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Aims: To assess the prevalence and risk factors for chronic kidney disease (CKD) among adults with type 2 diabetes within primary care. Methods: This cross-sectional study evaluated 1319 individuals receiving standard care across 26 primary units from July 2017 to January 2023. The estimated glomerular filtration rate (eGFR) and albuminuria were used for the diagnosis of CKD. CKD was defined by eGFR values of <60 mL/min/1.73 m2 and/or albumin-to-creatine ratio ≥30 mg/g. Logistic regression was applied to identify factors associated with CKD and study variables. Results: The median age of participants (60.6% females) was 55 years and the median diabetes duration was 10 years. The overall CKD prevalence in the study population was 39.2%. Within the CKD group, the prevalence rates of albuminuria, albuminuria coupled with low eGFR and isolated low eGFR were 72.1%, 19%, and 8.9%, respectively. The prevalence of CKD was 30.6% among participants under 40 years old and a higher value was observed in middle-aged adults with early-onset diabetes (at age <40 years) compared with the later-onset group. Multivariable analyses identified associations between CKD and factors such as age, the male sex, diabetes duration, hypertension, retinopathy, and metformin use. Conclusion: A relatively high prevalence of CKD, especially in non-elderly adults, was revealed in this primary care study. Early recognition strategies for CKD are crucial for timely prevention within primary care. [ABSTRACT FROM AUTHOR]

Objective: This study aimed to determine the frequency of albuminuria in urine among Type 2 diabetic patients attending primary healthcare and to assess the factors influencing albuminuria. Methods: The research was conducted as a cross-sectional descriptive study between June 1, 2020, and August 31, 2020, at Kanyon Family Health Center in the Vezirköprü district of Samsun province. The study included 211 individuals. After obtaining informed consent from the participants, a face-to-face study form was administered to gather sociodemographic characteristics, smoking habits, comorbidities, and medication information. Albuminuria was detected using test strips, and the color change in the strip was evaluated by the same researcher in daylight each time, and the albumin/creatinine ratio in instantaneous spot urine was approximately calculated. Data analysis was performed with SPSS 24.0 (SPSS 24.0 for Windows, SPSS Inc., Chicago, IL, USA). Results: Of the participants, 52.1% (n=110) were female. The average age was 59.8±13.3 years (min:25-max:80). Hypertension was diagnosed in 47.4%, atherosclerotic heart disease in 27%, hyperlipidemia in 23.7%, obesity in 22.7%, and cerebrovascular disease in 2.4%. When the duration of diabetes diagnosis was evaluated, 27.5% had been diagnosed with diabetes for 0-5 years, 26.6% for 6-10 years, 15.6% for 11-15 years, 14.2% for 16-20 years, and 16.1% for more than 20 years. In addition, 39.3% had been regular smokers for the last 6 months and 37% had never smoked in their lives. 78.7% (n=166) of the patients were normoalbuminuric, 19% (n=40) were microalbuminuria, and 2.4% (n=5) were macroalbuminuria when albumin/creatinine ratio in spot urine was evaluated. The incidence of microalbuminuria and severe albuminuria was significantly higher in older patients, those with longer durations of diabetes, and former smokers (all; p<0.001). A positive correlation was found between age, duration of diabetes, hypertension, obesity, and albuminuria (r: 0.48, r: 0.68, r: 0.47, r: 0.55; p≤0.05, respectively). Microalbuminuria levels were higher in patients who had smoked throughout their lives compared to smokers and never smokers (p≤0.05). Furthermore, patients diagnosed with Type 2 diabetes for 16-20 years and over 20 years had higher microalbuminuria levels than those newly diagnosed (p<0.001). Conclusion: In our study, age, duration of diabetes diagnosis, hypertension, obesity, and smoking history were associated with albuminuria. By integrating practical screening protocols and adopting a holistic approach to patient care, family physicians can play an important role in reducing the burden of diabetic nephropathy in primary health care and improving patient outcomes. [ABSTRACT FROM AUTHOR]

Sarcopenia was recently reported to be relevant to an increased macro-and microvascular disease risk. Sarcopenia index (SI) has been identified as a surrogate marker for sarcopenia. The aim of the present study was to investigate the association between macro- and microvascular disease and SI in patients with type 2 diabetes mellitus (T2DM). A total of 783 patients with T2DM were enrolled in this cross-sectional study. The SI was calculated by (serum creatinine [mg/dL]/cystatin C [mg/L]) × 100. The subjects were divided into three groups according to SI tertiles: T1 (41.27–81.37), T2 (81.38– 99.55), and T3 (99.56–192.31). Parameters of macro- and microvascular complications, including diabetic retinopathy (DR), micro- and macroalbuminuria (MAU), diabetic peripheral neuropathy (DPN), and lower extremity peripheral artery disease (LEAD) were evaluated. Multivariate logistic regression analysis revealed that when taking the top tertile of SI as a reference, an increasing trend of the prevalence of DR, MAU, DPN, and LEAD were presented (all Pfor trend < 0.05), where the OR (95% CI) for DR prevalence was 1.967 (1.252–3.090) in T2, 2.195 (1.278–3.769) in T1, for MAU was 1.805 (1.149–2.837) in T2, 2.537 (1.490–4.320) in T1, for DPN was 2.244 (1.485–3.391) in T2, 3.172 (1.884–5.341) in T1, and for LEAD was 2.017 (1.002–4.057) in T2, 2.405 (1.107–5.225) in T1 (all P < 0.05). Patients with lower SI were more inclined to have an increased risk of macro- and microvascular damage in T2DM population, which may be related to sarcopenia. [ABSTRACT FROM AUTHOR]

Diabetic kidney disease (DKD) is a leading cause of chronic kidney disease and affects approximately 40% of individuals with diabetes. Cases of DKD continue to rise globally as the prevalence of diabetes mellitus increases, with an estimated 415 million people living with diabetes in 2015 and a projected 642 million by 2040. DKD is associated with significant morbidity and mortality, representing 34% and 36% of all chronic kidney disease deaths in men and women, respectively. Common comorbidities including hypertension and ageing-related nephron loss further complicate disease diagnosis and progression. The progression of DKD involves several mechanisms including glomerular endothelial cell dysfunction, inflammation, and fibrosis. Targeting these mechanisms has formed the basis of several therapeutic agents. Renin-angiotensin-aldosterone system (RAAS) blockers, specifically angiotensin receptor blockers (ARBs), demonstrate significant reductions in macroalbuminuria. Sodium-glucose transporter type 2 (SGLT-2) inhibitors demonstrate kidney protection independent of diabetes control while also decreasing the incidence of cardiovascular events. Emerging agents including glucagon-like peptide 1 (GLP-1) agonists, anti-inflammatory agents like bardoxolone, and mineralocorticoid receptor antagonists show promise in mitigating DKD progression. Many novel therapies including monoclonal antibodies CSL346, lixudebart, and tozorakimab; mesenchymal stem/stromal cell infusion; and cannabinoid-1 receptor inverse agonism via INV-202 are currently in clinical trials and present opportunities for further drug development. [ABSTRACT FROM AUTHOR]

Objective: Diabetes retinopathy (DR) is one of the top listed world health issues. Screening is usually advised for diabetic cases on a routine basis. However, there is only partial access to ophthalmologists in all parts of the world. Irisin is a myokine that is being investigated for this reason. Our study aims to assess the role of irisin in detecting DR. Methods and materials: In a cross-sectional study, 140 diabetes cases, including 70 patients with diabetic retinopathy and 70 patients free from diabetic retinopathy, were enrolled. Demographic and anthropometric data were gathered, and the patients underwent physical examination. Also, microalbuminuria and serum irisin levels were assessed in both groups. The results were compared between the two study groups. Results: Among the enrolled cases, 55 (39.28%) were men, and 85 (60.72%) were women. The disease duration (p = 0.016) and the serum level of HBA1c (p = 0.014) were significantly higher in the diabetic retinopathy group compared to the group free from diabetic retinopathy. Moreover, irisin was significantly higher in the patients free from diabetic retinopathy (p = 0.007). Conclusion: Irisin may have value in screening diabetic retinopathy; however, further studies are needed for this proposal. [ABSTRACT FROM AUTHOR]

