Lower Glomerular Filtration Rate Research Articles

Prevalence and predictors of Sickle Cell Nephropathy A single-center experience.

Sickle cell disease (SCD) is the most common monogenic disorder in Saudi Arabia, which associates with an increased risk of organs damage, including the kidney. The aim of this study is to investigate the prevalence and predictors of sickle cell nephropathy (SCN) in the Saudi population. A retrospective study was conducted from April to October 2023, and included 343 adult patients with SCD who were recruited from the hereditary blood diseases center (HBDC), Al-Ahsa, Saudi Arabia. Spot protein-to-creatinine ratio was measured and glomerular filtration rate (GFR) was estimated from serum creatinine using the Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) equation. As per KIDGO guidelines, CKD was diagnosed in 93 (27.1%) patients. Based on the CKD-EPI equation, 2% of patients had low GFR (eGFR < 60mL/min), 28.3% had high GFR (eGFR > 140 mL/min), and 69.7% had normal GFR. Among SCD patients, proteinuria was observed in 26.5% of the patients. SCD patients with CKD were significantly older than non-CKD patients (p < 0.001) and had higher prevalence of diabetes mellitus (DM) and hypertension (HTN) (p = 0.045 and 0.001 respectively). The multivariate analysis showed that age (P = 0.001; OR 1.035; 95% CI 1.014-1.056) and low hemoglobin level (p = 0.034; OR -0.851; 95% CI 0.721-0.980) were independent risk factors for the development of SCN. Nephropathy is a common complication among patients with SCD as early as the third decade of life, although they remain asymptomatic. Advances in age and low hemoglobin levels are the main predictors of nephropathy. In addition, SCD patients with coexistent comorbidities, particularly DM and HTN, were at increased risk of developing kidney disease.

Acute Kidney Injury Following CAR-T Cell Therapy: A Nephrologist Perspective

Abstract Chimeric antigen receptor T-cell (CAR-T cell) therapy, an emerging personalized immunotherapy for various hematologic malignancies, autoimmune diseases, and other conditions, involves the modification of patients’ T cells to express a chimeric antigen receptor which recognizes tumor or autoimmune cell antigens. Thereby CAR-T cells destroy cancerous and other target cells selectively. Despite remarkable clinical improvements in patients, multiple adverse effects have been associated with CAR-T cell therapy. Among the most recognized adverse effects are cytokine release syndrome, immune effector cell-associated neurotoxicity syndrome, and tumor lysis syndrome. Even though less recognized, the incidence of acute kidney injury (AKI) ranges from 5% to 33%. The wide range of reported AKI incidence rates might depend on patient population characteristics and comorbidities and specific CAR-T cell therapy features. Even though the exact pathophysiology remains unknown, several key mechanisms including cytokine release syndrome, tumor lysis syndrome, and other factors such as direct renal toxicity of CAR-T cell therapy, conditioning regimens or other medications (e.g. antibiotics), and infectious complications (e.g. sepsis) have been proposed. Risk factors for CAR-T-related AKI include lower baseline glomerular filtration rate, higher rates of allopurinol or rasburicase use, intravenous contrast material exposure, elevated baseline lactate dehydrogenase, and grade 3 or higher cytokine release syndrome. Future prospective studies with larger patient populations are needed to gain more insight regarding the pathophysiology of CAR-T-related AKI, and, more importantly, to be able to prevent as well as to develop novel and more efficient treatment modalities. In this narrative review, we discuss the underlying pathophysiology, risk factors, potential interventions, and future directions related to AKI following CAR-T cell therapy.

Relation of albuminuria to some complications of chronic kidney disease in children: a single-center cross-sectional study

BackgroundChronic kidney disease is associated with several complications with higher prevalence and intensity at lower glomerular filtration rate. Albuminuria is the traditional biomarker of kidney damage. Although albuminuria can contribute to renal function decline, only a few studies have been published on whether albuminuria is associated with concurrent complications of chronic kidney disease. The aim of this work was to identify the relation between albuminuria and some of concurrent complications of chronic kidney disease among children.MethodsA cross-sectional study included fifty children with chronic kidney disease stages 2–5. Measurement of blood pressure, hemoglobin, serum bicarbonate, calcium, phosphorus, albumin, and lipid profile was done. Urinary albumin/creatinine ratio was determined. The relation between albuminuria and some of the complications of chronic kidney disease among children was studied.ResultsThe study included 50 patients aged 3–14 years. Dyslipidemia was present in 62% of the patients, acidosis in 56%, anemia in 38%, hyperphosphatemia in 34%, hypertension in 28%, and hypocalcemia in 22%. Eighty-eight percent had albuminuria, 26% had microalbuminuria, and 62% had macroalbuminuria. A statistically significant relation was found between the degree of albuminuria and presence of anemia and hyperphosphatemia. But no significant relation was found between the degree of albuminuria and presence of hypertension, dyslipidemia, acidosis, or hypocalcemia.ConclusionThere is a significant relation between the degree of albuminuria and presence of anemia and hyperphosphatemia among children with chronic kidney disease.

