Urinary Albumin-to-creatinine Ratio Levels Research Articles

Immunosuppressant Agents as Add-On Therapy Failed to Improve the Outcome of Immunoglobulin A Nephropathy with Crescent Score C1.

Background The renoprotective benefits of adding immunosuppressant therapy to corticosteroid (CS) treatment for immunoglobulin A nephropathy (IgAN) patients with less than 25% crescent formation (C1) remains uncertain, warranting further research. Methods A retrospective study was conducted on IgAN patients with crescent C1 lesions confirmed by renal biopsy at Xinqiao Hospital between May 1, 2017, and May 1, 2020. Patients were stratified into either the CS treatment group or the CS combined with an additional immunosuppressant therapy group. Follow-up assessments were conducted within 24 months. Propensity score analysis was used to match patients receiving CS and CS+immunosuppressant drug treatment in a 1:1 ratio. Primary outcomes included changes in estimated glomerular filtration rate (eGFR) and urine albumin-to-creatinine ratio (UACR). Subgroup analyses were performed to evaluate the benefits of different populations. Composite endpoint outcomes comprised a 30% eGFR decrease, end-stage kidney disease (ESKD) necessitating dialysis or transplant, or kidney disease-related mortality. Adverse events were also compared between the two groups. Results: 296 IgAN patients with C1 lesions were included in the analysis. Baseline characteristics indicated that IgAN patients in the CS+immunosuppressant group exhibited poorer renal function and higher UACR levels. Propensity score analysis effectively minimized the influence of baseline clinical characteristics, including age, serum creatinine, initial eGFR, UACR, and 24-hour proteinuria. Both treatment groups demonstrated continuous eGFR improvement and significant UACR reduction during follow-up, especially at 6 months. However, no significant differences in eGFR and UACR reduction rates were observed between the two groups throughout the entire follow-up period, both before and after matching. Subgroup analysis revealed improved eGFR in both treatment groups, notably among patients with an initial eGFR below 90 ml/min/1.73 m2. Conversely, IgAN patients with C1 lesions and a cellular crescent ratio exceeding 50% treated with CS and immunosuppressant therapy experienced a significant improvement in renal function and a decline in urinary protein creatinine ratio. Composite endpoint outcomes did not significantly differ between the two groups, while the incidence of adverse events was comparable. Conclusion Our findings suggest that the addition of immunosuppressant therapy to corticosteroid monotherapy did not confer significant therapeutic advantages in patients with C1 lesions compared to CS monotherapy, although some specific patient populations appeared to derive modest benefits from this combined approach.

Longitudinal albuminuria patterns predict coronary artery calcification progression: Findings from the coronary artery risk development in young adults study

Background and aimsAlbuminuria is an established risk factor for adverse cardiovascular outcomes. However, few studies have characterized longitudinal albuminuria patterns based on long-term measurement of urine albumin-to-creatinine ratio (UACR) levels. We aimed to evaluate the association between longitudinal albuminuria patterns in midlife adults and subsequent CAC progression. MethodsWe included 1919 participants with CAC assessment by computed tomography from CARDIA (Coronary Artery Risk Development in Young Adults) study. CAC progression was determined for each individual as the difference of logarithmic CAC scores at follow-up and baseline. Albuminuria patterns across a 10-year span were estimated by longitudinal UACR levels. Multivariable general linear models were used to evaluate the association of long-term albuminuria patterns with CAC progression. ResultsOf the 1919 included participants, 583 (30.4%) participants experienced CAC progression, and the mean (SD) age was 50.4 (3.5) years at year 25. A total of four dynamic albuminuria patterns were identified. After multivariable adjustment, there were significant differences in CAC progression by albuminuria patterns as demonstrated as percent change in CAC with 36.0% (SE, 1.5) progression for mid- and late-life normoalbuminuria group, 46.0% (SE, 7.6) for midlife normoalbuminuria and late-life high albuminuria group, 52.4% (SE, 7.1) for midlife high albuminuria and late-life normoalbuminuria group, and 54.5% (SE, 8.7) for mid- and late-life high albuminuria group (p = 0.019). Similar findings were also observed in CAC volume score changes. ConclusionsLongitudinal albuminuria patterns across a 10-year span were associated with worse CAC progression independent of baseline CAC level and albuminuria changes, suggesting that it may provide early identification of high-risk individuals with dynamic rises in albuminuria who may benefit from aggressive risk factor modification.

Accumulation of Microvascular Target Organ Damage in Systemic Lupus Erythematosus Patients Is Associated with Increased Cardiovascular Risk.

Background: Systemic lupus erythematosus (SLE) is a prototype autoimmune disease associated with increased cardiovascular (CV) burden. Besides increased arterial stiffness and subclinical atherosclerosis, microvascular dysfunction is considered an important component in the pathophysiology of CV disease. However, there is a lack of data regarding the effect of multiple target organ damage (TOD) on CV health. Objectives: This study aimed to evaluate (i) the presence of microvascular changes in SLE in various vascular beds, (ii) the possible associations between the accumulation of microvascular TOD and CV risk and (iii) whether Galectin-3 represents a predictor of combined microvascular TOD. Methods: Participants underwent (i) evaluation of skin microvascular perfusion (laser speckle contrast analysis), (ii) fundoscopy (non-mydriatic fundus camera), (iii) indirect assessment of myocardial perfusion (subendocardial viability ratio) and (iv) determination of urine albumin-to-creatinine ratio (UACR). CV risk was calculated using the QResearch Risk Estimator version 3 (QRISK3). Serum Galectin-3 levels were determined. Results: Forty-seven SLE patients and fifty controls were studied. SLE patients demonstrated impaired skin microvascular reactivity (160.2 ± 41.0 vs. 203.6 ± 40.1%), retinal arteriolar narrowing (88.1 ± 11.1 vs. 94.6 ± 13.5 μm) and higher UACR levels compared to controls. Furthermore, SLE individuals had significantly higher Galectin-3 levels [21.5(6.1) vs. 6.6(6.6) ng/dL], QRISK3 scores [7.0(8.6) vs. 1.3(3.6)%] and a greater chance for microvascular dysfunction. In the SLE group, patients with multiple TOD exhibited higher QRISK3. In the multivariate analysis, the accumulation of TOD correlated with disease activity and Galectin-3 (p < 0.05). Conclusions: Our study showed for the first time that SLE patients exhibit a greater number of cases of TOD. The accumulation of TOD was associated with increased CV risk. Clinicians dealing with SLE should be aware and seek microvascular alterations.