Background: Diabetes mellitus is an important independent risk factor for the development of cardiovascular and renal disease which has been the cause of death in majority of the diabetic population. Albuminuria has been shown to predict cardiovascular morbidity and mortality in diabetics. Objective: The purpose of this study was to correlate microalbuminuria and left ventricular diastolic dysfunction (earliest manifestation of heart disease) in type 2 diabetes mellitus to aid in subclinical diagnosis, risk stratification, and prompt management of cardiovascular disease in diabetic patients. Methods: This study assessed the incidence of left ventricular diastolic dysfunction (LVDD) using echocardiography and its correlation with microalbuminuria and with other parameters like age, gender, BMI, duration of diabetes mellitus, and glycosylated hemoglobin in 90 normotensive, type 2 diabetic patients in a tertiary care hospital in Western India. Results: The prevalence of LVDD in our study is 59% (n = 53). The mean age of the study subjects was 60.7 years. Out of 59 subjects with BMI ≥ 25 kg/m2, diastolic dysfunction was seen in 31 patients. The mean duration of diabetes mellitus in our study is 11.5 years. Good glycemic control, i.e., HbA1c ≤ 7.0, was seen in 13 patients with LVDD. Out of 53 subjects with LVDD, 48 (90.5%) subjects had microalbuminuria. Conclusion: There is a significant correlation between microalbuminuria and LVDD in type 2 diabetes mellitus, independent of other parameters studied (age, sex, BMI, glycemic control, and duration of diabetes). [ABSTRACT FROM AUTHOR]

Diabetic nephropathy remains the leading cause of end-stage kidney disease in many countries, and additional therapeutic targets are needed to prevent its development and progression. Some angiogenic factors are involved in the pathogenesis of diabetic nephropathy. Vasohibin-2 (VASH2) is a novel proangiogenic factor, and our previous study showed that glomerular damage is inhibited in diabetic Vash2 homozygous knockout mice. Therefore, we established a VASH2-targeting peptide vaccine as a tool for anti-VASH2 therapy in diabetic nephropathy. In this study, the preventive effects of the VASH2-targeting peptide vaccine against glomerular injury were examined in a streptozotocin (STZ)-induced diabetic mouse model. The mice were subcutaneously injected with the vaccine at two doses 2 wk apart and then intraperitoneally injected with 50 mg/kg STZ for 5 consecutive days. Glomerular injury was evaluated 20 wk after the first vaccination. Treatment with the VASH2-targeting peptide vaccine successfully induced circulating anti-VASH2 antibody without inflammation in major organs. Although the vaccination did not affect blood glucose levels, it significantly prevented hyperglycemia-induced increases in urinary albumin excretion and glomerular volume. The vaccination did not affect increased VASH2 expression but significantly inhibited renal angiopoietin-2 (Angpt2) expression in the diabetic mice. Furthermore, it significantly prevented glomerular macrophage infiltration. The preventive effects of vaccination on glomerular injury were also confirmed in db/db mice. Taken together, the results of this study suggest that the VASH2-targeting peptide vaccine may prevent diabetic glomerular injury in mice by inhibiting Angpt2-mediated microinflammation. NEW & NOTEWORTHY: This study demonstrated preventive effects of VASH2-targeting peptide vaccine therapy on albuminuria and glomerular microinflammation in STZ-induced diabetic mouse model by inhibiting renal Angpt2 expression. The vaccination was also effective in db/db mice. The results highlight the importance of VASH2 in the pathogenesis of early-stage diabetic nephropathy and the practicability of anti-VASH2 strategy as a vaccine therapy. [ABSTRACT FROM AUTHOR]

Objective To investigate the clinical significance and serum changes of asprosin (ASP) levels in patients with essential hypertension and early renal damage. Methods According to urinary albumin / creatinine ratio (UACR), 160 patients with essential hypertension were divided into the simple hypertension group (78 cases) and the early renal damage group (82 cases). Another 60 healthy subjects were selected as the control group. The differences of serum ASP, interleukin6 (IL-6) and UACR levels were compared between groups. The correlation between ASP and blood pressure, IL-6 and UACR was analyzed. Logistic regression analysis was used to analyze the factors influencing early renal damage in essential hypertension. Receiver operating characteristic (ROC) curve was used to analyze the predictive value of each index for early renal injury. Results The serum levels of ASP, IL-6 and UACR were higher in the early renal damage group than those in the control group and the simple hypertension group (all P＜0.05). The serum levels of ASP and IL-6 showed an increasing trend with the increase of blood pressure. ASP was positively correlated with systolic blood pressure (SBP), diastolic blood pressure (DBP) and IL-6 levels in patients with essential hypertension (all P＜0.05). Serum ASP was positively correlated with SBP, UACR and IL-6 levels in essential hypertension patients (P＜0.05), and serum ASP was positively correlated with UACR and IL-6 levels in the early renal damage group (P＜0.05). Logistic regression analysis showed that higher levels of SBP, ASP and IL-6 were independent risk factors for early renal damage. ROC curve showed that ASP had the largest area under the curve (AUC) of 0.972 (95%CI: 0.950-0.993). The AUC of combined detection of ASP+IL-6+SBP was 0.986 (95%CI: 0.972-0.999). Conclusion The increased serum ASP level in patients with early renal damage in essential hypertension is a good predictor of early renal damage. The combined detection of ASP+IL-6+SBP is better than single detection. [ABSTRACT FROM AUTHOR]

Approximately 30% of steroid-resistant nephrotic syndromes are attributed to monogenic disorders that involve 27 genes. Mutations in KANK family members have also been linked to nephrotic syndrome; however, the precise mechanism remains elusive. To investigate this, podocyte-specific Kank1 knockout mice were generated to examine phenotypic changes. In the initial assessment under normal conditions, Kank1 knockout mice showed no significant differences in the urinary albumin-creatinine ratio, blood urea nitrogen, serum creatinine levels, or histological features compared to controls. However, following kidney injury with adriamycin, podocyte-specific Kank1 knockout mice exhibited a significantly higher albumin-creatinine ratio and a significantly greater sclerotic index than control mice. Electron microscopy revealed more extensive foot process effacement in the knockout mice than in control mice. In addition, KANK1-deficient human podocytes showed increased detachment and apoptosis following adriamycin exposure. These findings suggest that KANK1 may play a protective role in mitigating podocyte damage under pathological conditions. [ABSTRACT FROM AUTHOR]

In June 2023, the European Society of Hypertension (ESH) presented and published the new 2023 ESH Guidelines for the Management of Arterial Hypertension, a document that was endorsed by the European Renal Association (ERA). Following the evolution of evidence in recent years, several novel recommendations relevant to the management of hypertension in patients with chronic kidney disease (CKD) appeared in these Guidelines. These include recommendations for target office blood pressure (BP) <130/80 mmHg in most and against target office BP <120/70 mmHg in all patients with CKD; recommendations for use of spironolactone or chlorthalidone for patients with resistant hypertension with estimated glomerular filtration rate (eGFR) higher or lower than 30 mL/min/1.73 m2, respectively; use of a sodium-glucose cotransporter 2 inhibitor for patients with CKD and estimated eGFR ≥20 mL/min/1.73 m2; use of finerenone for patients with CKD, type 2 diabetes mellitus, albuminuria, eGFR ≥25 mL/min/1.73 m2 and serum potassium <5.0 mmol/L; and revascularization in patients with atherosclerotic renovascular disease and secondary hypertension or high-risk phenotypes if stenosis ≥70% is present. The present report is a synopsis of sections of the ESH Guidelines that are relevant to the daily clinical practice of nephrologists, prepared by experts from ESH and ERA. The sections summarized are those referring to the role of CKD in hypertension staging and cardiovascular risk stratification, the evaluation of hypertension-mediated kidney damage and the overall management of hypertension in patients with CKD. [ABSTRACT FROM AUTHOR]

We aim to examine the association of sleep duration, sleep quality, late chronotype, and circadian misalignment with glycemic control and risk of complications in young adults with youth-onset type 2 diabetes followed in the Treatment Options for Type 2 Diabetes in Adolescents and Youth (TODAY) study. Self-reported sleep duration, quality, timing, and circadian misalignment were assessed via a modified Pittsburgh Sleep Quality Index (PSQI) questionnaire, and chronotype was assessed via the Morningness-Eveningness Questionnaire (MEQ). We examined diabetes complications including loss of glycemic control (defined as hemoglobin A1c ≥8%), hypertension, dyslipidemia, albuminuria, and diabetic peripheral neuropathy. Multivariable logistic regression models were constructed to assess associations between sleep and circadian measures with outcomes of interest, such as loss of glycemic control and diabetes complications. A total of 421 participants (34.2% male), mean age 23.6 ± 2.5 yr, mean body mass index (BMI) of 36.1 ± 8.3 kg/m2, and mean diabetes duration of 10.0 ± 1.5 yr were evaluated. Self-reported short sleep duration, daytime sleepiness, and sleep quality were not associated with loss of glycemic control or diabetes complications. Late self-reported bedtime (after midnight) on work/school nights, rather than self-expressed chronotype or circadian misalignment, was independently associated with loss of glycemic control. An association was seen between late bedtimes and albuminuria but was attenuated after adjusting for depression. In conclusion, late bedtime on work/school days, rather than short sleep duration, daytime sleepiness, or poor sleep quality, was independently associated with loss of glycemic control in this longitudinal cohort of young adults with youth-onset type 2 diabetes. NEW & NOTEWORTHY: The prevalence of type 2 diabetes in youth is increasing at an alarming rate. Identifying potentially modifiable factors modulating glycemic control is critically important to reduce micro and macrovascular complications. In a large cohort of youth-onset type 2 diabetes, self-reported late bedtime on work/school days was independently associated with loss of glycemic control in this longitudinal cohort of young adults with youth-onset type 2 diabetes. [ABSTRACT FROM AUTHOR]

