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Type 2 diabetes (T2D) is associated with increased risk for chronic kidney disease (CKD). It is estimated that 40 % of people with diabetes have CKD, which consequently leads to increase in morbidity and mortality from cardiovascular diseases (CVDs). Diabetic kidney disease (DKD) is leading cause of CKD and end-stage renal disease (ESRD) globally. On the other hand, DKD is independent risk factor for CVDs, stroke and overall mortality. According to the guidelines, using spot urine sample and assessing urine albumin-to-creatinine ratio (UACR) and estimated glomerular filtration rate (eGFR) are both mandatory methods for screening of CKD in T2D at diagnosis and at least annually thereafter. Diagnosis of CKD is confirmed by persistent albuminuria followed by a progressive decline in eGFR in two urine samples at an interval of 3 to 6 months. However, many patients with T2D remain underdiagnosed and undertreated, so there is an urgent need to improve the screening by detection of albuminuria at all levels of health care. This review discusses the importance of albuminuria as a marker of CKD and cardiorenal risk and provides insights into the practical aspects of methods for determination of albuminuria in routine clinical care of patients with T2D., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Aims: We aimed to examine the role of circulating immature granulocytes (IGs) in assessing Diabetic Nephropathy (DN) mainly and also associations of other leukocyte parameters with DN., Methods: In this retrospective cross-sectional study, a total of 164 Diabetes Mellitus patients were grouped as normoalbuminuric and microalbuminuric according to urinary albumin excretion in the course of admission. Neutrophil-lymphocyte ratio (NLR), IG count (IG#) and IG percentage (IG%) levels were compared between the groups. The value of IG# and IG% levels in detecting microalbuminuria was analyzed with the Receiver operating characteristic (ROC) curve., Results: NLR was remarkably higher in the microalbuminuric group (p = 0.036). Correlation results in the microalbuminuric group were as follows: A feeble positive correlation between neutrophil count (NEU#) and serum creatinine and albumin-to- creatinine ratio (ACR) (p = 0.036, r = 0.261; p = 0.005, r = 0.347, respectively), a feeble positive correlation between lymphocyte count (LYM#) and estimated glomerular filtration rate (p = 0.021, r = 0.285). Correlation results in the normooalbuminuric group were as follows: A feeble positive correlation between NEU# and ACR (p = 0.043, r = 0.204), a feeble negative correlation between LYM# and serum creatinine (p = 0.042, r = -0.205), a poor positive correlation between IG# and ACR and HBA1C% (p = 0.048, r = 0.199; p = 0.004, r = 0.290, respectively), a positive poor correlation between IG% and HBA1C% (p = 0.019, r = 0.235). Area under the ROC curve values for IG# and IG% were not statistically noteworthy in detecting microalbuminuria (p = 0.430; p = 0.510, respectively)., Conclusions: IG# and IG% values are insufficient to predict immediate microalbuminuria, but could be considered a weak biomarker for renal damage in normoalbuminuric (<30 mg/g) diabetic patients. Further researches are needed for the use of leukocyte parameters in evaluating DN., Competing Interests: Declaration of competing interest None., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Background: For the development of pharmaceutical products in kidney field, appropriate surrogate endpoints which can predict long-term prognosis are needed as an alternative to hard endpoints, such as end-stage kidney disease. Though international workshop has proposed estimated glomerular filtration rate (GFR) slope reduction of 0.5-1.0 mL/min/1.73 m /year and 30% decrease in albuminuria/proteinuria as surrogate endpoints in early and advanced chronic kidney disease (CKD), it was not clear whether these are applicable to Japanese patients., Methods: We analyzed J-CKD-DB and CKD-JAC, Japanese databases/cohorts of CKD patients, and J-DREAMS, a Japanese database of patients with diabetes mellitus to investigate the applicability of eGFR slope and albuminuria/proteinuria to the Japanese population. Systematic review on those endpoints was also conducted including the results of clinical trials published after the above proposal., Results: Our analysis showed an association between eGFR slope and the risk of end-stage kidney disease. A 30% decrease in albuminuria/proteinuria over 2 years corresponded to a 20% decrease in the risk of end-stage kidney disease patients with baseline UACR ≥ 30 mg/gCre or UPCR ≥ 0.15 g/gCre in the analysis of CKD-JAC, though this analysis was not performed on the other database/cohort. Those results suggested similar trends to those of the systematic review., Conclusion: The results suggested that eGFR slope and decreased albuminuria/proteinuria may be used as a surrogate endpoint in clinical trials for early CKD (including diabetic kidney disease) in Japanese population, though its validity and cutoff values must be carefully considered based on the latest evidence and other factors., (© 2024. The Author(s).)

Introduction and Objectives: Fatty liver disease is a multisystem disease. Metabolic dysfunction-associated fatty liver disease (MAFLD) is a more accurate indicator of chronic kidney disease (CKD) than nonalcoholic fatty liver disease (NAFLD). However, the relationship between recently defined metabolic dysfunction-associated steatotic liver disease (MASLD) and CKD is currently unclear. The objective of this cross-sectional study was to investigate the prevalence of CKD and albuminuria among individuals diagnosed with either MAFLD or MASLD., Patients and Methods: This study involved 5,492 participants who provided biochemical marker and liver ultrasound data from the U.S. National Health and Nutrition Examination Survey (2017-2020). Multiple logistic regression analyses were conducted to assess the independent associations of nonoverlapping MAFLD and MASLD with the presence of CKD or albuminuria (urinary albumin-to-creatinine ratio ≥ 3 mg/mmol)., Results: MAFLD and MASLD were identified in 47% and 44.5% of the participants, respectively. Individuals with MAFLD-only had a greater prevalence of CKD (24.7% vs. 8.3 %, P < 0.006) and albuminuria (18.6% vs. 5%, P < 0.01) than did those with MASLD-only. Importantly, after adjusting for factors such as sex, age, ethnicity, and alcohol use, it was demonstrated that individuals in the MAFLD-only group had a 4.73-fold greater likelihood of having prevalent CKD than those in the MASLD-only group (P < 0.03)., Conclusions: The MAFLD criteria better identify patients with CKD than do the MASLD criteria. Therefore, it is suggested that the MASLD criteria be reconsidered, as currently, the justification for changing from MAFLD to MASLD criteria may not be appropriate., Competing Interests: Conflicts of interest None., (Copyright © 2024 Fundación Clínica Médica Sur, A.C. Published by Elsevier España, S.L.U. All rights reserved.)

Albuminuria has been considered the golden standard biomarker for diabetic kidney disease (DKD), but appears once significant kidney damage has already occurred. Angiopoietin-2 (Angpt-2) has been implicated in the development and progression of DKD in adults. We aimed to explore the association of serum Angpt-2 levels with DKD in children and adolescents with type 1 diabetes mellitus (T1DM) of short duration (3-5 years) and to evaluate the predictive power of serum Angpt-2 in the early detection of DKD prior to the microalbuminuric phase. The current cross-sectional study included 90 children divided into three age and sex-matched groups based on urinary albumin-to-creatinine ratio (UACR): microalbuminuric diabetic group (n = 30), non-albuminuric diabetic group (n = 30), and control group (n = 30). All participants were subjected to anthropometric measurements, serum Angpt-2 and fasting lipid profile (total cholesterol, triglycerides, LDL-C, HDL-C, and Non-HDL-C) assessment. Glomerular filtration rate was estimated based on serum creatinine (eGFR-Cr). Higher serum Angpt-2 levels were detected in both diabetic groups compared to controls and in microalbuminuric compared to non-albuminuric diabetic group. There was no detected significant difference in eGFR-Cr values across the study groups. Serum Angpt-2 was positively correlated with triglycerides, LDL, Non-HDL-C, HbA1c, and UACR, while UACR, HbA1c, and Non-HDL-C were independent predictors for serum Angpt-2. Serum Angpt-2 at level of 137.4 ng/L could discriminate between microalbuminuric and non-albuminuric diabetic groups with AUC = 0.960 and at level of 115.95 ng/L could discriminate between the non-albuminuric diabetic group and controls with AUC = 0.976.Conclusion: Serum Angpt-2 is a promising potent biomarker for the detection of early stage of DKD in childhood T1DM before albuminuria emerges. What is Known? • Urine albumin-to-creatinine ratio (UACR) and glomerular filtration rate (GFR) are the golden standard but late biomarkers for DKD. • Angiopoietin-2 has been implicated in the development and progression of DKD in adults with diabetes, but has not been explored in T1DM children with DKD. What is New? • Higher serum angiopoietin-2 was detected in diabetic groups compared to controls and in microalbuminuric compared to non-albuminuric group. • Angiopoietin-2 correlated positively with triglycerides, LDL, Non-HDL-C, HbA1c, and UACR. • Serum angiopoietin-2 is a promising early diagnostic biomarker for DKD in children with T1DM., (© 2024. The Author(s).)

