Search

Background: Diabetic kidney disease (DKD) is the main cause of end-stage renal disease and has a high mortality rate. Currently, no effective treatments are available to reduce the progression of kidney damage associated with diabetes. Objectives: To explore the influence and predictive value of the atherogenic index of plasma (AIP) on early chronic kidney disease and liver injury in patients with type 2 diabetes mellitus (T2DM). Methods: Medical records of 1057 hospitalized adult patients with T2DM between January 2021 and December 2022 were collected. The predictive value of AIP, renal function, and liver injury in patients with T2DM were analyzed using Pearson's correlation, multiple logistic regression, and receiver operating characteristic (ROC) curve analyses. Results: AIP was a sensitive indicator of early liver and kidney injury in patients with T2DM. Patients in the DKD group showed increased AIP that positively correlated with serum creatinine, uric acid, and β2-microglobulin levels. Increased AIP negatively correlated with estimated glomerular filtration rate (eGFR). AIP significantly correlated with alanine aminotransferase and aspartate aminotransferase levels and glutamyl transpeptidase-to-platelet ratio (GPR). An eGFR of 60-100 mL/min/1.73 m2 significantly increased the risk of DKD as the AIP increased. At lower GPR levels, the risk of DKD significantly increased with increasing AIP. However, no significant difference was found between the 2 groups when the GPR was >0.1407. The ROC curve analysis showed that AIP could predict early liver injury. Conclusions: AIP is directly involved in early liver and kidney injury in T2DM and may be a sensitive indicator for early detection. Plain Language Summary: Diabetes and its complications are a global public health concern. Diabetic kidney disease (DKD) is the main cause of end-stage renal disease, and metabolism-related disease factors are found throughout the progression of DKD. This study identified common sensitive indicators of early metabolism-related damage to liver and kidney function in patients with T2DM. [ABSTRACT FROM AUTHOR]

Background: The aim of the study was to develop a technique for quantitative determination of rat urine metabolites by HPLC–MS/MS, which can be used to search for biomarkers of acute intoxication with organophosphates (OPs). Results: The content of metabolites in the urine of rats exposed to a single dose of paraoxon (POX1x); interval, twice daily administration of paraoxon (POX2x); exposure to 2-(o-cresyl)-4H-1, 3, 2-benzodioxaphosphorin-2-oxide and paraoxon (CBPOX) was investigated. New data were obtained on the content in the urine of intact rats as well as rats in 3 models of OP poisoning: 3-methylhistidine, threonine, creatine, creatinine, lactic acid, acetylcarnitine, inosine, hypoxanthine, adenine, 3-hydroxymethyl-butyrate and 2-hydroxymethyl-butyrate. Conclusions: The proposed assay procedure is a simple and reliable tool for urine metabolomic studies. Within 1–3 days after OP exposure in all three models of acute intoxication, the concentration of metabolites in rat urine, with the exception of adenine, changes similarly and symmetrically, regardless of the method of poisoning modeling, in all three models of acute intoxication. Further studies are needed to determine the specificity and reliability of using urinary metabolite concentration changes as potential biomarkers of acute organophosphate intoxication. [ABSTRACT FROM AUTHOR]

Background: Diabetic nephropathy (DN) is a life-threatening renal disease and needs urgent therapies. Wogonin is renoprotective in DN. This study aimed to explore the mechanism of how wogonin regulated high glucose (HG)-induced renal cell injury. Methods: Diabetic mice (db/db), control db/m mice, and normal glucose (NG)- or HG-treated human tubule epithelial cells (HK-2) were used to evaluate the levels of suppressor of cytokine signaling 3 (SOCS3), Toll-like receptor 4 (TLR4), inflammation and fibrosis. Lentivirus was used to regulate SOCS3 and TLR4 expressions. After oral gavage of wogonin (10 mg/kg) or vehicle in db/db mice, histological morphologies, blood glucose, urinary protein, serum creatinine values (Scr), blood urea nitrogen (BUN), superoxide dismutase (SOD), glutathione (GSH), and reactive oxygen species (ROS) were assessed. RT-qPCR and Western blot evaluated inflammation and fibrosis-related molecules. Results: HG exposure induced high blood glucose, severe renal injuries, high serumal Src and BUN, low SOD and GSH, and increased ROS. HG downregulated SOCS3 but upregulated TLR4 and JAK/STAT, fibrosis, and inflammasome-related proteins. Wogonin alleviated HG-induced renal injuries by decreasing cytokines, ROS, Src, and MDA and increasing SOD and GSH. Meanwhile, wogonin upregulated SOCS3 and downregulated TLR4 under HG conditions. Wogonin-induced SOCS3 overexpression directly decreased TLR4 levels and attenuated JAK/STAT signaling pathway-related inflammation and fibrosis, but SOCS3 knockdown significantly antagonized the protective effects of wogonin. However, TLR4 knockdown diminished SOCS3 knockdown-induced renal injuries. Conclusion: Wogonin attenuates renal inflammation and fibrosis by upregulating SOCS3 to inhibit TLR4 and JAK/STAT pathway. [ABSTRACT FROM AUTHOR]

Biomarkers that accurately reflect renal function are essential in management of chronic kidney diseases (CKD). However, in children, age/physique and medication often alter established renal biomarkers. We studied whether amino acid enantiomers in body fluids correlate with renal function and whether they are influenced by physique or steroid medication during development. We conducted a prospective study of children 2 to 18 years old with and without CKD. We analyzed associations of serine/asparagine enantiomers in body fluids with major biochemical parameters as well as physique. To study consequences of kidney dysfunction and steroids on serine/asparagine enantiomers, we generated juvenile mice with uninephrectomy, ischemic reperfusion injury, or dexamethasone treatment. We obtained samples from 27 children, of which 12 had CKD due to congenital (n = 7) and perinatal (n = 5) causes. Plasma d-asparagine and the d/l-serine ratio had robust, positive linear associations with serum creatinine and cystatin C, and detected CKD with high sensitivity and specificity, uninfluenced by body size or biochemical parameters. In the animal study, kidney dysfunction increased plasma d-asparagine and the d/l-serine ratio, but dexamethasone treatment did not. Thus, plasma d-asparagine and the d/l-serine ratio can be useful markers for renal function in children. [ABSTRACT FROM AUTHOR]

Objective This study aimed to establish prediction models for respiratory-related mortality in microscopic polyangiitis (MPA) complicated by interstitial lung disease (ILD) using clinical characteristics. Methods We enrolled patients with MPA with ILD between May 2005 and June 2021 in a multicentre cohort of Japanese patients with MPA (REVEAL cohort). We evaluated the demographic, clinical, laboratory, radiological findings, treatments and the presence of honeycombing 1 cm above the diaphragm using chest high-resolution CT (HRCT) on admission. We explored the risk factors predictive of respiratory-related mortality. Results Of 115 patients, 26 cases died of respiratory-related diseases during a median follow-up of 3.8 years. Eighteen patients (69%) died due to respiratory infection, three (12%) had diffuse alveolar haemorrhage, and five (19%) had exacerbation of ILD. In univariate analysis, older age, lower percent forced vital capacity (%FVC), lower percent diffusing capacity of carbon monoxide (%DLCO), and the presence of honeycombing in the right lower lobe were identified as risk factors. Additionally, in multivariate analysis adjusted for age and treatment, %FVC, %DLCO and the presence of honeycombing in the right lower lobe were independently associated with respiratory-related mortality. We created prediction models based on the values of %FVC, %DLCO and presence of honeycombing on chest HRCT (termed "MPF model"). The 5-year respiratory-related death-free rate was significantly different between patients with MPA with ILD stratified by the number of risk factors based on the MPF model. Conclusions Our study indicates that the MPF model may help predict respiratory-related death in patients with MPA with ILD. [ABSTRACT FROM AUTHOR]

Aim: The serum creatinine/cystatin C ratio (CCR) or sarcopenia index is considered a useful marker of muscle mass. However, its usefulness in late‐stage older adults remains unclear. We aimed to determine the usefulness of CCR as an indicator of sarcopenia in community‐dwelling Japanese adults aged >75 years. Methods: Our study recruited participants aged 70, 80, and 90 ± 1 years during the baseline years, and included a 3‐year follow‐up in the Septuagenarians, Octogenarians, Nonagenarians, Investigation with Centenarians study. From 2015 to 2018, 955 participants were eligible: 367 in their 70s, 304 in their 80s, and 284 in their 90s. The diagnostic components of sarcopenia, including "low muscle mass, plus low muscle strength, and/or low physical performance," were evaluated using the bioelectrical impedance analysis‐measured skeletal muscle mass index (SMI), handgrip strength, and short physical performance battery (SPPB) score, respectively, in accordance with the Asia Working Group for Sarcopenia 2019 criteria. Separate analyses were performed between each component and CCR, adjusting for sex, body mass index, and other blood biomarkers in each group. Results: The relationship between CCR and sarcopenia components was significant for handgrip strength (β = 0.21, 0.13, 0.19, and P < 0.0001, =0.0088, <0.0001, for the 70s, 80s, and 90s age groups, respectively); however, it was limited for SMI (β = 0.14; P = 0.0022, only for the 90s) and not significant for the SPPB score. Conclusion: CCR is a limited indicator of sarcopenia in late‐stage older adults. Although its association with muscle strength was significant, its relationship with muscle mass and physical performance was less pronounced. Geriatr Gerontol Int 2024; 24: 529–536. [ABSTRACT FROM AUTHOR]