Background Albuminuria could potentially emerge as a novel marker of congestion in acute heart failure. However, the current evidence linking albuminuria and congestion in patients with congestive heart failure (CHF) remains somewhat scarce. This study aimed to evaluate the prevalence of albuminuria in a cohort of patients with CHF, identify the independent factors associated with albuminuria and analyse the correlation with different congestion parameters. Methods This is a subanalysis of the Spanish Cardiorenal Registry, in which we enrolled 864 outpatients with heart failure and a value of urinary albumin:creatinine ratio (UACR) at the first visit. Results The median age was 74 years, 549 (63.5%) were male and 438 (50.7%) had a reduced left ventricular ejection fraction. A total of 350 patients (40.5%) had albuminuria. Among these patients, 386 (33.1%) had a UACR of 30–300 mg/g and 64 (7.4%) had a UACR >300 mg/g. In order of importance, the independent variables associated with higher UACR were estimated glomerular filtration rate determined by the Chronic Kidney Disease Epidemiology Collaboration equation (R 2 = 57.6%), systolic blood pressure (R 2 = 21.1%), previous furosemide equivalent dose (FED; R 2 = 7.5%), antigen carbohydrate 125 (CA125; R 2 = 6.1%), diabetes mellitus (R 2 = 5.6%) and oedema (R 2 = 1.9%). The combined influence of oedema, elevated CA125 levels and the FED accounted for 15.5% of the model's variability. Conclusions In patients with chronic stable heart failure, the prevalence of albuminuria is high. The risk factors of albuminuria in this population are chronic kidney disease and hypertension. Congestion parameters are also associated with increased albuminuria. [ABSTRACT FROM AUTHOR]

Background: Diabetes mellitus has become increasingly common worldwide, with many serious complications. Diabetic nephropathy is one such complication that affects the kidney and leads to end-stage renal failure worldwide. Microalbuminuria represents an abnormal elevation in urine albumin levels, which is an early marker of diabetic nephropathy. It is likely to be found in one-third or more of diabetic patients. Early recognition of microalbuminuria in diabetic nephropathy permits successful therapeutic intervention and significant postponement of terminal renal failure. Objective: To investigate the prevalence of microalbuminuria in type 2 diabetes patients attending AL-Thawra Hospital and Saref Medical Centre in Sana'a City. Materials and Methods: This study was carried out in AL-Thawra Hospital and Saref Medical Center in Sana'a City, during the period (from 1 February to 30 April 2021). 125 Type 2 diabetic patients (diagnosed according to American Diabetes Association (ADA) criteria for diagnosis of diabetes) were selected). Medical records were used to collect data on duration of diabetes, gender, age and body mass index (BMI). Microalbuminuria was assessed using mispa-i3 kits in spot of the morning urine samples. Results: The prevalence of microalbuminuria and macroalbuminuria among type 2 diabetic patients was 44.8% and 12 %, respectively. Microalbuminuria had a statistically significant association with longer duration (P = 0.031), and no statistically significant association was found between microalbuminuria and gender (P = 0.419), age (P = 0.299) and body mass index (P = 0.390). Conclusion: The prevalence of microalbuminuria in this study was considerably high (44.8%) in type 2 diabetes. 44.8% (nearly half) of type 2 diabetic patients in this study are at risk of developing kidney disease due to their high microalbuminuria level. This calls for regular and early screening for microalbuminuria is recommended for all diabetic patients, as early treatment is critical for reducing the progression to the late stage of diabetic nephropathy (overt proteinuria and end-stage renal disease). [ABSTRACT FROM AUTHOR]

Background: Despite albumin‐creatinine ratio (urine) testing being recommended for detection of chronic kidney disease among adults with diabetes, testing rates are suboptimal. Aim: We implemented and evaluated a quality improvement project in an inner‐city diabetes population in London, UK to assess the feasibility and acceptability of implementing novel home‐based urinalysis using smartphone technology. Methods: After eligible patients were identified and consented, testing kits were sent to the patient's home. Test results and patient feedback were collected through the smartphone application. Focus group discussions were conducted to evaluate primary care staff perspectives on uptake and delivery of the service. Results: In total 2370 patients agreed to take part. Of these, 1244 completed the test (61% of those eligible) and of these, 465 (37%) had clinically significant albuminuria. 98% of patients found the test easy or very easy to use. Staff in primary care found the service to be beneficial for patients, and reported ease of set up and minimal administrative processes. Concerns regarding barriers among patients with lower digital literacy and non‐English speakers were raised although these concerns were not substantiated. Conclusion: Home‐based albumin‐creatinine ratio urine testing may improve the testing rates of people with diabetes at higher risk of chronic kidney disease. This is important post‐pandemic, as healthcare services are trying to return to pre‐pandemic levels of care. The study also found that the use of smartphone technology in an underserved (deprived) community is feasible, despite reservations about levels of digital literacy and possible language barriers. Further evaluation of effectiveness and costs is required. [ABSTRACT FROM AUTHOR]

Urinary microalbumin (mALB) serves as an exceptionally sensitive indicator for the early detection of kidney damage, playing a pivotal role in identifying chronic renal failure and kidney lesions in individuals. Nevertheless, the current fluorescent methodologies for point‐of‐care (POC) diagnosis of mALB in real urine still exhibit suboptimal performance. Herein, the development and synthesis of QM‐N2, an albumin‐activated near‐infrared (NIR) aggregation‐induced emission (AIE) fluorescent probe, are presented. The strategic incorporation and positioning of quaternary ammonium salts within the quinoline‐malononitrile (QM) scaffold significantly influence solubility and luminescence characteristics. Specifically, the quaternary ammonium salt‐free variant, QM‐OH, and the quaternary ammonium salt integrated at the donor function group (DFG) site, QM‐N1, display limited solubility in aqueous solutions while demonstrating a distinct fluorescence signal. Conversely, the incorporation of quaternary ammonium salt at the conformational functional group (CFG) site in QM‐N2 imparts superior dispersibility in water and reduces the initial fluorescence. Furthermore, the integration of a well‐defined D‐π‐A structure within QM‐N2 enables itself with near‐infrared emission, which is crucial for mitigating interference from autofluorescence present in urine samples. Upon interaction with albumin, QM‐N2 forms a tight bond with the IIA site of the subdomain of human serum albumin (HSA), inducing alterations in protein configuration and constraining the intrinsic motion of fluorescent molecules. This interaction induces fluorescence, facilitating the sensitive detection of trace albumin. Ultimately, QM‐N2 is applied for POC testing of mALB using portable equipment, particularly in the diagnosis of mALB‐related diseases, notably chronic renal failure. This positioning underscores its potential as an ideal candidate for self‐health measurement at home or in community hospitals. [ABSTRACT FROM AUTHOR]

The beneficial effects of sodium–glucose cotransporter 2 (SGLT2) inhibitors in patients with chronic kidney disease (CKD) with low albuminuria levels have not been established. This study aimed to compare the effects of dapagliflozin on kidney injury biomarkers in patients with CKD stratified by albuminuria level. We prospectively enrolled healthy volunteers (HVs; n = 20) and patients with CKD (n = 54) with and without diabetes mellitus. Patients with CKD were divided into two age‐matched and sex‐matched subgroups according to urinary albumin–creatinine ratio (uACR) levels (<300 mg/g and ≥300 mg/g). The CKD group received dapagliflozin (10 mg/day). Urine samples were collected before treatment and after 3 and 6 months of dapagliflozin. Urinary kidney injury molecule‐1 (KIM‐1), interleukin‐1β (IL‐1β), and mitochondrial DNA nicotinamide adenine dinucleotide dehydrogenase subunit‐1 (mtND1) copy number were measured. The estimated glomerular filtration rate (eGFR) of patients with CKD was lower than that of HVs (P < 0.001). During the study period, eGFR decreased and uACR did not change in the CKD group. Kidney injury markers were significantly elevated in patients with CKD compared with those in HVs. Dapagliflozin reduced urinary KIM‐1, IL‐1β, and mtDNA copy number in patients with CKD after 6 months of treatment. In further, the levels of urinary KIM‐1 and IL‐1β, patients with CKD decreased after 6 months of dapagliflozin treatment regardless of albuminuria level. Dapagliflozin reduced urinary kidney injury biomarkers in patients with CKD, regardless of albuminuria level. These findings suggest that SGLT2 inhibitors may also attenuate the progression of low albuminuric CKD. [ABSTRACT FROM AUTHOR]