Background: Albuminuria is considered an early and sensitive marker of kidney dysfunction, but also an independent cardiovascular risk factor. Considering the possible relationship among metabolic liver disease, cardiovascular disease and chronic kidney disease, we aimed to evaluate the risk of developing albuminuria regarding the presence of epicardial adipose tissue and the steatotic liver disease status., Methods: A retrospective long-term longitudinal study including 181 patients was carried out. Epicardial adipose tissue and steatotic liver disease were assessed by computed tomography. The presence of albuminuria at follow-up was defined as the outcome., Results: After a median follow up of 11.2 years, steatotic liver disease (HR 3.15; 95% CI, 1.20-8.26; p = 0.02) and excess amount of epicardial adipose tissue (HR 6.12; 95% CI, 1.69-22.19; p = 0.006) were associated with an increased risk of albuminuria after adjustment for visceral adipose tissue, sex, age, weight status, type 2 diabetes, prediabetes, hypertriglyceridemia, hypercholesterolemia, arterial hypertension, and cardiovascular prevention treatment at baseline. The presence of both conditions was associated with a higher risk of developing albuminuria compared to having steatotic liver disease alone (HR 5.91; 95% CI 1.15-30.41, p = 0.033). Compared with the first tertile of visceral adipose tissue, the proportion of subjects with liver steatosis and abnormal epicardial adipose tissue was significantly higher in the second and third tertile. We found a significant correlation between epicardial fat and steatotic liver disease (rho = 0.43 [p < 0.001])., Conclusions: Identification and management/decrease of excess adiposity must be a target in the primary and secondary prevention of chronic kidney disease development and progression. Visceral adiposity assessment may be an adequate target in the daily clinical setting. Moreover, epicardial adipose tissue and steatotic liver disease assessment may aid in the primary prevention of renal dysfunction., (© 2024. The Author(s).)

Objectives: The main aim was to determine the diagnostic performance of an albuminuria point-of-care test (POC) for diagnosis of chronic kidney disease among young people living with HIV (YPLHIV) in Uganda., Design: We conducted a cross-sectional study comparing the diagnostic performance of MicroalbuPHAN (Erba Lachema, Czech Republic), an albuminuria POC test against the laboratory-measured albumin and creatinine as the reference standard., Setting: The study was set in seven HIV clinics in Kampala, Uganda that provide antiretroviral therapy to adults and children living with HIV. The study took place from April to August 2023., Participants: 497 YPLHIV aged 10-24 years who were diagnosed with HIV before 10 years of age were randomly selected from the HIV clinics. Pregnant YPLHIV were excluded., Procedures: Participants provided a spot urine sample that was tested for albumin and creatinine using the POC and in the laboratory and proteinuria using urine dipstick. The sensitivity, specificity, negative and positive predictive values (NPV, PPV) of the POC versus the laboratory test were calculated, and factors associated with having a positive POC test were estimated using logistic regression., Outcome Measures: The primary outcome was a diagnosis of albuminuria defined as an albumin creatinine ratio above 30 mg/g., Results: Of the 497 participants enrolled, 278 (55.9%) were female and 331 (66.8%) were aged 10-17 years. The POC test had a sensitivity of 74.5% (95% CI 70.6% to 78.4%) and specificity of 68.1% (95% CI 63.9% to 72.3%). The PPV was 21.5% (95% CI 17.8% to 25.1%) and the NPV was 95.8% (95% CI 94.0% to 97.6%), with an accuracy of 68.8%. There was strong evidence that a positive POC test was associated with having proteinuria (OR 2.82; 95% CI 1.89 to 4.22, p<0.001); body mass index <19.5 (OR 1.69 95% CI 1.17 to 2.45, p=0.005) and being male (OR 1.48; 95% CI 1.02 to 2.14, p=0.04)., Conclusions: The albuminuria POC test had low sensitivity and specificity. However, it can be used to exclude kidney disease given its high NPV. It should be validated against the 24-hour urinary excretion rate to further determine its diagnostic performance., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2024. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Diabetic nephropathy (DN) has become the main cause of end-stage renal disease worldwide, causing significant health problems. Early diagnosis of the disease is quite inadequate. To screen urine biomarkers of DN and explore its potential mechanism, this study collected urine from 87 patients with type 2 diabetes mellitus (which will be classified into normal albuminuria, microalbuminuria, and macroalbuminuria groups) and 38 healthy subjects. Twelve individuals from each group were then randomly selected as the screening cohort for proteomics analysis and the rest as the validation cohort. The results showed that humoral immune response, complement activation, complement and coagulation cascades, renin-angiotensin system, and cell adhesion molecules were closely related to the progression of DN. Five overlapping proteins (KLK1, CSPG4, PLAU, SERPINA3, and ALB) were identified as potential biomarkers by machine learning methods. Among them, KLK1 and CSPG4 were positively correlated with the urinary albumin to creatinine ratio (UACR), and SERPINA3 was negatively correlated with the UACR, which were validated by enzyme-linked immunosorbent assay (ELISA). This study provides new insights into disease mechanisms and biomarkers for early diagnosis of DN.

Background: Chronic kidney disease is associated with increased rates of incidence, morbidity, and mortality in lower-extremity peripheral artery disease (PAD). No specific marker for a functional risk assessment of kidney disease in PAD is known, especially at the early stages. Thus, we speculated that urinary vanin-1 (uVNN1), a marker of oxidative stress even in early kidney injury, could further stratify outcome assessment in patients with PAD., Methods: Patients with stable PAD ( n = 304) of the Vienna medical cohort were followed up for up to 10 years and the outcome was assessed by central death database queries. uVNN1 was measured by enzyme-linked immunosorbent assay (ELISA) at study inclusion and normalized to urinary creatinine (uVNN1/Cr). During the observation time (9.3, 7.0-9.8 years), 104 patients died, 54.8% of which were due to cardiovascular causes., Results: uVNN1/Cr was associated with a urine albumin-creatinine ratio (UACR) ( R = 0.166, p = 0.004) but not with an estimated glomerular filtration rate ( R = 0.102, p = 0.077). Levels of uVNN1/Cr did not differ between asymptomatic and symptomatic PAD ( p = 0.406). Kaplan-Meier curves showed a clear-cut association with higher all-cause (log-rank p = 0.034) and cardiovascular mortality (log-rank p = 0.032) with higher uVNN1/Cr levels. Similarly, significant associations for all-cause (hazard ratio [HR] 1.34, 95% CI [1.08-1.67], p = 0.009) and cardiovascular mortality (HR 1.45, 95% CI [1.06-1.99], p = 0.020) could be seen in multivariable Cox regression models., Conclusions: uVNN1/Cr showed an independent association with both all-cause and cardiovascular mortality in patients with PAD and was associated with early kidney disease. Thus, uVNN1 could be a useful marker for risk stratification of kidney disease in PAD., Competing Interests: Declaration of conflicting interestsThe authors declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Albuminuria is a marker of diabetic kidney disease. Raised albuminuria in children and young people with diabetes is associated with an increased risk of microvascular and macrovascular complications. This review provides guidance for paediatricians caring for children and young people with type 1 and type 2 diabetes on screening, investigations and treatments for albuminuria in line with relevant national and international recommendations., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2024. No commercial re-use. See rights and permissions. Published by BMJ.)

Background: Despite improved glycemic treatment, the impact of glycation on pathological consequences may persist and contribute to adverse clinical outcomes in diabetes. In the present study we investigated the association between serum protein glycation products and progression of kidney disease as well as incident major adverse cardiovascular events (MACE) in type 1 diabetes., Methods: Fructosamine, advanced glycation end products (AGEs), and methylglyoxal-modified hydro-imidazolone (MG-H1) were measured from baseline serum samples in the FinnDiane study (n = 575). Kidney disease progression was defined as steep eGFR decline (> 3 mL/min/1.73 m 2 /year) or progression of albuminuria (from lower to higher stage of albuminuria). MACE was defined as acute myocardial infarction, coronary revascularization, cerebrovascular event (stroke), and cardiovascular death., Results: Fructosamine was independently associated with steep eGFR decline (OR 2.15 [95% CI 1.16-4.01], p = 0.016) in the fully adjusted model (age, sex, baseline eGFR). AGEs were associated with steep eGFR decline (OR 1.58 per 1 unit of SD [95% CI 1.07-2.32], p = 0.02), progression to end-stage kidney disease (ESKD) (HR 2.09 per 1 unit of SD [95% CI 1.43-3.05], p < 0.001), and pooled progression (to any stage of albuminuria) (HR 2.72 per 1 unit of SD [95% CI 2.04-3.62], p < 0.001). AGEs (HR 1.57 per 1 unit of SD [95% CI 1.23-2.00], p < 0.001) and MG-H1 (HR 4.99 [95% CI 0.98-25.55], p = 0.054) were associated with incident MACE. MG-H1 was also associated with pooled progression (HR 4.19 [95% CI 1.11-15.89], p = 0.035). Most AGEs and MG-H1 associations were no more significant after adjusting for baseline eGFR., Conclusions: Overall, these findings suggest that protein glycation products are an important risk factor for target organ damage in type 1 diabetes. The data provide further support to investigate a potential causal role of serum protein glycation in the progression of diabetes complications., (© 2024. The Author(s).)

