German Clinical Practice Guideline on Microhematuria in Children and Young Adults: Evaluating Early Detection of Kidney Disease.

Background and Clinical Significance: Autosomal dominant tubulointerstitial kidney disease caused by a mutation in the uromodulin gene (ADTKD-UMOD) is a rare kidney disorder characterized by progressive tubulointerstitial damage and a slowly progressive loss of renal function. ADTKD is often under-recognized in the clinical setting. Diagnosis of ADTKD-UMOD can be challenging due to its nonspecific symptoms and is confirmed by genetic testing alone. Case presentation: We report the case of a 42-year-old male patient referred for evaluation of renal dysfunction, which was accidentally discovered during routine laboratory checks. He had no significant medical history and no known family history of kidney disease or gout. Physical examination was unremarkable. Renal dysfunction was confirmed, with serum creatinine at 1.44 mg/dL and eGFR at 59.5 mL/min/1.73 m2. Urinalysis was within physiological limits, proteinuria being 75 mg/day. Uric acid was mildly elevated (7.5 mg/dL) without a history of gout. Other laboratory findings, including autoantibodies, were in the normal range. The patient underwent a kidney biopsy, though it was not diagnostic, showing mild focal tubular atrophy and interstitial fibrosis without glomerular involvement. Immunofluorescence staining was negative for complement and immunoglobulins. Given the above nonspecific findings, the patient was suspected of having possible ADTKD. Genetic investigation using a clinical exome next-generation sequencing approach identified a novel heterozygous missense variant in the UMOD gene (c.409T>C; p.Cysteine137Arginine (p.Cys137Arg)) that is likely pathogenic. The patient is under regular clinical-laboratory monitoring. After one year, his overall health is good, renal function is stable with no proteinuria, and uric acid is mildly increased without gout attacks. Conclusions: Increased clinical awareness is crucial for detecting ADTKD-UMOD. Genetic testing can help to resolve clinical diagnostic challenges in patients with unexplained decreased kidney function.

Interest in plasma biomarkers for neurodegenerative disorders is growing, but their reliance on glomerular filtration makes kidney function a key potential confounder. This study assesses the effect of kidney function (eGFR) on plasma biomarkers of neurodegeneration and on their accuracy for detecting cerebral amyloidosis. This observational study aims at studying the effect of kidney function on blood biomarkers through simultaneous measurements of creatinine, plasma, and CSF biomarkers (Aβ42, Aβ40, p-tau181, p-tau217, neurofilament light chain [NfL], glial fibrillary acidic protein [GFAP], and brain-derived tau [BD-tau]), as well as plasma biomarker ratios (Aβ42/Aβ40, p-tau217/Aβ42, NfL/p-tau217, and p-tau181/Aβ42), in the ALZAN cohort of patients. This prospective multicenter cohort (#NCT05427448), recruited across Montpellier, Nîmes, and Perpignan hospitals, included patients from November 2022 to July 2024 who met the following criteria: age ≥18 years, informed consent, and concomitant CSF and blood sampling. To determine the association between plasma biomarkers and kidney function, we performed univariable linear regression analyses. A total of 420 patients were included (mean age: 71.1 years, %female: 53.2) and subdivided into 3 groups according to eGFR value (ml/minute/1.73 m2): <60 (n = 36), [60-90] (n = 194), and >90 (n = 190). All mean plasma biomarker levels were significantly higher in the eGFR < 60 group. Except for p-tau217, a statistically significant inverse correlation was observed between eGFR and individual plasma biomarkers. Furthermore, age-adjusted univariable linear regression analysis revealed an association between eGFR and all plasma biomarkers. Kidney dysfunction significantly impaired the specificity of several biomarkers (p-tau181, GFAP, NfL, and BD-tau; p < 0.001) for detecting cerebral amyloidosis (CSF Aβ42/Aβ40 < 7%), whereas p-tau217 was unaffected. It is important to note that ratio-based plasma biomarkers were not influenced by reduced kidney function. Impaired kidney function was linked to increased plasma cerebral amyloidosis biomarkers, but ratio-based measures (especially p-tau217/Aβ42) showed stable sensitivity and specificity for detecting cerebral amyloidosis across all eGFR groups. Additional studies including more patients with lower eGFR values in diverse diagnostic settings are needed to clarify the influence of kidney function on these biomarkers. This Class II evidence shows that kidney function influences individual blood biomarkers used for cerebral amyloidosis detection, but not their ratios. NCT05427448.

