Early Kidney Research Articles

Association of urinary EGF, FABP3, and VCAM1 levels with the progression of early diabetic kidney disease

Introduction Diabetic kidney disease (DKD) is a common cause of chronic kidney disease with around 25-40% of patients with diabetes being affected. The course of DKD is variable and estimated glomerular filtration rate (eGFR) and albuminuria, the currently used clinical markers, are not able to accurately predict the individual disease trajectory, in particular in early stages of the disease. The aim of this study was to assess the association of urine levels of selected protein biomarkers with the progression of DKD at an early stage of disease. Methods We measured 22 protein biomarkers using the Mesoscale Discovery platform in 461 urine samples of the PROVALID cohort, an observational study of patients with type 2 diabetes mellitus followed at the primary health care level for a minimum of four years. Odds ratios (OR) were estimated for the effect of marker values above median on fast progression using unadjusted and adjusted logistic regression models. RNA expression at the single cell level in kidney biopsy samples obtained from a cohort of young persons with type 2 diabetes mellitus was in addition determined for markers showing significant associations with disease progression. Results Increased urinary levels of epidermal growth factor (EGF) were linked to lower odds of fast progression (defined as annual eGFR decline greater than 2.58 ml/min per 1.73 m2) with an odds ratio (OR) of 0.60 (95% CI 0.46, 0.78). The association with outcome was even stronger when adjusting for a set of 14 baseline clinical parameters including age, biological sex, eGFR, body mass index, albuminuria, and HbA1c. Elevated urinary levels of fatty acid binding protein 3 (FABP3) and vascular cell adhesion molecule 1 (VCAM1) were each significantly associated with fast progression with an OR of 1.44 (95% CI 1.11, 1.87) and an OR of 1.41 (95% CI 1.08, 1.83), respectively. Enriched expression of EGF and FABP3 was observed in distal convoluted tubular cells and VCAM1 in parietal epithelial cells at single cell level from biopsies of patients with early DKD. Conclusion In summary we show that lower urinary levels of EGF and higher urinary levels of FABP3 and VCAM1 are significantly associated with DKD progression in early-stage disease.

Acute kidney injury during transplantation and the role of inflammasomes: A brief review.

The increasing demand for an effective therapeutic modality in the form of organ transplantation leads to the need to improve the long-term outcomes of the process. Ischemia/reperfusion injuries (IRI) are an integral part of the kidney transplantation process, contributing to inflammation, oxidative stress and activation of the immune system. Inflammasomes, as a component of the immune response, in the form of inflammatory mediators during infection or tissue damage, initiate cell death called pyroptosis. In this context, we have defined the process of inflammasome activation in response to IRI, which is a potential cause of early kidney rejection due to increased susceptibility of the kidneys to ischemia. This review focuses on analyzing the modulation of inflammasome activity in kidney transplants and the activation of the NLRP3 inflammasome as a crucial element of kidney injury during the transplantation procedure, which could be a potential target for future preventive/therapeutic strategies.

Angiotensin-Converting Enzyme-Dependent Intrarenal Angiotensin II Contributes to CTP: Phosphoethanolamine Cytidylyltransferase Downregulation, Mitochondrial Membranous Disruption, and Reactive Oxygen Species Overgeneration in Diabetic Tubulopathy.

