest risk. [ABSTRACT FROM AUTHOR]

Objective: To assess the association between glycated haemoglobin (HbA1c) variability and risk of renal function decline in type 2 diabetes mellitus (T2DM). Research Design and Methods: A comprehensive search was carried out in PubMed, Embase, Web of Science and the Cochrane Library (until 12 March 2024). The Preferred Reporting Items for Systematic Reviews and Meta‐Analyses (PRISMA) statement guidelines were followed for this meta‐analysis. HbA1c variability was presented as indices of the standard deviation (SD), coefficient of variation (CV), HbA1c variability score (HVS) and haemoglobin glycation index (HGI). This meta‐analysis was performed using random‐effect models. Results: Eighteen studies met the objectives of this meta‐analysis. The analyses showed positive associations between HbA1c variability and kidney function decline, with hazard ratio (HR) 1.26 (95% confidence interval [CI] 1.15–1.38) for high versus low SD groups, HR 1.47 (95% CI 1.30–1.65) for CV groups, HR 1.32 (95% CI 1.10–1.57) for HVS groups and HR 1.53 (95% CI 1.05–2.23) for HGI groups. In addition, each 1% increase in SD and CV was linked to kidney function decline, with HR 1.26 (95% CI 1.17–1.35), and 1.13 (95% CI 1.03–1.23), respectively. Also, each 1‐SD increase in SD of HbA1c was associated with deterioration in renal function, with HR 1.17 (95% CI 1.07–1.29). Conclusions: The four HbA1c variability indicators were all positively associated with renal function decline progression; therefore, HbA1c variability might play an important and promising role in guiding glycaemic control targets and predicting kidney function decline progression in T2DM. [ABSTRACT FROM AUTHOR]

Background: Children with overweight and obesity are at risk for developing chronic kidney disease (CKD). During lifestyle adjustment, the first step in the treatment of childhood obesity, body proportions are likely to change. The aim of this study was to examine how lifestyle intervention affects creatinine-based kidney function estimation in children with overweight and obesity. Methods: This longitudinal lifestyle intervention study included 614 children with overweight and obesity (mean age 12.17 ± 3.28 years, 53.6% female, mean BMI z-score 3.32 ± 0.75). Loss to follow-up was present: 305, 146, 70, 26, and 10 children were included after 1, 2, 3, 4, and 5 (about yearly) follow-up visits, respectively. Serum creatinine (SCr) was rescaled using Q-age and Q-height polynomials. Results: At baseline, 95–97% of the children had a SCr/Q-height and SCr/Q-age in the normal reference range [0.67–1.33]. SCr/Q significantly increased each (about yearly) follow-up visit, and linear mixed regression analyses demonstrated slopes between 0.01 and 0.04 (corresponding with eGFR FAS reduction of 1.1–4.1 mL/min/1.73 m2) per visit. BMI z-score reduced in both sexes and this reduction was significantly higher in males. No correlation between change in rescaled SCr and BMI z-score reduction could be demonstrated. Conclusions: Rescaled serum creatinine (SCr/Q) slightly increases during multidiscipline lifestyle intervention in this cohort of children with overweight and obesity. This effect seems to be independent from change in BMI z-score. Whether this minor decrease in estimated kidney function has clinical consequences in the long term remains to be seen in trials with a longer follow-up period. Clinical Trial registration: ClinicalTrial.gov; Registration Number: NCT02091544. [ABSTRACT FROM AUTHOR]

Determination of serum creatinine concentrations and subsequent calculation of estimated glomerular filtration rates (eGFR) is a cornerstone of clinical medicine. Crucial clinical decisions such as drug treatment discontinuations are based on eGFR calculated from serum creatinine measurements. However, creatinine is not only filtered in the kidneys, but also actively secreted into urine. Creatinine transporters such as OCT2, OCT3, MATE1, MATE2‐K, and OAT2 expressed in proximal tubular cells are responsible for active renal secretion of creatinine. Multiple drugs (e.g., oral antitumor drugs) inhibit these transporters thereby causing a pseudo‐worsening of kidney function with an increase in serum creatinine concentrations and a decrease in eGFR while other methods for eGFR determination (e.g., by cystatin C) reveal normal kidney function. Since US Prescribing Information (PI) and European Summaries of Product Characteristics (SmPCs) are the most relevant source of information for physicians, we investigated the quality of information in US PI/German SmPCs of drugs with clear evidence for pseudo‐worsening of kidney function. 514 drugs putatively interacting with creatinine transporters were identified. For 149 of those drugs, an increase in serum creatinine concentrations has been described. Available data confirmed the existence of pseudo‐worsening of kidney function for 30 of those drugs, for the remaining 119 drugs existing data are insufficient. Only 23.5% (12/51) of the 30 drugs' PI/SmPCs contained unambiguous statements on this proven pseudo‐worsening of kidney function and gave clear recommendations for clinical management. Taken together, inadequate information provided in PI or SmPCs on the pseudo‐worsening of kidney function poses patients at unnecessary risks. [ABSTRACT FROM AUTHOR]

ABSTRACT Introduction Materials and Methods Results Conclusions Nutritional management is crucial in patients with chronic kidney disease. Therefore, it is important to assess nutritional status and detect malnutrition, especially in patients with diabetes. However, there is currently a lack of evidence regarding the relationship between nutritional indices and renal function in patients with type 2 diabetes. This study investigated whether the geriatric nutritional risk index (GNRI) is related to renal prognosis in type 2 diabetes patients.The study included 946 type 2 diabetes patients enrolled in the Fukushima Cohort Study. The primary endpoint of this study was a renal event, defined as a combination of a 50% decline in eGFR from baseline and end‐stage kidney disease. All‐cause death and new cardiovascular events were also measured as secondary outcomes. The association between GNRI and these endpoints was assessed using Cox regression analysis.The median patient age was 66 years, 57% were men, the median eGFR was 67.9 mL/min/1.73 m2, and the median GNRI was 100.0. Compared to patients in the highest GNRI tertile, patients in the lowest tertile had a significantly increased risk of the renal event (HR 5.15, 95% CI 2.51–10.6) and all‐cause death (HR 2.30, 95% CI 1.20–4.42). A significant association was not observed between GNRI levels and cardiovascular events.We observed an association between poor nutritional status, assessed by GNRI, and adverse outcomes in patients with type 2 diabetes. Nutritional status assessment has potential utility as a prognostic tool for individuals with type 2 diabetes. [ABSTRACT FROM AUTHOR]

Aim Method Results Conclusion Recently, substantial studies have been accumulated to indicate the important role of gut microbiota in diabetic kidney disease (DKD). The abnormal change of bacterial‐derived products could imply specific injuries or play beneficial or harmful roles in DKD progression. In this study, we examined the presence and contribution of the Klebsiella oxytoca gene in the circulation of patients with DKD.We enrolled a total of 16 healthy participants, 17 patients with DKD, 5 patients with DKD requiring haemodialysis (HD), and 7 patients with CKD without diabetes. Bacterial‐derived DNA (16S rDNA and a specific K. oxytoca gene) in the blood was detected using droplet digital PCR, then investigated the relationship with clinical characteristics.We identified an increase in K. oxytoca genes in the blood of DKD patients. Interestingly, blood K. oxytoca copies and K. oxytoca/ 16S DNA ratio correlated with higher blood creatinine and BUN levels together with lower eGFR in DKD patients. K. oxytoca levels were also associated with higher neutrophil percentage, lower lymphocyte frequency, and increased neutrophil‐to‐lymphocyte ratio.Collectively, the presence of the K. oxytoca gene in the circulation could serve as a biomarker reflecting reduced renal function in DKD patients. [ABSTRACT FROM AUTHOR]

Cannabinoids are a class of drugs derived from the Cannabis plant that are widely used for the treatment of various medical conditions and recreational use. Common examples include Δ9‐tetrahydrocannabinol (THC), cannabidiol (CBD), spice, and 2‐arachidonoylglycerol (2‐AG). With more than 100 cannabinoids identified, their influence on the nervous system, role in pain management, and effects due to illicit use have been extensively studied. However, their effects on peripheral organs, such as the kidneys, require further examination. With dramatic rises in use, production, and legalization, it is essential to understand the impact and mechanistic properties of these drugs as they pertain to renal and cardiovascular physiology. The goal of this review is to summarize prior literature on the expression of cannabinoid receptors and how cannabinoids influence renal function. This review first discusses the interaction of the endocannabinoid system (ECS) and renal physiology and pathophysiology. Following, we briefly discuss the role of the ECS in various kidney diseases and the potential therapeutic applications of drugs targeting the cannabinoid system. Lastly, recent studies have identified several detrimental effects of cannabinoids, not only on the kidney but also in contributing to adverse cardiovascular outcomes. Thus, the negative impact of cannabinoids on renal function and the development of various cardiovascular diseases is also discussed. [ABSTRACT FROM AUTHOR]