Introduction: Syndecan (SDC)-1 is a transmembrane heparan sulfate proteoglycan and is a major component of endothelial glycocalyx (EG). This study aimed to investigate the association of serum SDC-1 concentration as a marker of EG degradation with albuminuria in type 2 diabetes., Methods: We included 370 patients with type 2 diabetes and 219 individuals with no diabetes. The individuals with estimate glomerular filtration rate <30 mL/min/1.73 m 2 were excluded., Results: Serum SDC-1 concentration was higher in type 2 diabetes than in no diabetes. The presence of diabetes was independently associated with log [SDC-1] in multivariate analysis. In type 2 diabetes, serum SDC-1 concentration was correlated with log [urinary albumin-to-creatinine ratio (ACR)]. Moreover, log [SDC-1] was an independent determinant of log [ACR] after adjustment for known risk factors of albuminuria., Conclusions: Serum SDC-1 concentration was higher in patients with type 2 diabetes compared to individuals with no diabetes and an independent determinant of ACR. This study implicates the role of the EG degradation in albuminuria in type 2 diabetes., Competing Interests: Declaration of conflicting interestsThe author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Diabetic nephropathy represents a microvascular complication related to type 2 diabetes mellitus (T2DM) that ultimately causes end-stage renal disease. Our study aimed to evaluate the association of plasma type IV collagen with albuminuria status and to assess the clinical significance of plasma type IV collagen as a potential biomarker in the early stage of diabetic nephropathy. The study comprised 75 participants diagnosed with T2DM allocated equally (n=25) into three groups: (A) normal albuminuria levels, (B) microalbuminuria, and (C) macroalbuminuria, depending on their urine albumin-to-creatinine ratio. A comparative analysis was conducted between these groups and a control group (D, n=15). The enzyme-linked immunosorbent assay (ELISA) method was employed for measuring plasma type IV collagen levels. The results revealed that plasma type IV collagen levels were significantly higher in T2DM groups than in the control group. Moreover, diabetic patients without albuminuria had significantly higher plasma type IV collagen levels than the control group (p < 0.001). Furthermore, albuminuria levels among diabetic patient groups were significantly increased as albuminuria categories increased (p < 0.001). A significant positive correlation existed between plasma type IV collagen and glycated hemoglobin (HbA1c) levels in the macroalbuminuric diabetic group. Our study employed the receiver operating characteristic (ROC) curve analysis to determine plasma type IV collagen diagnostic utility in macroalbuminuria prediction. The ROC curve analysis revealed that type IV collagen can significantly determine macroalbuminuric patients at a cutoff value of 2.25 with sensitivity, specificity, positive predictive value, and negative predictive value of 68%, 100%, 100%, and 75.8%, respectively (p < 0.001). In conclusion, plasma type IV collagen levels might serve as a valuable predictor of albuminuria onset in patients with T2DM., (Copyright© by the Egyptian Association of Immunologists.)

An increased risk of target organ damage (TOD) has been reported in patients with primary aldosteronism (PA). However, there is relatively little related research on the correlation between the degree of TOD and those with and without PA in newly diagnosed hypertensive patients. The aim of this study was to assess the association between PA and TOD among patients with newly diagnosed hypertension. Newly diagnosed hypertensive patients were consecutively recruited from January 2015 to June 2020 at the University of Hong Kong-Shenzhen Hospital. Patients were stratified into those with and without PA. Data for left ventricular mass index (LVMI), carotid intima-media thickness (CIMT) and plaque, and microalbuminuria were systematically collected. A total of 1044 patients with newly diagnosed hypertension were recruited, 57 (5.5%) of whom were diagnosed with PA. Patients with PA had lower blood pressure, serum lipids, body mass index, and plasma renin activity and a higher incidence of hypokalemia than those without PA. In contrast, the prevalence of left ventricular hypertrophy, increased CIMT, and microalbuminuria was higher in patients with PA than in those without PA. Multivariable regression analysis demonstrated that PA was independently associated with increased LVMI, CIMT and microalbuminuria. Among patients with newly diagnosed hypertension, those with PA had more severe TOD, including a higher LVMI, CIMT and microalbuminuria, than those without PA. These findings emphasize the need for screening TOD in newly diagnosed hypertension due to underlying PA., (© 2024 The Authors. The Journal of Clinical Hypertension published by Wiley Periodicals LLC.)

Rationale & Objective: Evidence has demonstrated that albuminuria is a key diagnostic and prognostic marker of diabetic chronic kidney disease, but the impact of its day-to-day variability has not been adequately considered. This study quantified within-individual variability of albuminuria in people with type 2 diabetes to inform clinical albuminuria monitoring., Study Design: Descriptive cross-sectional analysis., Setting & Participants: People with type 2 diabetes (n=826, 67.1 [IQR, 60.3-72.4] years, 64.9% male) participating in the Progression of Diabetic Complications (PREDICT) cohort study., Exposure: Four spot urine collections for measurement of urinary albumin-creatinine ratio (UACR) within 4 weeks., Outcome: Variability of UACR., Analytical Approach: We characterized within-individual variability (coefficient of variation [CV], 95% limits of random variation, intraclass correlation coefficient), developed a calculator displaying probabilities that any observed difference between a pair of UACR values truly exceeded a 30% difference, and estimated the ranges of diagnostic uncertainty to inform a need for additional UACR collections to exclude or confirm albuminuria. Multiple linear regression examined factors influencing UACR variability., Results: We observed high within-individual variability (CV 48.8%; 95% limits of random variation showed a repeated UACR to be as high/low as 3.78/0.26 times the first). If a single-collection UACR increased from 2 to 5mg/mmol, the probability that UACR actually increased by at least 30% was only 50%, rising to 97% when 2 collections were obtained at each time point. The ranges of diagnostic uncertainty were 2.0-4.0mg/mmol after an initial UACR test, narrowing to 2.4-3.2 and 2.7-2.9mg/mmol for the mean of 2 and 3 collections, respectively. Some factors correlated with higher (female sex; moderately increased albuminuria) or lower (reduced estimated glomerular filtration rate and sodium-glucose cotransporter 2 inhibitor/angiotensin-converting enzyme inhibitor/angiotensin receptor blocker treatment) within-individual UACR variability., Limitations: Reliance on the mean of 4 UACR collections as the reference standard for albuminuria., Conclusions: UACR demonstrates a high degree of within-individual variability among individuals with type 2 diabetes. Multiple urine collections for UACR may improve capacity to monitor changes over time in clinical and research settings but may not be necessary for the diagnosis of albuminuria., Plain-Language Summary: Albuminuria (albumin in urine) is a diagnostic and prognostic marker of diabetic chronic kidney disease. However, albuminuria can vary within an individual from day to day. We compared 4 random spot urinary albumin-creatinine ratio (UACR) samples from 826 participants. We found that a second UACR collection may be as small as a fourth or as large as almost 4 times the first sample's UACR level. This high degree of variability presents a challenge to our ability to interpret changes in albuminuria. Multiple collections have been suggested as a solution. We have constructed tools that may aid clinicians in deciding how many urine collections are required to monitor and diagnose albuminuria. Multiple urine collections may be required for individual monitoring but not necessarily for diagnosis., (Copyright © 2024 National Kidney Foundation, Inc. Published by Elsevier Inc. All rights reserved.)

Fluorescent probes have been reported for monitoring urinary albumin (u-ALB) to enable early diagnosis of kidney diseases and facilitate regular point-of-care testing (POCT) for chronic kidney disease (CKD) patients. However, the albumin can bind hydrophobic drugs through host-guest interactions, which may result in decreased accuracy of probes at regular drug sites and hamper POCT of albuminuria since CKD patients often need to take medications routinely. Herein, we reported a novel fluorescent probe (NC-2) by molecular engineering of a reported AIEgen (NC-1). The introduction of a non-conjugated ring moiety to the molecular rotor granted the NC-2 enhanced sensitivity with a limit of detection in urine of 8.7 mg/L, which is below l the threshold of microalbuminuria (30 mg/L). Moreover, the NC-2 was found to preferentially bind to the FA1 site of ALB, conferring it with excellent anti-interference capacities against exogenous drug molecules and metabolites. Simulation experiments using lab-spiked urine samples containing common drugs taken by CKD patients demonstrated that the probe could provide satisfied detecting accuracy (80-90 %). Furthermore, a paper-based device was constructed and achieved on-site detection of u-ALB in qualitative and semi-quantitative manners. Findings in this work were of great significance to the development of fluorescent probes for accurate detection of ALB in complex urine samples and the further achievement of fluorescence-based POCT for CKD., Competing Interests: Declaration of competing interest The authors declared that there were no competing financial interests nor personal relationship that could influence the work in this paper., (Copyright © 2024. Published by Elsevier B.V.)