Correlations of Serum Retinol-Binding Protein and Stromal Cell-Derived Factor-1 with Renal Function in Patients with Diabetic Kidney Disease.

The aim is to investigate the correlations of serum retinol-binding protein (RBP) and stromal cell-derived factor-1 (SDF-1) with renal function in patients with diabetic kidney disease (DKD). A total of 438 patients with type 2 diabetes mellitus (T2DM) treated from October 2017 to October 2020 were enrolled in this prospective study and divided into simple T2DM and DKD groups. According to urinary albumin-to-creatinine ratio (UACR), DKD patients were divided into moderate, severe, and nephrotic groups. They were assigned to one of the following categories of estimated glomerular filtration rate (eGFR): G1, G2, G3a, G3b, G4, and G5 stages. The correlations of RBP and SDF-1 with renal function were analyzed. The DKD group had a longer T2DM course and higher RBP, uric acid (UA), blood urea nitrogen (BUN), β2-microglobulin (β2-MG), serum creatinine (Scr) levels and UACR, and lower SDF-1 level and eGFR than those of simple T2DM group (p < 0.05). The areas under the receiver operating characteristic curves of RBP and SDF-1 for identifying DKD were 0.903 and 0.868, and the optimal cutoff values were 70.71 mg/L and 5.69 ng/mL, respectively. With increasing urinary albumin and clinical stage, RBP, UA, BUN, β2-MG and Scr levels and UACR significantly rose, while SDF-1 level and eGFR declined (p < 0.05). In patients with DKD, RBP was correlated positively with UACR, UA, BUN, β2-MG, and Scr (r = 0.764/0.787/0.693/0.577/0.801, p < 0.0001), and negatively with eGFR (r = -0.782, p < 0.0001). SDF-1 was correlated negatively with UACR, UA, BUN, β2-MG and Scr (r = -0.744/-0.794/-0.666/-0.605/-0.820, p < 0.0001), and positively with eGFR (r = 0.767, p < 0.0001). The multiple linear regression equation was RBP = 29.852 + 0.007 x UACR + 0.101 x UA + 0.497 x BUN + 0.034 x Scr-0.083 x eGFR (p < 0.001). RBP and SDF-1 can identify DKD in patients with T2DM, and the degree of renal function damage is correlated positively with RBP and negatively with SDF-1. Elevated levels of UA, BUN, Scr and UACR as well as reduced eGFR are risk factors for evaluating RBP.

Lower urinary albumin-to-creatinine ratio predicted all-cause and cardiovascular mortality in Chinese population with diabetes and prediabetes-The Shanghai Changfeng cohort study.

Elevated urinary albumin-to-creatinine ratio (UACR) was associated with increased mortality in general population and diabetic patients. However, whether the association remains similar in the subjects with different status of glucose metabolism was unclear. The optimal level of UACR in predicting mortality also remained unknown. This study aims to investigate the relationship between UACR with all-cause and cardiovascular mortality in population with different status of glucose metabolism and explore the predictive cutoff point of UACR. Six thousand three hundred and eighty-six community-dwelling individuals aged ≥45 years were enrolled and followed for an average of 5.3 years. Cox proportional hazards model was performed to analysis the association of baseline UACR and all-cause as well as cardiovascular mortality according to the status of glucose metabolism. Receiver operating characteristic curve was plotted to explore the optimal predictive cutoff point of UACR. With UACR increasing, both the prevalence of all-cause and cardiovascular death increased. Cox analyses showed baseline UACR independently predicted the risk of all-cause and cardiovascular mortality in the patients with prediabetes mellitus (pre-DM) and diabetes mellitus (DM) but not in subjects with normal glucose tolerance (NGT). When divided by quartiles of UACR, the cumulative survival rate decreased acrossing the quartiles. Compared to the subjects with lowest quartile of UACR, participants with UACR ≥7.40 mg/gCr had a higher risk of all-cause mortality, and participants with UACR ≥16.60 mg/gCr had an increased risk of cardiovascular mortality in all hyperglycemia subjects. The optimal predictive cutoff point of UACR was about 17 mg/gCr. UACR was an independent predictor of all-cause and cardiovascular mortality in population with pre-DM and DM but not in the subjects with NGT. The optimal predictive cutoff point of UACR is about 17 mg/gCr, which was far below the diagnostic cutoff point of microalbuminuria. Earlier interventions of albuminuria should be initiated from very early stage of hyperglycemia to reduce the burden of death in all patients whose glucose metabolism are impaired.