Background: Patients with anemia have poorer outcomes following cardiac surgery than do those without anemia. To improve outcomes, the Enhanced Recovery After Surgery cardiac recommendations include optimizing patients' condition, including treating anemia, before surgery. Local Problem: Despite implementing Enhanced Recovery After Surgery initiatives, a midwestern cardiothoracic surgery group recognized a care gap in preoperative patients with anemia. No standardized protocol was in use. Methods: An anemia optimization protocol was developed for perioperative care of patients with anemia. Data from retrospective medical record review were analyzed to determine relationships between protocol use and secondary outcomes. The protocol was created using best evidence and expert consensus. Cardiac surgery and hematology specialists revised the protocol and agreed on a final version. The protocol was integrated into the consultation process for cardiac surgery patients. Results: During the implementation period, 23 of 55 patients with anemia (42%) received interventions via the anemia optimization protocol. The mean quantity of packed red blood cells transfused perioperatively per patient was 1.9 U in the protocol group and 3.5 U in the nonprotocol group. In the subgroup of patients experiencing postoperative acute kidney injury, the mean increase in creatinine level was 0.65 mg/dL in the protocol group and 1.52 mg/dL in the nonprotocol group. Four patients in the protocol group (17%) and 6 patients in the nonprotocol group (19%) experienced postoperative acute kidney injury. Conclusion: Preoperative anemia is associated with poorer cardiac surgical outcomes. Incorporating the anemia optimization protocol into practice may mitigate the risk of postoperative complications for patients with anemia. Continued use of the protocol is recommended. [ABSTRACT FROM AUTHOR]

Background: The mortality rate of pediatric patients who require continuous renal replacement therapy is approximately 42%, and outcomes vary considerably depending on underlying disease, illness severity, and time of dialysis initiation. Delay in the initiation of such therapy may increase mortality risk, prolong intensive care unit stay, and worsen clinical outcomes. Local Problem: In the pediatric intensive care unit of an urban level I trauma children's hospital, continuous renal replacement therapy initiation times and factors associated with delays in therapy were unknown. Methods: This quality improvement process involved a retrospective review of data on patients who received continuous dialysis in the pediatric intensive care unit from January 1, 2017, to December 31, 2021. The objectives were to examine the characteristics of the children requiring continuous renal replacement therapy, therapy initiation times, and factors associated with initiation delays that might affect unit length of stay and mortality. Results: During the study period, 175 patients received continuous renal replacement therapy, with an average initiation time of 11.9 hours. Statistically significant associations were found between the degree of fluid overload and mortality (P <.001) and between the presence of acute kidney injury and prolonged length of stay (P =.04). No significant association was found between therapy initiation time and unit length of stay or mortality, although the average initiation time of survivors was 5.9 hours shorter than that of nonsurvivors. Conclusion: Future studies are needed to assess real time delays and to evaluate if the implementation of a standardized initiation process decreases initiation time. [ABSTRACT FROM AUTHOR]

The goal of this study was to evaluate whether topical administration of tacrolimus (TAC) and mycophenolic acid (MPA) at the transplant site enables vascularized composite allograft (VCA) survival with significant minimization of the dose and adverse effects of systemic TAC (STAC) immunosuppression. Lewis (Lew) rats received orthotopic hind limb allotransplants from fully mismatched Brown Norway (BN) donors. Group 1 (Controls) received no treatment. Other groups were treated with STAC at a dose of 1 mg/kg/day for 7 days. On post-operative day (POD) 8, the STAC dose was dropped to 0.1 mg/kg/day for Group 2 and maintained at 1 mg/kg for Group 3. Group 4 received topical application of TAC and MPA on the transplanted (Tx) limb starting POD 8 without STAC. Group 5 received topical TAC and MPA on the contralateral non-Tx limb and Group 6 received topical TAC and MPA on the Tx limb starting POD 8 along with low dose STAC (0.1 mg/kg/day). Treatment was continued until the study end point was reached, defined as either grade 3 rejection or allograft survival exceeding 100 days..We conducted sequential LC-MS/MS measurements to assess TAC and MPA concentrations in both blood/plasma and allograft tissues. Additionally, we evaluated markers indicative of organ toxicity associated with STAC immunosuppression. Compared to controls, topical therapy with TAC+MPA significantly prolonged allograft survival beyond 100 daysat very low dose STAC (0.1 mg/kg/day) (Group 6). The histopathological assessment of the grafts was consistent with the clinical outcomes..Drug levels in blood/plasma remained low or undetectable, while allograft tissues showed higher drug concentrations compared to contralateral limb tissues (P <0.05).. Urinary creatinine clearance remained within the normal range at 2.5 mL/min. Combination therapy with topical TAC and MPA synergizes with a very low dose, corticosteroid- free-STAC regimen and facilitates rejection-free, prolonged VCA survival without morbidity. [ABSTRACT FROM AUTHOR]

Background: This study evaluated urinary sphingolipids as a marker of diabetic kidney disease (DKD) in adolescents and young adults with youth-onset type 1 and type 2 diabetes. Methods: A comprehensive panel of urinary sphingolipids, including sphingomyelin (SM), glucosylceramide (GC), ceramide (Cer), and lactosylceramide (LC) species, was performed in patients with youth-onset diabetes from the SEARCH for Diabetes in Youth cohort. Sphingolipid levels, normalized to urine creatinine, were compared in 57 adolescents and young adults with type 1 diabetes, 59 with type 2 diabetes, and 44 healthy controls. The association of sphingolipids with albumin-to-creatinine (ACR) ratio and estimated glomerular filtration rate (eGFR) was evaluated. Results: The median age (interquartile range [IQR]) of participants was 23.1 years (20.9, 24.9) and the median duration of diabetes was 9.3 (8.5, 10.2) years. Urinary sphingolipid concentrations in patients with and without DKD (ACR ≥ 30 mg/g) were significantly elevated compared to healthy controls. There were no significant differences in sphingolipid levels between participants with type 1 and type 2 diabetes. In multivariable analysis, many sphingolipid species were positively correlated with ACR. Most significant associations were evident for the following species: C18 SM, C24:1 SM, C24:1 GC, and C24:1 Cer (all p < 0.001). Sphingolipid levels were not associated with eGFR. However, several interaction terms (diabetes type*sphingolipid) were significant, indicating diabetes type may modify the association of sphingolipids with eGFR. Conclusion: Urinary sphingolipids are elevated in adolescents and young adults with youth-onset diabetes and correlate with ACR. Urinary sphingolipids may therefore represent an early biomarker of DKD. [ABSTRACT FROM AUTHOR]

Background: We aimed to examine temporal changes in the annual rate of acute kidney injury (AKI) in Danish children and associated changes in patient characteristics including potential underlying risk factors. Methods: In this population-based cohort study, we used plasma creatinine measurements from Danish laboratory databases to identify AKI episodes in children aged 0–17 years from 2007 to 2021. For each child, the first AKI episode per calendar year was included. We estimated the annual crude and sex- and age-standardized AKI rate as the number of children with an AKI episode divided by the total number of children as reported by census numbers. Using Danish medical databases, we assessed patient characteristics including potential risk factors for AKI, such as use of nephrotoxic medication, surgery, sepsis, and perinatal factors. Results: In total, 14,200 children contributed with 16,345 AKI episodes over 15 years. The mean annual AKI rate was 148 (95% CI: 141–155) per 100,000 children. From 2007 to 2021, the annual AKI rate demonstrated minor year-to-year variability without any discernible overall trend. The highest AKI rate was recorded in 2007 at 174 (95% CI: 161–187) per 100,000 children, while the lowest rate occurred in 2012 at 129 (95% CI: 118–140) per 100,000 children. In 2021, the AKI rate was 148 (95% CI: 141–155) per 100,000 children. Characteristics of children with AKI were similar throughout the study period. Conclusion: The rate of AKI among Danish children was stable from 2007 to 2021 with little variation in patient characteristics over time. [ABSTRACT FROM AUTHOR]

Background: Sodium-glucose cotransporter 2 inhibitors (SGLT2i) have been shown to improve outcomes in patients with heart failure (HF) and are now included in guideline-directed medical therapy. Trials reporting the change in loop diuretic dose following SGLT2i initiation have indicated conflicting results. There is no clear guidance on whether reducing loop diuretic doses following SGLT2i initiation is appropriate. Objective: The purpose of this study is to assess the impact of SGLT2i initiation on diuretic adjustment in hospitalized patients with known or new HF. Methods: This was a retrospective, single health-system study assessing the change in loop diuretic dose in the 60 days following discharge for patients with HF initiated on SGLT2i therapy during a hospital admission or upon discharge. Secondary outcomes assessed effect on renal function and discontinuation of SGLT2i within the 60 day follow up period. Results: Forty percent of patients required loop diuretic dose adjustment, with 29% requiring a dose reduction within the 60 days following discharge. There was minimal change in serum creatinine or blood urea nitrogen. The SGLT2i was discontinued in 6 patients. Conclusions: After inpatient initiation of SGLT2is, approximately one-third of patients required a reduction in loop diuretic dose within 60 days following hospital discharge. Further study is recommended to confirm if empiric diuretic dose adjustments are appropriate in this HF population. [ABSTRACT FROM AUTHOR]

Objective: MODY (maturity onset diabetes of the young) is a rare, monogenic, autosomal dominant form of diabetes occurring in young (< 25 years) individuals. It has a wide phenotypic variability and can be misdiagnosed as type 1 diabetes mellitus (T1DM). Appropriate detection of MODY has therapeutic and genetic implications. This study aimed to detect MODY among long standing, clinically diagnosed T1DM patients with preserved C-peptide levels. Methods: This was a hospital-based cross-sectional study from central South India which included 100 clinically diagnosed T1DM patients (according to ADA criteria), with a duration of > 3 years. MODY probability score, urinary C-peptide to creatinine ratio (UCPCR), and relevant biochemical investigations were performed. Targeted next-generation sequencing (NGS) for MODY-related genes (13 genes) was done for individuals with UCPCR > 0.2. Results: A UCPCR value of > 0.2 (suggestive of preserved endogenous insulin secretion) was observed in eight individuals. The mean HbA1c values were lower, and the MODY probability score was higher in individuals with preserved endogenous insulin (8.07% vs 9.53% and 2.8% vs 1.5%; p-value: 0.005 and 0.004 respectively). One of the eight individuals (12.5%) had a non-pathogenic gene variant in KLF11. Conclusion: In a South Indian cohort of T1DM with preserved C-peptide, we could not find any case of MODY through targeted NGS. UCPCR can be used as a screening tool to identify cases needing genetic testing for MODY. Larger studies utilizing whole exome sequencing should be conducted to know the actual prevalence of MODY among T1DM. [ABSTRACT FROM AUTHOR]