Aims: The limited therapeutic options for diabetic tubulopathy (DT) in early diabetic kidney disease (DKD) reflect the difficulty of targeting renal tubular compartment. While renin-angiotensin-aldosterone system (RAS) inhibitors are commonly utilized in the management of DKD, how intrarenal RAS contributes to diabetic tubular injury is not fully understood. Mitochondrial disruption and reactive oxygen species (ROS) overgeneration have been involved in diabetic tubular injury. Herein, we aim to test the hypothesis that angiotensin-converting enzyme (ACE)-dependent intrarenal angiotensin II (AngII) disrupts tubular mitochondrial membranous homeostasis and causes excessive ROS generation in DT. Results: Mice suffered from renal tubular mitochondrial disruption and ROS overgeneration following high-fat diet/streptozocin-type 2 diabetic induction. Intrarenal AngII generation is ACE-dependent in DT. Local AngII accumulation in renal tissues was achieved by intrarenal artery injection. ACE-dependent intrarenal AngII-treated mice exhibit markedly elevated levels of makers of tubular injury. CTP: Phosphoethanolamine cytidylyltransferase (PCYT2), the primary regulatory enzyme for the biosynthesis of phosphatidylethanolamine, was enriched in renal tubules according to single-cell RNA sequencing. ACE-dependent intrarenal AngII-induced tubular membranous disruption, ROS overgeneration, and PCYT2 downregulation. The diabetic ambiance deteriorated the detrimental effect of ACE-dependent intrarenal AngII on renal tubules. Captopril, the ACE inhibitor (ACEI), showed efficiency in partially ameliorating ACE-dependent intrarenal AngII-induced tubular deterioration pre- and post-diabetic induction. Innovation and Conclusion: This study uncovers a critical role of ACE-dependent intrarenal AngII in mitochondrial membranous disruption, ROS overgeneration, and PCYT2 deficiency in diabetic renal tubules, providing novel insight into DT pathogenesis and ACEI-combined therapeutic targets. Antioxid. Redox Signal. 00, 000-000.

The Impact of Heart Failure Chronic Treatment Prior to Cardiac Transplantation on Early Outcomes

Background and Objectives: Cardiac transplantation represents the option for patients with end-stage heart failure (HF), providing the best survival rate. However, the postoperative complications of transplant patients remain a challenge for clinicians. The objective of our study was to evaluate the effect of preoperative chronic HF treatment on the occurrence of in-hospital complications. Materials and Methods: We retrospectively included a total of 50 patients who underwent cardiac transplantation between January 2011 and December 2023 from the Emergency Institute for Cardiovascular Diseases and Transplantation of Targu Mures. We correlated the preoperative chronic HF treatment with the postoperative complications by Spearmen’s correlation coefficient, respectively. With logistic regression, the associations between the treatment and specific complications were determined. Results: Significant negative correlations were found between Carvedilol treatment with 2-month mortality (r = −0.30; 95% CI: −0.53–−0.02; p = 0.03), Ramipril with hospital stay (r = −0.38; 95% CI: −0.60–-0.12; p < 0.01) and intensive care unit (ICU) stay (r = −0.37; 95% CI: −0.59–−0.11; p = 0.01), and Spironolactone usage with hospitalization duration (r = −0.28; 95% CI: −0.52–−0.01; p = 0.04). Furthermore, Carvedilol treatment represented a protective factor against early acute kidney injury (AKI) (OR: 0.22; 95% CI: 0.05–0.91; p = 0.03). Spironolactone treatment was a protective factor against AGR (OR: 0.12; 95% CI: 0.02–0.66; p = 0.01) treatment, in contrast to angiotensin-converting enzyme inhibitor (ACEI) therapy (OR: 5.30; 95% CI: 1.03–27.17; p = 0.04). Conclusions: Pre-transplant Carvedilol treatment was negatively correlated with the 2-month mortality rate. Ramipril and Spironolactone therapy were negatively correlated with hospitalization duration, and Ramipril was additionally correlated with ICU stay. Moreover, Carvedilol therapy represented a protective factor against early AKI. Pre-transplant Spironolactone was associated with lower event rates of AGR, in contrast to ACEI treatment. Prospective studies with larger cohorts are needed in order to draw drastic conclusions.

Early acute kidney injury after tacrolimus administration in heart transplant recipients receiving basiliximab induction therapy.

