Renin–angiotensin–aldosterone system blockers effect in chronic kidney disease progression in hypertensive elderly patients without proteinuria: PROERCAN trial / Efecto de los bloqueantes del sistema renina-angiotensina-aldosterona en la progresión de enfermedad renal crónica en pacientes hipertensos añosos sin proteinuria: ensayo clínico Progresión de Enfermedad Renal Crónica en Ancianos

Introduction: Evidence about nefroprotective effect with RAAS blockers in elderly patients with chronic kidney disease (CKD) without proteinuria is lacking. The primary outcome of our study is to evaluate the impact of RAAS blockers in CKD progression in elderly patients without proteinuria. Materials and methods: Multicenter open-label, randomized controlled clinical trial including patients over 65 year-old with hypertension and CKD stages 3–4 without proteinuria. Patients were randomized in a 1:1 ratio to either receive RAAS blockers or other antihypertensive drugs and were followed up for three years. Primary outcome is estimated glomerular filtration rate (eGFR) decline at 3 years. Secondary outcome measures include BP control, renal and cardiovascular events and mortality. Results: 88 patients were included with a mean age of 77.9±6.1 years and a follow up period of 3 years: 40 were randomized to RAAS group and 48 to standard treatment. Ethiology of CKD was: 53 vascular, 16 interstitial and 19 of unknown ethiology. In the RAAS group eGFR slope during follow up was −4.3±1.1ml/min, whereas in the standard treatment group an increase on eGFR was observed after 3 years (+4.6±0.4ml/min), p=0.024. We found no differences in blood pressure control, number of antihypertensive drugs, albuminuria, potassium serum levels, incidence of cardiovascular events nor mortality during the follow up period. Conclusions: In elderly patients without diabetes nor cardiopathy and with non proteinuric CKD the use of RAAS blockers does not show a reduction in CKD progression. The PROERCAN (PROgresión de Enfermedad Renal Crónica en ANcianos) trial (trial registration: NCT03195023). (AU)

Introducción: Actualmente no existe suficiente evidencia sobre el efecto nefroprotector de los bloqueantes del sistema renina-angiotensina-aldosterona (BSRAA) en pacientes añosos con enfermedad renal crónica (ERC) sin proteinuria y sin cardiopatía. El objetivo es evaluar el efecto de los BSRAA en la progresión de la ERC en este grupo poblacional. Métodos: Se trata de un estudio prospectivo, aleatorizado, que compara la eficacia de los BSRAA vs. otros tratamientos antihipertensivos en la progresión renal en personas mayores de 65 años con ERC estadios 3 y 4 e índice albúmina/creatinina<30mg/g. Aleatorización 1:1 BSRAA o tratamiento antihipertensivo estándar. Se recogieron cifras tensionales y parámetros analíticos de un año previo a la aleatorización y durante el seguimiento. Resultados: Se incluyeron 88 pacientes seguidos durante tres años con edad media de 77,9±6,1 años. De estos, se aleatorizaron 40 al grupo BSRAA y 48 al estándar. La etiología de ERC fue: 53 vascular, 16 intersticial y 19 no filiada. En el primer grupo se observó una progresión de la ERC con una caída del filtrado glomerular estimado (FGe) de -4,3±1,1mL/min, mientras que en el grupo estándar un aumento del FGe durante el seguimiento de 4,6±0,4mL/min, p=0,024. No se apreciaron diferencias entre ambos en el control tensional, el número de antihipertensivos, la albuminuria, los niveles de potasio, la incidencia de eventos cardiovasculares ni la mortalidad durante el seguimiento. Conclusiones: En pacientes añosos no diabéticos con ERC no proteinúrica y sin cardiopatía el uso de BSRAA no añade beneficio en la progresión de la ERC. Ensayo clínico Progresión de Enfermedad Renal Crónica en Ancianos (PROERCAN) (NCT03195023). (AU)

Association of Albuminuria With Chronic Kidney Disease Progression in Persons With Chronic Kidney Disease and Normoalbuminuria : A Cohort Study.