Introduction: Cytoreductive surgery combined with hyperthermic intraperitoneal chemotherapy (CRS/HIPEC) has been established as an effective treatment for peritoneal cancer (PC). However, this kind of combination therapy is associated with a high lactate level. Moreover, studies have suggested that the rate of complications early after surgery directly increased with elevated lactate levels. Glucose-insulin-potassium (GIP), a potent cardioprotective intervention, has been demonstrated to adjust blood glucose (BG) levels and reduce lactate levels. However, the insulin-glucose ratio should be adjusted according to the surgery performed. Here, we aimed to evaluate the advantages of using modified GIP during CRS/HIPEC to reduce the lactate level at the end of surgery and further reduce the incidence of early postoperative complications. Methods and analysis: The modified GIP versus conventional management during surgery study is a single-center, randomized, single-blinded outcome assessment clinical trial of 80 patients with PC who are between 18 and 64 years old and undergoing CRS/HIPEC. Participants will be randomly allocated to receive modified GIP or conventional treatment (1:1). The primary outcome will be the plasma lactate level at the end of surgery. The secondary outcomes will include the highest levels and fluctuation ranges of lactate and BG during surgery, extubation time, APACHE-II score 24 h after surgery, postoperative defecation and exhaust time, postoperative lactate clearance time, postoperative liver and kidney function, incidence of complications within 7 days after surgery, length of intensive care unit stay (LIS), length of hospital stay (LHS), and total cost of hospitalization. Ethics and dissemination: The trial protocol was approved by the Scientific Research Ethics Committee of Beijing Shijitan Hospital Affiliated with Capital Medical University, approval number sjtky11-1x-2022(118). The results will be published in international peer-reviewed journals. Trial registration: ChiCTR2200057258. Registered on March 5, 2022. [ABSTRACT FROM AUTHOR]

Introduction: Early administration of appropriate antibiotics has been shown to be among the most effective interventions to reduce mortality in septic patients. We evaluated the attainment of efficacy and safety targets at 24 h associated with the use of intensive beta‐lactam therapy in patients admitted to the intensive care unit for sepsis. Methods: This was a prospective study with patients who received beta‐lactams for sepsis or septic shock between February 2023 and September 2023. The antibiotic dose was unadjusted for renal function and administered by a loading dose followed by extended infusions, according to local practices. Blood samples were taken at the trough 24 h after the start of the beta‐lactam to obtain serum levels. These levels were compared to efficacy and innocuity thresholds found in the literature. Results: Among 36 included patients, all of them achieved serum concentrations above the minimum inhibitory concentration (MIC) for 100% of the therapeutic interval and 75% of them achieved serum concentrations above four times the MIC for 100% of the therapeutic interval. The predefined toxicity thresholds were reached by 8.3% of patients. Renal impairment was the factor most associated with the achievement of higher serum levels. Conclusion: Nonrenally adjusted doses of beta‐lactams administered by extended infusion showed good attainment of effective concentrations and few toxic concentrations in critically ill patients with sepsis or septic shock. Further studies are needed to better define the association between toxic concentrations and toxicity manifestations. [ABSTRACT FROM AUTHOR]

Introduction: Chloride is the most abundant extracellular anion; however, abnormalities of serum chloride (dyschloremia) are often overlooked. This study aimed to study the association of dyschloremia with AKI and major adverse kidney events at Day 30 (MAKE30) in critically ill patients with sepsis. Materials and Methods: This prospective single‐center cohort study included adult patients with sepsis admitted in a tertiary care hospital in India. Patients with advanced chronic kidney disease, requiring dialysis at admission, or with hospital stay of less than 72 h were excluded. Hyperchloremia and hypochloremia were defined as chloride levels of > 110 mEq/L and < 95 mEq/L, respectively. The primary outcome measure was MAKE30—a composite of death, need for dialysis, or sustained loss of kidney function at Day 30. Results: In a cohort of 400 patients with a mean age of 60 (±15) years, AKI was seen in 301 (75.2%) and MAKE30 in 171 (42.8%). Hyperchloremia and hypochloremia were seen in 19.3% (n = 77) and 32.3% (n = 129), respectively, in the first 72 h of ICU stay. Hypochloremia, but not hyperchloremia, was independently associated with both MAKE30 (OR: 2.56, 95% CI: 1.13–5.79; p = 0.024) and new‐onset or worsening AKI (OR: 2.52, 95% CI: 1.17–5.41; p = 0.019). There was no association between hyperchloremia and either MAKE30 (OR: 1.07, 95% CI: 0.43–2.69; p = 0.882) or new‐onset/worsening AKI (OR: 0.89, 95% CI: 0.38–2.09; p = 0.781). Conclusion: Hypochloremia, but not hyperchloremia, was associated with MAKE30 in this cohort of critically ill patients with sepsis. Trial Registration: Clinical Trial Registry identifier: CTRI//2022/02/040519 [ABSTRACT FROM AUTHOR]

Background: Currently, there is an irrational use of drugs in the treatment of hypoproteinemia. This study evaluates the value of 12 injections to provide a basis for drug selection for the treatment of hypoproteinemia. Methods: The content of the first restrictive amino acid, the comprehensive quality of the total essential amino acid, and the closeness to the whole egg protein or FAO/WHO model were evaluated to compare their value in the amino acid synthesis of human serum albumin. A comparison was made between the matching degree of HA and therapeutic amino acids with the human plasma amino acid profile. Furthermore, the value and safety of synthetic human serum albumin were compared. Results: The lowest synthetic value of human serum albumin was 18AA-V, and the highest was 18AA-II. The CS values of HA, 18AA-V, 18AA-II, 18AA-Ip, 18AA-IIp, and 19AA-Ip were 0.18, 0.58, 0.78, 0.55, 0.54, and 0.59, respectively. The similarity to egg protein was 0.81, 0.92, 0.94, 1.00, 1.18, and 1.18, respectively. The proximity values to FAO/WHO standards were 0.81, 0.85, 0.90, 1.36, 1.54, and 1.54, respectively. The changes in 3AA and the amino acid profile were matched when liver function was abnormal. When the renal function was abnormal, 9AA was matched. During trauma, 18AA-VII was matched. The amino acid profile of HA did not correspond. Conclusion: Patients with normal liver and kidney function should choose compound balanced amino acid injection, while patients with abnormalities should choose 3AA. Patients with renal dysfunction should choose 9AA. Trauma patients should choose 18AA-VII. [ABSTRACT FROM AUTHOR]

Chronic kidney disease‐mineral bone disorder (CKD‐MBD) is a syndrome commonly observed in subjects with impaired renal function. Phosphate metabolism has been implicated in the pathogenesis of CKD‐MBD and according to the phosphorocentric hypothesis may be the key player in the pathogenesis of these abnormalities. As phosphorous is an essential component for life, absorption from the bowel, accumulation and release from the bones, and elimination through the kidneys are all homeostatic mechanisms that maintain phosphate balance through very sophisticated feedback mechanisms, which comprise as main actors: vitamin D (VD), parathyroid hormone (PTH), calciproteins particles (CPPs), fibroblast growth factor‐23 (FGF‐23) and other phosphatonins and klotho. Indeed, as the renal function declines, factors such as FGF‐23 and PTH prevent phosphate accumulation and hyperphosphatemia. However, these factors per se may be responsible for the organ damages associated with CKD‐MBD, such as bone osteodystrophy and vascular calcification. We herein review the current understanding of the CKD‐MBD focusing on phosphorous metabolism and the impact of phosphate manipulation on surrogate and hard outcomes. [ABSTRACT FROM AUTHOR]

Acute Kidney Injury (AKI) is frequently observed in hospitalized patients in intensive care units, often caused by renal ischemia-reperfusion injury (IRI). IRI disrupts the function of various 'remote organs' such as the lungs, pancreas, intestine, liver, heart, and brain through inflammation, oxidative stress, apoptosis, leukocyte infiltration, and increased urea and creatinine levels. Gender differences in renal IRI-induced injury are noted. H2S, an endogenous gaseous modulator, shows potential in vasodilation, bronchodilation, and hypotension and can regulate apoptosis, inflammation, angiogenesis, metabolism, and oxidative stress. This study aims to investigate the protective effects of NaHS on brain, heart, and lung injuries following renal IR and to assess the oxidative system status as a potential mechanism in male and female rats. Forty-eight Wistar rats were randomly divided into eight groups (n = 6): Control/Saline, Sham/Saline, IR/Saline, and IR/NaHS in both sexes. Forty-five minutes of bilateral renal ischemia followed by 24-hour reperfusion was induced in the IR groups. NaHS (100µM/Kg, IP) was administered 10 min before clamp release in treated groups. BUN, SCr, BUN/SCr, albuminuria, histopathology, and oxidative stress biomarkers of the brain, heart, and lung were assessed as remote organs. IR increased serum markers of renal function, albuminuria, malondialdehyde levels, and tissue injury scores while reducing nitrite levels and superoxide dismutase and glutathione peroxidase activities. NaHS treatment reversed the adverse effects of IR in remote organs in both sexes, although it showed limited improvement in renal function. Our findings demonstrate that NaHS has a beneficial effect on remote organ injury following renal IR by mitigating oxidative stress, with noted tissue-specific and gender-specific differences in response. These findings suggest NaHS as a potential therapeutic agent for mitigating multi-organ injury after renal IR, with effects varying by tissue and gender. [ABSTRACT FROM AUTHOR]