In this study, we aimed to analyze the association among the timing of tacrolimus initiation, time required to reach the target blood concentration, and early acute kidney injury (AKI) after tacrolimus administration in heart transplant recipients who received basiliximab induction therapy. 88 patients treated with tacrolimus-based immunosuppressive therapy were retrospectively reviewed. Induction therapy was administered to 52 patients. AKI was evaluated within 7 days of tacrolimus administration. The rate of increase in tacrolimus trough concentration to the target trough concentration of 10 µg/mL early after its administration was set to be similar in the basiliximab induction and non-induction group; 8 and 2 patients developed AKI in the induction and non-induction group, respectively. In the induction group, there was no significant difference in the timing of tacrolimus initiation and the time required to reach the target concentration between patients who developed and did not develop AKI. In contrast, the cumulative incidence of AKI was significantly different between patients with an estimated glomerular filtration rate below and those with an estimated glomerular filtration rate above 43 mL/min/1.73m2 at the start of tacrolimus administration (37.5% and 11.4%, respectively; p=0.045). In patients receiving basiliximab induction therapy, the timing of tacrolimus initiation and the time to reach the target concentration are unlikely to be associated with early AKI after tacrolimus administration. However, the recovery of sufficient renal function after heart transplantation is important for determining the start time of tacrolimus.

GLIS3: a novel transcriptional regulator of mitochondrial functions and metabolic reprogramming in postnatal kidney and polycystic kidney disease

Background and aimsDeficiency in the transcription factor (TF) GLI-Similar 3 (GLIS3) in humans and mice leads to the development of polycystic kidney disease (PKD). In this study, we investigate the role of GLIS3 in the regulation of energy metabolism and mitochondrial functions in relation to its role in normal kidney and metabolic reprogramming in PKD pathogenesis. Approach and resultsTranscriptomics, cistromics, and metabolomics were used to obtain insights into the role of GLIS3 in the regulation of energy homeostasis and mitochondrial metabolism in normal kidney and PKD pathogenesis using GLIS3-deficient mice. Transcriptome analysis showed that many genes critical for mitochondrial biogenesis, oxidative phosphorylation (OXPHOS), fatty acid oxidation (FAO), and the tricarboxylic acid (TCA) cycle, including Tfam, Tfb1m, Tfb2m, Ppargc1a, Ppargc1b, Atp5j2, Hadha, and Sdha, are significantly suppressed in kidneys from both ubiquitous and tissue-specific Glis3-deficient mice. ChIP-Seq analysis demonstrated that GLIS3 is associated with the regulatory region of many of these genes, indicating that their transcription is directly regulated by GLIS3. Cistrome analyses revealed that GLIS3 binding loci frequently located near those of hepatocyte nuclear factor 1-Beta (HNF1B) and nuclear respiratory factor 1 (NRF1) suggesting GLIS3 regulates transcription of many metabolic and mitochondrial function-related genes in coordination with these TFs. Seahorse analysis and untargeted metabolomics corroborated that mitochondrial OXPHOS utilization is suppressed in GLIS3-deficient kidneys and showed that key metabolites in glycolysis, TCA cycle, and glutamine pathways were altered indicating increased reliance on aerobic glycolysis and glutamine anaplerosis. These features of metabolic reprogramming may contribute to a bioenergetic environment that supports renal cyst formation and progression in Glis3-deficient mice kidneys. ConclusionsWe identify GLIS3 as a novel positive regulator of the transition from aerobic glycolysis to OXPHOS in normal early postnatal kidney development by directly regulating the transcription of mitochondrial metabolic genes. Loss of GLIS3 induces several features of renal cell metabolic reprogramming. Our study identifies GLIS3 as a new participant in an interconnected transcription regulatory network, that includes HNF1B and NRF1, critical in the regulation of mitochondrial-related gene expression and energy metabolism in normal postnatal kidneys and PKD pathogenesis in Glis3-deficient mice.