BACKGROUND: Albuminuria is a major risk factor for chronic kidney disease (CKD) progression, especially when categorized as moderate (30 to 300 mg/g) or severe (>300 mg/g). However, there are limited data on the prognostic value of albuminuria within the normoalbuminuric range (<30 mg/g) in persons with CKD. OBJECTIVE: To estimate the increase in the cumulative incidence of CKD progression with greater baseline levels of albuminuria among persons with CKD who had normoalbuminuria (<30 mg/g). DESIGN: Multicenter prospective cohort study. SETTING: 7 U.S. clinical centers. PARTICIPANTS: 1629 participants meeting criteria from the CRIC (Chronic Renal Insufficiency Cohort) study with CKD (estimated glomerular filtration rate [eGFR], 20 to 70 mL/min/1.73 m2) and urine albumin-creatinine ratio (UACR) less than 30 mg/g. MEASUREMENTS: Baseline spot urine albumin divided by spot urine creatinine to calculate UACR as the exposure variable. The 10-year adjusted cumulative incidences of CKD progression (composite of 50% eGFR decline or kidney failure [dialysis or kidney transplantation]) from confounder adjusted survival curves using the G-formula. RESULTS: Over a median follow-up of 9.8 years, 182 of 1629 participants experienced CKD progression. The 10-year adjusted cumulative incidences of CKD progression were 8.7% (95% CI, 5.9% to 11.6%), 11.5% (CI, 8.8% to 14.3%), and 19.5% (CI, 15.4% to 23.5%) for UACR levels of 0 to less than 5 mg/g, 5 to less than 15 mg/g, and 15 mg/g or more, respectively. Comparing persons with UACR 15 mg/g or more to those with UACR 5 to less than 15 mg/g and 0 to less than 5 mg/g, the absolute risk differences were 7.9% (CI, 3.0% to 12.7%) and 10.7% (CI, 5.8% to 15.6%), respectively. The 10-year adjusted cumulative incidence increased linearly based on baseline UACR levels. LIMITATION: UACR was measured once. CONCLUSION: Persons with CKD and normoalbuminuria (<30 mg/g) had excess risk for CKD progression, which increased in a linear fashion with higher levels of albuminuria. PRIMARY FUNDING SOURCE: None.

[InspeCKD - Analysis of the use of diagnostics in patients at high risk for chronic kidney disease in German general practitioner (GP) practices]. / InspeCKD - Analyse zur Nutzung von Labordiagnostik im Kontext der chronischen Nierenerkrankung : Daten von Risikopatientinnen und -patienten in deutschen Hausarztpraxen.

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.

Exercise in Diabetic Nephropathy: Protective Effects and Molecular Mechanism.

Diabetic nephropathy (DN) is a serious complication of diabetes, and its progression is influenced by factors like oxidative stress, inflammation, cell death, and fibrosis. Compared to drug treatment, exercise offers a cost-effective and low-risk approach to slowing down DN progression. Through multiple ways and mechanisms, exercise helps to control blood sugar and blood pressure and reduce serum creatinine and albuminuria, thereby alleviating kidney damage. This review explores the beneficial effects of exercise on DN improvement and highlights its potential mechanisms for ameliorating DN. In-depth understanding of the role and mechanism of exercise in improving DN would pave the way for formulating safe and effective exercise programs for the treatment and prevention of DN.

Dietary Fructose and Sodium Consumed during Early Mid-Life Are Associated with Hypertensive End-Organ Damage by Late Mid-Life in the CARDIA Cohort.

We aimed to investigate how dietary fructose and sodium impact blood pressure and risk of hypertensive target organ damage 10 years later. Data from n = 3116 individuals were obtained from the Coronary Artery Risk Development in Young Adults (CARDIA) study. Four groups were identified based on the four possible combinations of the lower and upper 50th percentile for sodium (in mg) and fructose (expressed as percent of total daily calories). Differences among groups were ascertained and logistic regression analyses were used to assess the risk of hypertensive target organ damage (diastolic dysfunction, coronary calcification and albuminuria). Individuals in the low-fructose + low-sodium group were found to have lower SBP compared to those in the low-fructose + high-sodium and high-fructose + high-sodium groups (p < 0.05). The highest risk for hypertensive target organ damage was found for albuminuria only in the high-fructose + high-sodium group (OR = 3.328, p = 0.006) while female sex was protective across all groups against coronary calcification. Our findings highlight that sodium alone may not be the culprit for hypertension and hypertensive target organ damage, but rather when combined with an increased intake of dietary fructose, especially in middle-aged individuals.