Cardioprotective pharmacotherapy in patients with type 2 diabetes across the Middle East and Africa: the PACT-MEA study

Abstract Background There is limited information about the management of cardiovascular (CV) risk in patients with type 2 diabetes (T2D) in the Middle East and Africa. For patients with T2D and established atherosclerotic cardiovascular disease (eASCVD) or those at risk for ASCVD, global guidelines recommend the use of antidiabetic medications with proven cardiovascular and kidney benefit (glucagon-like peptide-1 receptor agonists [GLP-1 RAs] and sodium-glucose cotransporter-2 inhibitors [SGLT2is]), in addition to lipid lowering, blood pressure lowering, and antiplatelet therapy, independent of baseline HbA1c or metformin use. Purpose To determine the use of pharmacotherapy among a population of patients with T2D and eASCVD or high/very high ASCVD risk in seven countries across the Middle East and Africa. Methods Adult patients with T2D were enrolled in a cross-sectional, observational study in Bahrain, Egypt, Jordan, Kuwait, Qatar, South Africa, and United Arab Emirates. Pharmacotherapy data extracted from the medical charts of patients during a routine scheduled clinic visit in 2022 were analysed. Descriptive statistics were used to characterize patients with T2D and their glucose-lowering pharmacotherapy use by age, diabetes duration, body mass index, HbA1c, microvascular complications, estimated glomerular filtration rate (eGFR), and urinary albumin to creatinine ratio (UACR). Results Of the 3726 patients in the overall study sample (mean age, 58 ± 12; male, 53%), one in five had eASCVD (21%) and nearly all were classified as being at high (69%)/very high risk (30%, includes eASCVD), according to European Society of Cardiology (ESC) 2021 guidelines. About one-third (36%) of patients were taking SGLT2is (Table 1, range across countries: 20%-64%). Use of SGLT2is was similar across age and BMI but more patients with T2D for ≥10 years (40%) received these medications than those with T2D for &amp;lt;10 years (31%). More males than females were on SGLT2is (40% vs 32%). Use of SGLT2is was also higher among patients with HbA1c ≥7% (42% vs 33%, Table 2). SGLT2i use was similar by eGFR and UACR levels. Few (13%) of the overall sample of patients with T2D received GLP-1 RAs (Table 1, range across countries: 3%-25%), the use of which declined with age. More females than males were taking GLP1-RAs (16% vs 11%). More patients with obesity (BMI ≥30 kg/m2) received GLP-1 RAs than those without obesity (18% vs 8%); use was also higher among patients with eGFR ≥60 (14% vs 9%, Table 2). Conclusions Despite availability of cardio-renal therapy in each of the seven participating countries in the Middle East and Africa, few patients with T2D who had eASCVD or were at high/very high risk for ASCVD received SGLT2is or GLP-1 RAs, as recommended by guidelines. Active prioritization of cardio-renal protective therapies based on CV risk and renal target organ damage should be addressed given the high burden of disease and complications in the region.Table 1Table 2

Dyslipidaemia and its management in patients with type 2 diabetes across the Middle East and Africa: the PACT-MEA study

Abstract Background There is a scarcity of high-quality epidemiological data on the clinical burden of type 2 diabetes (T2D) and cardiovascular risk (CV) in the Middle East and Africa due to under-representation of these regions in contemporary diabetes and cardiovascular trials. Multiple risk factors, including dyslipidaemia, increase CV risk in patients with T2D and established atherosclerotic cardiovascular disease (eASCVD) and those at risk for ASCVD. According to the European Society of Cardiology (ESC) 2021 Guidelines, target low-density lipoprotein cholesterol (LDL-C) for patients with T2D is &amp;lt;1.8 mmol/L (&amp;lt;1.4 mmol/L in patients with eASCVD or at very high risk). Purpose To establish the status of dyslipidaemia and its management in patients with T2D and eASCVD or high/very high ASCVD risk across the Middle East and Africa. Methods Adult patients with T2D participating in a cross-sectional, observational study in seven Middle East and African countries were included in the analysis. Laboratory and medication data were collected from medical charts of patients attending a routine health visit in 2022. Descriptive statistics were used to characterize the lipid profile and management of patients with T2D by age, diabetes duration, body mass index, HbA1c, microvascular complications, estimated glomerular filtration rate (eGFR), and urinary albumin to creatinine ratio (UACR). Results There were 3726 patients in the overall study sample (mean age, 58 ± 12; male, 53%), almost all of whom were at high (69%)/very high (30%, includes eASCVD) risk according to ESC 2021 guidelines. In patients for whom data was available in the medical record, median LDL-C (n=2525) was 2.2 mmol/L (IQR, 1.7 to 3.0), HDL-C (n=2453) was 1.1 mmol/L (IQR, 0.9 to 1.3), and triglycerides (n=2488) were 1.6 mmol/L (IQR, 1.2 to 2.3). Of the patients with high/very high ASCVD risk (n=2313), 30% met the ESC guideline-recommended target for LDL-C of &amp;lt;1.8 mmol/L and 16% met the target of &amp;lt;1.4mmol/L. Most patients were on statin therapy (77%, range across countries: 60%-87%, Table 1), with use increasing with age and duration of diabetes. More patients with T2D for ≥10 years were on high intensity statin therapy than those with T2D &amp;lt;10 years (37% vs 33%). A similar pattern was observed for patients with HbA1c levels ≥7% (37% vs 31%, Table 2). Most patients with nephropathy were on statins (87%); use increased with lower eGFR and higher UACR levels. Very few patients were on Ezetimibe (6.4%), fibrates (4.8%), fish oil (including icosapent ethyl) (1.4%), or proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitors (0.5%). Conclusions Utilization of moderate intensity statin therapy (less than 50% LDL reduction) despite high and very high CV risk leads to failure to achieve cardioprotective LDL targets in most patients. Given the high burden of ASCVD in patients with T2D, prioritization of high intensity lipid lowering therapy is recommended.Table 1Table 2

Association Between Monocyte-to-High-Density Lipoprotein (HDL) Cholesterol Ratio and Proteinuria in Patients With Type 2 Diabetes Mellitus: A Prospective Observational Study.