Background: Uric acid closely relates to both kidney disease and atrial fibrillation (AF), yet the extent to which it influences the kidney-AF association remains uncertain. We examined the relationship between kidney function and risk of AF, accounting for uric acid levels. Methods: A total of 308,509 individuals in the Swedish Apolipoprotein-Related Mortality Risk (AMORIS) cohort were included and their serum creatinine and uric acid were measured during 1985–1996. Ten-year incident AF was identified via linkage with the national registers. Glomerular filtration rate (eGFR) (ml/min/1.73 m2) was calculated with the 2009 Chronic Kidney Disease Epidemiology Collaboration equation. Hyperuricemia was defined as > 420 µmol/L for men and > 360 µmol/L for women. Results: Over a mean follow-up of 9.4 years, 10,007 (3.2%) incident AF cases occurred. After adjusting for age, sex, cardiovascular diseases, total cholesterol, triglycerides, and glucose, individuals with low eGFR (< 30 and 30–59 ml/min/1.73 m2) had a higher risk of AF compared to those with normal eGFR (60–89) (hazard ratio (HR) = 1.72, 95% confidence interval (CI):1.29–2.30; HR = 1.10, 95% CI: 1.03–1.18, respectively). After further adjusting for uric acid levels, the association disappeared (HR = 0.97, 95% CI: 0.72–1.30; HR = 0.93, 95% CI: 0.86-1.00, respectively). When stratifying by hyperuricemia yes/no, eGFR < 30 ml/min/1.73 m2 was associated with higher AF risk in a small group of individuals without hyperuricemia (HR = 2.58, 95% CI: 1.64–4.07). Conclusion: Uric acid largely accounted for the relationship between eGFR and AF in this study. However, in individuals without hyperuricemia, eGFR in the lowest range (< 30 ml/min/1.73 m2) was still associated with increased risk of AF. [ABSTRACT FROM AUTHOR]

AbstractA low eGFRcystatin C/eGFRcreatinine-ratio is characteristic of a group of serious kidney disorders called ‘Selective Glomerular Hypofiltration Syndromes’. This study examines if such a low ratio can also be used to evaluate the risk for women with hypertensive disorders in pregnancy to develop severe maternal morbidity. All women discharged from the perinatal ward at the Skåne University Hospital in Lund during the period of 1-9-2016 to 31-8-2017 under one of the diagnoses within hypertensive disorders in pregnancy were considered for inclusion in the study. After delivery and discharge from the hospital, records from included patients were reviewed and all registered measures of renal function were analysed. An eGFRcystatin C/eGFRcreatinine-ratio ≤0.60 in a sample drawn not earlier than three days before delivery was considered as defining a high risk for severe maternal morbidity. A strong association (p-value: 0.035) between severe maternal morbidity and an eGFRcystatin C/eGFRcreatinine-ratio ≤0.60 was found in a subgroup of 32 women diagnosed with ‘preeclampsia with severe features’. A total of 69 women were included in the study. Fifty were defined as high-risk and seventeen of them (34%) developed severe maternal morbidity. Among the nineteen women defined as low-risk only two (10.5%) developed severe maternal morbidity (p-value: 0.051). A low eGFRcystatin C/eGFRcreatinine-ratio seems promising as a predictive marker for maternal morbidity in hypertension in pregnancy. Its performance as a tool in the monitoring of progressing disease should be evaluated further in larger cohorts. Delivery before the eGFRcystatin C/eGFRcreatinine-ratio decreases to, or below, 0.60 might help avoid maternal complications. [ABSTRACT FROM AUTHOR]

Aim Methods Results Conclusion 2,3‐bisphosphoglycerate mutase (BPGM) is traditionally recognized for its role in modulating oxygen affinity to hemoglobin in erythrocytes. Recent transcriptomic analyses, however, have indicated a significant upregulation of BPGM in acutely injured murine and human kidneys, suggesting a potential renal function for this enzyme. Here we aim to explore the physiological role of BPGM in the kidney.A tubular‐specific, doxycycline‐inducible Bpgm‐knockout mouse model was generated. Histological, immunofluorescence, and proteomic analyses were conducted to examine the localization of BPGM expression and the impact of its knockout on kidney structure and function. In vitro studies were performed to investigate the metabolic consequences of Bpgm knockdown under osmotic stress.BPGM expression was localized to the distal nephron and was absent in proximal tubules. Inducible knockout of Bpgm resulted in rapid kidney injury within 4 days, characterized by proximal tubular damage and tubulointerstitial fibrosis. Proteomic analyses revealed involvement of BPGM in key metabolic pathways, including glycolysis, oxidative stress response, and inflammation. In vitro, Bpgm knockdown led to enhanced glycolysis, decreased reactive oxygen species elimination capacity under osmotic stress, and increased apoptosis. Furthermore, interactions between nephron segments and immune cells in the kidney suggested a mechanism for propagating stress signals from distal to proximal tubules.BPGM fulfills critical functions beyond the erythrocyte in maintaining glucose metabolism in the distal nephron. Its absence leads to metabolic imbalances, increased oxidative stress, inflammation, and ultimately kidney injury. [ABSTRACT FROM AUTHOR]

We tested whether older adults, compared with young adults, exhibit greater gastrointestinal permeability and kidney injury during heat stress. Nine young (32 ± 3 years) and nine older (72 ± 3 years) participants were heated using a model of controlled hyperthermia (increasing core temperature by 2°C via a water‐perfused suit). Gastrointestinal permeability was assessed using a multi‐sugar drink test containing lactulose, sucrose and rhamnose. Blood and urine samples were assayed for markers of intestinal barrier injury [plasma intestinal fatty acid binding protein (I‐FABP), plasma lipopolysaccharide binding protein (LBP) and plasma soluble cluster of differentiation 14 (sCD14)], inflammation (serum cytokines), kidney function (plasma creatinine and cystatin C) and kidney injury [urine arithmetic product of IGFBP7 and TIMP‐2 (TIMP‐2 × IGFBP7), neutrophil gelatinase‐associated lipocalin and kidney injury molecule‐1]. The lactulose‐to‐rhamnose ratio was increased in both young and older adults (group‐wide: Δ0.11 ± 0.11), but the excretion of sucrose was increased only in older adults (Δ1.7 ± 1.5). Young and older adults showed similar increases in plasma LBP (group‐wide: Δ0.65 ± 0.89 µg/mL), but no changes were observed for I‐FABP or sCD14. Heat stress caused similar increases in plasma creatinine (group‐wide: Δ0.08 ± 0.07 mg/dL), cystatin C (group‐wide: Δ0.16 ± 0.18 mg/L) and urinary IGFBP7 × TIMP‐2 [group‐wide: Δ0.64 ± 0.95 (pg/min)2] in young and older adults. Thus, the level of heat stress used herein caused modest increases in gastrointestinal permeability, resulting in a mild inflammatory response in young and older adults. Furthermore, our data indicate that older adults might be more at risk for increases in gastroduodenal permeability, as evidenced by the larger increases in sucrose excretion in response to heat stress. Finally, our findings show that heat stress impairs kidney function and elevates markers of kidney injury; however, these responses are not modulated by age. [ABSTRACT FROM AUTHOR]

Tenofovir disoproxil fumarate (TDF) requires dosage adjustments from the standard 300 mg once daily to every 48‐96 h for moderate‐to‐severe renal impairment to avoid excessive exposure. However, this extended interval can lead to variable drug exposure and inconvenience. This study aimed to utilize the population pharmacokinetic (PPK) models to optimize TDF dosing regimens for HIV‐infected patients with renal impairment. A systematic literature search was conducted across PubMed, Cochrane Library, and Scopus databases to identify relevant PPK studies of TDF in HIV‐infected patients. From the included studies, the PPK models and associated parameters were extracted. Monte Carlo simulations (n = 2000) were performed to generate concentration–time profiles and derive PK parameters compared against reference ranges. For moderate renal impairment, the TDF 150 mg once‐daily regimen achieved cumulative exposure comparable to the approved 300 mg every‐other‐day regimen. In severe renal impairment, TDF 75‐100 mg administered once daily provided similar cumulative exposure as 300 mg every 72‐96 h regimen while maintaining daily exposure comparable to the standard dose in patients with normal renal function. The approved extended dosing intervals of 72‐96 h exhibited high drug exposure variability, initially resulting in supratherapeutic levels followed by suboptimal levels preceding the subsequent dose administration. In conclusion, administering smaller once‐daily doses of TDF maintains consistent daily drug exposure comparable to the standard dose in patients with normal renal function while reducing variability in drug exposure, potentially mitigating the risk of nephrotoxicity. However, additional clinical studies are required to confirm these findings. [ABSTRACT FROM AUTHOR]