Associations between exposure to polycyclic aromatic hydrocarbons and biomarkers of acute kidney injury among Chilean agricultural workers.

Atrial and brain natriuretic peptides activate GC-A/NPRA (guanylyl cyclase-A/natriuretic peptide receptor-A) and regulate blood pressure and electrolyte homeostasis. Renal tubule (RT) dysfunction results in decreased kidney function and increased blood pressure. We determined the sex-specific consequences of RT cell-specific deletion of Npr1 (encoding NPRA) on blood pressure and renal hemodynamics. Mice were generated with inducible RT knockout by breeding lox-flanked (flox/flox: f/f) exons 1 to 2 in Npr1 with mice expressing the Pax8-rtTA-LC-1-Cre transgene. Doxycycline-treated RT cell-specific Npr1 knockout (Npr1 f/-), heterozygous (HT; Npr1 f/+), and wild-type (Npr1 f/f) male and female mice were used. Proximal tubule, distal tubule, and cortical collecting duct were isolated from RT-Npr1 knockout mice and did not express Npr1 mRNA or protein. RT cell-specific male knockout and HT mice showed significantly lower glomerular filtration rate, creatinine clearance, and urinary sodium excretion than female mice, compared with wild-type mice. The effect of Npr1 deletion was more severe on high-salt diets than their normal-diet counterparts. Loss of Npr1 in RT segments significantly increased systolic blood pressure and mean arterial pressure in a sex-specific manner. Mutant male mice showed higher total urinary protein and albumin-creatinine ratios than female mice. On a high-salt diet, male knockout and HT mice showed greater salt sensitivity than female mice. Loss of Npr1 along the nephron tubules leads to arterial hypertension and abnormal renal functional hemodynamic changes that are more pronounced in male mice compared with female mice.

Introduction Supratherapeutic exposures to pharmaceuticals are a considerable cause of seizures, often leading to severe complications. This study aimed to identify the drugs most frequently associated with seizures in overdose and to evaluate their seizure potential, focusing on dosage and age-related differences. Methods A retrospective analysis of single-agent pharmaceutical exposures, mostly overdoses, reported to Tox Info Suisse from 1 January 2011 to 31 December 2023 was conducted. Cases with seizures were compared to all cases (“seizure rate”) and to all cases involving the same substance (“seizure potential”). The median ingested dose was compared to the maximum approved daily dosage (“relative overdose”), and relative overdose in seizure versus non-seizure cases with the same substance was compared (“seizure overdose ratio”). Results There were 20,176 single-agent pharmaceutical exposures, with seizures reported in 233 cases (1.2%). Antidepressants were the most frequently implicated drug class (34.3%). Mefenamic acid (15.7%), quetiapine (10%), and bupropion (10%) were most commonly associated with seizures. Cefepime (37.5%) and bupropion (23.7%) showed the highest seizure potentials. Seizures occurred at low relative overdoses for clozapine, chlorprothixene, and trimipramine (1.3×, 2.0×, 2.8×, respectively). Tricyclic antidepressants (notably trimipramine), mefenamic acid, tolperisone, and bupropion exhibited low seizure overdose ratios (1.4, 2.0, 2.1, 2.1, respectively). Age-related seizure rates did not differ significantly between adolescents (1.7%) and adults (1.5%). Discussion Besides the established seizure association of antidepressants, this analysis confirmed the high seizure risk of overdoses of mefenamic acid and bupropion. A comparative assessment using relative overdoses and seizure overdose ratios revealed that even mild overdoses of clozapine or chlorprothixene induce seizures. For mefenamic acid, tolperisone and bupropion, seizures occurred at overdoses only about twice those not associated with seizures. Seizures from intravenously administered cefepime were caused by not adapting the posology to decreased kidney function. Conclusion Overdoses of mefenamic acid, quetiapine, bupropion, venlafaxine and tramadol, respectively, were most commonly associated with seizures. Cefepime exhibited the highest seizure potential, in patients with impaired renal function. Tricyclic antidepressants (trimipramine, amitriptyline), tolperisone, mefenamic acid and bupropion were associated with seizures at relatively small overdoses compared to respective non-seizure cases.