Background Diabetes mellitus (DM) refers to a group of metabolic disorders that share the phenotype of hyperglycemia. "Diabetic nephropathy (DN)" is a microvascular complication of DM, and it is the leading cause of end-stage renal failure. Increased urinary albumin excretion (UAE) and a decrease in glomerular filtration rate (GFR) are associated with DN along with elevated blood pressure and end-stage renal disease (ESRD). The purpose of this study is to analyze the prognostic significance of the monocyte-to-high-density lipoprotein (HDL) cholesterol ratio (MHR) in DN patients. Materials and methods This prospective observational study was carried out over a period of 1.5 years, with patients being followed up for three months. One hundred twenty participants were enrolled and allotted into groups based on the measure of urine albumin-to-creatinine ratio (UACR). The participants were categorized into healthy individuals, normoalbuminuric diabetic patients, microalbuminuric diabetic patients, and macroalbuminuric diabetic patients group. The MHR, neutrophil-to-lymphocyte ratio (NLR), and platelet-to-lymphocyte ratio (PLR) were estimated and compared between the baseline measurements. Conclusion The MHR, NLR, and PLR showed a positive correlation with UACR levels which could serve as an inflammatory marker and be used as an inexpensive and accessible prognostic marker in DN patients.

Effects of esaxerenone on blood pressure, urinary albumin excretion, serum levels of NT-proBNP, and quality of life in patients with primary aldosteronism.

Primary aldosteronism (PA) is typically managed with mineralocorticoid receptor antagonists (MRAs) barring adrenalectomy. The efficacy of esaxerenone, a nonsteroidal MRA, were explored in patients with PA. Various parameters such as the urinary albumin to creatinine ratio (UACR) and serum levels of N-terminal prohormone of brain natriuretic peptide (NT-proBNP) were evaluated in 25 PA patients before and 3 and 6 months after esaxerenone treatment. Systolic and diastolic blood pressure (BP), and the estimated glomerular filtration rate decreased after treatment, while serum levels of potassium and active renin increased. Significant reductions were observed in UACR 3 and 6 months after treatment. A significant decrease in NT-proBNP was evident at 6 months but not 3 months after treatment. Correlation analysis indicated that the reductions in BP and UACR at 3 months were independent of estimated daily salt intake. Furthermore, the effect of esaxerenone treatment on lowering UACR and NT-proBNP levels was independent of BP reduction. Responders whose systolic BP decreased 6 months after esaxerenone treatment by more than 10 mmHg compared to pretreatment had higher pretreatment NT-proBNP and similar UACR before and after treatment when compared with nonresponders. Esaxerenone improved mental, physical, and social quality of life (QOL) 6 months after treatment compared to healthy controls and increased over time. No patients discontinued treatment due to severe hyperkalemia or renal dysfunction. In conclusion, esaxerenone is a safe and effective MRA for PA treatment, offering significant benefits in terms of hypertension, albuminuria, NT-proBNP levels, and QOL improvement. Esaxerenone effectively lowers BP, UACR, and serum levels of NT-proBNP independent of dietary salt intake in mild PA patients. ARC active renin concentration, DBP diastolic blood pressure, MR mineralocorticoid receptor, MRA mineralocorticoid receptor antagonist, NT-proBNP N-terminal pro-brain natriuretic peptide, PA primary aldosteronism, QOL quality of life,SBP systolic blood pressure,SF-36Medical Outcomes Study 36-Item Short-Form Health Survey,UACR urinary albumin to creatinine ratio.

Prospective Cohort Study of Soluble Urokinase Plasminogen Activation Receptor and Cardiovascular Events in Patients With CKD

Soluble urokinase plasminogen activation receptor (suPAR) is an immune-derived pathogenic factor for kidney and atherosclerotic disease. Whether the association between suPAR and cardiovascular (CV) outcomes is dependent on the severity of underlying kidney disease is unclear. We measured serum suPAR levels in 4994 participants (mean age 60 years; 60% men; 36% with diabetes mellitus; mean estimated glomerular filtration rate (eGFR) 49 ml/min per 1.73 m2, SD 18) of the German Chronic Kidney Disease (GCKD) cohort and examined its association with all-cause death, CV death, and major CV events (MACE) across the range of eGFR and urine albumin-to-creatinine ratio (UACR). The median suPAR level was 1771 pg/ml (interquartile range [IQR] 1447-2254 pg/ml). SuPAR levels were positively and independently correlated with age, eGFR, UACR, and parathyroid hormone levels. There were 573 deaths, including 190 CV deaths and 683 MACE events at a follow-up time of 6.5 years. In multivariable analyses, suPAR levels (log2) were associated with all-cause death (hazard ratio [HR] 1.36, 95% confidence interval [CI] 1.21-1.53), CV death (HR 1.27, 95% CI 1.03-1.57), and MACE (HR 1.13, 95% CI 1.00-1.28), and were not found to differ according to diabetes mellitus status, baseline eGFR, UACR, or parathyroid hormone levels. In mediation analysis, suPAR's direct effect on all-cause death, CV death, and MACE accounted for 77%, 67%, and 60% of the total effect, respectively; whereas the effect mediated through eGFR accounted for 23%, 34%, and 40%, respectively. In a large cohort of individuals with chronic kidney disease (CKD), suPAR levels were associated with mortality and CV outcomes independently of indices of kidney function, consistent with its independent role in the pathogenesis of atherosclerosis.