Radish red protects against early diabetic kidney disease through inhibiting inflammation, pyroptosis and insulin resistance via IRAK1 signaling suppression

Diabetic kidney disease (DKD) is a major diabetic complication and a leading cause of end-stage renal disease (ESRD), but the therapeutic strategies for DKD are still limited. Red radishes (Raphanus sativus L.) are a rich source of natural anthocyanins that have antioxidant, anti-apoptotic and anti-inflammatory activities. In this study, we attempted to explore the effects of natural pigment anthocyanin called radish red (RR) extracted from red radishes on DKD progression and the underlying molecular mechanisms. RR dose-dependently reduced the tubular cell injury, indicated by the decreased expression of kidney injury molecule 1 (KIM1). Furthermore, releases of pro-inflammatory cytokines including interleukin-1β (IL-1β), IL-6 and tumor necrosis factor-α (TNF-α) stimulated by HF were strongly relieved by RR. Inflammatory response and pyroptosis were also identified to be induced by HF stimulation but were mitigated by RR in HK2 cells through repressing nuclear factor-κB (NF-κB) activation and NLR family, pyrin domain-containing 3 (NLRP3) inflammasome. IR and lipogenesis due to HF exposure were also significantly ameliorated by RR in HK2 cells. Mechanistically, RNA-Seq analysis showed that RR strongly depressed interleukin-1 receptor-associated kinase-1 (IRAK1)-mediated NLRP3 inflammasome, pyroptosis, IR and lipid deposition. Importantly, IRAK1 overexpression almost diminished the beneficial effects of RR, while being rescued upon NLRP3 knockdown in HF-treated HK2 cells, revealing that RR performed its nephroprotective functions in diabetic kidney via inactivating the IRAK1-NLRP3 signaling pathway. Similarly, animal studies confirmed that RR supplementation efficiently ameliorated HFF-caused metabolic disturbance, IR, renal dysfunctions in mice and improved structural kidney damage. Consistently, RR consumption dramatically reduced lipid accumulation, inflammatory response and pyroptosis in kidney tissues of HFF-challenged mice mainly through repressing IRAK1-NLRP3 axis. Our results demonstrated that dietary supplementation with RR may serve as an IRAK1-NLRP3 inhibitor for preventing and treating diabetic nephropathy.

Development and validation of an early acute kidney injury risk prediction model for patients with sepsis in emergency departments

In this study, we aimed to develop and validate a nomogram to predicting the risk of sepsis-associated acute kidney injury (SA-AKI) in patients admitted to emergency departments (EDs). We randomly divided a retrospective dataset of 391 patients with sepsis into a 294-person training cohort and a 97-person validation cohort, and developed three predictive models using multivariate logistic regression analysis and clinical insight. No difference was observed between the three models using the DeLong test and Model 3 was selected as the risk prediction model based on the principle of least inclusion indicators. The use of vasopressor drugs, patient age, platelet count, procalcitonin, and D-dimer levels were included. The training and validation cohorts had a consistency index of 0.832 and 0.866, respectively, indicating high accuracy and stability in predicting SA-AKI risk. The area under the receiver operating characteristic curve was 0.832, showing excellent discrimination. The calibration curves for the training and validation cohorts showed excellent calibration. The decision curve and clinical impact curve analyses showed that the net clinical benefit of using the nomogram was greatest over a probability threshold of 0.05–0.90. In addition, the model showed moderate validity in predicting the 30-day survival and the incidence of major adverse renal events within 30 days. The nomogram developed for SA-AKI risk assessment in patients in EDs showed good discriminability and clinical utility. It can provide a theoretical basis for emergency physicians to prevent SA-AKI.

Associations of the TyG index with albuminuria and chronic kidney disease in patients with type 2 diabetes.