Early Acute Kidney Injury in Stroke Patients Submitted to Endovascular Treatment: A Cohort Study

Background/Objectives: Acute kidney injury (AKI) is a potential complication of cardiovascular disorders and is associated with worse outcome. The aim of this study was to assess the incidence of early AKI after endovascular therapy for acute ischemic stroke, identify predictors for this complication, and test the association between AKI and mortality or death or dependency. Methods: This was a single-center cohort study involving consecutive patients with acute ischemic stroke submitted to endovascular therapy between 2015 and 2022. AKI was defined according to the KDIGO criteria and evaluated at 48 h. Other outcomes of interest were vital status and functional dependency at 3 months using the modified Rankin Scale, with death or dependency being defined as a score &gt; 2. An adjustment for potential confounders was performed using logistic regression. Results: Overall, 1150 patients were included in the analysis, with a mean age of 74 years and a slight female preponderance (56%). The median NIHSS was 15, the mean onset-to-groin time was 392 min, and 92% of patients were successfully recanalized. The overall incidence rate of AKI was 6%. On univariate analysis, patients with AKI were older (p = 0.002), had a longer time to EVT (p = 0.042), higher NIHSS (p = 0.006), higher blood glucose (p = 0.033), and lower baseline glomerular filtration rate (GFR) (p &lt; 0.001). After adjustment for confounders, AKI was independently associated with NIHSS (p = 0.012), time to treatment (p = 0.004), and lower baseline GFR (p &lt; 0.001). AKI was also independently associated with higher mortality (OR = 2.302, p = 0.003). Conclusions: Patients with impaired baseline renal function and more severe stroke are at higher risk of AKI, and AKI begets worse stroke outcome. Better strategies are required to optimize treatment outcome in these patients and avert this vicious cycle.

Evaluation of the Accuracy of Point-of-Care Urine Chloride Measured via Strip Test in Patients with Heart Failure

Background: In clinical practice, patient self-monitoring is crucial in achieving therapeutic goals in various diseases. In heart failure (HF), it is particularly important due to the increasing role of urine composition. Therefore, we proposed this study to assess the accuracy of urine chloride (uCl−) assessment via strip test in relation to chloride and sodium (uNa+) measurements in a gold-standard laboratory method. Methods: Urine samples were collected before administering morning medications. Afterwards, they were analyzed concurrently using the strip test and gold-standard laboratory method. Results: The study cohort comprised 66 patients (82% male, mean age 68 ± 12 years), of whom 65% were diagnosed with HF and 35% without HF. Across the entire cohort, a strong correlation was observed between uCl− measured by both methods (r = 0.85; p &lt; 0.001). However, the strip test was found to underestimate uCl− relative to the laboratory measurements (mean difference of 18 mmol/L). Furthermore, strong correlations were observed between the methods among patients with HF and without HF (r = 0.88 vs. r = 0.71, respectively; p &lt; 0.001 for both), where they presented similar relationship patterns. Interestingly, in patients with a low glomerular filtration rate (eGFR ≤ 60 mL/min/1.73 m2), the correlation between both methods was greater compared to those with high eGFR (&gt;60 mL/min/1.73 m2) (r = 0.94 vs. r = 0.76, respectively; p &lt; 0.001 for both). The relationship between uCl− from the strip test and uNa+ from the laboratory measurement was weaker than for uCl−, but it was significant. Conclusions: These findings suggest that point-of-care strip tests for assessing urinary chloride demonstrate high accuracy and potential utility, particularly in patients with reduced eGFR.

Impact of changes in proteinuria on the risk of atrial fibrillation in patients with diabetes mellitus: a nationwide population-based study

Abstract Background Diabetes mellitus (DM) is a well-known risk factor for atrial fibrillation (AF). Proteinuria is also considered as an independent predictor for AF. However, there is limited data on whether the changes in proteinuria severity can impact the risk of AF among patients with DM. Purpose We aimed to evaluate the association between changes in proteinuria over time detected using a urine dipstick test and the risk of AF among patients with DM. Methods A total of 1,605,495 patients with DM who underwent two biennial health checkups provided by the National Health Insurance Service (NHIS) between January 2013 and December 2016 were included. All patients had two consecutive urine dipstick tests during the checkups. We divided the study population into four groups based on their glomerular filtration rate (GFR): &amp;gt; 90 ml/min, 60-90 ml/min, &amp;lt; 60 ml/min, and those with end-stage renal disease (ESRD). We evaluated the association between the changes in proteinuria over time detected using a urine dipstick test and the risk of AF and their changes by GFR. Results During a median 4.0-year follow-up, AF occurred in 32,391 persons (5.22 per 1,000 person-years). Among 1,605,495 patients who underwent two consecutive urine dipstick tests, 1,453,116 (90.51%) patients had a negative proteinuria on both tests (negative or trace result on both urine dipstick tests), and 68,979 (4.3%) patients had an aggravated proteinuria (from negative to more than 1+ result on subsequent urine dipstick test). While 48,357 (3.01%) patients had a resolved proteinuria (from positive to negative results on subsequent tests) and 35,043 (2.18%) patients had a persistent proteinuria (positive result on both tests). Those with aggravated or resolved or persistent proteinuria showed an increased risk of AF (HR 1.39, 95% CI 1.33-1.46; HR 1.37, 95% CI 1.30-1.45; HR 1.95, 95% CI 1.85-2.06) compared with most subjects who showed subsequent negative results on proteinuria. This result was consistent within every GFR group. However, the tendency of increment of AF risk by changes in proteinuria was more prominent in lower GFR groups (Table). In subgroup analysis, there was no significant difference between male and female. However, the younger aged (&amp;lt; 65 years) group had a more prominent tendency of increased AF risk by changes in proteinuria. Conclusion Changes in proteinuria showed a significant association with the risk of AF in patients with DM. This tendency was prominent in patients with lower GFR. Therefore, careful monitoring of AF risk based on proteinuria changes could be beneficial for those with DM.