WCN26-3512 ANALYSIS OF COMPETING RISKS IN DECISIONS REGARDING RENAL REPLACEMENT THERAPY FOR OLDER PATIENTS: A NATIONWIDE COHORT STUDY IN JAPAN

Background: This scoping review aimed to identify gaps in the literature regarding medication therapy problems (MTPs) among hospitalized adults with decreased kidney function. Specifically, it aimed to answer the following questions: (1) What types of MTPs have been reported? (2) What is the reported prevalence of MTPs? (3) Do MTPs differ by type of kidney disease? (4) What gaps exist regarding MTPs and pharmacists' involvement? Methods: Studies involving adult patients with decreased kidney function that investigated MTPs were included. Studies focused exclusively on post-transplant care, chemotherapy, or a single MTP type were excluded. Literature searches were conducted in PubMed, EMBASE, Cochrane Library, Web of Science, and International Pharmaceutical Abstracts. Two independent reviewers screened and extracted data, with a third reviewer resolving discrepancies. All identified MTPs were re-categorized using the Pharmacy Quality Alliance (PQA) framework and the Pharmaceutical Care Network Europe (PCNE) classification. Results: A total of 23 studies met the inclusion criteria, including two conference proceedings, encompassing 7151 patients. The most common MTP framework was the PCNE classification (13 studies, 57%). Reclassification using the PQA yielded 10,596 MTPs, most frequently "Safety-dosage too high" (n = 2464) and "Effectiveness-dosage too low" (n = 2262). Reclassification using the PCNE yielded 11,574 MTPs, most frequently "Drug selection" (n = 6974) and "Dose selection" (n = 2636). All studies involved patients with chronic kidney disease (CKD), and two also included acute kidney injury (AKI). Conclusions: Dosage-related MTPs were most prevalent among hospitalized patients with decreased kidney function. Variability in MTP definitions, limited representation of patients with AKI and AKD, and minimal reporting on pharmacists' roles reveal important gaps. Addressing these gaps through standardized MTP classification and further research in understudied kidney disease populations may enhance patient safety and support clinical pharmacists' contributions to optimizing medication safety across the kidney disease continuum.

Patients with schizophrenia exhibit decreased kidney function biomarkers in cross-sectional studies, despite their elevated risk of chronic kidney disease. Evidence from large-scale longitudinal studies to better understand this phenomenon remains limited. We aimed to explore the long-term trajectories of kidney biomarkers in patients with schizophrenia. On the basis of the West China Hospital Alliance Longitudinal Epidemiology wellness (WHALE) study, an ongoing prospective cohort comprising approximately 680,000 participants, 510 schizophrenia patients, and 1490 non-schizophrenia controls were included. Biomarkers, including metabolic waste products, original estimate glomerular filtration rates (eGFRs), and derived eGFRs, were extracted from the electronic health records. Latent class mixed model identified distinct trajectories, and logistic regression assessed the associations between schizophrenia and the identified trajectories. Distinct kidney biomarkers trajectories were identified. Schizophrenia was associated with increased odds of the stable-to-decline trajectory in the 2012 cystatin C-based equation (eGFRcys12) (odds ratio [OR]=4.608, PFDR<0.001), the decreasing trajectory (OR=4.300, PFDR<0.001) in the combined creatinine-cystatin C equation (eGFRcc), the low stable-to-decline pattern for the mean of the eGFRcys12 and the 2021 creatinine-based equation (mean eGFR) (OR=2.563, PFDR=0.018), and the stable-to-decline pattern for the difference of the eGFRcys12 and the 2021 creatinine-based equation (eGFRdiff) (OR=11.424, PFDR<0.001). Schizophrenia patients tend to exhibit higher levels of eGFRcys12 and lower levels of mean eGFR and eGFRcc. Heterogeneity in the temporal sensitivity of kidney biomarkers suggests the need for tailored approaches to kidney disease monitoring in this population.