Frail hypertensive older adults with prediabetes and chronic kidney disease: insights on organ damage and cognitive performance - preliminary results from the CARYATID study.

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.

Determinants of early chronic kidney disease in patients with recently diagnosed type 2 diabetes mellitus: a retrospective study from the Taiwan Diabetes Registry.

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.

Increasing obstructive sleep apnea risk is associated with albuminuria in Korean adults: cross-sectional analysis.

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 < 0.001). The proportion of subjects with values of 30 ≤ ACR < 300 mg/g (11.9% vs 6.1%; P < 0.001) and ACR > 300 mg/g (2.1% vs 0.7%; P < 0.001) was significantly higher in high OSA risk group. Multivariate logistic regression results confirmed that microalbuminuria (OR 1.279, 95% confidence interval (CI) 1.068-1.532, P = 0.008) was significantly correlated with high OSA risk. In addition, significant correlation with high OSA risk was also found in macroalbuminuria (OR 1.684, 95% CI 1.073-2.530, P = 0.022) and proteinuria (OR 1.355, 95% CI 1.030-1.783, P = 0.030). We confirmed a significant correlation between high OSA risk and albuminuria/proteinuria in Korean adults. Therefore, renal function evaluation is required in high OSA risk patients, and OSA diagnosis through PSG test and treatment is necessary.

SGLT2 inhibition, high-density lipoprotein, and kidney function: a mendelian randomization study.

BACKGROUND: Sodium-glucose cotransporter 2 (SGLT2) inhibition is recognized for its evident renoprotective benefits in diabetic renal disease. Recent data suggest that SGLT2 inhibition also slows down kidney disease progression and reduces the risk of acute kidney injury, regardless of whether the patient has diabetes or not, but the mechanism behind these observed effects remains elusive. The objective of this study is to utilize a mendelian randomization (MR) methodology to comprehensively examine the influence of metabolites in circulation regarding the impact of SGLT2 inhibition on kidney function. METHODS: We used a MR study to obtain associations between genetic proxies for SGLT2 inhibition and kidney function. We retrieved the most recent and comprehensive summary statistics from genome-wide association studies (GWAS) that have been previously published and involved kidney function parameters such as estimated glomerular filtration rate (eGFR), urine albumin-to-creatinine ratio (UACR), and albuminuria. Additionally, we included blood metabolite data from 249 biomarkers in the UK Biobank for a more comprehensive analysis. We performed MR analyses to explore the causal relationships between SGLT2 inhibition and kidney function and two-step MR to discover potential mediating metabolites. RESULTS: The study found that a decrease in HbA1c levels by one standard deviation, which is genetically expected to result in SGLT2 inhibition, was linked to a decreased likelihood of developing type 2 diabetes mellitus (T2DM) (odds ratio [OR] = 0.55 [95% CI 0.35, 0.85], P = 0.007). Meanwhile, SGLT2 inhibition also protects eGFR (ß = 0.05 [95% CI 0.03, 0.08], P = 2.45 × 10- 5) and decreased UACR (-0.18 [95% CI -0.33, -0.02], P = 0.025) and albuminuria (-1.07 [95% CI -1.58, -0.57], P = 3.60 × 10- 5). Furthermore, the study found that of the 249 metabolites present in the blood, only one metabolite, specifically the concentration of small high-density lipoprotein (HDL) particles, was significantly correlated with both SGLT2 inhibition and kidney function. This metabolite was found to play a crucial role in mediating the improvement of renal function through the use of SGLT2 inhibition (ß = 0.01 [95% CI 0.005, 0.018], P = 0.001), with a mediated proportion of 13.33% (95% CI [5.71%, 26.67%], P = 0.020). CONCLUSIONS: The findings of this investigation provide evidence in favor of a genetically anticipated biological linkage between the inhibition of SGLT2, the presence of circulating metabolites, and renal function. The findings demonstrate that the protective effect of SGLT2 inhibition on renal function is mostly mediated by HDL particle concentrations in circulating metabolites. These results offer significant theoretical support for both the preservation of renal function and a better comprehension of the mechanisms underlying SGLT2 inhibition.