Amyloid beta, a marker of vascular aging and cardiovascular disease, is associated with accelerated progression of renal dysfunction

Abstract Background Amyloid-beta (1-40) (Αb1-40), a proinflammatory and pro-atherosclerotic peptide, is involved in Alzheimmer’s disease and vascular aging and is considered an emerging prognostic marker of atherosclerotic cardiovascular disease (ASCVD) and heart failure. Because Ab1-40 clearance is largely dependent on renal function while clinical data consistently associate this peptide with renal function, we hypothesized that Ab1-40 circulating levels would serve as a predictor of progression of renal dysfunction. Purpose To examine the potential cross-sectional and prospective bidirectional association of Ab1-40 levels with renal function in a population with a wide range of ASCVD risk. Methods In the settings of the Athens Cardiometabolic registry, data from consecutively recruited subjects with (n=137) and without clinically overt ASCVD (n=674) with available both Ab1-40 plasma levels and GFR values (total n=811) were analyzed. Αb1-40 was measured by enzyme-linked immunosorbent assay and renal function was assessed by estimation of glomerular filtration rate (GFR). Of these subjects, 182 individuals consented to be followed up and re-assessed after a minimum period of 12 months in order to examine a potential bidirectional link between changes in Ab1-40 levels and GFR. Results Patients with increased Ab1-40 levels at baseline had significantly worse renal function, reflected as lower GFR values, compared with their counterparts with lower Ab1-40 levels (GFR= 74.8 vs 93.3 vs 100.2 ml/min/1.73m2 for high, middle and low tertile of Ab1-40 levels, p&amp;lt;0.001). Elevated Ab1-40 levels were associated with chronic kidney disease (CKD) stage 2 [odds ratio (OR)=2.29, 95% confidence intervals (CI)= 1.58-3.31, p&amp;lt;0.001] and CKD stage 3 (OR=3.67, 95% CI=2.37-5.70, p&amp;lt;0.001) at baseline. Furthermore, increased Ab1-40 at baseline was prospectively associated with accelerated progression of renal dysfunction as assessed by changes in GFR values between baseline and follow-up [mean adjusted rate of decrease=-7.20 (95% CI=-1.33, -13.07) for higher vs lowest tertiles of Ab1-40 levels across a follow-up period of 12 months, p=0.017 for interaction). On the contrary, baseline GFR values were not prospectively associated with Ab1-40 levels at follow-up visits (p&amp;gt;0.05). Conclusion In a population with a wide range of ASCVD risk, high Αb1-40 levels at baseline were associated both with renal function at baseline and with accelerated rate of progression of GFR deterioration at follow-up irrespective of its baseline levels. These findings suggest a mechanistic background for the established association of Ab1-40 with renal function and warrant further research to clarify the clinical value of monitoring its circulating levels as a novel biomarker which could reflect enhanced risk for renal dysfunction.

The prothrombotic state in patients with type 2 diabetes mellitus and ischemic heart failure: an association with endothelial dysfunction