This study aimed to evaluate the ability of pentoxifylline when compared to lovastatin and chlorpromazine as nephroprotective substances in cases of renal ischemia and reperfusion syndrome (IRI). A total of 36 adult male animals were randomly allocated into four groups (untreated control group, pentoxifylline group, lovastatin group, and chlorpromazine group), each consisting of nine animals. All groups were submitted to experimental ischemia and reperfusion procedures. The animals were evaluated 24, 72 and 120 hours after IRI, including physical examinations, serum urea and creatinine measurements, as well as histopathological, morphometric, and stereological analyses of the renal tissue. Results indicated that 24 hours after IRI, only chlorpromazine was effective in controlling azotemia. At the 72-hour mark, both chlorpromazine and pentoxifylline exhibited efficacy. After 120 hours, all three substances demonstrated renal protective qualities. Pentoxifylline was the most effective in preserving the structural integrity of kidney tissue, followed by chlorpromazine. In conclusion, all three treatments (pentoxifylline, chlorpromazine, and lovastatin) were effective. Pentoxifylline proved to be promising in the response against acute tubular necrosis, although chlorpromazine presented earlier renoprotective effects in terms of maintaining renal function. [ABSTRACT FROM AUTHOR]

Background: Sickle cell disease (SCD) is a genetic blood disorder characterized by a painful vaso-occlusive crisis due to the sickling of red blood cells in capillaries. Complications often lead to liver and renal dysfunctions, contributing to morbidity and mortality, particularly for children under 5. This systematic review and meta-analysis aimed to evaluate the liver and renal functions of people with SCD (HbSS) compared to those without it (HbAA) in Africa. Methods: The protocol was registered with PROSPERO (CRD42022346771). We searched PubMed, Embase, Web of Science, and Google Scholar using the keywords "liver function", "renal function", "sickle cell disease", and "Africa" on 6th May 2023 for peer-reviewed articles with abstracts in English. We included case-control studies comparing SCD (HbSS) with controls without hemoglobinopathies (HbAA). We used the random-effect model to calculate the pooled average values for the blood tests of people with SCD in RStudio version 4.2.2. Results: Overall, 17 articles were analyzed from five African countries involving 1312 people with SCD and 1558 controls. The pooled mean difference of liver enzymes aspartate transaminase (AST) was 8.62 (95% CI − 2.99–20.23, I2 = 97.0%, p < 0.01), alanine transaminase (ALT) 7.82 (95% CI − 0.16–15.80, I2 = 99%, p < 0.01) and alkaline phosphatase (ALP) − 2.54 (95% CI − 64.72 – 59.64, I2 = 99%, p < 0.01) compared to controls. The pooled mean difference for the renal biochemical profiles creatinine − 3.15 (95% CI − 15.02; 8.72, I2=99%, p < 0.01) with a funnel plot asymmetry of t = 1.09, df = 9, p = 0.3048 and sample estimates bias of 6.0409. The pooled mean difference for serum urea was − 0.57 (95% CI − 3.49; 2.36, I2 = 99%, p < 0.01), and the estimated glomerular filtration (eGFR) rate was 19.79 (95% CI 10.89–28.68 mL/min/1.73 m2, I2 = 87%, p < 0.01) compared to controls. Conclusion: People with SCD have slightly elevated liver enzymes and estimated glomerular filtration rates compared to controls in Africa. With all the heterogeneity (I2) > 50%, there was substantial variation in the reported articles' results. Systematic review registration: PROSPERO CRD42022346771 [ABSTRACT FROM AUTHOR]

Our previous study first reported the efficacy of FURL using 365 μm fibers with holmium: yttrium aluminum garnet (Ho: YAG) laser lithotripsy. This study evaluates the 16-week safety of this procedure. A prospective cohort study was conducted, and the clinical characteristics of patients who underwent FURL using 365 μm fibers with Ho: YAG laser were retrospectively collected. Descriptive statistics were reported, and logistic regression analysis was conducted to identify risk factors influencing the stone-free rate (SFR). Infection-related laboratory parameters, including white blood cell count (WBC), procalcitonin (PCT), and C-reactive protein (CRP), were collected. Regression analysis was conducted to identify risk factors for the development of urosepsis post-surgery. Additionally, a 16-week follow-up was conducted in outpatient clinics, and kidney function was assessed. A total of 274 patients participated in this study. The 4-week stone-free rate (SFR) following FURL with 365 μm fibers of Ho: YAG laser was significantly associated with stone size and composition. No severe complications were observed following FURL procedures. There were no significant differences in white blood cell count (WBC), C-reactive protein (CRP), and procalcitonin (PCT) in peripheral blood before and after FURL procedures. Urosepsis was diagnosed in 1.82% of patients. Preoperative white blood cell count (WBC) in urine and preoperative urine culture results were identified as significant risk factors. Kidney function remained stable at 4 and 16 weeks following FURL. This prospective cohort study demonstrated the high safety of FURL with 365 μm fibers of Ho: YAG laser, as infection-related parameters during the perioperative period showed no significant differences, and kidney function remained stable throughout the 16-week follow-up. [ABSTRACT FROM AUTHOR]

Background: Chronic kidney disease (CKD) contributes to decreased life expectancy. We examined the association between leisure-time physical activity (LTPA), non-leisure-time physical activity (non-LTPA) and kidney function. Methods: This was a cross-sectional study including 32 162 community-dwelling adults aged ≥ 20 years from the Tohoku Medical MegaBank community-based cohort study. Kidney function was evaluated using cystatin C-based estimated glomerular filtration rate (eGFR) as well as self-reported LTPA and non-LTPA. CKD was defined as either eGFR decline (≤ 60 mL/min/1.73 m2) or presence of albuminuria (albumin-creatinine ≥ 30 mg/g). The association between domain-specific physical activity and kidney function, and CKD prevalence was examined using multivariable-adjusted ordinary least squares and modified Poisson models. Results: The mean eGFR was 98.1 (± 13.2) mL/min/1.73 m2. 3 185 (9.9%) participants were classified as having CKD. The mean LTPA and non-LTPA levels were 2.9 (± 4.2) and 16.6 (± 14.2) METs-hour/day, respectively. For LTPA, in the adjusted model, the quartile groups with higher levels had a higher kidney function (β, 0.36; 95% confidence intervals [CI], [0.06, 0.66]; p = 0.019 for the 2nd quartile, β, 0.82; 95% CI, [0.51, 1.14]; p < 0.001 for the 3rd quartile, and β, 1.16; 95% CI, [0.83, 1.49]; p < 0.001 for the 4th quartile), whereas there were no apparent associations for prevalence of CKD. For non-LTPA, 4th quartile was associated with decreased eGFR (β, -0.42; 95% CI, [-0.72, -0.11]; p = 0.007) and higher prevalence of CKD prevalence (Prevalence ratio, 1.12; 95% CI, [1.02, 1.24]; p = 0.022). These associations with kidney function remained consistent in the subgroup analyses divided by demographic and biological variables. Conclusions: We observed a positive association between higher LTPA levels and better kidney function, but not association with CKD prevalence. In contrast, higher non-LTPA was negatively associated with both kidney function and CKD prevalence. These findings suggest that promoting LTPA is beneficial for kidney function. [ABSTRACT FROM AUTHOR]

Background: Difelikefalin is a selective kappa opioid receptor agonist that is approved for the treatment of moderate-to-severe pruritus associated with chronic kidney disease in adults undergoing hemodialysis (HD). In this study, we assessed the pharmacokinetics (PK) of intravenous (IV) difelikefalin in healthy subjects, in non–dialysis-dependent (NDD) subjects with varying stages of kidney disease, and in subjects with end-stage renal disease (ESRD) undergoing HD. Methods: The PK and safety of single IV doses of difelikefalin (3.0 mcg/kg) were initially evaluated in NDD subjects with mild, moderate, or severe renal impairment compared with matched healthy subjects. Based on those data, the PK and safety of 3 dose levels of IV difelikefalin (0.5, 1.0, or 2.5 mcg/kg) were compared with matched placebo in subjects undergoing HD with each dose administered following dialysis, 3 times over a 1-week treatment period). Results: Single IV dosing of difelikefalin in NDD subjects (N = 36) with mild renal impairment demonstrated comparable exposure to healthy subjects with normal renal function, while subjects with moderate or severe renal impairment had higher total exposure. NDD subjects with severe renal impairment had higher total exposure compared with those with moderate renal impairment (i.e., exposure in severe NDD > moderate NDD > mild NDD ≈ healthy subjects). Clearance of difelikefalin correspondingly decreased with increasing renal impairment. In the multiple-dose study in subjects with ESRD undergoing HD (N = 19), IV difelikefalin demonstrated dose proportionality and was shown to be mostly cleared by dialysis; steady state was achieved with the second dose on day 3. Safety findings for all subjects were consistent with the known profile of IV difelikefalin. Conclusions: IV difelikefalin was well tolerated. Similar exposure was observed in NDD subjects with mild renal impairment compared with healthy subjects with normal renal function, with reduced clearance and higher exposure in NDD subjects with moderate or severe renal impairment. Dose proportionality was demonstrated in subjects with ESRD undergoing HD administered IV difelikefalin 3 times per week following dialysis and was shown to be mostly cleared by dialysis. Trial registration: Single-dose study: NA; multiple-dose study: ClinicalTrials.gov registration number NCT02229929, first registration 03/09/2014. [ABSTRACT FROM AUTHOR]