Human umbilical cord mesenchymal stem cell therapy for renal dysfunction in Alport syndrome: protocol for an open-label, single-arm trial in China.

INTRODUCTION: Alport syndrome (AS) is one of the most common fatal hereditary renal diseases in human, with a high risk of progressing to end-stage renal disease without effective treatments. Mesenchymal stem cells (MSCs) have recently emerged as a promising therapeutic strategy for chronic kidney disease. However, the safety and therapeutic potential of MSC transfusion for patients with AS are still need to be confirmed. Therefore, we have designed a clinical trial to evaluate the hypothesis that intravenous infusion of human umbilical cord-derived MSC (hUC-MSC) is safe, feasible, and well-tolerated in children with AS. METHODS AND ANALYSIS: We report the protocol of the first prospective, open-label, single-arm clinical trial to evaluate the safety and preliminary efficacy of hUC-MSC transfusion in children with early-stage AS. Paediatric patients diagnosed with AS who have persistent albuminuria will be candidates for screening. Twelve eligible patients are planned to recruit and will receive hUC-MSC infusions under close safety monitoring, and complete the efficacy assessments at scheduled follow-up visits. The primary endpoints include the occurrence of adverse events to assess safety and the albuminuria level for efficacy evaluation. Secondary endpoint assessments are based on haematuria and glomerular filtration measurements. Each patient's efficacy endpoints will be evaluated against their baseline levels. Additionally, the underlying mechanism of hUC-MSC therapy will be explored through transcriptomic and proteomic analysis of blood and urine samples. ETHICS AND DISSEMINATION: The protocol (V.1.0, date 17 January 2015) was approved by the institutional review board of the Affiliated Taihe Hospital of Hubei University of Medicine (ethical approval 03 March 2015). Written informed consent will be obtained from the patient and/or guardians before study specific process. In addition to publication in a peer-reviewed scientific journal, a lay summary of study will be available for participants and the public on the Chinese Organization for Rare Disorders website (http://www.cord.org.cn/). TRIAL REGISTRATION NUMBER: ISRCTN62094626.

Risk factors for lower renal compensation after nephrectomy: an analysis of living kidney donors in an Amazonian cohort.

INTRODUCTION: Living donor kidney transplantation is considered the ideal renal replacement therapy because it has a lower complication rate and allows an efficient response to the high demand for grafts in the healthcare system. Careful selection and adequate monitoring of donors is a key element in transplantation. Individuals at greater risk of developing kidney dysfunction after nephrectomy must be identified. OBJECTIVE: To identify risk factors associated with a renal compensation rate (CR) below 70% 12 months after nephrectomy. METHODS: This observational retrospective longitudinal study included living kidney donors followed up at the Lower Amazon Regional Hospital between 2016 and 2022. Data related to sociodemographic variables, comorbid conditions and kidney function parameters were collected. RESULTS: The study enrolled 32 patients. Fourteen (43.75%) had a CR < 70% 12 months after kidney donation. Logistic regression found obesity (Odds Ratio [95%CI]: 10.6 [1.7-65.2]), albuminuria (Odds Ratio [95%CI]: 2.41 [1.2-4.84]) and proteinuria (Odds Ratio [95%CI]: 1.14 [1.03-1.25]) as risk factors. Glomerular filtration rate was a protective factor (Odds Ratio [95% CI]: 0.92 [0.85-0.99]). CONCLUSION: Obesity, albuminuria and proteinuria adversely affected short-term renal compensation rate. Further studies are needed to uncover the prognostic implications tied to these risk factors. Our findings also supported the need for careful individualized assessment of potential donors and closer monitoring of individuals at higher risk.

Azilsartan improves urinary albumin excretion in hypertension mice.