Abstract Background Heart failure (HF) is associated with a substantial prothrombotic state and an increased risk of thromboembolism, regardless of the presence of atrial fibrillation (AF). Although oral anticoagulation in HF with known AF is recommended, there is no conclusive evidence supporting clinical benefits of chronic anticoagulation in HF subjects without AF. Other factors enhancing prothrombotic state, often concomitant with HF, are type 2 diabetes mellitus (T2D) and coronary artery disease (CAD). T2D as well as CAD are independently associated with a hypercoaguability due to multiple mechanisms including endothelial dysfunction and oxidative stress. Dysfunction of endothelium was observed in patients with HF, however a little is known about its influence on prothrombotic state in a very high risk HF population. Purpose This study aimed to investigate whether the prothrombotic state in patients with T2D, CAD, and HF, depends on the left ventricular ejection fraction (LVEF) or endothelial function. Methods We assessed 54 patients with stable chronic HF, CAD, and T2D. Based on the echocardiography examination 28 of them were those with HF with reduced ejection fraction (HFrEF) and 26 of them were classified as HF with preserved ejection fraction (HFpEF) according to current guidelines. Fibrin clot density reflected by clot permeability (Ks) and thrombin generation were evaluated. Endothelial function was determined in flow-mediated (FMD) and nitroglycerin-mediated dilatation (NMD) tests of the brachial artery. Results Subjects in both groups were comparable in terms of cardiovascular risk factors except for lower glomerular filtration rate (GFR) by 18.1%. HFrEF patients had lower Ks by 20.3%, along with higher endogenous thrombin potential (ETP) by 18.9% and maximum thrombin level (Peak) by 24.1% as compared with HFpEF. While there were no differences in FMD and NMD between subjects, we found negative correlations of NMD with ETP and Peak (r=-0.448, P=0.001; r=-0.304, P=0.034, respectively). Moreover, the proportion of NMD and FMD along with GFR and LVEF were also significantly associated with both thrombogram parameters (&amp;lt;0.01 for all). By the multivariate analysis of the whole population, NMD, LVEF, low-density lipoprotein and GFR were independent predictors of ETP (R2=0.530, P&amp;lt;0.001) while NMD, LVEF, and GFR predicted Peak levels (R2=0.327, P=0.002). Conclusion We showed for the first time that patients with ischemic etiology of HFrEF and T2D presented altered fibrin clot properties and enhanced thrombin generation compared to HFpEF subjects. It might be hypothesized that endothelial dysfunction induced by T2D could intensify hypercoagulability in patients with HF.Figurę 1

Enhanced Creatinine Level in Diabetic Patients Maximizing the Possibilities of Nephropathy and Its Association With Blood Urea Nitrogen and Glomerular Filtration Rate.

Diabetes mellitusis a common metabolic disorder that is sometimes responsible for kidney diseases, especially in the form of diabetic nephropathy. In this study, we tried to investigate the markers associated with kidney diseases within diabetic patients as compared to non-diabetic participants. In this study, among 237 participants, 81 patients were diabetic, whereas 156 were non-diabetic participants. The level and association of serum creatinine, blood urea nitrogen (BUN), and glomerular filtration rate (GFR) were investigated using the enzymatic method and CKD-EPI equation respectively. We found significantly higher creatinine and BUN levels and lower GFR in the diabetic group compared to the non-diabetic group. Besides, we determined a positive association between creatinine and BUN, and an inverse relationship between GFR and creatinine and BUN respectively which was highly scattered in the case as compared to the non-diabetic group. Further analysis of the participants with high creatinine levels only supported the main outcomes. Conclusion: Our investigation of kidney markers suggests a significant association between diabetes and kidney complications. Leading a healthy lifestyle and maintaining blood sugar and pressure may help to slow down the progress of diabetic nephropathy for diabetic patients.

Comparison of Autologous and Allogeneic Adipose-Derived Stem Cells in Kidney Transplantation: Immunological Considerations and Therapeutic Efficacy.

Regenerative medicine shows significant potential in treating kidney diseases through the application of various types of stem and progenitor cells, including mesenchymal stem cells (MSCs), renal stem/progenitor cells, embryonic stem cells (ESCs), and induced pluripotent stem cells (iPSCs). Stem cells possess the unique ability to repair injured organs and improve impaired functions, making them a key element in the research of therapies for kidney tissue repair and organ regeneration. In kidney transplantation, reperfusion injury can cause tissue destruction, leading to an initially low glomerular filtration rate and long-term impact on function by creating irreversible interstitial fibrosis. MSCs have proven useful in repairing early tissue injury in animal models of kidney, lung, heart, and intestine transplantation. The use of stem cell therapies in solid organ transplantation raises the question of whether autologous or allogeneic cells should be preferred. Adipose-derived stem cells (ASCs), characterized by the lack of HLA Class II molecules and low expression of HLA Class I and co-stimulatory signals, are considered immune-privileged. However, the actual risk of graft rejection associated with allogeneic ASCs remains unclear. It has been demonstrated that donor-derived ASCs can promote the development of Treg cells in vitro, and some degree of tolerance induction has been observed in vivo. Nevertheless, a study comparing the efficacy of autologous and allogeneic ASCs in a rat model with a total MHC mismatch for kidney transplantation showed that donor-derived administration of ASCs did not improve the grafts' survival and was associated with increased mortality through an immunologically mediated mechanism. Given the lack of data, autologous ASCs appear to be a safer option in this research context. The aim of this review was to examine the differences between autologous and allogeneic ASCs in the context of their application in kidney transplantation therapies, considering potential immune reactions and therapeutic efficacy. Some have argued that ASCs harvested from end-stage renal disease (ESRD) patients may have lower regenerative potential due to the toxic effects of uremia, potentially limiting their use in transplantation settings. However, evidence suggests that the beneficial properties of ASCs are not affected by uremia or dialysis. Indeed, some investigators have demonstrated that ASCs harvested from chronic kidney disease (CKD) patients exhibit normal characteristics and function, maintaining consistent proliferative capacity and genetic stability over time, even after prolonged exposure to uremic serum Furthermore, no differences were observed in the response of ASCs to immune activation or their inhibitory effect on the proliferation of alloantigen-activated peripheral blood mononuclear cells between patients with normal or impaired renal function. This review presents the current achievements in stem cell research aimed at treating kidney diseases, highlighting significant progress and ongoing efforts in the development of stem cell-based therapies. Despite the encouraging results, further research is needed to overcome the current limitations and fully realize the potential of these innovative treatments. Advances in this field are crucial for developing effective therapies that can address the complex challenges associated with kidney damage and failure.