Diabetes-related kidney disease reduces patients' quality of life, increases the risk of death, and is associated with insulin resistance (IR). The triglyceride-glucose (TyG) index is a simple and inexpensive alternative to IR measurement. Furthermore, the relationship between albuminuria and chronic kidney disease (CKD) in type 2 diabetes mellitus (T2DM) remains unclear. Therefore, we aimed to investigate the association of TyG index with albuminuria and CKD in patients with T2DM. Data from 01/2013-12/2017 period were obtained from the Population Health Data Archive's Diabetes Complications Data Set. A total of 1048 patients with T2DM were included in this study. CKD is defined as an estimated glomerular filtration rate < 60 ml/min-1.1.73 m-2 or a urinary albumin-to-creatinine ratio (UACR) ≥ 30 mg/g. Albuminuria is defined as a UACR ≥ 30 mg/g. The TyG index is calculated by measuring the triglyceride and fasting blood glucose levels. Logistic regression models were used to analyze the association between albuminuria, CKD with T2DM and TyG index. We identified 1048 subjects, 63.03% of whom were men. The mean age was 46.21 years, and the mean body mass index was 26.742 kg/m2. CKD and albuminuria detection rates showed an increasing trend in the different TyG subgroups. (p = 0.008, p = 0.006). Using the Q1 group as a baseline, the risk of albuminuria and CKD was significantly greater in the group Q3 (OR = 1.514, 95% CI 1.121-2.047 P = 0.05), and the same result was obtained after adjusting for covariates (OR = 2.241, 95% CI 1.245-4.034, P = 0.007). Subgroup analyses revealed a significant increase in the incidence of albuminuria and CKD in the group Q3 compared to that in the Q1 group. The TyG index is positively associated with albuminuria and CKD in patients with T2DM and may be a marker for predicting the occurrence of early kidney injury in patients with T2DM. Clinicians should test this indicator early to detect lesions and improve patient prognosis.

ANKS6 Variants Underlie Polycystic Kidneys in Prenatal and Neonatal Cases

Background: Nephronophthisis (NPHP) is an autosomal recessive genetic disorder that can cause early-onset kidney failure. ANKS6 plays an important role in early kidney development and encodes a protein that interacts with other proteins within the primary cilium. ANKS6 mutations are known to cause nephronophthisis 16 (NPHP-16). Little is known regarding fetal ultrasound imaging and the antenatal diagnosis of fetuses with ANKS6-associated kidney disease. Here, we report the detection of ANKS6 variants in consanguineous families with polycystic kidney antenatally and in the early stages of life. Methods: Three unrelated Saudi Arabian patients (two prenatal patients and one neonate) were investigated. These cases were referred to the hospital due to the presence of echogenic kidneys on antenatal scanning. After clinical and phenotypic evaluation, whole-exome sequencing (WES) was performed on the cord and peripheral blood to identify the molecular genetic causes associated with the echogenic kidney phenotypes. Results: Two homozygous sequence variants were detected in ANKS6. The homozygous missense novel variant ANKS6: c.1159A&gt;C was detected in Families 1 and 2. In the third family, the known homozygous loss-of-function variant ANKS6: c.907+2T&gt;A was detected. Conclusions: We identified homozygous ANKS6 variants in three families presenting with antenatal polycystic kidney disease. The findings provide an expanded clinical presentation of ANKS6 and emphasize the utility of WES in the diagnosis of echogenic kidneys in prenatal settings.

Targeting Sepsis: Disease Tolerance, Immune Resilience, and Compartmentalized Immunity

Introduction: Sepsis remains a major contributor to critical care mortality and morbidity worldwide. Despite advances in understanding its complex immunopathology, the compartmentalized nature of immune responses across different organs has yet to be fully translated into targeted therapies. This review explores the burden of sepsis on organ-specific immune dysregulation, immune resilience, and epigenetic reprogramming, emphasizing translational challenges and opportunities. Methods: We implemented a systematic literature search strategy, incorporating data from studies published between 2010 and 2024, to evaluate the role of molecular profiling techniques, including transcriptomics and epigenetic markers, in assessing the feasibility of targeted therapies. Results: Sepsis-induced immune dysregulation manifests differently in various organs, with lung, heart, liver, and kidney responses driven by unique local immune environments. Organ-specific biomarkers, such as the Spns2/S1P axis in lung macrophages, mitochondrial dysfunction in the heart, proenkephalin for early acute kidney injury (AKI), and adrenomedullin for predicting multi-organ failure, offer promising avenues for timely intervention. Furthermore, immune resilience, particularly through regulatory T-cell modulation and cytokine targeting (e.g., IL-18), is crucial for long-term recovery. Epigenetic mechanisms, including histone modification and trained immunity, present opportunities for reprogramming immune responses but require more precision to avoid unintended inflammatory sequelae. Conclusions: A deeper understanding of compartmentalized immune responses and the dynamic immune landscape in sepsis is critical for developing precision therapies. Real-time immune monitoring and organ-targeted interventions could revolutionize sepsis management, although significant barriers remain in clinical translation. Further research is required to establish biomarkers and treatment timing that optimize therapeutic efficacy while minimizing systemic risks.