Background. Today, diabetes mellitus is an actual problem, characterized by a progressive increase in the number of patients with a high frequency of complications that require early diagnosis and timely treatment. Diabetic nephropathy is among the most common microvascular lesions. Patients may have clinical manifestations of diabetic kidney disease that go beyond the classic symptoms and have extrarenal consequences in the form of bone mineral disorders. The purpose of the work is to carry out a comprehensive assessment of early markers of kidney damage and changes in bone disorder indicators in patients with type 2 diabetes and to identify correlations between the studied parameters. Materials and methods. Eighty patients with type 2 diabetes participated in the study. They were divided according to the glomerular filtration rate: GFR < 60 ml/min/m² (1st group, n = 26), GFR ≥ 60 ml/min/m² (2nd group, n = 54). Results. Analysis of early markers of kidney damage revealed some significant differences between the groups. Indicators of daily urine albumin-creatinine ratio, serum cystatin C, parathyroid hormone, uric acid, and vitamin D-binding protein were significantly higher in patients with GFR < 60 ml/min/m². The average level of vitamin D (25OH) in both groups corresponded to a deficient state, and the 1st group was marked by a statistically significantly lower level compared to the 2nd group: 12.32 ± 4.84 and 16.72 ± 5.82 ng/ml, respectively (p = 0.001). In the 1st group, vitamin D deficiency was observed in 92.3 % of cases, and in the 2nd group, in 74.1 % (p = 0.56). According to the correlation analysis, some reliable relationships were found: in the 1st group, there was a negative correlation between GFR and parathyroid hormone (r = –0.816, p < 0.001). An inverse correlation was revealed between GFR and cystatin C in the 1st (r = –0.862, p < 0.001) and 2nd groups (r = –0.322, p = 0.18). Among all examined participants, there was a linear negative correlation between GFR and uric acid (r = –0.452, p < 0.001). Vitamin D (25OH) didn’t have a significant relationship with GFR, however, we found a negative correlation with the daily urine albumin-creatinine ratio (r = –0.253, р = 0.024) and cystatin C (r = –0.303, p = 0.006), which confirms the role of cholecalciferol in mineral bone disorders in patients with chronic kidney disease. In our study, an inverse correlation was found between GFR and vitamin D-binding protein in the 1st (r = –0.436, p = 0.26) and 2nd group (r = –0.283, p = 0.038), which probably indicates a possible compensatory response of transport protein to initial mineral bone disorders in patients with diabetic kidney disease. Conclusions. Early detection of bone mineral disorders in diabetic kidney disease is important to increase the efficiency of managing patients with type 2 diabetes and timely treatment, prevention of cardiovascular complications and bone metabolism disorders. [ABSTRACT FROM AUTHOR]

Markers of glomerular disease, estimated glomerular filtration rate (eGFR) and albuminuria, are associated with cardiac structural abnormalities and incident cardiovascular disease (CVD). We aimed to determine whether biomarkers of kidney tubule injury, function, and systemic inflammation are associated with cardiac structural abnormalities. Among 393 Multi-Ethnic Study of Atherosclerosis participants without diabetes, CVD, or chronic kidney disease, we assessed the association of 12 biomarkers of kidney tubule injury, function, and systemic inflammation with the left ventricular mass/volume ratio (LVmvr) and left ventricular ejection fraction (LVEF) on cardiac magnetic resonance imaging using linear regression. The average age was 60 ± 10 years; 48% were men; mean eGFR was 96±16 ml/min/1.73 m2; mean LVmvr was 0.93±0.18 g/ml, and mean LVEF was 62±6%. Each twofold greater concentration of plasma soluble urokinase plasminogen activator receptor was associated with a 0.04 g/ml (95% confidence interval [CI] 0.01 to 0.08 g/ml) higher LVmvr and 2.1% (95% CI 0.6 to 3.5%) lower LVEF, independent of risk factors for CVD, eGFR, and albuminuria. Each twofold greater plasma monocyte chemoattractant protein 1 was associated with higher LVmvr with a similar coefficient to that of plasma soluble urokinase plasminogen activator receptor. Each twofold greater concentration of plasma chitinase-3-like protein 1 and urine alpha-1-microglobulin was associated with a 1.1% (95% CI 0.4 to 1.7%) and 1.2% (95% CI 0.2 to 2.2%) lower LVEF, respectively. In conclusion, abnormal kidney tubule health may lead to cardiac dysfunction above and beyond eGFR and albuminuria.

Abstract Glucagon‐like peptide‐1 receptor agonists (GLP‐1RAs) have gained increasing attention for their potential benefits in people with type 2 diabetes mellitus (T2DM) with chronic kidney disease (CKD). Most supportive evidence of a kidney‐protective effect of the GLP‐1RA class of medications has been derived from kidney‐related outcomes reported from cardiovascular outcome trials (CVOTs). GLP‐1RAs have been shown to reduce albuminuria, mitigate cardiovascular risk, and possibly attenuate estimated glomerular filtration rate (eGFR) decline. The kidney‐protective effects of GLP‐1RAs are thought to be attributed to their anti‐inflammatory, antioxidant, and vasodilatory properties. Despite these promising findings, the use of GLP‐RAs has yet to be definitively shown to slow progression to chronic kidney failure in people with T2DM. The Research Study to See How Semaglutide Works Compared to Placebo in People With Type 2 Diabetes and Chronic Kidney Disease (FLOW trial) is the first major trial assessing the potential of a GLP‐1RA to slow progression of kidney disease in people with established CKD to clinically important kidney end points. On March 5, 2024, the top line result from FLOW was announced with semaglutide 1.0 mg being reported to reduce the primary end point of the trial by a significant 24% compared with placebo. Here, we summarize the kidney outcomes reported from CVOTs for the GLP‐1RA class of medication and briefly describe kidney outcomes from other major GLP‐1RAs trials. We also discuss a potential role of the dual GLP‐1/glucose‐dependent insulinotropic polypeptide (GIP) receptor agonist, tirzepatide, as a kidney‐protective agent.

Abstract Background and Aims Literature suggests that oxidative stress plays a crucial role in the progression of diabetes. Since poor glycemic control enhances the formation of advanced glycation end‐products (AGEs) and advanced oxidation protein products (AOPP) in individuals with diabetes, exploring the association between glycation and oxidative states in diabetes could also shed light on potential consequences. This study evaluated the effects of albuminuria on AGEs and AOPP levels and measured their relationship in participants with type 2 diabetes (T2D) with or without albuminuria. Methods A cross‐sectional, matched case‐control study was designed, including 38 T2D subjects with albuminuria and 38 matched T2D subjects with normoalbuminuria. Patients were matched by their body mass index (BMI), age, and duration of diabetes. The unadjusted and adjusted correlation between AGEs and AOPP in the studied groups were analyzed by multiple logistic regression. Using ggplot2, the ties between these two biochemical factors in cases and controls were plotted. Results This study elucidated a significant association between AGEs and AOPP in participants with normoalbuminuria (r = 0.331, p‐value