Introduction: Long working hours are likely associated with the decreased of kidney function, while physical activity (PA) was linked to improvements in kidney function. However, whether PA can offset the negative impact of long working hours on kidney function was unclear, which is the focus of this study. Methods: A cross-sectional study was conducted. Three approaches were adopted to distinguish the association between long working hours and regular working hours. Moderate to vigorous physical activity (PA) was assessed by a structured questionnaire. eGFR and chronic kidney disease (CKD) or not were utilized to evaluate the kidney function. Linear and logistic regression analyses were conducted to assess the association between weekly working hours, PA, and kidney function. Results: A total of 18,431 adults were enrolled in this study, including 9981 males (54.2%) and 8450 females (45.8%). The average eGFR was (99.54 ± 17.55 mL/min/1.73 m2). The people worked more than 40 h/wk (98.89 ± 17.06 mL/min/1.73 m2) had lower eGFR compared to those worked less than 40 h/wk (99.93 ± 17.83 mL/min/1.73 m2) (p < 0.05). Individuals working longer hours exhibited lower eGFR (β = -0.772, 95% CI: -1.241, -0.303, for > 40 h/wk compared to working ≤ 40 h/wk). Engagement in moderate to vigorous PA was associated with higher eGFR values (β = 1.159, 95% CI: 0.699, 1.619) compared to low PA ( < 150 minutes/wk), but this association did not reach statistical significance for the prevalence of CKD. Furthermore, PA was insufficient to reverse the decline of eGFR related to prolonged working hours. Discussion: Prolonged working hours were associated with a decline in eGFR, while PA was found to have a protective effect on kidney function. However, PA alone may not fully mitigate the negative impact of prolonged working hours on renal health. More robust measures to protect renal function should be implemented to mitigate the damage caused by prolonged working hours. [ABSTRACT FROM AUTHOR]

Background: Existing studies investigating the impact of serum calcium (Ca), phosphate (P), 25 hydroxyvitamin D (25[OH]D), and parathyroid hormone (PTH) levels on kidney function have produced inconsistent results. Further research is needed to establish the direct causal relationship between these factors and kidney function. Methods: The study used genome-wide association study datasets for exposure and outcome, mainly derived from the UK Biobank and CKDGen Consortium, with sample sizes ranging from 3,310 to 480,699 individuals of European ancestry. Heritability and genetic correlations among these phenotypes were assessed using linkage disequilibrium score regression (LDSC) and phenotypes with a heritability z-score <4 were excluded from further analyses. Pleiotropic analyses were performed to identify potential horizontal pleiotropic variants at gene and LD-independent locus levels. Mendelian randomization (MR) analysis, using instrumental variables (IVs) based on two distinct selection criteria, was conducted to investigate the potential causal relationships between serum Ca, P, 25(OH)D, PTH, and kidney function. Results: PTH was excluded from further analysis due to a heritability z-score < 4. Genetic correlations were observed between serum Ca and urine albumin-tocreatinine ratio (UACR) (rg = 0.202, P-value = 5.0E-04), between serum 25(OH)D and estimated glomerular filtration rate using serum creatinine (eGFRcrea) (rg = -0.094; P-value = 1.4E-05), and between serum25(OH)D and blood urea nitrogen (BUN) (rg = 0.127; P-value = 1.7E-06). In univariableMR analysis using IVs based on two different selection criteria, it consistently demonstrated that genetically predicted serum Ca consistently showed an increase in UACR (beta 0.11, P-value 2.0E-03; beta 0.13, P-value 2.0E-04). Similarly, serum P was associated with a decrease in eGFRcrea (beta -0.01, P-value 2.0E-04; beta -0.005, P-value 2.0E -03) and an increase in BUN (beta 0.02, P-value 3.0E-03; beta 0.02, P-value 7.5E -07). The influence of serum P on kidney function was further supported in multivariable MR analysis. However, genetically predicted 25(OH)D did not have a significant impact on kidney function. Conclusions: Elevated serum Ca or P levels could both impair kidney function, whereas 25(OH)D has no impact on renal function. [ABSTRACT FROM AUTHOR]

Sepsis is an inevitable stage of bacterial invasion characterized by an uncontrolled inflammatory response resulting in a syndrome of multiorgan dysfunction. Most conventional antibiotics used to treat sepsis are efficacious, but they have undesirable side effects. The green synthesised Ag NPs were synthesized by 5 g of the earthworm extract dissolved in a volume of 500mL of distilled water and then added to 2,500 mL aqueous solution of 1mM silver nitrate at 40 °C. After 4 h, the mixture was then allowed to dry overnight at 60 °C. Later, Ag NPs were washed and collected. They were characterized by X-ray diffraction, ultraviolet-visible spectroscopy, and transmission electron microscopy. Sepsis model as induced by feces-intraperitoneal injection method. Eighteen male mice were assigned into three main groups: the control group, the sepsis-model group, and the Ag NPs-treated group. The control group received a single oral dose of distilled water and, after two days, intraperitoneally injected with 30% glycerol in phosphate buffer saline. The Sepsis-model group received a single oral dose of distilled water. Ag NPs - The treated group received a single oral dose of 5.5 mg/kg of Ag NPs. After two days, the sepsis-model group and Ag NPs-treated group were intraperitoneally injected with 200 µL of faecal slurry. Ag NPs treatment in septic mice significantly decreased liver enzyme activities, total protein, and serum albumin. Moreover, Ag NPs significantly enhanced kidney function, as indicated by a significant decrease in the levels of creatinine, urea, and uric acid. In addition, Ag NPs showed a powerful antioxidant effect via the considerable reduction of malondialdehyde and nitric oxide levels and the increase in antioxidant content. The histopathological investigation showed clear improvement in hepatic and kidney architecture. Our findings demonstrate the protective efficacy of biogenic Ag NPs against sepsis-induced liver and kidney damage. [ABSTRACT FROM AUTHOR]

Reference ranges are invaluable in laboratory medicine, as these are indispensable tools for the interpretation of laboratory test results. When assessing measurements on a single analyte, univariate reference intervals are required. In many cases, however, measurements on several analytes are needed by medical practitioners to diagnose more complicated conditions such as kidney function or liver function. For such cases, it is recommended to use multivariate reference regions, which account for the cross-correlations among the analytes. Traditionally, multivariate reference regions (MRRs) have been constructed as ellipsoidal regions. The disadvantage of such regions is that they are unable to detect component-wise outlying measurements. Because of this, rectangular reference regions have recently been put forward in the literature. In this study, we develop methodologies to compute rectangular MRRs that incorporate covariate information, which are often necessary in evaluating laboratory test results. We construct the reference region using tolerance-based criteria so that the resulting region possesses the multiple use property. Results show that the proposed regions yield coverage probabilities that are accurate and are robust to the sample size. Finally, we apply the proposed procedures to a real-life example on the computation of an MRR for three components of the insulin-like growth factor system. [ABSTRACT FROM AUTHOR]

Aims Methods Results Conclusions The aim of this study was to develop a population pharmacokinetics model for sugemalimab, a monoclonal antibody that targets programmed death‐ligand 1 (PD‐L1), using data from Phase I–III trials and to assess clinical factors affecting sugemalimab exposure.A nonlinear mixed‐effect modelling approach was employed to analyse pooled data from nine studies involving 1628 subjects to characterize the PopPK of sugemalimab. This investigation examined the influence of various covariates on sugemalimab pharmacokinetics (PK), encompassing demographics, baseline hepatic and renal function‐related covariates, and others (including anti‐drug antibody [ADA], combination treatment, Eastern Cooperative Oncology Group [ECOG] performance score, tumour burden and tumour type). Estimation accuracy and predictive ability of the final model were evaluated using various methods. The influence of covariates on sugemalimab exposure was assessed by simulation from the final model.A two‐compartment model with first‐order elimination and time‐varying clearance effectively described the PK of sugemalimab. Covariate analyses revealed significant relationships between sugemalimab clearance and body weight, albumin, gender, ADA, tumour burden and tumour type. The statistically significant covariates on central volume were body weight, albumin, gender and tumour type. No significant relationships were found in the final model for age, race, alanine aminotransferase, aspartate aminotransferase, creatinine, total bilirubin, alkaline phosphatase, combination treatment, creatinine clearance, ECOG, renal function or hepatic function. All significant covariates demonstrated less than a 20% effect on sugemalimab exposure.The PopPK model adequately described the pharmacokinetic profile of sugemalimab with no clinically meaningful impact observed on its exposure across all covariates. Dose adjustment does not appear to be necessary. [ABSTRACT FROM AUTHOR]