Association of Angiotensin Converting Enzyme (insertion\deletion) and Angiotensin II Type 1 Receptor (A1166C) gene polymorphisms with diabetic nephropathy in Iraqi type 2 diabetic patients

Renin-angiotensin-aldosterone system abnormalities are the most prevalent cause of renal hemodynamic abnormalities, and candidate genes in this system are involved in the etiology of diabetic nephropathy (DN). A polymorphism in the angiotensin converting enzyme (ACE) gene I(insertion)\D(deletion) has been correlated to plasma ACE levels. Furthermore, the Angiotensin II Type 1 Receptor AGT1R (A1166C) expression pattern is highly related to nephropathy. The objectives of this study involved evaluating the frequency of the ACE (I/D) and AGT1R (A1166C) gene polymorphisms and investigating the association of these polymorphism with the development of DN in Iraqi patients with Type 2 diabetes mellitus (T2DM) and evaluating the levels of several urinary and serum markers in relation to studied polymorphisms. This is a cross-sectional study that included 161 T2DM patients whom were divided into two groups: T2DM with DN(included 98 patients) and normalbuminuric T2DM (included 63 patients). ACE gene polymorphism analysis revealed that the D allele was far more prevalent in DN patients compared to normalbuminuric patients (60.2% vs. 50.8%), while the I allele frequency was 39.8% in DN and 49.2% in normoalbuminuric patients. In addition, DN patients carrying the DD genotype had higher serum kidney injury molecule 1 (KIM1), serum cystatin C (CysC), and HbA1C and lower glomerular filtration rate (GFR) compared to ID+II genotypes. For AGT1R (A1166C), both DN and normalbuminuric patients had a comparable high prevalence of the AA genotype, followed by the AC genotype, while the CC genotype had been seen only in 3 patients. In conclusion, among the studied T2DM patients, individuals with DD genotype had higher frequency of DN and had 2-fold risk for DN compared to II genotype which had the lowest risk for DN. Also the current study shows that the A1166C polymorphisms of AGT1R distribution frequency were similar for both study groups with higher frequency for A allele compared to C allele and not associated with risk of DN in Iraqi T2DM Keywords: Angiotensin Converting Enzyme (I\D) gene polymorphism, Angiotensin II Type 1 Receptor (A166C) gene polymorphisms, Cystatin C, Diabetic nephropathy, Kidney injury molecule1.

Impact of sex on clinical and laboratory parameters in patients with heart failure: insights from the Colombian Heart Failure Registry (RECOLFACA)

Introduction Heart failure (HF) is one of the leading causes of morbidity and mortality worldwide. This study aimed to assess the impact of sex on sociodemographic, clinical, and laboratory parameters in patients with HF who were included in the Colombian Heart Failure Registry (RECOLFACA). Methods This was a cross-sectional analytical research. All 2528 patients included in RECOLFACA were analysed. The Mann–Whitney U test was used to compare median values as well as first and third quartiles (Q1–Q3). The age-related trend of NT-proBNP levels for both men and women groups was statistically evaluated. Results The study included 2528 patients with HF (1072 women and 1456 men). The echocardiographic evidence showed that men presented reduced left ventricular ejection fraction (LVEF) (79.63 vs. 69.75%, respectively; p < 0.001) more often than women, which had a significantly higher proportion of preserved LVEF (20.46 vs.11.24%, respectively; p < 0.001). Women displayed a higher value of systolic blood pressure (p < 0.001) and heart rate (p = 0.014) compared to men. Haemoglobin, creatinine, and sodium levels were significantly higher in men. Men had a considerably lower glomerular filtration rate value, with the median reaching a G3a value for chronic renal failure. According to age, the levels of NT-proBNP in each sex increased equivalently with age. Conclusion Sex differences presented in this study are comparable to those discovered in other nations. However, certain variations show that these sex differences may differ by geographical area, which should encourage further investigations to describe them.

Apixaban plasma concentrations before and after catheter ablation for atrial fibrillation.