BackgroundWith the emergence of disease-modifying anti-amyloid-beta (Aβ) therapies for Alzheimer’s disease (AD), early and accurate quantitative measures of Aβ burden are critical. Blood-based biomarkers are a scalable and minimally invasive diagnostic solution; plasma tau phosphorylated at threonine 217 (pTau217) is a promising marker for Aβ pathology. The clinical performance of the prototype ElecsysⓇ Phospho-Tau (217P) Plasma immunoassay (Roche Diagnostics) to detect Aβ burden was investigated in an unselected cohort reflective of clinical practice.MethodsPlasma was prospectively collected from participants aged 55 to 80 years with objective or subjective cognitive decline under evaluation for AD. Participants were recruited at multiple clinical sites spanning primary and secondary care. Plasma pTau217 concentrations measured using the prototype pTau217 plasma immunoassay were compared with amyloid positron emission tomography centiloid-based classification at different cutoffs, with further analyses performed at centiloid cutoff 30.OutcomesAmong 588 participants, plasma pTau217 demonstrated high concordance with centiloid-based classification at selected cutoffs. The discriminative ability of plasma pTau217 to detect Aβ pathology peaked at centiloid cutoff 32 (area under the curve=0.933). Subgroup analyses at centiloid cutoff 30 demonstrated good discrimination of Aβ positivity/negativity by clinical diagnosis, age, and sex. Moderately decreased kidney function to kidney failure was found to influence plasma pTau217 levels.InterpretationThe prototype pTau217 plasma immunoassay showed high accuracy in reflecting Aβ burden among individuals presenting with cognitive complaints across diverse clinical settings. These findings support its potential implementation into routine clinical practice for early detection of AD, alongside standard clinical and neuropsychologic assessments.

Whether the interdependence of symptom burden and kidney function over time differ by gender remain unknown. Here we aim to describe longitudinal trajectories of symptom burden in older men and women with advanced CKD over time, and in relation to the trajectory of kidney function. In the prospective, observational multi-center cohort study in Europe; The European QUALity (EQUAL) study on treatment in advanced chronic kidney disease, patients with incident eGFR <20mL/min per 1.73 m2 not on dialysis, ≥65 years of age were followed for over 5 years, or until initiation of kidney replacement therapy. Symptom number and burden were assessed at 3-6-month intervals using the dialysis symptoms index. The evolution of symptom burden was modelled over time and eGFR for men and women separately, using generalized additive models. Over the follow-up, 4730 symptoms measurements were collected in 1135 patients. Overall symptom progression was relatively slow. The number of symptoms increased on average by 0.47 (95% CI 0.37-0.58) symptoms per year, and by 0.75 (95% CI 0.58-0.91) symptoms per 5mL/min/1.73m2 decrease in kidney function. Women reported more symptoms on average than men throughout follow-up, although the increase in symptom number with declining kidney function was almost three times greater in men (0.97 per 5mL/min/1.73m2, 95% CI 0.78-1.16) than in women (0.34 per 5mL/min/1.73m2, 95% CI 0.03-0.64). This difference was especially evident towards lower eGFR levels. Women experience more symptoms on average than men, but symptoms progressed faster in men, relative to kidney decline. Further research should focus on how patient-reported outcome measures (PROMs) can routinely be implemented in nephrology care, and how to use PROMs effectively in patient-nephrologist communication with regards to shared decision making.

Additional investigations into the causal effects of kidney function on various metabolites, particularly lipoprotein lipids in detailed subfractions of lipoprotein particles, in the general population are warranted. Integrated cross-sectional observational and Mendelian randomization (MR) analyses. We included 157,541 participants aged 40-69 years from the UK Biobank study, a population-scale prospective cohort. Genetic instruments for estimated glomerular filtration rate (eGFR) were developed from the Chronic Kidney Disease Genetics genome-wide association study meta-analysis results, which comprised 567,460 individuals of European ancestry. eGFR for observational analysis and genetically predicted eGFR for MR analysis. Each of the 178 metabolites from recently updated metabolomics data, including detailed lipoprotein components within 14 subclasses of lipoprotein particles. Observational analysis was performed using multivariate linear regression adjusted for various clinicodemographic characteristics. A 2-sample MR analysis was performed using the random-effects inverse-variance weighted method as the main MR method. In the integrated results of the observational and MR analyses, 25 metabolites were causally associated with eGFR. A lower eGFR causally decreased lipoprotein components of high-density lipoprotein and several of its subclasses, particularly medium-sized high-density lipoprotein. Conversely, a lower eGFR causally increased triglyceride levels in smaller-sized very low-density lipoprotein and intermediate-density lipoprotein, as well as increased lipoprotein particle concentrations and total lipids in small very low-density lipoprotein. Additionally, a lower eGFR causally increased the ratio of monounsaturated fatty acids to total fatty acids and that of apolipoprotein B to apolipoprotein A-1. Possibility of false-negative findings when integrating observational and MR analyses. Decreased kidney function causally aggravates lipoprotein lipid profiles; therefore, clinicians should closely monitor the lipid profiles of individuals with impaired kidney function.