Background: This study aimed to evaluate the blood pressure (BP) status, including arterial stiffness parameters, hemodynamic indicators, circadian profile, and its association with albuminuria in adolescents with type 1 diabetes mellitus (DM1)., Methods: The analysis included 46 patients, with diabetes duration of 7.38 ± 3.48 years. Ambulatory blood pressure monitoring (ABPM) was conducted using an oscillometric device, the Mobil-O-Graph, which is a Pulse Wave Analysis Monitor., Results: Hypertension (HT) was diagnosed in 31 adolescents (67% of patients), primarily due to isolated nocturnal BP (21 cases, 68% of HT cases). The HT group exhibited significantly increased diastolic load (DL). Pulse wave velocity (PWV, a measure of arterial stiffness) values showed a strong correlation with both peripheral systolic BP (r = 0.954) and central systolic BP (r = 0.838). Additionally, non-dipping status was found in 61% of the HT group. Urinary albumin excretion (UAE) was positively correlated with diastolic BP (particularly nocturnal) peripheral and central BP, DL, heart rate, augmentation index (AIx@75), and nocturnal total vascular resistance (TVR). Diastolic non-dippers exhibited a significant increase in UAE., Conclusions: Hypertension is a common complication in adolescents with type 1 diabetes mellitus, primarily caused by elevated nocturnal diastolic BP. Albuminuria is mainly associated with diastolic BP, especially during the nocturnal period and in cases of diastolic non-dipping status. The association of UAE with AIx@75 and nocturnal TVR suggests the presence of early-stage vascular disease in diabetic adolescents., (© 2024. The Author(s).)

Moderately elevated albuminuria (30-300 mg/g) is a marker of renal dysfunction and a risk factor of cardiovascular disease. Additionally, several recent studies have reported a relationship between moderately elevated albuminuria and triglyceride (TG) levels. Therefore, we aimed to evaluate the relationship between the urine albumin-to-creatinine ratio (UACR) and total cholesterol (TC), TG, and high-density lipoprotein C (HDL-C) levels. We analyzed data from 19,340 patients from the 2011-2014 and 2019-2020 from the Korea National Health and Nutrition Examination Surveys. Multivariate linear regression analysis showed that the UACR was positively associated with TC and TG levels and negatively associated with HDL-C levels in both Korean women and men. These results were reanalyzed according to the degree of proteinuria (normal, moderately elevated albuminuria, and severely elevated albuminuria (≥ 300 mg/g)). We found a positive relationship between UACR and TC and TG levels, but a negative association with HDL-C levels, except for TC (moderately elevated albuminuria) and HDL-C (moderately elevated albuminuria) in Korean men and TC (severely elevated albuminuria), TG (severely elevated albuminuria), and HDL-C (normal range albuminuria) in Korean women. The correlation between albuminuria and lipid profiles became more evident as albuminuria shift from normal to the severely elevated albuminuria. Thus our multivariate linear regression analysis showed that lipid profiles (TG, TC, and HDL-C levels) were associated with the UACR., (© 2024. The Author(s).)

Background: In the UK, chronic kidney disease (CKD) is a prevalent, silent and strong predictor of cardiovascular disease. Identification of CKD is poor in primary care, particularly in minority ethnic and socio-economically deprived groups., Aim: To investigate feasibility of remote ACR testing to improve the detection and management of CKD in underserved groups., Method: 13 591 tests were sent out across South East London. Individuals with diabetes and no ACR in the past year were offered a remote ACR test to complete at home with a smartphone using a validated app (Healthy.io). We extracted data on demographics, medical comorbidities and medication. Analyses (Stata) describe who completed the test., Results: Twenty-seven practices agreed to participate. Analyses of 6082 tests sent show the test completion rate was 46.8%. Adjusted odds ratios demonstrated that people were less likely to complete testing if over 70 years (OR 0.71, 95% CI 0.57 to 0.89) and over 80 (OR 0.43, CI 95% 0.33 to 0.56) compared to <40 years old; people from CORE20 groups (most deprived quintile) were also less likely to complete testing (OR 0.68, 95% CI 0.61 to 0.76) and those with missing data and those with no recorded healthcare interactions within the last 5 years were also less likely to complete testing., Discussion: Remote ACR testing presents an opportunity to diagnose early CKD but there is still inequity in who completes testing. Engagement with stakeholders is needed to explore innovative ways to implement remote ACR testing to achieve equitable CKD screening., (© British Journal of General Practice 2024.)

The first orientation test for proteinuria typing is electrophoresis. However, this technique has several drawbacks, such as delayed turnaround time and subjective readings. Some laboratories therefore use quantitative assays of glomerular markers combined with tubular markers. However, the cost of reagents and the instability of certain markers are significant drawbacks for some peripheral laboratories. The aim of this study is to evaluate the implementation of an algorithm based on parameters that can be used by all laboratories for proteinuria typing within a timeframe compatible with the urgency of the situation. Albuminuria and urinary IgG were determined on 161 urines. ROC curves were produced, using urine electrophoresis read by an expert center as the reference method. The decision thresholds used are: glomerular proteinuria is defined by a Albumin+IgGproteinsratio greater than 75.4% (100% specificity), and tubular or overload proteinuria is defined by by a Albuminproteinsratio less than 37.3% (100% sensitivity). Agreement between the results of the algorithm selected and the reference method used in our study was 88 %, with a kappa value of 0.807 (95% CI [0.729 to 0.885]). The algorithm's performance suggests that it can find its place in the diagnostic strategy for clinically significant proteinuria, despite its limited indications. It is up to each biologist to assess the value of this algorithm in relation to the recruitment, habits and needs of clinicians.

Background and Aims: The urinary albumin‒creatinine ratio (UACR) and estimated glomerular filtration rate (eGFR) are important markers of renal dysfunction, but few studies have simultaneously examined their impact on long-term mortality in patients with heart failure (HF)., Methods and Results: This study included patients with HF from the National Health and Nutrition Survey from 1999 to 2018. The fully adjusted Cox proportional risk model was adopted, and propensity score matching (PSM) was also used for risk adjustment. Among 988 patients, a median follow-up of 7.75 years was recorded. A higher UACR corresponded to a higher risk of cardiovascular death (P < 0.001 for trend). No statistically significant difference was found in the trend of eGFR risk stratification on the risk of cardiovascular death (P = 0.09 for trend). After PSM, the results showed that when grouped by UACR, the high-risk group had a higher risk of cardiovascular death regardless of a cutoff value of 30 or 300 mg/g (all P < 0.05). When grouped by eGFR, regardless of a cutoff value of 45 or 30 mL/min/1.73 m 2 , compared to the low-risk group, the high-risk group did not have a statistically significant increase in cardiovascular death (P = 0.086 and P = 0.093, respectively). The subgroup analysis of the main outcome showed an interaction between the UACR and eGFR (P = 0.044)., Conclusions: Both the UACR and eGFR are markers for predicting the progression of HF, but the UACR may be a more important indicator than the eGFR, and they synergistically and complementarily reflect the long-term cardiovascular risk of HF patients., Competing Interests: Declaration of competing interest The authors declare that they have no confict of interest., (Copyright © 2024 The Italian Diabetes Society, the Italian Society for the Study of Atherosclerosis, the Italian Society of Human Nutrition and the Department of Clinical Medicine and Surgery, Federico II University. Published by Elsevier B.V. All rights reserved.)

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., (© 2023 The Authors. Journal of Renal Care published by John Wiley & Sons Ltd on behalf of European Dialysis & Transplant Nurses Association/European Renal Care Association.)

Diabetic kidney disease (DKD) poses a significant health challenge for individuals with diabetes. At its initial stages, DKD often presents asymptomatically, and the standard for non-invasive diagnosis, the albumin-creatinine ratio (ACR), employs discrete categorizations (normal, microalbuminuria, macroalbuminuria) with limitations in sensitivity and specificity across diverse population cohorts. Single biomarker reliance further restricts the predictive value in clinical settings. Given the escalating prevalence of diabetes, our study uses proteomic technologies to identify novel urinary proteins as supplementary DKD biomarkers. A total of 158 T1D subjects provided urine samples, with 28 (15 DKD; 13 non-DKD) used in the discovery stage and 131 (45 DKD; 40 pDKD; 46 non-DKD) used in the confirmation. We identified eight proteins (A1BG, AMBP, AZGP1, BTD, RBP4, ORM2, GM2A, and PGCP), all of which demonstrated excellent area-under-the-curve (AUC) values (0.959 to 0.995) in distinguishing DKD from non-DKD. Furthermore, this multi-marker panel successfully segregated the most ambiguous group (microalbuminuria) into three distinct clusters, with 80% of subjects aligning either as DKD or non-DKD. The remaining 20% exhibited continued uncertainty. Overall, the use of these candidate urinary proteins allowed for the better classification of DKD and offered potential for significant improvements in the early identification of DKD in T1D populations., Competing Interests: Declaration of competing interest J-X.S. is CEO of Jinfiniti Precision medicine. However, the individual declares there are no competing interest or benefit received to them or the company in relation to this project. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Background: Urinary albumin-creatinine ratio (UACR) and estimated glomerular filtration rates (eGFR) help predict worsening diabetic kidney disease (DKD) but have their limitations. Soluble tumor necrosis factor receptor type 1 (sTNFR1) is a biomarker of DKD. The predictive abilities of sTNFR1 and UACR plus eGFR have not been compared., Methods: This prospective cohort study included patients with type 2 diabetes (T2D) to identify the risk factors of worsening DKD. Renal events were defined as > 30 % loss in eGFR based on consecutive tests after 6 months. The associations of sTNFR1, UACR, and eGFR levels and the risks of renal events were tested using a Cox regression model and the area under the curve (AUC) was compared between sTNFR1 levels and UACR plus eGFR using receiver-operating characteristic (ROC) analysis. The accuracy of stratification was evaluated using Kaplan-Meier analysis., Results: Levels of sTNFR1 and UACR were associated with risks of > 30 % decline in eGFR after adjusting for relevant factors. The association between sTNFR1 levels and renal outcomes was independent of UACR and eGFR at baseline. The AUC of sTNFR1 level was comparable with that of combined UACR and eGFR (0.73 vs. 0.71, respectively, p = 0.72) and the results persisted for quartile groups of sTNFR1 and risk categories of Kidney Disease: Improving Global Outcomes (KDIGO) (0.70 vs. 0.71, respectively, p = 0.84). Both stratifications by sTNFR1 levels and KDIGO were accurate., Conclusion: sTNFR1 could be an alternative marker for identifying patients with diabetes at risk of declining renal function., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Author(s). Published by Elsevier B.V. All rights reserved.)