408-P: Associations between Apolipoprotein B (apoB): Apolipoprotein A1 (apoA1) Ratio and Metabolic and Kidney Disease in Youth with Type 1 Diabetes

ApoA1 is a major protein component of high-density lipoprotein (HDL) and apoB the main protein component of low-density lipoprotein (LDL). The ratio between apoB and apoA1 (ApoB:ApoA1) is often used to measure cardiovascular disease (CVD) risk in adults, yet little is known about its relationship with insulin resistance, central adiposity and early kidney disease, important CVD risk factors, in youth with T1D. In a study of 50 youth with type 1 diabetes, glomerular filtration rate (GFR) and renal plasma flow (RPF) were assessed using iohexol and p-aminohippurate clearance, and urine albumin-to-creatinine ratio (UACR) was also measured. Central adiposity was assessed using DXA and insulin sensitivity was estimated (eIS). Intraglomerular pressure was estimated using the Gomez equations. The study participants were 16±3.0 years old, 50% were female, and their average HbA1c was 8.7±1.3%. They had an average T1D duration of 5.7±2.6 years, with UACR levels of 6[5-14] mg/g and GFR of 189±40 ml/min. Concentrations of apoA1 and apoB were quantified by targeted nuclear magnetic resonance spectroscopy. ApoA1 (185±35 vs. 150±36 mg/dl, p=0.001) and apoB (108±29 vs. 90±27 mg/dl, p=0.03) were higher in girls vs. boys, but the apoB:apoA1 ratio was similar between the sexes (p=0.59). ApoB correlated with PGLO (r: 0.42, p=0.01), log UACR (r: 0.33, p=0.02), and trunk mass (r: 0.34, p=0.02), whereas ApoB:ApoA1 correlated with GFR (r: 0.44, p=0.002), PGLO (r: 0.48, p=0.01), log UACR (r: 0.38, p=0.008), trunk mass (r: 0.45, p=0.001), BMI (r: 0.40, p=0.004) and inversely with eIS (-0.44, p=0.001). The ratio of apoB to apoA1 associated with markers of metabolic and kidney disease in youth with T1D. Further research is needed to fully understand the mechanisms behind these associations and to identify potential strategies for preventing or mitigating cardiovascular disease in young persons with T1D. Disclosure L.Remmers: None. C.Birznieks: None. D.Carrasco: None. S.Gross: None. J.K.Snell-bergeon: None. L.A.Hall: None. K.J.Nadeau: None. P.Bjornstad: Advisory Panel; AstraZeneca, Novo Nordisk, Lilly, Horizon Therapeutics plc, Boehringer Ingelheim (Canada) Ltd., LG Chem, Consultant; Bayer Inc., Bristol-Myers Squibb Company. K.L.Tommerdahl: None.

#3113 BURDEN OF KIDNEY DISEASES IN THE GENERAL POPULATION OF THE VAL VENOSTA/VINSCHGAU DISTRICT

Abstract Background and Aims Chronic kidney disease (CKD) is a public health burden affecting &amp;gt;10% of the population worldwide. Population-based studies are essential to assess CKD prevalence and its determinants. However, questionnaires to survey CKD and other kidney diseases in the general population are scarce. We developed a novel questionnaire to identify several types of kidney disease in the general population and implemented it in a large central-European population study. We integrated questionnaire responses with standard renal biochemical measurements to estimate CKD prevalence in the Val Venosta/Vinschgau district. We aimed to assess the degree of CKD underdiagnosis and to describe the kidney health status of study participants. Method Within the Cooperative Health Research In South Tyrol (CHRIS) study, we conducted a cross-sectional assessment of kidney health on 11684 adults (mean age 45 years; females 53.8%) with interviewer-administered kidney questionnaire and measured fasting serum creatinine and albuminuria. The questionnaire covered retrospectively various kidney diseases, including reduced renal function and renal surgeries (Fig. 1). Questions asked if a doctor had ever diagnosed the specific condition and the age at diagnosis. We defined CKD based on combinations of self-reported diagnosis of reduced kidney function (Q6), CKD-EPI 2021 estimated glomerular filtration rate (eGFR) levels, and microalbuminuria (Table 1). Prevalence was estimated via the Clopper-Pearson method and adjusted to the general target population via relative sampling weights. Using factor analysis we explored the underlying correlation structures within and between questionnaire items and laboratory markers. Results Participants had median eGFR and urinary albumin-to-creatinine ratio (UACR) of 98.4 ml/min/1.73 m2 (IQR: 87.8-108.8) and 5.7 mg/g (IQR: 3.8-10.0), respectively. Overall, 744 reported only one and 179 reported at least two types of kidney diseases (Fig. 1). Glomerulonephritis (n = 359; 3.14%), kidney stones (n = 311; 2.93%) and other kidney diseases (n = 200; 1.91%) were the most frequent types. Males reported kidney stones (M: 3.2%; F: 2.2%; p-value = 0.0013) and renal surgeries (M: 0.9%; F: 0.5%; p-value = 0.0116) more frequently than females. Females reported a higher proportion of glomerulonephritis (M: 0.6%; F: 5.2%; p-value&amp;lt;0.0001). The population-weighted CKD prevalence varied between 0.71% to 9.29% depending on the definition (Table 1), with a KDIGO estimate of 8.79% (95%CI 8.28%-9.31%). Questionnaire items showed low sensitivity and high specificity to identify low eGFR or high UACR levels. Factor analysis revealed two clearly separated latent factors: one representing “reduced renal function”, which included eGFR, UACR, and the question Q6 on reduced kidney function; and one representing “all other kidney diseases”. Conclusion In the Val Venosta/Vinschgau district, CKD prevalence is aligned to Western-European countries. In general population studies, questionnaire-based CKD assessment may severely underestimate CKD prevalence as compared to eGFR- and UACR-based estimates. Our analysis highlights that the large majority of individuals with CKD according to KDIGO guidelines were unaware of the disease. On the other hand, the questionnaire has allowed identifying several specific kidney diseases that usually go undetected in population studies. The limited discriminant ability of questionnaire items and the identifiable correlation structure support the use of the survey questionnaire as an integrative tool to study the kidney health status in general population.