The number of elderly individuals continues to increase globally, accompanied by a high prevalence of chronic diseases, particularly hypertension and musculoskeletal disorders. This condition makes geriatric patients vulnerable to polypharmacy, which increases the risk of drug interactions, one of which is between antihypertensives and non-steroidal anti-inflammatory drugs (NSAIDs). Such interactions can potentially reduce therapy effectiveness, cause electrolyte disturbances, and lead to acute kidney injury (AKI). This study aims to comprehensively examine the interaction between antihypertensives and NSAIDs in geriatric patients and its impact on therapy safety. The method used is a literature review by selecting national and international articles published between 2015 and 2025, written in either Indonesian or English, specifically investigating interactions between antihypertensives (β-blockers, ACE inhibitors, ARBs, diuretics, and CCBs) and NSAIDs. The review results indicate that most interactions are pharmacodynamic, involving either antagonism or negative synergism. NSAIDs can reduce the effectiveness of antihypertensive therapy through mechanisms such as sodium retention, afferent arteriolar vasoconstriction, and decreased renal perfusion. In certain combinations, such as the triple whammy phenomenon (NSAIDs, diuretics, and RAAS inhibitors), the risk of AKI and hyperkalemia increases significantly. This risk is higher in geriatric patients with decreased kidney function, comorbidities, and concurrent use of multiple drugs. In conclusion, the interaction between antihypertensives and NSAIDs in the elderly population is an important clinical issue. Therefore, close monitoring of kidney function and electrolytes, using the lowest effective dose for the shortest possible duration, and patient education to avoid self-medication are necessary to ensure therapy safety.

Before elective surgery, direct oral anticoagulants (DOACs) are discontinued following a standardized protocol. However, this could result in insufficient lowering of DOAC levels that could increase bleeding risk. To estimate the proportion of patients with elevated DOAC levels at the time of elective surgery, evaluate factors associated with DOAC levels, and examine associated blood loss. This cohort study (DOAC Level Prior to Incision [DALI]) assessed adult patients prescribed a DOAC (apixaban, dabigatran, or rivaroxaban) for any indication and at any dose, undergoing an elective procedure requiring DOAC interruption between May 27, 2018, and February 25, 2024, at 2 Dutch hospitals. Standardized interruption protocol (1 day before moderate- and 2 days before high bleeding-risk procedures) with interruption adjustments for the patient's kidney function. Blood was drawn immediately before surgery to determine DOAC levels (by liquid chromatography-mass spectrometry). Proportions of preoperative DOAC levels of 30 ng/mL or higher and their 95% CIs were estimated, stratified by DOAC type and surgical bleeding risk. Factors associated with DOAC levels were identified through multivariable linear regression. Surgical blood loss and 30-day postoperative complications were described according to DOAC concentrations. The study was terminated after including 257 patients (100 receiving apixaban, 100 receiving rivaroxaban, and 57 receiving dabigatran due to the slow inclusion rate of those receiving dabigatran; median [IQR] age, 72 [66-78] years; 173 male [67%]); 212 patients (82%) underwent a high bleeding-risk operation. Preprocedural DOAC levels were 30 ng/mL or higher in 7.6% (95% CI, 4.9%-11.6%) of patients. Dabigatran and rivaroxaban had similar proportions, whereas 13.1% (95% CI, 7.8%-21.2%) of patients treated with apixaban had levels of 30 ng/mL or higher. Treatment with apixaban, decreased kidney function, and a shorter interruption time were associated with higher levels. Surgical blood loss (median [range], 0 [0-4250] mL) was not associated with DOAC levels. Twelve patients (4.7%; 95% CI, 2.7%-8.0%), who all had DOAC levels less than 30 ng/mL, experienced major bleeding. In this cohort study, most patients following the current protocol had DOAC levels less than 30 ng/mL, although the proportion of patients with elevated levels was higher for apixaban. Preoperative DOAC levels were not associated with blood loss during surgery.