Previous observational studies have investigated the association between urinary albumin excretion and the risk of colorectal cancer (CRC), but the results have been inconsistent. This study aimed to explore the causal association between urine albumin-to-creatinine ratio (ACR) and CRC risk through a two-sample Mendelian randomization (MR) analysis. The genome-wide association study (GWAS) data of ACR (n = 382,500) and CRC (CRC: 6,509 cases and 287,137 controls) were obtained from the IEU OpenGWAS project website and the FinnGen database, respectively. The TwoSampleMR and MR-PRESSO R packages were used to search for and analyze genetic variations that served as instrumental variables for ACR. The odds ratios (ORs) and 95% confidence intervals (95% CIs) were calculated using the inverse-variance weighted method, MR-Egger, and weighted median. Genetically predicted ACR was not associated with CRC risk (all P > 0.05). Further analysis based on the site of onset (colon or rectum) also did not show a significant association (all P > 0.05). MR-PRESSO, MR-Egger regression and leave-one-out sensitivity analysis all indicated that the current results were robust and reliable. These findings suggest that ACR does not affect CRC risk and may not be used as a marker of CRC risk in clinical practice. However, relevant studies especially in ethnically diverse populations are still needed to confirm the current findings.

Purpose of Review: The conventional definition of chronic kidney disease (CKD) primarily relies on the identification of albuminuria or a decline in estimated glomerular filtration rate (eGFR). For many years, a straightforward eGFR threshold of <60 ml/min/1.73 m 2 has been widely adopted as the standard for defining CKD. Nonetheless, this criterion fails to consider the natural aging process of the kidney, and this oversight may affect the accurate diagnosis of kidney disease particularly at the extremes of age., Recent Findings: The fixed eGFR threshold of <60 ml/min/1.73 m 2 for defining CKD misses crucial opportunities for risk prevention. Studies have revealed that the eGFR threshold at which the risks for adverse long-term health outcomes such as mortality, cardiovascular events, and kidney failure begin to rise varies substantially by age. Specifically, this threshold is lower for the elderly and higher for young adults. Consequently, this results in the over-diagnosis of kidney disease in the elderly and the under-diagnosis of kidney disease in young adults., Summary: To address these limitations of the current CKD definition, we discuss a number of proposed age-adapted eGFR criteria and weigh their pros and cons against the current, simple, and universally accepted approach., (Copyright © 2024 Wolters Kluwer Health, Inc. All rights reserved.)

A new analytical method for chronic kidney disease (CKD) detection utilizing paper spray mass spectrometry (PS-MS) combined with machine learning is presented. The analytical protocol is rapid and simple, based on metabolic profile alterations in urine. Anonymized raw urine samples were deposited (10 μL each) onto pointed PS-MS sample strips. Without waiting for the sample to dry, 75 μL of acetonitrile and high voltage were applied to the strips, using high resolution mass spectrometry measurement (15 s per sample) with polarity switching to detect a wide range of metabolites. Random forest machine learning was used to classify the resulting data. The diagnostic performance for the potential diagnosis of CKD was evaluated for accuracy, sensitivity, and specificity, achieving results >96% for the training data and >91% for validation and test data sets. Metabolites selected by the classification model as up- or down-regulated in healthy or CKD samples were tentatively identified and in agreement with previously reported literature. The potential utilization of this approach to discriminate albuminuria categories (normo, micro, and macroalbuminuria) was also demonstrated. This study indicates that PS-MS combined with machine learning has the potential to be used as a rapid and simple diagnostic tool for CKD.

Background: We tried to identify the risk factor associate with early chronic kidney disease (CKD) in recently diagnosed type 2 diabetes mellitus patients by utilizing real-world data from Taiwan Diabetes Registry., Materials and Methods: Patients with type 2 diabetes mellitus recently diagnosed within 1 year. We divided the study participants into control group and early CKD group. Early CKD was defined as either CKD stage G1 with albuminuria, CKD stage G2 with albuminuria, or CKD stage G3a regardless of albuminuria (Urine-albumin to creatinine ratio (UACR) ≥ 3 mg/mmol). Control group was defined as CKD G1 or CKD G2 without albuminuria. Logistic regression analyses were used to compare differences in clinical characteristics between the subgroups. Linear regression models were employed to examine the factors predicting estimated glomerular filtration rate (eGFR) and UACR., Results: Total 2217 patients with recently diagnosed type 2 diabetes mellitus were included. 1545 patients were assigned to control group and 618 patients were assigned to the early CKD group. Age (odds ratio (OR) 1.215, 95% confidence interval [CI] 1.122-1.316), systolic blood pressure (OR 1.203, 95% CI 1.117-1.296), glycated hemoglobin (OR 1.074, 95% CI 1.023-1.129) and triglyceride (OR 2.18, 95% CI 1.485-3.199) were found to be significant risk factors. Further, presence of bidirectional association between UACR and eGFR was found., Conclusions: We reported factors associated with early CKD in recently diagnosed type 2 diabetes mellitus patients. Variables that associated with eGFR and UACR were identified respectively, included a mutual influence between UACR and eGFR., (© 2024. The Author(s).)

Background: Hypertension and chronic kidney disease (CKD) pose significant public health challenges, sharing intertwined pathophysiological mechanisms. Prediabetes is recognized as a precursor to diabetes and is often accompanied by cardiovascular comorbidities such as hypertension, elevating the risk of pre-frailty and frailty. Albuminuria is a hallmark of organ damage in hypertension amplifying the risk of pre-frailty, frailty, and cognitive decline in older adults. We explored the association between albuminuria and cognitive impairment in frail older adults with prediabetes and CKD, assessing cognitive levels based on estimated glomerular filtration rate (eGFR)., Methods: We conducted a study involving consecutive frail older patients with hypertension recruited from March 2021 to March 2023 at the ASL (local health unit of the Italian Ministry of Health) of Avellino, Italy, followed up after three months. Inclusion criteria comprised age over 65 years, prior diagnosis of hypertension without secondary causes, prediabetes, frailty status, Montreal Cognitive Assessment (MoCA) score < 26, and CKD with eGFR > 15 ml/min., Results: 237 patients completed the study. We examined the association between albuminuria and MoCA Score, revealing a significant inverse correlation (r: 0.8846; p < 0.0001). Subsequently, we compared MoCA Score based on eGFR, observing a significant difference (p < 0.0001). These findings were further supported by a multivariable regression analysis, with albuminuria as the dependent variable., Conclusions: Our study represents the pioneering effort to establish a significant correlation between albuminuria and eGFR with cognitive function in frail hypertensive older adults afflicted with prediabetes and CKD., (© 2024. The Author(s).)

Objective: The hemoglobin A1c (HbA1c) diagnostic threshold for type 2 diabetes (T2D) of 6.5 % (48 mmol/mol) was based on the prevalence of retinopathy found in populations not known to have T2D. It is unclear if nephropathy has a similar HbA1c threshold, partly because it is a rarer complication of early diabetes. This cohort study investigated a very high diabetes prevalence population to determine if a better diagnostic HbA1c value can be established for predicting nephropathy rather than retinopathy in subjects without T2D., Methods: The urine albumin:creatinine ratios (UACRs) of 2920 healthy individuals from the Qatar Biobank who had an HbA1c ≥ 5.6 %. were studied. Nephropathy was defined as a UACR≥30 mg/g and its prediction by HbA1c was assessed using cut-points ranging from 5.7 to 7.0 % to dichotomize high from low HbA1c., Results: Although there was a significant trend for an increased prevalence of abnormal UACR as the HbA1c threshold increased (p < 0.01), significance was due mostly to subjects with HbA1c ≥ 7.0 % (53 mmol/mol). The odds ratios for abnormal UACR were similar over the 5.7-6.9 % HbA1c threshold range, with a narrow odds ratio range of 1.2-1.6. Utilizing area-under-receiver-operating characteristic curves, no HbA1c threshold <7.0 % was identified as the best predictor of nephropathy., Conclusion: Even in a population with a high prevalence of known and unknown diabetes, no HbA1c threshold <7.0 % could be found predicting an increased prevalence of nephropathy. This means there is not a requirement to change the existing retinopathy-based HbA1c threshold of 6.5 % to also accommodate diabetes nephropathy risk., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Research Trust of DiabetesIndia (DiabetesIndia) and National Diabetes Obesity and Cholesterol Foundation (N-DOC). Published by Elsevier Ltd. All rights reserved.)