Proteomic Analysis Uncovers Multi-Protein Signatures Associated with Early Diabetic Kidney Disease in Youth with Type 2 Diabetes Mellitus.

The onset of diabetic kidney disease (DKD) in youth with type 2 diabetes mellitus often occurs early, leading to complications in young adulthood. Risk biomarkers associated with the early onset of DKD are urgently needed in youth with type 2 diabetes. We conducted an in-depth analysis of 6596 proteins (SomaScan 7K) in 374 baseline plasma samples from the Treatment Options for Type 2 Diabetes in Adolescents and Youth (TODAY) study to identify multi-protein signatures associated with the onset of albuminuria (urine albumin-to-creatinine ratio [UACR] ≥30 mg/g), a rapid decline in estimated glomerular filtration rate (eGFR) [annual eGFR decline >3 mL/min/1.73m2 and/or ≥3.3% at two consecutive visits], and hyperfiltration (≥135 mL/min/1.73m2 at two consecutive visits). Elastic net Cox regression with 10-fold cross-validation was applied to the top 100 proteins (ranked by p-value) to identify multi-protein signatures of time to development of DKD outcomes. Participants in the TODAY study (14±2 years old, 63% female, 7±6 months diabetes duration) experienced high rates of early DKD: 43% developed albuminuria, 48% hyperfiltration, and 16% rapid eGFR decline. Increased levels of seven and three proteins were predictive of shorter time to develop albuminuria and rapid eGFR decline, respectively; 118 proteins predicted time to development of hyperfiltration. Elastic net Cox proportional hazards model identified multi-protein signatures of time to incident early DKD with concordance for models with clinical covariates and selected proteins between 0.81 and 0.96, while the concordance for models with clinical covariates only was between 0.56 and 0.63. Our research sheds new light on proteomic changes early in the course of youth-onset type 2 diabetes that associate with DKD. Proteomic analyses identified promising risk factors that predict DKD risk in youth with type 2 diabetes and could deepen our understanding of DKD mechanisms and potential interventions.

Early metabolic and hemodynamic indicators of kidney dysfunction in mice offspring from parental low protein diet

BackgroundParental malnutrition, particularly a low-protein diet (LPD), causes oligonephropathy at birth and predisposes offspring to hypertension and chronic kidney disease later in life. The onset of adult kidney disease varies based on genetics and environmental factors, often with subclinical alterations in kidney function being overlooked. This study aimed to examine changes in kidney morphology before significant kidney function decline in the offspring of mice fed a low-protein diet.MethodsUsing a combination of histological analysis, kidney metabolic and hemodynamic panel assessments, and advanced statistical techniques such as Linear Discriminant Analysis (LDA) and Principal Component Analysis (PCA), we investigated the initial impact of a maternal low-protein diet (LPD) on kidney development and function. Our study utilized 12-week-old F1 mice from F0 parents fed either a low-protein diet (LPD) or a normal-protein diet (NPD) before the onset of hypertension.ResultsThe offspring (F1 generation) of parents (F0 generation) fed an LPD show reduced body weight from birth to P20. The kidney weight was also reduced compared to F1 offspring from parents fed an NPD. At 12 weeks of age, body weight normalized, but kidney weight remained low. Offspring of parents fed an LPD displayed abnormal kidney morphology, including dilated tubules, oligonephropathy, and fluid-filled cysts which had worsened with age. A kidney metabolic panel analysis at 12 weeks revealed a slight but consistent increase in urine albumin, plasma creatinine, mean urea, and BUN concentrations. Although no significant changes in hemodynamic variables were observed, 2/12 mice, both males, showed alterations in systolic blood pressure, suggesting sex-specific effects when comparing F1 mice from F0 fed either diet. Overall, kidney metabolic changes were strongly correlated to parental LPD.ConclusionOur findings indicate that significant kidney damage must accumulate in the F1 generation from parents fed an LPD before any detectable changes in blood pressure occur. Our study suggests that small variations in kidney metabolic function may point to early kidney damage and should not be overlooked in the offspring of these malnourished mice and likely humans.