Background: Type 2 diabetes exposes the body to a state of high blood sugar for a long time and causes varying degrees of hardening of the arteries, making it more prone to cardiovascular emergencies. Objective: The aim of the study was to explore the risk factors of early arterial stiffness in patients with type 2 diabetes mellitus (T2DM). Methods: A retrospective study was conducted on 316 T2DM patients without macroangiopathy in The First Hospital of Qinhuangdao. Early arterial stiffness was evaluated by brachial-ankle pulse wave velocity (baPWV). Results: Ninety patients (28.5%) had baPWV≥1800cm/s. baPWV showed positive correlation with systolic blood pressure (r=0.456, p<0.001), diastolic blood pressure (r=0.133, p=0.018), urine albumin-creatinine ratio (UACR) (r=0.232, p<0.001), neutrophil lymphocyte ratio (NLR) (r=0.185, p=0.001), and visceral fat area (r=0.139, p=0.014). In multiple linear regression analysis, systolic blood pressure (β=6.240, p<0.001), UACR (β=3.805, p=0.019), NLR (β=43.722, p=0.013), and visceral fat area (β=0.778, p=0.030) were significant independent predictors for baPWV. Conclusion: The decline of arterial elasticity was common in T2DM patients without macroangiopathy. Elevated blood pressure, microangiopathy, chronic inflammation, and visceral fat accumulation were the risk factors of early arterial stiffness in patients with T2DM. [ABSTRACT FROM AUTHOR]

OBJECTIVES: Accurate glomerular filtration rate (GFR) assessment is essential in critically ill patients. GFR is often estimated using creatinine-based equations, which require surrogates for muscle mass such as age and sex. Race has also been included in GFR equations, based on the assumption that Black individuals have genetically determined higher muscle mass. However, race-based GFR estimation has been questioned with the recognition that race is a poor surrogate for genetic ancestry, and racial health disparities are driven largely by socioeconomic factors. The American Society of Nephrology and the National Kidney Foundation (ASN/NKF) recommend widespread adoption of new "race-free" creatinine equations, and increased use of cystatin C as a race-agnostic GFR biomarker. DATA SOURCES: Literature review and expert consensus. STUDY SELECTION: English language publications evaluating GFR assessment and racial disparities. DATA EXTRACTION: We provide an overview of the ASN/NKF recommendations. We then apply an Implementation science methodology to identify facilitators and barriers to implementation of the ASN/NKF recommendations into critical care settings and identify evidence-based implementation strategies. Last, we highlight research priorities for advancing GFR estimation in critically ill patients. DATA SYNTHESIS: Implementation of the new creatinine-based GFR equation is facilitated by low cost and relative ease of incorporation into electronic health records. The key barrier to implementation is a lack of direct evidence in critically ill patients. Additional barriers to implementing cystatin C-based GFR estimation include higher cost and lack of test availability in most laboratories. Further, cystatin C concentrations are influenced by inflammation, which complicates interpretation. CONCLUSIONS: The lack of direct evidence in critically ill patients is a key barrier to broad implementation of newly developed "race-free" GFR equations. Additional research evaluating GFR equations in critically ill patients and novel approaches to dynamic kidney function estimation is required to advance equitable GFR assessment in this vulnerable population. [ABSTRACT FROM AUTHOR]

Context The metabolic response to stress can deplete the remaining thiamine stores, leading to thiamine deficiency. Objective This study is the first meta-analysis of the effectiveness of thiamine supplementation on clinical and biochemical outcomes in adult patients admitted to the intensive care unit (ICU). Data Sources Scopus, PubMed, and Cochrane databases were searched to select studies up to 20 November 2022. Study Selection Studies investigating the effect of thiamine supplementation on serum lactate and creatinine levels, the need for renal replacement therapy, length of ICU stay, and mortality rate in ICU patients were selected. Data Extraction After excluding studies based on title and abstract screening, 2 independent investigators reviewed the full texts of the remaining articles. In the next step, a third investigator resolved any discrepancy in the article selection process. Results Of 1628 retrieved articles, 8 were selected for final analysis. This study showed that thiamine supplementation reduced the serum creatinine level (P =.03) compared with placebo. In addition, according to subgroup analysis, serum creatinine concentration was significantly lower in patients >60 years old (P < .00001). However, there was no statistically significant difference in the lactate level between the thiamine supplementation and placebo groups (P =.26). Thiamine supplementation did not decrease the risk of all-cause mortality (P =.71) or the need for renal replacement therapy (P =.14). The pooled results of eligible randomized controlled trials also showed that thiamine supplementation did not reduce the length of ICU stay in comparison to the placebo group (P =.39). Conclusion This meta-analysis provides evidence that thiamine supplementation has a protective effect against blood creatinine increase in ICU patients. However, further high-quality trials are needed to discover the effect of thiamine supplementation on clinical and biochemical outcomes in ICU patients. Systematic Review Registration PROSPERO no. CRD42023399710 (https://www.crd.york.ac.uk/prospero/display_record.php?RecordID=399710). [ABSTRACT FROM AUTHOR]

Aim: Early diagnosis of acute pancreatitis is crucial, and urinary trypsinogen has been recently reported as a useful biomarker for diagnosing acute pancreatitis. We aimed to evaluate the impact of renal dysfunction on the diagnostic performance of urinary trypsinogen‐2 for acute pancreatitis. Methods: We conducted a retrospective study using the clinical data of patients who visited the Department of Emergency and Critical Care at the University of Tokyo Hospital between 1 October, 2021, and 30 June, 2022. Patients with available data on qualitative urinary trypsinogen‐2 levels were identified. We compared the urinary trypsinogen‐2 levels among patients who were clinically diagnosed with acute pancreatitis. We further stratified the patients according to renal function parameters, such as serum creatinine level, blood urea nitrogen level, and estimated glomerular filtration rate, and evaluated the performance of urinary trypsinogen‐2 as a biomarker for acute pancreatitis. Results: Within 9 months, 35 patients were identified. Of them, 22 patients showed positive results and 13 showed negative results on the urinary trypsinogen‐2 test. The sensitivity, specificity, positive predictive value, and negative predictive value were 0.80, 0.40, 0.18, and 0.92, respectively. Based on the blood urea nitrogen level and estimated glomerular filtration rate, the prevalence of false‐positive results was significantly higher in patients with reduced renal function than in those with normal renal function. Conclusion: In patients with reduced renal function, the urinary trypsinogen‐2 qualitative test results might be interpreted with caution when used for diagnosing acute pancreatitis. [ABSTRACT FROM AUTHOR]

The determination of the appropriate initial dose for tacrolimus is crucial in achieving the target concentration promptly and avoiding adverse effects and poor prognosis. However, the trial‐and‐error approach is still common practice. This study aimed to establish a prediction model for an initial dosing algorithm of tacrolimus in patients receiving a lung transplant. A total of 210 lung transplant recipients were enrolled, and 26 single nucleotide polymorphisms (SNP) from 18 genes that could potentially affect tacrolimus pharmacokinetics were genotyped. Associations between SNPs and tacrolimus concentration/dose ratio were analyzed. SNPs that remained significant in pharmacogenomic analysis were further combined with clinical factors to construct a prediction model for tacrolimus initial dose. The dose needed to reach steady state tacrolimus concentrations and achieve the target range was used to validate model prediction efficiency. Our final model consisted of 7 predictors—CYP3A5 rs776746, SLCO1B3 rs4149117, SLC2A2 rs1499821, NFATc4 rs1955915, alanine aminotransferase, direct bilirubin, and hematocrit—and explained 41.4% variance in the tacrolimus concentration/dose ratio. It achieved an area under the receiver operating characteristic curve of 0.804 (95% confidence interval, 0.746‐0.861). The Hosmer‐Lemeshow test yielded a nonsignificant P value of.790, suggesting good fit of the model. The predicted dose exhibited good correlation with the observed dose in the early postoperative period (r = 0.748, P less than.001). Our study provided a genotype‐guided prediction model for tacrolimus initial dose, which may help to guide individualized dosing of tacrolimus in the lung transplant population in clinical practice. [ABSTRACT FROM AUTHOR]

Objective: To analyze the clinical characteristics, incidence, and distribution of drug-associated muscle adverse reactions (DAMAR) in real-world inpatients, to provide valuable references for clinical medication use. Methods: We conducted an automatic retrospective monitoring of inpatients from May 1, 2022, to April 30, 2023, to collect information on adverse drug reactions (ADR) of patients and conducted subsequent analyses. Results: Among 102,430 hospitalizations, 1106 cases of DAMARs were identified, yielding an incidence of 1.08%, including 125 cases of rhabdomyolysis at an incidence of 0.12%. Seventy-five percent of the patients experienced muscle adverse reactions within 5 days after taking medication, with a median elevated creatine kinase (CK) value of 420.4 IU/L. Risk factors of DAMAR include age ≥ 65, male sex, obesity, hypertension, hepatic and renal insufficiency, and anemia. No significant correlation was observed between the duration of surgery and CK elevation, while the surgical procedure itself had an impact. The 114 drugs associated were predominantly nervous system drugs, anti-infectives for systemic use, and cardiovascular system drugs, with levofloxacin, pregabalin, and parecoxib being the most frequently associated drugs. Conclusion: Healthcare professionals should be vigilant with patients exhibiting the identified risk factors. Monitoring creatine kinase and related indices when using myotoxic drugs is crucial to preventing serious adverse reactions, ultimately preserving patients' quality of life. [ABSTRACT FROM AUTHOR]