Hypertension is one of the most important risk factors for chronic kidney diseases, leading to hypertensive nephrosclerosis, including excessive albuminuria. Azilsartan, an angiotensin II type 1 receptor blocker, has been widely used for the treatment of hypertension. However, the effects of Azilsartan on urinary albumin excretion in hypertension haven't been reported before. In this study, we investigated whether Azilsartan possesses a beneficial property against albuminuria in mice treated with angiotensin II and a high-salt diet (ANG/HS). Compared to the control group, the ANG/HS group had higher blood pressure, oxidative stress, and inflammatory response, all of which were rescued by Azilsartan dose-dependently. Importantly, the ANG/HS-induced increase in urinary albumin excretion and decrease in the expression of occludin were reversed by Azilsartan. Additionally, it was shown that increased fluorescence intensity of FITC-dextran, declined trans-endothelial electrical resistance (TEER) values, and reduction of occludin and krüppel-like factor 2 (KLF2) were observed in ANG/HS-treated human renal glomerular endothelial cells (HrGECs), then prevented by Azilsartan. Moreover, the regulatory effect of Azilsartan on endothelial monolayer permeability in ANG/HS-treated HrGECs was abolished by the knockdown of KLF2, indicating KLF2 is required for the effect of Azilsartan. We concluded that Azilsartan alleviated diabetic nephropathy-induced increase in Uterine artery embolization (UAE) mediated by the KLF2/occludin axis.

Association between short-term blood pressure variability and target organ damage in non-dialysis patients with chronic kidney disease.

BACKGROUND: It is unclear whether short-term blood pressure variability (BPV) is associated with target organ damage in patients with non-dialysis chronic kidney disease (CKD). METHODS: A cross-sectional, single-center study was conducted among 3442 non-dialysis CKD patients hospitalized in the department of Nephrology of the Fifth Affiliated Hospital of Sun Yat-sen University from November 2017 to July 2022 and collected the demographic, laboratory, clinic blood pressure, ambulatory blood pressure data, and short-term BPV assessed by the weighted standard deviation (wSD) derived from ambulatory blood pressure monitoring (ABPM). Multivariate logistic analyses were used to evaluate the independent effects between short-term BPV and subclinical target organ damage, including left ventricular hypertrophy (LVH), abnormal carotid intima-media thickness (CIMT), low estimated glomerular filtration rate (eGFR), and albuminuria. RESULTS: The average age of the participants was 47.53 ± 14.06 years and 56% of participants were male. The baseline eGFR was 69 mL/min/1.73 m2. Based on the tertile distribution of wSD according to equal numbers, patients were divided into three categories with T1(< 9.66 mmHg), T2(9.66-12.23 mmHg), and T3(> 12.23 mmHg) of SBPV; T1(< 8.17 mmHg), T2(8.17-9.93 mmHg), and T3(> 9.93 mmHg) of DBPV. The participants with the higher wSD group had a higher prevalence of target organ damage than their counterparts (P-trend < 0.05). An increasing trend in short-term variability was present with advancing CKD stages (P-trend < 0.001). Multivariate logistic analyses results showed that the odds ratio (OR) of SBP wSD was (1.07 [1.03,1.11], P < 0.001) for LVH, (1.04 [1.01,1.07, P = 0.029) for abnormal CIMT, (1.05 [1.02,1.08], P = 0.002) for low eGFR, and (1.06 [1.02,1.09], P = 0.002) for albuminuria; The OR of DBP wSD was (1.07 [1.02,1.12], P = 0.005) for LVH, (1.05 [1.01,1.09], P = 0.028) for abnormal CIMT, (1.05 [1.01,1.09], P = 0.022) for low eGFR, and (1.05 [1.01,1.10], P = 0.025) for albuminuria when adjusted for confounding factors and mean BP. CONCLUSIONS: In conclusion, short-term BPV is associated with target organ damage, and irresponsible of average blood pressure levels, in Chinese non-dialysis CKD participants.

Microalbuminuria in Rats Treated with D-Nitroarginine Methyl Ether.