Cardiovascular-kidney-metabolic (CKM) syndrome represents a distinct entity describing a highly comorbid group of patients and is disproportionately found in patients with kidney disease. This syndrome manifests as early presentations of cardiovascular disease even with mildly decreased kidney function and markedly increased rates of mortality as a result. However, there is currently a dearth of suitable preclinical tools to investigate and understand the progression and development of CKM.1 In this issue of Kidney360, Lotfollahzadeh et al.2 report data from a new murine model designed to recapitulate the complexities of CKM, in renal, metabolic, and cardiovascular pathophysiology, with peripheral arterial disease (PAD) as a functional manifestation. This model combines three interventions: high-fat diet obesity-related metabolic dysfunction, adenine-induced kidney disease, and finally overlaying a hind-limb ischemia model to represent PAD. Integrating Interventions The new model effectively combines key domains of CKM. First, renal injury with features such as tubular atrophy and glomerulomegaly, which are consistent with obesity-related hyperfiltration superimposed onto CKD damage.3 Second, metabolic disruption including hypercholesterolemia, impaired glucose tolerance, and hepatic steatosis (which was absent in adenine only mice). Third, cardiovascular involvement with myocardial fibrosis and reduced postischemic hind limb reperfusion to reflect impaired angiogenesis and microvascular rarefaction.4 Finally, skeletal muscle pathology with loss of type-2 fibers and reduced cross-sectional area.5 An essential strength is the inclusion of both sexes. Female mice showed synergistic deficits in endurance, grip strength, and fatigue resistance without a corresponding difference in perfusion, to suggest some intrinsic dysfunction. This aligns well with corresponding human data showing female patients with PAD experience greater functional impairment despite similar disease burden.6 The Importance of PAD in CKM PAD is often underemphasized in CKM despite its high prevalence and prognostic merit. PAD acts as a signal for wider vascular disease, but is also responsible for impaired quality of life by limiting exercise and increasing amputation risk.7 By including PAD in their model, the authors effectively include clinically relevant end points—endurance capacity, strength, and postexercise perfusion which mimic patient outcomes such as walking distance and claudication severity.7 Translational Potential The current model represents more than the sum of its individual parts. Previous studies have focused on renal progression alone,8 without the cardiovascular components so essential to insights into the holistic picture of CKM in clinical practice. These results may allow studies investigating therapies such as: Pleiotropic therapies like sodium-glucose cotransporter 2 inhibitors,9 glucagon-like peptide 1 inhibitors,10 or anti-fibrotic agents that may have efficacy across all arms of CKM, cardiovascular, renal, and metabolic. Investigate shared mechanisms like inflammation through TNF-α, and IL-6, oxidative stress and subsequent endothelial dysfunction, TGF-β mediated fibrosis and uremic toxin effects like aryl hydrocarbon signaling.1 Further understand sex differences to form and drive tailored therapeutic strategies. Lotfollahzadeh et al. acknowledge that adenine induced CKD is a very rapid aggressive induction of kidney disease akin to stage 3 or 4 in humans. This may potentially obscure additive progressive inductions of cardiovascular changes by metabolic stressors at milder levels of kidney damage. There is an opportunity to combine the other interventions with a milder form of CKD like nephrectomy and extend the experimental window to further understand synergistic nuanced changes. Relatedly, the model captures many features of CKM, but not all the readouts were synergistic between CKD and metabolic injuries. Seemingly, a disadvantage, but human data show ten distinct and highly-diverse CKM trajectories driven by wide variability in how risk factors combine.1 From this perspective, a partially additive set of interventions may actually be a strength. Additional interpretation of the murine response to diet and surgical interventions must be cautious, but nonetheless the model's design lends itself to hypothesis-driven testing of pathophysiology, therapeutics, and new candidate drug targets. A New CKM Research Landscape This study is timely because CKM and multiorgan interactions are rapidly moving from conceptual frameworks into well-distinguished clinical manifestations with defined staging systems and new diagnostic criteria.1 There remains a significant unmet clinical need and knowledge gap in the disproportionate cardiovascular disease risk in CKD patients with metabolic dysfunction, which this model potently pushes forward. This reproducible integrated multidomain platform expands the toolkit for researchers seeking to understand CKM and develop tools to ease the disease burden. Conclusion CKM represents a complex deeply heterogenous syndrome with a paucity of effective clinical interventions. The new murine adenine+high fat diet with peripheral artery disease imposition is a new way to unpick this complexity in vivo. The model may be further refined, but it presents fertile ground for further mechanistic exploration and therapeutic innovation. While the recognition of the import of CKM continues to increase, models like the one described here by Lotfollahzadeh et al. will be essential to alter the trajectory of disease for patients.