Objective The random urine protein-to-creatinine ratio (UPCR) is a screening test used for predicting clinically significant proteinuria (urine protein ≥ 300 mg) during pregnancy. No consensus exists on the optimal random UPCR cutoff for performing follow-up 24 hour urine (24H) total protein collection. We aim to evaluate the test performance of random UPCR in predicting proteinuria in a contemporary cohort. Study Design This was a retrospective cohort study of pregnant patients at our institution from 2014 to 2018 with a random UPCR and follow-up 24H protein collection. The primary analysis estimated the test characteristics (sensitivity, specificity, positive and negative predictive values) of using random UPCR for the detection of proteinuria defined as urine protein ≥300 mg on 24H protein collection. UPCR cutoffs from 0.10 to 0.30 mg/dL were evaluated, receiver operator characteristic (ROC) curve was constructed, and area under the curve (AUC) was determined. A secondary analysis examined the correlation between UPCR and 24H protein using least squares regression and Pearson correlation. Results Paired UPCR and 24H collection results were available for 1,120 patients. Mean gestational age at time of UPCR was 31.1 ± 5.1 weeks and 687 (61.3%) of patients had a 24H ≥300 mg. UPCR <0.10 mg/dL effectively excluded proteinuria ≥300 mg on 24H collection, while UPCR ≥0.18 mg/dL correctly classifies proteinuria with 91% sensitivity, 57% specificity, 77% positive predictive value, and 79% negative predictive value. UPCR ≥1.07 mg/dL had 100% specificity for 24 hour proteinuria. The area under ROC curve was 0.86. UPCR and 24H collection were highly correlated with a Pearson correlation coefficient of 0.85. After our institution lowered the threshold to obtain a 24H from UPCR ≥0.20 mg/dL to ≥0.10 mg/dL in May 2017, the percentage of patients meeting criteria for 24H collection increased from 57.8 to 84.4%. Conclusion The AUC and Pearson correlation suggest random UPCR is a high performance test for the prediction of proteinuria on 24H. Optimal test performance is dependent upon clinical consideration and upon the implications of the disease or condition. A random UPCR screen positive threshold of 0.18 mg/dL maximizes sensitivity to identify clinically significant proteinuria. Key Points Random urine protein to creatinine ratio is a high performance test for proteinuria. A random UPCR threshold of 0.18 mg/dL maximizes sensitivity to identify proteinuria. Optimal test performance is dependent on the disease or clinical condition. [ABSTRACT FROM AUTHOR]

Aim: To compare the risk of developing kidney outcomes with use of glucagon‐like peptide‐1 receptor agonists (GLP‐1RAs) versus use of sodium‐glucose cotransporter‐2 (SGLT2) inhibitors among individuals with diabetes. Materials and Methods: In this retrospective observational study, we analysed 12 338 individuals with diabetes who newly initiated SGLT2 inhibitors or GLP‐1RAs using data from the JMDC claims database. The primary outcome was change in the estimated glomerular filtration rate (eGFR), estimated using a linear mixed‐effects model. A 1:4 propensity‐score‐matching algorithm was used to compare the changes in eGFR between GLP‐1RA and SGLT2 inhibitor users. Results: After propensity‐score matching, 2549 individuals (median [range] age 52 [46–58] years, 80.6% men) were analysed (510 GLP‐1RA new users and 2039 SGLT2 inhibitor new users). SGLT2 inhibitor use was associated with a slower eGFR decline when compared with GLP‐1RA use (−1.41 [95% confidence interval −1.63 to −1.19] mL/min/1.73 m2 vs. −2.62 [95% confidence interval −3.15 to −2.10] mL/min/1.73 m2). Conclusions: Our analysis demonstrates the potential advantages of SGLT2 inhibitors over GLP‐1RAs in terms of kidney outcomes in individuals with diabetes. [ABSTRACT FROM AUTHOR]

Aims. This study aimed to analyze the effects of the surgery preparation time on patient outcomes. Background. Postoperative complications have a decisive effect on postoperative survival. The anesthesia time is a crucial determinant of such complications. Competent operating room nurses can shorten the surgery preparation time, which is the time from when anesthesia is first administered to the making of the surgical incision. The shortening of this preparation time can shorten the anesthesia time and may reduce postoperative complications. However, discussion of this preparation time is insufficient. Therefore, this study analyzed the effect of the surgery preparation time on patient outcomes. Methods. From electronic health records data, this retrospective cohort study used the data of 1,944 patients who had been immediately admitted to the ICU after their surgery between 2017 and 2020. The patients were divided into two groups: ≥30 minutes preparation time and <30 minutes preparation time groups. We performed chi-squared tests and t-tests to determine differences in preoperation, intraoperation, and postoperation characteristics of the patients and patient outcomes based on the surgery preparation time. Furthermore, we performed a multiple logistic regression by including 12 adjusted variables to determine the influence of the surgery preparation time on patient outcomes. Results. Among the 1,944 patients, 820 were in the ≥30 minutes preparation time group and 1,124 in the <30 minutes preparation time group. The multiple logistic regression analysis showed that the surgery preparation time affects alertness (OR = 1.44; 95% CI: [1.09, 1.90]), ventilator application (OR = 1.32; 95% CI: [1.03, 1.70]), and length of stay in the ICU (OR = 1.69; 95% CI [1.16, 2.47]). Conclusions. The surgery preparation time affects postoperative patient outcomes. The competence of operating room nurses is the most essential aspect of the surgery preparation time. Implications for Nursing Management. It is important to analyze operating room nurses' tasks, standardize the tasks, and educate nurses according to their experience level to reduce the surgery preparation time and improve patient outcomes. [ABSTRACT FROM AUTHOR]

Background & objective: : While oxidative stress is the key player driving diabetic nephropathy (DN), firm glycemic control remains the pillar prophylactic measure. Purslane was extensively described as a potent hypoglycemic and hypolipidemic agent owing to its rich content of antioxidants. Therefore, this report aimed to assess the renoprotective potentials of methanol (MO) and methylene chloride (MC) fixed oil extracts of purslane seeds in a diabetic nephropathy (DN) model. Methods: Purslane seeds were extracted using absolute methanol and methylene chloride, and type-1 diabetes was induced with a single 55 mg/kg dose of Streptozotocin (STZ) dissolved in 100 mmol/L citrate buffer (pH 4.5), and then diabetic animals were received MO, MC, for 42 consecutive days to compare their antidiabetic effect relative to the reference drug "Losartan". Renal functions and DN biomarkers were weekly assessed, and the relative expression of different oxido-inflammatory mediators was quantified in diabetic kidneys by RT-PCR. Data were statistically analyzed using GraphPad Prism 9.0.2. Results: The oral administration of MO and MC extracts (250 mg/kg/day) significantly ameliorated the body weight loss (P < 0.0001 / each), fasting blood glucose levels (FBG) (P < 0.0001 / each), urine volume (P < 0.0001 / each), as well as serum creatinine (P < 0.0001 / each), uric acid (P = 0.0022, 0.0052), and blood urea nitrogen (BUN) (P = 0.0265, 0.0338); respectively, compared with the untreated diabetic rats. In addition, both extracts restored the effectuality of antioxidative machinery in diabetic kidneys as indicated by a significant reduction of ROS accumulation and lipid peroxidation; higher GSH content, and promoted activity of glutathione reductase and superoxide dismutase antioxidant enzymes (P < 0.0001 / each). Histologically, both extracts alleviated the DN-structural alterations including the glomerular congestion and tubular degeneration, with MC-treated kidneys showing near to normal architecture. The transcription profiles of all treated kidneys revealed a significantly downregulated expression of TNF-α, IL-6, Keap1 and NF-κB genes, concomitant with a significant upregulation of SDF-1, IL-10, Nrf2, HO-1, and PPARγ gene expression (P < 0.0001 / all). Conclusion: These findings highlight the remarkable DN-prophylactic potentials of purslane extracts mediated by neutralizing the hyperglycemia-induced ROS accumulation, and circumventing the downstream inflammatory cascades, surpassing the reference angiotensin receptor blocker; i.e. Losartan. [ABSTRACT FROM AUTHOR]

The meta-analysis is to evaluate the predictive value of the blood urea nitrogen / creatinine ratio (BCR) for long-term outcomes in patients with heart failure (HF). PubMed, EMBASE, the Cochrane library, and Web of Science were searched for relevant studies from inception to October 2023. STATA SE 14.0 software was used for statistical analysis. A total of 2036 reports were identified with 14 studies meeting pre-designed inclusion criteria. Three long-term outcomes were investigated. In patients with HF, the increase of BCR level indicated a greater risk of all-cause mortality (HR = 1.67, 95% CI 1.38–2.00; I2 = 90.8%, P = 0.000). The acute HF (AHF) subgroup demonstrated a higher risk of all-cause mortality (HR = 1.79, 95% CI 1.15–2.79; I2 = 93.9%, P = 0.000) as did the non-AHF subgroup (HR = 1.51, 95% CI 1.34–1.71; I2 = 37.1%, P = 0.122). The subgroup (≤ 70 years old) demonstrated a lower risk of all-cause mortality in patients with HF (HR = 1.62, 95% CI 1.35–1.94; I2 = 68.3%, P = 0.004) as did the subgroup (> 70 years old) (HR = 1.67, 95% CI 1.19–2.34; I2 = 88.3%, P = 0.000). In addition, this study did not support the predictive value of BCR in CVD mortality (HR = 1.48, 95% CI 0.91–2.43; I2 = 63%, P = 0.100) and HF hospitalization (HR = 1.28, 95% CI 0.73–2.24; I2 = 77.5%, P = 0.035). Sensitivity analysis showed that all the results were robust. In summary, the results showed that the blood urea nitrogen / creatinine ratio (BCR) had a significant predictive value for all-cause mortality in patients with heart failure and was a fairly promising predictor obviously. Moreover, more studies are needed to further determine the predictive value of BCR in other long-term outcomes such as CVD mortality, HF hospitalization or aborted cardiac arrest. [ABSTRACT FROM AUTHOR]

High cost, inherent destabilization, and intricate fixing of enzyme molecules are the main drawbacks of enzyme-based creatinine sensors. The design of a low-cost, stabilizable, and enzyme-free creatinine sensing probe is essential to address these limitations. In this work, an integrated three-dimensional (3D) free-standing electrode was designed to serve as a non-enzymatic creatinine sensing platform and was fabricated by rapid electrodeposition of a dense copper nanoparticle film on nickel foam (Cu NP film/NF). This low-cost, stable, easy-to-fabricate, and binder-free Cu NP film/NF electrode has abundant active sites and excellent electrochemical performance. Cyclic voltammetry measurements show a wide linear range (0.25–24 mM), low detection limit (0.17 mM), and high sensitivity (306 μA mM−1 cm−2). The developed sensor shows high recovery of creatinine concentration in real urine. Besides, it has better specificity, reproducibility, and robustness in detecting creatinine. These excellent results suggest that a non-enzymatic creatinine sensor based on an integrated 3D free-standing Cu NP film/NF electrode has good potential for non-invasive detection of urinary creatinine. [ABSTRACT FROM AUTHOR]