Cardiovascular disease (CVD) is the leading cause of end-stage mortality in chronic kidney disease (CKD) patients. However, CVD and CKD are inextricably linked, as microalbuminuria is an independent risk factor for CVD. Herein, we investigated changes in cardiac function and its risk factors in CKD patients who had different urine albumin-to-creatinine ratios (UACRs) and estimated glomerular filtration rates (eGFRs). We prospectively enrolled 182 CKD patients, classified into three groups based on UACRs and eGFRs. Fifty healthy volunteers were included as controls. Changes in clinical and echocardiographic parameters were assessed in each group, and factors independently associated with strain parameters were further analyzed. Compared with those in the control group, the albuminuria but unimpaired renal function (ALB-CKD G1-2), albuminuria and impaired renal function (ALB-CKD G3), and normoalbuminuric CKD (NACKD) groups had decreased left ventricular (LV), right ventricular (RV), and left atrial (LA) strains, the LA contractile strain being the only statistically comparable parameter. Stepwise multiple linear regression analysis revealed varying factors independently correlating with the LV global longitudinal strain. The LA reservoir and conduit strains independently correlated with LV diastolic function in stage 3 CKD associated with comorbid albuminuria or normoalbuminuria. LV function was a partial determinant of LA and RV function in the ALB-CKD G3 group, whereas ventricular and atrial function were independent of each other in the ALB-CKD G1-2 and NACKD groups. Clinical intervention should focus on specific factors affecting cardiac function in patients to reduce the risk of CVD-related death., (© 2024. The Author(s), under exclusive licence to Springer Nature B.V.)

Background: Despite the high prevalence of chronic kidney disease (CKD) in Germany, only a small proportion of patients are currently diagnosed with CKD. Patients with hypertension, diabetes mellitus, and/or cardiovascular disease have a significantly increased risk of developing CKD and rapid disease progression and should therefore be screened and monitored in accordance with the guidelines., Objectives: The aim of this retrospective, cross-sectional study was to gain insights into appropriate diagnosis of patients at risk for CKD in German general practitioner practices., Method: For the analysis of the use of CKD-relevant diagnostics, electronic patient records from German general practitioner practices were analyzed. Adults with hypertension and/or diabetes mellitus and/or cardiovascular disease with a documented observation period of at least one year were included in the study., Results: Data from a total of 448,837 patients from 1244 general practitioner practices were analyzed. 75.8% of patients had hypertension, 35.1% had cardiovascular disease, and 32.4% had diabetes mellitus. During a mean observation period of 1.7 years, serum creatinine was assessed at least once in 45.5% of patients. A urine dipstick test for albuminuria was performed in 7.9% of patients and in 0.4% of patients, urine albumin-to-creatine ratio (UACR) was measured. Laboratory diagnostics were initiated a little more frequently in high-risk patients compared to the overall cohort., Conclusions: The study highlights that despite known risk factors, guideline compliant CKD screening is rarely performed in German general practitioner practices, which implicates the need to increase the awareness of early diagnosis of CKD in patients at risk., (© 2024. Springer Medizin Verlag GmbH, ein Teil von Springer Nature.)

In Mexico, chronic kidney disease of unknown origin is highly prevalent. Screening studies in adolescents have shown persistent microalbuminuria (pACR), adaptive podocytopathy and decreased kidney volume (KV). Here, we sought to develop normality tables of kidney dimensions by ultrasound in the Mexican state of Aguascalientes pediatric population (0 to 18y) and evaluate the relationship between the KV and pACR among the region's adolescents in a cross-sectional study. Kidney length (KL) and KV were determined by ultrasound. Our findings were compared with those in international literature of different populations where tables and graphs of normal kidney dimensions by ultrasound were reported. We compared organ dimensions in individuals above the age of 11 without albuminuria with those in patients with pACR recruited through screening studies in adolescents in Aguascalientes. This included 1068 individuals to construct percentile tables and graphs of the KL. Kidney dimensions were significantly lower when compared with all international comparisons. From a total 14,805 screen individuals, we compared 218 adolescents with pACR and 377 individuals without significant albuminuria. The Total KV adjusted to body surface (TKVBS) was significantly associated with pACR (odds ratio 1.03, 95% confidence interval 1.02-1.03). The upper quartile of TKVBS was highly associated with pACR (7.57, 4.13-13.87), hypertension (2.53, 1.66-3.86), and hyperfiltration (26 vs 11.5%). Thus, TKVBS is directly associated with pACR while greater KV, arterial hypertension, and hyperfiltration in patients with pACR suggest that the increase in volume is secondary to kidney hypertrophy. Additionally, the adaptative podocytopathy with low fibrosis seen on kidney biopsy which was performed in a subset of patients, and the smaller kidney dimensions in our population point to prenatal oligonephronia as the primary cause of the detected kidney disease., (Copyright © 2024 International Society of Nephrology. Published by Elsevier Inc. All rights reserved.)

Background and Aims: Chronic Kidney Disease (CKD) is characterized by a high inflammation status with ever-increasing prevalence, and defined as low estimated glomerular filtration rate (eGFR) or albuminuria. Both low eGFR and albuminuria can have independent effects on the body. The dietary inflammatory index (DII) is a validated tool used to assess the inflammatory potential of the diet. We aim to explore not only the association between DII and CKD, but also the associations of DII with low eGFR and albuminuria, respectively. In addition, their associations in different subgroups remain to be explored., Methods and Results: 18,070 participants from the 2011-2018 NHANES with complete data of dietary intake and laboratory data were involved in our study. The data of 24-hour dietary recall interview was used to calculate DII, CKD could be reflected by laboratory data of creatinine and albumin. Then weighted multivariate logistic regression models and subgroup analyses were performed. The prevalence of low eGFR, albuminuria and CKD were 6.8%, 9.8% and 14.5%, respectively. A positive association between DII and low eGFR was observed (OR=1.12, 95%CI: 1.05-1.21), Q2, Q3 and Q4 are positively associated with a significant 39%, 65% and 71% increased risk of low eGFR compared with Q1 (P for trend<0.05). DII was also associated with CKD (OR=1.06, 95%CI: 1.01-1.11)., Conclusion: Significant positive associations of DII with CKD and low eGFR were observed. But we didn't find such association between DII and albuminuria., Competing Interests: Declaration of competing interest There are no conflicts of interest., (Copyright © 2023 The Italian Diabetes Society, the Italian Society for the Study of Atherosclerosis, the Italian Society of Human Nutrition and the Department of Clinical Medicine and Surgery, Federico II University. Published by Elsevier B.V. All rights reserved.)

Background: There is a need for accurate and rapid biomarkers for the early diagnosis of diabetic nephropathy (DN). We aimed to study the accuracy of urinary neutrophil gelatinase-associated lipocalin (uNGAL), urinary kidney injury molecule-1 (uKIM-1), and blood NGAL (bNGAL) in type 2 diabetics as biomarkers for diagnosis of DN., Methods: The study was a retrospective case-control study that included 30 control subjects, 40 diabetics with normo-albuminuria < 30 mg/g and eGFR > 60 mL/minute/1.73 m2, and 30 diabetics with albuminuria > 30mg/g and eGFR < 60mL/minute/1.73 m2. Blood and urine samples were obtained to determine levels of bNGAL, uNAGAL, and uKIM1., Results: There was a significant increase in bNGAL, uNGAL, uKIM 1, uNGAL/creatinine and uKIM 1/creatinine among diabetics with albuminuria compared to diabetics with normoalbuminuria and normal control (p < 0.001 for all markers). For diagnosis of early DN, both bNGAL and uKIM 1 had sensitivity and specificity of 100% for each at cutoff values of 322.5 pg/mL and 74.25 ng/mL, respectively. uNGAL had a sensitivity of 97.5% and a spec-ificity of 100% at a cutoff point of 565 ng/mL. uKIM1/creatinine at a cutoff of 51.2 had a sensitivity of 100% and specificity of 100%., Conclusions: The present study highlights the accuracy of urinary KIM1 and NGAL and blood NGAL as biomarkers for the diagnosis of nephropathy in the early stage of diabetic nephropathy. There were positive correlations with kidney function tests creatinine, blood urea nitrogen, and the presence of albuminuria.