Catheter ablation in patients with atrial fibrillation is associated with a transient increase in thromboembolic risk and adequate anticoagulation is highly important. When patients are anticoagulated with apixaban, monitoring of plasma concentrations of the drug is not routinely performed. This study aimed to assess the influence of clinical patient characteristics, concomitant drug treatment and self-reported adherence on apixaban concentrations, and to describe the intra- and inter-individual variability in apixaban concentrations in this group of patients. Method Apixaban concentrations from 141 patients were measured in plasma one week before ablation and two, six and ten weeks after ablation, employing ultra-high performance liquid chromatography coupled with tandem mass spectrometry. In samples not obtained at trough, apixaban concentrations were adjusted to trough levels. Self-reported adherence was registered by means of the 8-item Morisky Medication Adherence Scale before and after ablation. There were statistically significant, positive correlations between apixaban concentrations and increased age, female sex, lower glomerular filtration rate, higher CHA2DS2-VASc score, use of cytochrome P450 3A4 and/or p-glycoprotein inhibitors, and use of amiodarone. Self-reported adherence was generally high. The mean intra-individual and inter-individual coefficients of variation were 29% and 49%, respectively. In patients undergoing catheter ablation for atrial fibrillation, age, sex, renal function, interacting drugs and cerebrovascular risk profile were all associated with altered plasma apixaban concentration. In this group of patients with a generally high self-reported adherence, intra-individual variability was modest, but the inter-individual variability was substantial, and similar to those previously reported in other patient apixaban-treated populations. If a therapeutic concentration range is established, there might be a need for a more flexible approach to apixaban dosing, guided by therapeutic drug monitoring.

Genetic association of diabetic retinopathy with long noncoding RNA CDKN2B-AS1 gene polymorphism.

We attempted to test the influences of cyclin dependent kinase inhibitor 2B antisense RNA 1 (CDKN2B-AS1) gene polymorphisms on the susceptibility to Diabetic retinopathy (DR). Five single-nucleotide polymorphisms (SNPs) of the CDKN2B-AS1 gene, rs564398, rs1333048, rs1537373, rs2151280, and rs8181047 were examined in 280 DR cases and 455 DR-free diabetic controls. Among these loci tested, we demonstrated that diabetic carriers of at least one polymorphic allele (G) of rs2151280 (AG and GG; AOR, 1.613; 95% CI, 1.040-2.501; p = 0.033) are more susceptible to proliferative DR but not non-proliferative DR. This genetic association with the risk of developing proliferative DR was further strengthened in homozygotes for the polymorphic allele (G) of rs2151280 (GG; AOR, 2.194; 95% CI, 1.117-4.308; p = 0.023). We detected a significant association of the polymorphic allele (G) of rs2151280 with proliferative DR patients (OR, 1.503; 95% CI, 1.112-2.033; p = 0.008) but not with the entire DR or non-proliferative DR group. Moreover, as compared to those who do not possess the polymorphic allele of rs2151280 (AA), DR patients carrying at least one polymorphic allele of rs2151280 (AG + GG) exhibited a lower glomerular filtration rate and HDL cholesterol level, revealing a promotive role of rs2151280 in renal and cardiovascular complications of diabetes. Taken together, our findings implicate an impact of CDKN2B-AS1 gene polymorphisms on the progression of DR.

Underrepresentation of black individuals in pivotal trials for novel anticancer drugs: Potential consequence of using estimated creatinine clearance to assess kidney function?

BackgroundBlack individuals are historically underrepresented in oncology clinical trials. One potential reason for this is the prevalence of kidney disease in Black individuals, utilization of estimated creatinine clearance as a surrogate for glomerular filtration rate (GFR) in oncology, and GFR-based trial eligibility criteria. We characterized the representation of racial minorities in anticancer agent pivotal trials and examined if GFR-based trial eligibility criteria impact the proportion of Black individuals in trial populations. MethodsWe constructed a data repository for anticancer drugs FDA-approved from 2015 to 2019 and associated pivotal trials, from which we extracted trial population racial compositions and GFR-based trial eligibility criteria. We calculated the participation-to-incidence ratio (PIR) and participation-to-mortality ratio (PMR) for a variety of cancer sites, where PIR or PMR >1.2 and <0.8 indicate overrepresentation and underrepresentation, respectively. We evaluated the relationship between GFR eligibility cutoffs and the proportion of Black enrollees with Spearman rank correlation coefficient. ResultsWe assessed 24,698 patients in 74 trials. Black individuals were underrepresented in all trials (PIR ≤0.48, PMR ≤0.50). For trials with GFR-based eligibility criteria (n = 49), a lower GFR cutoff was modestly associated with a higher proportion of Black enrollees (r = −0.29, p = 0.039). This relationship was strengthened for trials that only used estimated creatinine clearance to estimate GFR (r = −0.43, p = 0.004). ConclusionsGFR-related eligibility, and specifically the use of estimated creatinine clearance, may contribute to Black individuals being disproportionately excluded from cancer clinical trials. This highlights the need for implementation of contemporary GFR equations and other interventions to boost racial minority trial enrollment.