Rationale: Acute renal failure (ARF) is one of the most serious complications of cardiopulmonary bypass (CPB) surgery. Serum creatinine level is a key compound examined to understand whether renal function is normal. However, its level may vary based on age, gender, race, muscle mass, nutrition, and drugs taken by an individual. In addition, it may not be detected without a 50% reduction in renal function and may lead to delays in treatment. New markers are needed for early diagnosis of ARF. They were determined for early diagnosis of ARF after CPB. Metabolic differences in plasma samples of individuals who developed and did not develop ARF after cardiopulmonary bypass were determined. Methods: This study was the first to perform an untargeted metabolomics analysis for early diagnosis of ARF after CPB surgery. Plasma samples were taken from 105 patients (9 ARF patients) at five time points to identify the time at which a more accurate ARF diagnosis can be made. A total of 687 samples, including quality control samples, were analyzed. Results: Two hundred twenty‐six metabolites were identified using retention index libraries. Based on the statistical evaluations, tryptophan, threonine, and methionine were found in lower concentrations in patients with ARF compared to the control group at all time points. Whereas gluconic acid, hypoxanthine, and lactic acid showed a decreasing trend over time, longitudinal analysis showed that cysteine, hippuric acid, and uric acid levels increased over time in the ARF group. Conclusions: These metabolites are candidate biomarkers for early diagnosis of ARF as well as biomarkers for tracking the recovery of ARF patients. [ABSTRACT FROM AUTHOR]

Diabetes mellitus resulting from hyperglycemia stands as the primary cause of diabetic kidney disease. Emerging evidence suggests that plasma concentrations of soy isoflavones, substances with well-established antidiabetic properties, rise following supplemental inulin administration. The investigation encompassed 36 male Sprague–Dawley (SD) rats segregated into two cohorts: non-diabetic and diabetic, induced with type 2 diabetes (high-fat diet + two intraperitoneal streptozotocin injections). Each cohort was further divided into three subgroups (n = 6): control, isoflavone-treated, and isoflavone plus inulin-treated rats. Tail blood glucose and ketone levels were gauged. Upon termination, blood samples were drawn directly from the heart for urea, creatinine, and HbA1c/HbF analyses. One kidney per rat underwent histological (H-E) and immunohistochemical assessments (anti-AQP1, anti-AQP2, anti-AVPR2, anti-SLC22A2, anti-ACC-alpha, anti-SREBP-1). The remaining kidney underwent fatty acid methyl ester analysis. Results unveiled notable alterations in water intake, body and kidney mass, kidney morphology, fatty acids, AQP2, AVPR2, AcetylCoA, SREBP-1, blood urea, creatinine, and glucose levels in control rats with induced type 2 diabetes. Isoflavone supplementation exhibited favorable effects on plasma urea, plasma urea/creatinine ratio, glycemia, water intake, and kidney mass, morphology, and function in type 2 diabetic rats. Additional inulin supplementation frequently modulated the action of soy isoflavones. [ABSTRACT FROM AUTHOR]

Simple Summary: Despite the increased risk of developing renal cell carcinoma (RCC) in patients with advanced chronic kidney disease (ACKD), little is known about the patient clinical characteristics and genetic mutations found in these RCC tumors. Using a multi-institutional research network, this study compiled clinical records and somatic tumor whole exome sequencing data of 296 adult patients with RCC, 61 of whom had ACKD. Patients with RCC and ACKD were more likely to be male, present with earlier stage RCC at diagnosis, and have lower rates of BAP1 mutations. Median overall survival was not reached in either group over a median follow-up of 31.3 months. These findings suggest RCC in patients with ACKD develops via a BAP1-independent mutational driver and further support BAP1 loss as a marker of disease aggressiveness. Background: Patients with advanced chronic kidney disease (ACKD) are at an increased risk of developing renal cell carcinoma (RCC), but molecular alterations in RCC specimens arising from ACKD and overall survival (OS) in affected patients are not well defined. Patients and Methods: Using the Oncology Research Information Exchange Network (ORIEN) Total Cancer Care® protocol, 296 consented adult patients with RCC and somatic tumor whole exome sequencing were included. Patients with ACKD were defined as those with serum creatinine ≥1.5 mg/dL prior to RCC diagnosis. Results: Of 296 patients with RCC, 61 met the criteria for ACKD. The most common somatic mutations in the overall cohort were in VHL (126, 42.6%), PBRM1 (102, 34.5%), and SETD2 (54, 18.2%). BAP1 had a decreased mutational frequency in RCC specimens from patients without ACKD as compared to those with ACKD (10.6% versus 1.6%), but this was not statistically significant in univariable (OR 0.14, p = 0.056) or multivariable (OR 0.15, p = 0.067) analysis. Median OS was not reached in either cohort. Conclusions: Using the clinicogenomic ORIEN database, our study found lower rates of BAP1 mutations in RCC specimens from patients with ACKD, which may reflect a BAP1-independent mutational driver of RCC in patients with ACKD. [ABSTRACT FROM AUTHOR]

The age, creatinine, and ejection fraction (ACEF) score has been accepted as a predictor of poor outcome in elective operations. This study aimed to investigate the predictive value of ACEF score in acute type A aortic dissection (AAAD) patients after total arch replacement. A total of 227 AAAD patients from July 2021 and June 2022 were enrolled and divided into Tertiles 1 (ACEF ≤ 0.73), Tertiles 2 (0.73 < ACEF ≤ 0.95), and Tertiles 3 (ACEF > 0.95). Using inverse probability processing weighting (IPTW) to balance the baseline characteristics and compare the outcomes. Cox logistic regression was used to further evaluate the survival prediction ability of ACEF score. The in-hospital mortality was 9.8%. After IPTW, in the baseline characteristics reached an equilibrium, a higher ACEF score before operation still associated with higher in-hospital mortality. After 1 year follow-up, 184 patients (90.6%) survival. Multivariable analysis revealed that ACEF score (adjusted hazard ratio 1.68; 95% confidence interval 1.34–4.91; p = 0.036) and binary ACEF score (adjusted HR 2.26; 95% CI 1.82–6.20; p < 0.001) was independently associated with 1-year survival. In addition, net reclassification improvement (NRI) and integrated differentiation improvement (IDI) verified that the ACEF score and binary ACEF score is an accurate predictive tool in clinical settings. In conclusions, ACEF score could be considered as a useful tool to risk stratification in patients with AAAD before operation in daily clinical work. [ABSTRACT FROM AUTHOR]

High cost, inherent destabilization, and intricate fixing of enzyme molecules are the main drawbacks of enzyme-based creatinine sensors. The design of a low-cost, stabilizable, and enzyme-free creatinine sensing probe is essential to address these limitations. In this work, an integrated three-dimensional (3D) free-standing electrode was designed to serve as a non-enzymatic creatinine sensing platform and was fabricated by rapid electrodeposition of a dense copper nanoparticle film on nickel foam (Cu NP film/NF). This low-cost, stable, easy-to-fabricate, and binder-free Cu NP film/NF electrode has abundant active sites and excellent electrochemical performance. Cyclic voltammetry measurements show a wide linear range (0.25–24 mM), low detection limit (0.17 mM), and high sensitivity (306 μA mM−1 cm−2). The developed sensor shows high recovery of creatinine concentration in real urine. Besides, it has better specificity, reproducibility, and robustness in detecting creatinine. These excellent results suggest that a non-enzymatic creatinine sensor based on an integrated 3D free-standing Cu NP film/NF electrode has good potential for non-invasive detection of urinary creatinine. [ABSTRACT FROM AUTHOR]

Background: This study aimed to assess the anthropometric measures and pubertal growth of children and adolescents with Type 1 diabetes mellitus (T1DM) and to detect risk determinants affecting these measures and their link to glycemic control. Patients and methods: Two hundred children and adolescents were assessed using anthropometric measurements. Those with short stature were further evaluated using insulin-like growth factor 1 (IGF-1), bone age, and thyroid profile, while those with delayed puberty were evaluated using sex hormones and pituitary gonadotropins assay. Results: We found that 12.5% of our patients were short (height SDS < -2) and IGF-1 was less than -2 SD in 72% of them. Patients with short stature had earlier age of onset of diabetes, longer duration of diabetes, higher HbA1C and urinary albumin/creatinine ratio compared to those with normal stature (p < 0.05). Additionally, patients with delayed puberty had higher HbA1c and dyslipidemia compared to those with normal puberty (p < 0.05). The regression analysis revealed that factors associated with short stature were; age at diagnosis, HbA1C > 8.2, and albumin/creatinine ratio > 8 (p < 0.05). Conclusion: Children with uncontrolled T1DM are at risk of short stature and delayed puberty. Diabetes duration and control seem to be independent risk factors for short stature. [ABSTRACT FROM AUTHOR]

Background Primary hyperoxaluria (PH) is a rare, severe genetic disorder, characterized by increased urinary excretion of calcium oxalate, which is responsible for kidney damage and systemic clinical manifestations. Since the year 2020, a new molecule, lumasiran, based on RNA interference (RNAi) technology, has been added to the traditional therapeutic approach. The aim of this analysis was to define the baseline characteristics of a PH1 pediatric population treated with lumasiran in a compassionate-use program setting, and to evaluate the medium-term efficacy of this drug in the routine clinical setting. Methods A retrospective observational analysis was conducted in nine pediatric patients (male:female 5:4; median age at lumasiran start 1.9 years, range 0–14.1). Data concerning oxalate concentration in plasma and urine, kidney stones events, ultrasound and kidney function were collected during the study period (follow-up, mean ± standard deviation: 15.3 ± 5 months). Results In this analysis, a reduction in the urinary oxalate to creatinine ratio (reduction range within the sixth month of treatment from 25.8% to 69.6%, median 51.2%) as well as plasma oxalate concentration under the limit of supersaturation of oxalate in all the patients. Only one patient presented new stone events; kidney ultrasonographic findings related to nephrocalcinosis remained stable in eight out of nine patients. Glomerular filtration rate remained stable during treatment. No adverse events related to lumasiran were noted. Conclusion Data from this analysis support the efficacy and safety of lumasiran in a pediatric clinical setting, especially if administrated in early life. [ABSTRACT FROM AUTHOR]