Background: Albuminuria, an important marker of decreased kidney function in chronic kidney disease (CKD), is not routinely used for CKD detection or proteinuria appearance. Its relationships with biochemical parameters and blood pressure in dogs are poorly understood., Objectives: This study aimed to evaluate the relationship of albuminuria with various CKD markers, its correlation with the urinary protein to creatinine ratio (UPC), and hypertension in dogs with early stages of CKD. It also sought to determine the usability of the urinary albumin to creatinine ratio (UAC) for CKD screening., Methods: The study reviewed records of 102 dogs, categorising them into four groups based on disease status. UAC and UPC ratio, biochemistry and haematology variables, age, and systolic blood pressure were determined., Results: The Pearson's correlation coefficient between log-transformed values of UPC and UAC was r = 0.902 (95% CI: 0.87 to 0.93). Median UAC ratio values were 2.1 mg/g for the Healthy control group (n = 17), 54.2 mg/g for early stages CKD (n = 42), 5.8 mg/g for Acute sick control (n = 30), and 104 mg/g for Chronic sick control (n = 13). Thresholding UAC ratio as an indicator for impaired kidney function with the threshold of 10 mg/g (established based on the receiver operating characteristic curve) had a sensitivity 81.8%, specificity of 89.4%, positive predictive value (PPV) 90%, and negative predictive value (NPV) 80.1%. The correlation of UAC with biochemistry and haematology variables was statistically significant; for SDMA (μg/L), it was r = 0.566 and for other variables, it was weak to moderate. UAC was markedly elevated in cases of severe hypertension., Conclusions: UAC ratio was significantly different among dogs with impaired and not impaired kidney function. The correlation strength for the UAC and UPC ratios was high. UAC ratio may be a promising marker for proteinuria analysis in dogs with CKD or other kidney function alterations., (© 2024 The Authors. Veterinary Medicine and Science published by John Wiley & Sons Ltd.)

Albuminuria is a crucial urine biomarker of human unhealthy events such as kidney diseases, cardiovascular diseases, and diabetes. However, the accurate diagnosis of albuminuria poses a significant challenge owing to the severe interference from urine fluorescence and urine drugs. Here, we report a novel flavone-based fluorescent probe, DMC, by incorporating the FA1-targeting methylquinazoline group into a flavone skeleton with the extend π-conjugation. DMC exhibited a rapid response time, high sensitivity, and selectivity towards human serum albumin (HSA) in urine. Moreover, the red-shifted fluorescence and the FA1-targeted HSA-binding of DMC efficiently mitigated the interference from both urine fluorescence and urine drug metabolites. Furthermore, the establishment of a portable testing system highlighted the potential for point-of-care testing, offering a user-friendly and accurate approach to diagnose A2-level and A3-level albuminuria. We expect that the success of this DMC-based diagnostic platform in real urine samples can signify a significant advancement in early clinical diagnosis of albuminuria and its associated diseases., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024. Published by Elsevier B.V.)

Purpose of Review: Kidney function declines with normal aging. But it also declines with the progression of some diseases. This review calls for a more nuanced interpretation of kidney function in the geriatric population, who may have frailty and comorbidities., Recent Findings: GFR declines with healthy aging kidneys. Aging kidney changes include decreased cortical volume, senescent global glomerulosclerosis, and reduced nephron numbers. Yet normal aging is not associated with increased glomerular volume or single-nephron GFR. The prevalence of GFR less than 60 ml/min/1.73 m 2 in the geriatric population is high. However, the decline in GFR with normal aging may not reflect true CKD without albuminuria. Although the risk of ESKD and mortality increases in all age groups when eGFR less than 45 ml/min/m 2 , there is no significant increased relative risk of ESKD and mortality in the geriatric population when eGFR 45-59 ml/min/m 2 in the absence of albuminuria. Innovative approaches are needed to better estimate GFR and define CKD in the geriatric population., Summary: The expected GFR decline in the geriatric population is consistent with normal aging kidney changes. To avoid CKD overdiagnosis and unnecessary referrals to nephrology for possible CKD, age-adapted definitions of CKD in the absence of albuminuria are needed., (Copyright © 2023 Wolters Kluwer Health, Inc. All rights reserved.)

Background: Developing and implementing new patient-centric strategies for drug trials lowers the barrier to participation for some patients by reducing the need to travel to research sites. In early chronic kidney disease (CKD) trials, albuminuria is the key measure for determining treatment effect prior to pivotal kidney outcome trials., Methods: To facilitate albuminuria sample collection outside of a clinical research site, we developed 2 quantitative microsampling methods to determine the urinary albumin to creatinine ratio (UACR). Readout was performed by LC-MS/MS., Results: For the Mitra device the within-batch precision (CV%) was 2.8% to 4.6% and the between-batch precision was 5.3% to 6.1%. Corresponding data for the Capitainer device were 4.0% to 8.6% and 6.7% to 9.0%, respectively. The storage stability at room temperature for 3 weeks was 98% to 103% for both devices. The recovery for the Mitra and Capitainer devices was 104% (SD 7.0%) and 95 (SD 7.4%), respectively. The inter-assay comparison of UACR assessment generated results that were indistinguishable regardless of microsampling technique. The accuracy based on LC-MS/MS vs analysis of neat urine using a clinical chemistry analyzer was assessed in a clinical setting, resulting in 102 ± 8.0% for the Mitra device and 95 ± 10.0% for the Capitainer device., Conclusions: Both UACR microsampling measurements exhibit excellent accuracy and precision compared to a clinical chemistry analyzer using neat urine. We applied our patient-centric sampling strategy to subjects with heart failure in a clinical setting. Precise UACR measurements using quantitative microsampling at home would be beneficial in clinical drug development for kidney therapies., (© Association for Diagnostics & Laboratory Medicine 2023. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Background: Non-alcoholic fatty liver disease (NAFLD), identified by the Fatty Liver Index (FLI), is associated with increased mortality and cardiovascular (CV) outcomes. Whether this also applies to type 1 diabetes (T1D) has not been yet reported., Methods: We prospectively observed 774 subjects with type 1 diabetes (males 52%, 30.3 ± 11.1 years old, diabetes duration (DD) 18.5 ± 11.6 years, HbA1c 7.8 ± 1.2%) to assess the associations between FLI (based on BMI, waist circumference, gamma-glutamyl transferase and triglycerides) and all-cause death and first CV events., Results: Over a median 11-year follow-up, 57 subjects died (7.4%) and 49 CV events (6.7%) occurred among 736 individuals with retrievable incidence data. At baseline, FLI was < 30 in 515 subjects (66.5%), 30-59 in 169 (21.8%), and ≥ 60 in 90 (11.6%). Mortality increased steeply with FLI: 3.9, 10.1, 22.2% (p < 0.0001). In unadjusted Cox analysis, compared to FLI < 30, risk of death increased in FLI 30-59 (HR 2.85, 95% CI 1.49-5.45, p = 0.002) and FLI ≥ 60 (6.07, 3.27-11.29, p < 0.0001). Adjusting for Steno Type 1 Risk Engine (ST1-RE; based on age, sex, DD, systolic BP, LDL cholesterol, HbA1c, albuminuria, eGFR, smoking and exercise), HR was 1.52 (0.78-2.97) for FLI 30-59 and 3.04 (1.59-5.82, p = 0.001) for FLI ≥ 60. Inclusion of prior CV events slightly modified HRs. FLI impact was confirmed upon adjustment for EURODIAB Risk Engine (EURO-RE; based on age, HbA1c, waist-to-hip ratio, albuminuria and HDL cholesterol): FLI 30-59: HR 1.24, 0.62-2.48; FLI ≥ 60: 2.54, 1.30-4.95, p = 0.007), even after inclusion of prior CVD. CV events incidence increased with FLI: 3.5, 10.5, 17.2% (p < 0.0001). In unadjusted Cox, HR was 3.24 (1.65-6.34, p = 0.001) for FLI 30-59 and 5.41 (2.70-10.83, p < 0.0001) for FLI ≥ 60. After adjustment for ST1-RE or EURO-RE, FLI ≥ 60 remained statistically associated with risk of incident CV events, with trivial modification with prior CVD inclusion., Conclusions: This observational prospective study shows that FLI is associated with higher all-cause mortality and increased risk of incident CV events in type 1 diabetes., (© 2024. The Author(s).)