Summary Although chronic kidney disease (CKD) is associated with obesity, few studies have used visceral adipose tissue (VAT) as an indicator to investigate its causal effect on CKD. Therefore, Mendelian randomization (MR) was employed to study the causal effects of VAT on CKD and its potential mediation by hypertension. Genome‐wide association study (GWAS) statistics on VAT exposure were obtained from the UK Biobank, while GWAS datasets of CKD outcomes were obtained from CKDGen and FinnGen (validation study). Furthermore, VAT was considered the exposure, with the estimated glomerular filtration rate based on creatinine (eGFR (crea)), estimated glomerular filtration rate based on cystatin C (eGFR(cys)), and blood urea nitrogen (BUN) employed to assess the causal effect of VAT on kidney test indicators. Lastly, a two‐step MR method was used to study the mediating role of hypertension in the pathogenesis of VAT among patients with CKD. VAT exhibited a positive causal association with CKD, irrespective of whether the GWAS datasets from CKDGen (odds ratio [OR] = 1.18, 95% CI: 1.08 to 1.29, P = 1.433140e−04) or FinnGen (1.47, 1.30 to 1.67, p = 2.500000e−09). VAT was not causally associated with eGFR (crea) (1.00, 0.99 to 1.00, p = 0.53), was negatively associated with eGFR (cys) (0.95, 0.93 to 0.97, P = 5.070000e−10), and was positively associated with BUN (1.02,1.01 to 1.02, P = 7.824860e−04). The mediating effect of VAT on CKD via hypertension was 45.8% (95% CI: 26.4 65.1). VAT has a positive causal effect on CKD, with hypertension playing a significant role. However, the effects of VAT on renal function indicators require further investigation. [ABSTRACT FROM AUTHOR]

Intestinal microbiota and its metabolites are involved in many physiological processes of the human body and play a vital role in maintaining human health. The occurrence of kidney disease can cause intestinal microbiota imbalance, resulting in diarrhea. The change of intestinal microbiota and its metabolites content can aggravate renal function injury, which has a bidirectional regulating effect. The theory of renal-intestinal axis further clarified that the impaired renal function is related to the imbalance of intestinal microorganisms, and the impaired intestinal barrier is related to the accumulation of toxin products. Because of its unique therapeutic advantages, Traditional Chinese Medicine can treat diarrhea by enhancing the growth of beneficial bacteria, inhibiting pathogenic bacteria and immune regulation, and slow down the continuous deterioration of kidney disease. This paper focuses on the relationship between intestinal microbiota and its metabolites and diarrhea, the influence of Traditional Chinese Medicine on intestinal microbiota in the treatment of diarrhea, and the role of intestinal microbiota and its metabolites in the renal-intestinal axis. It provides a theoretical basis for Traditional Chinese Medicine to regulate intestinal microbiota and its metabolites based on the renalintestinal axis theory to treat nephrology-induced diarrhea, and also provides a new idea and method for Traitional Chinese Medicine to treat nephrologyinduced diarrhea. [ABSTRACT FROM AUTHOR]

Background: Renal quantitative measurements are important descriptors for assessing kidney function. We developed a deep learning-based method for automated kidney measurements from computed tomography (CT) images. Methods: The study datasets comprised potential kidney donors (n = 88), both contrast-enhanced (Dataset 1 CE) and noncontrast (Dataset 1 NC) CT scans, and test sets of contrast-enhanced cases (Test set 2, n = 18), cases from a photon-counting (PC)CT scanner reconstructed at 60 and 190 keV (Test set 3 PCCT, n = 15), and low-dose cases (Test set 4, n = 8), which were retrospectively analyzed to train, validate, and test two networks for kidney segmentation and subsequent measurements. Segmentation performance was evaluated using the Dice similarity coefficient (DSC). The quantitative measurements' effectiveness was compared to manual annotations using the intraclass correlation coefficient (ICC). Results: The contrast-enhanced and noncontrast models demonstrated excellent reliability in renal segmentation with DSC of 0.95 (Test set 1 CE), 0.94 (Test set 2), 0.92 (Test set 3 PCCT) and 0.94 (Test set 1 NC), 0.92 (Test set 3 PCCT), and 0.93 (Test set 4). Volume estimation was accurate with mean volume errors of 4%, 3%, 6% mL (contrast test sets) and 4%, 5%, 7% mL (noncontrast test sets). Renal axes measurements (length, width, and thickness) had ICC values greater than 0.90 (p < 0.001) for all test sets, supported by narrow 95% confidence intervals. Conclusion: Two deep learning networks were shown to derive quantitative measurements from contrast-enhanced and noncontrast renal CT imaging at the human performance level. Relevance statement: Deep learning-based networks can automatically obtain renal clinical descriptors from both noncontrast and contrast-enhanced CT images. When healthy subjects comprise the training cohort, careful consideration is required during model adaptation, especially in scenarios involving unhealthy kidneys. This creates an opportunity for improved clinical decision-making without labor-intensive manual effort. Key Points: Trained 3D UNet models quantify renal measurements from contrast and noncontrast CT. The models performed interchangeably to the manual annotator and to each other. The models can provide expert-level, quantitative, accurate, and rapid renal measurements. [ABSTRACT FROM AUTHOR]

Introduction: Malakoplakia is a rare and chronic granulomatous disease that is pathologically characterized by the presence of Michaelis-Gutmann bodies and large macrophage clusters. Malakoplakia of the renal parenchyma is especially rare. In this report, we describe the long-term prognosis of a patient who was diagnosed with and treated for renal parenchymal malakoplakia in infancy. Case Presentation: Seventeen years after malakoplakia onset, the patient presented to us with worsening proteinuria. Computed tomography revealed structural abnormalities in the kidney, and focal segmental glomerulosclerosis (FSGS) was diagnosed based on renal biopsy findings. No Michaelis-Gutmann bodies were observed in von Kossa-stained biopsy specimens. Regular outpatient monitoring during the next 9 years showed gradual deterioration of renal function and a moderately high protein/creatinine ratio. Conclusion: Our findings suggest that structural changes due to malakoplakia can cause FSGS. Moreover, structural changes indicate the healing of malakoplakia in infancy and the disappearance of its characteristic lesions over time. Owing to its long-term observation period, this unique case provides new insights into the outcomes of patients with renal parenchymal malakoplakia. [ABSTRACT FROM AUTHOR]

Background: Chronic kidney disease (CKD) patients face the risk of rapid kidney function decline leading to adverse outcomes like dialysis and mortality. Lipid metabolism might contribute to acute kidney function decline in CKD patients. Here, we utilized the Mendelian Randomization approach to investigate potential causal relationships between drug target-mediated lipid phenotypes and rapid renal function decline. Methods: In this study, we utilized two methodologies: summarized data-based Mendelian randomization (SMR) and inverse variance-weighted Mendelian randomization (IVW-MR), to approximate exposure to lipid-lowering drugs. This entailed leveraging expression quantitative trait loci (eQTL) for drug target genes and genetic variants proximal to drug target gene regions, which encode proteins associated with low-density lipoprotein (LDL) cholesterol, as identified in genome-wide association studies. The objective was to investigate causal associations with the progression of rapid kidney function decline. Results: The SMR analysis revealed a potential association between high expression of PCSK9 and rapid kidney function decline (OR = 1.11, 95% CI= [1.001–1.23]; p = 0.044). Similarly, IVW-MR analysis demonstrated a negative association between LDL cholesterol mediated by HMGCR and kidney function decline (OR = 0.74, 95% CI = 0.60–0.90; p = 0.003). Conclusion: Genetically predicted inhibition of HMGCR is linked with the progression of kidney function decline, while genetically predicted PCSK9 inhibition is negatively associated with kidney function decline. Future research should incorporate clinical trials to validate the relevance of PCSK9 in preventing kidney function decline. [ABSTRACT FROM AUTHOR]