Association between change of albuminuria and left ventricular diastolic function in type 2 diabetes

Abstract Funding Acknowledgements Type of funding sources: None. Background Albuminuria is associated with left ventricular (LV) hypertrophy and diastolic dysfunction in patients with type 2 diabetes (T2DM), however the role of change in albuminuria and cardiac structure and function changes remain unclear. The aim of our study was to investigate the impact of change in albuminuria on changes of echocardiography parameters. Methods Patients with T2DM without cardiovascular disease at baseline were recruited from 2012 to 2016. All patients were performed with detailed echocardiography examination and received urine albumin to creatinine ratio (UACR) or 24-h urine albumin excretion (UAE) test at baseline and follow-up. Multivariable linear regression was applied to estimate the association between albuminuria and changes of echocardiography parameters. Results A total of 199 patients with T2DM were recruited (female, 47.2%; mean age, 61±10 years). Patients were divided into 4 albuminuria change groups according to baseline UACR or UAE level, 8 patients were in macroalbuminuria to none-macroalbuminuria group, 93 in none-macroalbuminuria-stable group, 68 in macroalbuminuria-stable group, and 30 in none-macroalbuminuria to macroalbuminuria group. There was a significant difference in the change of LV diastolic function (estimated by average E/e’) by albuminuria change groups (mean [SD] average E/e’: macroalbuminuria to none-macroalbuminuria, −1.40 [2.83]; none-macroalbuminuria-stable, 0.64 [2.16]; macroalbuminuria-stable, 0.97 [2.59]; non-macroalbuminuria to macroalbuminuria, 1.27 [2.71]; P=0.04). However, the changes in LV mass index (LVMi), ejection fraction (LVEF), E/A, and left atrial volume index (LAVi) between patients in different albuminuria change groups were insignificant. Multivariable regression demonstrated non-macroalbuminuria to macroalbuminuria was associated with increase in average E/e’, compared to patients with macroalbuminuria to none-macroalbuminuria (ß = 1.92, P &amp;lt; 0.05) after adjusting age, sex, hypertension, body mass index, eGFR, and diabetes duration. Conclusion The progression of none-macroalbuminuria to macroalbuminuria was associated with greater deterioration of LV diastolic function.

Positive correlation between hypertensive retinopathy and albuminuria in hypertensive adults

PurposeWe investigated the association between albuminuria and hypertensive retinopathy (HR) in hypertensive adults.MethodsThis was a cross-sectional subgroup analysis of data from the China Stroke Primary Prevention Trial. We enrolled 2,964 hypertensive adults in this study. Keith-Wagener-Barker stages was used to assess HR. The urinary albumin to creatinine ratio (UACR) was calculated to evaluate albuminuria.ResultsHR was found in 76.6% (n = 2, 271) of the participants, albuminuria was found in 11.1% (n = 330). The UACR levels were significantly higher in subjects with HR than in those without HR (grade 1, β = 1.42, 95% confidence intervals [CI]: -0.12, 2.95, p = 0.070; grade 2, β = 2.62, 95% CI: 0.56, 4.67, p = 0.013; grade 3, β = 5.17, 95% CI: 1.13, 9.20, p = 0.012). In the subgroup analyses, the association between HR and UACR was stronger in current smokers (p for interaction = 0.014). The correlation between HR grades 1 and 2 and UACR was stronger in subjects with higher triglyceride levels (≥ 1.7 mmol/L), but for grade 3 HR, this correlation was stronger in subjects with lower triglycerides levels (< 1.7 mmol/L, p for interaction = 0.023). The odds of albuminuria were significantly higher in subjects with HR than in those without HR (grade 1, odds ratio [OR] = 1.57, 95% CI: 1.08, 2.29, p = 0.019; grade 2, OR = 2.02, 95% CI: 1.28, 3.18, p = 0.002; grade 3, OR = 2.12, 95% CI: 0.99, 4.55, p = 0.053). In the subgroup analyses, the association between HR grades 1 and 2 and albuminuria was stronger in subjects with higher triglycerides levels (≥ 1.7 mmol/L), but for grade 3 HR, this correlation was stronger in subjects with lower triglyceride levels (< 1.7 mmol/L, p for interaction = 0.014).ConclusionHR was positively correlated with albuminuria in hypertensive Chinese adults. This correlation was more remarkable when the population was stratified by triglycerides levels and smoking status. HR can be used as an indicator of early renal injury.

Neck-to-height ratio is positively associated with diabetic kidney disease in Chinese patients with type 2 diabetes mellitus.

The aim of this study was to investigate the associations of neck circumference (NC) and neck-to-height (NHR) with diabetic kidney disease (DKD) in Chinese patients with type 2 diabetes mellitus (T2DM). A total of 2,615 patients with prevalent T2DM were enrolled. NHR was calculated through NC (cm) divided by height (cm), and prevalent DKD was defined as the urinary albumin-to-creatinine ratio (UACR) ≥ 30 mg/g or the estimated glomerular filtration rate (eGFR) < 60 ml/min per 1.73 m2 in the absence of other primary kidney diseases. The levels of NC and NHR were higher in DKD patients compared with non-DKD patients (38.22 vs. 37.71, P = 0.003; 0.232 vs. 0.227, P < 0.001, respectively). After full adjustments, individuals at the highest tertile of NHR had higher odds of DKD than those at the lowest tertile (multivariate-adjusted OR = 1.63, 95% CI: 1.22, 2.18), but this association was not pronounced with NC (multivariate-adjusted OR = 1.24, 95% CI: 0.87, 1.76). Individuals at the highest tertile of NHR had lower eGFR (β = -4.64, 95% CI: -6.55, -2.74) and higher UACR levels (β = 0.27, 95% CI: 0.10, 0.45) than those at the lowest tertile. The adverse association between NHR and prevalent DKD remained statistically significant among most of the subgroups analyzed and no interaction effects were observed. The increase in NHR was adversely and independently associated with DKD in this Chinese T2DM population.

The association of thyroid parameters with markers of chronic kidney disease in euthyroid patients with type 2 diabetes.