Background: Microalbuminuria is an early indicator for renal and cardiovascular diseases, especially among patients with diabetes mellitus (DM) and hypertension (HTN). We determined the prevalence and the factors associated with microalbuminuria among patients with type 2 DM and/or HTN in the urban areas of the Puducherry district in India., Methods: We included 225 patients aged 40-69 years with DM and/or HTN from a non-communicable diseases (NCDs) survey conducted during 2019-2020 in the urban areas of Puducherry district. The prevalence of microalbuminuria and various biological risk factors of NCDs were assessed as per the WHO STEPS methodology. The prevalence of microalbuminuria was presented as proportions (95% CI), and the adjusted prevalence ratio (aPR) was estimated using weighted forward stepwise generalized linear modelling. P-value ≤0.05 was considered statistically significant., Results: The mean (SD) age of the patients was 54 (11) years. Over one-third (38.2%) (95% CI: 31.6-44.4) of patients with DM and/or HTN had microalbuminuria. The prevalence was highest among those having both DM and HTN 48% (95% CI: 37-59), followed by those having only DM 40.6% (95% CI: 29-52.2) and only HTN 27.7% (95% CI: 18.1-38.6). The prevalence of microalbuminuria was twice (aPR = 2.1, 95% CI: 1.1-3.9) higher among women and 2.4 times (95% CI: 1.12-5.1) higher among those having both DM and HTN as compared to those with only HTN., Conclusion: The prevalence of microalbuminuria among patients with DM and/or HTN is concerningly high. Population-based screening for microalbuminuria, especially among women and those having both DM and HTN, needs to be undertaken in the urban areas of Puducherry district., (© The Author(s) 2024. Published by Oxford University Press. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Background: Although albuminuria is the gold standard for defining chronic kidney disease (CKD), total proteinuria has also been widely used in real-world clinical practice. Moreover, the superiority of the prognostic performance of albuminuria over proteinuria in patients with CKD remains inconclusive. Therefore, we aimed to compare the predictive performances of albuminuria and proteinuria in these patients., Methods: From the Korean Cohort Study for Outcome in Patients with CKD we included 2099 patients diagnosed with CKD grades 1-5 who did not require kidney replacement therapy. We measured the spot urine albumin:creatinine ratio (mACR) and protein:creatinine ratio (PCR) and estimated the ACR (eACR) using the PCR. Kidney failure risk equation (KFRE) scores were calculated using the mACR, PCR and eACR. The primary outcome was the 5-year risk of kidney failure with replacement therapy (KFRT)., Results: The eACR significantly underestimated mACR in patients with low albuminuria levels. The time-dependent area under the receiver operating characteristics curve showed excellent predictive performance for all KFRE scores from the mACR, PCR and eACR. However, eACR was inferior to mACR based on the continuous net reclassification index (cNRI) and integrated discrimination improvement index (IDI) in all CKD cause groups, except for the group with an unclassified aetiology. Moreover, the cNRI and IDI statistics indicated that both eACR and PCR were inferior to mACR in patients with low albuminuria (<30 mg/g). Conversely, the predictive performance of PCR was superior in severe albuminuria and nephrotic-range proteinuria, in which the IDI and cNRI of the PCR were greater than those of the mACR., Conclusions: The mACR, eACR and PCR showed excellent performance in predicting KFRT in patients with CKD. However, eACR was inferior to mACR in patients with low albuminuria, indicating that measuring rather than estimating albuminuria is preferred for these patients., (© The Author(s) 2023. Published by Oxford University Press on behalf of the ERA.)

Background: In Tunisia, the prevalence of diabetes mellitus increased from 15.5% on 2016 to 23% by 2023. While Chronic Kidney Disease (CKD) stills the most dreaded complications of diabetes, studies on the prevalence of chronic kidney disease non-dialysis diet are scarce. The aim of this study was to assess the prevalence of chronic kidney disease among the Tunisian diabetic population based on investigators' specialty, demographic criteria (gender, age, duration of diabetes and geographic distribution) and diagnosis criteria (albuminuria and/or eGFR)., Methods: This observational, multicentric, and cross-sectional study enrolled all diabetic subjects from all regions of Tunisia with at least 3 months of follow-up before the inclusion date, from 09 January to 08 February 2023. CKD diagnosis was established based on the KDIGO guidelines. The study was carried out at medical departments and ambulatory clinics of different healthcare providers. Baseline data were collected by investigators using an electronic case report form (eCRF). Continuous variables were described by means, median, standard deviation, and quartiles. Categorical data were tabulated in frequencies and percentages., Results: The overall prevalence of CKD among the 10,145 enrolled patients with diabetes mellitus was 38.7% with a 95%CI [37.8-39.6%]. 50.9% were male, with a mean age of 67.5 (± 11.3) years. The mean diabetes duration was 16.1 years (± 8.9). The highest CKD prevalence was noted among nephrologists (82.2%), while it was similar between the cardiologists and the primary care physicians (30.0%). CKD prevalence was highest among males (43.0% versus 35.1%) and increased proportionally with patients' age and diabetes duration. CKD was more frequent in the Mid-East Area when compared to other regions (49.9% versus 25.3 to 40.1% in other regions). Albuminuria was present within 6.6% of subjects with CKD, and it was found an estimated glomerular filtration rate (eGFR) < 60 ml/min/1.73 m² within 13.3% of subjects wit h CKD. 18.9% had both criteria., Conclusions: In Tunisia, CKD among diabetics had a prevalence of 38.7%, approaching European prevalence. The prevalence discrepancy worldwide of CKD can be improved with a larger population size and by implementing standardized practices., (© 2024. The Author(s).)

Background: This study aimed to evaluate the correlation between serum methylmalonic acid (MMA) levels and cognition function in patients with chronic kidney disease (CKD)., Methods: In this cross-sectional study, we included 537 CKD individuals aged ≥ 60-year-old with albuminuria from the National Health and Nutrition Examination Survey (NHANES) 2011-2014. Four cognitive tests including the Digit Symbol Substitution Test (DSST), the Consortium to Establish a Registry for Alzheimer's Disease (CERAD) Delayed Recall and Word Learning tests, and the Animal Fluency test (AF) were performed. Associations between MMA and cognition scores were assessed with linear regression models., Results: MMA level was negatively associated with residual renal function and nutrition status. After multivariate adjustment, elevated serum MMA levels were independently correlated with decline of cognition in CKD patients with albuminuria., Conclusion: Our study showed that higher serum MMA levels were independently associated with the presence of cognition dysfunction in CKD patients. The exact pathogenesis of MMA and cognition needs further research., (© 2024. The Author(s).)

Albuminuria is a clinical condition associated with poor kidney function, diagnosed by determining the ratio of albumin to creatinine concentrations in patient urine samples. We present a high-throughput paper spray mass spectrometry (PS-MS) method for simultaneous quantitation of urinary albumin and creatinine for potential diagnosis of albuminuria. Minimal (urine dilution) or no sample preparation is required. The analytical performance of the method was evaluated, achieving linear calibration curves ( R 2 > 0.99) with little inter-day variability in the slope ( N = 5 days), exhibiting coefficient of variation (CV) of 8% and 3% for albumin and creatinine, respectively. LOD and LOQ for albumin were 2.1 and 7.0 mg L -1 , and for creatinine were 0.01 and 0.03 mmol L -1 , respectively. Intra- and inter-day ( N = 5) precisions (%CV) and accuracies (%bias) were <10% and ±11%, respectively, for both analytes. The method was applied to determine albumin-to-creatinine ratios in anonymous human patient urine samples ( N = 56), and a correlation of R 2 = 0.9744 was achieved between the PS-MS results and validated clinical method results. This work demonstrates the utility of PS-MS to simultaneously quantify a large (albumin) and a small (creatinine) molecule directly in patient urine samples, and its potential as a tool for clinical albuminuria diagnostics.

Introduction: Kidney disease is common after pediatric heart transplantation. Serum creatinine-based glomerular filtration rate is the most frequently reported measure of kidney function. Albuminuria is an additional marker of kidney dysfunction and is not well described in this population. In this study, we evaluate the prevalence and degree of albuminuria and describe clinical factors associated with albuminuria in a cohort of pediatric heart transplant recipients., Methods: This was a cross-sectional study of pediatric heart transplant recipients. Albuminuria was assessed using spot urine albumin-to-creatinine ratio collected at the most recent annual screening cardiac catheterization through August 2019., Results: In 115 patients at a median duration of 10.2 years post-transplant, 39% had albuminuria. Stage 3 or greater chronic kidney disease was present in 6%. The immunosuppressive regimen at the time of measurement contained a calcineurin inhibitor (CNI) in 88% and a proliferation signal inhibitor (PSI) in 62%. In multivariable modeling, lower eGFR, PSI use, and younger age at transplant were associated with higher levels of albuminuria, whereas CNI use was associated with lower levels of albuminuria., Conclusion: Albuminuria is a prevalent finding in medium-term follow up of pediatric heart transplant recipients, reflecting kidney injury, and is associated with other markers of kidney dysfunction, such as low eGFR. Younger age at transplant, lower eGFR, and PSI use were among the associations with albuminuria., (© 2024 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Objective: This study aimed to investigate the association between baseline albuminuria and the progression of diabetic kidney disease (DKD) in patients newly diagnosed with type 2 diabetes mellitus (DM)., Methods: A retrospective cohort study was conducted among 604 patients aged ≥18 years who were newly diagnosed with type 2 DM between January 2014 and 31 December 2017 at an outpatient clinic in a tertiary hospital in China. The incidence of albuminuria was determined and the associations between albuminuria at baseline and the progression of DKD estimated by estimated glomerular filtration rate slope were evaluated using binary logistic regression analysis., Results: At diagnosis of type 2 DM, 18.8% of patients had albuminuria, with 17.4% having microalbuminuria and the other 1.4% having macroalbuminuria. During the 5-year follow-up period, patients with albuminuria at the baseline experienced a more rapid decline of estimated glomerular filtration rate over time than patients with normoalbuminuria at baseline (-2.6 vs -1.5 mL/min/1.73 m 2 per year, P =.01). Albuminuria at baseline is independently associated with the progression of DKD., Conclusions: The prevalence of albuminuria is 18.8% in patients newly diagnosed with type 2 diabetes and the occurrence of albuminuria can predict steeper annual decline in kidney function., Competing Interests: Disclosure The authors have no conflicts of interest to disclose., (Copyright © 2024. Published by Elsevier Inc.)