Rationale & Objective: Estimates of the incidence of hyperkalemia in patients with chronic kidney disease (CKD) vary widely. Our objective was to estimate hyperkalemia incidence in patients with CKD from routine clinical care, including by level of kidney damage or function and among important patient subgroups. Study Design: Retrospective cohort study. Setting & Participants: 1,771,900 patients with stage 1-4 CKD identified from the US Optum De-Identified electronic health records database. Exposures or Predictors: Impaired kidney damage or function level at baseline based on urinary albumin-creatinine ratio (UACR) and estimated glomerular filtration rate (eGFR), respectively, and selected patient subgroups. Outcomes: Hyperkalemia: 2 elevated serum potassium values (≥5.5 mmol/L) from the inpatient setting (2-24 hours apart) or outpatient setting (maximum 7 days apart), or 1 elevated serum potassium value plus pharmacotherapy initiation or hyperkalemia diagnosis (maximum 3 days apart). Analytical Approach: Incidence rates of hyperkalemia were calculated. Estimates were stratified by UACR and eGFR level at baseline and patient subgroups. Results: Over a mean follow-up of 3.9 years, the incidence of hyperkalemia was 3.37 events/100 person-years (95% confidence intervals, 3.36-3.38). Higher incidence rates were observed with increased UACR and lower eGFR. Highest rates were observed with UACR ≥3,500 (up to 19.1/100 person-years) irrespective of decreased eGFR level. High rates also occurred in patients with type 2 diabetes mellitus (T2DM, 5.43/100 person-years), heart failure (8.7/100 person-years), and those prescribed steroidal mineralocorticoid receptor antagonists (sMRAs, 7.7/100 person-years). Limitations: Potential misclassification of variables from possible medical coding errors; potential data incompleteness issues if patients received care at institutions not included in Optum. Conclusions: Hyperkalemia is a frequent occurrence in CKD, particularly in patients with T2DM, heart failure, or prescribed sMRAs, indicating the need for regular serum potassium and UACR monitoring in this patient population to help mitigate risk. Plain-Language Summary: People with chronic kidney disease (CKD) have a higher risk of illness, hospitalization, and death than those without CKD. Medicines that are commonly used to slow down CKD progression can sometimes lead to hyperkalemia, where levels of potassium in the blood are higher than normal and which can be potentially dangerous. Concerns about hyperkalemia have led some people with CKD to stop taking their medication. Our study of 1.7 million patients from the United States found that patients with severe kidney damage, as well as those with type 2 diabetes mellitus or heart failure, have a higher risk of hyperkalemia than other patients, indicating they are priority groups for having their potassium levels and level of kidney damage checked regularly.

Abstract Background We examined the trajectory of estimated glomerular filtrate rate (eGFR), associated risk factors, and its relationship with end‐stage kidney disease (ESKD) among a multiethnic patient population with type 2 diabetes in Singapore. Methods A follow‐up study included 62 080 individuals with type 2 diabetes aged ≥18 years in a multi‐institutional SingHealth Diabetes Registry between 2013 and 2019. eGFR trajectories were analyzed using latent class linear mixed models. Factors associated with eGFR trajectories were evaluated using multinomial logistic regression. The association of eGFR trajectories with ESKD was assessed via competing risk models. Results Trajectory of kidney function, determined by eGFR, was nonlinear. The trajectory pattern was classified as stable initially then gradual decline (75%), progressive decline (21.9%), and rapid decline (3.1%). Younger age, female sex, Malay ethnicity, lower‐income housing type, current smoking, higher glycated hemoglobin, lower low‐density lipoprotein, higher triglyceride, uncontrolled blood pressure, albuminuria, cardiovascular disease, hypertension, and higher eGFR levels each were associated with progressive or rapid decline. Compared with the trajectory of stable initially then gradual eGFR decline, progressive decline increased the hazard of ESKD by 6.14‐fold (95% confidence interval [CI]: 4.96–7.61)) and rapid decline by 82.55 folds (95% CI: 55.90–121.89). Conclusions Three nonlinear trajectory classes of kidney function were identified among multiethnic individuals with type 2 diabetes in Singapore. About one in four individuals had a progressive or rapid decline in eGFR. Our results suggest that eGFR trajectories are correlated with multiple social and modifiable risk factors and inform the risk of ESKD.

Abstract Background Current definition of chronic kidney disease (CKD) identifies only advanced stages, but effective management demands early detection. Urinary albumin‐to‐creatinine ratio (ACR) 30 mg/g is a cut‐off point for CKD clinical diagnosis. Patients with lower values (normoalbuminuria) and eGFR > 60 mL/min/1.73 m2 are considered at no increased cardiorenal risk. However, higher incidence of renal function decline and cardiovascular events have been shown within the normoalbuminuria range. Novel subclinical indicators may help to identify higher‐risk patients. Urinary extracellular vesicles (uEVs) are sentinels of renal function non‐invasively. Here we aimed to approach the early assessment of cardiorenal risk by investigating the protein cargo of uEVs. Methods Hypertensive patients were classified in control group (C) with ACR 6200 uEVs proteins identified, 43 define a panel significantly altered in HN patients without variation in urine, mostly annotated in the tubule (39 out of 43). The tubular transporter long‐chain fatty acid transport protein 2 (SLC27A2) and the apical membrane protein amnionless (AMN) confirmed their alteration in HN patients evidencing impaired tubular reabsorption. SLC27A2 showed tubular expression and significantly reduced levels in patients with diagnostic criteria for CKD. Conclusions Alterations in the EV‐mediated molecular profile are evident before pathological ACR levels are reached. Direct quantitation of SLC27A2 and AMN in uEVs helps identifying normoalbuminuric subjects with higher cardiorenal risk in early monitoring of CKD.

Background Despite the high burden of diabetes and cardiovascular risk factors in American Indian communities in the United States, prospective studies of heart failure (HF) in this population group are scarce, and the generalizability of previous HF risk scales may be limited. We developed a parsimonious HF risk prediction equation that accounts for relevant risk factors affecting American Indian communities, focusing on diabetes and kidney damage. Methods and Results A total of 3059 participants from the SHS (Strong Heart Study) (56±8 years of age, 58% women) were included. Five hundred seven developed HF. Progressively adjusted Cox proportional hazards models were used to identify risk factors for HF and HF subtypes. Predictors of risk at 5 and 10 years included older age (hazard ratio [HR], 1.79 [95% CI, 1.43–2.25]; HR, 1.68 [95% CI, 1.44–1.95]), smoking (HR, 2.26 [95% CI, 1.23–4.13]; HR, 2.08 [95% CI, 1.41–3.06]), macroalbuminuria (HR, 8.38 [95% CI, 4.44–15.83]; HR, 5.20 [95% CI, 3.42–7.9]), microalbuminuria (HR, 2.72 [95% CI, 1.51–4.90]; HR, 1.92 [95% CI, 1.33, 2.78]), and previous myocardial infarction (HR, 6.58 [95% CI, 2.54–17.03]; HR, 3.87 [95% CI, 2.29–6.54]), respectively. These predictors, together with diabetes diagnosis and glycated hemoglobin were significant at 10 and 28 years. High discrimination performance was achieved (C index, 0.81 [95% CI, 0.76–0.84]; C index, 0.78 [95% CI, 0.75–0.81]; and C index, 0.77 [95% CI, 0.74–0.78] at 5, 10, and up to 28 years of follow up, respectively). Some associations varied across HF subtypes, although diabetes, albuminuria, and previous myocardial infarction were associated with all subtypes. Conclusions This prospective study of HF risk factors in American Indian communities identifies that smoking, body mass index, and indicators of diabetes control and kidney damage (glycated hemoglobin and albuminuria) are major determinants of HF. Our findings can improve HF risk assessment in populations with a high burden of diabetes.

BackgroundPatients with early chronic kidney disease (CKD) or underlying risk factors are often unaware of their kidney test results, common causes of CKD, and ways to lower risk of disease onset/progression.ObjectiveTo test feasibility of a pharmacist-led intervention targeting patient education and risk factors in patients with early CKD and those at risk for CKD.Practice descriptionAmbulatory care pharmacists in community-based primary care clinics delivered kidney health education, ordered labs, and recommended medication adjustments.Practice innovationWe identified patients with a moderate rate of decline (≥2 mL/min/1.73 m2 per year) in estimated glomerular filtration (eGFR) at-risk for CKD or early stage CKD. An interactive workbook was designed to teach patients about kidney test results and self-management of risk factors including hypertension, type 2 diabetes, cigarette smoking, and chronic oral nonsteroidal anti-inflammatory drug use.Evaluation methodsOutcomes included visit uptake, completion of annual albuminuria screening, and initiation of guideline-directed medications for CKD. Patients were surveyed pre- and post-intervention for kidney health knowledge and perceptions regarding pharmacist-provided information.ResultsOur sample of 20 participants had a mean eGFR of 59 mL/min/1.73 m2 and the mean eGFR decline was -4.6 mL/min/1.73 m2 per year. There were 47 visits during the pilot period from February 2021 to October 2021. Thirteen patients were missing albuminuria screening within 12 months; 2 of 9 patients with resulting labs had new microalbuminuria and were started on renoprotective medications. Patients had improved understanding of their kidney function test results and most did not consider the information scary or confusing.ConclusionBarriers to enrollment included fewer participants with multiple risk factors for CKD. The pharmacists were able to engage patients in learning the importance of monitoring and self-management of kidney health. A collaborative practice agreement may enhance a similar intervention that includes initiation of renoprotective medications.