Background: To evaluate the prognostic value of blood urea nitrogen/creatinine ratio (BUN/SCr) and cystatin C (Cys C) in patients with renal cell carcinoma (RCC) after radical nephrectomy. Methods: The study analysed 348 patients with RCC who underwent radical nephrectomy. The optimal cut-off was obtained based on the ROC of specific survival outcomes and the maximum Youden index. The patients were divided into four groups: Group 1 (low BUN/SCr-low Cys C), Group 2 (low BUN/SCr-high Cys C), Group 3 (high BUN/SCr-low Cys C), and Group 4 (high BUN/SCr-high Cys C). The primary endpoint was cancer-specific survival (CSS), and the secondary endpoint was disease-free survival (DFS). Results: A strong positive correlation was shown between BUN/SCr value and Cys C level. Patients with a higher BUN/SCr ratio (17.41) and Cys C level (3.98 mg/L) had poorer survival outcomes. Notably, patients in group 4 showed the worst CSS and DFS rates, while patients in groups 1 and 2 had better survival outcomes with no significant difference between the two groups. A higher BUN/SCr ratio (17.41) and high Cys C serum level (3.98 mg/L) were independent predictors of CSS and DFS, in addition to preoperative tumour size and pathological T (pT) stage. Conclusion: This study provides the first evidence of the independent prognostic importance of BUN/SCr ratio and Cys C in patients with RCC after radical nephrectomy. [ABSTRACT FROM AUTHOR]

Objective: This work measures the intra‐operative bleeding in end‐stage renal disease patients and assesses whether laboratory coagulation tests and nitrogenous compounds are related to a higher bleeding risk. Methods: Laboratory tests were performed on the day of surgery and some patients with thrombocytopenia and values above the normal levels of international normalised ratio (INR), thrombin time (TT) and activated partial thromboplastin time (aPTT) were identified. Results: Haemostatic time ranged from 2 to 35 min (mean of 8.51 min) after suture. Bleeding volume ranged from 0.02 to 67.06 mL (mean of 4.38 mL) and the bleeding volume per minute ranged from 0.05 to 2.10 mL/min (median of 0.6 mL/min). Only seven patients (16.27%) had abnormal bleeding (more than 0.6 mL/min). Spearman's coefficient showed weak correlations between bleeding volume (mL/min) and serum urea (r = 0.226), TT (r = 0.227), plasma urea (r = 0.148) and creatinine (r = 146), as well as very weak correlations with all other variables (r < 0.140) such as age, haemodialysis time, glycaemia, glycated haemoglobin, platelets, INR, aPTT and fibrinogen. Conclusion: It was not possible to associate any laboratory test or nitrogenous compounds present in the blood and saliva with an increased bleeding. [ABSTRACT FROM AUTHOR]

BACKGROUND: Vitamin D deficiency is common in postmenopausal women and is associated with low vitamin D intake, increased age, decreased absorption. Especially at advanced age, vitamin D deficiency may increase muscle weakness and disbalance resulting in increased risk of fracture. OBJECTIVES: This study aims to explore the correlation between 25(OH) vitamin D3 levels and quadriceps muscle strength in postmenopausal women. METHODS: We evaluated bilateral qadriceps muscle strength in postmenopausal women with isokinetic test. We evaluated the correlation of muscle power with measurements of parathormone, vitamin D, Calcium, creatinine, alanine transaminase, alkaline phosphatase, total creatine kinase. RESULTS: The mean vitamin D level of 95 participants included in the study was 18.24 ± 8.94 ng/ml. Vitamin D levels were found to be deficient (< 10 ng/ml) in 23 (24.1%), insufficient in 62 (65.26%) and normal in 10 (10.53%) of the 95 participants. A weak negative correlation was observed between participants' vitamin D levels and PT values (r = - 0.271, p = 0.012). A moderate negative correlation was found between ALP and vitamin D levels (r = - 0.317, p = 0.002). However, there was no significant correlation between vitamin D levels and the 60∘ and 90∘ flexion and extension peak torque values (All p values > 0.05). CONCLUSIONS: Vitamin D levels and muscle strength weren't statistically significant. Few studies are available in the related literature, highlighting the need for further research to achieve a clearer consensus. [ABSTRACT FROM AUTHOR]

Aims: Dolutegravir increases serum creatinine by inhibiting its renal tubular secretion and elimination. We investigated determinants of early changes in serum creatinine in a southern African cohort starting first‐line dolutegravir‐based antiretroviral therapy (ART). Methods: We conducted a secondary analysis of data from participants in a randomized controlled trial of dolutegravir, emtricitabine and tenofovir disoproxil fumarate (TDF) or tenofovir alafenamide fumarate (TAF) (ADVANCE, NCT03122262). We assessed clinical, pharmacokinetic and genetic factors associated with change in serum creatinine from baseline to Week 4 using linear regression models adjusted for age, sex, baseline serum creatinine, HIV‐1 RNA concentration, CD4 T‐cell count, total body weight and co‐trimoxazole use. Results: We included 689 participants, of whom 470 had pharmacokinetic data and 315 had genetic data. Mean change in serum creatinine was 11.3 (SD 9.9) μmol.L−1. Factors that were positively associated with change in serum creatinine at Week 4 were increased log dolutegravir area under the 24‐h concentration–time curve (change in creatinine coefficient [β] = 2.78 μmol.L−1 [95% confidence interval (CI) 0.54, 5.01]), TDF use (β = 2.30 [0.53, 4.06]), male sex (β = 5.20 [2.92, 7.48]), baseline serum creatinine (β = −0.22 [−0.31, −0.12]) and UGT1A1 rs929596 A→G polymorphism with a dominant model (β = −2.33 [−4.49, −0.17]). The latter did not withstand correction for multiple testing. Conclusions: Multiple clinical and pharmacokinetic factors were associated with early change in serum creatinine in individuals initiating dolutegravir‐based ART. UGT1A1 polymorphisms may play a role, but further research on genetic determinants is needed. [ABSTRACT FROM AUTHOR]

Background: Paclitaxel (PAX) is a widely used chemotherapy drug for various cancer types but often induces significant toxicity in multiple organ systems. Silymarin (SIL), a natural flavonoid, has shown therapeutic potential due to its multiple benefits. Aims: To evaluate the therapeutic efficacy of SIL in mitigating liver and kidney damage induced by PAX in rats, focusing on oxidative stress, inflammation, and apoptosis pathways. Study Design: Experimental animal model. Methods: The study included 28 male Wistar rats aged 12-14 weeks weighing 270-300 g. The rats were divided into four groups: control, SIL, PAX, and PAX + SIL, with seven in each group. The rats received intraperitoneal (i.p.) injections at a dose of 2 mg per kilogram of body weight of PAX for 5 successive days, followed by oral gavage with 200 mg/ kg body mass of SIL for 10 uninterrupted days. We examined the effect of SIL on specific serum biochemical parameters using an autoanalyzer and rat-specific kits. The spectrophotometric methods was used to investigate oxidative stress indicators in kidney and liver tissues. Aquaporin-2 (AQP-2), B-cell lymphoma-2 (Bcl-2), cysteine aspartate-specific protease-3 (caspase-3), interleukin-6 (IL-6), nuclear factor kappa B (NF-κB), and streptavidin-biotin staining were used to assess immunoreactivity in PAX-induced liver and kidney injury models. Results: SIL treatment significantly reduced serum levels of alanine aminotransferase, aspartate aminotransferase, creatinine, urea, and C-reactive protein, indicating its effectiveness in treating PAX-induced liver and kidney injury. SIL treatment significantly reduced oxidative stress by increasing essential antioxidant parameters, such as superoxide dismutase, catalase, glutathione peroxidase, and glutathione. It also reduced malondialdehyde levels in liver and kidney tissues of SIL-PAX groups (p < 0.05). SIL administration reduced NF-κB, caspase-3, and IL-6 expression while increasing Bcl-2 and AQP2 levels in liver and kidney tissues of rats treated with SIL and PAX (p < 0.05). Conclusion: Our findings indicate the potential of SIL to alleviate PAX-induced liver and kidney damage in rats by reducing oxidative stress, inflammation, and apoptotic processes. [ABSTRACT FROM AUTHOR]

Background: Augmented renal clearance (ARC) holds a risk of subtherapeutic drug concentrations. Knowledge of patient-, disease-, and therapy-related factors associated with ARC would allow predicting which patients would benefit from intensified dosing regimens. This study aimed to identify ARC predictors and to describe ARC time-course in critically ill children, using iohexol plasma clearance (CLiohexol) to measure glomerular filtration rate (GFR). Methods: This is a retrospective analysis of data from the "IOHEXOL" study which validated GFR estimating formulas (eGFR) against CLiohexol. Critically ill children with normal serum creatinine were included, and CLiohexol was performed as soon as possible after pediatric intensive care unit (PICU) admission (CLiohexol1) and repeated (CLiohexol2) after 48–72 h whenever possible. ARC was defined as CLiohexol exceeding normal GFR for age plus two standard deviations. Results: Eighty-five patients were included; 57% were postoperative patients. Median CLiohexol1 was 122 mL/min/1.73 m2 (IQR 75–152). Forty patients (47%) expressed ARC on CLiohexol1. Major surgery other than cardiac surgery and eGFR were found as independent predictors of ARC. An eGFR cut-off value of 99 mL/min/1.73 m2 and 140 mL/min/1.73 m2 was suggested to identify ARC in children under and above 2 years, respectively. ARC showed a tendency to persist on CLiohexol2. Conclusions: Our findings raise PICU clinician awareness about increased risk for ARC after major surgery and in patients with eGFR above age-specific thresholds. This knowledge enables identification of patients with an ARC risk profile who would potentially benefit from a dose increase at initiation of treatment to avoid underexposure. Trial registration: ClinicalTrials.gov NCT05179564, registered retrospectively on January 5, 2022. [ABSTRACT FROM AUTHOR]