Random survival forest for predicting the combined effects of multiple physiological risk factors on all-cause mortality

Understanding the combined effects of risk factors on all-cause mortality is crucial for implementing effective risk stratification and designing targeted interventions, but such combined effects are understudied. We aim to use survival-tree based machine learning models as more flexible nonparametric techniques to examine the combined effects of multiple physiological risk factors on mortality. More specifically, we (1) study the combined effects between multiple physiological factors and all-cause mortality, (2) identify the five most influential factors and visualize their combined influence on all-cause mortality, and (3) compare the mortality cut-offs with the current clinical thresholds. Data from the 1999–2014 NHANES Survey were linked to National Death Index data with follow-up through 2015 for 17,790 adults. We observed that the five most influential factors affecting mortality are the tobacco smoking biomarker cotinine, glomerular filtration rate (GFR), plasma glucose, sex, and white blood cell count. Specifically, high mortality risk is associated with being male, active smoking, low GFR, elevated plasma glucose levels, and high white blood cell count. The identified mortality-based cutoffs for these factors are mostly consistent with relevant studies and current clinical thresholds. This approach enabled us to identify important cutoffs and provide enhanced risk prediction as an important basis to inform clinical practice and develop new strategies for precision medicine.

Early Diagnostic and Management of Acute Heart Failure: Can Cardiogenic Shock be Prevented?

Background: Heart failure is a growing health concern, affecting about 2% of the adult population. It emphasizes the importance of recognizing and addressing a specific subgroup of patients suffering from acute heart failure (AHF). AHF is described as a critical clinical condition often overlooked in diagnosis, leading to catastrophic outcomes if not promptly identified. Given its potential severity, understanding the unique characteristics of AHF, along with appropriate therapeutic interventions, is crucial for improving patient outcomes and reducing mortality rates. Methods: The study included 20 patients with heart failure and reduced ejection fraction who presented with decompensated clinical conditions characteristic of acute heart failure. Data were collected preoperatively, perioperatively, and postoperatively up to a 30-day follow-up period. Results: The primary outcome was the 30-day mortality, which was found to be 20%. Among the patients with AHF, 60% had congestive heart failure with an average ejection fraction of 29.8%, indicating severe ventricular dysfunction. Additionally, 45% of patients presented with chronic kidney injury, characterized by a low mean glomerular filtration rate and elevated urea and creatinine levels. The presence of acute congestive and retention syndrome was evident in these patients, exacerbating the underlying disease. Notably, 10% of patients required left ventricular assistance devices, and associated procedures were performed as part of the surgical management of heart failure. Conclusion: The failure to recognize the diagnosis of this serious acute condition can quickly lead to patient’s death. Although, AHF showed 30-days high mortality rate, early diagnose, decongestive therapy and myocardial revascularization had avoided worst outcomes in cardiogenic shock.

Metabolic Dysfunction-Associated Steatotic Liver Disease in Severe Obesity and Concordance between Invasive (Biopsy) and Noninvasive (OWLiver®) Diagnoses

Introduction: Nonalcoholic fatty liver disease (NAFLD), now termed metabolic dysfunction-associated steatotic liver disease (MASLD), is an escalating health concern linked to obesity and type 2 diabetes. Despite liver biopsy being the gold standard, its invasiveness underscores the need for noninvasive diagnostic methods. Methods: A cross-sectional study was performed to assess MASLD using the noninvasive OWLiver® serum lipidomics test in a cohort of 117 patients with severe obesity undergoing bariatric surgery, comparing outcomes with liver biopsy. Exclusions (n = 24) included insufficient data, liver disease etiology other than MASLD, corticosteroid treatment, excessive alcohol consumption, low glomerular filtration rate, and declination to participate. Comprehensive laboratory tests, demographic assessments, and liver biopsies were performed. Serum metabolites were analyzed using OWLiver®, a serum lipidomic test that discriminates between healthy liver, steatosis, metabolic dysfunction-associated steatohepatitis (MASH), and MASH with fibrosis ≥2 by means of three algorithms run sequentially. Results: Liver biopsy revealed a MASLD prevalence of 95.7%, with MASH present in 28.2% of cases. OWLiver® demonstrated a tendency to diagnose more severe cases. Body mass index (BMI), rather than the presence of type 2 diabetes, emerged as the sole independent factor linked to the probability of concordance. Therefore, the all-population concordance of 63.2% between OWLiver® and liver biopsy notably raised to 77.1% in patients with a BMI <40 kg/m2. These findings suggest a potential correlation between lower BMI and enhanced concordance between OWLiver® and biopsy. Conclusion: This study yields valuable insights into the concordance between liver biopsy and the noninvasive serum lipidomic test, OWLiver®, in severe obesity. OWLiver® demonstrated a tendency to amplify MASLD severity, with BMI values influencing concordance. Patients with BMI <40 kg/m2 may derive optimal benefits from this noninvasive diagnostic approach.