Introduction Methods Results Conclusion Treatment for people with HIV‐1 and end‐stage kidney disease (ESKD) on haemodialysis (HD) has previously required complex dose‐adjusted regimens, with limited data on the use of a single‐tablet regimen in this population. Our aim was to assess the efficacy and safety of once‐daily bictegravir/emtricitabine/tenofovir alafenamide (B/F/TAF) and to evaluate the pharmacokinetics of bictegravir (BIC) in adults with HIV‐1 and ESKD on HD.We performed an open‐label extension (OLE) of an open‐label, multicentre, single‐group phase 3b study (NCT02600819) of adults with ESKD on HD and HIV‐1 with virological suppression. Participants switched to elvitegravir/cobicistat/F/TAF (E/C/F/TAF) 150/150/200/10 mg for 96 weeks, following which a subgroup of US participants entered an OLE phase in which they switched to B/F/TAF 50/200/25 mg for 48 weeks, returning for study visits at weeks 4 and 12, and every 12 weeks thereafter. Study assessments included virological response, safety and pharmacokinetic analysis of BIC.Ten participants entered the OLE (median age, 55 years). Virological suppression (HIV‐1 RNA <50 copies/mL) was maintained in all participants over 48 weeks of B/F/TAF treatment. B/F/TAF was well tolerated, with no treatment discontinuations. Mean BIC trough concentrations were lower than those previously reported for people with HIV‐1 with normal kidney function, but remained four‐ to seven‐fold higher than the established protein‐adjusted 95% effective concentration against wild‐type HIV‐1.These findings support the use of the once‐daily B/F/TAF single‐tablet regimen for people with HIV‐1 and ESKD on HD. This regimen offers a convenient treatment option for this population as it reduces the need for dose adjustment, eases pill burden and avoids potential drug–drug interactions associated with alternatives that may impact individuals on multiple medications or awaiting transplantation. [ABSTRACT FROM AUTHOR]

ABSTRACT Biomarkers of kidney function, including glomerular, tubular, and fibrotic markers, have been associated with blood pressure in elderly populations and individuals with kidney and cardiovascular diseases. However, limited information is available in young adults. In this study, we compared levels of several kidney function biomarkers between normotensive and hypertensive young adults and explored the associations of these biomarkers with blood pressure within these groups. In this cross‐sectional assessment, twenty‐four‐hour (24‐h) blood pressure measurements of 1055 participants (mean age = 24.6 years) were used to classify hypertension as per the 2018 ESC/ESH guidelines. Biomarkers of kidney function included estimated glomerular filtration rate, urinary albumin, alpha‐1 microglobulin (uA1M), neutrophil gelatinase‐associated lipocalin (uNGAL), uromodulin (uUMOD), and the CKD273 classifier. All urinary biomarkers, except for the CKD273 classifier, were standardized for urinary creatinine (Cr). In the hypertensive group (61.0% White; 73.2% men), urinary albumin‐to‐creatinine ratio (uACR), uNGAL/Cr and uUMOD/Cr were lower than the normotensive group. In multiple regression analyses, 24‐h systolic blood pressure (SBP) (β = 0.14; p = 0.042), 24‐h diastolic blood pressure (DBP) (β = 0.14; p = 0.040), and 24‐h mean arterial pressure (MAP) (β = 0.16; p = 0.020) associated positively with uA1M/Cr in the hypertensive group, while 24‐h MAP positively associated with uACR (β = 0.17; p = 0.017). In exploratory factor analysis, positive associations of 24‐h DBP and 24‐h MAP with a factor pattern including tubular biomarkers were observed in the hypertensive group (24‐h DBP: β = 0.18; p = 0.026, 24‐h MAP: β = 0.17; p = 0.032). In the setting of hypertension, high perfusion pressure in the kidneys may play a role in the development of proximal tubule damage and promote early deterioration in kidney function in young adults.Trial Registration: ClinicalTrials.gov identifier: NCT03292094 [ABSTRACT FROM AUTHOR]

To address challenges in screening for chronic kidney disease (CKD), we devised a deep learning-based CKD screening model named UWF-CKDS. It utilizes ultra-wide-field (UWF) fundus images to predict the presence of CKD. We validated the model with data from 23 tertiary hospitals across China. Retinal vessels and retinal microvascular parameters (RMPs) were extracted to enhance model interpretability, which revealed a significant correlation between renal function and RMPs. UWF-CKDS, utilizing UWF images, RMPs, and relevant medical history, can accurately determine CKD status. Importantly, UWF-CKDS exhibited superior performance compared to CTR-CKDS, a model developed using the central region (CTR) cropped from UWF images, underscoring the contribution of the peripheral retina in predicting renal function. The study presents UWF-CKDS as a highly implementable method for large-scale and accurate CKD screening at the population level. [ABSTRACT FROM AUTHOR]

Background: The Banff Working Group has updated the histological classification of BK virus nephropathy (BKVN), highlighting the importance of early detection. However, an early detection strategy for BKVN using biopsy has not yet been established. Our investigation aimed to assess the efficacy of protocol biopsy for the diagnosis of BKVN. Methods: We performed a retrospective cohort study of 314 patients who had undergone kidney transplantation between 2006 and 2021. Kidney allograft biopsies were performed as part of a protocol biopsy at 3 months and 1 year post‐transplantation. Following the diagnosis of BKVN, the immunosuppressant dose was reduced. Results: Twelve patients (3.8%) were diagnosed with BKVN by biopsy. Most diagnoses are established during the early stages of BKVN (polyomavirus nephropathy class 1 in six, class 2 in five, and class 3 in one). Following the reduction in immunosuppressant dose, kidney allograft function did not deteriorate in any patients. Additionally, test for BK virus DNA in the blood was negative. All but one patient demonstrated histological resolution of BKVN, and the other had a very slight positivity for the simian virus 40 large T antigen. The median follow‐up time after BKVN diagnosis was 6 years. One patient developed de novo donor‐specific antibody and subclinical acute antibody‐mediated rejection that was successfully cured. Conclusions: Our analysis indicates that protocol biopsy may enable the early detection of BKVN, resulting in the preservation of kidney function. [ABSTRACT FROM AUTHOR]

Background: The glomerular filtration rate (GFR) is estimated by the serum or plasma concentration of creatinine and/or cystatin C using equations that include demographic data. The equations worldwide most widely used are those of the Chronic Kidney Disease Epidemiology Collaboration (CKD‐EPI) consortium and updated in 2021 to remove the Afro‐American racial correction factor. In 2021 and then in 2023, the European Kidney Function Consortium also developed equations based on creatinine and cystatin C, usable across the full age spectrum, and constructed by including the Q value (i.e. the median creatinine or cystatin C in healthy men and women, which is customizable for specific populations). Methods: The aim of this narrative review is to examine the strengths and weaknesses of each biomarker. Results: Both biomarkers have non‐GFR determinants, namely muscle mass, protein intake and tubular secretion for creatinine; dysthyroidism and systemic corticosteroids for cystatin C, as well as other more debated determinants (diabetes, obesity, proteinuria, inflammatory syndrome). These non‐GFR determinants are the reason why no equation based on a single endogenous biomarker has an accuracy within 30% greater than 90% over the entire age spectrum (in at least one patient in 10, estimated GFR is at least 30% higher or at least 30% lower than the measured GFR). Conclusion: Equations combining the two biomarkers provide a better estimate of GFR, particularly in the subgroup of patients whose estimates based on each of the biomarkers are highly discordant. These patients must also be identified as being at increased risk of morbidity, particularly cardiovascular, and mortality. [ABSTRACT FROM AUTHOR]

Background: Renal dysfunction in patients with psoriasis is multifactorial and is seen more commonly with severe psoriasis, disease of long duration and psoriatic arthritis. Material and Method: Single-center cross-sectional observational study was conducted in tertiary care Medical College Hospital, Chennai, India to compared renal function parameters in patients with Psoriasis with psoriatic arthritis (PsA), psoriatic without psoriatic arthritis and control. Total of 60 adult patients, 20 in each group, those with psoriasis having PsA; psoriasis without PsA and control were included. Blood urea, Serum creatinine, Urine albumin, and 24-hour urine protein were done and values analyzed. Results: Prevalence of psoriatic arthritis was greater in males. Patients with psoriatic arthritis had statistically significant elevation in serum creatinine, urine albumin and 24-hour urine protein. There was no statistically significant elevation of blood urea level in patients with psoriasis having psoriatic arthritis. Conclusion: Serum creatinine, urine albumin and 24-hour urine protein maay be considered as parameters which can be done for adult psoriasis patients as a screening test to suspect PsA. Early detection of PsA and appropriate management can help prevent crippling of joints and patients with renal involvement may be helped with precision therapy in future. [ABSTRACT FROM AUTHOR]

Background: Patients with stage 3-4 chronic kidney disease (CKD) are at high risk for cardiovascular complications. Sodium restriction is commonly recommended for blood pressure control and reducing cardiovascular events, but its broader effects on other outcomes in CKD are not well studied. Objective: This study aims to evaluate the impact of dietary sodium restriction on cardiovascular outcomes, including blood pressure, left ventricular hypertrophy (LVH), hospitalizations due to heart failure, kidney function, and quality of life in patients with stage 3-4 CKD. Methods: A total of 150 patients with stage 3-4 CKD were enrolled in this 12-month observational study. Seventy-five patients followed a sodium-restricted diet (= 2.3 g/day), while 75 patients adhered to a standard diet (> 2.3 g/day). Key outcomes measured included changes in blood pressure, LVH regression, hospitalization rates due to heart failure, estimated glomerular filtration rate (eGFR), electrolyte levels, and quality of life (QoL). Results: Patients on the sodium-restricted diet had significant reductions in systolic (12 mmHg) and diastolic (8 mmHg) blood pressure compared to the standard diet group (p < 0.001 and p < 0.01, respectively). LVH regression was more prevalent in the sodiumrestricted group (20% vs. 8%, p = 0.02). Hospitalization rates for heart failure were significantly lower in the sodium-restricted group (6.7% vs. 20%, p = 0.004), with shorter hospital stays (4 vs. 7 days, p = 0.03). Kidney function declined more slowly in the sodium-restricted group (eGFR: 4.5 vs. 6.8 mL/min/1.73 m², p = 0.03). QoL scores improved by 15% in the sodium-restricted group (p < 0.01). Conclusion: Sodium restriction in CKD patients significantly improves cardiovascular outcomes, slows kidney function decline, and enhances quality of life. [ABSTRACT FROM AUTHOR]