Five-year outcomes of a holistic programme for managing early chronic kidney disease in primary care

Five-year outcomes of a holistic programme for managing early chronic kidney disease in primary care

Plasma bioactive adrenomedullin predicts mortality and need for dialysis in critical COVID-19

COVID-19 is a severe respiratory disease affecting millions worldwide, causing significant morbidity and mortality. Adrenomedullin (bio-ADM) is a vasoactive hormone regulating the endothelial barrier and has been associated with COVID-19 mortality and other adverse events. This prospective cohort pilot study included 119 consecutive patients with verified SARS-CoV-2 infection admitted to two intensive care units (ICUs) in Southern Sweden. Bio-ADM was retrospectively analysed from plasma on ICU admission, and days 2 and 7. Information on comorbidities, adverse events and mortality was collected. The primary outcome was 90-day mortality, and secondary outcomes were markers of disease severity. The association between bio-ADM and outcomes was analysed using survival analysis and logistic regression. Bio-ADM on admission, day 2, and day 7 only moderately predicted 90-day mortality in univariate and multivariate Cox regression. The relative change in bio-ADM between sample times predicted 90-day mortality better even when adjusting for the SAPS3 score, with an HR of 1.09 (95% CI 1.04–1.15) and a C-index of 0.82 (95% CI 0.72–0.92) for relative change between day 2 and day 7. Bio-ADM had a good prediction of the need for renal replacement therapy in multivariate Cox regression adjusting for creatinine, where day 2 bio-ADM had an HR of 3.18 (95% CI 1.21–8.36) and C-index of 0.91 (95% CI 0.87–0.96). Relative changes did not perform better, possibly due to a small sample size. Admission and day 2 bio-ADM was associated with early acute kidney injury (AKI). Bio-ADM on ICU admission, day 2 and day 7 predicted 90-day mortality and dialysis needs, highlighting bio-ADM’s importance in COVID-19 pathophysiology. Bio-ADM could be used to triage patients with a risk of adverse outcomes and as a potential target for clinical interventions.

New Markers of Early Kidney Damage in Children and Adolescents with Simple Obesity

The impact of obesity on kidney injury and the development of chronic kidney disease (CKD) is well documented. Unfortunately, the early stages of CKD are asymptomatic, leading to a delayed diagnosis and a worse prognosis. There is a need for more sensitive indicators of kidney damage than those currently used. We aimed to assess the usefulness of serum t-CAF, urinary netrin-1, α-GST, π-GST, calbindin, and calprotectin as biomarkers of early kidney damage in obese children and to investigate the relationship between these indicators and the degree of obesity. A total of 125 simple obese, normoalbuminuric children and 33 non-obese children as controls were selected. Patients were divided into 2 subgroups according to SDS BMI (I: 2 ≤ 4, II: &gt;4). Serum t-CAF was significantly higher in the obese group compared to the controls, as were urinary α-GST, netrin-1, π-GST, and calprotectin. No difference was found between the two obese groups. In normoalbuminuric obese children and adolescents without significant metabolic disorders, serum t-CAF may be a new biomarker for the early detection of renal dysfunction, and urinary netrin-1, α-GST, π-GST, and calprotectin may be better indicators for the detection of early tubular damage, independent of the severity of obesity.

Evaluation of Early Renal Changes in Type 2 Diabetes Mellitus Using Multiparametric MR Imaging.