This study was established to explore the association of thyroid parameters including thyroid hormone and thyroid sensitivity indices with chronic kidney disease (CKD) in euthyroid patients with type 2 diabetes (T2D). CKD markers were defined by estimated glomerular filtration rate (eGFR) based on serum creatinine (Scr) (eGFRcr), eGFR based on cystatin C (cys C) (eGFRcys), and urinary albumin-to-creatinine ratio (UACR). Thyroid parameters, including triiodothyronine (FT3), free thyroxin (FT4), thyroid-stimulating hormone (TSH), FT3/FT4 ratio, TSH index (TSHI), and thyrotroph T4 resistance index (TT4RI), were measured. The prevalence rates of CKD defined by eGFRcys, eGFRcr, and UACR was 19.9%, 14.1%, and 50.6%, respectively. The eGFRcys and eGFRcr levels increased with increasing FT3 and FT3/FT4 tertiles, while the UACR levels increased with decreasing FT3 tertiles. Spearman's analysis demonstrated that FT3 and FT3/FT4 were positively associated with eGFRcys and eGFRcr, and negatively associated with UACR. In logistic regression analyses, compared with the lowest FT3 tertile (≤4.12 pmol/L), the adjusted ORs for CKD (eGFRcys <60 mL/min/1.73 m2) in the middle FT3 tertile (4.12-4.74 pmol/L) and higher FT3 tertile (>4.74 pmol/L) were 0.248 and 0.153, respectively, but prominent associations of thyroid parameters with eGRFcr <60 mL/min/1.73 m2 and UACR were not observed after adjustment. Linear regression analysis demonstrated that eGFRcys was more strongly associated with FT3 than eGFRcr or UACR in the adjusted model. Among euthyroid patients with T2D, FT3 in the normal range was the independent factor most strongly related to CKD. Additionally, eGFRcys rather than eGFRcr or UACR was the CKD marker most associated with FT3.

Association of Empagliflozin Treatment With Albuminuria Levels in Patients With Heart Failure

Albuminuria, routinely assessed as spot urine albumin-to-creatinine ratio (UACR), indicates structural damage of the glomerular filtration barrier and is associated with poor kidney and cardiovascular outcomes. Sodium-glucose cotransporter-2 (SGLT2) inhibitors have been found to reduce UACR in patients with type 2 diabetes, but its use in patients with heart failure (HF) is less well studied. To analyze the association of empagliflozin with study outcomes across baseline levels of albuminuria and change in albuminuria in patients with HF across a wide range of ejection fraction levels. This post hoc analysis included all patients with HF from the EMPEROR-Pooled analysis using combined individual patient data from the international multicenter randomized double-blind parallel-group, placebo-controlled EMPEROR-Reduced and EMPEROR-Preserved trials. Participants in the original trials were excluded from this analysis if they were missing baseline UACR data. EMPEROR-Preserved was conducted from March 27, 2017, to April 26, 2021, and EMPEROR-Reduced was conducted from April 6, 2017, to May 28, 2020. Data were analyzed from January to June 2022. Randomization to empagliflozin or placebo. New-onset macroalbuminuria and regression to normoalbuminuria and microalbuminuria. A total of 9673 patients were included (mean [SD] age, 69.9 [10.4] years; 3551 [36.7%] female and 6122 [63.3%] male). Of these, 5552 patients had normoalbuminuria (UACR <30 mg/g) and 1025 had macroalbuminuria (UACR >300 mg/g). Compared with normoalbuminuria, macroalbuminuria was associated with younger age, races other than White, obesity, male sex, site region other than Europe, higher levels of N-terminal pro-hormone brain natriuretic peptide and high-sensitivity troponin T, higher blood pressure, higher New York Heart Association class, greater HF duration, more frequent previous HF hospitalizations, diabetes, hypertension, lower eGFR, and less frequent use of angiotensin-converting enzyme inhibitors or angiotensin receptor blockers and mineralocorticoid receptor antagonists. An increase in events was observed in individuals with higher UACR levels. The association of empagliflozin with cardiovascular mortality or HF hospitalization was consistent across UACR categories (hazard ratio [HR], 0.80; 95% CI, 0.69-0.92 for normoalbuminuria; HR, 0.74; 95% CI, 0.63-0.86 for microalbuminuria; HR, 0.78; 95% CI, 0.63-0.98 for macroalbuminuria; interaction P trend = .71). Treatment with empagliflozin was associated with lower incidence of new macroalbuminuria (HR, 0.81; 95% CI, 0.70-0.94; P = .005) and an increase in rate of remission to sustained normoalbuminuria or microalbuminuria (HR, 1.31; 95% CI, 1.07-1.59; P = .009) but not with a reduction in UACR in the overall population; however, UACR was reduced in patients with diabetes, who had higher UACR levels than patients without diabetes (geometric mean for diabetes at baseline, 0.91; 95% CI, 0.85-0.98 and for no diabetes at baseline, 1.08; 95% CI, 1.01-1.16; interaction P = .008). In this post hoc analysis of a randomized clinical trial, compared with placebo, empagliflozin was associated with reduced HF hospitalizations or cardiovascular death irrespective of albuminuria levels at baseline, reduced progression to macroalbuminuria, and reversion of macroalbuminuria. ClinicalTrials.gov Identifiers: NCT03057977 and NCT03057951.