Introduction: Decreased renal function is a significant public health issue, increasing the risk of various adverse outcomes. Thus, identifying potentially modifiable factors associated with the onset of chronic kidney disease (CKD) is imperative. Although CKD has been demonstrated to impact thyroid function through various mechanisms; there remains insufficient and contentious data regarding the association between albuminuria and thyroid function in patients diagnosed with CKD. This study aimed to elucidate the association between albuminuria and thyroid function tests in patients with CKD. Methods: We conducted a cross-sectional analysis involving 232 patients with CKD. Patients were categorized on the basis of albuminuria levels, measured by the urinary albumin/creatinine ratio (ACR), following the KDIGO 2012 criteria: ACR1 300 mg/gr. Thyroid stimulating hormone (TSH), free thyroxine (free T4), and free triiodothyronine (free T3) levels were measured to assess thyroid function. Results: The ACR among subjects ranged from 1.0 mg/g to 10260.0 mg/g, with a mean urinary ACR of 485.7±1250.9 mg/g. Among the patients, 47.4% (n=110) had an ACR 300 mg/g. TSH levels ranged from 0.3 to 14 mU/L, free T3 ranged between 0.6 and 4.8 ng/L, and free T4 ranged from 5.5 to 17.8 ng/L. No significant differences were observed in TSH, free T4, and free T3 values among the ACR1, ACR2, and ACR3 groups (p>0.05). A significant positive correlation was found between glomerular filtration rate and free T3 (r=0.395, p

Abstract Protein misfolding in the endoplasmic reticulum (ER) of podocytes contributes to the pathogenesis of glomerular diseases. Protein misfolding activates the unfolded protein response (UPR), a compensatory signaling network. We address the role of the UPR and the UPR transducer, inositol-requiring enzyme 1α (IRE1α), in streptozotocin-induced diabetic nephropathy in mice. Diabetes caused progressive albuminuria in control mice that was exacerbated in podocyte-specific IRE1α knockout (KO) mice. Compared to diabetic controls, diabetic IRE1α KO mice showed reductions in podocyte number and synaptopodin. Glomerular ultrastructure was altered only in diabetic IRE1α KO mice; the major changes included widening of podocyte foot processes and glomerular basement membrane. Activation of the UPR and autophagy was evident in diabetic control, but not diabetic IRE1α KO mice. Analysis of human glomerular gene expression in the JuCKD-Glom database demonstrated induction of genes associated with the ER, UPR and autophagy in diabetic nephropathy. Thus, mice with podocyte-specific deletion of IRE1α demonstrate more severe diabetic nephropathy and attenuation of the glomerular UPR and autophagy, implying a protective effect of IRE1α. These results are consistent with data in human diabetic nephropathy and highlight the potential for therapeutically targeting these pathways.

Kai Guo,1,2 Yuqin Zhu,3 Qian Yu,4 Hong Chen,5 Wei Cheng,2 Xiaoyan Zhang,2 Xuelian Zhang,2 Biwen Liu,2 Zunhai Zhou,2 Xingya Kuang5 1School of Medicine, Tongji University, Shanghai, 200092, People’s Republic of China; 2Department of Endocrinology, Yangpu Hospital, School of Medicine, Tongji University, Shanghai, 200090, People’s Republic of China; 3Department of Emergency, Yangpu Hospital, School of Medicine, Tongji University, Shanghai, 200090, People’s Republic of China; 4Department of Dermatology, Shanghai Tenth People’s Hospital, School of Medicine, Tongji University, Shanghai, 200072, People’s Republic of China; 5Department of Occupational Medicine, Yangpu Hospital, School of Medicine, Tongji University, Shanghai, 200090, People’s Republic of ChinaCorrespondence: Xingya Kuang, Department of Occupational Medicine, Yangpu Hospital, School of Medicine, Tongji University, No. 1015, Hejian Road, Shanghai, 200090, People’s Republic of China, Tel +86-15021904362, Email kuangxingya@163.com Zunhai Zhou, Department of Endocrinology, Yangpu Hospital, School of Medicine, Tongji University, No. 450, Tengyue Road, Shanghai, 200090, People’s Republic of China, Tel +86-18001779479, Email zhouzunhai5008@163.comPurpose: Elevated urine albumin-to-creatinine ratio (UACR) is an established risk factor for microvascular disease in the general population. However, it is unclear whether UACR is associated with arterial stiffness in diabetes. We aimed to assess the relationship between UACR levels and the risk of arterial stiffness in patients with diabetes.Methods: From July 2021 to February 2023, a total of 1039 participants were assessed for the risk of arterial stiffness, which was evaluated by brachial-ankle pulse wave velocity (baPWV). The value of UACR≥ 30 mg/g was defined as high UACR. The UACR level had an abnormal distribution and was log2-transformed for analyses to reduce skewness and volatility. High baPWV was evaluated as categorical variables divided by the highest quartile of the values by sex. The relationship between UACR and arterial stiffness was analyzed by linear curve fitting analyses. Multiple logistic regression models were used to analyze the crude and adjusted odds ratio (OR) of UACR for high baPWV with 95% confidence interval (CI). In addition to applying non-adjusted and multivariate-adjusted models, interaction and stratified analyses were also carried out.Results: The baPWV level was significantly higher in the high UACR group compared with that in the normal UACR group (1861.84 ± 439.12 cm/s vs 1723.13 ± 399.63 cm/s, p< 0.001). Adjusted smoothed plots suggested that there are linear relationships between log2-transformed UACR and high baPWV, and Spearman correlation coefficient was 0.226 (0.176– 0.276, p< 0.001). The OR (95% CI) between log2-transformed UACR and high baPWV were 1.26 (1.19– 1.33, p< 0.001), and 1.16 (1.08– 1.25, p< 0.001) respectively in diabetic patients before and after adjusting for potential confounders.Conclusion: The elevated UACR was associated with arterial stiffness in Chinese patients with diabetes.Plain Language Summary: 1. The mean baPWV level was significantly higher in the high UACR group compared with that in the normal UACR group.2. The sex-specific hierarchical analysis revealed that baPWV levels and the incidence of high baPWV were significantly elevated with increased UACR.3. Curvilinear relationships between log2-transformed UACR and the risk of high baPWV.4. Positive association between UACR and high baPWV in patients with diabetes.Keywords: diabetic kidney disease, cardiovascular diseases, albuminuria, pulse wave velocity, biomarker, prognosis

Background Further study is warranted to determine the association between estimated glomerular filtration rate (eGFR) or albuminuria and the risk of death from diverse causes. Methods We screened >10 million general health screening examinees who received health examinations conducted in 2009 using the claims database of Korea. After the exclusion of those previously diagnosed with renal failure and those with missing data, 9,917,838 individuals with available baseline kidney function measurements were included. The primary outcome was mortality and cause-specific death between 2009 and 2019 identified through death certificates based on the diagnostic codes of International Classification of Diseases, 10th revision. Multivariable Cox regression analysis adjusted for various clinicodemographic and social characteristics was used to assess mortality risk. Results The hazard ratio of death was significantly high in both the eGFR

Background The elderly tend to coexist with multiple chronic diseases (such as diabetes and hypertension) , while diabetes and hypertension can lead to chronic kidney damage, and fewer studies have been conducted on chronic kidney disease in older adults. Objective To investigate the proteinuria and renal dysfunction in the elderly population and provide guidance for the management of chronic kidney disease in the community-dwelling older adults by collecting the clinical data of physical examination of the elderly residents in community. Methods A total of 13 080 elderly residents who underwent physical examination in Zhuanqiao Community Health Service Center of Minhang District, Shanghai from 2020 to 2021 were included as the study objects. General information, physical examination results and laboratory examination data of study objects were collected. Subjects with estimated glomerular filtration rate (eGFR)

People with type 2 diabetes mellitus have increased risk of chronic kidney disease and atherosclerotic cardiovascular disease. Improved care delivery and implementation of guideline-directed medical therapy have contributed to the declining incidence of atherosclerotic cardiovascular disease in high-income countries. By contrast, the global incidence of chronic kidney disease and associated mortality is either plateaued or increased, leading to escalating direct and indirect medical costs. Given limited resources, better risk stratification approaches to identify people at risk of rapid progression to end-stage kidney disease can reduce therapeutic inertia, facilitate timely interventions and identify the need for early nephrologist referral. Among people with chronic kidney disease G3a and beyond, the kidney failure risk equations (KFRE) have been externally validated and outperformed other risk prediction models. The KFRE can also guide the timing of preparation for kidney replacement therapy with improved healthcare resources planning and may prevent multiple complications and premature mortality among people with chronic kidney disease with and without type 2 diabetes mellitus. The present review summarizes the evidence of KFRE to date and call for future research to validate and evaluate its impact on cardiovascular and mortality outcomes, as well as healthcare resource utilization in multiethnic populations and different healthcare settings.