Severe COVID-19 frequently involves multi-organ dysfunction, including acute kidney injury (AKI), which affects up to 85% of critically ill patients. While both direct viral infection and systemic effects are implicated, the role of renal microthrombosis remains poorly defined in COVID-19 and AKI. Angiopoietin-2, a pro-inflammatory cytokine, and cleaved thrombomodulin is elevated in plasma in severe COVID-19 and has been linked to endothelial dysfunction and hypercoagulability. We hypothesize that renal microthrombi can contribute to decreased kidney function in critically ill COVID-19 patients. We performed histopathological and molecular analyses of postmortem kidney tissue from seven critically ill COVID-19 patients. Control tissue was obtained from nephrectomy specimens (n = 6) and postmortem tissue (n = 7). We assessed microthrombi, tubular necrosis, glomerulosclerosis, fibrosis, and expression of angiopoietin-2 and thrombomodulin. Immunofluorescence and SARS-CoV-2 nucleoprotein staining were used alongside clinical data. AKI was observed in six of seven COVID-19 patients. Compared to controls, COVID-19 kidneys showed a significant reduction in tubular nuclear area (P < 0.0003), presence of viral antigen in tubular epithelium, and marked glomerular and peritubular microthrombi (15.2 vs. 1.3 thrombi/mm²; P < 0.0001). THBD expression was significantly reduced bith peritubular capillaries and glomeruli in COVID-19 kidneys. Glomerulosclerosis, glomerular area, and tubulointerstitial fibrosis were variable in both control and COVID-19 patients with no significant differences. This study identifies widespread renal microthrombi, tubular necrosis, and reduced THBD expression in COVID-19 patients with AKI, supporting a role for endothelial dysfunction and microvascular thrombosis in COVID-19-associated renal injury. The data implicates the disruption of endothelial anticoagulant signaling through thrombomodulin as a contributing mechanism.

Diabetic Kidney Disease (DKD) is the leading cause of End Stage Renal Disease (ESRD). Arginine Vasopressin (AVP) plays pivotal roles in osmoregulation and renal water conservation. As patients with DKD are prone to develop osmotic irregularities, AVP is therefore, a potential pathophysiological target for disruption. Copeptin, a surrogate marker of AVP, is preferred over AVP due to comparatively greater stability and longer half-life. The study is designed to correlate the copeptin levels among subjects with Type 2 Diabetes Mellitus (DM) with worsening renal outcomes. It was a comparative cross-sectional study on 120 subjects with T2DM who were stratified into progressive deteriorating stages of chronic kidney disease (CKD) as per NKF KDOQI guidelines. Different biochemical variables HbA1c, serum BUN, serum creatinine UACR and GFR were done from the affiliated lab. Serum copeptin levels were determined using Copeptin sandwich ELISA technique. Data was analyzed through Statistical Program for Social Sciences (SPSS). Out of the 120 subjects that were recruited for study, 30% of subjects (n = 36) developed severely decreased kidney function with GFR less than 30mL/min/1.73m2. Copeptin levels were seen to be increased with progressive stages of albuminuria (175.8 ± 148.4 pg/ml, 221.2 ± 213.1 pg/ml and 385.3 ± 288.4 pg/ml at UACR stage 1, 2 and 3, respectively) with positive correlation i.e. r = 0.375, p = ≤ 0.001. It was also found to be negatively correlated with declining GFR i.e. from 195.8 ± 174.1 pg/ml at stage 1 CKD to 291.7 ± 268.8 pg/ml at stage 5 CKD (r = -0.409, p = ≤ 0.001). Increase in serum copeptin levels from stage 1 to stage 5 of CKD suggest its predictive role in T2DM associated nephropathy, supporting its potential role as an early biomarker. Early detection may help delay ESRD progression through timely interventions.