Background: Renal dysfunction is a common complication after heart transplantation (Htx). Glomerular filtration rate (GFR) can be assessed by various estimating equations (eGFR). We evaluated the correlation, agreement, and accuracy between eGFR and mGFR and the ability of eGFR to track changes in mGFR early after Htx. Methods: A single‐center prospective observational study on 55 patients undergoing Htx. Serum creatinine and mGFR (plasma clearance of Cr51‐EDTA or iohexol) were measured preoperatively and on the fourth postoperative day. The accuracy of eGFR to predict true mGFR was calculated as the percentage of patients with an eGFR within 30% of mGFR (P30). The agreement between eGFR and mGFR was assessed according to Bland and Altman. A four‐quadrant plot was made to evaluate the ability of eGFR to track changes in mGFR. Results: The accuracy of eGFR to assess mGFR was 52%. The bias was 11.2 ± 17.4 mL/min/1.72 m2. The limits of agreement were −23.0 to 45.4 mL/min/1.72 m2 and the error 58%. The concordance rate between eGFR and mGFR was 72%. Conclusions: eGFR underestimated mGFR and the agreement between eGFR and mGFR was low with an unacceptably large between‐group error and low accuracy. Furthermore, the ability of eGFR to assess changes in mGFR, postoperatively, was poor. Thus, the use of estimating equations from serum creatinine will not adequately assess renal function early after major heart surgery. To gain adequate information on renal function early after Htx, GFR needs to be measured, not estimated. [ABSTRACT FROM AUTHOR]

Introduction: Neuroendocrine carcinoma (NEC) is characterized by a poor prognosis and is generally treated with platinum and etoposide combination therapy as first-line chemotherapy. However, it remains uncertain whether carboplatin and etoposide combination therapy (CE) and cisplatin and etoposide combination therapy (PE) have comparable treatment efficacy. In this retrospective analysis, we compared the efficacy and safety of CE and PE in patients with NEC. Methods: We retrospectively reviewed the patient's clinical record from 2005 to 2022 at the Department of Medical Oncology, Tohoku University Hospital. Patients who received either CE or PE were included in the study. Statistical analyses were performed using JMP Pro 16.0 (SAS Institute Inc., Cary, NC, USA). Results: A total of 104 patients were enrolled, with 73 patients assigned to the CE group and 31 patients assigned to the PE group. Statistically, the response rate, progression-free survival time and overall survival time were 42.6%, 5.1 months (95% CI: 3.5–6.3) and 13.6 months (95% CI: 8.9–17.4), respectively, in the CE groups and 44.4%, 5.6 months (95% CI: 3.1–7.0) and 12.5 months (95% CI: 11.2–14.6), respectively, in the PE groups. There was no significant difference in treatment efficacy between the CE and the PE groups. However, the number of patients with elevated creatinine (3.35 mg/dL and 3.88 mg/dL in 2 patients, respectively) was significantly higher in the PE group than in the CE group. Conclusion: The efficacy of CE and PE in patients with NEC is comparable. However, the incidence of renal dysfunction was found to be significantly higher in the PE group than in the CE group. [ABSTRACT FROM AUTHOR]

Objective(s): Rhabdomyolysis leads to the release of myoglobin, sarcoplasmic proteins, and electrolytes into the blood circulation causing acute kidney injury (AKI). Thymoquinone, a natural compound found in Nigella sativa seeds, has antioxidant and anti-inflammatory effects. This investigation assessed the renoprotective effect of thymoquinone on rhabdomyolysis-induced AKI in rats. Materials and Methods: Male Wistar rats were categorized into six groups (n = 6): 1. Control: (normal saline), 2. Glycerol (50 ml/kg, single dose, IM), 3-5: Glycerol + thymoquinone (1, 2.5 and 5 mg/kg, 4 days, IP), 6. Thymoquinone (5 mg/kg). On day 5, serum and kidney tissue were isolated and the amounts of serum creatinine and blood urea nitrogen (BUN), renal malondialdehyde (MDA), glutathione (GSH.), tumor necrosis factor-alpha (TNF-α), neutrophil gelatinase-associated lipocalin (NGAL), and pathological changes were evaluated. Results: Glycerol increased creatinine, BUN, MDA, TNF-α, and NGAL levels. It decreased GSH amounts and caused renal tubular necrosis, glomerular atrophy, and myoglobin cast in kidney tissue. Co-administration of glycerol and thymoquinone reduced creatinine, BUN, histopathological alterations, and MDA levels, and enhanced GSH amounts. Administration of glycerol and thymoquinone (5 mg/kg) had no significant effect on TNF-α amount but decreased NGAL protein levels. The administration of thymoquinone (5 mg/kg) alone did not display a significant difference from the control group. Conclusion: Rhabdomyolysis from glycerol injection in rats can cause kidney damage. Thymoquinone may attenuate renal dysfunction and oxidative stress. However, the TNF-α level was not significantly affected. Further studies are needed to explore the potential therapeutic effects of thymoquinone in managing AKI. [ABSTRACT FROM AUTHOR]

Background Intraindividual differences between estimated glomerular filtration rate (eGFR) based on cystatin C (eGFRcys) and creatinine (eGFRcr) can convey important clinical information regarding health status. However, the clinical implications of these differences (eGFRdiff) for risk of cognitive decline and motoric cognitive risk (MCR) syndrome remains unclear. We aimed to investigate the longitudinal associations of eGFRdiff with cognitive trajectories and incident MCR. Methods Based on the China Health and Retirement Longitudinal Study, we identified two study subcohorts: one for cognitive trajectory follow-up (6423 participants, 2011–2018) and another for incident MCR follow-up (2477 participants, 2011–2015). The eGFRdiff was defined as eGFRcys − eGFRcr. Adjusted ordinal and binary logistic regression models were separately used to assess the associations of eGFRdiff with cognitive trajectories and incident MCR. We also performed discordance analyses for eGFRdiff versus eGFRcys, eGFRcr or eGFR based on both creatinine and cystatin C (eGFRcys-cr). Results In the first subcohort, four distinct 7-year cognitive trajectories were identified. Each 1 standard deviation (SD) higher eGFRdiff (value for eGFRcys − eGFRcr) was associated with a lower risk of poorer cognitive trajectories {odds ratio 0.909 [95% confidence interval (CI) 0.877–0.942]}. In the second subcohort, 121 participants developed incident MCR after a 4-year follow-up. Each 1-SD higher eGFRdiff (value for eGFRcys − eGFRcr) was linked with a 25.3% (95% CI 16.6–33.2) decreased risk for MCR. The above associations persisted in individuals with normal kidney function. Additionally, the risk for cognitive decline and incident MCR was more strongly associated with eGFRcys than eGFRcr and eGFRcys-cr. For the discordance analyses, the 'discordantly high eGFRdiff/low eGFR' group but not the 'discordantly low eGFRdiff/high eGFR' exhibited a significantly lower risk of poorer cognitive trajectories and MCR compared with the concordant group. Conclusions A large negative difference between eGFRcys and eGFRcr (eGFRcys < eGFRcr) was associated with a higher risk of cognitive decline and incident MCR. The eGFRdiff could capture additional valuable risk information beyond eGFRcys, eGFRcr and eGFRcys-cr. [ABSTRACT FROM AUTHOR]

This study intended to investigate the impact of long‐term tenofovir fumarate (TDF) antiviral regimen on renal function in human immunodeficiency virus (HIV)‐infected patients with low‐risk of kidney injury. The observational study involving 100 HIV‐infected patients without underlying diseases who achieved virological suppression and immunological recovery after sustained antiviral regimen of TDF+ lamivudine+ efavirenz (TLE) for 3.19 years. Renal function, including estimated glomerular filtration rate (eGFR), blood and urine β2 microglobulin, and other parameters, was assessed every 3 months over a period of 2.5 years. The eGFR showed a slight increasement from 116.0 at month 0 to 119.7 at month 30. Blood β2 microglobulin increased from 2.02 mg/L at month 0 to 2.77 mg/L at month 30. Compared to month 0, the difference in blood β2 microglobulin was statistically significant at month 6 and months 12‐30 (P <.05). The incidence of proximal renal tubular dysfunction fluctuated from 2% at month 0 to 2.5% at month 30. The urine β2 microglobulin fluctuated from 0.5 (0.3‐1.1) to 0.8 (0.5‐1.35) mg/L at months 18‐30, which was higher than 0.41 (0.18‐1.1) mg/L at month 0 (P <.05). The abnormal concentration proportion of urine β2 microglobulin fluctuated from 72.7% to 81.3% at months 18‐30, which was higher than the proportion of 57.0% at month 0. The abnormal proportion of blood β2 microglobulin, urine β2 microglobulin, and proximal renal tubular dysfunction were not correlated with eGFR (r1 = 0.119, r2 = −0.008, r3 = −0.165, P >.05). Long‐term TDF antiviral regimen in low‐risk of kidney injury HIV‐infected patients may lead to damage in the proximal renal tubules and glomeruli. Blood and urine β2 microglobulin levels may be helpful in screening for renal dysfunction. [ABSTRACT FROM AUTHOR]

Objectives: Urine is the most used matrix in drug analysis; however, it is susceptible to adulteration or tampering. Urine creatinine is the most important urine integrity parameter used as an indicator of dilution. This study aimed to evaluate the prevalence of diluted urine samples and the change in positivity after creatinine normalization. Methods: Urine samples screened by the LC-MS/MS method over a 3.5-year period (n=21,927) were included in the study. Positivity rates were evaluated in both total and diluted urine samples. Additionally, the impact of creatinine normalization on samples with substance concentrations above the limit of quantitation (LOQ) and below the cut-off was investigated. Results: A total of 350,832 tests were conducted on 21,927 urine samples, resulting in an overall positivity rate of 21.2% (n=4652). The ratio of diluted urine was 1.6% (n=343), with 61.5% (n=211) testing negative (cut-off), and 15.2% (n=52) testing above LOQ and below cut-off. After creatinine normalization in diluted urines, the sample positivity rate increased from 23.3% (n=80) to 33.8% (n=116) (p<0.001), and the substance positivity rate increased from 2.3% (n=125) to 3.9% (n=212) (p<0.001). Conclusion: Precautions should be taken in reporting diluted urine samples to avoid reporting false negative results. The creatinine normalization approach shows promise in laboratories using quantitative screening methods such as LC-MS/MS for samples with substance concentrations above the LOQ and below the cut-off. However, more clinical and laboratory collaboration is needed for its routine application. [ABSTRACT FROM AUTHOR]