Abstract Several studies have shown an association between albuminuria and obstructive sleep apnea (OSA). However, studies on the relationship between the STOP-BANG questionnaire that can screen for OSA and microalbuminuria are still insufficient. Therefore, this study attempted to clarify the relationship between microalbuminuria and OSA risk using the STOP-BANG questionnaire in Korean adults. A total of 7478 participants (3289 men and 4189 women) aged over 40 were enrolled in the Korean National Health and Nutrition Examination Survey from 2019 to 2020. STOP-BANG questionnaire to screen OSA was obtained from subjects. The urinary albumin/creatinine ratio (ACR) and proteinuria were measured via a single dipstick to evaluate renal function. The high OSA risk group had a higher mean ACR value than the low OSA risk group (36.8 ± 172.2 vs 17.7 ± 82.5; P 300 mg/g (2.1% vs 0.7%; P

Abstract Background The utility of urine dipsticks for the quantification of proteinuria is limited because of the influence of urine specific gravity (USG). To circumvent the need for urine protein creatinine ratios (UPCR) some have proposed a calculated dipstick urine protein to USG ratio (DUR) for the detection of proteinuria. However, the performance of DUR has not been evaluated in veterinary patients. Objectives Evaluate the correlation between DUR and UPCR, while also assessing the effect of urine characteristics on this relationship and evaluating the performance of DUR in detecting proteinuria. Animals Urine samples from 308 dogs and 70 cats. Methods Retrospective cohort study of urinalyses and UPCRs from dogs and cats collected between 2016 and 2021. Results Both canine and feline urine samples showed a positive moderate correlation between the UPCR and DUR. The correlation was not influenced by the presence of active urine sediment, glucosuria, or urine pH. In detecting canine urine samples with a UPCR >0.5, an optimal DUR of 1.4 had sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) of 89%, 83%, 96%, and 63%, respectively. In detecting feline urine samples with a UPCR >0.4, an optimal DUR of 2.1 had sensitivity, specificity, PPV, and NPV of 70%, 100%, 100%, and 75%, respectively. Conclusions and Clinical Importance Use of the DUR can be a relatively reliable method for identification of proteinuria. However, given its poor NPV, the DUR cannot be recommended for exclusion of proteinuric patients.

Abstract Background Albuminuria, the presence of excess of protein in urine, is a well-known risk factor for early kidney damage among diabetic/prediabetic patients. There is a complex interaction between physical activity (PA) and albuminuria. However, the relationship of specific-domain PA and albuminuria remained obscure. Methods Albuminuria was defined as urinary albumin/creatinine ratio (ACR) > 30 mg/g. PA was self-reported by participants and classified into transportation-related PA (TPA), occupation-related PA (OPA), and leisure-time PA (LTPA). Weighted logistic regression was conducted to compute the odds ratios (ORs) and 95% confidence intervals (CIs). Restricted cubic spline (RCS) was used to evaluate the dose–response of PA domains with the risk of albuminuria. Results A total of 6739 diabetic/prediabetic patients (mean age: 56.52 ± 0.29 years) were enrolled in our study, including 3181 (47.20%) females and 3558 (52.80%) males. Of them, 1578 (23.42%) were identified with albuminuria, and 5161(76.58%) were without albuminuria. Diabetic/prediabetic patients who adhered the PA guidelines for total PA had a 22% decreased risk of albuminuria (OR = 0.78, 95%CI 0.64–0.95), and those met the PA guidelines for LTPA had a 28% decreased of albuminuria (OR = 0.72, 95%CI 0.57–0.92). However, OPA and TPA were both not associated with decreased risk of albuminuria. RCS showed linear relationship between the risk of albuminuria with LTPA. Conclusions Meeting the PA guideline for LTPA, but not OPA and TPA, was inversely related to the risk of albuminuria among diabetic/prediabetic patients. Additionally, achieving more than 300 min/week of LTPA conferred the positive effects in reducing albuminuria among diabetic/prediabetic patients.

Angiotensin II receptor blockers (ARBs) are one of the standard treatments for diabetic kidney disease (DKD). Some patients may opt for Chinese herbal medicine (CHM) of their own free will. However, there is no real-world evidence regarding the effectiveness and safety of CHM. We aimed to explore the effectiveness of CHM for DKD in comparison to ARBs. We enrolled 732 DKD patients (72 used only CHM and 661 used ARBs) from 2007 to 2016, and all patients were followed until December 2016 at China Medical University Hospital in Taiwan. A total of 355 ARB users and 71 CHM users were analyzed after propensity score matching. The estimated glomerular filtration rate (eGFR) after treatment was 84.9 ± 28.1 ml/min/1.73 m2 in CHM users, which was higher than that (67.8 ± 35.4 ml/min/1.73 m2) in ARB users (p

Background Previous studies have revealed an underlying connection between abnormal lipid metabolism and albuminuria. We aim to investigate the causal relationship between lipid metabolism disorders and the risk of albuminuria from both a population and genetic perspective.Methods A cross-sectional study was conducted by using data from the National Health and Nutrition Examination Survey (NHANES) 2001-2018. Multivariable-adjusted logistic regression, subgroup analysis, interaction tests and restricted cubic spline (RCS) were employed statistically. Mendelian randomization (MR) analysis was performed to validate the causal relationship between exposure and outcome to mitigate confounding factors and reverse causation interference.Results After adjusting for confounders, HDL levels (1.03-2.07 nmol/L) were associated with a reduced risk of albuminuria. In contrast, elevated cholesterol levels (>6.2 nmol/L) and triglyceride levels (>2.3 nmol/L) were associated with an increased risk of albuminuria. Serum triglyceride concentration emerged as a potential risk factor for albuminuria. In MR analysis, a reduced risk of albuminuria was associated with serum total HDL level (IVW: OR = 0.91, 95% CI = 0.86-0.97, p = 0.002). In contrast, cholesterol esters in medium VLDL (IVW: OR = 1.05, 95% CI = 1.00-1.10, p = 0.032), chylomicrons and extremely large VLDL (IVW: OR = 1.08, 95% CI = 1.03-1.14, p = 0.003), and triglycerides (IVW: OR = 1.14, 95% CI = 1.09-1.19, p

Introduction Glomerular hyperfiltration is highly frequent, theoretically dependent on cardiac output, low systemic vascular resistance and hemolysis markers. In sickle cell disease (SCD), hyperfiltration is an extremely common phenomenon and occurred in young and early adult patients. Despite the fact that the glomerular hyperfiltration is known as the early manifestations of sickle cell nephropathy, its burden among adult sickle cell disease in sub-Saharan is poor studied. This study aimed to determine the prevalence and associated factors of hyperfiltrationMethods This was an analytical multicentric cross-sectional study involving stable adult sickle cell patients in Kinshasa, recruited between March and October 2023. Parameters of interest encompasses demographic, clinical, biological, echocardiographic and pulse wave measurement data. Hyperfiltration was defined using the CDK-EPI equation based on cystatin C; eGFR >130 for women and >140 ml/min/1.73m2 for men. We used multivariate logistic regression analysis to search determinants of glomerular hyperfiltration.Results Two hundred and fourty six (246) patients with SCD were enrolled. The prevalence of hyperfiltration was 20.7%. In multiple logistic regression analysis, hyperfiltration status was independently associated with age (< 25 years) [3.57 (1.78-7.49); p = 0.027)], female sex [4.36 (2.55-5.62); p = 0.031), CRP (< 6 mg/l) [0.77 (0.61-0.97); p = 0.028)], central systolic pressure (< 100 mmHg) and central diastolic pressure (< 60 mmHg) [0.86(0.74-0.98), p = 0.028)], [(0.83 (0.71-0.98); p = 0.032)].Conclusion One out of five SS adults exhibits hyperfiltration, which is associated with young age and female sex, whereas low CRP and blood pressure were negative risk factors.