To evaluate the clinical value of early renal changes in type 2 diabetes mellitus (T2DM) using multiparameter MRI. The study included 41 diabetics (normoalbuminuria: n = 23; microalbuminuria: n = 18) and 30 healthy controls. All subjects underwent intravoxel incoherent motion diffusion-weighted imaging (IVIM), blood oxygen level dependent (BOLD) and arterial spin labeling (ASL) examinations. One-way analysis of variance was used to compare MRI parameters among the three groups. Pearson correlation analysis was used to evaluate the relationship between MRI parameters and estimated glomerular filtration rate (eGFR) and albumin-creatinine ratio (ACR). Receiver operating characteristic analysis was performed to assess the diagnostic performance. There were statistical differences in cortical D, D*, f, renal blood flow (RBF) and medulla D, D*, f, R2* among the three groups (P < 0.05). The cortical or medullary D, cortical f, and RBF were significantly positively correlated with eGFR (all P < 0.01). The cortical or medullary D, D*, f, cortical RBF were negatively correlated with ACR (all P < 0.05).To evaluate early kidney changes and degree of diabetes, cortical combined D and RBF (AUC [area under the curve] = 0.796 and 0.947, respectively) was better than single D or RBF (all P > 0.05); medullary combined D and R2* (AUC = 0.899 and 0.923, respectively) was better than single D or R2* (all P > 0.05), except single D (P = 0.005) in differentiating normoalbuminuria group from control group. The early changes of renal diffusion and perfusion, oxygenation level, and blood flow in T2DM could be evaluated noninvasively and quantitatively using IVIM, BOLD and ASL. Renal medullary combined IVIM-derived D and BOLD-derived R2* and cortical combined IVIM-derived D and ASL-derived RBF were better for evaluating early renal changes in T2DM.

Ephrin Signaling and the Development of Early Progressive Kidney Function Decline

Ephrin Signaling and the Development of Early Progressive Kidney Function Decline

Exploring the Subtle, Novel, and Early Kidney Pathological Changes in Diabetic Nephropathy Using Clustering with Deep Learning

Exploring the Subtle, Novel, and Early Kidney Pathological Changes in Diabetic Nephropathy Using Clustering with Deep Learning

Evaluation of Novel Biomarker of Early Atherosclerosis in Patients With Chronic Kidney Disease in Wasit Governorate

The aim of the study was to evaluate some Biomarkers in patients with athreoscelerosis in Wasit Province. Atherosclerosis is a chronic arterial disease and a major cause of vascular death. Fatty streaks in arterial walls gradually develop into atheroma and characteristic plaques. The acute rupture of these atheromatous plaques causes local thrombosis, leading to partial or total occlusion of the affected artery. The clinical consequences of these plaques depend on their site and the degree and speed of vessel occlusion . Its major clinical manifestations include ischemic heart disease (IHD), ischemic stroke, and peripheral arterial disease. The study took place in the a hemodialysis unit Al-Zahraa Teaching Hospital in Wasit Governorate during the period from November 2023 to April 2024. This study aimed to examine risk factors (age, gender, high blood pressure, smoking, left ventricular hypertrophy, diabetes mellitus, dyslipidemia, physical inactivity) for atherosclerosis in the general population and patients with chronic kidney disease. Also studying the effect of some novel biomarkers (Homocysteine, Fibrinogen, myeloperoxidase, lipoprotein-associated phospholipase A2, pentraxin 3). The study include (90) samples: (60) patients suffering from early atherosclerosis and chronic kidney disease (dialysis stage) and 30 samples of healthy people (control group), their ages ranged from (40 to 70 years). The samples were divided into two age groups, where the first group had an average age of 40-55 years and the second group was 56-70 years old , the categories were divided equally into males and females Samples were collected based on the incidence of kidney disease first, and then the main risk factors of early atherosclerosis were relied upon, which are (smoking, age, sex, dyslipidemia, hypertension, diabetes, left ventricle valve, physical inactivity). The results of our study regarding diagnostic markers of atherosclerosis showed a significant increase in biomarkers (MPO, PTX3, HCy, FG and LpPLA2)of infected people at p ≥ 0.5. In patients with atherosclerosis the level of new biomarkers showed a significant increase in serum of infected people compared to healthy people at p&lt;0.5. This is an important indication of the importance of these biomarkers in detecting the disease.