Glomerular filtration rate (GFR) estimating equations based on rescaled serum creatinine (SCr/Q) have shown better performance, where Q represents the median SCr for age- and sex-specific healthy populations. However, there remains a scarcity of investigations in China to determine this value. We aimed to develop Chinese age- and sex-specific reference intervals (RIs) and Q-values for SCr and to validate the equations incorporating new Q-values. We included 117,345 adults from five centers for establishing RIs and Q-values, and 3,692 participants with reference GFR (rGFR, 99mTc-DTPA renal dynamic imaging measurement) for validation. Appropriate age partitioning was determined using the decision tree method. Lower and upper reference limits and medians were calculated using the refineR algorithm, and Q-values were determined accordingly. We evaluated the full age spectrum (FAS) and European Kidney Function Consortium (EKFC) equations incorporating different Q-values considering bias, precision (interquartile range, IQR), and accuracy (percentage of estimates within ±20 % [P20] and ±30 % [P30] of rGFR). RIs for males were: 18–79 years, 55.53–92.50 μmol/L; ≥80 years, 54.41–96.43 μmol/L. RIs for females were: 18–59 years, 40.42–69.73 μmol/L; 60–79 years, 41.16–73.69 μmol/L; ≥80 years, 46.50–73.20 μmol/L. Q-values were set at 73.82 μmol/L (0.84 mg/dL) for males and 53.80 μmol/L (0.61 mg/dL) for females. After validation, we found that the adjusted equations exhibit less bias, improved precision and accuracy, and increased agreement of GFR categories. We determined Chinese age- and sex-specific RIs and Q-values for SCr. The adjustable Q-values provide an effective alternative to obtain valid equations for estimating GFR. [ABSTRACT FROM AUTHOR]

Urea and creatinine concentrations in plasma are used to guide hemodialysis (HD) in patients with end-stage renal disease (ESRD). To support individualized HD treatment in a home situation, there is a clinical need for a non-invasive and continuous alternative to plasma for biomarker monitoring during and between cycles of HD. In this observational study, we therefore established the correlation of urea and creatinine concentrations between sweat, saliva and plasma in a cohort of ESRD patients on HD. Forty HD patients were recruited at the Dialysis Department of the Catharina Hospital Eindhoven. Sweat and salivary urea and creatinine concentrations were analyzed at the start and at the end of one HD cycle and compared to the corresponding plasma concentrations. A decrease of urea concentrations during HD was observed in sweat, from 27.86 mmol/L to 12.60 mmol/L, and saliva, from 24.70 mmol/L to 5.64 mmol/L. Urea concentrations in sweat and saliva strongly correlated with the concentrations in plasma (ρ 0.92 [p<0.001] and 0.94 [p<0.001], respectively). Creatinine concentrations also decreased in sweat from 43.39 μmol/L to 19.69 μmol/L, and saliva, from 59.00 μmol/L to 13.70 μmol/L. However, for creatinine, correlation coefficients were lower than for urea for both sweat and saliva compared to plasma (ρ: 0.58 [p<0.001] and 0.77 [p<0.001], respectively). The results illustrate a proof of principle of urea measurements in sweat and saliva to monitor HD adequacy in a non-invasive and continuous manner. Biosensors enabling urea monitoring in sweat or saliva could fill in a clinical need to enable at-home HD for more patients and thereby decrease patient burden. [ABSTRACT FROM AUTHOR]

Donor‐derived cell‐free DNA (dd‐cfDNA) has been widely studied as biomarker for non‐invasive allograft rejection monitoring. Earlier rejection detection enables more prompt diagnosis and intervention, ultimately improving patient treatment and outcomes. This multi‐centre study aims to verify analytical performance of a next‐generation sequencing‐based dd‐cfDNA assay at end‐user environments. Three independent laboratories received the same experimental design and 16 blinded samples to perform cfDNA extraction and the dd‐cfDNA assay workflow. dd‐cfDNA results were compared between sites and against manufacturer validation to evaluate concordance, reproducibility, repeatability and verify analytical performance. A total of 247 sample libraries were generated across 18 runs, with completion time of <24 h. A 96.0% first pass rate highlighted minimal failures. Overall observed versus expected dd‐cfDNA results demonstrated good concordance and a strong positive correlation with linear least squares regression r2 = 0.9989, and high repeatability and reproducibility within and between sites, respectively (p > 0.05). Manufacturer validation established limit of blank 0.18%, limit of detection 0.23% and limit of quantification 0.23%, and results from independent sites verified those limits. Parallel analyses illustrated no significant difference (p = 0.951) between dd‐cfDNA results with or without recipient genotype. The dd‐cfDNA assay evaluated here has been verified as a reliable method for efficient, reproducible dd‐cfDNA quantification in plasma from solid organ transplant recipients without requiring genotyping. Implementation of onsite dd‐cfDNA testing at clinical laboratories could facilitate earlier detection of allograft injury, bearing great potential for patient care. [ABSTRACT FROM AUTHOR]

Introduction: Obesity is a risk factor for the development of diabetes, and these two are directly implicated in an individual's risk of developing Non Alcoholic Fatty Liver Disease (NAFLD), which is a major factor in Metabolic Syndrome (MS). NAFLD and Type 2 Diabetes Mellitus (T2DM) are known to frequently coexist and act synergistically to elevate the risk of hepatic as well as extrahepatic complications. Aim: To determine the levels of renal profile, electrolytes, Glycosylated Haemoglobin (HbA1c), and Body Mass Index (BMI) in T2DM patients with and without NAFLD, as well as in control subjects, and to assess the correlation of BMI and HbA1c with renal profile and electrolytes in T2DM patients with and without NAFLD. Materials and Methods: This case-control study was conducted in the Department of Biochemistry and the Diabetes Speciality Clinic in the Department of General Medicine at MGM Medical College and Hospital, Navi Mumbai, Maharashtra, India, from December 2021 to March 2023. The study included a total of 90 subjects divided into three groups (30 in each): Group 1-Control, Group 2-T2DM with NAFLD, and Group 3-T2DM without NAFLD. Aseptic blood collection was performed, and Renal Function Test (RFT), electrolytes, and HbA1c levels were analysed. Group comparisons were done using unpaired t-tests, and correlation analysis was conducted using Pearson's correlation with Statiistical Package for Social Sciences (SPSS) software version 25.0. Results: The authors found that 57% of the total enrolled population were female, while the remaining 43% were male, with a mean age of (49.03±5.09) years. Mean levels of HbA1c (9.55±1.78, 8.61±1.42%), BMI (28.84±4.19, 23.51±2.09) kg/m², Urea (31.62±6.28, 33.02±5.11) mg/dL, Creatinine (1.29±0.18, 1.36±0.10) mg/dL, and Uric acid (6.74±1.19, 6.01±0.83) mg/dL were found to be significantly higher in Group 2 and Group 3, respectively, compared to controls. A positive significant correlation of BMI with uric acid, HbA1c with urea, creatinine, and uric acid in Group 2 and 3 was observed. However, no derangement was observed concerning electrolytes in any group. Conclusion: The correlation of urea, creatinine, and uric acid with HbA1c provides the authors with information on impaired renal function in diabetic as well as NAFLD participants. Hyperuricaemia in these individuals can aggravate the risk of T2DM and NAFLD, leading to its progression in Non Alcoholic Steatohepatitis (NASH), respectively. [ABSTRACT FROM AUTHOR]

Older patients (≥75 years) after coronary angiography constitute an increasing proportion, but only limited data are available regarding the prognosis of geriatric contrast-associated acute kidney injury (CA-AKI). Patients (≥75 years) undergoing coronary angiography between December 2010 and September 2013 were consecutively enrolled. CA-AKI was defined as an increase in serum creatinine of 25% or.5 mg/dL from the baseline within 48–72 h of contrast exposure. All-cause mortality was assessed during median 7.5 years (interquartile range [IQR] 6.7–8.7 years) follow-up period. In total, 571 patients aged >75 years undergoing coronary angiography were enrolled in a single center study; 82 (14.4%) patients had CA-AKI. The all-cause mortality during the median 7.5 years follow-up period was 22.0% in patients with CA-AKI and 13.1% in patients without CA-AKI (P =.015). After adjusting for potential confounding factors, the multivariable analysis indicated that CA-AKI was related to an increased risk of all-cause mortality during the median 7.5-year follow-up (hazard ratio [HR]: 2.46; 95% CI: 1.29–4.7; P =.006). CA-AKI is a significant and independent predictor of long-term mortality for patients aged over 75 years who underwent coronary angiography. [ABSTRACT FROM AUTHOR]

Objective: To find the correlation of serum uric acid with microalbuminuria in Type-2 diabetic patients with normal creatinine. Methods: This cross-sectional study was conducted in the Department of Diabetes, Endocrinology and Metabolic diseases, Hayatabad Medical Complex, Peshawar, Pakistan from 1st April, 2022 to 30th September, 2022. Total 160 diabetic patients between the age of 30 and 65 years were enrolled in the study. Type-2 diabetic patients with microalbuminuria between 2.5 and 30 mg/mmol were included. The demographic details of patients were recorded in the questionnaire after taking consent. Fasting Uric acid, lipid profile and glucose along with creatinine and HbA1C were estimated from patient's venous blood samples. Ratio of albumin to creatinine (ACR) in the random spot urine sample was used to detect microalbuminuria. Results: Out of 160 participants enrolled in the study there were 86 (54%) males and 74 (46%) females with the mean age of 50.15 ± 11.1 years and BMI of 20.93 kg/m2. Ninety six (60%) of the patients had Type-2 DM for less than five years, while remaining 64 (40%) were more than five years diabetic. Mean serum uric acid calculated was 6.85±2.06(mg/ dl), while microalbuminuria was calculated as 8.02±0.78 (mg/mmol). The Pearson correlation of serum uric acid and microalbuminuria based on sex and age was statistically significant(p<0.05). Conclusion: We found that uric acid level was significantly associated with microalbuminuria in people with Type-2 diabetes with normal serum creatinine. Uric acid level can be a potential screening tool for early detection of DKD. [ABSTRACT FROM AUTHOR]