Microalbuminuria is an early symptom and prognostic marker of the progression of renal pathology. The analysis of the role of anionic components of the renal glomeruli in the albumin retention and the development of a model of minimal changes in the glomerular filter leading to the appearance of microalbuminuria are relevant. The effect of organic cations D-arginine methyl esters (D-AME) and D-nitroarginine (D-NAME) on the excretion of albumin by the kidneys in rats was studied. D-AME had no effect on urinary albumin excretion in rats. D-NAME caused microalbuminuria, which persisted for more than a day and sharply increased after injection of vasopressin. The number of anionic sites labeled with polyethyleneimine decreased in the structures of the glomerular filter. D-NAME-induced microalbuminuria can later serve as a model for studying nephroprotective or damaging factors.

Association between albuminuria and retinal microvascular parameters measured with swept-source optical coherence tomography angiography in patients with diabetic retinopathy.

PURPOSE: To evaluate the relationship between urine albumin excretion (UAE) and retinal microvascular parameters assessed using swept-source optical coherence tomography angiography (SS-OCTA) in patients with diabetic retinopathy (DR). METHODS: This retrospective cross-sectional study included 180 patients with diabetes and 50 age-matched controls. Patients with diabetes were grouped according to the five-stage DR severity, combined with the presence of albuminuria. All subjects underwent 12×12mm2 field SS-OCTA. The foveal avascular zone metrics, vessel density, and capillary nonperfusion area (NPA) were quantified using a semi-automatic software algorithm on three different rectangular fields (3×3 mm2, 6×6 mm2, and 10×10 mm2). The correlations between albuminuria and the four OCTA parameters were analyzed. RESULTS: A total of 105 subjects had normal UAE, and 75 subjects had albuminuria. Of the 102 subjects whose DR severity was higher than mild non-proliferative DR (NPDR), capillary NPA on the 3×3 mm2, 6×6 mm2, and 10×10 mm2 fields was significantly larger in the albuminuria group. None of the OCTA parameters were significantly different between the two groups in subjects with mild NPDR or without DR. Multiple logistic regression analysis showed that an increase in NPA in the 6×6 mm2 and 10×10 mm2 fields was a significant risk factor for the presence of albuminuria (odds ratio = 1.92 and 1.35). CONCLUSION: An increase in capillary NPA was independently associated with albuminuria in patients with clinically significant DR levels. SS-OCTA imaging can be a useful marker for the early detection of diabetic nephropathy.

Association between systemic inflammation response index and chronic kidney disease: a population-based study.

Introduction: Our objective was to explore the potential link between systemic inflammation response index (SIRI) and chronic kidney disease (CKD). Methods: The data used in this study came from the National Health and Nutrition Examination Survey (NHANES), which gathers data between 1999 and 2020. CKD was diagnosed based on the low estimated glomerular filtration rate (eGFR) of less than 60 mL/min/1.73 m2 or albuminuria (urinary albumin-to-creatinine ratio (ACR) of more than 30 mg/g). Using generalized additive models and weighted multivariable logistic regression, the independent relationships between SIRI and other inflammatory biomarkers (systemic immune-inflammation index (SII), monocyte/high-density lipoprotein ratio (MHR), neutrophil/high-density lipoprotein ratio (NHR), platelet/high-density lipoprotein ratio (PHR), and lymphocyte/high-density lipoprotein ratio (LHR)) with CKD, albuminuria, and low-eGFR were examined. Results: Among the recruited 41,089 participants, males accounted for 49.77% of the total. Low-eGFR, albuminuria, and CKD were prevalent in 8.30%, 12.16%, and 17.68% of people, respectively. SIRI and CKD were shown to be positively correlated in the study (OR = 1.24; 95% CI: 1.19, 1.30). Furthermore, a nonlinear correlation was discovered between SIRI and CKD. SIRI and CKD are both positively correlated on the two sides of the breakpoint (SIRI = 2.04). Moreover, increased SIRI levels were associated with greater prevalences of low-eGFR and albuminuria (albuminuria: OR = 1.27; 95% CI: 1.21, 1.32; low-eGFR: OR = 1.11; 95% CI: 1.05, 1.18). ROC analysis demonstrated that, compared to other inflammatory indices (SII, NHR, LHR, MHR, and PHR), SIRI exhibited superior discriminative ability and accuracy in predicting CKD, albuminuria, and low-eGFR. Discussion: When predicting CKD, albuminuria, and low-eGFR, SIRI may show up as a superior inflammatory biomarker when compared to other inflammatory biomarkers (SII, NHR, LHR, MHR, and PHR). American adults with elevated levels of SIRI, SII, NHR, MHR, and PHR should be attentive to the potential risks to their kidney health.