Low platelet count at admission has an adverse impact on outcome in patients with acute coronary syndromes: from the START Antiplatelet registry

Some previous observations suggest that a low platelet count is associated with an increased risk of adverse outcomes in patients with acute coronary syndromes (ACS). However, most of the data come from post-hoc analyses of randomized controlled trials and from studies including thrombocytopenia developed during hospital stay. Our aim was to assess the impact of low platelet count at admission on cardiovascular outcomes and treatment approach in patients hospitalized for ACS in a current real-life setting in Italy. Patients admitted to Italian coronary care units for ACS were enrolled in the START-ANTIPLATELET registry. Baseline clinical characteristics and treatment at discharge were recorded. Patients were followed-up at 6 months, 1 year and yearly thereafter. Low platelet count was defined as a count at admission < 150 > 100 k/µl or < 100 k/µL. Among 1894 enrolled patients, 157 (8.3%) had a platelet count < 150 > 100 k/µl and 30 (1.6%) < 100 k/µl. The median follow-up was 12.3 months (0.4–50.1). patients with low platelets were older (72 ± 10.4 vs 66 ± 12.4 years, p = 0.006), more frequently males (82.9 vs 72.1%, p = 0.001), hypertensive (90.0% vs 70.4%, p = 0.03), with non-valvular atrial fibrillation (NVAF) (17.1 vs 8.6%, p = 0.02), and peripheral arterial disease (11.5 vs 6.2% p = 0.01) and/or had a previous myocardial infarction (40 vs 18.7%, p = 0.008) and/or a PCI (14.6 vs 7.8%, p = 0.001) than patients with normal platelets. A slightly, but significantly, lower percentage of thrombocytopenic patients were treated with primary PCI (78.1 vs 84.4%, p = 0.04) and they were more frequently discharged on aspirin plus clopidogrel rather than aspirin plus newer P2Y12 antagonists (51.9 vs 65.4%, p = 0.01). MACE-free survival was significantly shorter in thrombocytopenic patients compared to patients with normal platelets (< 150 > 100 k/µl: 37.6 vs 41.8 months, p = 0.002; HR = 2.7, 95% CIs 1.4–5.2; < 100 k/µl: 31.7 vs 41.8 months, p = 0.01; HR = 6.5, 95% CIs 1.5–29.1). At multivariate analysis, low platelet count, age at enrollment, low glomerular filtration rate, low ejection fraction, a previous ischemic stroke and NVAF were independent predictors of MACE. A low platelet count at admission identifies a subgroup of ACS patients with a significantly increased risk of MACE and these patients should be managed with special care to prevent excess adverse outcomes.

Kidney function, but not nitrogen excretion, differs between Brown Swiss and Holstein dairy cows

Brown Swiss (BS) cows have greater urea concentrations in milk and blood compared with Holstein (HO) cows. We tested the hypothesis that BS and HO cows differ in kidney function and nitrogen excretion. Blood, saliva, urine, and feces were sampled in 31 multiparous BS and 46 HO cows kept under identical feeding and management conditions. Samples were collected at different lactational stages after the monthly DHIA control test-day. To test the glomerular filtration rate (GFR) and urea excretion, concentrations of creatinine and urea were measured in serum, urine, and saliva. As an additional marker to estimate GFR, we determined symmetric dimethylarginine (SDMA) in serum. Feces were analyzed for dry matter content and nitrogen concentration. Data on milk urea and protein concentrations, and daily milk yield were obtained from the monthly DHIA test-day records. The effects of breed, time, and parity number on blood, saliva, urine, feces, and milk parameters were evaluated with the GLM procedure with breed, time, and parity number as fixed effects. Differences between BS and HO were assessed by the Tukey-corrected t-test at P < 0.05. Concentrations of urea, creatinine, and SDMA in serum, were greater in BS than in HO cows (P < 0.01): 5.46 ± 0.19 vs 4.72 ± 0.13 mmol/L (urea), 105.96 ± 2.23 vs 93.07 ± 1.50 mmol/l (creatinine), and 16.78 ± 0.69 vs 13.39 ± 0.44 µg/dL (SDMA). We observed a greater urea concentration in BS cows (25.8 ± 0.7 vs 21.8 ± 0.7 mg/dL) and protein content in milk (3.70 ± 0.08 vs 3.45 ± 0.07%) than in HO cows (P < 0.01). Urea and creatinine concentrations in urine and saliva did not differ among breeds. No differences between BS and HO were observed for milk yield, fecal DM, and fecal nitrogen content. Dry matter intake and body weight were similar in BS and HO cows (P > 0.05). Despite greater urea, creatinine, and SDMA concentrations in blood as well as a higher milk urea content in BS compared with HO, respective concentrations in urine did not differ between breeds. In conclusion, our results demonstrate a lower renal GFR in BS compared with HO cows, thereby contributing to the greater plasma urea concentration in BS cows. However, estimation of nitrogen excretion via milk, urine, and feces does not entirely reflect nitrogen turnover within the animal.