Background: The use of continuous infusion or IV boluses to treat acute decompensated heart failure (ADHF) with loop diuretics is still debatable. Aim and Objective: To evaluate differences between the two administration routes on the thoracic fluid content (TFC) and the renal functions. Methods: Sixty patients with ADHF admitted to the critical care medicine department, Saifee Hospital, Mumbai, were initially enrolled in the study. Twenty patients were excluded due to EF > 40%, myocardial infarction within 30 days, and baseline serum creatinine level > 4.0 mg/dL. Furosemide (120 mg/day) was given to the remaining 50 pts who continued the study after 1:1 randomization to either continuous infusion (group-I, 25 pts) or three equal intermittent daily doses (group-II, 25 pts). Subsequent dose titration was allowed after 24 h, but not earlier, according to patient's response. No other diuretic medications were allowed. All patients were daily evaluated for NYHA class, urine output, TFC, body weight, serum K+, and renal chemistry. Results: The mean and SD age (Q1-Q3) was 55.95±5.27years old with 28 (56%) males. Apart from TFC which was significantly higher in group-I, the admission demographic, clinical, laboratory and comorbid conditions were similar in both groups. There was statistically insignificant tendency for increased urine output during the 1st and 2nd days in group-I compared to group-II (p = .08). The mean and SD values of TFC on admission were high for all patients 66.52±6.84 kΩ-1 compared to normal range of 25-35 kΩ-1 [20] reflecting pulmonary congestion. In both groups, the TFC was significantly reduced after 24 h of furosemide therapy compared to baseline. It decreased from 1 to 66.52±6.84 kΩ-1 in group I (P = <0.001) and from 51±7.65kΩ-1 to 50.5 (41-60.8) in group II (P = .001). The admission TFC values were significantly higher in group I compared to group II (P = .0001). Conclusions: Continuous furosemide infusion in ADHF patients may result in increased diuresis and decreased TFC, but at the expense of a higher risk of renal function degradation and a lack of symptom relief or shorter ICU stays. [ABSTRACT FROM AUTHOR]

Acute kidney injury (AKI) is a cluster of clinical syndromes with diverse etiologies that ultimately result in a swift decline in kidney function. Regrettably, AKI lacks effective therapeutic agents at present. Neferine, a bioactive alkaloid derived from Lotus Plumule, has been reported to alleviate AKI triggered by cisplatin, ischemia/reperfusion (I/R), and sepsis by inhibiting inflammatory pathways. However, the precise molecular mechanisms underpinning its renoprotective effects remain elusive. Peroxisome proliferator-activated receptor alpha (PPAR-α), a regulator of lipid metabolism with anti-inflammatory properties, was investigated in this study to examine its role in neferine's renoprotective effects in cellular and mouse models of AKI. We found that neferine pretreatment in both I/R- or lipopolysaccharide (LPS)-induced AKI models inhibited the activation of the NF-κB inflammatory pathway and reversed PPAR-α deficiency. In NRK-52E cells exposed to hypoxia/reoxygenation (H/R) or LPS, overexpression of PPAR-α resulted in inhibition of the NF-κB pathway and TNF-α production, while PPAR-α silencing via siRNA transfection negated neferine's anti-inflammatory effects. Furthermore, pretreatment with neferine not only reduced lipid accumulation but also reversed the downregulation of FAO-related enzymes induced by LPS. Our findings suggest that neferine's renoprotective effects against AKI are partially mediated through the reversal of renal PPAR-α deficiency and subsequent inhibition of the inflammatory NF-κB pathway. Therefore, regulating renal PPAR-α expression by neferine could represent a promising therapeutic strategy for AKI. [ABSTRACT FROM AUTHOR]

Due to changes in pharmacokinetics and pharmacodynamics, patients with impaired renal function suffer an increased risk of suboptimal and potentially harmful medication treatment. This necessitates careful consideration of medications affected by impaired renal function when performing medication reviews. The aim of this study was to develop a quick guide (a list of recommendations) for assessing renal risk medications in medication reviews led by hospital pharmacists. The list was based on the 100 most frequently used medications in Danish hospitals and primary care. After combining the 200 records, 29 duplicates were excluded resulting in a pool of 171 medications. Assessment by two clinical pharmacists led to the exclusion of 121 medications. Of the remaining 50 medications, seven were discussed among the two pharmacists, and two of these were also in the research group to reach a consensus. The renal risk quick guide comprised 50 medications. The most prevalent medications on the list were from Anatomical Therapeutic Chemical Classification System (ATC)‐group N, C and L. Recommendations from two databases were included in the quick guide in order to provide clinical pharmacists with existing, updated evidence on medication use in impaired renal function. The next step is to test the feasibility of the quick guide in daily practice when performing medication reviews. [ABSTRACT FROM AUTHOR]

Objective: To assess the predictive abilities of Doppler‐based resistive index and plasma biomarkers of endothelial cell activation in identifying persistent acute kidney injury (pAKI) among patients with septic shock. Method: Patients diagnosed with septic shock were categorized into none AKI (n = 25), transient AKI (tAKI, n = 47), and pAKI (n = 48) groups. Kidney function parameters (urine output, serum creatinine, and serum urea) were measured within the initial 24 h upon intensive care unit (ICU) admission. The Doppler‐based resistive index, and the plasma biomarkers [fractalkine, soluble E‐Selectin (sE‐Selectin), and soluble intercellular adhesion molecule‐1 (sICAM‐1)] were evaluated upon admission to the ICU. Results: The predictive capacity of Doppler‐based resistive index for distinguishing pAKI at day 3 from none AKI/tAKI in septic shock patients was moderate, with sensitivity of 47.92% and specificity of 76.39%. Fractalkine levels displayed significant differences across groups and exhibited a favorable predictive ability for pAKI at day 3 (AUC = 0.800), while sE‐Selectin and sICAM‐1 showed moderate predictive abilities (AUC = 0.636 and 0.634, respectively). Comparative analysis of predictive models demonstrated that incorporating kidney function parameters, Doppler‐based resistive index, and plasma biomarkers yielded the highest AUC of 0.903, followed closely by the model utilizing serum creatinine, urine output, and plasma fractalkine, with an AUC of 0.896. Conclusion: Integrating kidney function parameters, along with Doppler‐based resistive index and plasma biomarkers of endothelial cell activation, yielded the strongest predictive model for pAKI. Additionally, the combination of serum creatinine, urine output, and plasma fractalkine shows promise in risk assessment and management strategies for pAKI. [ABSTRACT FROM AUTHOR]

Objective: To characterize our single institutional experience with robotic and open uretero-enteric stricture (UES) repair. Materials and Methods: We queried our ureteral reconstructive database for UES repair between 01/2017 and 10/2023. Patients with <3 months follow-up were excluded. Prior to surgery, patients underwent ureteral rest (4 weeks) with conversion to nephrostomy tube. Clinical characteristics, complications, reconstructive success (uretero-enteric patency), need for repeat intervention, and renal function were assessed in patients undergoing open and robotic UES reconstruction. Results: Of 50 patients undergoing UES repair during the study period, 45 were included for analysis due to complete follow-up (34 [76%] robotic and 11 [24%] open repair). UES repair was performed in 50 renal units a median of 13 months (interquartile range 7–30) from index surgery, and most often involved the left renal unit (34/50; 68%). Compared with robotic, open cases were significantly more likely to have undergone open cystectomy (100% vs 68%, p = 0.04), have longer strictures (median 4 vs 1 cm, p < 0.001), require tissue substitution (27% vs 3%, p = 0.04), and have lengthier postoperative hospitalization (5 vs 2 days, p < 0.001). There was no significant difference in total operative time (410 vs 322 minutes) or 30d major complications (18% vs 21%). At a follow-up of 13 months, per patient reconstructive success was 100% (11/11) for open and 97% (33/34) for robotic, respectively. Conclusion: In select patients with short UES unlikely to require advanced reconstructive techniques, a robotic-assisted approach can be considered. Careful patient selection is associated with limited morbidity and high reconstructive success. [ABSTRACT FROM AUTHOR]