Aims Finerenone has been approved for treating diabetic kidney disease (DKD) with reducing cardiorenal risk. Real-world data on finerenone treatment for the management of DKD are presently lacking. This study aimed to investigate the effect of finerenone on the renal parameters of the Chinese DKD population in the real-world medical setting for the first time, especially in combination with renin–angiotensin system inhibitors (RASi) and sodium-glucose cotransporter 2 inhibitors (SGLT2i).Methods Forty-two DKD patients were selected and completed a 6-month finerenone treatment. Renal parameters and adverse effects were collected at every visit.Results The median urine albumin-to-creatinine ratio (UACR) was 1426.11 (755.42, 3638.23) mg/g. Among them, the proportion of patients with a UACR of 300–5000 mg/g was 76.2%, and the proportion of patients with a UACR of >5000 mg/g was 14.3%. The median estimated glomerular filtration rate (eGFR) was 54.50 (34.16, 81.73) mL/min/1.73 m2. Finerenone decreased the UACR significantly throughout the study period (p .05). One patient each discontinued finerenone due to hyperkalemia (2.4%) and acute kidney injury (2.4%). No patient reported hypotension, breast pain, and gynecomastia.Conclusions This study from China first demonstrated finerenone decreased UACR with manageable safety in real-world DKD treatment. A triple regimen of RASi, SGLT2i, and finerenone may be a promising treatment strategy for lowering albuminuria and reducing hyperkalemia risk in advanced DKD patients.

Previous studies indicate a strong correlation between the incidence of chronic kidney disease (CKD) and lower economic status. However, these studies often struggle to delineate a clear cause–effect relationship, leaving healthcare providers uncertain about how to manage kidney disease in a way that improves patients’ financial outcomes. Our study aimed to explore and establish a causal relationship between CKD and socioeconomic status, identifying critical influencing factors. We utilized summary meta-analysis data from the CKDGen Consortium and UK Biobank. Genetic variants identified from these sources served as instrumental variables (IVs) to estimate the association between CKD and socioeconomic status. The presence or absence of CKD, estimated glomerular filtration rate (eGFR), and albuminuria were used as exposures, while income and regional deprivation were analyzed as outcomes. We employed the R packages ‘TwoSampleMR’ and ‘Mendelianrandomization’ to conduct both univariable and multivariable Mendelian randomization (MR) analyses, assessing for potential pleiotropy and heterogeneity. Our univariable MR analysis revealed a significant causal relationship between high levels of albuminuria and lower income (OR = 0.84, 95% CI: 0.73–0.96, p = 0.013), with no significant pleiotropy detected. In the multivariable MR analysis, both CKD (OR = 0.867, 95% CI: 0.786–0.957, p = 0.0045) and eGFR (OR = 0.065, 95% CI: 0.010–0.437, p = 0.0049) exhibited significant effects on income. This study underscores that higher albuminuria levels in CKD patients are associated with decreased income and emphasizes the importance of effective management and treatment of albuminuria in CKD patients to mitigate both social and personal economic burdens.

Background Renal impairment has been previously linked to peripheral eosinophil count (PEC), prompting an investigation into its potential relationship with chronic kidney disease (CKD). This cross-sectional study utilized data from the National Health and Nutrition Examination Survey (NHANES 1999–2018) to comprehensively explore the association between PEC and CKD.Methods Survey-weighted generalized multivariate linear regression was employed to evaluate the associations between PEC, urinary albumin-to-creatinine ratio (UACR), and estimated glomerular filtration rate (eGFR), with meticulous adjustment for potential covariates. To assess non-linear correlations, a restricted cubic spline analysis was conducted. Sensitivity analysis was performed to test the stability of results.Results The study included a total of 9224 participants with non-dialysis CKD. In the multivariate linear regression model, after comprehensive adjustment for potential covariates, PEC showed a negative association with eGFR (β per 100 cells/uL increase in PEC, −0.71; 95% CI, −1.04, −0.37), while demonstrating a positive trend with UACR (β per 100 cells/uL increase in PEC, 10.21; 95% CI, 1.37, 19.06). The restrictive cubic spline curve analysis suggested that these associations occurred within the range of 0 to 400 cells/uL for PEC. Sensitivity analysis supported the stability of the observed results.Conclusions Circulating eosinophil levels are negatively correlated with eGFR and demonstrate a positive trend with UACR, when PEC falls within the range of less than 400 cells/uL among adults with CKD. Further research is warranted to validate these findings.

Introduction Inflammation and oxidative stress play significant roles in the development of chronic kidney disease (CKD). Given the recognized antioxidant properties of vitamin C, our study aimed to explore the correlation between CKD and serum vitamin C levels.Methods Data were gathered from the 2017–2018 National Health and Nutrition Examination Survey. Participants below 18 years of age, pregnant individuals, those lacking essential data for CKD diagnosis, or individuals with incomplete serum vitamin C data were excluded. Subgroup and weighted multivariable logistic regression analyses were performed to assess the potential correlation between serum vitamin C and CKD.Results Our study comprised 4969 participants, revealing an overall CKD prevalence of 15.0%. The results indicated that individuals with reduced serum vitamin C levels were more likely to be male, possess lower educational attainment, have a diminished poverty-income ratio, engage in heavy drinking, and be current smokers. Additionally, they exhibited a higher prevalence of obesity and diabetes. Significantly, participants in the third quartile group experienced a 37.0%, 47.0%, and 46.6% decrease in the risk of developing albuminuria, low estimated glomerular filtration rate (eGFR), and CKD, respectively. Subgroup analysis demonstrated that individuals between 65 and 80 years of age showed a statistically reduced risk of developing CKD and low eGFR when their serum vitamin C levels fell in the third and fourth quartile groups.Conclusions Our findings reveal a correlation between elevated serum vitamin C levels and a decreased risk of developing albuminuria, low eGFR, and CKD. Appropriately increasing serum vitamin C levels may hold promise in protecting renal function, particularly among older individuals.

AIMS: The 2021 European Society of Cardiology (ESC) guideline on cardiovascular disease (CVD) prevention categorizes moderate and severe chronic kidney disease (CKD) as high and very-high CVD risk status regardless of other factors like age and does not include estimated glomerular filtration rate (eGFR) and albuminuria in its algorithms, systemic coronary risk estimation 2 (SCORE2) and systemic coronary risk estimation 2 in older persons (SCORE2-OP), to predict CVD risk. We developed and validated an Add-on to incorporate CKD measures into these algorithms, using a validated approach. METHODS: In 3,054 840 participants from 34 datasets, we developed three Add-ons [eGFR only, eGFR + urinary albumin-to-creatinine ratio (ACR) (the primary Add-on), and eGFR + dipstick proteinuria] for SCORE2 and SCORE2-OP. We validated C-statistics and net reclassification improvement (NRI), accounting for competing risk of non-CVD death, in 5,997 719 participants from 34 different datasets. RESULTS: In the target population of SCORE2 and SCORE2-OP without diabetes, the CKD Add-on (eGFR only) and CKD Add-on (eGFR + ACR) improved C-statistic by 0.006 (95%CI 0.004-0.008) and 0.016 (0.010-0.023), respectively, for SCORE2 and 0.012 (0.009-0.015) and 0.024 (0.014-0.035), respectively, for SCORE2-OP. Similar results were seen when we included individuals with diabetes and tested the CKD Add-on (eGFR + dipstick). In 57 485 European participants with CKD, SCORE2 or SCORE2-OP with a CKD Add-on showed a significant NRI [e.g. 0.100 (0.062-0.138) for SCORE2] compared to the qualitative approach in the ESC guideline. CONCLUSION: Our Add-ons with CKD measures improved CVD risk prediction beyond SCORE2 and SCORE2-OP. This approach will help clinicians and patients with CKD refine risk prediction and further personalize preventive therapies for CVD.

INTRODUCTION: Hypertriglyceridemia, a component of the metabolic syndrome, is a known independent predictor of albuminuria and chronic kidney disease (CKD) in the general population. Previous studies have shown that the relationship of triglycerides (TGs) with outcomes changes across stages of CKD. Our objective was to examine the association of TG independent of other metabolic syndrome components with renal outcomes in diabetic patients with or without CKD. METHODS: This retrospective cohort study included diabetic US veteran patients with valid data on TGs, estimated glomerular filtration rate (eGFR), and albuminuria (urinary albumin/creatinine ratio) between fiscal years 2004 and 2006. Using Cox models adjusted for clinical characteristics and laboratory markers, we evaluated the relationship of TG with incident albuminuria (stratified by eGFR category) and based on eGFR (stratified by baseline albuminuria categories). To evaluate the relationship of TG with time to end-stage renal disease (ESRD), we stratified models by baseline CKD stage (eGFR category) and baseline albuminuria stage ascertained at time of TG measurement. RESULTS: In a cohort of 138,675 diabetic veterans, the mean ± SD age was 65 ± 11 years old and included 3% females and 14% African Americans. The cohort also included 28% of patients with non-dialysis-dependent CKD (eGFR