BackgroundMyelodysplastic syndromes(MDSs) have been known to be associated with various forms of kidney disease; however, whether they predispose to a longitudinal decrease in kidney function in the general population is unknown. This study aimed to investigate the association between MDSs and the risk of kidney function decline using a large-scale population-based cohort.MethodsWe retrospectively analysed nationwide administrative claims and health checkup data collected between April 2014 and August 2024. MDSs were identified using International Classification of Diseases, 10th Revision codes. Individuals were categorized into two groups according to the presence of MDSs. The primary outcome was a composite kidney outcome, defined as incident end-stage kidney disease, initiation of kidney replacement therapy or a ≥30% decline in estimated glomerular filtration rate.ResultsAmong 1 659 421 individuals {median age 68 years [interquartile range (IQR) 61–72]; 41.9% male}, MDSs were identified in 901 individuals (0.05%). During a median follow-up of 1092 days (IQR 631–1520), 33 335 individuals experienced the composite kidney outcome. Cumulative incidence curves demonstrated a higher incidence of kidney function decline in individuals with MDSs compared with those without MDSs (P < .001, logrank test). In multivariable Cox regression analysis, the presence of MDSs was independently associated with an increased risk of kidney function decline [hazard ratio 2.28 (95% confidence interval 1.66–3.13)].ConclusionsIn this large-scale nationwide cohort, MDSs were significantly associated with an increased risk of kidney function decline, positioning MDSs as a clinically relevant kidney risk condition and supporting closer kidney monitoring in this population.

Background: Regardless of the etiology, chronic kidney disease (CKD) is characterized by decreased kidney function seen by a glomerular filtration rate (GFR) of less than 60 mL/min per 1.73 m2, kidney damage markers, or both for at least three months. Chronic kidney disease, a degenerative illness for which there is not a solution yet, is linked to high rates of morbidity and death. Compared to the general population, individuals with diabetes and hypertension are more likely to have it. This research aimed to investigate the effects of hemodialysis on some biomarkers among patients with chronic kidney disease CKD. Patient and methods: This research is cross-sectional and conducted in a hospital setting. The study included 30 control samples and 60 patients with CKD. Results: Asignificant increase in the biochemucal parameters for urea, creatinine and uric acid while the revers effect shown with that of albumin.

BackgroundHigher plasma p‐tau217 levels have been related to cognitive decline in predominantly European American and European adult samples. Some studies suggest cardiovascular disease (CVD) and kidney disease, comorbidities more common in African American (AA) adults, are associated with cognitive dysfunction and elevated p‐tau217; consequently, these comorbidities may confound associations between p‐tau217 and cognition. Using p‐tau217 thresholds for amyloid (A) and tau (T) positive status, we examined if AT status associated with cognitive decline in an AA sample and if significant associations persisted when adjusting for comorbidities also identified as significant predictors of worsening cognition.MethodN = 199 African Americans Fighting Alzheimer's in Midlife (AA‐FAIM) study participants, without baseline dementia, had cognitive data and plasma (EDTA) p‐tau217 (AlzPath, Inc.) for analysis (Table 1). N = 130 had baseline estimated‐glomerular‐filtration‐rate (eGFR) to assess kidney function. CVD was defined as baseline history of myocardial‐infarction, congestive‐heart‐failure, or stroke. p‐tau217 thresholds for amyloid‐ and tau‐positive status (A+>.35pg/mL; T+>.556pg/mL) were derived from previous receiver‐operating‐characteristic‐curve analyses of AA‐FAIM amyloid‐ and tau‐PET data. Separate mixed effects models tested whether AT status (A+T+, A+T‐, A‐T‐[reference]), eGFR, 3‐level kidney function variable (mild‐to‐severe, mild, normal[reference]), and CVD moderated relationships between age and decline in: Rey‐auditory‐verbal‐learning‐test (RAVLT: immediate‐ and delayed‐recall), log‐transformed Trails A and B, semantic fluency, and preclinical‐Alzheimer's‐cognitive‐composite. If AT status, CVD and/or kidney‐function were significantly related to same cognitive outcome, the association between AT status and cognition was re‐tested adjusting for the comorbidity and age*comorbidity interaction. See Table 2 for covariates.ResultA+T+ status was related to greater decline in log‐transformed Trails B and RAVLT immediate‐recall; CVD predicted greater decline in log‐transformed Trails B; association between mild‐to‐severely decreased kidney function and decline in RAVLT immediate‐recall was not significant (p = .10) (Table 2). AT status and comorbidities were not associated with other cognitive outcomes. A+T+ status was associated with greater declines in log‐transformed Trails B and RAVLT immediate‐recall when adjusting, respectively, CVD and impaired kidney function and their interactions with age (Table 2; Figure 1).ConclusionIn AA‐FAIM, plasma p‐tau217 A+T+ status was related to greater decline in executive function and immediate‐recall, even following comorbidity adjustment. Replication is needed in samples having larger proportions with medical comorbidities.