SGLT2 inhibitors attenuate nephrin loss and enhance TGF-β1 secretion in type 2 diabetes patients with albuminuria: a randomized clinical trial

To evaluate the effect of SGLT2 inhibitor (SGLT2i) on albuminuria, nephrin (NPH) and transforming-growth-factor-beta1 (TGF-β1) levels in urine and low-grade inflammation in type 2 diabetes (T2D) patients. A randomized, blank-controlled clinical trial included 68 T2D patients and 10 controls. Based on the urinary albumin-to-creatinine ratio (UACR), 68 diabetic patients were stratified into three levels, UACR < 30 mg/g, UACR ≧ 30 mg/g to ≦ 300 mg/g and UACR ˃ 300 mg/g, who were randomized (1:1:1) to receive SGLT2i treatment for 12 weeks. The concentrations of NPH and TGF-β1 in urine were measured as indications of podocyte injury and renal fibrosis. Low-grade inflammation was assessed by the levels of IL-6, TNFα and hsCRP. After 12 weeks of SGLT2i treatment, the levels of UACR and NPH decreased, UTGF-β1 increased in the T2D with microalbuminuria and macroalbuminuria groups, NPH (1.12 [0.59, 1.29] vs. 0.71 [0.41, 1.07] µg/ml, P = 0.022) and (1.29 [0.99, 1.96] vs. 0.93 [0.57, 1.31] µg/ml, P = 0.002), UTGF-β1 (4.88 ± 1.31 vs. 7.27 ± 1.21 pg/ml, P  < 0.001) and (4.30 ± 1.34 vs. 6.78 ± 2.59 pg/ml, P  < 0.001), respectively. The changes in NPH were positively correlated with the UACR and negatively correlated with UTGF-β1 in T2D with albuminuria. SGLT2i alleviate nephrin loss and enhance TGF-β1 excretion in urine in T2DM with albuminuria. The anti-albuminuric effect of SGLT2i could be attributed to mitigating podocyte apoptosis and attenuating renal fibrosis.Trial registration This clinical trial was registered on 15/10/2019, in ClinicalTrials.gov, and the registry number is NCT04127084.

Association of Strongyloides stercoralis infection and type 2 diabetes mellitus in northeastern Thailand: Impact on diabetic complication-related renal biochemical parameters.

BackgroundSeveral studies have demonstrated that helminth infections provide a degree of protection against Type 2 diabetes mellitus (T2DM). However, the relationship between Strongyloides stercoralis infection and T2DM has scarcely been investigated and the protective effect of infection against development of diabetic complications is unclear. In this study, we aimed to investigate the relationship between S. stercoralis infection and T2DM in a rural area of Khon Kaen Province, Thailand. The impact of S. stercoralis infection on diabetic complication-related kidney function biochemical parameters and body-mass index (BMI) was also assessed.MethodologyUsing a cross-sectional study design, S. stercoralis infection and T2DM assessments were conducted between October 2020 and May 2021. Associations between S. stercoralis infection, T2DM, and socioeconomic factors were analyzed using multivariable logistic regression analyses. Diabetic complication-related biochemical parameters relating largely to kidney function (estimated glomerular filtration rate (eGFR), urine albumin-to-creatinine ratio (UACR), serum creatinine, uric acid, alanine transaminase (ALT), and low-density lipoprotein cholesterol (LDL-C)) and BMI of participants with and without T2DM were compared between groups with or without S. stercoralis infection.ResultsOne hundred and seven out of 704 individuals (15.20%) were positive for S. stercoralis, and 283 people were diagnosed with T2DM. Of those with T2DM, 11.31% (32/283) were infected with S. stercoralis and of those without T2DM, 17.82% (75/421) were infected with S. stercoralis. Multivariate analysis revealed that T2DM was inversely correlated with S. stercoralis infection (Adjusted OR  =  0.49; 95% CI: 0.30, 0.78; p  = 0.003), while male, increasing age, lower education level, and alcohol intake were positively associated with infection. Those infected with S. stercoralis had lower eGFR levels and higher ALT and UACR levels than those in the uninfected group.ConclusionThis finding indicates that S. stercoralis infection was inversely associated with T2DM in northeastern Thailand, but participants infected with S. stercoralis had lower eGFR levels and higher ALT and UACR levels. Infection with S. stercoralis might lead to worse complication-related renal biochemical parameters.

Association Between the Risk of Non-Alcoholic Fatty Liver Disease in Patients with Type 2 Diabetes and Chronic Kidney Disease.

ObjectiveTo explore the relationship between non-alcoholic fatty liver disease (NAFLD) and chronic kidney disease (CKD) in patients with type 2 diabetes mellitus (T2DM).MethodsA total of 1168 patients with T2DM were divided into the non-CKD and CKD groups, and the difference in the prevalence of NAFLD was compared. The differences in serum creatinine (SCr) and urine albumin-to-creatinine ratio (UACR) levels were compared between the non-NAFLD and NAFLD groups. Patients with T2DM were divided into three groups according to their UACR levels (UACR < 30 mg/g [U1 group]; UACR ≤ 30 mg/g to < 300 mg/g [U2 group]; and UACR ≥ 300 mg/g [U3 group]) or estimated glomerular filtration rate (eGFR) levels (≥ 90 mL/min [G1 group]; eGFR ≤ 60 mL/min to < 90 mL/min [G2 group]; and eGFR < 60 mL/min (G3 group]). The difference in the prevalence and risks of NAFLD in the different UACR or eGFR level groups was analyzed.ResultsThe prevalence of NAFLD in the CKD group was higher than that in the non-CKD group (63.5% vs 50.5%, p < 0.001). The SCr and UACR levels in the NAFLD group were higher than those in the non-NAFLD group (both p<0.05). The prevalence of NAFLD in the U3 group (75.6%) was higher than that in the U1 (50.5%, p < 0.05) and U2 (60.1%, p < 0.05) groups, and the prevalence of NAFLD in the U2 group (60.1%) was higher than that in the U1 group (50.5%, p < 0.05). The risk of NAFLD in the U3 group was higher than that in the U2 group (odds ratio [OR] = 3.032 and 1.473). Despite adjusting the parameters further, the NAFLD risk in the U3 group remained higher than that in the U2 group (OR = 1.660 and 2.342).ConclusionThe risk of NAFLD in patients with T2DM is closely related to CKD.