Non-linear relationship between body roundness index and albuminuria among children and adolescents aged 8-19 years: A cross-sectional study.

INTRODUCTION: Obesity has been found to be correlated with numerous health issues, including an elevated risk of albuminuria in adults. However, this correlation is still controversial among children and adolescents, as several recent large-scale cross-sectional studies have observed a negative correlation between obesity and albuminuria. Our study aimed to investigate the link between the body roundness index (BRI) and albuminuria among children and adolescents, in order to further understand the correlation between obesity and albuminuria in this demographic. METHODS: We employed information from the National Health and Nutrition Examination Survey (NHANES) 1999-2010 for cross-sectional analysis. Weighted logistic regression was employed to explore the linear relationship between BRI and albuminuria, with subgroup analyses performed for more detailed insights. Weighted linear regression analysis was employed to explore the relationship between BRI and the urine albumin-creatinine ratio (UACR). Additionally, we applied smooth curve fitting to investigate their non-linear relationship and conducted threshold effect analysis to identify any turning point. RESULTS: In this study of 15,487 participants aged 8-19 years, multivariate logistic regression analysis revealed a significant negative correlation between BRI and albuminuria (OR = 0.616, 95%CI: 0.526-0.722). The relationship between BRI and UACR, as shown by multivariate linear regression analysis, was significantly inversely correlated (ß: -5.424, 95%CI: -7.416 to -3.433). Furthermore, smooth curve fitting and threshold effect analysis showed a non-linear relationship between BRI and albuminuria, with a BRI inflection point identified at 2.906. CONCLUSIONS: These findings of our study suggest a significant nonlinear negative association between BRI and the presence of albuminuria among children and teenagers, and maintaining an appropriate BRI may decrease the occurrence of albuminuria in this population.

Study of Neutrophil Gelatinase Associated Lipocalin and Kidney Injury Molecule-1 in Patients with Type 2 Diabetes Mellitus Nephropathy.

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.

Association of domain-specific physical activity with albuminuria among prediabetes and diabetes: a large cross-sectional study.

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.

Circulating metabolomic markers linking diabetic kidney disease and incident cardiovascular disease in type 2 diabetes: analyses from the Hong Kong Diabetes Biobank.

AIMS/HYPOTHESIS: The aim of this study was to describe the metabolome in diabetic kidney disease (DKD) and its association with incident CVD in type 2 diabetes, and identify prognostic biomarkers. METHODS: From a prospective cohort of individuals with type 2 diabetes, baseline sera (N=1991) were quantified for 170 metabolites using NMR spectroscopy with median 5.2 years of follow-up. Associations of chronic kidney disease (CKD, eGFR<60 ml/min per 1.73 m2) or severely increased albuminuria with each metabolite were examined using linear regression, adjusted for confounders and multiplicity. Associations between DKD (CKD or severely increased albuminuria)-related metabolites and incident CVD were examined using Cox regressions. Metabolomic biomarkers were identified and assessed for CVD prediction and replicated in two independent cohorts. RESULTS: At false discovery rate (FDR)<0.05, 156 metabolites were associated with DKD (151 for CKD and 128 for severely increased albuminuria), including apolipoprotein B-containing lipoproteins, HDL, fatty acids, phenylalanine, tyrosine, albumin and glycoprotein acetyls. Over 5.2 years of follow-up, 75 metabolites were associated with incident CVD at FDR<0.05. A model comprising age, sex and three metabolites (albumin, triglycerides in large HDL and phospholipids in small LDL) performed comparably to conventional risk factors (C statistic 0.765 vs 0.762, p=0.893) and adding the three metabolites further improved CVD prediction (C statistic from 0.762 to 0.797, p=0.014) and improved discrimination and reclassification. The 3-metabolite score was validated in independent Chinese and Dutch cohorts. CONCLUSIONS/INTERPRETATION: Altered metabolomic signatures in DKD are associated with incident CVD and improve CVD risk stratification.